Bio

Clinical Focus


  • Pediatric Neuroradiology
  • Neuroradiology

Academic Appointments


Professional Education


  • Fellowship:Stanford University Neuroradiology Fellowship (2008) CA
  • Residency:UCLA Medical Center Radiology Fellowship (2006) CA
  • Medical Education:University of Michigan GME Training Verifications (2001) MI
  • Board Certification: Neuroradiology, American Board of Radiology (2008)
  • Board Certification: Diagnostic Radiology, American Board of Radiology (2006)
  • Fellowship, Stanford University, Neuroradiology (2008)
  • Internship:Oakwood Healthcare System (2002) MI

Research & Scholarship

Clinical Trials


  • In Vivo Characterization of Macrophages in Pediatric Patients With Malignant Brain Tumors Using Ferumoxytol-enhanced MRI Recruiting

    This pilot early phase I trial studies how well ferumoxytol-enhanced magnetic resonance imaging (MRI) correlates with inflammatory (macrophage) responses in pediatric patients with malignant brain tumors. If there is good correlation, ferumoxytol-enhanced MRI can serve as a noninvasive imaging biomarker of inflammation.

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Teaching

2018-19 Courses


Publications

All Publications


  • Long-term Supratentorial Radiological Effects of Surgery and Local Radiation in Children with Infratentorial Ependymoma. World neurosurgery Yecies, D., Azad, T. D., Esparza, R., Quon, J., Forkert, N., MacEachern, S. J., Bruckert, L., Maleki, M., Edwards, M., Grant, G., Yeom, K. 2018

    Abstract

    OBJECT: Current standard of care for children with infratentorial ependymoma includes maximal safe resection and local radiation of 54-59gy. High-dose local radiation has been associated with declines in multiple cognitive domains. The anatomic and physiologic correlates of this cognitive decline remain undefined and there have been no radiographic studies on the long-term effects of this treatment paradigm.METHODS: A comprehensive database of pediatric brain tumor patients treated at Stanford Children's from 2004-2016 was queried. Seven patients with posterior fossa ependymoma were identified who were treated with surgery and local radiation alone, who had no evidence of recurrent disease, and had imaging suitable for analysis. Diffusion-weighted MRI (DWI) datasets were used to calculate apparent diffusion coefficient (ADC) maps for each subject, while arterial spin labeling (ASL) datasets were used to calculated maps of cerebral blood flow (CBF). DWI and ASL datasets of 52 age-matched healthy children were a analyzed in the same fashion to enable group comparisons.RESULTS: Several statistically significant differences were detected between the two groups. CBF was lower in the caudate and pallidum and higher in the nucleus accumbens in the ependymoma cohort compared to controls. ADC was increased in the thalamus and trended towards decreased in the amygdala.CONCLUSIONS: Surgery and local radiation for posterior fossa ependymoma are associated with supratentorial ADC and CBF alterations, which may represent an anatomic and physiologic correlate to the previously published decline in neurocognitive outcomes in this population.

    View details for DOI 10.1016/j.wneu.2018.11.039

    View details for PubMedID 30448581

  • Deep-learning-assisted diagnosis for knee magnetic resonance imaging: Development and retrospective validation of MRNet. PLoS medicine Bien, N., Rajpurkar, P., Ball, R. L., Irvin, J., Park, A., Jones, E., Bereket, M., Patel, B. N., Yeom, K. W., Shpanskaya, K., Halabi, S., Zucker, E., Fanton, G., Amanatullah, D. F., Beaulieu, C. F., Riley, G. M., Stewart, R. J., Blankenberg, F. G., Larson, D. B., Jones, R. H., Langlotz, C. P., Ng, A. Y., Lungren, M. P. 2018; 15 (11): e1002699

    Abstract

    BACKGROUND: Magnetic resonance imaging (MRI) of the knee is the preferred method for diagnosing knee injuries. However, interpretation of knee MRI is time-intensive and subject to diagnostic error and variability. An automated system for interpreting knee MRI could prioritize high-risk patients and assist clinicians in making diagnoses. Deep learning methods, in being able to automatically learn layers of features, are well suited for modeling the complex relationships between medical images and their interpretations. In this study we developed a deep learning model for detecting general abnormalities and specific diagnoses (anterior cruciate ligament [ACL] tears and meniscal tears) on knee MRI exams. We then measured the effect of providing the model's predictions to clinical experts during interpretation.METHODS AND FINDINGS: Our dataset consisted of 1,370 knee MRI exams performed at Stanford University Medical Center between January 1, 2001, and December 31, 2012 (mean age 38.0 years; 569 [41.5%] female patients). The majority vote of 3 musculoskeletal radiologists established reference standard labels on an internal validation set of 120 exams. We developed MRNet, a convolutional neural network for classifying MRI series and combined predictions from 3 series per exam using logistic regression. In detecting abnormalities, ACL tears, and meniscal tears, this model achieved area under the receiver operating characteristic curve (AUC) values of 0.937 (95% CI 0.895, 0.980), 0.965 (95% CI 0.938, 0.993), and 0.847 (95% CI 0.780, 0.914), respectively, on the internal validation set. We also obtained a public dataset of 917 exams with sagittal T1-weighted series and labels for ACL injury from Clinical Hospital Centre Rijeka, Croatia. On the external validation set of 183 exams, the MRNet trained on Stanford sagittal T2-weighted series achieved an AUC of 0.824 (95% CI 0.757, 0.892) in the detection of ACL injuries with no additional training, while an MRNet trained on the rest of the external data achieved an AUC of 0.911 (95% CI 0.864, 0.958). We additionally measured the specificity, sensitivity, and accuracy of 9 clinical experts (7 board-certified general radiologists and 2 orthopedic surgeons) on the internal validation set both with and without model assistance. Using a 2-sided Pearson's chi-squared test with adjustment for multiple comparisons, we found no significant differences between the performance of the model and that of unassisted general radiologists in detecting abnormalities. General radiologists achieved significantly higher sensitivity in detecting ACL tears (p-value = 0.002; q-value = 0.019) and significantly higher specificity in detecting meniscal tears (p-value = 0.003; q-value = 0.019). Using a 1-tailed t test on the change in performance metrics, we found that providing model predictions significantly increased clinical experts' specificity in identifying ACL tears (p-value < 0.001; q-value = 0.006). The primary limitations of our study include lack of surgical ground truth and the small size of the panel of clinical experts.CONCLUSIONS: Our deep learning model can rapidly generate accurate clinical pathology classifications of knee MRI exams from both internal and external datasets. Moreover, our results support the assertion that deep learning models can improve the performance of clinical experts during medical imaging interpretation. Further research is needed to validate the model prospectively and to determine its utility in the clinical setting.

    View details for DOI 10.1371/journal.pmed.1002699

    View details for PubMedID 30481176

  • Deep learning for chest radiograph diagnosis: A retrospective comparison of the CheXNeXt algorithm to practicing radiologists. PLoS medicine Rajpurkar, P., Irvin, J., Ball, R. L., Zhu, K., Yang, B., Mehta, H., Duan, T., Ding, D., Bagul, A., Langlotz, C. P., Patel, B. N., Yeom, K. W., Shpanskaya, K., Blankenberg, F. G., Seekins, J., Amrhein, T. J., Mong, D. A., Halabi, S. S., Zucker, E. J., Ng, A. Y., Lungren, M. P. 2018; 15 (11): e1002686

    Abstract

    BACKGROUND: Chest radiograph interpretation is critical for the detection of thoracic diseases, including tuberculosis and lung cancer, which affect millions of people worldwide each year. This time-consuming task typically requires expert radiologists to read the images, leading to fatigue-based diagnostic error and lack of diagnostic expertise in areas of the world where radiologists are not available. Recently, deep learning approaches have been able to achieve expert-level performance in medical image interpretation tasks, powered by large network architectures and fueled by the emergence of large labeled datasets. The purpose of this study is to investigate the performance of a deep learning algorithm on the detection of pathologies in chest radiographs compared with practicing radiologists.METHODS AND FINDINGS: We developed CheXNeXt, a convolutional neural network to concurrently detect the presence of 14 different pathologies, including pneumonia, pleural effusion, pulmonary masses, and nodules in frontal-view chest radiographs. CheXNeXt was trained and internally validated on the ChestX-ray8 dataset, with a held-out validation set consisting of 420 images, sampled to contain at least 50 cases of each of the original pathology labels. On this validation set, the majority vote of a panel of 3 board-certified cardiothoracic specialist radiologists served as reference standard. We compared CheXNeXt's discriminative performance on the validation set to the performance of 9 radiologists using the area under the receiver operating characteristic curve (AUC). The radiologists included 6 board-certified radiologists (average experience 12 years, range 4-28 years) and 3 senior radiology residents, from 3 academic institutions. We found that CheXNeXt achieved radiologist-level performance on 11 pathologies and did not achieve radiologist-level performance on 3 pathologies. The radiologists achieved statistically significantly higher AUC performance on cardiomegaly, emphysema, and hiatal hernia, with AUCs of 0.888 (95% confidence interval [CI] 0.863-0.910), 0.911 (95% CI 0.866-0.947), and 0.985 (95% CI 0.974-0.991), respectively, whereas CheXNeXt's AUCs were 0.831 (95% CI 0.790-0.870), 0.704 (95% CI 0.567-0.833), and 0.851 (95% CI 0.785-0.909), respectively. CheXNeXt performed better than radiologists in detecting atelectasis, with an AUC of 0.862 (95% CI 0.825-0.895), statistically significantly higher than radiologists' AUC of 0.808 (95% CI 0.777-0.838); there were no statistically significant differences in AUCs for the other 10 pathologies. The average time to interpret the 420 images in the validation set was substantially longer for the radiologists (240 minutes) than for CheXNeXt (1.5 minutes). The main limitations of our study are that neither CheXNeXt nor the radiologists were permitted to use patient history or review prior examinations and that evaluation was limited to a dataset from a single institution.CONCLUSIONS: In this study, we developed and validated a deep learning algorithm that classified clinically important abnormalities in chest radiographs at a performance level comparable to practicing radiologists. Once tested prospectively in clinical settings, the algorithm could have the potential to expand patient access to chest radiograph diagnostics.

    View details for DOI 10.1371/journal.pmed.1002686

    View details for PubMedID 30457988

  • Rapid-sequence brain magnetic resonance imaging for Chiari I abnormality JOURNAL OF NEUROSURGERY-PEDIATRICS Pan, J., Quon, J. L., Johnson, E., Lanzman, B., Chukus, A., Ho, A. L., Edwards, M. B., Grant, G. A., Yeom, K. W. 2018; 22 (2): 158–64

    Abstract

    OBJECTIVE Fast magnetic resonance imaging (fsMRI) sequences are single-shot spin echo images with fast acquisition times that have replaced CT scans for many conditions. Introduced as a means of evaluating children with hydrocephalus and macrocephaly, these sequences reduce the need for anesthesia and can be more cost-effective, especially for children who require multiple surveillance scans. However, the role of fsMRI has yet to be investigated in evaluating the posterior fossa in patients with Chiari I abnormality (CM-I). The goal of this study was to examine the diagnostic performance of fsMRI in evaluating the cerebellar tonsils in comparison to conventional MRI. METHODS The authors performed a retrospective analysis of 18 pediatric patients with a confirmed diagnosis of CM-I based on gold-standard conventional brain MRI and 30 controls without CM-I who had presented with various neurosurgical conditions. The CM-I patients were included if fsMRI studies had been obtained within 1 year of conventional MRI with no surgical intervention between the studies. Two neuroradiologists reviewed the studies in a blinded fashion to determine the diagnostic performance of fsMRI in detecting CM-I. For the CM-I cohort, the fsMRI and T2-weighted MRI exams were randomized, and the blinded reviewers performed tonsillar measurements on both scans. RESULTS The mean age of the CM-I cohort was 7.39 years, and 50% of these subjects were male. The mean time interval between fsMRI and conventional T2-weighted MRI was 97.8 days. Forty-four percent of the subjects had undergone imaging after posterior fossa decompression. The sensitivity and specificity of fsMRI in detecting CM-I was 100% (95% CI 71.51%-100%) and 92.11% (95% CI 78.62%-98.34%), respectively. If only preoperative patients are considered, both sensitivity and specificity increase to 100%. The authors also performed a cost analysis and determined that fsMRI was significantly cost-effective compared to T2-weighted MRI or CT. CONCLUSIONS Despite known limitations, fsMRI may serve as a useful diagnostic and surveillance tool for CM-I. It is more cost-effective than full conventional brain MRI and decreases the need for sedation in young children.

    View details for DOI 10.3171/2018.2.PEDS17523

    View details for Web of Science ID 000440632500007

    View details for PubMedID 29749883

  • Safety of Dynamic MRI of the Cervical Spine in Children Performed Without Neurosurgical Supervision. World neurosurgery Yecies, D., Fogel, N., Edwards, M., Grant, G., Yeom, K. W., Cheshier, S. 2018

    Abstract

    OBJECT: The need for neurosurgical supervision as well as the general safety and utility of dynamic MRI of the cervical spine in children remains controversial. We present the largest descriptive cohort study of cervical flexion-extension MRIs in a pediatric population to help elucidate the safety and utility of this technique.METHODS: All cervical spine MRIs performed at Lucile Packard Children's Hospital at Stanford from 2009-2015 were retrospectively reviewed. Sixty-six dynamic cervical MRIs performed in 45 children and two young adults were identified for further study.RESULTS: Forty-three scans were imaged under general anesthesia. All imaging was performed by the neuroradiology team with no direct supervision by the neurosurgery team. There were no adverse events. Dynamic MRI detected significant instability that was not clearly seen on dynamic radiographs (5 patients) as well as cord compression not seen on static MR scans (9 patients). One patient with asymptomatic instability found on flexion-extension radiographs had no cord compression with movement on MRI and was managed conservatively. Two neonates with significant congenital malformations of the cervical spine were cleared for OR positioning for cardiac procedures based on flexion-extension MR imaging.CONCLUSIONS: Dynamic MRI represents a safe and useful tool for evaluating the cervical spine and cervicomedullary junction in a variety of pediatric patient populations and can be performed safely without direct neurosurgical supervision. Additionally, we describe for the first time the use of flexion-extension MRI to clear neonates with severe congenital cervical spine abnormalities for complex operative positioning and ICU care.

    View details for DOI 10.1016/j.wneu.2018.05.210

    View details for PubMedID 29883828

  • ASL PERFUSION IMAGING OF THE FRONTAL LOBES PREDICTS THE OCCURRENCE AND RESOLUTION OF POSTERIOR FOSSA SYNDROME Yecies, D., Shpanskaya, K., Grant, G., Cheshier, S., Hong, D., Edwards, M., Yeom, K. OXFORD UNIV PRESS INC. 2018: 170
  • Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI). Magnetic resonance in medicine Terem, I., Ni, W. W., Goubran, M., Rahimi, M. S., Zaharchuk, G., Yeom, K. W., Moseley, M. E., Kurt, M., Holdsworth, S. J. 2018

    Abstract

    PURPOSE: Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm.METHODS: Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output.RESULTS: Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient.CONCLUSION: Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

    View details for DOI 10.1002/mrm.27236

    View details for PubMedID 29845645

  • Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys SCIENTIFIC REPORTS O'Shea, D. J., Kalanithi, P., Ferenczi, E. A., Hsueh, B., Chandrasekaran, C., Goo, W., Diester, I., Ramakrishnan, C., Kaufman, M. T., Ryu, S. I., Yeom, K. W., Deisseroth, K., Shenoy, K. V. 2018; 8: 6775

    Abstract

    Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.

    View details for DOI 10.1038/s41598-018-24362-7

    View details for Web of Science ID 000431108000001

    View details for PubMedID 29712920

    View details for PubMedCentralID PMC5928036

  • Framework for shape analysis of white matter fiber bundles NEUROIMAGE Glozman, T., Bruckert, L., Pestilli, F., Yecies, D. W., Guibas, L. J., Yeom, K. W. 2018; 167: 466–77

    Abstract

    Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain.

    View details for DOI 10.1016/j.neuroimage.2017.11.052

    View details for Web of Science ID 000427529200042

    View details for PubMedID 29203454

    View details for PubMedCentralID PMC5845796

  • Clinical Evaluation of Silent T1-Weighted MRI and Silent MR Angiography of the Brain AMERICAN JOURNAL OF ROENTGENOLOGY Holdsworth, S. J., Macpherson, S. J., Yeom, K. W., Wintermark, M., Zaharchuk, G. 2018; 210 (2): 404–11

    Abstract

    New MRI sequences based on rapid radial acquisition have reduced gradient noise. The purpose of this study was to compare Silent T1-weighted and unenhanced MR angiography (MRA) against conventional sequences in a clinical population.The study cohort consisted of 40 patients with suspected brain metastases (median age, 60 years; range, 23-91 years) who underwent T1-weighted contrast-enhanced MRI and 51 patients with suspected vascular lesions or cerebral ischemia (median age, 60 years; range, 16-94 years) who underwent unenhanced intracranial MRA. Three neuroradiologists reviewed the images blindly and rated several measures of image quality on a 5-point Likert scale. Reviewers recorded the number of enhancing lesions and whether Silent images were better than, worse than, or equivalent to conventional images.For T1-weighted MR images, ratings were slightly lower for Silent versus conventional images, except for diagnostic confidence. Although more lesions were detected on conventional images, this difference was not statistically significant; agreement was seen in 88% of cases. In 48% of cases, T1-weighted scans were deemed equivalent, but when a preference existed, it was usually for conventional images (38% vs 14%). Conventional MRA images were rated higher on all image quality metrics and were strongly preferred (reviewers preferred conventional images in 69% of cases, rated the images as equivalent in 27% of cases, and preferred Silent images in 4% of cases). In some cases, artifacts on Silent images caused reduced vessel caliber, vessel irregularities, and even absent vessels.Although conventional T1-weighted images were preferred overall, most Silent T1-weighted images were rated as equivalent to or better than conventional images and represent a potential alternative for imaging of noise-averse patients. Silent MRA scored significantly worse and could not be recommended at this time, suggesting that it requires additional refinement before routine clinical use.

    View details for DOI 10.2214/AJR.17.18247

    View details for Web of Science ID 000423108800032

    View details for PubMedID 29112472

  • Isolated Intraorbital Frontosphenoidal Synostosis. The Journal of craniofacial surgery Mittermiller, P. A., Yeom, K. W., Menard, R. M. 2018; 29 (1): 82–87

    Abstract

    Unilateral anterior plagiocephaly is most commonly the result of deformational plagiocephaly or unilateral coronal synostosis, a premature fusion of the frontoparietal suture. However, other sutures within the coronal ring have been implicated in producing anterior cranial asymmetries. These fusions can occur in isolation or in concert with adjacent sutures. The frontosphenoidal suture is one such suture within the coronal ring that has been involved both concomitantly with and independently of frontoparietal suture fusion. Although isolated frontosphenoidal synostosis has been presented previously in the literature, these reports include patients with fusion of the extraorbital portion of the frontosphenoidal suture. This clinical report presents the first clearly documented patient of isolated frontosphenoidal synostosis that occurs entirely within the intraorbital region.The patient presented to Plastic Surgery Clinic at 3 months of age with left frontal flattening, supraorbital rim retrusion, and temporal bulging that was noted soon after birth. Computed tomography analysis revealed an isolated fusion of the greater and lesser wings of the sphenoid bone to the frontal bone on the left side. The patient had no family history of cranial anomalies and genetic testing was negative for mutations. The infant was treated with a cranial orthotic for 3 months, underwent open fronto-orbital advancement and cranial vault remodeling at 6 months, and continued wearing a cranial orthotic for another 4.5 months. Following surgical and orthotic treatment, the patient achieved a satisfactory result.

    View details for DOI 10.1097/SCS.0000000000004074

    View details for PubMedID 29068968

  • Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study. Radiology Iv, M., Samghabadi, P., Holdsworth, S., Gentles, A., Rezaii, P., Harsh, G., Li, G., Thomas, R., Moseley, M., Daldrup-Link, H. E., Vogel, H., Wintermark, M., Cheshier, S., Yeom, K. W. 2018: 181204

    Abstract

    Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2018181204

    View details for PubMedID 30398435

  • High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations. Journal of neurosurgery. Pediatrics Iv, M., Choudhri, O., Dodd, R. L., Vasanawala, S. S., Alley, M. T., Moseley, M., Holdsworth, S. J., Grant, G., Cheshier, S., Yeom, K. W. 2018: 1–10

    Abstract

    OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

    View details for DOI 10.3171/2018.3.PEDS17723

    View details for PubMedID 29882734

  • The Utility of Collaterals as a Biomarker in Pediatric Unilateral Intracranial Arteriopathy PEDIATRIC NEUROLOGY Elbers, J., Armstrong, D., Benseler, S. M., Dlamini, N., Steinberg, G. K., Yeom, K. W. 2018; 78: 27–34

    Abstract

    Intracranial arteriopathies are frequent causes of pediatric stroke and important risk factors for stroke recurrence. Without tissue diagnosis, vascular imaging is relied upon to identify the underlying etiology and prognosis. We hypothesized that children with unilateral intracranial arteriopathy with lenticulostriate collaterals would demonstrate distinct vascular outcomes compared with children without collaterals.We retrospectively identified children with unilateral intracranial arteriopathy from two institutions. Two blinded raters from each institution reviewed magnetic resonance or digital subtraction angiography at baseline and ≥12 months. Patients were grouped according to presence or absence of lenticulostriate collaterals. Clinical features and vascular imaging outcomes were compared using univariate analysis and multivariate logistic regression.Forty-four children were included: 22 males, median age 8.2 years (range two to 16.9 years), and further stratified into the collateral group (n = 20) and non-collateral group (n = 24), with median follow-up of 25.5 months and 23 months, respectively. Both groups demonstrated similar rates of progression on vascular imaging at ≥12 months, 50% in the collateral group versus 37.5% in the non-collateral group (P > 0.05). The collateral group was associated with asymptomatic clinical presentation, normal brain MRI, border zone infarcts, and either vascular stabilization or new contralateral disease. The non-collateral group demonstrated either vascular improvement or discordant progression (combination of improved and progressive lesions). Using a multivariate model, collaterals continued to be an independent predictor of vascular outcome.This study suggests that lenticulostriate collaterals in children with unilateral intracranial arteriopathy may serve as a useful neuroimaging biomarker that helps to stratify patients with distinct clinical features and patterns of vascular evolution.

    View details for DOI 10.1016/j.pediatrneurol.2017.08.009

    View details for Web of Science ID 000423419400005

    View details for PubMedID 29174857

  • Prediction of cognitive and motor development in preterm children using exhaustive feature selection and cross-validation of near-term white matter microstructure NEUROIMAGE-CLINICAL Schadl, K., Vassar, R., Cahill-Rowley, K., Yeom, K. W., Stevenson, D. K., Rose, J. 2018; 17: 667–79
  • Fractal structure in the volumetric contrast enhancement of malignant gliomas as a marker of oxidative metabolic pathway gene expression TRANSLATIONAL CANCER RESEARCH Miller, K. J., Berendsen, S., Seute, T., Yeom, K., Gephardt, M. H., Grant, G. A., Robe, P. A. 2017; 6 (6): 1275-+
  • CORRELATION OF VASARI-BASED MRI PHENOTYPES WITH MGMT AND IDH STATUS ACROSS GLIOMA GRADES: A STATISTICAL ANALYSIS IN 372 PATIENTS Das, D., Yoon, B., Golden, L., Samghabadi, P., Vogel, H., Yeom, K., Iv, M., Massoud, T. OXFORD UNIV PRESS INC. 2017: 150
  • THE EFFECT OF PATIENT AGE AT GLIOMA PRESENTATION ON MRI PHENOTYPE: A COMPREHENSIVE ANALYSIS OF VASARI-BASED FEATURE-SET CRITERIA IN 711 PATIENTS Das, D., Yoon, B., Golden, L., Samghabadi, P., Vogel, H., Yeom, K., Iv, M., Massoud, T. OXFORD UNIV PRESS INC. 2017: 158
  • The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival NEURO-ONCOLOGY Thompson, E. M., Keir, S. T., Venkatraman, T., Lascola, C., Yeom, K. W., Nixon, A. B., Liu, Y., Picard, D., Remke, M., Bigner, D. D., Ramaswamy, V., Taylor, M. D. 2017; 19 (9): 1217–27

    Abstract

    Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survival in Group 3 medulloblastoma.VEGFA mRNA expression and survival from several patient cohorts were analyzed. Group 3 xenografts were implanted intracranially in nude rats. Dynamic susceptibility weighted (DSC) MRI and susceptibility weighted imaging (SWI) were obtained. DSC MRI was used to calculate relative cerebral blood volume (rCBV) and flow (rCBF). Tumor vessel density and rat vascular endothelial growth factor alpha (VEGFA) expression were determined.Patient VEGFA mRNA levels were significantly elevated in Group 3 compared with the other subgroups (P < 0.001) and associated with survival. Xenografts D283, D341, and D425 were identified as Group 3 by RNA hierarchical clustering and MYC amplification. The D283 group had the lowest rCBV and rCBF, followed by D341 and D425 (P < 0.05). These values corresponded to histological vessel density (P < 0.05), rat VEGFA expression (P < 0.05), and survival (P = 0.002). Gene set enrichment analysis identified 5 putative genes with expression profiles corresponding with these findings: RNH1, SCG2, VEGFA, AGGF1, and PROK2. SWI identified 3 xenograft-independent categories of intratumoral vascular architecture with distinct survival (P = 0.004): organized, diffuse microvascular, and heterogeneous.Angiogenesis plays an important role in Group 3 medulloblastoma pathogenesis and survival. DSC MRI and SWI are clinically relevant biomarkers for tumor vascularity and overall survival and can be used to direct the use of antivascular therapies for patients with Group 3 medulloblastoma.

    View details for DOI 10.1093/neuonc/nox033

    View details for Web of Science ID 000407788800008

    View details for PubMedID 28379574

    View details for PubMedCentralID PMC5570262

  • Chemoradiation impairs normal developmental cortical thinning in medulloblastoma. Journal of neuro-oncology Kundu, P., Li, M. D., Durkee, B. Y., Hiniker, S. M., Bush, K., von Eyben, R., Monje, M. L., Yeom, K. W., Donaldson, S. S., Gibbs, I. C. 2017

    Abstract

    Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.

    View details for DOI 10.1007/s11060-017-2453-5

    View details for PubMedID 28534154

  • Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors. journal of pediatrics Li, M. D., Forkert, N. D., Kundu, P., Ambler, C., Lober, R. M., Burns, T. C., Barnes, P. D., Gibbs, I. C., Grant, G. A., Fisher, P. G., Cheshier, S. H., Campen, C. J., Monje, M., Yeom, K. W. 2017

    Abstract

    To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction.We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure.Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P < .05), whereas patients with PA (all treated with surgery alone) had normal CBF. ADC was decreased specifically in the hippocampus and amygdala of patients with MB and within the amygdala of patients with PA but otherwise remained normal after therapy. In the patients with tumor previously evaluated for IQ, regional ADC, but not CBF, correlated with IQ (R(2) = 0.33-0.75).The treatment for MB, but not PA, was associated with globally reduced CBF. Treatment in both tumor types was associated with diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes.

    View details for DOI 10.1016/j.jpeds.2017.01.019

    View details for PubMedID 28187964

  • Radiomics in Brain Tumor: Image Assessment, Quantitative Feature Descriptors, and Machine-Learning Approaches. AJNR. American journal of neuroradiology Zhou, M., Scott, J., Chaudhury, B., Hall, L., Goldgof, D., Yeom, K. W., Iv, M., Ou, Y., Kalpathy-Cramer, J., Napel, S., Gillies, R., Gevaert, O., Gatenby, R. 2017

    Abstract

    Radiomics describes a broad set of computational methods that extract quantitative features from radiographic images. The resulting features can be used to inform imaging diagnosis, prognosis, and therapy response in oncology. However, major challenges remain for methodologic developments to optimize feature extraction and provide rapid information flow in clinical settings. Equally important, to be clinically useful, predictive radiomic properties must be clearly linked to meaningful biologic characteristics and qualitative imaging properties familiar to radiologists. Here we use a cross-disciplinary approach to highlight studies in radiomics. We review brain tumor radiologic studies (eg, imaging interpretation) through computational models (eg, computer vision and machine learning) that provide novel clinical insights. We outline current quantitative image feature extraction and prediction strategies with different levels of available clinical classes for supporting clinical decision-making. We further discuss machine-learning challenges and data opportunities to advance radiomic studies.

    View details for DOI 10.3174/ajnr.A5391

    View details for PubMedID 28982791

  • A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study. Radiology Theruvath, A. J., Ilivitzki, A., Muehe, A., Theruvath, J., Gulaka, P., Kim, C., Luna-Fineman, S., Sakamoto, K. M., Yeom, K. W., Yang, P., Moseley, M., Chan, F., Daldrup-Link, H. E. 2017: 170073

    Abstract

    Purpose To develop a positron emission tomography (PET)/magnetic resonance (MR) imaging protocol for evaluation of the brain, heart, and joints of pediatric cancer survivors for chemotherapy-induced injuries in one session. Materials and Methods Three teams of experts in neuroimaging, cardiac imaging, and bone imaging were tasked to develop a 20-30-minute PET/MR imaging protocol for detection of chemotherapy-induced tissue injuries of the brain, heart, and bone. In an institutional review board-approved, HIPAA-compliant, prospective study from April to July 2016, 10 pediatric cancer survivors who completed chemotherapy underwent imaging of the brain, heart, and bone with a 3-T PET/MR imager. Cumulative chemotherapy doses and clinical symptoms were correlated with the severity of MR imaging abnormalities by using linear regression analyses. MR imaging measures of brain perfusion and metabolism were compared among eight patients who were treated with methotrexate and eight untreated age-matched control subjects by using Wilcoxon rank-sum tests. Results Combined brain, heart, and bone examinations were completed within 90 minutes. Eight of 10 cancer survivors had abnormal findings on brain, heart, and bone images, including six patients with and two patients without clinical symptoms. Cumulative chemotherapy doses correlated significantly with MR imaging measures of left ventricular ejection fraction and end-systolic volume, but not with the severity of brain or bone abnormalities. Methotrexate-treated cancer survivors had significantly lower cerebral blood flow and metabolic activity in key brain areas compared with control subjects. Conclusion The feasibility of a single examination for assessment of chemotherapy-induced injuries of the brain, heart, and joints was shown. Earlier detection of tissue injuries may enable initiation of timely interventions and help to preserve long-term health of pediatric cancer survivors. (©) RSNA, 2017 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2017170073

    View details for PubMedID 28777701

  • FRACTAL STRUCTURE IN THE VOLUMETRIC CONTRAST ENHANCEMENT OF MALIGNANT GLIOMAS AS A MARKER OF OXIDATIVE METABOLIC PATHWAY GENE EXPRESSION Miller, K., Berendsen, S., Seute, T., Yeom, K., Gephardt, M., Grant, G., Robe, P. OXFORD UNIV PRESS INC. 2016: 173
  • Central Nervous System Perfusion Patterns in Childhood Langerhans Cell Histiocytosis Yeom, K., Kim, C., Iv, M., Jeng, M. WILEY-BLACKWELL. 2016: S36
  • Sclerotherapy for lymphatic malformations of the head and neck in the pediatric population. Journal of neurointerventional surgery Tu, J. H., Do, H. M., Patel, V., Yeom, K. W., Teng, J. M. 2016

    Abstract

    Sclerotherapy is one of the most commonly used minimally invasive interventions in the treatment of macrocystic lymphatic malformations (LMs). Several different sclerosing agents and injection protocols have been reported in the literature, each with varying degrees of success. The safety and efficacy of the treatments have not been evaluated comparatively in the pediatric population.Chart review of pediatric patients with macrocystic/mixed head and neck LMs who underwent sclerotherapy using OK-432, doxycycline, or ethanolamine oleate at Lucile Packard Children's Hospital at Stanford during 2000-2014. Clinical evaluation and radiographic imaging were reviewed to assess lesion characteristics and response to sclerotherapy following each treatment session. The post-intervention clinical response was categorized as excellent, good, fair, or poor.Among the 41 pediatric cases reviewed, 10 patients were treated with OK-432, 19 patients received doxycycline, and 12 patients received ethanolamine. In univariate analysis, different sclerosants had similar effectiveness after the first injection and final clinical outcome (p=0.5317). In multivariate analysis controlling for disease severity stage as well as disease characteristics (macrocystic vs mixed subtypes), different sclerosants also had similar effectiveness after the first injection (p=0.1192). Radiologic analysis indicated an 84.5% average volume reduction, with similar effectiveness between the different sclerosants (p=0.9910).In this series of LM cases treated at Stanford, we found that doxycycline, OK-432, and ethanolamine oleate sclerotherapy appear to have a similar safety and efficacy profile in the treatment of macrocystic and mixed LMs of the head and neck in the pediatric population.

    View details for DOI 10.1136/neurintsurg-2016-012660

    View details for PubMedID 27707871

  • Diagnosis and treatment of pediatric frontotemporal pits: report of 2 cases JOURNAL OF NEUROSURGERY-PEDIATRICS Bliss, M., Grant, G., Tittler, E., Loven, T., Yeom, K. W., Sidell, D. 2016; 18 (4): 471-474

    Abstract

    In contrast to more common nasal and cervical lesions, the frontotemporal pit is a rarely encountered lesion that is often associated with a dermoid and may track intracranially. Due to delays in diagnosis, the propensity to spread intracranially, and the risk of infection, awareness of these lesions and appropriate diagnosis and management are important. The authors present 2 cases of frontotemporal pits from a single institution. Epidemiology, presentation, and management recommendations are discussed.

    View details for DOI 10.3171/2016.5.PEDS1687

    View details for Web of Science ID 000383938500015

    View details for PubMedID 27391653

  • FRACTAL STRUCTURE ON GADOLINEUM-ENHANCED MRI SCANS CORRELATES WITH OXIDATIVE METABOLISM AND VEGF EXPRESSION IN GLIOBLASTOMA Berendsen, S., Miller, K. J., Spliet, W. M., Van Hecke, W., Seute, T., Yeom, K., Hayden, M. G., Grant, G. A., Robe, P. A. OXFORD UNIV PRESS INC. 2016: 38
  • Gray Matter Growth Is Accompanied by Increasing Blood Flow and Decreasing Apparent Diffusion Coefficient during Childhood. AJNR. American journal of neuroradiology Forkert, N. D., Li, M. D., Lober, R. M., Yeom, K. W. 2016; 37 (9): 1738-1744

    Abstract

    Normal values of gray matter volume, cerebral blood flow, and water diffusion have not been established for healthy children. We sought to determine reference values for age-dependent changes of these parameters in healthy children.We retrospectively reviewed MR imaging data from 100 healthy children. Using an atlas-based approach, age-related normal values for regional CBF, apparent diffusion coefficient, and volume were determined for the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens.All gray matter structures grew rapidly before the age of 10 years and then plateaued or slightly declined thereafter. The ADC of all structures decreased with age, with the most rapid changes occurring prior to the age of 5 years. With the exception of the globus pallidus, CBF increased rather linearly with age.Normal brain gray matter is characterized by rapid early volume growth and increasing CBF with concomitantly decreasing ADC. The extracted reference data that combine CBF and ADC parameters during brain growth may provide a useful resource when assessing pathologic changes in children.

    View details for DOI 10.3174/ajnr.A4772

    View details for PubMedID 27102314

  • Sirolimus for the treatment of venolymphatic and lymphatic malformations in children: A volumetric analysis Tu, J. H., Cohn, H. I., Do, H. M., Yeom, K., Marqueling, A., Sofilos, M., Jeng, M., Teng, J. ELSEVIER SCIENCE INC. 2016: S45
  • Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas AMERICAN JOURNAL OF NEURORADIOLOGY Liu, T. T., Achrol, A. S., MITCHELL, L. A., Du, W. A., Loya, J. J., Rodriguez, S. A., Feroze, A., Westbroek, E. M., Yeom, K. W., Stuart, J. M., Chang, S. D., Harsh, G. R., Rubin, D. L. 2016; 37 (4): 621-628

    Abstract

    Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes.Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions.Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies.Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

    View details for DOI 10.3174/ajnr.A4631

    View details for Web of Science ID 000373346900014

  • Case Series: Fractional Anisotropy Profiles of the Cerebellar Peduncles in Adolescents Born Preterm With Ventricular Dilation JOURNAL OF CHILD NEUROLOGY Travis, K. E., Leitner, Y., Ben-Shachar, M., Yeom, K. W., Feldman, H. M. 2016; 31 (3): 321-327

    Abstract

    This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities.

    View details for DOI 10.1177/0883073815592223

    View details for Web of Science ID 000370429700008

    View details for PubMedID 26116381

  • Tract Profiles of the Cerebellar White Matter Pathways in Children and Adolescents CEREBELLUM Leitner, Y., Travis, K. E., Ben-Shachar, M., Yeom, K. W., Feldman, H. M. 2015; 14 (6): 613-623

    Abstract

    Intact development of cerebellar connectivity is essential for healthy neuromotor and neurocognitive development. To date, limited knowledge about the microstructural properties of the cerebellar peduncles, the major white matter tracts of the cerebellum, is available for children and adolescents. Such information would be useful as a comparison for studies of normal development, clinical conditions, or associations of cerebellar structures with cognitive and motor functions. The goal of the present study was to evaluate the variability in diffusion measures of the cerebellar peduncles within individuals and within a normative sample of healthy children. Participants were 19 healthy children and adolescents, aged 9-17 years, mean age 13.0 ± 2.3. We analyzed diffusion magnetic resonance imaging (dMRI) data with deterministic tractography. We generated tract profiles for each of the cerebellar peduncles by extracting four diffusion properties (fractional anisotropy (FA) and mean, radial, and axial diffusivity) at 30 equidistant points along each tract. We were able to identify the middle cerebellar peduncle and the bilateral inferior and superior cerebellar peduncles in all participants. The results showed that within each of the peduncles, the diffusion properties varied along the trajectory of the tracts. However, the tracts showed consistent patterns of variation across individuals; the coefficient of variation for FA across individual profiles was low (≤20 %) for each tract. We observed no systematic variation of the diffusion properties with age. These cerebellar tract profiles of the cerebellar peduncles can serve as a reference for future studies of children across the age range and for children and adolescents with clinical conditions that affect the cerebellum.

    View details for DOI 10.1007/s12311-015-0652-1

    View details for Web of Science ID 000364576900001

    View details for PubMedID 25648754

    View details for PubMedCentralID PMC4524802

  • Neonatal brain microstructure correlates of neurodevelopment and gait in preterm children 18-22 mo of age: an MRI and DTI study PEDIATRIC RESEARCH Rose, J., Cahill-Rowley, K., Vassar, R., Yeom, K. W., Stecher, X., Stevenson, D. K., Hintz, S. R., Barnea-Goraly, N. 2015; 78 (6): 700-708

    Abstract

    Near-term brain structure was examined in preterm infants in relation to neurodevelopment. We hypothesized that near-term macrostructural brain abnormalities identified using conventional magnetic resonance imaging (MRI), and white matter (WM) microstructure detected using diffusion tensor imaging (DTI), would correlate with lower cognitive and motor development and slower, less-stable gait at 18-22 mo of age.One hundred and two very-low-birth-weight preterm infants (≤1,500 g birth weight; ≤32 wk gestational age) were recruited prior to routine near-term brain MRI at 36.6 ± 1.8 wk postmenstrual age. Cerebellar and WM macrostructure was assessed on conventional structural MRI. DTI was obtained in 66 out of 102 and WM microstructure was assessed using fractional anisotropy and mean diffusivity (MD) in six subcortical brain regions defined by DiffeoMap neonatal atlas. Neurodevelopment was assessed with Bayley-Scales-of-Infant-Toddler-Development, 3rd-Edition (BSID-III); gait was assessed using an instrumented mat.Neonates with cerebellar abnormalities identified using MRI demonstrated lower mean BSID-III cognitive composite scores (89.0 ± 10.1 vs. 97.8 ± 12.4; P = 0.002) at 18-22 mo. Neonates with higher DTI-derived left posterior limb of internal capsule (PLIC) MD demonstrated lower cognitive and motor composite scores (r = -0.368; P = 0.004; r = -0.354; P = 0.006) at 18-22 mo; neonates with higher genu MD demonstrated slower gait velocity (r = -0.374; P = 0.007). Multivariate linear regression significantly predicted cognitive (adjusted r(2) = 0.247; P = 0.002) and motor score (adjusted r(2) = 0.131; P = 0.017).Near-term cerebellar macrostructure and PLIC and genu microstructure were predictive of early neurodevelopment and gait.

    View details for DOI 10.1038/pr.2015.157

    View details for Web of Science ID 000367114900015

    View details for PubMedID 26322412

  • Are Neuroanatomical Changes in Pediatric Medulloblastoma Radiation Specific? Kundu, P., Li, M., von Eyben, R., Bush, K., Durkee, B. Y., Monje-Deisseroth, M., Campen, C., Yeom, K., Gibbs, I. C. ELSEVIER SCIENCE INC. 2015: S34
  • Predicting Neuropsychological Late Effects in Medulloblastoma With Post Radiation Hippocampal Volume Kundu, P., Moghbel, M., Li, M., von Eyben, R., Sweetin, J., Bush, K., Durkee, B. Y., Monje-Deisseroth, M., Campen, C., Yeom, K., Donaldson, S. S., Gibbs, I. C. ELSEVIER SCIENCE INC. 2015: E507
  • Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Science translational medicine Itakura, H., Achrol, A. S., Mitchell, L. A., Loya, J. J., Liu, T., Westbroek, E. M., Feroze, A. H., Rodriguez, S., Echegaray, S., Azad, T. D., Yeom, K. W., Napel, S., Rubin, D. L., Chang, S. D., Harsh, G. R., Gevaert, O. 2015; 7 (303): 303ra138-?

    Abstract

    Glioblastoma (GBM) is the most common and highly lethal primary malignant brain tumor in adults. There is a dire need for easily accessible, noninvasive biomarkers that can delineate underlying molecular activities and predict response to therapy. To this end, we sought to identify subtypes of GBM, differentiated solely by quantitative magnetic resonance (MR) imaging features, that could be used for better management of GBM patients. Quantitative image features capturing the shape, texture, and edge sharpness of each lesion were extracted from MR images of 121 single-institution patients with de novo, solitary, unilateral GBM. Three distinct phenotypic "clusters" emerged in the development cohort using consensus clustering with 10,000 iterations on these image features. These three clusters--pre-multifocal, spherical, and rim-enhancing, names reflecting their image features--were validated in an independent cohort consisting of 144 multi-institution patients with similar tumor characteristics from The Cancer Genome Atlas (TCGA). Each cluster mapped to a unique set of molecular signaling pathways using pathway activity estimates derived from the analysis of TCGA tumor copy number and gene expression data with the PARADIGM (Pathway Recognition Algorithm Using Data Integration on Genomic Models) algorithm. Distinct pathways, such as c-Kit and FOXA, were enriched in each cluster, indicating differential molecular activities as determined by the image features. Each cluster also demonstrated differential probabilities of survival, indicating prognostic importance. Our imaging method offers a noninvasive approach to stratify GBM patients and also provides unique sets of molecular signatures to inform targeted therapy and personalized treatment of GBM.

    View details for DOI 10.1126/scitranslmed.aaa7582

    View details for PubMedID 26333934

    View details for PubMedCentralID PMC4666025

  • Pediatric Semicircular Canal Dehiscence: Radiographic and Histologic Prevalence, With Clinical Correlation OTOLOGY & NEUROTOLOGY Meiklejohn, D. A., Corrales, C. E., Boldt, B. M., Sharon, J. D., Yeom, K. W., Carey, J. P., Blevins, N. H. 2015; 36 (8): 1383-1389

    Abstract

    To determine the prevalence of radiographic and histologic superior semicircular canal dehiscence (SSCD) and posterior semicircular canal dehiscence (PSCD) and associated changes in temporal bone thickness in children aged 0 to 7 years.Retrospective chart review and histopathologic review of cadaveric bone specimens.Two tertiary referral centers.Children younger than 7 years who underwent high-resolution computed tomography scan including the temporal bones between 1998 and 2013 and temporal bones harvested from children younger than 7 years.Two hundred twenty-eight computed tomography studies and 58 temporal bone specimens were reviewed. Available patient demographics were tabulated.Prevalence of SSCD and PSCD and bone thickness over semicircular canals, with comparison across age groups. Clinical data were extracted for patients with radiographic dehiscence.Prevalence by ear of SSCD was 11.9%, 4.9%, 2.8%, and 0% and of PSCD was 16.7%, 2.4%, 1.4%, and 0% in children aged less than 6 months, 6 to 11 months, 12 to 35 months, and 3 to 7 years, respectively. SSCD was statistically more common before 1 year of age and PSCD before 6 months of age. Bone thickness overlying both the SSC and the PSC increased with age. Radiographic PSC bone was significantly thicker than SSC bone in patients older than 12 months. No dehiscences were found in the histologic specimens.Radiographic dehiscence of the canals is common in the first 6 months of life, with thin bone seen histologically. Prevalence decreases with increasing age as the bone overlying the canals increases in thickness.

    View details for DOI 10.1097/MAO.0000000000000811

    View details for Web of Science ID 000360488000015

  • Focal Cerebral Arteriopathy: The Face With Many Names. Pediatric neurology Tolani, A. T., Yeom, K. W., Elbers, J. 2015; 53 (3): 247-252

    Abstract

    Focal cerebral arteriopathy is a term used to describe unilateral intracranial arteriopathy involving the distal internal carotid artery and proximal segments of the middle and anterior cerebral artery. We describe the disease course of 10 pediatric arterial ischemic stroke patients with focal cerebral arteriopathy from a single quaternary-care center.We retrospectively reviewed pediatric stroke patients with focal cerebral arteriopathy without lenticulostriate collaterals treated at our institution between 2005 and 2014. Angiography was reviewed by a child neurologist and a pediatric neuroradiologist, and chart reviews were performed.Ten individuals with focal cerebral arteriopathy were identified. At the time of stroke presentation, four patients were diagnosed with arterial dissection, two with moyamoya disease, one with embolic occlusion, one with hemorrhagic stroke, and two with arterial dissection or vasculitis. At last follow-up, six patients had a change in diagnosis: four were diagnosed with transient cerebral arteriopathy, two with arterial dissection, and four with moyamoya disease. Four children experienced stroke recurrence. All were administered aspirin, one was administered heparin, two were administered intravenous tissue plasminogen activator, and five underwent surgical revascularization.Among pediatric stroke patients with a similar angiographic appearance, there is variable concordance between diagnosis, prognosis and treatment choice. Improved consensus-based diagnostic criteria and further research is needed to identify disease biomarkers and predictors of arterial progression.

    View details for DOI 10.1016/j.pediatrneurol.2015.05.008

    View details for PubMedID 26122406

  • Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain JOURNAL OF MAGNETIC RESONANCE IMAGING Liu, C., Li, W., Tong, K. A., Yeom, K. W., Kuzminski, S. 2015; 42 (1): 23-41

    Abstract

    Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging. J. Magn. Reson. Imaging 2015;42:23-41. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24768

    View details for Web of Science ID 000356625500003

    View details for PubMedID 25270052

    View details for PubMedCentralID PMC4406874

  • Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging PLOS ONE Yeom, K. W., Straka, M., Iv, M., Moseley, M. E., Barnes, P. D., Skare, S., Holdsworth, S. J. 2015; 10 (6)

    Abstract

    Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

    View details for DOI 10.1371/journal.pone.0129325

    View details for Web of Science ID 000356327000065

    View details for PubMedID 26069959

  • IMPACT OF MOLECULAR SUB-TYPE AND CRANIOSPINAL IRRADIATION (CSI) DOSE ON RELAPSE OF MEDULLOBLASTOMA Wang, A., Partap, S., Yeom, K., Martinez, M., Vogel, H., Donaldson, S., Fisher, P., Perreault, S., Cho, Y., Gibbs, I. OXFORD UNIV PRESS INC. 2015: 22
  • Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging. Journal of magnetic resonance imaging Holdsworth, S. J., Yeom, K. W., Moseley, M. E., Skare, S. 2015; 41 (5): 1447-1453

    Abstract

    Susceptibility-weighted imaging (SWI) in neuroimaging can be challenging due to long scan times of three-dimensional (3D) gradient recalled echo (GRE), while faster techniques such as 3D interleaved echo-planar imaging (iEPI) are prone to motion artifacts. Here we outline and implement a 3D short-axis propeller echo-planar imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI.Experiments were conducted on a 3T MRI system. The 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. The 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically.The 3D GRE images had a better target resolution (0.47 × 0.94 × 2 mm, scan time = 5 min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2 mm) were acquired in a faster scan time (1:52 min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data.While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24675

    View details for PubMedID 24956237

    View details for PubMedCentralID PMC4275419

  • Decreased tumor apparent diffusion coefficient correlates with objective response of pediatric low-grade glioma to bevacizumab JOURNAL OF NEURO-ONCOLOGY Hsu, C. H., Lober, R. M., Li, M. D., Partap, S., Murphy, P. A., Barnes, P. D., Fisher, P. G., Yeom, K. W. 2015; 122 (3): 491-496

    Abstract

    Recent small, retrospective series suggest bevacizumab may be a therapeutic option for recurrent pediatric low-grade glioma (LGG). Assessment of therapeutic responses is complicated by the unpredictable natural history of these tumors. Because diffusion-weighted imaging quantifies microscopic water motion affected by cellular density and histologic features, we hypothesized that it may be helpful in monitoring therapeutic response of LGG to bevacizumab. We retrospectively reviewed eight consecutive patients, median age 4.8 (range 2.3-12.3) years at initiation of bevacizumab therapy for recurrent or refractory LGG. Patients received 10 mg/kg/dose every 2 weeks (median 16 doses/therapy course). Mean apparent diffusion coefficient (ADC) was measured and analyzed in respect to tumor volume. Following the first treatment course, seven of eight patients had reduced tumor volume (≥25 %) and ADC. The median decrease in tumor volume was 47% (range -6 to 78 %) and the median decrease in ADC was 14 % (range -5 to 30 %). The ADC was significantly decreased during therapy, whereas the decrease in volume was seen only after therapy completion. There was a positive correlation between percent change in tumor volume and ADC (p < 0.05). We report a decrease in tumor ADC during initial bevacizumab therapy that is accompanied by a decrease in volume following therapy. Imaging changes in microscopic water motion associated with histology may be useful in monitoring the therapeutic response of LGG to bevacizumab.

    View details for DOI 10.1007/s11060-015-1754-9

    View details for Web of Science ID 000354717800008

    View details for PubMedID 25758812

  • Citrate concentrations increase with hypoperfusion in pediatric diffuse intrinsic pontine glioma JOURNAL OF NEURO-ONCOLOGY Yeom, K. W., Lober, R. M., Nelson, M. D., Panigrahy, A., Blueml, S. 2015; 122 (2): 383-389

    Abstract

    Citrate, a tricarboxylic acid cycle intermediate, is present in high concentrations in pediatric diffuse intrinsic pontine gliomas (DIPG). Since citrate increases during hypoxia in animal studies, we hypothesized that it accumulates in DIPG when hypoperfused. Relative tumor blood volumes (rTBV) were determined, using dynamic susceptibility contrast-enhanced magnetic resonance imaging, in twelve children [median age 8.2 (range 3.2-14.5) years] with DIPG and compared to citrate concentrations measured with in vivo proton magnetic resonance spectroscopy ((1)H MRS). Tissue perfusion and metabolite concentration were assessed at initial presentation and over the clinical course, yielding 36 and 46 perfusion and MR spectroscopy datasets, respectively. At presentation, DIPG blood volume was 60 ± 27 % of that measured for normal cerebellum. Citrate, which is not detectable in normal brain tissue, was present in DIPG at concentrations of 3.81 ± 1.44 mmol/kg tissue. Over the course of the disease and treatment, rTBV increased and citrate decreased (both p < 0.05) with an inverse correlation (p = 0.028). Citrate accumulation is associated with tissue hypoperfusion in DIPG.

    View details for DOI 10.1007/s11060-015-1726-0

    View details for Web of Science ID 000351856300017

    View details for PubMedID 25670389

  • Imaging Neck Masses in the Neonate and Young Infant SEMINARS IN ULTRASOUND CT AND MRI Tranvinh, E., Yeom, K. W., Iv, M. 2015; 36 (2): 120-137

    Abstract

    Head and neck masses occurring in the neonatal period and early infancy consist of vascular tumors, vascular malformations, benign and malignant soft tissue tumors, and other developmental lesions. Although some lesions can be diagnosed on clinical grounds, others can only be diagnosed by imaging. Beyond diagnosis, imaging plays a significant role in evaluating the location and extent of a lesion for possible intervention. In this article, we review the clinical presentation and imaging appearance of common and rare masses that may be encountered in this age group. We also highlight current treatment strategies for specific lesions.

    View details for DOI 10.1053/j.sult.2015.01.004

    View details for Web of Science ID 000355575300003

    View details for PubMedID 26001942

  • Congenital Brain Malformations in the Neonatal and Early Infancy Period SEMINARS IN ULTRASOUND CT AND MRI Kim, C., Yeom, K. W., Iv, M. 2015; 36 (2): 97-119

    Abstract

    Congenital brain malformations are a major cause of morbidity and mortality in pediatric patients who are younger than 2 years. Optimization of patient care requires accurate diagnosis, which can be challenging as congenital brain malformations include an extensive variety of anomalies. Radiologic imaging helps to identify the malformations and to guide management. Understanding radiologic findings necessitates knowledge of central nervous system embryogenesis. This review discusses the imaging of congenital brain malformations encountered in patients who are younger than 2 years in the context of brain development.

    View details for DOI 10.1053/j.sult.2015.01.003

    View details for Web of Science ID 000355575300002

    View details for PubMedID 26001941

  • Effect of number of acquisitions in diffusion tensor imaging of the pediatric brain: optimizing scan time and diagnostic experience. Journal of neuroimaging Soman, S., Holdsworth, S. J., Skare, S., Andre, J. B., Van, A. T., Aksoy, M., Bammer, R., Rosenberg, J., Barnes, P. D., Yeom, K. W. 2015; 25 (2): 296-302

    Abstract

    Diffusion tensor imaging (DTI) is useful for multiple clinical applications, but its routine implementation for children may be difficult due to long scan times. This study evaluates the impact of decreasing the number of DTI acquisitions (NEX) on interpretability of pediatric brain DTI.15 children with MRI-visible neuropathologies were imaged at 3T using our motion-corrected, parallel imaging- accelerated DT-EPI technique with 3 NEX (scan time 8.25 min). Using these acquisitions, NEX = 1 (scan time 2.75 min) and NEX = 2 (scan time 5.5 min) images were simulated. Two neuroradiologists scored diffusion-weighted images (DWI), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and first eigenvector color-encoded (EV) images from each NEX for perceived SNR, lesion conspicuity and clinical confidence. ROI FA/ADC and image SNR values were also compared across NEX.NEX = 2 perceived SNR, lesion conspicuity, and clinical confidence were not inferior to NEX = 3 images. NEX = 1 images showed comparable lesion conspicuity and clinical confidence as NEX = 3, but inferior perceived SNR. FA and ADC ROI measurements demonstrated no significant difference across NEX. The greatest SNR increase was seen between NEX = 1 and NEX = 2.Reducing NEX to shorten imaging time may impact clinical utility in a manner that does not directly correspond with SNR changes.

    View details for DOI 10.1111/jon.12093

    View details for PubMedID 24593174

  • Carbon dioxide laser for corpus callosotomy in the pediatric population. Journal of neurosurgery. Pediatrics Choudhri, O., Lober, R. M., Camara-Quintana, J., Yeom, K. W., Guzman, R., Edwards, M. S. 2015; 15 (3): 321-327

    Abstract

    OBJECT The authors describe the application of a flexible CO2 laser for corpus callosotomy in children with epilepsy. METHODS This retrospective case series reviews all cases in which pediatric patients underwent a corpus callosotomy performed using the CO2 OmniGuide laser between May 2005 and October 2012. Data were collected from 8 corpus callosotomy procedures in 6 pediatric patients presenting with medically refractory epilepsy marked by drop attacks. RESULTS Complete corpus callosotomies were performed in 6 patients (3 boys, 3 girls; ages 5-14 years). In 4 patients the complete callosotomy occurred as a single procedure, and in 2 patients an anterior two-thirds callosotomy was performed first. These 2 patients subsequently required a complete callosotomy due to inadequate control of their drop attacks. In all cases there was clean lesioning of the tract with preservation of the ependymal plane and less inadvertent thermal tissue damage due to low penetration of the laser through cerebrospinal fluid. All patients had resolution or improvement of drop attacks after surgery. No complications were encountered, and imaging demonstrated a clean sectioning of callosal fibers with preservation of normal ventricular anatomy. CONCLUSIONS These cases illustrate the use of this device in completing corpus callosotomy in pediatric patients. The low-profile laser fiber tip was well suited for working in the depths of the interhemispheric fissure with minimal brain retraction. The flexible CO2 laser allows a precise callosal lesioning through an interhemispheric approach and is a useful adjunct to be employed in these cases.

    View details for DOI 10.3171/2014.10.PEDS13498

    View details for PubMedID 25525931

  • Clinical applications of iron oxide nanoparticles for magnetic resonance imaging of brain tumors NANOMEDICINE Iv, M., Telischak, N., Feng, D., Holdsworth, S. J., Yeom, K. W., Daldrup-Link, H. E. 2015; 10 (6): 993-1018

    Abstract

    Current neuroimaging provides detailed anatomic and functional evaluation of brain tumors, allowing for improved diagnostic and prognostic capabilities. Some challenges persist even with today's advanced imaging techniques, including accurate delineation of tumor margins and distinguishing treatment effects from residual or recurrent tumor. Ultrasmall superparamagnetic iron oxide nanoparticles are an emerging tool that can add clinically useful information due to their distinct physiochemical features and biodistribution, while having a good safety profile. Nanoparticles can be used as a platform for theranostic drugs, which have shown great promise for the treatment of CNS malignancies. This review will provide an overview of clinical ultrasmall superparamagnetic iron oxides and how they can be applied to the diagnostic and therapeutic neuro-oncologic setting.

    View details for DOI 10.2217/NNM.14.203

    View details for Web of Science ID 000352806000009

    View details for PubMedID 25867862

  • Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging. PloS one Yeom, K. W., Straka, M., Iv, M., Moseley, M. E., Barnes, P. D., Skare, S., Holdsworth, S. J. 2015; 10 (6)

    Abstract

    Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

    View details for DOI 10.1371/journal.pone.0129325

    View details for PubMedID 26069959

  • GLIOBLASTOMA SUBTYPES DEFINED BY QUANTITATIVE IMAGING MAP TO DIFFERENT CANONICAL SIGNALING PATHWAYS Itakura, H., Achrol, A., Loya, J., Mitchell, L., Azad, T., Echegaray, S., Yeom, K., Napel, S., Harsh, G., Gevaert, O. OXFORD UNIV PRESS INC. 2014
  • Impact of Molecular Subtype and Craniospinal Irradiation (CSI) Dose on Relapse of Medulloblastoma Wang, A., Partap, S., Yeom, K., Martinez, M., Vogel, H., Donaldson, S. S., Fisher, P. G., Perreault, S., Cho, Y., Gibbs, I. C. ELSEVIER SCIENCE INC. 2014: S720–S721
  • GLIOBLASTOMA SUBTYPES DEFINED BY QUANTITATIVE IMAGING MAP TO DIFFERENT CANONICAL SIGNALING PATHWAYS Itakura, H., Achrol, A., Loya, J., Mitchell, L., Azad, T., Echegaray, S., Yeom, K., Napel, S., Harsh, G., Gevaert, O. OXFORD UNIV PRESS INC. 2014
  • MRI surrogates for molecular subgroups of medulloblastoma. AJNR. American journal of neuroradiology Perreault, S., Ramaswamy, V., Achrol, A. S., Chao, K., Liu, T. T., Shih, D., Remke, M., Schubert, S., Bouffet, E., Fisher, P. G., Partap, S., Vogel, H., Taylor, M. D., Cho, Y. J., Yeom, K. W. 2014; 35 (7): 1263-1269

    Abstract

    Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups.All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes.Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%-100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%-100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%-98%). When we used the MR imaging feature-based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort.Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.

    View details for DOI 10.3174/ajnr.A3990

    View details for PubMedID 24831600

  • Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke. AJNR. American journal of neuroradiology Holdsworth, S. J., Yeom, K. W., Antonucci, M. U., Andre, J. B., Rosenberg, J., Aksoy, M., Straka, M., Fischbein, N. J., Bammer, R., Moseley, M. E., Zaharchuk, G., Skare, S. 2014; 35 (7): 1293-1302

    Abstract

    Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging.Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information.Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts.Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

    View details for DOI 10.3174/ajnr.A3921

    View details for PubMedID 24763417

  • Hydrocephalus decreases arterial spin-labeled cerebral perfusion. AJNR. American journal of neuroradiology Yeom, K. W., Lober, R. M., Alexander, A., Cheshier, S. H., Edwards, M. S. 2014; 35 (7): 1433-1439

    Abstract

    Reduced cerebral perfusion has been observed with elevated intracranial pressure. We hypothesized that arterial spin-labeled CBF can be used as a marker for symptomatic hydrocephalus.We compared baseline arterial spin-labeled CBF in 19 children (median age, 6.5 years; range, 1-17 years) with new posterior fossa brain tumors and clinical signs of intracranial hypertension with arterial spin-labeled CBF in 16 age-matched controls and 4 patients with posterior fossa tumors without ventriculomegaly or signs of intracranial hypertension. Measurements were recorded in the cerebrum at the vertex, deep gray nuclei, and periventricular white matter and were assessed for a relationship to ventricular size. In 16 symptomatic patients, we compared cerebral perfusion before and after alleviation of hydrocephalus.Patients with uncompensated hydrocephalus had lower arterial spin-labeled CBF than healthy controls for all brain regions interrogated (P < .001). No perfusion difference was seen between asymptomatic patients with posterior fossa tumors and healthy controls (P = 1.000). The median arterial spin-labeled CBF increased after alleviation of obstructive hydrocephalus (P < .002). The distance between the frontal horns inversely correlated with arterial spin-labeled CBF of the cerebrum (P = .036) but not the putamen (P = .156), thalamus (P = .111), or periventricular white matter (P = .121).Arterial spin-labeled-CBF was reduced in children with uncompensated hydrocephalus and restored after its alleviation. Arterial spin-labeled-CBF perfusion MR imaging may serve a future role in the neurosurgical evaluation of hydrocephalus, as a potential noninvasive method to follow changes of intracranial pressure with time.

    View details for DOI 10.3174/ajnr.A3891

    View details for PubMedID 24651817

  • Successful Treatment with Temozolomide Combined with Chemoradiotherapy and Surgery of a Metastatic Undifferentiated Soft Tissue Sarcoma with Relapse in the Central Nervous System of a Young Adult JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Hsu, C. H., Daldrup-Link, H. E., Yeom, K. W., Donaldson, S. S., Million, L., Hazard, F. K., Rangaswami, A. 2014; 3 (2): 100-103
  • UNRAVELING THE TALE OF MEDULLOBLASTOMA: IMPACT OF MOLECULAR SUB-TYPE AND CRANIOSPINAL IRRADIATION (CSI) DOSE ON RELAPSE Gibbs, I. C., Partap, S., Yeom, K., Martinez, M., Vogel, H., Donaldson, S. S., Fisher, P., Perreault, S., Cho, Y. OXFORD UNIV PRESS INC. 2014: 82–83
  • Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies. Medical physics Weizman, L., Sira, L. B., Joskowicz, L., Rubin, D. L., Yeom, K. W., Constantini, S., Shofty, B., Bashat, D. B. 2014; 41 (5): 052303-?

    Abstract

    Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans.The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a "gold standard" was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution.Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard.The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

    View details for DOI 10.1118/1.4871040

    View details for PubMedID 24784396

    View details for PubMedCentralID PMC4000396

  • Time-dependent structural changes of the dentatothalamic pathway in children treated for posterior fossa tumor. AJNR. American journal of neuroradiology Perreault, S., Lober, R. M., Cheshier, S., Partap, S., Edwards, M. S., Yeom, K. W. 2014; 35 (4): 803-807

    Abstract

    Injury to the dentatothalamic pathway that originates in the cerebellum has been suggested as a mechanism for neurologic complications in children treated for posterior fossa tumors. We hypothesized that time-dependent changes occur in the dentatothalamic pathway.Diffusion tensor evaluation was performed in 14 children (median age, 4.1 years; age range, 1-20 years) who underwent serial MR imaging at 3T as part of routine follow-up after posterior fossa tumor resection with or without adjuvant therapy. Tensor metrics were obtained in the acute (≤1 week), subacute (1 to <6 months), and chronic (≥6 months) periods after surgery. We evaluated the following dentatothalamic constituents: bilateral dentate nuclei, cerebellar white matter, and superior cerebellar peduncles. Serial dentate nuclei volumes were also obtained and compared with the patient's baseline.The most significant tensor changes to the superior cerebellar peduncles and cerebellar white matter occurred in the subacute period, regardless of the tumor pathology or therapy regimen, with signs of recovery in the chronic period. However, chronic volume loss and reduced mean diffusivity were observed in the dentate nuclei and did not reverse. This atrophy was associated with radiation therapy and symptoms of ataxia.Longitudinal diffusion MR imaging in children treated for posterior fossa tumors showed time-dependent tensor changes in components of the dentatothalamic pathway that suggest evolution of structural damage with inflammation and recovery of tissue directionality. However, the dentate nuclei did not show tensor or volumetric recovery, suggesting that the injury may be chronic.

    View details for DOI 10.3174/ajnr.A3735

    View details for PubMedID 24052507

  • Tectal pineal cyst in a 1-year-old girl. Human pathology Plowey, E. D., Vogel, H., Yeom, K. W., Jung, H., Chao, K., Edwards, M. S. 2014; 45 (3): 653-656

    Abstract

    Glial cysts of the pineal gland can frequently be found in adults and children, but only rarely do they enlarge to become clinically relevant. We report a unique presentation of a pineal cyst in the midbrain tectum of a 16-month-old girl who initially presented with ptosis and strabismus. Preoperative imaging studies and intraoperative findings revealed no continuity between the tectal cyst and the pineal gland proper. We surmise that this tectal pineal cyst may have arisen from duplicated pineal gland tissue.

    View details for DOI 10.1016/j.humpath.2013.10.002

    View details for PubMedID 24411061

  • Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma. Journal of neuro-oncology Lober, R. M., Cho, Y., Tang, Y., Barnes, P. D., Edwards, M. S., Vogel, H., Fisher, P. G., Monje, M., Yeom, K. W. 2014; 117 (1): 175-182

    Abstract

    While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

    View details for DOI 10.1007/s11060-014-1375-8

    View details for PubMedID 24522717

  • Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI. Journal of neuro-oncology Perreault, S., Lober, R. M., Carret, A., Zhang, G., Hershon, L., Décarie, J., Vogel, H., Yeom, K. W., Fisher, P. G., Partap, S. 2014; 116 (3): 617-623

    Abstract

    Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97 % of all relapses occurred in the brain and 3 % were isolated to the spine. Relapse was identified in 226 (8 %) brain and 48 (4 %) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

    View details for DOI 10.1007/s11060-013-1347-4

    View details for PubMedID 24401959

  • Arterial spin-labeled perfusion of pediatric brain tumors. AJNR. American journal of neuroradiology Yeom, K. W., MITCHELL, L. A., Lober, R. M., Barnes, P. D., Vogel, H., Fisher, P. G., Edwards, M. S. 2014; 35 (2): 395-401

    Abstract

    Pediatric brain tumors have diverse pathologic features, which poses diagnostic challenges. Although perfusion evaluation of adult tumors is well established, hemodynamic properties are not well characterized in children. Our goal was to apply arterial spin-labeling perfusion for various pathologic types of pediatric brain tumors and evaluate the role of arterial spin-labeling in the prediction of tumor grade.Arterial spin-labeling perfusion of 54 children (mean age, 7.5 years; 33 boys and 21 girls) with treatment-naive brain tumors was retrospectively evaluated. The 3D pseudocontinuous spin-echo arterial spin-labeling technique was acquired at 3T MR imaging. Maximal relative tumor blood flow was obtained by use of the ROI method and was compared with tumor histologic features and grade.Tumors consisted of astrocytic (20), embryonal (11), ependymal (3), mixed neuronal-glial (8), choroid plexus (5), craniopharyngioma (4), and other pathologic types (3). The maximal relative tumor blood flow of high-grade tumors (grades III and IV) was significantly higher than that of low-grade tumors (grades I and II) (P < .001). There was a wider relative tumor blood flow range among high-grade tumors (2.14 ± 1.78) compared with low-grade tumors (0.60 ± 0.29) (P < .001). Across the cohort, relative tumor blood flow did not distinguish individual histology; however, among posterior fossa tumors, relative tumor blood flow was significantly higher for medulloblastoma compared with pilocytic astrocytoma (P = .014).Characteristic arterial spin-labeling perfusion patterns were seen among diverse pathologic types of brain tumors in children. Arterial spin-labeling perfusion can be used to distinguish high-grade and low-grade tumors.

    View details for DOI 10.3174/ajnr.A3670

    View details for PubMedID 23907239

  • Improved T2* Imaging without Increase in Scan Time: SWI Processing of 2D Gradient Echo. AJNR. American journal of neuroradiology Soman, S., Holdsworth, S. J., Barnes, P. D., Rosenberg, J., Andre, J. B., Bammer, R., Yeom, K. W. 2013; 34 (11): 2092-2097

    Abstract

    BACKGROUND AND PURPOSE:2D gradient-echo imaging is sensitive to T2* lesions (hemorrhages, mineralization, and vascular lesions), and susceptibility-weighted imaging is even more sensitive, but at the cost of additional scan time (SWI: 5-10 minutes; 2D gradient-echo: 2 minutes). The long acquisition time of SWI may pose challenges in motion-prone patients. We hypothesized that 2D SWI/phase unwrapped images processed from 2D gradient-echo imaging could improve T2* lesion detection.MATERIALS AND METHODS:2D gradient-echo brain images of 50 consecutive pediatric patients (mean age, 8 years) acquired at 3T were retrospectively processed to generate 2D SWI/phase unwrapped images. The 2D gradient-echo and 2D SWI/phase unwrapped images were compared for various imaging parameters and were scored in a blinded fashion.RESULTS:Of 50 patients, 2D gradient-echo imaging detected T2* lesions in 29 patients and had normal findings in 21 patients. 2D SWI was more sensitive than standard 2D gradient-echo imaging in detecting T2* lesions (P < .0001). 2D SWI/phase unwrapped imaging also improved delineation of normal venous structures and nonpathologic calcifications and helped distinguish calcifications from hemorrhage. A few pitfalls of 2D SWI/phase unwrapped imaging were noted, including worsened motion and dental artifacts and challenges in detecting T2* lesions adjacent to calvaria or robust deoxygenated veins.CONCLUSIONS:2D SWI and associated phase unwrapped images processed from standard 2D gradient-echo images were more sensitive in detecting T2* lesions and delineating normal venous structures and nonpathologic mineralization, and they also helped distinguish calcification at no additional scan time. SWI processing of 2D gradient-echo images may be a useful adjunct in cases in which longer scan times of 3D SWI are difficult to implement.

    View details for DOI 10.3174/ajnr.A3595

    View details for PubMedID 23744690

  • Increased focal hemosiderin deposition in pediatric medulloblastoma patients receiving radiotherapy at a later age. Journal of neurosurgery. Pediatrics Yeom, K. W., Lober, R. M., Partap, S., Telischak, N., Tsolinas, R., Barnes, P. D., Edwards, M. S. 2013; 12 (5): 444-451

    Abstract

    Object Focal hemosiderin deposition (FHD) is commonly observed on brain MRI scans of patients treated for childhood medulloblastoma (MB). The authors sought to determine the clinical significance of FHD and its relationship to patient age, radiation dose, and cognitive outcomes. Methods A single-institution retrospective study of 93 MB patients at Lucile Packard Children's Hospital at Stanford from 1998 to 2011 identified 41 patients with a negative baseline MRI scan and at least 2 posttreatment MRI scans obtained with T2* gradient recalled echo (GRE). The number and cumulative rate of FHDs detectable by GRE were compared between patients aged 6 years and younger (early age) and aged 7-21 years (late age) at the time of radiotherapy (RT) and between low-dose (1800-2340 cGy) and high-dose (2920-3960 cGy) RT. Results The median age at MB diagnosis was 7.3 years (range 0.9-21.0 years), the median clinical follow-up period was 5.8 years (range 0.8-13.4 years), and the median 5-year overall survival was 81% ± 7%. Of 30 school-aged children with MB, 21 (70%) required special education, and the median IQ of 10 tested patients was 100 (range 50-118). Thirty-three patients (80%) had FHD after a median latency of 1.9 years (range 0.1-5.9 years). Ninety-four percent (436 of 466) of the lesions arose in the supratentorial region of the brain, whereas 29 (6%) resided in the brainstem or the cerebellum. No spinal lesions were observed on routine spine MRI scans using T2 fast spin echo imaging. The mean cumulative lesion rate per year was 2.23 ± 3.05, and this rate was higher in older children at the time of RT compared with younger children (3.23 vs 0.67 per year, p = 0.002) but did not differ among different RT doses (p = 0.395). A child's IQ or need for special education showed no significant correlation with the rate of lesion development or number of lesions. None of the lesions resulted in symptomatic hemorrhage that required surgical intervention. Conclusions More FHD was observed in children treated for MB at the older ages than in those treated at the younger ages. There was no significant association of the incidence of FHD with radiation dose or cognitive outcomes, and none of the lesions required surgical intervention.

    View details for DOI 10.3171/2013.7.PEDS1330

    View details for PubMedID 23992236

  • Relapse patterns in pediatric embryonal central nervous system tumors JOURNAL OF NEURO-ONCOLOGY Perreault, S., Lober, R. M., Carret, A., Zhang, G., Hershon, L., Decarie, J., Yeom, K., Vogel, H., Fisher, P. G., Partap, S. 2013; 115 (2): 209-215

    Abstract

    Embryonal tumors of the central nervous system (CNS) share histological features and were therefore initially grouped as primitive neuroectodermal tumors (PNET) and treated similarly. We sought to determine the relapse patterns of specific embryonal CNS tumors. We conducted a historical cohort study of children diagnosed with CNS embryonal tumors from January 2000 to December 2011 in two pediatric neuro-oncology centers. Patients of 21 years of age or younger at time of presentation with a diagnosis of medulloblastoma, supratentorial PNET, pineoblastoma or atypical teratoid/rhabdoid tumor (ATRT) and at least one surveillance MRI were included. A total of 133 patients met inclusion criteria and 49 (37 %) patients relapsed during the observation period. The majority (79 %) of sPNET relapses were local, whereas all (100 %) PB relapses were associated with diffuse leptomeningeal disease. Relapse patterns for MB were more diverse with local recurrence in 27 %, distant recurrence in 35 % and diffuse leptomeningeal disease in 38 %. The frequency of relapses involving the spine differed (p < 0.001) between tumor types (MB 28/55 [51 %], sPNET 3/33 [9 %], ATRT 3/7 [43 %] and PB 12/12 [100 %]). No sPNET patients had isolated spinal relapse (0/14). Embryonal tumors were found to have divergent patterns of recurrence. While medulloblastoma has variable relapse presentations, sPNET relapses locally and pineoblastoma recurs with diffuse leptomeningeal disease involving the spine. These results point toward possibly new upfront treatment stratification among embryonal tumors in accordance with relapse pattern.

    View details for DOI 10.1007/s11060-013-1213-4

    View details for Web of Science ID 000325821900009

    View details for PubMedID 23921420

  • Reduced Cerebral Arterial Spin-Labeled Perfusion in Children with Neurofibromatosis Type 1 AMERICAN JOURNAL OF NEURORADIOLOGY Yeom, K. W., Lober, R. M., Barnes, P. D., Campen, C. J. 2013; 34 (9): 1823-1828

    Abstract

    BACKGROUND AND PURPOSE:Neurofibromatosis type 1 is associated with increased risk for stroke, cerebral vasculopathy, and neurocognitive deficits, but underlying hemodynamic changes in asymptomatic children remain poorly understood. We hypothesized that children with neurofibromatosis type 1 have decreased cerebral blood flow.MATERIALS AND METHODS:Arterial spin-labeled CBF was measured in 14 children with neurofibromatosis type 1 (median age, 9.7 years; mean, 10.2 years; range, 22 months to 18 years) and compared with age-matched control subjects on 3T MR imaging. Three-dimensional pseudocontinuous spin-echo arterial spin-labeled technique was used. Measurements were obtained at cortical gray matter of bilateral cerebral hemispheres and centrum semiovale by use of the ROI method. Comparison by Mann-Whitney test was used, with Bonferroni-adjusted P values ≤.004 judged as significant.RESULTS:We identified 7 of 12 areas with significantly diminished arterial spin-labeled CBF in patients with neurofibromatosis type 1 compared with control subjects. These areas included the anterior cingulate gyrus (P = .001), medial frontal cortex (P = .004), centrum semiovale (P = .004), temporo-occipital cortex (P = .002), thalamus (P = .001), posterior cingulate gyrus (P = .002), and occipital cortex (P = .001). Among patients with neurofibromatosis type 1, there were no significant differences in these regions on the basis of the presence of neurofibromatosis type 1 spots or neurocognitive deficits.CONCLUSIONS:Reduced cerebral perfusion was seen in children with neurofibromatosis type 1, particularly in the posterior circulation and the vascular borderzones of the middle and posterior cerebral arteries.

    View details for DOI 10.3174/ajnr.A3649

    View details for Web of Science ID 000329848800034

    View details for PubMedID 23764727

  • Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma. Journal of neuro-oncology Yeom, K. W., Lober, R. M., Andre, J. B., Fisher, P. G., Barnes, P. D., Edwards, M. S., Partap, S. 2013; 113 (3): 479-483

    Abstract

    Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.

    View details for DOI 10.1007/s11060-013-1140-4

    View details for PubMedID 23673514

  • Case series: fractional anisotropy along the trajectory of selected white matter tracts in adolescents born preterm with ventricular dilation. Journal of child neurology Myall, N. J., Yeom, K. W., Yeatman, J. D., Gaman-Bean, S., Feldman, H. M. 2013; 28 (6): 774-780

    Abstract

    This case series assesses white matter microstructure in 3 adolescents born preterm with nonshunted ventricular dilation secondary to intraventricular hemorrhage. Subjects (ages 12-17 years, gestational age 26-29 weeks, birth weight 825-1624 g) were compared to 3 full-term controls (13-17 years, 39-40 weeks, 3147-3345 g) and 3 adolescents born preterm without ventricular dilation (10-13 years, 26-29 weeks, 630-1673 g). Tractography using a 2 region of interest method reconstructed the following white matter tracts: superior longitudinal/arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and corticospinal tract. Subjects showed increased fractional anisotropy and changes in the pattern of fractional anisotropy along the trajectory of tracts adjacent to the lateral ventricles. Tensor shape at areas of increased fractional anisotropy demonstrated increased linear anisotropy at the expense of planar and spherical anisotropy. These findings suggest increased axonal packing density and straightening of fibers secondary to ventricular enlargement.

    View details for DOI 10.1177/0883073812449693

    View details for PubMedID 22859695

  • Diffusion-weighted MRI: distinction of skull base chordoma from chondrosarcoma. AJNR. American journal of neuroradiology Yeom, K. W., Lober, R. M., Mobley, B. C., Harsh, G., Vogel, H., Allagio, R., Pearson, M., Edwards, M. S., Fischbein, N. J. 2013; 34 (5): 1056-?

    Abstract

    Chordoma and chondrosarcoma of the skull base are rare tumors with overlapping presentations and anatomic imaging features but different prognoses. We hypothesized that these tumors might be distinguished by using diffusion-weighted MR imaging.We retrospectively reviewed 19 patients with pathologically confirmed chordoma or chondrosarcoma who underwent both conventional and diffusion-weighted MR imaging. Differences in distributions of ADC were assessed by the Kruskal-Wallis test. Associations between histopathologic diagnosis and conventional MR imaging features (T2 signal intensity, contrast enhancement, and tumor location) were assessed with the Fisher exact test.Chondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10(-6) mm(2)/s) and was significantly different from classic chordoma (1474 ± 117 × 10(-6) mm(2)/s) and poorly differentiated chordoma (875 ± 100 × 10(-6) mm(2)/s) (P < .001). Poorly differentiated chordoma was characterized by low T2 signal intensity (P = .001), but other conventional MR imaging features of enhancement and/or lesion location did not reliably distinguish these tumor types.Diffusion-weighted MR imaging may be useful in assessing clival tumors, particularly in differentiating chordoma from chondrosarcoma. A prospective study of a larger cohort will be required to determine the value of ADC in predicting histopathologic diagnosis.

    View details for DOI 10.3174/ajnr.A3333

    View details for PubMedID 23124635

  • Comparison of Readout-Segmented Echo-Planar Imaging (EPI) and Single-Shot EPI in Clinical Application of Diffusion-Weighted Imaging of the Pediatric Brain. AJR. American journal of roentgenology Yeom, K. W., Holdsworth, S. J., Van, A. T., Iv, M., Skare, S., Lober, R. M., Bammer, R. 2013; 200 (5): W437-43

    View details for DOI 10.2214/AJR.12.9854

    View details for PubMedID 23617511

  • Diffusion-Weighted MRI: Distinction of Skull Base Chordoma from Chondrosarcoma. AJNR. American journal of neuroradiology Yeom, K. W., Lober, R. M., Mobley, B. C., Harsh, G., Vogel, H., Allagio, R., Pearson, M., Edwards, M. S., Fischbein, N. J. 2013; 34 (5): 1056-1061

    View details for DOI 10.3174/ajnr.A3333

    View details for PubMedID 23124635

  • Case Report of Subdural Hematoma in a Patient With Sturge-Weber Syndrome and Literature Review: Questions and Implications for Therapy JOURNAL OF CHILD NEUROLOGY Lopez, J., Yeom, K. W., Comi, A., Van Haren, K. 2013; 28 (5): 672-675

    Abstract

    Sturge-Weber syndrome is a neurocutaneous disorder associated with vascular abnormalities in the skin, eye, and brain leading to both acute and chronic cerebral hypoperfusion and, in some affected children, brain injury. Aspirin can reduce stroke-like events and seizure episodes and prevent further brain injuries in these patients. Although a few cases of intracranial hemorrhage in patients with Sturge-Weber syndrome have been reported, prior reports have not discussed this complication with regard to particular therapies. The authors present a toddler with Sturge-Weber syndrome who developed a subdural hematoma in the setting of a mechanical fall with minor head trauma. They discuss the possible role of aspirin in contributing to, or perhaps protecting against, intracranial hemorrhage in patients with Sturge-Weber syndrome. Further data are needed to establish the utility of aspirin in Sturge-Weber syndrome.

    View details for DOI 10.1177/0883073812449514

    View details for Web of Science ID 000317683900018

    View details for PubMedID 22805242

  • Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the staging of retinoblastoma EUROPEAN RADIOLOGY Khurana, A., Eisenhut, C. A., Wan, W., Ebrahimi, K. B., Patel, C., O'Brien, J. M., Yeom, K., Daldrup-Link, H. E. 2013; 23 (5): 1271-1280

    Abstract

    To compare the diagnostic value of magnetic resonance (MR) imaging and ophthalmoscopy for staging of retinoblastoma.MR and ophthalmoscopic images of 36 patients who underwent enucleation were evaluated retrospectively following institutional review board approval. Histopathology being the standard of reference, the sensitivity and specificity of both diagnostic modalities were compared regarding growth pattern, iris neoangiogenesis, retinal detachment, vitreous seeds and optic nerve invasion. Data were analysed via McNemar's test.Both investigations showed no significant difference in accuracy for the detection of different tumour growth patterns (P = 0.80). Vitreous seeding detection was superior by ophthalmoscopy (P < 0.001). For prelaminar optic nerve invasion, MR imaging showed similar sensitivity as ophthalmoscopy but increased specificity of 40 % (CI 0.12-0.74) vs. 20 % (0.03-0.56). MR detected optic nerve involvement past the lamina cribrosa with a sensitivity of 80 % (0.28-0.99) and a specificity of 74 % (0.55-0.88). The absence of optic nerve enhancement excluded histopathological infiltration, but the presence of optic nerve enhancement included a high number of false positives (22-24 %).Ophthalmoscopy remains the method of choice for determining extent within the globe while MR imaging is useful for evaluating extraocular tumour extension. Thus, both have their own strengths and contribute uniquely to the staging of retinoblastoma.• Ophthalmoscopy: method of choice for determining extent of retinoblastoma within the globe. • MR imaging provides optimal evaluation of extrascleral and extraocular tumour extension. • Positive enhancement of the optic nerve on MRI does not necessarily indicate involvement.

    View details for DOI 10.1007/s00330-012-2707-8

    View details for Web of Science ID 000317427500015

    View details for PubMedID 23160663

  • Distinctive MRI Features of Pediatric Medulloblastoma Subtypes AMERICAN JOURNAL OF ROENTGENOLOGY Yeom, K. W., Mobley, B. C., Lober, R. M., Andre, J. B., Partap, S., Vogel, H., Barnes, P. D. 2013; 200 (4): 895-903

    Abstract

    We hypothesized that the apparent diffusion coefficient (ADC) and other MRI features can be used to predict medulloblastoma histologic subtypes, as defined by the World Health Organization (WHO) in WHO Classification of Tumours of the Central Nervous System.A retrospective review of pediatric patients with medulloblastoma between 1989 and 2011 identified 38 patients with both pretreatment MRI and original pathology slides. The mean and minimum tumor ADC values and conventional MRI features were compared among medulloblastoma histologic subtypes.The cohort of 38 patients included the following histologic subtypes: 24 classic medulloblastomas, nine large cell (LC) or anaplastic medulloblastomas, four desmoplastic medulloblastomas, and one medulloblastoma with extensive nodularity. The median age at diagnosis was 8 years (range, 1-21 years) and the median follow-up time was 33 months (range, 0-150 months). The mean ADC (× 10(-3) mm(2)/s) was lower in classic medulloblastoma (0.733 ± 0.046 [SD]) than in LC or anaplastic medulloblastoma (0.935 ± 0.127) (Mann-Whitney test, p = 0.004). Similarly, the minimum ADC was lower in classic medulloblastoma (average ± SD, 0.464 ± 0.056) than in LC or anaplastic medulloblastoma (0.630 ± 0.053) (p = 0.004). The MRI finding of focal cysts correlated with the classic and desmoplastic subtypes (Fisher exact test, p = 0.026). Leptomeningeal enhancement positively correlated with the LC or anaplastic medulloblastoma subtype and inversely correlated with the classic medulloblastoma and desmoplastic medulloblastoma subtypes (p = 0.04). Ring enhancement correlated with tumor necrosis (p = 0.022) and with the LC or anaplastic medulloblastoma histologic subtype (p < 0.001).The LC or anaplastic medulloblastoma subtype was associated with increased ADC and with ring enhancement, the latter of which correlated with tumor necrosis. These features could be considered in the evaluation of high-risk medulloblastoma subtypes.

    View details for DOI 10.2214/AJR.12.9249

    View details for Web of Science ID 000316622100045

    View details for PubMedID 23521467

  • Language and reading skills in school-aged children and adolescents born preterm are associated with white matter properties on diffusion tensor imaging NEUROPSYCHOLOGIA Feldman, H. M., Lee, E. S., Yeatman, J. D., Yeom, K. W. 2012; 50 (14): 3348-3362

    Abstract

    Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks gestation (n=23, mean±SD age 12.5±2.0 years, gestational age 28.7±2.5 weeks, birth weight 1184±431 g) and controls born after 37 weeks gestation (n=19, 13.1±2.1 years, 39.3±1.0 weeks, 3178±413 g) underwent a battery of language and reading tests. Diffusion tensor imaging (DTI) scans were processed using tract-based spatial statistics to generate a core white matter skeleton that was anatomically comparable across participants. Fractional anisotropy (FA) was the diffusion property used in analyses. In the full-term group, no regions of the whole FA-skeleton were associated with language and reading. In the preterm group, regions of the FA-skeleton were significantly associated with verbal IQ, linguistic processing speed, syntactic comprehension, and decoding. Combined, the regions formed a composite map of 22 clusters on 15 tracts in both hemispheres and in the ventral and dorsal streams. ROI analyses in the preterm group found that several of these regions also showed positive associations with receptive vocabulary, verbal memory, and reading comprehension. Some of the same regions showed weak negative correlations within the full-term group. Exploratory multiple regression in the preterm group found that specific white matter pathways were related to different aspects of language processing and reading, accounting for 27-44% of the variance. The findings suggest that higher performance in language and reading in a group of preterm but not full-term children is associated with higher fractional anisotropy of a bilateral and distributed white matter network.

    View details for DOI 10.1016/j.neuropsychologia.2012.10.014

    View details for Web of Science ID 000313142700020

    View details for PubMedID 23088817

    View details for PubMedCentralID PMC3631607

  • Diffusion tensor imaging (DTI) with retrospective motion correction for large-scale pediatric imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Holdsworth, S. J., Aksoy, M., Newbould, R. D., Yeom, K., Van, A. T., Ooi, M. B., Barnes, P. D., Bammer, R., Skare, S. 2012; 36 (4): 961-971

    Abstract

    To develop and implement a clinical DTI technique suitable for the pediatric setting that retrospectively corrects for large motion without the need for rescanning and/or reacquisition strategies, and to deliver high-quality DTI images (both in the presence and absence of large motion) using procedures that reduce image noise and artifacts.We implemented an in-house built generalized autocalibrating partially parallel acquisitions (GRAPPA)-accelerated diffusion tensor (DT) echo-planar imaging (EPI) sequence at 1.5T and 3T on 1600 patients between 1 month and 18 years old. To reconstruct the data, we developed a fully automated tailored reconstruction software that selects the best GRAPPA and ghost calibration weights; does 3D rigid-body realignment with importance weighting; and employs phase correction and complex averaging to lower Rician noise and reduce phase artifacts. For select cases we investigated the use of an additional volume rejection criterion and b-matrix correction for large motion.The DTI image reconstruction procedures developed here were extremely robust in correcting for motion, failing on only three subjects, while providing the radiologists high-quality data for routine evaluation.This work suggests that, apart from the rare instance of continuous motion throughout the scan, high-quality DTI brain data can be acquired using our proposed integrated sequence and reconstruction that uses a retrospective approach to motion correction. In addition, we demonstrate a substantial improvement in overall image quality by combining phase correction with complex averaging, which reduces the Rician noise that biases noisy data.

    View details for DOI 10.1002/jmri.23710

    View details for Web of Science ID 000308884300022

    View details for PubMedID 22689498

    View details for PubMedCentralID PMC3443529

  • DIFFERENT RELAPSE PATTERNS IN EMBRYONAL CNS TUMORS Perreault, S., Lober, R. M., Zhang, G., Hershon, L., Decarie, J., Yeom, K., Vogel, H., Partap, S., Carret, A., Fisher, P. G. OXFORD UNIV PRESS INC. 2012: 123
  • Application of diffusion tensor tractography in pediatric optic pathway glioma. Journal of neurosurgery. Pediatrics Lober, R. M., Guzman, R., Cheshier, S. H., Fredrick, D. R., Edwards, M. S., Yeom, K. W. 2012; 10 (4): 273-280

    Abstract

    Magnetic resonance imaging is commonly used in diagnosis and surveillance for optic pathway glioma (OPG). The authors investigated the role of diffusion tensor (DT) tractography in assessing the location of visual pathway fibers in the presence of tumor.Data in 10 children with OPG were acquired using a 3T MRI generalized autocalibrating parallel acquisitions DT-echo planar imaging sequence (25 isotropic directions with a b value of 1000 seconds/mm(2), slice thickness 3 mm). Fiber tractography was performed, with seed regions placed within the optic chiasm and bilateral nerves on the coronal plane, including the tumor and surrounding normal-appearing tissue. Tracking was performed with a curvature threshold of 30°.For prechiasmatic lesions, fibers either stopped abruptly at the tumor or traversed abnormally dilated nerve segments. Similar findings were seen with chiasmatic lesions, with an additional arrangement in which fibers diverged around the tumor. For each patient, DT tractography provided additional information about visual fiber arrangement in relation to the tumor that was not evident by using conventional MRI methods. Retrospective reconstruction of visual fibers in 1 patient with new postoperative hemianopia revealed an unexpected superior displacement of the optic tract that might have been helpful information had it been applied to preoperative planning or surgical navigation.Optic pathway DT tractography is feasible in patients with OPG and provides new information about the arrangement of visual fibers in relation to tumors that could be incorporated into surgical navigation for tumor biopsy or debulking procedures.

    View details for DOI 10.3171/2012.7.PEDS1270

    View details for PubMedID 22900485

  • White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and cognitive function in adolescents born preterm DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Feldman, H. M., Lee, E. S., Loe, I. M., Yeom, K. W., Grill-Spector, K., Luna, B. 2012; 54 (9): 809-814

    Abstract

    Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm- and term-born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures.Participants (n=121; 66 females, 55 males) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born at less than 36 weeks' gestation (mean 29.4 wks; birthweight 1289g) and 63 term children (site 1, n=40; site 2, n=23) born at more than 37 weeks' gestation. DTI was analyzed using tract-based spatial statistics. Diffusion measures were fractional anisotropy, axial, radial, and mean diffusivity.In no region of the white matter skeleton was fractional anisotropy lower in the preterm group at either site. Within the preterm groups, fractional anisotropy was significantly associated with white matter injury score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated with IQ.DTI contributes to understanding individual differences after preterm birth but may not differentiate a relatively high-functioning group of preterm children from a matched group of term-born children.

    View details for DOI 10.1111/j.1469-8749.2012.04378.x

    View details for Web of Science ID 000307468700011

    View details for PubMedID 22803787

    View details for PubMedCentralID PMC3683593

  • Oculomotor Assessments of Executive Function in Preterm Children JOURNAL OF PEDIATRICS Loe, I. M., Luna, B., Bledsoe, I. O., Yeom, K. W., Fritz, B. L., Feldman, H. M. 2012; 161 (3): 427-?

    Abstract

    To use objective, nonverbal oculomotor tasks to assess executive function and infer the neural basis of impairments in preterm children.Cross-sectional study of preterm children age 9-16 years (n = 69; mean gestational age 29 weeks) and full-term controls (n = 43). Tasks assessed sensorimotor function (reflexive prosaccades); resistance to peripheral distracters (fixation); response inhibition, response preparation, and execution of a voluntary saccade (antisaccades); and spatial working memory (memory-guided saccades). Group differences were analyzed using ANOVA. We used linear regression to analyze the contributions of age, sex, gestational age, and white matter category to task performance.Preterm children did not differ from controls on basic sensorimotor function, response inhibition, and working memory. Compared with controls, preterm children showed greater susceptibility to peripheral distracters (P = .008) and were slower to initiate an inhibitory response (P = .003). Regression models showed contributions of age and white matter category to task performance.Preterm children show intact basic sensorimotor function and demonstrate difficulties in processes underlying executive control, including increased distractibility and prolonged response preparation. These limitations may reflect specific neural abnormalities in fronto-subcortical executive control of behavior.

    View details for DOI 10.1016/j.jpeds.2012.02.037

    View details for Web of Science ID 000308141700015

    View details for PubMedID 22480696

    View details for PubMedCentralID PMC3638733

  • High-Resolution MR Imaging of the Orbit in Patients with Retinoblastoma RADIOGRAPHICS Rauschecker, A. M., Patel, C. V., Yeom, K. W., Eisenhut, C. A., Gawande, R. S., O'Brien, J. M., Ebrahimi, K. B., Daldrup-Link, H. E. 2012; 32 (5): 1307-1326

    Abstract

    Retinoblastoma is the most common intraocular childhood malignancy, with a prevalence of one in 18,000 children younger than 5 years old in the United States. In 80% of patients, retinoblastoma is diagnosed before the age of three, and in 95% of patients, retinoblastoma is diagnosed before the age of five. Although reports exist of retinoblastoma in adults, onset beyond 6 years of age is rare. Broadly, retinoblastoma may be classified into two groups: sporadic and heritable. In either case, the origin of the tumor is a biallelic mutation in primitive neuroepithelial cells. Although their details vary, several staging schemes are used to describe the extent of retinoblastoma according to the following four general criteria: intraocular location, extraocular (extraorbital) location, central nervous system disease, and systemic metastases. In the past decade, substantial changes have taken place in terms of staging and monitoring treatment in patients with retinoblastoma. Diagnosis and treatment of retinoblastoma involve a multidisciplinary approach, for which imaging is a vital component. Increasing awareness and concerns about the effects of radiation in patients with retinoblastoma have led to a shift away from external-beam radiation therapy and toward chemotherapy and locoregional treatment, as well as the establishment of magnetic resonance imaging as the most important imaging modality for diagnosis, staging, and treatment monitoring.

    View details for DOI 10.1148/rg.325115176

    View details for Web of Science ID 000308632900010

    View details for PubMedID 22977020

  • Response to Larry R. White's Letter to the Editor Titled "Comparison of CT, PET, and PET/CT for Staging of Patients with Indolent Non-Hodgkin's Lymphoma: Statistical Errors in Fueger et al. (2009)" MOLECULAR IMAGING AND BIOLOGY Fueger, B. J., Yeom, K., Czernin, J., Sayre, J. W., Phelps, M. E., Allen-Auerbach, M. S. 2012; 14 (4): 399–401
  • INJURY TO DENTATE NUCLEI AND EFFERENT FIBERS BY PEDIATRIC POSTERIOR FOSSA TUMORS Lober, R., Perrault, S., Partap, S., Edwards, M., Fisher, P., Yeom, K. OXFORD UNIV PRESS INC. 2012: 132–33
  • SURVEILLANCE SPINE MRIS TO DETECT TUMOR RELAPSE IN PATIENTS WITH MEDULLOBLASTOMA Perreault, S., Lober, R., Yeom, K., Carret, A., Vogel, H., Partap, S., Fisher, P. OXFORD UNIV PRESS INC. 2012: 143
  • CLUES TO PONTINE GLIOMAGENESIS FROM CHILDHOOD PONTINE GLIOGENESIS Lober, R., Freret, M., Fisher, P., Edwards, M., Yeom, K., Monje, M. OXFORD UNIV PRESS INC. 2012: 27
  • ASL CEREBRAL PERFUSION DIFFERENCES BETWEEN HIGH-GRADE AND LOW-GRADE PEDIATRIC BRAIN TUMORS 16th Annual Scientific Meeting of the Society-for-Neuro-Oncology (SNO)/AANS/CNS Section on Tumors Campen, C. J., Soman, S., Fisher, P. G., Edwards, M. S., Yeom, K. W. OXFORD UNIV PRESS INC. 2011: 142–142
  • PROGNOSTIC ROLE OF DIFFUSION-WEIGHTED MRI IN PEDIATRIC OPTIC PATHWAY GLIOMA Yeom, K., Rosenberg, J., Andre, J. B., Fisher, P. G., Edwards, M. S., Barnes, P. D., Partap, S. OXFORD UNIV PRESS INC. 2011: 139–40
  • Diminished ASL intracranial perfusion in children with Neurofibromatosis Type 1 Campen, C. J., Rosenberg, J. K., Yeom, K. W. WILEY-BLACKWELL. 2011: S118
  • Clinical Application of Readout-Segmented-Echo-Planar Imaging for Diffusion-Weighted Imaging in Pediatric Brain AMERICAN JOURNAL OF NEURORADIOLOGY Holdsworth, S. J., Yeom, K., Skare, S., Gentles, A. J., Barnes, P. D., Bammer, R. 2011; 32 (7): 1274-1279

    Abstract

    RS-EPI has been suggested as an alternative approach to EPI for high-resolution DWI with reduced distortions. To determine whether RS-EPI is a useful approach for routine clinical use, we implemented GRAPPA-accelerated RS-EPI DWI at our pediatric hospital and graded the images alongside standard accelerated (ASSET) EPI DWI used routinely for clinical studies.GRAPPA-accelerated RS-EPI DWIs and ASSET EPI DWIs were acquired on 35 pediatric patients using a 3T system in 35 pediatric patients. The images were graded alongside each other by using a 7-point Likert scale as follows: 1, nondiagnostic; 2, poor; 3, acceptable; 4, standard; 5, above average; 6, good; and 7, outstanding.The following were the average scores for EPI and RS-EPI, respectively: resolution, 3.5/5.2; distortion level, 2.9/6.0; SNR, 3.4/4.1; lesion conspicuity, 3.3/5.9; and diagnostic confidence, 3.2/6.0. Overall, the RS-EPI had significantly improved diagnostic confidence and more reliably defined the extent and structure of several lesions. Although ASSET EPI scans had better SNR per scanning time, the higher spatial resolution as well as reduced blurring and distortions on RS-EPI scans helped to better reveal important anatomic details at the cortical-subcortical levels, brain stem, temporal and inferior frontal lobes, skull base, sinonasal cavity, cranial nerves, and orbits.This work shows the importance of both resolution and decreased distortions in the clinics, which can be accomplished by a combination of parallel imaging and alternative k-space trajectories such as RS-EPI.

    View details for DOI 10.3174/ajnr.A2481

    View details for Web of Science ID 000294275100023

    View details for PubMedID 21596809

  • Effect of chronic red cell transfusion therapy on vasculopathies and silent infarcts in patients with sickle cell disease AMERICAN JOURNAL OF HEMATOLOGY Gyang, E., Yeom, K., Hoppe, C., Partap, S., Jeng, M. 2011; 86 (1): 104-106

    Abstract

    Regular, chronic red cell transfusions (CTX) have been shown to be effective prophylaxis against stroke in sickle cell disease (SCD) in those at risk. Because serial brain imaging is not routinely performed, little is known about the impact of CTX on silent infarcts (SI) and cerebral vascular pathology. Thus, we retrospectively evaluated the magnetic resonance imaging reports of a cohort of SCD patients who were prescribed CTX for either primary or secondary stroke prophylaxis. Seventeen patients with Hb SS were included (mean age 15 years, mean follow-up 4.3 years). Eight patients were on CTX for primary prophylaxis. New SI occurred in 17.6% of patients corresponding to an SI rate of 5.42 per 100 patient-years. Vasculopathy of the cerebral arteries was present in 65% of patients and progressed in 63% of these patients. Those who developed progressive vasculopathy were on CTX for an average of 8 years before lesions progressed. Patients on CTX for secondary prophylaxis had more SIs and evidence of progressive vascular disease than patients on CTX for primary prophylaxis. We conclude that adherence to CTX does not necessarily prevent SI or halt cerebral vasculopathy progression, especially in those with a history of overt stroke.

    View details for DOI 10.1002/ajh.21901

    View details for Web of Science ID 000285421300025

    View details for PubMedID 21117059

  • USE OF DIFFUSION TENSOR IMAGING IN THE EVALUATION OF BRAIN INJURY IN ADOLESCENTS BORN PRETERM Gaman-Bean, S., Yeatman, J., Lee, E., Yeom, K., Feldman, H. LIPPINCOTT WILLIAMS & WILKINS. 2011: 95–96
  • Loss of SMARCB1/INI1 expression in poorly differentiated chordomas ACTA NEUROPATHOLOGICA Mobley, B. C., McKenney, J. K., Bangs, C. D., Callahan, K., Yeom, K. W., Schneppenheim, R., Hayden, M. G., Cherry, A. M., Gokden, M., Edwards, M. S., Fisher, P. G., Vogel, H. 2010; 120 (6): 745-753

    Abstract

    Chordomas are malignant neoplasms that typically arise in the axial spine and primarily affect adults. When chordomas arise in pediatric patients they are more likely to display unusual histological features and aggressive behavior. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry in an index case of poorly differentiated chordoma of the sacrum, leading us to further examine SMARCB1/INI1 expression as well as that of brachyury, a highly specific marker of notochordal differentiation, in 3 additional poorly differentiated chordomas of the clivus, 10 typical chordomas, and 8 atypical teratoid/rhabdoid tumors (AT/RTs). All 4 poorly differentiated chordomas and all AT/RTs lacked nuclear expression of SMARCB1/INI1, while the 10 typical chordomas maintained strong nuclear SMARCB1/INI1 immunoreactivity. All 10 typical and 4 poorly differentiated chordomas expressed brachyury; all 8 AT/RTs were brachyury immunonegative. Cytogenetic evaluation utilizing FISH probes near the SMARCB1/INI1 locus on chromosome 22q was also performed in all of the poorly differentiated chordomas in this series. Three of the four poorly differentiated chordomas had evidence for deletion of this region by FISH. Analysis of the SMARCB1/INI1 gene sequence was performed using formalin-fixed paraffin-embedded tissue in all cases and no point mutations were observed. In summary, all poorly differentiated chordomas in this series showed the absence of SMARCB1/INI1 expression, and were reliably distinguished from AT/RTs, clinically by their characteristic primary sites of origin and pathologically by strong nuclear brachyury expression. Our findings reveal a likely role for SMARCB1/INI1 in a subset of chordomas with aggressive features.

    View details for DOI 10.1007/s00401-010-0767-x

    View details for Web of Science ID 000284593200005

    View details for PubMedID 21057957

  • Langerhans cell histiocytosis in a 5-month-old presenting with biparietal masses Case report JOURNAL OF NEUROSURGERY-PEDIATRICS Pricola, K. L., Karamchandani, J., Vogel, H., Dahl, G. V., Yeom, K. W., Edwards, M. S., Guzman, R. 2010; 6 (4): 393-397

    Abstract

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder that occurs most commonly in the pediatric population as a result of pathological clonal proliferation of Langerhans cells with subsequent damage and destruction to surrounding tissue. Clinically, LCH presents in a variety of ways, which often results in prolonged time to diagnosis and subsequently poorer outcomes. In this case report, the authors describe an unusually early presentation of multisystem LCH in a patient at birth, which resulted in a 5-month delay to diagnosis and treatment. This patient presented both atypically young and with an uncommon initial manifestation of multisystem disease with multiple soft-tissue swellings rather than early skin involvement. Additionally, this patient had an unusual radiographic appearance with biparietal skull destruction on initial skull radiographs and biparietal soft-tissue lesions on CT resembling cephalohematoma at 3 months of age. The clinical and radiological evaluation, pathology, and treatment strategies are discussed, with particular attention paid to the importance of further workup of atypical nonresolving cephalohematomas to prevent disease progression and poorer outcomes.

    View details for DOI 10.3171/2010.7.PEDS10149

    View details for Web of Science ID 000282244400020

    View details for PubMedID 20887116

  • PROGNOSTIC FEATURES OF CHILDHOOD MEDULLOBLASTOMA BY MAGNETIC RESONANCE IMAGING Yeom, K., Andre, J. B., Rosenburg, J. K., Mobley, B. C., Vogel, H., Fisher, P. G., Edwards, M. B., Barnes, P. D., Partap, S. OXFORD UNIV PRESS INC. 2010: II7
  • EFFECT OF PATIENT AGE AND RADIOTHERAPY DOSAGE ON THE INCIDENCE OF MAGNETIC RESONANCE IMAGING (MRI) DETECTED MICROHEMORRHAGE FOLLOWING TREATMENT FOR PEDIATRIC MEDULLOBLASTOMA Partap, S., Rosenburg, J. K., Telischak, N., Minn, Y., Fisher, P. G., Edwards, M. B., Barnes, P. D., Yeom, K. OXFORD UNIV PRESS INC. 2010: II115
  • Recurrent Pediatric Ganglion Cell Tumors Mobley, B., Minn, Y., Yeom, K., Fisher, P., Vogel, H. LIPPINCOTT WILLIAMS & WILKINS. 2010: 537–38
  • Cerebrovascular disease in childhood cancer survivors A Children's Oncology Group Report NEUROLOGY Morris, B., Partap, S., Yeom, K., Gibbs, I. C., Fisher, P. G., King, A. A. 2009; 73 (22): 1906-1913

    Abstract

    Curative therapy for childhood cancer has dramatically improved over past decades. Therapeutic radiation has been instrumental in this success. Unfortunately, irradiation is associated with untoward effects, including stroke and other cerebrovascular disease (CVD). The Children's Oncology Group (COG) has developed guidelines for screening survivors at risk for persistent or late sequelae of cancer therapy.This review summarizes the pathophysiology and relevant manifestations of radiation-induced CVD and outlines the specific patient groups at risk for early-onset stroke. The reader will be alerted to the availability of the COG recommendations for monitoring, and, when applicable, specific screening and treatment recommendations will be highlighted.A multidisciplinary task force critically reviewed the existing literature and scored the evidence to establish the current COG guidelines for monitoring health of survivors treated with head and neck irradiation.Previous head and neck exposure to therapeutic radiation is associated with latent CVD and increased risk for stroke in some patient groups. Common manifestations of radiation-induced CVD includes steno-occlusive disease, moyamoya, aneurysm, mineralizing microangiopathy, vascular malformations, and strokelike migraines.Risk for stroke is increased in survivors of pediatric CNS tumors, Hodgkin lymphoma, and acute lymphoblastic leukemia who received radiation to the brain and/or neck. As the population of survivors ages, vigilance for stroke and cerebrovascular disease needs to continue based on specific exposures during curative cancer therapy.

    View details for DOI 10.1212/WNL.0b013e3181c17ea8

    View details for Web of Science ID 000272205200015

    View details for PubMedID 19812380

    View details for PubMedCentralID PMC2788797

  • Comparison of CT, PET, and PET/CT for Staging of Patients with Indolent Non-Hodgkin's Lymphoma MOLECULAR IMAGING AND BIOLOGY Fueger, B. J., Yeom, K., Czernin, J., Sayre, J. W., Phelps, M. E., Allen-Auerbach, M. S. 2009; 11 (4): 269-274

    Abstract

    The aim was to investigate the potential impact of positron emission tomography (PET)/computed tomography (CT) as compared to PET and CT on the staging of patients with indolent lymphoma.PET/CTs from 45 patients with indolent lymphoma undergoing staging or restaging were studied. Clinical follow-up, additional imaging, and histology served as the gold standard.PET/CT correctly diagnosed 92 nodal regions as positive for lymphomatous involvement and 458 as disease free vs 68 and 449 for PET and 64 and 459 for CT, respectively. The respective sensitivities, specificities, and accuracies were 99%, 100%, and 99.8% for PET/CT, 68%, 97.5%, and 92.2% for PET, and 70%, 100%, and 94.7% for CT. PET/CT performed significantly better than PET (p < 0.001 for sensitivity, specificity, and accuracy) and CT (p < 0.001 for sensitivity and accuracy). PET/CT also correctly identified significantly more extra-nodal lesions (22) than CT (14) and PET (nine).PET/CT provides significantly more accurate information compared to PET and CT for the staging and re-staging of patients with indolent lymphoma.

    View details for DOI 10.1007/s11307-009-0200-9

    View details for Web of Science ID 000266830700009

    View details for PubMedID 19326177

  • Severe Encephalomyelitis in an Immunocompetent Adult with Chromosomally Integrated Human Herpesvirus 6 and Clinical Response to Treatment with Foscarnet plus Ganciclovir CLINICAL INFECTIOUS DISEASES Troy, S. B., Blackburn, B. G., Yeom, K., Caulfield, A. K., Bhangoo, M. S., Montoya, J. G. 2008; 47 (12): E93-E96

    Abstract

    Human herpesvirus 6 has rarely been identified as a cause of encephalitis in immunocompetent adults. We describe a patient who had severe encephalomyelitis, hypoglycorrhachia, and human herpesvirus 6 identified in his cerebrospinal fluid and serum and who recovered after treatment with foscarnet and ganciclovir. Human herpesvirus 6 should be considered in immunocompetent patients with encephalitis.

    View details for DOI 10.1086/593315

    View details for Web of Science ID 000261163600035

    View details for PubMedID 18991511

  • Evaluation of suspected local recurrence in head and neck cancer: A comparison between PET and PET/CT for biopsy proven lesions EUROPEAN JOURNAL OF RADIOLOGY Halpern, B. S., Yeom, K., Fueger, B. J., Lufkin, R. B., Czernin, J., Allen-Auerbach, M. 2007; 62 (2): 199-204

    Abstract

    (18)F-FDG PET has a high accuracy for re-staging of head and neck cancer. The purpose of this study was to determine whether the diagnostic accuracy can be further improved with integrated PET/CT.Forty-nine patients with a mean age of 59+/-18 years were studied retrospectively. Histo-pathological verification was available either from complete tumor resection with or without lymph node dissection (n=27) or direct endoscopic biopsy (n=16) or ultrasound guided biopsy (n=6). Two reviewers blinded to the pathological findings read all PET images in consensus. An experienced radiologist was added for the interpretation of the PET/CT images.Tissue verification was available for 110 lesions in 49 patients. Sixty-seven lesions (61%) were biopsy positive and 43 (39%) were negative for malignant disease. PET and PET/CT showed an overall accuracy for cancer detection of 84 and 88% (p=0.06), respectively. Sensitivity and specificity for PET were 78 and 93% versus 84 (p=NS) and 95% (p=NS) with PET/CT. A patient-by-patient analysis yielded a sensitivity, specificity and accuracy for PET of 80, 56 and 76%, compared to 88% (p=NS), 78% (p=NS) and 86% (p=0.06) for PET/CT.The results of this study indicate that PET/CT does not significantly improve the detection of recurrence of head and neck cancer. However, a trend towards improved accuracy was observed (p=0.06).

    View details for DOI 10.1016/j.ejrad.2006.11.037

    View details for Web of Science ID 000246613700010

    View details for PubMedID 17223003

  • Standard PET/CT of the chest during shallow breathing is inadequate for comprehensive staging of lung cancer JOURNAL OF NUCLEAR MEDICINE Allen-Auerbach, M., Yeom, K., Park, J., Phelps, M., Czernin, J. 2006; 47 (2): 298-301

    Abstract

    The incidence of malignancy associated with subcentimeter pulmonary nodules (micronodules) in patients with malignant disease has been reported to be as high as 58%. Thus, detection of small lung nodules is important for appropriate staging of lung cancer. Because of respiratory motion, small parenchymal lung lesions can be missed on CT acquired during shallow breathing. Micronodules are usually too small to be characterized reliably with 18F-FDG PET. We aimed to determine the incidence of missed pulmonary micronodules on PET/CT studies acquired during shallow breathing.The study included 142 consecutive cancer patients (62 male and 80 female; mean age, 54 y) who underwent whole-body PET/CT during shallow breathing and breath-hold CT of the chest during maximal inspiration. CT findings were reviewed independently, and noncalcified nodules missed on the shallow-breathing scan were evaluated for size, location, and metabolic activity.Breath-hold chest CT detected an additional 125 parenchymal lung nodules (mean size, 3.4 +/- 1.6 mm; range, 1-9 mm) in 48 (34%) of the 142 patients. In these patients, 3 nodules, on average, were missed during shallow breathing. In 18 patients (13%), micronodules were identified exclusively on breath-hold images. None of the missed nodules demonstrated 18F-FDG uptake.Acquisition of standard PET/CT chest images during shallow breathing is inadequate for comprehensive cancer staging.

    View details for Web of Science ID 000235283500030

    View details for PubMedID 16455636

  • Computed tomographic scanning reduces cost and time of complete spine evaluation 16th Annual Meeting of the Eastern-Association-for-the-Surgery-of-Trauma Brandt, M. M., Wahl, W. L., Yeom, K., Kazerooni, E., Wang, S. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: 1022–26

    Abstract

    We hypothesize that data collected from computed tomographic (CT) scans obtained for workup of chest or abdominal injuries provide data that are sufficient to screen for spinal fractures and will decrease the cost and time of spine evaluation after trauma.We reviewed plain radiographs from 55 selected trauma patients who also underwent CT scanning of the chest, abdomen, and pelvis. We also timed the radiologic workup of 50 consecutive trauma patients to determine the time required to complete radiographic spine evaluation.Forty-seven patients had thoracolumbar fractures. Thirteen patients were found to have 33 thoracolumbar spine fractures identified by CT scan but not plain radiography. Fractures were found on initial trauma CT scans of the chest, abdomen, and pelvis obtained to evaluate for visceral injuries. No injuries seen on plain film were missed on CT scan.We recommend using the data acquired from CT scans to evaluate the spine, supplementing them with additional studies only when needed for further clarification.

    View details for DOI 10.1097/01.TA.0000124304.68584.2C

    View details for Web of Science ID 000221703200022

    View details for PubMedID 15179241

  • Antibodies to HSP-70 in normal donors and autoimmune hearing loss patients Midwinter Meeting of the Association-for-Research-in-Otolaryngology Yeom, K., Gray, J., Nair, T. S., Arts, H. A., Telian, S. A., Disher, M. J., El-Kashlan, H., Sataloff, R. T., Fisher, S. G., Carey, T. E. JOHN WILEY & SONS INC. 2003: 1770–76

    Abstract

    To evaluate serum antibody to heat shock protein (HSP) 70 as a marker for autoimmune sensorineural hearing loss (AISNHL).Sera from 20 patients with rapidly progressive sensorineural HL and 20 control volunteers without HL were tested for antibody reactivity against multiple HSP 70 substrates. Substrates included recombinant human HSP (rHuHSP) 72, purified bovine brain heat shock cognate (HSC) 73 and HSP 72, as well as heat-shocked and non-heat-shocked protein extracts from bovine kidney (MDBK) cells. All serum donors were previously tested for antibody to guinea pig inner ear supporting cells; 17 of 20 patients but none (0 of 20) of the controls were positive.Sera were tested using Western blots.Reactivity with rHuHSP 70 was observed in 16 patients and 17 controls. Similarly, 15 of 20 patients and 17 of 20 controls stained for both HSP 72 and HSC 73 from the bovine brain. When tested against the heat-shock-induced and control MDBK extracts, six patients and nine controls had greater reactivity with the induced HSP 72.The frequency of antibodies to HSP substrates did not differ in patients and controls. Prior studies reported that HSP 72 is the 68 kD antigen commonly detected by AISNHL sera. However, we show that HSP 72 antibodies are no more prevalent in patients than in normal controls. Thus, it is unlikely that the 68 kD protein is HSP 72. Therefore, HSPs are not appropriate substrates for serodiagnosis of AISNHL.

    View details for Web of Science ID 000185871500019

    View details for PubMedID 14520104