Robert M. Lober

Arterial Spin-Labeled Perfusion of Pediatric Brain Tumors

ASL was used to evaluate 54 children with recently diagnosed brain tumors using a pseudocontinuous technique and blood flow was calculated for all masses. Blood flow was higher in grade 3 and 4 tumors than in lower grade ones. Although ASL was unable to separate tumors by histology, perfusion was found to be higher in medulloblastomas than in pylocytic astrocytomas. BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Diffusion-Weighted MRI: Distinction of Skull Base Chordoma from Chondrosarcoma

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Chondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10−6 mm2/s) and was significantly different from classic chordoma (1474 ± 117 × 10−6 mm2/s) and poorly differentiated chordoma (875 ± 100 × 10−6 mm2/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. CONCLUSIONS: 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.

Distinctive MRI Features of Pediatric Medulloblastoma Subtypes

OBJECTIVE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.

Comparison of Readout-Segmented Echo-Planar Imaging (EPI) and Single-Shot EPI in Clinical Application of Diffusion-Weighted Imaging of the Pediatric Brain

OBJECTIVE Readout-segmented echo-planar imaging (EPI) has been suggested as an alternative to single-shot EPI for diffusion-weighted imaging (DWI) with reduced distortion. However, clinical comparisons of readout-segmented EPI and EPI DWI are limited by unmatched imaging parameters and reconstruction procedures. Our goal was to compare the clinical utility of generalized autocalibrating partial parallel acquisition (GRAPPA)-accelerated readout-segmented EPI DWI with GRAPPA-accelerated EPI DWI for visualization of the pediatric brain in regions prone to distortion, such as the orbit, skull base, and posterior fossa. SUBJECTS AND METHODS Thirty consecutive patients (mean age, 7.8 years) presenting with orbital, skull base, and posterior fossa neuropathologic abnormalities were scanned at 3 T. Images were obtained using GRAPPA-accelerated readout-segmented EPI and GRAPPA-accelerated EPI with an identical scanning time, acceleration factor, target resolution, and image postprocessing procedure. The two datasets were independently reviewed by two blinded neuroradiologists. Imaging studies were evaluated for resolution, signal-to-noise ratio (SNR), contrast, distortion, lesion conspicuity, and diagnostic confidence and graded using a 7-point Likert scale (1, nondiagnostic; 7, outstanding). RESULTS There was good reader agreement in the scores (κ = 0.66; 95% CI, 0.54-0.78). The mean scores for EPI and readout-segmented EPI, respectively, were as follows: resolution, 5.0 and 6.0; SNR, 5.5 and 3.0; contrast, 3.7 and 3.2; distortion, 4.8 and 6.0; lesion conspicuity, 4.6 and 5.1; and diagnostic confidence, 4.7 and 5.4. Readout-segmented EPI was superior in resolution, distortion reduction, lesion conspicuity, and diagnostic confidence, whereas EPI scored better in SNR and contrast. Readout-segmented EPI was considered the better sequence overall in 85% of the cases. CONCLUSION This study shows the benefits of improved resolution and reduced distortion of readout-segmented EPI in evaluating the orbit, skull base, and posterior fossa, sites of common neuropathologic abnormalities in children.

Application of diffusion tensor tractography in pediatric optic pathway glioma

OBJECT 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. METHODS 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°. RESULTS 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. CONCLUSIONS 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.

Pediatric primary intramedullary spinal cord glioblastoma

Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245–88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed.

Carbon dioxide laser for corpus callosotomy in the pediatric population

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.

Hydrocephalus Decreases Arterial Spin-Labeled Cerebral Perfusion

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Time-Dependent Structural Changes of the Dentatothalamic Pathway in Children Treated for Posterior Fossa Tumor

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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 patients baseline. RESULTS: 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. CONCLUSIONS: 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.

Endonasal Access to the Upper Cervical Spine, Part One: Radiographic Morphometric Analysis

Objectives To determine the anatomical relationships that may influence endonasal access to the upper cervical spine. Setting We retrospectively analyzed computed tomography of 100 patients at a single institution. Participants Participants included adults with imaging of the hard palate, clivus, and cervical spine without evidence of fracture, severe spondylosis, or previous instrumentation. Main Outcome Measures Morphometric analyses of hard palate length and both distance and angle between the hard palate and odontoid process were based on radiographic measurements. Descriptive zones were assigned to cervical spine levels, and endoscopic visualization was simulated with projected lines at 0, 30, and 45 degrees from the hard palate to the cervical spine. Results We found an inverse relationship between hard palate length and the lowest zone of the cervical spine potentially visualized by nasal endoscopy. The distance between the posterior tip of the hard palate and the odontoid tip, and the angle formed between the two, directly influenced the lowest possible cervical exposure. Conclusions Radiographic relationships between hard palate length, distance to the odontoid, and the angle formed between the two predict the limits of endonasal access to the cervical spine. These results are supported by cadaveric data in Part Two of this study.