Faculty Bibliography

RATIONALE AND OBJECTIVES: Despite recent advances in the treatment of high-grade gliomas, overall survival (OS) remains poor, which underlines the importance of searching for and determining prognostic imaging biomarkers. The purpose of our retrospective study was to correlate patient survival with relative cerebral blood volume (rCBV) and permeability surface area-product (PS) measured using perfusion computed tomography (PCT) in patients with high-grade gliomas. METHODS: This study was composed of 54 patients with high-grade gliomas (World Health Organization [WHO] grade III, n = 14; WHO grade IV, n = 40) who underwent pretreatment PCT. Kaplan-Meier survival estimates were computed to describe OS for patients with high-versus-low PCT parameters, as well as grade III and IV gliomas. RESULTS: Differences in OS between high and low rCBV, PS, and rCBV + PS were significant (P < .001) for all high-grade gliomas. After adjustment for WHO grade, rCBV (P = .041) and rCBV + PS (P = .013) estimates remained significant, whereas PS estimates were not (P = .214). PS estimates showed a statistically significant difference for OS in the grade III glioma group (P = .011), whereas for grade IV gliomas, rCBV estimates were statistically significant (P = .019). rCBV + PS was statistically significant for OS in both grade III (P = .001) and grade IV (P = .004) glioma groups. CONCLUSIONS: Blood volume and permeability estimates measured using PCT can help predict survival in patients with high-grade gliomas. Patients with high PCT parameters showed worse OS compared to the patients with low PCT. Both rCBV and rCBV + PS remained statistically significant even after adjustment for WHO grade, suggesting these may be better predictors of OS than histological grade.

PURPOSE: To correlate tumor blood volume, measured by using dynamic susceptibility contrast material-enhanced T2*-weighted magnetic resonance (MR) perfusion studies, with patient survival and determine its association with molecular subclasses of glioblastoma (GBM). MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by institutional review board. Fifty patients underwent dynamic susceptibility contrast-enhanced T2*-weighted MR perfusion studies and had gene expression data available from the Cancer Genome Atlas. Relative cerebral blood volume (rCBV) (maximum rCBV [rCBV(max)] and mean rCBV [rCBV(mean)]) of the contrast-enhanced lesion as well as rCBV of the nonenhanced lesion (rCBV(NEL)) were measured. Patients were subclassified according to the Verhaak and Phillips classification schemas, which are based on similarity to defined genomic expression signature. We correlated rCBV measures with the molecular subclasses as well as with patient overall survival by using Cox regression analysis. RESULTS: No statistically significant differences were noted for rCBV(max), rCBV(mean) of contrast-enhanced lesion or rCBV(NEL) between the four Verhaak classes or the three Phillips classes. However, increased rCBV measures are associated with poor overall survival in GBM. The rCBV(max) (P = .0131) is the strongest predictor of overall survival regardless of potential confounders or molecular classification. Interestingly, including the Verhaak molecular GBM classification in the survival model clarifies the association of rCBV(mean) with patient overall survival (hazard ratio: 1.46, P = .0212) compared with rCBV(mean) alone (hazard ratio: 1.25, P = .1918). Phillips subclasses are not predictive of overall survival nor do they affect the predictive ability of rCBV measures on overall survival. CONCLUSION: The rCBV(max) measurements could be used to predict patient overall survival independent of the molecular subclasses of GBM; however, Verhaak classifiers provided additional information, suggesting that molecular markers could be used in combination with hemodynamic imaging biomarkers in the future.

BACKGROUND AND PURPOSE: The National Emergency X-Radiography Utilization Study Low-Risk Criteria were established to identify patients with a low probability of cervical spine injury in whom imaging of the cervical spine was unnecessary. The purpose of this study was to ascertain the number of unnecessary cervical spine CT studies on the basis of proper application of established clinical guidelines and, secondarily, to determine indications for ordering studies in the absence of guideline criteria. MATERIALS AND METHODS: All patients presenting to a level I trauma center for whom a screening cervical spine CT was ordered in the setting of blunt trauma were eligible for enrollment. For each study, the requesting clinician completed a survey regarding study indications. CT examinations were evaluated by a board-certified radiologist blinded to survey data to determine the presence or absence of cervical spine injury. RESULTS: Of 507 CT examinations, 5 (1%) were positive and 497 (98.0%) were negative for acute cervical spine injury. Five studies (1%) were indeterminate for acute injury but demonstrated no abnormality on subsequent imaging and clinical follow-up. Of the 502 studies without cervical spine injury, 81 (16.1%) were imaged despite meeting all 5 NEXUS criteria for nonimaging. Of these, the most common study indication was dangerous mechanism of injury (48.1%) followed by subjective neck pain (40.7%). CONCLUSIONS: Strict application of NEXUS criteria could potentially reduce the number of screening cervical spine CT scans in the setting of blunt trauma; this change would avoid a considerable amount of unnecessary radiation and cost.

Purpose: The purpose of this study was to evaluate whether DTI could demonstrate the water diffusivity changes in the corpus callosum (CC), which were not visible on the morphologic imaging in patients with glioblastoma multiforme (GBM) and brain metastases with no midline CC infiltration. Materials and Methods: Twenty-seven patients with treatment naive unilateral GBM and eleven patients with a solitary brain metastasis with no midline CC infiltration underwent DTI. Ten controls with normal brain MRI were also included. Based on the tensors, the principal diffusion directions, the anisotropy values, and the prior information about the diffusivity pattern in CC, a similarity measure was proposed. Subsequently, the CC was automatically divided into the Witelson subdivisions. Results: We observed significantly decreased fractional anisotropy values in all the regions of CC in the patients with GBM and metastases as compared to those in the controls. The mean diffusivity values showed a significant increase in all the regions of CC, except the splenium in patients with GBM and the isthmus in the patients with metastases, as compared to that in the controls respectively. Conclusion: In conclusion, DTI is more sensitive than the morphologic MR imaging in the evaluation of changes within the CC, in brain tumours which do not infiltrate the CC. However, these changes of the DTI metrics in the CC are due to a Wallerian degeneration rather than a tumour infiltration, as was shown by our results, as similar changes were seen in the GBM as well as the non-infiltrating metastases patients.

BACKGROUND: Clinically significant spontaneous bilateral iliopsoas hematoma is a rare complication of anticoagulation therapy. Definitive treatment of spontaneous iliopsoas hematomas is not well-established and varies between observation and surgical intervention. The intramuscular hematoma causes severe pain, muscle dysfunction, and occasionally nerve palsy with the femoral nerve most commonly affected. Most patients are neurologically normal but when a significant neurological deficit is associated with iliopsoas hematoma, optimal treatment recommendations vary. We report a case of spontaneous bilateral iliopsoas hematomas causing significant bilateral femoral nerve dysfunction. CASE DESCRIPTION: The authors present the case of a 63-year-old female who developed bilateral femoral nerve palsy due to anticoagulation bleeding complication. Magnetic resonance imaging demonstrated large bilateral intramuscular psoas hematomas causing femoral nerve compression. Surgical evacuation and decompression of the femoral nerves was performed with rapid neurological improvement. CONCLUSION: Management recommendations depend on the volume and cause of the hematoma, timing of diagnosis, and the degree of neurological impairment. A conservative approach with bed rest and correction of bleeding abnormalities to allow the hematoma to spontaneously resorb has been utilized for patients with small hematomas and little to no neurological symptoms. In contrast, more aggressive recommendations have been made for patients with large hematomas, severe motor function deficits, or hemodynamic instability.

BACKGROUND AND PURPOSE: Integration of imaging and genomic data is critical for a better understanding of gliomas, particularly considering the increasing focus on the use of imaging biomarkers for patient survival and treatment response. The purpose of this study was to correlate CBV and PS measured by using PCT with the genes regulating angiogenesis in GBM. MATERIALS AND METHODS: Eighteen patients with WHO grade IV gliomas underwent pretreatment PCT and measurement of CBV and PS values from enhancing tumor. Tumor specimens were analyzed by TCGA by using Human Gene Expression Microarrays and were interrogated for correlation between CBV and PS estimates across the genome. We used the GO biologic process pathways for angiogenesis regulation to select genes of interest. RESULTS: We observed expression levels for 92 angiogenesis-associated genes (332 probes), 19 of which had significant correlation with PS and 9 of which had significant correlation with CBV (P < .05). Proangiogenic genes such as TNFRSF1A (PS = 0.53, P = .024), HIF1A (PS = 0.62, P = .0065), KDR (CBV = 0.60, P = .0084; PS = 0.59, P = .0097), TIE1 (CBV = 0.54, P = .022; PS = 0.49, P = .039), and TIE2/TEK (CBV = 0.58, P = .012) showed a significant positive correlation; whereas antiangiogenic genes such as VASH2 (PS = -0.72, P = .00011) showed a significant inverse correlation. CONCLUSIONS: Our findings are provocative, with some of the proangiogenic genes showing a positive correlation and some of the antiangiogenic genes showing an inverse correlation with tumor perfusion parameters, suggesting a molecular basis for these imaging biomarkers; however, this should be confirmed in a larger patient population.

We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 x 10(-6)mm(2)/s +/- 224 (SD), and mean LCP was 0.71 +/- 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L <1,209 and LCP >0.71 versus ADC-L >1,209 and LCP <0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study.