Faculty Bibliography

PURPOSE: The aim of this study was to determine the effect of a clinical education initiative on the appropriate utilization of screening cervical spine CT in the emergency department. The purpose was to assess if clinical education can produce stricter adherence to the ACR Appropriateness Criteria and improve the utilization of screening CT examinations in the emergency department. METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. All adult patients presenting to a level 1 trauma center with blunt trauma prompting screening cervical spine CT were eligible. For each study, the requesting clinician completed a survey selecting all clinical indications. CT examinations were evaluated by a board-certified radiologist blinded to survey data. Results were compared with retrospective and prospective studies performed before the institution of the education initiative. RESULTS: Of the 388 cervical spine CT examinations performed, 12 (3.1%) were positive for acute cervical spine injury, compared to only 1.0% before the clinical education program (phase 2). Of the 376 examinations without injury, 13% met all 5 National Emergency X-Radiography Utilization Study criteria for nonimaging (down from 16.1% in phase 2), and 15 (4%) required no imaging when both National Emergency X-Radiography Utilization Study and abbreviated Canadian cervical spine rule criteria were applied. CONCLUSIONS: Implementation of a clinical education initiative resulted in improved adherence to ACR Appropriateness Criteria and improved clinical effectiveness of the studies by increasing fracture detection rate. Initiatives such as these could potentially influence imaging overutilization without burdening emergency department clinicians with excessive roadblocks to image ordering.

The aim of the study was to determine the antiangiogenic efficacy of vatalanib, sunitinib, and AMD3100 in an animal model of human glioblastoma (GBM) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumor protein expression analysis. Orthotopic GBM-bearing animals were randomly assigned either to control group or vatalanib, sunitinib, and AMD3100 treatment groups. Following 2 weeks of drug treatment, tumor growth and vascular parameters were measured using DCE-MRI. Expression of different angiogenic factors in tumor extracts was measured using a membrane-based human antibody array kit. Tumor angiogenesis and invasion were determined by immunohistochemistry. DCE-MRI showed a significant increase in tumor size after vatalanib treatment. AMD3100-treated group showed a significant decrease in a number of vascular parameters determined by DCE-MRI. AMD3100 significantly decreased the expression of different angiogenic factors compared to sunitinib or vatalanib; however, there were no significant changes in vascular density among the groups. Sunitinib-treated animals showed significantly higher migration of the invasive cells, whereas in both vatalanib- and AMD3100-treated animals the invasive cell migration distance was significantly lower compared to that of control. Vatalanib and sunitinib resulted in suboptimal therapeutic effect, but AMD3100 treatment resulted in a significant reduction in tumor growth, permeability, interstitial space volume, and invasion of tumor cells in an animal model of GBM.

Various imaging techniques have been employed to evaluate blood-brain-barrier leakiness in brain tumors, as higher tumor vascular leakiness is known to be associated with higher grade and malignant potential of the tumor, and hence can help provide additional diagnostic and prognostic information. These imaging techniques range from routine post-contrast T1 -weighted images that highlight degree of contrast enhancement to absolute measurement of quantitative metrics of vascular leakiness employing complex pharmacokinetic modeling. The purpose of this article is to discuss the clinical applications of available imaging techniques, and in particular dynamic contrast-enhanced T1 -weighted MR imaging (DCE-MRI), to evaluate tumor vascular leakiness.

BACKGROUND: RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS). METHODS: Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression. RESULTS: Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively). CONCLUSION: Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.

PURPOSE: To conduct a comprehensive analysis of radiologist-made assessments of glioblastoma (GBM) tumor size and composition by using a community-developed controlled terminology of magnetic resonance (MR) imaging visual features as they relate to genetic alterations, gene expression class, and patient survival. MATERIALS AND METHODS: Because all study patients had been previously deidentified by the Cancer Genome Atlas (TCGA), a publicly available data set that contains no linkage to patient identifiers and that is HIPAA compliant, no institutional review board approval was required. Presurgical MR images of 75 patients with GBM with genetic data in the TCGA portal were rated by three neuroradiologists for size, location, and tumor morphology by using a standardized feature set. Interrater agreements were analyzed by using the Krippendorff alpha statistic and intraclass correlation coefficient. Associations between survival, tumor size, and morphology were determined by using multivariate Cox regression models; associations between imaging features and genomics were studied by using the Fisher exact test. RESULTS: Interrater analysis showed significant agreement in terms of contrast material enhancement, nonenhancement, necrosis, edema, and size variables. Contrast-enhanced tumor volume and longest axis length of tumor were strongly associated with poor survival (respectively, hazard ratio: 8.84, P = .0253, and hazard ratio: 1.02, P = .00973), even after adjusting for Karnofsky performance score (P = .0208). Proneural class GBM had significantly lower levels of contrast enhancement (P = .02) than other subtypes, while mesenchymal GBM showed lower levels of nonenhanced tumor (P < .01). CONCLUSION: This analysis demonstrates a method for consistent image feature annotation capable of reproducibly characterizing brain tumors; this study shows that radiologists' estimations of macroscopic imaging features can be combined with genetic alterations and gene expression subtypes to provide deeper insight to the underlying biologic properties of GBM subsets.

Pseudo-progression (PsP) refers to the paradoxical increase of contrast enhancement within 12 weeks of chemo-radiation therapy in gliomas attributable to treatment effects rather than early tumor progression (ETP). This study was performed to evaluate the utility of morphologic imaging features, diffusion tensor imaging (DTI) and radiation dosimetric analysis of magnetic resonance imaging (MRI) changes in differentiating PsP from ETP. Serial MRI examinations of 163 patients treated for high-grade glioma were reviewed. 46 patients showed a recurrent or progressive enhancing lesion within 12 weeks of radiotherapy. We used an in-house modified scoring system based on 20 different morphologic features (modified VASARI features) to assess the MRI studies. DTI analyses were performed in 24 patients. MRI changes were defined as recurrent volume (Vrec) and registered with pretreatment computed tomography dataset, and the actual dose received by the Vrec during treatment was calculated using dose-volume histograms. Bidimensional product of T2-FLAIR signal abnormality and enhancing component was larger in the ETP group. DTI metrics revealed no significant difference between the two groups. There was no statistically significant difference in the location of Vrec between PsP and ETP groups. Morphologic MRI features and DTI have a limited role in differentiating between PsP and ETP. The larger sizes of the T2-FLAIR signal abnormality and the enhancing component of the lesion favor ETP. There was no correlation between the pattern of MRI changes and radiation dose distribution between PsP and ETP groups.