Faculty Bibliography

Perfusion imaging of brain tumors has been performed by using various tracer and nontracer modalities and can provide additional physiologic and hemodynamic information, which is not available with routine morphologic imaging. Tumor vascular perfusion parameters obtained by using CT or MR perfusion have been used for tumor grading, prognosis, and treatment response in addition to differentiating treatment/radiation effects and non-neoplastic lesions from neoplasms. This article is an overview of the utility of PCT for assessment of brain tumors and describes the technique, its advantages, and limitations.

Differentiating treatment-induced necrosis (TIN) from recurrent/progressive tumor (RPT) in brain tumor patients using conventional morphologic imaging features is a very challenging task. Functional imaging techniques also offer moderate success due to the complexity of the tissue microenvironment and the inherent limitation of the various modalities and techniques. The purpose of this retrospective study was to assess the utility of nonmodel-based semiquantitative indices derived from dynamic contrast-enhanced T1-weighted MR perfusion (DCET1MRP) in differentiating TIN from RPT. Twenty-nine patients with previously treated brain tumors who showed recurrent or progressive enhancing lesion on follow-up MRI underwent DCET1MRP. Another 8 patients with treatment-naive high-grade gliomas who also underwent DCET1MRP were included as the control group. Semiquantitative indices derived from DCET1MRP included maximum slope of enhancement in initial vascular phase (MSIVP), normalized MSIVP (nMSIVP), normalized slope of delayed equilibrium phase (nSDEP), and initial area under the time-intensity curve (IAUC) at 60 and 120 s (IAUC(60) and IAUC(120)) obtained from the enhancement curve. There was a statistically significant difference between the 2 groups (P < .01), with the RPT group showing higher MSIVP (15.78 vs 8.06), nMSIVP (0.046 vs 0.028), nIAUC(60) (33.07 vs 6.44), and nIAUC(120) (80.14 vs 65.55) compared with the TIN group. nSDEP was significantly lower in the RPT group (7.20 x 10(-5) vs 15.35 x 10(-5)) compared with the TIN group. Analysis of the receiver-operating-characteristic curve showed nMSIVP to be the best single predictor of RPT, with very high (95%) sensitivity and high (78%) specificity. Thus, nonmodel-based semiquantitative indices derived from DCET1MRP that are relatively easy to derive and do not require a complex model-based approach may aid in differentiating RPT from TIN and can be used as robust noninvasive imaging biomarkers.

OBJECTIVE: The objective of our study was to analyze the use of screening cervical spine CT performed after trauma and establish the opportunity of potentially avoidable studies when evidence-based clinical criteria are applied before imaging. MATERIALS AND METHODS: All cervical spine CT examinations performed in the emergency department of a level 1 trauma center between January and December 2008 on adult patients with trauma were analyzed; 1589 studies were evaluated. Radiology reports and clinical data were reviewed for the presence of fracture or ligamentous injury and for the mode of injury. We also looked for documentation of clinical criteria used to perform the CT study. In particular, we looked for mention of posterior midline cervical tenderness, focal neurologic deficit, level of alertness, evidence of intoxication, and clinically apparent distracting injury. These five criteria were established by the National Emergency X-Radiography Utilization Study (NEXUS) to identify patients with a low probability of cervical spine injury who consequently needed no cervical spine imaging. RESULTS: Of the 1589 studies reviewed, 41 (2.6%) were positive for an acute cervical spine injury and 1524 (95.9%) were negative. The remaining 24 studies (1.5%) were indeterminate on the initial CT examination but subsequent imaging and clinical follow-up failed to show acute injury. Of the 1524 examinations with no acute injury, 364 (23.9%) had no documentation of any of the five NEXUS low-risk criteria. CONCLUSION: The strict application of the NEXUS low-risk criteria could potentially reduce the number of screening cervical spine CT examinations in the setting of trauma in more than 20% of cases, thereby avoiding a significant amount of unnecessary radiation and significant cost.

RATIONALE AND OBJECTIVES: The purpose of this study was to correlate the status of magnetic resonance contrast enhancement with immunohistologic vascular parameters such as microvascular cellular proliferation (MVCP), microvascular density (MVD), vascular endothelial growth factor receptor-2 (VEGFR-2) expression, and World Health Organization (WHO) grade obtained from image-guided biopsy specimens. We also compared perfusion computed tomography (PCT) parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and permeability surface area-product (PS) with the presence or absence of contrast enhancement. MATERIALS AND METHODS: A total of 26 image-guided biopsy specimens in 16 patients with treatment naive gliomas were obtained from contrast-enhancing (CE) and nonenhancing (NE) regions of the glioma. Contrast enhancement status was correlated with MVD, MVCP, VEGFR-2 expression, and WHO grade obtained from the biopsy specimen as well as with the PCT parameters. RESULTS: Contrast enhancement showed statistically significant correlation with MVCP (P = .003) and PS (P = .007) when compared with various immunohistologic and perfusion vascular parameters. WHO grade of the biopsy specimen showed statistically significant correlation with contrast enhancement (P = .002), MVCP (P < .001), and PS values (P = .028). CONCLUSION: Contrast enhancement in gliomas is primarily from a break in blood-brain barrier as evidenced by its correlation with PS and MVCP, whereas it was not statistically correlated with CBV and MVD even though it showed a positive trend. Contrast enhancement also showed significant correlation with WHO grade suggesting a biopsy from CE region in a heterogeneous glioma probably will still yield the most aggressive part of the glioma is also shown by its association with MVCP and PS estimates.

The purpose of this study was to determine the usefulness of perfusion CT (PCT) parameters particularly blood volume and neovascular permeability estimates (permeability surface area-product, PS) in the evaluation of oligodendrogliomas (OG), correlation with genetic subtypes of OGs (with or without loss of heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was retrospectively correlated with our previously published PCT data for 32 patients with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700, 2008). All OGs were also analyzed for genetic subtypes of with or without LOH. PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire lesion and a statistical analysis done to correlate various histopathological variants. Low grade OGs (n = 13) showed slightly lower CBV (1.42 vs. 1.72 ml/100 g; P value 0.391) and PS (0.56 vs. 0.95 ml/100 g/min; P value 0.099) as compared to high grade OGs (n = 8), though not statistically significant. LOH positive OGs (n = 13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n = 8), although not statistically significant. Low grade OGs (n = 13) showed higher mean CBV 1.42 ml/100 g as compared to low grade astroglial tumors (n = 8) 0.95 ml/100 g (P value = 0.08), however no statistically significant difference was noted for PS (0.56 vs. 0.52 ml/100 g/min, P value 0.695). Statistically significant differences were observed in CBV and PS values of high grade OGs and high grade astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79 vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value < 0.01), however this difference was not significant if only comparing grade III OGs with grade III astroglial tumors. PCT perfusion parameters including PS values do not help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs. Similarly LOH positive OGs also showed slightly higher CBV, but again failed to reach any statistically significant level. Low grade OGs showed slightly higher CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed significantly lower PS values as compared to higher grade astroglial tumors despite showing high CBV.

BACKGROUND AND PURPOSE: Differentiating treatment effects from RPT is a common yet challenging task in a busy neuro-oncologic practice. PS probably represents a different aspect of angiogenesis and vasculature and can provide additional physiologic information about recurrent/progressive enhancing lesions. The purpose of the study was to use PS measured by using PCT to differentiate TIN from RPT in patients with previously irradiated brain tumor who presented with a recurrent/progressive enhancing lesion. MATERIALS AND METHODS: Seventy-two patients underwent PCT for assessment of a recurrent/progressive enhancing lesion from January 2006 to November 2009. Thirty-eight patients who underwent surgery and histopathologic diagnosis were included in this analysis. Perfusion parameters such as PS, CBV, CBF, and MTT were obtained from the enhancing lesion as well as from the NAWM. RESULTS: Of 38 patients, 11 were diagnosed with pure TIN and 27 had RPT. Patients with TIN showed significantly lower mean PS values than those with RPT (1.8 +/- 0.8 versus 3.6 +/- 1.6 mL/100 g/min; P value=.001). The TIN group also showed lower rCBV (1.2 +/- 0.3 versus 2.1 +/- 0.7; P value<.001), lower rCBF (1.2 +/- 0.5 versus 2.6 +/- 1.7; P value=.004), and higher rMTT (1.4 +/- 0.4 versus 1.0 +/- 0.4; P value=.018) compared with the RPT group. CONCLUSIONS: PCT and particularly PS can be used in patients with previously treated brain tumors to differentiate TIN from RPT. PS estimates can help increase the accuracy of PCT in differentiating these 2 entities.

BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo correlation of perfusion imaging parameters with angiogenic markers can help in better understanding the role of perfusion imaging as an imaging biomarker. The purpose of this study was to correlate PCT parameters such as CBV and PS with histologic and molecular angiogenic markers in gliomas. MATERIALS AND METHODS: Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression, tumor cellularity, and WHO grade of the image-guided biopsy specimens with the PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34, and VEGFR-2 and examined under a light microscope. These histologic and molecular angiogenic markers were correlated with perfusion parameters of the region of interest corresponding to the biopsy specimen. Pearson correlation coefficients and multiple regression analyses by using clustering methods were performed to assess these correlations. RESULTS: CBV showed a significant positive correlation with MVD (r = 0.596, P < .001), whereas PS showed a significant positive correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade. VEGFR-2 positive specimens showed higher PS and CBV; however, neither was statistically significant at the .05 level. CONCLUSIONS: CBV showed a significant positive correlation with MVD, whereas PS showed a significant positive correlation with MVCP, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels; hence, in vivo evaluation of these could be important in a better understanding of tumor angiogenesis.

To describe the morphologic magnetic resonance imaging (MRI) findings in histologically proven therapy-induced cerebral necrosis. We retrospectively reviewed the morphologic MRI findings in patients with therapy-induced cerebral necrosis. Images were reviewed for size, location, and characteristics of signal intensity abnormalities and T1-contrast enhancement. Images were also assessed for mass effect, necrosis, cyst, atrophy, cortical thinning, and leukoencephalopathy. The individual imaging characteristics were correlated with clinical and treatment variables. There were 44 patients. Seventy percent had a glioma, all patients had received radiation, and 57% had received chemotherapy in close proximity to radiation. All images demonstrated contrast enhancement, predominantly in the white matter. Enhancement was present in the periventricular/subependymal region in 50% of cases and the corpus callosum in 27%. The most common pattern of lesion peripheral enhancement was "spreading wavefront" and of interior enhancement was "Swiss cheese/soap bubble." The enhancing lesion was single in 60% of cases. Mass effect was present in 93% of patients. Location and patterns of enhancement were significantly associated with the interval from brain radiation to the diagnosis of therapy-induced cerebral necrosis, tumor histology, patient age, type of radiation, and administration of systemic chemotherapy. This is the largest study of the morphologic conventional MRI findings in pathologically confirmed therapy-induced cerebral necrosis. We characterized the imaging findings in a variety of tumor types following a variety of radiation treatments and other antineoplastic therapy. These findings may be of value in identifying therapy-induced cerebral necrosis in patients treated for a brain tumor.