Faculty Bibliography

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.

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.

In modern medicine brain imaging is an essential prerequisite not only to acute stroke triage but also to determining the specific therapy indicated. This article reviews the need for imaging the brain in acute stroke, penumbral pathophysiology, penumbral imaging techniques, as well as current status of various imaging modalities that are being employed to select patients for specific therapeutic approaches.

PURPOSE: To retrospectively correlate various diffusion tensor imaging (DTI) metrics in patients with glioblastoma multiforme (GBM) with patient survival analysis and also degree of tumor proliferation index determined histologically. MATERIALS AND METHODS: Thirty-four patients with histologically confirmed treatment naive GBMs underwent DTI on a 3.0 Tesla (T) scanner. Region-of-interest was placed on the whole lesion including the enhancing as well as nonenhancing component of the lesion to determine the various DTI metrics. Kaplan-Meier estimates and Cox proportional hazards regression methods were used to assess the relationship of DTI metrics (minimum and mean values) and Ki-67 with progression free survival (PFS). To study the relationship between DTI metrics and Ki-67, Pearson's correlation coefficient was computed. RESULTS: Univariate analysis showed that patients with fractional anisotropy (FA)(mean) 0.68 and Ki-67 > 0.3 had lower PFS rate. The multivariate analysis demonstrated that only CP(min) was the best predictor of survival in these patients, after adjusting for age, Karnofsky performance scale and extent of resection. No significant correlation between DTI metrics and Ki-67 were observed. CONCLUSION: DTI metrics can be used as a sensitive and early indicator for PFS in patients with glioblastomas. This could be useful for treatment planning as high-grade gliomas with lower ADC(min), FA(mean), CP(min), and higher CS(mean) values may be treated more aggressively.

Stereotactic Radiotherapy (SRT) is more commonly used for skull base tumors in conjunction with the technical development of radiation intensity modulation. Purpose of this study is to correlate clinical and radiographic characteristics of delayed radiation injury (RI) occurring around central skull base following SRT with SRT dosimetric data. Total of six patients were identified to have developed RI in the vicinity of SRT target volume out of 141 patients who received SRT in he center or near-center of the skull base. The images and medical records were retrospectively reviewed. The analysis was performed for RI location, time of development, imaging and clinical characteristics and evolution of RI and correlated with SRT dosimetric analysis using image fusion with follow-up MRI scans. Mean follow-up time was 24 +/- 9 months. During the follow-up period, twelve sites of RI were found in 6 patients. They were clinically symptomatic in 4/6 patients (66.6%) at median 12.5 months after SRT. Mean time interval between SRT and detection of RI was 9 +/- 3, 18.5 +/- 5, and 13.5 months for brainstem, temporal lobe, and cerebellum/labyrinth lesions, respectively. All RI lesions were included in the region of high SRT doses. After steroid and symptomatic treatment, 50% of RI lesions showed complete response, and 40% showed partial response. RI can occur around the skull base because of irregular shape of target tumor, its close proximity to normal brain parenchyma, and inhomogeneity of dose distribution. Brainstem lesions occurred earlier than temporal lobe RI. The majority of the RI lesions, not mixed with the tumor in this study, showed radiographic and clinical improvement with steroid and symptomatic treatments.