Rajiv Mangla

Changes in Relative Cerebral Blood Volume 1 Month after Radiation-Temozolomide Therapy Can Help Predict Overall Survival in Patients with Glioblastoma

PURPOSE To evaluate perfusion parameter changes in patients with glioblastoma multiforme by comparing the perfusion magnetic resonance (MR) imaging measurements obtained before combined radiation and temozolomide therapy (RT-TMZ) with the follow-up MR imaging measurements obtained 1 month after completion of this treatment. MATERIALS AND METHODS Institutional review board approval was obtained, and HIPAA guidelines were followed. The data of 36 patients (24 male [median age, 63 years]; 12 female [median age, 59 years]) with glioblastoma multiforme who were treated with RT-TMZ were retrospectively reviewed. The hypothesis was that a change in relative cerebral blood volume (rCBV) 1 month after RT-TMZ is predictive of overall survival. Linear regression analysis was performed to correlate changes in tumor size and perfusion parameters with overall survival. Receiver operating characteristic (ROC) curves were evaluated for 1-year survival. Overall survival was assessed with Kaplan-Meir survival curves and log-rank testing. RESULTS Percentage change in rCBV at 1 month after RT-TMZ correlated with overall survival. Increased rCBV after treatment was a strong predictor of poor survival (median survival, 235 days versus 529 days with decreased rCBV) (P < .008, log-rank test). The ROC curves for 1-year survival showed a greater area under the curve (0.806; 95% confidence interval [CI]: 0.698, 0.970) (P = .005) with rCBV than with tumor size (0.556; 95% CI: 0.342, 0.729) (P = .382). The overall survival for patients with increased tumor size, based on Macdonald criteria, was shorter than that for patients who showed no progression (stable or partial response), but the difference was not significant (median survival, 442 days versus 598 days) (P = .761, log-rank test). CONCLUSION Change in rCBV after RT-TMZ appears to correlate with overall survival.

Border Zone Infarcts: Pathophysiologic and Imaging Characteristics

Border zone or watershed infarcts are ischemic lesions that occur in characteristic locations at the junction between two main arterial territories. These lesions constitute approximately 10% of all brain infarcts and are well described in the literature. Their pathophysiology has not yet been fully elucidated, but a commonly accepted hypothesis holds that decreased perfusion in the distal regions of the vascular territories leaves them vulnerable to infarction. Two types of border zone infarcts are recognized: external (cortical) and internal (subcortical). To select the most appropriate methods for managing these infarcts, it is important to understand the underlying causal mechanisms. Internal border zone infarcts are caused mainly by hemodynamic compromise, whereas external border zone infarcts are believed to result from embolism but not always with associated hypoperfusion. Various imaging modalities have been used to determine the presence and extent of hemodynamic compromise or misery perfusion in association with border zone infarcts, and some findings (eg, multiple small internal infarcts) have proved to be independent predictors of subsequent ischemic stroke. A combination of several advanced techniques (eg, diffusion and perfusion magnetic resonance imaging and computed tomography, positron emission tomography, transcranial Doppler ultrasonography) can be useful for identifying the pathophysiologic process, making an early clinical diagnosis, guiding management, and predicting the outcome.

Percentage Signal Recovery Derived from MR Dynamic Susceptibility Contrast Imaging Is Useful to Differentiate Common Enhancing Malignant Lesions of the Brain

BACKGROUND AND PURPOSE: Differentiation of enhancing malignant lesions on conventional MR imaging can be difficult and various newer imaging techniques have been suggested. Our aim was to evaluate the role of PSR obtained from DSC perfusion measurements in differentiating lymphoma, GBM, and metastases. The effectiveness of PSR was compared with that of rCBV. We hypothesized that the newly defined parameter of PSR is more sensitive and specific in differentiating these lesions. MATERIALS AND METHODS: This retrospective study included 66 patients (39 men and 27 women; age range: 27–82 years) with a pathologically proved diagnosis of primary CNS lymphoma, GBM, or metastases (22 patients in each group). Mean PSR, min PSR, max PSR, and rCBV were calculated. The classification accuracy of these parameters was investigated by using ROC. RESULTS: Mean PSR was high (113.15 ± 41.59) in lymphoma, intermediate in GBM (78.22 ± 14.27), and low in metastases (53.46 ± 12.87) with a P value < .000. F values obtained from 1-way ANOVA analysis for mean, min, and max PSR ratios were 29.9, 39.4, and 23.4, respectively, which were better than those of rCBV (11.1) in differentiating the 3 groups. Max PSR yielded the best ROC characteristics with an Az of 0.934 (95% CI, 0.877–0.99) in differentiating lymphoma from metastases and GBM. The Az for mean and min PSR of 0.938 (95% CI, 0.0.884–0.990) and 0.938 (95% CI, 0.884–0.991), respectively, was better than rCBV (Az, 0.534; 95% CI, 0.391–0.676) in the differentiation of metastases from GBM and lymphoma (P ≤ .0001). CONCLUSIONS: PSR appears to be a parameter that helps in differentiating intracerebral malignant lesions such as GBM, metastases, and lymphoma.

Correlation of Diffusion and Perfusion MRI With Ki-67 in High-Grade Meningiomas

OBJECTIVE Atypical and anaplastic meningiomas have a greater likelihood of recurrence than benign meningiomas. The risk for recurrence is often estimated using the Ki-67 labeling index. The purpose of this study was to determine the correlation between Ki-67 and regional cerebral blood volume (rCBV) and between Ki-67 and apparent diffusion coefficient (ADC) in atypical and anaplastic meningiomas. MATERIALS AND METHODS A retrospective review of the advanced imaging and immunohistochemical characteristics of atypical and anaplastic meningiomas was performed. The relative minimum ADC, relative maximum rCBV, and specimen Ki-67 index were measured. Pearsons correlation was used to compare these parameters. RESULTS There were 23 cases with available ADC maps and 20 cases with available rCBV maps. The average Ki-67 among the cases with ADC maps and rCBV maps was 17.6% (range, 5-38%) and 16.7% (range, 3-38%), respectively. The mean minimum ADC ratio was 0.91 (SD, 0.26) and the mean maximum rCBV ratio was 22.5 (SD, 7.9). There was a significant positive correlation between maximum rCBV and Ki-67 (Pearsons correlation, 0.69; p = 0.00038). However, there was no significant correlation between minimum ADC and Ki-67 (Pearsons correlation, -0.051; p = 0.70). CONCLUSION Maximum rCBV correlated significantly with Ki-67 in high-grade meningiomas.

CT perfusion in acute stroke: Know the mimics, potential pitfalls, artifacts, and technical errors

The CT perfusion (CTP) imaging of brain has been established as a clinically useful tool in multimodality imaging of acute stroke. All abnormalities seen on perfusion CT are not specifically related to acute infarct. There are many neurologic diseases causing symptoms simulating cerebrovascular disease produce an alteration of brain perfusion and thus can result in perfusion CT abnormalities. There are many pitfalls and artifacts in acquiring the data, calculation of maps and choosing arterial input function. We analyze and classify all these aspects, to allow the technician and the radiologist to know exactly what to avoid and what to choose, and we indicate the way to improve the quality of examination. The knowledge of mimics and pitfalls in acute stroke imaging can be helpful in accurate interpretation of these examinations.

Correlation between Dynamic Contrast-enhanced Perfusion MRI Relative Cerebral Blood Volume and Vascular Endothelial Growth Factor Expression in Meningiomas

PURPOSE To determine whether there is a correlation between vascular endothelial growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging (MRI) and to correlate the perfusion characteristics in high- versus low-grade meningiomas. METHODS AND MATERIALS A total of 48 (24 high-grade and 24 low-grade) meningiomas with available dynamic susceptibility-weighted MRI were retrospectively reviewed for maximum CBV and semiquantitative VEGF immunoreactivity. Correlation between normalized CBV and VEGF was made using the Spearman rank test and comparison between CBV in high- versus low-grade meningiomas was made using the Wilcoxon test. RESULTS There was a significant (P = .01) correlation between normalized maximum CBV and VEGF scores with a Spearman correlation coefficient of 0.37. In addition, there was a significant (P < .01) difference in normalized maximum CBV ratios between high-grade meningiomas (mean 12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard deviation 5.2). CONCLUSION The data suggest that CBV accurately reflects VEGF expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially serve as a useful biomarker for meningiomas, pending prospective studies.

Diffusion-weighted imaging of skull lesions.

Diffusion-weighted imaging can increase the conspicuity of skull lesions and be applied toward noninvasive differentiation of malignant from benign lesions. Malignant skull lesions generally display lower diffusivity than benign lesions, although there are exceptions, and clinical parameters and conventional imaging modalities should also be considered in the evaluation of skull lesions. Nevertheless, in some instances diffusion-weighted imaging (DWI) can be used for problem solving when conventional imaging features are indeterminate, such as with skull base involvement by nasopharyngeal carcinoma versus osteomyelitis. In addition, DWI may be useful for monitoring treatment effects. The use of readout segmented technique, parallel imaging, multishot acquisition, turbo spin-echo DWI, diffusion tensor imaging, and higher field strengths can improve image quality. The feasibility of implementing DWI for characterizing skull lesions, the DWI findings of benign and malignant skull lesions, and technical considerations are discussed in this article.

Neuroimaging in myotonic dystrophy type 1

A 56-year-old woman with a 10-year history of myotonic dystrophy type 1 (MD) presented with progressive lower extremity weakness. MRI showed multiple discrete and confluent areas of abnormal signal intensity throughout the subcortical white matter with predominant involvement of …

Usefulness of enhancement-perfusion mismatch in differentiation of CNS lymphomas from other enhancing malignant tumors of the brain

Background Surgical planning and treatment options for primary or secondary central nervous system lymphomas (PCNSL or SCNSL) are different from other enhancing malignant lesions such as glioblastoma multiforme (GBM), anaplastic gliomas and metastases; so, it is critical to distinguish them preoperatively. We hypothesized that enhancement-perfusion (E-P) mismatch on dynamic susceptibility weighted magnetic resonance (DSC-MR) perfusion imaging which corresponds to low mean relative cerebral blood volume (mean rCBV) in an enhancing portion of the tumor should allow differentiation of CNS lymphomas from other enhancing malignant lesions. Methods We retrospectively reviewed pre-treatment MRI exams, including DSC-MR perfusion images of 15 lymphoma patients. As a control group, pre-treatment DSC-MR perfusion images of biopsy proven 18 GBMs (group II), 13 metastases (group III), and 10 anaplastic enhancing gliomas (group IV) patients were also reviewed. Region of interests (ROIs) were placed around the most enhancing part of tumor on contrast-enhanced T1WI axial images and images were transferred onto co-registered DSC perfusion maps to obtain CBV in all 4 groups. The mean and maximum relative CBV values were obtained. Statistical analysis was performed on SPSS software and significance of the results between the groups was done with Mann-Whitney test, whereas optimal thresholds for tumor differentiation were done by receiver operating characteristic (ROC) analysis. Results The enhancing component of CNS lymphomas were found to have significantly lower mean rCBV compared to enhancing component of GBM (1.2 versus 4.3; P<0.001), metastasis (1.2 versus 2.7; P<0.001), and anaplastic enhancing gliomas (1.2 versus 2.4; P<0.001). Maximum rCBV of enhancing component of lymphoma were significantly lower than GBM (3.1 versus 6.5; P<0.001) and metastasis (3.1 versus 4.9; P<0.013), and not significantly lower than anaplastic enhancing gliomas (3.9 versus 4.2; P<0.08). On the basis of ROC analysis, mean rCBV provided the best threshold [area under the curve (AUC) =0.92] and had better accuracy in differentiating malignant lesions. Conclusions E-P mismatch in DSC perfusion MR, i.e., low mean rCBV in an enhancing portion of the tumor is strongly suggestive of lymphoma and should allow differentiation of CNS lymphoma from other enhancing malignant lesions.

The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBVmean and rCBVmax), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBVperi-tumor) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBVmax and mTOR based on Pearson’s correlations with Benjamini–Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBVperi-tumor showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBVperi-tumor value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBVperi-tumor and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBVperi-tumor has better prognostic value than genomic biomarkers alone.