Quantifying metal-induced susceptibility artifacts of the instrumented spine at 1.5T using fast-spin echo and 3D-multispectral MRI.

PURPOSE: To evaluate magnetic resonance imaging (MRI) artifacts near metallic spinal instrumentation using both conventional metal artifact reduction sequences (MARS) and 3D multispectral imaging sequences (3D-MSI). MATERIALS AND METHODS: Both MARS and 3D-MSI images were acquired in 10 subjects with titanium spinal hardware on a 1.5T GE 450W scanner. Clinical computed tomography (CT) images were used to measure the volume of the implant using seed-based region growing. Using 30-40 landmarks, the MARS and 3D-MSI images were coregistered to the CT images. Three independent users manually segmented the artifact volume from both MR sequences. For five L-spine subjects, one user independently segmented the nerve root in both MARS and 3D-MSI images. RESULTS: For all 10 subjects, the measured artifact volume for the 3D-MSI images closely matched that of the CT implant volume (absolute error: 4.3 ± 2.0 cm3 ). The MARS artifact volume was ∼8-fold higher than that of the 3D-MSI images (30.7 ± 20.2, P = 0.002). The average nerve root volume for the MARS images was 24 ± 7.3% lower than the 3D-MSI images (P = 0.06). CONCLUSION: Compared to 3D-MSI images, the higher-resolution MARS images may help study features farther away from the implant surface. However, the MARS images retained substantial artifacts in the slice-dimension that result in a larger artifact volume. These artifacts have the potential to obscure physiologically relevant features, and can be mitigated with 3D-MSI sequences. Hence, MR study protocols may benefit with the inclusion both MARS and 3D-MSI sequences to accurately study pathology near the spine. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:51-58.

Spinal osteoblastic meningioma with hematopoiesis: radiologic-pathologic correlation and review of the literature.

Spinal meningiomas associated with bone formation and hematopoiesis are rare tumors with only 3 prior case reports in the literature. We describe a case report of a woman who presented with back pain and an isolated event of urinary incontinence. A calcified spinal canal mass at T8 was identified on computed tomographic and magnetic resonance imaging. A gross total resection of the tumor was performed and pathologic examination showed a meningioma, World Health Organization grade 1, containing bone and bone marrow elements. A review of previously reported cases and a discussion of possible mechanisms of bone and hematopoiesis development in meningioma are presented.

Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study.

PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) was used to investigate the associations between intervertebral disc degeneration and changes in perfusion and diffusion in the disc endplates. METHODS: 56 participants underwent MRI scans. Changes in DCE-MRI signal enhancement in the endplate regions were analyzed. Also, a group template was generated for the endplates and enhancement maps were registered to this template for group analysis. RESULTS: DCE-MRI enhancement changed significantly in cranial endplates with increased degeneration. A similar trend was observed for caudal endplates, but it was not significant. Group-averaged enhancement maps revealed major changes in spatial distribution of endplate perfusion and diffusion with increasing disc degeneration especially in peripheral endplate regions. CONCLUSIONS: Increased enhancement in the endplate regions of degenerating discs might be an indication of ongoing damage in these tissues. Therefore, DCE-MRI could aid in understanding the pathophysiology of disc degeneration. Moreover, it could be used in the planning of novel treatments such as stem cell therapy.

Comprehensive characterization of glioblastoma tumor tissues for biomarker identification using mass spectrometry-based label-free quantitative proteomics.

Cancer is a complex disease; glioblastoma (GBM) is no exception. Short survival, poor prognosis, and very limited treatment options make it imperative to unravel the disease pathophysiology. The critically important identification of proteins that mediate various cellular events during disease is made possible with advancements in mass spectrometry (MS)-based proteomics. The objective of our study is to identify and characterize proteins that are differentially expressed in GBM to better understand their interactions and functions that lead to the disease condition. Further identification of upstream regulators will provide new potential therapeutic targets. We analyzed GBM tumors by SDS-PAGE fractionation with internal DNA markers followed by liquid chromatography-tandem mass spectrometry (MS). Brain tissue specimens obtained for clinical purposes during epilepsy surgeries were used as controls, and the quantification of MS data was performed by label-free spectral counting. The differentially expressed proteins were further characterized by Ingenuity Pathway Analysis (IPA) to identify protein interactions, functions, and upstream regulators. Our study identified several important proteins that are involved in GBM progression. The IPA revealed glioma activation with z score 2.236 during unbiased core analysis. Upstream regulators STAT3 and SP1 were activated and CTNNα was inhibited. We verified overexpression of several proteins by immunoblot to complement the MS data. This work represents an important step towards the identification of GBM biomarkers, which could open avenues to identify therapeutic targets for better treatment of GBM patients. The workflow developed represents a powerful and efficient method to identify biomarkers in GBM.

Effects of perfusion on diffusion changes in human brain tumors.

PURPOSE: To characterize the influence of perfusion on the measurement of diffusion changes over time when ADC is computed using standard two-point methods. MATERIALS AND METHODS: Functional diffusion maps (FDMs), which depict changes in diffusion over time, were compared with rCBV changes in patients with brain tumors. The FDMs were created by coregistering and subtracting ADC maps from two time points and categorizing voxels where ADC significantly increased (iADC), decreased (dADC), or did not change (ncADC). Traditional FDMs (tFDMs) were computed using b = 0,1000 s/mm(2). Flow-compensated FDMs (fcFDMs) were calculated using b = 500,1000 s/mm(2). Perfusion's influence on FDMs was determined by evaluating changes in rCBV in areas where the ADC change significantly differed between the two FDMs. RESULTS: The mean ΔrCBV in voxels that changed from iADC (dADC) on the tFDM to ncADC on the fcFDM was significantly greater (less) than zero. In addition, mean ΔrCBV in iADC (dADC) voxels on the tFDM was significantly higher (lower) than in iADC (dADC) voxels on the fcFDM. CONCLUSION: The ability to accurately identify changes in diffusion on traditional FDMs is confounded in areas where perfusion and diffusion changes are colocalized. Flow-compensated FDMs, which use only non-zero b-values, should therefore be the standard approach.

The role of pre-treatment white matter abnormalities in developing white matter changes following whole brain radiation: a volumetric study.

White matter injury is a known complication of whole brain radiation (WBRT). Little is known about the factors that predispose a patient to such injury. The current study used MR volumetrics to examine risk factors, in particular the influence of pre-treatment white matter health, in developing white matter change (WMC) following WBRT. Thirty-four patients with unilateral metastatic disease underwent FLAIR MRI pre-treatment and at several time points following treatment. The volume of abnormal FLAIR signal in the white matter was measured in the hemisphere contralateral to the diseased hemisphere at each time point. Analyses were restricted to the uninvolved hemisphere to allow for the measurement of WBRT effects without the potential confounding effects of the disease on imaging findings. The relationship between select pre-treatment clinical variables and the degree of WMC following treatment was examined using correlational and regression based analyses. Age when treated and volume of abnormal FLAIR prior to treatment were significantly associated with WMC following WBRT; however, pre-treatment FLAIR volume was the strongest predictor of post-treatment WMCs. Age did not add any predictive value once white matter status was considered. No significant relationships were found between biological equivalent dose and select cerebrovascular risk factors (total glucose, blood pressure, BMI) and development of WMCs. The findings from this study identify pre-treatment white matter health as an important risk factor in developing WMC following WBRT. This information can be used to make more informed decisions and counsel patients on their risk for treatment effects.

Spatially quantifying microscopic tumor invasion and proliferation using a voxel-wise solution to a glioma growth model and serial diffusion MRI.

The purpose of this study was to develop a voxel-wise analytical solution to a glioma growth model using serial diffusion MRI. These cell invasion, motility, and proliferation level estimates (CIMPLE maps) provide quantitative estimates of microscopic tumor growth dynamics. After an analytical solution was found, noise simulations were performed to predict the effects that perturbations in apparent diffusion coefficient values and the time between apparent diffusion coefficient map acquisitions would have on the accuracy of CIMPLE maps. CIMPLE maps were then created for 53 patients with gliomas with WHO grades of II-IV. MR spectroscopy estimates of the choline-to-N-acetylaspartate ratio were compared to cell proliferation estimates in CIMPLE maps using Pearson's correlation analysis. Median differences in cell proliferation and diffusion rates between WHO grades were compared. A strong correlation (R(2) = 0.9714) and good spatial correspondence were observed between MR spectroscopy measurements of the choline-to-N-acetylaspartate ratio and CIMPLE map cell proliferation rate estimates. Estimates of cell proliferation and diffusion rates appear to be significantly different between low- (WHO II) and high-grade (WHO III-IV) gliomas. Cell diffusion rate (motility) estimates are highly dependent on the time interval between apparent diffusion coefficient map acquisitions, whereas cell proliferation rate estimates are additionally influenced by the level of noise present in apparent diffusion coefficient maps.

Volumetric analysis of functional diffusion maps is a predictive imaging biomarker for cytotoxic and anti-angiogenic treatments in malignant gliomas.

Anti-angiogenic agents targeting brain tumor neovasculature may increase progression-free survival in patients with recurrent malignant gliomas. However, when these patients do recur it is not always apparent as an increase in enhancing tumor volume on MRI, which has been the standard of practice for following patients with brain tumors. Therefore alternative methods are needed to evaluate patients treated with these novel therapies. Furthermore, a method that can also provide useful information for the evaluation of conventional therapies would provide an important advantage for general applicability. Diffusion-weighted magnetic resonance imaging (DWI) has the potential to serve as a valuable biomarker for these purposes. In the current study, we explore the prognostic ability of functional diffusion maps (fDMs), which examine voxel-wise changes in the apparent diffusion coefficient (ADC) over time, applied to regions of fluid-attenuated inversion recovery (FLAIR) abnormalities in patients with malignant glioma, treated with either anti-angiogenic or cytotoxic therapies. Results indicate that the rate of change in fDMs is an early predictor of tumor progression, time to progression and overall survival for both treatments, suggesting the application of fDMs in FLAIR abnormal regions may be a significant advance in brain tumor biomarker technology.

Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity.

PURPOSE: To present comprehensive examinations of the assumptions made in functional diffusion map (fDM) analyses and provide a biological basis for fDM classification. MATERIALS AND METHODS: Sixty-nine patients with gliomas were enrolled in this study. To determine the sensitivity of apparent diffusion coefficients (ADCs) to cellularity, cell density from stereotactic biopsy specimens was correlated with preoperative ADC maps. For definition of ADC thresholds used for fDMs, the 95% confidence intervals (CI) for changes in voxel-wise ADC measurements in normal appearing tissue was analyzed. The sensitivity and specificity to progressing disease was examined using both radiographic and neurological criteria. RESULTS: Results support the hypothesis that ADC is inversely proportional to cell density with a sensitivity of 1.01 x 10(-7) [mm(2)/s]/[nuclei/mm(2)]. The 95% CI for white matter = 0.25 x 10(-3) mm(2)/s, gray matter = 0.31 x 10(-3) mm(2)/s, a mixture of white and gray matter = 0.40 x 10(-3) mm(2)/s, and a mixture of white matter, gray matter, and cerebrospinal fluid = 0.75 x 10(-3) mm(2)/s. Application of these measurements as ADC thresholds produce varying levels of sensitivity and specificity to disease progression, which were all significantly better than chance. CONCLUSION: This study suggests fDMs are valid biomarkers for brain tumor cellularity.

Utility of functional diffusion maps to monitor a patient diagnosed with gliomatosis cerebri.

Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive imaging biomarker for tumor cellularity. Functional diffusion maps (fDMs), which examine voxel-by-voxel changes in the apparent diffusion coefficient (ADC) calculated from serial DWIs, have previously been applied to regions of contrast-enhancement; however, application of fDMs to non-enhancing brain tumors has not been pursued. In this case study we demonstrate the utility of applying fDMs to regions of abnormal FLAIR signal intensity in a patient diagnosed with gliomatosis cerebri: a relatively rare, infiltrative, non-enhancing brain tumor. The absolute volume of hypercellularity extracted from fDMs was useful in tracking tumor growth, which correlated in time with a progressive decline in neurological status despite no change in traditional magnetic resonance images. Results of this study demonstrate the value of fDMs, applied to regions of FLAIR abnormal signal intensity, for localizing regions of hypercellularity and for monitoring overall tumor status.

Pulsed Reduced Dose Rate Radiotherapy in Conjunction With Bevacizumab or Bevacizumab Alone in Recurrent High-grade Glioma: Survival Outcomes.

PURPOSE: Dismal prognosis and limited treatment options for recurrent high-grade glioma have provoked interest in various forms of reirradiation. Pulsed reduced dose rate radiation therapy (pRDR) is a promising technique that exploits low-dose hyper-radiosensitivity of proliferating tumor cells while sparing adjacent nonproliferating normal brain tissue. Large radiation treatment volumes can thus be used to target both contrast-enhancing and FLAIR abnormalities thought to harbor recurrent gross and microscopic disease, respectively. The aim of this retrospective study was to determine whether the addition of pRDR to bevacizumab improves survival over bevacizumab alone for recurrent high-grade glioma. METHODS AND MATERIALS: Eighty patients with recurrent high-grade glioma were included in this study; 47 patients received bevacizumab monotherapy (BEV), and 33 patients received pRDR with bevacizumab (BEV/pRDR). Progression-free survival (PFS) and overall survival were compared between the BEV and BEV/pRDR groups. Regression analysis was performed to identify and control for confounding influences on survival analyses. RESULTS: Significant (P < .05) advantages in PFS (12 vs 4 months; hazard ratio = 2.37) and OS (16 vs. 9 months; hazard ratio = 1.68) were observed with BEV/pRDR compared with BEV alone. CONCLUSIONS: This retrospective analysis suggests that treatment with pRDR in addition to bevacizumab could significantly prolong PFS and overall survival compared with bevacizumab alone for recurrent high-grade glioma.

Acid ceramidase confers radioresistance to glioblastoma cells.

Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine­1-phosphate (Sph-1P). Moreover, inhibition of ASAH1 and Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e. carmofur), or a combination of both, led to suppression of GBM cell growth. These results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1.

Acid ceramidase and its inhibitors: a de novo drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency.

Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies. Proteomic analysis of more than 600 glioblastoma-specific proteins revealed, for the first time, that expression of acid ceramidase (ASAH1) is associated with poor glioblastoma survival. CD133+ GSCs express significantly higher ASAH1 compared to CD133- GSCs and serum-cultured glioblastoma cell lines, such as U87MG. These findings implicate ASAH1 as a plausible independent prognostic marker, providing a target for a therapy tailored toward GSCs. We further demonstrate that ASAH1 inhibition increases cellular ceramide level and induces apoptosis. Strikingly, U87MG cells, and three different patient-derived glioblastoma stem-like cancer cell lines were efficiently killed, through apoptosis, by three different known ASAH1 inhibitors with IC50's ranging from 11-104 µM. In comparison, the standard glioblastoma chemotherapy agent, temozolomide, had minimal GSC-targeted effects at comparable or even higher concentrations (IC50 > 750 µM against GSCs). ASAH1 is identified as a de novo glioblastoma drug target, and ASAH1 inhibitors, such as carmofur, are shown to be highly effective and to specifically target glioblastoma GSCs. Carmofur is an ASAH1 inhibitor that crosses the blood-brain barrier, a major bottleneck in glioblastoma treatment. It has been approved in Japan since 1981 for colorectal cancer therapy. Therefore, it is poised for repurposing and translation to glioblastoma clinical trials.

Acid ceramidase is a novel drug target for pediatric brain tumors.

Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4.6-50 µM). This data suggests acid ceramidase as a novel drug target for adjuvant pediatric brain tumor therapies. Of these acid ceramidase inhibitors, carmofur has seen clinical use in Japan since 1981 for colorectal cancers and is a promising drug to undergo further animal studies and subsequently a clinical trial as a treatment for pediatric patients with brain tumors.

Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma.

PURPOSE: The purpose of this study is to evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused with planning computed tomography (CT) on tumor localization, which guided intensity-modulated radiotherapy (IMRT) of patients with head-and-neck carcinoma. METHODS AND MATERIALS: From October 2002 through April 2005, we performed FDG-PET/CT guided IMRT for 28 patients with head-and-neck carcinoma. Patients were immobilized with face masks that were attached with five fiducial markers. FDG-PET and planning CT scans were performed on the same flattop table in one session and were then fused. Target volumes and critical organs were contoured, and IMRT plans were generated based on the fused images. RESULTS: All 28 patients had abnormal increased uptake in FDG-PET/CT scans. PET/CT resulted in CT-based staging changes in 16 of 28 (57%) patients. PET/CT fusions were successfully performed and were found to be accurate with the use of the two commercial planning systems. Volume analysis revealed that the PET/CT-based gross target volumes (GTVs) were significantly different from those contoured from the CT scans alone in 14 of 16 patients. In addition, 16 of 28 patients who were followed for more than 6 months did not have any evidence of locoregional recurrence in the median time of 17 months. CONCLUSION: Fused images were found to be useful to delineate GTV required in IMRT planning. PET/CT should be considered for both initial staging and treatment planning in patients with head-and-neck carcinoma.

Magnetic Resonance Imaging-Based Radiomic Profiles Predict Patient Prognosis in Newly Diagnosed Glioblastoma Before Therapy.

Magnetic resonance imaging (MRI) is used to diagnose and monitor brain tumors. Extracting additional information from medical imaging and relating it to a clinical variable of interest is broadly defined as radiomics. Here, multiparametric MRI radiomic profiles (RPs) of de novo glioblastoma (GBM) brain tumors is related with patient prognosis. Clinical imaging from 81 patients with GBM before surgery was analyzed. Four MRI contrasts were aligned, masked by margins defined by gadolinium contrast enhancement and T2/fluid attenuated inversion recovery hyperintensity, and contoured based on image intensity. These segmentations were combined for visualization and quantification by assigning a 4-digit numerical code to each voxel to indicate the segmented RP. Each RP volume was then compared with overall survival. A combined classifier was then generated on the basis of significant RPs and optimized volume thresholds. Five RPs were predictive of overall survival before therapy. Combining the RP classifiers into a single prognostic score predicted patient survival better than each alone (P < .005). Voxels coded with 1 RP associated with poor prognosis were pathologically confirmed to contain hypercellular tumor. This study applies radiomic profiling to de novo patients with GBM to determine imaging signatures associated with poor prognosis at tumor diagnosis. This tool may be useful for planning surgical resection or radiation treatment margins.

Dexamethasone normalizes brain tumor hemodynamics as indicated by dynamic susceptibility contrast MRI perfusion parameters.

The purpose of this study is to demonstrate the utility of dynamic susceptibility contrast (DSC) MRI-derived perfusion parameters to characterize the hemodynamic effects of dexamethasone in a 9L gliosarcoma tumor model. Twenty-four rats underwent intracerebral inoculation with 9L tumor cells. Fifteen were treated with a total of 3mg/kg of dexamethasone on days 10-14 post-inoculation, while the remaining 9 rats served as controls. Fourteen days post-inoculation, MRI images, sensitive to total and micro-vascular cerebral blood flow (CBF), mean transit time (MTT), and intravoxel transit time distributions (TTD)s were obtained using a simultaneous gradient-echo(GE)/spin-echo(SE) DSC-MRI method. Dexamethasone-treated animals had a microvascular (SE) tumor CBF that was 45.9% higher (p = 0.0008) and a MTT that was 47.8% lower (p = 0.0005) than untreated animals. With treatment, there was a non-significant 91.3% increase in total (GE) vascular CBF (p = 0.35), and a significant decrease in MTT (49.1%, p = 0.02). The total vascular and microvascular TTDs from the treated tumors were similar to normal brain, unlike the TTDs in the untreated tumors. These findings demonstrate that DSC-MRI perfusion methods can be used to non-invasively detect the morphological and functional changes in tumor vasculature that occur in response to dexamethasone treatment.

Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps.

Depending on dose, dexamethasone has been shown to inhibit or stimulate growth of rat 9L gliosarcoma and decrease the expression of vascular endothelial growth factor (VEGF), an important mediator of tumor-associated angiogenesis. We demonstrate, by constructing relative cerebral blood volume (rCBV) maps with MRI, that dexamethasone also decreases total blood volume while increasing microvascular blood volume in Fischer rats bearing intracranial 9L gliosarcoma. Animals were inoculated with 1 x 10(5) 9L gliosarcoma tumor cells. On days 10-14 after tumor cell inoculation, animals were intra-peritoneally injected with dexamethasone (3 mg/kg) over 5 days. MRI-derived gradient echo (GE) and spin-echo (SE) rCBV maps were created to demonstrate total vasculature (GE) and microvasculature (SE). After MRI studies were performed, the rat's vasculature was perfused with a latex compound. Total vessel volume and diameters were assessed by microscopy. Dexamethasone decreased the tumor-enhancing area of postcontrast T1-weighted images (P < 0.0001) and total tumor volume(P = 0.0085). In addition, there was a greater than 50% decrease in GE rCBV (total vasculature) (P = 0.007) as well as a significant decrease in total fractional blood volume, as validated by histology (P = 0.0007). Conversely, there was an increase in SE rCBV signal (microvasculature) in animals treated with dexamethasone (P = 0.05), which was consistent with microscopy (P < 0.0001). These data demonstrate that (1) dexamethasone selectively treats tumor vasculature, suggesting a vessel-size selective effect and (2) MRI-derived rCBV is a noninvasive technique that can be used to evaluate changes in blood volume and vascular morphology.

Characterization of a first-pass gradient-echo spin-echo method to predict brain tumor grade and angiogenesis.

BACKGROUND AND PURPOSE: No widespread clinical method provides specific information about the angiogenic characteristics of gliomas. We characterized blood volume and vascular morphologic parameters from combined gradient-echo (GE) and spin-echo (SE) MR imaging and assessed their relationship to tumor grade, a known correlate of glioma angiogenesis. METHODS: Simultaneous GE and SE echo-planar imaging was performed with bolus gadolinium administration (0.20-0.25 mmol/kg) in 73 patients with glioma. To diminish possible T1 changes due to contrast agent extravasation, a preload (0.05-0.10 mmol/kg) was administered before the study, and a postprocessing correction algorithm was applied. Image maps of total (GE) and microvascular (SE) relative cerebral blood volume (rCBV) and the mean vessel diameter (mVD) calculated from the ratio of GE and SE relaxation rate changes (DeltaR2*/DeltaR2) were compared with tumor grade. A nonparametric K nearest-neighbor decision rule was applied to determine if the combined data could be used to distinguish low-grade (I-II) from high-grade (III-IV) tumors on a per-patient basis. RESULTS: For whole tumors, significant correlations were found between GE rCBV and grade (P < .0001) and between mVD and grade (P = .0001) but not between SE rCBV and grade (P = .08). For areas of highest SE rCBV (microvascular hotspots), SE rCBV and tumor grade were significantly correlated (P = .0007). In terms of differentiation, 69% of low-grade tumors and 96% of high-grade tumors were correctly classified. CONCLUSION: Combined GE and SE MR imaging provides information consistent with neoplastic angiogenesis, demonstrating its potential to aid in optimizing treatments, categorizing lesions, and influencing patient care.