Recommended Resting-State fMRI Acquisition and Preprocessing Steps for Preoperative Mapping of Language and Motor and Visual Areas in Adult and Pediatric Patients with Brain Tumors and Epilepsy.

Resting-state (rs) fMRI has been shown to be useful for preoperative mapping of functional areas in patients with brain tumors and epilepsy. However, its lack of standardization limits its widespread use and hinders multicenter collaboration. The American Society of Functional Neuroradiology, American Society of Pediatric Neuroradiology, and the American Society of Neuroradiology Functional and Diffusion MR Imaging Study Group recommend specific rs-fMRI acquisition approaches and preprocessing steps that will further support rs-fMRI for future clinical use. A task force with expertise in fMRI from multiple institutions provided recommendations on the rs-fMRI steps needed for mapping of language, motor, and visual areas in adult and pediatric patients with brain tumor and epilepsy. These were based on an extensive literature review and expert consensus.Following rs-fMRI acquisition parameters are recommended: minimum 6-minute acquisition time; scan with eyes open with fixation; obtain rs-fMRI before both task-based fMRI and contrast administration; temporal resolution of ≤2 seconds; scanner field strength of 3T or higher. The following rs-fMRI preprocessing steps and parameters are recommended: motion correction (seed-based correlation analysis [SBC], independent component analysis [ICA]); despiking (SBC); volume censoring (SBC, ICA); nuisance regression of CSF and white matter signals (SBC); head motion regression (SBC, ICA); bandpass filtering (SBC, ICA); and spatial smoothing with a kernel size that is twice the effective voxel size (SBC, ICA).The consensus recommendations put forth for rs-fMRI acquisition and preprocessing steps will aid in standardization of practice and guide rs-fMRI program development across institutions. Standardized rs-fMRI protocols and processing pipelines are essential for multicenter trials and to implement rs-fMRI as part of standard clinical practice.

Functional MRI Shows Altered Deactivation and a Corresponding Decrease in Functional Connectivity of the Default Mode Network in Patients with Gliomas.

BACKGROUND AND PURPOSE: The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. MATERIALS AND METHODS: In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. RESULTS: Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. CONCLUSIONS: Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

Glioma-Induced Disruption of Resting-State Functional Connectivity and Amplitude of Low-Frequency Fluctuations in the Salience Network.

BACKGROUND AND PURPOSE: Cognitive challenges are prevalent in survivors of glioma, but their neurobiology is incompletely understood. The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on resting-state functional connectivity and amplitude of low-frequency fluctuations of the salience network, a key neural network associated with cognition. MATERIALS AND METHODS: Sixty-nine patients with glioma (mean age, 48.74 [SD, 14.32] years) who underwent resting-state fMRI were compared with 31 healthy controls (mean age, 49.68 [SD, 15.54] years). We identified 4 salience network ROIs: left/right dorsal anterior cingulate cortex and left/right anterior insula. Average salience network resting-state functional connectivity and amplitude of low-frequency fluctuations within the 4 salience network ROIs were computed. RESULTS: Patients with gliomas showed decreased overall salience network resting-state functional connectivity (P = .001) and increased amplitude of low-frequency fluctuations in all salience network ROIs (P < .01) except in the left dorsal anterior cingulate cortex. Compared with controls, patients with left-sided gliomas showed increased amplitude of low-frequency fluctuations in the right dorsal anterior cingulate cortex (P = .002) and right anterior insula (P < .001), and patients with right-sided gliomas showed increased amplitude of low-frequency fluctuations in the left anterior insula (P = .002). Anterior tumors were associated with decreased salience network resting-state functional connectivity (P < .001) and increased amplitude of low-frequency fluctuations in the right anterior insula, left anterior insula, and right dorsal anterior cingulate cortex. Patients with high-grade gliomas had decreased salience network resting-state functional connectivity compared with healthy controls (P < .05). The right anterior insula showed increased amplitude of low-frequency fluctuations in patients with grade II and IV gliomas compared with controls (P < .01). CONCLUSIONS: By demonstrating decreased resting-state functional connectivity and an increased amplitude of low-frequency fluctuations related to the salience network in patients with glioma, this study adds to our understanding of the neurobiology underpinning observable cognitive deficits in these patients. In addition to more conventional functional connectivity, amplitude of low-frequency fluctuations is a promising functional-imaging biomarker of tumor-induced vascular and neural pathology.

Resting-State Functional Connectivity of the Middle Frontal Gyrus Can Predict Language Lateralization in Patients with Brain Tumors.

BACKGROUND AND PURPOSE: A recent study using task-based fMRI demonstrated that the middle frontal gyrus is comparable with Broca's area in its ability to determine language laterality using a measure of verbal fluency. This study investigated whether the middle frontal gyrus can be used as an indicator for language-hemispheric dominance in patients with brain tumors using task-free resting-state fMRI. We hypothesized that no significant difference in language lateralization would occur between the middle frontal gyrus and Broca area and that the middle frontal gyrus can serve as a simple and reliable means of measuring language laterality. MATERIALS AND METHODS: Using resting-state fMRI, we compared the middle frontal gyrus with the Broca area in 51 patients with glial neoplasms for voxel activation, the language laterality index, and the effect of tumor grade on the laterality index. The laterality index derived by resting-state fMRI and task-based fMRI was compared in a subset of 40 patients. RESULTS: Voxel activations in the left middle frontal gyrus and left Broca area were positively correlated (r = 0.47, P < .001). Positive correlations were seen between the laterality index of the Broca area and middle frontal gyrus regions (r = 0.56, P < .0005). Twenty-seven of 40 patients (67.5%) showed concordance of the laterality index based on the Broca area using resting-state fMRI and the laterality index based on a language task. Thirty of 40 patients (75%) showed concordance of the laterality index based on the middle frontal gyrus using resting-state fMRI and the laterality index based on a language task. CONCLUSIONS: The middle frontal gyrus is comparable with the Broca area in its ability to determine hemispheric dominance for language using resting-state fMRI. Our results suggest the addition of resting-state fMRI of the middle frontal gyrus to the list of noninvasive modalities that could be used in patients with gliomas to evaluate hemispheric dominance of language before tumor resection. In patients who cannot participate in traditional task-based fMRI, resting-state fMRI offers a task-free alternate to presurgically map the eloquent cortex.

[Evaluation of vascular reactivity to overcome limitations of neurovascular uncoupling in BOLD fMRI of malignant brain tumors]. / Otsenka vazoreaktivnosti dlia preodoleniia ogranichenii neirovaskuliarnogo razobshcheniia BOLD fMRT pri zlokachestvennykh opukholiakh golovnogo mozga.

The sensitivity of fMRI in identification of eloquent cortical centers in the case of large infiltrative growing tumors and pronounced peritumoral edema may be reduced or significantly limited in some cases. The main cause is an attenuated Blood-Oxygen-Level-Dependent response (BOLD) caused by pathological vascular reactivity and subsequent neurovascular uncoupling of fMRI. In our study, we attempted to overcome these limitations and increase the sensitivity of this technique in identification of eloquent cortical areas adjacent to brain tumors by using vasoreactivity features of a breath-holding test and including these data in the BOLD analysis. Local vasoreactivity using a breath-holding paradigm with the same block design of both motor and speech tests was determined in 5 healthy volunteers and 3 patients in the preoperative period (two patients with high grade gliomas and one patient with single metastasis). A coherence-based model was developed for analysis of BOLD fMRI, which took into account altered hemodynamics in peritumoral zones. Obtained coherence maps demonstrated clinically more significant activation zones that were not seen with standard methods of fMRI processing. Thus, neurovascular uncoupling that is known to affect the accuracy of the BOLD fMRI response adjacent to brain tumors may be partially overcome by including an independent measurement of vasoreactivity using a breath-holding test in the BOLD analysis.

Differentiating Atypical Hemangiomas and Metastatic Vertebral Lesions: The Role of T1-Weighted Dynamic Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: Vertebral hemangiomas are benign vascular lesions that are almost always incidentally found in the spine. Their classic typical hyperintense appearance on T1- and T2-weighted MR images is diagnostic. Unfortunately, not all hemangiomas have the typical appearance, and they can mimic metastases on routine MR imaging. These are generally referred to as atypical hemangiomas and can result in misdiagnosis and ultimately additional imaging, biopsy, and unnecessary costs. Our objective was to assess the utility of dynamic contrast-enhanced MR imaging perfusion in distinguishing vertebral atypical hemangiomas and malignant vertebral metastases. We hypothesized that permeability and vascular density will be increased in metastases compared with atypical hemangiomas. MATERIALS AND METHODS: Consecutive patients from 2011 to 2015 with confirmed diagnoses of atypical hemangiomas and spinal metastases from breast and lung carcinomas with available dynamic contrast-enhanced MR imaging were analyzed. Time-intensity curves were qualitatively compared among the groups. Perfusion parameters, plasma volume, and permeability constant were quantified using an extended Tofts 2-compartment pharmacokinetic model. Statistical significance was tested using the Mann-Whitney U test. RESULTS: Qualitative inspection of dynamic contrast-enhanced MR imaging time-intensity curves demonstrated differences in signal intensity and morphology between metastases and atypical hemangiomas. Quantitative analysis of plasma volume and permeability constant perfusion parameters showed significantly higher values in metastatic lesions compared with atypical hemangiomas (P < .001). CONCLUSIONS: Our data demonstrate that plasma volume and permeability constant perfusion parameters and qualitative inspection of contrast-enhancement curves can be used to differentiate atypical hemangiomas from vertebral metastatic lesions. This work highlights the benefits of adding perfusion maps to conventional sequences to improve diagnostic accuracy.

T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma.

BACKGROUND AND PURPOSE: Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy. MATERIALS AND METHODS: Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy. RESULTS: Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05). CONCLUSIONS: Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity-time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.

Diagnostic Accuracy of T1-Weighted Dynamic Contrast-Enhanced-MRI and DWI-ADC for Differentiation of Glioblastoma and Primary CNS Lymphoma.

BACKGROUND AND PURPOSE: Glioblastoma and primary CNS lymphoma dictate different neurosurgical strategies; it is critical to distinguish them preoperatively. However, current imaging modalities do not effectively differentiate them. We aimed to examine the use of DWI and T1-weighted dynamic contrast-enhanced-MR imaging as potential discriminative tools. MATERIALS AND METHODS: We retrospectively reviewed 18 patients with primary CNS lymphoma and 36 matched patients with glioblastoma with pretreatment DWI and dynamic contrast-enhanced-MR imaging. VOIs were drawn around the tumor on contrast-enhanced T1WI and FLAIR images; these images were transferred onto coregistered ADC maps to obtain the ADC and onto dynamic contrast-enhanced perfusion maps to obtain the plasma volume and permeability transfer constant. Histogram analysis was performed to determine the mean and relative ADCmean and relative 90th percentile values for plasma volume and the permeability transfer constant. Nonparametric tests were used to assess differences, and receiver operating characteristic analysis was performed for optimal threshold calculations. RESULTS: The enhancing component of primary CNS lymphoma was found to have significantly lower ADCmean (1.1 × 10-3 versus 1.4 × 10-3; P < .001) and relative ADCmean (1.5 versus 1.9; P < .001) and relative 90th percentile values for plasma volume (3.7 versus 5.0; P < .05) than the enhancing component of glioblastoma, but not significantly different relative 90th percentile values for the permeability transfer constant (5.4 versus 4.4; P = .83). The nonenhancing portions of glioblastoma and primary CNS lymphoma did not differ in these parameters. On the basis of receiver operating characteristic analysis, mean ADC provided the best threshold (area under the curve = 0.83) to distinguish primary CNS lymphoma from glioblastoma, which was not improved with normalized ADC or the addition of perfusion parameters. CONCLUSIONS: ADC was superior to dynamic contrast-enhanced-MR imaging perfusion, alone or in combination, in differentiating primary CNS lymphoma from glioblastoma.

T1-Weighted Dynamic Contrast-Enhanced MRI as a Noninvasive Biomarker of Epidermal Growth Factor Receptor vIII Status.

BACKGROUND AND PURPOSE: Epidermal growth factor receptor variant III is a common mutation in glioblastoma, found in approximately 25% of tumors. Epidermal growth factor receptor variant III may accelerate angiogenesis in malignant gliomas. We correlated T1-weighted dynamic contrast-enhanced MR imaging perfusion parameters with epidermal growth factor receptor variant III status. MATERIALS AND METHODS: Eighty-two consecutive patients with glioblastoma and known epidermal growth factor receptor variant III status who had dynamic contrast-enhanced MR imaging before surgery were evaluated. Volumes of interest were drawn around the entire enhancing tumor on contrast T1-weighted images and then were transferred onto coregistered dynamic contrast-enhanced MR imaging perfusion maps. Histogram analysis with normalization was performed to determine the relative mean, 75th percentile, and 90th percentile values for plasma volume and contrast transfer coefficient. A Wilcoxon rank sum test was applied to assess the relationship between baseline perfusion parameters and positive epidermal growth factor receptor variant III status. The receiver operating characteristic method was used to select the cutoffs of the dynamic contrast-enhanced MR imaging perfusion parameters. RESULTS: Increased relative plasma volume and increased relative contrast transfer coefficient parameters were both significantly associated with positive epidermal growth factor receptor variant III status. For epidermal growth factor receptor variant III-positive tumors, relative plasma volume mean was 9.3 and relative contrast transfer coefficient mean was 6.5; for epidermal growth factor receptor variant III-negative tumors, relative plasma volume mean was 3.6 and relative contrast transfer coefficient mean was 3.7 (relative plasma volume mean, P < .001, and relative contrast transfer coefficient mean, P = .008). The predictive powers of relative plasma volume histogram metrics outperformed those of the relative contrast transfer coefficient histogram metrics (P < = .004). CONCLUSIONS: Dynamic contrast-enhanced MR imaging shows greater perfusion and leakiness in epidermal growth factor receptor variant III-positive glioblastomas than in epidermal growth factor receptor variant III-negative glioblastomas, consistent with the known effect of epidermal growth factor receptor variant III on angiogenesis. Quantitative evaluation of dynamic contrast-enhanced MR imaging may be useful as a noninvasive tool for correlating epidermal growth factor receptor variant III expression and related tumor neoangiogenesis. This potential may have implications for monitoring response to epidermal growth factor receptor variant III-targeted therapies.

Identification of the Corticobulbar Tracts of the Tongue and Face Using Deterministic and Probabilistic DTI Fiber Tracking in Patients with Brain Tumor.

BACKGROUND AND PURPOSE: The corticobulbar tract of the face and tongue, a critical white matter tract connecting the primary motor cortex and the pons, is rarely detected by deterministic DTI fiber tractography. Detection becomes even more difficult in the presence of a tumor. The purpose of this study was to compare identification of the corticobulbar tract by using deterministic and probabilistic tractography in patients with brain tumor. MATERIALS AND METHODS: Fifty patients with brain tumor who underwent DTI were studied. Deterministic tractography was performed by using the fiber assignment by continuous tractography algorithm. Probabilistic tractography was performed by using a Monte Carlo simulation method. ROIs were drawn of the face and tongue motor homunculi and the pons in both hemispheres. RESULTS: In all subjects, fiber assignment by continuous tractography was ineffectual in visualizing the entire course of the corticobulbar tract between the face and tongue motor cortices and the pons on either side. However, probabilistic tractography successfully visualized the corticobulbar tract from the face and tongue motor cortices in all patients on both sides. No significant difference (P < .08) was found between both sides in terms of the number of voxels or degree of connectivity. The fractional anisotropy of both the face and tongue was significantly lower on the tumor side (P < .03). When stratified by tumor type, primary-versus-metastatic tumors, no differences were observed between tracts in terms of the fractional anisotropy and connectivity values (P > .5). CONCLUSIONS: Probabilistic tractography successfully reconstructs the face- and tongue-associated corticobulbar tracts from the lateral primary motor cortex to the pons in both hemispheres.

Challenges in Identifying the Foot Motor Region in Patients with Brain Tumor on Routine MRI: Advantages of fMRI.

BACKGROUND AND PURPOSE: Accurate localization of the foot/leg motor homunculus is essential because iatrogenic damage can render a patient wheelchair- or bed-bound. We hypothesized the following: 1) Readers would identify the foot motor homunculus <100% of the time on routine MR imaging, 2) neuroradiologists would perform better than nonradiologists, and 3) those with fMRI experience would perform better than those without it. MATERIALS AND METHODS: Thirty-five attending-level raters (24 neuroradiologists, 11 nonradiologists) evaluated 14 brain tumors involving the frontoparietal convexity. Raters were asked to identify the location of the foot motor homunculus and determine whether the tumor involved the foot motor area and/or motor cortex by using anatomic MR imaging. Results were compared on the basis of prior fMRI experience and medical specialty by using Mann-Whitney U test statistics. RESULTS: No rater was 100% correct. Raters correctly identified whether the tumor was in the foot motor cortex 77% of the time. Raters with fMRI experience were significantly better than raters without experience at foot motor fMRI centroid predictions (13 ± 6 mm versus 20 ± 13 mm from the foot motor cortex center, P = 2 × 10(-6)) and arrow placement in the motor gyrus (67% versus 47%, P = 7 × 10(-5)). Neuroradiologists were significantly better than nonradiologists at foot motor fMRI centroid predictions (15 ± 8 mm versus 20 ± 14 mm, P = .005) and arrow placement in the motor gyrus (61% versus 46%, P = .008). CONCLUSIONS: The inability of experienced readers to consistently identify the location of the foot motor homunculus on routine MR imaging argues for using fMRI in the preoperative setting. Experience with fMRI leads to improved accuracy in identifying anatomic structures, even on routine MR imaging.

Characterizing hypervascular and hypovascular metastases and normal bone marrow of the spine using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: The role of DCE-MR imaging in the study of bone marrow perfusion is only partially developed, though potential applications for routine use in the clinical setting are beginning to be described. We hypothesize that DCE-MR imaging can be used to discriminate between hypervascular and hypovascular metastases based on measured perfusion variables. MATERIALS AND METHODS: We conducted a retrospective study of 26 patients using conventional MR imaging and DCE-MR imaging. Patients were assigned to a hypervascular or hypovascular group based on tumor pathology. ROIs were drawn around normal-appearing bone marrow (internal controls) and enhancing tumor areas. Average wash-in enhancement slope, average peak enhancement signal percentage change, and average peak enhancement signal percentage change in areas of highest wash-in enhancement slope were calculated. Indices were compared among control, hypervascular, and hypovascular groups. Conventional imaging was assessed by calculating pre- to postgadolinium signal percentage changes in hypervascular and hypovascular lesions. RESULTS: Hypervascular and hypovascular tumors differed significantly with regard to wash-in enhancement slope (P < .01; hypervascular 95% CI, 22.5-26.5 AU/s; hypovascular 95% CI, 14.1-20.9 AU/s) and peak enhancement signal percentage change in areas of highest wash-in enhancement slope (P < .01; hypervascular 95% CI, 174.1-323.3%; hypovascular 95% CI, 39.5-150.5%). Peak enhancement signal percentage change over all voxels was not significant (P = .62). Areas of normal-appearing marrow showed no appreciable contrast enhancement. Conventional contrast-enhanced MR imaging was unable to differentiate between hypervascular and hypovascular tumors (P = .58). CONCLUSIONS: Our data demonstrate that, unlike conventional MR imaging sequences, DCE-MR imaging may be a more accurate technique in discriminating hypervascular from hypovascular spinal metastases.

Somatotopic organization of motor pathways in the internal capsule: a probabilistic diffusion tractography study.

BACKGROUND AND PURPOSE: The location of the motor pathways in the PLIC remains controversial. In the current study, we trace the fibers from the tongue, face, hand, and foot motor cortices by using probabilistic diffusion tractography and define their somatotopic organization in the PLIC. MATERIALS AND METHODS: Twenty subjects were retrospectively studied. Fiber tracts were separately calculated between ROIs in the cerebral peduncle and in the 4 different motor regions in the precentral gyrus. Probabilistic connectivity maps were generated, and the voxel with the highest probability was designated as the position of the motor pathway. The PI and LI were defined as the relative anteroposterior and mediolateral locations of the motor pathways. RESULTS: Tongue pathways were located anteromedial to face in 16 hemispheres (40%), with P < .05 for the PI and LI. Face pathways were located anteromedial to hand in 25 hemispheres (62.5%) with P < .05 for PI and LI. Hand pathways were anteromedial to foot in 14 hemispheres (35%) and anterior in 11 hemispheres (27.5%), with P < .05 for PI but P > .13 for LI. Group analysis showed that the somatotopic arrangement of the bilateral hemispheres was symmetric. CONCLUSIONS: Probabilistic tractography demonstrated the anteroposterior alignment of the motor pathways along the long axis in the PLIC. Probabilistic tractography successfully tracked the motor pathways of the tongue, face, hand, and foot from the precentral gyrus through their intersection with the larger superior longitudinal fasciculus to the PLIC in all cases, overcoming limitations of standard (nonprobabilistic) tractography methods.

Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience.

BACKGROUND: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab. METHODS: We retrospectively identified patients with ICH who received bevacizumab between 1 January 2001 and 10 January 2009. RESULTS: We identified 1024 patients with ICH, 4191 patients who received bevacizumab and 12 (0.3%) who met both our criteria. There were eight women and four men with a median age of 66 years. Primary cancers were ovarian (n = 3), NSCLC (n = 3), colon (n = 1), angiosarcoma (n = 1) and GBM (n = 4). Intracranial tumors were present in 9 of the 12 patients; the remaining three (25%) had no evidence of intracranial pathology. Two hundred and fifty-seven patients with these same primary pathologies and brain tumors were treated with bevacizumab; ICH was seen in nine (3.7%), which was comparable to the 3.6% frequency seen in comparable patients not receiving bevacizumab. CONCLUSIONS: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen.

Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma.

OBJECTIVE: To examine the potential utility of conventional MRI signs in differentiating pseudoprogression (PsP) from early progression (EP). METHODS: This retrospective study reviewed initial postradiotherapy MRI scans of 321 patients with glioblastoma undergoing chemotherapy and radiotherapy. A total of 93 patients were found to have new or increased enhancing mass lesions, raising the possibility of PsP. Final diagnosis of PsP or EP was established upon review of surgical specimens from a second resection or by clinical and radiologic follow-up. A total of 11 MRI signs potentially helpful in the differentiation between PsP and EP were examined on the initial post-RT MRI and were correlated with the final diagnosis through χ(2) or Fisher exact test. RESULTS: Sixty-three (67.7%) of the 93 patients had EP, of which 22 (34.9%) were diagnosed by pathology. Thirty patients (32.3%) had PsP; 6 (16.7% of the 30) were diagnosed by pathology. Subependymal enhancement was predictive for EP (p = 0.001) with 38.1% sensitivity, 93.3% specificity, and 41.8% negative predictive value. The other 10 signs had no predictive value (p = 0.06-1.0). CONCLUSIONS: Conventional MRI signs have limited utility in diagnosing PsP in patients with recently treated glioblastomas and worsening enhancing lesions. We did not find a sign with a high negative predictive value for PsP that would have been the most useful for the clinical physician. When present, subependymal spread of the enhancing lesion is a useful MRI marker in identifying EP rather than PsP.

Isolated diffusion restriction precedes the development of enhancing tumor in a subset of patients with glioblastoma.

BACKGROUND AND PURPOSE: Most response criteria for patients with glioblastoma rely on increases in the contrast enhancing abnormality to determine tumor progression. Our aim was to determine retrospectively in patients with glioblastoma whether diffusion restriction can predict the development of new enhancing mass lesions. MATERIALS AND METHODS: We reviewed the brain MR imaging scans (including DWI and ADC maps) of 208 patients with glioblastoma. Patients with restricted diffusion in or adjacent to the tumor were identified, with further analysis only performed on those patients with low-ADC lesions without enhancement. These patients were followed to determine if new concordant enhancement developed at the site of the low-ADC lesion. A Wilcoxon signed rank test, competing risk analysis, and Kaplan-Meier curves were used to compare the mean drop in ADC values, assess enhancement-free survival, and determine overall survival, respectively. RESULTS: In 67 of the 208 patients (32.2%), visibly detectable restricted diffusion was seen during treatment. The study cohort was formed by the 27 patients with low-ADC lesions and no corresponding enhancement. Twenty-three (85.2%) patients developed gadolinium-enhancing tumor at the site of restricted diffusion a median of 3.0 months later (95% CI, 2.6-4.1 months). The mean decrease in ADC was 22.9% from baseline (P < .001). The 3-month enhancement-free survival probability was 0.481 (95% CI, 0.288-0.675). The 12-month overall survival probability was 0.521 (95% CI, 0.345-0.788). Restricted diffusion predicted enhancement regardless of antiangiogenic therapy with bevacizumab. CONCLUSIONS: In a subset of patients with glioblastoma, development of a new focus of restricted diffusion during treatment may precede the development of new enhancing tumor.

Apparent diffusion coefficient of glial neoplasms: correlation with fluorodeoxyglucose-positron-emission tomography and gadolinium-enhanced MR imaging.

BACKGROUND AND PURPOSE: Gd-enhancement provides essential information in the assessment of brain tumors. However, enhancement does not always correlate with histology or disease activity, especially in the setting of current therapies. Our aim was to compare FDG-PET scans to ADC maps and Gd-enhanced MR images in patients with glial neoplasms to assess whether DWI might offer information not available on routine MR imaging sequences and whether such findings have prognostic significance. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective review, which was conducted in full compliance with HIPAA regulations. Twenty-one patients (11 men and 10 women) with glial tumors underwent FDG-PET and MR imaging, including ADC and Gd- enhancement. Subjectively, regions of interest were drawn around the following areas: 1) increased FDG uptake, 2) decreased signal intensity on ADC maps, and 3) Gd-enhancement. Objectively, FDG-PET and MR images were co-registered, and pixel-by-pixel comparison of ADC to PET values was made for all regions of interest. Correlation coefficients (r values) were calculated for each region of interest. Percentage overlap between regions of interest was calculated for each case. RESULTS: Subjective evaluation showed 60% of patients with excellent or good correlation between ADC maps and FDG-PET. Pixel-by-pixel comparison demonstrated r values that ranged from -0.72 to -0.21. There was significantly greater overlap between decreased ADC and increased FDG-PET uptake (67.1 +/- 15.5%) versus overlap between Gd-enhancement and increased FDG-PET uptake (54.4 +/- 27.5%) (P < .05). ADC overlap was greater with increased FDG-PET than with Gd-enhancement in 8/9 cases. Survival data revealed that the presence of restricted diffusion on ADC correlated with patient survival (P < .0001). CONCLUSIONS: ADC maps in patients with brain tumors provide unique information that is analogous to FDG-PET. There is a greater overlap between ADC and FDG-PET compared with Gd-enhancement. ADC maps can serve to approximate tumor grade and predict survival.

Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors. The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index (LI) for a group of controls, patients with tumor without prior surgery, and patients with tumor and prior surgery. MATERIALS AND METHODS: Seven controls, 9 patients with tumor without prior surgery, and 4 patients with tumor and prior surgery performed verb-generation, phonemic fluency, and semantic fluency language tasks during fMRI. Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs. LIs were compared within each group, between groups, and between language tasks. Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth. RESULTS: The language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Although patients and controls followed a similar shape in the LI curve, there was no optimal P value for determining the LI. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. Verb generation was the least variable task both between tasks and across groups. CONCLUSION: For preoperative patients with tumor, the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability. Our data suggest that the LI may be threshold- and task-dependent, particularly in the presence of adjacent tumor.

Meningioma of the mandible: imaging with CT.

We present the first description of CT of a meningioma of the mandible in the literature. Extracranial meningiomas are exceedingly rare. There have been 3 cases of meningioma of the mandible described in the literature, but none characterized with cross-sectional imaging. We describe the clinical and CT features used to establish the diagnosis as well as how to differentiate this lesion from other pathology of the mandible.