Functional MRI in Neuro-Oncology: State of the Art and Future Directions.

Since its discovery in the early 1990s, functional MRI (fMRI) has been used to study human brain function. One well-established application of fMRI in the clinical setting is the neurosurgical planning of patients with brain tumors near eloquent cortical areas. Clinical fMRI aims to preoperatively identify eloquent cortices that serve essential functions in daily life, such as hand movement and language. The primary goal of neurosurgery is to maximize tumor resection while sparing eloquent cortices adjacent to the tumor. When a lesion presents in the vicinity of an eloquent cortex, surgeons may use fMRI to plan their best surgical approach by determining the proximity of the lesion to regions of activation, providing guidance for awake brain surgery and intraoperative brain mapping. The acquisition of fMRI requires patient preparation prior to imaging, determination of functional paradigms, monitoring of patient performance, and both processing and analysis of images. Interpretation of fMRI maps requires a strong understanding of functional neuroanatomy and familiarity with the technical limitations frequently present in brain tumor imaging, including neurovascular uncoupling, patient compliance, and data analysis. This review discusses clinical fMRI in neuro-oncology, relevant ongoing research topics, and prospective future developments in this exciting discipline.

Effect of tumor genetics, pathology, and location on fMRI of language reorganization in brain tumor patients.

OBJECTIVES: Language reorganization may follow tumor invasion of the dominant hemisphere. Tumor location, grade, and genetics influence the communication between eloquent areas and tumor growth dynamics, which are drivers of language plasticity. We evaluated tumor-induced language reorganization studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness). METHODS: The study was retrospective cross-sectional. We included patients with left-hemispheric tumors (study group) and right-hemispheric tumors (controls). We calculated five fMRI laterality indexes (LI): hemispheric, temporal lobe, frontal lobe, Broca's area (BA), Wernicke's area (WA). We defined LI ≥ 0.2 as left-lateralized (LL) and LI < 0.2 as atypical lateralized (AL). Chi-square test (p < 0.05) was employed to identify the relationship between LI and tumor/patient variables in the study group. For those variables having significant results, confounding factors were evaluated in a multinomial logistic regression model. RESULTS: We included 405 patients (235 M, mean age: 51 years old) and 49 controls (36 M, mean age: 51 years old). Contralateral language reorganization was more common in patients than controls. The statistical analysis demonstrated significant association between BA LI and patient sex (p = 0.005); frontal LI, BA LI, and tumor location in BA (p < 0.001); hemispheric LI and fibroblast growth factor receptor (FGFR) mutation (p = 0.019); WA LI and O6-methylguanine-DNA methyltransferase promoter (MGMT) methylation in high-grade gliomas (p = 0.016). CONCLUSIONS: Tumor genetics, pathology, and location influence language laterality, possibly due to cortical plasticity. Increased fMRI activation in the right hemisphere was seen in patients with tumors in the frontal lobe, BA and WA, FGFR mutation, and MGMT promoter methylation. KEY POINTS: • Patients harboring left-hemispheric tumors present with contralateral translocation of language function. Influential variables for this phenomenon included frontal tumor location, BA location, WA location, sex, MGMT promoter methylation, and FGFR mutation. • Tumor location, grade, and genetics may influence language plasticity, thereby affecting both communication between eloquent areas and tumor growth dynamics. • In this retrospective cross-sectional study, we evaluated language reorganization in 405 brain tumor patients by studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness).

Association of Lack of Speech Arrest During Cortical Stimulation With Interhemispheric Reorganization of the Functional Language Network in Patients With Brain Tumors.

BACKGROUND. Brain tumors induce language reorganization, which may influence the extent of resection in surgical planning. Direct cortical stimulation (DCS) allows definitive language mapping during awake surgery by locating areas of speech arrest (SA) surrounding the tumor. Although functional MRI (fMRI) combined with graph theory analysis can illustrate whole-brain network reorganization, few studies have corroborated these findings with DCS intraoperative mapping and clinical language performance. OBJECTIVE. We evaluated whether patients with low-grade gliomas (LGGs) without SA during DCS show increased right-hemispheric connections and better speech performance compared with patients with SA. METHODS. We retrospectively recruited 44 consecutive patients with left perisylvian LGG, preoperative language task-based fMRI, speech performance evaluation, and awake surgery with DCS. We generated language networks from ROIs corresponding to known language areas (i.e., language core) on fMRI using optimal percolation. Language core connectivity in the left and right hemispheres was quantified as fMRI laterality index (LI) and connectivity LI on the basis of fMRI activation maps and connectivity matrices. We compared fMRI LI and connectivity LI between patients with SA and without SA and used multivariable logistic regression (p < .05) to assess associations between DCS and connectivity LI, fMRI LI, tumor location, Broca area and Wernicke area involvement, prior treatments, age, handedness, sex, tumor size, and speech deficit before surgery, within 1 week after surgery, and 3-6 months after surgery. RESULTS. Patients with SA showed left-dominant connectivity; patients without SA lateralized more to the right hemisphere (p < .001). Between patients with SA and those without, fMRI LI was not significantly different. Patients without SA showed right-greater-than-left connectivity of Broca area and premotor area compared with patients with SA. Regression analysis showed significant association between no SA and right-lateralized connectivity LI (p < .001) and fewer speech deficits before (p < .001) and 1 week after (p = .02) surgery. CONCLUSION. Patients without SA had increased right-hemispheric connections and right translocation of the language core, suggesting language reorganization. Lack of interoperative SA was associated with fewer speech deficits both before and immediately after surgery. CLINICAL IMPACT. These findings support tumor-induced language plasticity as a compensatory mechanism, which may lead to fewer postsurgical deficits and allow extended resection.

Decreased Hand Motor Resting-State Functional Connectivity in Patients with Glioma: Analysis of Factors including Neurovascular Uncoupling.

Background Resting-state functional MRI holds substantial potential for clinical application, but limitations exist in current understanding of how tumors exert local effects on resting-state functional MRI readings. Purpose To investigate the association between tumors, tumor characteristics, and changes in resting-state connectivity, to explore neurovascular uncoupling as a mechanism underlying these changes, and to evaluate seeding methodologies as a clinical tool. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant observational retrospective study of patients with glioma who underwent MRI and resting-state functional MRI between January 2016 and July 2017. Interhemispheric symmetry of connectivity was assessed in the hand motor region, incorporating tumor position, perfusion, grade, and connectivity generated from seed-based correlation. Statistical analysis was performed by using one-tailed t tests, Wilcoxon rank sum tests, one-way analysis of variance, Pearson correlation, and Spearman rank correlation, with significance at P < .05. Results Data in a total of 45 patients with glioma (mean age, 51.3 years ± 14.3 [standard deviation]) were compared with those in 10 healthy control subjects (mean age, 50.3 years ± 17.2). Patients showed loss of symmetry in measures of hand motor resting-state connectivity compared with control subjects (P < .05). Tumor distance from the ipsilateral hand motor (IHM) region correlated with the degree (R = 0.38, P = .01) and strength (R = 0.33, P = .03) of resting-state connectivity. In patients with World Health Organization grade IV glioblastomas 40 mm or less from the IHM region, loss of symmetry in strength of resting-state connectivity was correlated with tumor perfusion (R = 0.74, P < .01). In patients with gliomas 40 mm or less from the IHM region, seeding the nontumor hemisphere yielded less asymmetric hand motor resting-state connectivity than seeding the tumor hemisphere (connectivity seeded:contralateral = 1.34 nontumor vs 1.38 tumor hemisphere seeded; P = .03, false discovery rate threshold = 0.01). Conclusion Hand motor resting-state connectivity was less symmetrical in a tumor distance-dependent manner in patients with glioma. Differences in resting-state connectivity may be false-negative results driven by a neurovascular uncoupling mechanism. Seeding from the nontumor hemisphere may attenuate asymmetry in patients with tumors near ipsilateral hand motor cortices. © RSNA, 2020 Online supplemental material is available for this article.

T1-weighted Dynamic Contrast-enhanced MRI to Differentiate Nonneoplastic and Malignant Vertebral Body Lesions in the Spine.

Background Dynamic contrast agent-enhanced (DCE) perfusion MRI may help differentiate between nonneoplastic and malignant lesions in the spine. Purpose To investigate the correlation between fractional plasma volume (Vp), a parameter derived from DCE perfusion MRI, and histopathologic diagnosis for spinal lesions. Materials and Methods In this retrospective study, patients who underwent DCE perfusion MRI and lesion biopsy between May 2015 and May 2018 were included. Inclusion criteria were short time interval (<30 days) between DCE perfusion MRI and biopsy, DCE perfusion MRI performed before biopsy, and DCE perfusion MRI performed at the same spine level as biopsy. Exclusion criteria were prior radiation treatment on vertebrae of interest, poor DCE perfusion MRI quality, nondiagnostic biopsy, and extensive spinal metastasis or prior kyphoplasty. One hundred thirty-four lesions were separated into a nonneoplastic group (n = 51) and a malignant group (n = 83) on the basis of histopathologic analysis. Two investigators manually defined regions of interest in the vertebrae. DCE perfusion MRI parameter Vp was calculated by using the Tofts pharmacokinetic two-compartment model. Vp was quantified, normalized to adjacent normal vertebrae, and compared between the two groups. A Mann-Whitney U test and receiver operating characteristic analysis was performed to verify the difference in Vp between the nonneoplastic and malignant groups. Reproducibility was assessed by calculating the Cohen κ coefficient. Results One hundred patients (mean age, 65 years ± 11 [standard deviation]; 52 men) were evaluated. Vp was lower in nonneoplastic lesions versus malignant lesions (1.6 ± 1.3 vs 4.2 ± 3.0, respectively; P < .001). The sensitivity of Vp was 93% (77 of 83; 95% confidence interval [CI]: 85%, 97%), specificity was 78% (40 of 51; 95% CI: 65%, 89%), and area under the receiver operating characteristic curve was 0.88 (95% CI: 0.82, 0.95). Cohen κ coefficient suggested substantial agreement in both intra- (κ = 0.72) and interreader (κ = 0.70) reproducibility. Conclusion This study indicated that dynamic contrast agent-enhanced perfusion MRI parameter, fractional plasma volume, was able to differentiate between nonneoplastic spinal lesions and malignant lesions. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Haller in this issue.

DCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy.

PURPOSE: It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify pseudoprogression in melanoma brain metastases. METHODS: Patients with melanoma brain metastases who underwent immunotherapy and DCE-MRI were identified. Enhancing lesions ≥  5mm in diameter on DCE-MRI and that were new or increased in size between a week from beginning the treatment, and a month after completing the treatment were included in the analysis. The 90th percentiles of rVp and rKtrans and the presence or absence of hemorrhage were recorded. Histopathology served as the reference standard for pseudoprogression. If not available, pseudoprogression was defined as neurological and radiographic stability or improvement without any new treatment for ≥ 2 months. RESULTS: Forty-four patients were identified; 64% received ipilimumab monotherapy for a median duration of 9 weeks (range, 1-138). Sixty-four lesions in 44 patients were included in the study. Of these, nine lesions in eight patients were determined to be pseudoprogression and seven lesions were previously irradiated. Forty-four progression lesions and eight pseudoprogression lesions were hemorrhagic. Median lesion volume for pseudoprogression and progression were not significantly different, at 2.3 cm3 and 3.2 cm3, respectively (p = 0.82). The rVp90 was smaller in pseudoprogression versus progression, at 2.2 and 5.3, respectively (p = 0.02), and remained significant after false discovery rate adjustment (p = 0.04). CONCLUSIONS: Pseudoprogression exhibited significantly lower rVp90 on DCE-MRI compared with progression. This knowledge can be useful for managing growing lesions in patients with melanoma brain metastases who are receiving immunotherapy.

Correction to: Paradoxical Activation in the Cerebellum During Language fMRI in Patients with Brain Tumors: Possible Explanations Based on Neurovascular Uncoupling and Functional Reorganization.

The original version of this article unfortunately contained mistake in Funding information section.

Paradoxical Activation in the Cerebellum During Language fMRI in Patients with Brain Tumors: Possible Explanations Based on Neurovascular Uncoupling and Functional Reorganization.

The cerebellum is known for its crossed activation pattern with the contralateral cerebral hemisphere during language functional magnetic resonance imaging (fMRI) tasks in healthy patients. Crossed cerebro-cerebellar activation has been previously shown to occur in patients with brain tumors not affecting the activation areas. However, the presence of a tumor in left Broca's area in the inferior frontal gyrus is known to disrupt cerebral activation during language tasks. This study investigated if crossed cerebro-cerebellar activation patterns for language tasks would still occur in such patients. A total of 43 right-handed patients with a glioma affecting left Broca's area were examined for their cerebral and cerebellar activation during an fMRI language task. Only 13 of the 43 patients exhibited crossed cerebro-cerebellar activation patterns. Statistically significant differences of atypical cerebro-cerebellar activation patterns were found between cerebral right-dominant (RD) and cerebral co-dominant (CD) (p < 0.001) as well as cerebral RD and cerebral left-dominant (LD) patients (p < 0.01), while no differences were found when patients were divided based on cerebellar dominance (p > 0.75) or tumor grade (p > 0.5). No relation was found between the cerebellar and cerebral laterality index (LI) values (ρ = - 0.20; p = 0.21). Atypical activation patterns are suspected to have been caused by the tumor, perhaps a result of contralateral reorganization in some cases and false negative activation in left Broca's area from neurovascular uncoupling (NVU) in others. Cerebellar activation may also potentially indicate cerebral false negative behavior and future cerebral contralateral reorganization.

Pretreatment dynamic contrast-enhanced MRI biomarkers correlate with progression-free survival in primary central nervous system lymphoma.

PURPOSE: Prediction of clinical outcomes in patients with primary central nervous system lymphoma (PCNSL) is important for optimization of treatment planning. Quantitative imaging biomarkers for PCNSL have not yet been established. This study evaluated the prognostic value of pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging for progression-free survival (PFS) in patients with PCNSL. METHODS: Pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging were retrospectively analyzed in 18 immunocompetent patients with PCNSL. Volumes of interest encompassing the tumors were assessed for measurements of blood plasma volume (Vp), volume transfer constant (Ktrans), and apparent diffusion coefficient. Patients were divided into short and long PFS groups based on median PFS. Imaging and clinical variables were correlated with PFS. RESULTS: Median PFS was 19.6 months. Lower Vpmean and Ktransmean values increased risk for rapid progression (< 19.6 months). Receiver operating characteristic curve analysis demonstrated an optimal Vpmean cutoff value of 2.29 (area under the curve [AUC] = 0.74, sensitivity and specificity = 0.78, p = 0.023) for separating patients with short and long PFS. The optimal Ktransmean cutoff was 0.08 (AUC = 0.74, sensitivity = 0.67, specificity = 0.78, p = 0.025). Kaplan-Meier survival analysis with log-rank test demonstrated significantly (p = 0.015) increased risk of rapid progression for patients with Vpmean < 2.29. Vpmean was significantly (p = 0.03) associated with PFS on univariate Cox analysis. Apparent diffusion coefficient values and clinical factors did not influence PFS. CONCLUSIONS: Pretreatment Vp and Ktrans derived from dynamic contrast-enhanced MRI may be novel prognostic quantitative imaging biomarkers of progression-free survival in patients with PCNSL. These data should be prospectively validated in larger patient cohorts.

Dynamic contrast-enhanced magnetic resonance imaging of osseous spine metastasis before and 1 hour after high-dose image-guided radiation therapy.

OBJECTIVE High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies. METHODS Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (Vp) and vascular permeability (Ktrans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT. RESULTS The authors observed a precipitous drop in Vp within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between Vp values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in Vp (p = 0.31) and Ktrans (p = 0.1) from 1 hour after RT to the first follow-up. CONCLUSIONS The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in Vp. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.

Brain Tumors: The Influence of Tumor Type and Routine MR Imaging Characteristics at BOLD Functional MR Imaging in the Primary Motor Gyrus.

Purpose To evaluate the effects of histologic features and anatomic magnetic resonance (MR) imaging characteristics of brain tumors on the functional MR imaging signal in the primary motor cortex (PMC), as false-negative blood oxygen level-dependent (BOLD) functional MR imaging activation can limit the accurate localization of eloquent cortices. Materials and Methods Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. It comprised 63 patients referred between 2006 and 2014 for preoperative functional MR imaging localization of the Rolandic cortex. The patients had glioblastoma multiforme (GBM) (n = 20), metastasis (n = 21), or meningioma (n = 22). The volumes of functional MR imaging activation were measured during performance of a bilateral hand motor task. Ratios of functional MR imaging activation were normalized to PMC volume. Statistical analysis was performed for the following: (a) differences between hemispheres within each histologic tumor type (paired Wilcoxon test), (b) differences across tumor types (Kruskal-Wallis and Fisher tests), (c) pairwise tests between tumor types (Mann-Whitney U test), (d) relationships between fast fluid-attenuated inversion recovery (FLAIR) data and enhancement volume with activation (Spearman rank correlation coefficient), and (e) differences in activation volumes by tumor location (Mann-Whitney U test). Results A significant interhemispheric difference was found between the activation volumes in GBMs (mean, 511.43 voxels ± 307.73 [standard deviation] and 330.78 voxels ± 278.95; P < .01) but not in metastases (504.68 voxels ± 220.98 and 460.22 voxels ± 276.83; P = .15) or meningiomas (424.07 voxels ± 247.58 and 415.18 voxels ± 222.36; P = .85). GBMs showed significantly lower activation ratios (median, 0.49; range, 0.04-1.15) than metastases (median, 0.79; range, 0.28-1.66; P = .043) and meningiomas (median, 0.91; range, 0.52-2.05; P < .01). There was a moderate correlation with the volumes of FLAIR abnormality in metastases (ρ = -0.50) and meningiomas (ρ = -0.55). Enhancement volume (ρ = -0.11) and tumor distance from the PMC (median, 0.73 and range, 0.04-2.05 for near and median, 0.82 and range, 0.39-1.66 for far; P = .14) did not influence activation. Conclusion BOLD functional MR imaging activation in the ipsilateral PMC is influenced by tumor type and is significantly reduced in GBMs. FLAIR abnormality correlates moderately with the activation ratios in metastases and meningiomas. © RSNA, 2016 Online supplemental material is available for this article.

fMRI activation in the middle frontal gyrus as an indicator of hemispheric dominance for language in brain tumor patients: a comparison with Broca's area.

INTRODUCTION: Functional MRI (fMRI) can assess language lateralization in brain tumor patients; however, this can be limited if the primary language area-Broca's area (BA)-is affected by the tumor. We hypothesized that the middle frontal gyrus (MFG) can be used as a clinical indicator of hemispheric dominance for language during presurgical workup. METHODS: Fifty-two right-handed subjects with solitary left-hemispheric primary brain tumors were retrospectively studied. Subjects performed a verbal fluency task during fMRI. The MFG was compared to BA for fMRI voxel activation, language laterality index (LI), and the effect of tumor grade on the LI. RESULTS: Language fMRI (verbal fluency) activated more voxels in MFG than in BA (MFG = 315, BA = 216, p < 0.001). Voxel activations in the left-hemispheric MFG and BA were positively correlated (r = 0.69, p < 0.001). Mean LI in the MFG was comparable to that in BA (MFG = 0.48, BA = 0.39, p = 0.06). LIs in MFG and BA were positively correlated (r = 0.62, p < 0.001). Subjects with high-grade tumors demonstrate lower language lateralization than those with low-grade tumors in both BA and MFG (p = 0.02, p = 0.02, respectively). CONCLUSION: MFG is comparable to BA in its ability to indicate hemispheric dominance for language using a measure of verbal fluency and may be an adjunct measure in the clinical determination of language laterality for presurgical planning.

Differentiating benign from malignant vertebral fractures using T1 -weighted dynamic contrast-enhanced MRI.

PURPOSE: To differentiate pathologic from benign vertebral fractures, which can be challenging. We hypothesized that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can aid in the noninvasive distinction between pathologic and benign fractures. MATERIALS AND METHODS: Consecutive patients with vertebral fractures who underwent DCE-MRI, biopsy, and kyphoplasty were reviewed. Forty-seven fractures were separated into pathologic and benign fractures. Benign fractures were in turn separated into acute and chronic fractures for further comparison. Regions of interest (ROIs) were placed over fractured vertebral bodies. Perfusion parameters: plasma volume (Vp ), K(trans) , wash-in slope, peak enhancement, and area under the curve (AUC) were measured and compared between the three different groups of fractures. A Mann-Whitney U-test was conducted to assess the difference between the groups. RESULTS: Pathologic fractures had significantly higher (P < 0.01) perfusion parameters (Vp , K(trans) , wash-in slope, peak enhancement, and AUC) compared with benign fractures. We also found significant differences (P < 0.001) in all parameters between chronic and acute fractures. Vp and K(trans) were able to differentiate between pathologic and acute fractures (P < 0.01). No significant differences were found with peak enhancement (P = 0.21) and AUC (P = 0.4) between pathologic and acute fractures. CONCLUSION: Our data demonstrate that T1 -weighted DCE-MRI has potential to differentiate between pathologic vs. benign, acute vs. chronic, and most important, benign acute vs. pathologic vertebral fractures.

Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma.

Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85% sensitivity and 79% specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69% sensitivity and 79% specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI.

Resection of glioma in an fMRI-defined "split" Broca's area.

Gross total resection of gliomas can be limited by the involvement of tumor in eloquent areas. Moreover, lesions can impart cortical reorganization and make the precise determination of hemispheric dominance and localization of language function even more difficult. Preoperative mapping with functional magnetic resonance imaging (fMRI), intraoperative imaging modalities, and intraoperative direct cortical stimulation enable surgeons to map the functional topography of the brain in relation to the tumor and perform a safe maximal resection. In this report, we present a patient with left frontal glioma of complex morphology, wherein the tumor was enveloped by Broca's area on fMRI. Intraoperative mapping and intraoperative magnetic resonance imaging (iMRI) allowed gross total resection of the tumor with preservation of language function and illustrate the utility of multiple contemporary modalities in the surgical management of low-grade gliomas located in eloquent cortices.

Probabilistic fiber tracking of the language and motor white matter pathways of the supplementary motor area (SMA) in patients with brain tumors.

BACKGROUND AND PURPOSE: Accurate localization of anatomically and functionally separate SMA tracts is important to improve planning prior to neurosurgery. Using fMRI and probabilistic DTI techniques, we assessed the connectivity between the frontal language area (Broca's area) and the rostral pre-SMA (language SMA) and caudal SMA proper (motor SMA). MATERIALS AND METHODS: Twenty brain tumor patients completed motor and language fMRI paradigms and DTI. Peaks of functional activity in the language SMA, motor SMA and Broca's area were used to define seed regions for probabilistic tractography. RESULTS: fMRI and probabilistic tractography identified separate and unique pathways connecting the SMA to Broca's area - the language SMA pathway and the motor SMA pathway. For all subjects, the language SMA pathway had a larger number of voxels (P<0.0001) and higher connectivity (P<0.0001) to Broca's area than did the motor SMA pathway. In each patient, the number of voxels was greater in the language and motor SMA pathways than in background pathways (P<0.0001). No differences were found between patients with ipsilateral and those with contralateral tumors for either the language SMA pathway (degree of connectivity: P<0.36; number of voxels: 0.35) or the motor SMA pathway (degree of connectivity, P<0.28; number of voxels, P<0.74). CONCLUSION: Probabilistic tractography can identify unique white matter tracts that connect language SMA and motor SMA to Broca's area. The language SMA is more significantly connected to Broca's area than is the motor subdivision of the SMA proper.

Dynamic Contrast Enhanced MR Perfusion and Diffusion-Weighted Imaging of Marrow-Replacing Disorders of the Spine: A Comprehensive Review.

Significant advancements in cancer treatment have led to improved survival rates for patients, particularly in the context of spinal metastases. However, early detection and monitoring of treatment response remain crucial for optimizing patient outcomes. Although conventional imaging methods such as bone scan, PET, MR imaging, and computed tomography are commonly used for diagnosing and monitoring treatment, they present challenges in differential diagnoses and treatment response monitoring. This review article provides a comprehensive overview of the principles, applications, and practical uses of dynamic contrast-enhanced MR imaging and diffusion-weighted imaging in the assessment and monitoring of marrow-replacing disorders of the spine.

Tumors Affect the Metabolic Connectivity of the Human Brain Measured by 18F-FDG PET.

PURPOSE: 18F-FDG PET captures the relationship between glucose metabolism and synaptic activity, allowing for modeling brain function through metabolic connectivity. We investigated tumor-induced modifications of brain metabolic connectivity. PATIENTS AND METHODS: Forty-three patients with left hemispheric tumors and 18F-FDG PET/MRI were retrospectively recruited. We included 37 healthy controls (HCs) from the database CERMEP-IDB-MRXFDG. We analyzed the whole brain and right versus left hemispheres connectivity in patients and HC, frontal versus temporal tumors, active tumors versus radiation necrosis, and patients with high Karnofsky performance score (KPS = 100) versus low KPS (KPS < 70). Results were compared with 2-sided t test (P < 0.05). RESULTS: Twenty high-grade glioma, 4 low-grade glioma, and 19 metastases were included. The patients' whole-brain network displayed lower connectivity metrics compared with HC (P < 0.001), except assortativity and betweenness centrality (P = 0.001). The patients' left hemispheres showed decreased similarity, and lower connectivity metrics compared with the right (P < 0.01), with the exception of betweenness centrality (P = 0.002). HC did not show significant hemispheric differences. Frontal tumors showed higher connectivity metrics (P < 0.001) than temporal tumors, but lower betweenness centrality (P = 4.5-7). Patients with high KPS showed higher distance local efficiency (P = 0.01), rich club coefficient (P = 0.0048), clustering coefficient (P = 0.00032), betweenness centrality (P = 0.008), and similarity (P = 0.0027) compared with low KPS. Patients with active tumor(s) (14/43) demonstrated significantly lower connectivity metrics compared with necroses. CONCLUSIONS: Tumors cause reorganization of metabolic brain networks, characterized by formation of new connections and decreased centrality. Patients with frontal tumors retained a more efficient, centralized, and segregated network than patients with temporal tumors. Stronger metabolic connectivity was associated with higher KPS.

Longitudinal Evaluation of DCE-MRI as an Early Indicator of Progression after Standard Therapy in Glioblastoma.

Background and Purpose: Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI. Methods: We identified 26 patients from 2011 to 2023 with newly diagnosed primary glioblastoma by histopathology and gross or subtotal resection of the tumor. Then, we classified them into two groups: patients with progression of disease (POD) confirmed by pathology or change in chemotherapy and patients with stable disease without evidence of progression or need for therapy change. Finally, at least three DCE-MRI scans were performed prior to POD for the progression cohort, and three consecutive DCE-MRI scans were performed for those with stable disease. The volume of interest (VOI) was delineated by a neuroradiologist to measure the maximum values for Ktrans and plasma volume (Vp). A Friedman test was conducted to evaluate the statistical significance of the parameter changes between scans. Results: The mean interval between subsequent scans was 57.94 days, with POD-1 representing the first scan prior to POD and POD-3 representing the third scan. The normalized maximum Vp values for POD-3, POD-2, and POD-1 are 1.40, 1.86, and 3.24, respectively (FS = 18.00, p = 0.0001). It demonstrates that Vp max values are progressively increasing in the three scans prior to POD when measured by routine MRI scans. The normalized maximum Ktrans values for POD-1, POD-2, and POD-3 are 0.51, 0.09, and 0.51, respectively (FS = 1.13, p < 0.57). Conclusions: Our analysis of the longitudinal scans leading up to POD significantly correlated with increasing plasma volume (Vp). A longitudinal study for tumor perfusion change demonstrated that DCE perfusion could be utilized as an early predictor of tumor progression.

Differentiating Low-Grade from High-Grade Intracranial Ependymomas: Comparison of Dynamic Contrast-Enhanced MRI and Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: The aim of this study was to determine the diagnostic value of fractional plasma volume derived from dynamic contrast-enhanced perfusion MR imaging versus ADC, obtained from DWI in differentiating between grade 2 (low-grade) and grade 3 (high-grade) intracranial ependymomas. MATERIALS AND METHODS: A hospital database was created for the period from January 2013 through June 2022, including patients with histologically-proved ependymoma diagnosis with available dynamic contrast-enhanced MR imaging. Both dynamic contrast-enhanced perfusion and DWI were performed on each patient using 1.5T and 3T scanners. Fractional plasma volume maps and ADC maps were calculated. ROIs were defined by a senior neuroradiologist manually by including the enhancing tumor on every section and conforming a VOI to obtain the maximum value of fractional plasma volume (Vpmax) and the minimum value of ADC (ADCmin). A Mann-Whitney U test at a significance level of corrected P = .01 was used to evaluate the differences. Additionally, receiver operating characteristic curve analysis was applied to assess the sensitivity and specificity of Vpmax and ADCmin values. RESULTS: A total of 20 patients with ependymomas (10 grade 2 tumors and 10 grade 3 tumors) were included. Vpmax values for grade 3 ependymomas were significantly higher (P < .002) than those for grade 2. ADCmin values were overall lower in high-grade lesions. However, no statistically significant differences were found (P = .12114). CONCLUSIONS: As a dynamic contrast-enhanced perfusion MR imaging metric, fractional plasma volume can be used as an indicator to differentiate grade 2 and grade 3 ependymomas. Dynamic contrast-enhanced perfusion MR imaging plays an important role with high diagnostic value in differentiating low- and high-grade ependymoma.