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The objectives of this study are to describe central nervous system modulation associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis. Serial functional magnetic resonance imaging scans were performed before as well as one and six months after thyroplasty. Paradigms consisting of four voice production tasks and a motor control task were completed. Volumes of activation within regions activated during each task were measured. Acoustic and aerodynamic measures were also obtained. A widespread network of neural activations was shown for all tasks. Differences in volumes of activation 1-month postsurgery positively correlated with acoustic and aerodynamic improvements. Sixth months following medialization, lesser volumes of activation were observed in all regions. Prior to this session, however, the patient's mediastinal disease progressed, leading to a significant deterioration in voice. Functional differences between patient brain maps yield new information about the central nervous system's ability to reorganize sensorimotor representations associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis (UVFP). [ABSTRACT FROM AUTHOR]

Advanced magnetic resonance imaging (MRI) techniques, such as spectroscopy, perfusion, and functional imaging, have improved the imaging of brain tumors. In addition to the anatomic or structural information available with conventional MRI, advanced MRI techniques also provide physiologic information about tumor metabolism and hemodynamics. The authors review the physiology, techniques, and clinical applications of perfusion MRI, spectroscopy, functional MRI, and diffusion tensor imaging in the setting of neuro-oncology. [ABSTRACT FROM AUTHOR]

Purpose: 18 F-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 18 F-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., Competing Interests: Conflicts of interest and sources of funding: Andrei Holodny is the Owner/President of fMRI Consultants, LLC, a purely educational entity. This study was supported by NIH/NCI Cancer Center Support Grant P30 CA008748 (PI: Vickers), NIH/NIBIB R01 EB022720 (PIs: Makse and Holodny), and NIH/NCI R21 CA220144 (PIs: Holodny and Peck)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 (Vp max ) and the minimum value of ADC (ADC min ). 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 Vp max and ADC min values., Results: A total of 20 patients with ependymomas (10 grade 2 tumors and 10 grade 3 tumors) were included. Vp max values for grade 3 ependymomas were significantly higher ( P  < .002) than those for grade 2. ADC min 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., (© 2024 by American Journal of Neuroradiology.)

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.

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., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2024 by American Journal of Neuroradiology.)

Background and Purpose: Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure., Materials and Methods: This retrospective study included 49 patients (mean age, 63 [SD, 13] years; 29 men) with metastatic lesions treated with radiation therapy who underwent dynamic contrast-enhanced MR imaging. The median time between radiation therapy and follow-up dynamic contrast-enhanced MR imaging was 62 days. We divided patients into 2 groups: clinical success ( n = 38) and failure ( n = 11). Failure was defined as PET recurrence ( n = 5), biopsy-proved ( n = 1) recurrence, or an increase in tumor size ( n = 7), while their absence defined clinical success. A Mann-Whitney U test was performed to assess differences between groups., Results: The reduction in plasma volume was greater in the success group than in the failure group (-57.3% versus +88.2%, respectively; P < .001). When we assessed the success of treatment, the sensitivity of plasma volume was 91% (10 of 11; 95% CI, 82%-97%) and the specificity was 87% (33 of 38; 95% CI, 73%-94%). The sensitivity of size measurements was 82% (9 of 11; 95% CI, 67%-90%) and the specificity was 47% (18 of 38; 95% CI, 37%-67%)., Conclusions: The specificity of plasma volume was higher than that of conventional size measurements, suggesting that dynamic contrast-enhanced MR imaging is a powerful tool to discriminate between treatment success and failure., (© 2023 by American Journal of Neuroradiology.)

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.

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., (© RSNA, 2023.)

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)., (© 2023. The Author(s).)

Recent therapeutic advances have led to increased survival times for patients with metastatic disease. Key to survival is early diagnosis and subsequent treatment as well as early detection of treatment failure allowing for therapy modifications. Conventional MR imaging techniques of the spine can be at times suboptimal for identifying viable tumor, as structural changes and imaging characteristics may not differ pretreatment and posttreatment. Advanced imaging techniques such as DCE-MRI can allow earlier and more accurate noninvasive assessment of viable disease by characterizing physiologic changes and tumor microvasculature., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Resting-state functional magnetic resonance imaging (rsfMRI) has been proposed as an alternative to task-based fMRI including clinical situations such as preoperative brain tumor planning, due to advantages including ease of performance and time savings. However, one of its drawbacks is the limited ability to accurately lateralize language function., Methods: Using the rsfMRI data of healthy controls, we carried out a power spectra analysis on three regions of interest (ROIs): Broca's area (BA) in the frontal cortex for language, hand motor (HM) area in the primary motor cortex, and the primary visual cortex (V1). Spike removal, motion correction, linear trend removal, and spatial smoothing were applied. Spontaneous low-frequency fluctuations (0.01-0.1 Hz) were filtered to enable functional integration., Results: BA showed greater power on the left hemisphere relative to the right (p = .0055), while HM (p = .1563) and V1 (p = .4681) were not statistically significant. A novel index, termed the power laterality index (PLI), computed to estimate the degree of power lateralization for each brain region, revealed a statistically significant difference between BA and V1 (p < .00001), where V1 was used as a control since the primary visual cortex does not lateralize. Validation studies used to compare PLI to a laterality index computed using phonemic fluency, a task-based, language fMRI paradigm, demonstrated good correlation., Conclusions: The power spectra for BA revealed left language lateralization, which was not replicated in HM or V1. This work demonstrates the feasibility and validity of an ROI-based power spectra analysis on rsfMRI data for language lateralization., (© 2023 American Society of Neuroimaging.)

Aim: Because the tongue is a midline structure, studies on the neural correlates of lateralized tongue function are challenging and remain limited. Patients with tongue cancer who undergo unilateral partial glossectomy may be a unique cohort to study tongue-associated cortical activation, particularly regarding brain hemispheric lateralization. This longitudinal functional magnetic resonance imaging (fMRI) study investigated cortical activation changes for three tongue tasks before and after left-sided partial glossectomy in patients with squamous cell carcinoma of the tongue., Methods: Seven patients with squamous cell carcinoma involving the left tongue who underwent fMRI before and 6 months after unilateral partial glossectomy were studied. Post-surgical changes in laterality index (LI) values for tongue-associated precentral and postcentral gyri fMRI activation were calculated for the dry swallow, tongue press, and saliva sucking tasks. Group analysis fMRI activation maps were generated for each of the three tasks., Results: There were significant differences in changes in LI values post-surgery between the tongue press ( p < 0.005; median: +0.24), saliva sucking (-0.10), and dry swallow tasks (-0.16). Decreased contralateral activation (change in LI ≥+0.20) was observed post-surgery during tongue press in six of seven patients, but only in two patients during saliva sucking and one patient during dry swallow ( p < 0.05). There was also increased activation in the supplementary motor area following surgery., Conclusion: Post-surgical fMRI changes following left-sided partial glossectomy may suggest task-specific sensitivities to cortical activation changes following unilateral tongue deficits that may reflect the impacts of surgery and adaptive responses to tongue impairment.

Dynamic contrast-enhanced MRI (DCE) is an emerging modality in the study of vertebral body malignancies. DCE-MRI analysis relies on a pharmacokinetic model, which assumes that contrast uptake is simultaneous in the feeding of arteries and tissues of interest. While true in the highly vascularized brain, the perfusion of the spine is delayed. This delay of contrast reaching vertebral body lesions can affect DCE-MRI analyses, leading to misdiagnosis for the presence of active malignancy in the bone marrow. To overcome the limitation of delayed contrast arrival to vertebral body lesions, we shifted the arterial input function (AIF) curve over a series of phases and recalculated the plasma volume values (V p ) for each phase shift. We hypothesized that shifting the AIF tracer curve would better reflect actual contrast perfusion, thereby improving the accuracy of V p maps in metastases. We evaluated 18 biopsy-proven vertebral body metastases in which standard DCE-MRI analysis failed to demonstrate the expected increase in V p . We manually delayed the AIF curve for multiple phases, defined as the scan-specific phase temporal resolution, and analyzed DCE-MRI parameters with the new AIF curves. All patients were found to require at least one phase-shift delay in the calculated AIF to better visualize metastatic spinal lesions and improve quantitation of V p . Average normalized V p values were 1.78 ± 1.88 for zero phase shifts (P0), 4.72 ± 4.31 for one phase shift (P1), and 5.59 ± 4.41 for two phase shifts (P2). Mann-Whitney U tests obtained p -values = 0.003 between P0 and P1, and 0.0004 between P0 and P2. This study demonstrates that image processing analysis for DCE-MRI in patients with spinal metastases requires a careful review of signal intensity curve, as well as a possible adjustment of the phase of aortic AIF to increase the accuracy of V p .

Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and standardized language assessment. We hypothesized that functional networks obtained from tb-fMRI would show connectivity changes over time, with increased right-hemispheric participation. We recruited five right-handed patients (4M, mean age 47.6Y) with left-hemispheric LGG. Tb-fMRI and language assessment were conducted pre-operatively (pre-op), and post-operatively: post-op1 (4-8 months), post-op2 (10-14 months) and post-op3 (16-23 months). We computed the individual functional networks applying optimal percolation thresholding. Language dominance and hemispheric connectivity were quantified by laterality indices (LI) on fMRI maps and connectivity matrices. A fixed linear mixed model was used to assess the intra-patient correlation trend of LI values over time and their correlation with language performance. Individual networks showed increased inter-hemispheric and right-sided connectivity involving language areas homologues. Two patterns of language reorganization emerged: Three/five patients demonstrated a left-to-codominant shift from pre-op to post-op3 (type 1). Two/five patients started as atypical dominant at pre-op, and remained unchanged at post-op3 (type 2). LI obtained from tb-fMRI showed a significant left-to-right trend in all patients across timepoints. There were no significant changes in language performance over time. Type 1 language reorganization may be related to the treatment, while type 2 may be tumor-induced, since it was already present at pre-op. Increased inter-hemispheric and right-side connectivity may represent the initial step to develop functional plasticity.

Background: Language function may reorganize to overcome focal impairment; however, the relation between functional and structural changes in patients with brain tumors remains unclear. We investigated the cortical volume of atypical language dominant (AD) patients with left frontal-insular high-grade (HGG) and low-grade glioma (LGG). We hypothesized atypical language being associated with areas of increased cortical volume in the right hemisphere, including language areas homologues., Methods: Patient were recruited following the criteria: left frontal-insular glioma; functional MRI and 3DT1-weighted images; no artifacts. We calculated an hemispheric language laterality index (LI), defined as: AD if LI < .2; left-dominant (LD) if LI ≥ .2. We measured cortical volume in three voxel-based morphometry (VBM) analyses: total AD vs. LD patients; AD vs. LD in HGG; AD vs. LD in LGG. We repeated the analysis in AD vs. LD healthy controls (HC). A minimum threshold of t > 2 and corrected p < .025 (Bonferroni) was employed., Results: We recruited 119 patients (44LGG, 75HGG). Hemispheric LI demonstrated 64/119AD and 55/119LD patients. The first VBM analysis demonstrated significantly increased cortical volume in AD patients in the right inferior frontal gyrus (IFG), right superior temporal gyrus (STG), right insula, right fusiform gyrus (FG), right precentral gyrus, right temporal-parietal junction, right posterior cingulate cortex (PCC), right hippocampus, right- and left cerebellum. AD patients with HGG showed the same areas of significantly increased cortical volume. AD patients with LGG displayed significantly increased cortical volume in right IFG, right STG, right insula, right FG, right anterior cingulate cortex, right PCC, right dorsal-lateral prefrontal cortex. HC showed no significant results., Conclusion: Right-sided (atypical) language activations in patients with left-hemispheric gliomas are associated with areas of increased cortical volume. Additionally, default mode network nodes showed greater cortical volume in AD patients regardless of the tumor grade, supporting the idea of these cortices participating in the development of language plasticity., Competing Interests: Conflict of interest AH: Owner/President of fMRI Consultants, LLC, a purely educational entity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The ability of functional MRI (fMRI) to localize patient-specific eloquent areas has proved worthwhile in efforts to maximize resection while minimizing risk of iatrogenic damage in patients with brain tumors. Although cortical reorganization has been described, the frequency of its occurrence and the factors that influence incidence are not well understood. The authors investigated changes in language laterality between 2 fMRI studies in patients with brain tumors to elucidate factors contributing to cortical reorganization., Methods: The authors analyzed 33 patients with brain tumors involving eloquent language areas who underwent 2 separate presurgical, language task-based fMRI examinations (fMRI1 and fMRI2). Pathology consisted of low-grade glioma (LGG) in 15, and high-grade glioma (HGG) in 18. The mean time interval between scans was 35 ± 38 months (mean ± SD). Regions of interest were drawn for Broca's area (BA) and the contralateral BA homolog. The laterality index (LI) was calculated and categorized as follows: > 0.2, left dominance; 0.2 to -0.2, codominance; and < -0.2, right dominance. Translocation of language function was defined as a shift across one of these thresholds between the 2 scans. Comparisons between the 2 groups, translocation of language function (reorganized group) versus no translocation (constant group), were performed using the Mann-Whitney U-test., Results: Nine (27%) of 33 patients demonstrated translocation of language function. Eight of 9 patients with translocation had tumor involvement of BA, compared to 5/24 patients without translocation (p < 0.0001). There was no difference in LI between the 2 groups at fMRI1. However, the reorganized group showed a decreased LI at fMRI2 compared to the constant group (-0.1 vs 0.53, p < 0.01). The reorganized cohort showed a significant difference between LI1 and LI2 (0.50 vs -0.1, p < 0.0001) whereas the constant cohort did not. A longer time interval was found in the reorganized group between fMRI1 and fMRI2 for patients with LGG (34 vs 107 months, p < 0.002). Additionally, the reorganized cohort had a greater proportion of local tumor invasion into eloquent areas at fMRI2 than the constant group. Aphasia was present following fMRI2 in 13/24 (54%) patients who did not exhibit translocation, compared to 2/9 (22%) patients who showed translocation., Conclusions: Translocation of language function in patients with brain tumor is associated with tumor involvement of BA, longer time intervals between scans, and is seen in both LGG and HGG. The reduced incidence of aphasia in the reorganized group raises the possibility that reorganization supports the conservation of language function. Therefore, longitudinal fMRI is useful because it may point to reorganization and could affect therapeutic planning for patients.

Brain tumors lead to modifications of brain networks. Graph theory plays an important role in clarifying the principles of brain connectivity. Our objective was to investigate network modifications related to tumor grade and location using resting-state functional magnetic resonance imaging (fMRI) and graph theory. We retrospectively studied 30 low-grade (LGG), 30 high-grade (HGG) left-hemispheric glioma patients and 20 healthy controls (HC) with rs-fMRI. Tumor location was labeled as: frontal, temporal, parietal, insular or occipital. We collected patients’ clinical data from records. We analyzed whole-brain and hemispheric networks in all patients and HC. Subsequently, we studied lobar networks in subgroups of patients divided by tumor location. Seven graph-theoretical metrics were calculated (FDR p < 0.05). Connectograms were computed for significant nodes. The two-tailed Student t-test or Mann−Whitney U-test (p < 0.05) were used to compare graph metrics and clinical data. The hemispheric network analysis showed increased ipsilateral connectivity for LGG (global efficiency p = 0.03) and decreased contralateral connectivity for HGG (degree/cost p = 0.028). Frontal and temporal tumors showed bilateral modifications; parietal and insular tumors showed only local effects. Temporal tumors led to a bilateral decrease in all graph metrics. Tumor grade and location influence the pattern of network reorganization. LGG may show more favorable network changes than HGG, reflecting fewer clinical deficits.

When the language-dominant hemisphere is damaged by a focal lesion, the brain may reorganize the language network through functional and structural changes known as adaptive plasticity. Adaptive plasticity is documented for triggers including ischemic, tumoral, and epileptic focal lesions, with effects in clinical practice. Many questions remain regarding language plasticity. Different lesions may induce different patterns of reorganization depending on pathologic features, location in the brain, and timing of onset. Neuroimaging provides insights into language plasticity due to its non-invasiveness, ability to image the whole brain, and large-scale implementation. This review provides an overview of language plasticity on MRI with insights for patient care. First, we describe the structural and functional language network as depicted by neuroimaging. Second, we explore language reorganization triggered by stroke, brain tumors, and epileptic lesions and analyze applications in clinical diagnosis and treatment planning. By comparing different focal lesions, we investigate determinants of language plasticity including lesion location and timing of onset, longitudinal evolution of reorganization, and the relationship between structural and functional changes., Competing Interests: AH is the Owner/President of fMRI Consultants, LLC, a purely educational entity. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pasquini, Di Napoli, Rossi-Espagnet, Visconti, Napolitano, Romano, Bozzao, Peck and Holodny.)

Brain tumors can have far-reaching impacts on functional networks. Language processing is typically lateralized to the left hemisphere, but also involves the right hemisphere and cerebellum. This resting-state functional MRI study investigated the proximal and distal effects of left-hemispheric brain tumors on language network connectivity in the ipsilesional and contralesional hemispheres. Separate language resting-state networks were generated from seeding in ipsilesional (left) and contralesional (right) Broca's Area for 29 patients with left-hemispheric brain tumors and 13 controls. Inclusion criteria for all subjects included language left-dominance based on task-based functional MRI. Functional connectivity was analyzed in each network to the respective Wernicke's Area and contralateral cerebellum. Patients were assessed for language deficits prior to scanning. Compared to controls, patients exhibited decreased connectivity in the ipsilesional and contralesional hemispheres between the Broca's Area and Wernicke's Area homologs (mean connectivity for patients/controls: left 0.51/0.59, p < 0.002; right 0.52/0.59, p < 0.0002). No differences in mean connectivity to the contralateral cerebellum were observed between groups (p > 0.09). Crossed cerebro-cerebellar connectivity was correlated in controls (rho = 0.59, p < 0.05), patients without language deficits (rho = 0.74, p < 0.0002), and patients with high-grade gliomas (rho = 0.78, p < 0.0002), but not in patients with language deficits or low-grade gliomas (p > 0.l). These findings demonstrate that brain tumors impact the language network in the contralesional hemisphere and cerebellum, which may reflect neurological deficits and lesion-induced cortical reorganization., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021 by American Journal of Neuroradiology.)

Background and Purpose: Assessment of the essential white matter fibers of arcuate fasciculus and corticospinal tract (CST), required for preoperative planning in brain tumor patients, relies on the reliability of diffusion tensor imaging (DTI). The recent development of multiband DTI (mb-DTI) based on simultaneous multislice excitation could maintain the overall quality of tractography while not exceeding standard clinical care time. To address this potential, we performed quantitative analyses to evaluate tractography results of arcuate fasciculus and CST acquired by mb-DTI in brain tumor patients., Methods: We retrospectively analyzed 44 patients with brain lesions who underwent presurgical single-shot DTI (s-DTI) and mb-DTI. We measured DTI parameters: fractional anisotropy (FA) and mean diffusivity (MD [mm 2 s -1 ]) in whole brain and tumor regions; and the tractography parameters: fiber FA, MD (mm 2 s -1 ), volume (mm 3 ), and length (mm) in the whole brain, arcuate fasciculus, and CST. Additionally, three neuroradiologists performed a blinded visual assessment comparing s-DTI with mb-DTI., Results: The mb-DTI showed higher mean FA and lower MD (r > .95, p < .002) in whole brain and tumor regions of interest; slightly higher fiber FA, volume, and length; and slightly lower fiber MD in whole brain, arcuate fasciculus, and CST than in s-DTI. These differences were significant for fiber FA in all tracts; length (mm) in arcuate fasciculus; and fiber MD (mm 2 s -1 ) and volume (mm 3 ) in all patients with tumor involved in the arcuate fasciculus, CST, and whole brain tracts (p = .001). Visual assessment demonstrated that both techniques produced visually similar tracts., Conclusions: This study demonstrated the clinical potential and significant advantages of preoperative mb-DTI in brain tumor patients., (© 2021 American Society of Neuroimaging.)

Bilingualism requires control of multiple language systems, and may lead to architectural differences in language networks obtained from clinical fMRI tasks. Emerging connectivity metrics such as k-core may capture these differences, highlighting crucial network components based on resiliency. We investigated the influence of bilingualism on clinical fMRI language tasks and characterized bilingual networks using connectivity metrics to provide a patient care benchmark. Sixteen right-handed subjects (mean age 42-years; nine males) without neurological history were included: eight native English-speaking monolinguals and eight native Spanish-speaking (L1) bilinguals with acquired English (L2). All subjects underwent fMRI with gold-standard clinical language tasks. Starting from active clusters on fMRI, we inferred the persistent functional network across subjects and ran centrality measures to characterize differences. Our results demonstrated a persistent network "core" consisting of Broca's area, the pre-supplementary motor area, and the premotor area. K-core analysis showed that Wernicke's area was engaged by the "core" with weaker connection in L2 than L1.

There are many technical and nontechnical steps involved in a successful clinical functional MRI (fMRI) scan. The output from scanning and analysis can only be as good as the input, so task instruction and rehearsal are the most important steps during an clinical fMRI procedure. Properly pre-processed data significantly affects statistical analysis, which has a great impact on image interpretation. Even though there is general agreement on how to process clinical fMRI data, such as algorithms for head motion detection and correction, the theory and practicalities associated with data processing remain complex and constantly evolving., Competing Interests: Disclosure K.K. Peck and N.S. Cho have nothing to disclose. AH is the Owner/President of fMRI Consultants, LLC, a purely educational entity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 ( V p ), 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 V p was calculated by using the Tofts pharmacokinetic two-compartment model. V p 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 V p 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. V p was lower in nonneoplastic lesions versus malignant lesions (1.6 ± 1.3 vs 4.2 ± 3.0, respectively; P < .001). The sensitivity of V p 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.

Competing Interests: Declaration of competing interest None.

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.

Functional magnetic resonance imaging (fMRI) is widely used in clinical applications to highlight brain areas involved in specific cognitive processes. Brain impairments, such as tumors, suppress the fMRI activation of the anatomical areas they invade and, thus, brain-damaged functional networks present missing links/areas of activation. The identification of the missing circuitry components is of crucial importance to estimate the damage extent. The study of functional networks associated with clinical tasks but performed by healthy individuals becomes, therefore, of paramount concern. These "healthy" networks can, indeed, be used as control networks for clinical studies. In this work we investigate the functional architecture of 20 healthy individuals performing a language task designed for clinical purposes. We unveil a common architecture persistent across all subjects under study, that we call "core" network, which involves Broca's area, Wernicke's area, the premotor area, and the pre-supplementary motor area. We study the connectivity of this circuitry by using the k -core centrality measure, and we find that three of these areas belong to the most robust structure of the functional language network for the specific task under study. Our results provide useful insights on primarily important functional connections., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2019 Massachusetts Institute of Technology.)

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 cm 3 and 3.2 cm 3 , respectively (p = 0.82). The rVp 90 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 rVp 90 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.

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Background and Purpose: We examined the resting-state functional connectivity (RSFC) of the supplementary motor area (SMA) in brain tumor patients. We compared the SMA subdivisions (pre-SMA, SMA proper, central SMA) in terms of RSFC projected from each region to the motor gyrus and language areas., Methods: We retrospectively identified 14 brain tumor patients who underwent task-based and resting-state fMRI, and who completed motor and language paradigms that activated the SMA proper and pre-SMA, respectively. Regions of interest (ROIs) obtained from task-based fMRI were generated in both areas and the central SMA to produce RSFC maps. Degree of RSFC was measured from each subdivision to the motor gyrus and Broca's area (BA)., Results: All patients showed RSFC between the pre-SMA and language centers and between the SMA proper and motor gyrus. Thirteen of 14 patients showed RSFC from the central SMA to both motor and language areas. There was no significant difference between subdivisions in degree of RSFC to BA (pre-SMA, r = .801; central SMA, r = .803; SMA proper; r = .760). The pre-SMA showed significantly less RSFC to the motor gyrus (r = .732) compared to the central SMA (r = .842) and SMA proper (r = .883) (P = .016, P = .001, respectively)., Conclusions: The region between the pre-SMA and SMA proper produces reliable RSFC to the motor gyrus and language areas in brain tumor patients. This study is the first to examine RSFC of the central SMA in this population. Consequently, our results provide further validation to previous studies, supporting the existence of a central SMA with connectivity to both motor and language networks., (© 2019 by the American Society of Neuroimaging.)

Purpose: Preoperative functional MRI (fMRI) is limited by a muted BOLD response caused by abnormal vasoreactivity and resultant neurovascular uncoupling adjacent to malignant brain tumors. We propose to overcome this limitation and more accurately identify eloquent areas adjacent to brain tumors by independently assessing vasoreactivity using breath-holding and incorporating these data into the fMRI analysis., Methods: Local vasoreactivity using a breath-holding paradigm with the same timing as the functional motor and language tasks was determined in 16 patients (9 glioblastomas, 1 anaplastic astrocytoma, 5 low grade astrocytomas, and 1 metastasis) and 6 healthy control subjects. We derived an fMRI model based on an observed vaso-task response dependency that takes into account the altered hemodynamics adjacent to brain tumors., Results: In both healthy controls and brain tumor subjects, we found a statistical dependency between breath-hold and task BOLD response. In tumor subjects, activation maps that take into account this vaso-task dependency demonstrated clinically meaningful areas of activation that were not seen using the task-only analysis in about half of the cases studied. This included localization of language areas adjacent to brain tumors., Conclusions: The present preliminary results demonstrate that neurovascular uncoupling known to affect the accuracy of BOLD fMRI adjacent to brain tumors may be, at least partially, overcome by incorporating an observed vaso-task dependency in the BOLD signal analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 (K trans ), 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 Vp mean and K trans mean values increased risk for rapid progression (< 19.6 months). Receiver operating characteristic curve analysis demonstrated an optimal Vp mean 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 K trans mean 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 Vp mean < 2.29. Vp mean 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 K trans 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.

The primary hand motor region is classically believed to be in the "hand knob" area in the precentral gyrus (PCG). However, hand motor task-based activation is often localized outside this area. The purpose of this study is to investigate the structural and functional connectivity driven by different seed locations corresponding to the little, index, and thumb in the PCG using probabilistic diffusion tractography (PDT) and resting-state functional magnetic resonance imaging (rfMRI). Twelve healthy subjects had three regions of interest (ROIs) placed in the left PCG: lateral to the hand knob (thumb area), within the hand knob (index finger area), and medial to the hand knob (little finger area). Connectivity maps were generated using PDT and rfMRI. Individual and group level analyses were performed. Results show that the greatest hand motor connectivity between both hemispheres was obtained using the ROI positioned just lateral to the hand knob in the PCG (the thumb area). The number of connected voxels in the PCG between the two hemispheres was greatest in the lateral-most ROI (the thumb area): 279 compared with 13 for the medial-most ROI and 9 for the central hand knob ROI. Similarly, the highest white matter connectivity between the two hemispheres resulted from the ROI placed in the lateral portion of PCG (p < 0.003). The maximal functional and structural connectivity of the hand motor area between hemispheres occurs in the thumb area, located laterally at the "hand knob." Thus, this location appears maximal for rfMRI and PDT seeding of the motor area.

Calcifying pseudoneoplasms of the neuraxis are extremely rare calcified lesions that can occur anywhere in the central nervous system. These non-neoplastic lesions have been reported to arise both in the brain and spine with similar frequency and can be found intra-axially as well as extra-axially. The associated symptoms are generally due to mass effect rather than local invasion as calcifying pseudoneoplasms of the neuraxis are usually considered to be benign non-infiltrative lesions. We report a unique case of a 67-year-old male patient who developed lower extremity weakness and gait instability with imaging and histological features of calcifying pseudoneoplasm of the neuraxis occurring in the spine with adhesive features and intradural extension. Calcifying pseudoneoplasms are benign, slow-growing masses that can present with a wide variety of symptoms depending on the size and location of the tumor. The differential diagnosis for these entities can be narrowed taking into consideration relevant imaging features as well as important clinical information.

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.

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., (© 2018 by American Journal of Neuroradiology.)

Background and Purpose: The corpus callosum (CC) has an important role in regulating interhemispheric transfer and is thought to be instrumental in contralateral brain reorganization in patients with brain tumors, as suggested by a previous study reporting callosal differences between language dominance groups through diffusion tensor imaging (DTI) characteristics. The purpose of this study was to explore the structural differences in the CC between high-grade gliomas (HGGs) and metastatic tumors (METs) using the DTI characteristics of fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD)., Methods: HGG (n = 30) and MET (n = 20) subjects with Magnetic Resonance Imaging (MRI) scans including DTI were retrospectively studied. The tumor and CC were segmented using the 3-dimensional T1-weighted scans to determine their volumes. The region of interest (ROI; mean volume of the ROI = 3,090 ± 464 mm 3 ) of the body of the CC was overlaid onto the DTI parametric maps to obtain the averaged FA, MD, and AD values., Results: There were significant differences in the distributions of FA and MD values between the two patient groups (mean FA for HGG/MET = .691/.646, P < .05; mean MD for HGG/MET = .894×10-3 mm 2/ second /.992×10-3 mm 2 /second, P < .01), while there was no correlation between the DTI parameters and the anatomical volumes., Conclusion: These results suggest that there is more contralateral brain reorganization in HGG patients than MET patients and that neither the tumor nor callosal volume impact the degree of contralateral brain reorganization., (Copyright © 2017 by the American Society of Neuroimaging.)

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.

Purpose: Dynamic contrast-enhanced magnetic resonance imaging offers noninvasive characterization of the vascular microenvironment and hemodynamics. Stereotactic radiosurgery, or stereotactic body radiation therapy, engages a vascular component of the tumor response which may be detectable using dynamic contrast-enhanced magnetic resonance imaging. The purpose of this study is to examine whether dynamic contrast-enhanced magnetic resonance imaging can be used to predict local tumor recurrence in patients with spinal bone metastases who undergo high-dose radiotherapy with stereotactic radiosurgery., Materials and Methods: We conducted a study of 30 patients with spinal metastases who underwent dynamic contrast-enhanced magnetic resonance imaging before and after radiotherapy. Twenty patients received single-fraction stereotactic radiosurgery (24 Gy), while 10 received hypofractionated stereotactic radiosurgery (3-5 fractions, 27-30 Gy total). Kaplan-Meier analysis was used to estimate the actuarial local recurrence rates. Two perfusion parameters (K trans : permeability and V p : plasma volume) were measured for each metastasis. Percentage change in parameter values from pre- to posttreatment was calculated and compared., Results: At 20-month median follow-up, 5 of the 30 patients had pathological evidence of local recurrence. One- and 3-year actuarial local recurrence rates were 24% and 44% for the hypofractionated stereotactic radiosurgery cohort versus 5% and 16% for the single-fraction stereotactic radiosurgery cohort ( P = .20). The average change in V p and K trans for patients without local recurrence versus those with local recurrence was -76% and -66% versus +28% and -14% ( P < .01 for both). With a cutoff point of -20%, V p had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 98%, 91%, and 100%, respectively, for the detection of local recurrence following high-dose radiotherapy. Using this definition, dynamic contrast-enhanced magnetic resonance imaging identified local recurrence up to 18 months (mean [standard deviation], 6.6 [6.8] months) earlier than standard magnetic resonance imaging., Conclusions: We demonstrated that changes in perfusion parameters, particularly V p , after high-dose radiotherapy to spinal bone metastases were predictive of local tumor recurrence. These changes predicted local recurrence on average >6 months earlier than standard imaging did.

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., (© 2017 by American Journal of Neuroradiology.)

An abundance of evidence points to the role of a presupplementary motor area (pre-SMA) in human language. This study explores the pre-SMA resting state connectivity network and the nature of its connections to known language areas. We tested the hypothesis that by seeding the pre-SMA, one would be able to establish language laterality to known cortical and subcortical language areas. We analyzed data from 30 right-handed healthy controls and performed the resting state functional MRI. A seed-based analysis using a manually drawn pre-SMA region of interest template was applied. Time-course signals in the pre-SMA region of interest were averaged and cross-correlated to every voxel in the brain. Results show that the pre-SMA has significant left-lateralized functional connectivity to the pars opercularis within Broca's area. Among cortical regions, pre-SMA functional connectivity is strongest to the pars opercularis In addition, pre-SMA connectivity was shown to exist to other cortical language-association regions, including Wernicke's Area, supramarginal gyri, angular gyri, and middle frontal gyri. Among subcortical areas, considerable left-lateralized functional connectivity occurs to the caudate and thalamus, whereas cerebellar subregions show right lateralization. The current study shows that the pre-SMA most strongly connects to the pars opercularis within Broca's area and that cortical connections to language areas are left lateralized among a sample of right-handed patients. We provide resting state functional MRI evidence that the functional connectivity of the pre-SMA is involved in semantic language processing and that this identification may be useful for establishing language laterality in preoperative neurosurgical planning.

Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast-enhanced (DCE)-MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K trans ) derived from DCE-MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty-seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE-MRI. Regions of interest were manually drawn around the metastases to calculate Vp mean and Kmeantrans. The Mann-Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vp mean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vp mean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut-off value of 3.02 for Vp mean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P < 0.01) with 72% specificity. Our data show the DCE-MRI parameter Vp mean can differentiate between melanoma and NSCLC brain metastases. The ability to noninvasively predict tumor histology of brain metastases in patients with multiple malignancies can have important clinical implications., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)