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Double inversion recovery (DIR) imaging is used in multiple sclerosis (MS) clinical protocols to improve the detection of cortical and juxtacortical gray matter lesions by nulling confounding signals originating from the cerebrospinal fluid and white matter. Achieving a high isotropic spatial resolution, to depict the neocortex and its typically small lesions, is challenged by the reduced signal-to-noise ratio (SNR) determined by multiple tissue signal nulling. Here, we evaluate both conventional and optimized DIR implementations to improve tissue contrast (TC), SNR, and MS lesion conspicuity.DIR images were obtained from MS patients and healthy controls using both conventional and prototype implementations featuring a T2-preparation module (T2P), to improve SNR and TC, as well as an image reconstruction routine with iterative denoising (ID). We obtained quantitative measures of SNR and TC, and evaluated the visibility of MS cortical, cervical cord, and optic nerve lesions in the different DIR images.DIR implementations adopting T2P and ID enabled improving the SNR and TC of conventional DIR. In MS patients, 34% of cortical, optic nerve, and cervical cord lesions were visible only in DIR images acquired with T2P, and not in conventional DIR images. In the studied cases, image reconstruction with ID did not improve lesion conspicuity.DIR with T2P should be preferred to conventional DIR imaging in protocols studying MS patients, as it improves SNR and TC and determines an improvement in cortical, optic nerve, and cervical cord lesion conspicuity.

This study aims to investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in magnetic resonance imaging (MRI) and programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC). Twenty-one patients diagnosed with stage III NSCLC from April 2021 to April 2022 were included. The tumors were distinguished into two groups: no PD-L1 expression (

The study of patients after glioma resection offers a unique opportunity to investigate brain reorganization. It is currently unknown how the whole-brain connectomic profile evolves longitudinally after surgical resection of a glioma and how this may be associated with tumor characteristics and cognitive outcome. In this longitudinal study, we investigate the impact of tumor lateralization and grade on functional connectivity (FC) in highly connected networks, or hubs, and cognitive performance. Twenty-eight patients (17 high-grade, 11 low-grade gliomas) underwent longitudinal pre/post-surgery resting-state fMRI scans and neuropsychological assessments (73 total measures). FC matrices were constructed considering as functional hubs the default mode (DMN) and fronto-parietal networks. No-hubs included primary sensory functional networks and any other no-hubs nodes. Both tumor hemisphere and grade affected brain reorganization post-resection. In right-hemisphere tumor patients, regardless of grade and relative to left-hemisphere gliomas, FC increased longitudinally after the intervention, both in terms of FC within hubs (phubs = 0.0004) and FC between hubs and no-hubs (phubs-no-hubs = 0.005). Regardless of tumor side, only lower-grade gliomas showed longitudinal FC increases relative to high-grade tumors within a precise hub network, the DMN. The neurocognitive profile was longitudinally associated with spatial features of the connectome, mainly within the DMN. We provide evidence that clinical glioma features, such as lateralization and grade, affect post-surgical longitudinal functional reorganization and cognitive recovery. The data suggest a possible role of the DMN in supporting cognition, providing useful information for prognostic prediction and surgical planning.

BackgroundProton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied Diffusion-Tensor-Imaging (DTI) and Free-Water-Imaging (FWI) on diffusion-weighted Magnetic Resonance Imaging (dMRI) data to monitor microstructural changes during-PBT and after 8 months, in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM).MethodsWe evaluated conventional MRI and dMRI-derived indices from six MRI sessions in a child with a hypothalamic PA: at baseline (t0), during-PBT (t1-t4), and after 8 months (t5). Tumor voxels were classified as “solid” or “fluid” based on FWI.ResultsWhile during PBT tumor volume remained stable, dMRI analyses identified two different response patterns: i) an increase in fluid content and diffusivity with anisotropy reductions in solid voxels at t1, followed by ii) smaller variations in fluid content but higher anisotropy in solid voxels at t2-t4. At follow-up (t5), tumor volume, its fluid content, and diffusivity in solid voxels increased. NAWM showed dose-dependent microstructural changes.ConclusionsThe use of dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumor and surrounding tissues.

Explorations of the relation between brain anatomy and functional connections in the brain are crucial for shedding more light on network connectivity that sustains brain communication. In this study, by means of an integrative approach, we examined both the structural and functional connections of the default mode network (DMN) in a group of sixteen healthy subjects. For each subject, the DMN was extracted from the structural and functional resonance imaging data; the areas that were part of the DMN were defined as the regions of interest. Then, the target network was structurally explored by diffusion-weighted imaging, tested by neurophysiological means, and retested by means of concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG). A series of correlational analyses were performed to explore the relationship between the amplitude of early-latency TMS-evoked potentials and the indexes of structural connectivity (weighted number of fibres and fractional anisotropy). Stimulation of the left or right parietal nodes of the DMN-induced activation in the contralateral parietal and frontocentral electrodes within 60 ms; this activation correlated with fractional anisotropy measures of the corpus callosum. These results showed that distant secondary activations after target stimulation can be predicted based on the target’s anatomical connections. Interestingly, structural features of the corpus callosum predicted the activation of the directly connected nodes, i.e., parietal-parietal nodes, and of the broader DMN network, i.e., parietal-frontal nodes, as identified with functional magnetic resonance imaging. Our results suggested that the proposed integrated approach would allow us to describe the contributory causal relationship between structural connectivity and functional connectivity of the DMN.

Background Patterns of coordinated variations of gray matter (GM) morphology across individuals are promising indicators of disease. However, it remains unclear if they can help characterize first-episode psychosis (FEP) and symptoms’ severity. Methods Sixty-seven FEP and 67 matched healthy controls (HC) were assessed with structural MRI to evaluate the existence of distributed GM structural covariance patterns associated to brain areas belonging to salience network. Voxel-based morphometry (VBM) and structural covariance differences, investigated with salience network seed-based Partial Least Square, were applied to explore differences between groups. GM density associations with Raven's intelligent quotient (IQ) and Positive and Negative Syndrome Scale (PANSS) scores were investigated. Results Univariate VBM results gave trend without significant GM differences across groups. GM and IQ correlated positively in both groups: in FEP, mostly in hippocampus, insula, and fronto-temporal structures, while in HC mostly in amygdala, thalamus and fronto-temporal regions. GM and PANSS scores correlated negatively in FEP, with widespread clusters located in limbic regions. Multivariate analysis showed strong and opposite structural GM covariance with salience network for FEP and HC. Moreover, structural covariance of the salience network in FEP correlated negatively with severity of clinical symptoms. Conclusion Our study provides evidence supporting the insular dysfunction model of psychosis. Reduced structural GM covariance of the salience network, with its association to symptom's severity, appears a promising morphometry feature for FEP detection.

BACKGROUND Head motion during brain structural MRI scans biases brain morphometry measurements but quantitative retrospective methods estimating head motion from structural MRI have not been evaluated. PURPOSE To verify the hypothesis that two metrics retrospectively computed from MR images: 1) average edge strength (AES, reduced with image blurring) and 2) entropy (ENT, increased with blurring and ringing artifacts) could be sensitive to in-scanner head motion during acquisition of T1 -weighted MR images. STUDY TYPE Retrospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL In all, 83 healthy control (HC) and 120 Parkinson's disease (PD) patients. FIELD STRENGTH/SEQUENCE 3D magnetization-prepared rapid gradient-echo (MPRAGE) images at 3T. ASSESSMENT We 1) compared AES and ENT distribution between HC and PD; 2) evaluated the correlation between tremor score (TS) and AES (or ENT) in PD; and 3) investigated cortical regions showing an association between AES (or ENT) and local and network-level covariance measures of cortical thickness (CT), gray to white matter contrast (GWC) and gray matter density maps (GMx). STATISTICAL TESTS 1) Student's t-test. 2) Spearman's rank correlation. 3) General linear model and partial least square analysis. RESULTS AES, but not ENT, differentiated HC and PD (P = 0.02, HC median AES = 39.8, interquartile range = 9.8, PD median AES = 37.6, interquartile range = 8.1). In PD, AES correlated negatively with TS (ρ = -0.21, P = 0.02) and showed a significant relationship (|Z| >3, P

Head motion during brain structural MRI scans biases brain morphometry measurements but quantitative retrospective methods estimating head motion from structural MRI have not been evaluated.To verify the hypothesis that two metrics retrospectively computed from MR images: 1) average edge strength (AES, reduced with image blurring) and 2) entropy (ENT, increased with blurring and ringing artifacts) could be sensitive to in-scanner head motion during acquisition of TRetrospective.In all, 83 healthy control (HC) and 120 Parkinson's disease (PD) patients.3D magnetization-prepared rapid gradient-echo (MPRAGE) images at 3T.We 1) compared AES and ENT distribution between HC and PD; 2) evaluated the correlation between tremor score (TS) and AES (or ENT) in PD; and 3) investigated cortical regions showing an association between AES (or ENT) and local and network-level covariance measures of cortical thickness (CT), gray to white matter contrast (GWC) and gray matter density maps (GMx).1) Student's t-test. 2) Spearman's rank correlation. 3) General linear model and partial least square analysis.AES, but not ENT, differentiated HC and PD (P = 0.02, HC median AES = 39.8, interquartile range = 9.8, PD median AES = 37.6, interquartile range = 8.1). In PD, AES correlated negatively with TS (ρ = -0.21, P = 0.02) and showed a significant relationship (|Z|3, P 0.001) with structural covariance of CT and GWC in 54 out of 68 cortical regions.In clinical populations prone to head motion, AES can provide a reliable retrospective index of motion during structural scans, identifying brain areas whose morphometric measures covary with motion.3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:927-937.

OBJECTIVEResting-state functional MRI (rs-fMRI) represents a promising and cost-effective alternative to task-based fMRI for presurgical mapping. However, the lack of clinically streamlined and reliable rs-fMRI analysis tools has prevented wide adoption of this technique. In this work, the authors introduce an rs-fMRI processing pipeline (ReStNeuMap) for automatic single-patient rs-fMRI network analysis.METHODSThe authors provide a description of the rs-fMRI network analysis steps implemented in ReStNeuMap and report their initial experience with this tool after performing presurgical mapping in 6 patients. They verified the spatial agreement between rs-fMRI networks derived by ReStNeuMap and localization of activation with intraoperative direct electrical stimulation (DES).RESULTSThe authors automatically extracted rs-fMRI networks including eloquent cortex in spatial proximity with the resected lesion in all patients. The distance between DES points and corresponding rs-fMRI networks was less than 1 cm in 78% of cases for motor, 100% of cases for visual, 87.5% of cases for language, and 100% of cases for speech articulation mapping.CONCLUSIONSThe authors’ initial experience with ReStNeuMap showed good spatial agreement between presurgical rs-fMRI predictions and DES findings during awake surgery. The availability of the rs-fMRI analysis tools for clinicians aiming to perform noninvasive mapping of brain functional networks may extend its application beyond surgical practice.

Purpose (i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. Materials and Methods We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). Results Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%. Conclusion Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks). J. Magn. Reson. Imaging 2014;40:383–390. © 2013 Wiley Periodicals, Inc.

The aim of this study was to compare the relative effectiveness of 6 different commonly used language fMRI activation paradigms, including receptive and expressive, as well as semantic and phonological tasks, for hemispheric lateralization in brain tumor patients utilizing both threshold-dependent and threshold-independent approaches. We studied 46 right-handed patients with primary intra-axial brain tumors with BOLD fMRI on a 3-T MRI system. A linear fit of the laterality indices (LIs) as a function of the t-value (which varied from 2.0 to 6.5) was calculated and the slope (M) taken as measure of LI variability in the threshold-dependent LI approach; for the threshold-independent approach, the LIs were determined by comparing the integrated T-score weighted distributions of all positively task-correlated voxels of the left and the right hemispheric regions of interest. We demonstrated that silent word generation (SWG) and rhyming (R) were the two expressive tasks that provided the best hemispheric language lateralization in this group, based on concordant threshold-dependent and threshold-independent analyses. Furthermore, R (mean LI value = 61.91, M = 7.9 ± 1.5) had a higher mean LI value and was less threshold-dependent than SWG (mean LI = 52.97, M = 11.40 ± 0.64) for LI determination. SWG and R were able to provide effective language lateralization even in the subgroup of patients with lesions located in the left hemisphere and in the frontal or parietal lobes. The receptive language paradigms examined in this study (passive listening [PL], listening comprehension [LC], and reading comprehension [RC]) were less effective than SWG and R for language lateralization.

The development of new MRI techniques in the last two decades has provided neuroradiologists and neurosurgeons with additional noninvasive imaging tools for management and treatment of brain tumors. When coupled with standard structural MR sequences in imaging brain tumors, Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI), Perfusion Weighted Imaging (PWI) and Diffusion Tensor Imaging (DTI) provide additional physiologic information that is very useful for differential diagnosis, presurgical planning and prognosis. In this review after a brief technical description of BOLD fMRI, PWI and DTI, studies are described from the literature that have extensively validated these imaging techniques in comparison with invasive “gold standard” techniques such as intraoperative electrical cortical and subcortical stimulation mapping or biopsy. Additional studies are mentioned that demonstrate the positive impact of BOLD fMRI, PWI and DTI on brain tumor treatment and clinical outcome. In the final section an interesting clinical case treated at our institution is presented that highlights the clinical utility of this integrated physiologic brain tumor imaging approach.

Resting state fMRI (rs-fMRI) has recently been considered as a possible complement or alternative to task-based fMRI (tb-fMRI) for presurgical mapping. However, evidence of its usefulness remains scant, because existing studies have investigated relatively small samples and focused primarily on qualitative evaluation. The aim of this study is to investigate the clinical usefulness of rs-fMRI in the context of presurgical mapping of motor functions, and in particular to determine the degree of correspondence with tb-fMRI which, while not a gold-standard, is commonly used in preoperative setting. A group of 13 patients with lesions close to the sensorimotor cortex underwent rs-fMRI and tb-fMRI to localize the hand, foot and mouth motor areas. We assessed quantitatively the degree of correspondence between multiple rs-fMRI analyses (independent-component and seed-based analyses) and tb-fMRI, with reference to sensitivity and specificity of rs-fMRI with respect to tb-fMRI, and centre-of-mass distances. Agreement with electro-cortical stimulation (ECS) was also investigated, and a traditional map thresholding approach based on agreement between two experienced operators was compared to an automatic threshold determination method. Rs-fMRI can localize the sensorimotor cortex successfully, providing anatomical specificity for hand, foot and mouth motor subregions, in particular with seed-based analyses. Agreement with tb-fMRI was only partial and rs-fMRI tended to provide larger patterns of correlated activity. With respect to the ECS data available, rs-fMRI and tb-fMRI performed comparably, even though the shortest distance to stimulation points was observed for the latter. Notably, the results of both were on the whole robust to thresholding procedure. Localization performed by rs-fMRI is not equivalent to tb-fMRI, hence rs-fMRI cannot be considered as an outright replacement for tb-fMRI. Nevertheless, since there is significant agreement between the two techniques, rs-fMRI can be considered with caution as a potential alternative to tb-fMRI when patients are unable to perform the task.

BACKGROUND AND PURPOSE: The optimal paradigm choice for language mapping in clinical fMRI studies is challenging due to the variability in activation among different paradigms, the contribution to activation of cognitive processes other than language, and the difficulties in monitoring patient performance. In this study, we compared language localization and lateralization between 2 commonly used clinical language paradigms and 3 newly designed dual-choice semantic paradigms to define a streamlined and adequate language-mapping protocol. MATERIALS AND METHODS: Twelve healthy volunteers performed 5 language paradigms: Silent Word Generation, Sentence Completion, Visual Antonym Pair, Auditory Antonym Pair, and Noun-Verb Association. Group analysis was performed to assess statistically significant differences in fMRI percentage signal change and lateralization index among these paradigms in 5 ROIs: inferior frontal gyrus, superior frontal gyrus, middle frontal gyrus for expressive language activation, middle temporal gyrus, and superior temporal gyrus for receptive language activation. RESULTS: In the expressive ROIs, Silent Word Generation was the most robust and best lateralizing paradigm (greater percentage signal change and lateralization index than semantic paradigms at P < .01 and P < .05 levels, respectively). In the receptive region of interest, Sentence Completion and Noun-Verb Association were the most robust activators (greater percentage signal change than other paradigms, P < .01). All except Auditory Antonym Pair were good lateralizing tasks (the lateralization index was significantly lower than other paradigms, P < .05). CONCLUSIONS: The combination of Silent Word Generation and ≥1 visual semantic paradigm, such as Sentence Completion and Noun-Verb Association, is adequate to determine language localization and lateralization; Noun-Verb Association has the additional advantage of objective monitoring of patient performance.

(i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group.We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional).Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%.Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks).

Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus an relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.

The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion metrics obtained by T2* gadolinium perfusion MR imaging were compared to BOLD percentage signal change on BH CVR maps in a group of 19 patients with intracranial brain tumors of different nature and grade. Single pixel maximum rCBV and rCBF within holotumoral regions of interest (i.e., "ipsilesional" ROIs) were normalized to contralateral hemispheric homologous (i.e., "contralesional") normal tissue. Furthermore, percentage signal change on BH CVR maps within ipsilesional ROIs were normalized to the percentage signal change within contralesional homologous ROIs. Inverse linear correlation was found between normalized rCBF (r(flow)) or rCBV (r(vol)) and normalized CVR percentage signal change (r(CVR)) in grade IV lesions. In the grade III lesions a less steep inverse linear trend was seen that did not reach statistical significance, whereas no correlation at all was seen in the grade II group. Statistically significant difference was present for r(flow) and r(vol) between the grade II and IV groups and between the grade III and IV groups but not for r(CVR). The r(CVR) was significantly lower than 1 in every group. Our results demonstrate that while T2*MR perfusion maps and CVR maps are both adequate to map tumoral regions at risk of NVU in high grade gliomas, CVR maps can detect areas of decreased CVR also in low and intermediate grade gliomas where NVU may be caused by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95% concordance, thus confirming the capability of BH CVR mapping to effectively demonstrate areas of NVU. ed by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95% concordance, thus confirming the capability of BH CVR mapping to effectively demonstrate areas of NVU.

AIM: To evaluate neurovascular uncoupling (NVU) associated with low grade gliomas (LGG) using blood oxygen level dependent (BOLD) cerebrovascular reactivity mapping. METHODS: Seven patients with low grade gliomas referred by neurosurgeons for presurgical mapping were included in this pilot study. Cerebrovascular reactivity (CVR) mapping was performed by acquiring BOLD images while patients performed a block-design breath-hold (BH) hypercapnia task. CVR mapping was expressed as BOLD percentage signal change (PSC) from baseline associated with performance of the BH hypercapnia task. Standard T2* Dynamic Susceptibility Contrast perfusion imaging was performed and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) maps were generated. Structural T1 weighted MR images were also acquired. A correlation analysis between intratumoral normalized (via ratio with contralateral homologous regions) BOLD BH PSC [referred to as (nCVR)] and intratumoral normalized resting state rCBV (rCBF) values (i.e., nCBV and nCBF, respectively) was performed. RESULTS: No significant correlation was seen between the normalized BOLD BH PSC (i.e., nCBV) and nCBV or nCBF. However, the average nCVR (median = 0.50, z = -2.28, P = 0.01) was significantly less than 1.0, indicating abnormally reduced vascular responses in the tumor regions relative to normal contralesional homologous regions, whereas the average nCBV (median = 0.94, z = -0.92, P = 0.375) and nCBF (median = 0.93, z = -1.16, P = 0.25) were not significantly higher or lower than 1.0, indicating iso-perfusion in the tumor regions relative to normal contralesional homologous regions. These find ings suggest that in LGG, hyperperfusion that is seen in high grade gliomas is not present, but, nevertheless, abnormally decreased regional CVR is present within and adjacent to LGG. Since the patients all demonstrated at least some residual function attributable to the cortical regions of impaired CVR, but were incapable of producing a BOLD response in these regions regardless of the tasks performed, such regionally decreased CVR is indicative of NVU. The low nCVR ratios indicate high prevalence of NVU in this LGG cohort, which is an important consideration in the interpretation of clinical presurgical mapping with functional magnetic resonance (MR) imaging. CONCLUSION: Our preliminary study shows that BH CVR mapping is clinically feasible and demonstrates an unexpectedly high prevalence of NVU in patients with LGG.