A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease.

BACKGROUND: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. METHODS: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. RESULTS: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. CONCLUSIONS: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.

Qualitative and Visual Along-Tract Analysis of Diffusion-Based Parameters in Patients with Diffuse Gliomas.

BACKGROUND: Grade 2-3 diffuse gliomas (DGs) show extensive infiltration through white matter (WM) tracts. Along-tract analysis of WM tracts based on diffusion tensor tractography (DTI) can been performed to assess the microstructural integrity of WM tracts. The clinical implication of these DTI-related findings is still under debate, especially in tumor patients. The aim of this study was to analyze and compare diffusion-based parameters along WM tracts and variables specific to WM -tumor interactions in DGs and correlate them with preoperative neuropsychological assessment. METHODS: Fourteen patients with IDH-mutated grade 2-3 DGs were included. Tumor volumes were manually segmented on 3D-FLAIR images after spatial normalisation to MNI space. DTI was acquired using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data were reconstructed within the MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM tracts were reconstructed based on the HCP-1065 template. All WM tracts were stretched to the same length of 100 indices, and for each index diffusion-based parameters fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and quantitative anisotropy (QA) were sampled. Tumor-related parameters (TRP); tumor volume (Tv), maximum tumor presence (MTP) and the number of sequential indices in which a tumor is present (Te) were derived based on the along-tract analysis. Normal data were constructed by calculating the average and standard deviations of contralateral and not-affected WM tracts for each diffusion-based parameter, respectively. Affected WM tracts were individually compared to normal data using a z-test. Preoperative neuropsychological assessment was performed in all subjects and correlated to results from the along-tract analysis using correlation and logistic regression models. RESULTS: Abnormalities in diffusion-based parameters were detected in WM tracts. Topographical and quantitative information were presented within the same graph. AD and MD displayed the highest linear correlation with the TRPs. Abnormal QA showed a linear correlation with Tv per WM tract. Neuropsychological impairment was correlated with all the TRPs and with abnormal FA (p < 0.05) and abnormal QA (p < 0.01). Abnormal QA was the only independent variable able to predict the presence of neuropsychological impairment in the patients based on the linear regression analysis. CONCLUSIONS: Graphical presentation of the along-tract analysis presented in this study shows that it may be a sensitive and robust method to acquire and display topographical and qualitative information regarding WM tracts in close proximity to DGs. Further studies and refinements to the methods presented herein may advance current clinical methods for evaluating displacement and infiltrations and further aid the efforts of pre-planning surgical interventions with the goal to maximise EOR and tailor oncological treatment.

Cerebrovascular reserve in moyamoya disease: relation to cerebral blood flow, capillary dysfunction, oxygenation, and energy metabolism.

Background: Cerebral hemodynamics in moyamoya disease (MMD) is complex and needs further elucidation. The primary aim of the study was to determine the association of the cerebrovascular reserve (CVR) with cerebral blood flow (CBF) disturbances, oxygen extraction fraction (OEFmax), and energy metabolism (CMRO2max) in MMD, using arterial spin label magnetic resonance imaging (ASL-MRI) before and after acetazolamide administration. Methods: Thirty-nine ASL-MRI scans with a concurrent acetazolamide challenge from 16 MMD patients at the Uppsala University Hospital, Sweden, 2016-2021, were retrospectively analyzed. CBF was assessed before and 5, 15, and 25 min after acetazolamide administration, and the maximal response CVRmax was used for further analyses. Dynamic susceptibility contrast (DSC) MRI was performed 30 min after acetazolamide injection, and the data were analyzed using the Cercare Medical Neurosuite to assess capillary transit time heterogeneity (CTTH; indicating microvascular function), OEFmax, and CMRO2max. Results: In the ACA territory, a lower CVRmax was associated with lower baseline CBF, higher CTTH, and higher OEFmax but not with CMRO2max in generalized estimating equation models. In the MCA territory, lower CVRmax was associated with lower baseline CBF and higher CMRO2max but not with CTTH and OEFmax.. Conclusion: Altogether, a compromised CVR in MMD patients reflected disturbances in macro-/microvascular blood flow, oxygenation, and CMRO2. ASL-MRI with acetazolamide challenge is a feasible and radiation-free alternative to positron emission tomography (PET) imaging in MMD.

Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.

Introduction: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD. Methods: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography. Results: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol. Conclusion: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease.

PURPOSE: Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients. METHODS: Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery. RESULTS: Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events. CONCLUSION: Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.

Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions.

PRIMARY OBJECTIVE: Traumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood flow (CBF), cortical thickness, and 1H-magnetic resonance (MR) spectroscopy (MRS)) were associated to cognitive function, TBI severity, and sex. RESEARCH DESIGN: Eleven controls, 12 athletes symptomatic following ≥3SRCs and 6 patients with moderate-severe TBI underwent MR scanning for evaluation of cortical thickness, brain metabolites (MRS), and CBF using pseudo-continuous arterial spin labeling (ASL). Cognitive screening was performed using the RBANS cognitive test battery. MAIN OUTCOMES AND RESULTS: RBANS-index was impaired in both injury groups and correlated with the injury severity, although not with any neuroimaging parameter. Cortical thickness correlated with injury severity (p = 0.02), while neuronal density, using the MRS marker ((NAA+NAAG)/Cr, did not. On multivariate analysis, injury severity (p = 0.0003) and sex (p = 0.002) were associated with CBF. Patients with TBI had decreased gray (p = 0.02) and white matter (p = 0.02) CBF compared to controls. CBF was significantly lower in total gray, white matter and in 16 of the 20 gray matter brain regions in female but not male athletes when compared to female and male controls, respectively. CONCLUSIONS: Injury severity correlated with CBF, cognitive function, and cortical thickness. CBF also correlated with sex and was reduced in female, not male, athletes. Chronic CBF changes may contribute to the persistent injury mechanisms in TBI and rSRC.

Can diffusion tensor imaging (DTI) outperform standard magnetic resonance imaging (MRI) investigations in post-COVID-19 autoimmune encephalitis?

Background: Neurological and psychiatric manifestations related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are widely recognised. Standard magnetic resonance imaging (MRI) investigations are normal in 40-80% of symptomatic patients, eventually delaying appropriate treatment when MRI is unrevealing any structural changes. The aim of this study is to investigate white matter abnormalities during an early stage of post-COVID-19 (coronavirus disease 2019) encephalitis while conventional MRI was normal. Methods: A patient with post-COVID-19 autoimmune encephalitis was investigated by serial MRIs and diffusion tensor imaging (DTI). Ten healthy control individuals (HC) were utilised as a control group for the DTI analysis. Major projection, commissural and association white matter pathways were reconstructed, and multiple diffusion parameters were analysed and then compared to the HC average using a z-test for serial examinations. Results: Eleven days after the onset of neurological symptoms, DTI revealed early white matter changes, compared with HC, when standard MRI was normal. On day 68, DTI showed multiple white matter lesions compared with HC, visible at this time also by the MRI images, indicating inflammatory changes in different association and projection white matter pathways. Conclusion: We confirm a limitation in the sensitivity of conventional MRI at the acute setting of post-COVID-19 autoimmune encephalitis. A complementary DTI investigation could be a valuable diagnostic tool in early therapeutic decisions concerning COVID-19-related neurological symptoms.

Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches?

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Cerebral Pressure Autoregulation in Brain Injury and Disorders-A Review on Monitoring, Management, and Future Directions.

The role of cerebral pressure autoregulation (CPA) in brain injury and disorders has gained increased interest. The CPA is often disturbed as a consequence of acute brain injury, which contributes to further brain damage and worse outcome. Specifically, in severe traumatic brain injury, CPA disturbances predict worse clinical outcome and targeting an autoregulatory-oriented optimal cerebral perfusion pressure threshold may improve brain energy metabolism and clinical outcome. In aneurysmal subarachnoid hemorrhage, cerebral vasospasm in combination with distal autoregulatory disturbances precipitate delayed cerebral ischemia. The role of optimal cerebral perfusion pressure targets is less clear in aneurysmal subarachnoid hemorrhage, but high cerebral perfusion pressure targets are generally favorable in the vasospasm phase. In acute ischemia, autoregulatory disturbances may occur and autoregulatory-oriented blood pressure (optimal mean arterial pressure) management reduces the risk of hemorrhagic transformation, brain edema, and unfavorable outcome. In chronic occlusive disease such as moyamoya, the gradual reduction of the cerebral circulation leads to compensatory distal vasodilation and the residual CPA capacity predicts the risk for cerebral ischemia. In spontaneous intracerebral hemorrhage, the role of autoregulatory disturbances is less clear, but CPA disturbances correlate with worse clinical outcome. Also, in community-acquired bacterial meningitis, CPA dysfunction is frequent and correlates with worse clinical outcome, but autoregulatory management is yet to be evaluated. In this review, we discuss the role of CPA in different types of brain injury and disease, the strengths and limitations of the monitoring methods, the potentials of autoregulatory management, and future directions in the field.

Complete functional recovery in a child after endovascular treatment of basilar artery occlusion caused by spontaneous dissection: a case report.

Stroke caused by dissection of arteries of the vertebrobasilar system in children is still poorly investigated in terms of etiology, means of treatment, course of disease, and prognosis. The aim of this report was to describe the unusual course of a spontaneous dissection of the basilar artery (BA) in a child treated with endovascular techniques and to point out that the plasticity of the brain stem can fully compensate for structural damage caused by stroke. We report the case of a 15-year-old boy who suffered a wake-up stroke with BA occlusion caused by spontaneous dissection. A blood clot was aspirated from the false lumen and the true lumen re-opened, but the patient deteriorated a few hours later, and repeated angiography revealed that the intimal flap was detached, occluding the BA again. The lumen of BA was then reconstructed by a stent. Despite a large pons infarction, the patient was completely recovered 11 months after the onset. The case was analyzed with angiograms and magnetic resonance imaging, macroscopic and microscopic pathological analysis, computed tomographic angiography, magnetic resonance-based angiography, and diffusion tensor imaging. This case illustrates that applied endovascular techniques and intensive care measures can alter the course of potentially fatal brain stem infarction. Our multimodal analysis gives new insight into the anatomical basis for the plasticity mechanism of the brain stem.

The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging.

Diffuse low-grade gliomas (DLGG) display different preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Magnetic resonance imaging of sixty-seven diffuse low-grade gliomas patients were normalized to/and segmented in MNI space to create three probabilistic infiltration weighted gradient maps according to the molecular status of each tumor group (IDH mutated, IDH wild-type and IDH mutated/1p19q co-deleted). Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying regional differences in the grade of infiltration, averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, fiber diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration in each white matter bundle. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration (HIF and LIF) respectively. We detected differences in the white matter infiltration of five major white matter bundles in three groups. Astrocytomas IDHm infiltrated left fronto-temporal subcortical areas. Astrocytomas IDHwt were detected in the posterior-temporal and temporo-parietal regions bilaterally. Oligodendrogliomas IDHm/1p19q infiltrated anterior subcortical regions of the frontal lobes bilaterally. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis linked to different topographical variables. Our multimodal analysis showed that HIF regions, common to all the groups, displayed a smaller fiber diameter, lower FA and higher RD compared with LIF regions. Our results suggest that the both morphological features and diffusion parameters of the white matter may be different in regions linked to the preferential location of DLGG.

Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling.

Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.

Evaluation of Arterial Spin Labeling MRI-Comparison with 15O-Water PET on an Integrated PET/MR Scanner.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = -15 mL/100 g/min, lower and upper limits of agreements = -16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

White matter abnormalities in a patient with visual snow syndrome: New evidence from a diffusion tensor imaging study.

BACKGROUND: Visual snow syndrome (VSS) is a neurological condition characterized by flickering dots throughout the entire visual field. Both the pathophysiology and possible location of VSS are still under debate. White matter abnormalities were investigated using diffusion tensor imaging (DTI) in a patient with VSS. METHODS: A 28-year-old patient with VSS and 10 healthy controls were investigated with DTI. Diffusion parametric maps were calculated and reconstructed using q-space diffeomorphic reconstruction. White matter pathways of the dorsal, ventral, integrative visual streams and thalamic connectivity were tracked. Then, they were applied to each subject's parameter map, stretched to the same length, and sampled along the tracts for regional analyses of DTI parameters. RESULTS: Compared with healthy controls, our patient displayed higher axial diffusivity (AD) and radial diffusivity (RD) in the dorsal visual stream (cingulum, arcuate fasciculus, horizontal indirect anterior segment of the superior longitudinal fasciculus), in the ventral visual stream (fronto-occipital fasciculus, inferior longitudinal fasciculus) and in the integrative visual stream (indirect posterior component of the superior longitudinal fasciculus, vertical occipital fasciculus). Higher AD and RD were also detected in acoustic and optic radiations, and in thalamic radiations distal to the thalamus. CONCLUSION: This VSS patient displayed multiple, bilateral white matter changes in the temporo-parieto-occipital junction in white matter pathways related to vision. We encourage the study of white matter pathology using DTI in complex neurological syndromes including VSS.

Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas.

When diffuse gliomas (DG) affect the brain's potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

Tau aggregation and increased neuroinflammation in athletes after sports-related concussions and in traumatic brain injury patients - A PET/MR study.

Traumatic brain injury (TBI) and repeated sports-related concussions (rSRCs) are associated with an increased risk for neurodegeneration. Autopsy findings of selected cohorts of long-term TBI survivors and rSRC athletes reveal increased tau aggregation and a persistent neuroinflammation. To assess in vivo tau aggregation and neuroinflammation in young adult TBI and rSRC cohorts, we evaluated 9 healthy controls (mean age 26 ± 5 years; 4 males, 5 females), 12 symptomatic athletes (26 ± 7 years; 6 males, 6 females) attaining ≥3 previous SRCs, and 6 moderate-to severe TBI patients (27 ± 7 years; 4 males, 2 females) in a combined positron emission tomography (PET)/magnetic resonance (MR) scanner ≥6 months post-injury. Dual PET tracers, [18F]THK5317 for tau aggregation and [11C]PK11195 for neuroinflammation/microglial activation, were investigated on the same day. The Repeated Battery Assessment of Neurological Status (RBANS) scores, used for cognitive evaluation, were lower in both the rSRC and TBI groups (p < 0.05). Neurofilament-light (NF-L) levels were increased in plasma and cerebrospinal fluid (CSF; p < 0.05), and serum tau levels lower, in TBI although not in rSRC. In rSRC athletes, PET imaging showed increased neuroinflammation in the hippocampus and tau aggregation in the corpus callosum. In TBI patients, tau aggregation was observed in thalami, temporal white matter and midbrain; widespread neuroinflammation was found e.g. in temporal white matter, hippocampus and corpus callosum. In mixed-sex cohorts of young adult athletes with persistent post-concussion symptoms and in TBI patients, increased tau aggregation and neuroinflammation are observed at ≥6 months post-injury using PET. Studies with extended clinical follow-up, biomarker examinations and renewed PET imaging are needed to evaluate whether these findings progress to a neurodegenerative disorder or if spontaneous resolution is possible.

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Differences in the preferential location and invasiveness of diffuse low-grade gliomas and their impact on outcome.

BACKGROUND: Low-grade gliomas (LGGs) are primary diffuse slow-growing brain tumors derived from glial cells. The management of these tumors is dependent on their location, which often harbors eloquent areas. We retrospectively recorded the location of diffuse gliomas to identify whether specific differences exist between the histological types. METHODS: We analyzed 102 patients with previous histological diagnosis of WHO-II astrocytomas (62) and WHO-II oligodendrogliomas (40) according to WHO-2016 classification. MRI sequences (T2-FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations within the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was created and merged with a tractography atlas for infiltration analysis. RESULTS: Astrocytomas frequently infiltrated association and projection white matter pathways within fronto-temporo-insular regions on the left side. Oligodendrogliomas infiltrated larger white matter networks (association-commissural-projection) of the frontal lobe bilaterally. A critical number of infiltrated BG voxels (7 for astrocytomas, 10 for oligodendrogliomas) significantly predicted shorter overall survival (OS) in both groups. Bilateral tumor extension in astrocytomas and preoperative tumor volume in oligodendrogliomas were independent prognostic factors for shorter OS. CONCLUSIONS: Astrocytomas and oligodendrogliomas differ in preferential location, and this has an impact on the type and the extent of white matter involvement. The number of BG voxels infiltrated reflected different tumor invasiveness and its impact on OS in both groups. All this new information may be valuable in neurosurgical oncology to classify and plan treatment for patients with diffuse gliomas.