Spin Labeling Magnetic Resonance Imaging Research Articles

Influence of arterial transit time delays on the differentiation between tumor progression and pseudoprogression in glioblastoma by arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL-MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL-MRI and DSC-MRI scans were acquired at 3months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL-MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow-up until 9months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL-MRI and DSC-MRI was observed only for ASL images with moderate ATT severity (30%-65%). The perfusion assessment showed ASL-MRI tending more towards hyperperfusion than DSC-MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL-MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p= 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL-MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma.

Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset. Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups . Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.

The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment. Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers. Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers. APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.

A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum

ObjectivesDeep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. Materials and MethodsTwelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). ResultsVC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. ConclusionsThis study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Arterial spin labelling magnetic resonance imaging and perfusion patterns in neurocognitive and other mental disorders: a systematic review.

We reviewed 33 original research studies assessing brain perfusion, using consensus guidelines from a "white paper" issued by the International Society for Magnetic Resonance in Medicine Perfusion Study Group and the European Cooperation in Science and Technology Action BM1103 ("Arterial Spin Labelling Initiative in Dementia"; https://www.cost.eu/actions/BM1103/ ). The studies were published between 2011 and 2023 and included participants with subjective cognitive decline plus; neurocognitive disorders, including mild cognitive impairment (MCI), Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular cognitive impairment (VCI); as well as schizophrenia spectrum disorders, bipolar and major depressive disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, panic disorder and alcohol use disorder. Hypoperfusion associated with cognitive impairment was the major finding across the spectrum of cognitive decline. Regional hyperperfusion also was reported in MCI, AD, frontotemporal dementia phenocopy syndrome and VCI. Hypoperfused structures found to aid in diagnosing AD included the precunei and adjacent posterior cingulate cortices. Hypoperfused structures found to better diagnose patients with FTLD were the anterior cingulate cortices and frontal regions. Hypoperfusion in patients with DLB was found to relatively spare the temporal lobes, even after correction for partial volume effects. Hyperperfusion in the temporal cortices and hypoperfusion in the prefrontal and anterior cingulate cortices were found in patients with schizophrenia, most of whom were on medication and at the chronic stage of illness. Infratentorial structures were found to be abnormally perfused in patients with bipolar or major depressive disorders. Brain perfusion abnormalities were helpful in diagnosing most neurocognitive disorders. Abnormalities reported in VCI and the remaining mental disorders were heterogeneous and not generalisable.

Cerebral Blood Flow and Mood in Adolescents With Bipolar Disorder

ObjectiveMultiple prior studies have examined cerebral blood flow (CBF) in relation to mood states in adults with bipolar disorder (BD). This study examined CBF related to mood states in adolescents early in the course of BD, about which little is known. MethodThe study recruited 155 adolescents (mean [SD] age = 17.23 [1.62] years), including 81 with BD (32 hypomanic/mixed, 25 depressed, 24 euthymic) and 74 healthy controls. CBF was ascertained using pseudocontinuous arterial spin labeling magnetic resonance imaging. Region-of-interest analysis (amygdala, anterior cingulate cortex, middle frontal gyrus) controlling for age, sex, and race was complemented by whole-brain voxel-wise analyses. Within-BD regression analysis using age and sex as covariates examined the association of mania and depression severity with CBF. ResultsIn region-of-interest analyses, there were no group differences in CBF. Within the overall BD group, higher depression scores were associated with lower anterior cingulate cortex CBF (β = −.27, p = .01). In corrected voxel-wise analyses, CBF in the euthymic BD group was significantly higher compared with healthy controls in temporal and precentral regions. ConclusionThe finding of elevated regional CBF in adolescents with euthymic BD diverges from prior findings of reduced regional CBF in adults with BD. Higher CBF in adolescents with euthymic BD may reflect a developmentally specific compensatory perfusion mechanism required to maintain euthymia. However, longitudinal studies are needed to understand the temporal association of CBF and mood state in adolescents with BD, ideally followed into adulthood. Diversity & Inclusion StatementWe worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Genetic deletion of hormone-sensitive lipase in mice reduces cerebral blood flow but does not aggravate the impact of diet-induced obesity on memory.

Hormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL-/-, HSL+/-, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages), and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage of blood vessels, and morphology of astrocytes and microglia in brain slices. HSL deletion reduced CBF, most prominently in cortex and hippocampus, while HFD feeding only lowered CBF in the hippocampus of wild-type mice. CBF was positively correlated with lectin-stained vessel density. HSL deletion did not exacerbate HFD-induced microgliosis in the hippocampus and hypothalamus. HSL-/- mice showed preserved memory performance when compared to wild-type mice, and HSL deletion did not significantly aggravate HFD-induced memory impairment in object recognition tests. In contrast, HSL deletion conferred protection against HFD-induced obesity, glucose intolerance, and insulin resistance. Altogether, this study points to distinct roles of HSL in periphery and brain during diet-induced obesity. While HSL-/- mice were protected against metabolic syndrome development, HSL deletion reduced brain perfusion without leading to aggravated HFD-induced neuroinflammation and memory dysfunction.

Multimodal imaging measures in the prediction of clinical response to deep brain stimulation for refractory depression: A machine learning approach

Objectives This study compared machine learning models using unimodal imaging measures and combined multi-modal imaging measures for deep brain stimulation (DBS) outcome prediction in treatment resistant depression (TRD). Methods Regional brain glucose metabolism (CMRGlu), cerebral blood flow (CBF), and grey matter volume (GMV) were measured at baseline using 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography (PET), arterial spin labelling (ASL) magnetic resonance imaging (MRI), and T1-weighted MRI, respectively, in 19 patients with TRD receiving subcallosal cingulate (SCC)-DBS. Responders (n = 9) were defined by a 50% reduction in HAMD-17 at 6 months from the baseline. Using an atlas-based approach, values of each measure were determined for pre-selected brain regions. OneR feature selection algorithm and the naïve Bayes model was used for classification. Leave-out-one cross validation was used for classifier evaluation. Results The performance accuracy of the CMRGlu classification model (84%) was greater than CBF (74%) or GMV (74%) models. The classification model using the three image modalities together led to a similar accuracy (84%0 compared to the CMRGlu classification model. Conclusions CMRGlu imaging measures may be useful for the development of multivariate prediction models for SCC-DBS studies for TRD. The future of multivariate methods for multimodal imaging may rest on the selection of complementing features and the developing better models.Clinical Trial Registration: ClinicalTrials.gov (#NCT 01983904)

Perfusion Hyperintensities in Patients With Seizures: Evaluation With Arterial Spin Labeling Magnetic Resonance Imaging Within 24 Hours After Onset

Perfusion Hyperintensities in Patients With Seizures: Evaluation With Arterial Spin Labeling Magnetic Resonance Imaging Within 24 Hours After Onset

Physical Exercise Alters Egress Pathways for Intrinsic CSF Outflow: An Investigation Performed with Spin-labeling MR Imaging.

Cerebrospinal fluid (CSF) clearance is essential for maintaining a healthy brain and cognition by removal of metabolic waste from the central nervous system. Physical exercise has been shown to improve human health; however, the effect of physical exercise on intrinsic CSF outflow in humans remains unexplored. The purpose of this study was to investigate intrinsic CSF outflow pathways and quantitative metrics of healthy individuals with active and sedentary lifestyles. In addition, the effect of exercise was investigated among the sedentary subjects before and after 3 weeks of physical activity. This study was performed on 18 healthy adults with informed consent, using a clinical 3-Tesla MRI scanner. We classified participants into two groups based on reported time spent sitting per day (active group: < 7 hours sitting per day and sedentary group: ≥ 7 hours sitting per day). To elucidate the effect of exercise, sedentary individuals increased their activity to 3.5 hours for 3 weeks. We show that there are two intrinsic CSF egress pathways of the dura mater and lower parasagittal dura (PSD). The adults with an active lifestyle had greater intrinsic CSF outflow metrics than adults with a more sedentary lifestyle. However, after increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was particularly notable at the lower PSD, where outflow metrics were highest among the active group. Our findings describe the relationship between physical activity and intrinsic CSF outflow and show a potential selective outflow pathway with increasing physical activity in the lower PSD pathway, potentially from the perivascular space or cortical venous subpial space.

The effect of aquaporin-4 inhibition on cerebrospinal fluid-tissue water exchange in mouse brain detected by magnetization transfer indirect spin labeling MRI.

The fluid transport of cerebrospinal fluid (CSF) and interstitial fluid in surrounding tissues plays an important role in the drainage pathway that facilitates waste clearance from the brain. This pathway is known as the glymphatic or perivascular system, and its functions are dependent on aquaporin-4 (AQP4). Recently, magnetization transfer indirect spin labeling (MISL) magnetic resonance imaging (MRI) has been proposed as a noninvasive and noncontrast-enhanced method for detecting water exchange between CSF and brain tissue. In this study, we first optimized the MISL sequence at preclinical 3 T MRI, and then studied the correlation of MISL in CSF with magnetization transfer (MT) in brain tissue, as well as the altered water exchange under AQP4 inhibition, using C57BL/6 mice. Results showed a strong correlation of MISL signal with MT signal. With the AQP4 inhibitor, we observed a significant decrease in MISL value (P < 0.05), suggesting that the hampered AQP4 activity led to decreased water exchange between CSF and brain tissue or the impairment of the glymphatic function. Overall, our findings demonstrate the potential application of MISL in assessing brain water exchange at 3 T MRI and its potential clinical translation.

Differences between Acute Embolic and Atherosclerotic Middle Cerebral Artery Occlusion in Multiphase Arterial Spin-labeling Imaging.

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR1.5, 0.73 vs. 0.32 for ICR2.0, and 0.92 vs. 0.37 for ICR2.5). The ΔICR of PLD 1.5-2.0 (ΔICR2.0) and 2.5 (ΔICR2.5) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR2.0, and 92.6% vs. 42.9% for ΔICR2.5). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity

BackgroundImproving brain insulin sensitivity, which can be assessed by measuring regional cerebral blood flow (CBF) responses to intranasal insulin, may prevent age-related metabolic and cognitive diseases. ObjectivesThis study aimed to investigate longer-term effects of mixed nuts on brain insulin sensitivity in older individuals with overweight/obesity. MethodsIn a randomized, single-blinded, controlled, crossover trial, 28 healthy adults (mean ± standard deviation: 65 ± 3 years; body mass index: 27.9 ± 2.3 kg/m2) received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period. Throughout the study, participants were instructed to adhere to the Dutch food-based dietary guidelines. During follow-up, brain insulin action was assessed by quantifying acute effects of intranasal insulin on regional CBF using arterial spin labeling magnetic resonance imaging. Furthermore, effects on peripheral insulin sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers were assessed. ResultsBody weight and composition did not change. Compared with control, mixed nut consumption improved regional brain insulin action in 5 clusters located in the left (difference in CBF responses to intranasal insulin: −4.5 ± 4.7 mL/100 g/min; P < 0.001; −4.6 ± 4.8 mL/100 g/min; P < 0.001; and −4.3 ± 3.6 mL/100 g/min; P = 0.007) and right occipital lobes (−4.3 ± 5.6 mL/100 g/min; and −3.9 ± 4.9 mL/100 g/min; P = 0.028). A fifth cluster was part of the left frontal lobe (−5.0 ± 4.6 mL/100 g/min; P < 0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (−0.7%-point; 95% CI: −1.3%-point to −0.1%-point; P = 0.027), serum low-density lipoprotein cholesterol concentration (−0.24 mmol/L; 95% CI: −0.44 to −0.04 mmol/L; P = 0.019), and systolic blood pressure (−5 mm Hg; 95% CI: −8 to −1 mm Hg; P = 0.006) were lower after the mixed nut intervention. ConclusionsLonger-term mixed nut consumption affected insulin action in brain regions involved in the modulation of metabolic and cognitive processes in older adults with overweight/obesity. Intrahepatic lipid content and different cardiometabolic risk markers also improved, but peripheral insulin sensitivity was not affected.This trial was registered at clinicaltrials.gov as NCT04210869.

Relationship between Arterial Transit Time and Framingham Risk Score in the U.S. POINTER lifestyle intervention trial

AbstractBackgroundThe U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a two‐year randomized controlled trial designed to evaluate the effects of lifestyle interventions on older adults aged 60‐79 years. The POINTER Imaging ancillary study employs arterial spin labeling (ASL) magnetic resonance imaging (MRI) with two inversion times, enabling the mapping of arterial transit time (ATT) and the investigation of its relationship with dementia risk factors. This study examines the effect of the Framingham Risk Score (FRS) on ATT, which provides hemodynamic information on the cerebral vasculature.MethodA subset of POINTER Imaging participants (n = 134; F/M = 81/53; age = 68.1±5.1; FRS = 11.3±10.4) from two imaging sites underwent two ASL MRI scans during the baseline session. Two 3D Pulsed ASL scans were obtained with TI1 of 790ms and TI2 values of 2000ms or 2750ms, providing delay times (between labeling and imaging) of 1210ms or 1960ms. ATT, the time required for blood to travel from the neck to the tissue, was estimated in the range of 1210ms and 1960ms using a kinetic model (Figure 1). ATT maps were normalized to a standard space, and a voxel‐wise linear regression (ATT∼age+sex+log(FRS)) was performed on ATT maps in gray matter to assess the effect of FRS on ATT. To control false positives, clusters smaller than 1.4ml were removed based on a simulation with α = 0.05.ResultFigure 2 depicts three clusters found in the occipital, precuneus and frontal gray matter regions, all of which demonstrate a positive relationship between ATT and log(FRS). Participants with higher FRS exhibit prolonged mean ATT values in the clusters as shown in Figure 3. After stratifying into sex groups, both groups show the same direction.ConclusionAlthough the detectable range of ATT with two ASL scans was limited, the analysis suggests that an increased risk of cardiovascular disease, as quantified by the Framingham Risk Score, can serve as an indicator of potential cerebrovascular disease leading to prolonged ATT, which is associated with arterial stiffness, and vascular resistance. The clusters demonstrating the association between FRS and ATT are the brain regions that may have heightened vulnerability to vascular risk factors, according to previous studies.

Regional cerebral blood flow is associated with PET and plasma biomarkers of tau pathology in middle age

AbstractBackgroundCerebrovascular dysfunction and vascular brain injury are associated with risk and progression of clinical Alzheimer’s disease (AD), but it is unclear whether they contribute directly to disease pathogenesis. Animal models of small vessel cerebrovascular disease suggest that transient cerebral hypoperfusion may promote tau pathology independent of amyloidosis. In the current study, we used pulsed arterial spin labeling (PASL) magnetic resonance imaging (MRI) to examine the association of regional cerebral blood flow (CBF) with two biomarkers of tau pathology, plasma phosphorylated tau 181 (ptau181) concentrations and PET MK6240 SUVR, in middle aged adult participants from the Offspring Study of Mechanisms for Racial Disparities in Alzheimer’s Disease.MethodAt the time of analysis, 469 Offspring Study participants (54.0±10.6‐years‐old; 64% women; 67% Latinx, 22% non‐Latinx Black, 6% non‐Latinx white) had available PASL and ptau181 plasma concentrations (Quanterix Simoa HDx platform). Sixty‐four participants (59.9±5.4‐years‐old age; 67% women; 64% Latinx, 22% non‐Latinx Black, 8% Latinx white) with PASL CBF data received tau PET imaging with MK6240 and mean SUVR was computed across all grey matter regions for each participant. Voxelwise correlational analyses were run to examine the relationship between ptau181 concentrations and regional CBF and between tau PET SUVR and regional CBF.ResultIncreased ptau181 concentrations were associated with clusters of decreased CBF in frontal grey matter, striatum, hippocampus, and periventricular white matter. These correlations were asymmetrical, with the largest clusters found in the left hemisphere. Higher PET SUVR was associated with clusters of lower CBF in frontal, parietal, and occipital grey matter.ConclusionThese findings demonstrate a codependency between regional blood flow and tau pathology, indexed by fluidic and imaging biomarkers. Future studies will clarify the directionality and possible causality of these associations, but these cross‐sectional findings are consistent with a hypothesis that subtle diminished blood flow gives rise to tau abnormalities.

Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy-induced seizures.

Postictal symptoms may result from cerebral hypoperfusion, which is possibly a consequence of seizure-induced vasoconstriction. Longer seizures have previously been shown to cause more severe postictal hypoperfusion in rats and epilepsy patients. We studied cerebral perfusion after generalized seizures elicited by electroconvulsive therapy (ECT) and its relation to seizure duration. Patients with a major depressive episode who underwent ECT were included. During treatment, 21-channel continuous electroencephalogram (EEG) was recorded. Arterial spin labeling magnetic resonance imaging scans were acquired before the ECT course (baseline) and approximately 1 h after an ECT-induced seizure (postictal) to quantify global and regional gray matter cerebral blood flow (CBF). Seizure duration was assessed from the period of epileptiform discharges on the EEG. Healthy controls were scanned twice to assess test-retest variability. We performed hypothesis-driven Bayesian analyses to study the relation between global and regional perfusion changes and seizure duration. Twenty-four patients and 27 healthy controls were included. Changes in postictal global and regional CBF were correlated with seizure duration. In patients with longer seizure durations, global decrease in CBF reached values up to 28 mL/100 g/min. Regional reductions in CBF were most prominent in the inferior frontal gyrus, cingulate gyrus, and insula (up to 35 mL/100 g/min). In patients with shorter seizures, global and regional perfusion increased (up to 20 mL/100 g/min). These perfusion changes were larger than changes observed in healthy controls, with a maximum median global CBF increase of 12 mL/100 g/min and a maximum median global CBF decrease of 20 mL/100 g/min. Seizure duration is a key factor determining postictal perfusion changes. In future studies, seizure duration needs to be considered as a confounding factor due to its opposite effect on postictal perfusion.

Are there network differences between the ipsilateral and contralateral hemispheres of pain in patients with episodic migraine without aura?

Background: We aimed to identify any differences in the structural covariance network based on structural volume and those in the functional network based on cerebral blood flow between the ipsilateral and contralateral hemispheres of pain in patients with episodic migraine without aura.Methods: We prospectively enrolled 27 patients with migraine without aura, all of whom had unilateral migraine pain. We defined the ipsilateral hemisphere as the side of migraine pain. We measured structural volumes on three-dimensional T1-weighted images and cerebral blood flow using arterial spin labeling magnetic resonance imaging. We then analyzed the structural covariance network based on structural volume and the functional network based on cerebral blood flow using graph theory. Results: There were no significant differences in structural volume or cerebral blood flow between the ipsilateral and contralateral hemispheres. However, there were significant differences between the hemispheres in the structural covariance network and the functional network. In the structural covariance network, the betweenness centrality of the thalamus was lower in the ipsilateral hemisphere than in the contralateral hemisphere. In the functional network, the betweenness centrality of the anterior cingulate and paracingulate gyrus was lower in the ipsilateral hemisphere than in the contralateral hemisphere, while that of the opercular part of the inferior frontal gyrus was higher in the former hemisphere.Conclusions: The present findings indicate that there are significant differences in the structural covariance network and the functional network between the ipsilateral and contralateral hemispheres of pain in patients with episodic migraine without aura.

Auto-Classification of Parkinson's Disease with Different Motor Subtypes Using Arterial Spin Labelling MRI Based on Machine Learning.

The purpose of this study was to automatically classify different motor subtypes of Parkinson's disease (PD) on arterial spin labelling magnetic resonance imaging (ASL-MRI) data using support vector machine (SVM). This study included 38 subjects: 21 PD patients and 17 normal controls (NCs). Based on the Unified Parkinson's Disease Rating Scale (UPDRS) subscores, patients were divided into the tremor-dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype. The subjects were in a resting state during the acquisition of ASL-MRI data. The automated anatomical atlas 3 (AAL3) template was registered to obtain an ASL image of the same size and shape. We obtained the voxel values of 170 brain regions by considering the location coordinates of these regions and then normalized the data. The length of the feature vector depended on the number of voxel values in each brain region. Three binary classification models were utilized for classifying subjects' data, and we applied SVM to classify voxels in the brain regions. The left subgenual anterior cingulate cortex (ACC_sub_L) was clearly distinguished in both NCs and PD patients using SVM, and we obtained satisfactory diagnostic rates (accuracy = 92.31%, specificity = 96.97%, sensitivity = 84.21%, and AUCmax = 0.9585). For the right supramarginal gyrus (SupraMarginal_R), SVM distinguished the TD group from the other groups with satisfactory diagnostic rates (accuracy = 84.21%, sensitivity = 63.64%, specificity = 92.59%, and AUCmax = 0.9192). For the right intralaminar of thalamus (Thal_IL_R), SVM distinguished the PIGD group from the other groups with satisfactory diagnostic rates (accuracy = 89.47%, sensitivity = 70.00%, specificity = 6.43%, and AUCmax = 0.9464). These results are consistent with the changes in blood perfusion related to PD subtypes. In addition, the sensitive brain regions of the TD group and PIGD group involve the brain regions where the cerebellothalamocortical (CTC) and the striatal thalamocortical (STC) loops are located. Therefore, it is suggested that the blood perfusion patterns of the two loops may be different. These characteristic brain regions could become potential imaging markers of cerebral blood flow to distinguish TD from PIGD. Meanwhile, our findings provide an imaging basis for personalised treatment, thereby optimising clinical diagnostic and treatment approaches.

Effect of Menopause Status on Brain Perfusion Hemodynamics.

The menopause transition is associated with an increasing risk of cerebrovascular disorders. However, the direct effect of menopause status on brain perfusion hemodynamics remains unclear. This study aimed to explore the influence of menopause status on cerebral blood flow (CBF) using arterial spin labeling magnetic resonance imaging. In this cross-sectional study, 185 subjects underwent arterial spin labeling magnetic resonance imaging at a hospital in China between September 2020 and December 2022, including 38 premenopausal women (mean age, 47.74±2.02 years), 42 perimenopausal women (mean age, 50.62±3.15 years), 42 postmenopausal women (mean age, 54.02±4.09 years), and 63 men (mean age, 52.70±4.33 years) of a similar age range. Mean CBF values in the whole brain, gray matter, white matter, cortical gray matter, subcortical gray matter, juxtacortical white matter, deep white matter, and periventricular white matter were extracted. ANCOVA was used to compare mean CBF among the 4 groups, controlling for confounding factors. Student t test was applied to compare mean CBF between the 3 female groups and age-matched males, respectively. Multivariable regression analysis was used to analysis the effect of age, sex, and menopause status on the CBF of the whole brain, gray matter, white matter, and subregions. Perimenopausal and postmenopausal women showed a higher proportion of white matter hyperintensities compared with the other 2 groups (P<0.001). Premenopausal women exhibited higher CBF in the whole brain, gray matter, white matter, and subregions, compared with perimenopausal, postmenopausal women and men (P≤0.001). Multivariable regression analysis demonstrated significant effect of age and insignificant effect of sex on CBF for all participants. In addition, menopause status and the interaction between age and menopause status on CBF of whole brain, gray matter, white matter, and the subregions were observed in female participants, except for the deep and periventricular white matter regions, with premenopausal women exhibited a slight increase in CBF with age, while perimenopausal and postmenopausal women exhibited declines in CBF with age. The current findings suggest that alterations of brain perfusion hemodynamics begin during the perimenopause period, which may be due to the increased burden of white matter hyperintensities.

Hyperperfusion of bilateral amygdala in patients with chronic migraine: an arterial spin-labeled magnetic resonance imaging study

BackgroundAmygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI).MethodsTwenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed.ResultsCompared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P < 0.05). There were no significant differences of CBF and aCBV values in the bilateral amygdala between the HC and EM groups, the EM and CM groups, as well as the CM without and with MOH groups (all P > 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI).ConclusionHyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.