Spin Labeling Magnetic Resonance Imaging Research Articles

Trial of the cerebral perfusion response to sodium nitrite infusion in patients with acute subarachnoid haemorrhage using arterial spin labelling MRI

Aneurysmal subarachnoid haemorrhage (SAH) is a devastating subset of stroke. One of the major determinants of outcome is an evolving multifactorial injury occurring in the first 72 hours, known as early brain injury. Reduced nitric oxide (NO) bioavailability and an associated disruption to cerebral perfusion is believed to play an important role in this process. We sought to explore this relationship, by examining the effect on cerebral perfusion of the in vivo manipulation of NO levels using an exogenous NO donor (sodium nitrite).We performed a double blind placebo controlled randomised experimental medicine study of the cerebral perfusion response to sodium nitrite infusion during the early brain injury period in 15 low grade (World Federation of Neurosurgeons grade 1–2) SAH patients. Patients were randomly assigned to receive sodium nitrite at 10 mcg/kg/min or saline placebo. Assessment occurred following endovascular aneurysm occlusion, mean time after ictus 66h (range 34–90h). Cerebral perfusion was quantified before infusion commencement and after 3 hours, using multi-post labelling delay (multi-PLD) vessel encoded pseudocontinuous arterial spin labelling (VEPCASL) magnetic resonance imaging (MRI).Administration of sodium nitrite was associated with a significant increase in average grey matter cerebral perfusion. Group level voxelwise analysis identified that increased perfusion occurred within regions of the brain known to exhibit enhanced vulnerability to injury. These findings highlight the role of impaired NO bioavailability in the pathophysiology of early brain injury.

Sex differences in gray matter, white matter, and regional brain perfusion in young, healthy adults.

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between gray and white matter or without assessing regional CBF. Thus fundamental sex differences in regional or whole brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total gray and white matter perfusion as well as regional gray matter perfusion. Adults 18-30 yr old (females = 22 and males = 26) were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by computational anatomy toolbox (CAT12) analysis in statistical parametric mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females = 62 ± 9 and males = 45 ± 10 mL/100 g/min, P < 0.001), gray matter (females = 75 ± 11 and males = 54 ± 12 mL/100 g/min, P < 0.001), and white matter (females = 44 ± 6 and males = 32 ± 7 mL/100 g/min, P < 0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14% to 66% higher. A second MRI approach (4-dimensional flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, gray, and white matter levels and across dozens of brain regions and offer new clarity into fundamental sex differences in global and regional CBF regulation before aging or pathology.NEW & NOTEWORTHY MRI used to measure cerebral blood flow (CBF) in gray matter, white matter, and 68 regions in healthy men and women. This study demonstrated that CBF is 40% higher in women, the highest sex difference reported, when controlling for numerous important clinical confounders like age, smoking, menstrual cycle, comorbidities, and medications.

Exploring the Impact of Hemoglobin on Cerebral Blood Flow in Arterial Territories and Surgical Outcomes: Potential Implications for Moyamoya Disease Treatment.

Changes in levels of hemoglobin would result in alterations of cerebral blood flow (CBF). However, the impact of hemoglobin on CBF in moyamoya disease (MMD) remains largely unknown. This study sought to determine whether CBF would be influenced by hemoglobin before surgical revascularization and to analyze the relationships between hemoglobin and CBF with clinical outcome after surgery in patients with MMD. We prospectively enrolled adult patients with MMD undergoing surgical revascularization between June 2020 and December 2022. Preoperative CBF was measured in the territories of anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA, respectively) using 3-dimensional pseudo-continuous arterial spin labeling magnetic resonance imaging. Clinical outcome at 1 year after surgery was evaluated using the modified Rankin Scale. A total of 60 patients with MMD were included, with 25% (n=15) experiencing unfavorable outcomes. Patients with MMD exhibited lower CBF (ACA: P=0.007; MCA: P<0.001; PCA: P=0.014), compared with healthy controls (n=40). Hemoglobin was negatively and significantly associated with CBF (ACA: β=-0.45, P<0.001; MCA: β=-0.38, P<0.001; PCA: β=-0.54, P<0.001). CBF rather than hemoglobin was significantly related with clinical outcome (ACA: P<0.001; MCA: P<0.001; PCA: P=0.001), and CBF showed high discrimination in predicting clinical outcome (ACA: area under the curve, 0.84; MCA: area under the curve, 0.84; PCA: area under the curve, 0.80). Our findings demonstrate that hemoglobin significantly influences CBF, and CBF has a high predictive value for clinical outcome in MMD. The optimal hemoglobin level before surgical revascularization should be further investigated.

Right anterior insula ASL hypoperfusion as a diagnostic biomarker of prodromal and mild dementia with Lewy bodies: preliminary evidence using a Bayesian approach.

Identifying and validating a biomarker with high specificity in early-stage dementia with Lewy bodies (DLB) using a feasible method is crucial to enhance the current suboptimal diagnostic procedure. Previous research revealed abnormalities, including hypoperfusion in the right anterior insular cortex at group level, in prodromal DLB. Exploring hypoperfusion of the right anterior insula, at an individual-level and assessing its relevance as a potential imaging biomarker in early DLB, has, to our knowledge, not been investigated. Our preliminary study aims to assess the feasibility of the technique and to provide a methodological framework for further investigation. We assessed the feasibility and accuracy of the hypoperfusion of the right anterior insula per arterial spin labelling magnetic resonance imaging (ASL-MRI) as a diagnostic biomarker in early DLB and provided rough estimates of its sensitivity and specificity. Defining the region of interest based on previous research, we established the biomarker as the hypoperfusion of the right anterior insula. Discriminative and analytical performances were assessed in comparison to a control group of treatment-resistant depression patients. Bayesian diagnostic reasoning was employed to assess the biomarker diagnostic usability in early DLB in two scenarios: healthy elderly controls and mild cognitive impairment. Additionally, we updated probabilities by integrating data from the Mayo-clinic cognitive fluctuations scale and real-time quaking-induced conversion (RT-QuIC) α-synuclein data. Lastly, a whole-brain perfusion analysis of DLB patients was conducted to identify further brain regions with discriminative abilities. We successfully replicated the right anterior insular hypoperfusion (RAI-Hypo) in all DLB patients at the individual level. The overall sensitivity of the biomarker was 96%, and the specificity was 92%. Bayesian testing revealed the biomarker's highest performance in early-stage DLB with cognitive fluctuations, showcasing a diagnostic potential associated with a high precision and moderate accuracy. In a cognitively non-impaired population, the RAI-Hypo showed a limited usability and lacked in selectivity to qualify as a screening tool. The exploratory whole-brain analysis revealed perfect discriminative capacities in the bilateral anterior insulae and the left inferior parietal lobule. Further studies are needed to confirm our preliminary results. If performance is maintained in subsequent studies and is compared to a more suitable control population, the proposed biomarker may be eventually sufficient to discriminate early-stage DLB from non-DLB.

Spatial coefficient of variation of arterial spin labeling magnetic resonance imaging can predict decreased cerebrovascular reactivity measured by acetazolamide challenge single-photon emission tomography.

The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate decreased cerebrovascular reactivity (CVR) measured with single-photon emission computed tomography (SPECT) and acetazolamide challenge in patients with atherosclerotic stenosis of intra- or extracranial arteries. We evaluated the data of 27 atherosclerotic stenosis patients who underwent pseudocontinuous ASL and SPECT. After spatial normalization, regional values were measured using the distributed middle cerebral artery territorial atlas of each patient. We performed comparisons, correlations, and receiver operating characteristic (ROC) curve analyses between ASL-cerebral blood blow (CBF), ASL-CoV, SPECT-CBF and SPECT-CVR. Although the ASL-CBF values were positively correlated with SPECT-CBF values (r = 0.48, 95% confidence interval (CI) = 0.28-0.64), no significant difference in ASL-CBF values was detected between regions with and without decreased CVR. However, regions with decreased CVR had significantly greater ASL-CoV values than regions without decreased CVR. SPECT-CVR was negatively correlated with ASL-CoV (ρ = -0.29, 95% CI = -0.49 - -0.06). The area under the ROC curve of ASL-CoV in predicting decreased CVR (0.66, 95% CI = 0.51-0.81) was greater than that of ASL-CBF (0.51, 95% CI = 0.34-0.68). An ASL-CoV threshold value of 42% achieved a high specificity of 0.93 (sensitivity = 0.42, positive predictive value = 0.77, and negative predictive value = 0.75). ASL-CoV acquired by single postlabeling delay without an acetazolamide challenge may aid in the identification of patients with decreased CVR on SPECT.

The effect of post-labeling delay on cerebral blood flow is influenced by age and sex: a study based on arterial spin-labeling magnetic resonance imaging.

Whether the effect of post-labeling delay (PLD) on cerebral blood flow (CBF) is influenced by age and sex in adults is unknown. In this study, we mainly aimed to explore the potential influence of age and sex on the effect of PLD on CBF. This prospective study enrolled 90 healthy adult volunteers (49.47±15.63 years of age; age range, 20-77 years; 47 female; 43 male). All participants underwent 3-dimensional (3D) pseudo-continuous arterial spin labeling (ASL) imaging with 3 different PLDs (1,525, 2,025, and 2,525 ms). The CBF values for each PLD, the arterial transit time (ATT), and the spatial coefficient of variation (spatial CoV) were computed for 21 regions of interest (ROIs) in every participant. Multivariate regression analysis was conducted to assess the potential influence of age and sex on the effect of PLD on CBF and the relationships among CBF, ATT, PLD, age, sex, and spatial CoV. The CBF increased for 7.32 to 9.87 mL/100 g/min as the PLD increased per 1 second in the global gray matter, bilateral frontal, temporal lobes, the vascular territories of bilateral anterior and middle carotid artery. When the age increased per 1 year, the speed of the changes for CBF decreased for 0.26 to 0.3 mL/100 g/min/s in these regions. However, the CBF decreased for 12 to 17 mL/100 g/min as the PLD increased per 1 second in the bilateral limbic lobes, insula, and deep gray matter. In these regions, the speed of the changes for CBF increased for 0.2 to 0.28 mL/100 g/min/s as the age increased per 1 year. Furthermore, compared to the female, the speed of the changes for CBF decreased for 3.58 to 4.6 mL/100 g/min/s for the male in global gray matter, bilateral frontal, limbic lobes, and the vascular territories of bilateral anterior carotid artery, and the speed increased 4.49 to 5.09 mL/100 g/min/s for the male in the limbic lobes. In addition, the CBF decreased with aging and the CBF tended to be higher in females compared to males. At the same time, we found that the ATT of all ROIs increased with age and manifested higher in males than females. Moreover, we found that CBF decreased with the increase of ATT, and the effect of ATT on CBF was less influenced by PLD. Finally, we found that the spatial CoV of ASL in certain regions increased with the increase of ATT and age, and was greater in males. The effect of PLD on CBF can be influenced by age and sex. The relationships among CBF, ATT, PLD, age, sex, and spatial CoV found in this study may have certain significance for the study of ASL imaging in the future.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5T or 3T. Healthy controls were investigated with both 1.5T and 3T ASL-MRI. We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56years, range 18-82years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50years, range 21-77years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2mL/100g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Abnormal cerebral blood flow in children with developmental stuttering.

Stuttering affects approximately 5% of children; however, its neurological basis remains unclear. Identifying imaging biomarkers could aid in early detection. Accordingly, we investigated resting-state cerebral blood flow (CBF) in children with developmental stuttering. Pulsed arterial spin labelling magnetic resonance imaging was utilised to quantify CBF in 35 children with developmental stuttering and 27 healthy controls. We compared normalised CBF between the two groups and evaluated the correlation between abnormal CBF and clinical indicators. Compared with healthy controls, the stuttering group exhibited decreased normalised CBF in the cerebellum lobule VI bilaterally, right cuneus, and left superior occipital gyrus and increased CBF in the right medial superior frontal gyrus, left rectus, and left dorsolateral superior frontal gyrus. Additionally, normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus was positively correlated with stuttering severity. Children who stutter display decreased normalised CBF primarily in the cerebellum and occipital gyrus, with increased normalised CBF in the frontal gyrus. Additionally, the abnormal CBF in the left cerebellum lobule VI and leftsuperior occipital gyrus was associated with more severe symptoms, suggesting that decreased CBF in these areas may serve as a novel neuroimaging clue for stuttering. Stuttering occurs in 5% of children and often extends into adulthood, which may negatively affect quality of life. Early detection and treatment are essential. We used pulsed arterial spin labelling magnetic resonance imaging to visualise the resting-state cerebral blood flow (CBF) in children who stutter and healthy children. Normalised CBF was decreased in stutterers in the cerebellum and occipital gyrus and increased in the frontal gyrus. Stuttering severity was linked to abnormal normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus, suggesting that CBF may serve as a novel neuroimaging clue for stuttering.

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.

Aged HIV-1 Tg26 Transgenic Mice display Vascular Dysfunction with No Alterations in Neurocognitive Function or Cerebral Blood Flow

Although combination antiretroviral therapy (cART) has markedly reduced HIV mortality and increased life expectancy, people living with HIV (PLWH) develop premature cognitive and brain aging, classified as HIV-associated neurocognitive disorder (HAND). Vascular dysfunction and expression of HIV-derived proteins have independently been associated with cognitive impairment without causality being established. Thus, we investigated the role of HIV viral proteins in endothelial dysfunction and cognitive impairment in an aged mouse model of HIV. We used 18-month-old Tg26 mice and their wild-type littermate controls. Tg26 mice express 7 out of the 9 HIV viral proteins under the control of the long-term repeat promoter and have previously been shown to exhibit signs of cognitive impairment at eight months of age. Conduction of concentration-response curves to acetylcholine in mesenteric arteries using wire myography revealed impaired endothelium-dependent relaxation in Tg26 mice compared to WT mice. Measurements of brain perfusion with arterial spin labeling magnetic resonance imaging showed no differences in the whole brain and hippocampal cerebral blood flow. In addition, there were no changes in the hippocampus volume, which has been reported to be reduced with cognitive impairments. Two methods were employed to assess the cognitive abilities of the mice: Morris water maze (MWM) and the IntelliCage system. MWM requires human handling while the IntelliCage system is fully automated enabling the testing of mouse cognitive function during their active period and independently of human handling. Tg26 and WT mice underwent ten days of MWM testing and eight days of IntelliCage testing to assess spatial learning and memory. Tg26 mice showed no significant differences in latency to platform, distance swam to platform, or swim velocity when compared to their WT littermates. The IntelliCage results showed no differences in total visits, total visits with nose pokes, or total licks during the reversal learning period. Additionally, there were no significant differences in percent side error or place error indicating that cognitive function is not impaired in Tg26 mice. The Y-maze test further showed no differences in spontaneous alteration, a measure of spatial working memory. Altogether, our data shows that although 18-month-old female Tg26 mice develop endothelial dysfunction, they display no alterations in cerebral blood flow and no cognitive impairment indicating that systemic viral protein expression and vascular dysfunction might minimally contribute to neurocognitive impairment in HIV. R01HL130301 &amp; R01HL155265 (E.J.B). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

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.

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)

Cerebral blood flow in the paracentral lobule is associated with poor subjective sleep quality among patients with a history of methadone maintenance treatment.

Sleep disorders are prevalent and significant among individuals receiving methadone maintenance treatment (MMT), adversely affecting their quality of life and treatment adherence. While cerebral blood flow (CBF) plays a crucial role in the development of various diseases, its relationship with sleep disorders remains uncertain. This observational study focuses on possible correlations between CBF and poor subjective sleep quality in MMT patients. A total of 75 participants with a history of MMT were recruited and assessed using pseudo-continuous arterial spin labeling magnetic resonance imaging to determine CBF. A LAASO regression model was employed to identify the region of interest (ROI) most associated with sleep disturbance. The association between the CBF of the ROI and the Pittsburgh Sleep Quality Index (PSQI) was examined using regression analyses. Age, gender, BMI, history of hypertension, diabetes, hyperlipidemia, and methadone withdrawal were included as covariates. Among MMT patients with poor subjective sleep quality, significantly higher CBF was observed in the right paracentral lobule (56.1057 ± 11.1624 ml/100 g/min, p = 0.044), right cerebelum_3 (56.6723 ± 15.3139 ml/100 g/min, p = 0.026), right caudate nucleus (48.9168 ± 6.9910 ml/100 g/min, p = 0.009), and left caudate nucleus (47.6207 ± 6.1374 ml/100 g/min, p = 0.006). Furthermore, a positive correlation was found between CBF in the right paracentral lobule and the total PSQI score (β = 0.1135, p = 0.0323), with the association remaining significant even after adjustment for covariates (β = 0.1276, p = 0.0405). MMT patients with poor subjective sleep quality exhibited significantly altered CBF in multiple brain regions. The association between increased CBF in the right paracentral lobule and subjective sleep quality in MMT patients could be crucial in understanding sleep disorders in individuals undergoing MMT. https://www.chictr.org.cn/, identifier: ChiCTR2100051931.

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