Pseudo-continuous Arterial Spin Labeling Research Articles

Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial.

Vascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown. OxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent-magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q. In 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, -0.01 to 0.05; P=0.18), or versus cilostazol (-0.01, -0.04 to 0.02; P=0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5-9.07; P<0.001; ∆ end-diastolic velocity, 1.98, 0.66-3.29; P=0.004). Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23-1.42; P=0.007), CVR-WMH (0.07, 0-0.14; P=0.043), CVR-normal-appearing white matter (0.06, 0.00-0.12; P=0.048), perfusion (WMH: 1.82 mL/100 g per minutes, 0.5-3.15; P=0.008; and normal-appearing white matter, 2.12, 0.66-3.6; P=0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05-0.10; P=4.9×10-8; cilostazol-placebo, 0.06, 0.03-0.09; P=5.1×10-5). Both drugs increased headaches (P=1.1×10-4), while cilostazol increased moderate-severe diarrhea (P=0.013). Sildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03855332.

Hypoperfusion of Amygdala in Chronic Migraine: An Exploratory Quantitative Perfusion Imaging Using 3D Pseudo-Continuous Arterial Spin Labeling.

Although the amygdala has structural and functional abnormalities in Chronic Migraine (CM), less is known about the altered perfusion of the amygdala in CM. The current study aimed to assess amygdala perfusion in CM using a contrast agent-free and quantitative approach. 15 Normal Controls (NC) and 13 patients with CM during the migraine interval were assessed for brain structure and subjected to 3D Pseudo- Continuous Arterial Spin Labeling (3D-PCASL) MR imaging. The Cerebral Blood Flow (CBF) value of the amygdala was automatically extracted based on the individual amygdala mask for all participants. The independent sample t-test, Receiver Operating Characteristic (ROC) curve, and correlation analysis were used to evaluate the perfusion changes in CM. Bilateral amygdala cerebral perfusion was lower in CM (left amygdala, 42.21±4.49 ml/100mg/min; right amygdala, 42.38±4.41 ml/100mg/min) than in NC (left amygdala, 48.31±6.92 ml/100mg/min; right amygdala, 47.88±6.53 ml/100mg/min) (left, p = 0.01; right, p = 0.02). There was no significant correlation between the perfusion of bilateral amygdalas and the clinical variables. Also, there was no significant difference in the volume of bilateral amygdalas between the two groups. The Area Under the Curve (AUC) of the CBF values of the left and right amygdala was 0.78 (95%CI: 0.58-0.91) and 0.75 (95%CI: 0.55-0.89), respectively. The cut-off value was 44.24 ml/100mg/min (left amygdala, with sensitivity 76.90% and specificity 78.70%) and 46.75 ml/100mg/min (right amygdala, with sensitivity 92.3% and specificity 58.80%), respectively. CM presented bilateral hypoperfusion in the amygdala, offering potential diagnostic value in distinguishing CM from NC. The 3D-PCASL could be regarded as a simple and efficient neuroimaging tool to assess the perfusion status in CM patients.

Imaging Assessments and Clinical Significance of Brain Frailty in Moyamoya Disease.

Imaging assessment of brain frailty in ischemic stroke has been extensively studied, while the correlation between brain frailty and Moyamoya disease remains obscure. This study aimed to investigate the imaging characteristics of brain frailty and its clinical applications in Moyamoya disease. This study included 60 patients with Moyamoya disease (107 hemispheres). All patients were divided into stroke and nonstroke groups based on clinical symptoms and imaging findings. The modified brain frailty score was adapted to consider 4 imaging signs: white matter hyperintensity, enlargement of perivascular space, old vascular lesions, and cerebral microbleed. The relative CBF of the MCA territory was quantified using pseudocontinuous arterial-spin labeling. Surgical outcome after revascularization surgery was defined by the Matsushima grade. The relative CBF of the MCA territory decreased as the modified brain frailty score and periventricular white matter hyperintensity grades increased (ρ = -0.22, P = .02; ρ = -0.27, P = .005). Clinically, the modified brain frailty score could identify patients with Moyamoya disease with stroke (OR = 2.00, P = .02). Although the modified brain frailty score showed no predictive value for surgical outcome, basal ganglia enlargement of the perivascular space had a significant correlation with the postoperative Matsushima grade (OR = 1.29, P = .03). The modified brain frailty score could reflect a cerebral perfusion deficit and clinical symptoms of Moyamoya disease, and its component basal ganglia enlargement of perivascular space may be a promising marker to predict surgical outcome and thus aid future clinical decision-making.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study

BackgroundPrior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods.MethodsWe evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored.ResultsCompared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05).ConclusionsPatients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Comparing two MRI methods to assess fundamental sex differences in resting cerebral blood flow

Background: Cerebral blood flow (CBF) is a critical measurement for understanding healthy brain physiology prior to aging or neurologic diseases. Patterns of stroke and neurologic pathologies are often sex-specific. Therefore, it is important to understand basic sex differences in CBF, which are often associated with poor brain outcomes. Furthermore, prior literature examining sex differences in CBF is confounded by age, comorbidities, medications, lack of control of menstrual cycle and/or hormonal contraceptive use, and methodological discrepancies. The objective of this study was to compare two different magnetic resonance imaging (MRI) methods of quantifying CBF in young adults while controlling for the aforementioned confounding factors. We hypothesized that females would display higher CBF than males, and that there would be a high reliability between Arterial Spin Labeling (ASL) and 4D Flow MRI. Methods: 30 males and 26 females (23 ± 4yr) were studied on a single MRI (3T) visit. Subjects were fasted 8 hours and withheld caffeine, exercise, and NSAIDs for at least 24 hours. Females were not taking hormonal contraception and were studied on days 1-7 of the menstrual cycle. Microvascular CBF (mL/100g/min) was assessed via pseudo-continuous ASL (pcASL) while 4D Flow MRI acquired with Phase Contrast Vastly undersampled Isotropic Projection Reconstruction (PC VIPR) yielded macrovascular flow via the larger cerebral arteries, summing the internal carotid arteries and basilar artery for total CBF (mL/min). A T1-weighted MRI scan was used to provide brain volumes, allowing CBF from PC VIPR to be normalized and compared to ASL (mL/100g/min). The scans were taken consecutively, with subjects breathing normoxic gas while hemodynamics and end tidal CO2 were monitored. Regression analysis was used to determine reliability of two measures to test a sex difference in CBF. Results: Linear regression analysis demonstrated reliability between measurements of resting CBF via ASL and PC VIPR (p&lt;0.001, R2=0.621). However, ASL measured significantly higher blood flows than PC VIPR in females (63.40 ± 8.55 vs. 56.47 ± 8.48 mL/100g/min, p&lt;0.001) while male subjects had similar flows measured by both methods (45.75 ± 9.39 vs. 46.69 ± 8.19 mL/100g/min, p=0.464). Females displayed an increase in resting CBF compared to males, being 27.8% and 17.3% higher in the ASL and PC VIPR flow measurements (both p&lt;0.001), respectively. Conclusions: These results demonstrate that ASL and PC VIPR CBF display a strong correlation, and that females have greater resting CBF compared to males that is detected by both MRI methods of quantification. However, ASL resulted in greater flow measurements in females, resulting in larger differences being observed (27.8% versus 17.3%). This discrepancy in CBF quantification warrants further investigation to determine the optimal mode of CBF measurement and comparison. Funding by NIH (HL150361). 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.

The Influence of Cholesterol on Resting Brain Blood Flow and Cognition in Middle-Aged Adults

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. 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.

Day-to-day repeatability of total and regional cerebral blood flow

Background: Measuring cerebral blood flow (CBF) has been crucial in understanding brain function and health. Most studies use a resting CBF value for comparison when testing different experimental conditions on different days; however, it is unclear whether resting condition values can be repeated between days. This has important implications for intervention or mechanistic studies. We hypothesize that resting CBF will be repeatable across different days in a well-controlled setting using MRI based pseudo-continuous arterial spin labeling (pcASL). Methods: Seven subjects (1F, 6M) were studied on two separate occasions after abstaining from caffeine, NSAIDs and exercise for 24 hours, and fasting for 8 hours. The end tidal CO2 had to be within 2mmHg between visits. Female subjects were on days 1-7 of their menstrual cycle and were not taking any hormonal contraception. CBF was quantified via MRI based pseudo-continuous Arterial Spin Labeling (pcASL) during both visits and expressed relative to gray and white matter (mL/min/100g). Data focuses on total grey matter, total white matter, and 8 emotional and memory regions. The repeatability of all CBF values was tested between both MRI visits using linear regression. Results: Scans were completed 113± 81 days apart. R2 values showed a weak effect size for grey matter (R2 =0.454) and a moderate effect size for white matter (R2 =0.527). When measuring for the 8 regions of the brain, there were no significant p-values, and weak R2 effect size for the accumbens (p=0.107, R2 =0.454), amygdala (p=0.204, R2 =0.299), anterior cingulate (p=0.092, R2 =0.463), caudate (p=0.122, R2 =0.409) hippocampus (p=0.175, R2 =0.332), and parahippocampus (p=0.183, R2 =0.323). In brain regions involved with memory, the entorhinal cortex indicated a R2 value of moderate effect size (p=0.068, R2 =0.519) t (p=0.068), as well as the precuneus (p=0.060, R2 =0.54) Conclusion: The results suggest that resting CBF demonstrates low repeatability between days. Noteworthy trends exist in the entorhinal cortex and precuneus, which both are involved in memory. These findings suggest that when comparing resting CBF, researchers may want to consider collecting new resting CBF measurements every time they are testing for reactivity since there might be variability in areas such as the accumbens, amygdala, anterior cingulate, caudate, hippocampus and parahippocampus. Funding: NIH R01 HL150361. 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.

Evaluating Ocular Blood Flow in Diabetic Macular Edema using Three-dimensional Pseudocontinuous Arterial Spin Labeling

Background: Alterations in ocular blood flow play an important role in the pathogenesis of diabetic macular edema; however, this remains unclear. Objectives: This study aimed to investigate ocular blood flow in eyes with or without diabetic macular edema using arterial spin labeling. Methods: This cross-sectional study included 118 eyes of 65 patients with diabetic retinopathy analyzed between November 2018 and December 2019. We included a total of 53 eyes without diabetic macular edema (mean [SD] age, 57.83 [7.23] years; 29 men [54.7%]) and 65 eyes with diabetic macular edema (mean [SD] age, 60.11 [7.63] years; 38 men [58.5%]). Using a 3.0-T magnetic resonance imaging, participants were imaged with arterial spin labeling with multiple post-labeling delays. Results: The mean ocular blood flow at post-labeling delays of 1.5 and 2.5 s was significantly lower in eyes with diabetic macular edema among patients with diabetic retinopathy compared with the remaining subgroups (P=0.022 and P &lt;0.001, respectively). The mean ocular blood flow exhibited a significant decrease in eyes with diabetic macular edema when the post-labeling delay was set at 2.5 s in the nonproliferative and proliferative diabetic retinopathy groups, compared with the remaining subgroups (P=0.005 and P=0.002, respectively). The cutoff points of ocular blood flow at post-labeling delays of 1.5 s and 2.5 s were 9.40 and 11.10 mL/100 g/min, respectively. Conclusion: Three-dimensional pseudocontinuous arterial spin labeling can identify differences in the ocular blood flow of patients with diabetic eyes with and without diabetic macular edema.

A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease.

To investigate the abnormalities of the three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD). 3D PCASL images of 53 cognitive normal (CN) subjects, 43 subjects with MCI, and 30 subjects with AD were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Whole-brain CBF maps were calculated using PCASL and proton density-weighted images (PDWI). The 246 regional CBF values, including the cortex and subcortex, were obtained after registering the Brainnetome Atlas to the individual CBF maps. The Pearson correlation coefficient between every two regions across subjects was calculated to construct the CBF correlation network. Then the topologies of CBF networks with regard to global properties (global network efficiency, clustering coefficient, characteristic path length, and small-world properties), hub regions, nodal properties (betweenness centrality, BC), and connections were compared among CN, MCI, and AD. Significant changes in the global and nodal properties were observed in the permutation tests, and connections with significant differences survived after the z-statistic and false discovery rate (FDR) correction. The CBF correlation networks of CN, MCI, and AD all showed small-world properties. Compared with CN, global efficiency decreased significantly in AD. Significant differences in nodal properties and a loss of hub regions are noted in the middle temporal lobe in both MCI and AD. In the frontal lobe, BC is reduced in MCI while it is increased in the occipital lobe in AD. The identified altered hub regions with significant differences in MCI and AD were mainly distributed in the hippocampus and entorhinal cortex. In addition, disrupted hub regions in AD with significantly decreased connections were mainly found in the precuneus/posterior cingulate cortex (PCC) and hippocampus-cortical cortex. Noninvasive 3D PCASL-based CBF correlation networks are capable of showing changes in topological organization in subjects with MCI and AD, and the observed disruption in the topological organization may underlie cognitive decline in MCI and AD.

Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.

Elevated hippocampal perfusion has been observed in people at clinical highrisk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that peripubertal treatment with diazepam can prevent the development of psychosis-relevant phenotypes. The present experimental medicine study examined whether diazepam can normalize hippocampal perfusion in CHR-P individuals. Using a randomized, double-blind, placebo-controlled, crossover design, 24 CHR-P individuals were assessed with magnetic resonance imaging (MRI) on two occasions, once following a single oral dose of diazepam (5 mg) and once following placebo. Regional cerebral blood flow (rCBF) was measured using 3D pseudo-continuous arterial spin labeling and sampled in native space using participant-specific hippocampus and subfield masks (CA1, subiculum, CA4/dentate gyrus). Twenty-two healthy controls (HC) were scanned using the same MRI acquisition sequence, but without administration of diazepam or placebo. Mixed-design ANCOVAs and linear mixed-effects models were used to examine the effects of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on rCBF in the hippocampus as a whole and by subfield. Under the placebo condition, CHR-P individuals (mean [±SD] age: 24.1 [±4.8] years, 15 F) showed significantly elevated rCBF compared to HC (mean [±SD] age: 26.5 [±5.1] years, 11 F) in the hippocampus (F(1,41) = 24.7, pFDR < 0.001) and across its subfields (all pFDR < 0.001). Following diazepam, rCBF in the hippocampus (and subfields, all pFDR < 0.001) was significantly reduced (t(69) = -5.1, pFDR < 0.001) and normalized to HC levels (F(1,41) = 0.4, pFDR = 0.204). In conclusion, diazepam normalized hippocampal hyperperfusion in CHR-P individuals, consistent with evidence implicating medial temporal GABAergic dysfunction in increased vulnerability for psychosis.

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.

Retrospective correction of second-order concomitant fields in 3D axial stack-of-spirals imaging on a high-performance gradient system.

MRI using 3D stack-of-spirals (SoS) readout on a high-performance gradient system is subject to strong second-order, spatially varying concomitant fields, which can lead to signal dropout and blurring artifacts that become more significant at locations farther from the gradient isocenter. A method for compensating for second-order concomitant fields in 3D axial SoS image reconstruction is described. We retrospectively correct for second-order concomitant field-induced phase error in the 3D SoS data by slice-dependent k-space phase compensation based on the nominal spiral readout trajectories. The effectiveness of the method was demonstrated in phantom and healthy volunteer scans in which 3D pseudo-continuous arterial spin labeling imaging was performed with SoS fast spin-echo readout at 3 T. Substantial reduction in blurring was observed with the proposed method. In phantom scans, blurring was reduced by about 53% at 98 mm from the gradient isocenter. In the in vivo 3D pseudo-continuous arterial spin labeling scans, differences of up to 10% were observed at 78 mm from the isocenter, especially around the white-matter and gray-matter interfaces, between the corrected and uncorrected proton density images, perfusion-weighted images, and cerebral blood flow maps. The described retrospective correction method provides a means to correct erroneous phase accruals due to second-order concomitant fields in 3D axial stack-of-spirals imaging.

Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington’s disease

BackgroundHuntington’s disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD.MethodsUsing pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type (WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13 months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15 months of age.ResultsWe found increased perfusion in cortical regions of zQ175DN HET mice at 3 months of age, and a reduction of this anomaly at 6 and 9 months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6 months of age, for only somatosensory and retrosplenial cortices at 9 months of age, and brain-wide by 15 months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9 months, with whole brain reactivity diminished at 15 months of age. Interestingly, blood vessel density was increased in the motor cortex at 3 months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6 months of age.ConclusionOur findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.

Application of 3D-PCASL combined with t-ASL and MRA in the diagnosis of patients with isolated vertigo induced by posterior circulation ischemia

ObjectivesIsolated vertigo induced by posterior circulation ischemia (PCIV) can further progress into posterior circulation infarction. This study aimed to explore the diagnostic values of three-dimensional pseudo-continuous arterial spin labeling (3D-PCASL) combined with territorial arterial spin labeling (t-ASL) and magnetic resonance angiography (MRA) in visualizing and evaluating PCIV, seeking improved diagnostic tools for clinical guidance. Methods28 PCIVs (11 males, 17 females, aged from 55 to 83 years, mean age: 69.68 ± 9.01 years) and 28 healthy controls (HCs, 12 male, 16 female, aged from 56 to 87 years, mean age: 66.75 ± 9.86 years) underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), MRA, 3D-PCASL, and t-ASL. We compared the incidence of anatomic variants of the posterior circle of Willis in MRA, cerebral blood flow (CBF) and anterior collateral blood flow on postprocessing maps obtained from 3D-PCASL and t-ASL sequence between PCIVs and HCs. Chi-square test and paired t-test were analyzed statistically with SPSS 24.0 software. Results7 PCIVs (7/28, 25%) and 6 HCs (6/28, 21%) showed fetal posterior cerebral artery (FPCA) on MRA, including 1 HC, and 6 PCIVs with FPCA appeared hypoperfusion. 18 PCIVs (64%) and 2 HCs (7%) showed hypoperfusion in the posterior circulation (PC), including 1 HC and 7 PCIVs displayed anterior circulation collateral flow. Chi-square analyses demonstrated a difference in PC hypoperfusion between PCIVs and HCs, whether in the whole or FPCA-positive group assessment (P < 0.05). Paired t-test showed that the CBF values were significant difference for the bilateral PC asymmetrical perfusion in the PCIVs (P < 0.01). When compared to the bilateral PC symmetrical non-hypoperfusion area in the PCIVs and HCs, the CBF values were not significant (P > 0.05). The CBF values of the PC in PCIVs were lower than in HCs (P < 0.05). The reduction rate in the hypoperfusion side of the bilateral PC asymmetrical perfusion of the PCIVs ranged from 4% to 37%, while the HCs reduction rate was 7.7%. The average PC symmetrical perfusion average reduction rate of the PCIVs was 52.25%, while the HCs reduction rate was 42.75%. Conclusion3D-PCASL is a non-invasive and susceptible method for detecting hypoperfusion in PC, serving as a potential biomarker of PCIV. The suspected hypoperfusion in PC may be attributed to the emergence of FPCA and the manifestation of anterior collateral flow when combining t-ASL and MRA sequences. These findings demonstrated that 3D-PCASL combined with t-ASL and MRA sequences are the potential method to identify PCIV, leading to early diagnosis of PCIV and reducing the risk of progressing into infarction.

Decreased Cerebral Perfusion in Chronic Migraine: A Voxel-based Cerebral Blood Flow Analysis Using 3D Pseudo-continuous Arterial Spin Labeling.

A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.

349 Brain Functional Imaging of Pain States Using Resting-State fMRI and Multi-Delay PCASL in Chronic Low-Back Pain Patients Implanted With Thoracic Spinal Cord Stimulation

INTRODUCTION: A treatment of chronic low-back pain is implantation of a thoracic spinal cord stimulator (tSCS), which has been shown to reduce pain. The functional changes in pain processing regions of the brain as assessed by resting-state fMRI and multi-delay pseudocontinuous arterial spin labeling (PCASL) have never been studied. METHODS: PCASL data based on 5 post-label delays (0.5–2.5s) as well as rsfMRI were acquired in five patients (1F) post-tSCS with cLBP and five healthy subjects (2F). Patient MRI scans were taken post-implantation with the SCS device turned off. Three PCASL measures and four rsfMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from the pain ROI atlas were extracted and compared between patients and controls. Statistics were conducted following Box-Cox transformation of data. RESULTS: Arterial transit time derived from PCASL showed a significant difference in the OFC, SMA, and PSG of patients, but other ASL measures showed no effect. Several regions across the rs-fMRI measures showed significant differences, including those involved in cognition (DLPFC, PCC), and pain processing (PSG) and sensation (S2). CONCLUSIONS: Functional imaging showed that cLBP patients treated with SCS display differences in resting-state function and brain perfusion across several pain regions of the brain. These areas are mainly part of the cognitive and behavioral components of the pain circuitry.

354 Feasibility and Clinical Imaging of Pain States Based on Multi-Delay Arterial Spin Labeling in Chronic Low Back Pain Patients Implanted With Thoracic Spinal Cord Stimulation

INTRODUCTION: Multi-delay, pseudo-continuous arterial spin labelling (PCASL) is a novel technique capable of perfusion imaging without contrast. It overcomes the limitation of a low signal-to-noise ratio of pulsed-ASL, and multiple post-label delays allow it to account for and measure arterial transit time (ATT). This makes it a suitable tool for the perfusion assessment. To date, there have been no studies to assess changes in ASL-measured perfusion in chronic low-back pain (cLBP) patients treated with thoracic spinal cord stimulation (tSCS). METHODS: PCASL data was acquired in five patients post-tSCS and five healthy subjects. ATT was estimated using weighted delays from multiple delay times, and it was used to calculate cerebral blood flow (CBF) and cerebral blood volume (CBV). Maps were normalized into MNI space and smoothed. Averaged values of ATT, CBF and CBV from pain ROI atlas were extracted and compared between cLBP and healthy control groups. Statistics comparing perfusion changes between patients and healthy subjects were conducted after Box-Cox transformation of data using Wilcoxon rank sum. RESULTS: Our results demonstrated the feasibility of MRI scanning with ASL sequence in patients with SCS. Specific absorption rates ranged from 0.031–0.042W/kg. Wilcoxon test indicated that ATT was significantly greater in cLBP patients within the supplementary motor area, posterior short gyrus, and the orbitofrontal cortex. There were no significant differences in patients and controls in CBF or CBV. CONCLUSIONS: Rate of perfusion as indexed by PCASL-derived ATT is reduced in cLBP treated with SCS patients in regions associated with pain processing, cognition, and motor planning. Insignificant results in CBF and CBV measures are likely due to low sample size of patients.

Lesion volume and spike frequency on EEG impact perfusion values in focal cortical dysplasia: a pediatric arterial spin labeling study

Arterial spin labelling (ASL), an MRI sequence non-invasively imaging brain perfusion, has yielded promising results in the presurgical workup of children with focal cortical dysplasia (FCD)-related epilepsy. However, the interpretation of ASL-derived perfusion patterns remains unclear. Hence, we compared ASL qualitative and quantitative findings to their clinical, EEG, and MRI counterparts. We included children with focal structural epilepsy related to an MRI-detectable FCD who underwent single delay pseudo-continuous ASL. ASL perfusion changes were assessed qualitatively by visual inspection and quantitatively by estimating the asymmetry index (AI). We considered 18 scans from 15 children. 16 of 18 (89%) scans showed FCD-related perfusion changes: 10 were hypoperfused, whereas six were hyperperfused. Nine scans had perfusion changes larger than and seven equal to the FCD extent on anatomical images. Hyperperfusion was associated with frequent interictal spikes on EEG (p = 0.047). Perfusion changes in ASL larger than the FCD corresponded to larger lesions (p = 0.017). Higher AI values were determined by frequent interictal spikes on EEG (p = 0.004). ASL showed FCD-related perfusion changes in most cases. Further, higher spike frequency on EEG may increase ASL changes in affected children. These observations may facilitate the interpretation of ASL findings, improving treatment management, counselling, and prognostication in children with FCD-related epilepsy.

DYNAMIC ASSESSMENT OF CEREBRAL PERFUSION BLOOD FLOW IN THE EARLY POST-STROKE PERIOD ACCORDING TO NON-CONTRAST MRI DATA

HighlightsThe non-contrast perfusion MR sequence pCASL (pseudocontinuous arterial spin labeling) is a technique that allows specialist to quantify and trace the changes in cerebral blood flow in the early post-stroke period. At the same time, there is a change in perfusion indices not only in the ischemic stroke area, but also in visually intact areas of the ipsilateral and contralateral hemispheres of the brain, which indicates the involvement of the blood supply area and the brain as a whole in the pathological process. The obtained data on the dynamics in perfusion, verified by the results of cognitive tests, open up the prospect of a comprehensive study of stroke as a complex brain disease with the possibility of predictive assessment of rehabilitation. Aim. To assess the dynamics of microcirculatory changes in the brain in the early post-stroke period by non-contrast perfusion MRI.Methods. The study included 42 patients with acute ischemic stroke. The patients were examined by 3T MRI using the following sequences: DWI-EPI, 3D FLAIR-SPIR, T2-TSE, T1W 3D-TFE, and pseudocontinuous arterial spin labeling (pCASL) on 1–3 days, 7–10 days and 3 months later after the manifestation of acute ischemic stroke. The cerebral blood flow (CBF) was obtained in 4 supratentorial regions of the brain: in the ischemic stroke and contralateral areas, as well as in a visually intact area of the ipsilateral and contralateral hemispheres (mL/100g/min).Results. In the ischemic stroke area, CBF increased from 19.86±5.69 (mean+Std) to 27.57±4.86 by first to the second examination, which was associated with the infusion therapy, local inflammatory response and compensatory reperfusion. By the 3rd examination CBF decreased to 14.48±3.66 (Student t-test, p&lt;0.05), which reflects cystic and atrophic transformation of the affected area. In visually intact white matter of the ipsilateral and contralateral hemispheres, CBF increased from hypoperfused to normoperfused from the first to the third examination. There was a significant decrease (p&lt;0.001) in tissue blood flow (by 54% for the 1st, 38% for the 2nd, 67% for the 3rd examination) in the ischemia area relative to intact parts of the brain.Conclusion. The pCASL allowed us to assess CBF in the post-stroke period in the ischemic area and in visually intact area, nevertheless, it requires additional pre- and postprocessing of data to obtain quantitative values. At the same time, we observed changes in perfusion in the ischemic stroke area, and in the visually intact areas of the ipsilateral and contralateral hemispheres of the brain, indicating the involvement of the cerebral blood flow and brain as a whole in the pathological process.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. Prospective. Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. 2 TECHNICAL EFFICACY: Stage 3.