Continuous Arterial Spin Labeling Research Articles

Insomnia in patients with MRI-negative epilepsy: The associated factors and 3D-pCASL cerebral blood flow perfusion changes

ObjectiveThis study aimed to identify the factors associated with insomnia in MRI-negative epilepsy and uncover the underlying pathological mechanism driving insomnia within the context of epilepsy. MethodsWe conducted a retrospective study of patients with MRI-negative epilepsy recruited consecutively from December 2021 to December 2022. All subjects completed the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Additionally, some subjects underwent the three-dimensional pseudo continuous arterial spin labeling(3D-pCASL) imaging examination. Bilateral frontal lobe, temporal lobe, hippocampus, thalamus, amygdala, caudate nucleus and lenticular nucleus were selected as regions of interest(ROI) and cerebral blood flow(CBF) values were measured in these regions. Subjects were classified into insomnia (ISI ≥ 10) or non-insomnia (ISI < 10) groups, and univariate and stepwise logistic regression analyses were employed to identify the factors associated with insomnia. Furthermore, CBF values in each ROI were compared between the two groups to identify the brain regions potentially related to the underlying pathological mechanism of insomnia in epilepsy. ResultsA total of 73 patients with MRI-negative epilepsy were recruited in this study(men, 49.3 %). Among them, 14 patients(19.2 %) had insomnia. Univariate regression revealed that nocturnal seizures, number of anti-seizure medication(ASM), anxiety, use of valproic acid(VPA), depression, and excessive daytime sleepiness(EDS) may be associated with insomnia in MRI-negative epilepsy (all p＜0.05). Stepwise regression demonstrated that nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy (OR[95 %CI]P: 14.64[2.02–106.27]0.008,49.35[3.06–796.61]0.006, 13.28[1.25–140.66]0.032, respectively). Furthermore, CBF values in the left amygdala were significantly lower in patients with MRI- negative epilepsy who had insomnia. ConclusionThe prevalence of insomnia in MRI-negative epilepsy is 19.2%. Nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy. The noteworthy decrease in CBF values in the left amygdala might be connected to the underlying pathological mechanism of insomnia in epilepsy.

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.

Multi‑parameter quantitative magnetic resonance imaging in the early assessment of radiation‑induced parotid damage in patients with nasopharyngeal carcinoma following intensity‑modulated radiotherapy.

The present study aimed to investigate the value of intravoxel incoherent motion imaging (IVIM) and three-dimensional pulsed continuous arterial spin labeling (ASL) in assessing dynamic changes of the parotid gland in patients with nasopharyngeal carcinoma (NPC) following radiotherapy (RT). A total of 18 patients with NPC who underwent intensity-modulated RT were enrolled in the present study. All patients underwent conventional magnetic resonance imaging, plus IVIM and ASL imaging of the bilateral parotid glands within 2 weeks prior to RT, and 1 week (1W) and 3 months (3M) following RT. Pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (F) and blood flow (BF) were analyzed. D and BF values were significantly increased from pre-RT to 1W post-RT [change rate: Median (IQR), ΔD1W%: 39.28% (38.23%) and ΔBF1W%: 60.84% (54.88%)] and continued to increase from 1W post-RT to 3M post-RT [55.44% (40.56%) and ΔBF%: 120.39% (128.74%)]. In addition, the F value was significantly increased from pre-RT to 1W post-RT, [change rate: Median (IQR), ΔF1W%: 28.13% (44.66%)], and this decreased significantly from 1W post-RT to 3M post-RT. However, no significant differences were observed between pre-RT and 3M post-RT. Results of the present study also demonstrated that the D* value was significantly decreased from pre-RT to 1W post-RT and 3M post-RT [change rate: Median (IQR), ΔD*1w%: -41.86% (51.71%) and ΔD*3M: -29.11% (42.67%)]. No significant difference was observed between the different time intervals post-RT. There was a significant positive correlation between percentage change in ΔBF1W and radiation dose (ρ=0.548, P=0.001). Thus, IVIM-diffusion-weighted imaging and ASL may aid in the detection and prediction of radiation-induced parotid damage in the early stages following RT. They may contribute to further understanding the potential association between damage to the parotid glands and patient-/treatment-related variables, through the assessment of individual microcapillary perfusion and tissue diffusivity.

Time‐encoded ASL shows higher sensitivity to detect cerebral blood flow reductions in AD

AbstractBackgroundPseudo continuous arterial spin labelling (pcASL) is an MRI technique to quantify cerebral blood flow (CBF). Time encoded ASL (te‐ASL) is a multiple time‐point pcASL variant that by acquiring several post‐label delays (PLD) to have more accurate CBF estimation allowing to measure arterial‐transit time (ATT). The aim of this study was to assess the performance of te‐ASL in detecting CBF and ATT changes in the Alzheimer’s disease (AD) continuum.MethodThe sample consisted of 59 subjects: 25 healthy controls (HC), 17 cognitively unimpaired individuals with positive cerebrospinal fluid (CSF) biomarkers (Ab42&lt;1.098pg/mL; p‐Tau181&gt;19pg/mL; Elecsys® ‐Roche Diagnostics) (preAD) and 17 patients with clinical diagnosis of AD (Ab42/p‐Tau181 ratio &lt;10.25; Lumipulse‐Fujirebio). The MRI protocol comprised of anatomical T1, and ASL sequences (M0 and te‐ASL). CBF and ATT maps were calculated in the oxford_asl toolbox in FSL. CBF and ATT maps were spatially normalized to the MNI, smoothed (12mm FWHM) and intensity normalized to the cerebellar gray matter. To detect patterns of lower CBF, voxel‐wise one way 3‐group ANOVA and post‐hoc paired t‐tests were performed using age and sex as confounders (SPM12; statistical threshold: p&lt;0.001 uncorrected; k&gt;100 voxels (∼0.33cm3) in all analyses). We compared results with those obtained using a single PLD by computing CBF from the last PLD (perfusion block, nominal PLD time of 2000ms) of the te‐ASL schema.ResultTable 1 displays the descriptive statistics of the sample. Figure 1 shows that, with te‐ASL, AD patients displayed lower CBF (yellow) in extensive bilateral pareto‐temporal, cingulate and occipital areas. Preclinical AD participants showed an overlapping pattern (green), albeit reduced in extension. When using pcASL, the detected pattern of lower CBF in the AD group was less extended and did not overlap with that of the PreAD groups. No ATT differences were found associated to AD.Conclusionte‐ASL was more sensitive to detect CBF differences across the AD continuum than single PLD ASL. The pattern of lower CBF in the AD group covered expected areas, and that in the preclinical AD group partially overlapped.

ASL lexicon and reporting recommendations: A consensus report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

The 2015 consensus statement published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group and the European Cooperation in Science and Technology ( COST) Action ASL in Dementia aimed to encourage the implementation of robust arterial spin labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ASL Lexicon and Reporting Recommendations for perfusion imaging and analysis, aiming to (1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as for the physiological constants required for quantitative analysis; and (2) provide a community-endorsed recommendation of the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/papers. In this paper, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL, and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Multimodal neuroimaging data from a 5-week heart rate variability biofeedback randomized clinical trial

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform.

Modulation Effects of Repeated Transcranial Direct Current Stimulation at the Dorsolateral Prefrontal Cortex: A Pulsed Continuous Arterial Spin Labeling Study.

Transcranial direct current stimulation (tDCS) is a promising non-invasive method to modulate brain excitability. The aim of this study was to better understand the cerebral blood flow (CBF) changes during and after repeated tDCS at the right dorsolateral prefrontal cortex (DLPFC) in healthy participants using pulsed continuous arterial spin labeling (pCASL). Elucidating CBF changes associated with repeated tDCS may shed light on the understanding of the mechanisms underlying the therapeutic effects of tDCS. tDCS was applied for three consecutive days for 20 min at 2 mA, and MRI scans were performed on day 1 and 3. During anodal tDCS, increased CBF was detected in the bilateral thalamus on day 1 and 3 (12% on day 1 and of 14% on day 3) and in the insula on day 1 (12%). After anodal tDCS on day 1, increased CBF was detected in the cerebellum and occipital lobe (11.8%), while both cathodal and sham tDCS were associated with increased CBF in the insula (11% and 10%, respectively). Moreover, anodal tDCS led to increased CBF in the lateral prefrontal cortex and midcingulate cortex in comparison to the sham. These findings suggest that tDCS can modulate the CBF and different tDCS modes may lead to different effects.

Sex‐specific decoupling of cerebral blood flow and glucose metabolism in Alzheimer’s disease mouse model

AbstractBackgroundCerebral blood flow (CBF) dysregulation and neurovascular impairment are central to Alzheimer’s disease (AD) etiology1. Even though two‐thirds of the AD patients are women, the sex differences in vascular and metabolic risk factors are still unclear2. Previously, we described sex‐specific CBF trajectories in mouse model of AD3. In the present study, we connect these CBF changes with cerebral glucose metabolism in the same males and females. We quantify the correlation between metabolic rate and vascular flow and identify unique points of divergence across lifespan.MethodWe used 9.4T MRI of APPswe.PSEN1dE9 mice (23 males, 24 females; young 3‐7 months, middle age 7‐15 months, and old 15‐24 months) and B6C3F1/J controls (n=20). We quantified CBF (qCBF) using T1‐weighted mapping and continuous arterial spin labeling (CASL) as previously described3.The glucose uptake rate (ΔR1ρ) was measured using chemical exchange‐sensitive spin lock (CESL) and computed as the difference between the steady state before and after intravenous injection of 2‐Deoxy‐d‐glucose (2DG)4. Region of interests were drawn manually on the cortex and subcortical areas.ResultWe found that AD females, but not AD males had lower cortical glucose metabolism than age‐matched controls, while both AD groups had lower CBF than controls. These differences were not significant in the subcortical regions. The metabolic trajectory during aging was similar between AD males and females (Fig 1A), however, the CBF trajectory of AD males showed a transient increase from young to middle age, while the female group showed an opposite trend (Fig 1B). The sex‐specific divergence between glucose consumption and CBF appeared during middle age. Male AD mice had higher positive correlation between glucose metabolism and CBF in the cortex compared to females (Fig 2A). Additionally, in both AD groups, this correlation was positive in the cortex but not in the subcortical region (Fig 2).ConclusionWhen interpreting metabolic rate of glucose and CBF as AD biomarkers, age, sex and brain region should be taken into consideration.

Choroid plexus tissue perfusion and blood to CSF barrier function in rats measured with continuous arterial spin labeling

The choroid plexus (ChP) of the cerebral ventricles is a source of cerebrospinal fluid (CSF) production and also plays a key role in immune surveillance at the level of blood-to-CSF-barrier (BCSFB). In this study, we quantify ChP blood perfusion and BCSFB mediated water exchange from arterial blood into ventricular CSF using non-invasive continuous arterial spin labelling magnetic resonance imaging (CASL-MRI). Systemic administration of anti-diuretic hormone (vasopressin) was used to validate BCSFB water flow as a metric of choroidal CSF secretory function. To further investigate the coupling between ChP blood perfusion and BCSFB water flow, we characterized the effects of two anesthetic regimens known to have large-scale differential effects on cerebral blood flow. For quantification of ChP blood perfusion a multi-compartment perfusion model was employed, and we discovered that partial volume correction improved measurement accuracy. Vasopressin significantly reduced both ChP blood perfusion and BCSFB water flow. ChP blood perfusion was significantly higher with pure isoflurane anesthesia (2-2.5%) when compared to a balanced anesthesia with dexmedetomidine and low-dose isoflurane (1.0 %), and significant correlation between ChP blood perfusion and BCSFB water flow was observed, however there was no significant difference in BCSFB water flow. In summary, here we introduce a non-invasive, robust, and spatially resolved in vivo imaging platform to quantify ChP blood perfusion as well as BCSFB water flow which can be applied to study coupling of these two key parameters in future clinical translational studies.

Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation.

This review article provides an overview of the current status of velocity‐selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in‐depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo‐) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Relationships of Cerebral Perfusion With Gait Speed Across Systolic Blood Pressure Levels and Age: A Cohort Study.

This study aimed to examine if the association of cerebral perfusion with gait speed differs across systolic blood pressure (SBP) and age. Cerebral perfusion was measured via arterial spin labeled (ASL)-MRI among community-dwelling adults aged 31-94 years in the population-based Mayo Clinic Study of Aging. Usual gait speed was assessed over 5.6 meters on an electronic mat. Sex- and body mass index (BMI)-adjusted linear regression models estimated cross-sectional gait speed associations with ASL and modifying effects of age and SBP using 3-way and 2-way interaction terms between continuous age, SBP, and ASL. Results report estimated differences in gait speed per standard deviation (SD) lower ASL for exemplar SBPs and ages. Among 479 participants (mean age 67.6 years; 44% women; mean gait speed 1.17 m/s), ASL relations to gait speed varied by age (ASL-x-age interaction: p = .001) and SBP (ASL-x-SBP interaction: p = .009). At an SBP of 120 mmHg, each SD lower ASL was associated with a 0.04 m/s (95% confidence interval [CI]: 0.01, 0.07) slower gait speed at 65 years, 0.07 m/s (0.04, 0.10) at 75 years, and 0.09 m/s (0.05, 0.13) at 85 years. At an SBP of 140 mmHg, ASL associations with gait speed were attenuated to 0.01 (-0.01, 0.04), 0.04 (0.02, 0.06), and 0.06 (0.04, 0.09) m/s slower gait speed at ages 65, 75, and 85, respectively. Poorer cerebral perfusion is associated with clinically meaningful slower gait speeds, particularly with older age, while higher perfusion markedly attenuates age differences in gait speed.

Cerebral perfusion changes of the basal ganglia and thalami in full-term neonates with hypoxic-ischaemic encephalopathy: a three-dimensional pseudo continuous arterial spin labelling perfusion magnetic resonance imaging study.

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the common causes of neurological injury in full-term neonates following perinatal asphyxia. The conventional magnetic resonance technique has low sensitivity in detecting variations in cerebral blood flow in patients with HIE. This article evaluates the clinical diagnostic value of three-dimensional pseudo-continuous arterial spin labelling (3-D pcASL) perfusion magnetic resonance imaging (MRI) for early prediction of neurobehavioral outcomes in full-term neonates with HIE. All neonates diagnosed with HIE underwent MRI (conventional and 3-D pcASL perfusion MRI). Cerebral blood flow values were measured in the basal ganglia (caudate nuclei, lenticular nuclei), thalami and white matter regions (frontal lobes, corona radiata). After 1-month follow-up, the Neonatal Behavioral Neurological Assessment scores were used to divide patients into favourable outcome group versus adverse outcome group. Twenty-three patients were enrolled in this study. There were no statistical differences between the symmetrical cerebral blood flow values of bilateral basal ganglia, thalami and white matter regions. However, the cerebral blood flow values of grey matter nuclei were higher than the white matter regions. The average value of cerebral blood flow in the basal ganglia and thalami in the adverse outcome group was 37.28±6.42ml/100g/min, which is greater than the favourable outcome group (22.55 ± 3.21ml/100g/min) (P<0.01). The area under the curve (AUC) of 3-D pcASL perfusion MRI was 0.992 with a cutoff value of 28.75ml/100g/min, with a Youden's index of 0.9231. The sensitivity and specificity were 92.3% and 100%, respectively. The 3-D pcASL demonstrated higher perfusion alteration in the basal ganglia and thalami of neonatal HIE with adverse outcomes. The 3-D pcASL perfusion MRI has the potential to predict neurobehavioral outcomes of neonates with HIE.

Concordance of regional hypoperfusion by pCASL MRI and 15O-water PET in frontotemporal dementia: Is pCASL an efficacious alternative?

BackgroundClinical diagnosis of frontotemporal dementia (FTD) remains a challenge due to the overlap of symptoms among FTD subtypes and with other psychiatric disorders. Perfusion imaging by arterial spin labeling (ASL) is a promising non-invasive alternative to established PET techniques; however, its sensitivity to imaging parameters can hinder its ability to detect perfusion abnormalities. PurposeThis study evaluated the similarity of regional hypoperfusion patterns detected by ASL relative to the gold standard for imaging perfusion, PET with radiolabeled water (15O-water). Methods and materialsPerfusion by single-delay pseudo continuous ASL (SD-pCASL), free-lunch Hadamard encoded pCASL (FL_TE-pCASL), and 15O-water data were acquired on a hybrid PET/MR scanner in 13 controls and 9 FTD patients. Cerebral blood flow (CBF) by 15O-water was quantified by a non-invasive approach (PMRFlow). Regional hypoperfusion was determined by comparing individual patients to the control group. This was performed using absolute (aCBF) and CBF normalized to whole-brain perfusion (rCBF). Agreement was assessed based on the fraction of overlapping voxels. Sensitivity and specificity of pCASL was estimated using hypoperfused regions of interest identified by 15O-water. ResultsRegion of interest (ROI) based perfusion measured by 15O-water strongly correlated with SD-pCASL (R = 0.85 ± 0.1) and FL_TE-pCASL (R = 0.81 ± 0.14). Good agreement in terms of regional hypoperfusion patterns was found between 15O-water and SD-pCASL (sensitivity = 70%, specificity = 78%) and between 15O-water and FL_TE-pCASL (sensitivity = 71%, specificity = 73%). However, SD-pCASL showed greater overlap (43.4 ± 21.3%) with 15O-water than FL_TE-pCASL (29.9 ± 21.3%). Although aCBF and rCBF showed no significant differences regarding spatial overlap and metrics of agreement with 15O-water, rCBF showed considerable variability across subtypes, indicating that care must be taken when selecting a reference region. ConclusionsThis study demonstrates the potential of pCASL for assessing regional hypoperfusion related to FTD and supports its use as a cost-effective alternative to PET.

Sex‐specific cerebral blood flow trajectories in mouse models of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) therapies targeting the aggregation of amyloid‐beta during the late stages have been largely unsuccessful. Growing evidence indicates that cerebral blood flow (CBF) plays a key role during the early AD stages by limiting the energy supply to the brain and impairing the clearance of harmful metabolites1. Recent studies suggest that CBF can be used as a predictor of AD2. Despite the CBF potential as a biomarker, its sex‐specific changes during AD progression are still poorly characterized. In the present study we quantify CBF trajectories in male and female mouse model of AD across lifespan. We also measure the tissue plaques and the vascular deposits in the form of cerebral amyloid angiopathy (CAA) to assess their relationship with CBF.MethodWe used 9.4T MRI of APPswe.PSEN1dE9 mice (12 male,10 female, 6‐24 months) and matched controls (n=15). We quantified CBF (qCBF) using T1‐weighted mapping (TE=12ms, TR=10 sec, 9 inversion times between 15‐8000ms and continuous arterial spin labeling (CASL) with TE=0.32ms and TR=2625ms with a label offset 12mm, duration 2.4s. Both had 64×64 matrix with 210 μm/voxel. We computed qCBF as previously described.3 Smooth muscle actin (SMA) and X34 staining was performed on free floating sections. Two‐way ANOVA was used to evaluate the age and sex effects on parenchymal plaques, CAA and qCBF.ResultWe found CBF to be significantly reduced in AD mice compared to controls (Fig 1, t‐test p=0.00017). Two‐way ANOVA showed a significance in the effects of sex and AD as factors on CBF (p=0.015) and an impact of both sex and age on the tissue plaque accumulation (Fig 2A), CAA was affected by age, with trend for higher CAA in females (Fig 2B), particularly after 13 months when qCBF declined.ConclusionWhen interpreting blood flow as AD biomarker both age and sex should be taken into consideration. The accumulation of tissue and vascular plaques appears to occur at different rates and depends both on age and sex. Further studies are needed on the CAA and CBF interaction and the sex‐specific vascular contributions to AD onset and progression. 1.Kisler et al. (2017). 2.Iturria‐Medina et al. (2015). 3.Zhang et al. (1992).

Aberrant interhemispheric functional connectivity and cerebral blood flow in vascular dementia (VD) and non‐amyloid mild cognitive impairment (NamyMCI)

AbstractBackgroundPrevious studies have demonstrated that functional connectivity and relative cerebral blood flow were altered in patients suffered from Alzheimer’s disease (AD) and Mild cognitive impairment (MCI). However, the application on vascular dementia (VD) and non‐amyloid mild cognitive impairment (VMCI) are still unclear.Method65 participants (18 healthy controls HC, 16 AD, 18 NamyMCI, 13 vascular dementia (VD)) were recruited, from the university hospital memory clinic, to undergo MRI scanning. All participants underwent structural MRI, resting state functional MRI (rs‐fMRI) scanning and pseudo continuous arterial spin labelling (pCASL) with post‐labelling delay time at 2000ms in the same session. Voxel Mirrored Homotopic Connectivity (VMHC) was calculated based on the method used by Kelly et al., 2011 [1] and Zuo et al., 2010 [2]. The analysis of pCASL images performed using ASL‐MRICloud by Li et al., 2017 [3]. White matter hypointensities on T1‐weighted 3D anatomical images of each individual was calculated using FreeSurfer image analysis suite 6.0. Group differences in VMHC, absolute CBF and relative CBF were determined by performing whole brain voxel‐wise ANCOVA analysis on subject‐specific VMHC maps, absolute CBF maps and relative CBF maps respectively, with age, gender and GM volume as covariates. To identify the significant associations between IFC and CBF, a voxel‐wise correlation analysis was conducted using the DPABI v 4.0.ResultBoth IFC and CBF were reduced in AD group. However there is no significant relationship found in correlation analysis. For NamyMCI group, negative correlation were found in precuneus, cuneus, calcarine, superior frontal gyrus and insula. For VD, positive correlation was found in superior frontal gyrus, inferior frontal orbital gyrus, rolandic operculum and superior temporal gyrus. Also, the T1 white matter hypointensity volume was significantly larger than that of the other groups (p&lt;0.001).ConclusionIFC reduction in AD was independent to CBF reduction, probably related amyloid deposition. For NamyMCI, negative correlation suggested that CBF increases to compensate the attenuated IFC to maintain daily functions. For VD, CBF reduction relates positively with IFC, suggested the CBF reduction is one of the factors contributed to IFC reduction in VD.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer’s dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer’s disease.

49-OR: Changes in Regional Cerebral Blood Flow during Hypoglycemia in T1DM

Regulation of cerebral blood flow (CBF) during hypoglycemia (HYPO) is critical for maintaining adequate glucose delivery to the brain; however, specific changes in regional CBF during HYPO are not well defined. We measured CBF in 14 T1DM (mean ± SD age 31 ± 7 yrs, DM duration 16 ± 5 yrs, A1c 7.2 ± 1.0 %) and 13 healthy controls (CON; age 35 ± 11 yrs, A1c 5.2 ± 0.5 %) using 3.0 T MRI continuous arterial spin labeling during fasting baseline (BAS), a hyperinsulinemic (2 mU/kg/min) euglycemic clamp (EUG; 90 mg/dl), followed by a hypoglycemic clamp (HYPO; 50 mg/dl). Global and regional changes in CBF were measured in 15 regions of interest (ROI). At BAS, gray matter CBF was similar in CON and T1DM (58 ± 16 vs. 61 ± 11 ml/100 gm brain/min). No significant changes in CBF were observed from BAS to EUG in any brain region in either CON or T1DM. However, during HYPO in T1DM, CBF increased by 10% in gray matter and 16% in brainstem, both p &amp;lt;0.05. CBF also increased by 10% - 18% in specific ROIs involved in awareness of internal states, reward and emotion (orbitofrontal cortex, insula, anterior cingulate cortex, thalamus, and substantia nigra; p&amp;lt;0.01 to p&amp;lt;0.05). Minimal increases in CBF (1% - 6%) were observed in regions primarily involved in sensory or motor function, (occipital cortex, motor cortex, cerebellum, caudate, putamen) or in the posterior cingulate (all p &amp;gt; 0.30). In CON, no significant global or regional changes in CBF occurred during HYPO. In all subjects, higher A1c correlated with greater increases in CBF during HYPO (p&amp;lt;0.05). Conclusions: 1) Hyperinsulinemia per se does not alter CBF in T1DM or CON, 2) During HYPO, brain blood flow increases more in T1DM vs. CON, especially in regions involved in integration of internal awareness, reward and emotion, compared to sensory or motor function, and 3) Greater increases in CBF in subjects with higher A1c suggest that compensatory physiologic mechanisms enable subjects with chronic exposure to hyperglycemia to maintain adequate cerebral glucose supply when plasma glucose levels are suddenly reduced. Disclosure D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. N. R. Bolo: None. J. Theberge: None. G. Musen: None. A. M. Jacobson: None. Funding National Institutes of Health (DK073843)

Quantification of Regional Cerebral Blood Flow Using Diffusion Imaging With Phase Contrast.

The perfusion-related diffusion coefficient obtained from triexponential diffusion analysis is closely correlated with regional cerebral blood flow (rCBF), as assessed by arterial spin labeling (ASL) methods. However, this provides only a semiquantitative measure of rCBF, thereby making absolute rCBF quantification challenging. To obtain rCBF in a noninvasive manner using a novel diffusion imaging method with phase contrast (DPC), in which the total CBF from phase-contrast (PC) MRI was utilized to convert perfusion-related diffusion coefficients to rCBF values. Prospective. Eleven healthy volunteers (nine men and two women; mean age, 23.9 years) participated in this study. A 3.0 T, single-shot diffusion echo-planar imaging with multiple b-values (0-3000 s/mm2 ), PC-MRI, pulsed continuous ASL, and 3D T1 -weighted fast field echo. rCBF and its correlations in the gray matter (GM) and white matter (WM) were compared between DPC and ASL methods. rCBF in the GM and WM and the GM/WM ratio were compared with the literature values obtained using [15 O]-water positron emission tomography (15 O-H2 O PET). Spearman's correlation coefficient and Wilcoxon signed-rank test were used. Significance was set at P < 0.05. A significant positive correlation between DPC and ASL in terms of rCBF was observed in GM (R=0.9), whereas the correlation between the two methods was poor in WM (R=0.09). The rCBF in GM and WM and the GM/WM ratio obtained using DPC were consistent with the literature values assessed using 15 O-H2 O PET. The rCBF value obtained using DPC was significantly higher in the GM and WM than that using ASL. DPC enabled noninvasive quantification of rCBF. 2 TECHNICAL EFFICACY: Stage 1.

Can Hybrid Arterial Spin Labeling-Tagged Zero-Echo-Time Magnetic Resonance Angiography Be an Effective Candidate in the Evaluation of Intracranial Artery Diseases? A Clinical Feasibility Study.

Flow related artifacts in continuous arterial spin labeling (cASL) zero-echo-time (ZTE) magnetic resonance angiography (MRA) could influence the vasculature visualization. To investigate the clinical feasibility for the intracranial artery diseases assessment by utilizing hybrid ASL-ZTE-MRA (hASL-ZTE-MRA). Prospective, technical development. Sixty-seven subjects with known/suspected cerebrovascular diseases. Gradient echo based cASL-/hASL- ZTE-MRA at 3.0 T. Subjective/objective evaluation for sound-levels. Image quality (IQ), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed within artery segments. Stenotic grading, aneurysm measurement, and signal intensity of lesions were further analyzed. Kolmogorov-Smirnov test for data normality check. Between two MRAs: Wilcoxon signed-rank test for sound experience/IQ ratings analysis; Paired t test for SNR/CNR comparison. One-way analysis of variance for sound intensity comparison. For stenosis grading/aneurysm measurement: Kendall's W test/intraclass correlation coefficient (ICC) for interobserver agreement test within each modality, weighted kappa statistics/ICC for intermodality agreement test between each MRA and computed tomography angiography. Sound-level perception/intensity was similar (P=0.86, P=0.55) between MRAs. The mean IQ score for hASL-ZTE-MRA was on diagnostic scale and slightly higher (P < 0.05) than that of cASL-ZTE-MRA. hASL-ZTE-MRA provided higher (P < 0.05) SNR/CNR than that of cASL-ZTE-MRA. Signal uniformity was improved on hASL-ZTE-MRA, particularly among the anterior circulation (P < 0.05). Comparing to cASL-ZTE-MRA, on hASL-ZTE-MRA, stenotic lesions were accurately assessed; flow in the stent or aneurysm remnant was better depicted (P < 0.05); AVM nidus was preferred with increased SNR (P < 0.05). No significant differences for the aneurysm measurement were found between MRAs (P=0.95), in addition to the slightly higher SNR (P < 0.05) on hASL-ZTE-MRA. Comparing to cASL-ZTE-MRA, hASL-ZTE-MRA is robust and feasible for the evaluation of intracranial artery diseases with diagnostic IQ, improved vessel contrast, and better signal heterogeneity. 2 TECHNICAL EFFICACY: 2.

Cardiovascular, Cerebral and Behavioral Response to Anti‐Hypertensive Treatment in Female Dahl Salt Sensitive Rats

Background Cerebrovascular disease is associated with central arterial stiffness (CAS), which can lead to reduced brain blood supply, neuronal density loss and cognitive impairment. Dahl salt sensitive (DSS) rats represent a model of vascular dementia and have a compromised renin-angiotensin system, develop CAS, hypertension, and hippocampal memory decline with age on a normal salt (NS) diet. Lisinopril (LIS), an angiotensin converting enzyme inhibitor, effectively treated this pathology in aged male DSS rats. We investigated the relationship between systolic blood pressure (SBP), pulse wave velocity (PWV), a marker of CAS, hippocampal blood flow (CBF), neuronal density and anxiety in female DSS rats treated with LIS. Methods Female DSS rats (n=23) were fed a NS diet (0.5% NaCl) for the duration of the study. Rats were administered LIS (15mg/kg BW/day in drinking water, n=12) or control treatment (CTRL; n=11) for 7-mo beginning at 6-mo of age. The following measurements were assessed at 6-mo (baseline; BL) and at 13-mo of age: SBP (by plethysmography), PWV (by echocardiography), CBF (by continuous arterial spin labeling), and hippocampal N-acetyl aspartate concentration (NAA; by proton magnetic resonance spectroscopy). In open field test (OFT; a metric of anxiety, a precursor to symptoms of dementia) travel activity (distance) and rearing durations (vertical activity; VA) in the center of the field were collected as measures of exploratory behavior. Pearson's correlation matrix and 2-way ANOVA mixed effects model analyses were performed. Results At BL, the treatment groups were not different in any parameters except heart rate (HR). At 13-mo CTRL, SBP and PWV increased, CBF, total distance, total VA and distance in center of the OFT decreased compared to BL. In 13-mo LIS group, SBP and PWV were lower compared to 13-mo CTRL; 13-mo LIS group had higher HR and lower SBP, CBF and total VA in OFT compared to BL (Table 1). At 6-mo, NAA and VA were marginally correlated. HR and central distance were significantly correlated (Table 2A). For 13-mo CTRL, SBP positively correlated with PWV and NAA. NAA negatively correlated with distance in center. HR negatively correlated with distance in center and VA in center (Table 2B). This relationship with HR was reversed for 13-mo LIS group, for which PWV and CBF were negatively associated with central distance and central VA, while NAA was negatively correlated with central VA only (Table 2C). Conclusion In both CTRL and LIS groups, advancing age adversely affected hippocampal perfusion, but not neuronal density. ChronicLIS treatment reduced hypertension and PWV but did not affect cerebral parameters in aged female DSS rats. Increased level of anxiety, known to predate cognitive decline, was associated with PWV for LIS group, suggesting that CAS can adversely affect brain structures and function. CTRL and LIS groups showed differences in associations between cerebral, behavioral, and cardiovascular parameters. Further analyses will be conducted to investigate the role of sex hormones and their associations with age in the patterns observed.