Arterial Spin Labeling MRI Research Articles

Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.

Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer's Disease Biomarker-Positive Older Adults.

Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.

Associations Between Carotid Plaque Characteristics and Perioperative Cerebral Blood Flow Determined by Arterial Spin Labeling Imaging in Patients With Moderate-to-Severe Stenosis Undergoing Carotid Endarterectomy.

PurposeTo examine the associations between carotid plaque characteristics and perioperative cerebral blood flow (CBF) by arterial spin labeling (ASL) imaging.Materials and MethodsPatients with unilateral moderate-to-severe carotid stenosis referred for carotid endarterectomy (CEA) were recruited and underwent carotid vessel wall and brain ASL magnetic resonance imaging. The following imaging features were measured: relative CBF (rCBF = CBFindex−hemisphere/CBFcontralateral−hemisphere) in the middle cerebral artery territory; plaque burden and the presence of lipid-rich necrotic core; intraplaque hemorrhage (IPH); calcification; ulcer and fibrous-cap rupture; and the volume and maximum plaque components' area percentages. The associations between plaque characteristics and perioperative CBF were analyzed.ResultsSixty-one patients (mean age, 66.6 ± 7.8 years; 55 males) were included. Univariate linear regression showed that rCBFpre−CEA was associated with stenosis [β, −0.462; 95% confidence interval (CI), from −0.797 to −0.126; p = 0.008], calcification (β, 0.103; 95% CI, 0.005–0.201; p = 0.040), maximum IPH area percentage (β, −0.127; 95% CI, from −0.223 to −0.030; p = 0.012), and ulcer (β, 0.069; 95% CI, 0.025–0.113; p = 0.005); rCBFpost−CEA was associated with the IPH volume (β, −0.060; 95% CI, from −0.107 to −0.014; p = 0.013). After adjusting for the confounding factors, the associations of calcification with rCBFpre−CEA (β, 0.099; 95% CI, from 0.004 to −0.194; p = 0.042) and IPH volume with rCBFpost−CEA (β, −0.060; 95% CI, from −0.109 to −0.011; p = 0.020) remained statistically significant, while those of rCBFpre−CEA with maximum IPH area percentage (β, −0.089; 95% CI, from −0.188 to 0.011; p = 0.080) and ulcer (β, 0.050; 95% CI, from −0.012 to 0.112; p = 0.100) did not remain statistically significant.ConclusionThe compositional characteristics of carotid atherosclerotic plaques, particularly IPH, were associated with perioperative CBF in patients with unilateral moderate-to-severe carotid stenosis undergoing CEA. Our findings indicated that the patients with larger carotid IPH could expect smaller improvement in CBF following CEA.

Incipient chronic traumatic encephalopathy in active American football players: neuropsychological assessment and brain perfusion measures

Background and aimsChronic traumatic encephalopathy (CTE) is a degenerative disease caused by repetitive traumatic brain injury (TBI). Because CTE can be definitely diagnosed only post-mortem, it would be important to explore clinical and radiological correlates of CTE and TBI. The aims of this study were to assess (1) the relationship between the neuropsychological profile of active American football players and the traumatic load; (2) whether traumatic brain injury associated with American football activity has a specific cerebral perfusion pattern; and (3) whether this perfusion pattern correlates with neuropsychological performances.MethodsIn 20 American football players [median age [25th–75th percentile] 25.0 [21.6–31.2] years, all males], we evaluated history, traumatic load and symptoms using the TraQ (Trauma Questionnaire), and cognitive performances on neuropsychological tests. Brain perfusion was estimated using arterial spin labeling MRI and compared to a group of 19 male age-matched (28.0 [24.8–32.3] years) healthy subjects.ResultsWe found different cognitive performances between American football players stratified according to field position and career length. Linemen had poorer executive, verbal, and visual performances; a career > 7 years was associated with poorer verbal fluency performances. American football players had statistically significant reduced cerebral blood flow values in sensory-motor areas in comparison with healthy controls. Poorer neuropsychological performances correlated with lower perfusion in specific brain areas.ConclusionsOur study seems to confirm that CTE in American football players is influenced by the field position and the career length, and correlates with lower cognitive performances linked to lower perfusion in specific brain areas.

Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge.

To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p=0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p=0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6months after the study without noticeable aberrant behavior or appearance. We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.

A Beginner's Guide to Arterial Spin Labeling (ASL) Image Processing.

Arterial spin labeling (ASL) is a non-invasive and cost-effective MRI technique for brain perfusion measurements. While it has developed into a robust technique for scientific and clinical use, its image processing can still be daunting. The 2019 Ann Arbor ISMRM ASL working group established that education is one of the main areas that can accelerate the use of ASL in research and clinical practice. Specifically, the post-acquisition processing of ASL images and their preparation for region-of-interest or voxel-wise statistical analyses is a topic that has not yet received much educational attention. This educational review is aimed at those with an interest in ASL image processing and analysis. We provide summaries of all typical ASL processing steps on both single-subject and group levels. The readers are assumed to have a basic understanding of cerebral perfusion (patho) physiology; a basic level of programming or image analysis is not required. Starting with an introduction of the physiology and MRI technique behind ASL, and how they interact with the image processing, we present an overview of processing pipelines and explain the specific ASL processing steps. Example video and image illustrations of ASL studies of different cases, as well as model calculations, help the reader develop an understanding of which processing steps to check for their own analyses. Some of the educational content can be extrapolated to the processing of other MRI data. We anticipate that this educational review will help accelerate the application of ASL MRI for clinical brain research.

P.147 Evaluation of Arterial Spin Labeling (ASL) perfusion imaging in poorly- defined focal epilepsy in children

Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and &gt;18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.

1310-P: Effects of Insulin Resistance on Brain Responses to Caloric Sugars and Nonnutritive Sweetener

Evidence suggests that insulin resistance (IR) affects feeding behavior by modulating neural responses to post-ingestive signals, including nutrients and taste. We examined associations between IR and activation of the hypothalamus and insula, brain regions involved in homeostasis and taste processing, to ingestion of sugars and the non-nutritive sweetener (NNS) , sucralose. Seventy-four participants (23.4±4 years; 42%male; BMI 27.2±5; HOMA-IR 5.3±5) completed 4 MRI visits with ingestion of drinks containing 75g sucrose, 75g glucose, sucralose, or water in a randomized cross-over design. Arterial spin labeling MRI was performed before, 15min and 30min after drink ingestion to measure cerebral blood flow (CBF) . Primary outcomes were associations between HOMA-IR and hypothalamic and insular CBF responses to glucose vs. sucrose, sucralose vs. water, and sucrose vs. sucralose. Mixed effects models included the following factors: drink contrasts, sex, time point, and BMI and HOMA-IR as continuous variables. Bonferroni-Holm was used to adjust for multiple comparisons. In the hypothalamus, HOMA-IR, independent of BMI, was associated with a greater hypothalamic CBF response to sucralose vs. water (p&amp;lt;0.03) , but there was no association between HOMA-IR and hypothalamic response to sugar. In the insula, there was a drink by HOMA-IR interaction in the insular response to sucralose vs. water (p&amp;lt;0.02) ; persons with IR showed greater increases in CBF after sucralose vs. water. We also found a main effect of HOMA-IR; persons with higher IR had greater insular CBF increases to sugar (p&amp;lt;0.05) , and a drink by HOMA-IR interaction revealed a stronger association between IR and insular response to glucose vs. sucrose (p&amp;lt;0.03) . There was no association between HOMA-IR and brain responses to sucralose vs. sucrose. These findings show that IR is associated with greater activation of brain regions involved in taste and energy homeostasis to ingestion of sugar and NNS, which may promote eating behavior. Disclosure S. Kullmann: Other Relationship; Novo Nordisk. R. Veit: None. K. Jann: None. S.H. Luo: None. B.C. Angelo: None. J.M. Alves: None. J.R. Monterosso: None. K.A. Page: None. Funding NIDDK R01DK102794

Subclinical cognitive deficits are associated with reduced cerebrovascular response to visual stimulation in mid-sixties men

Reduced cerebrovascular response to neuronal activation is observed in patients with neurodegenerative disease. In the present study, we examined the correlation between reduced cerebrovascular response to visual activation (ΔCBFVis.Act) and subclinical cognitive deficits in a human population of mid-sixties individuals without neurodegenerative disease. Such a correlation would suggest that impaired cerebrovascular function occurs before overt neurodegenerative disease. A total of 187 subjects (age 64–67 years) of the Metropolit Danish Male Birth Cohort participated in the study. ΔCBFVis.Act was measured using arterial spin labelling (ASL) MRI. ΔCBFVis.Act correlated positively with cognitive performance in: Global cognition (p = 0.046), paired associative memory (p = 0.025), spatial recognition (p = 0.026), planning (p = 0.016), simple processing speed (p < 0.01), and with highly significant correlations with current intelligence (p < 10−5), and more complex processing speed (p < 10−3), the latter two explaining approximately 11–13% of the variance. Reduced ΔCBFVis.Act was independent of brain atrophy. Our findings suggest that inhibited cerebrovascular response to neuronal activation is an early deficit in the ageing brain and associated with subclinical cognitive deficits. Cerebrovascular dysfunction could be an early sign of a trajectory pointing towards the development of neurodegenerative disease. Future efforts should elucidate if maintenance of a healthy cerebrovascular function can protect against the development of dementia.

359-OR: Imaging Pancreatic Blood Flow during Stimulation of Insulin Secretion in Humans

Non-invasive imaging of endocrine pancreatic function could provide valuable insights into the magnitude and temporal pattern of β-cell dysfunction in diabetes. Islets comprise 1-2% of pancreatic mass, but receive about 10-20% of pancreatic blood flow, which increases further during stimulation of insulin secretion. We examined the relationship between pancreatic blood flow (PBF) and insulin secretory dynamics in 12 healthy volunteers (6M / 6F, age = 29 ± 5 yrs, BMI = 24.0 ± 2.7 kg/m², HbA1c = 5.1 ± 0.3 %, FPG = 88 ± mg/dl, fasting insulin = 3.7 ± 2.3 μU/ml) . PBF was measured by pseudo-continuous arterial spin labeling (ASL) MRI, with the labeling plane positioned 5-6 cm superior to the imaging slice to label blood in the descending aorta. Fasting subjects were placed in a 3T scanner, and PBF was measured during 1) a 15 min basal period, 2) a +100 mg/dl hyperglycemic clamp for 40 min, followed by 3) a 5 gm bolus of arginine to assess maximal acute insulin response (AIRmax) . First phase (0-min) insulin response to hyperglycemia was 181 ± 96 μU/ml · min, and AIRmax after arginine + hyperglycemia (40-50 min) was 1097 ± 629 μU/ml · min. Basal PBF (188 ± 53 ml/100 gm/min) increased during first phase insulin release, peaking at 212 ± 66 at 12 min, subsequently returned to basal levels (176 ± 59) from 10-40 min during sustained hyperglycemia,and peaked again at 2± 62 at 2 min after arginine. Although there were no significant correlations between glucose, insulin or c-peptide levels and PBF, time-series Granger causality analysis demonstrated that the time-derivative of c-peptide and insulin concentrations, reflectingacute changes in insulin secretion, preceded the increase in PBF (p=0.03 for d[c-peptide]/dt, and p = 0.for d[insulin]/dt) . Conclusions: 1) Changes in PBF during stimulation of insulin secretion in humans can be imaged non-invasively by ASL, 2) Insulin secretion precedes changes in PBF, and 3) The rate of change in insulin and c-peptide release predicts subsequent modulation of PBF. Disclosure D.C.Simonson: Stock/Shareholder; GI Windows, Phase V Technologies, Inc. M.Taso: Research Support; GE Healthcare Systems. C.Mcgrath: None. S.A.Waldman: None. F.Papadopoulou: None. D.C.Alsop: Other Relationship; GE Healthcare Systems, Hitachi, Ltd., Philips Healthcare, Siemens, UIH America, Research Support; GE Healthcare Systems.

ASLPrep: a platform for processing of arterial spin labeled MRI and quantification of regional brain perfusion.

Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data.

Blood flow and perfusion lateralization in border zone infarct using 4D flow and arterial spin labeling.

Hemodynamics may play an important role in border zone infarct (BZI), but macroscopic and microscopic hemodynamics of BZI still remain unclear. This study aims to investigate arterial flow and tissue perfusion differences between BZI and non-BZI in patients with unilateral middle cerebral artery (MCA) territory infarcts. Subacute ischemic stroke patients with unilateral infarcts at MCA territory were included. Imaging protocols included 4D flow, ASL (arterial spin labeling), and routine clinical brain MRI scan. A total of 56 patients (56.1 ± 11.9years, 39 male) were included and divided as BZI (n = 26) and non-BZI (n = 30). BZI was further subdivided as cortical BZI (CBZI, n = 9), internal BZI (IBZI, n = 11), and mixed BZI (n = 6). Average blood flow (Flowavg), regional average cerebral blood flow (CBFavg) were compared between infarct and contralateral sides to test hemodynamic lateralization. Flow-index and CBF-index (infarct sides/contralateral sides) were compared between groups and subgroups. Flowavg and CBFavg showed significant lateralization in both BZI and non-BZI as well as CBZI and IBZI. Flow-index (0.51 ± 0.37 vs. 0.87 ± 0.36, p < 0.01) and CBF-index (0.70 ± 0.21 vs. 0.90 ± 0.19, p < 0.01) were significantly different between BZI and non-BZI but were not significantly different between CBZI and IBZI. In summary, hemodynamic lateralization can occur in subacute stroke patients with BZI and non-BZI and the one that occurs in BZI tends to be more severe in view of arterial flow and tissue perfusion.

PD-0245 Changes in cortical blood flow >1 year after radiation for glioma using arterial spin labelling MRI

PD-0245 Changes in cortical blood flow >1 year after radiation for glioma using arterial spin labelling MRI

Effect of Cyclooxygenase Inhibitor on Hypoxia Stimulated Cerebral Blood Flow Using Arterial Spin Labeling Magnetic Resonance

IntroductionThe purpose of this study was twofold: 1) to determine microvascular cerebral blood flow (CBF) during hypoxia and 2) to investigate the effect of Ketorolac, a cyclooxygenase (COX) inhibitor, on hypoxia stimulated CBF. Acute exposure to hypoxic conditions leads to an increase in CBF, which may be regionally specific. Studies investigating the effect of hypoxia on CBF have utilized varying gradations and durations of hypoxia and different measuring techniques (transcranial doppler ultrasound or magnetic resonance imaging (MRI)). COX has been shown to significantly contribute to CBF at rest, however during hypoxia research has shown conflicting data on COX contribution to hypoxic CBF. Utilizing arterial spin labeling (ASL), an MRI technique that provides microvascular global and regional perfusion, during hypoxia stimulated CBF and the role of COX. We hypothesized hypoxia will increase CBF non‐uniformly, and COX inhibition with Ketorolac will reduce hypoxic dilation in some, but not all brain regions.Methods6 healthy young adults subjects (24 ± 3 years, 22.4 ± 0.7 BMI, 4 male) were included in this analysis using an institutional review board (IRB)‐approved protocol. Subjects completed an ASL MRI scans (5.5 min each) under the 3 distinct conditions: normoxia, hypoxia, and hypoxia + ketorolac drug infusion. The first ASL scan occurred while the subject breathed ambient air (baseline). Isocapnic hypoxia was then induced by breathing reduced O2 (9‐13%) to reduce arterial saturation to 80‐85% for steady state hypoxia followed by the first hypoxia ASL scan. While hypoxia was maintained, Ketorolac was infused at a rate of 0.495 mg/kg over 3 minutes (average dose 33.9 ± 2.8 mg), the third ASL scan was then completed (hypoxia+ketorolac). ASL analysis included smoothing grey matter, co‐registering and normalizing raw data, brain masking and region of interest processing. Statistics were determined using a Two‐Way Repeated Measures ANOVA with Tukey’s post‐hoc analysis.ResultsData are mean ± SD. SpO2 (98 ± 1%, 82 ± 2%, 82 ± 1%) and ETCO2 (36 ± 1mmHg, 35 ± 2mmHg, 34 ± 2) at baseline, hypoxia, and hypoxia+ketorolac, respectively. Baseline Global CBF (58 ± 15 ml/100g‐1/min‐1) was not significantly different from hypoxia (61 ± 14 ml/100g‐1/min‐1) (p=0.47). Regionally, CBF between baseline and hypoxia were not different in the right/left temporal, occipital, parietal, or frontal lobes (R/L: p=0.47/p=0.98, p=0.59/p=0.49, p=0.46/p=0.63, and p=0.18/0.19, respectively). Ketorolac did not change global CBF during hypoxia (60 ± 17 ml/100g‐1/min‐1) (p=0.96). Regional CBF during hypoxia and hypoxia+ketorolac was not changed in the right/left temporal, occipital, parietal, or frontal lobes (R/L: p=0.96/0.91, p=0.57/0.88, p=0.86/0.99, and p=0.38/0.35, respectively).DiscussionContrary to our hypothesis CBF did not change globally or regionally with hypoxia stimulation. Furthermore, COX inhibition via Ketorolac did not change CBF during hypoxia in any region. This finding corroborates previous studies in animals and macrovascular flow in humans that COX inhibitor Ketorolac acts differently in the brain compared to Indomethacin, despite similar pharmacology. In conclusion, acute hypoxia exposure with Ketorolac did not alter microvascular CBF.

The Role of 3D-pCASL MRI in the Differential Diagnosis of Glioblastoma and Brain Metastases.

PurposeThe first aim of this study was to compare the intratumoral and peritumoral blood flow parameters in glioblastomas and brain metastases measured by pseudocontinuous arterial spin labeling MRI (3D pCASL). The second aim of this study was to determine whether pCASL could aid in identifying the source of brain metastases.Materials and MethodsThis study included 173 patients aged 12 to 83 years (median age—61 years), who were observed at the National Medical Research Center for Neurosurgery. All patients underwent preoperative MRI with pCASL perfusion. Thereafter patients were operated on and received histological diagnosis. No patients received preoperative chemo or radiotherapy.ResultsThe values of maximum and normalized intratumoral blood flow were significantly higher in the group with gliblastoma than in the group with brain metastases: 168.98 + −91.96 versus 152.1 + −173.32 and 7.6 + −8.4 versus 9.3 + −5.33 respectively (p <0.01). However, ROC analysis showed low AUC specificity and sensitivity (0.64, 70%, 60% for mTBF and 0.66, 77%, 62% for nTBF). Peritumoral blood flow parameters were also higher in the glioblastoma group (29.61 + −22.89 versus 16.58 + −6.46 for mTBF and 1.63 + −1.14 versus 0.88 + −0.38 for nTBF, respectively; p <0.01). ROC analysis showed the following measurements of AUC, specificity, and sensitivity (0.75, 68%, 73% for mTBF and 0.77, 58%, 91% for nTBF). Regarding pCASL and various histological subsets of brain metastases, the study found statistically significant differences between the lung and melanoma metastases and the lung and kidney metastases. ROC analysis gave the following values for lung and melanoma metastases: AUC—0.76, specificity—75%, and sensitivity—73% for mTBF; 0.83, 67%, and 93% respectively, for nTBF. For lung and kidney metastases: AUC—0.74, specificity—70%, and sensitivity—93% for mTBF; 0.75, 70%, and 93% respectively, for nTBF.ConclusionspCASL could aid in differential diagnosis between glioblastoma and brain metastases. Measurement of peritumoral blood flow demonstrates higher specificity and sensitivity than with intratumoral blood flow. Moreover, pCASL provides the ability to distinguish lung metastases from kidney and melanoma metastases.

Caveolin-1 Promoted Collateral Vessel Formation in Patients With Moyamoya Disease.

BackgroundCaveolin-1 (Cav-1) plays pivotal roles in the endothelial function and angiogenesis postischemia. Moyamoya disease (MMD) is characterized by progressive artery stenosis with unknown etiology. We aim to determine whether serum Cav-1 levels of patients with MMD were associated with collateral vessel formation after bypass surgery.MethodsWe studied serum Cav-1 levels of 130 patients with MMD (16 with RNF213 p.R4810K mutation and 114 without RNF213 p.R4810K mutation), 15 patients with acute stroke, and 33 healthy controls. Cerebral perfusion and collateral circulation were evaluated preoperation and at 6 months after operation using pseudocontinuous arterial spin labeling MRI (pCASL-MRI) and digital subtraction angiography (DSA), respectively. Endothelial expression of Cav-1 was verified in the superficial temporal artery (STA) wall of patients with MMD by immunofluorescence double staining. We also investigated whether overexpression of Cav-1 affects cell migration and tube formation using human microvascular endothelial cells (HMECs).ResultsThe serum Cav-1 level of patients with MMD intermediated between the stroke group and healthy controls and it was enhanced after the bypass surgery (681.87 ± 311.63 vs. 832.91 ± 464.41 pg/ml, p = 0.049). By 6 months after bypass surgery, patients with MMD with better collateral compensation manifested higher postoperative/preoperative Cav-1 ratio (rCav-1) than bad compensation patients. Consistently, cerebral blood flow (CBF) determined by pCASL-MRI (nCBFMCA ratio) was positively in line with rCav-1 ratio (r = 0.8615, p < 0.0001). Cav-1 was expressed in the endothelial cells of the STA vessels of patients with MMD. Overexpression of Cav-1 by plasmid transfection in HMECs promoted tube formation and cell migration.ConclusionThis study indicated that Cav-1 may be a potential driver to promote angiogenesis and collateral formation after bypass surgery in patients with MMD, providing a better understanding of MMD pathophysiology and potential non-surgical targets of MMD.

Shared and specific characteristics of regional cerebral blood flow and functional connectivity in unmedicated bipolar and major depressive disorders

BackgroundIdentifying brain similarities and differences between bipolar disorder (BD) and major depressive disorder (MDD) can help us better understand their pathophysiological mechanisms and develop more effective treatments. However, the features of whole-brain regional cerebral blood flow (CBF) and intrinsic functional connectivity (FC) underlying BD and MDD have not been directly compared. MethodsEighty-eight unmedicated BD II depression patients, 95 unmedicated MDD patients, and 96 healthy controls (HCs) underwent three-dimensional arterial spin labeling (3D ASL) and resting-state functional MRI (rs-fMRI). The functional properties of whole brain CBF and seed-based resting-state FC further performed based on those regions with changed CBF were analyzed between the three groups. ResultsThe patients with BD and MDD showed commonly increased CBF in the left posterior lobe of the cerebellum and the left middle temporal gyrus (MTG) compared with HCs. The CBF of the left MTG was positively associated with 24-items Hamilton Depression Rating Scale scores in MDD patients. Decreased FC between the left posterior lobe of the cerebellum and the left inferior frontal gyrus (IFG) was observed only in patients with BD compared with HCs. ConclusionPatients with BD and those with MDD shared common features of CBF in the posterior lobe of the cerebellum and the MTG. The altered posterior lobe of the cerebellum-IFG FC can be considered as a potential biomarker for the differentiation of patients with BD from those with MDD.

Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

BackgroundPostictal phenomena as delirium, headache, nausea, myalgia, and anterograde and retrograde amnesia are common manifestations after seizures induced by electroconvulsive therapy (ECT). Comparable postictal phenomena also contribute to the burden of patients with epilepsy. The pathophysiology of postictal phenomena is poorly understood and effective treatments are not available. Recently, seizure-induced cyclooxygenase (COX)-mediated postictal vasoconstriction, accompanied by cerebral hypoperfusion and hypoxia, has been identified as a candidate mechanism in experimentally induced seizures in rats. Vasodilatory treatment with acetaminophen or calcium antagonists reduced postictal hypoxia and postictal symptoms. The aim of this clinical trial is to study the effects of acetaminophen and nimodipine on postictal phenomena after ECT-induced seizures in patients suffering major depressive disorder. We hypothesize that (1) acetaminophen and nimodipine will reduce postictal electroencephalographic (EEG) phenomena, (2) acetaminophen and nimodipine will reduce magnetic resonance imaging (MRI) measures of postictal cerebral hypoperfusion, (3) acetaminophen and nimodipine will reduce clinical postictal phenomena, and (4) postictal phenomena will correlate with measures of postictal hypoperfusion.MethodsWe propose a prospective, three-condition cross-over design trial with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design). Thirty-three patients (age > 17 years) suffering from a depressive episode treated with ECT will be included. Randomly and alternately, single doses of nimodipine (60 mg), acetaminophen (1000 mg), or water will be given two hours prior to each ECT session with a maximum of twelve sessions per patient. The primary outcome measure is ‘postictal EEG recovery time’, expressed and quantified as an adapted version of the temporal brain symmetry index, yielding a time constant for the duration of the postictal state on EEG. Secondary outcome measures include postictal cerebral perfusion, measured by arterial spin labelling MRI, and the postictal clinical ‘time to orientation’.DiscussionWith this clinical trial, we will systematically study postictal EEG, MRI and clinical phenomena after ECT-induced seizures and will test the effects of vasodilatory treatment intending to reduce postictal symptoms. If an effect is established, this will provide a novel treatment of postictal symptoms in ECT patients. Ultimately, these findings may be generalized to patients with epilepsy.Trial registrationInclusion in SYNAPSE started in December 2019. Prospective trial registration number is NCT04028596 on the international clinical trial register on July 22, 2019.

Towards free breathing 3D ASL imaging of the human liver using prospective motion correction.

Measurements of liver perfusion yield valuable information about certain diseases like carcinomas and cirrhosis. To assess perfusion, noninvasive arterial spin labeling (ASL) MRI has the potential to become an important alternative to contrast agent-based methods. Unfortunately, ASL perfusion-weighted images are highly susceptible to breathing motion. This work presents a prospective motion-compensation technique, tackling breathing motion during ASL experiments of the human liver. Feasibility of 3D pseudo-continuous ASL imaging under free breathing is investigated by using a prospective motion-compensation technique with fat signal in additional 2D-EPI navigators. The proposed technique is compatible with strong signal suppression, occurring in background-suppressed pseudo-continuous ASL imaging. An additional retrospective 2D elastic registration algorithm is proposed to correct for residual elastic deformations. The technique is validated in 8 healthy volunteers. The prospective technique allowed a significant reduction of the cranial-caudal liver shifts during free breathing pseudo-continuous ASL experiments. Additional 2D elastic image registration allowed reduction of cranial-caudal liver motion to levels of timed breathing protocols. Artifacts in perfusion-weighted images could be reduced when compared with free-breathing ASL images without motion correction. The proposed technique is suitable for prospective compensation of liver motion in background-suppressed 3D pseudo-continuous ASL imaging. Future work focuses on further improving the quality of perfusion-weighted images.

Genetic ablation of smooth muscle KIR2.1 is inconsequential to the function of mouse cerebral arteries

Cerebral blood flow is a finely tuned process dependent on coordinated changes in arterial tone. These changes are strongly tied to smooth muscle membrane potential and inwardly rectifying K+ (KIR) channels are thought to be a key determinant. To elucidate the role of KIR2.1 in cerebral arterial tone development, this study examined the electrical and functional properties of cells, vessels and living tissue from tamoxifen-induced smooth muscle cell (SMC)-specific KIR2.1 knockout mice. Patch-clamp electrophysiology revealed a robust Ba2+-sensitive inwardly rectifying K+ current in cerebral arterial myocytes irrespective of KIR2.1 knockout. Immunolabeling clarified that KIR2.1 expression was low in SMCs while KIR2.2 labeling was remarkably abundant at the membrane. In alignment with these observations, pressure myography revealed that the myogenic response and K+-induced dilation were intact in cerebral arteries post knockout. At the whole organ level, this translated to a maintenance of brain perfusion in SMC KIR2.1−/− mice, as assessed with arterial spin-labeling MRI. We confirmed these findings in superior epigastric arteries and implicated KIR2.2 as more functionally relevant in SMCs. Together, these results suggest that subunits other than KIR2.1 play a significant role in setting native current in SMCs and driving arterial tone.