Absolute Cerebral Blood Flow Research Articles

Perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: Preliminary data.

To demonstrate the feasibility of mapping cerebral perfusion metrics with BOLD MRI during modulation of pulmonary venous oxygen saturation. A gas blender with a sequential gas delivery breathing circuit was used to implement rapid isocapnic changes in the partial pressure of oxygen of the arterial blood. Partial pressure of oxygen was initially lowered to a baseline of 40 mmHg. It was then rapidly raised to 95 mmHg for 20 s before rapidly returning to baseline. The induced cerebral changes in deoxyhemoglobin concentration were tracked over time using BOLD MRI in 6 healthy subjects and 1 patient with cerebral steno-occlusive disease. BOLD signal change, contrast-to-noise ratio, and time delay metrics were calculated. Perfusion metrics such as mean transit time, relative cerebral blood volume, and relative cerebral blood flow were calculated using a parametrized method with a mono-exponential residue function. An arterial input function from within the middle cerebral artery was used to scale relative cerebral blood volume and calculate absolute cerebral blood volume and cerebral blood flow. In normal subjects, average gray and white matter were: BOLD change = 6.3 ± 1.2% and 2.5 ± 0.6%, contrast-to-noise ratio = 4.3 ± 1.3 and 2.6 ± 0.7, time delay = 2.3 ± 0.6 s and 3.6 ± 0.7 s, mean transit time = 3.9 ± 0.6 s and 5.5 ± 0.6 s, relative cerebral blood volume = 3.7 ± 0.9 and 1.6 ± 0.4, relative cerebral blood flow = 70.1 ± 8.3 and 20.6 ± 4.0, cerebral blood flow volume = 4.1 ± 0.9 mL/100 g and 1.8 ± 0.5 mL/100 g, and cerebral blood flow = 97.2 ± 18.7 mL/100 g/min and 28.7 ± 5.9 mL/100 g/min. This study demonstrates that induced abrupt changes in deoxyhemoglobin can function as a noninvasive vascular contrast agent that may be used for cerebral perfusion imaging.

Treatment evaluation of Kami Guibi-tang on participants with amnestic mild cognitive impairment using magnetic resonance imaging on brain metabolites, gamma-aminobutyric acid, and cerebral blood flow.

PurposeTo evaluate the effectiveness of Kami Guibi‐tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF).MethodsWe randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point‐RESolved Spectroscopy (PRESS) single‐voxel spectroscopy, gamma‐aminobutyric acid (GABA) neurotransmitter using Mescher–Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated‐measure analysis of variance to evaluate between‐subject group effect, within‐subject treatment condition effect, and interaction of group by condition (group x condition).ResultsThe GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest–based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024).ConclusionsAlthough a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini‐mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.

Absolute cerebral blood flow: Assessment with a novel low-radiation-dose dynamic CT perfusion technique in a swine model

Rationale and objectivesTo validate the accuracy of a novel low-dose dynamic CT perfusion technique in a swine model using fluorescent microsphere measurement as the reference standard. Materials and methodsContrast-enhanced dynamic CT perfusion was performed in five swine at baseline and following brain embolization. Reference microspheres and intravenous contrast (370 mg/ml iodine, 1 ml/kg) were injected (5 ml/s), followed by dynamic CT perfusion. Scan parameters were 320×0.5 mm, 100 kVp and 200 mA. On average, 47 contrast-enhanced volume scans were acquired per acquisition to capture the time attenuation curve. For each acquisition, only two systematically selected volume scans were used to quantify brain perfusion with first-pass analysis technique. The first volume scan was selected at the base, simulating bolus tracking, while the second volume at the peak of the time attenuation curve similar to a CT angiogram. Regional low-dose CT perfusion measurements were compared to the microsphere perfusion measurements with t-test, linear regression and Bland-Altman analysis. The radiation dose of the two-volume CT perfusion technique was determined. ResultsLow-dose CT perfusion measurements (PCT) showed excellent correlation with reference microsphere perfusion measurements (PMICRO) by PCT = 1.15 PMICRO - 0.01 (r = 0.93, p ≤ 0.01). The CT dose index and dose-length product for the two-volume CT perfusion technique were 25.6 mGy and 409.6 mGy, respectively. ConclusionsThe accuracy and repeatability of a low-dose dynamic CT perfusion technique was validated in a swine model. This technique has the potential for accurate diagnosis and follow up of stroke and vasospasm.

Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke.

Background and PurposeVarious imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. MethodsProspective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared. ResultsOf 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. ConclusionsSimpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Cerebral and tumoral blood flow in adult gliomas: a systematic review of results from magnetic resonance imaging.

Objective:Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics obtained from MRI modalities in adult supratentorial gliomas.Methods:MEDLINE, EMBASE and the Cochrane database were queried 01/01/2000–31/12/2019. Studies measuring blood flow in adult Grade II–IV supratentorial gliomas using dynamic susceptibility contrast (DSC) MRI, dynamic contrast enhanced MRI (DCE-MRI) or arterial spin labelling (ASL) were included. Absolute and relative cerebral blood flow (CBF), peritumoral blood flow and tumoral blood flow (TBF) were reported.Results:34 studies were included with 1415 patients and 1460 scans. The mean age was 52.4 ± 7.3 years. Most patients had glioblastoma (n = 880, 64.6%). The most common imaging modality was ASL (n = 765, 52.4%) followed by DSC (n = 538, 36.8%). Most studies were performed pre-operatively (n = 1268, 86.8%). With increasing glioma grade (II vs IV), TBF increased (70.8 vs 145.5 ml/100 g/min, p < 0.001) and CBF decreased (85.3 vs 49.6 ml/100 g/min, p < 0.001). In Grade IV gliomas, following treatment, CBF increased in ipsilateral (24.9 ± 1.2 vs 26.1 ± 0.0 ml/100 g/min, p < 0.001) and contralateral white matter (25.6 ± 0.2 vs 26.0± 0.0 ml/100 g/min, p < 0.001).Conclusion:Our findings demonstrate that increased mass effect from high-grade gliomas impairs blood flow within the surrounding brain that can improve with surgery.Advances in knowledge:This systematic review demonstrates how mass effect from brain tumours impairs blood flow in the surrounding brain parenchyma that can improve with treatment.

Impaired Cerebral Autoregulation After Subarachnoid Hemorrhage: A Quantitative Assessment Using a Mouse Model.

Subarachnoid hemorrhage (SAH) is a common form of hemorrhagic stroke associated with high rates of mortality and severe disability. SAH patients often develop severe neurological deficits days after ictus, events attributed to a phenomenon referred to as delayed cerebral ischemia (DCI). Recent studies indicate that SAH-induced DCI results from a multitude of cerebral circulatory disturbances including cerebral autoregulation malfunction. Cerebral autoregulation incorporates the influence of blood pressure (BP) on arterial diameter in the homeostatic regulation of cerebral blood flow (CBF), which is necessary for maintaining constant brain perfusion during physiological swings in systemic BP. In this study, we quantitatively examined the impact of SAH on cerebral autoregulation using a mouse endovascular perforation model and a newly developed approach combining absolute and relative CBF measurements. This method enables a direct quantitative comparison of cerebral autoregulation between individual animals (e.g., SAH vs. control or sham-operated mice), which cannot be done solely using relative CBF changes by laser Doppler flowmetry. Here, absolute CBF was measured via injection of fluorescent microspheres at a baseline BP. In separate groups of animals, in vivo laser Doppler flowmetry was used to measure relative CBF changes over a range of BP using phlebotomy and the pressor phenylephrine to lower and raise BP, respectively. Absolute CBF measurements from microspheres were then used to calibrate laser Doppler measurements to calculate the relationship between CBF and BP, i.e., “cerebral autoregulation curves.” Un-operated and sham-operated groups exhibited similar cerebral autoregulatory curves, showing comparable levels of relatively constant CBF over a range of BP from ~80 mmHg to ~130 mmHg. In contrast, SAH animals exhibited a narrower autoregulatory range of BP, which was primarily due to a decrease in the upper limit of BP whereby cerebral autoregulation was maintained. Importantly, SAH animals also exhibited a marked decrease in CBF throughout the entire range of BP. In sum, this study provides evidence of the dramatic reduction in cortical CBF and the diminished range of autoregulation after SAH. Furthermore, this novel methodology should pave the way for future studies examining pathological mechanisms and/or therapeutic strategies targeting impaired cerebral autoregulation, a pathology common to many cardiovascular and cerebrovascular disorders.

Evaluation of Arterial Spin Labeling MRI-Comparison with 15O-Water PET on an Integrated PET/MR Scanner.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

Can 3D Pseudo-Continuous Territorial Arterial Spin Labeling Effectively Diagnose Patients With Recanalization of Unilateral Middle Cerebral Artery Stenosis?

Unilateral middle cerebral artery (MCA) stenosis, as an independent risk factor for stroke, requires an intervention operation for vessel recanalization. Accurate perfusion measurement is thus essential after the operation. To explore the feasibility of three-dimensional (3D) pseudo-continuous territorial arterial-spin-labeling (tASL) in evaluating MCA recanalization. Prospective and longitudinal. Forty-seven patients with unilateral MCA stenosis or occlusion. A 3.0 T, 3D time-of-flight fast-field-echo magnetic resonance (MR) angiography sequence, spin-echo echo-planar diffusion-weighted imaging sequence, 3D fast-spin-echo pseudo-continuous ASL (pcASL) and tASL sequences. All patients underwent MR examination before and after MCA recanalization and scored using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admission and discharge. An mRS score <2 was defined as a good prognosis. 3D-pcASL and tASL cerebral blood flow (CBF) maps were obtained, and the corresponding Alberta Stroke Program Early CT Score (ASPECTS)-based scores were evaluated. The Kolmogorov-Smirnov test, intra-class correlation coefficient, paired t-test, receiver operating characteristic (ROC) curve, and multivariable logistic regression analysis. After recanalization, tASL derived absolute CBFs between the affected and contralateral sides were significantly higher than before the operation (mean: 34.3 ± 8.5 mL/100 g/min vs. 40.6 ± 9.2 mL/100 g/min, 42.6 ± 9.8 mL/100 g/min vs. 43.5 ± 9.9 mL/100 g/min, both P < 0.05). In ROC analysis, tASL provided good prognosis (area under ROC curve [AUC]=0.829; 95% CI: 0.651-1.000, P < 0.05), while pcASL had lower prognostic value (AUC=0.760; 95% CI: 0.574-0.946, P < 0.05). The NIHSS score before recanalization, pcASL, and tASL-based ASPECTS scores were significantly associated with good clinical outcome (P < 0.05). Multivariable analysis revealed that ASPECTS-based scores of pcASL and tASL before and after surgery were independent predictors of good clinical outcome (all P < 0.05). DATA CONCLUSION: tASL can determine hypoperfusion in the responsible vascular perfusion area and predict clinical outcome. 4 TECHNICAL EFFICACY: Stage 2.

Cerebral Blood Flow Predicts Recovery in Children with Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury.

Persistent post-concussion symptoms (PPCS) following pediatric mild traumatic brain injury (mTBI) are associated with differential changes in cerebral blood flow (CBF). Given its potential as a therapeutic target, we examined CBF changes during recovery in children with PPCS. We hypothesized that CBF would decrease and that such decreases would mirror clinical recovery. In a prospective cohort study, 61 children and adolescents (mean age 14 [standard deviation = 2.6] years; 41% male) with PPCS were imaged with three-dimensional (3D) pseudo-continuous arterial spin-labelled (pCASL) magnetic resonance imaging (MRI) at 4-6 and 8-10 weeks post-injury. Exclusion criteria included any significant past medical history and/or previous concussion within the past 3 months. Twenty-three participants had clinically recovered at the time of the second scan. We found that relative and mean absolute CBF were higher in participants with poor recovery, 44.0 (95% confidence interval [CI]: 43.32, 44.67) than in those with good recovery, 42.19 (95% CI: 41.77, 42.60) mL/min/100 g gray tissue and decreased over time (β = -1.75; p < 0.001). The decrease was greater in those with good recovery (β = 2.29; p < 0.001) and predicted outcome in 77% of children with PPCS (odds ratio [OR] 0.54, 95% CI: 0.36, 0.80; p = 0.002). Future studies are warranted to validate the utility of CBF as a useful predictive biomarker of outcome in PPCS.

Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease.

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis.

We investigated the influence of arterial ( ) with and without acutely elevated arterial pH and bicarbonate ([HCO3- ]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso-oxic alterations in (i.e. cerebrovascular CO2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO3- ) to acutely elevate arterial pH and [HCO3- ]. Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of , indicating that CBF is acutely regulated by rather than arterial pH. The cerebrovascular responses to changes in arterial H+ /pH were altered in keeping with the altered relationship between and H+ /pH following NaHCO3- infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO3- infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO3- independent of levels. Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial ( ), pH and cerebrovascular tone; however, pre-clinical studies indicate that intrinsic sensitivity to pH, independent of changes in or intravascular bicarbonate ([HCO3- ]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso-oxic alterations in (hypocapnia: -5, -10mmHg; hypercapnia: +5, +10 mmHg) prior to and following i.v. sodium bicarbonate (NaHCO3- ; 8.4%, 50 mEq50mL-1 ) to elevate pH (7.408±0.020 vs. 7.461±0.030; P<0.001) and [HCO3- ] (26.1±1.4 vs. 29.3±0.9 mEqL-1 ; P<0.001). Absolute CBF was not different at each stage of CO2 reactivity (P=0.629) following NaHCO3- , irrespective of a higher pH (P<0.001) at each matched stage of (P=0.927). Neither hypocapnic (3.44±0.92 vs. 3.44±1.05% permmHg ; P=0.499), nor hypercapnic (7.45±1.85 vs. 6.37±2.23% permmHg ; P=0.151) reactivity to were altered pre- to post-NaHCO3- . When indexed against arterial [H+ ], the relative hypocapnic CVR was higher (P=0.019) and hypercapnic CVR was lower (P=0.025) following NaHCO3- , respectively. These changes in reactivity to [H+ ] were, however, explained by alterations in buffering between and arterial H+ /pH consequent to NaHCO3- . Lastly, CBF was higher (688±105 vs. 732±89 mLmin-1 , 7%±12%; P=0.047) following NaHCO3- during isocapnic breathing providing support for a direct influence of HCO3- on cerebrovascular tone independent of . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by rather than arterial pH.

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients. Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008). Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke

The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5-49.3) ml in the NTG group and 32.6 (8.6-96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7-44.2) ml) than the NTG group (3.2 (0.5-16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer's Disease.

Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer's disease (AD). We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort. Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors. After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions. Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

Developmental patterns of CBF and BOLD responses to visual stimulus

To investigate the developmental changes of cerebral blood flow (CBF) and hemodynamic responses to changing neural activity, we used the arterial spin label (ASL) technique to measure resting CBF and simultaneous CBF / blood-oxygen-level dependent (BOLD) signal changes during visual stimulation in 97 typically developing children and young adults (age 13.35 [6.02, 25.25] (median [min, max]) years old at the first time point). The longitudinal study protocol included three MRIs (2.7 ± 0.06 obtained), one year apart, for each participant. Mixed-effect linear and non-linear statistical models were used to analyze age effects on CBF and BOLD signals. Resting CBF decreased exponentially with age (p = 0.0001) throughout the brain, and developmental trajectories differed across brain lobes. The absolute CBF increase in visual cortex during stimulation was constant over the age range, but the fractional CBF change increased with age (p = 0.0001) and the fractional BOLD signal increased with age (p = 0.0001) correspondingly. These findings suggest that the apparent neural hemodynamic coupling in visual cortex does not change after age six years, but age-related BOLD signal changes continue through adolescence primarily due to the changes with age in resting CBF.

ASL perfusion in acute ischemic stroke: The value of CBF in outcome prediction

ObjectiveThe application of novel advanced magnetic resonance imaging (MRI) techniques in clinical practice has significantly improved diagnostic accuracy in early detection of acute ischemic stroke (AIS), additionally allowing outcome prediction. The introduction of arterial spin labeling (ASL) perfusion sequence as a standard in MRI protocols is a significant milestone in neuroradiology. The aim of the present study was to demonstrate the potential of ASL sequence for the detection of absolute (aCBF) and relative (rCBF) cerebral blood flow values for an ischemic area and to examine the correlation of the obtained values with the functional outcome of patients. Patients and MethodsThe study included 205 patients of both sexes over the age of 18 years, suspected with AIS, who met the inclusion criteria. Brain MRI examination according to the protocol for ischemia with fast three-dimensional pseudocontinuous (3D PCASL) ASL technique was used. Statistical analysis of the collected data was performed with SPSS 15.0. ResultsThe appearance of the ROC curve indicated good diagnostic characteristics of aCBF in assessing a favorable stroke outcome, demonstrating a high statistical significance (p < 0.001), and high conclusion validity. The value of the rCBF was significantly higher in patients with a favorable outcome compared with patients with a poor outcome (p < 0.001). The sum of sensitivity and specificity was the highest using aCBF cut-off value of 19.140 mL/100 g/min, and rCBF cut-off of 49.700 of the contralateral side percentage value. ConclusionOur study shows that ASL perfusion sequence allows precise detection of perfusion values and provides a reliable insight into outcome prediction.

Holding up under pressure: a complex interplay between cerebral blood flow and ventilatory responses to alterations in carbon dioxide.

Holding up under pressure: a complex interplay between cerebral blood flow and ventilatory responses to alterations in carbon dioxide.

Quantification of ASL Perfusion MRI in MCI Patients Using Single-Post Labeling Delay Model-Fitting Approach

Purpose: Neuroimaging techniques hold many promises to detect Alzheimer Disease (AD) at early stages before clinical symptoms fully develop, suggesting decreased regional Cerebral Blood Flow (CBF). Perfusion deficiencies are present from very early clinical phases of AD, i.e. Mild Cognitive Impairment (MCI) and persist well into the latest stages, demonstrating a pattern of increased hypo-perfusion with the disease development. Accurate quantification such as quantification model and noise reduction method is necessary to achievement of good results in insufficient Post Labeling Delay (PLD) time. Materials and Methods: Arterial Spin Labeling (ASL) is a non-invasive MRI technique to extract brain regional CBF, which in recent years gained wide acceptance for its value in clinical and neuroscience applications. In the present work, 44 participants in 2 groups were imaged (normal control and MCI) using single-Post Label Delay (single-PLD) model-fitting ASL Perfusion at 1.5T. Images were de-noised with Independent Component Analysis (ICA) algorithm and then preprocessing such as motion correction, distortion correction, normalization, and tissue segmentation analyzed with SPM12. Calibration image that needed to calculate absolute perfusion was estimated from the data by fitting a curve to the control images in the dataset. Absolute CBF values were finally extracted from the kinetic model quantification. Results: Perfusion decreases in the right precuneus (28%), right inferior partial cortex (22%) and right middle frontal cortex (20%) cortex in MCI subjects. Conclusion: According to the results, ASL-MRI is able to calculate perfusion changes associated with MCI.

Quantification of cerebral blood flow in adults by contrast-enhanced near-infrared spectroscopy: Validation against MRI

The purpose of this study was to assess the accuracy of absolute cerebral blood flow (CBF) measurements obtained by dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) using indocyanine green as a perfusion contrast agent. For validation, CBF was measured independently using the MRI perfusion method arterial spin labeling (ASL). Data were acquired at two sites and under two flow conditions (normocapnia and hypercapnia). Depth sensitivity was enhanced using time-resolved detection, which was demonstrated in a separate set of experiments using a tourniquet to temporally impede scalp blood flow. A strong correlation between CBF measurements from ASL and DCE-NIRS was observed (slope = 0.99 ± 0.08, y-intercept = −1.7 ± 7.4 mL/100 g/min, and R2 = 0.88). Mean difference between the two techniques was 1.9 mL/100 g/min (95% confidence interval ranged from −15 to 19 mL/100g/min and the mean ASL CBF was 75.4 mL/100 g/min). Error analysis showed that structural information and baseline absorption coefficient were needed for optimal CBF reconstruction with DCE-NIRS. This study demonstrated that DCE-NIRS is sensitive to blood flow in the adult brain and can provide accurate CBF measurements with the appropriate modeling techniques.