State Cerebral Blood Flow Research Articles

The relationship between the state of cerebral blood flow and volemic status in patients with ischemic stroke in the acute period

The objective was to assess the relationship between the state of cerebral blood flow and volemic status in patients with acute ischemic stroke using the laboratory and instrumental parameters.Materials and methods. 51 patients with newly diagnosed ischemic stroke confirmed by MSCT/MRI of the brain were examined within less than 24 hours from the onset of the disease, and 20 practically healthy individuals (control group). To determine cerebral blood flow, the hemodynamic parameters of transcranial Doppler imaging were used: blood flow rates (maximum systolic, diastolic, averaged over time), Gosling’s pulsatility index and Purcelo’s index of peripheral resistance in the anterior, posterior, middle and main cerebral arteries from the affected and intact sides. Volemic status was assessed using laboratory (serum sodium and brain natriuretic peptide NT-pro-BNP) and instrumental parameters (echocardiography – end-diastolic volume of the left ventricle, left ventricular ejection fraction, diameter and degree of collapse on inhalation of the inferior vena cava).Results. Deterioration of the state of cerebral blood flow by speed indicators and an increase in the resistance parameters of the vascular wall was noted in the studied affected and intact arteries against the background of violations of the volemic status by the level of brain natriuretic peptide, end-diastolic volume of the left ventricle, diameter of the inferior vena cava, left ventricular ejection fraction and degree of collapse of the inferior vena cava. There is a correlation of vascular wall resistance parameters with laboratory and instrumental indicators of volemia, since both the development of deficiency and volume overload negatively affect cerebral perfusion.Conclusions. The cerebral blood flow parameters are correlated with the volemic status of patients with ischemic stroke in the acute period.

A new method of intraoperative assessment of the dynamics of cortical blood flow using imaging photoplethysmography

Background. Intraoperative assessment of changes in cerebral blood flow is an important component of objective quality control of surgical treatment of cerebral artery aneurysms. Various techniques have been tried to solve this task, but they all have their drawbacks, which forces us to look for new ways of blood flow monitoring. We propose to use the technology of imaging photoplethysmography (IPPG) – a technically simple, contactless, safe and cheap optical method for assessing the perfusion of biological tissues.Aim. To demonstrate the possibility of using IPPG to assess the dynamics of cerebral blood flow parameters during aneurysm clipping surgery, as well as to identify early changes in blood supply to the cerebral cortex.Materials and methods. The study was carried out during six surgeries of clipping aneurysms of the anterior part of the Willis’s circle, both in the acute stage of rupture (n = 1) and in a planned manner (n = 5). The IPPG system, which is an LED illuminator in a single unit with a digital video camera, was located on a tripod 25 cm from the intervention zone. During each operation, two one-minute recordings of the illuminated surface of the cerebral cortex were performed: after dissection of the dura mater and before its suturing at the end of the main stage of the intervention. To improve the measurement accuracy, video frames of the studied area were recorded synchronously with the registration of an electrocardiogram. After recording, two IPPG parameters were calculated and compared: the amplitude of the pulsatile component and the pulse wave transit time. Thereafter, the obtained data were compared with the results of computed tomography. Statistical analysis was performed using pairwise comparison tests in the GraphPad Prism software package.Results. Clipping of cerebral vessel aneurysms are accompanied by significant changes in the parameters of cerebral blood flow. Analysis of the data for all patients revealed significant differences in IPPG parameters before and after surgery, namely, statistically significant increase in amplitude of the pulsatile component (n = 3) and decrease in pulse wave transit time (n = 5). The absence of significant changes in both parameters was found only in one patient who had mechanical damage in the cortex in the region of video recording.Conclusion. The IPPG system is capable to quantify changes in blood supply to the cortex during surgical treatment of cerebral artery aneurysms and to identify areas with either increased or decreased blood supply. In-depth studies are required to obtain additional markers of the postoperative state of cerebral blood flow.

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

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

Clinical efficacy and safety of Picamilon in patients with progressive chronic cerebral ischemia

To study the efficacy and safety of the drug Picamilon with various therapy regimens in patients with stage II chronic cerebral ischemia (CCI). An open cohort clinical study involved 50 patients diagnosed with stage II CCI aged 51 to 69 years (average age 62.2±8.98 years). Patients received Picamilon first parenterally 200 mg (100 mg/ml, 2 ml) intravenously for 10 days, then orally in 50 mg tablets 3 times a day for 60 days. The total duration of therapy in the group was 70 days. The study included 3 visits (before treatment, after completion of the course, 1.5 months after completion of treatment). The dynamics of cognitive status according to the Montreal Cognitive Assessment Scale, vegetative disorders according to the A.M. Vane scale, neurological disorders according to the A.I. Fedin scale, and sleep quality according to the Ya. I. Levin scale were compared. The state of cerebral blood flow and endothelium was studied before and after treatment: dopplerography of cranial vessels, assessment of the level of methylated forms of arginine (ADMA, MMA, SDMA) and their ratios. The registration of adverse events against the background of therapy and the tolerability of treatment by patients was also carried out. Against the background of Picamilon treatment, a significant positive dynamics of the MoCA scale results was observed in the general sample of patients, increasing in the delayed period (20.9, 24.6 and 25.9, p<0.0001 and p=0.0006); sleep normalization was observed in 55% of patients by Visit 2 and in 81% of patients by Visit 3 (p<0.0001 and p=0.0025). Improvement of neurological functions is noted in 84% of patients, the score on the Fedin A.I. scale significantly decreases after treatment from 17.4±9.34 to 8.06±6.84 (p<0.0001) and to 5.31±5.71 in the delayed period (p=0.0002). Normalization of vegetative status was observed in 38% of patients with stage II CCI, and in 60% of cases there was a decrease in the severity of vegetative dystonia syndrome (p=0.0001). Picamilon therapy has high efficacy in assessing clinical outcomes (100%), good tolerability in 98% of patients and is characterized by a favorable safety profile (in 92% of patients). Picamilon significantly affects the parameters of cerebral hemodynamics: increases the linear velocity of blood flow, reduces the thickness of the intima-media complex and the resistance index. It affects markers of NO metabolism and endothelial function: significantly reduces elevated levels of ADMA and ADMA/MMA and (ADMA+SDMA)/MMA ratios. The use of Picamilon is effective in patients with stage II CCI in the form of step therapy contributes to a significant regression of neurological deficit, cognitive impairment, improvement of sleep quality and autonomic function; improves vascular endothelial function, reduces the risk of cardiovascular complications. Picamilon is a pathogenetic therapy agent that prevents the progression of CCI.

Integrative assessment of the effectiveness and safety of outpatient use of Picamilon

To study the efficacy and safety of the use of the drug Picamilon with various therapy regimens in patients with stage I of chronic cerebral ischemia (CCI). Material and methods. An open randomized comparative clinical trial included 44 patients with stage CCI aged 46 to 67 years (average age 55.6±6.76 years). Patients were randomized into two groups, patients of group 1 (n=23) received Picamilon orally in tablets of 50 mg 3 times/day for 60 days; group 2 (n=21) received Picamilon first parenterally at 100 mg i/m for 10 days, then in tablets of 50 mg 3 times/day for 50 days. The total duration of therapy was 60 days. The study included 4 visits (before treatment, 10 days later, 60 days later, 1.5 months after completion of treatment). The dynamics of cognitive status were assessed according to the Montreal Cognitive Function Assessment Scale (MoCA), vegetative disorders on the A.M. Wayne scale, neurological disorders on the A.I. Fedin scale, and sleep quality on the Ya.I. Levin scale. The study of the state of cerebral blood flow (dopplerography of intracranial vessels) and endothelial function (assessment of the level of methylation. During treatment, in the total sample of patients, there was a positive trend in the results of the MoCA scale, increasing in the delayed period (24.9/26.5/28.3 points, p=0.022 and p<0.001); improvement in sleep quality in 50% of patients by visit 3 and in 84% by visit 4, in the 2nd group the effect occurred in 28% of patients, in the 1st - in 11%, by the end of the study the effect was comparable (p=0.508). Improvement according to Fedin A.I. scale noted in 77% of patients, values decreased from 11.9±8.3 to 6±6.1 points (p<0.0001) and to 2.77±4.43 points by visit 4 (p<0.0001). Normalization of autonomic functions was observed in 29% of patients (p=0.024) without intergroup differences. Picamilon therapy showed high efficacy in terms of clinical outcomes (up to 89%), good tolerability (98% of patients) and a favorable safety profile (less than 8.6% of AEs). The use of Picamilon was accompanied by an increase in the linear velocity of blood flow, a decrease in the thickness of the intima-media complex and the resistance index; a decrease in elevated ADMA concentrations and ADMA/MMA and (ADMA+SDMA)/MMA ratios. The use of Picamilon is effective in patients with stage I CCI, contributes to a significant regression of neurological deficits, cognitive impairment, improved sleep quality and autonomic function; improves vascular endothelial function, reduces the risk of atherosclerosis and cardiovascular complications in patients. The optimal duration of therapy with Picamilon in stage I of chronic cerebral ischemia is 2 months.

ACE and AT2R1 gene polymorphism in patients with chronic vascular encephalopathy: association with neuroimaging changes and cognitive functioning

Background. Given the synergistic effect of the ACE and AT2R1 genes and their impact on the maintenance of homeostatic processes, the aim of our research was to identify the associations of the studied polymorphic variants of the ACE and AT2R1 genes with neuroimaging changes, data from arterial duplex ultrasound and cognitive functioning in patients with chronic vascular encephalopathy (CVE). Materials and methods. A retrospective analysis of 145 medical records of patients with CVE was conducted, of which 18 patients underwent a molecular genetic study. The control group consisted of 12 people representative in terms of age and gender. Neuroimaging was performed using multislice computed tomography or magnetic resonance imaging. The state of cerebral blood flow was studied using transcranial duplex ultrasound of intracranial and extracranial vessels. The cognitive functioning was tested using the Montreal Cognitive Assessment. Results. When analyzing the associations of polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene with neuroimaging changes and parameters of cerebral hemodynamics in CVE among carriers of I and D alleles of the ACE gene, a probable relationship was found between their frequency distribution and the presence/absence of gliosis phenomena (62.69 % of D allele carriers were diagnosed with gliosis, p &lt; 0.05); a probable relationship between the frequency distribution of the D/D genotype of the ACE gene and the presence of angiospasm (in 72.73 % of patients), insufficiency of blood flow in the carotid system (72.73 % of cases) and vertebrobasilar insufficiency (in 36.36 % of people). When evaluating the dependence of cognitive functions based on the Montreal Cognitive Assessment score in patients with CVE on the polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene, probable changes were revealed in the frequency distribution of genotypes and alleles of the polymorphic I/D variant of the ACE gene (χ2 = 11.33; p = 0.023), while all carriers of the D/D genotype have impaired cognitive functioning (moderate in 36.36 % and mild in 63.64 % of cases), which also corresponds to the frequency of the D allele distribution in this cohort of patients (29.63 % of people have a moderate cognitive impairment and 70.37 % — a mild cognitive impairment, p = 0.013). Conclusions. The study results indicate that the ACE gene may be involved in the development of neuroimaging changes and cognitive decline in CVE.

The study of Associations between TNFα GENE G308A polymorphism and clinical-neurological, neuroimaging, hemodynamic characteristics and cognitive dysfunction in patients with post-infectious encephalopathy

Introduction. Infectious diseases can affect brain function and cause the development of encephalopathy, even if the pathogen does not directly affect the central nervous system. Infections caused by viruses, bacteria, or parasites can lead to a secondary inflammatory response in the brain, commonly known as neuroinflammation, through the action of inflammatory mediators that affect the brain endothelium and parenchyma, and the response of brain cells to these mediators. Neurological consequences associated with infectious diseases are poorly understood. Nowadays, there is no established strategy for the treatment or prevention of neurological damage associated with peripheral infections. Aim of study was: to establish probable associations of the G308A polymorphic variant of the TNFα gene with clinical-neurological, neuroimaging, hemodynamic characteristics and cognitive dysfunction in patients with post-infectious encephalopathy. Material and methods. 128 patients with PIE who were undergoing treatment in the neurological departments of the communal non-profit enterprise "Ternopil Regional Clinical Psychoneurological Hospital" during 2021-2022 were examined. 26 patients underwent molecular genetic analysis. The control group consisted of 12 practically healthy persons, representative in terms of age and sex. All patients met the inclusion criteria for the study. Neuroimaging was performed using multispiral computed tomography (CT) or magnetic resonance imaging (MRI). The state of cerebral blood flow was studied using transcranial duplex scanning (TCI) of intracranial vessels and extracranial brachiocephalic vessels on a Philips HDI device. Research in the cognitive sphere was carried out using the Montreal Cognitive Test (The Montreal Cognitive Assessment, MoCA). The molecular genetic study of the G308A polymorphic variant of the TNFα gene was carried out according to standard protocols developed in the molecular genetic laboratory of the state institution "Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine". The results. Analyzing the dependence of clinical-neurological syndromes, neuroimaging, hemodynamic characteristics, and cognitive dysfunction on the polymorphic variant G308A of the TNFα gene in patients with PIE, probable differences in the distribution of genotype frequencies were established only for clinical-neurological syndromes (cephalic syndrome, p=0.005 and movement disorder syndrome, p =0.038) and neuroimaging changes (gliosis phenomenon, p=0.026). Regarding the frequency distribution of alleles of the G308A polymorphic variant of the TNFα gene in patients with PIE, a probable predominance of carriers of the A allele among persons with cephalic syndrome compared to persons without cephalic syndrome was found (91.67% vs. 8.33%). Conclusions. Thus, the allelic polymorphism of the TNFα gene affects the course of PIE, which determines the expediency of further research.

Arterial spin labeling for moyamoya angiopathy: A preoperative and postoperative evaluation method.

Studies have shown that arterial spin labeling (ASL) effectively replaces traditional MRI perfusion imaging for detecting cerebral blood flow (CBF) in patients with Moyamoya angiopathy (MMA). However, there are few reports on the relationship between neovascularization and cerebral perfusion in patients with MMA. The aim of this study is to investigate the effects of neovascularization on cerebral perfusion with MMA after bypass surgery. We selected patients with MMA in the Department of Neurosurgery between September 2019 and August 2021 and enrolled them based on the inclusion and exclusion criteria. ASL imaging was used to monitor the baseline CBF level before surgery and determine the changes in cerebral vessels at postoperative 1 week and 6 months, respectively. The Alberta stroke grade, modified Rankin Scale (mRS), and digital subtraction angiography images were used to evaluate the effect of postoperative CBF status and prognosis. Ninety hemispheres from 51 patients were included in this study. There were no significant differences in the baseline data of the enrolled patients. At 1 week and 6 months post-surgery, the CBF state in the operation area was significantly changed compared with that at baseline (P < 0.05). The preoperative Alberta score (t = 2.714, P = 0.013) and preoperative mRS score (t = 6.678, P < 0.001) correlated with postoperative neovascularization. ASL is an effective method for detecting CBF and plays an important role in the long-term follow-up of patients with MMA. Combined cerebral revascularization significantly improves CBF in the operation area both in the short and long terms. Patients with lower preoperative Alberta scores and higher mRS scores were more likely to benefit from combined cerebral revascularization surgery. However, regardless of the type of patient, CBF reconstruction can effectively improve prognosis.

Association between gray matter atrophy, cerebral hypoperfusion, and cognitive impairment in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most severe neurodegenerative diseases leading to dementia in the elderly. Cerebral atrophy and hypoperfusion are two important pathophysiological characteristics. However, it is still unknown about the area-specific causal pathways between regional gray matter atrophy, cerebral hypoperfusion, and cognitive impairment in AD patients. Forty-two qualified AD patients and 49 healthy controls (HC) were recruited in this study. First, we explored voxel-wise inter-group differences in gray matter volume (GMV) and arterial spin labeling (ASL) -derived cerebral blood flow (CBF). Then we explored the voxel-wise associations between GMV and Mini-Mental State Examination (MMSE) score, GMV and CBF, and CBF and MMSE to identify brain targets contributing to cognitive impairment in AD patients. Finally, a mediation analysis was applied to test the causal pathways among atrophied GMV, hypoperfusion, and cognitive impairment in AD. Voxel-wise permutation test identified that the left middle temporal gyrus (MTG) had both decreased GMV and CBF in the AD. Moreover, the GMV of this region was positively correlated with MMSE and its CBF, and CBF of this region was also positively correlated with MMSE in AD (p < 0.05, corrected). Finally, mediation analysis revealed that gray matter atrophy of left MTG drives cognitive impairment of AD via the mediation of CBF (proportion of mediation = 55.82%, β = 0.242, 95% confidence interval by bias-corrected and accelerated bootstrap: 0.082 to 0.530). Our findings indicated suggested that left MTG is an important hub linking gray matter atrophy, hypoperfusion, and cognitive impairment for AD, and might be a potential treatment target for AD.

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling (pCASL) technique at 7T that offers the capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 ms shorter than in middle/deep layers revealing the time course of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN.MethodsAs part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females (n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation.ResultsNo group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation.ConclusionsThis exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.Trial registrationISRCTN14329415, registered 23rd July 2015.

211-OR: Differential Cerebral Blood Flow in Controlled and Uncontrolled Patients with Type 2 Diabetes Mellitus

Introduction: Patients with type 2 diabetes mellitus (T2DM) show variable brain tissue changes and mood and cognitive symptoms, which may result from altered cerebral blood flow (CBF). However, the regional CBF status in controlled and uncontrolled T2DM patients remains unclear, which can be examined with arterial spin labeling (ASL) imaging. Our aim was to examine regional CBF between controlled and uncontrolled T2DM patients using ASL imaging procedures. Methods: We collected hemoglobin A1c (A1C) data and 3D pseudo-continuous ASL data from 32 T2DM patients (16 controlled [A1C &amp;lt; 7%], age, 56.5±6.5 years; BMI, 29.6±6.2 kg/m2; 8 female; 16 uncontrolled [A1C ≥ 7%], age, 57.6±7.5 years; BMI, 30.0±5.1 kg/m2; 11 female) using a 3.0-Tesla MRI. A1C was measured by point-of-care testing. Whole-brain CBF maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. uncontrolled T2DM patients) using analysis of covariance (SPM12; covariates, age and sex; p&amp;lt;0.05). Results: No significant differences in age or sex appeared between groups. Multiple brain areas showed decreased CBF values in the cingulate, caudate, putamen, insula, hippocampus, amygdala, thalamus, hypothalamus, midbrain, cerebellum, prefrontal and frontal, and temporal cortices in uncontrolled T2DM patients over controlled T2DM patients. However, few brain sites in controlled T2DM patients, including the cerebellum, pons, medulla, parahippocampal gyrus, and temporal cortices showed reduced CBF over uncontrolled T2DM patients. Conclusion: Uncontrolled T2DM patients show significant reduction in CBF compared to controlled T2DM in areas that are involved in mood and cognition regulation. The findings suggest that uncontrolled levels may contribute to reduce regional CBF leading to site-specific tissue changes resulting to mood and cognition deficits in the condition. Disclosure S. E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott Diabetes, Novo Nordisk Inc. R. Kumar: None. Funding National Institutes of Health (1R01NR017190-03, 3R01NR017190-03S1)

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.

Characteristics of cerebral hemodynamics in patients with chronic brain ischemia

Background. Literature sources report conflicting results regarding the severity of clinical symptoms of hydrocephalus (HC) and their association with cerebral arterial blood flow (CABF); most studies do not show a direct relationship, while some suggest a link between clinical severity and progressive decrease in CABF. The study of hemodynamic changes in the brain of patients with chronic brain ischemia (CBI), elucidation of their relationship with cognitive impairments helps to improve diagnostic approaches and optimize the prognosis of the disease. The purpose of this study is to investigate the state of cerebral hemodynamics and to establish its relationship with changes in cognitive functions in patients with CBI and HC. Materials and Methods. A comprehensive examination of 110 patients with CBI and HC was performed. The localization of the HC and results of Montreal Cognitive Test (MoCA scale) were taken into account. Computed tomography of the brain was performed with subsequent determination of morphometric parameters and indices. The state of cerebral blood flow and structural changes of blood vessels were studied using transcranial color-coded duplex ultrasonography (TCCS) of intracranial vessels and extracranial divisions. Microsoft Excel 2011 and Statistica were used for statistical processing of the results. Results. It was found that there was a significantly larger diameter of both common carotid arteries (CCA), thickness of complex intima\media (CIM), maximum systolic velocity (Vs), velocity at the end of the diastolic cycle (Vd), as well as peripheral resistance (IR) in left CCA (p &lt;0,05) in patients with CBI and HC compared with patients with CBI without HC. Significantly larger diameter of left internal carotid artery (ICA), Vs, Vd and IR was revealed; Vs and Vd in the right ICA; Vd in the extracranial devision of vertebral artery (VA) in patients with HC. A significant relationship was found between the following blood flow parameters and the values of the MoCA scale: Vs MCA/MoCA (r = 0,45, p &lt;0,05), Vs ACA/MoCA (r = 0,38, p &lt;0.05), ICA diameter/MoCA (r = -0,51, p &lt;0,05). It was found that the diameter of CCA and the thickness of CIM were significantly larger in patients with CBI with internal HC in comparison with patients with CBI with external HC (p &lt;0,01). Vs and Vd in patients with internal hydrocephalus were significantly lower, and IR was significantly higher compared with patients with external hydrocephalus (p &lt;0,01). The diameter of ICA and IR in patients with CBI with internal HC was significantly higher, and Vs was significantly lower compared with patients with CBI and external HC (p &lt;0,01). Significantly different values were found in Vs and IR meanings in middle cerebral artery (MCA) and Vs in anterior cerebral artery (ACA) in patients with CBI with internal HC compared with patients with CBI with external HC.Conclusions. Functional parameters of blood flow and structural changes of cerebral arteries in patients with CBI with concomitant hydrocephalus differed significantly from those in patients without hydrocephalus and depended on the type and severity of hydrocephalus. ICA occlusion, ICA stenosis &gt;50%, and intracranial venous stasis were significantly more common in patients with severe and moderate HC compared with those with mild HC. A weak relationship was found between the structure of carotid arteries and blood flow in intracranial arteries in patients with CBI and HC. There was a significant relationship between blood flow indices and the values of the MoCA scale, which indicated the effect of changes in the vessels of the anterior circular basin on the cognitive functions and the lack of such connection with blood flow indices in vertebrobasilar basin.

The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure.

Previous work indicates that dynamic cerebral blood flow (CBF) regulation is impaired during hypercapnia; however, less is known about the impact of resting hypercapnia on regional CBF regulation during hypovolemia. Furthermore, there is disparity within the literature on whether differences between anterior and posterior CBF regulation exist during physiological stressors. We hypothesized: (a) lower-body negative pressure (LBNP)-induced reductions in cerebral blood velocity (surrogate for CBF) would be more pronounced during hypercapnia, indicating impaired CBF regulation; and (b) the anterior and posterior cerebral circulations will exhibit similar responses to LBNP. In 12 healthy participants (6 females), heart rate (electrocardiogram), mean arterial pressure (MAP; finger photoplethosmography), partial pressure of end-tidal carbon dioxide (PETCO2), middle cerebral artery blood velocity (MCAv) and posterior cerebral artery blood velocity (PCAv; transcranial Doppler ultrasound) were measured. Cerebrovascular conductance (CVC) was calculated as MCAv or PCAv indexed to MAP. Two randomized incremental LBNP protocols were conducted (-20, -40, -60 and -80mmHg; three-minute stages), during coached normocapnia (i.e., room air), and inspired 5% hypercapnia (~ + 7mmHg PETCO2 in normoxia). The main findings were: (a) static CBF regulation in the MCA and PCA was similar during normocapnic and hypercapnic LBNP trials, (b) MCA and PCA CBV and CVC responded similarly to LBNP during normocapnia, but (c) PCAv and PCA CVC were reduced to a greater extent at -60mmHg LBNP (P = 0.029; P < 0.001) during hypercapnia. CBF regulation during hypovolemia was preserved in hypercapnia, and regional differences in cerebrovascular control may exist during superimposed hypovolemia and hypercapnia.

Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.

Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) and arterial spin labeling (ASL) datasets on a group of 26 early PD (66.8 ± 8 years, 22 males, median [interquartile range] Hoehn and Yahr = 1.5 [1]) and 18 age- and sex-matched healthy controls (HCs). In addition, a T1-weighted MPRAGE was also acquired in the same scan session. After a standard preprocessing, resting state networks (RSNs) and CBF maps were extracted from rsfMRI and ASL dataset, respectively. Then, by means of a dual regression algorithm performed on RSNs, a cluster of FC differences between groups was obtained and used to mask CBF maps in the subsequent voxel-wise group comparison. Furthermore, a gray matter (GM) volumetric assessment was performed within the FC cluster in order to exclude tissue atrophy as a source of functional changes. Reduced FC for a PD patient with respect to HC group was found within a sensory-motor network (SMN, pFWE = 0.01) and visual networks (VNs, primary pFWE = 0.022 and lateral pFWE = 0.01). The latter was accompanied by a decreased CBF (primary pFWE = 0.037, lateral pFWE = 0.014 VNs), while no GM atrophy was detected instead. The FC alteration found in the SMN of PD might be likely due to a dopaminergic denervation of the striatal pathways causing a functional disconnection. On the other hand, the changes in connectivity depicted in VNs might be related to an altered non-dopaminergic system, since perfusion was also reduced, revealing a compromised NVC. Finally, the absence of GM volume loss might imply that functional changes may potentially anticipate neurodegeneration. In this framework, FC and CBF might be proposed as early functional biomarkers providing meaningful insights in evaluating both disease progression and therapeutic/rehabilitation treatment outcome.

Relationship between ischaemic symptoms during the early postoperative period in patients with moyamoya disease and changes in the cerebellar asymmetry index

ObjectiveThe aim of this study was to clarify the relationship between ischaemic symptoms during the early postoperative period in patients with moyamoya disease and changes in the cerebellar asymmetry index (AI), a parameter used to quantitatively identify crossed cerebellar diaschisis (CCD). Patients and methodsWe analysed the data of 18 patients with moyamoya disease who underwent quantitative IMP-cerebral blood flow SPECT at least once during the follow-up period. Cerebellar AI scores were calculated using the CBF of the cerebellum calculated automatically from multiple slices of SPECT images with automated ROI setup software and categorized and statistically examined according to the presence or absence of ischaemic symptoms. ResultsThe cerebellar AI calculated from SPECT performed in the patients who presented with ischaemic symptoms was 0.094 ± 0.023 (mean ± SD), which was significantly elevated compared to the value of 0.013 ± 0.025 (mean ± SD) calculated from SPECT performed when the patients did not present with ischaemic symptoms (p < 0.0001). Limiting the time of SPECT to calculate the cerebellar AI to be compared to the acute phase within 2 weeks after surgery did not change this trend, and again, the cerebellar AI was statistically significantly elevated in the presence of ischaemic symptoms (0.094 ± 0.023 (mean ± SD)) compared to the AI in the absence of ischaemic symptoms (0.000081 ± 0.026 (mean ± SD)) (p = 0.0003). In patients who underwent quantitative SPECT in the acute phase during the first postoperative week, the cerebellar AI values calculated from the results of SPECT performed during the preoperative period as well as multiple times during postoperative period were followed over time in each case. The cerebellar AI increased in patients who presented with symptoms of ischaemia postoperatively but then tended to decrease reversibly and approach zero with the disappearance of symptoms of ischaemia. ConclusionsSince the cerebellar AI reflects the symptom of ischaemia in patients with moyamoya disease, especially in the early stage after revascularization surgery, and is a parameter that improves with symptom improvement, it seems to be useful for understanding the state of cerebral blood flow after bypass surgery in patients with moyamoya disease.

Regional resting state perfusion variability and delayed cerebrovascular uniform reactivity in subjects with chronic carotid artery stenosis

The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis.Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥90% on the ipsilateral side and ≤50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection.The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon’s test. Normality assumption was examined using W Shapiro-Wilk test.The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe – ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe – ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe – ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe – ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6). The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3). The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue [ml/100g/min]. Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population.Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.

Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains.

Regional resting state perfusion variability and delayed cerebrovascular uniform reactivity in subjects with chronic carotid artery stenosis.

The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis. Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥ 90% on the ipsilateral side and ≤ 50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection. The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon's test. Normality assumption was examined using W Shapiro-Wilk test. The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe - ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe - ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe - ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe - ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6). The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3). The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue (ml/100g/min). Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population. Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.