Cerebral Blood Flow Distribution Research Articles

Circle of Willis and Its Anatomical Relevance

The Circle of Willis is an arterial network located at the base of the brain, formed by the interconnection of the anterior, middle, and posterior cerebral arteries, along with the anterior and posterior communicating arteries. It connects the internal carotid arteries to the vertebral arteries, allowing the distribution of cerebral blood flow. Its significance lies in its ability to offer an alternative pathway in cases of arterial obstruction, helping to prevent cerebral ischemia. However, anatomical variations of this structure are common, and only 20% to 25% of the population has a "complete" or symmetrical configuration. Such variations can influence the risk of cerebrovascular diseases, such as stroke, as they may compromise the efficiency of the compensatory mechanism. These anatomical variations have a direct impact on the diagnosis and treatment of neurological conditions. The integrity of the Circle of Willis can influence the severity of symptoms in cases of ischemic strokes, as well as affect aneurysm formation and its clinical implications. Advances in imaging techniques, such as CT angiography and magnetic resonance imaging, have enabled more accurate diagnoses and the development of more effective treatments for conditions associated with the Circle of Willis, making its anatomical understanding essential for the prevention and management of cerebrovascular diseases.

Regional heterogeneity of cerebral blood flow immediately after the onset of ventricular pacing in anesthetized rats.

Selective distribution of cerebral blood flow (CBF) to vital brain regions likely occurs during rapid severe hypotension caused by tachyarrhythmia, but has not yet been demonstrated. In this study, we aimed to test the hypothesis that CBF is differentially preserved between brain regions depending on the degree of hypotension. In anesthetized rats, CBF was measured in the motor cortex (MC), medial prefrontal cortex, amygdala, thalamus, dorsal hypothalamus, hippocampus, ventral tegmental area, dorsolateral periaqueductal gray (dlPAG), and parabrachial nucleus (PB) by using laser-Doppler flowmetry. Ventricular pacing was performed for 30 s at 550-800 beats/min. The cerebrovascular CO2 response time and reactivity were evaluated during 5% CO2 exposure. During 1-4 s of ventricular pacing, mean arterial pressure (MAP) rapidly decreased, with minor changes in central venous and intracranial pressures. CBF was relatively well maintained in brain regions other than the MC (Ps ≤ 0.012) when moderate hypotension occurred (-34 mmHg ≤ ΔMAP ≤ -15 mmHg), whereas severe hypotension (-54 mmHg ≤ ΔMAP ≤ -35 mmHg) induced selective CBF distribution to regions other than the MC, thalamus, and dlPAG. The cerebrovascular CO2 response time/reactivity was rapid or high in the thalamus, dlPAG, and PB, which almost completely differed from the brain regions in which CBF was relatively maintained during pacing-induced severe hypotension. These results suggest that regional heterogeneity of CBF arises depending on the degree of tachyarrhythmia-induced hypotension. Clarifying the mechanisms and functions of CBF maintenance would be beneficial to syncope and cerebral ischemia management in patients with arrhythmia.

Evaluating the accuracy of cerebrovascular computational fluid dynamics modeling through time-resolved experimental validation

Accurate modeling of cerebral hemodynamics is crucial for better understanding the hemodynamics of stroke, for which computational fluid dynamics (CFD) modeling is a viable tool to obtain information. However, a comprehensive study on the accuracy of cerebrovascular CFD models including both transient arterial pressures and flows does not exist. This study systematically assessed the accuracy of different outlet boundary conditions (BCs) comparing CFD modeling and an in-vitro experiment. The experimental setup consisted of an anatomical cerebrovascular phantom and high-resolution flow and pressure data acquisition. The CFD model of the same cerebrovascular geometry comprised five sets of stationary and transient BCs including established techniques and a novel BC, the phase modulation approach. The experiment produced physiological hemodynamics consistent with reported clinical results for total cerebral blood flow, inlet pressure, flow distribution, and flow pulsatility indices (PI). The in-silico model instead yielded time-dependent deviations between 19–66% for flows and 6–26% for pressures. For cerebrovascular CFD modeling, it is recommended to avoid stationary outlet pressure BCs, which caused the highest deviations. The Windkessel and the phase modulation BCs provided realistic flow PI values and cerebrovascular pressures, respectively. However, this study shows that the accuracy of current cerebrovascular CFD models is limited.

Precuneal hyperperfusion in patients with attention-deficit/hyperactivity disorder-comorbid nociplastic pain.

Nociplastic pain (NP), a third category of chronic pain, offers a framework for elucidating its pathophysiology and treatment strategies. One of the characteristics of NP is comorbidity of symptoms other than pain, such as psychological and cognitive problems; therefore, these can be clues to understanding NP. Recently, we reported several cases with comorbid symptoms of attention-deficit/hyperactivity disorder (ADHD). Notably, ADHD medications, including methylphenidate (MP) and atomoxetine, improved chronic pain as well as the symptoms of ADHD. However, in clinical settings, identifying comorbid ADHD in patients with chronic pain is challenging, and underlying mechanisms have not been elucidated. To explore the common characteristics of brain function in patients with ADHD-comorbid NP, we identified brain regions where cerebral blood flow (CBF) distributions changed between pre- and post-treatment using single-photon emission computed tomography (SPECT). Additionally, we examined brain regions where CBF values correlated with clinical scores. We retrospectively studied 65 patients (mean age 53 ± 14years; 30 males and 35 females) with ADHD-comorbid NP who underwent CBF-SPECT before and after ADHD medication initiation. Clinical scores included the clinical global impression severity (CGI-S), pain numerical rating scale, hospital anxiety and depression scale, pain catastrophizing scale, and Conners' adult ADHD rating scale-self report scores. Voxel-based statistical methods were used to compare pre- and post-treatment CBF-SPECT images to identify significant differences and investigate brain regions correlated with clinical scores. The CBF was higher in the precuneus, insular gyrus, and thalamus before treatment than after treatment (paired t-test, cluster-definition p < 0.001, cluster-extent threshold p < 0.05, with family-wise error [FWE] correction). The hyperperfusion in the precuneus was positively correlated with the CGI-S score and significantly reduced after treatment with MP (paired t-test, cluster-definition p < 0.005, cluster-extent threshold p < 0.05, with FWE correction). The finding of precuneal hyperperfusion may provide insight into the mechanisms of NP and help identify patients who would benefit most from ADHD medications.

Role of Histogram Features on Arterial Spin Labeling Perfusion Magnetic Resonance Imaging in Identifying Isocitrate Dehydrogenase Genotypes and Glioma Malignancies.

To explore the use of histogram features on noninvasive arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in differentiating isocitrate dehydrogenase mutant-type (IDH-mut) from isocitrate dehydrogenase wild-type (IDH-wt) gliomas, and lower-grade gliomas (LGGs) from glioblastomas. This retrospective study included 131 patients who underwent ASL MRI and anatomic MRI. Cerebral blood flow (CBF) maps were calculated, from which 10 histogram features describing the CBF distribution were extracted within the tumor region. Correlation analysis was performed to determine the correlations between histogram features as well as tumor grades and IDH genotypes. The independent t-test and Fisher's exact test were used to determine differences in the extracted histogram features, age at diagnosis, and sex in different glioma subtypes. Multivariate binary logistic regression analysis was performed, and diagnostic performances were evaluated with the receiver operating characteristic curves. CBF histogram features were significantly correlated with tumor grades and IDH genotypes. These features can effectively differentiate LGGs from glioblastomas, and IDH-mut from IDH-wt gliomas. The area under the receiving operating characteristic curve of the model calculated using combined CBF 30th percentile and age at diagnosis in differentiating LGGs from glioblastomas was 0.73. Integrating age at diagnosis and CBF 10th percentile could be more effective in differentiating IDH-mut from IDH-wt gliomas. Furthermore, the combined model had a better area under the receiving operating characteristic curve at 0.856 (sensitivity: 84.4%, specificity: 82.9%). The histogram features on ASL were significantly correlated with tumor grade and IDH genotypes. Moreover, the use of these features could effectively differentiate glioma subtypes. The combined application of age at diagnosis and perfusion histogram features resulted in a more comprehensive identification of tumor subtypes. Therefore, ASL can be a noninvasive tool for the pre-surgical evaluation of gliomas.

MRI-based parameter inference for cerebral perfusion modelling in health and ischaemic stroke

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on the spatial distribution of cerebral blood flow (CBF) in the human brain. To estimate treatment efficacy based on CBF, perfusion simulations need to become suitable for group-level investigations and thus account for physiological variability between individuals. However, computational perfusion modelling to date has been restricted to a few patient-specific cases. This study set out to establish automated parameter inference for perfusion modelling based on neuroimaging data and thus enable CBF simulations of groups. Magnetic resonance imaging (MRI) data from 75 healthy senior adults were utilised. Brain geometries were computed from healthy reference subjects’ T1-weighted MRI. Haemodynamic model parameters were determined from spatial CBF maps measured by arterial spin labelling (ASL) perfusion MRI. Thereafter, perfusion simulations were conducted in 75 healthy cases followed by 150 acute ischaemic stroke cases representing an occlusion and CBF cessation in the left and right middle cerebral arteries. The anatomical fitness of the brain geometries was evaluated by comparing the simulated grey (GM) and white matter (WM) volumes to measurements in healthy reference subjects. Strong positive correlations were found in both tissue types (GM: Pearson’s r 0.74, P<0.001; WM: Pearson’s r 0.84, P<0.001). Haemodynamic parameter tuning was verified by comparing the total volumetric blood flow rate to the brain in healthy reference subjects and simulations (Pearson’s r 0.89, P<0.001). In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based estimate was 197±25 ml. Computational predictions were in agreement with anatomical and haemodynamic values from the literature concerning T1-weighted, T2-weighted, and phase-contrast MRI measurements in healthy scenarios and acute ischaemic stroke cases. The acute stroke simulations did not capture small infarcts (left tail of the distribution), which could be explained by neglected compensatory mechanisms, e.g. collaterals. The proposed parameter inference method provides a foundation for group-level CBF simulations and for in silico clinical stroke trials which could assist in medical device and drug development.

Cerebral autoregulation and blood flow distribution in the precerebral arteries for determining indications of extra-intracranial bypass in patients with carotid artery occlusion

Background. Prevention of ischemic stroke in patients with carotid artery occlusion is conventionally associated with performing cerebral revascularization. However, determining the indications for it is still an actual problem. The informative value of noninvasive assessment of cerebral autoregulation and blood flow distribution in the precerebral arteries in patients with carotid artery stenosis is shown. At the same time, in patients with carotid artery occlusion, these indicators have been studied to a lesser extent.Aim. To evaluate the informative value of cerebral autoregulation and blood flow distribution in the precerebral arte ries for determination the indications of extra‑intracranial bypass in patients with carotid occlusion.Materials and methods. 54 patients (aged from 41 to 83 y. o.) with carotid artery occlusion were studied. Blood flow velocity in intracranial arteries was determined with transcranial Doppler (system Multi‑Dop X), whereas flow velocity index in precerebral arteries – with duplex scanning (system Vivid Е). Cerebral autoregulation was assessed based on phase shift between spontaneous oscillations of blood flow velocity in basal cerebral arteries and systemic blood pressure within the range of Mayer’s waves (80–120 mHz).Results. The state of cerebral autoregulation was imparied on both sides in 90 % patients with the symptomatic carotid occlusion (0.3 ± 0.3 rad ipsilateral, 0.7 ± 0.6 rad contralateral). The state of cerebral autoregulation was not impaired in 79 % patients with asymptomatic carotid occlusion (1.0 ± 0.3 rad ipsilateral, 1.1 ± 0.4 rad contralateral). The flow velocity index in the contralateral internal carotid artery (306 ± 109 ml / min) and the ipsilateral vertebral (139 ± 69 ml / min) and external carotid (175 ± 72 ml / min) arteries was increased.Conclusions. Noninvasive preoperative assessment of cerebral autoregulation and blood flow distribution in the precerebral arteries makes to evaluate the state of the cerebrovascular reserve to quantify and can be used to determining indications for cerebral revascularization in patients with carotid occlusion.

Association between Cognitive Decline and Altered Cerebral Perfusion in Adults with Moyamoya Disease after Revascularization

Introduction: Certain studies have observed that patients with moyamoya disease (MMD) have cognitive decline after revascularization. Thus, this study analyzed the relationship between cognitive decline and altered cerebral perfusion after revascularization. Methods: Here, 313 adult patients with MMD underwent single unilateral revascularization. First, cognitive function was scored using a Mini-Mental Scale (MMSE) and Montreal cognitive function scale (MoCA) before and 3 months after the operation (superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis). Then, computed tomography perfusion was performed before and 1 week after the operation to assess the cerebral perfusion. Results: Our data showed that cognitive function decreased in 55 cases (17.6%) after revascularization. Furthermore, the incidence of cerebral hyperperfusion (CHP) was significantly higher in the cognitive decline group (49/55) than in the cognitive nondecline group (89.1% vs. 5.4%, p < 0.001). Results also showed that although all 55 patients had postoperative cognitive decline, 47 experienced relative cerebral blood flow (CBF) decrease at a relatively distant area of the anastomosis compared with that before the operation, which was significantly higher than in patients without cognitive decline (85.5% vs. 1.94%, p < 0.001). In addition, 41 patients had a simultaneous occurrence of local CHP and paradoxical CBF decrease at a relatively distant anastomosis area, which indicated the incident of watershed shift (WS). As observed, WS occurred in 74.5% of patients with cognitive decline, significantly higher than in patients without cognitive decline (74.5% vs. 0%, p < 0.0001). Through multiple logistic regression analysis, WS was also observed to be a strong independent risk factor for predicting postoperative cognitive decline 3 months after revascularization (odds ratio 17.780, 95% confidence interval 1.668–18.564; p = 0.017). Conclusion: Therefore, cognitive decline in patients with MMD after revascularization is related to WS, leading to an uneven distribution of CBF.

Characteristics of Regional Cerebral Blood Flow in Alzheimer Disease and Amnestic Mild Cognitive Impairment by Single-Photon Emission Computerized Tomography: A Cross-Sectional Study

Introduction: The regional cerebral blood flow (rCBF) distribution can affect brain functioning, leading to amnestic mild cognitive impairment (aMCI) and mild Alzheimer disease (AD). This study aimed to clarify the detailed characteristics of rCBF distribution in patients with mild AD and aMCI. Methods: This cross-sectional study from April 2015 to March 2018 included 103 older adults (mean age 78.9 years; 60% females), out of a total of 302 adults, and categorized them into 3 groups according to cognitive symptoms. The normal control (NC), aMCI, and mild AD groups included 20, 50, and 33 participants, respectively. The primary outcome was rCBF, which was compared among the 3 groups using a 2-sample t test without correction for multiple comparisons. Results: In the aMCI group, the rCBF decreased in the bilateral parietal and left frontal association cortex and the bilateral premotor cortex (p < 0.01) but increased in the bilateral cerebellum (p < 0.01). In the mild AD group, the rCBF decreased in the bilateral parietal and occipital association cortex, the bilateral premotor cortex, the left temporal and frontal association cortex, and the left limbic lobe (p < 0.01). Conversely, the rCBF increased in some parts of the cerebellum, the bilateral frontal and temporal association cortex, the left occipital association cortex, and the right premotor cortex (p < 0.01). Conclusion: Based on the analysis of the values obtained, it was inferred that the rCBF undergoes reduction and elevation in aMCI and AD patients.

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle‐aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99mTc‐HMPAO single‐photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel‐based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

Impaired cerebral microcirculation in isolated REM sleep behaviour disorder.

During the prodromal period of Parkinson's disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of mood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whether patients with isolated REM sleep behaviour disorder, a parasomnia considered to be a prodromal phenotype of α-synucleinopathies, reveal microvascular flow disturbances consistent with disrupted central blood flow control. We applied dynamic susceptibility contrast MRI to characterize the microscopic distribution of cerebral blood flow in the cortex of 20 polysomnographic-confirmed patients with isolated REM sleep behaviour disorder (17 males, age range: 54-77 years) and 25 healthy matched controls (25 males, age range: 58-76 years). Patients and controls were cognitively tested by Montreal Cognitive Assessment and Mini Mental State Examination. Results revealed profound hypoperfusion and microvascular flow disturbances throughout the cortex in patients compared to controls. In patients, the microvascular flow disturbances were seen in cortical areas associated with language comprehension, visual processing and recognition and were associated with impaired cognitive performance. We conclude that cortical blood flow abnormalities, possibly related to impaired neurogenic control, are present in patients with isolated REM sleep behaviour disorder and associated with cognitive dysfunction. We hypothesize that pharmacological restoration of perivascular neurotransmitter levels could help maintain cognitive function in patients with this prodromal phenotype of parkinsonism.

Effects of notoginseng leaf triterpenes on small molecule metabolism after cerebral ischemia/reperfusion injury assessed using MALDI-MS imaging.

BackgroundNotoginseng leaf triterpenes (PNGL) is believed to have neuroprotective effects via the inhibition of inflammatory response and neuronal apoptosis. However, its mechanisms underlying the anti-ischemia/reperfusion (I/R) injury effects on the regulation of small molecule metabolism in rat brain remains unclear. The purpose of this study was thus to explore the mechanisms of PNGL on the regulation of small molecule metabolism in rat brain after I/R injury using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI).MethodsAs a model of in vivo cerebral I/R injury, male Sprague-Dawley (SD) rats were established with a middle cerebral artery occlusion/reperfusion (MCAO/R) model after PNGL administration with 40 mg·kg-1 through intraperitoneal injection (i.p.) for 7 days. We assessed the neurological behavior, regional cerebral blood flow (r CBF), neuron injury, and spatial distribution of metabolic small molecules.ResultsOur in vivo results suggested that PNGL increased cerebral blood flow and relieved neurological dysfunction. Furthermore, using MALDI-MSI, we demonstrated that PNGL regulated 16 endogenous small molecules implicated in metabolic networks including tricarboxylic acid (TCA) cycle, adenosine triphosphate (ATP) metabolism, malate-aspartate shuttle, metal ions, and antioxidants underwent noticeable changes after reperfusion for 24 h.ConclusionsPNGL is a novel cerebrovascular agent that can improve cerebral blood flow and attenuate adverse neurological disorders. The mechanisms are closely correlated with relative metabolic pathways, which offers insight into exploring new mechanisms in PNGL for the treatment of cerebral I/R injury.

Speckle contrast diffuse correlation tomography of cerebral blood flow in perinatal disease model of neonatal piglets.

We adapted and tested an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system for 3D imaging of cerebral blood flow (CBF) variations in perinatal disease models utilizing neonatal piglets, which closely resemble human neonates. CBF variations were concurrently measured by the scDCT and an established diffuse correlation spectroscopy (DCS) during global ischemia, intraventricular hemorrhage, and asphyxia; significant correlations were observed. Moreover, CBF variations associated reasonably with vital pathophysiological changes. In contrast to DCS measurements of mixed signals from local scalp, skull and brain, scDCT generates 3D images of CBF distributions at prescribed depths within the head, thus enabling specific determination of regional cerebral ischemia. With further optimization and validation in animals and human neonates, scDCT has the potential to be a noninvasive imaging tool for both basic neuroscience research in laboratories and clinical applications in neonatal intensive care units.

Characteristic Pattern of the Cerebral Hemodynamic Changes in the Acute Stage After Combined Revascularization Surgery for Adult Moyamoya Disease: N-isopropyl-p-[123I] iodoamphetamine Single-Photon Emission Computed Tomography Study.

Surgical revascularization for moyamoya disease (MMD) prevents cerebral ischemic attack by improving cerebral blood flow (CBF) and could also reduce the risk of re-bleeding in hemorrhagic-onset patients. We sought to clarify the cerebral hemodynamic changes in the acute stage after revascularization surgery for adult MMD. The present study includes 54 consecutive adult patients with MMD (21-76years old, 43.1 average), undergoing superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis on 65 affected hemispheres. We prospectively performed single-photon emission computed tomography (SPECT) at postoperative day (POD) 1 and 7 of 65 surgeries. Perioperative management was conducted with strict blood pressure control (100-130mmHg) and minocycline hydrochloride administration. The outcome of 65 surgeries was favorable except for one (1.5%), which manifested as delayed intracerebral hemorrhage due to local hyperperfusion. The postoperative SPECT revealed the characteristic CBF improvement pattern with transient local hyperperfusion (POD1) and subsequent distribution of CBF in wider vascular territory (POD7) on 37 hemispheres (56.9%, 37/65). The revascularization surgery is a safe and effective treatment for adult MMD, while transient local hyperperfusion should be strictly managed by intensive perioperative care.

Arterial and venous cerebral blood flow responses to long-term head-down bed rest in male volunteers.

What is the central question of this study? A heterogeneous cerebral blood flow (CBF) response in the cerebral arteries has been demonstrated in several physiological conditions, and it might be attributable to different physiological properties. However, the whole cerebral haemodynamic response to weightlessness remains unknown. What is the main finding and its importance? Long-term head-down bed rest caused a heterogeneous CBF response between the anterior and posterior cerebral arteries and between the cerebral arteries and veins. Especially, in contrast to the anterior cerebral circulation, the posterior arterial and venous CBFs were well maintained throughout weightlessness. In this study, we investigated the whole cerebral haemodynamic response to long-term head-down bed rest (HDBR). We hypothesized that long-term exposure to weightlessness influences cerebral blood flow (CBF) or CBF distribution among cerebral arteries and veins because of the different physiological roles of each cerebral vessel. To test this hypothesis, 10 male volunteers were exposed to -6deg HDBR for 60days. Blood flows in the internal carotid artery, external carotid artery and vertebral artery or internal jugular vein and vertebral vein were measured using ultrasonography before and on days30 and 57 of the HDBR. The internal carotid artery blood flow was reduced on day30 (P=0.019) and had returned to the baseline level by day57. In contrast, the vertebral artery blood flow remained unaltered throughout the HDBR (P=0.626). The internal jugular vein blood flow was reduced on day30 (P=0.009), whereas the vertebral vein blood flow remained unaltered (P=0.397). These findings suggest that long-term HDBR causes a heterogeneous CBF response between the anterior and posterior cerebral circulation in the both arteries and veins. The posterior arterial and venous CBFs were well maintained throughout HDBR, and these CBF responses to HDBR were different from the anterior cerebral circulation.

Cerebral Blood Flow Distribution During Parabolic Flight-induced Microgravity

Cerebral Blood Flow Distribution During Parabolic Flight-induced Microgravity

Noninvasive noncontact speckle contrast diffuse correlation tomography of cerebral blood flow in rats

Continuous and longitudinal imaging of cerebral blood flow (CBF) variations provide vital information to investigate pathophysiology and interventions for a variety of neurological and cerebral diseases. An innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system was downscaled and adapted for noninvasive imaging of CBF distributions in rat brain through intact scalp and skull. Algorithms for 2D mapping and 3D image reconstruction of CBF distributions were developed and optimized. The continuous imaging capability of the system was shown by imaging global CBF increases during CO2 inhalations and regional CBF decreases across two hemispheres during sequential unilateral and bilateral common carotid artery ligations. The longitudinal imaging capability was demonstrated by imaging CBF variations over a long recovery period of 14 days after an acute stroke. Compared to the 2D mapping method, the 3D imaging method reduces partial volume effects, but needs more computation time for image reconstruction. Results from this study generally agree with those reported in the literature using similar protocols to induce CBF changes in rats. The scDCT enables a relatively large penetration depth (up to ∼10 mm), which is sufficient for transcranial brain measurements in small animals and human neonates. Ultimately, we expect to provide a noninvasive noncontact cerebral imager for basic neuroscience research in small animal models and clinical applications in human neonates.

Simultaneous phase-contrast MRI and PET for noninvasive quantification of cerebral blood flow and reactivity in healthy subjects and patients with cerebrovascular disease.

H215 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion. To demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H215 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI. Observational. Twelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease. 3T/2D cardiac-gated phase-contrast MRI and H215 O-PET. PC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis. The mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H215 O-PET in future studies. 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183-194.

Semi-automated analysis of 4D flow MRI to assess the hemodynamic impact of intracranial atherosclerotic disease.

This study evaluated the feasibility of using 4D flow MRI and a semi-automated analysis tool to assess the hemodynamic impact of intracranial atherosclerotic disease (ICAD). The ICAD impact was investigated by evaluating pressure drop (PD) at the atherosclerotic stenosis and changes in cerebral blood flow distribution in patients compared to healthy controls. Dual-venc 4D flow MRI was acquired in 25 healthy volunteers and 16 ICAD patients (ICA, N = 3; MCA, N = 13) with mild (<50%), moderate (50-69%), or severe (>70%) intracranial stenosis. A semi-automated analysis tool was developed to quantify velocity and flow from 4D flow MRI and to evaluate cerebral blood flow redistribution. PD at stenosis was estimated using the Bernoulli equation. The PD calculation was examined by an in vitro phantom study against flow simulations. Flow analysis in controls indicated symmetry in blood flow rate (FR) and peak velocity (PV) between the brain hemispheres. For patients, PV in the affected hemisphere was significantly (65%) higher than the normal side (P = 0.002). However, FR to both hemispheres of the brain was the same. The PD depicted significant correlation with PV asymmetry in patients (ρ = 0.67 and P = 0.02), and it was significantly higher for severe compared to moderate stenosis (3.73 vs. 2.30 mm Hg, P = 0.02). 4D flow MRI quantification enables assessment of the hemodynamic impact of ICAD. The significant difference of the PD between patients with severe and moderate stenosis and its correlation with PV asymmetry suggest that PD may be a pertinent hemodynamic biomarker to evaluate ICAD.

The effects of aging on the distribution of cerebral blood flow with postural changes and mild hyperthermia.

Cerebral blood flow (CBF) would be impaired with dual stresses of heat and orthostatic changes, even if those stresses are mild, in the elderly with declined cardio- and cerebrovascular functions with aging. To test the hypothesis, we compared the response of blood flow in the internal carotid artery (ICA) and vertebral artery (VA) to dual stresses of heat and orthostatic changes between the elderly and young individuals. Nine elderly and eight young healthy men (71.3 ± 3.0 and 23.3 ± 3.1 years, mean ± SD, respectively) underwent measurements of blood flow in the ICA, VA and external carotid artery (ECA) via ultrasonography. The measurements were obtained in sitting and supine positions under normothermic (NT) and mildly hyperthermic (HT) conditions (ambient temperature 28°C). Esophageal temperatures increased from NT (36.4 ± 0.2°C, mean ± SE) to HT (37.4 ± 0.2°C) with lower legs immersion in 42°C water. With heat stress, ECA blood flow increased in both postures in both age groups (effect of heat, p < 0.001), whereas ICA blood flow remained unchanged. With postural changes from supine to sitting, ECA blood flow remained unchanged whereas ICA blood flow decreased (effect of posture, p = 0.027) by 18% in NT in the young and by 20% in HT in the elderly. VA blood flow remained unchanged under both heat stress and postural changes. The CBF is impaired under dual stresses of heat and orthostatic changes in healthy aged individuals, even if the levels of the stresses are mild.