Cerebral Blood Flow Studies Research Articles

A multi-site 99mTc-HMPAO SPECT study of cerebral blood flow in a community sample of patients with major depression

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18–65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18–65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.

Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain's response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain's electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

Alterations of Cerebral Blood Flow and its Connectivity Patterns Measured with Arterial Spin Labeling in Mild Cognitive Impairment.

Cerebral blood flow (CBF) is an important index for measuring brain function. Studies have shown that regional CBF changes inconsistently in mild cognitive impairment (MCI). Arterial spin labeling (ASL) is widely used in the study of CBF in patients with MCI. However, alterations in CBF connectivity in these patients remain poorly understood. In this study, 3D pseudo-continuous arterial spin labeling (3D-pCASL) technology was used to investigate the changes in regional CBF and CBF connectivity between 32 MCI patients and 32 healthy controls. The normalized CBF was used to reduce inter-subject variations. Both group comparisons in the CBF and correlations between CBF alterations and cognitive scores were assessed. CBF connectivity of brain regions with regional CBF differences was also compared between groups. We found that compared with that in controls, the CBF was significantly reduced in the left superior parietal gyrus in MCI patients, whereas it was increased in the left precentral gyrus, right superior temporal gyrus, right putamen, and left supplementary motor area. In patients with MCI, significant correlations were identified between CBF and neuropsychological scales. Importantly, MCI patients exhibited CBF disconnections between the left supplementary motor area and the left superior parietal gyrus. This study found that there are not only changes in regional CBF but also in CBF connectivity patterns in MCI patients compared with controls. These observations may provide a novel explanation for the neural mechanism underlying the pathophysiology in patients with Alzheimer's disease and MCI.

Transcranial Doppler Remote Positioning System with Virtual Reality Integration for Vestibular Studies.

Transcranial doppler (TCD) ultrasound probes are an invaluable tool in cerebral blood flow (CBF) studies. Their operation demands maintaining consistent pose on the subject throughout the experimental protocol. However, the displacement of the TCD probe during vestibular studies is common and substantially prolongs the experiment or even terminates it. This is a significant challenge for integrating motion-based vestibular studies with CBF investigations. In response, a mechatronics system is designed to allow remote repositioning of the TCD probe during data collection experiments while the subject is wearing a head mounted virtual reality (VR) display and seated in a vestibular disorientation device. This paper presents the design, prototype, and operation of this mechatronics apparatus.Clinical Relevance- The mechatronics apparatus of this paper can enable motion-based vestibular studies that entail the use of CBF velocity measurement and head-mounted virtual reality display.

Amyloid and tau pathology are associated with cerebral blood flow in a mixed sample of nondemented older adults with and without vascular risk factors for Alzheimer’s disease

Identification of biomarkers for the early stages of Alzheimer’s disease (AD) is an imperative step in developing effective treatments. Cerebral blood flow (CBF) is a potential early biomarker for AD; generally, older adults with AD have decreased CBF compared to normally aging peers. CBF deviates as the disease process and symptoms progress. However, further characterization of the relationships between CBF and AD risk factors and pathologies is still needed. We assessed the relationships between CBF quantified by arterial spin-labeled magnetic resonance imaging, hypertension, APOEε4, and tau and amyloid positron emission tomography in 77 older adults: cognitively normal, subjective cognitive decline, and mild cognitive impairment. Tau and amyloid aggregation were related to altered CBF, and some of these relationships were dependent on hypertension or APOEε4 status. Our findings suggest a complex relationship between risk factors, AD pathologies, and CBF that warrants future studies of CBF as a potential early biomarker for AD.

Dynamic 3D imaging of cerebral blood flow in awake mice using self-supervised-learning-enhanced optical coherence Doppler tomography

Cerebral blood flow (CBF) is widely used to assess brain function. However, most preclinical CBF studies have been performed under anesthesia, which confounds findings. High spatiotemporal-resolution CBF imaging of awake animals is challenging due to motion artifacts and background noise, particularly for Doppler-based flow imaging. Here, we report ultrahigh-resolution optical coherence Doppler tomography (µODT) for 3D imaging of CBF velocity (CBFv) dynamics in awake mice by developing self-supervised deep-learning for effective image denoising and motion-artifact removal. We compare cortical CBFv in awake vs. anesthetized mice and their dynamic responses in arteriolar, venular and capillary networks to acute cocaine (1 mg/kg, i.v.), a highly addictive drug associated with neurovascular toxicity. Compared with awake, isoflurane (2-2.5%) induces vasodilation and increases CBFv within 2-4 min, whereas dexmedetomidine (0.025 mg/kg, i.p.) does not change vessel diameters nor flow. Acute cocaine decreases CBFv to the same extent in dexmedetomidine and awake states, whereas decreases are larger under isoflurane, suggesting that isoflurane-induced vasodilation might have facilitated detection of cocaine-induced vasoconstriction. Awake mice after chronic cocaine show severe vasoconstriction, CBFv decreases and vascular adaptations with extended diving arteriolar/venular vessels that prioritize blood supply to deeper cortical capillaries. The 3D imaging platform we present provides a powerful tool to study dynamic changes in vessel diameters and morphology alongside CBFv networks in the brain of awake animals that can advance our understanding of the effects of drugs and disease conditions (ischemia, tumors, wound healing).

Case Report: Cerebral Edema and Tonsillar Herniation Leading to Brain Death After Cocaine Use in a Patient with End-Stage Renal Disease

The effect of cocaine use on the cerebral vasculature is well understood, with potential for ischemic or hemorrhagic stroke. The risk of adverse effects can be prolonged and amplified in patients with renal dysfunction and uremia. Uremia-induced osmotic gradients and upregulation of aquaporin channels along with cocaine-induced blood-brain barrier degradation may act synergistically. We present the first known case of a non-compliant dialysis patient who suffers cerebral edema, tonsillar herniation, and brain death following cocaine use. A 32-year-old female with end-stage renal disease presented with shortness of breath and flu-like symptoms for one week and was alert and oriented with no neurologic deficits. The patient had missed her last 5 dialysis treatments and labs revealed hyperkalemia and uremia. Urine drug screen was positive for cocaine, opiates, and tetrahydrocannabinol (THC). Following dialysis and metabolic correction, she developed an irregular respiratory pattern and stridor and received neck computed tomography (CT). The patient became unresponsive with dilated and nonreactive pupils. CT revealed absent intraluminal carotid and vertebral artery flow at the skull base, cerebellar tonsil herniation, and anoxic brain injury. Vital signs were maintained, and cerebral edema was managed with 45-degree head-of-bed elevation and mannitol. Following cerebral edema treatment, the patient had preserved respiratory drive, fixed and dilated pupils, no corneal reflex, no cough or gag reflex, and negative oculocephalic reflex. Repeat cranial CT angiography revealed bilateral hemispheric edema, basal subarachnoid hemorrhage, and confirmed absent intracranial blood flow. Brain death was diagnosed with a radioisotope cerebral blood flow study. The use of cocaine in patients with renal dysfunction may increase the risk of cerebral edema and tonsillar herniation due to synergistic physiologic effects. Physicians should be aware of this interaction to allow for preventative measures.

ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ФУНКЦИОНАЛЬНОЙ ПРОБЫ МОЗГОВОГО КРОВОТОКА С АДЕНОЗИНТРИФОСФАТОМ ПО ДАННЫМ ОФЭКТ С 99mTc-ГМПАО У ПАЦИЕНТОВ С АТЕРОСКЛЕРОЗОМ СОННЫХ АРТЕРИЙ

Introduction: Previously, a functional test with intravenous administration of adenosine triphosphate (ATP) was proposed to assess the reactivity of cerebral circulation and the functional significance of internal carotid artery stenoses, with evaluation by brain SPECT (neuroSPECT) with 99mTc-HMPAO. The types of the reaction of the cerebral blood flow during it were identified, with different ratios of internal carotid artery stenoses and the degree of ischemic brain damage assessed according to brain MRI data. However, the prognostic value of the results of the ATP test of cerebral blood flow in relation to disorders of cerebral circulation (NMC) remains unknown. Purpose: In a retrospective study, we tried to study the prognostic value of the ATP test of cerebral blood flow in relation to the risk of subsequent disorders of cerebral circulation. Material and methods: The retrospective study included 37 patients with atherosclerotic stenosis of the carotid arteries, who in 2002–2005 underwent functional studies of cerebral blood flow with a sample with intravenous administration of ATP solution. Brain damage was quantified according to MRI data (Magnetom Open, Siemens) in a T2-weighted mode, according to a previously developed technique. Denoting Iliq – the intensity of the T2 signal from the cerebrospinal fluid in the ventricles of the brain, Iinsult – in the area affected by ischemia, and Inorm – in the area of the unaffected brain, the volume of the damaged tissue (VDT) was calculated as the sum taken from all sections i, where the area of brain damage is visible: VDT=Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i, where d is the thickness of the slice, and Si is the area of the ischemia area on the slice i. The quota of damaged tissue in the physical volume of the lesion area is then obviously eqal to : QD={Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i}/{Σid·Si}. NeuroSPECT with 99mTc-HMPAO (540 MBq) in each patient was carried out at rest and with intravenous administration of ATP solution (100 μg / kg of weight, intravenously slowly for 1 min under ECG control). The asymmetry of the cerebral blood flow was evaluated at rest and in a sample with ATP as the 99mTc-HMPAO accumulation asymmetry index (AI) – the interhemispheric ratio of the average 99mTc-HMPAO absorption score in the middle cerebral artery basin. Results: In accordance with the previously presented classification, patients were assigned to one of three groups – with different types of brain blood flow reaction to a stress test with ATP. In 14 individuals (type 1), a symmetrical distribution of blood flow at rest was noted (AI=0.98±0.01), while the ATP test caused an asymmetry in the uptake of 99mTc-HMPAO (AI=0.91±0.04), due to a decrease on the side of the stenosis-dependent hemisphere (unilateral stenosis of the common and/or internal carotid arteries, exceeding 55 %), without signs of damage to the cerebral cortex. In 11 patients with previous ischemic brain injuries (type 2), proven by MRI, the carotid arteries were patent, including after carotid endarterectomy (5 patients) or after correction of stenosis with a stent (three). Rest asymmetry of blood flow was present (AI=0.92±0.03). The ATP test increased blood supply on the side of injury if, according to T2-weighted MRI in the ischemic area, QD<0.35. Due to this, in general, there was a significant decrease in the absorption asymmetry of 99mTc-HMPAO (AI=0.96±0.03) during the ATP test. In 12 patients (type 3) with predominantly unilateral 50‒90 % carotid artery stenosis and ischemic stroke on the same side (group III), the hemispheric asymmetry of blood supply to the brain, noted already at rest (AI=0.96±0.03), increased (AI=0.93±0.03) with an adenosine test. When analyzing the results of a two-year follow-up, it turned out that frequent transient ishemic attacs, minor strokes and strokes developed only in patients in whom the adenosine test induced or increased the interhemispheric asymmetry of 99mTc-HMPAO accumulation by more than 5 % – four with type 1 reactivity, and three with type 3 reactivity Conclusions: Thus, perfusion neuroSPECT with 99mTc-HMPAO and ATP stress-test can be employed to identify patients with a reduced reserve of cerebral perfusion, who have an increased risk of ischemic stroke. Quantitative analysis of T2-weighted MRI gives an estimate of the proportion of viable brain tissue in the focus of the past ischemia, in which reactivity is preserved.

Cerebral Perfusion Patterns of Anxiety State in Patients With Pulmonary Nodules: A Study of Cerebral Blood Flow Based on Arterial Spin Labeling.

Background and PurposeThe proportion of patients with somatic diseases associated with anxiety is increasing each year, and pulmonary nodules have become a non-negligible cause of anxiety, the mechanism of which is unclear. The study focus on the cerebral blood flow (CBF) of anxiety in patients with pulmonary nodules to explore the cerebral perfusion pattern of anxiety associated with pulmonary nodules, blood perfusion status and mode of pulmonary nodule induced anxiety state.Materials and MethodsPatients with unconfirmed pulmonary nodules were evaluated by Hamilton Anxiety Scale (HAMA). The total score > 14 was defined as anxiety group, and the total score ≤ 14 points was defined as non-anxiety group. A total of 38 patients were enrolled, of which 19 patients were the anxiety group and 19 were the non-anxiety group. All subjects underwent arterial spin labeling imaging using a 3.0 T MRI. A two-sample t-test was performed to compare the CBF between the two groups. The CBF was extracted in brain regions with difference, and Spearman correlation was used to analyze the correlation between CBF and HAMA scores; ROC was used to analyze the performance of CBF to distinguish between the anxiety group and the non-anxiety group.ResultsThe CBF in the right insula/Heschl’s cortex of the anxiety group decreased (cluster = 109, peak t = 4.124, and P < 0.001), and the CBF in the right postcentral gyrus increased (cluster = 53, peak t = −3.912, and P < 0.001) in the anxiety group. But there was no correlation between CBF and HAMA score. The ROC analysis of the CBF of the right insula/Heschl’s cortex showed that the AUC was 0.856 (95%CI, 0.729, 0.983; P < 0.001), the optimal cutoff value of the CBF was 50.899, with the sensitivity of 0.895, and specificity of 0.789. The ROC analysis of CBF in the right postcentral gyrus showed that the AUC was 0.845 (95%CI, 0.718, 0.972; P < 0.001), the optimal cutoff value of CBF was 43.595, with the sensitivity of 0.737, and specificity of 0.842.ConclusionThe CBF of the right insula/Heschl’s cortex decreased and the CBF of the right postcentral gyrus increased in patients with pulmonary nodules under anxiety state, and the CBF of the aforementioned brain regions can accurately distinguish the anxiety group from the non-anxiety group.

Paradoxical symptomatic cerebral blood flow decreases after combined revascularization surgery for patients with pediatric moyamoya disease: illustrative case.

BACKGROUNDTransient neurological deficits (TNDs) develop after cerebral revascularization in patients with moyamoya disease (MMD). The authors report a rare pediatric MMD case with extensive decreased cerebral blood flow (CBF) and prolonged TNDs after combined revascularization.OBSERVATIONSA 9-year-old boy presented with transient left upper limb weakness, and MMD was diagnosed. A right-sided combined surgery was performed. Two years after the surgery, frequent but transient facial (right-sided) and upper limb weakness appeared. The left internal carotid artery terminal stenosis had progressed. Therefore, a left combined revascularization was performed. The patient’s motor aphasia and right upper limb weakness persisted for approximately 10 days after surgery. Magnetic resonance angiography showed that the direct bypass was patent, but extensive decreases in left CBF were observed using single photon emission tomography. With adequate fluid therapy and blood pressure control, the neurological symptoms eventually disappeared, and CBF improved.LESSONSThe environment of cerebral hemodynamics is heterogeneous after cerebral revascularization for MMD, and the exact mechanism of CBF decreases was not identified. TNDs are significantly associated with the onset of stroke during the early postoperative period. Therefore, appropriate treatment is desired after determining complex cerebral hemodynamics using CBF studies.

Hypertension and race affect cerebral blood flow and cognition in older adults without dementia

AbstractBackgroundIt is known that African Americans have a higher prevalence of AD than white Americans, but it is not fully understood why this is the case. One potential explanation is that African Americans also have a higher prevalence of cardiovascular risk factors, which also confer a risk for AD. Racial differences in several AD‐specific and cardiovascular disease biomarkers have been reported, but these findings are generally not conclusive. In addition, very few papers have assessed racial differences in cerebral blood flow (CBF), an important noninvasive biomarker for AD/dementia. We investigated the relationships between cerebral blood flow (CBF), race and hypertension in a cohort of older individuals without dementia.MethodParticipants included 116 older individuals, 21 (18%) African American, who were cognitively normal (CN), had subjective cognitive decline (SCD), or had mild cognitive impairment (MCI). 3D pseudo‐continuous arterial spin label (pCASL) MRI on a Prisma 3T and cardiovascular risk factors and cognitive domain z‐scores from the time of scan were analyzed. Multiple regression was used to assess the relationships between race, hypertension, and CBF on a region‐of‐interest and voxel‐wise basis with age, sex, diagnostic group and total grey matter volume as covariates.ResultRegion‐of‐interest and voxel‐wise CBF was decreased in African Americans and in individuals with hypertension. While there was overlap between the affected regions, especially temporal lobes, hypertensive individuals also had decreased CBF in anterior brain regions, while African Americans had decreased CBF in posterior brain regions. The effect of race on CBF remained after hypertension was included as a covariate. Despite the regional overlap, there was no interaction of race and hypertension on CBF. Perfusion in affected brain regions was positively correlated with attention in all participants, as well as with visuospatial function in African Americans.ConclusionHypertensive individuals and African Americans have decreased CBF in partially overlapping brain regions. Decreased CBF in these regions was differentially associated with cognitive function according to race. Further study of CBF in larger diverse samples is warranted.

Translational research to unravel the mechanism of action of vagus nerve stimulation

Abstract Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with drug resistant epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond better to VNS, may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the field of the search for mechanisms of action animal experiments can provide essential clues such as crucial neuranatomical structures that are involved in the seizure-suppressing effect of VNS. The nucleus of the solitary tract as well as the locus coeruleus have been identified to play such a role. With the development of animal models that mimic human refractory epilepsy more reliably such as the kindling model, the status epilepeticus model and genetic models more valuable and usable information for human applicability may become available. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing VNS. Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Further elucidation of the mechanism of action may increase the clinical efficacy of VNS and provide inspiration for the development of new therapeutic modalities in the field of neurostimulation and epilepsy. Keywords: vagus nerve stimulation, mechanism of action, epilepsy

Accuracy of diffuse correlation spectroscopy measurements of cerebral blood flow when using a three-layer analytical model.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical technology for the assessment of an index of cerebral blood flow (CBFi). Analytical methods that model the head as a three-layered medium (i.e., scalp, skull, brain) are becoming more commonly used to minimize the contribution of extracerebral layers to the measured DCS signal in adult cerebral blood flow studies. However, these models rely on a priori knowledge of layer optical properties and thicknesses. Errors in these values can lead to errors in the estimation of CBFi, although the magnitude of this influence has not been rigorously characterized. Herein, we investigate the accuracy of measuring cerebral blood flow with a three-layer model when errors in layer optical properties or thicknesses are present. Through a series of in silico experiments, we demonstrate that CBFi is highly sensitive to errors in brain optical properties and skull and scalp thicknesses. Relative changes in CBFi are less sensitive to optical properties but are influenced by errors in layer thickness. Thus, when using the three-layer model, accurate estimation of scalp and skull thickness are required for reliable results.

Normalization of Cerebral Hemodynamics after Hematopoietic Stem Cell Transplant in Children with Sickle Cell Anemia

▪BackgroundChildren with Sickle Cell Anemia (SCA) are at high risk for overt or silent strokes, and this risk may be mitigated by hematopoietic stem cell transplant (HSCT). Our research group has shown that when cerebral oxygen delivery is compromised due to anemia in SCA, the cerebral blood flow (CBF) and brain oxygen extraction fraction (OEF) increase to maintain brain tissue oxygen delivery. We used novel magnetic resonance imaging (MRI) sequences to measure OEF and CBF in children with SCA treated with HSCT, testing the hypothesis that after HSCT, OEF and CBF will be similar to control values.MethodsChildren with SCA were enrolled in a pilot prospective, observational study of MRI-measured OEF and CBF. Brain MRI exams were performed without sedation on a 3T Siemens scanner. The MRI protocol included fluid-attenuated inverse recovery (FLAIR) sequences in two planes to evaluate for strokes, asymmetric spin echo to measure tissue-level OEF, and pseudo-continuous arterial spin labeling perfusion-weighted imaging to measure CBF. HSCT recipients underwent paired brain MRI 1-2 months before and >1 year after HSCT. Controls, non-anemic siblings of SCA patients, had a single brain MRI. Pre- and post-HSCT CBF and OEF were compared within subjects and between the HSCT and control cohorts using non-parametric tests. Bivariate correlations between OEF or CBF and hemoglobin (Hb) or Hb S concentrations were tested with Spearman's rho. The level of significance was specified as p < 0.05 after adjustment by the Benjamini-Hochberg procedure.ResultsFour children (two male, median age 10 years, range 8-21 years) underwent HSCT: one had prior overt stroke, one had silent strokes, and two had no neuroimaging abnormalities. All received a reduced intensity preparative regimen of alemtuzumab, melphalan, and fludarabine. One subject received marrow from an HLA-matched unrelated donor without Hb S trait; two received marrow from HLA-identical siblings. One child who had rejected a HSCT from an HLA-identical sibling underwent re-conditioning with antithymocyte globulin and cyclophosphamide and received CD-34-selected peripheral stem cells from the same donor. All sibling donors had Hb S trait. Brain MRIs of 20 non-anemic sibling controls of median age 11 years (range 6-17 years) were included for comparison.Median OEF and CBF were significantly elevated pre-HSCT compared to controls (OEF median 0.355 vs 0.288, p = 0.012; CBF median 99.8 vs 65.1 ml/100 g/min, p = 0.018; Figure). Median post-HSCT OEF and CBF were lower than pre-HSCT values (OEF median 0.270 vs 0.355, CBF median 65.1 vs 99.8 ml/100 g/min, p = 0.13 for both), but these analyses had low power to detect significant differences due to the small sample size. Post-HSCT, recipients' OEF and CBF were similar to controls (OEF median 0.270 vs 0.288, p=0.18; CBF median CBF 65.1 vs 75.8 ml/100 g/min, p = 0.42). None of the HSCT recipients had new overt or silent strokes on FLAIR imaging or developed severe acute or chronic GVHD after HSCT.Pre-HSCT, recipients were anemic compared to controls (median Hb 9.8 vs 12.8 g/dl, p = 0.018). Pre-HSCT Hb S concentrations were lower than expected for SCA due to recent red blood cell transfusions (median 50.6%, range 39.7-77.6%). At the post-HSCT imaging timepoint, recipients' anemia had resolved (median Hb 12.4 g/dl, range 11.3-15.7 g/dl), and Hb S concentrations were consistent with their donors' levels. When all pre- and post-HSCT measurements were compared, OEF had a strong negative correlation with Hb (Spearman's rho = -0.905, p = 0.002) and a strong positive correlation with Hb S concentration (Spearman's rho = 0.970, p < 0.001). CBF had a weaker negative correlation with Hb (Spearman's rho = -0.714, p = 0.047) and positive correlation with Hb S concentration (Spearman's rho = 0.731, p = 0.040).ConclusionIn this cohort, children with SCA had normalization of OEF and CBF after successful HSCT. OEF elevation was strongly correlated with Hb S concentration and inversely correlated with Hb concentration in these HSCT recipients. Our data suggest that when curative HSCT corrects hemolytic anemia, OEF and CBF normalize. This physiologic change may provide protection against strokes following HSCT for SCA. [Display omitted] DisclosuresHulbert:Pfizer: Other: Spouse employment at Pfizer. Fields:Proclara Biosciences: Equity Ownership.

Differential regional cerebral blood flow reactivity to alterations in end-tidal gases in healthy volunteers.

Anesthesia is associated with alterations in end-tidal (ET) respiratory gases from the awake state. These alterations result in marked vasoactive changes in regional cerebral blood flow (rCBF). Altered regional cerebrovascular reactivity (rCVR) is linked to neurologic dysfunction. We examined these differences in reactivity from prior work by focusing on the ratio of vasoconstriction with hyperoxia/hypocapnia (HO/hc):vasodilation with hypercapnia (HC) using magnetic resonance imaging pseudo-continuous arterial spin labelling (pCASL) to measure rCBF and compare rCVR The distribution and magnitude of these ratios could provide insights into rCBF during clinical anesthesia and inform future research into the origins of postoperative delirium (POD). Ten healthy subjects underwent cerebral blood flow (CBF) studies using pCASL with computer-controlled delivery of ET gases to assess flow effects of hyperoxia, hypercapnia, and hyperoxia/hypocapnia as part of a larger study into cerebrovascular reactivity. The vasoconstrictor stimulus was compared with the vasodilator stimulus by the ratio HO/hc:HC. Hyperoxia minimally decreased whole brain CBF by -0.6%/100 mm Hg increase in ETO2. Hypercapnia increased CBF by +4.6%/mm Hg carbon dioxide (CO2) and with HO/hc CBF decreased by -5.1%/mm Hg CO2. The brain exhibited markedly different rCVR-regional HO/hc:HC ratios varied from 7.2:1 (greater response to vasoconstriction) to 0.49:1 (greater response to vasodilation). Many of the ratios greater than 1, where vasoconstriction predominated, were seen in regions associated with memory, cognition, and executive function, including the entorhinal cortex, hippocampus, parahippocampus, and dorsolateral prefrontal cortex. In awake humans, marked rCBF changes occurred with alterations in ET respiratory gases common under anesthesia. Such heterogeneous reactivity may be relevant to future studies to identify those at risk of POD.

Cerebral blood flow changes during aging process and in cognitive disorders: A review.

We aimed to summarize the available evidence on cerebral blood flow (CBF) changes in normal aging and common cognitive disorders. We searched PubMed for studies on CBF changes in normal aging and cognitive disorders up to 1 January 2019. We summarized the milestones in the history of CBF assessment and reviewed the current evidence on the association between CBF and cognitive changes in normal aging, vascular cognitive impairment (VCI) and Alzheimer’s disease (AD). There is promising evidence regarding the utility of CBF studies in cognition research. Age-related CBF changes could be related to a progressive neuronal loss or diminished activity and synaptic density of neurons in the brain. While a similar cause or outcome theory applies to VCI and AD, it is possible that CBF reduction might precede cognitive decline. Despite the diversity of CBF research findings, its measurement could help early detection of cognitive disorders and also understanding their underlying etiology.

Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia.

This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SDϕ), single-slope intensity and phase (SSI and SSϕ), and dual-slope intensity and phase (DSI and DSϕ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVRSDϕ was greater than CVRSDI (p < 0.01), whereas CVRDSI and CVRDSϕ showed no significant difference (p > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness (L ec ), which caused CVRDSϕ to become significantly greater than CVRDSI (p < 0.05). CVRSS measurements yielded similar results as CVRDS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVRDSI and CVRDSϕ depend on L ec . Specifically, the sensitivity to the brain is greater for DSI than DSϕ for a thin extracerebral layer (L ec < 13 mm), whereas it is greater for DSϕ than DSI for a thicker extracerebral layer.

MRI study of cerebral blood flow, vascular reactivity, and vascular coupling in systemic hypertension

Chronic hypertension alters cerebrovascular function, which can lead to neurovascular pathologies and increased susceptibility to neurological disorders. The purpose of this study was to utilize in vivo MRI methods with corroborating immunohistology to evaluate neurovascular dysfunction due to progressive chronic hypertension. The spontaneously hypertensive rat (SHR) model at different stages of hypertension was studied to evaluate: i) basal cerebral blood flow (CBF), ii) cerebrovascular reactivity (CVR) assessed by CBF and blood-oxygenation level dependent (BOLD) signal changes to hypercapnia, iii) neurovascular coupling from CBF and BOLD changes to forepaw stimulation, and iv) damage of neurovascular unit (NVU) components (microvascular, astrocyte and neuron densities). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR (mild hypertension), basal CBF was higher (p < 0.05), CVR trended higher, and neurovascular coupling response was higher (p < 0.05), compared to normotensive rats. In 40-week SHR (severe hypertension), basal CBF, CVR, and neurovascular coupling response were reversed to similar or below normotensive rats, and were significantly different from 10-week SHR (p < 0.05). Immunohistological analysis found significantly reduced microvascular density, increased astrocytes, and reduced neuronal density in SHR at 40 weeks (p < 0.05) but not at 10 weeks (p > 0.05) in comparison to age-matched controls. In conclusion, we observed a bi-phasic basal CBF, CVR and neurovascular coupling response from early to late hypertension using in vivo MRI, with significant changes prior to changes in the NVU components from histology. MRI provides clinically relevant data that might be useful to characterize neurovascular pathogenesis on the brain in hypertension.

Brain Death Evaluation in Children With Suspected or Confirmed Coronavirus Disease 2019.

Objectives:To discuss the challenges of conducting a death by neurologic criteria or brain death evaluation in the coronavirus disease 2019 era and provide guidance to mitigate viral transmission risk and maintain patient safety during testing.Design:Not applicable.Setting:Not applicable.Patients:Children with suspected or confirmed coronavirus disease 2019 who suffer catastrophic brain injury due to one of numerous neurologic complications or from an unrelated process and require evaluation for death by neurologic criteria.Interventions:Not applicable.Measurements and Main Results:There is a risk to healthcare providers from aerosol generation during the neurologic examination and apnea test for determination of death by neurologic criteria. In this technical note, we provide guidance to mitigate transmission risk and maintain patient safety during each step of the death by neurologic criteria evaluation. Clinicians should put on appropriate personal protective equipment before performing the death by neurologic criteria evaluation. Risk of aerosol generation and viral transmission during the apnea test can be mitigated by using continuous positive airway pressure delivered via the ventilator as a means of apneic oxygenation. Physicians should assess the risk of transporting coronavirus disease 2019 patients to the nuclear medicine suite to perform a radionucleotide cerebral blood flow study, as disconnections to and from the ventilator for transport and inadvertent ventilator disconnections during transport can increase transmission risk.Conclusions:When conducting the neurologic examination and apnea test required for death by neurologic criteria determination in patients with suspected or confirmed coronavirus disease 2019, appropriate modifications are needed to mitigate the risk of viral transmission and ensure patient safety.

Age and Sex Differences in Cerebral Circulation in Patients with Cerebral Atherosclerosis and Diabetes mellitus

Cerebrovascular pathology and metabolic disorders are problems of modern health care, which are of colossal medical and social significance. A high percentage of not only mortality, but also disability determines the extreme urgency of studying their various aspects, and the presence of combined pathology requires the development of a personalized approach to the tactics of managing such patients.The objective: was to determine sex and age differences in the structural and functional state of the vessels of the carotid and vertebro-basilar basins in patients with stage I–III cerebral atherosclerosis (CA) and type 2 diabetes mellitus.Materials and methods. A comprehensive clinical and instrumental study involved 229 patients with stageI–IIICA and type 2 diabetes mellitus. The patients were divided into 2 groups: I – the general group of patients who had an ischemic atherothrombotic stroke in the middle cerebral artery basin – CA III; II – with CA I–II stages. All patients underwent conventional clinical, laboratory and instrumental studies (Doppler ultrasound of the vessels of the head and neck – study of cerebral blood flow in the extra- and intracranial sections of the main arteries of the head and neck using the Aplio XG device (Toshiba).Results. In patients of group I, there were no age or sex differences in the linear systolic blood flow velocity (LSBFV) of the vessels of the carotid and vertebro-basilar basins. In group II patients over 60 years of age, the LSBFV in both internal carotid arteries was statistically significantly higher than in middle-aged patients, while the LSBFV in the left vertebral, posterior cerebral arteries and the basilar artery was statistically significantly higher in middle-aged patients than in the elderly. In our opinion, these differences can be explained by statistically significant differences in fasting blood glucose levels. It is important to note that statistically significant sex differences were found only for LSBFV in both common carotid arteries: in women with CA stages I-II, the rate of cerebral blood flow was higher than in men.Conclusions. For patients with stage III CA and T2DM, age and sex differences in the parameters of cerebral circulation both in the vessels of the carotid and in the vessels of the vertebro-basilar basins have not been established. Elderly patients with stage I–II CA and T2DM, in comparison with middle-aged patients, are characterized by a statistically significantly higher LSBFV in the vessels of the carotid basin and lower in the vessels of the vertebro-basilar basin. The rate of cerebral blood flow in female patients with stage I–II CA and diabetes mellitus is statistically significantly higher in both common carotid arteries, in contrast to the corresponding LSBFV indicators in male patients.