Whole Brain Cerebral Blood Research Articles

Diurnal variation of cerebral blood flow in healthy humans under normal entrained conditions.

The presence of a circadian cycle of cerebral blood flow may have implications for the occurrence of daily variations in cerebrovascular events in humans, but how cerebral blood flow varies throughout the day and its mechanism are still unclear. The study aimed to explore the diurnal variation of cerebral blood flow in healthy humans and its possible mechanisms. Arterial spin labelling images were collected at six time-points (09:00 hours, 13:00 hours, 17:00 hours, 21:00 hours, 01:00 hours, 05:00 hours) from 18 healthy participants (22-39 years old; eight females) to analyse diurnal variations in cerebral blood flow. Resting heart rate and blood pressure at six time-points and blood indicators (20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids, prostaglandin E2, noradrenaline and nitric oxide) related to cerebral vascular tone at two time-points (09:00 hours and 21:00 hours) were collected to analyse possible influences on diurnal variations in cerebral blood flow. From 21:00 hours to 05:00 hours, parietal cortical relative cerebral blood flow tended to increase, while frontal cortical and cerebellar relative cerebral blood flow tended to decrease. There was a time-dependent negative correlation between parietal cortical relative cerebral blood flow and resting heart rate, whereas there was a time-dependent positive correlation between cerebellar relative cerebral blood flow and resting heart rate. The change of parietal cortical relative cerebral blood flow was positively correlated with the change of nitric oxide. There was also a time-dependent positive correlation between mean arterial pressure and mean whole-brain cerebral blood flow. The findings indicated that parietal cortical relative cerebral blood flow and frontal cortical/cerebellar relative cerebral blood flow showed roughly opposite trends throughout the day. The diurnal variations in relative cerebral blood flow were regional-specific. Diurnal variation of nitric oxide and neurogenic regulation may be potential mechanisms for diurnal variation in regional relative cerebral blood flow.

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study.

Coronavirus disease 2019 (COVID-19) results in severe inflammation at the acute stage. Chronic neuroinflammation and abnormal immunological response have been suggested to be the contributors to neuro-long-COVID, but direct evidence has been scarce. This study aims to determine the integrity of the blood-brain barrier (BBB) in COVID-19 intensive care unit (ICU) survivors using a novel MRI technique. COVID-19 ICU survivors (n=7) and age and sex-matched control participants (n=17) were recruited from June 2021 to March 2023. None of the control participants were hospitalized due to COVID-19 infection. The COVID-19 ICU survivors were studied at 98.6 ± 14.9 days after their discharge from ICU. A non-invasive MRI technique was used to assess the BBB permeability to water molecules, in terms of permeability surface area-product (PS) in the units of mL/100 g/min. PS was significantly higher in COVID-19 ICU survivors (p=0.038) when compared to the controls, with values of 153.1 ± 20.9 mL/100 g/min and 132.5 ± 20.7 mL/100 g/min, respectively. In contrast, there were no significant differences in whole-brain cerebral blood flow (p=0.649) or brain volume (p=0.471) between the groups. There is preliminary evidence of a chronic BBB breakdown in COVID-19 survivors who had a severe acute infection, suggesting a plausible contributor to neurological long-COVID symptoms.

Altered resting-state neurovascular coupling in patients with pontine infarction

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neurovascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease

AbstractChildren with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (−19.4 mL/100 g/min) and OEF (−8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, −0.9 mL/100 g/min; P = .024; OEF, −3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.

Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow

Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion. To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF). This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021. Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg. The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF. Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 [95% CI, -2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05). Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease. ClinicalTrials.gov Identifier: NCT01206062.

A CBF decrease in the left supplementary motor areas: New insight into postoperative pediatric cerebellar mutism syndrome using arterial spin labeling perfusion MRI

Postoperative pediatric cerebellar mutism syndrome (pCMS), characterized mainly by delayed onset transient mutism is a poorly understood complication that may occur after pediatric medulloblastoma (MB) resection. Our aim was to investigate postoperative changes in whole-brain cerebral blood flow (CBF) at rest in pCMS patients using arterial spin labeling (ASL) perfusion imaging. This study compared preoperative and postoperative T2-weighted signal abnormalities and CBF using a voxel-wise, whole-brain analysis in 27 children undergoing MB resection, including 11 patients who developed mutism and 16 who did not. Comparison of postoperative T2 signal abnormalities between patients who developed pCMS (mean age 7.0 years) and those who did not showed that pCMS (mean age 8.9 years) patients were significantly more likely to present with T2-weighted hyperintensities in the right dentate nucleus (DN) (p = 0.02). Comparison of preoperative and postoperative CBF in patients with pCMS showed a significant postoperative CBF decrease in the left pre-supplementary motor area (pre-SMA) (p = 0.007) and SMA (p = 0.009). In patients who did not develop pCMS, no significant differences were observed. Findings provide evidence of an association between pCMS, injury to the right DN, and left pre-SMA/SMA hypoperfusion, areas responsible for speech. This supports the relevance of CBF investigations in pCMS.

Fetal Hemoglobin Improves Cerebral Blood Flow and Decreases Brain Inflammation in Transgenic- Sickle Mice

Introduction: Fetal hemoglobin (HbF) inhibits the deoxygenation-induced polymerization of sickle hemoglobin (HbS), the underlying pathophysiology of sickle cell disease (SCD). Higher HbF levels are associated with reduced sickle related pathology (Lettre G, Bauer DE. The Lancet 2016; 387(10037): 2554-64.). A major therapeutic approach to SCD has been to try to increase HbF levels, primarily by hydroxyurea administration. While hydroxyurea improves HbF and reduces sickling, its mechanism of action remains controversial, and even less is known regarding its effects on sickle-related cerebral pathology. We studied transgenic Berkeley sickle mice (BERK) (Paszty C et. al., Science 1997; 278(5339): 876-8.) with different HbF levels using in vivo MRI in an effort to estimate the ameliorative effects of HbF on cerebral blood flow and brain inflammation.Methods: BERK mice, expressing exclusively human a- and bS-globins with low (LF, n=7), medium (MF, n=8) and high (HF, n=6) HbF levels were studied at 9.4 T MRI system under isoflurane anesthesia. C57BL/6J mice were used as controls (n=9). We measured whole-brain cerebral blood flow (CBF-WB) using MRI. Diffusion tensor imaging was used to measure whole-brain mean diffusivity (MD-WB), a measure of brain edema and inflammation, and white matter fractional anisotropy (FA-WM) a biomarker of neuropathology. Tail vein blood was employed to obtain hematological parameters prior to MRI.Results: Select MRI and related data are shown in Table 1. BERK-LF mice (~3% HbF) exhibited lower mean cell hemoglobin concentration (MCHC) and hematocrit (Hct) compared with C57BL mice. BERK-MF mice (~20% HbF) showed increased MCHC compared with BERK-LF mice. BERK-HF mice (~30% HbF) had the highest MCHC and Hct of all BERK mice, but MCHC was still lower than levels seen in C57BL mice. The low MCHC and Hct levels in BERK-LF mice were associated with high CBF and MD . CBF was significantly elevated in BERK-LF and BERK-MF mice by 130% and 120%, respectively, compared to C57BL mice. BERK-HF mice, on the other hand, exhibited normalized CBF (187.0±27.5 vs. 180.0±30.5 ml/100g/min, BERK-HF vs. C57BL respectively), despite lower MCHC and Hct levels compared to C57BL mice. Brain inflammation (elevated MD levels) were also observed in BERK-LF mice compared to controls. In contrast, BERK-MF and BERK-HF mice showed reduced MD; both were significantly lower than BERK-LF mice and not different from control. Only the BERK-LF demonstrated significantly lower FA values (reduced microstructuraly complexity) compared to controls.CBF in all mice (BERK and C57BL) was inversely related to Hct (r=-0.433, p=0.019) and MCHC (r=-0.527, p=0.003). However, when controls were excluded from this analysis, only HbF level significantly predicted CBF (r=-0.485, p=0.030) and MD (r=-0.636, p=0.003), shown in Figure 1. HbF level also positively predicted MCHC (r=0.832, p<0.0001) and Hct (r=0.448, p=0.042) in BERK mice.Conclusions: Cerebral perfusion is markedly elevated in BERK mice compared to C57BL control mice and is inversely correlated with Hct, MCHC and total fetal Hb level. These data suggest that increased HbF can significantly reduce CBF, and in our study CBF levels in high-gamma BERK (~30%) were indistinguishable from control CBF, despite the lower Hct levels. We also demonstrate that brain edema, as reflected in lower MD, is improved when HbF levels reach ~20%.The improved CBF and reduced edema with higher HbF may be due to several factors: an antisickling effect on HbS, reduced oxidative stress, improved NO activity, and improved blood oxygen carrying capacity. HbF levels approaching 30% improved CBF, improved FA and reduced MD, suggesting that increased HbF levels may reduce cerebral insults stemming from cerebral hyperemia.These data suggest that new therapeutic approaches to further increase HbF to even higher levels than that achieved with hydroxyurea may provide greater hematologic and neuropathologic improvements in patients with SCD. If hydroxyuyrea induced HbF increases cannot be further improved, additional or combined therapeutic approaches (such as Pegylated Hb) may be combined with HbF therapies to improve oxygen delivery, reduce oxidative stress and reduce CBF toward normal levels. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Enhanced brainstem cerebral blood flow accompanies symptoms of anhedonia in young adults

Study: Midbrain serotonergic projections are of crucial theoretical significance for mood disorders. Furthermore, learned helplessness (LH) is associated with enhanced metabolic activity in rodent serotonergic midbrain models. However, little evidence supports serotonergic projections in predicting illness severity. We employed arterial spin labeling (ASL) to measure whole brain cerebral blood flow (CBF) in distressed and healthy individuals varying in anxiety and anhedonia. Methods: 36 distressed (27 females; mean age=22.2, SD=2.1) and 34 healthy (19 females; mean age=21.5, SD=1.8) individuals underwent a resting acquisition. Blood flow was measured using a multiband pseudo continuous ASL sequence. Regional cerebral perfusion data was collected with 25 slices, multiband factor=5, 4mm slick thickness, FA=90, 64x64 resolution, FOV=192x912, TR/TE=3.5s/19ms, labeling time=1.5s and postlabeling delay=1.7s. Anhedonia was measured using the Mood and Anxiety Symptom Questionnaire Anhedonic Depression Scale (MASQ-ADS), with the Snaith–Hamilton Pleasure Scale (SHAPS) as a secondary measure. Anxiety was measured using the MASQ General Distress Anxious Symptoms Scale. Anhedonia, anxiety and group were included in the regression model. Results: Anhedonia (MASQ-ADS) was associated with increased CBF in the midbrain (T=5.24, p_FWE=0.033), proximal to putative locations of the dorsal/median raphe nuclei (-12, -34, -26). Similar, although weaker, findings were observed with the SHAPS. Conclusion: Anhedonia is associated with altered CBF in the midbrain in a young adult population showing heterogeneous symptoms of distress. Significance: ASL may provide a particularly promising tool to examine enhanced local perfusion, potentially reflecting underlying midbrain serotonergic activity, which is predicted on the basis of LH studies in rodents but has thus far been difficult to investigate in humans.

Optimization of phase-contrast MRI for the quantification of whole-brain cerebral blood flow.

Whole-brain cerebral blood flow (CBF) measured by phase-contrast MRI (PC-MRI) provides an important index for brain function. This work aimed to optimize the PC-MRI imaging protocol for accurate CBF measurements. Two studies were performed on a 3 Tesla system. In Study 1 (N = 12), we optimized in-plane resolution of PC-MRI acquisition for CBF quantification by considering accuracy, precision, and scan duration. In Study 2 (N = 7), we assessed the detrimental effect of nonperpendicular imaging slice orientation on CBF quantification. Both One-way analysis of variance with repeated measurement and Friedman test were used to examine the effects of resolution and angulation on CBF quantification. Additionally, we evaluated the inter-rater reliability in PC-MRI data processing. Our results showed that CBF measurement with 0.7 mm resolution could be overestimated by up to 13.3% when compared with 0.4 mm resolution. Moreover, CBF could also be overestimated by up to 18.8% when the slice orientation is deviated by 30° from the ideal angulation. However, within 10° of the ideal slice orientation, estimated CBF was not significantly different from each other (P = 0.23 and 0.45 for internal carotid artery and vertebral artery, respectively). Inter-rater difference was <3%. For fast and accurate quantification of whole-brain CBF with PC-MRI, we recommend the use of an imaging resolution of 0.5 mm and a slice orientation that is less than 10° from vessel's axial plane.

William M. Feinberg award for excellence in clinical stroke: hemodynamics and stroke risk in carotid artery occlusion.

Five percent to 15% of patients with carotid territory transient ischemic attacks or cerebral infarctions have complete occlusion of the internal carotid artery.1,2 Their risk of recurrent stroke during the next 2 years while on medical therapy is 5% to 9% per year for all stroke and 2% to 8% per year for ipsilateral ischemic stroke.3–6 Debate on the best means to prevent recurrence has centered on whether embolic or hemodynamic mechanisms are most important. In the late 1970s and early 1980s, embolism of atherothrombotic material from the persisting proximal stump of the occluded internal carotid artery through external carotid artery collaterals was put forward as the most common cause for recurrent cerebral ischemic events.7,8 At this same time, extracranial–intracranial (EC-IC) bypass was increasingly used to prevent recurrent stroke by improving the hemodynamic status of the cerebral circulation distal to the occluded vessel.9,10 From 1977 to 1985, an international, multicenter, randomized trial was conducted to determine the efficacy of EC-IC bypass for the prevention of subsequent stroke. Among 808 randomized patients with symptomatic carotid occlusion, no benefit of surgery was demonstrated.11 Some concluded that the reason for the negative results was that the majority of strokes were because of emboli, whereas others criticized the trial for failing to identify patients with hemodynamic cerebral ischemia because of poor collateral circulation for whom surgical revascularization would be of benefit.12,13 However, the pattern of arteriographic collaterals failed to identify a subgroup who benefitted from surgery.14 At the time of the EC-IC Bypass Study, there was no reliable method for assessing the hemodynamic effects of carotid artery occlusion on cerebral circulation. Although direct measurements of arterial-jugular venous oxygen differences had demonstrated that reductions in whole-brain cerebral blood …

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease

The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in Alzheimer's disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG-PET. We used a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched control subjects. Paired FDG-PET and ASL-MRI images from 19 control subjects and 15 AD patients were included for qualitative analysis, and paired images from 18 control subjects and 13 AD patients were suitable for quantitative analyses. The combined imaging protocol was well tolerated. Both modalities revealed similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD after visual review by two expert readers. Interobserver agreement was better for FDG-PET (κ: 0.75, standard error: 0.12) than ASL-MRI (κ: 0.51, standard error: 0.15); intermodality agreement was moderate to strong (κ: 0.45-0.61); and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral fluorodeoxyglucose uptake (FDG-PET) or whole-brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under receiver operating characteristic curves of 0.90 for FDG-PET (95% confidence interval: 0.79-0.99) and 0.91 for ASL-MRI (95% confidence interval: 0.80-1.00). Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.

The Q10 ratio for basal cerebral metabolic rate for oxygen in rats.

Previously the authors showed that hypothermia exerts a greater effect on the cerebral metabolic rate for oxygen (CMRO2) that is associated with the maintenance of cellular viability, or "basal" CMRO2, than on electroencephalogram (EEG)-associated CMRO2 or "functional" CMRO2. On the basis of their findings, the authors hypothesized that the ratio of CMRO2 over a 10 degrees C temperature range (Q10) for basal CMRO2 was greater than that for functional and total CMRO2. They tested their hypothesis by determining the Q10 for basal CMRO2 from 38 degrees C to 28 degrees C. They measured whole-brain cerebral blood flow (CBF) and CMRO2 in six rats during progressive hypothermia at a brain temperature of 38 degrees C and, after induction of an isoelectric EEG signal (50 microV/cm) with thiopental sodium, they repeated the measurements at 38 degrees C, 34 degrees C, 30 degrees C, and 28 degrees C. In a control group (five rats), six sequential measurements of CBF and CMRO2 were made while the animals were anesthetized by 0.5% isoflurane/70% N2O/30% O2 at a brain temperature of 38 degrees C over a time span equivalent to the hypothermic group, that is, approximately 3 hours. The Q10 for basal CMRO2 calculated over 38 degrees C to 28 degrees C was 5.2 +/- 0.92. However, the decrease in basal CMRO2 between 38 degrees C and 28 degrees C was nonlinear on a log plot, revealing a two-component response: a high temperature sensitivity component between 38 degrees C and 30 degrees C with a Q10 of 12.1, and a lower temperature sensitivity component between 30 degrees C and 28 degrees C with a Q10 of 2.8. The combined overall Q10 for basal CMRO2 between 38 degrees and 28 degrees C was 5.2. The energy-requiring processes associated with these high and low temperature sensitivity components of basal CMRO2 have yet to be identified.