Cerebral Blood Flow Abnormalities Research Articles

Age-specific sex-differences in cerebral blood flow velocity in relation to haemoglobin levels.

Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease. In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors. Of 958 eligible subjects (mean age/SD = 68.04/14.26, 53.2% male), younger women (age < 55 years) had higher CBF velocities than men (mean sex difference in PSV at age < 55 years = 16.31 cm/s; p < 0.001), but this difference declined with age (interaction p < 0.001), such that it was no longer significant at age 75-84 (∆PSV = 3.26 cm/s; p = 0.12) and was reversed at age ⩾ 85 (∆PSV = -7.42 cm/s; p = 0.05). These changes mirrored trends in levels of Hb, which were higher in men at age < 55 (∆Hb = 1.92 g/dL; p < 0.001), but steadily decreased with age in men but not in women (interaction p < 0.001), with no residual sex-difference at age ⩾ 85 (∆Hb = 0.12 g/dL; p = 0.70). There was an inverse correlation between Hb and PSV in both women and men (both p ⩽ 0.01), and the sex-difference in PSV at age < 55 was substantially diminished after adjustment for Hb (∆PSV = 6.92; p = 0.036; ∆PSV = 5.92, p = 0.13 with further adjustment for end-tidal CO2). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking). CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.

Long-term outcomes after formation of a low-flow STA-MCA bypass for treatment of symptomatic occlusion of the internal carotid artery

Aim. To evaluate short‑ and long‑term effectiveness of low‑flow bypass between superficial temporal artery and M4 segment of middle cerebral artery (low‑flow STA‑MCA bypass) in patients with symptomatic occlusion of the internal carotid artery (ICA).Materials and methods. Between 2016 and 2019 at the Department of Neurosurgery of the N. V. Sklifosovsky Research Institute of Emergency Medicine, 54 patients who underwent low‑flow STA‑MCA bypass formation at the side of symptomatic ICA occlusion between 2013 and 2015 were examined. Symptomatic ICA occlusion was more common in men than in women (7:1 ratio). Patient age varied between 48 and 73 years (mean age was 62 years).During low‑flow STA‑MCA bypass formation surgery for symptomatic ICA occlusion, intraoperative flowmetry was used in 52 (96 %) patients, in 2 (4 %) patients this diagnostic method was impossible to perform due to technical difficulties. The main examination methods in the long term after cerebral revascularization were evaluation of neurological status dynamics per the National Institute of Health Stroke Scale (NIHSS); modified Rankin scale; Rivermead mobility index; computed tomography angiography of the extra‑intracranial arteries; ultrasound (US) examination of the STA‑MCA bypass for eval uation of linear and volumetric blood flow velocities; single‑photon emission computed tomography. The type and size of trephination were evaluated, and operative time was taken into account.The patients were divided into 3 groups: group 1 included patients with follow‑up period of 1–2 years after cerebral revascularization, group 2 – 3–4 years, group 3 – 5–6 years. All results were compared to preoperative, early, and longterm measurements.Results. In the long‑term postoperative period between 1 and 6 years after cerebral revascularization, 54 patients were examined. Computed tomography angiography and US showed functioning STA‑MCA bypass in 53 (98 %) patients. According to single‑photon emission computed tomography of the brain, regional cerebral blood flow in the longterm postoperative period varied between 28 and 40 mL / 100 g / min, median regional cerebral blood flow in the long‑term postoperative period was 38 mL / 100 g / min. Intraoperative flowmetry was performed in 52 (96 %) patients, median was 15.5 mL / min. US showed that linear blood flow velocity in the STA‑MCA bypass varied between 20 and 95 cm / s, median was 49 cm / s. Volumetric blood flow varied between 30 and 85 mL / min with median of 75 mL / min.Resection trephination was performed in 36 (67 %) patients, mean size of trephination hole was 3 cm3. In the study, operative time was measured: mean value was 212 min; no significant correlation between operative time and trephination size was observed.Improved neurological status was observed in all study groups. Per the NIHSS, in group 1 (1–2 years) improvement was observed in 59 % of patients, in group 2 (3–4 years) in 48 %, in group 3 (5–6 years) in 47 %. Per the modified Rankin scale, in group 1 improvement was observed in 36.4 % of patients, in group 2 – in 48 %, in group 3 – in 42.9 %. Per the Rivermead mobility index, in group 1 improvement was observed in 63.3 % patients, in group 2 – in 56 %; in group 3 – in 57.1 %. The best outcomes were observed in group 1 (63.3 %).Conclusion. Instrumental diagnostic methods and evaluation of neurological status showed positive dynamics both in the postoperative period and in long‑term period between 1 and 6 years after low‑flow STA‑MCA bypass formation. In the long term, repeat abnormalities of cerebral blood flow of ischemic type and repeat transient ischemic attacks were not observed. Correct selection of patients in the preoperative period and comprehensive treatment including drug therapy in the postoperative and long‑term periods allow to prevent repeat ischemic cerebrovascular disease and therefore improve patients’ quality of life.

Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Longitudinal trajectories of cognitive decline and cerebral blood flow abnormalities in octogenarian men with normal global cognition

AimsCognitive and perfusion changes have been previously observed in older men with Mini Mental State Examination scores>24 points. We aimed to investigate time change in cognitive domains in a cohort of non-demented men between age 68 and 82, and how they are expressed in regional defects estimated by Cerebral Blood Flow (rCBF). Methods103 men at age 81 with MMSE scores >24 (mean 28.4 ± 1.7), no dementia or stroke, were examined with the same cognitive test battery at age 68 and age 81: Synonyms (SRB-1), Block design (SRB-3), Paired Associates, Digit Symbol Substitution and Benton Visual Retention test. rCBF was estimated using 99mTc-HMPAO SPECT at age 82. ResultsBetween ages 68 and 82 we observed a relative decline (Δ%) of cognitive test scores: SRB-3 and Benton tests, -33.7 % (SD 16,8) and -25.8 % (SD 23.9) respectively, followed by Digit Symbol test: -22,6 % (SD 15,6). The cluster of men (46 %) could be detected, grouped on the largest test score decline and highest overall test predictors’ importance in decreasing order: Δ% SRB-3, Δ% Paired Associates, Δ% Digit Symbol, Δ% Benton VR and Δ% SRB-1. Compared to the cluster with stable cognitive functions, it expressed lower rCBF in frontal and parietal lobes, and in subcortical areas. ConclusionNearly half of the studied, community-dwelling cohort of non-demented, octogenarian men with MMSE > 24, had a combination of decreasing visuospatial ability and episodic memory during preceding years, expressed by widespread rCBF changes in fronto-subcortical areas.

Worsening Symptoms Is Associated with Larger Cerebral Blood Flow Abnormalities during Tilt-Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Background and Objectives: During tilt testing, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients experience an abnormal reduction in cerebral blood flow (CBF). The relationship between this CBF reduction and symptom severity has not been examined in detail. Our hypothesis was that ME/CFS severity is related to the degree of the CBF reduction during tilt testing. Materials and Methods: First, from our database, we selected ME/CFS patients who had undergone assessments of ME/CFS symptomatology and tilt tests on the same day, one at the first visit and the second during a follow-up. The change in symptomatology was related to the change in CBF during the tilt test. Second, we combined the data of two previously published studies (n = 219), where disease severity as defined by the 2011 international consensus criteria (ICC) was available but not published. Results: 71 patients were retested because of worsening symptoms. The ICC disease severity distribution (mild-moderate-severe) changed from 51/45/4% at visit-1 to 1/72/27% at follow-up (p < 0.0001). The %CBF reduction changed from initially 19% to 31% at follow-up (p < 0.0001). Of 39 patients with stable disease, the severity distribution was similar at visit-1 (36/51/13%) and at follow-up (33/49/18%), p = ns. The %CBF reduction remained unchanged: both 24%, p = ns. The combined data of the two previously published studies showed that patients with mild, moderate, and severe disease had %CBF reductions of 25, 29, and 33%, respectively (p < 0.0001). Conclusions: Disease severity and %CBF reduction during tilt testing are highly associated in ME/CFS: a more severe disease is related to a larger %CBF reduction. The data suggest a causal relationship where a larger CBF reduction leads to worsening symptoms.

Goreisan regulates cerebral blood flow according to barometric pressure fluctuations in female C57BL/6J mice

Goreisan is a Kampo medicine used to treat headaches associated with climate change. Here, by using an implantable complementary metal-oxide-semiconductor (CMOS) device, we evaluated the effects of Goreisan and loxoprofen on cerebral blood flow (CBF) dynamics associated with barometric pressure fluctuations in freely moving mice. In the vehicle group, decreasing barometric pressure increased CBF that was prevented by Goreisan and loxoprofen. Notably, Goreisan, but not loxoprofen, reduced CBF after returning to atmospheric pressure. These results indicate that, unlike the mechanism of action of antipyretic analgesics, Goreisan normalizes CBF abnormalities associated with barometric pressure fluctuations by actively reducing CBF increase.

The Correlation of Inflammation, Oxidative Stress, and Hippocampal Perfusion in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

Impact of the 2014 NHLBI Hydroxyurea Guidelines on Cerebrovascular Events in Sickle Cell Disease

Background: Cerebrovascular disease (CVD) is a common cause of morbidity in patients with sickle cell disease (SCD). An estimated 37% of children with SCD have silent cerebral infarcts (SCI) by age 14, leading to increased stroke risk and neurocognitive impairment. In the DISPLACE trial (Kanter et al, 2021), 2.9% of patients had abnormal cerebral blood flow as measured on transcranial Doppler ultrasound (TCD). The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend hydroxyurea (HU) for all patients with SCD-SS and SCD-Sβ 0 starting at age 9 months, a significant shift from prior practice. In patients who have already developed TCD abnormalities, HU is protective against stroke and CVD progression. The real-world impact of universal early HU on the development of CVD, particularly on SCI, is not well defined . We hypothesize that the 2014 guidelines led to an increase in HU use and a reduction in the initial development of CVD. Methods: We performed a single center, retrospective cohort study investigating trends in HU prescriptions and CVD before and after the publication of the 2014 NHLBI guidelines. Patients with SCD-SS and SCD-Sβ 0 who initiated hematology care at the Children's Hospital of Philadelphia between 2009 and 2023 were identified using an institutional registry. Incident HU was defined as the first outpatient HU prescription in patients with a minimum of two orders. Incident CVD was defined as a composite outcome consisting of the first documentation of: abnormal TCD, brain magnetic resonance imaging (MRI) with silent infarct, or overt ischemic stroke. Patients with known CVD before care initiation, prematurity &amp;lt; 28 weeks gestational age, or non-SCD neurologic disease were excluded. For time-to-HU analysis, patients with HU prescriptions before enrollment at our center also were excluded. Patients were followed from their first hematology visit until the outcome of interest or censoring. Censoring criteria included loss to follow up, transition of care, or bone marrow transplant. All brain MRI and TCD reports were manually reviewed. Ages at HU initiation pre- and post- guideline were compared using the Wilcoxon rank-sum test . Times to 1) HU and 2) CVD were summarized using Kaplan-Meier estimators, with the guideline publication date of September 1, 2014 incorporated as a time-varying exposure. Unadjusted associations were calculated using a Cox proportional hazard regression. Results: A total of 446 patients met inclusion criteria and contributed to analyses. Median age at baseline was 2.4 months, and median duration of follow-up was 5.0 years (IQR: 2.3-8.7). Most patients (430/446, 96%) had SCD SS, and 51% were male. The proportion of patients ever prescribed HU increased with time (Fig 1), with a peak prevalence of 82% in 2022. Of 385 patients not exposed to HU at baseline, 277 (72%) were prescribed HU during study follow-up. Incident HU prescriptions significantly increased after NHLBI guideline publication (HR 3.40, CI: 2.50 to 4.63, p &amp;lt; 0.001) with an older age at HU initiation before (median 4.0 y, IQR 2.5-7.7) than after (median 2.9 y, IQR 1.1-5.8) publication of the guideline (p = 0.002). Over a total of 2,395 person-years of follow-up, 66 incident CVD outcomes occurred in this longitudinal cohort, corresponding to a cumulative incidence of 14.8%. These events included 53 SCI, 10 abnormal TCD, and 3 overt ischemic strokes. CVD outcome occurrence was lower after guideline publication than before (HR 0.58, CI: 0.32-1.05), though the association did not reach statistical significance (p = 0.071, Fig. 2). Discussion: After the NHLBI guideline publication, HU prescriptions increased significantly at our center.Our data suggest that the 2014 guideline-directed care may have led to a greater than 40% reduction in CVD, though this reduction was not statistically significant in our small sample size. Despite guideline recommendations and strong evidence for the role of HU in reducing pain and acute chest syndrome, few patients across the United States are prescribed HU therapy. Adherence and care continuity challenges further lessen the number of patients benefitting from HU. Evidence of efficacy of early and universal HU in CVD prevention would strengthen guideline recommendations and improve clinical care in patients with SCD. Ongoing analysis includes an expanded cohort and adjustment for clinical covariates to better examine the direct impact of early HU on CVD.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

A computational study of fluid transport characteristics in the brain parenchyma of dementia subtypes

The cerebral environment is a complex system consisting of parenchymal tissue and multiple fluids. Dementia is a common class of neurodegenerative diseases, caused by structural damages and functional deficits in the cerebral environment. In order to better understand the pathology of dementia from a cerebral fluid transport angle and provide clearer evidence that could help differentiate between dementia subtypes, such as Alzheimer’s disease and vascular dementia, we conducted fluid–structure interaction modelling of the brain using a multiple-network poroelasticity model, which considers both neuropathological and cerebrovascular factors. The parenchyma was further subdivided and labelled into parcellations to obtain more localised and detailed data. The numerical results were converted to computed functional images by an in-house workflow. Different cerebral blood flow (CBF) and cerebrospinal fluid (CSF) clearance abnormalities were identified in the modelling results, when comparing Alzheimer’s disease and vascular dementia. This paper presents our preliminary results as a proof of concept for a novel clinical diagnostic tool, and paves the way for a larger clinical study.

Disrupted resting-state functional connectivity and network topology in mild traumatic brain injury: an arterial spin labelling study.

Mild traumatic brain injury can cause different degrees of cognitive impairment and abnormal brain structure and functional connectivity, but there is still a lack of research on the functional connectivity and topological organization of cerebral blood flow fluctuations. This study explored the cerebral blood flow, functional connectivity and topological organization of the cerebral blood flow network in acute mild traumatic brain injury patients. In total, 48 mild traumatic brain injury patients and 46 well-matched healthy controls underwent resting-state arterial spin labelling perfusion MRI and neuropsychological assessments. The functional connectivity and topological organization of the cerebral blood flow network were analysed. Then, the correlation between the changes in cerebral blood flow network characteristics and cognitive function was explored. Acute mild traumatic brain injury patients showed decreased cerebral blood flow in the right insula and increased cerebral blood flow in the right inferior temporal gyrus and left superior temporal gyrus. Abnormal cerebral blood flow network connection patterns mainly occur in sensorimotor network, default mode network, cingulo-opercular network and occipital network-related regions. Furthermore, mild traumatic brain injury disrupted the topological organization of the whole brain, which manifested as (i) reduced global efficiency; (ii) abnormal degree centrality, betweenness centrality, nodal clustering coefficient and nodal efficiency; and (iii) decreased intermodular connectivity between the occipital network and sensorimotor network. Finally, the change in network topology was correlated with the cognitive score of the mild traumatic brain injury. This study provided evidence of abnormal functional connectivity and network topology based on cerebral blood flow in acute mild traumatic brain injury patients, revealing their potential use as early markers for mild traumatic brain injury, which may contribute to both disease diagnosis and assessment.

Abnormal cerebral blood flow in patients with Leber's hereditary optic neuropathy.

The study aimed to unravel abnormal cerebral blood flow (CBF) in patients with Leber's hereditary optic neuropathy (LHON) using arterial spin labeling (ASL) and to investigate the associations among disrupted CBF, disease duration, and neuro-ophthalmological impairment. ASL perfusion imaging data was collected from 20 patients with acute LHON, 29 patients with chronic LHON, and 37 healthy controls. We used a one-way analysis of covariance to test the intergroup differences in CBF. Linear and nonlinear curve fit models were applied to explore the associations among CBF, disease duration, and neuro-ophthalmological metrics. Brain regions differed in LHON patients, including the left sensorimotor and bilateral visual areas (p < 0.05, cluster-wise family-wise error correction). Acute and chronic LHON patients demonstrated lower CBF in bilateral calcarine than the healthy controls. Chronic LHON had lower CBF in the left middle frontal gyrus and sensorimotor cortex, and temporal-partial junction than the healthy controls and acute LHON. A significant logarithmic negative correlation was shown between CBF of left middle frontal gyrus and disease duration. A significant linear positive correlation was found between retinal nerve fiber layer thickness and CBF in left middle frontal gyrus, and negative correlations between loss of variance and CBF in left middle frontal gyrus and sensorimotor cortex (p < 0.05, Bonferroni correction). LHON patients exhibited reduced CBF in the visual pathway, sensorimotor and higher-tier cognitive areas. Disease duration and neuro-ophthalmological impairments can influence the metabolism of non-visual areas.

Abnormal cerebral blood flow and brain function in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) lead to impaired cerebral blood perfusion, which leads to changes in brain function and affects the cognitive function of patients. In this study, cerebral blood flow (CBF) was used to evaluate the effect of T2DM on cerebral perfusion, and functional connectivity (FC) analysis was further used to explore whether the FC between the abnormal CBF region and the whole brain was changed. In addition, amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were used to investigate the changes in spontaneous activity and connectivity strength of the brain network. We recruited 40 T2DM patients and 55 healthy controls (HCs). They underwent 3D-T1WI, rs-fMRI, arterial spin labeling (ASL) sequence scans and a series of cognitive tests. Cognitive test scores and brain imaging indicators were compared between the two groups, and the relationships among laboratory indicators, cognitive test scores, and brain imaging indicators were explored in the T2DM group. Compared to HCs, The CBF values of Calcarine_L and Precuneus_R in the T2DM group were lower. The DC value of Paracentral_Lobule_L and Precuneus_L, and the ALFF value of Hippocampus_L in the T2DM group were higher. In addition, the CBF values of Calcarine_L was negatively correlated with fasting insulin and HOMA_IR. This study found that there were regions of cerebral hypoperfusion in T2DM patients, which are associated with insulin resistance. In addition, we found abnormally elevated brain activity and enhanced functional connectivity in T2DM patients, which we speculated was the compensatory mechanism of brain neural activity.

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

Role of omentin-1 in susceptibility to anxiety and depression like behaviors

Neuro-inflammation and blood-brain barrier (BBB) dysfunction are associated with depression. Evidence shows that adipokines enter the brain from the circulation, which regulates depressive behaviors. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about its role in neuro-inflammation and mood-relevant behavior. Our results showed omentin-1 knockout mice (Omentin-1−/−) increased susceptibility to anxiety and depressive-like behaviors, which are associated with abnormalities of cerebral blood flow (CBF) and impaired BBB permeability. Moreover, omentin-1 depletion significantly increased hippocampal pro-inflammatory cytokines (IL-1β, TNFα, IL-6), caused microglial activation, inhibited hippocampus neurogenesis, and resulted in autophagy impairment by dysregulating ATG genes. Omentin-1 deficiency also sensitized mice to the behavioral changes induced by lipopolysaccharide (LPS), suggesting that omentin-1 could rescue neuro-inflammation by acting as an anti-depressant. Our in vitro microglia cell culture data confirmed that recombinant omentin-1 suppresses microglial activation and pro-inflammatory cytokine expression induced by LPS. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of depression by providing a barrier-promoting effect and an endogenous anti-inflammatory balance to downregulate the proinflammatory cytokines.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brainperfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.

Ceramide in cerebrovascular diseases.

Ceramide, a bioactive sphingolipid, serves as an important second messenger in cell signal transduction. Under stressful conditions, it can be generated from de novo synthesis, sphingomyelin hydrolysis, and/or the salvage pathway. The brain is rich in lipids, and abnormal lipid levels are associated with a variety of brain disorders. Cerebrovascular diseases, which are mainly caused by abnormal cerebral blood flow and secondary neurological injury, are the leading causes of death and disability worldwide. There is a growing body of evidence for a close connection between elevated ceramide levels and cerebrovascular diseases, especially stroke and cerebral small vessel disease (CSVD). The increased ceramide has broad effects on different types of brain cells, including endothelial cells, microglia, and neurons. Therefore, strategies that reduce ceramide synthesis, such as modifying sphingomyelinase activity or the rate-limiting enzyme of the de novo synthesis pathway, serine palmitoyltransferase, may represent novel and promising therapeutic approaches to prevent or treat cerebrovascular injury-related diseases.

Deep learning-based middle cerebral artery blood flow abnormality detection using flow velocity waveform derived from transcranial Doppler ultrasound

Since the brain is unlike any other organ in that it cannot store energy and has a high metabolic demand, constant blood flow is essential for healthy brain function. The maximum flow velocity waveform that is produced by transcranial doppler echo ultrasonography has different qualities for a healthy subject and a critically ill patient with conditions such as intraparenchymal or subarachnoid hemorrhage, hydrocephalus, or traumatic brain injury. Depending on the degree of the injury, the symptoms of traumatic brain damage can present themselves right away or not until days or weeks later. To aid in the early and accurate detection of patients with severe brain conditions, a classification system is proposedthat can distinguish between healthy control and patient utilizing the maximum flow velocity waveform derived from Transcranial doppler ultrasound. In this research, we manually labelled the data to remove mediocre and corrupted signals and pre-processed low-quality signals into high-quality ones using a Cycle Generative Adversarial Network (CycleGAN). This study proposes a two-stream deep learning model, DopplerNet2+, based on a Self-organized Operational Neural Network (Self-ONN), which achieves an overall accuracy, precision, recall, sensitivity, f1 score, and specificity of 99.45%, 99.45%, 99.45%, and 99.37% for the classification issue. DopplerNet2+ has a better area under the curve (AUC) of 1.00 and a better Kolmogorov-Smirnov (KS) statistic of 0.996 at the 0.812 thresholds than 11 other Self-ONN models trained with different inputs. The results show that the proposed models can successfully carry out the targeted classification task.

Abstract P103: Associations Between Brain Volumes and Cerebral Blood Flow and Sex Hormones in the Look AHEAD Brain MRI Cohort

Background: Females have greater relative brain volume (BV) and cerebral blood flow (CBF) compared to males. BV decreases after menopause suggesting a possible role of sex hormones. We studied the association of BV, abnormal white matter hyperintensity volumes (WMHV) and cerebral blood flow (CBF) with sex hormones in adults with type 2 diabetes (T2DM), which is associated with risk of brain atrophy. Methods: The sample was 215 participants with overweight or obesity and T2DM from the Look AHEAD Brain MRI cohort (mean age 68 years [SD: 6.3], 27% male, 73% female [all postmenopausal]; without exogenous hormones), who had brain MRIs to evaluate their total BV, WMHV and CBF. The ratio of brain measurements to intracranial volume was analyzed to account for body size. Estradiol (E2) and testosterone levels (T) were estimated with electrochemoluminescence assays. In females, who have low E2 and T levels, we compared brain measures in those with detectable (vs. undetectable) hormone levels (E2&lt;20 pg/mL, 79%; T&lt;0.02 pg/mL, 37%). In males, we used Spearman correlation to assess the association between brain measures and sex hormone levels. The associations between BV, WMHV and E2 and T were adjusted for age and BMI using linear regression. Results: Females with detectable (vs. undetectable) T levels had higher BV (p=0.04) (Table), which was attenuated after adjustment for age and BMI. WMHV and CBF were not statistically associated with sex hormone levels in females. In males, no brain measures were significantly associated with sex hormones levels. Conclusions: In postmenopausal females with T2DM, detectable levels of T were associated greater BV, but not associated any CBF or WMHV. In males, none of the brain measures were associated with sex hormones. Our findings are limited by a small, convenient sample size and low sensitivity of hormone assays with a high proportion of undetectable levels. Our findings suggest that larger samples with high sensitivity hormone assays are needed to assess clinically important differences.

Cerebral blood flow changes and their genetic mechanisms in major depressive disorder: a combined neuroimaging and transcriptome study.

Extensive research has shown abnormal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) that is a heritable disease. The objective of this study was to investigate the genetic mechanisms of CBF abnormalities in MDD. To achieve a more thorough characterization of CBF changes in MDD, we performed a comprehensive neuroimaging meta-analysis of previous literature as well as examined group CBF differences in an independent sample of 133 MDD patients and 133 controls. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were conducted to identify genes whose expression correlated with CBF changes in MDD, followed by a set of gene functional feature analyses. We found increased CBF in the reward circuitry and default-mode network and decreased CBF in the visual system in MDD patients. Moreover, these CBF changes were spatially associated with expression of 1532 genes, which were enriched for important molecular functions, biological processes, and cellular components of the cerebral cortex as well as several common mental disorders. Concurrently, these genes were specifically expressed in the brain tissue, in immune cells and neurons, and during nearly all developmental stages. Regarding behavioral relevance, these genes were associated with domains involving emotion and sensation. In addition, these genes could construct a protein-protein interaction network supported by 60 putative hub genes with functional significance. Our findings suggest a cerebral perfusion redistribution in MDD, which may be a consequence of complex interactions of a wide range of genes with diverse functional features.