Cerebral Blood Flow Connectivity Research Articles

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study

BackgroundPrior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods.MethodsWe evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored.ResultsCompared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05).ConclusionsPatients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

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.

Altered cerebral neurovascular coupling in medication-overuse headache: A study combining multi-modal resting-state fMRI with 3D PCASL.

Structural and functional changes in the brain have been identified in individuals with medication-overuse headache (MOH) using MRI. However, it has not been clearly established whether neurovascular dysfunction occurs in MOH, which could be elucidated by examining neurovascular coupling (NVC) from the viewpoints of neuronal activity and cerebral blood flow. The aim of this study was to investigate potential alterations in NVC function of the brain in individuals with MOH using resting-state functional MRI (rs-fMRI) and 3D pseudo-continuous arterial spin labeling (3D PCASL) imaging techniques. A total of 40 patients with MOH and 32 normal controls (NCs) were recruited, and rs-fMRI and 3D PCASL data were obtained using a 3.0 T MR scanner. Standard preprocessing of the rs-fMRI data was performed to generate images representing regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC); cerebral blood flow (CBF) images were generated using 3D PCASL sequence data. These functional maps were all normalized into Montreal Neurological Institute (MNI) space, and NVC was subsequently determined on the basis of Pearson correlation coefficients between the rs-fMRI maps (ReHo, fALFF, and DC) and CBF maps. The statistical significance of differences between the MOH and NC groups in terms of NVC in different brain regions was established via Z-test. Further analysis was performed to examine correlations between NVC in the brain regions with NVC dysfunction and clinical variables among patients with MOH. NVC mainly presented a negative correlation in patients with MOH and NCs. No significant difference between the two groups was detected in terms of average NVC over the entire gray matter area. However, several brain regions with significantly decreased NVC in patients with MOH compared to NCs were identified: the left orbital region of the superior frontal gyrus, the bilateral gyrus rectus, and the olfactory cortex (P < 0.05). A correlation analysis revealed that the DC of the brain regions with NVC dysfunction was significantly positively correlated with disease duration (r = 0.323, P = 0.042), and DC-CBF connectivity was negatively correlated with VAS score (r = -0.424, P = 0.035). The current study demonstrated that cerebral NVC dysfunction occurs in patients with MOH, and the NVC technique could function as a new imaging biomarker in headache research.

Cerebral blood flow network differences correlated with cognitive impairment in mild traumatic brain injury.

PurposeTo examine whether the cerebral blood flow (CBF) and CBF connectivity differences are sex-specific and whether these differences are correlated with cognitive impairment in mTBI.MethodsResting-state perfusion magnetic resonance imaging was performed in 40 patients with acute mTBI and 40 healthy controls by using pseudocontinuous arterial spin labeling within 14 days following injury. The differences in normalized CBF were first compared and CBF connectivity of the brain regions with significant CBF differences were compared next. The association between the normalized CBF and CBF connectivity differences and cognitive function were further investigated.ResultsMen patients had lower normalized CBF in the frontal gyrus, temporal gyrus and hippocampus and decreased negative CBF connectivity between brain regions including the hippocampus, temporal gyrus, postcentral gyrus and lenticular nucleus, putamen, compared with men controls. Women patients had lower normalized CBF in the frontal gyrus, however had higher normalized CBF in the temporal gyrus and hippocampus, compared with women controls. Additionally, women patients showed increased positive CBF connectivity between the seed region of interest (ROI) of the right inferior temporal gyrus and temporal gyrus and frontal gyrus, and had increased positive CBF connectivity between the seed ROI of the right hippocampus and the temporal gyrus. Furthermore, men patients had higher CBF in the right middle temporal gyrus and left precentral gyrus than women patients.ConclusionThis study provides evidence of sex differences in both decreased and increased CBF and CBF connectivity and association with cognitive outcome in the acute stage after mTBI.

Alterations of Cerebral Blood Flow and Its Connectivity in Olfactory-Related Brain Regions of Type 2 Diabetes Mellitus Patients

To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using arterial spin labeling (ASL). Sixty-nine patients with T2DM and 63 healthy controls (HCs) underwent ASL scanning using 3.0T magnetic resonance imaging. We compared the CBF values of the olfactory-related brain regions between the two groups and analyzed the correlation between their changes and clinical variables. We also used these regions as seeds to explore the differences in CBF connectivity patterns in olfactory-related brain regions between the T2DM patients and HCs. Compared with the HC group, the CBF of the right orbital part of the inferior frontal gyrus (OIFG), right insula, and bilateral olfactory cortex was decreased in the T2DM patients. Moreover, the duration of the patients was negatively correlated with the CBF changes in the right OIFG, right insula, and right olfactory cortex. The CBF changes in the right OIFG were positively correlated with the Self-Rating Depression Scale scores, those in the right insula were negatively correlated with the max blood glucose of continuous glucose, and those in the right olfactory cortex were negatively correlated with the mean blood glucose of continuous glucose. In addition, the T2DM patients also showed decreased CBF connectivity between the right OIFG and the left temporal pole of the middle temporal gyrus and increased CBF connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus and between the right olfactory cortex and the bilateral caudate and the left putamen. Patients with T2DM have decreased CBF and altered CBF connectivity in multiple olfactory-related brain regions. These changes may help explain why olfactory dysfunction occurs in patients with T2DM, thus providing insights into the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2DM patients.

Cerebral Blood Flow and its Connectivity Deficits in Patients With Lung Cancer After Chemotherapy.

Purpose: This study was performed to investigate the regional cerebral blood flow (CBF) and CBF connectivity in the chemotherapy-induced cognitive impairment of patients with lung cancer by using arterial spin labeling. Methods: Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging and neuropsychological tests were performed for 21 patients with non-small cell lung cancer who had received chemotherapy CT (+) and 25 non-small cell lung cancer patients who need chemotherapy but did not yet received CT (-). The CT (+) group previously received platinum-based therapy for 3 months to 6 months (the time from their first chemotherapy to the MRI scan). Group comparisons were performed in the regional normalized CBF and CBF connectivity, and the relationship between the regional normalized CBF and cognitive impairment were detected. Results: The CT (+) group exhibited higher CBF in the left insula, right caudate, right superior occipital gyrus, left superior temporal gyrus (STG), and right middle frontal gyrus (MFG). MoCA scores as well as the memory scores were negatively correlated with the increased CBF in the right MFG (r = −0.492, p = 0.023; r = −0.497, p = 0.022). Alterations in the CBF connectivity were detected only in the CT (+) group between the following: right MFG and the right precentral gyrus; the right caudate and the right lingual gyrus; right caudate and right precuneus; left STG and the bilateral MFG; and the left STG and the right middle cingulum. Conclusion: These findings indicated that chemotherapy is associated with abnormalities in the CBF and connectivity alterations, which may contribute to the cognitive impairment in patients with lung cancer.

Cerebral Blood Flow Difference Between Acute and Chronic Tinnitus Perception: A Perfusion Functional Magnetic Resonance Imaging Study.

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus.Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics.Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013).Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity Strength in Cervical Spondylotic Myelopathy Patients.

Background: Changes in regional neural activity and functional connectivity in cervical spondylotic myelopathy (CSM) patients have been reported. However, resting-state cerebral blood flow (CBF) changes and coupling between CBF and functional connectivity in CSM patients are largely unknown.Methods: Twenty-seven CSM patients and 24 sex/age-matched healthy participants underwent resting-state functional MRI and arterial spin labeling imaging to compare functional connectivity strength (FCS) and CBF between the two groups. The CBF–FCS coupling of the whole gray matter and specific regions of interest was also compared between the groups.Results: Compared with healthy individuals, CBF–FCS coupling was significantly lower in CSM patients. The decrease in CBF–FCS coupling in CSM patients was observed in the superior frontal gyrus, bilateral thalamus, and right calcarine cortex, whereas the increase in CBF–FCS coupling was observed in the middle frontal gyrus. Moreover, low CBF and high FCS were observed in sensorimotor cortices and visual cortices, respectively.Conclusion: In general, neurovascular decoupling at cortical level may be a potential neuropathological mechanism of CSM.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling

BackgroundMigraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine.MethodsThis study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated.ResultsIn comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R.ConclusionsOur results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.

AimsNeuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signalling is implicated in cerebrovascular ischaemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesized that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow (CBF), as well as changes in functional brain connectivity.Methods and resultsWe investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF and brain functional connectivity in healthy human volunteers (n = 19). We performed a randomized, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. SMTC infusion induced an ∼4% decrease in resting global CBF [−2.3 (−0.3, −4.2) mL/100g/min, mean (95% confidence interval, CI), P = 0.02]. In a whole-brain voxel-wise factorial-design comparison of CBF maps, we identified a localized decrease in regional blood flow in the right hippocampus and parahippocampal gyrus following SMTC vs. placebo (2921 voxels; T = 7.0; x = 36; y = −32; z = −12; P < 0.001). This was accompanied by a decrease in functional connectivity to the left superior parietal lobule vs. placebo (484 voxels; T = 5.02; x = −14; y = −56; z = 74; P = 0.009). These analyses adjusted for the modest changes in mean arterial blood pressure induced by SMTC as compared to placebo [+8.7 mmHg (+1.8, +15.6), mean (95% CI), P = 0.009].ConclusionsThese data suggest a fundamental physiological role of nNOS in regulating regional CBF and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease.

Changes in resting-state cerebral blood flow and its connectivity in patients with focal to bilateral tonic-clonic seizures

Arterial spin labeling (ASL) is an important tool for understanding cerebral perfusion in epilepsy patients. The aim of this study was to explore patterns of change in cerebral blood flow (CBF) and CBF connectivity in patients with focal to bilateral tonic-clonic seizures (FBTCS).High-resolution three-dimensional (3-D) T1-weighted and 3-D pseudo-continuous ASL magnetic resonance imaging (MRI) was collected from 32 patients with FBTCS and 16 healthy volunteers using a 3.0 T MRI scanner. Cerebral blood flow and its connectivity were compared between the FBTCS and control group. Correlation analysis was used to explore relationships of CBF and its connectivity changes with clinical parameters. Cerebral blood flow data of spatial standardization and normalization were used to improve statistical power.Patients with FBTCS exhibited increased CBF in the bilateral thalamus, caudate nucleus, olfactory cortex, and gyrus rectus, but decreased CBF in the bilateral supplementary motor areas (SMA) and middle cingulate cortex (MCC). Patients with FBTCS showed significant positive correlation between CBF and gray matter volume (GMV) in bilateral SMA and MCC. No significant correlations between CBF and clinical parameters were found among FBTCS patients. The anterior cingulate cortex (ACC) showed positive CBF connectivity with the bilateral SMA and MCC, and these CBF connectivity measures differed significantly between groups (cluster-level, FWE-corrected, P < 0.001).These findings suggest that patients with FBTCS have changes in cerebral CBF and CBF connectivity, which may relate to the underlying neuropathology of FBTCS.

The chronic effect of cortisol on orchestrating cerebral blood flow and brain functional connectivity: evidence from Cushing's disease

BackgroundCortisol has long been considered to play a crucial role in the pathogenesis of stress-related disorders. Cushing’s disease (CD) provides an excellent “hyperexpression model” to investigate the chronic effects of cortisol on brain physiology and cognition. Previous studies have shown that cortisol is associated with neurophysiological alterations in animal models, which has also been examined by neural activity and cerebral blood flow (CBF) in human studies. However, the manner in which cortisol affects the coupling between brain activity and metabolic demand remains largely unknown. MethodsHere we used functional magnetic resonance imaging and arterial-spin-labeling imaging to investigate neurophysiological coupling by examining the ratio of CBF and functional connectivity strength (FCS) in 100 participants (47 CD patients and 53 healthy controls). ResultsThe results showed that CD was associated with lower CBF-FCS coupling predominantly in regions involving cognitive processing, such as the left dorsolateral prefrontal cortex and precuneus, as well as greater CBF-FCS coupling in subcortical structures, including the bilateral thalamus, right putamen, and hippocampus (P < 0.05, false discovery rate corrected). Moreover, regions with disrupted CBF-FCS coupling were associated with cortisol dosage and cognitive decline in CD patients. ConclusionsTogether, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain.

Effects of alfaxalone on cerebral blood flow and intrinsic neural activity of rhesus monkeys: A comparison study with ketamine

ObjectiveAlfaxalone has been used increasingly in biomedical research and veterinary medicine of large animals in recent years. However, its effects on the cerebral blood flow (CBF) physiology and intrinsic neuronal activity of anesthetized brains remain poorly understood. MethodsFour healthy adult rhesus monkeys were anesthetized initially with alfaxalone (0.125 mg/kg/min) or ketamine (1.6 mg/kg/min) for 50 min, then administrated with 0.8% isoflurane for 60 min. Heart rates, breathing beats, and blood pressures were continuously monitored. CBF data were collected using pseudo-continuous arterial spin-labeling (pCASL) MRI technique and rsfMRI data were collected using single-shot EPI sequence for each anesthetic. ResultsBoth the heart rates and mean arterial pressure (MAP) remained more stable during alfaxalone infusion than those during ketamine administration. Alfaxalone reduced CBF substantially compared to ketamine anesthesia (grey matter, 65 ± 22 vs. 179 ± 38 ml/100g/min, p<0.001; white matter, 14 ± 7 vs. 26 ± 6 ml/100g/min, p < 0.05); In addition, CBF increase was seen in all selected cortical and subcortical regions of alfaxalone-pretreated monkey brains during isoflurane exposure, very different from the findings in isoflurane-exposed monkeys pretreated with ketamine. Also, alfaxalone showed suppression effects on functional connectivity of the monkey brain similar to ketamine. ConclusionAlfaxalone showed strong suppression effects on CBF of the monkey brain.The residual effect of alfaxalone on CBF of isoflurane-exposed brains was evident and monotonous in all the examined brain regions when used as induction agent for inhalational anesthesia. In particular, alfaxalone showed similar suppression effect on intrinsic neuronal activity of the brain in comparison with ketamine. These findings suggest alfaxalone can be a good alternative to veterinary anesthesia in neuroimaging examination of large animal models. However, its effects on CBF and functional connectivity should be considered.

Cerebral Blood Flow and Its Connectivity Deficits in Mild Traumatic Brain Injury at the Acute Stage

Objective The influence of cognitive impairment after mild traumatic brain injury (mTBI) on cerebral vascular perfusion has been widely concerned, yet the resting-state cerebral blood flow (CBF) connectivity alterations based on arterial spin labeling (ASL) in mild traumatic brain injury (mTBI) remain unclear. This study investigated region CBF and CBF connectivity features in acute mTBI patients, as well as the associations between CBF changes and cognitive impairment. Materials and Methods Forty-five acute mTBI patients and 42 health controls underwent pseudocontinuous arterial spin labeling (pCASL) perfusion magnetic resonance imaging (MRI). The alterations in regional CBF and relationship between the CBF changes and cognitive impairment were detected. The ASL-CBF connectivity of the brain regions with regional CBF significant differences was also compared between two groups. Neuropsychological tests covered seven cognitive domains. Associations between the CBF changes and cognitive impairment were further investigated. Results Compared with the healthy controls, the acute mTBI patients exhibited increased CBF in the bilateral inferior temporal gyrus (ITG) and decreased CBF in the right middle frontal gyrus (MFG), the bilateral superior frontal gyrus (SFG), and the right cerebellum posterior lobe (CPL). In the mTBI patients, significant correlations were identified between the CBF changes and cognitive impairment. Importantly, the acute mTBI patients exhibited CBF disconnections between the right CPL and right fusiform gyrus (FG) as well as bilateral ITG, between the left SFG and left middle occipital gyrus (MOG), and between the right SFG and right FG as well as right parahippocampal gyrus. Conclusion Our results suggest that acute mTBI patients exhibit both regional CBF abnormalities and CBF connectivity deficits, which may underlie the cognitive impairment of the acute mTBI patients.

Long-term Pingju Opera Training Induces Plasticity Changes in Cerebral Blood Flow: An Arterial Spin Labelling MRI Study

Professional Pingju actors have been shown to exhibit practice-induced plastic changes in spontaneous regional brain activity; however, whether these changes are present in resting-state regional cerebral blood flow (CBF) remains largely unclear. Here, twenty professional Pingju opera actors and 20 age-, sex-, and handedness-matched untrained subjects were recruited, and resting-state CBF maps were obtained by using a three-dimensional pseudocontinuous arterial spin labelling sequence. Voxel-based comparisons of the CBF maps between the two groups were performed with two-sample t-tests, and correlation analyses between the CBF changes and years of training in the actor group were conducted. In addition, the CBF connectivity between regions with CBF alterations and the whole brain was computed and compared between the two groups. Compared with untrained subjects, the actors showed significantly higher CBF in the right inferior temporal gyrus, right middle temporal gyrus, left temporal pole, and left inferior frontal gyrus, whereas significantly lower CBF was not found in the actor group (voxel-level uncorrected p < 0.001, cluster-level family-wise error corrected p < 0.05). Furthermore, there was no correlation between the mean CBF values from significantly different clusters and the years of training, and no significant alterations in CBF connectivity were found in the actor group. Overall, these results provided preliminary evidence that neural plastic changes in CBF are present in professional Pingju opera actors, which may correspond to specific experiences associated with Pingju opera training.

Altered cerebral blood flow in patients with anti-NMDAR encephalitis.

This study aimed to identify to resting-state cerebral blood flow (CBF) connectivity alterations in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Three-dimensional pseudo-continuous arterial spin labeling (pcASL) imaging was performed to measure the resting-state CBF in 23 patients with anti-NMDAR encephalitis at the peak stage of the disease and 32 healthy subjects. CBF was normalized to reduce variations among subjects. CBF was compared between the groups, and the correlations between the CBF alterations and clinical parameters were assessed. Differences in CBF connectivity in specific brain regions were also compared between groups. Compared with the healthy subjects, the patients with anti-NMDAR encephalitis exhibited increased CBF in the left insula (L_insula), left superior temporallobe (L_STL), L_hippocampus, L_pallidum, bilateral putamen (Bi_putamen), and Bi_caudate, and decreased CBF in the bilateral precuneus (Bi_Pc) and bilateral occipital lobe (Bi_OL) (P < 0.05, FEW corrected). Compared with healthy subjects, the patients with anti-NMDAR encephalitis exhibited increased negative CBF connectivity between the Bi_Pc, Bi_OL and L_TL, L_insula (P < 0.05, FEW corrected). Anti-NMDAR encephalitis patients with behavioral changes exhibited higher CBF in the L_insula and lower CBF in the R_Pc, Bi_calcarine, Bi_cuneus, and Bi_lingual than patients without behavioral changes and health controls. The ROC curve shows changed CBF in the L_insula, and R_Pc, Bi_calcarine, Bi_cuneus, and Bi_lingual served as a predictor of behavioral changes in patients with anti-NMDAR encephalitis. Our results suggest that patients with anti-NMDAR encephalitis may exhibit both regional CBF abnormalities and deficits in CBF connectivity, which may underlie the clinical symptoms of anti-NMDAR encephalitis.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging.

Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Aberrant Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Wilson's Disease.

Both abnormalities of resting-state cerebral blood flow (CBF) and functional connectivity in Wilson’s disease (WD) have been identified by several studies. Whether the coupling of CBF and functional connectivity is imbalanced in WD remains largely unknown. To assess this possibility, 27 patients with WD and 27 sex- and age-matched healthy controls were recruited to acquire functional MRI and arterial spin labeling imaging data. Functional connectivity strength (FCS) and CBF were calculated based on standard gray mask. Compared to healthy controls, the CBF–FCS correlations of patients with WD were significantly decreased in the basal ganglia and the cerebellum and slightly increased in the prefrontal cortex and thalamus. In contrast, decreased CBF of patients with WD occurred predominately in subcortical and cognitive- and emotion-related brain regions, including the basal ganglia, thalamus, insular, and inferior prefrontal cortex, whereas increased CBF occurred primarily in the temporal cortex. The FCS decrease in WD patients was predominately in the basal ganglia and thalamus, and the increase was primarily in the prefrontal cortex. These findings suggest that aberrant neurovascular coupling in the brain may be a possible neuropathological mechanism underlying WD.

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

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

Assessment of cerebral perfusional and functional connectivity in schizophrenia using magnetic resonance imaging

Schizophrenia is a significant mental disorder that compromises structural and functional aspects of the brain, with an extreme effect on the patient’s thoughts, feelings, and behavior. Physiologically, in addition to functional and structural abnormalities, changes in neuronal activity are reported. Since the cerebral blood flow (CBF) is directly related to neuronal activity, the magnetic resonance imaging (MRI) technique called arterial spin labeling (ASL), which allows the quantification of CBF, is a useful tool in brain perfusional evaluation. In addition, ASL can be used to assess functional connectivity, which is efficient in investigating functional impairment between regions of the brain. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 schizophrenia patients in treatment and 28 age-matched healthy controls. Static CBF and connectivity patterns were assessed. Decreased CBF and functional connectivity were observed in regions that forms two resting brain networks, default mode (DMN) and salience (SN), for schizophrenia patients. Previous studies related the features of this pathology with altered resting CBF and functional disconnections. Therefore, using a noninvasive technique, we were able to find CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder.