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Aneurysmal subarachnoid haemorrhage (SAH) is a devastating subset of stroke. One of the major determinants of outcome is an evolving multifactorial injury occurring in the first 72 hours, known as early brain injury. Reduced nitric oxide (NO) bioavailability and an associated disruption to cerebral perfusion is believed to play an important role in this process. We sought to explore this relationship, by examining the effect on cerebral perfusion of the in vivo manipulation of NO levels using an exogenous NO donor (sodium nitrite). We performed a double blind placebo controlled randomised experimental medicine study of the cerebral perfusion response to sodium nitrite infusion during the early brain injury period in 15 low grade (World Federation of Neurosurgeons grade 1–2) SAH patients. Patients were randomly assigned to receive sodium nitrite at 10 mcg/kg/min or saline placebo. Assessment occurred following endovascular aneurysm occlusion, mean time after ictus 66h (range 34–90h). Cerebral perfusion was quantified before infusion commencement and after 3 hours, using multi-post labelling delay (multi-PLD) vessel encoded pseudocontinuous arterial spin labelling (VEPCASL) magnetic resonance imaging (MRI). Administration of sodium nitrite was associated with a significant increase in average grey matter cerebral perfusion. Group level voxelwise analysis identified that increased perfusion occurred within regions of the brain known to exhibit enhanced vulnerability to injury. These findings highlight the role of impaired NO bioavailability in the pathophysiology of early brain injury. • Early brain injury occurs in the first 72 h following subarachnoid haemorrhage. • Reduced NO availability and associated cerebral perfusion disruption may play a role. • Using arterial spin labelling MRI we examined the role of NO pathway on perfusion. • In vivo manipulation NO levels with sodium nitrite increased cerebral perfusion. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common encephalopathy syndrome among Japanese children. We report, for the first time, a case of AESD, in which magnetic resonance imaging (MRI) showed no diffusion abnormalities, but hyperperfusion was detected by arterial spin labelling (ASL). A previously healthy Japanese 1-year and 5-month-old boy was transferred to our hospital due to a consciousness disorder after >60 min of status epilepticus on the first day of fever. Brain MRI on the first day revealed no abnormal findings. On the fourth day, focal seizures of the left upper and lower limbs were observed. Thereafter, the patient's condition progressed without seizures. Diffusion-weighted imaging (DWI) on day 6 showed no abnormal findings, including a bright tree appearance. However, ASL showed hyperperfusion in the frontoparietal lobes. MRI scans on days 19 and 39 revealed that the hyperperfusion lesions on day 6 had transitioned to hypoperfusion on ASL and displayed high signal intensity on T2-weighted and fluid-attenuated inversion recovery imaging. Cerebral atrophy was also observed. Based on the clinical course and imaging findings during the chronic phase, a diagnosis of AESD was made. ASL may be more sensitive than DWI for detecting AESD lesions and should be performed in children with suspected AESD. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients. [ABSTRACT FROM AUTHOR]

Abstract Hypothalamus is a crucial deep brain area that is responsible for the integration and coordination of various brain functions. The altered perfusion of hypothalamus during headache caused by medication-overuse headache (MOH) was previously unknown. In the current study, the altered perfusion of hypothalamic subregions in MOH patients was investigated using state-of-the-art 3D pseudo-continuous arterial spin labeling (PCASL) MR imaging. In this study, 29 normal controls subjects (NCs) and 29 MOH patients underwent 3D PCASL and brain structural MR imaging. The hypothalamus was automatically segmented into 10 subunits and the volume of each subunit was automatically determined using Freesurfer software (v7.4.1). All segmented hypothalamic subunits were converted to individual hypothalamic subunit masks. The cerebral blood flow (CBF) images were coregistered with the raw brain structural images and resliced. The CBF value of each hypothalamic subunit was extracted from the warped CBF images. The volume and CBF value of each hypothalamic subunit were analyzed using the independent sample T test and Mann–Whitney U test, receiver operating characteristic (ROC) curve analysis, and Pearson and Spearman correlation analysis. Hypothalamic subunits with significantly decreased perfusion were located in the left posterior, left tubular superior, right anterior–inferior, right tubular inferior, right tubular superior, right posterior subunit and the entire right hypothalamus [CBF value for MOH vs NC (mL/100 g·min): 48.41 ± 6.75 vs 54.08 ± 11.47, 44.44 ± 4.79 vs 48.11 ± 7.73, 41.49 (32.90, 61.46) vs 49.38 ± 10.47, 46.62 ± 7.04 vs 53.90 ± 11.75, 42.12 ± 5.74 vs 47.02 ± 9.99, 42.79 ± 5.15 vs 47.93 ± 10.48 and 43.58 ± 5.06 vs 48.65 ± 9.33, respectively] in MOH compared to NC (P

Abstract Background Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. Methods Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. Discussion This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. Trial registration ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Yu-Lin Zhong,1,&ast; Rui-Yang Hu,2,&ast; Xin Huang1 1Department of Ophthalmology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China; 2School of Ophthalmology and Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Huang, Department of Ophthalmology, Jiangxi Provincial People’s Hospital, No. 152, Ai Guo Road, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 15879215294, Email 334966891@qq.comBackground: Previous imaging studies have demonstrated that diabetic retinopathy (DR) is linked to structural and functional abnormalities in the brain. However, the extent to which DR patients exhibit abnormal neurovascular coupling remains largely unknown.Methods: Thirty-one patients with DR and 31 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) to calculate functional connectivity strength (FCS) and arterial spin-labeling imaging (ASL) to calculate cerebral blood flow (CBF). The study compared CBF-FCS coupling across the entire grey matter and CBF/FCS ratios (representing blood supply per unit of connectivity strength) per voxel between the two groups. Additionally, a support vector machine (SVM) method was employed to differentiate between diabetic retinopathy (DR) patients and healthy controls (HC).Results: In DRpatients compared to healthy controls, there was a reduction in CBF-FCS coupling across the entire grey matter. Specifically, DR patients exhibited elevated CBF/FCS ratios primarily in the primary visual cortex, including the right calcarine fissure and surrounding cortex. On the other hand, reduced CBF/FCS ratios were mainly observed in premotor and supplementary motor areas, including the left middle frontal gyrus.Conclusion: An elevated CBF/FCS ratio suggests that patients with DR may have a reduced volume of gray matter in the brain. A decrease in its ratio indicates a decrease in regional CBF in patients with DR. These findings suggest that neurovascular decoupling in the visual cortex, as well as in the supplementary motor and frontal gyrus, may represent a neuropathological mechanism in diabetic retinopathy.Keywords: neurovascular coupling, diabetic retinopathy, arterial spin labelling, cerebral blood flow, functional connectivity strength, resting-state, SVM

Abstract Objective The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. Methods Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. Results The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. Conclusions Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.

Hypothalamus is a crucial deep brain area that is responsible for the integration and coordination of various brain functions. The altered perfusion of hypothalamus during headache caused by medication-overuse headache (MOH) was previously unknown. In the current study, the altered perfusion of hypothalamic subregions in MOH patients was investigated using state-of-the-art 3D pseudo-continuous arterial spin labeling (PCASL) MR imaging. In this study, 29 normal controls subjects (NCs) and 29 MOH patients underwent 3D PCASL and brain structural MR imaging. The hypothalamus was automatically segmented into 10 subunits and the volume of each subunit was automatically determined using Freesurfer software (v7.4.1). All segmented hypothalamic subunits were converted to individual hypothalamic subunit masks. The cerebral blood flow (CBF) images were coregistered with the raw brain structural images and resliced. The CBF value of each hypothalamic subunit was extracted from the warped CBF images. The volume and CBF value of each hypothalamic subunit were analyzed using the independent sample T test and Mann–Whitney U test, receiver operating characteristic (ROC) curve analysis, and Pearson and Spearman correlation analysis. Hypothalamic subunits with significantly decreased perfusion were located in the left posterior, left tubular superior, right anterior–inferior, right tubular inferior, right tubular superior, right posterior subunit and the entire right hypothalamus [CBF value for MOH vs NC (mL/100 g·min): 48.41 ± 6.75 vs 54.08 ± 11.47, 44.44 ± 4.79 vs 48.11 ± 7.73, 41.49 (32.90, 61.46) vs 49.38 ± 10.47, 46.62 ± 7.04 vs 53.90 ± 11.75, 42.12 ± 5.74 vs 47.02 ± 9.99, 42.79 ± 5.15 vs 47.93 ± 10.48 and 43.58 ± 5.06 vs 48.65 ± 9.33, respectively] in MOH compared to NC (P < 0.05). ROC analysis for these positive subunits revealed that area under the curve was 0.658–0.693, and ROC curve for left posterior subunit had the highest specificity of 93.10% while the entire right hypothalamus had the highest sensitivity of 72.41%. Further correlation analysis showed that the CBF value of the left posterior, right anterior–inferior, right tubular superior, whole right hypothalamus presented significantly negative correlation with Hamilton Depression Scale (HAMD) score (P < 0.05). Hypoperfusion of hypothalamic subunits may contribute to the understanding of MOH pathogenesis, and the 3D PCASL could be considered as a potential diagnostic and assessment tool for MOH. [ABSTRACT FROM AUTHOR]

Information on tissue perfusion in the foot is important when treating patients with chronic limb-threatening ischemia. This study aims to test the reliability of different magnetic resonance sequences when measuring perfusion in the foot. Sixteen healthy volunteers had their right foot scanned in a test/retest study with six different magnetic resonance sequences (BOLD, multi-echo gradient echo (mGRE), 2D and 3D pCASL, PASL FAIR, and DWI with intravoxel incoherent motion (IVIM) with quantitative measurements of perfusion. For five sequences, cuff-induced ischemia followed by a hyperactive response was measured. Images of the feet were segmented into angiosomes and perfusion data were extracted from the five angiosomes. BOLD, PASL FAIR, mGRE, and DWI with IVIM had low mean differences between the first and second scans, while the results of 2D and 3D pCASL had the highest differences. Based on a paired t -test, BOLD, and FAIR were able to distinguish between perfusion and no perfusion in all angiosomes with p -values below 0.01. This was not the case with 2D and 3D pCASL with p -values above 0.05 in all angiosomes. The mGRE could not distinguish between perfusion and no perfusion in the lateral side of the foot. BOLD, mGRE, pASL FAIR, and DWI with IVIM seem to give more robust results compared to 2D and 3D pCASL. Further studies on patients with peripheral artery disease should explore if the sequences can have clinical relevance when assessing tissue ischemia and results of revascularization. This study provides knowledge that could be used to improve the diagnosis of patient with chronic limb-threatening ischemia to explore tissue perfusion. [ABSTRACT FROM AUTHOR]

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of −25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2; susceptometry‐based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: −0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is a broad medical term that describes the progressive cognitive decline of brain function due to disease or impairment, resulting in interference with daily activities. Magnetic Resonance Imaging (MRI) is commonly used for the clinical diagnosis of dementia by identifying cerebral atrophy and structural alterations. Furthermore, Magnetic Resonance Spectroscopy (MRS) can detect biochemical abnormalities in dementia patients, which may be beneficial for early diagnosis and treatment. Aim: To provide a comprehensive protocol and a guidance tool for radiologists to effectively diagnose dementia and its subtypes {Alzheimer’s Disease (AD), frontotemporal lobe dementia, etc.} based on radiological findings coupled with volumetry, spectroscopy, and Arterial Spin Labelling (ASL) findings. Materials and Methods: A retrospective observational study was conducted in the Department of Radiology, Nanavati Max Superspeciality Hospital, Mumbai, Maharashtra, India, between June 2022 and June 2023. A total of 125 patients were analysed to observe the correlation between whole brain volume, Intracranial Volume (ICV) of different cortical regions, hippocampal atrophy, and MRS findings. Descriptive statistics were used, and results were expressed as means and standard deviations for continuous variables, and as frequencies and percentages for categorical variables. Results: Out of 125 patients, 71 (56.8%) were males, and 54 (43.2%) were females, with ages ranging from 41 to 96 years. The majority presented with Mild Cognitive Impairment (MCI) 36 patients (28.8%) and Vascular Dementia (VaD) (18 patients - 14.4%). Some clinical features and imaging findings overlapped, resulting in some cases being a combination of different types of dementia. MRI, MRS, and Medial Temporal Atrophy (MTA) played a crucial role in allowing clinicians to perform a differential diagnosis. Conclusion: The use of MR volumetry and spectroscopy aids in classifying the type of dementia, which, in turn, gives treating clinicians a better perspective for further treatment and its outcomes.

Abstract Background During pregnancy, the placenta plays an important role in the development of the fetus by supplying it with oxygen and nutrition, eliminating waste, and acting as an immunological barrier. Pseudo-continuous arterial spin labelling (pCASL) MRI was recently shown to be a promising sequence for measuring perfusion in the placenta. The aim was to obtain the perfusion measurements of the placenta in normal pregnancies using 3 Tesla MRI from 19 to 38 weeks of gestational age. Results This was a cohort observational study. One hundred and sixty (160) singleton pregnancies from 19 to 38 weeks of gestational age were included. A 3D pCASL sequence was performed in the axial plane for placental blood flow (PBF). Data post-processing was performed on a workstation using Ready View software for 3D ASL with automated generation of quantitative placental pattern-based morphometry (PBM). The mean values of placental perfusion were extracted by averaging the data obtained. A significant positive correlation was observed between the PBF and increasing GA using Karl Pearson’s coefficient of correlation values (r-value 0.77, p-value

Standardized Workflow for Advanced Neuroimaging in Epilepsy (SWANe) software provides researchers with a platform to analyze multimodal imaging modalities and to automatically combine the data from each modality into an integrating three-dimensional fashion. The software comes with a GUI and is designed to be user-friendly and for the not-technical public. SWANe is implemented in Python language and falls within the MIT license. The toolbox builds on a combination of existing methods to improve the user's power to perform analyses on different types of structural, functional, and metabolic imaging. SWANe has been developed in principle for the study of focal epilepsies of any age but it might be prospectively applied in different neurological diseases and for presurgical planning.

Introduction: Dementia is a broad medical term that describes the progressive cognitive decline of brain function due to disease or impairment, resulting in interference with daily activities. Magnetic Resonance Imaging (MRI) is commonly used for the clinical diagnosis of dementia by identifying cerebral atrophy and structural alterations. Furthermore, Magnetic Resonance Spectroscopy (MRS) can detect biochemical abnormalities in dementia patients, which may be beneficial for early diagnosis and treatment. Aim: To provide a comprehensive protocol and a guidance tool for radiologists to effectively diagnose dementia and its subtypes {Alzheimer's Disease (AD), frontotemporal lobe dementia, etc.} based on radiological findings coupled with volumetry, spectroscopy, and Arterial Spin Labelling (ASL) findings. Materials and Methods: A retrospective observational study was conducted in the Department of Radiology, Nanavati Max Superspeciality Hospital, Mumbai, Maharashtra, India, between June 2022 and June 2023. A total of 125 patients were analysed to observe the correlation between whole brain volume, Intracranial Volume (ICV) of different cortical regions, hippocampal atrophy, and MRS findings. Descriptive statistics were used, and results were expressed as means and standard deviations for continuous variables, and as frequencies and percentages for categorical variables. Results: Out of 125 patients, 71 (56.8%) were males, and 54 (43.2%) were females, with ages ranging from 41 to 96 years. The majority presented with Mild Cognitive Impairment (MCI) 36 patients (28.8%) and Vascular Dementia (VaD) (18 patients - 14.4%). Some clinical features and imaging findings overlapped, resulting in some cases being a combination of different types of dementia. MRI, MRS, and Medial Temporal Atrophy (MTA) played a crucial role in allowing clinicians to perform a differential diagnosis. Conclusion: The use of MR volumetry and spectroscopy aids in classifying the type of dementia, which, in turn, gives treating clinicians a better perspective for further treatment and its outcomes. [ABSTRACT FROM AUTHOR]

Posterior fossa tumours (PFTs), which account for two-thirds of paediatric brain tumours, are successfully treated in about 70% of patients, but most survivors experience long-term cognitive impairment. We evaluated arterial spin labelling (ASL), a common, non-invasive magnetic resonance imaging (MRI) technique, as a biomarker of cognitive impairment in a paediatric PFT survivor population. Sixty participants were prospectively analysed. PFT survivors were at least 5 years post-treatment and had been treated as appropriate for their age and type of tumour. Group 1 had received radiotherapy and Group 2 had not. Group 3 were healthy controls matched to Group 1 for age, sex and handedness. All participants underwent cognitive assessment and multimodal MRI, including an ASL perfusion sequence. We used semi-quantitative ASL methods to assess differences in mean perfusion in the thalamus, caudate, putamen and hippocampus. Statistically, no significant associations between cognitive data and radiation doses were identified. Compared with healthy controls, Group 1 patients had significantly lower overall mean perfusion values (20–30% lower, depending on the cerebral structure) and Group 2 had slightly lower mean perfusion values (5–10% lower). Perfusion values did not correlate with total prescribed irradiation doses nor with doses received by different cerebral structures. Episodic and semantic memory test scores were significantly lower in Group 1 and correlated with lower mean absolute perfusion values in the hippocampus (P < 0.04). These preliminary results indicate that radiotherapy affects the perfusion of specific cerebral structures and identify perfusion as a potential biomarker of hippocampus-dependent memory deficit. • A semi-quantitative ASL method was used to quantify cognitive loss in PFT survivors. • Radiotherapy induced long-term overall cerebral semi-quantitative hypoperfusion in a paediatric PFT population. • Perfusion values tend to correlate significantly with the mean radiation dose received by the left hippocampus but not other brain structures examined. • A decrease in hippocampal perfusion is therefore a potential marker of memory impairment in irradiated children. [ABSTRACT FROM AUTHOR]

Abstract Introduction Advanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes. Main body Converging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures. Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as “migraine generators” from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura. Conclusion Although ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.

The purpose of this study was to automatically classify different motor subtypes of Parkinson's disease (PD) on arterial spin labelling magnetic resonance imaging (ASL-MRI) data using support vector machine (SVM). This study included 38 subjects: 21 PD patients and 17 normal controls (NCs). Based on the Unified Parkinson's Disease Rating Scale (UPDRS) subscores, patients were divided into the tremor-dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype. The subjects were in a resting state during the acquisition of ASL-MRI data. The automated anatomical atlas 3 (AAL3) template was registered to obtain an ASL image of the same size and shape. We obtained the voxel values of 170 brain regions by considering the location coordinates of these regions and then normalized the data. The length of the feature vector depended on the number of voxel values in each brain region. Three binary classification models were utilized for classifying subjects' data, and we applied SVM to classify voxels in the brain regions. The left subgenual anterior cingulate cortex (ACC_sub_L) was clearly distinguished in both NCs and PD patients using SVM, and we obtained satisfactory diagnostic rates (accuracy = 92.31%, specificity = 96.97%, sensitivity = 84.21%, and AUCmax = 0.9585). For the right supramarginal gyrus (SupraMarginal_R), SVM distinguished the TD group from the other groups with satisfactory diagnostic rates (accuracy = 84.21%, sensitivity = 63.64%, specificity = 92.59%, and AUCmax = 0.9192). For the right intralaminar of thalamus (Thal_IL_R), SVM distinguished the PIGD group from the other groups with satisfactory diagnostic rates (accuracy = 89.47%, sensitivity = 70.00%, specificity = 6.43%, and AUCmax = 0.9464). These results are consistent with the changes in blood perfusion related to PD subtypes. In addition, the sensitive brain regions of the TD group and PIGD group involve the brain regions where the cerebellothalamocortical (CTC) and the striatal thalamocortical (STC) loops are located. Therefore, it is suggested that the blood perfusion patterns of the two loops may be different. These characteristic brain regions could become potential imaging markers of cerebral blood flow to distinguish TD from PIGD. Meanwhile, our findings provide an imaging basis for personalised treatment, thereby optimising clinical diagnostic and treatment approaches. [ABSTRACT FROM AUTHOR]

A technique for quantifying regional blood–brain barrier (BBB) water exchange rates using contrast‐enhanced arterial spin labelling (CE‐ASL) is presented and evaluated in simulations and in vivo. The two‐compartment ASL model describes the water exchange rate from blood to tissue, kb, but to estimate kb in practice it is necessary to separate the intra‐ and extravascular signals. This is challenging in standard ASL data owing to the small difference in T1 values. Here, a gadolinium‐based contrast agent is used to increase this T1 difference and enable the signal components to be disentangled. The optimal post‐contrast blood T1 (T1,bpost) at 3 T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof‐of‐concept data were acquired in six healthy volunteers (five female, age range 24–46 years). The sensitivity analysis identified the optimal T1,bpost at 3 T as 0.8 s. Simulations showed that kb could be estimated in individual cortical regions with a relative error ϵ<1% and coefficient of variation CoV=30%; however, a high dependence on blood T1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time tA=1.15±0.49 s, cerebral blood flow f=58.0±14.3 mL blood/min/100 mL tissue and water exchange rate kb=2.32±2.49 s−1. CE‐ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measured T1 values. [ABSTRACT FROM AUTHOR]

Background: During pregnancy, the placenta plays an important role in the development of the fetus by supplying it with oxygen and nutrition, eliminating waste, and acting as an immunological barrier. Pseudo-continuous arterial spin labelling (pCASL) MRI was recently shown to be a promising sequence for measuring perfusion in the placenta. The aim was to obtain the perfusion measurements of the placenta in normal pregnancies using 3 Tesla MRI from 19 to 38 weeks of gestational age. Results: This was a cohort observational study. One hundred and sixty (160) singleton pregnancies from 19 to 38 weeks of gestational age were included. A 3D pCASL sequence was performed in the axial plane for placental blood flow (PBF). Data post-processing was performed on a workstation using Ready View software for 3D ASL with automated generation of quantitative placental pattern-based morphometry (PBM). The mean values of placental perfusion were extracted by averaging the data obtained. A significant positive correlation was observed between the PBF and increasing GA using Karl Pearson's coefficient of correlation values (r-value 0.77, p-value < 0.001), respectively. Average PBF values from 19 to 38 weeks were (89.4 ± 13.5 to 155.3 ± 2.8 ml/100 g/min). According to our intra-class correlation coefficient (ICC), inter-observer reproducibility of placental blood flow shows good agreement between observers (0.98). Conclusions: Normal PBF values using ASL in 3 T MRI from 19 to 38 weeks of gestational age were provided. Statistical analysis revealed a significant positive correlation between gestational age and placental blood flow. In the future, it may help to identify placental perfusion abnormalities like placental insufficiency, preeclampsia, and fetal growth restriction (FGR). [ABSTRACT FROM AUTHOR]

The no‑reflow phenomenon (NRP) after successful vascular recanalization in acute ischemic stroke (AIS) has become a major cause of poor clinical prognosis and ineffective recanalization. However, there is currently no clear definition or unified clinical assessment method for the NRP. Therefore, it is urgent to clarify the clinical evaluation criteria for the NRP and develop new no‑reflow evaluation techniques so that remedial treatment can be applied to AIS patients suffering from the NRP. In this brief review, a variety of NRP assessment methods and defining criteria for clinical practice are presented. [ABSTRACT FROM AUTHOR]

In humans, resting cerebral perfusion, oxygen consumption and energy metabolism demonstrate large intersubject variation regardless of methodology. Whether a similar large variation is also present longitudinally in individual subjects is much less studied, but knowing the time variance in reproducibility is important when designing and interpreting longitudinal follow-up studies examining brain physiology. Therefore, we examined the reproducibility of cerebral blood flow (CBF), global cerebral metabolic rate of oxygen (CMRO2), global arteriovenous oxygen saturation difference (A-V.O2), and cerebral lactate and N-acetyl-aspartate (NAA) concentrations measured using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques through repeatedmeasurements at 6 h, 24 h, 7 days and several weeks after initial baseline measurements in young healthy adults (N = 26, 13 females, age range 18-35 years). Using this setup, we calculated the correlation, limit of agreement (LoA) and within-subject coefficient of variation (CoVWS) between baseline values and the subsequent repeated measurements to examine the longitudinal variation in individual cerebral physiology. CBF and CMRO2 correlated significantly between baseline and all subsequent measurements. The strength of the correlations (R²) and reproducibility metrics (LoA and CoVWS) demonstrated the best reproducibility for the within-day measurements and generally declined with longer time between measurements. Cerebral lactate and NAA concentrations also correlated significantly for all measurements, except between baseline and the 7-day measurement for lactate. Similar to CBF and CMRO2, lactate and NAA demonstrated the best reproducibility for within-day repeated measurements. The gradual decline in reproducibility over time should be considered when designing and interpreting studies on brain physiology, for example, in the evaluation of treatment efficacy. [ABSTRACT FROM AUTHOR]

The no-reflow phenomenon (NRP) after successful vascular recanalization in acute ischemic stroke (AIS) has become a major cause of poor clinical prognosis and ineffective recanalization. However, there is currently no clear definition or unified clinical assessment method for the NRP. Therefore, it is urgent to clarify the clinical evaluation criteria for the NRP and develop new no-reflow evaluation techniques so that remedial treatment can be applied to AIS patients suffering from the NRP. In this brief review, a variety of NRP assessment methods and defining criteria for clinical practice are presented.

Background: Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response. Methods: We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14). Results: There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008). Conclusions: These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Parkinson's disease is a chronic progressive neurodegenerative disorder with standard structural MRIs often showing no gross abnormalities. Quantitative perfusion MRI modality Arterial Spin Labeling (ASL) is helpful in identifying PD specific perfusion patterns. Absolute Cerebral blood flow (CBF) measurement using ASL provides insights into regional perfusion abnormalities. We reviewed the role of ASL to identify specific brain regions responsible for motor, non-motor symptoms and neurovascular changes observed in PD. Challenges in assessing the blood perfusion level are discussed with future development for improving the evaluation of ASL perfusion maps.Materials and Methods: We included CBF quantification studies using ASL for PD diagnosis. A systematic search was performed in Pubmed, Scopus and Web of Science. The perfusion parameters CBF and arterial arrival time (AAT) measured using ASL were considered for brain region assessment. Clinical aspects of PD have been analyzed using ASL perfusion maps.Results: The systematic search identified 153 unique records. Thirty articles were selected after verification of inclusion and exclusion criteria. Voxel and region-based analyses in white and gray matter tissues have been performed to identify PD-specific perfusion patterns by reported articles. Predominant brain regions such as basal ganglia sub-regions, frontoparietal network, precuneus, occipital lobe, sensory motor area regions, visual network, which are associated with motor and non-motor symptoms in PD, were identified with CBF hypoperfusion, indicating neuronal loss and cerebrovascular dysfunction.Conclusion: CBF and AAT values derived from ASL can potentially be used as biomarkers to discriminate PD from similar brain-related disorders. [ABSTRACT FROM AUTHOR]

Introduction: Advanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes. Main body: Converging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures. Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as "migraine generators" from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura. Conclusion: Although ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral blood flow (CBF) is an important physiological parameter that can be quantified non-invasively using arterial spin labelling (ASL) imaging. Although most ASL studies are based on single-timepoint strategies, multi-timepoint approaches (multiple-PLD) in combination with appropriate model fitting strategies may be beneficial not only to improve CBF quantification but also to retrieve other physiological information of interest. Methods: In this work, we tested several kinetic models for the fitting of multiple-PLD pCASL data in a group of 10 healthy subjects. In particular, we extended the standard kinetic model by incorporating dispersion effects and the macrovascular contribution and assessed their individual and combined effect on CBF quantification. These assessments were performed using two pseudocontinuous ASL (pCASL) datasets acquired in the same subjects but during two conditions mimicking different CBF dynamics: normocapnia and hypercapnia (achieved through a CO2 stimulus). Results: All kinetic models quantified and highlighted the different CBF spatiotemporal dynamics between the two conditions. Hypercapnia led to an increase in CBF whilst decreasing arterial transit time (ATT) and arterial blood volume (aBV). When comparing the different kinetic models, the incorporation of dispersion effects yielded a significant decrease in CBF (~10-22%) and ATT (~17-26%), whilst aBV (~44-74%) increased, and this was observed in both conditions. The extended model that includes dispersion effects and the macrovascular component has been shown to provide the best fit to both datasets. Conclusion: Our results support the use of extended models that include the macrovascular component and dispersion effects when modelling multiple-PLD pCASL data. [ABSTRACT FROM AUTHOR]

Pilot study validating the animal model of depression – the bilateral olfactory bulbectomy in rats – by two nuclear magnetic resonance methods, indirectly detecting the metabolic state of the brain. Furthermore, the study focussed on potential differences in brain laterality. Arterial spin labelling assessed cerebral brain flow in prefrontal, sensorimotor, and piriform cortices, nucleus accumbens, hippocampus, thalamus, circle of Willis, and whole brain. Proton magnetic resonance spectroscopy provided information about relative metabolite concentrations in the cortex and hippocampus. Arterial spin labelling found no differences in cerebral perfusion in the group comparison but revealed lateralisation in the thalamus of the control group and the sensorimotor cortex of the bulbectomized rats. Lower Cho/tCr and Cho/NAA levels were found in the right hippocampus in bulbectomized rats. The differences in lateralisation were shown in the hippocampus: mI/tCr in the control group, Cho/NAA, NAA/tCr, Tau/tCr in the model group, and in the cortex: NAA/tCr, mI/tCr in the control group. Olfactory bulbectomy affects the neuronal and biochemical profile of the rat brain laterally and, as a model of depression, was validated by two nuclear magnetic resonance methods. [ABSTRACT FROM AUTHOR]

In humans, resting cerebral perfusion, oxygen consumption and energy metabolism demonstrate large intersubject variation regardless of methodology. Whether a similar large variation is also present longitudinally in individual subjects is much less studied, but knowing the time variance in reproducibility is important when designing and interpreting longitudinal follow-up studies examining brain physiology. Therefore, we examined the reproducibility of cerebral blood flow (CBF), global cerebral metabolic rate of oxygen (CMRO2), global arteriovenous oxygen saturation difference (A-V.O2), and cerebral lactate and N-acetyl-aspartate (NAA) concentrations measured using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques through repeated measurements at 6 h, 24 h, 7 days and several weeks after initial baseline measurements in young healthy adults (N = 26, 13 females, age range 18–35 years). Using this setup, we calculated the correlation, limit of agreement (LoA) and within-subject coefficient of variation (CoVWS) between baseline values and the subsequent repeated measurements to examine the longitudinal variation in individual cerebral physiology. CBF and CMRO2 correlated significantly between baseline and all subsequent measurements. The strength of the correlations (R2) and reproducibility metrics (LoA and CoVWS) demonstrated the best reproducibility for the within-day measurements and generally declined with longer time between measurements. Cerebral lactate and NAA concentrations also correlated significantly for all measurements, except between baseline and the 7-day measurement for lactate. Similar to CBF and CMRO2, lactate and NAA demonstrated the best reproducibility for within-day repeated measurements. The gradual decline in reproducibility over time should be considered when designing and interpreting studies on brain physiology, for example, in the evaluation of treatment efficacy.

Introduction: The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Methods: Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. Results: Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in wholebrain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. Conclusion: On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a major public health problem and its incidence is rising. The disease course is unpredictable with classic biomarkers, and the search for new tools to predict adverse renal outcomes is ongoing. Renal magnetic resonance imaging (MRI) now enables the quantification of metabolic and microscopic properties of the kidneys such as single-kidney, cortical and medullary blood flow, and renal tissue oxygenation and fibrosis, without the use of contrast media. A rapidly increasing number of studies show that these techniques can identify early kidney damage in patients with DKD, and possibly predict renal outcome. This review provides an overview of the currently most frequently used techniques, a summary of the results of some recent studies, and our view on their potential applications, as well as the hurdles to be overcome for the integration of these techniques into the clinical care of patients with DKD.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer’s disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life. Here, 160 young and cognitively healthy participants from the Chinese PREVENT cohort underwent 3 T arterial spin labelling and T1 MRI and genetic testing for APOE and MAPT rs242557 status. Using FSL, we performed a whole brain voxel-wise analysis and a global mean grey matter analysis comparing for the effects of both risk genes on cerebral perfusion. No significant alterations were seen for APOE genotype, but in MAPT rs242557 A carriers, we observed a significantly hyperperfusion in the left anterior cingulate cortex and left insular cortex. There were no effects of APOE or MAPT status on the global perfusion. These results are novel and may suggest that MAPT genotypes demonstrated a distinct hemodynamic profile in a very young age. [ABSTRACT FROM AUTHOR]

Abstract Background Nucleus accumbens (NAcc) played an important role in pain mediation, and presents changes of neuronal plasticity and functional connectivity. However, less is known about altered perfusion of NAcc in chronic migraine (CM). The aim of this study is to investigate the altered perfusion of the NAcc in CM using a MR three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) imaging. Methods Thirteen CM patients and 15 normal controls (NC) were enrolled and underwent 3D PCASL and brain structural imaging. The cerebral blood flow (CBF) images were co-registered with the brain structural images, and the volume and CBF value of NAcc were extracted from the raw brain structural images and co-registered CBF images using an individual NAcc mask, which was obtained from the AAL3 template under transformation by the inverse deformation field generated from the segmentation of the brain structural images. The independent sample t test and receiver operating characteristic (ROC) curve was used to investigate the altered volume and perfusion of the NAcc in CM patients. Results There was no significant difference for the volume of bilateral NAccs between CM and NC (p > 0.05). CM presented a lower CBF value (49.34 ± 6.09 ml/100 mg/min) compared with that of NC (55.83 ± 6.55 ml/100 mg/min) in left NAcc (p = 0.01), while right NAcc showed no significant difference between CM and NC (p = 0.11). ROC analysis identified that the area under the curve was 0.73 (95CI% 0.53–0.88) with cut-off value 48.63 ml/100 mg/min with sensitivity 50.00% and specificity 93.33%. The correlation analysis found a negative correlation between the CBF value of the left NAcc and VAS score (r = -0.61, p = 0.04). Conclusion Hypoperfusion of the left NAcc was observed in CM, which could be considered as a potential diagnostic imaging biomarker in CM.

Introduction: Cerebral blood flow (CBF) is an important physiological parameter that can be quantified non-invasively using arterial spin labelling (ASL) imaging. Although most ASL studies are based on single-timepoint strategies, multi-timepoint approaches (multiple-PLD) in combination with appropriate model fitting strategies may be beneficial not only to improve CBF quantification but also to retrieve other physiological information of interest.Methods: In this work, we tested several kinetic models for the fitting of multiple-PLD pCASL data in a group of 10 healthy subjects. In particular, we extended the standard kinetic model by incorporating dispersion effects and the macrovascular contribution and assessed their individual and combined effect on CBF quantification. These assessments were performed using two pseudo-continuous ASL (pCASL) datasets acquired in the same subjects but during two conditions mimicking different CBF dynamics: normocapnia and hypercapnia (achieved through a CO2 stimulus).Results: All kinetic models quantified and highlighted the different CBF spatiotemporal dynamics between the two conditions. Hypercapnia led to an increase in CBF whilst decreasing arterial transit time (ATT) and arterial blood volume (aBV). When comparing the different kinetic models, the incorporation of dispersion effects yielded a significant decrease in CBF (∼10–22%) and ATT (∼17–26%), whilst aBV (∼44–74%) increased, and this was observed in both conditions. The extended model that includes dispersion effects and the macrovascular component has been shown to provide the best fit to both datasets.Conclusion: Our results support the use of extended models that include the macrovascular component and dispersion effects when modelling multiple-PLD pCASL data.

IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.ConclusionOn this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0-2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P

Arterial spin labelling (ASL) plays an increasingly important role in neuroimaging pain research but does not provide molecular insights regarding how regional cerebral blood flow (rCBF) relates to underlying neurotransmission. Here, we integrate ASL with positron emission tomography (PET) and brain transcriptome data to investigate the molecular substrates of rCBF underlying clinically relevant pain states. Two data sets, representing acute and chronic ongoing pain respectively, were utilised to quantify changes in rCBF; one examining pre‐surgical versus post‐surgical pain, and the second comparing patients with painful hand Osteoarthritis to a group of matched controls. We implemented a whole‐brain spatial correlation analysis to explore associations between change in rCBF (ΔCBF) and neurotransmitter receptor distributions derived from normative PET templates. Additionally, we utilised transcriptomic data from the Allen Brain Atlas to inform distributions of receptor expression. Both datasets presented significant correlations of ΔCBF with the μ‐opioid and dopamine‐D2 receptor expressions, which play fundamental roles in brain activity associated with pain experiences. ΔCBF also correlated with the gene expression distributions of several receptors involved in pain processing. Overall, this is the first study illustrating the molecular basis of ongoing pain ASL indices and emphasises the potential of rCBF as a biomarker in pain research. [ABSTRACT FROM AUTHOR]

Background: Blood-brain barrier (BBB) dysfunction is suggested to be a potential mediator between vascular risk factors and cognitive impairment, leading to vascular cognitive impairment. Objective: To investigate the relationships between age, sex, and vascular risk factors and BBB water permeability as well as their relationship with cognition. Methods: To measure BBB permeability, a novel arterial spin labelling MRI technique (ME-ASL) was applied to derive the time of exchange (Tex), arterial time transit (ATT), and cerebral blood flow (CBF). The association of potential risk factors, such as age, sex, body mass index (BMI), blood pressure (BP), and medical history, with these BBB parameters were assessed in 144 community-dwelling adults (median age 59 years, 57% females). The relationship between BBB permeability and cognitive performance measured by the Montreal Cognitive Assessment (MoCA) was also assessed. Results: We found that increased BMI was significantly associated with decreased CBF (β = -0.06). Systolic BP and diastolic BP showed significant associations with all ASL parameters; systolic BP was negatively correlated with Tex (β = -0.02) and CBF (β = -0.01) but positively with ATT (β = 0.02). Diastolic BP was negatively associated with Tex (β = -0.03) and CBF (β = -0.03) but positively with ATT (β = 0.03). MoCA scores had a borderline significant association with Tex (OR = 1.51) and a significant association with CBF (OR = 1.84), which became non-significant after adjusting for confounders. Conclusions: These outcomes underscore the potential of using ME-ASL, warranting further research to strengthen these findings., Competing Interests: Declaration of conflicting interestsSaima Hilal is an Editorial Board Member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review.The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Georg Deutsch,1 Hrishikesh Deshpande,1 H Henry Lai,2 Jason J Kutch,3 Timothy J Ness4 1Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; 3Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA; 4Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Timothy J NessDepartment of Anesthesiology, University of Alabama at Birmingham, BMR2-208; 901 19th St. S, Birmingham, AL, 35205, USATel +1 205-975-9643Fax +1 205-934-7437Email tness@uabmc.eduPurpose: Fibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity.Patients and Methods: Female subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis of fibromyalgia as well as healthy control subjects (n = 41) underwent quantitative sensory testing. A subset of these patients (9 with and 9 without fibromyalgia) underwent brain perfusion studies using arterial spin labeled functional magnetic resonance imaging. An analysis was performed of absolute regional cerebral blood flow of regions-of-interest when experiencing a full bladder compared with an empty bladder.Results: Subjects with both interstitial cystitis and fibromyalgia were more hypersensitive than those without fibromyalgia as well as healthy controls in most sensory measures except heat. Subjects with interstitial cystitis, but no fibromyalgia, differed from healthy controls only in toleration of the ischemic forearm task. Other co-morbidities were more common in those subjects with both interstitial cystitis and fibromyalgia. Bladder fullness was associated with significantly greater whole brain gray matter blood flow in subjects with interstitial cystitis and fibromyalgia when compared with that of subjects with interstitial cystitis without fibromyalgia. Examination of regional cerebral blood flow in individual regions-of-interest demonstrated statistically significant differences between the subjects with interstitial cystitis with and those without fibromyalgia bilaterally in the thalamus, amygdala and hippocampus, as well as the right prefrontal cortex and greater responsiveness to changes in bladder fullness in the insula.Conclusion: Quantitative sensory testing and brain perfusion data support that there are two phenotypes of interstitial cystitis patients, which can be differentiated by a co-diagnosis of fibromyalgia. This may affect responsiveness to treatment and suggest the utility of stratifying interstitial cystitis patients according to their co-morbidities.Keywords: arterial spin labelling, fMRI, interstitial cystitis, QST

Background GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P

Background: Bipolar Disorder (BD) is a severe chronic psychiatric disorder whose aetiology is still largely unknown. However, increasing literature reported the involvement of neurovascular factors in the pathophysiology of BD, suggesting that a measure of Cerebral Blood Flow (CBF) could be an important biomarker of the illness. Therefore, since, to date, Magnetic Resonance Perfusion Weighted Imaging (PWI) techniques, such as Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labelling (ASL), are the most common approaches that allow non-invasive in-vivo perfusion measurements,this review aims to summarize the results from all PWI studies that evaluated the CBF in BD.Methods: A bibliographic search in PubMed up until May 2021 was performed. 16 PWI studies that used DSC or ASL sequences met our inclusion criteria.Results: Overall, the results supported the presence of hyper-perfusion in the cingulate cortex and fronto-temporal regions, as well as the presence of hypo-perfusion in the cerebellum in BD, compared with both healthy controls and patients with unipolar depression. CBF changes after cognitive and aerobic training, as well as in relation with other physiological, clinical, and neurocognitive variables were also reported.Limitations: The heterogeneity across the studies, in terms of experimental designs, sample selection, and methodological approach employed, limited the studies' comparison.Conclusions: These findings showed CBF alterations in the cingulate cortex, fronto-temporal regions, and cerebellum in BD, suggesting that CBF may be an important pathophysiological marker of BD that merits further investigation to clarify the extent of neurovascular alterations. [ABSTRACT FROM AUTHOR]

Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine's mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine's mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions. [ABSTRACT FROM AUTHOR]

AimsHeart failure (HF) patients show significant lateralized neural injury, accompanied by autonomic, mood and cognitive deficits. Both gray and white matter damage occurs and probably develops from altered cerebral blood flow (CBF), a consequence of impaired cardiac output. However, the distribution of regional CBF changes in HF patients is unknown, but is an issue in determining mechanisms of neural injury. Our aim was to compare regional CBF changes in HF with CBF in control subjects using non-invasive pseudo-continuous arterial spin labelling (ASL) procedures.Methods and resultsWe collected pseudo-continuous ASL data from 19 HF patients [mean age 55.5 ± 9.1 years; mean body mass index 27.7 ± 5.3 kg/m2 ; 13 male) and 29 control subjects (mean age 51.4 ± 5.3 years; mean body mass index 25.7 ± 3.6 kg/m2 ; 18 male), using a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Whole-brain CBF maps were calculated, normalized to a common space, smoothed and compared between groups using ANCOVA (covariates; age, gender and gray matter volume). Reduced CBF appeared in multiple sites in HF patients in comparison with controls, with principally lateralized lower flow in temporal, parietal and occipital regions. Areas with decreased CBF included the bilateral prefrontal, frontal, temporal and occipital cortex, thalamus, cerebellum, corona radiate, corpus callosum, hippocampus and amygdala.ConclusionsHeart failure patients showed lower, and largely lateralized, CBF in multiple autonomic, mood and cognitive regulatory sites. The reduced CBF is likely to contribute to the lateralized brain injury, leading to the autonomic and neuropsychological deficits found in the condition.

Abstract Background Cluster headache is an excruciating disorder with no cure. Greater occipital nerve blockades can transiently suppress attacks in approximately 50% of patients, however, its mechanism of action remains uncertain, and there are no reliable predictors of treatment response. To address this, we investigated the effect of occipital nerve blockade on regional cerebral blood flow (rCBF), an index of brain activity, and differences between treatment responders and non-responders. Finally, we compared baseline perfusion maps from patients to a matched group of healthy controls. Methods 21 male, treatment-naive patients were recruited while in a cluster headache bout. During a pain-free phase between headaches, patients underwent pseudo-continuous arterial spin labelled MRI assessments to provide quantitative indices of rCBF. MRIs were performed prior to and 7-to-21 days following treatment. Patients also recorded the frequency of their headache attacks in a daily paper diary. Neuropsychological assessment including anxiety, depression and quality of life measures was performed in a first, scanning free session for each patient. Results Following treatment, patients demonstrated relative rCBF reductions in posterior temporal gyrus, cerebellum and caudate, and rCBF increases in occipital cortex. Responders demonstrated relative rCBF increases, compared to non-responders, in medial prefrontal cortex and lateral occipital cortex at baseline, but relative reductions in cingulate and middle temporal cortices. rCBF was increased in patients compared to healthy controls in cerebellum and hippocampus, but reduced in orbitofrontal cortex, insula and middle temporal gyrus. Conclusions We provide new mechanistic insights regarding the aetiology of cluster headache, the mechanisms of action of occipital nerve blockades and potential predictors of treatment response. Future investigation should determine whether observed effects are reproducible and extend to other headache disorders.