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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.

Background: 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. [ABSTRACT FROM AUTHOR]

Plain English summary Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN). However, little is known about the neurobiological effects of this treatment. This study explored the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) before and after receiving 20 sessions (over 4 weeks) of real or sham rTMS. We found a greater reduction in amygdala CBF following real rTMS compared to sham rTMS. Participants with the greatest rTMS-related reduction in amygdala CBF showed the greatest sustained weight gain at an 18-month follow-up. Higher baseline CBF in the insula predicted greater weight gain during treatment and at a 4-month follow-up. This suggests that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should use longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.

Psychomotor retardation, characterized by slowing of speech, thoughts, and a decrease of movements, is frequent in patients with major depressive disorder (MDD). However, its neurobiological correlates are still poorly understood. This study aimed to explore if cerebral blood flow (CBF) and resting state functional connectivity (rs-FC) of the motor network are altered in patients with MDD and if these changes are associated with psychomotor retardation. Thirty-six right-handed patients with depression and 19 right-handed healthy controls (HC) that did not differ regarding age and sex underwent arterial spin labelling (ASL) and resting-state functional MRI (rs-fMRI) scans. Psychomotor retardation was assessed with the motoric items of the core assessment of psychomotor change (CORE) questionnaire. Patients with MDD had more pronounced psychomotor retardation scores than HC. Patients with MDD had reduced CBF in bilateral cingulate motor area (CMA) and increased resting-state functional connectivity (rs-FC) between the cluster in the CMA and a cluster localized in bilateral supplementary motor areas (SMA). Furthermore, increased rs-FC between the CMA and the left SMA was associated with more pronounced psychomotor retardation. Our results suggest that reduced perfusion of the CMA and increased rs-FC between the CMA and the SMA are associated with psychomotor retardation in patients with depression. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Methods: As part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females (n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation. Results: No group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation. Conclusions: This exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment. Trial registration: ISRCTN14329415, registered 23rd July 2015. Plain English summary: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN). However, little is known about the neurobiological effects of this treatment. This study explored the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) before and after receiving 20 sessions (over 4 weeks) of real or sham rTMS. We found a greater reduction in amygdala CBF following real rTMS compared to sham rTMS. Participants with the greatest rTMS-related reduction in amygdala CBF showed the greatest sustained weight gain at an 18-month follow-up. Higher baseline CBF in the insula predicted greater weight gain during treatment and at a 4-month follow-up. This suggests that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should use longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment. [ABSTRACT FROM AUTHOR]

Purpose: To identify the changes of intrinsic brain activity and regional cerebral blood flow in patients with chronic neck and shoulder pain (CNSP) by using amplitude of low-frequency fluctuation (ALFF) analysis and arterial spin labelling study. Material and methods: In total, 28 CNSP patients and 25 age-matched and sex-matched healthy controls (HCs) participated in the study. Resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labelling (ASL) MRI were acquired. Correlations between ALFF and cerebral blood flow (CBF) were analysed. Subsequently, the differences in ALFF and CBF were compared in the two groups. Finally, the visual analogue scale (VAS) was also assessed in the CNSP group. Results: Compared with HCs, CNSP patients showed significantly abnormal ALFF and CBF in several brain regions, including the cerebellum posterior lobe, middle orbitofrontal gyrus, medial superior frontal gyrus, middle temporal gyrus, precuneus, cingulate gyrus, middle occipital gyrus, middle frontal gyrus, postcentral gyrus, precentral gyrus, and superior parietal gyrus. Correlation analysis showed that the ALFF value of the medial superior frontal gyrus positively correlated with the VAS score. However, no correlation was found between the CBF values and the VAS score. Conclusions: The altered ALFF and CBF values in CNSP patients were observed in different pain-related brain regions that were involved in pain modulation and perception. The combination of rs-fMRI and ASL MRI might provide complementary information for increasing our understanding of the neuropathology in CNSP. [ABSTRACT FROM AUTHOR]

Objectives: We investigated changes of renal perfusion after topical and oral diclofenac administration in healthy volunteers using functional magnetic resonance imaging (MRI) with arterial spin labelling (ASL). Methods: Twenty‐four healthy human participants (21–51 years) underwent 1.5T MRI before and 1 h after a single oral dose of diclofenac (50 mg). Twelve of 24 participants underwent an additional MRI examination following 3‐day topical diclofenac administration. For renal perfusion imaging, a flow‐sensitive alternating inversion‐recovery TrueFISP ASL sequence was applied. Plasma concentrations of diclofenac and serum concentrations of thromboxane were determined. Key findings: After oral diclofenac application, large interindividual differences in plasma concentrations were observed (range <3–4604 nm). Topical diclofenac application did not result in relevant systemic diclofenac levels (range 5–75 nm). MRI showed a significant reduction of renal perfusion in individuals with diclofenac levels ≥225 nm (baseline: 347 ± 7 vs diclofenac: 323 ± 8 ml/min/100 g, P < 0.01); no significant differences were observed in participants with diclofenac levels <225 nm. Diclofenac levels correlated negatively with thromboxane B2 levels pointing towards target engagement. Conclusions: Single‐dose diclofenac caused a decrease in renal perfusion in participants with diclofenac levels ≥225 nm. We demonstrated that even a single dose of diclofenac can impair renal perfusion, which could be detrimental in patients with underlying chronic kidney disease or acute kidney injury. [ABSTRACT FROM AUTHOR]

Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis. [ABSTRACT FROM AUTHOR]

Background: Intracranial meningiomas may be amenable to presurgical embolization to reduce bleeding complications. Detailed information usually obtained by digital subtraction angiography (DSA) on the contribution of blood supply from internal and external carotid artery branches is required to prevent non-target embolization and is helpful for pre-surgical planning. Purpose: To investigate the contribution of the feeding vasculature to intracranial meningiomas with superselective arterial spin labelling (sASL) as an alternative to DSA. Material and methods: Consecutive patients presenting for meningioma resection were prospectively included. sASL perfusion images acquired on a clinical 3T MRI scanner were independently rated by two readers. Contribution of the external carotid artery (ECA), internal carotid artery (ICA) and vertebral/basilar artery (VA/BA) was rated as none, <50% or >50%. Correlation of sASL was performed in two patients undergoing DSA. Results: 32 patients (61 ± 13 years) harboring 42 meningiomas could be included. sASL was technically successful in all patients. 19 meningiomas had ICA dominant supply, 19 had ECA dominant supply. One meningioma had mixed supply and in three meningiomas a perfusion signal could not be detected. While exclusive unilateral ECA supply was common (n = 14) and exclusive unilateral ICA was rare (n = 4), mixed supply from multiple vessels (n = 20) was a frequent finding. Interrater agreement was substantial (κ = 0.73). Agreement with DSA was perfect within our predefined categories. Conclusion: sASL is able to identify the presence and extent of the feeding vasculature in intracranial meningiomas. [ABSTRACT FROM AUTHOR]

Abstract Functional magnetic resonance imaging (fMRI) is an essential workhorse of modern neuroscience, providing valuable insight into the functional organisation of the brain. The physiological mechanisms underlying the blood oxygenation level dependent (BOLD) effect are complex and preclude a straightforward interpretation of the signal. However, by employing appropriate calibration of the BOLD signal, quantitative measurements can be made of important physiological parameters including the absolute rate of cerebral metabolic oxygen consumption or oxygen metabolism (CMRO 2) and oxygen extraction (OEF). The ability to map such fundamental parameters has the potential to greatly expand the utility of fMRI and to broaden its scope of application in clinical research and clinical practice. In this review article we discuss some of the practical issues related to the calibrated-fMRI approach to the measurement of CMRO 2. We give an overview of the necessary precautions to ensure high quality data acquisition, and explore some of the pitfalls and challenges that must be considered as it is applied and interpreted in a widening array of diseases and research questions. Highlights • Dual calibrated fMRI can map the rate of cerebral metabolic oxygen consumption (CMRO2) and oxygen extraction fraction (OEF). • The techniques have recently been demonstrated in clinical research of dementia, ageing and pharmacological interventions. • We review the experimental and analysis methods used to estimate these physiological parameters. • We discuss the prospects for future clinical research use and the potential limitations of the methods. [ABSTRACT FROM AUTHOR]

Background and purpose: Arterial spin labeling(ASL)with magnetic resonance imaging (MRI) is an effective method for estimating cerebral blood flow (CBF). Furthermore, assessing perfusion territories of arteries is useful for determining the treatment strategy of patients with carotid artery stenosis. ASL with selective vessel labeling is an effective method to obtain perfusion mapping, however, the application for selective labeling is not installed on all MR scanners. The purpose of this study is to establish a method to selectively mask in the labeling area using material with high susceptibility instead of selectively labeling to obtain a partial perfusion image. Materials and methods: ASL perfusion images were performed in five volunteers. Masking was applied by placing a stainless-steel bolt and nuts on the neck. The area of artifacts extended to the carotid artery was confirmed by the localizer image. In the obtained masked ASL, blood flow of the left and right cerebrum and cerebellum was measured and compared with control ASL without masking. By subtracting masked ASL from the control ASL, the perfusion territory of the carotid artery on the masked side was identified. Results: Mean CBF which was 39.6 ml/(100 g × min) in control ASL decreased to 16.1 ml/(100 g × min) in masked ASL, and the masking ratio was 59.6%. There were no significant differences in the CBF of non-masked areas under the control ASL condition (39.6± 5.2 ml/[100 g × min]) btween that under the masked ASL condition (39.4 ± 7.0 ml/[100 g × min]). By subtracting masked ASL from control ASL, we successfully visualized the hemilateral carotid artery’s perfusion territory. Conclusion: Intentional susceptibility artifacts with non-magnetic metals on the neck can mask spin labeling of the carotid artery. Furthermore, hemilateral carotid artery perfusion territories can be visualized in hemilaterally masked ASL. [ABSTRACT FROM AUTHOR]

Typical simultaneous blood oxygenation-level dependent (BOLD) and arterial spin labeling (ASL) sequences acquire two echoes, one perfusion-sensitive and one BOLD-sensitive. However, for ASL, spatial resolution and brain coverage are limited due to the T1 decay of the labeled blood. This study applies a sequence combining a multiband acquisition with four echoes for simultaneous BOLD and pseudo-continuous ASL (pCASL) echo planar imaging (MBME ASL/BOLD) for block-design task-fMRI. A multiband acceleration of four was employed to increase brain coverage and reduce slice-timing effects on the ASL signal. Multi-echo independent component analysis (MEICA) was implemented to automatically denoise the BOLD signal by regressing non-BOLD components. This technique led to increased temporal signal-to-noise ratio (tSNR) and BOLD sensitivity. The MEICA technique was also modified to denoise the ASL signal by regressing artifact and BOLD signals from the first echo time-series. The MBME ASL/BOLD sequence was applied to a finger-tapping task functional MRI (fMRI) experiment. Signal characteristics and activation were evaluated using single echo BOLD, combined ME BOLD, combined ME BOLD after MEICA denoising, perfusion-weighted (PW), and perfusion-weighted after MEICA denoising time-series. The PW data was extracted using both surround subtraction and high-pass filtering followed by demodulation. In addition, the CBF/BOLD response ratio and CBF/BOLD coupling were analyzed. Results showed that the MEICA denoising procedure significantly improved the BOLD signal, leading to increased BOLD sensitivity, tSNR, and activation statistics compared to conventional single echo BOLD data. At the same time, the denoised PW data showed increased tSNR and activation statistics compared to the non-denoised PW data. CBF/BOLD coupling was also increased using the denoised ASL and BOLD data. Our preliminary data suggest that the MBME ASL/BOLD sequence can be employed to collect whole-brain task-fMRI with improved data quality for both BOLD and PW time series, thus improving the results of block-design task fMRI. [ABSTRACT FROM AUTHOR]

To characterize and interpret arterial spin labeling (ASL) reactive hyperemia of calf muscles for a better understanding of the microcirculation in peripheral arterial disease (PAD), we present a physiological model incorporating oxygen transport, tissue metabolism, and vascular regulation mechanisms. The model demonstrated distinct effects between arterial stenoses and microvascular dysfunction on reactive hyperemia, and indicated a higher sensitivity of 2-minute thigh cuffing to microvascular dysfunction than 5-minute cuffing. The recorded perfusion responses in PAD patients (n = 9) were better differentiated from the normal subjects (n = 7) using the model-based analysis rather than characterization using the apparent peak and time-to-peak of the responses. The analysis results suggested different amounts of microvascular disease within the patient group. Overall, this work demonstrates a novel analysis method and facilitates understanding of the physiology involved in ASL reactive hyperemia. ASL reactive hyperemia with model-based analysis may be used as a noninvasive microvascular assessment in the presence of arterial stenoses, allowing us to look beyond the macrovascular disease in PAD. A subgroup who will have a poor prognosis after revascularization in the patients with critical limb ischemia may be associated with more severe microvascular diseases, which may potentially be identified using ASL reactive hyperemia. [ABSTRACT FROM AUTHOR]

Arterial Spin Labeled (ASL) perfusion MRI enables non-invasive, quantitative measurements of tissue perfusion, and has a broad range of applications including brain functional imaging. However, ASL suffers from low signal-to-noise ratio (SNR), limiting image resolution. Acquisitions using 3D readouts are optimal for background-suppression of static signals, but can be SAR intensive and typically suffer from through-plane blurring. In this study, we investigated the use of accelerated 3D readouts to obtain whole-brain, high-SNR ASL perfusion maps and reduce SAR deposition. Parallel imaging was implemented along the partition-encoding direction in a pseudo-continuous ASL sequence with background-suppression and 3D RARE Stack-Of-Spirals readout, and its performance was evaluated in three small cohorts. First, both non-accelerated and two-fold accelerated single-shot versions of the sequence were evaluated in healthy volunteers during a motor-photic task, and the performance was compared in terms of temporal SNR, GM-WM contrast, and statistical significance of the detected activation. Secondly, single-shot 1D-accelerated imaging was compared to a two-shot accelerated version to assess benefits of SNR and spatial resolution for applications in which temporal resolution is not paramount. Third, the efficacy of this approach in clinical populations was assessed by applying the single-shot 1D-accelerated version to a larger cohort of elderly volunteers. Accelerated data demonstrated the ability to detect functional activation at the subject level, including cerebellar activity, without loss in the perfusion signal temporal stability and the statistical power of the activations. The use of acceleration also resulted in increased GM-WM contrast, likely due to reduced through-plane partial volume effects, that were further attenuated with the use of two-shot readouts. In a clinical cohort, image quality remained excellent, and expected effects of age and sex on cerebral blood flow could be detected. The sequence is freely available upon request for academic use and could benefit a broad range of cognitive and clinical neuroscience research. [ABSTRACT FROM AUTHOR]

Structural MRI (sMRI)-identified tissue “growth” after neuropsychological training has been reported in many studies but the origins of those apparent tissue changes (ATC) still remain elusive. One possible contributor to ATC is brain perfusion since T1-weighted MRI, the tool used to identify ATC, is sensitive to perfusion-change induced tissue T1 alterations. To test the hypothetical perfusion contribution to ATC, sMRI data were acquired before and after short-term global and regional perfusion manipulations via intaking a 200 mg caffeine pill and performing a sensorimotor task. Caffeine intake caused a global CBF reduction and apparent tissue density reduction in temporal cortex, anterior cingulate cortex, and the limbic area; sensorimotor task induced CBF increase and apparent tissue increase in spatially overlapped brain regions. After compensating CBF alterations through a voxel-wise regression, the ATC patterns demonstrated in both experiments were substantially suppressed. These data clearly proved existence of the perfusion contribution to short-term ATC, and suggested a need for correcting perfusion changes in longitudinal T1-weighted structural MRI analysis if a short-term design is used. [ABSTRACT FROM AUTHOR]

Objective: To determine if perfusion in surgical cavity wall enhancement (SCWE) obtained in early post-treatment MR imaging can stratify time-to-progression (TTP) in glioblastoma. Materials and methods: This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL). The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. Results: The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03) and borderline significantly for reader 1 (P = 0.08). A positive perfusion state and (P = 0.02) a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2). The contrast enhancement pattern did not become a TTP predictor. Conclusion: Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP. [ABSTRACT FROM AUTHOR]

A novel sequence has been introduced that combines multiband imaging with a multi-echo acquisition for simultaneous high spatial resolution pseudo-continuous arterial spin labeling (ASL) and blood-oxygenation-level dependent (BOLD) echo-planar imaging (MBME ASL/BOLD). Resting-state connectivity in healthy adult subjects was assessed using this sequence. Four echoes were acquired with a multiband acceleration of four, in order to increase spatial resolution, shorten repetition time, and reduce slice-timing effects on the ASL signal. In addition, by acquiring four echoes, advanced multi-echo independent component analysis (ME-ICA) denoising could be employed to increase the signal-to-noise ratio (SNR) and BOLD sensitivity. Seed-based and dual-regression approaches were utilized to analyze functional connectivity. Cerebral blood flow (CBF) and BOLD coupling was also evaluated by correlating the perfusion-weighted timeseries with the BOLD timeseries. These metrics were compared between single echo (E2), multi-echo combined (MEC), multi-echo combined and denoised (MECDN), and perfusion-weighted (PW) timeseries. Temporal SNR increased for the MECDN data compared to the MEC and E2 data. Connectivity also increased, in terms of correlation strength and network size, for the MECDN compared to the MEC and E2 datasets. CBF and BOLD coupling was increased in major resting-state networks, and that correlation was strongest for the MECDN datasets. These results indicate our novel MBME ASL/BOLD sequence, which collects simultaneous high-resolution ASL/BOLD data, could be a powerful tool for detecting functional connectivity and dynamic neurovascular coupling during the resting state. The collection of more than two echoes facilitates the use of ME-ICA denoising to greatly improve the quality of resting state functional connectivity MRI. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of cerebral blood flow (CBF) by using arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging to differentiate glioblastoma (GBM) from brain metastasis. Materials and Methods: The institutional review board of our hospital approved this retrospective study. The study population consisted of 128 consecutive patients who underwent surgical resection and were diagnosed as either GBM (n = 89) or brain metastasis (n = 39). All participants underwent preoperative MR imaging including ASL. For qualitative analysis, the tumors were visually graded into five categories based on ASL-CBF maps by two blinded reviewers. For quantitative analysis, the reviewers drew regions of interest (ROIs) on ASL-CBF maps upon the most hyperperfused portion within the tumor and upon peritumoral T2 hyperintensity area. Signal intensities of intratumoral and peritumoral ROIs for each subject were normalized by dividing the values by those of contralateral normal gray matter (nCBFintratumoral and nCBFperitumoral, respectively). Visual grading scales and quantitative parameters between GBM and brain metastasis were compared. In addition, the area under the receiver-operating characteristic curve was used to evaluate the diagnostic performance of ASL-driven CBF to differentiate GBM from brain metastasis. Results: For qualitative analysis, GBM group showed significantly higher grade compared to metastasis group (p = 0.001). For quantitative analysis, both nCBFintratumoral and nCBFperitumoral in GBM were significantly higher than those in metastasis (both p < 0.001). The areas under the curve were 0.677, 0.714, and 0.835 for visual grading, nCBFintratumoral, and nCBFperitumoral, respectively (all p < 0.001). Conclusion: ASL perfusion MR imaging can aid in the differentiation of GBM from brain metastasis. [ABSTRACT FROM AUTHOR]

Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data. This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements. Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations. [ABSTRACT FROM AUTHOR]

Although arterial spin labeling (ASL) is appealing for mapping long-term changes in functional activity, inter-sessional variations in basal blood flow, arterial transit times (ATTs), and alignment errors, can result in significant false activation when comparing images from separate sessions. By taking steps to reduce these sources of noise, this study assessed the ability of ASL to detect functional CBF changes between sessions. ASL data were collected in three sessions to image ATT, resting CBF and CBF changes associated with motor activation (7 participants). Activation maps were generated using rest and task images acquired in the same session and from sessions separated by up to a month. Good agreement was found when comparing between-session activation maps to within-session activation maps with only a 16% decrease in precision (within-session: 90 ± 7%) and a 13% decrease in the Dice similarity (within-session: 0.75 ± 0.07) coefficient after a month. In addition, voxel-wise reproducibility (within-session: 4.7 ± 4.5%) and reliability (within-session: 0.89 ± 0.20) of resting grey-matter CBF decreased by less than 18% for the between-session analysis relative to within-session values. ATT variability between sessions (5.0 ± 2.7%) was roughly half the between-subject variability, indicating that its effects on longitudinal CBF were minimal. These results demonstrate that conducting voxel-wise analysis on CBF images acquired on different days is feasible with only modest loss in precision, highlighting the potential of ASL for longitudinal studies. [ABSTRACT FROM AUTHOR]

Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O-water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 ± 0.08, slope: 0.87 ± 0.22, intercept: 6.1 ± 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 ± 0.41 sec and 1.12 ± 0.30 sec, respectively, p <0.0005). CBF measurement using pCASL with delay compensation was feasible and fairly accurate even in altered hemodynamic states. [ABSTRACT FROM AUTHOR]

To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = −0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis. [ABSTRACT FROM AUTHOR]

Sjögren’s syndrome (SS) is characterized by hypofunction of the salivary and lacrimal glands. The salivary function is largely dependent upon the blood supply in the glands. However, the diseased states of the gland perfusion are not well understood. The arterial spin labeling (ASL) technique allows noninvasive quantitative assessment of tissue perfusion without the need for contrast agent. Here, we prospectively compared the perfusion properties of the parotid glands between patients with SS and those with healthy glands using ASL MR imaging. We analyzed salivary blood flow (SBF) kinetics of 22 healthy parotid glands from 11 volunteers and 28 parotid glands from 14 SS patients using 3T pseudo-continuous ASL imaging. SBF was determined in resting state (base SBF) and at 3 sequential segments after gustatory stimulation. SBF kinetic profiles were characterized by base SBF level, increment ratio at the SBF peak, and the differences in segments where the peak appeared (SBF types). Base SBFs of the SS glands were significantly higher than those of healthy glands (59.2 ± 22.8 vs. 46.3 ± 9.0 mL/min/100 g, p = 0.01). SBF kinetic profiles of the SS glands also exhibited significantly later SBF peaks (p < 0.001) and higher SBF increment ratios (74 ± 49% vs. 47 ± 39%, p = 0.04) than the healthy glands. The best SBF criterion (= 51.2 mL/min/100 mg) differentiated between control subjects and SS patients with 71% sensitivity and 82% specificity. Taken together, these results showed that the SS parotid glands were mostly hyperemic and the SS gland responses to gustatory stimulation were stronger and more prolonged than those of the healthy glands. The ASL may be a promising technique for assessing the diseased salivary gland vascularization of SS patients. [ABSTRACT FROM AUTHOR]

Background: White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. Methods: Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). Results: CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. Conclusion: The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Functional magnetic resonance imaging (fMRI) techniques highlight cerebral vascular responses which are coupled to changes in neural activation. However, two major difficulties arise when employing these techniques in animal studies. First is the disturbance of cerebral blood flow due to anaesthesia and second is the difficulty of precise reproducible quantitative measurements. These difficulties were surmounted in the current study by using propofol and quantitative arterial spin labelling (QASL) to measure relative cerebral blood volume of labelled water (rCBVlw), mean transit time (MTT) and capillary transit time (CTT). The ASL method was applied to measure the haemodynamic response in the primary somatosensory cortex following forepaw stimulation in the rat. Following stimulation an increase in signal intensity and rCBVlw was recorded, this was accompanied by a significant decrease in MTT (1.97±0.06s to 1.44±0.04s) and CTT (1.76±0.06s to 1.39±0.07s). Two animals were scanned repeatedly on two different experimental days. Stimulation in the first animal was applied to the same forepaw during the initial and repeat scan. In the second animal stimulation was applied to different forepaws on the first and second days. The control and activated ASL signal intensities, rCBVlw on both days were almost identical in both animals. The basal MTT and CTT during the second scan were also very similar to the values obtained during the first scan. The MTT recorded from the animal that underwent stimulation to the same paw during both scanning sessions was very similar on the first and second days. In conclusion, propofol induces little physiological disturbance and holds potential for longitudinal QASL fMRI studies. [Copyright &y& Elsevier]

Abstract: Knowledge regarding neural pain processing is primarily the result of studies involving models of brief cutaneous pain; however, clinical pain generally originates in deep tissue and is prolonged. This study measured the dynamic neural activation associated with a muscular pain model incorporating both acute and tonic states. Hypertonic saline (5% NaCl) was infused into the brachioradialis muscle of eleven healthy volunteers for 15min after an initial bolus of 0.5mL. Ten controls followed the same protocol with normal saline (0.9% NaCl). Magnetic resonance images of cerebral blood flow (CBF) were acquired using an arterial spin labelling method. The imaging volume extended from the thalamus to the primary somatosensory cortices, but did not include the brainstem and cerebellum. Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9±0.6 and remained near 5 for the remainder of the trial. Controls experienced minimal pain, reporting a peak value of 1.8±0.4. Significant CBF increases in rostral and caudal anterior insula bilaterally, anterior mid-cingulate cortex (aMCC), bilateral thalamus, and contralateral posterior insula were observed. The time courses of CBF revealed significant differences in the activation pattern during tonic pain. In particular, a more rapid return to baseline in aMCC versus insula was interpreted as a preferential decrease in the affective component of pain. This conclusion was supported by the strong correlation between pain intensity ratings and CBF in the contralateral insula (R 2 =0.911, p <0.01), which is a region believed to be responsible for pain intensity processing. [Copyright &y& Elsevier]

Background Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. [ABSTRACT FROM AUTHOR]

Cortisol 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. Here 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). The 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. Together, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain. • Cortisol affected lower neurophysiological coupling in cortical cognitive regions. • Higher neurophysiological coupling in subcortical regions after cortisol exposure. • Cortisol dosage is associated with disrupted neurophysiological coupling. [ABSTRACT FROM AUTHOR]