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Background Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers. Methods ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning. Results 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%. Conclusions ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischaemia (DCI) is the major cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (SAH). Recent experimental evidence from animal models has highlighted the need for non-invasive and robust measurements of brain tissue perfusion in patients in order to help understand the pathophysiology underlying DCI. Quantitative, serial, whole-brain cerebral perfusion measurements were obtained with pseudo-continuous arterial spin labelling (PCASL) magnetic resonance imaging (MRI) in six SAH patients acutely following endovascular coiling. This technique requires no injected contrast or radioactive isotopes. MRI scanning was well tolerated. Artefact from endovascular coils was minimal. PCASL MRI was able to detect time-dependent and patient-specific changes in voxel-wise and regional cerebral blood flow. These changes reflected changes in clinical condition. Data obtained in healthy controls using the same experimental protocol confirm the reliability and reproducibility of these results. This is the first study to use whole-brain, quantitative PCASL to identify time-dependent changes in cerebral blood flow at the tissue level in the acute period following SAH. This technique has the potential to better understand changes in cerebral pathophysiology as a consequence of aneurysm rupture. [ABSTRACT FROM AUTHOR]

Rationale: Quantitative neuroimaging studies show that different neuroleptics have similar effects on resting metabolism/perfusion in the basal ganglia, but vary in their effect on the cortex, especially in the prefrontal and temporal lobes. These differences may represent signatures of the action of medication on distinctive receptor combinations. Objectives: This study seeks to determine the effect on cerebral perfusion at rest of low-dose amisulpride, a neuroleptic with a receptor profile relatively selective to dopaminergic D2-receptors and both antidepressant and antipsychotic efficacy. Methods: Continuous arterial spin labelling in a placebo-controlled, double blind, crossover study at steady state of N = 20 healthy male adults. Results: Relative to placebo, amisulpride was associated with extensive and significant cortical decrements in resting perfusion levels, particularly in the prefrontal lobes ( p = 0.01, corrected). Decrements spared the basal ganglia, where perfusion was slightly increased. Conclusions: In contrast to earlier reports on other neuroleptics, amisulpride was associated with intense cortical perfusion decrements at rest. These results are consistent with an existing model in which dopaminergic blockade is associated not only with metabolism/perfusion increases in the basal ganglia, but also with decreases in the cerebral cortex that in most neuroleptics are compensated by action on other receptor systems. The selective receptor profile of amisulpride may explain the extensive cortical decrements. [ABSTRACT FROM AUTHOR]

Objectives: To investigate myocardial relaxation times and perfusion values in spontaneously hypertensive rats (SHRs) at various stages of the disease, with or without anti-fibrotic therapy, and to correlate magnetic resonance imaging (MRI) findings with histopathological myocardial fibrosis and capillary density. Methods: Five groups of rats underwent MRI at 4.7 T. They were either untreated or treated with an aldosterone-synthase inhibitor. T1, T2 and T2* relaxation times were determined and myocardial perfusion was quantified from an arterial spin labelling sequence. MR relaxation times and perfusion values were compared with the fibrotic content and capillary density of the myocardium obtained at histology after euthanasia. Results: T1 values significantly increased during the course of hypertensive disease, and correlated with myocardial fibrosis ( R = 0.71, P < 0.001); T2 values also increased but were weakly correlated with myocardial fibrosis ( R = 0.27, P = 0.047). Myocardial perfusion and capillary density significantly decreased with hypertensive disease but they did not correlate. Following prolonged treatment, we observed a trend associating T1 decrease and improved perfusion compared with untreated SHRs. Conclusions: Myocardial T1 and T2 values increase with hypertensive disease, whereas myocardial perfusion decreases. The correlation between T1 values and collagen density suggests that the former could be considered as a non-invasive marker of myocardial fibrosis. Key Points: • MR is increasingly used to assess alteration in myocardial tissue content. • MR relaxometry and perfusion can be assessed in rats without exogenous contrast agents. • Myocardial T1 and T2 values significantly increase during the course of hypertensive heart disease. • T1 values correlate significantly with myocardial collagen content. • Myocardial perfusion values decrease with hypertensive disease. [ABSTRACT FROM AUTHOR]

While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults ( n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation. [ABSTRACT FROM AUTHOR]

Introduction: This study seeks to evaluate the diagnostic accuracy of cerebral perfusion imaging with arterial spin labelling (ASL) MR imaging in children with moyamoya disease compared to dynamic susceptibility contrast (DSC) imaging. Methods: Ten children (7 females; age, 9.2 ± 5.4 years) with moyamoya disease underwent cerebral perfusion imaging with ASL and DSC on a 3-T MRI scanner in the same session. Cerebral perfusion images were acquired with ASL (pulsed continuous 3D ASL sequence, 32 axial slices, TR = 5.5 s, TE = 25 ms, FOV = 24 cm, matrix = 128 × 128) and DSC (gradient echo EPI sequence, 35 volumes of 28 axial slices, TR = 2,000 ms, TE = 36 ms, FOV = 24 cm, matrix = 96 × 96, 0.2 ml/kg Gd-DOTA). Cerebral blood flow maps were generated. ASL and DSC images were qualitatively assessed regarding perfusion of left and right ACA, MCA, and PCA territories by two independent readers using a 3-point-Likert scale and quantitative relative cerebral blood flow (rCBF) was calculated. Correlation between ASL and DSC for qualitative and quantitative assessment and the accuracy of ASL for the detection of reduced perfusion per territory with DSC serving as the standard of reference were calculated. Results: With a good interreader agreement (κ = 0.62) qualitative perfusion assessment with ASL and DSC showed a strong and significant correlation (ρ = 0.77; p < 0.001), as did quantitative rCBF ( r = 0.79; p < 0.001). ASL showed a sensitivity, specificity and accuracy of 94 %, 93 %, and 93 % for the detection of reduced perfusion per territory. Conclusion: In children with moyamoya disease, unenhanced ASL enables the detection of reduced perfusion per vascular territory with a good accuracy compared to contrast-enhanced DSC. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

The interruption of blood flow results in impaired oxygenation and metabolism. This can lead to electrophysiological changes, functional impairment and symptoms in quick succession. Quantitative measures of organ perfusion, perfusion reserve and tissue oxygenation are crucial to assess normal tissue metabolism and function., Magnetic resonance imaging ( MRI) provides a number of quantitative methods to assess physiology in the kidney. Blood oxygenation level-dependent ( BOLD) MRI provides a method for the assessment of oxygenation. Blood flow to the kidney can be assessed using phase contrast MRI. Dynamic contrast-enhanced MRI and arterial spin labelling ( ASL) provide methods to assess tissue perfusion, ASL using the magnetization of endogenous water protons and thus providing a non-invasive method to assess perfusion. The application of diffusion-weighted MRI allows molecular motion in the kidney to be measured. Novel techniques can also be used to assess oxygenation in the renal arteries and veins and, combined with flow measures, provide an estimation of oxygen metabolism., Magnetic resonance imaging provides a synergy of non-invasive techniques to study renal function and the demand for these techniques is likely to be driven by the incentive to avoid the use of contrast media, to avoid radiation and to avoid complications with intervention procedures. [ABSTRACT FROM AUTHOR]

The article presents research that examines the influence of various magnetic resonance imaging (MRI) and clinical characteristics on cortical perfusion in multiple sclerosis (MS). The study shows the correlation between the perfusion and duration of the disease. It suggests that white matter lesions serve as a reduced perfusion and reduced metabolic demand at a cortical level.

Abstract: We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Nav1.7. The patient reported severe ongoing foot pain, which was exquisitely sensitive to limb cooling. We confirmed this heat hypersensitivity using quantitative sensory testing. Additionally, we employed a novel perfusion imaging technique in a simple block design to assess her baseline erythromelalgia pain vs cooling relief. Robust activations of key pain, pain-affect, and reward-related centres were observed. This combined approach allowed us to confirm the presence of a temperature-sensitive channelopathy of peripheral neurons and to investigate the neural correlates of tonic neuropathic pain and relief in a single subject. [Copyright &y& Elsevier]

Abstract: Arterial spin labelling (ASL) MRI offers a non-invasive means to create blood-borne contrast in vivo for dynamic angiographic imaging. By spatial modulation of the ASL process it is possible to uniquely label individual arteries over a series of measurements, allowing each to be separately identified in the resulting angiographic images. This separation requires appropriate analysis for which a general Bayesian framework has previously been proposed. Here this framework is adapted for clinical dynamic angiographic imaging. This specifically addresses the issues of computational speed of the algorithm and the robustness required to deal with real patient data. An algorithm is proposed that can incorporate planning information about the arteries being imaged whilst adapting for subsequent patient movement. A fast maximum a posteriori solution is adopted and shown to be only marginally less accurate than Monte Carlo sampling under simulation. The final algorithm is demonstrated on in vivo data with analysis on a time scale of the order of 10min, from both a healthy control and a patient with a vertebro-basilar occlusion. [Copyright &y& Elsevier]

Objective: We evaluated the sensitivity of pulsed Arterial Spin Labelling (pASL) for the detection of changes in regional cerebral blood perfusion (CBP) during and after intra-venous (i.v.) infusion of an opioid agonist (fentanyl) and an opioid antagonist (naloxone). Materials and methods: Twenty-three subjects were scanned four times, receiving i.v. infusion of fentanyl, naloxone, placebo and a second fentanyl administration, in four separate scanning sessions in randomised order. End-tidal CO, respiration rate and heart rate were recorded continuously throughout each scan. pASL time series were collected using single shot EPI for 15 min (including 5 min of baseline prior to infusion). Results: Significant increases in CBP were detected during and after administration of fentanyl, (when compared to placebo and naloxone), in most areas of high concentration of mu-opioid receptors (thalamus, lingual gyrus, para-hippocampal gyrus, and insula); near-significant increases were also observed in the insula. No increases in perfusion were observed during or after naloxone infusion. No correlation was found between regional rCBF changes and end-tidal CO, respiration rate or heart rate. Good reliability was found between the first and second fentanyl sessions but the regions of high reliability did not overlap completely with those of highest perfusion change. Conclusion: pASL is a suitable method for examining rapid, dynamic effects of opioid administration on brain physiology. [ABSTRACT FROM AUTHOR]

Object: Arterial spin labelling (ASL) can be used to measure renal perfusion non-invasively. The aim of this study was to determine the repeatability of this technique in healthy kidneys to vindicate its use in clinic. Materials and methods: Two groups of healthy volunteers were imaged two different days to assess intra- and inter-session repeatability. Oblique-coronal data volumes were acquired on a 1.5 T scanner with a dedicated abdominal 32-channel body phased array coil. ASL was performed using a multi-TI FAIR labelling scheme and 3D GRASE imaging module. Background suppression and respiratory triggering were used. T maps of the kidney were acquired using the same sequence with background suppression disabled. Results: For the group with multiple intra-session ASL measurements, the average cortical perfusion was 197 mL min100 g and average cortical T was 1265 ms. For both perfusion and T the variation shown by the within-subject standard deviation (SDws) (14.6 mL min100 g and 33.4 ms) and coefficient of variation (CVws) (7.52 and 2.69%, respectively) was small for all the analyses carried out. Bland-Altman plots were also used to visualise the variation between the same parameters collected from the different scanning sessions in both groups, and demonstrated good reproducibility. Conclusion: We have shown that in healthy volunteers, ASL parameters are repeatable over a short and long period. This supports the overall aim of using ASL in the clinic to assess longitudinal renal perfusion changes in patients. [ABSTRACT FROM AUTHOR]

Since its inception in the early 1990s, arterial spin labelling (ASL) has been developed in numerous variants. Tremendous improvements in both pulse sequences and hardware have allowed improved image quality and reduced scan time, to the point where the technique might be ready for clinical application. However, although now routinely used in research centres and universities, its application in daily clinical routine remains restricted to a few centres. Its popularity in magnetic resonance imaging (MRI) research centres and among physicists may have contributed to the lack of enthusiasm from the clinical community, as the variety of possible sequences available might deter even the most die-hard technology-driven neuroradiologist from using this technique. Therefore, a joint action directed towards the harmonisation of all the existing ASL pulse sequences and the development of a reliable and common post-processing pipeline to provide guidance for the major MRI manufacturers was recently endeavoured and dubbed the 'ASL Network' (). This network was established to provide a communication platform among physicists, engineers and clinicians who are keen to see this technique finally make it to daily clinical practice. Finally, a networking European Grant from the COST Office was secured to help fund some of the activities of the ASL Network, in particular as they pertain to the application of ASL in dementia (). Here, both the ASL Network and the COST Action are described, with their respective goals and aspirations. [ABSTRACT FROM AUTHOR]

Investigating pharmacological modulation of brain activity using magnetic resonance imaging (MRI) presents an exciting opportunity to bridge the gap between preclinical and clinical studies, and holds the potential to be a useful tool in the discovery and development of novel therapeutic agents. Most functional MRI studies to date have utilized the blood oxygen level dependent (BOLD) contrast mechanism. Although this has some advantages over other techniques and is widely available, BOLD has two significant limitations for the study of drug effects; it is an indirect measurement of neuronal function, and produces only a relative (non-quantitative) measure of blood dynamics. Here we describe the various experimental manipulations that have been used to reduce the impact of these limitations, and discuss new ways of collecting and analysing imaging data that allow us to assess functional connectivity of the brain. We recommend some complementary techniques (such as arterial spin labelling and magnetoencephalography) that, if used in conjunction with BOLD functional MRI, will increase the interpretability and thus the utility of MRI for pharmacology research. [ABSTRACT FROM PUBLISHER]

Objective: To compare measurements of the arterial blood volume (aBV), a perfusion parameter calculated from arterial spin labelling (ASL), and cerebral blood volume (CBV), calculated from dynamic susceptibility contrast (DSC) MRI. In the clinic, CBV is used for grading of intracranial tumours. Materials and methods: Estimates of aBV from the model-free ASL technique quantitative STAR labelling of arterial regions (QUASAR) experiment and of DSC-CBV were obtained at 3T in ten patients with eleven tumours (three grade III gliomas, four glioblastomas and four meningiomas, two in one patient). Parametric values of aBV and CBV were determined in the tumour as well as in normal grey matter (GM), and tumour-to-GM aBV and CBV ratios were calculated. Results: In a 4-pixel ROI representing maximal tumour values, the coefficient of determination R was 0.61 for the comparison of ASL-based aBV tumour-to-GM ratios and DSC-MRI-based CBV tumour-to-GM ratios and 0.29 for the comparison of parametric values of ASL-aBV and DSC-CBV, under the assumption of proportionality. Both aBV and CBV showed a non-significant tendency to increase when going from grade III gliomas to glioblastomas to meningiomas. Conclusion: These results suggest that measurement of aBV is a potential tool for non-invasive assessment of blood volume in intracranial tumours. [ABSTRACT FROM AUTHOR]

There is a need for objective imaging markers of Parkinson’s disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson’s disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson’s disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson’s disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson’s disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Abstract: This study investigates the emergence of characteristic patterns in clusters thresholded at uncorrected significance levels, using as a case study rest perfusion images obtained with the continuous arterial spin labelling technique (CASL). The origin of these patterns is traced back to the existence of large-scale spatial covariance, a violation of the stationarity assumption on the spatial distribution of residual errors. It is shown that in the presence of large-scale covariance, several principles or intuitions common among experimenters when evaluating the inferential strength of their analyses are not applicable. Thresholded maps and clusters are confounded by the spatial patterns of large-scale covariance, irrespective of the existence of a true effect, as shown in t maps constructed by resampling groups at random from a large pool of volumes. Filtering clusters according to their size made the problem worse, and corrections on cluster size based on random field theory models of smoothness had only a minor impact on their tendency to appear in characteristic locations. A formal analysis shows that the large-scale covariance at the origin of these problems is retained in the parametric map irrespective of sample size. Therefore, neither sample independence nor sample size protect from replications of effects being confounded by replications of the spatial covariance of residual errors. In contrast, cluster peaks were not affected by large-scale covariance but only by local differences in smoothness levels, as predicted by random field theory for the distribution of maxima, highlighting the different inferential robustness of cluster-based and maxima-based statistics. A framework is provided to generalize these results to mixed effects models with nested random effects, applicable also to activation studies. Large-scale nonstationarity is most problematic when the variance source at the origin of the characteristic patterns is not specific to a function or variable involved in the inferential process, as typically in observational studies of individual differences. These results raise the question of the existence and impact of large-scale nonstationarity in studies with data obtained with other techniques. [Copyright &y& Elsevier]

Abstract: Arterial spin labeling (ASL) is a promising non-invasive magnetic resonance imaging (MRI) technique for measuring regional cerebral blood flow (rCBF) or perfusion in vivo. To evaluate the feasibility of ASL as a biomarker for clinical trials, it is important to examine test-retest reproducibility. We investigated both inter- and intra-session reproducibility of perfusion MRI using a pulsed ASL (PASL) sequence PICORE Q2TIPS with an echo-planar imaging (EPI) readout. Structural MRI regions of interest (ROIs) were extracted individually by automated parcellation and segmentation methods using FreeSurfer. These cortical and subcortical ROIs were used to assess regional perfusion stability. Our results indicated regional variability in grey matter rCBF. Although rCBF measurements were characterized by intersubject variation, our results also indicated relatively less within-subject variability estimated as within-subject standard deviation (SDW) (intersession SDW: 2.0 to 8.8; intrasession SDW: 2.8 to 9.6) and acceptable reliabilities as measured using intraclass correlation coefficient (ICC) (intersession ICC: 0.68 to 0.94; intrasession ICC: 0.66 to 0.95) for regional MRI perfusion measurements using the PICORE Q2TIPS technique. Overall, our findings suggest that PASL is a technique with good within and between session reproducibility. Further reproducibility studies in target populations relevant for specific clinical trials of neurovascular related agents will be important and the present results provide a framework for such assessments. [ABSTRACT FROM AUTHOR]

Purpose: Principles of magnetic resonance imaging techniques providing perfusion-related contrast weighting without administration of contrast media are reported and analysed systematically. Especially common approaches to arterial spin labelling (ASL) perfusion imaging allowing quantitative assessment of specific perfusion rates are described in detail. The potential of ASL for perfusion imaging was tested in several types of tissue. Methods: After a systematic comparison of technical aspects of continuous and pulsed ASL techniques the standard kinetic model and tissue properties of influence to quantitative measurements of perfusion are reported. For the applications demonstrated in this paper a flow-sensitive alternating inversion recovery (FAIR) ASL perfusion preparation approach followed by true fast imaging with steady precession (true FISP) data recording was developed and implemented on whole-body scanners operating at 0.2, 1.5 and 3 T for quantitative perfusion measurement in various types of tissue. Results: ASL imaging provides a non-invasive tool for assessment of tissue perfusion rates in vivo. Images recorded from kidney, lung, brain, salivary gland and thyroid gland provide a spatial resolution of a few millimetres and sufficient signal to noise ratio in perfusion maps after 2–5 min of examination time. Conclusions: Newly developed ASL techniques provide especially high image quality and quantitative perfusion maps in tissues with relatively high perfusion rates (as also present in many tumours). Averaging of acquisitions and image subtraction procedures are mandatory, leading to the necessity of synchronization of data recording to breathing in abdominal and thoracic organs. [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]

Arterial spin labelling (ASL) can noninvasively isolate the MR signal from arterial blood water that has flowed into the brain. In gray matter, the labelled bolus is dispersed within three main compartments during image acquisition: the intravascular compartment; intracellular tissue space; and the extracellular tissue space. Changes in the relative volumes of the extracellular and intracellular tissue space are thought to occur in many pathologic conditions such as stroke and brain tumors. Accurate measurement of the distribution of the ASL signal within these three compartments will yield better understanding of the time course of blood delivery and exchange, and may have particular application in animal models of disease to investigate the relationship between the source of the ASL signal and pathology. In this study, we sample the transverse relaxation of the ASL perfusion weighted and control images acquired with and without vascular crusher gradients at a range of postlabelling delays and tagging durations, to estimate the tricompartmental distribution of labelled water in the rat cortex. Our results provide evidence for rapid exchange of labelled blood water into the intracellular space relative to the transit time through the vascular bed, and provide a more solid foundation for cerebral blood flow quantification using ASL techniques. [ABSTRACT FROM AUTHOR]

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]

Loss of pancreatic beta cell mass and function leads to the development of diabetes mellitus. Currently there is no technical way to non-invasively image islet function and mass. Murine models suggest that islets are highly vascularised organs that make a significant contribution to the total pancreatic blood flow. The current study was undertaken to test with arterial spin labelling (ASL) magnetic resonance imaging if islet mass and/or stimulation of human pancreatic islets by hyperglycaemia can differentially increase whole-pancreas perfusion, thereby distinguishing non-diabetic from type 1 diabetic patients. We assessed pancreatic blood flow using ASL at baseline, during a hyperglycaemia clamp study (glucose at 11 mmol/l) and during recovery to euglycaemia. Seventeen healthy volunteers and seven type 1 diabetic patients were studied. In healthy volunteers we observed no change in pancreatic blood flow during the three phases of the study. A trend for an increase in blood flow was observed in the two control tissues, the liver and kidney. Similarly, there was no significant difference in blood flow during the three stages (baseline, hyperglycaemia and recovery) in diabetic patients and there was no significant difference observed between diabetic patients and normal volunteers. Our data suggest that in humans neither increased demand nor islet mass has a substantial influence on pancreatic perfusion. It is possible, however, that the current state-of-the art imaging technology employed in this study might not be sensitive enough to distinguish between a true effect and noise. ClinicalTrials.gov NCT00280085 This study was fully funded by a grant from Pfizer. [ABSTRACT FROM AUTHOR]

Objective: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes. Materials and methods: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia. Results: The mean regional CBF was significantly lower in patients with MTBI (45.9 ± 9.8 ml/100 g min-1) as compared to normal controls (57.1 ± 8.1 ml/100 g min-1; p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients. Conclusions: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease. [ABSTRACT FROM AUTHOR]

• A case-control meta-analysis and meta-regression of arterial spin labelling studies in patients with major depression disorder. • Increased cerebral blood flow in the inferior parietal lobule, the striatum, and the bilateral thalamus was observed in patients. • Decreased cerebral blood flow in the inferior frontal gyrus, the insula, the middle occipital gyrus and the bilateral superior temporal gyrus was observed in patients. Accumulating evidence has suggested that patients with major depressive disorder (MDD) could exhibit resting-state cerebral blood flow (CBF) abnormalities. However, findings across studies are controversial. Our study aimed at identifying replicable CBF changes in MDD by conducting a case-control meta-analysis and meta-regression of arterial spin labelling studies using seed-based d mapping software. Fourteen studies encompassing 505 patients with MDD and 443 healthy controls were included. We found increased CBF in the inferior parietal lobule, the striatum, and the bilateral thalamus in all patients with MDD relative to healthy controls. While decreased CBF was observed in the inferior frontal gyrus, the insula, the middle occipital gyrus and the bilateral superior temporal gyrus in patients with MDD. Moreover, increased CBF of the bilateral thalamus was associated with more severe depressive symptoms in patients with MDD. The subgroup meta-analysis showed that patients with acute phase had increased CBF in the bilateral thalamus, and decreased CBF in the left middle occipital gyrus and the left middle frontal gyrus. Chronic patients had decreased CBF in the left insula, the right calcarine sulcus, the right inferior frontal gyrus, and the left parahippocampal gyrus. Patients with medication-free had increased CBF in the right anterior cingulate cortex/medial prefrontal cortex, and decreased CBF in the left middle occipital gyrus, the left inferior frontal gyrus, and the left precentral gyrus. These findings suggest an aberrant cerebral blood flow pattern of MDD involving the cortico-striatal-thalamic circuit, which may facilitate understanding of pathophysiology and suggest potential neural biomarkers for clinical assessment, monitoring and interventions of MDD. One important limitation is that eight recruited studies in our meta-analysis have recruited more males than females, which may have a selection bias of patients. [ABSTRACT FROM AUTHOR]

Despite improvement in the specific treatment, clinical and anatomo-functional central nervous system (CNS) abnormalities of various severities are still observed in cystinosis patients. Patients who develop CNS complications today have a worse compliance to cysteamine treatment. Radiological studies have shown that cortical or central (ventriculomegaly) atrophy is observed in more than two thirds of cystinosis patients' magnetic resonance imaging (MRI) and correlates with the intelligence quotient score. Half of cystinosis patients have marked aspecific white matter hyperintensities. The development of advanced neuroimaging techniques provides new tools to further investigate CNS complications. A recent neuroimaging study using a voxel-based morphometry approach showed that cystinosis patients present a decreased grey matter volume in the left middle frontal gyrus. Diffusion tensor imaging studies have shown white matter microstructure abnormalities in children and adults with cystinosis, respectively in areas of the dorsal visual pathway and within the corpus callosum's body. Finally, leucocyte cystine levels are associated with decreased resting cerebral blood flow, measured by arterial spin labelling, in the frontal cortex, which could be associated with the neurocognitive deficits described in these patients. These results reinforce the relevance of neuroimaging studies to further understand the mechanisms that underline CNS impairments. [ABSTRACT FROM AUTHOR]

Abstract: When modelling FMRI and other MRI time-series data, a Bayesian approach based on adaptive spatial smoothness priors is a compelling alternative to using a standard generalized linear model (GLM) on presmoothed data. Another benefit of the Bayesian approach is that biophysical prior information can be incorporated in a principled manner; however, this requirement for a fixed non-spatial prior on a parameter would normally preclude using spatial regularization on that same parameter. We have developed a Gaussian-process-based prior to apply adaptive spatial regularization while still ensuring that the fixed biophysical prior is correctly applied on each voxel. A parameterized covariance matrix provides separate control over the variance (the diagonal elements) and the between-voxel correlation (due to off-diagonal elements). Analysis proceeds using evidence optimization (EO), with variational Bayes (VB) updates used for some parameters. The method can also be applied to non-linear forward models by using a linear Taylor expansion centred on the latest parameter estimates. Applying the method to FMRI with a constrained haemodynamic response function (HRF) shape model shows improved fits in simulations, compared to using either the non-spatial or spatial-smoothness prior alone. We also analyse multi-inversion arterial spin labelling data using a non-linear perfusion model to estimate cerebral blood flow and bolus arrival time. By combining both types of prior information, this new prior performs consistently well across a wider range of situations than either prior alone, and provides better estimates when both types of prior information are relevant. [Copyright &y& Elsevier]

The article examines the magnetic resonance (MR) perfusion techniques and its potential benefits in the context of the diagnosis, staging, therapeutic response and prognosis in patients who have intracranial tumours. The two major MR methods that have been developed and applied to the assessment of brain perfusion are Dynamic Susceptibility Contrast (DSC) imaging and Arterial Spin Labelling (ASL). It cites that the implementation of individual patient quantitation when utilizing the DSC method may result to improve clinical utility by minimisation of normal variation and increase in pathological specificity. It suggests further study in the form of well controlled, large scale clinical studies are needed to assure the pathology-specific imaging efficacy of DSC and ASL techniques.

Arterial spin labelling (ASL) has proved to be a promising magnetic resonance imaging (MRI) technique to measure brain perfusion. In this study, volumetric three-dimensional (3D) gradient and spin echo (GRASE) ASL was used to produce cerebral blood flow (CBF) and arterial arrival time (AAT) maps during rest and during an infusion of remifentanil. Gradient and spin echo ASL perfusion-weighted images were collected at multiple inflow times (500 to 2,500 ms in increments of 250 ms) to accurately fit an ASL perfusion model. Fit estimates were assessed using z-statistics, allowing voxels with a poor fit to be excluded from subsequent analyses. Nonparametric permutation testing showed voxels with a significant difference in CBF and AAT between conditions across a group of healthy participants (N=10). Administration of remifentanil produced an increase in end-tidal CO2, an increase in CBF from 57±12.0 to 77±18.4 mL/100 g tissue per min and a reduction in AAT from 0.73±0.073 to 0.64±0.076 secs. Within grey matter, remifentanil produced a cerebrovascular response of 5.7±1.60 %CBF per mm Hg. Significant differences between physiologic conditions were observed in both CBF and AAT maps, indicating that 3D GRASE-ASL has the sensitivity to study changes in physiology at a voxel level.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1514–1522; doi:10.1038/jcbfm.2008.46; published online 28 May 2008 [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To identify regional arterial input functions (AIFs) using factor analysis of dynamic studies (FADS) when quantification of perfusion is performed using model-free arterial spin labelling. Material and Methods: Five healthy volunteers and one patient were examined on a 3-T Philips unit using quantitative STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved, one where the arterial signal had been crushed and another where it was retained. FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion maps were obtained using block-circulant SVD deconvolution and regional AIFs obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h. The patient was also examined using dynamic susceptibility contrast MRI. Results: In the healthy volunteers, CBF was 64±10 ml/[min 100 g] (mean±S.D.) in GM and 24±4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM. Discussion: Good CBF image quality and reasonable quantitative CBF values were obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a useful supplement in the evaluation of ASL data using QUASAR. [Copyright &y& Elsevier]

Graded levels of supplemental inspired oxygen were investigated for their viability as a noninvasive method of obtaining intravascular magnetic resonance image contrast. Administered hyperoxia has been shown to be effective as a blood oxygenation level-dependent contrast agent for magnetic resonance imaging (MRI); however, it is known that high levels of inspired fraction of oxygen result in regionally decreased perfusion in the brain potentially confounding the possibility of using hyperoxia as a means of measuring blood flow and volume. Although the effects of hypoxia on blood flow have been extensively studied, the hyperoxic regime between normoxia and 100% inspired oxygen has been only intermittently studied. Subjects were studied at four levels of hyperoxia induced during a single session while perfusion was measured using arterial spin labelling MRI. Reductions in regional perfusion of grey matter were found to occur even at moderate levels of hyperoxia; however, perfusion changes at all oxygen levels were relatively mild (less than 10%) supporting the viability of hyperoxia-induced contrast.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 69–75. doi:10.1038/sj.jcbfm.9600319; published online 3 May 2006 [ABSTRACT FROM AUTHOR]

Rationale and objective: This study sought to assess the feasibility of arterial spin labeling (ASL) blood flow (BF) magnetic resonance imaging (MRI) for the study of metastatic renal cell carcinoma (RCC) in the body, where the respiratory, cardiac, and peristaltic motions present challenges when applying ASL. Materials and methods: ASL was performed using a background-suppressed single-section flow-alternating inversion recovery (FAIR) preparation and a single-shot fast spin-echo imaging sequence on a 3.0-T whole body imager. Tumor BF was evaluated for 26 patients with RCC metastatic to the liver, bone, lung, or lymph nodes before VEGF receptor inhibitor therapy. Two cases with tumor size change after treatment were also scanned 1 month after therapy. For validation, kidney cortex BF in five normal volunteers was measured with the same technique and compared with literature values. Results: ASL was successfully performed in all normal volunteers and in 20 of 26 patients. The six failures resulted from a systematic error, which can be avoided in future studies. For normal volunteers, measured kidney cortex BF was 275 ± 14 mL/min/100 g, a value consistent with the literature. ASL determined tumor BF averaged across tumor volume and subjects was 194 mL/min/100 g (intersubject SD = 100), resulting in high perfusion signal and conspicuity of lesions. Bright signal was also seen in large vessels and occasionally in bowel. In the two cases studied 1 month after therapy, ASL perfusion changes were consistent with tumor size changes. Conclusion: With background suppression, ASL MRI is a feasible method for quantifying BF in patients with renal cell carcinoma. This technique may be useful for evaluating tumor response to antiangiogenic agents. [Copyright &y& Elsevier]

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test-retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test-retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM).We conclude that pCASL has high test-retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015)., (© 2021. The Author(s).)

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the common causes of neurological injury in full-term neonates following perinatal asphyxia. The conventional magnetic resonance technique has low sensitivity in detecting variations in cerebral blood flow in patients with HIE., Objective: This article evaluates the clinical diagnostic value of three-dimensional pseudo-continuous arterial spin labelling (3-D pcASL) perfusion magnetic resonance imaging (MRI) for early prediction of neurobehavioral outcomes in full-term neonates with HIE., Materials and Methods: All neonates diagnosed with HIE underwent MRI (conventional and 3-D pcASL perfusion MRI). Cerebral blood flow values were measured in the basal ganglia (caudate nuclei, lenticular nuclei), thalami and white matter regions (frontal lobes, corona radiata). After 1-month follow-up, the Neonatal Behavioral Neurological Assessment scores were used to divide patients into favourable outcome group versus adverse outcome group., Results: Twenty-three patients were enrolled in this study. There were no statistical differences between the symmetrical cerebral blood flow values of bilateral basal ganglia, thalami and white matter regions. However, the cerebral blood flow values of grey matter nuclei were higher than the white matter regions. The average value of cerebral blood flow in the basal ganglia and thalami in the adverse outcome group was 37.28±6.42 ml/100 g/min, which is greater than the favourable outcome group (22.55 ± 3.21 ml/100 g/min) (P<0.01). The area under the curve (AUC) of 3-D pcASL perfusion MRI was 0.992 with a cutoff value of 28.75 ml/100 g/min, with a Youden's index of 0.9231. The sensitivity and specificity were 92.3% and 100%, respectively., Conclusion: The 3-D pcASL demonstrated higher perfusion alteration in the basal ganglia and thalami of neonatal HIE with adverse outcomes. The 3-D pcASL perfusion MRI has the potential to predict neurobehavioral outcomes of neonates with HIE., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s).)