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

Noninvasive measurements of liver perfusion and fibrosis in cirrhotic small animals can help develop treatments for haemodynamic complications of liver disease. Here, we measure liver perfusion in cirrhotic rodents using flow‐sensitive alternating inversion recovery arterial spin labelling (FAIR ASL), evaluating agreement with previously validated caval subtraction phase‐contrast magnetic resonance imaging (PCMRI) total liver blood flow (TLBF). Baseline differences in cirrhotic rodents and the haemodynamic effects of acute inflammation were investigated using FAIR ASL and tissue T1. Sprague–Dawley rats (nine bile duct ligated [BDL] and ten sham surgery controls) underwent baseline hepatic FAIR ASL with T1 measurement and caval subtraction PCMRI (with two‐dimensional infra‐/supra‐hepatic inferior vena caval studies), induction of inflammation with intravenous lipopolysaccharide (LPS) and repeat liver FAIR ASL with T1 measurement after ~90 minutes. The mean difference between FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF was −51 ± 30 ml/min/100 g (Bland–Altman 95% limits‐of‐agreement ±258 ml/min/100 g). The FAIR ASL coefficient of variation was smaller than for caval subtraction PCMRI (29.3% vs 50.1%; P =.03). At baseline, FAIR ASL liver perfusion was lower in BDL rats (199 ± 32 ml/min/100 g vs sham 316 ± 24 ml/min/100 g; P =.01) but liver T1 was higher (BDL 1533 ± 50 vs sham 1256 ± 18 ms; P =.0004). Post‐LPS FAIR ASL liver perfusion response differences were observed between sham/BDL rats (P =.02), approaching significance in sham (+78 ± 33 ml/min/100 g; P =.06) but not BDL rats (−49 ± 40 ml/min/100 g; P =.47). Post‐LPS differences in liver tissue T1 were nonsignificant (P =.35). FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF agreement was modest, with significant baseline FAIR ASL liver perfusion and tissue T1 differences in rodents with advanced cirrhosis compared with controls. Following inflammatory stress, differences in hepatic perfusion response were detected between cirrhotic/control animals, but liver T1 was unaffected. Findings underline the potential of FAIR ASL in the assessment of vasoactive treatments for patients with chronic liver disease and inflammation. [ABSTRACT FROM AUTHOR]

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF‐CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look‐Locker flow‐sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBVa) using sequence parameters optimized for each contrast. Changes in total CBV (CBVtot) were measured using a gadolinium‐based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF‐CBVtot coupling constant αtot was measured as 0.16 ± 0.14 and the CBF‐CBVa coupling constant αa was measured as 0.65 ± 0.24. Using a two‐compartment model of the vasculature (arterial and venous), the change in venous CBV (CBVv) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD. The relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is critical to accurate modelling of the haemodynamics that underlie functional MRI. Three different techniques were used to measure changes in CBF, arterial CBV and total CBV in response to a visual stimulus. The coupling of these haemodynamic responses was assessed using a power law relationship. [ABSTRACT FROM AUTHOR]

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non-invasively; however, ASL techniques using only a single inflow time are not sufficient to fully characterize abnormal haemodynamic behaviour in SCA. This study investigated haemodynamic parameters from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18 years) children with SCA with and without silent cerebral infarction (SCI+/-) (n = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9 and 7 respectively). Compared with controls, CBF was elevated globally in both groups of patients. In the younger SCA patients, blood oxygen content was negatively correlated with CBF in the middle and posterior cerebral artery territories and significantly positively correlated with bolus arrival time (BAT) in the anterior and middle cerebral artery territories. In older children, SCA patients had significantly shorter BAT than healthy controls and there was a significant negative correlation between CBF and oxygen content only in the territory of the posterior cerebral artery, with a trend for a correlation in the anterior cerebral artery but no relationship for the middle cerebral artery territory. In the younger group, SCI+ patients had significantly higher CBF in the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI- mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached significance when two children with abnormal transcranial Doppler and one with haemoglobin SC disease were excluded, and there were no significant differences between patients with and without SCI in the older children. With age, there appears to be increasing disparity between patients and controls in terms of the relationship between CBF and oxygen content in the anterior circulation, potentially predicting the risk of acute and chronic compromise of brain tissue. [ABSTRACT FROM AUTHOR]

Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi-inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three-dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pulsed arterial spin labelling remains a non‐invasive and highly used method for the study of rodent cerebral blood flow (CBF). Flow‐sensitive alternating inversion recovery (FAIR) is one of the most commonly used MR‐sequences for this purpose and exists with many different strategies to record the images. This study investigates Look‐Locker (LL) TrueFISP readout for FAIR as an alternative to the standard EPI readout, which is provided by the manufacturer. The aim was to show the improved image quality using TrueFISP and to verify the reproducibility of the determination of the cerebral blood flow values. The measurement of many inversion points also allowed to investigate the influence of the correct blood relaxation rate on the fit of the CBF data. For the LL‐FAIR TrueFISP an in‐house written method was created. The method was tested on a group of C57BL/6 mice at the field strength of 9.4 T. The results show CBF maps with less distortion than for EPI and the values found are in good agreement with the literature. A comparison of the CBF values found with EPI and LL‐TrueFISP shows very small differences, most being not significant. In conclusion, the method presented gives equivalent CBF maps in comparison to standard FAIR‐EPI. Both methods have the same measurement time. TrueFISP has the advantage to EPI of producing undistorted images over larger areas of the mouse brain. It is advisable to check the value of the blood relaxation rate by measurement or to estimate it as a fitting parameter. [ABSTRACT FROM AUTHOR]