Consensus-based technical recommendations for clinical translation of renal ASL MRI

OBJECTIVES: This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. METHODS: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. RESULTS: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. DISCUSSION: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding

Consensus-based technical recommendations for clinical translation of renal ASL MRI

Objectives: To develop technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5T and 3T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-center clinical studies.Methods: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting.Results: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labeling with a single-slice spin-echo EPI readout with background suppression, and a simple but robust quantification model.Discussion: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data becomes available, since the renal ASL literature is rapidly expanding

Influence of labeling parameters and respiratory motion on velocity-selective arterial spin labeling for renal perfusion imaging

Purpose Arterial transit time uncertainties and challenges during planning are potential issues for renal perfusion measurement using spatially selective arterial spin labeling techniques. To mitigate these potential issues, a spatially non-selective technique, such as velocity-selective arterial spin labeling (VSASL), could be an alternative. This article explores the influence of VSASL sequence parameters and respiratory induced motion on VS-label generation. Methods VSASL data were acquired in human subjects (n= 15), with both single and dual labeling, during paced-breathing, while essential sequence parameters were systematically varied; (1) cutoff velocity, (2) labeling gradient orientation and (3) post-labeling delay (PLD). Pseudo-continuous ASL was acquired as a spatially selective reference. In an additional free-breathing single VSASL experiment (n= 9) we investigated respiratory motion influence on VS-labeling. Absolute renal blood flow (RBF), perfusion weighted signal (PWS), and temporal signal-to-noise ratio (tSNR) were determined. Results (1) With decreasing cutoff velocity, tSNR and PWS increased. However, undesired tissue labeling occurred at low cutoff velocities (<= 5.4 cm/s). (2) Labeling gradient orientation had little effect on tSNR and PWS. (3) For single VSASL high signal appeared in the kidney pedicle at PLD < 800 ms, and tSNR and PWS decreased with increasing PLD. For dual VSASL, maximum tSNR occurred at PLD = 1200 ms. Average cortical RBF measured with dual VSASL (264 +/- 34 mL/min/100 g) at a cutoff velocity of 5.4 cm/s, and feet-head labeling was slightly lower than with pseudo-continuous ASL (283 +/- 55 mL/min/100 g). Conclusion With well-chosen sequence parameters, tissue labeling induced by respiratory motion can be minimized, allowing to obtain good quality RBF maps using planning-free labeling with dual VSASL.Cardiovascular Aspects of Radiolog

Multi-organ comparison of flow-based arterial spin labeling techniques: spatially non-selective labeling for cerebral and renal perfusion imaging

Purpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]).Methods Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney).Results In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B-1-inhomogeneity. All ASL techniques were relatively robust to respiratory motion.Conclusion In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B-1-sensitivity of VSI-ASL is necessary to match the performance of FAIR.Neuro Imaging Researc

Measurements of Pre-Clinical Liver Perfusion Using Arterial Spin Labelling MRI

Magnetic Resonance Imaging (MRI) has been at the focus of medical research as its availability and fidelity has improved in the last thirty years. MRI offers both high spatial resolution and excellent soft tissue contrast compared to complimentary medical imaging techniques, without the need to expose patients to ionising radiation. Novel MRI methods that utilise the intrinsic body water signal are still being developed and refined. Arterial Spin Labelling (ASL) MRI provides a non-invasive method to measure tissue perfusion, which has been extensively applied in the brain, and demonstrated pre-clinically in the heart and kidneys. However, there is currently no literature reporting the development and use pre-clinical liver ASL – possibly due to complex methodology and quantification necessary in small animals. Clinical liver perfusion imaging is predominantly carried out using an injected Gadolinium-based contrast agent; this technique can be challenging to quantify, cannot be immediately re-administered and may have complications for patients with renal impairment. A methodology to measure liver perfusion without the need for a contrast agent would find utility in a number of different hepatic diseases; monitoring pathophysiology and therapy efficacy. This research investigates the feasibility of a pre-clinical measure of liver perfusion using ASL and its potential application to a pre-clinical model of hepatic disease. We aim to apply the method to monitor novel therapy efficacy in pre-clinical disease models, to eventually translate both therapy and hepatic ASL into the clinical environment

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status

Feasibility of using Arterial Spin Labeling for Detecting Longitudinal Changes in Cerebral Blood Flow

The ability of the perfusion MRI technique, arterial spin labeling (ASL), to quantify cerebral blood flow (CBF) makes it attractive for longitudinal studies of changes in brain function, such as those related to chronic pain. However, ASL\u27s poor spatial resolution makes image alignment between sessions difficult, leading to increased variance and greater Type-I errors. In addition, variability due to differences in basal blood flow between sessions and confounding effects such as the arterial transit time (ATT) have the potential to reduce reproducibility over time. The focus of this thesis is to investigate the ability of ASL to detect long-term changes in regional CBF within an individual on a voxel-wise level. It is hypothesized that ASL has the sensitivity to detect activation-induced CBF changes over periods as long as a month if the sources of variance that degrade between-session comparisons are minimized. To test this hypothesis rest and activation (motor task) CBF images were acquired from healthy subjects on three separate imaging sessions. Registration errors were minimized by using individual head molds to replicate the head position in successive sessions. Variations in resting CBF were controlled for by performing the imaging during the same time of day, and subjects were asked to refrain from using common substances, such as caffeine, that are known to affect CBF. Finally, ATT maps were generated on each session to investigate its stability. From these data sets, the within- and between-session variability in CBF was determined and motor-related activation maps were generated from rest and activation data acquired on from the same session and from sessions separated by a week and a month. The results demonstrated excellent reliability (intraclass correlation coefficients greater than 0.75) both within- (0.89 ± 0.2) and between-session (0.84 ± 0.15), and high reproducibility (within subject coefficient of variation, wsCV, greater than 20%) within- (wsCV = 4.7 ± 4.5%) and between-session (wsCV = 5.7 ± 4.4%). Between-session reproducibility of the ATT was high (wsCV = 5.0 ± 2.7%), suggesting that the confounding effect of ATT over a month was minimal. The similarity in within- and between-session variability and their activation maps indicated that registration errors between sessions were minimal. Measures of precision of activation demonstrated that less than ~20% of between-session activation were false positives. These results demonstrate the feasibility of conducting voxel-wise analysis of CBF images acquired on different days and highlight the potential of this technique for longitudinal studies

Drug and disease effects on the human brain studied by functional MRI

Background: With the advent of magnetic resonance imaging (MRI) technology, various functional MRI (fMRI) techniques have become available for non-invasive neuroscientific studies and clinical diagnostics, which have led to a better understanding of the human brain function in normal and diseased subjects. In order to interpret the fMRI results correctly and design optimal research studies it is important to understand both the potentials and limitations associated with each fMRI technique. In this thesis we used two fMRI techniques: arterial spin labeling (ASL) and resting-sate BOLD (blood-oxygen-level dependent) fMRI to study the effects of a CNS-active (central nervous system) drug and neurologic disorder on the human brain function. Purpose: The main research purposes of this thesis are the following: 1) We assess the reproducibility and reliability of rCBF (regional cerebral blood flow) measurements conducted at 3T with pCASL (pseudo continuous ASL) technique; 2) We study the pharmacokinetics of a CNS active drug in normal volunteers by conducting rCBF measurements as a function of time after intake of a single dose of 20 mg d-amphetamine with the pCASL technique; 3) We investigate the possible neurological abnormalities of mild traumatic brain injury (mTBI) patients with chronic fatigue by performing rCBF and resting-sate functional connectivity measurements before, during and after a 20 minute continuous psychomotor vigilance task (PVT). Conclusion: The results from these studies show that the pCASL technique is a relatively robust method for quantitative measurements of rCBF in both normal volunteers and patient subjects. Repeated rCBF measurements with the pCASL method is a non-invasive and sufficiently sensitive approach to assess pharmacokinetic response to CNS active chemicals and should be useful for studying the neurophysiological characteristics in vivo of potential CNS drugs. The results from the mTBI subjects demonstrate that the repeated measurements of rCBF and functional connectivity metrics before, during and after a PVT provide sensitive diagnostic imaging methods to assess neurological abnormality of mTBI patients without apparent neuroanatomical damage. In addition to the clinical diagnostic value, these studies also contribute to important knowledge for the design and analysis of brain functional imaging studies of drugs and neurological diseases

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status