Ananth J. Madhuranthakam, PhD

Ananth.Madhuranthakam@UTSouthwestern.edu

Highlights: ASL has become a mainstream application for brain perfusion, but still has challenges for renal perfusion. Various improvements including pseudo-continuous labeling combined with background suppression and timed-breathing approaches have enabled robust renal perfusion imaging.

Target Audience: Radiologists; Imaging Scientists; MR Physicists; Technologists;

Objectives: To learn different types of arterial spin labeling technique along with the acquisition methods and strategies for robust renal perfusion imaging without the administration of exogeneous contrast agent.

Arterial spin labeling (ASL) is a non-contrast MRI technique that can measure tissue perfusion (or capillary blood flow) without the administration of exogenous contrast agents. ASL uses highly permeable water as a tracer, by magnetically labeling the water protons in the arterial blood and measuring their accumulation in the tissue of interest. Various versions of ASL have been validated in animals using microspheres, and in humans using the gold standard positron emission tomography (PET) using 15O-labeled water in the brain (1). Compared to dynamic contrast-enhanced (DCE) or dynamic susceptibility contrast (DSC) perfusion measurements, ASL has a number of advantages. Specifically, ASL does not require exogenous agent alleviating the concerns of gadolinium accumulation (2) or nephrogenic systemic fibrosis (NSF) in patients with impaired renal function (3) and unlike DCE/DSC, the contribution of vascular permeability to ASL measured perfusion is negligible (4) enabling absolute perfusion quantification in physiological units (ml/100g/min). ASL has been extensively studied in humans to measure brain perfusion. ASL methods have been in development over two decades and have recently matured to become a mainstream non-contrast perfusion technique in the brain. All major MR vendors currently offer some type of ASL technique as a product sequence for brain applications. However, its application to measure renal perfusion has been limited so far. In the following section, I will describe various elements that are necessary for achieving robust renal perfusion images. There are two basic approaches with ASL. Continuous labeling inverts (or labels) blood as it passes through a narrow labeling plane, while pulsed ASL inverts a volume of blood outside the imaging region. Pulsed labeling, using a specific technique called flow alternating inversion recovery (FAIR), has been more widely applied to study renal perfusion (5). With this approach, two images are acquired, one with a selective inversion applied across the imaging slice and the other image acquired with a non-selective inversion. The difference between these two images will be proportional to the amount of tissue perfusion in the imaging plane. Typically, the slice-selective inversion thickness will be set three to four times the imaging plane thickness to ensure complete inversion of the spins in the imaging plane and the non-selective inversion is applied as a slab-selective inversion and set to approximately ten times the slice-selective inversion. After a post-label delay (or inversion time), the images are acquired, which when subtracted provides the tissue perfusion. Pulsed labeling including FAIR can be readily implemented on the clinical scanner for the evaluation of renal perfusion, but suffers from reduced signal to noise ratio (SNR) compared to continuous ASL, as demonstrated in brain perfusion studies (6). Continuous ASL was originally only feasible with short labeling durations on commercial scanners due to hardware limitations (7). The introduction of pseudo-continuous ASL (pCASL) marked a significant advancement by replacing the constant waveforms with pulsed waveforms, enabling continuous ASL on commercial scanners with longer labeling, on the order of seconds (8). pCASL has been the recommended choice of labeling technique for brain by the recent consensus paper, convened by the members of the perfusion study group of ISMRM (9) and is now commercially offered by major MR vendors for brain perfusion measurement. pCASL approach contains a train of radiofrequency (RF) and gradient pulses that selectively labels a plane of interest, for example, applied axially across the abdominal aorta for a labeling duration, e.g. 1.5 seconds. The arterial blood that flows through this labeling plane is inverted via flow driven adiabatic inversion. After a post-label delay (e.g. 1.5 seconds), the data are acquired (label image). The sequence is repeated again with the RF pulses phase-cycled during pCASL (control image), such that the blood flow is not inverted, but the magnetization transfer effects in the imaging volume are maintained between the label and the control acquisitions. The signal difference in ASL is less than 2% of the fully relaxed background signal. Hence, background suppression (BGS) is essential to improve the robustness of ASL in clinical applications by reducing the standard deviation of the flow measurements due to physiological and instrumental fluctuations (10). This necessity is even greater in body applications including renal perfusion imaging due to increased physiological variations such as cardiac and respiratory motion, bowel peristalsis etc. (11). BGS can be achieved by the application of multiple inversion pulses after the labeling, that can reduce background signal to <3% across a wide range of T1 values from 200 to 4200 ms, without affecting the perfusion signal. Additionally, the arrival of blood in the major vasculature after the labeling period has ended, may cause signal fluctuations leading to bright vascular signal in the perfusion imaging, that may undermine the tissue perfusion. Inflow saturation (IFS) pulses applied before the data acquisition can reduce the bright vascular signal. Nonlinear optimization schemes have been developed to determine the ideal BGS inversion times and IFS saturation times for a given label duration and post-label delay with both FAIR and PCASL (12).The majority of brain perfusion studies have been performed with 2D echo-planar imaging (EPI), either using single slice or multi-slice methods, due to its fast acquisition times. Recent studies have proposed volumetric acquisitions with spiral readouts using 3D fast/turbo spin echo (FSE/TSE) sequence for increased SNR (13). However, EPI and spiral readouts have limitations in the body applications due to increased off-resonance effects associated with larger fields of view. Hence, Cartesian based TSE readout using single-shot (SSFSE/SShTSE/HASTE) or segmented 3D TSE are robust for renal perfusion imaging (14). Alternatively, 2D balanced steady state free precession (bSSFP) has also been used with FAIR based pulsed ASL (5). Moreover, multiple signal averages are acquired to improve the SNR using some sort of respiratory gating. In our experience, timed-breathing approach, where the subjects are continuously coached to breath during the labeling and hold their breath during the acquisition, has worked robustly (11). ASL images are reconstructed by subtracting the label image from the control image. The SNR of the reconstructed images can be further increased by (2) using complex subtraction in the k-space prior to image reconstruction. The advantage of ASL acquisition is the ability to quantify absolute perfusion in physiological values of ml/100g/min. The standard models of pulsed ASL (equation 1) and continuous ASL (equation 2) can be used for perfusion quantification (f) (15). The variables for FAIR are: inversion time (TI); first IFS pulse (Tsat). The variables for pCASL are: label duration (τ); post-label delay (w); blood-tissue partition coefficient (λ=0.9); transit delay from the labeling plane to the tissue (δt); inversion efficiency (α = 0.6) for pCASL with background suppression. ΔM is the measured perfusion difference image between label and control and M0 is the measured proton density image using same acquisition parameters without any preparation pulses.