Introduction: Arterial spin labeling (ASL) MRI measures tissue perfusion by labeling arterial blood, and after a post-labeling delay (PLD, or TI), imaging the tissue (1). During PLD, the labeled blood transits from labeling site to imaging slice. To achieve high signal-to-noise ratio, PLD should be short enough that the longitudinal (T1) magnetization of the labeled blood has not recovered much. On the other hand, PLD should be longer than arterial transit time (ATT) so that any labeled blood has arrived at the imaging slice when the image is acquired.

For peripheral artery disease (PAD) patients, calf-muscle perfusion during or after exercise is an important indicator for muscle function. The presence of artery stenosis could increase both ATT and its spatial heterogeneity, which would make the selection of proper PLD and thus accurate quantification of calf-muscle perfusion more difficult. In this study using DCE MRI, we investigated the range and heterogeneity of ATT in calf muscle of both healthy and PAD subjects after exercise of different intensities. The knowledge we gain in this study will help guide proper data acquisition design for calf-muscle ASL.

Methods and materials: This study was approved by local institutional research board. We included 9 healthy volunteers and 5 PAD patients (ankle-brachial index 0.56-0.84, 0.69±0.14). Each subject was scanned at 3T (TimTrio, Siemens). To enhance calf-muscle perfusion, an MR-compatible plantar-flexion apparatus was set up in the scanner. Subjects performed single-leg plantar flexion at different workloads (4, 8 and 16 lbs at 1 Hz, or 2.7, 5.4 and 10.8 watts) for 3 min. With 0.05 mmol/kg gadoteridol injected 5 sec earlier, DCE MRI started immediately after exercise cessation, using a FLASH sequence prepared with saturation recovery: inversion time 300 ms, TR 527 ms, TE 1.42 ms, flip angle 15°, slice thickness 10 mm, number of averages 1, image matrix 128×128, field of view 180×180 mm. Each acquisition (~1.5 sec) covered three slices including an axial slice at maximal cross-sectional area of calf muscle. With measured equilibrium magnetization, gadolinium concentration was estimated for each post-contrast image frame. To estimate ATT, arterial input function (AIF) was sampled from peroneal artery in the muscle slice; a Heaviside step function was convolved with AIF, and ATT as an independent variable of the step function was optimized to match the convolution to concentration versus time curve of each muscle voxel. As a result, a map of ATT was obtained for each subject, and regions of interest (ROI) were manually drawn to estimate the average ATT for each muscle group.

Results: Example of ATT map is shown in Fig. 1. ATT values for all the subjects are listed in Table 1. The overall range of the ATT values was about 0.1 ~ 4 sec. Different muscle groups: peroneal and gastrocnemius muscles, which are supposed to be activated in plantar flexion, had shorter ATT (1~2 sec) than the other muscles; soleus’s ATT was the longest, ~3 sec. Different exercise loads: High exercise load is supposed to cause high cardiac output, thus high blood velocity and low ATT. Our results show that ATT did not decrease significantly until the load increased to 16 lbs. The ATT values for the muscles were comparable for exercises of 4 and 8 lbs. PAD vs. healthy subjects: For the PAD patients, ATT of peroneal and gastrocnemius muscles with 4-lbs exercise were higher than those in the healthy subjects, by about 0.6-0.7 sec, which could be due to the upstream stenosis. When exercise load increased to 8 lbs, ATT of gastrocnemius muscle for the PAD decreased to the healthy level, about 1.7 sec. As ATT of soleus muscle for the PAD also decreased when exercise load increased to 8 lbs (different from the healthy ones), it was possible that at exercise load of 8 lbs, cardiac output for the patients was pushed to so high a level that blood velocity towards both gastrocnemius and soleus increased significantly.

Discussion: Our study showed that ATT of calf muscle varied with multiple factors, including muscle compartment, exercise load and healthy status. Maximum ATT, ~5 sec, was mostly found in soleus after low-intensity exercise, while minimum ATT, ~0.1 sec, was found in gastrocnemius with high-intensity exercise. The wide range of ATT values indicates a wide range of blood velocity through calf muscle upon exercise. With such large range of transit time, no single PLD should be optimal for quantifying perfusion for the various muscles with ASL. Instead, ASL acquisition with multiple different delay times is necessary for accurately quantifying calf-muscle perfusion.