Evaluation of skeletal muscle microvascular perfusion of lower extremities by cardiovascular magnetic resonance arterial spin labeling, blood oxygenation level-dependent, and intravoxel incoherent motion techniques

Abstract

Background: Noninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD).

Methods: Fifteen healthy young subjects, 14 patients with PAD, and 10 age-matched healthy old subjects underwent ASL, BOLD, and IVIM CMR perfusion imaging. Healthy young and healthy old participants were subjected to a cuff-induced ischemia experiment with pressures of 20 mmHg and 40 mmHg above systolic pressure during imaging. Perfusion-related metrics, including blood flow, T2* relaxation time, perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D*, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Friedman, Mann-Whitney, Wilcoxon signed rank, and Spearman rank correlation tests were used for statistical analysis.

Results: In cases of significant differences determined by the Friedman test (P < 0.05), blood flow, T2*, and D values gradually decreased, while f values showed a tendency to increase in healthy subjects under cuff compression. No significant correlations were found among the ASL, BOLD, and IVIM parameters (all P > 0.05). Blood flow and T2* values showed significant positive correlations with transcutaneous oxygen pressure measurements (ρ = 0.465 and 0.522, respectively; both P ≤ 0.001), while f values showed a significant negative correlation in healthy young subjects (ρ = - 0.351; P = 0.018). T2* was independent of age in every muscle group. T2* values were significantly decreased in PAD patients compared with healthy old subjects and severe PAD patients compared with mild-to-moderate PAD patients (all P < 0.0125). Significant correlations were found between T2* and ankle-brachial index values in all muscle groups in PAD patients (ρ = 0.644-0.837; all P < 0.0125). Other imaging parameters failed to show benefits towards the diagnosis and disease severity evaluation of PAD.

Conclusions: ASL, BOLD, and IVIM provide complementary information regarding tissue perfusion. Compared with ASL and IVIM, BOLD may be a more reliable technique for assessing PAD in the resting state and could thus be applied together with angiography in clinical studies as a tool to comprehensively assess microvascular and macrovascular properties in PAD patients.

Keywords: Blood flow; Cardiovascular magnetic resonance; Diffusion-weighted imaging; Oxygenation; Perfusion.

Fig. 1

CMR imaging workflow. a Ischemia via arterial occlusion was induced in the lower extremity with an occlusive cuff tied around the middle of one thigh. The axial image slice was acquired at the widest part of the lower extremity. Four experimental statuses are defined as follows: baseline (Pre), cuff compression with a pressure of 20 mmHg above systolic pressure (Cuff-20), cuff compression with a pressure of 40 mmHg above systolic pressure (Cuff-40) and recovery period (Post). b T1-weighted anatomical images allow for the accurate delineation of muscle groups (1 = anterior, 2 = lateral, 3 = soleus, and 4 = gastrocnemius) in the lower extremity

Fig. 2

Graphs presenting serial measurements of imaging parameters from ASL (a), BOLD (b), and IVIM (c, d, e) for the anterior, lateral, soleus, and gastrocnemius muscle groups in healthy young subjects. Comparisons among all four statuses (1 = baseline; 2 = 20-mmHg cuff compression; 3 = 40-mmHg cuff compression; 4 = recovery) for every muscle group were performed using the Friedman test (n.s. = not significant; * = P < 0.05; ** = P < 0.01; *** = P < 0.001). Further pairwise comparisons were made with the Dunn test († = P < 0.05 compared with baseline; ‡ = P < 0.05 compared with 20-mmHg cuff compression; § = P < 0.05 compared with 40-mmHg cuff compression)

Fig. 3

Graphs presenting serial measurements of imaging parameters from ASL (a), BOLD (b), and IVIM (c, d, e) for the anterior, lateral, soleus, and gastrocnemius muscle groups in healthy old subjects. Comparisons among all four statuses (1 = baseline; 2 = 20-mmHg cuff compression; 3 = 40-mmHg cuff compression; 4 = recovery) for every muscle group were performed using the Friedman test (n.s. = not significant; * = P < 0.05; ** = P < 0.01; *** = P < 0.001). Further pairwise comparisons were made with the Dunn test († = P < 0.05 compared with baseline; ‡ = P < 0.05 compared with 20-mmHg cuff compression; § = P < 0.05 compared with 40-mmHg cuff compression)

Fig. 4

Graphs depicting relationships between normalized CMR imaging parameters of blood flow (a), T2* (b), f (c), D (d), and D* (e) and normalized TcPO2 measurements. Significant correlations were observed for (a), (b), and (c), with Spearman rank correlation coefficients (ρ) of 0.465, 0.522, and − 0.351, respectively

Fig. 5

Graphs depicting relationships between T2* in the anterior (a), lateral (b), soleus (c), and gastrocnemius (d) muscle groups and ABI in PAD patients. Significant correlations were observed for all muscle groups, with Spearman rank correlation coefficients (ρ) of 0.837, 0.820, 0.785, and 0.644, respectively