Exploring the Dynamics of Ischemia and Reactive Hyperemia With Skeletal Muscle Blood Oxygen Level Dependent MRI in Patients With Peripheral Artery Disease, Age-Matched Controls, and Young Healthy Subjects

J Magn Reson Imaging. 2026 Jan 28. doi: 10.1002/jmri.70204. Online ahead of print.

ABSTRACT

BACKGROUND: Skeletal muscle blood oxygen level dependent (BOLD) MRI is a technique for assessing vascular function in peripheral limbs. In patients, however, an increased frequency of atypical response patterns has been observed, warranting investigation into its underlying causes.

PURPOSE: To explore the dynamics of cuff-induced ischemia and reactive hyperemia with BOLD MRI, focusing on the occurrence, quantification, and interpretation of frequent atypical cuff-induced response patterns.

STUDY TYPE: Secondary assessment of prospectively collected datasets.

POPULATION: Seventeen peripheral artery disease (PAD) patients (age: 64-80 years, ankle-brachial index (ABI) range: 0.4-0.8), 8 age-matched controls (age: 64-82 years, ABI range: 1-1.2), and 14 young controls (age: 22-39 years). FIELD STRENGTH/SEQUENCE: $T_2^{*}$ -weighted multi-echo gradient-echo sequence with 11 equidistant echo-times at 3T.

ASSESSMENT: A transverse slice of the calf was imaged repeatedly during an upper-thigh cuff compression cycle consisting of 1-min baseline, 5-min arterial occlusion (cuff inflated) and 5-min reactive hyperemia (cuff deflated). $T_2^{*}$ -mapping with ROI-wise analysis of the soleus and gastrocnemius muscles produced $T_2^{*}$ -time curves and previously established metrics, including the hyperemic upslope ( ${\mathrm{HS}}_{\mathrm{up}}$ ) and time-to-peak (TTP) were assessed. The time-curves were surveyed to identify the frequency and type of deviations from expected. $T_2^{*}$ -time curves of soleus were further analyzed by fitting a parameterized function to derive additional metrics including depth of the undershoot on cuff release and deviation from a monotonic T2* decrease. Ankle-brachial index (ABI) served as a clinical reference for comparisons.

STATISTICAL TESTS: Non-parametric 2-tailed Wilcoxon rank-sum tests to assess differences between patients and age-matched controls. A p value < 0.05 was considered significant.

RESULTS: Atypical cuff-induced response patterns in PAD patients included a negative cuff-induced transient (42%, soleus) and non-monotonic declines in $T_2^{*}$ during cuffing (58%, soleus). While these contributed to increased variabilities in patients, $\text{there were significant differences in}{\mathrm{HS}}_{\mathrm{up}}$ (-0.63 ms/s) and TTP (62.8 s) between patients and age-matched controls.

DATA CONCLUSION: HS_up and TTP provided means to quantify calf muscle responses to cuffing. Specific cases of non-monotonous $T_2^{*}$ decrease during cuffing suggest the detection of venous valve leakages in inter-muscular veins. Insufficient cuff pressure produced curves with absent ischemic plateau and weak hyperemic responses, the recognition of which is important to prevent physiological misinterpretations of $T_2^{*}–\text{time}$ curves and derived metrics.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: 3.

PMID:41604213 | DOI:10.1002/jmri.70204