Introduction

Peripheral artery disease (PAD) is a common vascular disease caused by stenosis or occlusion of blood vessels due to atherosclerosis. In patients with PAD, the reduced blood supply to the lower extremities reduces muscle strength and walking ability, and may lead to limb-threatening complications.[1] Therefore, assessing lower extremity hemodynamics is important and was recently emphasized by the American Heart Association (AHA).[2] Reactive hyperemia experiments, measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI), permits the evaluation of changes in blood flow and oxygenation non-invasively and has tentatively been used in perfusion assessment of skeletal muscle in PAD.[3-5] However, there is little research in this area, and the value of perfusion assessment for clinical diagnosis is unclear. Therefore, this study aims to: 1) verify the feasibility of using BOLD MRI to measure perfusion in the lower limb in PAD patients and 2) explore the relationship between perfusion measurements and clinical features.

Methods

Thirteen patients (69.1 ± 7.1 years old, ten males) diagnosed with PAD by typical symptoms and atherosclerosis on computed tomography angiography (CTA) were recruited for this study. Informed consent was obtained. All subjects underwent clinical examinations, including ankle brachial index (ABI), walking performance measurement [6, 7], and BOLD. The BOLD imaging consisted of three phases: one-minute resting phase, followed by a five-minute cuff phase under 250 mmHg pressure of an inflatable thigh cuff, and finally a four-minute recovery phase with pressure released. The BOLD imaging was performed on a 3T scanner (MAGNETOM Vida, Siemens Healthcare, Erlangen, Germany), equipped with an 18-channel Flex coil. BOLD imaging was acquired with a single slice multi-echo gradient echo sequence, sampled at 3.3 seconds per measurement, with TR 55 ms, and nine echoes equally spaced from 4.0 to 40.0 ms. The field of view was 16 x 15 cm², and the matrix was 120 x 96. The BOLD T2* map of each measurement was fitted from the nine echoes and then non-rigidly registered to the first phase with the first echo of each measurement as the reference. The masks of muscle groups were hand-drawn on ITK-SNAP from the first echo BOLD image while avoiding major arteries. The T2* curve was normalized by the mean T2* during the resting phase to avoid the T2* heterogeneity induced by inhomogeneous B0 field. BOLD parameters, including minimum ischemia value (MIV), hyperemia peak value (HPV), time to half ischemia minimum (THIM), time to peak (TTP), and gradient (Grad) during reactive hyperemia (exemplified in Fig. 1e) were measured and reported as mean ± SD. Analysis of variance (ANOVA) was used to determine differences between muscle groups. Unpaired t-test and Pearson correlation was used in reporting the relationship between clinical features and BOLD imaging parameters. Data were analyzed with SPSS version 25.0 (SPSS, Chicago, Illinois). Statistical significance is defined as p values <0.05.

Results

The clinical characteristics of all the patients are described in Table 1. The walking performance, evaluated by six-minute walk and short physical performance battery (SPPB), is listed in the right column [7]. Longer distances or higher SPPB scores indicate better walking ability. Rutherford classification of included patients was mostly at grade 2 ~ 4, and patients with the same Rutherford classification showed different performances on functional measurement. BOLD results were shown in Table 2. In general, the changes in the soleus and medial gastrocnemius were greater, though the differences lacked statistical significance. Figure 2 shows the relationship between the clinical characteristics and BOLD parameters (mean value of all muscle groups of interest). Patients with an SPPB score of 0 ~ 8 had a significantly lower MIV than those with an SPPB score of 9 ~ 12 (p<0.05). Moreover, MIV was positively correlated with a six-min walking distance, indicating that subjects with larger MIV had more tolerance and better walking performance. We also found that ABI was positively correlated with Grad and negatively correlated with TTP (p<0.05). Interestingly, in three subjects we observed the plump of T2* immediately following the release of pressure in some muscle groups, particularly in the soleus (Figure 3), possibly due to the increased blood volume under hyperemia conditions and the pouring in of deoxygenated blood right after the cuff was released. This phenomenon has not been reported previously.

Discussion

Previous studies focused minimally on the relationship between perfusion and clinical function, and a few explored the relationship between ABI and perfusion parameters. However, whether perfusion, rather than stenosis, affects clinical function and outcome was unclear. This study included the six-minute walking and SPPB score as the clinical metrics and showed the feasibility of using BOLD MRI to measure perfusion in the lower limb in PAD patients.

Conclusion

In conclusion, perfusion images of lower limbs were collected by BOLD-MRI in PAD patients with high spatial and temporal resolution. The results of BOLD parameters were consistent with the walking performance, which is important for perfusion assessment to guide clinical diagnosis.

Acknowledgements

Not applicable.

References

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