A physiological model for interpretation of arterial spin labeling reactive hyperemia of calf muscles

Abstract

To characterize and interpret arterial spin labeling (ASL) reactive hyperemia of calf muscles for a better understanding of the microcirculation in peripheral arterial disease (PAD), we present a physiological model incorporating oxygen transport, tissue metabolism, and vascular regulation mechanisms. The model demonstrated distinct effects between arterial stenoses and microvascular dysfunction on reactive hyperemia, and indicated a higher sensitivity of 2-minute thigh cuffing to microvascular dysfunction than 5-minute cuffing. The recorded perfusion responses in PAD patients (n = 9) were better differentiated from the normal subjects (n = 7) using the model-based analysis rather than characterization using the apparent peak and time-to-peak of the responses. The analysis results suggested different amounts of microvascular disease within the patient group. Overall, this work demonstrates a novel analysis method and facilitates understanding of the physiology involved in ASL reactive hyperemia. ASL reactive hyperemia with model-based analysis may be used as a noninvasive microvascular assessment in the presence of arterial stenoses, allowing us to look beyond the macrovascular disease in PAD. A subgroup who will have a poor prognosis after revascularization in the patients with critical limb ischemia may be associated with more severe microvascular diseases, which may potentially be identified using ASL reactive hyperemia.

Perfusion measures for symptom severity and differential outcome of revascularization in limb ischemia: Preliminary results with arterial spin labeling reactive hyperemia

“…10,12 This study suggested that the shape of reactive hyperemia perfusion response may reflect multiple aspects of the pathophysiology, potentially including both macroand microvascular damage, and a more sophisticated analysis such as the model-based approach may be valuable. 15 The arterial resistance increased with symptom severity in the bilateral comparison and in the comparison between severity groups, and the standard macrovascular assessment by the ABI agreed with these results. On the other hand, we speculate that the "microvascular" indices reflect microvascular dysfunction.…”

“…The peak perfusion and model resistance reflected the macrovascular disease burden in accord with the results assessed by the ABI. As explained in the previous work, 15 the response characteristics in longer durations of flow arrest may be less specific to any particular microvascular regulatory mechanism. Furthermore, measures of macrovascular resistance were found to be related to the manifested symptom severity, whereas microvascular function seemed to be related to prognosis following revascularization.…”

“…In the earlier model development work, 15 an initial comparison between parameter estimates for healthy subjects vs. those with PAD included a subset of patients in the current study. The model indices included two macrovascular parameters, the arterial resistance R a and compliance C a , and two microvascular parameters, the microvascular sensitivity g ATP and response time s ATP of hypoxia-induced changes in microvascular resistance, as well as the baseline perfusion f r .…”

“…15 The model utilized five parameters to describe reactive hyperemia, including the influences of the macro-and microvascular effects, as summarized in Fig. 15 The model utilized five parameters to describe reactive hyperemia, including the influences of the macro-and microvascular effects, as summarized in Fig.…”

“…A theoretical model was developed recently to facilitate the interpretation of the vascular physiology involved in reactive hyperemia (see a brief summary of the theoretical framework in the Supplementary Material). 15 The model utilized five parameters to describe reactive hyperemia, including the influences of the macro-and microvascular effects, as summarized in Fig. 1.…”