Derivation and validation of a non-invasive optoacoustic imaging biomarker for detection of patients with intermittent claudication.

Background: Peripheral arterial disease (PAD) affects more than 200 million people worldwide, with symptoms ranging from none to severe. Despite these different diagnostic options, patients with unclear leg pain remain challenging to diagnose. The primary objective of this study was to evaluate whether multispectral optoacoustic tomography (MSOT) can discriminate between healthy volunteers (HV) and patients with intermittent claudication (IC) by assessing hemoglobin-related biomarkers in calf muscle tissue.

Method: In this monocentric, cross-sectional, observational diagnostic trial (NCT05373927) n = 102 patients were included in two independent derivation (DC, n = 51) and validation cohorts (VC, n = 51). MSOT was performed before and after standardized heel raise provocation and was compared to standardized PAD diagnostics including pulse palpation, ankle brachial index (ABI), duplex sonography, 6-minute walk test (6MWT), assessment of health-related quality of life (VASCUQOL-6), and angiography (aggregated TransAtlantic Inter-Society Consensus classification, aTASC).

Results: Here we show that MSOT is capable of differentiating IC and HV with an area under the receiver operator characteristics curve (AUROC) in DC by 0.99 (sensitivity: 100%, specificity: 95.8%) and in the VC by 0.95 (sensitivity: 96.2%, specificity: 96.0%). MSOT-derived oxygenation positively correlates with the ABI post-exercise (R = 0.83, P = 2.31 × 10^-26), the absolute walking distance in the 6MWT (R = 0.77, P = 3.40 × 10^-21), the VASCUQOL-6 (R = 0.79, P = 4.82 × 10^-23) and negatively with aTASC classification (R = -0.80, P = 2.92 × 10^-24).

Conclusions: Post-exercise MSOT-derived saturation in the calf muscle is validated as a non-invasive imaging biomarker to distinguish HV and IC patients yielding high sensitivity and specificity.