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

BackgroundMultispectral optoacoustic tomography (MSOT), a molecular sensitive ultrasound, offers a non-invasive diagnostic approach to image the deep-tissue biomarkers. ObjectivesThe authors aimed to investigate the diagnostic accuracy of MSOT to distinguish between healthy volunteers (HV) and patients with intermittent claudication (IC) by assessing hemoglobin-related biomarkers in calf muscle tissue. MethodsIn this monocentric, cross-sectional diagnostic trial using derivation (DC) and validation cohorts (VC) yll subjects underwent standardized PAD diagnostics. This included pulse palpation, ankle brachial index (ABI), duplex sonography, 6-minute walk test (6MWT), and assessment of health-related quality of life (VASCUQOL-6). The vascular occlusion profile in IC patients was confirmed by angiography (aggregated TransAtlantic Inter-Society Consensus classification, aTASC). MSOT imaging of calf muscle was performed before and after standardized heel raise provocation. ParticipantsOf 123 screened individuals, 102 completed the study. MSOT-derived oxygenation (msO2) after the exercise differentiated IC and HV with an area under curve the receiver operator characteristics curve (AUROC) in DC by 0.99 (95%CI 0.97;1.00, p<0.001, sensitivity: 100%, specificity: 95.8%) and in the VC by 0.95 (95%CI 0.95;1.00, p<0.001, sensitivity: 96.2%, specificity: 96.0%). mSO2 positively correlated with the ABI post-exercise (R=0.83, 95%CI 0.75;0.88, P<0.001), the absolute walking distance in the 6MWT (R=0.77, 95%CI 0.68;0.84, P<0.001), the VASCUQOL-6 (R=0.79, 95%CI 0.70;0.85, P<0.001) and negatively with aTASC classification (R=-0.80, 95%CI -0.86;-0.72, P<0.001). ConclusionsPost-exercise MSOT-derived saturation in the calf muscle was validated as a new and promising diagnostic biomarker to distinguish between HV and IC patients yielding high sensitivity and specificity. (NCT05373927)