Feasibility of [¹⁵O]H₂O PET-CT for quantifying lower limb muscle perfusion in peripheral arterial occlusive disease: a pilot study

Background: Assessing muscle tissue perfusion in patients with peripheral arterial occlusive disease (PAOD) is challenging, as conventional techniques such as computed tomography angiography and transcutaneous oxygen pressure (TcPO₂) do not capture perfusion within deeper muscle compartments, which are clinically relevant because symptoms such as claudication manifest in the muscles. [¹⁵O]H₂O positron emission tomography computed tomography (PET-CT) enables quantitative measurement of tissue blood flow but has not yet been systematically applied in PAOD. This exploratory study investigated the feasibility and reproducibility of using long axial field of view (LAFOV) [¹⁵O]H₂O PET-CT to quantify calf muscle perfusion in PAOD patients, comparing two VOI selection strategies and generating hypotheses for future studies. Methods: Patients with Rutherford stage 3–6 PAOD undergoing endovascular revascularization underwent [¹⁵O]H₂O PET-CT imaging before and after treatment. Muscle perfusion (K1 in mL/100 cm³/min) was calculated using a 1-tissue compartment model and image-derived input functions. VOIs were defined using either full muscle contours or standardized spherical volumes. Ten legs from five scanning sessions (each including pre- and post-treatment imaging) were analyzed twice by two observers. Agreement and variability between methods and observers were assessed. Results: K₁ values ranged from 1.54 to 5.22 mL/100 cm³/min. Both VOI methods enabled reproducible quantification of calf muscle perfusion. Intrarater intraclass correlation coefficients (ICCs) were ≥0.94 for both methods; interrater ICCs were 0.90 for spherical VOIs and 0.96 for muscle contours. Bland–Altman analysis showed no systematic bias. Muscle contours showed slightly higher reproducibility, likely due to anatomical accuracy. Conclusions: [¹⁵O]H₂O LAFOV PET-CT enables robust quantification of muscle perfusion in PAOD. This method is promising for future studies on treatment response and pathophysiology in vascular disease.