Vessel-by-vessel analysis of lower extremity 18F-NaF PET/CT imaging quantifies diabetes- and chronic kidney disease-induced active microcalcification in patients with peripheral arterial disease

Ting-Heng Chou, Eleanor T Rimmerman, Surina Patel, Molly K Wynveen, Susan N Eisert, Kumudha Narayana Musini, Sarah A Janse, Adam J Bobbey, Timur P Sarac, Said A Atway, Michael R Go, Mitchel R Stacy, Ting-Heng Chou, Eleanor T Rimmerman, Surina Patel, Molly K Wynveen, Susan N Eisert, Kumudha Narayana Musini, Sarah A Janse, Adam J Bobbey, Timur P Sarac, Said A Atway, Michael R Go, Mitchel R Stacy

Abstract

Background: Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (18F)-sodium fluoride (NaF) provides assessment of active vascular microcalcification, but its utility for evaluating diabetes mellitus (DM)- and chronic kidney disease (CKD)-induced atherosclerosis in peripheral arterial disease (PAD) has not been comprehensively evaluated. This study sought to use 18F-NaF PET/CT to quantify and compare active microcalcification on an artery-by-artery basis in healthy subjects, PAD patients with or without DM, and PAD patients with or without CKD. Additionally, we evaluated the contributions of DM, CKD, statin use and established CT-detectable calcium to 18F-NaF uptake for each lower extremity artery.

Methods: PAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18F-NaF PET/CT imaging. Fused PET/CT images guided segmentation of arteries of interest (i.e., femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal) and quantification of 18F-NaF uptake. 18F-NaF uptake was assessed for each artery and compared between subject groups. Additionally, established calcium burden was quantified for each artery using CT calcium mass score. Univariate and multivariate analyses were performed to evaluate DM, CKD, statin use, and CT calcium mass as predictors of 18F-NaF uptake in PAD.

Results: PAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18F-NaF uptake) for all arteries when compared to PAD patients without DM or CKD. Univariate and multivariate analyses revealed that concomitant DM or CKD was associated with increased microcalcification for all arteries of interest and this increased disease risk remained significant after adjusting for patient age, sex, and body mass index. Statin use was only associated with decreased microcalcification for the femoral-popliteal artery in multivariate analyses. Established CT-detectable calcium was not significantly associated with 18F-NaF uptake for 4 out of 5 arteries of interest.

Conclusions: 18F-NaF PET/CT imaging quantifies vessel-specific active microcalcification in PAD that is increased in multiple lower extremity arteries by DM and CKD and decreased in the femoral-popliteal artery by statin use. 18F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18F-NaF PET/CT imaging may provide an approach for non-invasively quantifying vessel-specific responses to emerging anti-atherogenic therapies or CKD treatment in patients with PAD.

Keywords: Chronic kidney disease; Diabetes mellitus; Peripheral arterial disease; Positron emission tomography; Sodium fluoride.

Conflict of interest statement

The authors declare that they have no competing financial interests.

© 2023. The Author(s).

Figures

Fig. 1
Fig. 1
Representative example of lower extremity artery segmentation from CT images acquired in a patient with peripheral arterial disease. ROIs are displayed for arteries of interest in the thigh and calf and shown in A axial, B coronal, and C sagittal planes
Fig. 2
Fig. 2
Representative 18F-NaF PET/CT imaging of the lower extremities in a patient with PAD and DM. Fused coronal 18F-NaF PET/CT imaging of both lower extremities demonstrated heterogenous macrocalcification detected by CT imaging and heterogenous arterial uptake of 18F-NaF detected by PET. Focused axial images at the level of the knee further revealed that increased 18F-NaF uptake was localized to arterial regions undergoing active microcalcification and were not yet fully detectable by CT imaging (denoted by white arrows)
Fig. 3
Fig. 3
Qualitative and quantitative analyses of lower extremity 18F-NaF PET/CT imaging in healthy control subjects and patients with PAD. Representative 18F-NaF PET/CT images of a A healthy control subject, B PAD patient without DM, and C PAD patient with DM, which reveal increasing arterial uptake of 18F-NaF and established calcium burden with worsening disease status. Quantitative vessel-by-vessel PET/CT image analysis demonstrates D DM- and E CKD-induced differences in arterial uptake of 18F-NaF between patient groups for each lower extremity artery of interest. White arrows denote regions of focal uptake of 18F-NaF in patients with PAD. Values represent means ± SEM

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