In Vivo Imaging of Enhanced Leukocyte Accumulation in Atherosclerotic Lesions in Humans

Background

Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets.

Objectives

The study evaluates an in vivo imaging approach to visualize peripheral blood mononuclear cell (PBMC) accumulation in atherosclerotic lesions of cardiovascular (CV) patients using hybrid single-photon emission computed tomography/computed tomography (SPECT/CT).

Methods

At baseline, CV patients and healthy controls underwent ¹⁸fluorodeoxyglucose positron emission tomography-computed tomography and magnetic resonance imaging to assess arterial wall inflammation and dimensions, respectively. For in vivo trafficking, autologous PBMCs were isolated, labeled with technetium-99m, and visualized 3, 4.5, and 6 h post-infusion with SPECT/CT.

Results

Ten CV patients and 5 healthy controls were included. Patients had an increased arterial wall inflammation (target-to-background ratio [TBR] right carotid 2.00 ± 0.26 in patients vs. 1.51 ± 0.12 in controls; p = 0.022) and atherosclerotic burden (normalized wall index 0.52 ± 0.09 in patients vs. 0.33 ± 0.02 in controls; p = 0.026). Elevated PBMC accumulation in the arterial wall was observed in patients; for the right carotid, the arterial-wall-to-blood ratio (ABR) 4.5 h post-infusion was 2.13 ± 0.35 in patients versus 1.49 ± 0.40 in controls (p = 0.038). In patients, the ABR correlated with the TBR of the corresponding vessel (for the right carotid: r = 0.88; p < 0.001).

Conclusions

PBMC accumulation is markedly enhanced in patients with advanced atherosclerotic lesions and correlates with disease severity. This study provides a noninvasive imaging tool to validate the development and implementation of interventions targeting leukocytes in atherosclerosis.