Molecular MRI monitoring of cyclodextrin therapy in murine abdominal aortic aneurysms

Abdominal aortic aneurysms (AAAs) are characterized by progressive extracellular matrix (ECM) degradation and inflammation of the aortic wall. 2-Hydroxypropyl-β-cyclodextrin (cyclodextrin) has shown potential in attenuating AAA progression via activation of transcription factor EB. This study evaluated whether molecular magnetic resonance imaging (MRI) enables non-invasive monitoring of therapeutic effects in a murine AAA model. Thirty-two male apolipoprotein-E knockout mice with angiotensin II-induced AAAs received either cyclodextrin (n = 8) or saline (n = 10) for three weeks. A dual molecular MRI approach was applied using a gadolinium-based elastin-specific probe to assess ECM integrity and ultrasmall superparamagnetic iron oxide particles (USPIO, iron oxide particles) to evaluate macrophage-driven inflammation. MRI was performed at pre-treatment baseline and at 2 and 3 weeks after treatment initiation. Cyclodextrin-treated animals demonstrated significantly smaller aortic cross-sectional areas (2.31 ± 0.36 mm² vs. 2.96 ± 0.62 mm²; p = 0.018) and lower elastin-specific signal enhancement (1.56 ± 0.26 vs. 2.15 ± 0.69; p = 0.038), indicating preserved ECM integrity. In contrast, no significant differences in iron oxide particles-related signal changes were observed between groups (p = 0.441), consistent with histological and molecular findings. This study shows that elastin-specific molecular imaging non-invasively monitors cyclodextrin's effects in AAA, whereas iron oxide particle imaging revealed no significant in vivo signal changes, consistent with ex vivo findings and indicating limited detectable inflammatory modulation associated with cyclodextrin treatment under the conditions of this study.