Bismuth Chelate-Mediated Computed Tomography Perfusion Imaging of Acute Ischemic Stroke In Vivo

Contrast-enhanced computed tomography perfusion (CTP) imaging is a critical clinical tool for evaluating cerebral blood flow after acute ischemic stroke (AIS), enabling accurate diagnosis and treatment planning. However, conventional iodine-based contrast agents may lead to allergic reactions and are contraindicated in patients with thyroid disorders. This study introduces Bi-DTPA dimeglumine, a renal-clearable and iodine-free bismuth chelate, for AIS perfusion assessment via CTP imaging. Bi-DTPA dimeglumine is synthesized through a simple and scalable process with nearly 100% yield (laboratory synthesis >100 g) and demonstrates excellent biocompatibility and efficient renal clearance. In a middle cerebral artery occlusion (MCAO) rat model, Bi-DTPA dimeglumine-enhanced CTP imaging accurately visualized vascular perfusion deficits, showing reduced cerebral blood volume (CBV) and cerebral blood flow (CBF), alongside prolonged time-to-maximum (T_max) and mean transit time (MTT). Compared to iohexol, Bi-DTPA dimeglumine provided superior vascular contrast in computed tomography angiography (CTA), with contrast-to-noise ratio (CNR) improvements of 129.8 and 93.5% in normal and MCAO rats, respectively. Notably, CTP imaging revealed distinct reperfusion dynamics in ischemic regions postrecanalization. This iodine-free imaging agent marks a significant advancement in precise AIS diagnosis and post-treatment evaluation, addressing key limitations of existing contrast agents while enhancing diagnostic accuracy and safety.