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Bismuth Chelate-Mediated Computed Tomography Perfusion Imaging of Acute Ischemic Stroke In Vivo
Lu Zhao1, Li Ma1, Xuetao Jia1
1Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
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 (Tmax) 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.
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 (Tmax) 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.
