Chou Ting-Heng, Nabavinia Mahboubeh, Tram Nguyen K, Rimmerman Eleanor T, Patel Surina, Musini Kumudha Narayana, Eisert Susan Natalie, Wolfe Tatiana, Wynveen Molly K, Matsuzaki Yuichi, Kitsuka Takahiro, Iwaki Ryuma, Janse Sarah A, Bobbey Adam J, Breuer Christopher K, Goodchild Laurie, Malbrue Raphael, Shinoka Toshiharu, Atway Said A, Go Michael R, Stacy Mitchel R
Center for Regenerative Medicine Research Institute at Nationwide Children's Hospital Columbus OH.
Biophysics Graduate Program Ohio State University Columbus OH.
J Am Heart Assoc. 2024 Feb 20;13(4):e031823. doi: 10.1161/JAHA.123.031823. Epub 2024 Feb 14.
Perfusion deficits contribute to symptom severity, morbidity, and death in peripheral artery disease (PAD); however, no standard method for quantifying absolute measures of skeletal muscle perfusion exists. This study sought to preclinically test and clinically translate a positron emission tomography (PET) imaging approach using an atherosclerosis-targeted radionuclide, fluorine-18-sodium fluoride (F-NaF), to quantify absolute perfusion in PAD.
Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic F-NaF PET/computed tomography imaging on the day of and 2 weeks after occlusion. Following 2-week imaging, calf muscles were harvested to quantify microvascular density. PET methodology was validated with microspheres in 4 additional pig studies and translated to patients with PAD (n=39) to quantify differences in calf perfusion across clinical symptoms/stages and perfusion responses in a case of revascularization. Associations between PET perfusion, ankle-brachial index, toe-brachial index, and toe pressure were assessed in relation to symptoms. F-NaF PET/computed tomography quantified significant deficits in calf perfusion in pigs following arterial occlusion and perfusion recovery 2 weeks after occlusion that coincided with increased muscle microvascular density. Additional studies confirmed that PET-derived perfusion measures agreed with microsphere-derived perfusion measures. Translation of imaging methods demonstrated significant decreases in calf perfusion with increasing severity of PAD and quantified perfusion responses to revascularization. Perfusion measures were also significantly associated with symptom severity, whereas traditional hemodynamic measures were not.
F-NaF PET imaging quantifies perfusion deficits that correspond to clinical stages of PAD and represents a novel perfusion imaging strategy that could be partnered with atherosclerosis-targeted F-NaF PET imaging using a single radioisotope injection.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.
灌注不足会导致外周动脉疾病（PAD）的症状严重程度、发病率和死亡率增加；然而，目前尚无用于量化骨骼肌灌注绝对指标的标准方法。本研究旨在临床前测试并在临床上应用一种正电子发射断层扫描（PET）成像方法，该方法使用一种靶向动脉粥样硬化的放射性核素——氟 - 18 - 氟化钠（F - NaF），来量化PAD中的绝对灌注。
8只约克夏猪在单侧股动脉结扎当天及闭塞后2周接受了动态F - NaF PET/计算机断层扫描成像。在2周成像后，取小腿肌肉以量化微血管密度。在另外4项猪研究中用微球对PET方法进行了验证，并将其应用于PAD患者（n = 39），以量化不同临床症状/阶段小腿灌注的差异以及血管重建病例中的灌注反应。评估了PET灌注、踝肱指数、趾肱指数和趾压之间与症状相关的关联。F - NaF PET/计算机断层扫描量化了猪动脉闭塞后小腿灌注的显著不足以及闭塞后2周的灌注恢复情况，这与肌肉微血管密度增加相吻合。其他研究证实，PET得出的灌注测量值与微球得出的灌注测量值一致。成像方法的临床应用表明，随着PAD严重程度的增加，小腿灌注显著降低，并量化了血管重建后的灌注反应。灌注测量值也与症状严重程度显著相关，而传统血流动力学测量值则不然。
F - NaF PET成像可量化与PAD临床阶段相对应的灌注不足，代表了一种新颖的灌注成像策略，该策略可与使用单一放射性同位素注射的靶向动脉粥样硬化的F - NaF PET成像相结合。
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