TY - JOUR
T1 - Quantification of Skeletal Muscle Perfusion in Peripheral Artery Disease Using 18 F-Sodium Fluoride Positron Emission Tomography Imaging
AU - Chou, Ting Heng
AU - Nabavinia, Mahboubeh
AU - Tram, Nguyen K.
AU - Rimmerman, Eleanor T.
AU - Patel, Surina
AU - Musini, Kumudha Narayana
AU - Eisert, Susan Natalie
AU - Wolfe, Tatiana
AU - Wynveen, Molly K.
AU - Matsuzaki, Yuichi
AU - Kitsuka, Takahiro
AU - Iwaki, Ryuma
AU - Janse, Sarah A.
AU - Bobbey, Adam J.
AU - Breuer, Christopher K.
AU - Goodchild, Laurie
AU - Malbrue, Raphael
AU - Shinoka, Toshiharu
AU - Atway, Said A.
AU - Go, Michael R.
AU - Stacy, Mitchel R.
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/2/20
Y1 - 2024/2/20
N2 - BACKGROUND: 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 (
18F-NaF), to quantify absolute perfusion in PAD.
METHODS AND RESULTS: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic
18F-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.
18F-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.
CONCLUSIONS:
18F-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
18F-NaF PET imaging using a single radioisotope injection.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.
AB - BACKGROUND: 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 (
18F-NaF), to quantify absolute perfusion in PAD.
METHODS AND RESULTS: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic
18F-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.
18F-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.
CONCLUSIONS:
18F-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
18F-NaF PET imaging using a single radioisotope injection.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.
KW - fluorine-18-sodium fluoride
KW - limb ischemia
KW - perfusion imaging
KW - peripheral artery disease
KW - positron emission tomography
KW - skeletal muscle
KW - Sodium Fluoride
KW - Humans
KW - Peripheral Arterial Disease/diagnostic imaging
KW - Animals
KW - Perfusion
KW - Swine
KW - Muscle, Skeletal/diagnostic imaging
KW - Positron-Emission Tomography/methods
UR - http://www.scopus.com/inward/record.url?scp=85185614464&partnerID=8YFLogxK
U2 - 10.1161/JAHA.123.031823
DO - 10.1161/JAHA.123.031823
M3 - Article
C2 - 38353265
AN - SCOPUS:85185614464
SN - 2047-9980
VL - 13
SP - e031823
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e031823
ER -