Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography.
Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture.
Washington University, Department of Biomedical Engineering, One Brookings Drive, St. Louis, Missouri 63110, United StatesbWashington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Dolonchampa
D
Maji
Washington University, Department of Biomedical Engineering, One Brookings Drive, St. Louis, Missouri 63110, United StatesbWashington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Metasebya
M
Solomon
Washington University School of Medicine, Center for Cardiovascular Research, Department of Internal Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, United States.
Annie
A
Nguyen
Washington University School of Medicine, Center for Cardiovascular Research, Department of Internal Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, United States.
Richard A
RA
Pierce
Washington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Pamela K
PK
Woodard
Washington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Walter J
WJ
Akers
Washington University, Department of Biomedical Engineering, One Brookings Drive, St. Louis, Missouri 63110, United StatesbWashington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Samuel
S
Achilefu
Washington University, Department of Biomedical Engineering, One Brookings Drive, St. Louis, Missouri 63110, United StatesbWashington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Joseph P
JP
Culver
Washington University School of Medicine, Center for Cardiovascular Research, Department of Internal Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, United States.
Dana R
DR
Abendschein
Washington University School of Medicine, Department of Radiology, 4525 Scott Avenue, St. Louis, Missouri 63110, United States.
Monica
M
Shokeen
D000818:Animals; D005263:Femoral Artery / Q000737:chemistry / Q000473:pathology; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D045265:Natriuretic Peptides / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000737:chemistry / Q000473:pathology*; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry / Q000378:metabolism; D041622:Tomography, Optical / Q000379:methods*
D045265:Natriuretic Peptides; D017461:Receptors, Atrial Natriuretic Factor