David Izquierdo-Garcia1, Pauline Désogère2, Anne L Philip3, Choukri Mekkaoui4, Rory B Weiner5, Onofrio A Catalano4, Yin-Ching Iris Chen4, Doreen DeFaria Yeh5, Moussa Mansour5, Ciprian Catana2, Peter Caravan2, David E Sosnovik6. 1. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA; Harvard-MIT Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. Electronic address: davidizq@nmr.mgh.harvard.edu. 2. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA; Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA. 3. Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 4. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. 5. Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 6. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA; Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA; Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abstract
OBJECTIVES: The authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [64Cu]FBP8. BACKGROUND: The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE). METHODS: The metabolism and pharmacokinetics of [64Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [64Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T1) in the LAA. RESULTS: [64Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUVMax) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUVMax threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T1 (T1Min) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUVMax and T1Min allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy. CONCLUSIONS: PET/CMR of [64Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320).
OBJECTIVES: The authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [64Cu]FBP8. BACKGROUND: The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE). METHODS: The metabolism and pharmacokinetics of [64Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [64Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T1) in the LAA. RESULTS: [64Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUVMax) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUVMax threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T1 (T1Min) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUVMax and T1Min allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy. CONCLUSIONS: PET/CMR of [64Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320).
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