18F-sodium fluoride positron emission tomography assessed microcalcifications in culprit and non-culprit human carotid plaques

Abstract

Background 18 F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18 F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18 F-NaF uptake with calcification visualized on microcomputed tomography (microCT). Methods Carotid plaques from stroke patients undergoing surgery were incubated in 18 F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18 F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18 F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. Results 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18 F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18 F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18 F-NaF PET VOI showed calcification on CT. Conclusions 18 F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18 F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development. Electronic supplementary material The online version of this article (10.1007/s12350-018-1325-5) contains supplementary material, which is available to authorized users.

Determinants of 18F-NaF uptake in femoral arteries in patients with type 2 diabetes mellitus

“…5 Sodium 18F-fluoride ( 18 F-NaF) PET/CT is a novel imaging technique that can visualize smaller calcifications. [6][7][8][9][10] In the femoral arteries, 18 F-NaF PET can visualize ongoing (medial and intimal) calcification. 11 In the coronaries 18 F-NaF PET is associated with high risk plaque features and plaque rupture.…”

Fluoride imaging of atherosclerotic plaques: Moving from macro to microcalcifications?

“…Carotid plaques of asymptomatic patients would have represented a better comparator to evaluate FNa binding in stable plaques, but are more difficult to collect as indications for carotid endarterectomy in this population are declining. The study of Hop, et al 5 confirms that FNa is binding to ruptured atherosclerotic plaques, but does not allow us rule on the interest of FNa to discriminate between highrisk and stable lesions.…”

“…A possible explanation for this finding is that plaque vulnerability is a systemic process 6 meaning that carotid lesions contralateral to the territory of the ischemic stroke often also present features of complicated plaques. Indeed, Hop et al 5 confirmed that all nonculprit lesions that bound FNa had features of complicated plaques on histology. Carotid plaques of asymptomatic patients would have represented a better comparator to evaluate FNa binding in stable plaques, but are more difficult to collect as indications for carotid endarterectomy in this population are declining.…”

“…In addition, microcalcifications in the vascular wall have an attenuation profile to X-rays that is too weak to be detected with CT explaining how FNa can be present in the vascular wall in absence of calcification on CT. Hop et al 5 confirmed after in vitro incubation of FNa of carotid atherosclerotic plaques, that regions with high FNa uptake on PET with no calcification on micro-CT did contain microcalcifications on histology, but also that FNa can bind to regions with macrocalcifications on CT. This is in accordance with the study of Derlin et al 8 who showed in a retrospective analysis of 75 patients imaged with wholebody FNa-PET-CT for oncological indications that only 12% of focal FNa signals detected in the aorta were located in regions without any calcification on CT, whereas only 12% of the vascular regions with calcifications on CT did bind FNa.…”

“…The FNa signal was present on PET in all ruptured carotid plaques and associated with evidence of active calcification, macrophage infiltration, apoptosis, and necrosis on histology. In the article published in this issue of the Journal of Nuclear Cardiology, Hop et al 5 aimed at confirming that culprit carotid plaques bind more FNa than nonculprit lesions. After in vitro incubation of carotid plaques with FNa, they, however, did not find any significant difference in the FNa signal between lesions obtained from carotid plaques ipsilateral vs contralateral to the ischemic stroke.…”