Atherosclerosis Imaging with 18F-Sodium Fluoride PET

Abstract

The evidence on atherosclerosis imaging with ¹⁸F-sodium-fluoride (NaF) positron emission tomography (PET) is hotly debated because of the different patient characteristics, methodology, vascular beds, etc. in reported studies. This review is a continuation of a previous review on this topic, which covered the period 2010-2018. The purpose was to examine whether some of the most important questions that the previous review had left open had been elucidated by the most recent literature. Using principles of a systematic review, we ended analyzing 25 articles dealing with the carotids, coronary arteries, aorta, femoral, intracranial, renal, and penile arteries. The knowledge thus far can be summarized as follows: by targeting active arterial microcalcification, NaF uptake is considered a marker of early stage atherosclerosis, is age-dependent, and consistently associated with cardiovascular risk. Longitudinal studies on NaF uptake, conducted in the abdominal aorta only, showed unchanged uptake in postmenopausal women for nearly four years and varying uptake in prostate cancer patients over 1.5 years, despite constant or increasing calcium volume detected by computed tomography (CT). Thus, uncertainty remains about the transition from active arterial wall calcification marked by increased NaF uptake to less active or consolidated calcification detected by CT. The question of whether early-phase atherosclerosis and calcification can be modified remains also unanswered due to lack of intervention studies.

Keywords: 18F-sodium fluoride; NaF; PET; atherosclerosis; calcification; quantification.

Figure 1

Fused NaF-positron emission tomography/computed tomography images of patient (top) and matched control (bottom). Note that the distribution of NaF uptake in the patient does not follow only the epicardial routes of the three coronary arteries, but is more dispersed, suggesting that NaF uptake is present in the walls of the entire cardiac arterial tree (with permission from reference [4]). Coronary arterial contrast-enhanced imaging would help address the issue.

Figure 2

(Top): Volume of interest (VOI) capturing a representative heart. VOIs were thresholded to exclude voxels under −50 HU before being superimposed onto corresponding PET images (reproduced with permission from reference [4]). (Left): three-dimensional (3D) rendering of coronary CT angiography with superimposed tubular whole-vessel volumes of interest (light green) employed for evaluation of NaF uptake (blue and red). Despite the relatively lower TBRmax due to multiple foci of increased NaF activity, the coronary microcalcification activity (CMA) in the right coronary artery (RCA) is only moderately lower than in the left anterior descending (LAD) coronary artery, which presented with a very high TBRmax (with permission from reference [39]).

Figure 3

Most follow-up or intervention studies apply one baseline measurement and a single follow-up determination. If the follow-up point is lower than the baseline point, this is usually interpreted as a decline, although in reality one cannot know whether it represents a measurement on a different course, which may even be an opposite one. Three potential courses are indicated (dotted green, orange, and purple lines) (with permission from reference [47]).