18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome

Abstract

Background MRI and fluorine 18-labeled sodium fluoride (¹⁸F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between ¹⁸F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this prospective observational cohort study (October 2017 to January 2020), participants underwent ¹⁸F-NaF PET/MRI. An experienced clinician determined the culprit carotid artery based on symptoms and record review. ¹⁸F-NaF uptake was quantified using standardized uptake values and tissue-to-background ratios. Statistical significance was assessed with the Welch, χ², Wilcoxon, or Fisher test. Multivariable models were used to evaluate the relationship between the imaging markers and the culprit versus nonculprit vessel. Results A total of 110 participants were evaluated (mean age, 68 years ± 10 [SD]; 70 men and 40 women). Of the 110, 34 (32%) had prior cerebrovascular disease, and 26 (24%) presented with amaurosis fugax, 54 (49%) with transient ischemic attack, and 30 (27%) with stroke. Compared with nonculprit carotids, culprit carotids had greater stenoses (≥50% stenosis: 30% vs 15% [P = .02]; ≥70% stenosis: 25% vs 4.5% [P < .001]) and had increased prevalence of MRI-derived adverse plaque features, including intraplaque hemorrhage (42% vs 23%; P = .004), necrotic core (36% vs 18%; P = .004), thrombus (7.3% vs 0%; P = .01), ulceration (18% vs 3.6%; P = .001), and higher ¹⁸F-NaF uptake (maximum tissue-to-background ratio, 1.38 [IQR, 1.12-1.82] vs 1.26 [IQR, 0.99-1.66], respectively; P = .04). Higher ¹⁸F-NaF uptake was positively associated with necrosis, intraplaque hemorrhage, ulceration, and calcification and inversely associated with fibrosis (P = .04 to P < .001). In multivariable analysis, carotid stenosis at or over 70% (odds ratio, 5.72 [95% CI: 2.2, 18]) and MRI-derived adverse plaque characteristics (odds ratio, 2.16 [95% CI: 1.2, 3.9]) were both associated with the culprit versus nonculprit carotid vessel. Conclusion Fluorine 18-labeled sodium fluoride PET/MRI characteristics were associated with the culprit carotid vessel in study participants with acute neurovascular syndrome. Clinical trial registration no. NCT03215550 and NCT03215563 © RSNA, 2022 Online supplemental material is available for this article.

Graphical abstract

Figure 1:

Consolidated Standards of Reporting Trials diagram of participant recruitment.

Figure 2:

Fluorine 18–labeled sodium fluoride (¹⁸F-NaF) PET/MRI carotid scans and ex vivo histologic analysis sample in a patient who experienced a left hemispheric transient ischemic attack. MR angiograph in a 60-year-old woman with left hemispheric transient ischemic attack shows a left carotid artery stenosis of greater than or equal to 70% severity (box, MR angiography [MRA] panel; arrow, time-of-flight [TOF] panel). MRI plaque analysis was used to identify intraplaque hemorrhage (arrow, T1 panel), lipid-rich necrotic core (arrow, T2 panel), and calcification (arrow, proton density [PD] panel). ¹⁸F-NaF PET/MRI showed focal uptake in the region of the intraplaque hemorrhage and lipid-rich necrotic core (orange arrow). The carotid plaque was excised at operation. Cross-sectional images through the carotid plaque are shown, with hematoxylin and eosin (H & E) and Movat pentachrome stains. The red arrow indicates the thin fibrous cap, the blue arrow highlights plaque erosion, the star denotes a rupture, the purple arrow shows intraplaque hemorrhage with a thrombus, the yellow arrowheads denote inflammation (shoulder and central regions), and the green arrowheads indicate lipid-rich necrotic cores.

Figure 3:

Tukey box and whisker plots show fluorine 18–labeled sodium fluoride uptake (mean tissue-to-background ratio [TBR_mean] and maximum tissue-to-background ratio [TBR_max]) stratified by the degree of carotid stenosis (expressed as percentages) in culprit (red) and nonculprit (blue) vessels. The box bounds the IQR (upper and lower quartile) divided by the median (solid horizontal midline); whiskers extend to the most extreme data points from the edge of the box; outliers beyond the whiskers are individually plotted by the solid dots.

Figure 4:

Tukey box and whisker plots show comparisons for fluorine 18–labeled sodium fluoride uptake in the (A) culprit vessel, (B) nonculprit vessel, and (C) aortic arch in patients with stenosis above or below 70% in the culprit vessel. The box bounds the IQR (upper and lower quartile) divided by the median (solid horizontal midline); whiskers extend to the most extreme data points from the edge of the box; outliers beyond the whiskers are individually plotted by the solid dots. TBR_mean = mean tissue-to-background ratio.

Figure 5:

Tukey box and whisker plots show comparisons for fluorine 18–labeled sodium fluoride uptake and MRI-defined plaque features. The box bounds the IQR (upper and lower quartile) divided by the median (solid horizontal midline); whiskers extend to the most extreme data points from the edge of the box; outliers beyond the whiskers are individually plotted by the solid dots. TBR_mean = mean tissue-to-background ratio.

Figure 6:

Multivariable models were constructed for the identification of culprit compared with nonculprit vessels, which included as covariates the presence of MRI-derived stenosis greater than or equal to 70%, one or more MRI-derived adverse plaque characteristics, and either mean tissue-to-background ratio (TBR_mean) or maximum tissue-to-background ratio (TBR_max). Dot plots show odds ratios, with blue lines representing 95% CIs. TBR_mean is per doubling [log₂(TBR_mean)]. *** = P < .001, ** = P < .01, * = P < .05, no asterisk = P ≥ .05.