Author + information
- Published online October 17, 2018.
- Jeong-Min Kim, MD, PhD,
- Eun Seong Lee, MD,
- Kwang-Yeol Park, MD, PhD∗ (, )
- Ju Won Seok, MD, PhD and
- Oh-Sang Kwon, MD, PhD
- ↵∗Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, 224-1, Heukseok-dong, Dongjak-gu, Seoul 156-755, Republic of Korea
The application of positron emission tomography (PET) with different radioisotopes in atherosclerosis can detect various pathological cascades within atheroma (1). The 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) ligand was the first radioisotope introduced in atherosclerosis study that measures inflammation activity (1). Recently, 18-F NaF ligand representing calcification activity within atheroma showed superior efficacy for detecting culprit coronary vessel when compared with the FDG ligand (2). We performed both FDG and NaF PET for stroke patients with carotid stenosis to determine whether NaF is also superior to FDG for detecting culprit atheroma.
The study protocol was approved by the institutional review board of Chung-Ang University Hospital. Twenty patients with acute ischemic stroke or transient ischemic attack with carotid artery stenosis >50% on brain computed tomography angiography were prospectively enrolled after providing written informed consent. We excluded patients with active cancer or autoimmune disease, uncontrolled diabetes mellitus with blood glucose more than 11 mmol/l at admission, and renal dysfunction with estimated glomerular filtration rate <45 ml/min/1.72 m2. The culprit (+) group consisted of individuals with a culprit carotid lesion, defined as a carotid stenosis that was ipsilateral to ischemic lesions in the absence of another embolic source. All other individuals were deemed to have a nonculprit carotid lesion, composing the culprit (–) group.
When a patient was stabilized, FDG and NaF PET imaging were performed on separate days by the same protocol (median time after stroke: 17 days). After fasting for 8 h, 259 to 370 MBq (7 to 10 mCi) of FDG or NaF was injected intravenously. Approximately 60 min after the injection, PET images were acquired at 5 min/bed for the head and 1 min/bed from the skull base to the proximal thigh right after computed tomography scan (120 kVp, 50 mA). The maximum standardized uptake value at the carotid level where the atheroma was largest was selected and divided by standardized uptake value of aortic blood to derive the maximum target-to-blood ratio.
We performed both person-to-person and vessel-to-vessel comparisons. First, the number of carotid atheroma showing visible uptake of radiotracers were compared between culprit (+) and culprit (–) groups by Fisher exact test. The maximal standardized uptake value and target-to-blood ratio of each radiotracer were compared between the 2 groups with Mann-Whitney U test. Second, radiotracer uptake in terms of 10 culprit and 30 nonculprit carotid arteries were compared by generalized estimating equation after adjusting for age with a random effects model to account for correlated observations within individuals. All statistical analyses were performed using SPSS (version 23.0, IBM, Armonk, New York).
The study population consisted of 10 patients in each group (mean age: 75 ± 9 years, with 10 female patients). The stroke etiology among culprit (–) group included 6 cardioembolic strokes, 3 patients with intracranial atherosclerosis, and 1 cancer-related stroke. The 2 groups had a considerable degree of stenosis and calcification burden (Figure 1A). The uptake of both radiotracers was prevalent in carotid atheroma and not significantly different between the 2 groups (Figure 1A). The vessel-to-vessel comparison of both radiotracer levels also revealed an insignificant difference (Figure 1B). Post hoc analysis after excluding 2 patients with concealed cancer showed that FDG uptake level was elevated in culprit segments versus nonculprit segments (culprit: 1.24 ± 0.30 vs. nonculprit: 1.08 ± 0.13; p = 0.04), but NaF level was not different (culprit: 1.53 ± 0.54 vs. nonculprit: 1.39 ± 0.45; p = 0.45). The target-to-blood ratio of 2 radiotracers showed significant correlation (Spearman rho = 0.319; p =0.045).
Our study found that both radiotracer signals were prevalent in carotid atheroma, with a wide overlap of their uptake intensities between culprit and nonculprit segments, reflecting high inflammation and calcification activity. A recent study reported that 18-F-fluoride PET highlights culprit carotid plaque among stroke patients compared with contralateral asymptomatic artery (3). Our result is different from the previous study because it is driven by a person-to-person comparison among stroke patients with moderate-to-severe carotid atherosclerosis that contains considerable calcification burden.
Please note: This study was supported by the Chung-Ang University Research Grants in 2016 and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2016R1D1A1B03933891). Dr. Kim conducted the statistical analysis. Drs. Kim and Lee contributed equally to this work and are joint first authors. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation