Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

Mechtouff, Laura; Sigovan, Monica; Douek, Philippe; Costes, Nicolas; Bars, Didier Le; Mansuy, Adeline; Haesebaert, Julie; Bani-Sadr, Alexandre; Tordo, Jérémie; Feugier, Patrick; Millon, Antoine; Luong, Stéphane; Collet-Benzaquen, Diane; Canet-Soulas, Emmanuelle; Bochaton, Thomas; Silva, Claire Crola Da; Paccalet, Alexandre; Magne, David; Berthezène, Yves; Nighoghossian, Norbert

doi:10.1007/s12350-020-02400-0

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…We observed that NaF uptake was higher in the carotid atheroma with severe calcification, but its uptake also tended to be elevated in the atheroma with a necrotic core 10 . Another studies also reported intense NaF uptake in infarcted brain tissue from brain CT 11 . Since hydroxyl ions are a major constituent of free radicals during necrosis, the active ion exchange with fluoride ions could be a plausible explanation.…”

Section: Discussionmentioning

confidence: 84%

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction

Kim

Lee

Jeong

et al. 2022

Sci Rep

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Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.

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Section: Discussionmentioning

confidence: 84%

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction

Kim

Lee

Jeong

et al. 2022

Sci Rep

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“…In fact, 18 F-NaF seems to have an increased uptake in the carotid bifurcation compared to 18 F-FDG, which in contrast demonstrates a more diffuse pattern of uptake 34 . One recent study used hybrid PET/MRI for the assessment of 18 F-NaF uptake in 12 carotid plaques and aimed to correlate the uptake to morphological criteria of plaque vulnerability on MRI 35 . Similar to our results, no such associations were established, however, the methodology for MRI assessment was rudimentarily described and therefore difficult to evaluate.…”

Section: Discussionmentioning

confidence: 99%

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study

Good

Ochoa-Figueroa

Ziegler

et al. 2021

Sci Rep

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Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s−1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was − 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.

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“…In a recent review on PET-MRI, Evans et al (2020) pointed out the importance of combining 18 F-NaF molecular calcification imaging and highresolution MRI plaque characterization. An initial study by our group found that 18 F-NaF-positive lesions were not associated with known MRI criteria of vulnerability (Mechtouff et al, 2020), but further longitudinal studies could helpfully use contrastenhanced MRI to check whether 18 F-NaF uptake precedes the vulnerable state. As longitudinal clinical studies are still lacking and are also rare in preclinical models of microcalcification (Hsu et al, 2020), the mechanisms underlying 18 F-NaF uptake and the link with specific inflammatory processes are not fully elucidated.…”

Section: Microcalcifications: New Suspects For Plaque Rupturementioning

confidence: 98%

The Elusive Origin of Atherosclerotic Plaque Calcification

Canet-Soulas

Bessueille

Mechtouff

et al. 2021

Front. Cell Dev. Biol.

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It has been known for decades or even centuries that arteries calcify as they age. Vascular calcification probably affects all adults, since virtually all have atherosclerotic plaques: an accumulation of lipids, inflammatory cells, necrotic debris, and calcium phosphate crystals. A high vascular calcium score is associated with a high cardiovascular mortality risk, and relatively recent data suggest that even microcalcifications that form in early plaques may destabilize plaques and trigger a cardiovascular event. If the cellular and molecular mechanisms of plaque calcification have been relatively well characterized in mice, human plaques appear to calcify through different mechanisms that remain obscure. In this context, we will first review articles reporting the location and features of early calcifications in human plaques and then review the articles that explored the mechanisms though which human and mouse plaques calcify.

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Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

Cited by 13 publications

References 41 publications

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study

The Elusive Origin of Atherosclerotic Plaque Calcification

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