Vulnerable Atherosclerotic Plaque Clinical Trial
Official title:
In Vivo Atherosclerotic Plaque Calcium Characterization for Predicting Ruptured Plaques
Recently, ultrashort echo time (UTE) MR, which allows detection of the ultrashort T2
components, has been used to image plaque calcification in ex vivo carotid and coronary
arteries. The results demonstrated that UTE images are able to identify plaque calcification
and enables accurate quantification of calcium volumes. However, gadolinium-based contrast
agents during in vivo CMR could not be performed in these ex vivo study. Agnese et al.
believed that calcifications with 18F-NaF PET uptake might be considered to represent dormant
areas where on-going mineralization, which is a key sign to identify and localise ruptured
and high risk coronary plaque. We, therefore, hypothesize that enhanced carotid calcification
presented by UTE MR may be a critical sign for symptomatic patients.
In this study, we will investigate the feasibility of enhanced UTE MR in human carotid
arteries in vivo. Furthermore, we analyzed the correlation between UTE MR and
microcalcification of in the carotid plaques. Based on the diagnostic ability of enhanced UTE
MR for microcalcification, we will investigate the potential of enhanced calcification to
distinguish symptomatic from asymptomatic patients with carotid atherosclerosis and research
the prognostic ability of enhance calcufication in UTE MR.
Atherosclerosis, characterized by the accumulation of lipids and inflammatory cells in the
large arteries, is one of the most common causes of morbidity and mortality in developed and
developing countries. Atherosclerotic plaque rupture-induced thrombosis or obstruction of
artery is the most important cause for the sudden and unpredictable onset of acute artery
stroke. Our understanding of specific characteristics of the vulnerable atherosclerotic
plaque has been enhanced by retrospective pathological studies, which have identified common
phenotypic features of the atherosclerotic plaque most prone to rupture and trigger
thrombotic events. A thin fibrous cap, a large lipid core, high macrophage count, and
intraplaque hemorrhage have all been identified as markers of the so-called "vulnerable"
plaque being related to a higher stroke risk.
Calcification of atherosclerotic lesions was long thought to be an age - related, passive
process where a combination of high local concentrations of phosphates and
phosphatidylserines from necrotic cells and an absence of calcification inhibitors results in
the precipitation of calcium phosphate particles. Recently increasingly data has revealed
that atherosclerotic calcification is a more active process, involving complex signaling
pathways and bone-like genetic programs. The distinction of early or active calcification as
a destabilizing process and late calcification as a more stable state has also been supported
by histological studies. This has lead to interest in characterizing early stages of
calcification metabolically by making use of the positron emission tomography (PET)/CT
imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF), which has recently been
reported having the potential to distinguish dormant areas with on-going mineralization and
quiescent atherosclerotic calcium. Nevertheless, PET/CT is an expensive and a radioactive
examination, which is not appropriate for large-scale screening or serial follow-up studies.
MRI is ideal for serial studies of lesions of atherosclerosis over time because it is
noninvasive and is superior to other imaging modalities in distinguishing soft tissue
contrast. In conventional gradient echo based MRI with TEs in the 1 to 2 ms range, however,
the very short T2 relaxation time of solid calcifications on the order of some μs causes
almost complete signal cancellation, which may cause significant overestimation of the
calcified region and could not provide information about calcium density. Moreover, the low
or zero signal from calcium with short T2 means that there is little opportunity to
manipulate conspicuity by using different pulse sequences or contrast agents.
Recently, ultrashort echo time (UTE) MR, which allows detection of the ultrashort T2
components, has been used to image plaque calcification in ex vivo carotid and coronary
arteries. The results demonstrated that UTE images are able to identify plaque calcification
and enables accurate quantification of calcium volumes. However, gadolinium-based contrast
agents during in vivo CMR could not be performed in these ex vivo study. Agnese et al.
believed that calcifications with 18F-NaF PET uptake might be considered to represent dormant
areas where on-going mineralization, which is a key sign to identify and localise ruptured
and high risk coronary plaque. We, therefore, hypothesize that enhanced carotid calcification
presented by UTE MR may be a critical sign for symptomatic patients.
In this study, we will investigate the feasibility of enhanced UTE MR in human carotid
arteries in vivo. Furthermore, we analyzed the correlation between UTE MR and
microcalcification of in the carotid plaques. Based on the diagnostic ability of enhanced UTE
MR for microcalcification, we will investigate the potential of enhanced calcification to
distinguish symptomatic from asymptomatic patients with carotid atherosclerosis and research
the prognostic ability of enhance calcufication in UTE MR.
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