The Vascular Biology of Atherosclerosis and Imaging Targets

Libby, Peter; DiCarli, Marcelo F.; Weissleder, Ralph

doi:10.2967/jnumed.109.069633

Cited by 111 publications

(94 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the initial stages of atherogenesis, modified lipoproteins recruit monocytes and T cells. Macrophages internalize the modified lipoproteins, resulting in the accumulation of high-oxygenconsuming, high-metabolic-rate, lipid-loaded macrophages (foam cells) in developing lesions (5,6). The combination of increased oxygen demand together with impaired oxygen diffusion capacity results in the presence of severe hypoxia (,1% oxygen) in macrophage-rich zones (150-300 mm) into the lesion (7)(8)(9).…”

mentioning

confidence: 99%

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

et al. 2016

View full text Add to dashboard Cite

The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64 Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. Methods: New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0-to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64 Cu-ATSM. After 24 h, a 0-to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18 F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 α subunit ). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. Results: Elevated uptake of 64 Cu-ATSM was found in the rabbits' IF compared with the SF. 64 Cu-ATSM imaging demonstrated IF-to-SF SUV mean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18 F-FDG imaging demonstrated IF-to-SF SUV mean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUV mean ratios were significantly higher (P , 0.001) than SF-to-BM SUV mean ratios both 4 and 8 wk after injury for 64 Cu-ATSM and 8 wk after injury for 18 F-FDG (P , 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1α. Conclusion: The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64 Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. At herosclerosis is a systemic degenerative and inflammatory vascular disease that develops over decades, leading to advanced lesions characterized by a lipid core separated from the lumen by a fibrous cap. It has been recognized that plaque composition more than the degree of luminal stenosis determines the risk of acute clinical events (e.g., stroke, myocardial infarction) (1). Macrophage-rich plaques with a thin fibrous cap, large lipid core, and abundance of leaky microvessels tend to be more vulnerable (1). The rupture or erosion of the fibrous cap in vulnerable plaque may lead to thromboembolization and arterial occlusion (2,3).According to the anoxemia theory of atherosclerosis, an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerotic lesions (4). In the initial s...

show abstract

mentioning

confidence: 99%

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

et al. 2016

View full text Add to dashboard Cite

show abstract

“…31 This has been identified as a potential role for molecularly targeted imaging. 32 This also opens the door for a complementary role of measures of coronary vasodilator function (eg, coronary flow reserve), 33 reflecting the integrated effects of diffuse atherosclerosis and endothelial dysfunction. Quantitative coronary flow reserve provides a sensitive, accurate, and reproducible measure of the effects of disease biology that, unlike circulating biomarkers, is specific to the coronary circulation.…”

Section: What Are the Clinical Implications Of The Integrated Ct-basementioning

confidence: 99%

Quantifying Plaque Burden and Morphology Using Coronary Computed Tomography Angiography to Predict Coronary Physiology

Carli

Blankstein

2015

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

C oronary computed tomography angiography (CTA) is a powerful noninvasive technique that can be used to visualize the presence, extent, and severity of both noncalcified and calcified plaque. When compared with other noninvasive imaging approaches, coronary CTA has the highest sensitivity to detect anatomic stenosis and, consequently, the highest negative predictive value to exclude obstructive coronary artery disease (CAD).1 However, once a coronary stenosis is identified, a limitation of CTA-which is equally problematic for invasive coronary angiography-is that the physiological consequences associated with those stenoses cannot be determined with any degree of accuracy.2,3 On the other hand, the presence and severity of ischemia are essential for understanding the pathophysiology of patient's symptoms and determining the potential role of coronary revascularization. Consequently, multiple techniques have been introduced to harness physiological data from CTA and infer whether a stenosis is hemodynamically significant. Some investigators have applied computational fluid dynamic modeling to estimate coronary pressure gradients and calculation of the fractional flow reserve across stenosis. 4 Others have relied on the use of iodinated contrast at rest and during pharmacological stress to assess myocardial perfusion (computed tomography [CT] perfusion) 5 in a similar manner to radionuclide scintigraphy and magnetic resonance imaging-based myocardial perfusion techniques. Recent clinical trials have demonstrated that in carefully selected patients, these techniques can provide useful information to understand the physiological significance of stenoses.6-9 So, it is clear that the paradigm of isolated stenosis quantification with angiography (noninvasive or invasive) has provided insufficient and, sometimes, misleading information for diagnosis and management of CAD. However, there is limited data addressing the question of whether a more complete quantification of the atherosclerotic burden with coronary CTA, including all stenosis dimensions and other plaque characteristics, can improve discrimination of flow-limiting lesions. See Article by Dey et alIn this issue of Circulation: Cardiovascular Imaging, Dey et al 10 evaluated the quantitative relationship between stenosis dimensions and x-ray-based characteristics of coronary plaques and myocardial blood flow and coronary flow reserve (CFR)-a validated measure of the functional severity of coronary stenosis. The study included 51 symptomatic patients with known or suspected CAD undergoing vasodilator stress positron emission tomography (PET) myocardial perfusion imaging followed by coronary CTA on an integrated PET/CT system. Coronary flow reserve was calculated as the ratio of myocardial blood flow (in mL/min/g) during vasodilator stress over that at rest. Total coronary plaque volume and burden (plaque volume index by vessel volume), percent stenosis, plaque length, vessel remodeling, and x-ray-based plaque characteristics (calcified and noncalcified) were also...

show abstract

“…20 Usually, disease-related biomarkers, which are upregulated during the pathological process of the diseases, are needed in molecular imaging to target specific cells or molecules. 5,[22][23][24] For AS diagnosis, molecular imaging with target-specific probes has shown great promise for noninvasive in vivo monitoring of biological processes of atheromatous plaques at molecular and cellular levels in both animals and humans. By targeting the specific molecules, the contrast agents can be located to atherosclerotic lesions accurately and signal intensity of different imaging techniques can thus be increased.…”

Section: Introductionmentioning

confidence: 99%

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

Anwaier

Chen

Cao

et al. 2017

IJN

View full text Add to dashboard Cite

Despite the fact that technological advancements have been made in diagnosis and treatment, cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity worldwide. Early detection of atherosclerosis (AS), especially vulnerable plaques, plays a crucial role in the prevention of acute coronary syndrome (ACS). Targeting the critical cytokines and molecules that are upregulated during the biological process of AS by in vivo molecular imaging has been widely used in plaque imaging. With their three-dimensional architecture, composition, and abundant terminal functional groups, dendrimers provide a platform for multitargeting and multimodal imaging. Thus, modified dendrimers with the key molecules upregulated in AS plaques will be an innovative attempt to achieve targeted imaging of AS plaques specifically and efficiently. This review was aimed to address some recent works on imaging of AS plaques using various types of image technology and further discuss the applications of dendrimers, an innovative yet seldom used method in imaging of AS plaques due to some limitations and challenges, and we highlight the bright future of the modified dendrimers in characterizing AS plaques.

show abstract

The Vascular Biology of Atherosclerosis and Imaging Targets

Cited by 111 publications

References 49 publications

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

Quantifying Plaque Burden and Morphology Using Coronary Computed Tomography Angiography to Predict Coronary Physiology

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

Contact Info

Product

Resources

About

The Vascular Biology of Atherosclerosis and Imaging Targets

Cited by 111 publications

References 49 publications

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

Quantifying Plaque Burden and Morphology Using Coronary Computed Tomography Angiography to Predict Coronary Physiology

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

Contact Info

Product

Resources

About

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model