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Background: Air pollution and noise exposures individually associate with major adverse cardiovascular events (MACE) via a mechanism involving arterial inflammation (ArtI); however, their combined impact on ArtI and MACE remains unknown. We tested whether dual (vs. one or neither) exposure associates with greater ArtI and MACE risk and whether MACE risk is mediated via ArtI., Methods: Individuals (N = 474) without active cancer or known cardiovascular disease with clinical 18 F-FDG-PET/CT imaging were followed for 5 years for MACE. ArtI was measured. Average air pollution (particulate matter ≤ 2.5 μm, PM 2.5 ) and transportation noise exposure were determined at individual residences. Higher exposures were defined as noise > 55 dBA (World Health Organization cutoff) and PM 2.5 ≥ sample median., Results: At baseline, 46%, 46%, and 8% were exposed to high levels of neither, one, or both pollutants; 39 experienced MACE over a median 4.1 years. Exposure to an increasing number of pollutants associated with higher ArtI (standardized β [95% CI: .195 [.052, .339], P = .008) and MACE (HR [95% CI]: 2.897 [1.818-4.615], P < .001). In path analysis, ArtI partially mediated the relationship between pollutant exposures and MACE (P < .05)., Conclusion: Air pollution and transportation noise exposures contribute incrementally to ArtI and MACE. The mechanism linking dual exposure to MACE involves ArtI., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Purpose: To further characterize the relationship between obstructive sleep apnea (OSA) and carotid atherosclerosis, we examined the structural and metabolic features of carotid plaque using hybrid 18-F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: We studied 46 individuals from the MESA-PET and MESA-Sleep ancillary studies. OSA was defined as an apnea hypopnea index [AHI] ≥ 15 events per hour (4% desaturation). PET/MRI was used to measure carotid plaque inflammation (using target-to-background-ratios [TBR]) and carotid wall thickness (CWT). Linear regression was used to assess the associations between OSA, CWT and TBR., Results: The mean age was 67.9 years (SD 8.53) and the mean BMI was 28.9 kg/m 2 (SD 4.47). There was a trend toward a higher mean CWT in the OSA (n = 11) vs. non-OSA group (n = 35), 1.51 vs. 1.41 (p = 0.098). TBR did not differ by OSA groups, and there was no significant association between OSA and carotid plaque inflammation (TBR) in adjusted analyses. Although there was a significant interaction between OSA and obesity, there were no statistically significant associations between OSA and vascular inflammation in stratified analysis by obesity., Conclusion: Despite a trend toward a higher carotid wall thickness in OSA vs. non-OSA participants, we did not find an independent association between OSA and carotid plaque inflammation using PET/MRI in MESA. Our findings suggest that simultaneous assessments of structural and metabolic features of atherosclerosis may fill current knowledge gaps pertaining to the influence of OSA on atherosclerosis prevalence and progression., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18 F-fluordeoxyglucose ( 18 F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18 F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18 F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18 F-FDG PET/CT., (© 2021. American Society of Nuclear Cardiology.)

Objectives: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls., Methods: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBR MEAN ) after correction for blood pool activity in the right atrium., Results: 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBR MEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBR MEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBR MEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004)., Conclusion: Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition., (© 2020. The Author(s).)

Background: Hybrid PET/MR imaging has significant potential in cardiology due to its combination of molecular PET imaging and cardiac MR. Multi-tissue-class MR-based attenuation correction (MRAC) is necessary for accurate PET quantification. Moreover, for thoracic PET imaging, respiration is known to lead to misalignments of MRAC and PET data that result in PET artifacts. These factors can be addressed by using multi-echo MR for tissue segmentation and motion-robust or motion-gated acquisitions. However, the combination of these strategies is not routinely available and can be prone to errors. In this study, we examine the qualitative and quantitative impacts of multi-class MRAC compared to a more widely available simple two-class MRAC for cardiac PET/MR., Methods and Results: In a cohort of patients with cardiac sarcoidosis, we acquired MRAC data using multi-echo radial gradient-echo MR imaging. Water-fat separation was used to produce attenuation maps with up to 4 tissue classes including water-based soft tissue, fat, lung, and background air. Simultaneously acquired 18F-fluorodeoxyglucose PET data were subsequently reconstructed using each attenuation map separately. PET uptake values were measured in the myocardium and compared between different PET images. The inclusion of lung and subcutaneous fat in the MRAC maps significantly affected the quantification of 18F-fluorodeoxyglucose activity in the myocardium but only moderately altered the appearance of the PET image without introduction of image artifacts., Conclusion: Optimal MRAC for cardiac PET/MR applications should include segmentation of all tissues in combination with compensation for the respiratory-related motion of the heart. Simple two-class MRAC is adequate for qualitative clinical assessment., (© 2020. American Society of Nuclear Cardiology.)

Background: 18 F-Fluoride uptake denotes calcification activity in aortic stenosis and atherosclerosis. While PET/MR has several advantages over PET/CT, attenuation correction of PET/MR data is challenging, limiting cardiovascular application. We compared PET/MR and PET/CT assessments of 18 F-fluoride uptake in the aortic valve and coronary arteries., Methods and Results: 18 patients with aortic stenosis or recent myocardial infarction underwent 18 F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary 18 F-fluoride uptake were evaluated independently. Both standard (Dixon) and novel radial GRE) MR attenuation correction (AC) maps were validated against PET/CT with results expressed as tissue-to-background ratios (TBRs). Visually, aortic valve 18 F-fluoride uptake was similar on PET/CT and PET/MR. TBR MAX values were comparable with radial GRE AC (PET/CT 1.55±0.33 vs. PET/MR 1.58 ± 0.34, P = 0.66; 95% limits of agreement - 27% to + 25%) but performed less well with Dixon AC (1.38 ± 0.44, P = 0.06; bias (-)14%; 95% limits of agreement - 25% to + 53%). In native coronaries, 18 F-fluoride uptake was similar on PET/MR to PET/CT regardless of AC approach. PET/MR identified 28/29 plaques identified on PET/CT; however, stents caused artifact on PET/MR making assessment of 18 F-fluoride uptake challenging., Conclusion: Cardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT. However, PET/MR is hampered by stent-related artifacts currently limiting clinical application., (© 2019. The Author(s).)

Background: The standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant K i expected from 18 F-Sodium Fluoride ( 18 F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18 F-NaF and 18 F-Fluorodeoxyglucose ( 18 F-FDG) PET/MR cardiovascular imaging., Methods: We introduce 5-class K i /MR-AC for (i) 18 F-NaF studies where the bones are segmented from Patlak K i images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class K i /MR-AC for (ii) 18 F-FDG-only data, with a streamlined simultaneous administration of 18 F-FDG and 18 F-NaF at 4:1 ratio (R4:1), or (iii) for 18 F-FDG-only or both 18 F-FDG and 18 F-NaF dual-tracer data, by administering 18 F-NaF 90 minutes after an equal 18 F-FDG dosage (R1:1). The K i -driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD)., Results: In rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18 F-NaF SUV mean scores when applying 5-class AC with K i -segmented bone (5-class K i /CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUV mean bias was reduced by 17.6% ( 18 F-NaF) and 15.4% (R4:1) with 5-class K i /CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18 F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18 F-FDG: 18 F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% ( 18 F-FDG) and 15.5% ( 18 F-NaF) at carotid bifurcations and 21.6% ( 18 F-FDG) and 22.5% ( 18 F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication., Conclusions: K i -driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18 F-NaF and 18 F-FDG contrast and quantification in bone tissues and carotid walls.

The past decade has witnessed the rapid development of new MRI technology for vessel wall imaging. Today, with advances in MRI hardware and pulse sequences, quantitative MRI of the vessel wall represents a real alternative to conventional qualitative imaging, which is hindered by significant intra- and inter-observer variability. Quantitative MRI can measure several important morphological and functional characteristics of the vessel wall. This review provides a detailed introduction to novel quantitative MRI methods for measuring vessel wall dimensions, plaque composition and permeability, endothelial shear stress and wall stiffness. Together, these methods show the versatility of non-invasive quantitative MRI for probing vascular disease at several stages. These quantitative MRI biomarkers can play an important role in the context of both treatment response monitoring and risk prediction. Given the rapid developments in scan acceleration techniques and novel image reconstruction, we foresee the possibility of integrating the acquisition of multiple quantitative vessel wall parameters within a single scan session.

Errors in quantification of carotid positron emission tomography (PET) in simultaneous PET/magnetic resonance (PET/MR) imaging when not incorporating bone in MR-based attenuation correction (MRAC) maps, and possible solutions, remain to be fully explored. In this study, we demonstrated techniques to improve carotid vascular PET/MR quantification by adding a bone tissue compartment to MRAC maps and deriving continuous Dixon-based MRAC (MRACCD) maps. We demonstrated the feasibility of applying ultrashort echo time-based bone segmentation and generation of continuous Dixon MRAC to improve PET quantification on five subjects. We examined four different MRAC maps: system standard PET/MR MRAC map (air, lung, fat, soft tissue) (MRACPET/MR), standard PET/MR MRAC map with bone (air, lung, fat, soft tissue, bone) (MRACPET/MRUTE), MRACCD map (no bone) and continuous Dixon-based MRAC map with bone (MRACCDUTE). The same PET emission data was then reconstructed with each respective MRAC map and a CTAC map (PETPET/MR, PETPET/MRUTE, PETCD, PECDUTE) to assess effects of the different attenuation maps on PET quantification in the carotid arteries and neighboring tissues. Quantitative comparison of MRAC attenuation values for each method compared to CTAC showed small differences in the carotid arteries with UTE-based segmentation of bone included and/or continuous Dixon MRAC; however, there was very good correlation for all methods in the voxel-by-voxel comparison. ROI-based analysis showed a similar trend in the carotid arteries with the lowest correlation to PETCTAC being PETPETMR and the highest correlation to PETCTAC being PETCDUTE. We have demonstrated the feasibility of applying UTE-based segmentation and continuous Dixon MRAC maps to improve carotid PET/MR vascular quantification.

Purpose of Review: Aortic valve disease is the most common form of heart valve disease in developed countries. Imaging remains central to the diagnosis and risk stratification of patients with both aortic stenosis and regurgitation and has traditionally been performed with echocardiography. Indeed, echocardiography remains the cornerstone of aortic valve imaging as it is cheap, widely available and provides critical information concerning valve hemodynamics and ventricular function., Recent Findings: Whilst diagnostic in the vast majority of patients, echocardiography has certain limitations including operator variability, potential for measurement errors and internal inconsistencies in severity grading. In particular, low-gradient severe aortic stenosis is common and challenging to diagnose. Aortic valve imaging may therefore be improved with alternative and complimentary multimodality approaches., Summary: This review investigates established and novel techniques for imaging both the aortic valve and the myocardial remodelling response including echocardiography, computed tomography, cardiovascular magnetic resonance and positron emission tomography. Moreover, we examine how the complementary information provided by each modality may be used in both future clinical practice and the research arena.

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.

In this pilot study, we hypothesize that dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has the potential to evaluate differences in atherosclerosis profiles in patients subjected to high (initial dust cloud) and low (after 13 September 2001) particulate matter (PM) exposure. Exposure to PM may be associated with adverse health effects leading to increased morbidity. Law enforcement workers were exposed to high levels of particulate pollution after working at "Ground Zero" and may exhibit accelerated atherosclerosis. 31 subjects (28 male) with high (n = 19) or low (n = 12) exposure to PM underwent DCE-MRI. Demographics (age, gender, family history, hypertension, diabetes, BMI, and smoking status), biomarkers (lipid profiles, hs-CRP, BP) and ankle-brachial index (ABI) measures (left and right) were obtained from all subjects. Differences between the high and low exposures were compared using independent samples t test. Using linear forward stepwise regression with information criteria model, independent predictors of increased area under curve (AUC) from DCE-MRI were determined using all variables as input. Confidence interval of 95 % was used and variables with p > 0.1 were eliminated. p < 0.05 was considered significant. Subjects with high exposure (HE) had significantly higher DCE-MRI AUC uptake (increased neovascularization) compared to subjects with lower exposure (LE). (AUC: 2.65 ± 0.63 HE vs. 1.88 ± 0.69 LE, p = 0.016). Except for right leg ABI, none of the other parameters were significantly different between the two groups. Regression model indicated that only HE to PM, CRP > 3.0 and total cholesterol were independently associated with increased neovascularization (in decreasing order of importance, all p < 0.026). HE to PM may increase plaque neovascularization, and thereby potentially indicate worsening atherogenic profile of "Ground Zero" workers.

Lipoproteins are natural nanoparticles composed of phospholipids and apolipoproteins that transport lipids throughout the body. As key effectors of lipid homeostasis, the functions of lipoproteins have been demonstrated to be crucial during the development of cardiovascular diseases. Therefore various strategies have been used to study their biology and detect them in vivo. A recent approach has been the production of lipoprotein biomimetic particles loaded with diagnostically active nanocrystals in their core. These include, but are not limited to: quantum dots, iron oxide or gold nanocrystals. Inclusion of these nanocrystals enables the utilization of lipoproteins as probes for a variety of imaging modalities (computed tomography, magnetic resonance imaging, fluorescence) while preserving their biological activity. Furthermore as some lipoproteins naturally accumulate in atherosclerotic plaque or specific tumor tissues, nanocrystal core lipoprotein biomimetics have been developed as contrast agents for early diagnosis of these diseases.

18F-FDG PET is a new noninvasive tool for inflammation functional imaging. Low spatial resolution is now compensated by coregistration with CT or MRI. New mechanistic insights have emerged from animal and histology to explain the obtained signals by hypoxia, macrophage infiltration, and differentiation. Mixed results have been found in biomarkers studies. Interesting data have come recently linking plaque anatomy and function in carotids and in aortic aneurysms as well as inflammation and events. In coronary arteries, plaque assessment is still hampered by myocardium uptake but developments are being made. 18-FDG PET has been able to monitor inflammation before and after several therapies in animals and humans but to date the lack of standardization and the absence of prospective event-driven studies prevent this promising technique to be used in clinical practice.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. New diagnostic and therapeutic strategies are needed to mitigate this public health issue. Advances in nanotechnology have generated innovative strategies for diagnosis and therapy in a variety of diseases, foremost in cancer. Based on these studies, a novel concept referred to as nanomedical theranostics, or the combinatory application of nanoparticulate agents to allow diagnostic therapy, is being explored to enable image-guided, personalized, or targeted treatment. Preclinically, theranostics have been gradually applied to CVD with several interesting and encouraging findings. This article summarizes studies and challenges of nanotheranostic strategies in CVD. It also evaluates nanotheranostic strategies that may potentially be utilized to benefit patients.

Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C-raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C-raising compounds are effective involve improvement of cholesterol uptake from macrophages in plaque for transport back to the liver, improvement of endothelial function, and anti-inflammatory effects. Vascular imaging can aid in the determination which HDL-C-raising compounds are effective. Ultrasound and MRI have proved suitable for assessment of structural changes of the vessel wall. Ultrasound can also be used or assessment of endothelial function. 18F-fluordeoxyglucose positron emission tomography has opened up the possibility to assess vessel wall inflammation. In this article we discuss these various imaging techniques and how they can assess efficacy as well as provide pathophysiologic information on the mechanism of action of novel HDL-C-raising drugs.

Atherosclerosis is a progressive systemic disease of the large arteries characterized by the formation of plaques in the vessel wall. Despite our knowledge of its pathogenesis, many vulnerable plaques still remain undiagnosed while in their asymptomatic phase and manifest for the first time with dramatic clinical events, such as stroke or myocardial infarction. In recent years, it is becoming clearer that sudden clinical events do not necessarily correlate with the degree of luminal obstruction caused by lesions, but rather with plaque composition. In particular, the degree of plaque inflammation is important in the pathogenesis of atherosclerosis and is considered a good marker of high-risk/vulnerable plaques. The presence of inflammatory infiltrate and plaque neovascularization are both histological hallmarks of atherosclerotic plaque inflammation. Therefore, plaque angiogenesis represents an attractive target to try and identify asymptomatic high-risk lesions. Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) is a technique that has been used extensively in the past to study the vascularity of tumors and its changes following therapeutic intervention. Recently, delayed and dynamic contrast enhanced (CE) MRI have been proposed as non-invasive tools to study the extent of plaque neovascularization in animals and patients with atherosclerosis. In this review, we will provide a brief introduction on DCE-MRI acquisition and analysis techniques. We will follow this with a description of contrast enhanced MR methods for the detection and quantification of neovasculature in atherosclerosis, with an emphasis on DCE-MRI. Finally, we will examine the current limitations and challenges faced by DCE-MRI and briefly discuss its future applications in the context of atherosclerosis.

Magnetic resonance (MR) imaging is a promising modality for the in vivo detection and characterization of atherosclerotic lesions in peripheral arteries. 2D imaging techniques for evaluation of peripheral artery disease (PAD) suffer from poor spatial coverage and have long scan times. The purpose of this study was to compare a diffusion prepared dark blood 3D steady state free precession (3D-DP-SSFP) sequence for evaluating atherosclerotic plaque burden in inguinal and thigh segments of the femoral artery and comparing the results obtained with 2D turbo spin echo (2D-TSE) techniques. A further goal of the study was to examine the inter observer reproducibility of MR plaque burden measures using the 3D DP-SSFP technique. Results of the study indicated higher signal to noise ratios for the 3D-DP-SSFP technique and higher CNR (better vessel-wall delineation) compared to the 2D-TSE technique. Furthermore, a good correlation between 3D-DP-SSFP and 2D-TSE techniques for the inguinal segment but poorer correlation for the thigh segment was observed. Inter-observer reproducibility for the 3D plaque burden measures was excellent. 3D-DP-SSFP may be a useful and reproducible technique for evaluating atherosclerosis in peripheral arteries.

We investigated the ability of fluorodeoxyglucose positron emission tomography (FDG PET) imaging to serially monitor macrophage content in a rabbit model of atherosclerosis. Atherosclerosis was induced in rabbits (n = 8) by a combination of atherogenic diet and balloon denudation of the aorta. At the end of nine months, the rabbits were randomized to a further six months of the same atherogenic diet (progression group) or normal diet (regression group). In vivo uptake of FDG by the thoracic aorta was measured using aortic uptake-to-blood radioactivity ratios at the start and end of the randomized period. A significant increase in FDG uptake of the progression group after continued cholesterol feeding (aortic uptake-to-blood radioactivity: 0.57 +/- 0.02 to 0.68 +/- 0.02, P = 0.001), and a corresponding fall in FDG uptake of the regression group after returning to a normal chow diet (aortic uptake-to-blood radioactivity ratios: 0.67 +/- 0.02 to 0.53 +/- 0.02, P < 0.0001). FDG PET can quantify in vivo macrophage content and serially monitor changes in FDG activity in this rabbit model.

Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel alphavbeta3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.

Objective: To optimize a methodology for ex vivo imaging of atherosclerotic vessel wall changes using multidetector-row computed tomography (MDCT) and multi-contrast magnetic resonance imaging (MRI)., Methods: In phantom studies and studies on intact ex vivo porcine and human hearts, various filling mixtures of MDCT and MRI contrast agents have been evaluated, to enable filling and distension of the coronary arteries for optimal visualization of atherosclerotic vessel wall changes with both techniques. Various proportions of methyl cellulose, iodine-containing CT contrast agent and paramagnetic MR contrast agent containing iron-oxide particles have been tested. Imaging parameters have been optimized for high resolution plaque imaging using a four detector-row CT scanner and a 1.5 T MR system., Results: Phantom studies and studies on ex vivo porcine and human hearts demonstrated optimal proportion of methyl cellulose and CT contrast agent to be 98% vs. 2%, and 75% vs. 25% of methyl cellulose vs. MR contrast agent, respectively. These proportions provided optimal opacification of the vessel lumen in the MDCT images with 250 Hounsfield Units, and good signal suppression within the vessel lumen in the MR images, resembling in vivo imaging techniques. After retrospective matching with histopathology, atherosclerotic lesions of the human ex vivo specimens could be identified on MRI and MDCT images., Conclusion: Using an optimized mixture of methyl cellulose, MDCT and MRI contrast agents, visualization of atherosclerotic vessel wall changes is feasible, and applicable to various ex vivo models.

The two most promising noninvasive imaging modalities for the study of atherosclerosis are magnetic resonance imaging (MRI) and computed tomography (CT). Both have been shown to be capable of imaging vessel wall structures and differentiating various stages of atherosclerotic wall changes. MRI has been applied in various in vivo human studies to image atherosclerotic plaques in coronary arteries, carotid arteries, and aorta. The latest generation of multidetector row computed tomography (MDCT) systems allows for the noninvasive characterization of different plaque components in various vascular structures. MDCT allows evaluation of the whole arterial vasculature. In addition, MDCT has the ability to visualize the vessel wall and to give a quantitative measurement of calcified and noncalcified plaque. Using either technique, the repeatable, noninvasive study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of disease progression and regression. MDCT and MRI, therefore, may help in selecting appropriate treatments.

The study of atherosclerotic disease during its natural history and after therapeutic intervention may enhance our understanding of the progression and regression of this disease and will aid in selecting the appropriate medical treatments or surgical interventions. Several invasive and non-invasive imaging techniques are available to assess atherosclerotic disease vessels. Most of these techniques are strong in identifying the morphological features of the disease such as lumenal diameter and stenosis or wall thickness, and in some cases provide an assessment of the relative risk associated with the atherosclerotic disease. However, none of these techniques can fully characterize the composition of the atherosclerotic plaque in the vessel wall and therefore are incapable of identifying the vulnerable plaques. High-resolution, multi-contrast, magnetic resonance (MR) can non-invasively image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus or calcium. Application of MR imaging opens up whole new areas for diagnosis, prevention, and treatment of atherosclerosis.

Background: High resolution magnetic resonance (MR) imaging of the coronary artery wall in vivo has been limited by the cardiac and respiratory motion, flow artifacts as well as the relatively small size of the coronary arteries. We sought to validate in vivo black blood MR imaging of the coronary artery wall using a double inversion recovery fast spin echo MR imaging sequence with limited breath-holding and cardiac gating for suppression of motion artifacts by comparison with ex vivo MR imaging., Methods: Yorkshire albino swine (n = 6) were used in this study and coronary lesions were induced with balloon angioplasty. Four weeks after balloon injury of the coronary arteries MR imaging of the coronary artery lesions was performed. High resolution in vivo and ex vivo images of the coronary artery wall and lesions were obtained using a double inversion recovery fast spin echo sequence in a 1.5 T MR system. There was a statistically significant agreement (p < 0.0001) between measurements of vessel wall area (r = 0.87, slope = 0.87) and maximal wall thickness (r = 0.84, slope = 0.88) from in vivo and ex vivo MR images of the coronary arteries. The mean differences between in vivo and ex vivo measurements were 0.56 +/- 1.98 mm2 for vessel wall area and 0.02 +/- 0.36 mm for maximal wall thickness., Conclusions: Using breathholding and cardiac gating, it is possible to perform high resolution MR imaging of the coronary artery wall in vivo with good suppression of motion artifacts with a double inversion recovery fast spin echo black blood imaging sequence.