Imaging Of Atherosclerotic Plaques Research Articles

Assessment of neovascularization in atherosclerotic carotid sinus plaques using quantitative contrast-enhanced ultrasound perfusion imaging

Aim. To assess the prospects of using quantitative contrast-enhanced ultrasound perfusion imaging of atherosclerotic carotid sinus plaques. Material and methods. The study included 5 men and 1 woman (59-76 years old, median 72) with symptomatic coronary sinus atherosclerosis. The inclusion criterion was history of ischemic stroke due to internal carotid artery lesion (NASCET >60%). We performed contrast-enhanced ultrasound perfusion imaging of the carotid arteries, endarterectomy, studying pathomorphology of the removed plaque with the calculation of the neovascular density and the total number of neovessels with a diameter <40 μm. Neovascularization was assessed by quantitative contrast-enhanced ultrasound 20 seconds after the 1 ml infusion of Sonovia (Bracco, Italy) and subsequent application of the flash. The analysis of dynamics of ultrasonic signal intensity in the atherosclerotic plaque was carried out by creating the curves of the ultrasonic signal intensity (dB)/time (s) over 3 segments of the cross section of the internal carotid artery long axis. The automatic calculation of the intensity dynamics took into account the parameter values in the studied areas within 20 s after the flash. The calculated coefficients (A, B, β) of the exponential equation for 3 atherosclerotic segments were recorded. Results. Perfusion and neovascularization were assessed in 27 segments of atherosclerotic plaques. The correlation relationships between the ultrasonic parameters of plaque perfusion and the severity of neovascularization were assessed according to the histological data. Significant correlations of the exponential curve coefficient β and histological parameters characterizing the prevalence of “young” vessels (<40 microns) in the atherosclerotic plaque were revealed. Spearman’s R for the density of neovessels was 0,54; for the number of neovessels with a diameter <40 μm. —0,66 (p<0,01). Conclusion. Diagnosis of atherosclerotic plaque neovascularization becomes possible to quantify, assessing not only the presence of neovascular vessels, but also the perfusion intensity. The novel approach replaces the qualitative and semi-quantitative method for calculating the number of carotid plaques neovessels in vivo.

Emerging Molecular Targets for Imaging of Atherosclerotic Plaque using Positron Emission Tomography.

Positron-emission-tomography (PET) using the radiopharmaceutical 18F-fluorodeoxyglucose (FDG) has become an established and validated molecular imaging modality for characterization of the inflammatory activity of atherosclerotic plaque. In the latest years, new innovative radiopharmaceuticals and applications have emerged, providing specific information on atherosclerotic plaque biology, particularly focused on inflammatory processes. To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers. A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the usefulness of nuclear hybrid imaging in atherosclerosis imaging using 18F-- sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET. Atherosclerosis imaging with PET using emerging, specific tracers holds promise in improving our understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. There is increasing, high-quality evidence on the usefulness of 18F-sodium fluoride PET and - to a lesser extent - CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy. F-sodium fluoride PET, CXCR4-targeted PET and amyloid-β-targeted PET may be used to obtain molecular information on different aspects of plaque biology. Further work is required to improve the technical aspects of these imaging techniques and to elucidate their ability to predict adverse cardiac events prospectively.

Pet tracers for vulnerable plaque imaging.

Most of the acute ischemic events, such as acute coronary syndromes and stroke, are attributed to vulnerable plaques. These lesions have common histological and pathophysiological features, including inflammatory cell infiltration, neo-angiogenesis, remodelling, haemorrhage predisposition, thin fibrous cap, large lipid core, and micro-calcifications. Early detection of the presence of a plaque prone to rupture could be life-saving for the patient; however, vulnerable plaques usually cause non-haemodynamically significant stenosis, and anatomical imaging techniques often underestimate, or may not even detect, these lesions. Although ultrasound techniques are currently considered as the "first-line" examinations for the diagnostic investigation and treatment monitoring in patients with atherosclerotic plaques, positron emission tomography (PET) imaging could open new horizons in the assessment of atherosclerosis, given its ability to visualize metabolic processes and provide molecular-functional evidence regarding vulnerable plaques. Moreover, modern hybrid imaging techniques, combining PET with computed tomography or magnetic resonance imaging, can evaluate simultaneously both functional and morphological parameters of the atherosclerotic plaques, and are expected to significantly expand their clinical role in the future. This review summarizes current research on the PET imaging of the vulnerable atherosclerotic plaques, outlining current and potential applications in the clinical setting.

18F]ZCDD083: A PFKFB3-Targeted PET Tracer for Atherosclerotic Plaque Imaging.

PFKFB3, a glycolysis-related enzyme upregulated in inflammatory conditions and angiogenesis, is an emerging target for diagnosis and therapy of atherosclerosis. The fluorinated phenoxindazole [18F]ZCDD083 was synthesized, radiolabeled in 17 ± 5% radiochemical yield and >99% radiochemical purity, and formulated for preclinical PET/CT imaging in mice. In vivo stability analysis showed no significant metabolite formation. Biodistribution studies showed high blood pool activity and slow hepatobiliary clearance. Significant activity was detected in the lung 2 h postinjection (pi) (11.0 ± 1.5%ID/g), while at 6 h pi no pulmonary background was observed. Ex vivo autoradiography at 6 h pi showed significant high uptake of [18F]ZCDD083 in the arch region and brachiocephalic artery of atherosclerotic mice, and no uptake in control mice, matching plaques distribution seen by lipid staining along with PFKFB3 expression seen by immunofluorescent staining. In vivo PET scans showed higher aortic region uptake of [18F]ZCDD083 in atherosclerotic ApoE-/-Fbn1C1039G+/- than in control mice (0.78 ± 0.05 vs 0.44 ± 0.09%ID/g). [18F]ZCDD083 was detected in aortic arch and brachiocephalic artery of ApoE-/- (with moderate atherosclerosis) and ApoE-/-Fbn1C1039G+/- (with severe, advanced atherosclerosis) mice, suggesting this tracer may be useful for the noninvasive detection of atherosclerotic plaques in vivo.

Inflammation imaging to define vulnerable plaque or vulnerable patient.

The role of nuclear imaging in the characterization of high-risk atherosclerotic plaque is increasing thanks to its high sensitivity to detect radiopharmaceuticals signal in tissues. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most studied and widely used radiopharmaceutical for the molecular imaging of atherosclerotic plaques with positron emission tomography (PET). [18F]FDG PET is a valuable tool to non-invasively detect, monitor and quantify inflammatory processes occurring in atherosclerotic plaques. The aim of this review is to gather insights provided by [18F]FDG PET to better understand the role of inflammation in the definitions of the vulnerable plaque and the vulnerable patient. Alternatives radiopharmaceuticals targeting inflammation and other potential high-risk plaque related processed are also discussed.

Molecular imaging of atherosclerotic plaque with lipid nanobubbles as targeted ultrasound contrast agents

Molecularly-targeted nanobubbles (NBs) offer opportunities to improve the ability of ultrasound imaging to identify specific pathological tissue from healthy tissue. In this work, we aimed to design ligands-conjugated, nanosized, lipid ultrasound contrast agents (UCAs) and apply the agents in the ultrasound imaging of atherosclerotic plaque. Anti-VEGFR-2 ligands were conjugated to UCAs using the noncovalent biotin-avidin linker method. Several investigations were used to determine the morphology and performance of the targeted UCAs, including surface morphology, size distribution and ligands conjunction efficiency. The prepared targeted UCAs were utilized in vivo ultrasound imaging to detect rabbit abdominal aorta atherosclerotic plaque and to investigate the acoustic behavior in a rabbit kidney model. The results implied that the nanosized UCAs carrying anti-VEGFR-2 ligands would facilitate site-specific recognition of atherosclerosis and can provide unique advantages in targeted ultrasound molecular imaging.

Intravascular imaging of atherosclerotic plaques in patients with cardiorenal syndrome: potential use of optical coherence tomography

Currently, kidney transplantation and hemodialysis are the primary therapies for end-stage renal disease. High mortality, mostly caused by cardiovascular disease, remains the main challenge in the treatment of this category of patients. It has been shown that in patients with end-stage chronic kidney disease undergoing hemodialysis, the risk of mortality due to cardiovascular disease is up to 20 times higher than in the sex- and age-matched general population. The indicated data determined the appropriateness of isolating cardiorenal relationships into a single cardiorenal syndrome (CRS). Due to the facts mentioned above, intravascular imaging methods, notably optical coherence tomography (OCT), are particularly important in diagnosing coronary artery lesions. This review analyses the data published to date on the features and capabilities of OCT in CRS patients.

Coronary Atherosclerosis Imaging.

Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. However, atherosclerosis is a dynamic process and the plaque morphology and composition may change over time. Most vulnerable plaques undergo progressive transformation from high-risk to more stable and heavily calcified lesions, while others undergo subclinical rupture and healing. Although extensive plaque calcification is often associated with stable atherosclerosis, the extent of coronary artery calcification strongly correlates with the degree of atherosclerosis and with the rate of future cardiac events. Inflammation has a central role in atherogenesis, from plaque formation to rupture, hence in the development of acute coronary events. Morphologic plaque assessment, both invasive and non-invasive, gives limited information as to the current activity of the atherosclerotic disease. The addition of nuclear imaging, based on radioactive tracers targeted to the inflammatory components of the plaques, provides a highly sensitive assessment of coronary disease activity, thus distinguishing those patients who have stable disease from those with active plaque inflammation.

Targeted Molecular Iron Oxide Contrast Agents for Imaging Atherosclerotic Plaque.

Overview: Cardiovascular disease remains a leading cause of death worldwide, with vulnerable plaque rupture the underlying cause of many heart attacks and strokes. Much research is focused on identifying an imaging biomarker to differentiate stable and vulnerable plaque. Magnetic Resonance Imaging (MRI) is a non-ionising and non-invasive imaging modality with excellent soft tissue contrast. However, MRI has relatively low sensitivity (micromolar) for contrast agent detection compared to nuclear imaging techniques. There is also an increasing emphasis on developing MRI probes that are not based on gadolinium chelates because of increasing concerns over associated systemic toxicity and deposits1. To address the sensitivity and safety concerns of gadolinium this project focused on the development of a high relaxivity probe based on superparamagnetic iron oxide nanoparticles for the imaging of atherosclerotic plaque with MRI. With development, this may facilitate differentiating stable and vulnerable plaque in vivo.Aim: To develop a range of MRI contrast agents based on superparamagnetic iron oxide nanoparticles (SPIONs), and test them in a murine model of advanced atherosclerosis.Methods: Nanoparticles of four core sizes were synthesised by thermal decomposition and coated with poly(maleicanhydride-alt-1-octadecene) (PMAO), poly(ethyleneimine) (PEI) or alendronate, then characterised for core size, hydrodynamic size, surface potential and relaxivity. On the basis of these results, one candidate was selected for further studies. In vivo studies using 10 nm PMAO-coated SPIONs were performed in ApoE-/- mice fed a western diet and instrumented with a perivascular cuff on the left carotid artery. Control ApoE-/- mice were fed a normal chow diet and were not instrumented. Mice were scanned on a 3T MR scanner (Philips Achieva) with the novel SPION contrast agent, and an elastin-targeted gadolinium agent that was shown previously to enable visualisation of plaque burden. Histological analysis was undertaken to confirm imaging findings through staining for macrophages, CX3CL1, elastin, tropoelastin, and iron.Results: The lead SPION agent consisted of a 10 nm iron oxide core with poly(maleicanhydride-alt-1-octadecene), (-36.21 mV, r2 18.806 mmol-1/s-1). The irregular faceting of the iron oxide core resulted in high relaxivity and the PMAO provided a foundation for further functionalisation on surface -COOH groups. The properties of the contrast agent, including the negative surface charge and hydrodynamic size, were designed to maximise circulation time and evade rapid clearance through the renal system or phagocytosis. In vitro testing showed that the SPION agent was non-toxic.In vivo results show that the novel contrast agent accumulates in similar vascular regions to a gadolinium-based contrast agent (Gd-ESMA) targeted to elastin, which accumulates in plaque. There was a significant difference in SPION signal between the instrumented and the contralateral non-instrumented vessels in diseased mice (p = 0.0411, student's t-test), and between the instrumented diseased vessel and control vessels (p = 0.0043, 0.0022, student's t-test). There was no significant difference between the uptake of either contrast agent between stable and vulnerable plaques (p = 0.3225, student's t-test). Histological verification was used to identify plaques, and Berlin Blue staining confirmed the presence of nanoparticle deposits within vulnerable plaques and co-localisation with macrophages.Conclusion: This work presents a new MRI contrast agent for atherosclerosis which uses an under-explored surface ligand, demonstrating promising properties for in vivo behaviour, is still in circulation 24 hours post-injection with limited liver uptake, and shows good accumulation in a murine plaque model.

Recent advances in molecular imaging of atherosclerotic plaques and thrombosis.

As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new diagnostic tools for the early detection of plaque instability and thrombosis is urgently needed. Advanced molecular imaging probes based on functional nanomaterials in combination with cutting edge imaging techniques are now paving the way for novel and unique approaches to monitor the inflammatory progress in atherosclerosis. This review focuses on the development of various molecular probes for the diagnosis of plaques and thrombosis in atherosclerosis, along with perspectives of their diagnostic applications in cardiovascular diseases. Specifically, we summarize the biological targets that can be used for atherosclerosis and thrombosis imaging. Then we describe the emerging molecular imaging techniques based on the utilization of engineered nanoprobes together with their challenges in clinical translation.

Molecular imaging of advanced atherosclerotic plaques with folate receptor-targeted 2D nanoprobes

Vulnerable atherosclerotic plaques are responsible for most cardiovascular diseases (CVDs). Folate receptor (FR) positive activated macrophages were thought to be a prominent component in the development of vulnerable plaque. The objective of this study is to develop folate conjugated two-dimensional (2D) Pd@Au nanomaterials (Pd@Au-PEG-FA) for targeted multimodal imaging of the FRs in advanced atherosclerotic plaques. Pharmacokinetic and imaging studies (single photon emission computed tomography (SPECT), computed tomography (CT) and photoacoustic (PA) imaging) were performed to confirm the prolonged blood half-life and enrichment of radioactivity in atherosclerotic plaques. Strong signals were detected in vivo with SPECT, CT and PA imaging in heavy atherosclerotic plaques, which were significantly higher than those of the normal aortas after injection of Pd@Au-PEG-FA. Blocking studies with preinjection of excess FA could effectively reduce the targeting ability of Pd@Au-PEG-FA in atherosclerotic plaques, further demonstrating the specific binding of Pd@Au-PEG-FA for plaque lesions. Histopathological characterization revealed that the signal of probe was in accordance with the high-risk plaques. In summary, the Pd@Au-PEG-FA has favorable pharmacokinetic properties and provides a valuable approach for detecting high-risk plaques in the presence of FRs in atherosclerotic plaques.

Dual-modality imaging of atherosclerotic plaques using ultrasmall superparamagnetic iron oxide labeled with rhodamine.

Aim: The diagnosis of vulnerable atherosclerotic plaques remains challenging. This study labeled ultrasmall superparamagnetic iron oxidewith rhodamine (USPIO-R) and evaluated USPIO-R for imaging atherosclerotic plaques. Methods: Apolipoprotein E-deficient mice were fed a high-fat diet and underwent MRI before and after an intravenous injection of USPIO-R. Subsequently, an aortic specimen from the mice was removed and sliced for fluorescence imaging and Prussian blue and immunofluorescent staining. Results: T2 signal loss appeared and persisted in the aortic plaque postinjection, and spontaneous fluorescence from the plaque was observed. The accumulated mechanism of USPIO-R by plaque was the macrophage internalization by Prussian blue and immunofluorescence. Conclusion: USPIO-R is a promising dual-modality probe for diagnosing and monitoring vulnerable atherosclerotic plaques.

Frontiers in positron emission tomography imaging of the vulnerable atherosclerotic plaque.

Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic cardiovascular disease. Positron emission tomography (PET) imaging with an appropriate radiotracer has the potential to achieve this goal. This review will discuss the biological hallmarks of plaque vulnerability before going on to evaluate and to present PET imaging approaches which target these processes. The focus of this review will be on techniques beyond [18F]FDG imaging, some of which are clinically advanced, and others which are on the horizon. As inflammation is the primary driving force behind atherosclerotic plaque development, we will predominantly focus on approaches which either directly, or indirectly, target this process.

Evaluating of the accurasy of cardiovascular events predicting using SCORE scale and ultrasound visualization of atherosclerotic plaque in patients of multi-disciplinary hospital in Saint-Petersburg: medium-term monitoring data

Aim. To compare the accuracy of predicting the risk of fatal and non-fatal cardiovascular events (CVE) based on SCORE scaling and ultrasound imaging of carotid atherosclerotic plaque (AP) in patients without manifested atherosclerotic cardiovascular disease (ACVD) in a multidisciplinary hospital. Material and methods. We examined 841 patients (353 men) (avearage age 54,9±8), with at least 1 traditional cardiovascular risk factor without manifested ACVD. Ultrasound examination of the carotid arteries was performed in all patients. Patients with nonstenotic AP constituted the AP+ group, and without AP — the AP-group (356 and 485 people, respectively). Median of follow-up time was 4 years, (minimum — 2, maximum — 6 years). The endpoints included: a verified diagnosis of acute coronary syndrome, chronic coronary artery disease, planned coronary revascularization, ischemic stroke, and/or transient ischemic attack, cardiac death. Results. Nonstenotic AP of carotid arteries was detected in 352 people (42%), including 64 (23%) in low and 182 (46%) in moderate SCORE risk. 127 CVE (178%) occurred during the follow-up, 84 (66% of the total) of them in the AP+ group. The actual frequency of development of the cumulative endpoint was significantly higher than the calculated rate (the ratio of actua predicted events was 1,6, 5,1 and 79 for high, moderate and low SCORE risk, respectively). According to the multivariate regression analysis, the OR for AP as a predictor of cardiovascular events cardiovascular events CVE was 2,54 (95% CI 1,6-4,04), and was significantly higher than the SCORE index (1,04, 95% CI 0,01-1,07). As a predictor of CVE, AP had the greatest value in the low SCORE risk group (the number of CVE in the low SCORE risk group was14 among patients with AP vs 10 among patients without AP, p=0,001). Conclusion. The use of SCORE scale underestimates the actual risk of CVE especially in patients with low and moderate calculated SCORE risk. Ultrasound visualization of AP of the carotid arteries in these patients predicts the risk of cardiovascular disease much more accurately.

Frequency-domain differential photoacoustic radar: theory and validation for ultrasensitive atherosclerotic plaque imaging.

.Lipid composition of atherosclerotic plaques is considered to be highly related to plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques’ necrotic core is desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. While, in the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications since lipids exhibit a strong absorption peak at that wavelength, the sensitivity problem arises in the conventional single-ended systems as other arterial tissues also show some degree of absorption near that spectral region, thereby generating undesirably interfering photoacoustic (PA) signals. A theory of the high-frequency frequency-domain differential photoacoustic radar (DPAR) modality is introduced as a unique detection technique for accurate and molecularly specific evaluation of vulnerable plaques. By assuming two low-power continuous-wave optical sources at and in a differential manner, DPAR theory and the corresponding simulation/experiment studies suggest an imaging modality that is only sensitive and specific to the spectroscopically defined imaging target, cholesterol.

Nanoparticle Imaging of Vascular Inflammation and Remodeling in Atherosclerotic Disease

The purpose of this review is to highlight some of the recent developments (within the last 5 years) in imaging atherosclerotic plaques using nanoparticles, with a focus on technologies that have been applied to in vivo models of disease. Structural and cellular components of atherosclerotic plaques are being imaged with greater definition and improved sensitivity. This is a result of both molecular targeting of nanoparticles to disease-relevant biomarkers through the use of nanoparticles of different shapes and sizes and tailoring pharmacokinetic parameters that allow for enhanced pharmacodynamic effects. Currently, there are no atherosclerotic plaque imaging techniques clinically validated to predict future clinical events. Considering the rapid pace of new nanomaterial discovery and development, along with the development of multimodality imaging systems, this goal seems within reach. These advancements are “nano” in name only.

Nuclear Imaging: Focus on Vascular Probes

Noninvasive imaging technologies offer to identify several anatomic and molecular features of high-risk plaques. For the noninvasive molecular imaging of atherosclerotic plaques, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 18F-fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical for molecular imaging of atherosclerotic plaques with positron emission tomography. The intensity of FDG uptake in the vascular wall correlates closely with the degree of macrophage infiltration in atherosclerotic plaques. FDG positron emission tomographic imaging has become a powerful tool to identify and monitor noninvasively inflammatory activities in atherosclerotic plaques over time. This review examines how FDG positron emission tomographic imaging has given us deeper insight into the role of inflammation in atherosclerotic plaque progression and discusses perspectives for alternative radiopharmaceuticals to FDG that could provide a more specific and simple identification of high-risk lesions and help improve risk stratification of atherosclerotic patients. Visual Overview- An online visual overview is available for this article.

Improved in vivo detection of atherosclerotic plaques with a tissue factor-targeting magnetic nanoprobe

Rupture of atherosclerotic plaques causes acute cardiovascular and cerebrovascular pathology. Tissue factor (TF) is a key factor that affects the development of atherosclerotic plaques and the formation of thrombus and thus constitutes a potential target for the detection of atherosclerotic plaques. In this study, the conjugation of the fusion protein ‘enhanced green fluorescent protein with the first epidermal growth factor domain’ (EGFP-EGF1) and superparamagnetic iron oxide nanoparticles (EGFP-EGF1-SPIONs) was explored for molecular imaging of TF-positive atherosclerotic plaques. EGFP-EGF1-SPIONs showed improved accuracy, superior contrast effects, and better cytocompatibility compared with common contrast agents in the detection of atherosclerotic plaques of apolipoprotein E knockout (ApoE−/−) mice using magnetic resonance imaging. In conclusion, EGFP-EGF1-SPION is a promising TF-targeting nanoprobe to precisely and specifically detect atherosclerotic plaques, which may improve molecular imaging diagnosis of cardiovascular and cerebrovascular events for the comprehensive evaluation of atherosclerosis. Statement of SignificanceTraditional methods can only display the status of atherosclerosis, but not forecast the progress of lesions efficiently. It remains challenging to evaluate the plaques specifically and sensitively. In this study, we constructed a tissue factor-targeted magnetic nanoprobe to specifically detect plaques by magnetic resonance imaging in vivo, which will improve the diagnostic technology for atherosclerotic plaques and offer molecular level guidance to treat atherosclerosis. Furthermore, this strategy has critical clinical significance on prevention, diagnosis and therapeutic evaluation of cardio-cerebral vascular events.

18F-PBR06 PET/CT imaging for evaluating atherosclerotic plaques linked to macrophage infiltration.

The present study explored the 18 kDa translocator protein radioligand [F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline (F-PBR06) targeting macrophages for PET imaging of atherosclerotic plaques and evaluating the vulnerability of atherosclerotic plaques toward rupture. F-PBR06 was synthesized using a Synthra RNplus module automatically. RAW264.7 cells were used for cell binding study with F-PBR06. In-vivo micro-PET/CT imaging for ApoE mice and C57 mice was performed 1 h after injection of F-PBR06. CD68 and F480 immunofluorescence stainings were performed in the aorta tissues. In-vitro cell studies showed uptake of F-PBR06 to RAW264.7 cells. Micro-PET/CT imaging identified the atherosclerotic lesions in the aortic arch of ApoE mice successfully, whereas no signal was observed in C57 mice. The ratio of plaque-to-muscle in ApoE mice of 32 weeks was significantly higher than that in ApoE mice of 22 weeks, which was confirmed by CD68 immunofluorescence staining and F480 immunofluorescence staining. TSPO radioligand F-PBR06 allows noninvasive PET/CT imaging of macrophage-abundant atherosclerotic plaques as well as positive correlation between PET imagings and ex-vivo immunofluorescence staining of plaques in mice with different ages, thereby representing a potential attractive tool for evaluating the vulnerability of atherosclerotic plaques towards rupture.

Biomedical risk assessment as an aid for smoking cessation.

A possible strategy for increasing smoking cessation rates could be to provide smokers with feedback on the current or potential future biomedical effects of smoking using, for example, measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer or other diseases. The main objective was to determine the efficacy of providing smokers with feedback on their exhaled CO measurement, spirometry results, atherosclerotic plaque imaging, and genetic susceptibility to smoking-related diseases in helping them to quit smoking. For the most recent update, we searched the Cochrane Tobacco Addiction Group Specialized Register in March 2018 and ClinicalTrials.gov and the WHO ICTRP in September 2018 for studies added since the last update in 2012. Inclusion criteria for the review were: a randomised controlled trial design; participants being current smokers; interventions based on a biomedical test to increase smoking cessation rates; control groups receiving all other components of intervention; and an outcome of smoking cessation rate at least six months after the start of the intervention. We used standard methodological procedures expected by Cochrane. We expressed results as a risk ratio (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate, we pooled studies using a Mantel-Haenszel random-effects method. We included 20 trials using a variety of biomedical tests interventions; one trial included two interventions, for a total of 21 interventions. We included a total of 9262 participants, all of whom were adult smokers. All studies included both men and women adult smokers at different stages of change and motivation for smoking cessation. We judged all but three studies to be at high or unclear risk of bias in at least one domain. We pooled trials in three categories according to the type of biofeedback provided: feedback on risk exposure (five studies); feedback on smoking-related disease risk (five studies); and feedback on smoking-related harm (11 studies). There was no evidence of increased cessation rates from feedback on risk exposure, consisting mainly of feedback on CO measurement, in five pooled trials (RR 1.00, 95% CI 0.83 to 1.21; I2 = 0%; n = 2368). Feedback on smoking-related disease risk, including four studies testing feedback on genetic markers for cancer risk and one study with feedback on genetic markers for risk of Crohn's disease, did not show a benefit in smoking cessation (RR 0.80, 95% CI 0.63 to 1.01; I2 = 0%; n = 2064). Feedback on smoking-related harm, including nine studies testing spirometry with or without feedback on lung age and two studies on feedback on carotid ultrasound, also did not show a benefit (RR 1.26, 95% CI 0.99 to 1.61; I2 = 34%; n = 3314). Only one study directly compared multiple forms of measurement with a single form of measurement, and did not detect a significant difference in effect between measurement of CO plus genetic susceptibility to lung cancer and measurement of CO only (RR 0.82, 95% CI 0.43 to 1.56; n = 189). There is little evidence about the effects of biomedical risk assessment as an aid for smoking cessation. The most promising results relate to spirometry and carotid ultrasound, where moderate-certainty evidence, limited by imprecision and risk of bias, did not detect a statistically significant benefit, but confidence intervals very narrowly missed one, and the point estimate favoured the intervention. A sensitivity analysis removing those studies at high risk of bias did detect a benefit. Moderate-certainty evidence limited by risk of bias did not detect an effect of feedback on smoking exposure by CO monitoring. Low-certainty evidence, limited by risk of bias and imprecision, did not detect a benefit from feedback on smoking-related risk by genetic marker testing. There is insufficient evidence with which to evaluate the hypothesis that multiple types of assessment are more effective than single forms of assessment.