Search PubMed⌕ Search

Biomedical subjects

Zahi A Fayad

Publications and source records attributed to Zahi A Fayad.

At least 19 recordsLinked to original sources
PubMed2026

Spatially Distinct Bone Marrow Sites Are Asymmetrically Impacted by Inflammatory Cardiovascular Disease.

Cardiovascular disease, a leading cause of mortality globally, is increasingly recognized to involve complex bone marrow-driven inflammatory mechanisms, yet the impact on spatially distinct bone marrow sites and comorbidities remains poorly understood. To address this, we developed MarrowMet, a methodology for whole-body, site-specific quantification of bone marrow activity. The approach involves intravenously injecting the metabolic tracer 18F-fluorodeoxyglucose (18F-FDG) in mice, followed by bone excision to quantify site-specific bone marrow activity, with values then superimposed on a whole-body mouse atlas. After establishing that 18F-FDG bone marrow uptake strongly correlated with inflammatory activity, we applied MarrowMet to map site-specific activation patterns across diverse cardiovascular pathologies, including mouse models of inflammatory atherosclerosis, acute ischemic events, acute respiratory distress syndrome, metabolic syndrome, and aging. MarrowMet guided the selection of bone marrow regions of interest for in-depth mass cytometric analyses, with the skull and sternum emerging as critical sites exhibiting distinct immune and metabolic profiles in cardiovascular disease. These results challenge the prevailing view that femoral marrow represents systemic activity. Together, this work lays a foundation for whole-body exploration of bone marrow heterogeneity, yielding critical insights into cardiovascular disease and associated inflammatory responses, and MarrowMet can be readily adopted to profile other immune mechanisms in a variety of pathologies, including cancer and autoimmune diseases.

(18)F-FDG↗
PubMed2007

Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI.

We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.

Animals↗
PubMed2007

Effect of bezafibrate therapy on atherosclerotic aortic plaques detected by MRI in dyslipidemic patients with hypertriglyceridemia.

Fibrates reduce triglycerides (TG) and increase HDL-cholesterol levels, but there was no report showing plaque regression by fibrates. Using MRI, we investigated the effects of bezafibrate on aortic plaques in 22 dyslipidemic patients. All patients were asked to receive 400mg bezafibrate, but 8 who declined to have bezafibrate became the control group. Changes in vessel wall area (VWA) and lumen area (LA) from baseline to 1-year were evaluated. Bezafibrate reduced TG (-55%) and increased HDL-cholesterol levels (+29%). Bezafibrate reduced HDL size and increased LDL size. In thoracic plaques, bezafibrate reduced VWA (-6%, P<0.001) with no LA change, but VWA slightly progressed without bezafibrate (+5%). In abdominal plaques, bezafibrate reduced VWA (-8%, P<0.001) with LA increase (+3%, P<0.02), but VWA progressed without bezafibrate (+6%). VWA changes in thoracic and abdominal plaques correlated with TG reduction and HDL-cholesterol increase. Notably, VWA change in only abdominal plaques correlated with HDL size reduction and LDL size increase. Thus, bezafibrate induced plaque regression in thoracic and abdominal aortas with marked TG reduction and HDL-cholesterol increase, but the processes of plaque regression and vascular remodeling may differ between thoracic and abdominal aortas. However, because our study was not a controlled, randomized trial, further study is needed.

Aged↗
PubMed2006

A possible association between coronary plaque instability and complex plaques in abdominal aorta.

OBJECTIVE: Coronary plaque instability causes myocardial infarction (MI). Angiographic lesions with such instability are complex lesions. Complex carotid plaques were reported to be prevalent in unstable angina. We investigated associations between coronary plaque instability, such as MI and angiographic complex coronary lesions, and aortic plaques. METHODS AND RESULTS: Aortic MRI was performed in 146 patients undergoing coronary angiography, of whom 108 had coronary artery disease (CAD) and 44 also had MI. Prevalence of plaques in thoracic and abdominal aortas was higher in patients with than without CAD (73% and 94% versus 32% and 79%), but it was similar in CAD patients with and without MI. Notably, complex plaques in abdominal aorta were more prevalent in CAD patients with than without MI (36% versus 14%; P<0.025). In multivariate analysis, abdominal complex plaques were associated with MI (odds ratio [OR], 4.5; 95% CI, 1.5 to 13.8). Among patients without MI, thoracic and abdominal complex plaques were more prevalent in patients with than without complex coronary lesions (22% and 33% versus 2% and 7%; P<0.05). Abdominal complex plaques were also associated with complex coronary lesions (OR, 9.8; 95% CI, 1.1 to 85.9). CONCLUSIONS: Complex plaques in abdominal aorta were associated with MI and complex coronary lesions, suggesting a link between coronary and aortic plaque instability.

Adult↗
PubMed2006

Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound.

OBJECTIVES: We evaluated the accuracy of a new 64-slice computed tomography (CT) scanner, compared with intravascular ultrasound, to visualize atherosclerosis in the proximal coronary system. BACKGROUND: Noninvasive determination of plaque composition and plaque burden may be important to improve risk stratification. METHODS: In 20 patients, a 64-slice CT scan (Sensation 64, Siemens Medical Solutions, Forchheim, Germany) and an intravascular ultrasound investigation of vessels without stenosis >50% was performed. Diagnostic image quality with 64-slice CT was obtained in 36 vessels in 19 patients. RESULTS: In these vessels, which were divided in 3-mm sections, 64-slice CT enabled a correct detection of plaque in 54 of 65 (83%) sections containing noncalcified plaques, 50 of 53 (94%) sections containing mixed plaques, and 41 of 43 (95%) sections containing calcified plaques. In 192 of 204 (94%) sections, atherosclerotic lesions were excluded correctly. In addition, 64-slice CT enabled the visualization of 7 of 10 (70%) sections revealing a lipid pool and could identify a spotty calcification pattern in 27 of 30 (90%) sections. The correlation coefficient to determine plaque volumes per vessel was r2 = 0.69 (p < 0.001) with an underestimation of mixed and noncalcified plaque volumes (p < 0.03) and a trend to overestimate calcified plaque volumes by 64-slice CT. The interobserver variability to determine plaque volumes was 37%. Interobserver agreement to identify atherosclerotic sections was good (Cohen's kappa coefficient = 0.75). CONCLUSIONS: We conclude that 64-slice CT reveals encouraging results to noninvasively detect different types of coronary plaques located in the proximal coronary system. The ability to determine plaque burden currently is hampered by mainly an insufficient reproducibility.

Coronary Angiography↗
PubMed2006

Multislice dark-blood carotid artery wall imaging: a 1.5 T and 3.0 T comparison.

PURPOSE: To compare two multislice turbo spin-echo (TSE) carotid artery wall imaging techniques at 1.5 T and 3.0 T, and to investigate the feasibility of higher spatial resolution carotid artery wall imaging at 3.0 T. MATERIALS AND METHODS: Multislice proton density-weighted (PDW), T2-weighted (T2W), and T1-weighted (T1W) inflow/outflow saturation band (IOSB) and rapid extended coverage double inversion-recovery (REX-DIR) TSE carotid artery wall imaging was performed on six healthy volunteers at 1.5 T and 3.0 T using time-, coverage-, and spatial resolution-matched (0.47 x 0.47 x 3 mm3) imaging protocols. To investigate whether improved signal-to-noise ratio (SNR) at 3.0 T could allow for improved spatial resolution, higher spatial resolution imaging (0.31 x 0.31 x 3 mm3) was performed at 3.0 T. Carotid artery wall SNR, carotid lumen SNR, and wall-lumen contrast-to-noise ratio (CNR) were measured. RESULTS: Signal gain at 3.0 T relative to 1.5 T was observed for carotid artery wall SNR (223%) and wall-lumen CNR (255%) in all acquisitions (P < 0.025). IOSB and REX-DIR images were found to have different levels of SNR and CNR (P < 0.05) with IOSB values observed to be larger. Normalized to a common imaging time, the higher spatial resolution imaging at 3.0 T and the lower spatial resolution imaging at 1.5 T provided similar levels of wall-lumen CNR (P = NS). CONCLUSION: Multislice carotid wall imaging at 3.0 T with IOSB and REX-DIR benefits from improved SNR and CNR relative to 1.5 T, and allows for higher spatial resolution carotid artery wall imaging.

Adult↗
PubMed2006

Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T.

Iron oxides are used for cell trafficking and identification of macrophages in plaque using MRI. Due to the negative contrast, differentiation between signal loss caused by iron and native low signal in tissue may be problematic. It is, therefore, preferable to achieve positive contrast. The purpose of this study was to test the efficacy of a new MRI sequence GRASP (GRe Acquisition for Superparamagnetic Particles) to generate a positive signal in phantoms containing iron. Membrane phantoms were constructed containing Ferumoxide at 7 concentrations. Standard GRE sequences were modified with user controlled z-gradient rephasing (+/- 100%). CNR values were determined as a function of echo time (TE) and % rephasing at 1.5T and 3T. T(2)* values were determined using multiple double-echo GRE. The GRASP sequence generated positive signal enhancement in phantoms containing iron. For all rephasing values <or=30%, positive contrast was observed. The CNR generated at 1.5T was greater than the values at 3T for all concentrations tested. Correlation between CNR at 0% and 100% rephasing was observed at 1.5T(R = 0.84). Additionally, correlation between field change across the volume and CNR was observed. In conclusion, GRASP sequences may be used to generate positive signal enhancement in the presence of iron using MRI.

Artifacts↗
PubMed2006

MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor.

The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.

Animals↗
PubMed2006

Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP.

In vivo markers that allow for detection of ferritin within atheromatous plaque may be useful for identifying iron-catalyzed hydroxyl-radical formation and subsequent lipid peroxidation. Recently, a positive contrast MR technique--GRadient echo Acquisition for Superparamagnetic particles/suscePtibility (GRASP)--was used to identify the presence of magnetic entities in phantom models. The aim of the current study was to determine the feasibility of using GRASP in conjunction with conventional T(2) (*)-weighted (T(2) (*)W) gradient-echo (GRE) sequences for identifying ferritin/hemosiderin deposition using in vitro and in vivo models of thrombus. In vitro thrombi were prepared by incubating blood with ferritin. MRI was performed using conventional GRE sequences and GRASP. The results indicate that GRASP was able to verify ferritin deposition in in vitro thrombi. In vivo thrombi were created using a crush injury model in rabbits. The signal enhancement obtained using conventional GRE sequences and GRASP was compared with the location of iron deposition by histology. In all of the animals the GRASP signal correlated with signal loss by conventional GRE, and ferritin/hemosiderin deposition by histology. GRASP sequences in combination with conventional GRE sequences may be used to detect the presence of ferritin deposition in in vitro thrombi and in vivo crush-injured rabbit carotid arteries.

Animals↗
PubMed2006

Gadolinium mixed-micelles: effect of the amphiphile on in vitro and in vivo efficacy in apolipoprotein E knockout mouse models of atherosclerosis.

Gadolinium (Gd) micelles are nanoparticles that incorporate phospholipids, surfactants, and lipophilic Gd complexes. Preliminary studies have shown that lipid-based nanoparticles may penetrate atherosclerotic plaque. The aim of the current study was to prepare, characterize, and evaluate in vivo the efficacy of two Gd micelle formulations using apolipoprotein E knockout (ApoE(-/-)) mouse models of atherosclerosis. Gd micelles were prepared using two different amphiphiles but similar GdDTPA lipids, surfactants, and fluorescent labels. The results indicate that the choice of amphiphile may affect the particle size, relaxivity, and blood clearance in wild-type mice (WT). However, the in vivo MR efficacy, with respect to uptake in the vessel wall of ApoE(-/-) mice, was not affected by the amphiphile used. Significant wall enhancement of ApoE(-/-) mice was observed following administration of 0.015 and 0.038 mmol Gd/kg of both micelle formulations. No significant enhancement of the vessel wall of WT mice was observed for any of the dosages or formulations tested. Additionally, liver uptake 24 hr post-injection (p.i.) was not influenced by the choice of amphiphile. The results of this study strongly suggest that liver uptake and wall enhancement may be regulated by the surface properties of the micelle and not by other factors, such as micelle size.

Animals↗
PubMed2006

Properties of a versatile nanoparticle platform contrast agent to image and characterize atherosclerotic plaques by magnetic resonance imaging.

The need for more specific and selective contrast agents for magnetic resonance imaging motivated us to prepare a new nanoparticle agent based on high-density lipoproteins (HDL). This second generation contrast agent can be prepared in three different ways. The HDL nanoparticles (rHDL) were fully characterized by FPLC and gel electrophoresis. The flexibility of the platform also allows us to incorporate optical probes into rHDL for localization ex vivo by confocal fluorescence microscopy. The contrast-agent-containing nanoparticles were injected into mice that develop atherosclerotic lesions. Magnetic resonance imaging of the animals showed clear enhancement of the atherosclerotic plaques.

Animals↗
PubMed2006

Carotid black blood MRI burden of atherosclerotic disease assessment correlates with ultrasound intima-media thickness.

The aim of this study was to correlate carotid black blood MRI based measurements with those obtained by ultrasound intima-media thickness (IMT). Seventeen patients with intermediate to high Framingham cardiovascular risk score underwent both carotid ultrasound and rapid extended coverage double inversion recovery black blood carotid MRI. Overall, there was good correlation between wall area, wall thickness, and plaque index measured by MRI and the IMT measurements obtained from the ultrasound images (max r2 = 0.72, p < 0.05). Patients with mean IMT > or = 1.2 mm had significantly higher values of wall area, plaque index and wall thickness compared to patients with mean IMT < 1.2 mm. Vessel wall measurements assessed by black-blood MRI may be potentially used clinically to evaluate plaque progression and regression.

Aged↗
PubMed2006

Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.

OBJECTIVES: We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. MATERIALS AND METHODS: The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. RESULTS: After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. CONCLUSIONS: The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

Animals↗
PubMed2006

Plaque imaging and characterization using magnetic resonance imaging: towards molecular assessment.

Identification of high-risk atherosclerotic lesions prone to rupture and thrombosis may greatly decrease the morbidity and mortality associated with atherosclerosis. High-resolution magnetic resonance imaging (MRI) has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor its progression. The development of MRI contrast agents that specifically target components of the atherosclerotic plaque may enable non-invasive detection of high-risk lesions. This review discusses the use of high-resolution MRI for plaque detection and characterization and the potentials of "Molecular Imaging" using a variety of molecules present in atherosclerotic plaques that may serve as targets for specific contrast agents to allow the identification of high-risk atherosclerotic lesions in-vivo. Ultimately, such agents may enable treatment of "high-risk" patients prior to lesion progression and occurrence of complications.

Animals↗