555 research outputs found

    Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density

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    <p>Abstract</p> <p>Background</p> <p>Proteins are major plaque components, and their degradation is related to the plaque instability. We sought to assess the feasibility of magnetization transfer (MT) magnetic resonance (MR) for identifying fibrin and collagen in carotid atherosclerotic plaques <it>ex vivo</it>.</p> <p>Methods</p> <p>Human carotid artery specimens (n = 34) were obtained after resection from patients undergoing endarterectomy. MR was completed within 12 hr after surgery on an 11.7T MR microscope prior to fixation. Two sets of T1W spoiled gradient echo images were acquired with and without the application of a saturation pulse set to 10 kHz off resonance. The magnetization transfer ratio (MTR) was calculated, and the degree of MT contrast was correlated with histology.</p> <p>Results</p> <p>MT with appropriate calibration clearly detected regions with high protein density, which showed a higher MTR (thick fibers (collagen type I) (54 ± 8%)) compared to regions with a low amount of protein including lipid (46 ± 8%) (p = 0.05), thin fibers (collagen type III) (11 ± 6%) (p = 0.03), and calcification (6.8 ± 4%) (p = 0.02). Intraplaque hemorrhage (IPH) with different protein density demonstrated different MT effects. Old (rich in protein debris) and recent IPH (rich in fibrin) had a much higher MTR 69 ± 6% and 55 ± 9%, respectively, compared to fresh IPH (rich in intact red blood cells)(9 ± 3%).</p> <p>Conclusions</p> <p>MT MR enhances plaque tissue contrast and identifies the protein-rich regions of carotid artery specimens. The additional information from MTR of IPH may provide important insight into the role of IPH on plaque stability, evolution, and the risk for future ischemic events.</p

    Biomarkers of atherosclerosis and the potential of MRI for the diagnosis of vulnerable plaque.

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    Atherosclerosis is a chronic inflammatory vascular disease. As it is an inflammation process, many cellular and molecular events are involved at each step of the progression of atherosclerosis from an early fatty streak lesion to a highly dangerous rupture-prone plaque. Magnetic resonance imaging (MRI) is a well-established diagnostic tool for many kinds of chronic inflammation in various systems and organs, and recent improvements in spatial resolution and contrast strategies make it a promising technique for the characterization of inflammatory vessel walls. The first part of this review will briefly introduce the main cellular and molecular processes involved in atherosclerotic lesions; the second part will focus on the use of high-resolution MRI and present-generation contrast agents for plaque characterization; and the third part will present some recent and ongoing cellular and molecular MRI studies of atherosclerosis

    Progress in atherosclerotic plaque imaging

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    Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods

    Imaging Atherosclerosis.

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    Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). M.D is supported by the British Heart Foundation (FS/14/78/31020). N.R.E. is supported by a research training fellowship from the Dunhill Medical Trust (RTF44/0114). A.J.B. is supported by the British Heart Foundation. J.H.F.R. is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/CIRCRESAHA.115.30624

    Carotid Artery Disease and Stroke: Assessing Risk with Vessel Wall MRI

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    Cardiovascular Magnetic Resonance Imaging in Experimental Models

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    Cardiovascular magnetic resonance (CMR) imaging is the modality of choice for clinical studies of the heart and vasculature, offering detailed images of both structure and function with high temporal resolution

    Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer's Disease

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    In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice

    In Vivo Cellular MRI In Experimental Traumatic Spinal Cord Injury

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    Spinal cord injury (SCI) remains one of the most devastating conditions in medicine; it is a complex medical condition with no cure currently available. Inflammation plays an important role in SCI as it can have both beneficial and detrimental effects. Cell therapy has emerged as a promising treatment for SCI due to the potential for stem cells, including multipotent mesenchymal stromal cells (MSC), for tissue regeneration and immunomodulation of the inflammatory cascade after the initial trauma. However, there are still important, unresolved questions regarding cell therapy that magnetic resonance imaging (MRI) can help to address by producing high-resolution images with exquisite soft tissue contrast in a non-invasive, non-destructive and three-dimensional (3D) manner, allowing a dynamic view of changing pathology and cellular events in vivo. In this thesis in vivo longitudinal imaging of SCI in mouse and rat models is presented using MRI. A resolution of 200μm in all three planes was achieved using a balanced steady state free precession (bSSFP) pulse sequence in a 3T whole-body clinical scanner. Using iron oxide particles as a contrast agent, cellular MRI was used to assess direct MSC transplantation in a mouse model and acute inflammation in a rat model. This was the first study to use cellular MRI for cell tracking in a mouse SCI model. We report on the use of cellular MRI to locate transplanted cells and monitor their overall distribution as well as to evaluate the delivery of transplanted cells to the target tissue in the early phase. Limitations of long-term cell tracking using iron oxide are also discussed. This is also the first study using cellular MRI to image in vivo cells associated with the inflammatory response within the lesion in a rat SCI model and the first demonstration of the use of bSSFP at 3T for rat body imaging. Having the tools for longitudinal in vivo cell monitoring in SCI will help gain a better understanding of both inflammation and response to cell therapy. As these tools are refined, they can be used to test different potential treatments for SCI and optimize them

    Atherosclerotic Plaque Characterization in Humans with Acoustic Radiation Force Impulse (ARFI) Imaging

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    Cardio- and cerebrovascular diseases (CVD) are among the leading causes of death and disability in the United States. A vast majority of heart attacks and strokes are linked to atherosclerosis; a condition characterized by inflammation and plaque accumulation in the arterial wall that can rupture and propagate an acute thrombotic event. Identification of plaques that are vulnerable to rupture is paramount to the prevention of heart attacks and strokes, but a noninvasive plaque characterization imaging technology that is cost-effective, safe, and accurate has remained elusive. The goal of this dissertation is to evaluate whether acoustic radiation force impulse (ARFI) imaging, an ultrasound-based elastography technique, can noninvasively characterize plaque components and identify features that have been shown to correlate with plaque vulnerability. Data are presented from preclinical studies, done in a porcine model of atherosclerosis, and clinical studies, performed in patients undergoing carotid endarterectomy (CEA), to demonstrate the sensitivity and specificity of ARFI for various plaque components. Additionally, the ability of ARFI to measure fibrous cap thickness is assessed with finite element method (FEM) modelling, and the limits of ARFI fibrous cap resolution are analyzed. Lastly, advanced ARFI-based plaque imaging methods are explored, including intravascular ARFI for coronary plaque characterization. Overall, these studies demonstrate that ARFI can delineate features consistent with vulnerable plaque in a clinical imaging context and suggest that ARFI has the potential to improve the current state of the art in atherosclerosis diagnostics.Doctor of Philosoph

    Optical coherence tomography for the assessment of coronary atherosclerosis and vessel response after stent implantation

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    Optical Coherence Tomography (OCT) is a light-based imaging modality that can provide in vivo high-resolution images of the coronary artery with a level of resolution (axial 10-20 µm) ten times higher than intravascular ultrasound. The technique, uses low-coherent near infrarred light to create high-resolution cross sectional images of the vessel. The technology refinement achieved in the last years has made this imaging modality less procedurally demanding opening its possibilities for clinical use. The present thesis provides im
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