Role of biomechanical forces in the natural history of coronary atherosclerosis.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203

Intravascular photoacoustics as a theranostic platform for atherosclerosis

textThe persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents.Biomedical Engineerin

Intravascular Ultrasound (IVUS): A Potential Arthroscopic Tool for Quantitative Assessment of Articular Cartilage

Conventional ultrasound examination of the articular cartilage performed externally on the body surface around the joint has limited accuracy due to the inadequacy in frequency used. In contrast to this, minimally invasive arthroscopy-based ultrasound with adequately high frequency may be a better alternative to assess the cartilage. Up to date, no special ultrasound transducer for imaging the cartilage in arthroscopic use has been designed. In this study, we introduced the intravascular ultrasound (IVUS) for this purpose. An IVUS system with a catheter-based probe (Ø ≈ 1mm) was used to measure the thickness and surface acoustical reflection of the bovine patellar articular cartilage in vitro before and after degeneration induced by enzyme treatments. Similar measurement was performed using another high frequency ultrasound system (Vevo) with a probe of much larger size and the results were compared between the two systems. The thickness measured using IVUS was highly correlated (r = 0.985, p < 0.001) with that obtained by Vevo. Thickness and surface reflection amplitude measured using IVUS on the enzymatically digested articular cartilage showed changes similar to those obtained by Vevo, which were expectedly consistent with previous investigations. IVUS can be potentially used for the quantitative assessment of articular cartilage, with its ready-to-use arthroscopic feature

Progress in atherosclerotic plaque imaging

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

Atherosclerotic plaque characterization using plaque area variation in IVUS images during compression: a computational investigation

INTRODUCTION: The rupture of atherosclerotic plaques causes millions of death yearly. It is known that the kind of predominant tissue is associated with its dangerousness. In addition, the mechanical properties of plaques have been proved to be a good parameter to characterize the type of tissue, important information for therapeutic decisions. METHODS: Therefore, we present an alternative and simple way to discriminate tissues. The procedure relies on computing an index, the ratio of the plaque area variation of a suspecting plaque, using images acquired with vessel and plaques, pre and post-deformation, under different intraluminal pressure. Numerical phantoms of coronary cross-sections with different morphological aspects, and simulated with a range of properties, were used for evaluation. RESULTS: The outcomes provided by this index and a widely used one were compared, so as to measure their correspondence. As a result, correlations up to 99%, a strong agreement with Bland-Altman and very similar histograms between the two indices, have shown a good level of equivalence between the methods. CONCLUSION: The results demonstrated that the proposed index discriminates highly lipidic from fibro-lipidic and calcified tissues in many situations, as good as the widely used index, yet the proposed method is much simpler to be computed.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Instituto de Ciência e Tecnologia Departamento de Ciência e TecnologiaUniversidade de São Paulo Escola Politécnica Departamento de Engenharia de Telecomunicações e ControleUNIFESP, Instituto de Ciência e Tecnologia Depto. de Ciência e TecnologiaSciEL

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Ex Vivo Porcine Arterial and Chorioallantoic Membrane Acoustic Angiography Using Dual-Frequency Intravascular Ultrasound Probes

The presence of blood vessels within a developing atherosclerotic plaque has been shown to be correlated to increased plaque vulnerability and ensuing cardiac events, however, detecting coronary intraplaque neovascularizations poses a significant challenge in the clinic. In this paper, we demonstrate in vivo a new intravascular ultrasound imaging method using a dual-frequency transducer to visualize contrast flow in microvessels with high specificity. This method uses a specialized transducer capable of exciting contrast agents at a low frequency (5.5 MHz) while detecting their nonlinear superhamonics at a much higher frequency (37 MHz). In vitro evaluation of the approach was performed in a microvascular phantom to produce 3D renderings of simulated vessel patterns and to determine image quality metrics as a function of depth. Furthermore, the ability of the system to detect microvessels is demonstrated both ex vivo using porcine arteries and in vivo using the chorioallantoic membrane of a developing chicken embryo with optical confirmation. Dual-frequency contrast specific imaging was able to resolve vessels of a similar size to those found in vulnerable atherosclerotic plaques at clinically relevant depths. The results of this study adds growing support for further evaluation and translation of contrast specific imaging in intravascular ultrasound for the detection of vulnerable plaques in atherosclerosis