Browsing by Author "Phinikaridou, Alkystis"
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- ItemAdvances in molecular imaging of atherosclerosis and myocardial infarction: shedding new light on in vivo cardiovascular biology(2012) Phinikaridou, Alkystis; Andía Kohnenkampf, Marcelo Edgardo; Shah, Ajay M.; Botnar, René M.Molecular imaging of the cardiovascular system heavily relies on the development of new imaging probes and technologies to facilitate visualization of biological processes underlying or preceding disease. Molecular imaging is a highly active research discipline that has seen tremendous growth over the past decade. It has broadened our understanding of oncologic, neurologic, and cardiovascular diseases by providing new insights into the in vivo biology of disease progression and therapeutic interventions. As it allows for the longitudinal evaluation of biological processes, it is ideally suited for monitoring treatment response. In this review, we will concentrate on the major accomplishments and advances in the field of molecular imaging of atherosclerosis and myocardial infarction with a special focus on magnetic resonance imaging.
- ItemAssessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy(2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
- ItemCharacterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS−/− mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(2023) Lavin, Begoña; Eykyn, Thomas; Phinikaridou, Alkystis; Xavier, Aline; Kumar, Shravan; Buqué, Xabier; Aspichueta, Patricia; Sing-Long C., Carlos A.; Arrese, Marco; Botnar, René Michael; Andía Kohnenkampf, Marcelo EdgardoNonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS−/− mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS−/− mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3−/− mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS−/− murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.
- ItemContrast-enhanced magnetic resonance imaging for the detection of ruptured coronary plaques in patients with acute myocardial infarction(2017) Jansen, Christian H. P.; Perera, Divaka; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Razavi, Reza M.; Rinaldi, Aldo; Marber, Mike S.; Greil, Gerald F.; Nagel, Eike; Botnar, René Michael; Maintz, David; Redwood, Simon; Makowski, Marcus
- ItemDevelopment of a tropoelastin-binding MR contrast agent for in vivo imaging of impaired elastogenesis in atherosclerosis(2015) Andía Kohnenkampf, Marcelo Edgardo; Botnar, René Michael; Phinikaridou, Alkystis; Lacerda, Sara
- ItemFlow-independent 3D whole-heart vessel wall imaging using an interleaved T2-preparation acquisition(2013) Andía Kohnenkampf, Marcelo Edgardo; Henningsson, Markus; Hussain, Tarique; Phinikaridou, Alkystis; Protti, Andrea; Greil, Gerald; Botnar, René Michael
- ItemImaging the extracellular matrix in prevalent cardiovascular diseases(MDPI AG, 2020) Chaher, Nadia; Hajhosseiny, Reza; Phinikaridou, Alkystis; Botnar, René MichaelThe extracellular matrix (ECM) is a highly complex macromolecular network present in all tissues and organs. The ECM is continuously remodelling under an orchestrated process facilitated by many matrix-degrading and matrix-synthesising enzymes in both health and disease. Disturbance of this balance can be the result of or can lead to various diseases. In cardiovascular diseases (CVDs), changes to the ECM are evident in conditions including: atherosclerosis, myocardial infarction (MI), venous thromboembolism (VTE) and abdominal aortic aneurysm (AAA). ECM proteins and ECM regulating enzymes are differently expressed in various CVDs. Most importantly, the altered deposition, macromolecule arrangement and activity of the ECM makes it an attractive marker of disease onset, pathogenesis and progression. Many medical imaging modalities allow disease assessment by exploiting native image contrast, by using non-targeted or by using protein or cell specific (targeted) imaging probes. However, the ability to directly visualise and quantify changes in specific ECM proteins enhances our understanding of the biological role of these proteins, enables monitoring of disease progression and response to treatment and may improve patient diagnosis and allocation of personalised therapies. This review focuses on the biochemistry of the major extracellular matrix proteins and advancements in the development of ECM-targeted probes for molecular imaging of CVD, particularly for applications of molecular magnetic resonance imaging (MRI) and position emission tomography (PET) imaging.
- ItemIncreased vascular permeability is a surrogate marker of atherosclerotic plaque instability(2015) Phinikaridou, Alkystis; Andía Kohnenkampf, Marcelo Edgardo; Plaza, Begona L.; Saha, Prakash; Smith, Alberto; Botnar, René Michael
- ItemInitial results of the Hyperion II DPET insert for simultaneous PET-MRI applied to atherosclerotic plaque imaging in New-Zealand white rabbits(IOP Publishing Ltd, 2024) Gebhardt, Pierre; Lavin, Begoña; Phinikaridou, Alkystis; Mackewn, Jane E.; Henningsson, Markus; Schug, David; Salomon, Andre; Marsden, Paul K.; Schulz, Volkmar; Botnar, René MichaelObjective. In preclinical research, in vivo imaging of mice and rats is more common than any other animal species, since their physiopathology is very well-known and many genetically altered disease models exist. Animal studies based on small rodents are usually performed using dedicated preclinical imaging systems with high spatial resolution. For studies that require animal models such as mini-pigs or New-Zealand White (NZW) rabbits, imaging systems with larger bore sizes are required. In case of hybrid imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI), clinical systems have to be used, as these animal models do not typically fit in preclinical simultaneous PET-MRI scanners. Approach. In this paper, we present initial imaging results obtained with the Hyperion IID PET insert which can accommodate NZW rabbits when combined with a large volume MRI RF coil. First, we developed a rabbit-sized image quality phantom of comparable size to a NZW rabbit in order to evaluate the PET imaging performance of the insert under high count rates. For this phantom, radioactive spheres with inner diameters between 3.95 and 7.86mm were visible in a warm background with a tracer activity ratio of 4.1 to 1 and with a total 18F activity in the phantom of 58MBq at measurement start. Second, we performed simultaneous PET-MR imaging of atherosclerotic plaques in a rabbit in vivo using a single injection containing 18F-FDG for detection of inflammatory activity, and Gd-ESMA for visualization of the aortic vessel wall and plaques with MRI. Main results. The fused PET-MR images reveal 18F-FDG uptake within an active plaques with plaque thicknesses in the sub-millimeter range. Histology showed colocalization of 18F-FDG uptake with macrophages in the aortic vessel wall lesions. Significance. Our initial results demonstrate that this PET insert is a promising system for simultaneous high-resolution PET-MR atherosclerotic plaque imaging studies in NZW rabbits.
- ItemMRI with gadofosveset : a potential marker for permeability in myocardial infarction(2018) Lavin, Begoña; Protti, Andrea; Lorrio, Silvia; Dong, Xuebin; Phinikaridou, Alkystis; Botnar, René Michael; Shah, Ajay
- ItemNon-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis(2024) Chaher, Nadia; Lacerda, Sara; Digilio, Giuseppe; Padovan, Sergio; Gao, Ling; Lavín, Begoña; Stefania, Rachele; Velasco Jimeno, Carlos; Cruz, Gastão; Prieto Vásquez, Claudia; Botnar, René Michael; Phinikaridou, AlkystisHeart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved. Here, we discovered the first imaging probe that binds to COL3 with high affinity and specificity, by screening candidate peptide-based probes. Characterisation of the probe showed favourable magnetic and biodistribution properties. The probe’s potential for in vivo molecular cardiac magnetic resonance imaging was evaluated in a murine model of myocardial infarction. Using the new probe, we were able to map and quantify, previously undetectable, spatiotemporal changes in COL3 after myocardial infarction and monitor response to treatment. This innovative probe provides a promising tool to non-invasively study the unexplored roles of COL3 in cardiac fibrosis and other cardiovascular conditions marked by changes in COL3.
- ItemNoninvasive Magnetic Resonance Imaging Evaluation of Endothelial Permeability in Murine Atherosclerosis Using an Albumin-Binding Contrast Agent(LIPPINCOTT WILLIAMS & WILKINS, 2012) Phinikaridou, Alkystis; Andia, Marcelo E.; Protti, Andrea; Indermuchle, Andreas; Shah, Ajay; Smith, Alberto; Warley, Alice; Botnar, Rene M.Backgound-Endothelial dysfunction promotes atherosclerosis and precedes acute cardiovascular events. We investigated wether in vivo magnetic resonance imaging with the use of an albumin-binding contrast agent, gadofosveset, could detect endothelial damage associated with atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Furthermore, we tested whether magnetic resonance imaging could noninvasively assess endothelial function by measuring the endothelial-dependent vasolidation in response to acetycholine.
- ItemOptimized Methods for the Surface Immobilization of Collagens and Collagen Binding Assays(2023) Chaher, Nadia; Digilio, Giuseppe; Lacerda, Sara; Botnar, Rene M.; Phinikaridou, AlkystisFibrosis occurs in various tissues as a reparative response to injury or damage. If excessive, however, fibrosis can lead to tissue scarring and organ failure, which is associated with high morbidity and mortality. Collagen is a key driver of fibrosis, with type I and type III collagen being the primary types involved in many fibrotic diseases. Unlike conventional protocols used to immobilize other proteins (e.g., elastin, albumin, fibronectin, etc.), comprehensive protocols to reproducibly immobilize different types of collagens in order to produce stable coatings are not readily available. Immobilizing collagen is surprisingly challenging because multiple experimental conditions may affect the efficiency of immobilization, including the type of collagen, the pH, the temperature, and the type of microplate used. Here, a detailed protocol to reproducibly immobilize and quantify type I and III collagens resulting in stable and reproducible gels/films is provided. Furthermore, this work demonstrates how to perform, analyze, and interpret in vitro time-resolved fluorescence binding studies to investigate the interactions between collagens and candidate collagen-binding compounds (e.g., a peptide conjugated to a metal chelate carrying, for example, europium [Eu(III)]). Such an approach can be universally applied to various biomedical applications, including the field of molecular imaging to develop targeted imaging probes, drug development, cell toxicity studies, cell proliferation studies, and immunoassays.
- ItemQuantitative MRI of Endothelial Permeability and (Dys)function in Atherosclerosis(2021) Lavín Plaza, Begoña; Andía Kohnenkampf, Marcelo Edgardo; Saha, Prakash; Botnar, René Michael; Phinikaridou, Alkystis
- ItemSimultaneous Assessment of Cardiac Inflammation and Extracellular Matrix Remodeling After Myocardial Infarction(2018) Ramos, Isabel T.; Henningsson, Markus; Nezafat, Maryam; Lavín, Begoña; Lorrio, Silvia; Gebhardt, Pierre; Protti, Andrea; Eykyn, Thomas R.; Andía Kohnenkampf, Marcelo Edgardo; Botnar, René Michael; Floögel, Ulrich; Phinikaridou, Alkystis; Shah, Ajay M.
- ItemSimultaneous bright- and black-blood whole-heart MRI for noncontrast enhanced coronary lumen and thrombus visualization(2018) Ginami, Giulia; Neji, Radhouene; Phinikaridou, Alkystis; Whitaker, John; Botnar, René Michael; Prieto Vásquez, Claudia
- ItemThe future of MRI in thoracic aortopathy: blueprint for the paradigm shift to improve management(2025) Nadel, James; Rodríguez Palomares, José; Phinikaridou, Alkystis; Prieto Vásquez, Claudia Del Carmen; Masci, Pier Giorgio; Botnar, René MichaelThoracic aortopathies result in aneurysmal expansion of the aorta that can lead to rapidly fatal aortic dissection or rupture. Despite the availability of abundant non-invasive imaging tools, the greatest contemporary challenge in the management of thoracic aortic aneurysm (TAA) is the lack of reliable metrics for risk stratification, with absolute aortic diameter, growth rate and syndromic factors remaining the primary determinants by which prophylactic surgical intervention is adjudged. Advanced MRI techniques present as a potential key to unlocking insights into TAA that could guide disease surveillance and surgical intervention. MRI has the capacity to encapsulate the aorta as a complex biomechanical structure, permitting the determination of aortic volume, morphology, composition, distensibility and fluid dynamics in a time-efficient manner. Nevertheless, current standard-of-care imaging protocols do not harness its full capacity. This state-of-the-art review explores the emerging role of MRI in the assessment of TAA and presents a blueprint for the required paradigm shift away from aortic size as the sole metric for risk stratifying TAA.
- ItemTropoelastin: A Novel Marker for Plaque Progression and Instability(2018) Phinikaridou, Alkystis; Lacerda, Sara; Lavin, Begona; Andía Kohnenkampf, Marcelo Edgardo; Smith, Alberto; Saha, Prakash; Botnar, René Michael
- ItemVenous Thrombosis Accelerates Atherosclerosis in Mice(2023) Saha, Prakash; Gutmann, Clemens; Kingdon, Jack; Dregan, Alexandru; Bertolaccini, Laura; Grover, Steven P.; Patel, Ashish S.; Modarai, Bijan; Lyons, Oliver; Schulz, Christian; Andía Kohnenkampf, Marcelo Edgardo; Phinikaridou, Alkystis; Botnar, René Michael; Smith, Alberto