Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance
Abstract Background Atherosclerosis is an arterial vessel wall disease characterized by slow, progressive lipid accumulation, smooth muscle disorganization, and inflammatory infiltration. Atherosclerosis often remains subclinical until extensive inflammatory injury promotes vulnerability of the athe...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Cardiovascular Magnetic Resonance |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12968-022-00897-7 |
| _version_ | 1797204022140076032 |
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| author | Erik N. Taylor Nasi Huang Sunni Lin Farzad Mortazavi Van J. Wedeen Jamila H. Siamwala Richard J. Gilbert James A. Hamilton |
| author_facet | Erik N. Taylor Nasi Huang Sunni Lin Farzad Mortazavi Van J. Wedeen Jamila H. Siamwala Richard J. Gilbert James A. Hamilton |
| author_sort | Erik N. Taylor |
| collection | DOAJ |
| description | Abstract Background Atherosclerosis is an arterial vessel wall disease characterized by slow, progressive lipid accumulation, smooth muscle disorganization, and inflammatory infiltration. Atherosclerosis often remains subclinical until extensive inflammatory injury promotes vulnerability of the atherosclerotic plaque to rupture with luminal thrombosis, which can cause the acute event of myocardial infarction or stroke. Current bioimaging techniques are unable to capture the pathognomonic distribution of cellular elements of the plaque and thus cannot accurately define its structural disorganization. Methods We applied cardiovascular magnetic resonance spectroscopy (CMRS) and diffusion weighted CMR (DWI) with generalized Q-space imaging (GQI) analysis to architecturally define features of atheroma and correlated these to the microscopic distribution of vascular smooth muscle cells (SMC), immune cells, extracellular matrix (ECM) fibers, thrombus, and cholesteryl esters (CE). We compared rabbits with normal chow diet and cholesterol-fed rabbits with endothelial balloon injury, which accelerates atherosclerosis and produces advanced rupture-prone plaques, in a well-validated rabbit model of human atherosclerosis. Results Our methods revealed new structural properties of advanced atherosclerosis incorporating SMC and lipid distributions. GQI with tractography portrayed the locations of these components across the atherosclerotic vessel wall and differentiated multi-level organization of normal, pro-inflammatory cellular phenotypes, or thrombus. Moreover, the locations of CE were differentiated from cellular constituents by their higher restrictive diffusion properties, which permitted chemical confirmation of CE by high field voxel-guided CMRS. Conclusions GQI with tractography is a new method for atherosclerosis imaging that defines a pathological architectural signature for the atheromatous plaque composed of distributed SMC, ECM, inflammatory cells, and thrombus and lipid. This provides a detailed transmural map of normal and inflamed vessel walls in the setting of atherosclerosis that has not been previously achieved using traditional CMR techniques. Although this is an ex-vivo study, detection of micro and mesoscale level vascular destabilization as enabled by GQI with tractography could increase the accuracy of diagnosis and assessment of treatment outcomes in individuals with atherosclerosis. |
| first_indexed | 2024-04-11T05:07:00Z |
| format | Article |
| id | doaj.art-f34b04915a2b4086afb5062aa6b8fa46 |
| institution | Directory Open Access Journal |
| issn | 1532-429X |
| language | English |
| last_indexed | 2024-04-24T08:28:37Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Cardiovascular Magnetic Resonance |
| spelling | doaj.art-f34b04915a2b4086afb5062aa6b8fa462024-04-16T21:04:36ZengElsevierJournal of Cardiovascular Magnetic Resonance1532-429X2022-12-0124111710.1186/s12968-022-00897-7Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonanceErik N. Taylor0Nasi Huang1Sunni Lin2Farzad Mortazavi3Van J. Wedeen4Jamila H. Siamwala5Richard J. Gilbert6James A. Hamilton7Department of Physiology & Biophysics, Boston University School of MedicineDepartment of Physiology & Biophysics, Boston University School of MedicineDepartment of Biomedical Engineering, Boston UniversityDepartment of Anatomy & Neurobiology, Boston University School of MedicineAA Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Molecular Pharmacology, Physiology, and Biotechnology, Warren Alpert Medical School of Brown UniversityResearch Service, Providence VA Medical Center and Warren Alpert Medical School of Brown UniversityDepartment of Physiology & Biophysics, Boston University School of MedicineAbstract Background Atherosclerosis is an arterial vessel wall disease characterized by slow, progressive lipid accumulation, smooth muscle disorganization, and inflammatory infiltration. Atherosclerosis often remains subclinical until extensive inflammatory injury promotes vulnerability of the atherosclerotic plaque to rupture with luminal thrombosis, which can cause the acute event of myocardial infarction or stroke. Current bioimaging techniques are unable to capture the pathognomonic distribution of cellular elements of the plaque and thus cannot accurately define its structural disorganization. Methods We applied cardiovascular magnetic resonance spectroscopy (CMRS) and diffusion weighted CMR (DWI) with generalized Q-space imaging (GQI) analysis to architecturally define features of atheroma and correlated these to the microscopic distribution of vascular smooth muscle cells (SMC), immune cells, extracellular matrix (ECM) fibers, thrombus, and cholesteryl esters (CE). We compared rabbits with normal chow diet and cholesterol-fed rabbits with endothelial balloon injury, which accelerates atherosclerosis and produces advanced rupture-prone plaques, in a well-validated rabbit model of human atherosclerosis. Results Our methods revealed new structural properties of advanced atherosclerosis incorporating SMC and lipid distributions. GQI with tractography portrayed the locations of these components across the atherosclerotic vessel wall and differentiated multi-level organization of normal, pro-inflammatory cellular phenotypes, or thrombus. Moreover, the locations of CE were differentiated from cellular constituents by their higher restrictive diffusion properties, which permitted chemical confirmation of CE by high field voxel-guided CMRS. Conclusions GQI with tractography is a new method for atherosclerosis imaging that defines a pathological architectural signature for the atheromatous plaque composed of distributed SMC, ECM, inflammatory cells, and thrombus and lipid. This provides a detailed transmural map of normal and inflamed vessel walls in the setting of atherosclerosis that has not been previously achieved using traditional CMR techniques. Although this is an ex-vivo study, detection of micro and mesoscale level vascular destabilization as enabled by GQI with tractography could increase the accuracy of diagnosis and assessment of treatment outcomes in individuals with atherosclerosis.https://doi.org/10.1186/s12968-022-00897-7Diffusion-weighted Q-space MRIAtherosclerosisCardiovascular diseaseInflammationCholesterolThrombosis |
| spellingShingle | Erik N. Taylor Nasi Huang Sunni Lin Farzad Mortazavi Van J. Wedeen Jamila H. Siamwala Richard J. Gilbert James A. Hamilton Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance Journal of Cardiovascular Magnetic Resonance Diffusion-weighted Q-space MRI Atherosclerosis Cardiovascular disease Inflammation Cholesterol Thrombosis |
| title | Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance |
| title_full | Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance |
| title_fullStr | Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance |
| title_full_unstemmed | Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance |
| title_short | Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance |
| title_sort | lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using q space cardiovascular magnetic resonance |
| topic | Diffusion-weighted Q-space MRI Atherosclerosis Cardiovascular disease Inflammation Cholesterol Thrombosis |
| url | https://doi.org/10.1186/s12968-022-00897-7 |
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