Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity
ABSTRACT: Background: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular m...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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Elsevier
2024-01-01
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| Ráidu: | Journal of Cardiovascular Magnetic Resonance |
| Fáttát: | |
| Liŋkkat: | http://www.sciencedirect.com/science/article/pii/S109766472401024X |
| _version_ | 1827111349031796736 |
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| author | Kei Nakata Selcuk Kucukseymen Xiaoying Cai Tuyen Yankama Jennifer Rodriguez Eiryu Sai Patrick Pierce Long Ngo Shiro Nakamori Nadine Tung Warren J. Manning Reza Nezafat |
| author_facet | Kei Nakata Selcuk Kucukseymen Xiaoying Cai Tuyen Yankama Jennifer Rodriguez Eiryu Sai Patrick Pierce Long Ngo Shiro Nakamori Nadine Tung Warren J. Manning Reza Nezafat |
| author_sort | Kei Nakata |
| collection | DOAJ |
| description | ABSTRACT: Background: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model. Methods: Female Yucatan miniature swine (n = 14) received doxorubicin (2 mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T1 and T2 mapping, and late gadolinium enhancement (LGE) were performed on the same day as doxorubicin administration and 3 weeks after the final chemotherapy cycle. In addition, magnetic resonance spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam were also performed in 3 Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam. Results: Of 13 swine completing 5 serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE was observed. Native T1, extracellular volume (ECV), and T2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p = 0.002, 27.4% vs. 24.5%, p = 0.03, and 38.1 ms vs. 36.4 ms, p = 0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T1, ECV, and T2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, analysis of variance, p = 0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes. Conclusion: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD. |
| first_indexed | 2025-03-20T11:12:46Z |
| format | Article |
| id | doaj.art-76aa526a21e64b3c8b8f08ae9a645c93 |
| institution | Directory Open Access Journal |
| issn | 1097-6647 |
| language | English |
| last_indexed | 2025-03-20T11:12:46Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Cardiovascular Magnetic Resonance |
| spelling | doaj.art-76aa526a21e64b3c8b8f08ae9a645c932024-09-19T10:20:10ZengElsevierJournal of Cardiovascular Magnetic Resonance1097-66472024-01-01261101033Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicityKei Nakata0Selcuk Kucukseymen1Xiaoying Cai2Tuyen Yankama3Jennifer Rodriguez4Eiryu Sai5Patrick Pierce6Long Ngo7Shiro Nakamori8Nadine Tung9Warren J. Manning10Reza Nezafat11Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; Siemens Medical Solutions USA, Inc., Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; Correspondence to: Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.ABSTRACT: Background: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model. Methods: Female Yucatan miniature swine (n = 14) received doxorubicin (2 mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T1 and T2 mapping, and late gadolinium enhancement (LGE) were performed on the same day as doxorubicin administration and 3 weeks after the final chemotherapy cycle. In addition, magnetic resonance spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam were also performed in 3 Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam. Results: Of 13 swine completing 5 serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE was observed. Native T1, extracellular volume (ECV), and T2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p = 0.002, 27.4% vs. 24.5%, p = 0.03, and 38.1 ms vs. 36.4 ms, p = 0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T1, ECV, and T2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, analysis of variance, p = 0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes. Conclusion: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD.http://www.sciencedirect.com/science/article/pii/S109766472401024XAnthracyclineCancer therapy-related cardiac dysfunctionCardiovascular magnetic resonanceMagnetic resonance spectroscopyMiniature swineNative T1 and T2 mapping |
| spellingShingle | Kei Nakata Selcuk Kucukseymen Xiaoying Cai Tuyen Yankama Jennifer Rodriguez Eiryu Sai Patrick Pierce Long Ngo Shiro Nakamori Nadine Tung Warren J. Manning Reza Nezafat Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity Journal of Cardiovascular Magnetic Resonance Anthracycline Cancer therapy-related cardiac dysfunction Cardiovascular magnetic resonance Magnetic resonance spectroscopy Miniature swine Native T1 and T2 mapping |
| title | Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity |
| title_full | Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity |
| title_fullStr | Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity |
| title_full_unstemmed | Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity |
| title_short | Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity |
| title_sort | cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy related cardiovascular toxicity |
| topic | Anthracycline Cancer therapy-related cardiac dysfunction Cardiovascular magnetic resonance Magnetic resonance spectroscopy Miniature swine Native T1 and T2 mapping |
| url | http://www.sciencedirect.com/science/article/pii/S109766472401024X |
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