Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic ... View Full Text


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Article Info

DATE

2021-06-17

AUTHORS

Heae Surng Park, Yoo Jin Hong, Kyunghwa Han, Pan Ki Kim, Eunkyung An, Ji Yeon Lee, Chul Hwan Park, Hye-Jeong Lee, Jin Hur, Young Jin Kim, Byoung Wook Choi

ABSTRACT

BackgroundChemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity.MethodsRat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed.ResultsFive control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores)ConclusionsQuantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity. More... »

PAGES

76

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12968-021-00767-8

DOI

http://dx.doi.org/10.1186/s12968-021-00767-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1138924515

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34134713


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24 schema:description BackgroundChemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity.MethodsRat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed.ResultsFive control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01).  Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores)ConclusionsQuantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.
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30 schema:keywords BackgroundChemotherapy
31 CMR parameters
32 ECV values
33 MethodsRat model
34 T1
35 T1 mapping cardiovascular magnetic resonance
36 T1 values
37 T2
38 T2 mapping
39 T2 mapping cardiovascular magnetic resonance
40 T2 mapping parameters
41 T2 mapping sequence
42 T2 values
43 adverse effects
44 aim
45 analysis
46 analysis model
47 anthracycline-induced cardiotoxicity
48 assessment
49 association
50 cardiotoxicity
51 cardiovascular magnetic resonance
52 changes
53 chemotherapy
54 control
55 control rats
56 correlation
57 diffuse myocardial changes
58 doxorubicin
59 edema
60 effect
61 ejection fraction
62 evaluation
63 examination
64 extracellular volume fraction
65 factors
66 features
67 fibrosis
68 fraction
69 high correlation
70 histopathologic changes
71 histopathological changes
72 histopathological examination
73 histopathological features
74 histopathological parameters
75 inflammation
76 inflammation score
77 injury
78 interstitial fibrosis
79 left ventricular ejection fraction
80 linear regression analysis model
81 magnetic resonance
82 magnetic resonance T1
83 main histopathological features
84 mapping
85 mapping parameters
86 mapping sequence
87 model
88 multiple linear regression analysis model
89 myocardial changes
90 myocardial injury
91 native T1
92 native T1 values
93 non-invasive tool
94 parameters
95 period
96 present study
97 rat model
98 rats
99 regression analysis model
100 resonance
101 scanner
102 scores
103 sequence
104 significant factor
105 study
106 subclinical myocardial changes
107 tool
108 treatment
109 treatment period
110 ultrahigh-field scanners
111 univariable analysis
112 useful non-invasive tool
113 vacuolar changes
114 validation
115 values
116 ventricular ejection fraction
117 volume fraction
118 weeks
119 weeks of treatment
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