Table 4.
CMR assessment of fibrosis post-therapeutic intervention in mice
| Pathological Model | Therapeutic Intervention | Imaging Technique for Assessing Fibrosis | Follow-Up Image | Major Outcomes from CMR |
|---|---|---|---|---|
| TAC In adult C57/BL6 male mice Stuckey et al. (50) |
Losartan—angiotensin II receptor blockade Provided in drinking water 1 wk before surgery |
• Native T1 • LGE • Postcontrast T1 • ECV |
All imaging techniques were performed at 7 days and 28 days post-TAC surgery | • Native T1 value elevated at 7 days post-TAC surgery vs. sham but not at 28 days. • ECV was elevated at 28 days post-TAC vs. sham but not at 7 days. • The ECV fraction was elevated in TAC vs. sham and showed a direct linear correlation with picrosirius red collagen volume fraction. • Treatment with losartan prevented an increase in ECV fraction, indicating that T1 mapping is sensitive to pharmacological prevention of fibrosis. • Study suggests suitability of ECV as an in vivo measure of diffuse fibrosis. |
| TAC In adult C57/BL6 male mice Glasenapp et al. (69) |
Reverse TAC (rTAC) at 3-wk post-TAC | • Native T1 | Baseline, 7–8 days, 3- and 6-wk post-TAC surgery, 7–8 days and 3-wk post-rTAC surgery. | • Native T1—elevated at 7–8 days post-TAC compared with baseline and age-matched sham, and remained elevated at 3- and 6-wk post-TAC but did not further elevate from 8 days post-TAC. • Mechanical ventricular unloading (rTAC) shown to attenuate the elevation in T1 vs. sham rTAC, observed at both 7–8 days and 3-wk postsurgical intervention. • T1 values showed a direct linear correlation with fibrotic area (picrosirius red staining), inflammation signal (68Ga-pentixafor PET signal) and cardiac function (ESV and EF). |
| Hypertensive mice Adult C57/BL6 male mice treated with a continuous angiotensin II (480 ± 34 ng/kg/min) infusion for 6 wk. Kwiecinski et al. (70) |
Discontinuation of angiotensin II infusion after 6-wk infusion | • Native T1 • LGE • Postcontrast T1 • ECV |
Baseline and every 2 wk during angiotensin II infusion. At 4 wk after discontinuation of angiotensin II infusion |
• Native T1, postcontrast T1, and ECV showed linear correlation with histological fibrosis (Picrosirius red). • During pressure loading, ECV showed a progressive increase with a similar pattern of change as the blood pressure and inverse correlation with the systolic function. However, the change in native T1 did not reach significance. • No observation of LGE focal replacement fibrosis. • In response to reverse pressure overload, LV mass and ECV regressed at 4 wk after removal of angiotensin II infusion vs. before infusion removal. However, the reverse remodeling was only partial as none of these measurements returned to the baseline values. |
| HFpEF Adult WT mice (l-NAME, 3 mg/mL in water-7 wk) Coelho-Filho et al. (71) |
Spironolactone subcutaneous pellets implantation (50 mg/kg/day) | • ECV | Baseline and 7 wk after therapy | • Mice treated with both l-NAME and spironolactone showed a lower myocardial ECV vs. treated l-NAME alone and no significant difference when compared with control mice. • The ECV fraction showed direct linear correlation with Masson’s Trichrome connective tissue fraction. • Study shows treatment with spironolactone prevented increased ECV fraction and suggests suitability of ECV as an in vivo measure of diffuse fibrosis. |
| MI In adult OF1 male mice (Reperfusion after 30-min ligation) Van Den Boomen et al. (72) |
UPy-hydrogel loaded IGF1 and VEGF (UPyGF-hydrogel) intramyocardial injection (10 µL) at 2 min before reperfusion | • LGE • T1 |
LGE: Day 1 post-MI T1: • 1-day pre-MI • Days 3 and 22 post-MI |
• LGE: showed similar infarct size for saline (12.4 ± 1.2 %) and UPyGF-hydrogel (11.1 ± 1.1%) treated mice at day 1 post-MI. • T1 values: At day 3, only T1 value of saline injected ischemic myocardium (2.172 ± 0.008 s) was significantly increased compared with the healthy myocardium (1.541 ± 0.030 s). At day 22, saline-injected infarcts T1 value remained significantly increased (2.077 ± 0.075 s) compared with the healthy myocardium. T1 value of UPyGF-hydrogel treated ischemic myocardium did not show significant difference when compared with healthy myocardium at both days 3 and 22. |
| Hypertensive Adult male C57BL/6J mice (1 kidney/DOCA/salt model) Li et al. (73) |
Serelaxin combined (0.5/mg/kg/day) with intravenous BM-MSC (25 μg of BM-MSC proteinper mouse) | • LGE • Native T1 • Postcontrast T1 • ECV |
7 day posttreatment | • Native T1 and postcontrast T1 values were not significantly altered in all groups. • 1 K/DOCA/salt-injured mice showed a trend toward having decreased average postcontrast T1 values and a significant increase in ECV. • Combined treatment group showed no significant difference with control in ECV. |
BM-MSCs, bone marrow-derived mesenchymal stromal cells; DOCA, deoxycorticosterone acetate; ECV, extracellular volume fraction; EF, ejection fraction; ESV, end systolic volume; HFpEF, heart failure with preserved ejection fraction; IGF1, insulin growth factor 1; LGE, late gadolinium enhancement; l-NAME, Nω-nitro-l-arginine methyl ester; LV, left ventricle; MI, myocardial infarction; PET, positron emission tomography; TAC, transverse aortic constriction; UPy, ureido-pyrimidinone; VEGF, vascular endothelial growth factor.