Myocardial strain assessment in the human fetus by cardiac MRI using Doppler ultrasound gating and feature tracking.

OBJECTIVES: Assessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating. METHODS: A total of 43 human fetuses (gestational age 28-41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating. FT-MRI was analyzed using dedicated post-processing software. Endo- and epicardial contours were manually delineated from fetal cardiac 4-chamber views, followed by automated propagation to calculate global longitudinal strain (GLS) of the left (LV) and right ventricle (RV), LV radial strain, and LV strain rate. RESULTS: Strain assessment was successful in 38/43 fetuses (88%); 23 of them had postnatally confirmed diagnosis of CHD (e.g., coarctation, transposition of great arteries) and 15 were heart healthy. Five fetuses were excluded due to reduced image quality. In fetuses with CHD compared to healthy controls, median LV GLS (- 13.2% vs. - 18.9%; p < 0.007), RV GLS (- 7.9% vs. - 16.2%; p < 0.006), and LV strain rate (1.4 s-1 vs. 1.6 s-1; p < 0.003) were significantly higher (i.e., less negative). LV radial strain was without a statistically significant difference (20.7% vs. 22.6%; p = 0.1). Bivariate discriminant analysis for LV GLS and RV GLS revealed a sensitivity of 67% and specificity of 93% to differentiate between fetuses with CHD and healthy fetuses. CONCLUSION: Myocardial strain was successfully assessed in the human fetus, performing dynamic fetal cardiac MRI with DUS gating. Our study indicates that strain parameters may allow for differentiation between fetuses with and without CHD. CLINICAL RELEVANCE STATEMENT: Myocardial strain analysis by cardiac MRI with Doppler ultrasound gating and feature tracking may provide a new diagnostic approach for evaluation of fetal cardiac function in congenital heart disease. KEY POINTS: • MRI myocardial strain analysis has not been performed in human fetuses so far. • Myocardial strain was assessed in human fetuses using cardiac MRI with Doppler ultrasound gating. • MRI myocardial strain may provide a new diagnostic approach to evaluate fetal cardiac function.

Effects of systemic pretreatment with CpG oligodeoxynucleotides on skin wound healing in mice.

Unmethylated CpG oligodeoxynucleotides (ODN) bind to the Toll-like receptor 9, thus stimulating the immune system. To study the effects of systemic pretreatment with CpG ODN on dermal regeneration, C57BL6/J Tyr mice were treated with CpG or control ODN 6 days prior to implantation of a dorsal skinfold chamber and skin wounding. Wound epithelialization was analyzed by planimetric microscopy. On day 18, wound tissues were taken for (immuno)histochemical staining. CpG ODN increased epithelialization compared with control ODN treatment. Histological analysis revealed reduced capillary density, reduced wound cellularity, and reduced numbers of infiltrating leukocytes, as well as reduced F4/80-positive macrophages, but increased numbers of RELM-α-positive M2 macrophages after CpG ODN treatment, reflecting a better quality of wound healing on day 18 compared with control ODN treatment. Reverse transcription-polymerase chain reaction analysis of Toll-like receptor 9 showed the receptor expression on both fibroblasts and keratinocytes. Fibroblasts showed an increase of migration upon increasing dosages of CpG and not control ODN, reaching ∼50% of the response of basic fibroblast growth factor-exposed cells. Keratinocytes dose-dependently responded to both CpG and control ODN up to values found in keratinocyte growth factor-exposed cells. In summary, CpG ODN support late tissue-remodeling processes that contribute to resolution of inflammation and solid wounds during skin regeneration.