Microarchitecture of the hearts in term and former‐preterm lambs using diffusion tensor imaging

Abstract

Diffusion tensor imaging (DTI) is an MRI technique that can be used to map cardiomyocyte tracts and estimate local cardiomyocyte and sheetlet orientation within the heart. DTI measures diffusion distances of water molecules within the myocardium, where water diffusion generally occurs more freely along the long axis of cardiomyocytes and within the extracellular matrix, but is restricted by cell membranes such that transverse diffusion is limited. DTI can be undertaken in fixed hearts and it allows the three‐dimensional mapping of the cardiac microarchitecture, including cardiomyocyte organization, within the whole heart. The objective of this study was to use DTI to compare the cardiac microarchitecture and cardiomyocyte organization in archived fixed left ventricles of lambs that were born either preterm (n = 5) or at term (n = 7), at a postnatal timepoint equivalent to about 6 years of age in children. Although the findings support the feasibility of retrospective DTI scanning of fixed hearts, several hearts were excluded from DTI analysis because of poor scan quality, such as ghosting artifacts. The preliminary findings from viable DTI scans (n = 3/group) suggest that the extracellular compartment is altered and that there is an immature microstructural phenotype early in postnatal life in the LV of lambs born preterm. Our findings support a potential time‐efficient imaging role for DTI in detecting abnormal changes in the microstructure of fixed hearts of former‐preterm neonates, although further investigation into factors that affect scan quality is required.

Altered Right Ventricular Filling at Four-dimensional Flow MRI in Young Adults Born Prematurely

“…If confirmed in humans, fibrosis-associated stiffness could explain the observed differences in diastolic KE. Another possible physiologic mechanism affecting diastolic function could be myocardial fiber orientation (44), although more data are needed in this area in animals and humans. Further investigation into the mechanisms of altered RV diastolic function in the human preterm heart will be required to assess the role of increased myocardial stiffness and fibrosis, as well as myocyte-level dysfunction, such as impaired calcium handling.…”

Preterm Birth With Neonatal Interventions Accelerates Collagen Deposition in the Left Ventricle of Lambs Without Affecting Cardiomyocyte Development

“…30 In a recent diffusion tensor imaging study by our laboratory, we showed that LV wall volume, cavity volume, length, and lateral wall width did not differ between former-preterm lambs and lambs born at term, by 5 months' TEA. 41 Similarly, an echocardiographic study showed that although body mass index and body surface area were reduced in 6-year-old children born extremely preterm compared with age-matched term controls, LV mass was unaffected after adjusting for body surface area. 40 However, LV length, width, and aortic valve annulus diameter were 3-5% smaller in the preterm group; this was associated with impaired LV systolic function.…”

Understanding the preterm human heart: What do we know so far?

“…Animal models and histomorphological studies have shown that the premature interruption of cardiac growth leads to cellular changes in the myocardium. In different reports on preterm‐born sheep, the myocardium was characterized by hypertrophied cardiomyocytes in both ventricles (Bensley et al, 2010), alterations in the extracellular compartment (Le, Ferreira, et al, 2021), and an increase in interstitial collagen deposition (Bensley et al, 2010; Le, Dahl, et al, 2021). Similarly, in a rat model of neonatal hyperoxia exposure to mimic preterm birth‐related conditions, the cardiomyocytes are hypertrophied and there is greater interstitial fibrosis, with in vivo signs of left ventricular (LV) dysfunction by echocardiography (Bertagnolli et al, 2014).…”