Native T1 mapping detects both acute clinical rejection and graft dysfunction in pediatric heart transplant patients

Abstract

Background Cardiovascular magnetic resonance (CMR) is emerging as an important tool for cardiac allograft assessment. Native T1 mapping may add value in identifying rejection and in assessing graft dysfunction and myocardial fibrosis burden. We hypothesized that CMR native T1 values and features of textural analysis of T1 maps would identify acute rejection, and in a secondary analysis, correlate with markers of graft dysfunction, and with fibrosis percentage from endomyocardial biopsy (EMB). Methods Fifty cases with simultaneous EMB, right heart catheterization, and 1.5 T CMR with breath-held T1 mapping via modified Look-Locker inversion recovery (MOLLI) in 8 short-axis slices and subsequent quantification of mean and peak native T1 values, were performed on 24 pediatric subjects. A single mid-ventricular slice was used for image texture analysis using nine gray-level co-occurrence matrix features. Digital quantification of Masson trichrome stained EMB samples established degree of fibrosis. Markers of graft dysfunction, including serum brain natriuretic peptide levels and hemodynamic measurements from echocardiography, catheterization, and CMR were collated. Subjects were divided into three groups based on degree of rejection: acute rejection requiring new therapy, mild rejection requiring increased ongoing therapy, and no rejection with no change in treatment. Statistical analysis included student’s t-test and linear regression. Results Peak and mean T1 values were significantly associated with acute rejection, with a monotonic trend observed with increased grade of rejection. Texture analysis demonstrated greater spatial heterogeneity in T1 values, as demonstrated by energy, entropy, and variance, in cases requiring treatment. Interestingly, 2 subjects who required increased therapy despite low grade EMB results had abnormal peak T1 values. Peak T1 values also correlated with increased BNP, right-sided filling pressures, and capillary wedge pressures. There was no difference in histopathological fibrosis percentage among the 3 groups; histopathological fibrosis did not correlate with T1 values or markers of graft dysfunction. Conclusion In pediatric heart transplant patients, native T1 values identify acute rejection requiring treatment and may identify graft dysfunction. CMR shows promise as an important tool for evaluation of cardiac grafts in children, with T1 imaging outperforming biopsy findings in the assessment of rejection.

Immunological Nuances and Complications of Pediatric Organ Transplant: A Narrative Review

“…Clinically, graft failure can only be established after evidence of organ damage. The presence of antibodies is not a reliable marker to diagnose graft dysfunction [ 33 , 44 ]. Richmann et al used cardiovascular magnetic resonance as one such investigation.…”

“…Richmann et al used cardiovascular magnetic resonance as one such investigation. The research also highlighted the requirement to develop reliable and repeatable investigations to detect and monitor transplant organ function [ 44 ].…”

A phantom for targeted endomyocardial biopsy training

“…Our recently published work discovered that special types of cardiac magnetic resonance imaging (MRI) images call native T1 parametric maps helped identify acute rejection requiring treatment in pediatric heart transplant patients. 12 Additionally, both T1 and T2 mapping also significantly correlated with prevalence of HF patients with reduced ejection fraction, but it was still recommended to use EMB to detect myocardial inflammation. 13 Therefore, our goal was to develop methodology for overlaying cardiac MRI T1 and T2 map images onto biplane fluoroscopy imaging for EMB guidance, with the goal of improving diagnosis of transplant rejection or inflammatory cardiomyopathies.…”

“…Our recently published work discovered that special types of cardiac magnetic resonance imaging (MRI) images call native T1 parametric maps helped identify acute rejection requiring treatment in pediatric heart transplant patients 12 . Additionally, both T1 and T2 mapping also significantly correlated with prevalence of HF patients with reduced ejection fraction, but it was still recommended to use EMB to detect myocardial inflammation 13 .…”