T1/T2 parametric mapping may reveal patterns of elevation (“hotspots”) in myocardial diseases, such as rejection in orthotopic heart transplant (OHT) patients. This study aimed to evaluate the diagnostic accuracy of free-breathing (FB) multi-parametric SAturation recovery single-SHot Acquisition (mSASHA) T1/T2 mapping in identifying hotspots present on conventional Breath-held Modified Look-Locker Inversion recovery (BH MOLLI) T1 and T2-prepared balanced steady-state free-precession (BH T2p-bSSFP) maps in pediatric OHT patients. Pediatric OHT patients underwent noncontrast 1.5T CMR with BH MOLLI T1 and T2p-bSSFP and prototype FB mSASHA T1/T2 mapping in 8 short-axis slices. FB and BH T1/T2 hotspots were segmented using semi-automated thresholding (ITK-SNAP) and their 3D coordinate locations were collected (3-Matic, Materialise, Leuven, Belgium). Receiver operator characteristic curve analysis and measures of central tendency were utilized. 40 imaging datasets from 23 pediatric OHT patients were obtained. FB mSASHA yielded a sensitivity of 82.8% for T1 and 80% for T2 maps when compared to the standard BH MOLLI, as well as 100% specificity for both T1 and T2 maps. When identified on both FB and BH maps, hotspots overlapped in all cases, with an average long axis offset between FB and BH hotspot centers of 5.8 mm (IQR 3.5–8.2) on T1 and 5.9 mm (IQR 3.5–8.2) on T2 maps. FB mSASHA T1/T2 maps can identify hotspots present on conventional BH T1/T2 maps in pediatric patients with OHT, with high sensitivity, specificity, and overlap in 3D space. Free-breathing mapping may improve patient comfort and facilitate OHT assessment in younger patient populations.

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.

Introduction: Endomyocardial biopsy (EMB) drives rejection diagnosis in pediatric heart transplant patients but is subject to false negatives. Cardiac magnetic resonance imaging (CMR) can detect and quantify fibrosis and edema with T1 and T2 mapping. Overlaying CMR data onto X-ray images may be used for EMB procedural guidance. Hypothesis: Overlaying segmented T1 and T2 map images onto X-ray for EMB guidance may improve diagnosis of rejection in pediatric transplant patients. Methods: 30 pediatric heart transplant patients referred for clinically indicated EMB underwent noncontrast CMR with T1 and T2 mapping prior to EMB. If present, regions of T1 and T2 elevation were segmented and exported as an overlay image. Biopsies were obtained without ( unguided ) and then with ( guided ) CMR overlay with T1 and T2 “hotspots”. Each biopsy specimen received a rejection grade, blinded to guided vs. unguided. As a surrogate for clinical rejection, treatment decisions were made without knowledge of CMR results, and logged as no change, oral therapy augmentation, or IV therapy initiation. Treatment category and pathologic grade were compared among biopsies with Fisher’s exact test and logistic regression. Results: 30 patients (median age 13 years (interquartile range (IQR) 8.8, 16.2), BSA 1.36 m2 (IQR 1.09, 1.86), 50% male) underwent 64 encounters for a total of 199 biopsied specimens (58 guided, 141 unguided). Hotspots were identified in 75% (48/64) of encounters, with 69% (33/48) in biopsied regions of the right ventricle allowing for guidance (25 T1 and 8 T2). Patients with T1 or T2 hotspots providing guided EMB were twice as likely to require any augmentation of therapy compared to those with unguided EMB (38% guided vs 17% unguided, p=0.001). Incidence of pathologic biopsy results (grade > 0) was not significantly different between guided and unguided biopsies from the same patients (41% vs 40%, p =0.99). Conclusions: Patients with T1/T2 hotspots on CMR and guided EMB require rejection treatment more frequently than patients with only unguided biopsies, although biopsy grade did not significantly differ within the same patient. Future work will evaluate relationship of CMR T1 and T2 hotspots to treatment, which may establish CMR as a superior screening tool for rejection.