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Dispersion of hyperenhancement in late gadolinium enhancement cardiovascular magnetic resonance measured with Moran's I is associated with a decrement in LVEF 6 months after cardiotoxic chemotherapy
Journal of Cardiovascular Magnetic Resonance volume 15, Article number: P156 (2013)
In animals and human subjects, an increase in background signal intensity observed on late gadolinium enhanced (LGE-SI) images is associated with a decrement in left ventricular ejection fraction (LVEF) during receipt of anthracycline chemotherapy. Moran's I statistic is a measurement of spatial dispersion of hyperenhanced voxels relative to the mean myocardial LGE-SI, ranging from highly clustered (I=+1) to highly diffuse (I=-1) (Figure 1). We hypothesize that a change in the distribution of hyperenhanced voxels (due to the development of high signal "micro clusters") is associated with a decrement in LVEF after cardiotoxic chemotherapy.
We performed a prospective, extramurally-funded longitudinal cohort study of 51 participants (43 women, 8 men; aged 52±2 years) scheduled to receive 3 to 4 months of potentially cardiotoxic chemotherapy (anthracycline or trastuzumab) for treatment of breast cancer or hematologic malignancy. Before and then 3 and 6 months after chemotherapy initiation, participants underwent cardiovascular magnetic resonance (CMR) assessments of LVEF, LGE-SI, and Moran's I statistic determined by personnel blinded to participant identifiers and all other aspects of the analyses. Results were analyzed using paired Student's t-tests to test for a difference between baseline and subsequent examinations, and one-way ANOVA to test for trending change. All values are reported as mean ± standard deviation with p-values<0.05 considered statistically signficant.
37 participants were treated for breast cancer and 14 for hematologic malignancy. A declining LVEF from baseline (58±6%) was observed three months (54±7%) and six months (53±7%) after beginning chemotherapy (p<0.0001 for trend, Figure 2A). Mean LGE-SI, reflecting a change in myocardial T1 relaxation, increased from 14.0±5.5 at baseline to 16.1±7.6 three months after starting chemotherapy (p=0.03, Figure 2B) and remained elevated at 6 months (15.7±6.8, p=0.07 from baseline). At baseline and 3 months, the patterns of LGE-SI hyperenhancement (Moran's I statistic) showed random distribution (-0.02±0.02 and -0.02±0.01, respectively; p=0.91). Six months after chemotherapy initiation, myocardial LGE-SI hyperenhanced voxels became more diffusely distributed as shown in Figure 2C (I=-0.12±0.14, p<0.001).
We observed that, six months after receipt of chemotherapy, increased late gadolinium enhancement signal intensity (LGE-SI) occurs in a diffusely distributed pattern within the myocardium concurrent with a declining LVEF. Moran's I statistic is a novel method to discriminate processes related to a diffuse increase in myocardial T1 (fibrosis, edema) from those related to a clustered increase in myocardial T1 (infarct); further investigations are warranted to study the utility of Moran's I statistic with T1 and T2 mapping.
This work was supported in part by the National Institutes of Health grant R33CA12196 (Hundley), American Heart Association Predoctoral Fellowship 09PRE2210050 (Jordan), and a grant from the Susan G. Komen Foundation BCTR07007769 (Hundley).
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Jordan, J.H., Hamilton, C.A., D'Agostino, R.B. et al. Dispersion of hyperenhancement in late gadolinium enhancement cardiovascular magnetic resonance measured with Moran's I is associated with a decrement in LVEF 6 months after cardiotoxic chemotherapy. J Cardiovasc Magn Reson 15, P156 (2013). https://doi.org/10.1186/1532-429X-15-S1-P156
- Breast Cancer
- Left Ventricular Ejection Fraction
- Cardiovascular Magnetic Resonance
- Hematologic Malignancy