Non-invasive MRI biomarkers for the early assessment of iron overload in a humanized mouse model of beta-thalassemia

作者：Jackson Laurence H; Vlachodimitropoulou Evangelia; Shangaris Panicos; Roberts Thomas A; Ryan Thomas M; Campbell Washburn Adrienne E; David Anna L; Porter John B; Lythgoe Mark F; Stuckey Daniel J^*

来源：Scientific Reports, 2017, 7(1): 43439.

DOI：10.1038/srep43439

beta-thalassemia (beta T) is a genetic blood disorder causing profound and life threatening anemia. Current clinical management of beta T is a lifelong dependence on regular blood transfusions, a consequence of which is systemic iron overload leading to acute heart failure. Recent developments in gene and chelation therapy give hope of better prognosis for patients, but successful translation to clinical practice is hindered by the lack of thorough preclinical testing using representative animal models and clinically relevant quantitative biomarkers. Here we demonstrate a quantitative and non-invasive preclinical Magnetic Resonance Imaging (MRI) platform for the assessment of beta T in the.gamma beta(0)/gamma beta(A) humanized mouse model of beta T. Changes in the quantitative MRI relaxation times as well as severe splenomegaly were observed in the heart, liver and spleen in beta T. These data showed high sensitivity to iron overload and a strong relationship between quantitative MRI relaxation times and hepatic iron content. Importantly these changes preceded the onset of iron overload cardiomyopathy, providing an early biomarker of disease progression. This work demonstrates that multiparametric MRI is a powerful tool for the assessment of preclinical beta T, providing sensitive and quantitative monitoring of tissue iron sequestration and cardiac dysfunction-parameters essential for the preclinical development of new therapeutics.

• 出版日期2017-2-27
• 单位NIH