Faculty Bibliography

In iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate (R(2)*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron-chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate (R(2)), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the 'reduced transverse relaxation rate' (RR(2)), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR(2) could detect changes produced by 1 week of iron-chelating therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the heart, initially after suspending iron-chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron-chelating therapy, significant decreases were observed in the mean myocardial RR(2) (7.8%, p < 0.01) and R(2) (5.5%, p < 0.05), but not in R(2)* (1.7%, p > 0.90). Although the difference between changes in RR(2) and R(2) was not significant (p > 0.3), RR(2) was consistently more sensitive than R(2) (and R(2)*) to the resumption of iron-chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR(2) may be a promising investigational method for the rapid assessment of the effects of iron-chelating therapy in the heart

Cardiac T(2) mapping is a promising method for quantitative assessment of myocardial edema and iron overload. We have developed a new multiecho fast spin echo (ME-FSE) pulse sequence for breath-hold T(2) mapping with acceptable spatial resolution. We propose to further accelerate this new ME-FSE pulse sequence using k-t focal underdetermined system solver adapted with a framework that uses both compressed sensing and parallel imaging (e.g., sensitivity encoding) to achieve higher spatial resolution. We imaged 12 control subjects in midventricular short-axis planes and compared the accuracy of T(2) measurements obtained using ME-FSE with generalized autocalibrating partially parallel acquisitions and ME-FSE with k-t focal underdetermined system solver. For image reconstruction, we used a bootstrapping two-step approach, where in the first step fast Fourier transform was used as the sparsifying transform and in the final step principal component analysis was used as the sparsifying transform. When compared with T(2) measurements obtained using generalized autocalibrating partially parallel acquisitions, T(2) measurements obtained using k-t focal underdetermined system solver were in excellent agreement (mean difference = 0.04 msec; upper/lower 95% limits of agreement were 2.26/-2.19 msec, respectively). The proposed accelerated ME-FSE pulse sequence with k-t focal underdetermined system solver is a promising investigational method for rapid T(2) measurement of the heart with relatively high spatial resolution (1.7 x 1.7 mm(2) ). Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc

With transfusional iron overload, almost all the excess iron is sequestered intracellularly as rapidly mobilizable, dispersed, soluble ferritin iron, and as aggregated, insoluble hemosiderin iron for long-term storage. Established magnetic resonance imaging (MRI) indicators of tissue iron (R(2), R(2)*) are principally influenced by hemosiderin iron and change slowly, even with intensive iron chelation. Intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool that can change rapidly with iron chelation. We have developed a new MRI method to separately measure ferritin and hemosiderin iron, based on the non-monoexponential signal decay induced by aggregated iron in multiple-spin-echo sequences. We have initially validated the method in agarose phantoms and in human liver explants and shown the feasibility of its application in patients with thalassemia major. Measurement of tissue ferritin iron is a promising new means to rapidly evaluate the effectiveness of iron-chelating regimens

Quantitative assessment of regional cardiac function can improve the accuracy of detecting wall motion abnormalities due to heart disease. While recently developed fast cine displacement-encoded with stimulated echoes (DENSE) MRI is a promising modality for the quantification of regional myocardial function, it has not been validated for clinical applications. The purpose of this study, therefore, was to validate the accuracy of fast cine DENSE MRI with numerical simulation and in vivo experiments. A numerical phantom was generated to model physiologically relevant deformation of the heart, and the accuracy of fast cine DENSE was evaluated against the numerical reference. For in vivo validation, 12 controls and 13 heart-disease patients were imaged using both fast cine DENSE and myocardial tagged MRI. Numerical simulation demonstrated that the echo-combination DENSE reconstruction method is relatively insensitive to clinically relevant resonance frequency offsets. The strain measurements by fast cine DENSE and the numerical reference were strongly correlated and in excellent agreement (mean difference = 0.00; 95% limits of agreement were 0.01 and -0.02). The strain measurements by fast cine DENSE and myocardial tagged MRI were strongly correlated (correlation coefficient = 0.92) and in good agreement (mean difference = 0.01; 95% limits of agreement were 0.07 and -0.04)