Pilot Study of Non-Invasive Assessment of Hepatic And Myocardial Iron Through T2* MRI In Patients With Iron Overload

Quantitative measurements of hepatic and cardiac iron by single-breath-hold MRI T2* will allow us to determine the value of this technique as a non-invasive method of monitoring liver and cardiac iron content. By obtaining T2 measurements, we will be able to compare two different techniques for non-invasive iron assessment. With regard to the liver, we will correlate T2* measurements with the gold standard, LIC on liver biopsy. Because it is not feasible to perform cardiac biopsies to evaluate the degree of cardiac hemosiderosis, we will evaluate the relationships between cardiac T2* values and left and right diastolic function, left ventricular ejection fraction, left ventricular end-systolic volume and left ventricular mass index obtained by echocardiography and MUGA scans that are performed as part of the routine clinical care of these patients. In order to estimate whether cardiac T2* values are clinically relevant, we will also investigate the relationship between T2* values and the need for cardiac medication due to cardiac hemosiderosis. Cardiac and hepatic T2* measurements will also be compared to their visual appearances on T2* MR images in order to investigate the relationship between these two assessments. Cardiac and hepatic T2* and their respective visual appearances on T2* MR images will be compared with serum ferritin to evaluate the potential relationships among these measurements of iron overload.

Amen T2* and T2 phantoms are devices that allow calibration of the MR measurements for absolute iron content. Phantoms are test tubes filled with aqueous solutions or gel compounds of materials that mimic various tissue relaxation times (T1, T2 and T2*). Phantoms are commonly used in MRI when quantification is desired. Our phantom will consist of a multitude of small vials which will be visible in the imaging plane. The relaxation times vary in the different vials of the phantom and are known very accurately, especially the T2 and T2* values, which vary over the physiological relevant range. This way the phantom can be used to calibrate the T2* values obtained from the patients heart and liver and eventually be correlated to absolute iron concentrations.

If accurate, the T2* MRI technique would ultimately allow a non-invasive method of quantitatively assessing myocardial and liver iron accumulation, and could predict the degree of morbidity due to iron overload. This new technique could greatly improve the care of our iron overloaded patients by offering a practical and risk free method for evaluation of body iron load. We plan to apply this preliminary information into future studies in this area. Eventually we plan to use the T2* MRI measurements in longitudinal studies of patients with iron overload, both to assess their degree of iron burden and monitor chelation therapy treatments.

Amen Dark blood applications are state-of-the-art in cardiac MRI and commonly applied. There is no risk associated with the dark blood preparation. Comparison of dark and bright blood measurements will show whether both sequences yield similar results and whether one technique is less susceptible to cardiac motion and associated artifacts, thereby offering a higher accuracy and a smaller error in the calculation of T2* and iron concentration.

Information about the heart function can be obtained using MRI techniques, however this information needs to be validated in different populations, such as patients with iron overload. If MR data show a high correlation with echocardiography and MUGA functional data, subsequent protocols could be conducted where the functional information can be gained with an MR measurement, thereby avoid acquiring a MUGA scan and eliminating the exposure to radiation as well as streamlining the protocol by just adding a few additional measurements to an already scheduled MR iron scan. Performing cardiac measurement in a few patients using the MRI technique will allow us to expand the use of this technique for future and larger studies.