Relaxivity-iron calibration in hepatic iron overload: probing underlying biophysical mechanisms using a Monte Carlo...

Iron overload is a serious condition for patients with β-thalassemia, transfusion-dependent sickle cell anemia, and inherited disorders of iron metabolism. MRI is becoming increasingly important in noninvasive quantification of tissue iron, overcoming the drawbacks of traditional techniques (liver biopsy). Effective transverse relaxation rate (1/effective transverse relaxation time) rises linearly with iron while transverse relaxation rate (1/T2) has a curvilinear relationship in human liver. Although recent work has demonstrated clinically valid estimates of human liver iron, the calibration varies with MRI sequence, field strength, iron chelation therapy, and organ imaged, forcing recalibration in patients. To understand and correct these limitations, a thorough understanding of the underlying biophysics is of critical importance. Toward this end, a Monte Carlo-based approach, using human liver as a "model" tissue system, was used to determine the contribution of particle size and distribution on MRI signal relaxation. Relaxivities were determined for hepatic iron concentrations ranging from 0.5 to 40 mg iron per gram dry tissue weight. Model predictions captured the linear and curvilinear relationship of effective transverse relaxation rate and transverse relaxation rate with hepatic iron concentrations, respectively, and were within in vivo confidence bounds; contact or chemical exchange mechanisms were not necessary. A validated and optimized model will aid understanding and quantification of iron-mediated relaxivity in tissues where biopsy is not feasible (heart and spleen).