Integrated quantitative susceptibility and R₂* mapping for evaluation of liver fibrosis: An ex vivo feasibility study

Abstract

To develop a method for noninvasive evaluation of liver fibrosis, we investigated the differential sensitivities of quantitative susceptibility mapping (QSM) and R 2 * mapping using corrections for the effects of liver iron. Liver fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix proteins. While collagen increases R 2 * relaxation, measures of R 2 * for fibrosis are confounded by liver iron, which may be present in the liver over a wide range of concentrations. The diamagnetic collagen contribution to susceptibility values measured by QSM is much less than the contribution of highly paramagnetic iron. In 19 ex vivo liver explants with and without fibrosis, QSM (χ), R 2 * and proton density fat fraction (PDFF) maps were constructed from multiecho gradient-recalled echo (mGRE) sequence acquisition at 3 T. Median parameter values were recorded and differences between the MRI parameters in nonfibrotic vs. advanced fibrotic/cirrhotic samples were evaluated using Mann-Whitney U tests and receiver operating characteristic analyses. Logistic regression with stepwise feature selection was employed to evaluate the utility of combined MRI measurements for detection of fibrosis. Median R 2 * increased in fibrotic vs. nonfibrotic liver samples (P = .041), while differences in χ and PDFF were nonsignificant (P = .545 and P = .395, respectively). Logistic regression identified the combination of χ and R 2 * significant for fibrosis detection (logit [prediction] = −8.45 + 0.23 R 2 * − 28.8 χ). For this classifier, a highly significant difference between nonfibrotic vs. advanced fibrotic/cirrhotic samples was observed (P = .002). The model exhibited an AUC of 0.909 (P = .003) for detection of advanced fibrosis/cirrhosis, which was substantially higher compared with AUCs of the individual parameters (AUC 0.591-0.784). An integrated QSM and R 2 * analysis of mGRE 3 T imaging data is promising for noninvasive diagnostic assessment of liver fibrosis.

Quantitative Susceptibility Mapping versus R2*-based Histogram Analysis for Evaluating Liver Fibrosis: Preliminary Results

“…Jafari et al showed that R2* in human fibrotic liver explant samples significantly increased compared with that in nonfibrotic samples, while the difference in susceptibility was nonsignificant. 27 In contrast, our study showed significant increase in susceptibility. Our study used WF separation method for QSM reconstruction, while the ex vivo study used simultaneous phase unwrapping and removal of chemical shift (SPURS).…”

“…26 To the best of our knowledge, few studies have compared QSM analysis and the status of liver fibrosis. An ex vivo feasibility study exists, 27 but there is no in vivo study.…”

Toward a realistic in silico abdominal phantom for QSM

“…[1][2][3][4] Over the past decade, QSM has proven to be a promising tool for various brain applications, including the assessment of iron deposits in deep gray matter, 2,5 demyelination in white matter, 2 differentiation of blood products and calcifications, 4,6 estimation of vessel oxygenation and geometry, 7,8 and its use as a potential biomarker of several neurodegenerative diseases. 2,4,5,[9][10][11] Recently, QSM has gained interest for applications outside the brain, for example, as a biomarker for hepatic iron overload 12,13 and fibrosis, 14,15 and chronic kidney disease. 16 Unlike in the brain, the application of QSM in the abdomen involves a series of additional challenges and restrictions 12,14,17 : reduced acquisition times and resolution, undesired signal contributions from fat and gases, rapid signal decay in tissues with high iron concentrations, and different kinds of motion.…”

“…24 Regardless of the chosen approach, abdominal QSM reconstructions tend to be over-regularized to minimize artifacts, resulting in maps with low details that only provide significant information for severe conditions or diseases. 12,14,16,25 Furthermore, the absence of a reliable ground-truth hinders the development of a more precise and effective dipole inversion approach for abdominal applications that could effectively manage such specific limitations. On the one hand, in vivo abdominal ground-truth data could not be developed using methods like COSMOS 26 or STI, 27 given the unfeasibility to acquire multiple orientation images in the abdomen.…”

“…2,4,5,[9][10][11] Recently, QSM has gained interest for applications outside the brain, for example, as a biomarker for hepatic iron overload 12,13 and fibrosis, 14,15 and chronic kidney disease. 16 Unlike in the brain, the application of QSM in the abdomen involves a series of additional challenges and restrictions 12,14,17 : reduced acquisition times and resolution, undesired signal contributions from fat and gases, rapid signal decay in tissues with high iron concentrations, and different kinds of motion. These considerations result in restrictive acquisition protocols and additional preprocessing steps, which might degrade the quality of the QSM reconstructions in the abdominal area.…”