Introduction

Assessment of hepatic iron content (HIC) by R2*-MRI has been increasingly used as a non-invasive alternative to liver biopsy. R2* (=1/T2*) is typically measured by quantifying the signal decay of a breath-hold multi-echo gradient echo (mGRE) sequence. R2* and HIC by biopsy are linearly related and R2*-based HIC is calculated using published calibration curves.^1-3 However, previous R2*-HIC biopsy studies have shown that their precision is limited for high HIC (>20 mg Fe/g) and might even fail for massive HIC (>25 mg Fe/g) because of the rapid signal decay associated with standard mGRE imaging. In this study, we investigate the impact of hepatic iron overload on T1 (=1/R1) relaxation times and if T1 values may have the potential to increase our confidence in the assessment of HIC in a large patient cohort with transfusional iron overload.

Methods

This prospective study was approved by the Institutional Review Board. 124 subjects with a history of ≥ 12 blood transfusions underwent MRI at 1.5T to assess HIC. Of these 124 subjects, 62 also had a 3T exam. All images were acquired axially at the location of the main portal vein in the central part of the liver. Quantitative T1 imaging and mapping was accomplished by using the ShMOLLI sequence (TE/TI/TIincrement=1.05/105/80ms, α=35°, FOV=323-400mm, matrix:384x312, slice-thickness=10 mm) and respective post-processing algorithm.⁴ For T2* analysis, subjects also underwent multi-echo gradient-echo (mGRE) imaging⁵ (TR/TE1/ΔTE=200/1.07/0.86ms, 20 echoes, α=35°, FOV= 250–400mm, matrix: 128x104, slice thickness=10 mm). Quantitative T2*/R2* maps were calculated using a nonlinear least-squares fit method in MATLAB.^{6, 7} Region of interest (ROI) analysis of T1 and T2* quantitative maps were performed offline using a custom-written program in MATLAB.⁸ Two ROI analysis techniques were used: small ROIs were drawn in a homogeneous area in the right hepatic lobe that approximately matches the area of liver biopsy resections. Hepatic T1 and T2* values were also extracted using whole liver ROI and histogram analysis that excluded signal from hepatic blood vessels.⁸ R2*-based HIC values were calculated using the R2* values obtained at 1.5T and a previously published calibration curve.^3,8 As the presence of fat affects T1 and T2* measurements, all patients were tested for hepatic steatosis¹⁰ and were excluded if the fat fraction ≥ 5%.

Results & Discussion

Patient demographics were summarized in Table 1. Four patients were excluded due to failed T1 or T2* fits at 1.5T and 8 at 3T. Further, 5 patients were excluded due to the presence of fat at 1.5T and 2 at 3T. Figure 1A compares the T1 results between the small ROI and whole liver ROI techniques. A strong linear correlation was found at 1.5T (slope = 1.03, R² = 0.95) and at 3T (slope = 0.96, R² = 0.91) between both ROI techniques. This suggests that T1 times (and thus iron) are homogeneously distributed throughout the liver in our patient cohort. Analysis using the whole liver ROI approach is preferable as it removes the ambiguities associated with the size and placement of ROI compared to the small ROI approach.⁸ Liver T1 times measured at 3T produced slopes of 1.2 and 1.4 when compared to those obtained at 3T using the whole liver and small ROI analyses, respectively. Figure 2 shows the results of comparing T1 and R1 values with R2*-based HIC. A monotonic decrease in T1 (increase in R1) was seen at both field strengths with increasing HIC. This trend however saturates around T1 = 300 ms for HIC > 15 mg Fe/g (i.e., R2* > 500 s^-1). The observed ‘saturation’ of T1 times could be explained by a systematic bias in the ShMOLLI sequence fitting algorithm. This algorithm has not been tested¹¹ for T2* < 2 ms (R2* > 500 s^-1) [HC1] which happens to be where our data begins to flatten out. However, there is a moderate linear relationship (R² = 0.5) between R1 and R2*-based HIC (Fig. 2B) for normal to moderate iron overloaded cases (0 – 15 mg Fe/g) and the slope obtained at 1.5T was close to that reported in literature.

Conclusion

T1 relaxation times in the liver can be quantified with ShMOLLI in normal and moderately iron overloaded cases. T1 values are relatively homogeneous throughout the liver. T1 values are associated with T2* values and consequently with HIC. T1 times plateau in highly overloaded cases, which likely is due to the fact that T2* times are too short for ShMOLLI to quantify accurately. Therefore, future work should focus on testing with a fast T1 sequence (e.g., snapshotFLASH) if there is indeed a plateau or a linear association also for severe HIC.

Acknowledgements

No acknowledgement found.

References

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