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. 2019 Jan;44(1):72-84.
doi: 10.1007/s00261-018-1701-2.

Reference Range of Liver Corrected T1 Values in a Population at Low Risk for Fatty Liver Disease-A UK Biobank Sub-Study, With an Appendix of Interesting Cases

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Free PMC article

Reference Range of Liver Corrected T1 Values in a Population at Low Risk for Fatty Liver Disease-A UK Biobank Sub-Study, With an Appendix of Interesting Cases

A Mojtahed et al. Abdom Radiol (NY). .
Free PMC article

Abstract

Purpose: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender.

Methods: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk.

Results: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values.

Conclusion: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

Keywords: Corrected T1; Multiparametric magnetic resonance imaging; Non-alcoholic fatty liver disease; Quantitative imaging biomarkers.

Conflict of interest statement

Conflict of interest

R.B. and S.N. are on the board of directors and shareholders of Perspectum Diagnostics, an Oxford University spin-out company. R.B. and S.N. have filed three patent applications related to the use of multiparametric M.R. for the diagnosis of chronic liver disease. C.K., A.H., S.K., A.M., M.K., and M.M. are employees and shareholders of Perspectum Diagnostics. H.W. is a shareholder of Perspectum Diagnostics.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Range of cT1 in the reference population. A Example images with three different cT1 values. B Beeswarm plot showing distribution of cT1 values in the reference population, with median (666.0 ms) and IQR (643.3–694.8 ms) shown
Fig. 3
Fig. 3
Boxplots showing distribution of cT1 in the reference population by age and gender. 62 individuals are not plotted as their age was missing from the dataset. Outliers not shown
Fig. 4
Fig. 4
Example case provided for an overview of the software results sheet. The results sheet depicts source images (A) with circular regions of interest (ROI) drawn (blue circles). The statistics summary (B) provides values for calculated proton density fat fraction (PDFF), T2*, and cT1 (with normal reference ranges for each). The cT1 value is calculated from a circular ROI which should be placed within hepatic parenchyma, avoiding any vessels. The results sheet also includes a colormap (C) for a pictorial representation of cT1
Fig. 5
Fig. 5
Cases 1 and 2: Patient 1 is a 64-year-old female with non-alcoholic steatohepatitis and patient 2 is a 42-year-old male with steatosis. Axial (B, E) and coronal (C, F) T2* weighted images of the liver provide anatomical information for each patient, but no sensitivity to detect underlying parenchymal disease. Results sheets for patient 1 (A) and 2 (D) demonstrate that both patients have elevated PDFF values, 15.3% for patient 1 and 8.2% for patient 2. An advantage of this method is that the level of fat, as well as its burden on the hepatic parenchyma, is instantly assessed. The colormaps demonstrate that the cT1 value of patient 1 is notably higher than patient 2, indicating a greater degree of inflammation and fibrosis. Patient 2 has a mildly elevated cT1 value, but has the opportunity for intervention (medical and/or lifestyle) before potentially progressing to the cT1 value of patient 1
Fig. 6
Fig. 6
Case 3: A 47-year-old female with polycystic liver disease listed for liver transplant. MRI was obtained to assess hepatic cyst burden and integrity of the remaining hepatic parenchyma. Anatomical axial (A) and coronal (B) T2-weighted images of the abdomen demonstrate innumerable cysts throughout the liver. Results sheet (C) demonstrates that liver fat, T2*, and cT1 are all within normal limits. The results are also displayed in pictorial format with the areas of remaining hepatic parenchyma coded in green (normal cT1) on the colormap. This case uniquely exemplifies the advantage of this methodology over other techniques to assess the pathophysiological state of hepatic parenchyma, such as ultrasound or MR elastography. These elastography methods would produce spurious results in this setting, as the extensive cyst burden would alter the acoustic wave propagation through the liver
Fig. 7
Fig. 7
Case 4: A 79-year-old male with autoimmune hepatitis (AIH). Axial (A) and coronal (B) images of the liver provide anatomical information, but are unable to provide any clarity regarding the underlying pathophysiologic process. Results sheet (C) shows the complexity of this individual’s disease. In a pattern characteristic of AIH, the spread of fibroinflammatory disease is heterogeneous with some areas clearly demonstrating higher cT1 values than others. Measuring cT1 in a single circular region of interest would yield varying results (e.g., normal in the right lobe as shown here, and abnormal in the left lobe). The colormap image also clearly demonstrates the size of the complicating ascites (purple/pink), a source of discomfort for the patient. Consequently, the results sheet and images provide a comprehensive assessment of this patient’s complex disease
Fig. 8
Fig. 8
Case 5: A 51-year-old male who had lived with hepatitis C virus infection since 1984. Patient had failed to get a sustained virologic response (SVR) after interferon treatment in 2014, and is now undergoing treatment with ledipasvir/sofosbuvir. Axial (B, E) and coronal (C, F) T2*-weighted images of the liver provide anatomical information but are unable to provide further tissue characterization. Result sheets from examinations at the 1st (A) and 7th (B) weeks of treatment are provided. These clearly show response to the treatment, with the cT1 value and cT1 colormap improving over the course of treatment. Patient achieved SVR at 12 and 24 weeks

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