Longitudinal assessment of structural and haemodynamic parameters in compensated cirrhosis using Quantitative Magnetic Resonance Imaging
Chris Bradley1, Eleanor F Cox1, David Harman2, Martin W James2, Guru P Aithal2, I Neil Guha2, and Susan T Francis1

1Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, 2NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, University of Nottingham, Nottingham, United Kingdom

Synopsis

We perform a longitudinal 3 year study to assess progression of disease in compensated cirrhosis (CC) using annual haemodynamic and structural MR measures, and compare with a healthy volunteer group. Longitudinal relaxation time (T1) correlates with liver disease severity, and shows a small variance across years in stable, compensated cirrhosis. In contrast a large variance is shown for liver stiffness measures using Fibroscan®. MR measures correlate well with Enhanced Liver Fibrosis (ELF) scores. This study suggests that MR provides a sensitive technique to assess changes in pathophysiology of CC.

Purpose

Monitoring early structural and haemodynamic changes in cirrhosis patients will provide clinicians/patients with important information on prognosis and provide a tool to assess early efficacy of novel drug therapies. There is no previous data describing the longitudinal changes of quantitative MRI parameters in liver cirrhosis. Here, we assess 1) haemodynamic and structural MR changes in stable cirrhosis at baseline in comparison to a) age/gender matched healthy volunteers and b) decompensated liver disease; 2) the annual change, over 3 years, of quantitative MRI parameters in compensated cirrhosis and its relationship to validated measures of liver injury (Fibroscan®,1 and Enhanced Liver Fibrosis Score (ELF)2).

Methods

50 patients were recruited to a prospective, longitudinal study of compensated cirrhosis (CC) (Child Pugh A of varying aetiology) all consenting to annual MRI visits, 10 patients with CC have completed up to Year 3 (Aetiology: 1 ALD, 2 Haemochromatosis (Haem), 3 HCV, 3 NAFLD, and 1 PSC). In addition, 10 age and gender matched Healthy Volunteers (HV) (6 male, aged 61±1 years at baseline) have completed MRI visits at baseline and Year 3, and 4 Decompensated Cirrhosis (DC) patients at baseline (1 male, aged 57±11 years). The CC group had a Fibroscan® to assess LSM and ELF blood test every 6 months during the study. All MRI scans were performed on a 1.5T Philips Achieva system using a body transmit coil with 16-channel SENSE Torso receive coil. Data was acquired to assess structure and haemodynamics in liver/splanchnic/cardiac/renal organs. Here we show longitudinal changes related to the liver alone.

Structure: Liver tissue T1 maps were formed using a modified respiratory-gated inversion-recovery sequence with spin-echo readout (TE 27 ms, SENSE 2, 3 sagittal slices with a 5 mm gap, FOV 288x288 mm, voxel size 3x3x8 mm3, temporal slice spacing 65 ms) at 13 inversion delays (100–1200 ms in 100 ms steps and 1500 ms). Readouts were collected at 1500 ms after the respiratory trigger synchronized to the global inversion pulse.3 Data were fit to create T1 and M0 maps, a ROI was drawn over the liver, and the mean T1 determined. In addition liver volume was estimated from balanced turbo field echo (bTFE) localisers.

Haemodynamics: Vessel flow (flux and velocity) was assessed using phase contrast (PC)-MRI with 15 phases across the cardiac cycle (TR/TE 6.9/3.7 ms, FA 25o, NEX 2, reconstructed resolution 1.17x1.17x6 mm3, TFE factor 4-6) with VENC (cm/s) = 100/50 for the hepatic artery (HA)/portal vein (PV). Liver perfusion was measured on the same 3 sagittal slices using respiratory-triggered flow alternating inversion recovery (FAIR) arterial spin labelling (ASL) with a bTFE readout (60 pairs, TE/TR 1.2/2.4 ms, SENSE 2, FA 60o, 3x3x8 mm3 voxel, post-label delay (TI) 1100 ms, in-plane pre-saturation). Transit time was estimated from 4 pairs of tag/control images acquired at TI = 300, 500, 700, 900 ms. MR measures were correlated with LSM and ELF scores.

Results

Figure 1 shows liver T1 for the CC, HV and DC groups. At baseline, an increase in T1 is found with liver disease severity (HV < CC < DC) (p<0.04), whilst a significant reduction in T1 is observed over the 3 years in the CC group (p<0.01). Figure 2A shows T1 measures for each CC patient and age/gender matched HV, a small standard deviation in T1 measures across visits is seen. In comparison, Figure 2B shows LSM over visits, with a much greater standard deviation. Figure 2C shows the normalised change across visits for T1 and LSM to highlight this further, and Figure 2D shows the poor correlation of T1 with LSM (R=0.41). There was no significant change in PV or HA flux over visits, but PV velocity was reduced in CC patients compared to HV at baseline (p<0.01) and tends to increase over visits (P<0.006) (Figure 3A). Figure 3B shows perfusion measures for each CC patient and age/gender matched HV, in the CC group perfusion is lower than in the HV group (p<0.006). Figure 4 shows liver T1 and PV velocity for all 4 MR visits correlated with ELF score, a significance is seen for liver T1 (R=0.74, p<0.0002) and PV velocity (R=0.66, p<0.002).

Conclusion

We show that at baseline, T1 and haemodynamic parameters delineate distinct differences in liver disease severity in healthy controls, compensated cirrhosis and decompensated cirrhosis. In compensated cirrhosis, the longitudinal change of all the quantitative MRI biomarkers over 3 years shows a reduced variance in contrast to LSM using Fibroscan®. This study provides evidence that MR may be a sensitive modality to assess changes in pathophysiology in liver cirrhosis.

Acknowledgements

Financial support from NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham.

References

[1] Sandrin et al. IEEE Trans Ultrason Ferroelectr Freq Control (2002) 49:436-46, [2] Rosenberg et al. Gastroenterol (2004) 127:1704-13, [3] Hoad et al. NMR Biomed. (2015) 28.6:706-14.

Figures

Figure 1: Liver tissue T1 for the compensated cirrhosis (CC), decompensated cirrhosis (DC) and healthy volunteer (HV) groups shown for annual visits. Standard error reflects the variance in the T1 value across subjects within each group.

Figure 2: A) Liver tissue T1 and B) LSM for each CC patient and age/gender matched HV. Standard deviation reflects the variance in T1/LSM measures across each annual visit. C) Normalised data illustrates the change in T1 and LSM from Year 1. D) Poor correlation between mean T1 and LSM.

Figure 3: A) Mean portal vein velocity with standard error across CC, DC, and HV groups. B) Mean perfusion with standard error across visits for the CC group and HV group.

Figure 4: Strong correlations between A) liver T1 and B) portal vein velocity against ELF score.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0158