Liver parenchymal T1: repeatability and studies in a rodent model of chronic liver disease at 9.4T
Manil Chouhan1, Rajiv Ramasawmy2, Adrienne Campbell-Washburn2, Alan Bainbridge3, Nathan Davies4, Shonit Punwani1, Rajeshwar Mookerjee4, Simon Walker-Samuel2, Mark Lythgoe2, and Stuart Taylor1

1UCL Centre for Medical Imaging, University College London, London, United Kingdom, 2UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 3Department of Medical Physics, University College London Hospitals NHS Trust, London, United Kingdom, 4UCL Institute for Liver and Digestive Health, University College London, London, United Kingdom

Synopsis

There is a growing interest in the use of hepatic parenchymal T1 for the assessment of hepatic fibrosis. Using Look-Locker T1 measurements at 9.4T in a rat model of cirrhosis, we demonstrate that these measurements are repeatable and significantly different in animals with and without chronic liver disease.

Purpose

There is a growing interest in the evaluation of intrinsic tissue T1 in the context of hepatic fibrosis, with increases in liver T1 observed in patients with progressive liver fibrosis (1-4). In this study we aim to (a) assess the feasibility and repeatability of hepatic T1 parenchymal measurements and (b) investigate any differences in hepatic parenchymal T1 in normal and cirrhotic rats.

Methods

Subjects

Healthy Sprague-Dawley rats were underwent bile-duct ligation (BDL) procedure (n=7) (5) or sham laparotomy (n=10). Animals were maintained for 4 weeks for development of hepatic fibrosis and features of chronic liver disease. After induction with isoflurane, anaesthetised animals were scanned using a 9.4T Agilent scanner, using a 72 mm birdcage coil (Oxford, UK).

T1 measurement and repeatability studies

An axial slice that enabled good visualisation of hepatic parenchyma was selected from respiratory-gated anatomical images. T1 measurements were undertaken using an end-expiration triggered, spoiled gradient-echo Look-Locker readout (FOV 60x60 mm2, 128x128 matrix, 2 mm slice thickness, TE=1.18 ms, TILook-Locker=110 ms, TRRF=2.3 ms, αLL=8˚, TRI=13 seconds, 50 inversion recovery readouts, 15 minute acquisition time). T1 measurements were repeated after 120 minutes for repeatability studies.

Post-processing

Data was analysed using in-house developed Matlab code. Images were retrospectively gated using an automated algorithm (6). T1 was estimated from pixel-wise, non-linear least-squares fitting with a Look-Locker correction(7).

Three identically sized circular ROIs were placed on the right, middle and left hepatic parenchyma (figure 1). ROIs were positioned to avoid major vascular structures and extra-hepatic tissues. T1 estimates were based on averages obtained from the three ROIs. Placement of ROIs was performed through joint consensus between a Radiologist (MC) and an Imaging Scientist (RR), both blinded to the presence of disease. For each subject, ROIs were positioned identically for repeatability measurements.

Results

At the time of scanning, mean BDL body weight (403.4±14.3g) was lower than mean sham body weight (463.2±6.6g; p=0.0009) but, mean BDL wet liver mass (30.0±1.9g) was higher than mean sham wet liver mass (14.0±0.6g; p < 0.0001), both in keeping with chronic liver disease.

Baseline mean hepatic parenchymal T1 in sham operated animals (1266±17.1 ms) was significantly lower in BDL animals (1523±43.4 ms, p<0.0001, figure 2). For repeatability measurements: the average time between repeat measurements across the entire cohort was 124.0±4.1 minutes. The mean difference between repeated T1 measurements for sham (4.1±3.3 ms) and BDL rats (-14.1±15.7 ms) was small. The Bland-Altman 95% Limit of Agreement for repeated measurements was smaller for sham (±18.8 ms) compared with BDL (±81.2 ms) animals (figure 3a). Strong and significant positive correlations were observed between repeated hepatic parenchymal T1 measurements (r=0.9845; p<0.0001, figure 3b).

Discussion

In this study, we have demonstrated good overall hepatic parenchymal T1 repeatability, albeit with greater BDL hepatic parenchymal T1 variability and poorer repeatability than their sham counterparts. This may reflect heterogeneity in the disease process. We have also demonstrated significant differences between sham and BDL hepatic parenchymal T1, a novel finding in a pre-clinical model. BDL animals demonstrate significantly greater hepatic T1, corroborated by published clinical data on T1 mapping and hepatic fibrosis stage (8). The Look-Locker T1 measurement method is well-established and well suited to in vivo imaging, but its reliance on the use of smaller flip angles results in a greater vulnerability to inhomogeneities in B1, especially at higher field strength. Further studies will investigate the pathological biochemical changes underpinning the increase in hepatic parenchymal T1 observed in liver disease.

Conclusion

Hepatic parenchymal Look-Locker T1 measurements are repeatable at 9.4T and are higher in BDL rats, in line with clinical studies of hepatic fibrosis.

Acknowledgements

We are grateful for the assistance of Abe Habtieson for preparing sham and BDL rats. This work was supported by a Wellcome Trust Clinical Research Training Fellowship (grant WT092186) and a Wellcome Trust Senior Research Fellowship (grant WT100247MA), an MRC Capacity Building Studentship and the British Heart Foundation, King’s College London and UCL Comprehensive Cancer Imaging Centre CR-UK & EPSRC, in association with the DoH (England).

References

1. Ding Y, Rao SX, Meng T, Chen C, Li R, Zeng MS. Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease. European radiology 2014;24(4):959-966.

2. Haimerl M, Verloh N, Zeman F, et al. Assessment of clinical signs of liver cirrhosis using T1 mapping on Gd-EOB-DTPA-enhanced 3T MRI. PloS one 2013;8(12):e85658.

3. Katsube T, Okada M, Kumano S, et al. Estimation of liver function using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Investigative radiology 2011;46(4):277-283.

4. Hoad CL, Palaniyappan N, Kaye P, et al. A study of T(1) relaxation time as a measure of liver fibrosis and the influence of confounding histological factors. NMR in biomedicine 2015;28(6):706-714.

5. Harry D, Anand R, Holt S, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat. Hepatology 1999;30(5):1198-1205.

6. Ramasawmy R, Campbell-Washburn AE, Wells JA, et al. Hepatic arterial spin labelling MRI: an initial evaluation in mice. NMR in biomedicine 2015;28(2):272-280.

7. Deichmann RH, A. Quantification of T1 values by SNAPSHOT-FLASH NMR imaging. J Magn Reson 1992;96(3):608-612.

8. Banerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol 2014;60(1):69-77.

Figures

Figure 1: T1 mapping and ROI placement

Anatomical images (a) were used to select a slice for quantification. The segmented area for quantitative analysis is demonstrated by the dashed white line. T1 maps were generated with consensus ROI placement (b).


Figure 2: Hepatic parenchymal T1 at baseline in sham and BDL rats

Baseline hepatic parenchymal T1 was found to be significantly higher in BDL rats.


Figure 3: Repeatability of ASL hepatic parenchymal T1 measurements

Data from sham (■) and BDL (Δ) rats. Repeated measurements were obtained on average 124±4.1 minutes apart. The overall Bland-Altman 95% Limit of Agreement was ±54.8 ms (a). A strong and significant correlation between repeated measurements was demonstrated (b).




Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3848