Chris R Bradley1,2, Rob E Scott2, Eleanor F Cox1,2, Naaventhan Palaniyappan2, Indra Neil Guha2, Guruprasad P Aithal2, and Susan T Francis1,2
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, 2NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom
Synopsis
We have
previously validated MRI as a surrogate measure of Hepatic Venous Pressure
Gradient (HVPG) at 1.5T using T1 relaxation time and splanchnic haemodynamics.
Here, we explore the use of quantitative 3T MRI to assess portal hypertension.
A strong correlation between HVPG and fat suppressed IR SE-EPI T1 (p<0.0001)
and a correlation with superior mesenteric artery (SMA) velocity (p=0.02) was
observed. MOLLI T1 showed a weak correlation with HVPG (p=0.11)
compared with SE-EPI (p<0.001) in a matched patient subset. A fat suppressed IR SE-EPI T1
scheme and SMA velocity can be used as a surrogate for HVPG at 3T.
Purpose
The majority of complications in liver cirrhosis
arise from portal hypertension. Hepatic Venous Pressure Gradient (HVPG) [1] is the gold standard
method for the assessment of portal hypertension, but is highly invasive and
performed only in a restricted number of centres. We have previously validated
MRI as a surrogate measure of HVPG at 1.5T using T1 relaxation time
and haemodynamics [2]. Here, in a new cohort, we aim to assess quantitative MRI at
3T to assess portal hypertension.Methods
43 patients were prospectively recruited (22
NAFLD/12 ALD/9 other. 59yrs (range 27-83). 27 male) after undergoing a HVPG
measurement for clinical indications, MRI was performed within 12 days of a HVPG measurement on a 3T
Philips Ingenia DDAS scanner.
MR Protocol:
Balanced Turbo Field Echo (bTFE) localisers were
acquired in 3 orthogonal planes to quantify liver and spleen volume and
identify vessels of interest. Longitudinal relaxation time (T1) of
the liver and spleen was measured using two methods (i) a respiratory triggered
inversion recovery fat-suppressed spin-echo EPI scheme (9 axial slices, 10
inversion times (TI) 100 - 1500ms, 58ms temporal slice spacing, acquired in ascending/descending
slice order to increase the TI dynamic range [2]) (ii) a 5-3-3 (Philips Cardiac Native) heart-rate triggered modified
Look-Locker inversion recovery (MOLLI) scheme [3] (1 slice per breath hold for 4 slices), the acquisition time of each
scheme was ~3 minutes. Transverse relaxation time (T2*) of the liver
was measured using a multishot-fast field echo (mFFE) sequence (12 echoes, TE1
2.5ms, ΔTE 2.5ms) to assess liver iron content. Liver and spleen fat fractions
were measured using mDIXON QUANT (Philips Medical Systems). Phase-contrast
(PC)-MRI was used to assess velocity, area and bulk flow in the splanchnic
circulation (splenic artery [SPA] and superior mesenteric artery [SMA]) [2].
Data Analysis:
SE-EPI T1 data at each inversion time
was motion corrected using a non-rigid body model, and then fit on a voxel-by-voxel
basis to generate M0 and T1 maps (MATLAB, Mathworks). MOLLI
T1 maps were produced online (Philips Medical Systems, Best NL).
mFFE data were fit on a voxel-by-voxel basis to generate T2* maps.
Fat fraction maps were created using mDIXON QUANT software (Philips Medical
systems, Best NL). Histogram analysis was performed to assess the distribution
of T1, T2* and fat within the liver, with the
mode of the distribution used to represent tissue T1/T2*/Fat
% and FWHM to assess heterogeneity. Q-flow software (Philips Medical Systems)
was used to analyse the PC-MRI data to compute mean vessel cross sectional
area, velocity, and flux over the cardiac cycle.
Statistical Analysis:
All data was Shapiro-Wilk normality tested, a
Pearson correlation test was used for normally distributed data and a Spearman
correlation test used for non-parametric data. Coefficients of variance have been
assessed previously [4, 5].
Results
The HVPG
measures ranged from 2-23 mmHg, with a strong correlation between HVPG and
SE-EPI T1 (p<0.0001) and a correlation with SMA velocity (p=0.02),
Figure 1. Figure 2 shows a subset of patients for whom both SE-EPI and MOLLI T1
measurements were collected, MOLLI T1 shows a weak correlation
with HVPG (p=0.11) compared with SE-EPI (p<0.001). Further, the difference
in measured T1 between the two schemes was associated with fat
fraction, a higher fat fraction leading to longer MOLLI T1 (Fig.2C). Splenic T1
as measured by both SE-EPI and MOLLI correlated equally well with HVPG up
to a portal pressure of 10mmHg (p=0.029, p=0.032 respectively), >10mmHg no
significance was observed (Figure 3). Figure 4 compares two patients with
similar liver tissue T1 measured by SE-EPI, but with differing
levels of liver tissue fat, illustrating the differing measured MOLLI T1
values.Discussion
In agreement with our work at 1.5T, we have
shown that 3T liver tissue T1 as measured with SE-EPI and SMA mean
velocity show a good correlation with degree of portal hypertension and so can
be used as a surrogate measure to the HVPG test. We show that an IR fat
suppressed SE-EPI sequence provides the optimal scheme for evaluating liver
tissue T1 when compared to MOLLI, as this method is independent of liver
tissue fat (which has previously been shown to limit MOLLI T1 values) [3]. The
IR SE-EPI scheme is also free breathing and so is less demanding on the
patient. Splenic Tissue T1 has strong correlation for clinically insignificant
HVPG measures but cannot be used to predict portal pressure above 10mmHg.Conclusion
As shown at 1.5T, T1
measured using a fat suppressed SE-EPI inversion recovery scheme and SMA mean
velocity over the cardiac cycle can be used as a surrogate for the HVPG test at
3T.Acknowledgements
Financial support from NIHR Nottingham Digestive Diseases Biomedical Research Centre, Nottingham University
Hospitals NHS Trust and University of Nottingham.References
- Groszmann
RJ, Wongcharatrawee S (2004) The hepatic venous pressure gradient: Anything
worth doing should be done right. Hepatology 39:280–283 . doi:
10.1002/hep.20062
- Palaniyappan
N, Cox E, Bradley C, et al (2016) Non-invasive assessment of portal
hypertension using quantitative magnetic resonance imaging. J Hepatol
65:1131–1139 . doi: 10.1016/j.jhep.2016.07.021
- Mozes FE,
Tunnicliffe EM, Pavlides M, Robson MD (2016) Influence of fat on liver T
1 measurements using modified Look-Locker inversion recovery (MOLLI)
methods at 3T. J Magn Reson Imaging 44:105–111 . doi: 10.1002/jmri.25146
- Cox EF,
Palaniyappan N, Aithal GP, et al (2018) Using MRI to study the alterations in
liver blood flow, perfusion, and oxygenation in response to physiological
stress challenges: Meal, hyperoxia, and hypercapnia. J Magn Reson Imaging. doi:
10.1002/jmri.26341
- Cox
EF, Palaniyappan N, Aithal GP, et al (2018) MRI assessment of altered dynamic
changes in liver haemodynamics following a meal challenge in compensated
cirrhosis. Eur Radiol Exp 2:26 . doi: 10.1186/s41747-018-0056-3