Quantitative magnetic resonance imaging predicts individual future liver performance after liver resection for cancer

Abstract

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: MK, GR, JJC, JMcG, RB, and JMB are employees and shareholders at Perspectum Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other actual or perceived conflicts of interest to declare.

Figures

Fig 1

(a) Image analysis pipeline. A 3D U-net was trained using hand labelled maps to delineate the liver on 3D T1-weighted images. The surgical plans and anatomical segments of Couinaud are semi-automatically delineated by placing anatomical landmarks. Quantitative tissue characteristics maps are overlaid onto the 3D liver rendering. Segmentectomies or wedge resections defined by the surgical plan are virtually performed to calculate the future liver remnant. (b) Two case studies indicating the proposed utility in clinical decision making.

Fig 2. Trial design.

(a) CONSORT diagram indicating enrolment in the HepaT1ca trial. Median and [IQR] or number and (%). (b) Venn diagram indicating the range of surgical procedures carried out.

Fig 3

(a-f) Quantitative MR images of the liver from six patients presenting with liver cancer using LiverMultiScan showing range of cT1 values found in the parenchyma. (g,h) Haematoxylin & eosin stains of parenchymal tissue taken from explant of patient with colorectal liver metastasis (c, white box) showing healthy liver tissue and a patient with hepatocellular carcinoma (f, white box) showing hepatocellular ballooning, clusters of inflammatory cells and regions of steatosis. (I, j, k) Box and Whisker plots of preoperative cT1 or proton density fat fraction (PDFF) against histopathological scoring of ballooning, inflammation or steatosis in explant tissue (1-way ANOVA with Tukey’s post-hoc test).

Fig 4. Length of stay.

Length of stay is 1.5 days longer if there is liver fibroinflammation measured by cT1 in patients with a predicted FLR 795ms; Wilcoxon rank sum test **P = 0.0053, n = 77).

Fig 5. Post-surgery outcomes.

(a) The modified Hyder-Pawlik score measured before and at each day following surgery (2.5*INR + 17.1*bilirubin + 88.4*creatinine). (b) Sum of the modified Hyder-Pawlik score over 5 days is significantly higher in patients presenting with high preoperative liver cT1 (P = 0.0076). (c) Receiver operating characteristic curve describing the diagnostic ability of the Hepatica score to discriminate the upper quartile of patients representing those with a poor post-operative outcome. (d) Achieved regeneration score (calculated by dividing pre-operative liver volume by the liver volume measured a median of 99 days following resection for liver cancer) correlated with the pre-operative Hepatica score (R2 = 0.48). (e, f) Exemplar pre-surgical cT1 map and T1-weighted image with FLR overlaid (red) of a patient presenting with a HCC lesion in the right lobe of the liver. (g, h) Post-surgical cT1 map and T1 weighted image of the same patient 3 months following surgery.