7-T MRI-based surrogate for histopathology examination of liver fibrosis

Abstract

Background: To demonstrate that 7-T magnetic resonance imaging (MRI) provides a surrogate for histopathology of fresh ex vivo liver tissue, using the case study of liver fibrosis.

Methods: We prospectively enrolled 20 patients undergoing surgical liver resection between November 2021 and April 2023. Each ex vivo fresh liver tissue specimen (~ 1 cm³) was sectioned in half. The first half, stained using Masson's Trichrome and Perls, was assessed by three pathologists using the METAVIR score (reference standard). The second half was imaged with 7-T MRI using a cryoprobe (fat-suppressed T2-weighted turbo/fast spin-echo sequence, spatial resolution 75 × 75 × 200 µm³) and assessed by three radiologists and the same three pathologists, using a newly developed MRI-METAVIR score.

Results: Five patients were excluded from the final analysis (one patient due to poor specimen quality, two due to surgery cancellation, and two previously published used for reader training). Of the remaining 15 patients, 10 (67%) presented with chronic liver diseases and 8/15 (53%) with advanced (F3 or F4) fibrosis. Radiologists achieved 88% sensitivity, 100% specificity, 93% accuracy (95% confidence interval 68-100%) and 0.94 Harrell's c-index (0.86-1.00). Pathologists achieved 88% sensitivity, 86% specificity, 87% accuracy (60-98%) and 0.87 Harrell's c-index (0.74-0.99). There were no statistically significant differences between MRI-based and pathologic reference standard stage (p ≥ 0.655).

Conclusion: With an in-plane spatial resolution of ~ 75 × 75 µm², MRI paralleled low-magnification histology, enabling the assessment of micro-architectural liver changes, and provided a surrogate for histopathology examination of fresh ex vivo liver tissue samples at a microscopic level.

Relevance statement: 7-T MRI provides a surrogate for histopathology visualisation of fresh ex vivo liver tissue, opening new research perspectives for clinical high-field MRI of the liver.

Key points: Using the newly developed MRI-METAVIR score, 7-T MRI data strongly correlated with histopathology, achieving excellent agreement and accuracy. 7-T MRI accurately differentiated advanced from minimal liver fibrosis. 7-T MRI visualises liver micro-architecture, enabling pathology-like, noninvasive three-dimensional imaging.

Keywords: Hepatitis; Histopathology; Liver diseases; Liver fibrosis; Magnetic resonance imaging.

Fig. 1

Schematic diagram of the overall workflow of the study

Fig. 2

Schematic illustrations of the MRI-METAVIR score with high-resolution liver magnetic resonance imaging and histopathology correlation (Masson’s Trichrome) in a normal liver (a, d), F3 liver T2 (b, e), and F4 (cirrhosis) liver (c, f). On a and d, the liver architecture is homogeneous with hyperintense punctate portal spaces (arrow) and centrilobular veins (arrowhead). On b and e, the liver architecture is distorted by numerous T2 hyperintense fibrotic septa (arrowhead) with lobules of different size, shape, and signal (arrow). On c and f, there are regenerative cirrhotic nodules (arrow) separated by fibrotic septa (arrowhead)

Fig. 3

Staging discrepancy between 7-T MRI and histological reference standard. 7-T MRI (a) was staged F2 because of early changes in the lobular architecture and rare fibrotic septa (arrow) seen between the portal spaces, while histology (b) was staged F3 because of numerous fibrotic septa (arrow). c and d illustrate another example where 7-T MRI (c) was staged F3 due to numerous fibrotic septa (arrow) while histology (d) was staged F4 due to regenerative nodules (star)