Correlation of the measured MRI parameters with the volume regeneration of the hepatectomized livers.

<p>The diagrams depict the correlation of longitudinal (A) and transverse relaxation (B), diffusion (C) and magnetization transfer (D) with the regenerating liver remnant shown for cPH, ePH, PLF and SHAM.</p

Prediction of small for size syndrome after extended hepatectomy: Tissue characterization by relaxometry, diffusion weighted magnetic resonance imaging and magnetization transfer

<div><p>This study aimed to monitor the course of liver regeneration by multiparametric magnetic-resonance imaging (MRI) after partial liver resection characterizing Small-for-Size Syndrome (SFSS), which frequently leads to fatal post-hepatectomy liver failure (PLF).</p><p>Twenty-two C57BL/6 mice underwent either conventional 70% partial hepatectomy (cPH), extended 86% partial hepatectomy (ePH) or SHAM operation. Subsequent MRI scans on days 0, 1, 2, 3, 5 and 7 in a 4.7T MR Scanner quantified longitudinal and transverse relaxation times, apparent diffusion coefficient (ADC) and the magnetization-transfer ratio (MTR) of the regenerating liver parenchyma. Histological examination was performed by hematoxylin-eosin staining. After hepatectomy, an increase of T1 time was detected being larger for ePH on day 1: 18% for cPH vs. 40% for ePH and on day 2: 24% for cPH vs. 49% for ePH. An increase in T2 time, again greater in ePH was most pronounced on day 5: 21% for cPH vs. 41% for ePH. ADC and MTR showed a decrease on day 1: 21% for ePH vs. 13% for cPH for ADC, 15% for ePH vs. 11% for cPH for MTR. Subsequently, all MR parameters converged towards initial values in surviving animals. Dying PLF animals exhibited the strongest increase of T1 relaxation time and most prominent decreases of ADC and MTR. The retrieved MRI biomarkers indicate SFSS and potentially developing PLF at an early stage, likely reflecting cellular hypertrophy with extended water content and concomitantly diluted cellular components as features of liver regeneration, appearing more intense in ePH as compared to cPH.</p></div

Study flowchart of all animals assigned to assigned either MRI experiments or histology.

<p>The study design comprised essentially two cohorts of mice. One cohort of mice was dedicated to MRI assessment after cPH, ePH or SHAM operation in a longitudinal study (nMRI = 22), the other cohort, requiring tissue harvest for histological assessment of the liver parenchyma corresponding to each time point of the MRI investigation was examined in a cross-sectional study after cPH, ePH or SHAM operation (nHistology = 36).</p

Liver regeneration was monitored by MR volumetry and by longitudinal T1 and transversal T2 relaxometry for all study groups, cPH, ePH, PLF and SHAM, prior surgery and on POD 1, 2, 3, 5, 7.

<p>Liver regeneration was monitored by MR volumetry and by longitudinal T1 and transversal T2 relaxometry for all study groups, cPH, ePH, PLF and SHAM, prior surgery and on POD 1, 2, 3, 5, 7.</p

Typical ROI drawing is depicted as red areas.

<p>Three independent polygonal ROIs were drawn in the right lobe under avoidance of large macroscopic vessels. The contour of the liver is indicated by a yellow line.</p

Liver regeneration assessed by multimodal MRI for animals having undergone partial hepatectomy or SHAM surgery.

<p>The diagrams depict the measurements of MR volumetry (A), longitudinal (B) and transverse relaxation (C), diffusion (D) and magnetization transfer (E) of the regenerating liver remnant. After its initial liver volume loss, the liver could already replenish liver parenchyma up to 50% for cPH and up to 30% for ePH one day after hepatectomy (A). T1 times, lesser the T2 times, increase after hepatectomy dependent on the extent of resection with almost complete recovery to baseline if the animal survives (B, C). There are further remarkable decreases in diffusion and magnetization transfer dependent on extent of resection (D, E). These observations appear plausible considering the reported hypertrophy of parenchymal cells, caused by an elevated lipid and fluid content early after resection. The cellular increase of water presumably prolongs the T1 relaxation, the cellular hypertrophy restricts diffusion whereas the cellular increase of water and lipids hampers magnetization transfer.</p

Representative images depicting H&E staining of regenerating liver parenchyma.

<p>Hematoxylin stained nuclei appear blue, whereas eosin stains proteins nonspecifically pink. The image shows formalin-fixed, paraffin embedded tissue sections of liver parenchyma after cPH on POD 1, 2, 3 and 5 (left panel) and parenchyma after ePH on POD 1, 2, 3 and 5 (right panel). The reported cellular hypertrophy leading to the early volume gain of the regenerating liver is mainly driven by an increased accumulation of fluids and lipids into parenchymal cells, resulting in the vacuolated appearance during the first few days [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192847#pone.0192847.ref009" target="_blank">9</a>]. For all images, scale bar is 20 μm.</p

Liver regeneration was monitored by diffusion-weighted MRI and magnetization transfer MRI for all study groups, cPH, ePH, PLF and SHAM, prior surgery and on POD 1, 2, 3, 5, 7.

<p>Liver regeneration was monitored by diffusion-weighted MRI and magnetization transfer MRI for all study groups, cPH, ePH, PLF and SHAM, prior surgery and on POD 1, 2, 3, 5, 7.</p