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Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis.

ABSTRACT: OBJECTIVE: The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. METHODS: 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann-Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. RESULTS: Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. CONCLUSION: The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. ADVANCES IN KNOWLEDGE: The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level.

SUBMITTER: Nilsson H

PROVIDER: S-EPMC3664988 | biostudies-other | 2013 Jun

REPOSITORIES: biostudies-other

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Project description:BackgroundNuclear protein Ki-67 indicates the status of cell proliferation and has been regarded as an attractive biomarker for the prognosis of HCC. The aim of this study is to investigate which radiomics model derived from different sequences and phases of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was superior to predict Ki-67 expression in hepatocellular carcinoma (HCC), then further to validate the optimal model for preoperative prediction of Ki-67 expression in HCC.MethodsThis retrospective study included 151 (training cohort: n = 103; validation cohort: n = 48) pathologically confirmed HCC patients. Radiomics features were extracted from the artery phase (AP), portal venous phase (PVP), hepatobiliary phase (HBP), and T2-weighted (T2W) images. A logistic regression with the least absolute shrinkage and selection operator (LASSO) regularization was used to select features to build a radiomics score (Rad-score). A final combined model including the optimal Rad-score and clinical risk factors was established. Receiver operating characteristic (ROC) curve analysis, Delong test and calibration curve were used to assess the predictive performance of the combined model. Decision cure analysis (DCA) was used to evaluate the clinical utility.ResultsThe AP radiomics model with higher decision curve indicating added more net benefit, gave a better predictive performance than the HBP and T2W radiomic models. The combined model (AUC = 0.922 vs. 0.863) including AP Rad-score and serum AFP levels improved the predictive performance more than the AP radiomics model (AUC = 0.873 vs. 0.813) in the training and validation cohort. Calibration curve of the combined model showed a good agreement between the predicted and the actual probability. DCA of the validation cohort revealed that at a range threshold probability of 30-60%, the combined model added more net benefit compared with the AP radiomics model.ConclusionsA combined model including AP Rad-score and serum AFP levels based on enhanced MRI can preoperatively predict Ki-67 expression in HCC.

Project description:Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.

Project description:High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co-option in regions of invasive growth (in which the blood-brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI. A multiparametric MRI approach, incorporating native measurements and both Gd-DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)-enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k-means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA-MB-231 LM2-4 breast adenocarcinomas in mice. Both tumour models presented with higher ?R1 (the change in transverse relaxation rate R1 induced by Gd-DTPA), fractional blood volume (fBV) and apparent diffusion coefficient than uninvolved regions of the brain. MDA-MB-231 LM2-4 tumours were less densely cellular than RG2 tumours and exhibited substantial local invasion, associated with oedema, whereas invasion in RG2 tumours was minimal. These additional features were reflected in the more heterogeneous appearance of MDA-MB-231 LM2-4 tumours on T2 -weighted images and maps of functional MRI parameters. Unsupervised cluster analysis separated subregions with distinct functional properties; areas with a low fBV and relatively impermeable blood vessels (low ?R1 ) were predominantly located at the tumour margins, regions of MDA-MB-231 LM2-4 tumours with relatively high levels of water diffusion and low vascular permeability and/or fBV corresponded to histologically identified regions of invasion and oedema, and areas of mismatch between vascular permeability and blood volume were identified. We demonstrate that dual contrast MRI and evaluation of tissue diffusion properties, coupled with cluster analysis, allows for the assessment of heterogeneity within invasive brain tumours and the designation of functionally diverse subregions that may provide more informative predictive biomarkers.

Project description:OBJECTIVE:The objective of this study is to evaluate if intensified pre-scan patient preparation (IPPP) that comprises custom-made educational material on dynamic phase imaging and supervised pre-imaging breath-hold training in addition to standard informative conversation with verbal explanation of breath-hold commands (standard pre-scan patient preparation-SPPP) might reduce the incidence of gadoxetate disodium (Gd-EOB-DTPA)-related transient severe respiratory motion (TSM) and severity of respiratory motion (RM) during dynamic phase liver MRI. MATERIAL AND METHODS:In this bi-institutional study 100 and 110 patients who received Gd-EOB-DTPA for dynamic phase liver MRI were allocated to either IPPP or SPPP at site A and B. The control group comprised 202 patients who received gadoterate meglumine (Gd-DOTA) of which each 101 patients were allocated to IPPP or SPPP at site B. RM artefacts were scored retrospectively in dynamic phase images (1: none- 5: extensive) by five and two blinded readers at site A and B, respectively, and in the hepatobiliary phase of the Gd-EOB-DTPA-enhanced scans by two blinded readers at either site. RESULTS:The incidence of TSM was 15% at site A and 22.7% at site B (p = 0.157). IPPP did not reduce the incidence of TSM in comparison to SPPP: 16.7% vs. 21.6% (p = 0.366). This finding was consistent at site A: 12% vs. 18% (p = 0.401) and site B: 20.6% vs. 25% (p = 0.590). The TSM incidence in patients with IPPP and SPPP did not differ significantly between both sites (p = 0.227; p = 0.390). IPPP did not significantly mitigate RM in comparison to SPPP in any of the Gd-EOB-DTPA-enhanced dynamic phases and the hepatobiliary phase in patients without TSM (all p≥0.072). In the Gd-DOTA control group on the other hand, IPPP significantly mitigated RM in all dynamic phases in comparison to SPPP (all p≤0.031). CONCLUSIONS:We conclude that Gd-EOB-DTPA-related TSM cannot be mitigated by education and training and that Gd-EOB-DTPA-related breath-hold difficulty does not only affect the subgroup of patients with TSM or exclusively the arterial phase as previously proposed.

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Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis.

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