Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of .Conclusion:Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.Peer reviewe

Comparison of clinical MRI liver iron content measurements using signal intensity ratios, R 2 and R 2

To compare three types of MRI liver iron content (LIC) measurement performed in daily clinical routine in a single center over a 6-year period. Patients undergoing LIC MRI-scans (1.5T) at our center between January 1, 2008 and December 31, 2013 were retrospectively included. LIC was measured routinely with signal intensity ratio (SIR) and MR-relaxometry (R 2 and R 2*) methods. Three observers placed regions-of-interest. The success rate was the number of correctly acquired scans over the total number of scans. Interobserver agreement was assessed with intraclass correlation coefficients (ICC) and Bland-Altman analysis, correlations between LICSIR, R 2, R 2*, and serum values with Spearman's rank correlation coefficient. Diagnostic accuracies of LICSIR, R 2 and serum transferrin, transferrin-saturation, and ferritin compared to increased R 2* (≥44 Hz) as indicator of iron overload were assessed using ROC-analysis. LIC MRI-scans were performed in 114 subjects. SIR, R 2, and R 2* data were successfully acquired in 102/114 (89%), 71/114 (62%), and 112/114 (98%) measurements, with the lowest success rate for R 2. The ICCs of SIR, R 2, and R 2* did not differ at 0.998, 0.997, and 0.999. R 2 and serum ferritin had the highest diagnostic accuracies to detect elevated R 2* as mark of iron overload. SIR and R 2* are preferable over R 2 in terms of success rates. R 2*'s shorter acquisition time and wide range of measurable LIC values favor R 2* over SIR for MRI-based LIC measuremen

New perspectives in the assessment of future remnant liver

In order to achieve microscopic radical resection margins and thus better survival, surgical treatment of hepatic tumors has become more aggressive in the last decades, resulting in an increased rate of complex and extended liver resections. Postoperative outcomes mainly depend on the size and quality of the future remnant liver (FRL). Liver resection, when performed in the absence of sufficient FRL, inevitably leads to postresection liver failure. The current gold standard in the preoperative assessment of the FRL is computed tomography volumetry. In addition to the volume of the liver remnant after resection, postoperative function of the liver remnant is directly related to the quality of liver parenchyma. The latter is mainly influenced by underlying diseases such as cirrhosis and steatosis, which are often inaccurately defined until microscopic examination after the resection. Postresection liver failure remains a point of major concern that calls for accurate methods of preoperative FRL assessment. A wide spectrum of tests has become available in the past years, attesting to the fact that the ideal methodology has yet to be defined. The aim of this review is to discuss the current modalities available and new perspectives in the assessment of FRL in patients scheduled for major liver resectio

Diffusion-weighted imaging of hepatocellular carcinoma before and after transarterial chemoembolization: role in survival prediction and response evaluation

Background: Survival outcomes of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) are heterogeneous. Measuring the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI) may improve overall survival prediction. Aim: To assess the value of measuring the ADC before and after TACE in predicting overall survival. Methods: A retrospective analysis was performed in HCC patients treated with TACE at a tertiary referral center between 2008 and 2017. The ADC values and changes in ADC value (ΔADC) of HCC lesions (≥ 1 cm) and liver parenchyma were assessed by DWI ≤ 3 months before and after first TACE. Pre- and post-TACE ADC values were compared with tumor response according to mRECIST and correlated with overall survival (OS) in a univariable and multivariable Cox-regression analysis. Results: A total of 89 patients were included, mostly Child–Pugh A (85%) and BCLC stage B (53%) with a median OS of 21.7 months (95% CI 17.6–25.9). Tumor ADC increased from 1081 mm 2 /s before (IQR 964–1225) to 1328 mm 2 /s (IQR 1197–1560) after TACE (p < 0.001). Responders according to mRECIST showed a higher ΔADC after first TACE than non-responders (26 vs. 14%, p = 0.048). Pre-TACE ADC and ΔADC were not significantly associated with OS in both univariable and multivariable analysis, whereas response according to mRECIST remained an independent predictor of OS. Conclusion: mRECIST was confirmed as an independent prognostic factor of OS, but pre- or post-TACE ADC measurements were not. Response according to mRECIST was associated with a higher increase in ADC than non-response

A new murine model to study musculoskeletal tuberculosis (short communication)

Musculoskeletal tuberculosis (TB) is a severe extrapulmonary manifestation of chronic Mycobacterium (M.) tuberculosis infection. Considering increasing incidence, multi-drug resistance and associated treatment difficulties, more preclinical research is needed. In this study we developed a murine model for musculoskeletal TB. Mice, intranasally infected with M. tuberculosis, were sacrificed after ten months. Mycobacterial growth was detected in lung and femur homogenates. Ziehl-Neelsen staining of paraffin-embedded femurs showed acid-fast rods in the myelum and Magnetic Resonance Imaging demonstrated osteomyelitis and macronodular tuberculomas. This new murine model of musculoskeletal TB might be of value to further investigate immunologic and radiologic response

Minimizing the Acquisition Time for Intravoxel Incoherent Motion Magnetic Resonance Imaging Acquisitions in the Liver and Pancreas

OBJECTIVES: The aim of this study was to determine the combination of b-values and signal averages for diffusion-weighted image acquisitions that render the minimum acquisition time necessary to obtain values of the intravoxel incoherent motion (IVIM) model parameters in vivo in the pancreas or liver with acceptable reproducibility. MATERIALS AND METHODS: For 16 volunteers, diffusion-weighted images, with 14 b-values and 9 acquisitions per b-value, were acquired in 2 scan sessions. The IVIM model was fitted to data from lesion-sized regions of interest (ROIs) (1.7 cm(3)) as well as organ-sized ROIs in the pancreas and liver. By deleting data during analyzes, the IVIM model parameters, D and f, could be determined as a function of the number of b-values as well as the number of measurements per b-value taken along. For the IVIM model parameters, we examined the behavior reproducibility, in the form of the within-subject coefficient of variation (CVw), as a function of the amount of data taken along in the fits. Finally, we determined the minimum acquisition time required as a function of CVw. RESULT: For the lesion-sized ROI, the intersession CVws were 8%/46% and 13%/55% for D/f in the pancreas and liver, respectively, when all data were taken along. For 1.2 times larger CVws, acquisition in the pancreas could be done in 5:15 minutes using 9 acquisitions per b-value at b = 0, 30, 50, 65, 100, 375, and 500 mm(-2)s and for the liver in 2:15 using 9 acquisitions per b-value at b = 0, 40, and 500 mm(-2)s. CONCLUSIONS: Acquiring 7 b-values in the pancreas and 3 b-values in the liver only decreases the reproducibility by 20% compared with an acquisition with 14 b-values. The understanding of the behavior of reproducibility as a function of b-values and acquisitions per b-values scanned will help researchers select the shortest IVIM protocol

Glycerophosphocholine and Glycerophosphoethanolamine Are Not the Main Sources of the In Vivo (31)P MRS Phosphodiester Signals from Healthy Fibroglandular Breast Tissue at 7 T

PURPOSE: The identification of the phosphodiester (PDE) (31)P MR signals in the healthy human breast at ultra-high field. METHODS: In vivo (31)P MRS measurements at 7 T of the PDE signals in the breast were performed investigating the chemical shifts, the transverse- and the longitudinal relaxation times. Chemical shifts and transverse relaxation times were compared with non-ambiguous PDE signals from the liver. RESULTS: The chemical shifts of the PDE signals are shifted -0.5 ppm with respect to glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), and the transverse and longitudinal relaxation times for these signals are a factor 3 to 4 shorter than expected for aqueous GPC and GPE. CONCLUSION: The available experimental evidence suggests that GPC and GPE are not the main source of the PDE signals measured in fibroglandular breast tissue at 7 T. These signals may predominantly originate from mobile phospholipids

Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study

PURPOSE: To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. MATERIALS AND METHODS: This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. RESULTS: Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P < .001 for NASH vs healthy control subjects). The area under the receiver operating characteristic curve to distinguish NASH from simple steatosis was 0.87 (95% confidence interval: 0.72, 1.00). CONCLUSION: This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis

Improved registration of DCE-MR images of the liver using a prior segmentation of the region of interest

In Dynamic Contrast-Enhanced MRI (DCE-MRI) of the liver, a series of images is acquired over a period of 20 minutes. Due to the patient's breathing, the liver is subject to a substantial displacement between acquisitions. Furthermore, due to its location in the abdomen, the liver also undergoes marked deformation. The large deformations combined with variation in image contrast make accurate liver registration challenging. We present a registration framework that incorporates a liver segmentation to improve the registration accuracy. The segmented liver serves as region-of-interest to our in-house developed registration method called ALOST (autocorrelation of local image structure). ALOST is a continuous optimization method that uses local phase features to overcome space-variant intensity distortions. The proposed framework can confine the solution field to the liver and allow for ALOST to obtain a more accurate solution. For the segmentation part, we use a level-set method to delineate the liver in a so-called contrast enhancement map. This map is obtained by computing the difference between the last and registered first volume from the DCE series. Subsequently, we slightly dilate the segmentation, and apply it as the mask to the other DCE-MRI volumes during registration. It is shown that the registration result becomes more accurate compared with the original ALOST approach.</p