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

Ristretto MRE: A generalized multi‐shot GRE‐MRE sequence

In order to acquire consistent k-space data in MR elastography, a fixed temporal relationship between the MRI sequence and the underlying period of the wave needs to be ensured. To this end, conventional GRE-MRE enforces synchronization through repeated triggering of the transducer and forcing the sequence repetition time to be equal to an integer multiple of the wave period. For wave frequencies below 100 Hz, however, this leads to prolonged acquisition times, as the repetition time scales inversely with frequency. A previously developed multi-shot approach (eXpresso MRE) to multi-slice GRE-MRE tackles this issue by acquiring an integer number of slices per wave period, which allows acquisition to be accelerated in typical scenarios by a factor of two or three. In this work, it is demonstrated that the constraints imposed by the eXpresso scheme are overly restrictive. We propose a generalization of the sequence in three steps by incorporating sequence delays into imaging shots and allowing for interleaved wave-phase acquisition. The Ristretto scheme is compared in terms of imaging shot and total scan duration relative to eXpresso and conventional GRE-MRE and is validated in three different phantom studies. First, the agreement of measured displacement fields in different stages of the sequence generalization is shown. Second, performance is compared for 25, 36, 40, and 60 Hz actuation frequencies. Third, the performance is assessed for the acquisition of different numbers of slices (13 to 17). In vivo feasibility is demonstrated in the liver and the breast. Here, Ristretto is compared with an optimized eXpresso sequence, leading to scan accelerations of 15% and 5%, respectively, without compromising displacement field and stiffness estimates in general. The Ristretto concept allows us to choose imaging shot durations on a fine grid independent of the number of slices and the wave frequency, permitting 2- to 4.5-fold acceleration of conventional GRE-MRE acquisitions

Unipolar MR elastography: Theory, numerical analysis and implementation

In MR elastography (MRE), zeroth moment balanced motion-encoding gradients (MEGs) are incorporated into MRI sequences to induce a phase shift proportional to the local displacement caused by external actuation. To maximize the signal-to-noise ratio (SNR), fractional encoding is employed, i.e., the MEG duration is reduced below the wave period. Here, gradients encode primarily the velocity of the motion-reducing encoding efficiency. Thus, in GRE-MRE, T2 * decay and motion sensitivity have to be balanced, imposing a lower limit on repetition times (TRs). We propose to use a single trapezoidal gradient, a "unipolar gradient", to directly encode spin displacement. Such gradients cannot be used in conventional sequences as they exhibit a large zeroth moment and dephase magnetization. By time-reversing a spoiled SSFP sequence, the spoiling gradient becomes an efficient unipolar MEG. The proposed "unipolar MRE" technique benefits from this approach in three ways: first, displacement encoding is split over multiple TRs increasing motion sensitivity; second, spoiler and MEG coincide, allowing a reduction in TR; third, motion sensitivity of a typical unipolar lobe is of an order of magnitude higher than a bipolar MEG of equal duration. In this work, motion encoding using unipolar MRE is analyzed using the extended phase graph (EPG) formalism with a periodic motion propagator. As an approximation, the two-transverse TR approximation for diffusion-weighted SSFP is extended to incorporate cyclic motion. A complex encoding efficiency metric is introduced to compare the displacement fields of unipolar and conventional GRE-MRE sequences in both magnitude and phase. The derived theoretical encoding equations are used to characterize the proposed sequence using an extensive parameter study. Unipolar MRE is validated against conventional GRE-MRE in a phantom study showing excellent agreement between measured displacement fields. In addition, unipolar MRE yields significantly increased octahedral shear strain-SNR relative to conventional GRE-MRE and allows for the recovery of high stiffness inclusions, where conventional GRE-MRE fails

Ristretto MRE:A generalized multi-shot GRE-MRE sequence

International audienc

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

Unipolar MR elastography: Theory, numerical analysis and implementation

International audienc

A natural history study of paediatric non-alcoholic fatty liver disease over 10 years

Background & Aims: The long-term outcome of paediatric non-alcoholic fatty liver disease (NAFLD) has not been well established. Between 2008 and 2012, an unselected cohort of 133 children with severe obesity was screened for NAFLD. The aim of this study was to determine the 10-year natural history of NAFLD in this cohort. Methods: All 133 participants of the original study were approached. Proton magnetic resonance spectroscopy (1H-MRS) and the Enhanced Liver Fibrosis® (ELF) test were used to assess longitudinal changes in steatosis and fibrosis, respectively. Risk factors for disease progression were explored. Results: Fifty-one of the 133 participants (38%) from the original cohort were included. The mean follow-up time was 10.3 years (range 7–13 years), 65% were female and 92% had persistent obesity. The proportion of participants with steatosis remained unchanged (47%). Nine individuals developed steatosis and in nine individuals steatosis resolved. Predefined relevant individual changes in 1H-MRS were seen in 38% of the participants. The mean ELF test did not change significantly (8.70 ± 0.58 vs. 8.51 ± 0.71, p = 0.22). However, 16% had a relevant increase in ELF test and 6% of those with NAFLD developed advanced fibrosis at follow-up. Changes in steatosis correlated with changes in established metabolic risk factors, alanine aminotransferase, and bariatric surgery. A change in the ELF test was associated with a change in triglycerides. Conclusions: This 10-year follow-up study shows that one-third of the young adults who had childhood obesity develop steatosis and in one-third steatosis resolves. Six percent of those with NAFLD had developed advanced fibrosis at follow-up. These data underscore the importance of screening for NAFLD and monitoring for progression to advanced NAFLD in young people with obesity. Impact and implications: Childhood obesity accompanied by fat accumulation in the liver persists into young adulthood in the vast majority, and 6% develop serious liver injury. Worsening of metabolic disturbances increases the risk of liver injury

Shear wave cardiovascular MR elastography using intrinsic cardiac motion for transducer-free non-invasive evaluation of myocardial shear wave velocity

Changes in myocardial stiffness may represent a valuable biomarker for early tissue injury or adverse remodeling. In this study, we developed and validated a novel transducer-free magnetic resonance elastography (MRE) approach for quantifying myocardial biomechanics using aortic valve closure-induced shear waves. Using motion-sensitized two-dimensional pencil beams, septal shear waves were imaged at high temporal resolution. Shear wave speed was measured using time-of-flight of waves travelling between two pencil beams and corrected for geometrical biases. After validation in phantoms, results from twelve healthy volunteers and five cardiac patients (two left ventricular hypertrophy, two myocardial infarcts, and one without confirmed pathology) were obtained. Torsional shear wave speed in the phantom was 3.0 ± 0.1 m/s, corresponding with reference speeds of 2.8 ± 0.1 m/s. Geometrically-biased flexural shear wave speed was 1.9 ± 0.1 m/s, corresponding with simulation values of 2.0 m/s. Corrected septal shear wave speeds were significantly higher in patients than healthy volunteers [14.1 (11.0–15.8) m/s versus 3.6 (2.7–4.3) m/s, p = 0.001]. The interobserver 95%-limits-of-agreement in healthy volunteers were ± 1.3 m/s and interstudy 95%-limits-of-agreement − 0.7 to 1.2 m/s. In conclusion, myocardial shear wave speed can be measured using aortic valve closure-induced shear waves, with cardiac patients showing significantly higher shear wave speeds than healthy volunteers. This non-invasive measure may provide valuable insights into the pathophysiology of heart failure.ISSN:2045-232

A novel magnetic resonance elastography transducer concept based on a rotational eccentric mass: preliminary experiences with the gravitational transducer

Background. Magnetic resonance elastography (MRE) is used to non-invasively estimate biomechanical tissue properties via the imaging of propagating mechanical shear waves. Several factors including mechanical transducer design, MRI sequence design and viscoelastic reconstruction influence data quality and hence the reliability of the derived biomechanical properties. Purpose. To design and characterize a novel mechanical MRE transducer concept based on a rotational eccentric mass, coined the gravitational transducer. Materials and methods. Table top measurements were performed using accelerometers to characterize the frequency response of the new transducer concept at different driving frequencies (f VIB) and different rotating masses. These were compared to a commercially available pneumatically driven MRE transducer. MR data were acquired on a 3T scanner using a fractionally encoded gradient echo MRE sequence in three healthy volunteers. Acceleration and displacement spectra were plotted in units of g and mm, respectively, and visually compared, emphasizing the ratio between the peaks at f VIB and its 2nd harmonic, a known cause of error in the reconstruction of biomechanical properties as is explored in more detail in numerical simulations here. No formal statistical testing was performed in this proof-of-principle paper. Results. The new transducer concept shows—as expected from theory—a quadratic or linear increase of acceleration amplitude with increase in f VIB or mass, respectively. Furthermore, different versions of the transducer show markedly lower 2nd harmonic-to-f VIB ratios compared to the commercially available pneumatically driven transducer. Displacement was constant over a range of f VIB, in accordance with theory. Phantom and in vivo data show low nonlinearity and excellent data quality. Conclusion. The table top measurements are in concordance with the theory behind a transducer based on a rotational eccentric mass. The resulting constant displacement amplitude irrespective of f VIB and low 2nd harmonic-to-f VIB ratio result in low nonlinearity and high data fidelity in both phantom and in vivo examples.ISSN:1361-6560ISSN:0031-915