Visco-Elastic Parameters at Three-Dimensional MR Elastography for Diagnosing Non-Alcoholic Steatohepatitis and Substantial Fibrosis in Mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is a growing cause of liver cirrhosis and cancer. The performance of the magnetic resonance elastography (MRE) visco-elastic parameters in diagnosing progressive forms of NAFLD, including nonalcoholic steatohepatitis (NASH) and substantial fibrosis (F ≥ 2), needs to be clarified. PURPOSE: To assess the value of three-dimensional MRE visco-elastic parameters as markers of NASH and substantial fibrosis in mice with NAFLD. STUDY TYPE: Prospective. ANIMAL MODEL: Two mouse models of NAFLD were induced by feeding with high fat diet or high fat, choline-deficient, amino acid-defined diet. FIELD STRENGTH/SEQUENCE: 7T/multi-slice multi-echo spin-echo MRE at 400 Hz with motion encoding in the three spatial directions. ASSESSMENT: Hepatic storage and loss moduli were calculated. Histological analysis was based on the NASH Clinical Research Network criteria. STATISTICAL TESTS: Mann-Whitney, Kruskal-Wallis tests, Spearman rank correlations and multiple regressions were used. Diagnostic performance was assessed with areas under the receiver operating characteristic curves (AUCs). P value <0.05 was considered significant. RESULTS: Among the 59 mice with NAFLD, 21 had NASH and 20 had substantial fibrosis (including 8 mice without and 12 mice with NASH). The storage and loss moduli had similar moderate accuracy for diagnosing NASH with AUCs of 0.67 and 0.66, respectively. For diagnosing substantial fibrosis, the AUC of the storage modulus was 0.73 and the AUC of the loss modulus was 0.81, indicating good diagnostic performance. Using Spearman correlations, histological fibrosis, inflammation and steatosis, but not ballooning, were significantly correlated with the visco-elastic parameters. Using multiple regression, fibrosis was the only histological feature independently associated with the visco-elastic parameters. CONCLUSION: MRE in mice with NAFLD suggests that the storage and loss moduli have good diagnostic performance for detecting progressive NAFLD defined as substantial fibrosis rather than NASH. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

Comparative Analysis of a Locally Resampling MR Elastography Reconstruction Algorithm in Liver Fibrosis.

BACKGROUND: In magnetic resonance elastography (MRE), the precision of the observed mechanical depends on the ratio between mechanical wavelength and spatial resolution. Since the mechanical wavelength may vary with actuation frequency, between patients and depending on position, a unique spatial resolution may not always generate an optimal ratio for multifrequency acquisitions, in patients with varying degrees of disease or in mechanically heterogeneous organs. PURPOSE: To describe an MRE reconstruction algorithm that adjusts the ratio between shear wavelength and pixel size, by locally resampling the matrix of shear displacement, and to assess its performance relative to existing reconstructions in different use cases. STUDY TYPE: Prospective. POPULATION: Four phantoms, 20 healthy volunteers (5 men, median age 34, range 20-56) and 46 patients with nonalcoholic fatty liver disease (37 men, median age 63, range 33-83). FIELD STRENGTH/SEQUENCE: A 3 T; gradient-echo elastography sequence with 40 Hz, 60 Hz, and 80 Hz frequencies. ASSESSMENT: For each algorithm, phantoms stiffness were compared against their nominal values, repeatability was calculated in healthy volunteers, and diagnostic performance in detecting advanced liver fibrosis was assessed in 46 patients. STATISTICAL TESTS: Linear regression was used to evaluate the agreement between stiffness values and phantoms stiffnesses. Bland-Altman method was used to evaluate repeatability in volunteers. The ability to diagnose advanced fibrosis was assessed by receiver operating curve analysis (with Youden index thresholds). Significance was considered at P value of 0.05. RESULTS: From the linear regression, the slope closest to 1 is provided by MARS (40 Hz) and k-MDEV (60H, 80 Hz). Repeatability index was best with MDEV (23%) and lowest with k-MDEV (53%). The best performance in detecting advanced fibrosis was provided by MARS at 40 Hz (area under the operating curve, AUC = 0.88), k-MDEV and MARS at 60 Hz (AUC = 0.91), and multimodel direct inversion (MMDI) and MARS at 80 Hz (AUC = 0.90). DATA CONCLUSION: MARS shows the best diagnostic performance to detect advanced fibrosis and the second-best results in phantoms after k-MDEV. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Multifrequency magnetic resonance elastography for elasticity quantitation and optimal tissue discrimination: A two-platform liver fibrosis mimicking phantom study.

In the framework of algebraic inversion, magnetic resonance elastography (MRE) repeatability, reproducibility and robustness were evaluated on extracted shear velocities (or elastic moduli). The same excitation system was implemented at two sites equipped with clinical MR scanners of 1.5 and 3 T. A set of four elastic, isotropic, homogeneous calibrated phantoms of distinct elasticity representing the spectrum of liver fibrosis severity was mechanically characterized. The repeatability of the measurements and the reproducibility between the two platforms were found to be excellent with mean coefficients of variations of 1.62% for the shear velocity mean values and 1.95% for the associated standard deviations. MRE velocities were robust to the amplitude and pattern variations of the displacement field with virtually no difference between outcomes from both magnets at identical excitation frequencies, even when the displacement field amplitude was six times smaller. However, MRE outcomes were very sensitive to the number of voxels per wavelength, s, of the recorded displacement field, with relative biases reaching 62% and precision loss by a factor of up to 23.5. For both magnetic field strengths, MRE accuracy and precision were largely degraded outside of established conditions of validity (6 ≲ s ≲ 9), resulting in estimated shear velocity values not significantly different between phantoms of increasing elasticity. When fulfilling the spatial sampling conditions, either prospectively in the acquisition or retrospectively before the reconstruction, MRE produced quantitative measurements that allowed to unambiguously discriminate, with infinitesimal p values, between the phantoms mimicking increasing severity of liver fibrosis.

Quantitative Gd-DOTA-based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE-MRI.

Asthma is a chronic respiratory disease, commonly treated with inhaled therapy. Better understanding of the mechanisms of aerosol deposition is required to improve inhaled drug delivery. Three-dimensional ultrashort echo time (UTE) MRI acquisitions at 1.5 T were combined with spontaneous nose-only inhalation of aerosolized gadolinium (Gd) to map the aerosol deposition and to characterize signal enhancement in asthmatic rat lungs. The rats were sensitized to ovalbumin (OVA) to develop asthmatic models and challenged before imaging by nebulization of OVA to trigger asthmatic symptoms. The negative controls were not sensitized or challenged by nebulization of saline. The animal lungs were imaged before and after administration of Gd-based aerosol in freely breathing rats, by using a T1 -weighted 3D UTE sequence. A contrast-enhanced quantitative analysis was performed to assess regional concentration. OVA-sensitized rats had lower signal enhancement and lower deposited aerosol concentration. Their enhancement dynamics showed large inter-subject variability. The signal intensity was homogeneously enhanced for controls while OVA-sensitized rats showed heterogeneous enhancement. Contrast-enhanced 3D UTE was applied with aerosolized Gd to efficiently measure spatially resolved deposition in asthmatic lungs. The small administered dose (around 1 µmol/kg body weight) and the use of standard clinical MRI suggest a potential application for the exploration of asthma.

Acquisition and reconstruction conditions in silico for accurate and precise magnetic resonance elastography.

Magnetic resonance elastography (MRE) is a non invasive imaging modality, which holds the promise of absolute quantification of the mechanical properties of human tissues in vivo. MRE reconstruction with algebraic inversion of the Helmholtz equation upon the curl of the shear displacement field may theoretically be flawless. However, its performances are challenged by multiple experimental parameters, especially the frequency and the amplitude of the mechanical wave, the voxel size and the signal-to-noise ratio of the MRE acquisition. A point source excitation was simulated and realistic displacement fields were analytically computed to simulate MRE data sets in an isotropic, homogeneous, linearly-elastic, and half-space infinite medium. Acquisition and reconstruction methods were challenged and the joint influence of the aforementioned parameters was studied. For a given signal-to-noise ratio, the conditions on the number of voxels per wavelength were determined for optimizing voxel-wise accuracy and precision in MRE. It was shown that, once data are acquired, the reconstruction quality could even be improved by effective interpolation or decimation so data could eventually fulfill favorable conditions for mechanical characterization of the tissue. Finally, the overall outcome, which is usually computed from the three acquired motion-encoded directions, may further be improved by appropriate averaging strategies that are based on adapted curl of shear displacement field quality-weighting.

Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones.

1-phenyl-3-methyl-4-benzoyl-5-pyrazolone 4-ethyl-thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C2H5OH·(1), [Cu(L)2]·H2O (2), [Cu(L)(Br)]·H2O·CH3OH (3), [Cu(L)(NO3)]·2C2H5OH (4), [VO2(L)]·2H2O (5), [Ni(L)2]·H2O (6), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, (1) H NMR and (13) C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico-chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) (2, 4), and vanadium(V) (5) complexes have been determined by single-crystal X-ray diffraction. The composition of the coordination polyhedron of the central atom in 2, 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4, it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL-60 cells was tested.