Comparison of ultrasound elastography, magnetic resonance elastography and finite element model to quantify nonlinear shear modulus.

Objective. The aim of this study is to validate the estimation of the nonlinear shear modulus (A) from the acoustoelasticity theory with two experimental methods, ultrasound (US) elastography and magnetic resonance elastography (MRE), and a finite element method.Approach. Experiments were performed on agar (2%)-gelatin (8%) phantom considered as homogeneous, elastic and isotropic. Two specific setups were built to ensure a uniaxial stress step by step on the phantom, one for US and a nonmagnetic version for MRE. The stress was controlled identically in both imaging techniques, with a water tank placed on the top of the phantom and filled with increasing masses of water during the experiment. In US, the supersonic shear wave elastography was implemented on an ultrafast US device, driving a 6 MHz linear array to measure shear wave speed. In MRE, a gradient-echo sequence was used in which the three spatial directions of a 40 Hz continuous wave displacement generated with an external driver were encoded successively. Numerically, a finite element method was developed to simulate the propagation of the shear wave in a uniaxially stressed soft medium.Main results. Similar shear moduli were estimated at zero stress using experimental methods,µ0US= 12.3 ± 0.3 kPa andµ0MRE= 11.5 ± 0.7 kPa. Numerical simulations were set with a shear modulus of 12 kPa and the resulting nonlinear shear modulus was found to be -58.1 ± 0.7 kPa. A very good agreement between the finite element model and the experimental models (AUS= -58.9 ± 9.9 kPa andAMRE= -52.8 ± 6.5 kPa) was obtained.Significance. These results show the validity of such nonlinear shear modulus measurement quantification in shear wave elastography. This work paves the way to develop nonlinear elastography technique to get a new biomarker for medical diagnosis.

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.

Necro-inflammatory activity grading in chronic viral hepatitis with three-dimensional multifrequency MR elastography.

The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71-0.93) vs. storage modulus AUC: 0.65 (0.50-0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79-0.98)] and cirrhosis F4 [0.97 (0.88-1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis.

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.

Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice.

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.

MRI Mapping of Renal T1: Basic Concept.

In renal MRI, measurement of the T1 relaxation time of water molecules may provide a valuable biomarker for a variety of pathological conditions. Due to its sensitivity to the tissue microenvironment, T1 has gained substantial interest for noninvasive imaging of renal pathology, including inflammation and fibrosis. In this chapter, we will discuss the basic concept of T1 mapping and different T1 measurement techniques and we will provide an overview of emerging preclinical applications of T1 for imaging of kidney disease.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Experimental Protocols for MRI Mapping of Renal T1.

The water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Analysis Protocols for MRI Mapping of Renal T1.

The computation of T1 maps from MR datasets represents an important step toward the precise characterization of kidney disease models in small animals. Here the main strategies to analyze renal T1 mapping datasets derived from small rodents are presented. Suggestions are provided with respect to essential software requirements, and advice is provided as to how dataset completeness and quality may be evaluated. The various fitting models applicable to T1 mapping are presented and discussed. Finally, some methods are proposed for validating the obtained results.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Assessing Tumor Mechanics by MR Elastography at Different Strain Levels.

BACKGROUND: Malignant tumors are associated with increased tissue rigidity, which can be an indicator of tumor progression. MR elastography (MRE) has the potential to study the variations of tumor mechanical properties. ex vivo studies have shown the ability of MRE to assess increase of mechanical properties; nevertheless, it has not yet been observed in vivo. PURPOSE: To propose a method to assess the increase in mechanical properties of tumors in vivo under static external compression using MRE. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Forty-six SCID mice with subcutaneous tumor implantation (patient-derived hepatocellular carcinoma xenografts, Model 1, n = 13, and Model 2, n = 33). FIELD STRENGTH/SEQUENCE: 7.0T; a spin echo sequence was used for anatomical images and a modified spin echo sequence for elastography acquisitions with a vibration frequency of 600 Hz. ASSESSMENT: An inflatable balloon was placed on the abdomen to apply a load to the tumor. MRE acquisitions were performed at the basal state and at increasing compression levels. Anatomical images were used to calculate the octahedral shear strain between the tumor at the basal strain state and each strain level. For six mice (Model 2), each static preloading scan was acquired twice consecutively without moving the mouse to evaluate repeatability. Statistical Tests: The Bland-Altman method was used to assess repeatability. Correlations between tumor stiffness and deformation were evaluated with Pearson correlation coefficients. RESULTS: For stiffness (G*), a good repeatability was obtained between the acquisitions; the limits of agreement of the Bland-Altman test were [-10.17%; 11.49%] with an absolute bias of 0.66%. A significant correlation between tumor stiffness and deformation was observed for both models (Model 1: r = 0.57, P < 0.0001 and Model 2: r = 0.31, P < 0.0001). DATA CONCLUSION: We establish that tumor mechanical properties can increase under mechanical compression. This increase can effectively be monitored using a proposed MRE setup. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1982-1989.

Obesity-induced pancreatopathy in rats is reversible after bariatric surgery.

Obesity is a risk factor for pancreatic diseases. Bariatric surgery is one of the most efficient treatments of morbid obesity. The aims were to assess pancreatic endocrine and exocrine lesions in obese rats, to analyze effects of bariatric surgery. Sixty-three male Wistar rats were included in five groups: 2 fed with high fat diet (HFD) or normal diet for 3 months, 2 fed with HFD or normal diet for 6 months; 1 group fed with HFD and undergoing bariatric surgery (n = 30). Quantitative MR imaging was performed in HFD6, ND6 and HFD3-BS. Pancreas specimens were analyzed after sacrifice for adipocyte infiltration, fibrosis, acinar-ductal metaplasia, abnormality of Langerhans islets (HHF: hypertrophy, hypervascularisation, fibrosis), and hemosiderin deposits in acinar or endocrine locations. We found that HFD6 rats had more fibro-inflammatory islets (P = 0.0139) and acinar-ducal metaplasia (P = 0.0843) than HFD3 rats. Rats with HFD3+6 had more fibro-inflammatory islets (P < 0.0001), hemosiderin deposits (p < 0.0001), fat infiltration (P = 0.0008) and acinar-ductal metaplasia lesions (P = 0.0424). Weight increase was associated with glycoregulation abnormalities (r = 0.44, P = 0.08) and adipocyte infiltrations (P = 0.009). After surgery, less fibro-inflammatory islets (P = 0.0004), fat and iron infiltrates (P = 0.005 and P = 0.06), and acino-ductal metaplasia (P = 0.05) were observed compared to HFD6 rats. MR image quantifications revealed increased elasticity, fat fraction, and R2 and a decreased elasticity wave dispersion coefficient in the high fat groups that reversed after surgery. MRI parameters were in strong correlation with respective histological counterparts. In conclusion, obese rats develop pancreatic inflammatory lesions with acinar-ductal metaplasia in acinar location and the endocrine-exocrine interface. These changes can be prevented by bariatric surgery. Quantitative MR imaging is accurate in identifying early pancreatic lesions.

Quantitative assessment of the flow distribution in the branches of the external carotid by non-injected flow MRI.

Owing to the lack of databases of blood flow distributions in the external carotid branches, surgeons currently rely on per-operative imaging and on their experience to choose the recipient vessels for microsurgical facial reconstructions. But, thanks to three-dimensional phase contrast angiography (PCA) and kinematic CINE phase contrast (PC) sequences, MRI technologies have the potential to provide quantitative anatomical and hemodynamic information without injection of contrast agent. Having developed and optimized PC-MRI sequences for the small facial vessels, our objective was to investigate the haemodynamic and blood flow distribution in the external carotid branches. We included 31 healthy volunteers in an MRI prospective study. Two-dimensional CINE PC-MRI sequences (average duration time of 2 min 40 s ± 24 s) were performed in the external carotid collaterals (n = 290). A statistical analysis of the flow measurements showed that, despite large interpersonal variabilities, a general flow distribution pattern was obtained by dividing the vessel flow rates by the external carotid artery one (providing local percentages of the incoming flow). The vessels could then be classified in three haemodynamic groups (p < 0.05 Student's test): "low flow" group (lingual artery-12.5 ± 5% of incoming flow), "intermediate flow" group (superior thyroid artery-16.5 ± 10%, internal maxillary artery-20.5 ± 11%, superficial temporal artery-18.4 ± 6%), "high flow" group (facial artery -26.6 ± 10%). Thanks to this general flow distribution mapping, it is now possible to estimate the flow rates in the distal branches of any individual from a single blood flow measurement in the external carotid artery.

Influence of principal component analysis acceleration factor on velocity measurement in 2D and 4D PC-MRI.

OBJECTIVE: The objective of the study was to determine how to optimize 2D and 4D phase-contrast magnetic resonance imaging (PC-MRI) acquisitions to acquire flow velocities in millimetric vessels. In particular, we search for the best compromise between acquisition time and accuracy and assess the influence of the principal component analysis (PCA). MATERIALS AND METHODS: 2D and 4D PC-MRI measurements are conducted within two in vitro vessel phantoms: a Y-bifurcation phantom, the branches of which range from 2 to 5 mm in diameter, and a physiological subject-specific phantom of the carotid bifurcation. The same sequences are applied in vivo in carotid vasculature. RESULTS: For a vessel oriented in the axial direction, both 2D and axial 4D PC-MRI provided accuracy measurements regardless of the k-t PCA factor, while the acquisition time is reduced by a factor 6 for k-t PCA maximum value. The in vivo measurements show that the proposed sequences are adequate to acquire 2D and 4D velocity fields in millimetric vessels and with clinically realistic time durations. CONCLUSION: The study shows the feasibility of conducting fast, high-resolution PC-MRI flow measurements in millimetric vessels and that it is worth maximizing the k-t PCA factor to reduce the acquisition time in the case of 2D and 4D axial acquisitions.

3T non-injected phase-contrast MRI sequences for the mapping of the external carotid branches: In vivo radio-anatomical pilot study for feasibility analysis.

An essential stage in head and neck microsurgical reconstruction is the choice of recipient vessels. To make relevant choices, surgeons must rely on accurate imaging techniques. The objective of the study was to examine the feasibility of Phase-Contrast sequences to conduct the pre-operative tests without injection and provide precise radio-anatomical data over the entire vessel region. The challenges were the large velocity range, the lack of contrast, and the large spatial resolution needed to image vessels below 5 mm in diameter. Thirty-one healthy volunteers were included in an MRI prospective study. The anatomical and morphometrical characteristics of the collaterals of the external carotid artery were determined associating 3D PCA and 2D Cine MRI-PC sequences (average protocole duration time of 49 min ± 4 min). The average diameter was measured to be 2.1 ± 1.4 mm for the superior thyroid artery, 2.2 ± 1.1 mm for the lingual artery, 2.7 ± 1.6 mm for the facial artery, 2.6 ± 1.4 mm for the internal maxillary artery, and 2 ± 1.4 mm for the superficial temporal artery. With a vessel identification success rate of 98%, the study showed for the first time that Phase Contrast MRI allowed non-invasive and non-operator dependent anatomical analyses of small caliber vessels without the use of agent contrast. It also proved that the designed sequences could be used on patients and provided valuable pre-operative information for head and neck surgery.