Evaluation of the Reproducibility of MR Elastography Measurements of the Lumbar Back Muscles.

BACKGROUND: MR elastography (MRE) may provide quantitative imaging biomarkers of lumbar back muscles (LBMs), complementing MRI in spinal diseases by assessing muscle mechanical properties. However, reproducibility analyses for MRE of LBM are lacking. PURPOSE: To assess technical failure, within-day and inter-day reproducibility, robustness with the excitation source positioning, and inter-observer agreement of MRE of muscles. STUDY TYPE: Prospective. SUBJECTS: Seventeen healthy subjects (mean age 28 ± 4 years; 11 females). FIELD STRENGTH/SEQUENCE: 1.5 T, gradient-echo MRE, T1-weighted turbo spin echo. ASSESSMENT: The pneumatic driver was centered at L3 level. Four MRE were performed during two visits, 2-4 weeks apart, each consisting of two MRE with less than 10 minutes inter-scan interval. At Visit 1, after the first MRE, the coil and driver were removed, then reinstalled. The MRE was repeated. At Visit 2, following the first MRE, only the driver was moved down 5 cm. The MRE was repeated. Two radiologists segmented the multifidus and erector spinae muscles. STATISTICAL TESTS: Paired t-test, analysis of variance, intraclass correlation coefficients (ICCs). P-values <0.05 were considered statistically significant. RESULTS: Mean stiffness of LBM ranged from 1.44 to 1.60 kPa. Mean technical failure rate was 2.5%. Inter-observer agreement was excellent (ICC ranging from 0.82 [0.64-0.96] to 0.99 [0.98-0.99] in the multifidus, and from 0.85 [0.69-0.92] to 0.99 [0.97-0.99] in the erector spinae muscles). Within-day reproducibility was fair in the multifidus (ICC: 0.53 [0.47-0.77]) and good in the erector spinae muscles (ICC: 0.74 [0.48-0.88]). Reproducibility after moving the driver was excellent in both multifidus (ICC: 0.85 [0.69-0.93]) and erector spinae muscles (ICC: 0.84 [0.67-0.92]). Inter-day reproducibility was excellent in the multifidus (ICC: 0.76 [0.48-0.89]) and poor in the erector spinae muscles (ICC: 0.23 [-0.61 to 0.63]). DATA CONCLUSION: MRE of LBM provides measurements of stiffness with fair to excellent reproducibility and excellent inter-observer agreement. However, inter-day reproducibility in the multifidus muscles indicated that the herein used MRE protocol may not be optimal for this muscle. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

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.

Automated estimation of aortic strain from steady-state free-precession and phase contrast MR images.

The strain values extracted from steady-state free-precession (SSFP) and phase contrast (PC) images acquired with a 1.5T scanner on a compliant flow phantom and within the thoracic aorta of 52 healthy subjects were compared. Aortic data were acquired perpendicular to the aorta at the level of the pulmonary artery bifurcation. Cross sectional areas were obtained by using an automatic and robust segmentation method. While a good correlation (r = 0.99) was found between the aortic areas extracted from SSFP and PC sequences, a lower correlation (r = 0.71) was found between the corresponding aortic strain values. Strain values estimated using SSFP and PC sequences were equally correlated with age. Interobserver reproducibility was better for SSFP than for PC. Strain values in the ascending and descending aorta were better correlated for SSFP (r = 0.8) than for PC (r = 0.65) and fitted with the expectation of a larger strain in the ascending aorta when using SSFP. The spatial and temporal resolutions of the acquisitions had a minor influence upon the estimated strain values. Thus, if PC acquisitions can be used to estimate both pulse wave velocity and aortic strain, an additional SSFP sequence may be useful to improve the accuracy in estimating the aortic strain.

Quantitative and Qualitative Approach for Shear Wave Elastography in Superficial Lymph Nodes.

The diagnostic contribution of 2-D shear-wave elastography (SWE) in management of superficial lymph nodes (LNs) of any origin was evaluated in 222 patients referred for needle core biopsy. Each patient underwent conventional B-mode/Doppler ultrasound examinations (conventional ultrasound) and SWE. Quantitative SWE parameters and qualitative SWE map features were extracted. Carcinomas were found to be significantly stiffer than benign LNs (29.5 ± 32.3 kPa vs. 6.7 ± 12.3 kPa). Lymphomas exhibited intermediate stiffness (11.4 ± 5.2 kPa). Qualitative SWE analysis provided color patterns specific to histopathology (stiff rim, nodular and undetermined patterns related to malignancy and blue pattern to benignity). Adding SWE to conventional ultrasound improved the sensitivity of LN diagnosis (from 81.1% to 92.0%) but decreased its specificity (from 73.2% to 67.6%) because of the high prevalence of lymphomas compared with carcinomas. Inter-observer agreement for quantitative SWE was good (intra-class correlation coefficient = 0.82) as was inter-observer diagnostic agreement for qualitative SWE (κ = 0.65). LN location and histology type were found to influence the reported diagnostic performance of SWE.

LIFEx: A Freeware for Radiomic Feature Calculation in Multimodality Imaging to Accelerate Advances in the Characterization of Tumor Heterogeneity.

Textural and shape analysis is gaining considerable interest in medical imaging, particularly to identify parameters characterizing tumor heterogeneity and to feed radiomic models. Here, we present a free, multiplatform, and easy-to-use freeware called LIFEx, which enables the calculation of conventional, histogram-based, textural, and shape features from PET, SPECT, MR, CT, and US images, or from any combination of imaging modalities. The application does not require any programming skills and was developed for medical imaging professionals. The goal is that independent and multicenter evidence of the usefulness and limitations of radiomic features for characterization of tumor heterogeneity and subsequent patient management can be gathered. Many options are offered for interactive textural index calculation and for increasing the reproducibility among centers. The software already benefits from a large user community (more than 800 registered users), and interactions within that community are part of the development strategy.Significance: This study presents a user-friendly, multi-platform freeware to extract radiomic features from PET, SPECT, MR, CT, and US images, or any combination of imaging modalities. Cancer Res; 78(16); 4786-9. ©2018 AACR.

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.

Quantification of tumor perfusion using dynamic contrast-enhanced ultrasound: impact of mathematical modeling.

Dynamic contrast-enhanced ultrasound has been proposed to monitor tumor therapy, as a complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a mouse tumor model, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated. Coefficients of variation (CV) of tissue blood volume (BV) and tissue blood flow (BF) based-parameters were estimated inside 32 sub-regions of the tumors, comparing the log-normal (LN) model with a one-compartment model fed by an arterial input function (AIF) and improved by the introduction of a time delay parameter. Relative perfusion parameters were also estimated by normalization of the LN parameters and normalization of the one-compartment parameters estimated with the AIF, using a reference tissue (RT) region. A direct estimation (rRTd) of relative parameters, based on the one-compartment model without using the AIF, was also obtained by using the kinetics inside the RT region. Results of test-retest studies show that absolute regional parameters have high CV, whatever the approach, with median values of about 30% for BV, and 40% for BF. The positive impact of normalization was established, showing a coherent estimation of relative parameters, with reduced CV (about 20% for BV and 30% for BF using the rRTd approach). These values were significantly lower (p < 0.05) than the CV of absolute parameters. The rRTd approach provided the smallest CV and should be preferred for estimating relative perfusion parameters.

Shear Wave Elastography in Thyroid Nodules with Indeterminate Cytology: Results of a Prospective Bicentric Study.

BACKGROUND: The clinical management of thyroid nodules with indeterminate cytology (IC) remains challenging. The role of shear wave elastography (SWE) in this setting is controversial. The aim of the study was to assess the performances of SWE in terms of prediction of malignancy, reproducibility, and combined analysis with ultrasound (US) examination in thyroid nodules with IC. METHODS: This prospective study was conducted in two referral centers. Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda class III-V) for which surgery had been recommended. Patients underwent a standardized US evaluation combined with a SWE exam followed by surgery. SWE parameters included mean (meanEI; kPa) and max (maxEI) elasticity values, and ratio (meanEI nodule/parenchyma). RESULTS: One hundred and thirty-one nodules (median size 30 mm) in 131 patients were studied. IC was class III in 28%, class IV in 64%, and class V in 8% of cases. After surgery, 21 (16%) nodules were malignant, including nine papillary thyroid cancers (PTC), six follicular thyroid cancers, five poorly differentiated carcinomas, and one large B-cell lymphoma. SWE parameters were similar in benign and malignant nodules, including meanEI (20.2 vs. 19.6 kPa), maxEI (34.3 vs. 32.5 kPa), and ratio (1.57 vs. 1.38). In malignant nodules, meanEI, maxEI, and ratio were higher in the classic PTC variants (n = 4) than in the other PTC variants (n = 5; p < 0.02) and in non-PTC tumors (n = 12; p < 0.005). Intra- and inter-observer coefficients of variations for meanEI in nodules were 23% and 26%, respectively. The French Thyroid Imaging Reporting and Data System score, the American Thyroid Association US classification, and the EU-Thyroid Imaging Reporting and Data System were not associated with malignancy. CONCLUSIONS: Despite high elasticity values in classic PTC variants, conventional SWE indexes failed to discriminate between benign and malignant tumors in thyroid nodules with IC.

Optimizing multicompression approaches to elasticity imaging.

Breast lesion visibility in static strain imaging ultimately is noise limited. When correlation and related techniques are applied to estimate local displacements between two echo frames recorded before and after a small deformation, target contrast increases linearly with the amount of deformation applied. However, above some deformation threshold, decorrelation noise increases more than contrast such that lesion visibility is severely reduced. Multicompression methods avoid this problem by accumulating displacements from many small deformations to provide the same net increase in lesion contrast as one large deformation but with minimal decorrelation noise. Unfortunately, multicompression approaches accumulate echo noise (electronic and sampling) with each deformation step as contrast builds so that lesion visibility can be reduced again if the applied deformation increment is too small. This paper uses signal models and analysis techniques to develop multicompression strategies that minimize strain image noise. The analysis predicts that displacement variance is minimal in elastically homogeneous media when the applied strain increment is 0.0035. Predictions are verified experimentally with gelatin phantoms. For in vivo breast imaging, a strain increment as low as 0.0015 is recommended for minimum noise because of the greater elastic heterogeneity of breast tissue.

Does motion affect liver stiffness estimates in shear wave elastography? Phantom and clinical study.

This study was undertaken to evaluate the impact of free-breathing (FB) vs. Apnea on Shear-wave elastography (SWE) measurements. Quantitative liver-stiffness measurements were obtained during FB and Apnea for 97 patients with various body-morphologies and liver textures. Quality indexes of FB and Apnea elasticity maps (percentage of non-filling (PNF), temporal (TV) and spatial (SV) variabilities) were computed. SWE measurements were also obtained from an homogeneous phantom at rest and during a mechanically-induced motion. Liver-stiffness values estimated from FB and Apnea acquisitions were correlated, particularly for homogeneous livers (r=0.76, P<0.001) and favorable body-morphologies (r=0.68, P<0.001). However FB values were consistently 20-25% lower than Apnea ones (P<0.001). FB also systematically resulted in degradation of TV (P<0.005) and PNF (P<0.001) compared to Apnea but had no impact on SV. With the phantom, no differences between SWE measurements at rest and during motion were observed. Apnea and FB measurements are highly correlated, although FB data quality is degraded compared to Apnea and estimated stiffness in FB is systematically lower than in Apnea. These discrepancies between rest and motion states were observed for patients but not for phantom data, suggesting that patient breath-holding impacts liver stiffness.

Automatic assessment of shear wave elastography quality and measurement reliability in the liver.

A strategy is proposed that accesses the quality of individual shear wave elastography (SWE) exams and the reliability of elasticity measurements in clinical practice. For that purpose, a confidence index based on temporal stability and SWE filling was defined to provide an automatic estimation of each scan quality: high (HG) or low (LG) grade. With this index, the intra-observer acquisition variability assessed by comparing consecutive scans of the same patient was 17% and 32% for HG and LG clips, respectively. The measurement quantification variability assessed by comparing the measurements of a radiologist with those of a trained operator and of two automatic measurements on a same clip averaged 13% and 22% for HG and LG exams, respectively. It was found that SWE measurements depend greatly on the quality of the acquired data. The proposed quality index (HG or LG) provides objective input on the accuracy and diagnostic reliability of SWE measurements.

Ultrasound elastography based on multiscale estimations of regularized displacement fields.

Elasticity imaging is based on the measurements of local tissue deformation. The approach to ultrasound elasticity imaging presented in this paper relies on the estimation of dense displacement fields by a coarse-to-fine minimization of an energy function that combines constraints of conservation of echo amplitude and displacement field continuity. The multiscale optimization scheme presents several characteristics aimed at improving and accelerating the convergence of the minimization process. This includes the nonregularized initialization at the coarsest resolution and the use of adaptive configuration spaces. Parameters of the energy model and optimization were adjusted using data obtained from a tissue-like phantom material. Elasticity images from normal in vivo breast tissue were subsequently obtained with these parameters. Introducing a smoothness constraint into motion field estimation helped solve ambiguities due to incoherent motion, leading to elastograms less degraded by decorrelation noise than the ones obtained from correlation-based techniques.

Gadolinium-enhanced T1-weighted renal and abdominal MR imaging: quantitative discrepancy between clinical and in vitro findings.

RATIONALE AND OBJECTIVES: This study was conducted to compare the magnetic resonance (MR) contrast medium enhancement of abdominal organs in vivo with the signal intensity (SI) values of known in vitro gadolinium solutions. MATERIALS AND METHODS: A phantom was imaged with the MR contrast medium gadodiamide (Omniscan; Nycomed, Princeton, NJ) of solutions at full-strength (0.5 mmol/mL), one-third, 1/10, and 1/100 concentrations. A fat-suppressed fast spoiled gradient-echo pulse sequence with flip angles ranging from 10 degrees to 170 degrees (at 20 degrees increments) was performed with a 1.5-T magnet. In 12 subjects, the SIs of abdominal organs were determined with identical imaging parameters, before and after administration of gadodiamide injection at 0.1 mmol/kg. RESULTS: As anticipated, the plot of SI in relation to gadodiamide concentration is nonlinear, with a decrease in SI due to T2 effects at concentrations above 0.05 mmol/mL. The kidney showed the highest SI after gadodiamide enhancement (125.2 +/- 11.6 [standard error] at 2.5 minutes), followed by the liver (76.5 +/- 11.5 at 1 minute) and spleen (57.26 +/- 9.35 at 30 seconds). The SI of the renal medulla (114.2 +/- 9.8 at 4.5 minutes) was approximately one-third that in phantom observations. CONCLUSION: The authors observed a marked discrepancy between empirical contrast medium performance in abdominal organs and SI values for comparable gadodiamide concentrations in vitro. One possible reason is the intracellular compartmentalization of water molecules in vivo. These results suggest a need for a better understanding of MR contrast medium performance in vivo.

Thyroid gland tumor diagnosis at US elastography.

PURPOSE: To prospectively evaluate the elastographic appearance of thyroid gland tumors and explore the potential sensitivity and specificity of ultrasonographic (US) elastography for differentiating benign and malignant tumors, with histopathologic analysis as the reference standard. MATERIALS AND METHODS: The study was institutional review board approved, and each patient gave written informed consent. Fifty-two thyroid gland lesions (22 malignant, 30 benign) in 31 consecutive patients (six men, 25 women; mean age, 49.7 years +/- 14.7 [standard deviation]) were examined with real-time elastography in the elasticity imaging mode implemented on a clinical US scanner modified for research. In addition, the radiofrequency echo data stored during US were exported from the scanner and used for off-line strain image reconstruction. All elastograms were evaluated for the lesion visibility, relative brightness, and margin regularity and definition by using a four-point scale. In addition, normal thyroid gland tissue and thyroid gland tumor strains were measured on off-line processed elastograms, and the thyroid gland-to-tumor strain ratio (ie, strain index) was calculated. The potential of elastographic criteria for the diagnosis of thyroid gland cancer was evaluated with univariate analysis and multivariate logistic regression. Qualitative variables were compared by using the chi2 test, and quantitative variables were compared by using the Mann-Whitney U test. P < .05 was considered to indicate significance. RESULTS: A strain index value greater than 4 on off-line processed elastograms was the strongest independent predictor of thyroid gland malignancy (P < .001); this criterion had 96% specificity and 82% sensitivity. Two other elastographic criteria, which were evaluated on real-time elastograms--a margin regularity score higher than 3 (88% specificity, 36% sensitivity) and a tumor area ratio higher than 1 (92% specificity, 46% sensitivity)--also were associated with malignancy (P < .05). However, the usefulness of these criteria was not considered to be high because of their low sensitivity. CONCLUSION: Elastography is a promising imaging technique that can assist in the differential diagnosis of thyroid cancer.

Viscoelastic imaging of breast tumor microenvironment with ultrasound.

Imaging systems are most effective for detection and classification when they exploit contrast mechanisms specific to particular disease processes. A common example is mammography, where the contrast depends on local changes in cell density and the presence of microcalcifications. Unfortunately the specificity for classifying malignant breast disease is relatively low for many current diagnostic techniques. This paper describes a new ultrasonic technique for imaging the viscoelastic properties of breast tissue. The mechanical properties of glandular breast tissue, like most biopolymers, react to mechanical stimuli in a manner specific to the microenvironment of the tissue. Elastic properties allow noninvasive imaging of desmoplasia while viscous properties describe metabolism-dependent features such as pH. These ultrasonic methods are providing new tools for studying disease mechanisms as well as improving diagnosis.