Comparison of inversion methods in MR elastography: An open-access pipeline for processing multifrequency shear-wave data and demonstration in a phantom, human kidneys, and brain.

PURPOSE: Magnetic resonance elastography (MRE) maps the viscoelastic properties of soft tissues for diagnostic purposes. However, different MRE inversion methods yield different results, which hinder comparison of values, standardization, and establishment of quantitative MRE markers. Here, we introduce an expandable, open-access, webserver-based platform that offers multiple inversion techniques for multifrequency, 3D MRE data. METHODS: The platform comprises a data repository and standard MRE inversion methods including local frequency estimation (LFE), direct-inversion based multifrequency dual elasto-visco (MDEV) inversion, and wavenumber-based (k-) MDEV. The use of the platform is demonstrated in phantom data and in vivo multifrequency MRE data of the kidneys and brains of healthy volunteers. RESULTS: Detailed maps of stiffness were generated by all inversion methods showing similar detail of anatomy. Specifically, the inner renal cortex had higher shear wave speed (SWS) than renal medulla and outer cortex without lateral differences. k-MDEV yielded higher SWS values than MDEV or LFE (full kidney/brain k-MDEV: 2.71 ± 0.19/1.45 ± 0.14 m/s, MDEV: 2.14 ± 0.16/0.99 ± 0.11 m/s, LFE: 2.12 ± 0.15/0.89 ± 0.06 m/s). CONCLUSION: The freely accessible platform supports the comparison of MRE results obtained with different inversion methods, filter thresholds, or excitation frequencies, promoting reproducibility in MRE across community-developed methods.

Validation of cardiac diffusion tensor imaging sequences: A multicentre test-retest phantom study.

Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish the accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI among 10 centres internationally. Phantoms comprising 0%-20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N = 10 sites) sequence, and a custom motion-compensated spin echo (SE; N = 5) or stimulated echo acquisition mode (STEAM; N = 5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1-9 days later, and the data were analysed centrally. The average mean diffusivities (MDs) in 0% PVP were (1.124, 1.130, 1.113) x 10-3  mm2 /s for PGSE, SE and STEAM, respectively, and accurate to within 1.5% of reference data from the literature. The coefficients of variation in MDs across sites were 2.6%, 3.1% and 2.1% for PGSE, SE and STEAM, respectively, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) x 10-5  mm2 /s (mean ± 1.96 SD). We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.

Simultaneous multislice rapid magnetic resonance elastography of the liver.

To design and validate a rapid Simultaneous Multi-slice (SMS) Magnetic Resonance Elastography technique (MRE), which combines SMS acquisition, in-plane undersampling and an existing rapid Magnetic Resonance Elastography (MREr) scheme to allow accelerated data acquisition in healthy volunteers and comparison against MREr. SMS-MREr sequence was developed by incorporating SMS acquisition scheme into an existing MREr sequence that accelerates MRE acquisition by acquiring data during opposite phases of mechanical vibrations. The MREr sequence accelerated MRE acquisition by acquiring data during opposite phases of mechanical vibrations. Liver MRE was performed on 23 healthy subjects using MREr and SMS-MREr sequences, and mean stiffness values were obtained for manually drawn regions of interest. Linear correlation and agreement between MREr- and SMS-MREr-based stiffness values were investigated. SMS-MREr reduced the scan time by half relative to MREr, and allowed acquisition of four-slice MRE data in a single 17-second breath-hold. Visual comparison suggested agreement between MREr and SMS-MREr elastograms. A Pearson's correlation of 0.93 was observed between stiffness values derived from MREr and SMS-MREr. Bland-Altman analysis demonstrated good agreement, with -0.08 kPa mean bias and narrow limits of agreement (95% CI: 0.23 to -0.39 kPa) between stiffness values obtained using MREr and SMS-MREr. SMS can be combined with other fast MRE approaches to achieve further acceleration. This pushes the limit on the acceleration that can be achieved in MRE acquisition, and makes it possible to conduct liver MRE exams in a single breath-hold.

Magnetic resonance elastography-derived stiffness of the kidneys and its correlation with water perfusion.

Stiffness plays an important role in diagnosing renal fibrosis. However, kidney stiffness is altered by perfusion changes in many kidney diseases. Therefore, the aim of the current study is to determine the correlation of kidney stiffness with water intake. We hypothesize that kidney stiffness will increase with 1 L of water intake due to increased water perfusion to the kidneys. Additionally, stiffness of the kidneys will correlate with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values before and after water intake. A 3 T MRI scanner was used to perform magnetic resonance elastography and diffusion tensor imaging of the kidneys on 24 healthy subjects (age range: 22-66 years) before and after water intake of 1 L. A 3D T1-weighted bladder scan was also performed to measure bladder volume before and after water intake. A paired t-test was performed to evaluate the effect of water intake on the stiffness of kidneys, in addition to bladder volume. A Spearman correlation test was performed to determine the association between stiffness, bladder volume, ADC and FA values of both kidneys before and after water intake. The results show a significant increase in stiffness in different regions of the kidney (ie, percentage increase ranged from 3.6% to 7.5%) and bladder volume after water intake (all P < 0.05). A moderate significant negative correlation was observed between change in kidney stiffness and bladder volume (concordance correlation coefficient = -0.468, P < 0.05). No significant correlation was observed between stiffness and ADC or FA values before and after water intake in both kidneys (P > 0.05). Water intake caused a significant increase in the stiffness of the kidneys. The negative correlation between the change in kidney stiffness and bladder volume, before and after water intake, indicates higher perfusion pressure in the kidneys, leading to increased stiffness.

Magnetic Resonance Elastography of kidneys: SE-EPI MRE reproducibility and its comparison to GRE MRE.

The purpose of this study is 1) to demonstrate reproducibility of spin echo-echo planar imaging (SE-EPI) magnetic resonance elastography (MRE) to estimate kidney stiffness; and 2) to compare SE-EPI MRE and gradient recalled echo (GRE) MRE-derived stiffness estimations in various anatomical regions of the kidney. Kidney MRE was performed on 33 healthy subjects (8 for SE-EPI MRE reproducibility and 25 for comparison with GRE MRE; age range: 22-66 years) in a 3 T MRI scanner. To demonstrate SE-EPI MRE reproducibility, subjects were scanned for the first scan and then asked to leave the scan room and repositioned again for the second (repeat) scan. Similar set-up was used for GRE MRE as well. The displacement data was then processed to obtain overall stiffness estimates of the kidney. Concordance correlation analyses were performed to determine SE-EPI MRE reproducibility and agreement between GRE MRE and SE-EPI MRE derived stiffness. A high concordance correlation (ρc  = 0.95; p-value<0.0001) was obtained for SE-EPI MRE reproducibility. Good concordance correlation was observed (ρc  = 0.84; p < 0.0001 for both kidneys, ρc  = 0.91; p < 0.0001 for right kidney and ρc  = 0.78; p < 0.0001 for left kidney) between GRE MRE and SE-EPI MRE derived stiffness measurements. Paired t-test results showed that stiffness value of medulla was significantly (p < 0.0001) greater than cortex using SE-EPI MRE as well as GRE MRE. SE-EPI MRE was reproducible and good agreement was observed in MRE-derived stiffness measurements obtained using SE-EPI and GRE sequences. Therefore, SE-EPI can be used for kidney MRE applications.

Magnetic resonance elastography of brain: Comparison between anisotropic and isotropic stiffness and its correlation to age.

PURPOSE: Noninvasive measurement of mechanical properties of brain tissue using magnetic resonance elastography (MRE) has been a promising method for investigating neurologic disorders such as multiple sclerosis, hydrocephalus, and Alzheimer's. However, because of the regional and directional dependency of brain stiffness, estimating anisotropic stiffness is important. This study investigates isotropic and anisotropic stiffness as a function of age as well as the correlation between isotropic and anisotropic stiffness. METHODS: MRE and diffusion tensor imaging (DTI) were performed on 28 healthy subjects with age ranges between 18-62 y. Isotropic and anisotropic stiffness was measured and compared with age for different regions of interest such as the thalamus, corpus callosum, gray matter, white matter, and whole brain. RESULTS: Isotropic stiffness in gray matter (rs = -0.57; P = 0.001) showed a significant decrease with age. Anisotropic stiffness in gray matter showed a significant decrease with age in C11 through C66 and in the thalamus, only in C33 . Between anisotropic and isotropic stiffness, gray matter showed a significant positive correlation in C11 through C66 , C22 and C66 showed a significant negative correlation in the thalamus and whole brain, and C44 showed a negative correlation in the corpus callosum. No significant difference between genders was observed in any measurements. CONCLUSION: This study demonstrated a change in isotropic and anisotropic stiffness with age in different regions of the brain along with a correlation of anisotropic stiffness to isotropic stiffness.

Magnetic resonance elastography to estimate brain stiffness: Measurement reproducibility and its estimate in pseudotumor cerebri patients.

This study determines the reproducibility of magnetic resonance elastography (MRE) derived brain stiffness in normal volunteers and compares it against pseudotumor patients before and after lumbar puncture (LP). MRE was performed on 10 normal volunteers for reproducibility and 14 pseudotumor patients before and after LP. During LP, opening and closing cerebrospinal fluid (CSF) pressures were recorded before and after removal of CSF and correlated to brain stiffness. Stiffness reproducibility was observed (r > 0.78; p < 0.008). Whole brain opening LP stiffness was significantly (p = 0.04) higher than normals, but no significant difference (p = 0.11) in closing LP measurements. No significant correlation was observed between opening and closing pressure and brain stiffness.

MR Elastography-derived Stiffness: A Biomarker for Intervertebral Disc Degeneration.

Purpose To determine the repeatability of magnetic resonance (MR) elastography-derived shear stiffness measurements of the intervertebral disc (IVD) taken throughout the day and their relationship with IVD degeneration and subject age. Materials and Methods In a cross-sectional study, in vivo lumbar MR elastography was performed once in the morning and once in the afternoon in 47 subjects without current low back pain (IVDs = 230; age range, 20-71 years) after obtaining written consent under approval of the institutional review board. The Pfirrmann degeneration grade and MR elastography-derived shear stiffness of the nucleus pulposus and annulus fibrosus regions of all lumbar IVDs were assessed by means of principal frequency analysis. One-way analysis of variance, paired t tests, concordance and Bland-Altman tests, and Pearson correlations were used to evaluate degeneration, diurnal changes, repeatability, and age effects, respectively. Results There were no significant differences between morning and afternoon shear stiffness across all levels and there was very good technical repeatability between the morning and afternoon imaging results for both nucleus pulposus (R = 0.92) and annulus fibrosus (R = 0.83) regions. There was a significant increase in both nucleus pulposus and annulus fibrosus MR elastography-derived shear stiffness with increasing Pfirrmann degeneration grade (nucleus pulposus grade 1, 12.5 kPa ± 1.3; grade 5, 16.5 kPa ± 2.1; annulus fibrosus grade 1, 90.4 kPa ± 9.3; grade 5, 120.1 kPa ± 15.4), and there were weak correlations between shear stiffness and age across all levels (R ≤ 0.32). Conclusion Our results demonstrate that MR elastography-derived shear stiffness measurements are highly repeatable, weakly correlate with age, and increase with advancing IVD degeneration. These results suggest that MR elastography-derived shear stiffness may provide an objective biomarker of the IVD degeneration process. © RSNA, 2017 Online supplemental material is available for this article.

Quantification of breast stiffness using MR elastography at 3 Tesla with a soft sternal driver: A reproducibility study.

PURPOSE: Previous studies of breast MR elastography (MRE) evaluated the technique at magnetic field strengths of 1.5 Tesla (T) with the breast in contact with the driver. The aim of this study is to evaluate breast stiffness measurements and their reproducibility using a soft sternal driver at 3T and compare the results with qualitative measures of breast density. MATERIALS AND METHODS: Twenty-two healthy volunteers each underwent two separate breast MRE scans in a 3T MRI. MRE vibrations were introduced into the breasts at 60 Hz using a soft sternal driver and axial slices were collected using a gradient echo MRE sequence. Mean stiffness measurements were calculated for each volunteer as well as a measure of reproducibility using concordance correlation between scans. Mean stiffness values for each volunteer were assessed and related to amounts of fibroglandular tissue (i.e., breast lobules, ducts, and fibrous connective tissue). RESULTS: The stiffness values were reproducible with a significant P-value < 0.0001 between two scans with concordance correlation of 0.87 and 0.91 for center slice and grouping all slices, respectively. Volunteers with dense breasts (i.e., higher grades of fibroglandular tissue) had mean stiffness values of 0.96 kPa (center slice) and 0.92 kPa (all slices) while those without dense breasts had mean stiffness values of 0.85 kPa (center slice) and 0.83 kPa (all slices) (P ≤ 0.05). CONCLUSION: Breast MRE is a reproducible technique at 3T using a soft sternal driver. Dense breasts had significantly higher stiffness measurements compared with nondense breasts. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1379-1384.

Quantification and comparison of 4D-flow MRI-derived wall shear stress and MRE-derived wall stiffness of the abdominal aorta.

PURPOSE: Aortic wall shear stress (WSSFlow ) alters endothelial function, which in-turn changes aortic wall stiffness leading to remodeling in different disease states. Therefore, the aims of this study are to determine normal physiologic correlations between: (1) Magnetic Resonance Elastography (MRE)-derived aortic wall stiffness (WSMRE ) and WSSFlow ; (2) WSMRE and mean velocity; (3) WSMRE and pulse wave velocity (PWV);( 4) WSMRE and mean peak flow; and (5) WSMRE , WSSFlow and age using MRE and 4D-flow MRI in the abdominal aorta in healthy human subjects. MATERIALS AND METHODS: Cardiac-gated aortic MRE and 4D-flow MRI data were acquired in 24 healthy volunteers using a 3 Tesla scanner. For MRE, 70 Hz external motion was applied to obtain wave images in all spatial directions in a separate breathhold. Whereas, 4D-flow data was acquired under free-breathing. Wave images in all the directions were processed to obtain three-dimensional-weighted stiffness map at end-systole (ES). WSSFlow , mean velocity, PWV and mean peak flow were obtained using 4D-flow data. Pearson correlation was performed to determine association between all variables. RESULTS: A significant negative correlation was observed between: (1) ES WSMRE and WSSFlow in both axial (r = -0.62; P = 0.006) and circumferential (r = -0.52; P = 0.016) directions; (2) ES WSMRE and mean velocity (r = -0.58; P = 0.012); and (3) age and WSSFlow in both axial (r = -0.71; P < 0.0001) and circumferential (r = -0.58; P = 0.0012) directions. A significant positive correlation was observed between: (1) ES WSMRE and PWV (r = 0.69; P < 0.0001); (2) ES WSMRE and mean peak flow (r = 0.53; P = 0.016); and (3) ES WSMRE and age (r = 0.63;P = 0.006). CONCLUSION: The negative significant correlation between aortic WSSFlow and WSMRE in normal volunteers demonstrates a relationship between WSMRE and WSSFlow . LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:771-778.