MR elastography and diffusion‐weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology

The purpose of this work was (1) to develop a magnetic resonance elastography (MRE) system for imaging of the ex vivo human prostate and (2) to assess the diagnostic power of mono‐frequency and multi‐frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. An electromagnetic driver was designed specifically for MRE studies in small‐bore MR scanners. Ex vivo prostate specimens (post‐fixation) of 14 patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power‐law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the receiver‐operator‐characteristic curves (AUC) were calculated. The methods were validated in a phantom study and it was demonstrated that (i) the driver does not interfere with the acquisition process and (ii) the driver can generate amplitudes greater than 100 µm for frequencies less than 1 kHz. In the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was distinguished from normal tissue in the peripheral zone (PZ) with an average AUC of 0.75 (G_d), 0.75 (G_l), 0.70 (Gamma‐G_d), 0.68 (apparent diffusion coefficient, ADC), and 0.82 (G_d + G_l + ADC). The differentiation between PZ and central gland was modest for G_d (p < 0.07), G_l (p < 0.06) but not significant for Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time of the prostate specimen and the stiffness of the tissue, which could affect the diagnostic power results. DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi‐frequency (Gamma) analysis did not appear to improve the results. However, in light of the effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed. Copyright © 2014 John Wiley & Sons, Ltd.     

Prostate MR elastography with transperineal electromagnetic actuation and a fast fractionally encoded steady‐state gradient echo sequence

Our aim is to develop a clinically viable, fast‐acquisition, prostate MR elastography (MRE) system with transperineal excitation. We developed a new actively shielded electromagnetic transducer, designed to enable quick deployment and positioning within the scanner. The shielding of the transducer was optimized using simulations. We also employed a new rapid pulse sequence that encodes the three‐dimensional displacement field in the prostate gland using a fractionally encoded steady‐state gradient echo sequence, thereby shortening the acquisition time to a clinically acceptable 8–10 min. The methods were tested in two phantoms and seven human subjects (six volunteers and one patient with prostate cancer). The MRE acquisition time for 24 slices, with an isotropic resolution of 2 mm and eight phase offsets, was 8 min, and the total scan, including positioning and set‐up, was performed in 15–20 min. The phantom study demonstrated that the transducer does not interfere with the acquisition process and that it generates displacement amplitudes that exceed 100 µm even at frequencies as high as 300 Hz. In the in vivo human study, average wave amplitudes of 30 µm (46 µm at the apex) were routinely achieved within the prostate gland at 70 Hz. No pain or discomfort was reported. Results in a single patient suggest that MRE can identify cancer tumors, although this result is preliminary. The proposed methods allow the integration of prostate MRE with other multiparametric MRI methods. The results of this study clearly motivate the clinical evaluation of transperineal MRE in patients. Copyright © 2014 John Wiley & Sons, Ltd.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.     

Rapid acquisition of multifrequency,multislice and multidirectional MR elastography data with a fractionally encoded gradient echo sequence

In MR elastography (MRE), periodic tissue motion is phase encoded using motion‐encoding gradients synchronized to an externally applied periodic mechanical excitation. Conventional methods result in extended scan time for quality phase images, thus limiting the broad application of MRE in the clinic. For practical scan times, researchers have been relying on one‐dimensional or two‐dimensional motion‐encoding, low‐phase sampling and a limited number of slices, and artifact‐prone, single‐shot, echo planar imaging (EPI) readout. Here, we introduce a rapid multislice pulse sequence capable of three‐dimensional motion encoding that is also suitable for simultaneously encoding motion with multiple frequency components. This sequence is based on a gradient‐recalled echo (GRE) sequence and exploits the principles of fractional encoding. This GRE MRE pulse sequence was validated as capable of acquiring full three‐dimensional motion encoding of isotropic voxels in a large volume within less than a minute. This sequence is suitable for monofrequency and multifrequency MRE experiments. In homogeneous paraffin phantoms, the eXpresso sequence yielded similar storage modulus values as those obtained with conventional methods, although with markedly reduced variances (7.11 ± 0.26 kPa for GRE MRE versus 7.16 ± 1.33 kPa for the conventional spin‐echo EPI sequence). The GRE MRE sequence obtained better phase‐to‐noise ratios than the equivalent spin‐echo EPI sequence (matched for identical acquisition time) in both paraffin phantoms and in vivo data in the liver (59.62 ± 11.89 versus 27.86 ± 3.81, 61.49 ± 14.16 versus 24.78 ± 2.48 and 58.23 ± 10.39 versus 23.48 ± 2.91 in the X, Y and Z components, respectively, in the case of liver experiments). Phase‐to‐noise ratios were similar between GRE MRE used in monofrequency or multifrequency experiments (75.39 ± 14.93 versus 86.13 ± 18.25 at 28 Hz, 71.52 ± 24.74 versus 86.96 ± 30.53 at 56 Hz and 95.60 ± 36.96 versus 61.35 ± 26.25 at 84Hz, respectively). Copyright © 2013 John Wiley & Sons, Ltd.     

Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono‐exponential (GAME) model

A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R₂^* mapping with Mono‐Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient‐echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono‐Exponential (GAME) decay model, in the prostate at 3T. Multi‐gradient‐echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR‐guided prostate biopsies. Data were fitted with both ME and GAME models. The information contents of these models were compared using Akaike's information criterion (second order, AIC_C), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions of interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R₂^* approached 40 s^?1. R₂^* mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, for example of oxygenation status.     

Apparent diffusion coefficient of the prostate in men prior to biopsy: determination of a cut-off value to predict malignancy of the peripheral zone

Determination of the apparent diffusion coefficient (ADC) of the prostate in men (n = 60) with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination (DRE) prior to transrectal ultrasound (TRUS) guided biopsy using endorectal DWI is reported. Patients were categorized into different groups based on their PSA levels. The mean ADC was calculated from a number of regions of interest (ROIs) for the whole of the peripheral zone (PZ) and the central gland (CG). A total of 1108 ROIs were analyzed from 60 patients. The mean ADC value of the PZ was higher than that of the CG in controls. A total of 23 out of 60 patients were positive for malignancy on biopsy, and the mean ADC of the PZ was lower in these patients compared with those who were negative. Moreover, the mean ADC obtained for the whole of the PZ of the prostate in different groups of patients and controls showed a decreasing trend. A plot between PSA and mean ADC for the PZ showed non-linear association with logarithmic decrease in ADC. The mean ADC of the CG was not significantly different in patients who were positive or negative for malignancy in biopsy. In addition, a cut-off value of 1.17 x 10(-3) mm2/s (sensitivity = 73% and specificity = 74%, area under the curve = 0.83) for the mean ADC for the whole of the PZ of patients was determined by using the receiver operating characteristic curve (ROC) to predict malignancy of the PZ.     

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.     

Overhauser‐enhanced magnetic resonance elastography

Magnetic resonance elastography (MRE) is a powerful technique to assess the mechanical properties of living tissue. However, it suffers from reduced sensitivity in regions with short T₂ and T₂* such as in tissue with high concentrations of paramagnetic iron, or in regions surrounding implanted devices. In this work, we exploit the longer T₂* attainable at ultra‐low magnetic fields in combination with Overhauser dynamic nuclear polarization (DNP) to enable rapid MRE at 0.0065 T. A 3D balanced steady‐state free precession based MRE sequence with undersampling and fractional encoding was implemented on a 0.0065 T MRI scanner. A custom‐built RF coil for DNP and a programmable vibration system for elastography were developed. Displacement fields and stiffness maps were reconstructed from data recorded in a polyvinyl alcohol gel phantom loaded with stable nitroxide radicals. A DNP enhancement of 25 was achieved during the MRE sequence, allowing the acquisition of 3D Overhauser‐enhanced MRE (OMRE) images with (1.5 × 2.7 × 9) mm³ resolution over eight temporal steps and 11 slices in 6 minutes. In conclusion, OMRE at ultra‐low magnetic field can be used to detect mechanical waves over short acquisition times. This new modality shows promise to broaden the scope of conventional MRE applications, and may extend the utility of low‐cost, portable MRI systems to detect elasticity changes in patients with implanted devices or iron overload. Copyright © 2016 John Wiley & Sons, Ltd.     

Assessment of the need for DCE MRI in the detection of dominant lesions in the whole gland: Correlation between histology and MRI of prostate cancer

The purpose of this study was to evaluate the utility of dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI) in the detection of dominant prostate tumors with multi‐parametric MRI of the whole gland. Combined diffusion tensor imaging (DTI) and DCE MRI from 16 patients with biopsy‐proven prostate cancer and no previous treatment were acquired with a 3.0‐T MRI scanner prior to radical prostatectomy, and used to identify dominant tumors. MRI results were validated by whole‐mount histology. Paired t‐test and Wilcoxon test, logistic generalized linear mixed effect models and receiver operating characteristic (ROC) analyses were used for the estimation of the statistical significance of the results. In the peripheral zone (PZ), the areas under the ROC curve (ROC‐AUC) were 0.98 (sensitivity, 96%; specificity, 98%) for DTI, 0.96 (sensitivity, 92%; specificity, 97%) for DCE and 0.99 (sensitivity, 98%; specificity, 98%) for DTI + DCE. In the entire prostate, the ROC‐AUC values were 0.96 (sensitivity, 84%; specificity, 95%) for DTI, 0.87 (sensitivity, 45%; specificity, 94%) for DCE and 0.96 (sensitivity, 88%; specificity, 98%) for DTI + DCE. The increase in ROC‐AUC by the addition of DCE was not statistically significant in either PZ or the entire prostate. The results of this study have shown that DTI identified dominant tumors with high accuracy in both PZ and the entire prostate, whereas the inclusion of DCE MRI had no significant impact on the identification of either PZ or entire prostate dominant lesions. Our results suggest that the inclusion of DCE MRI may not increase the accuracy of dominant lesion detection, allowing for faster, better tolerated imaging studies.     

An improved model for prostate diffusion incorporating the results of Monte Carlo simulations of diffusion in the cellular compartment

The purpose of this work was to refine a previously published model of prostate diffusion by incorporating improved estimates of cellular diffusivity obtained by Monte Carlo simulation. Stromal and epithelial cell size and intracellular volume fraction in different grades of cancer were determined from histological images. Diffusion in different mixtures of cells, corresponding to different tumor grades, was simulated and cellular apparent diffusion coefficient and kurtosis values determined. These values were incorporated into the previously published model of prostate diffusion and model predictions compared with values found in the literature. Stromal cell radius and intracellular volume fraction were 3.74 ± 0.96 μm and 13 ± 3% respectively in normal peripheral zone (PZ), and were similar in all grades of cancer. Epithelial cell radius and intracellular volume fraction were 3.40 ± 0.15 μm and 45 ± 5% respectively in normal PZ, rising to 4.75 ± 0.20 μm and 70 ± 8% in high grade cancer. Cellular apparent diffusion coefficient and kurtosis were 1.02 μm² ms^?1 and 0.58 respectively in normal PZ, and 0.61 μm² ms^?1 and 1.15 in high grade cancer (variation in simulation values are less than 0.1%). Agreement between model predictions and measurements were good, with a mean square error of 0.22 μm² ms^?1. Incorporation of cellular diffusion coefficient and kurtosis values obtained by Monte Carlo simulation into a model of prostate diffusion gives good agreement with published results.     

Stratification of the aggressiveness of prostate cancer using pre‐biopsy multiparametric MRI (mpMRI)

Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision‐making tool in prostate cancer management. As low‐grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre‐biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty‐six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25–45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low‐grade, intermediate‐grade and high‐grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10^–3 mm²/s) for low‐grade, intermediate‐grade and high‐grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre‐biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.     

Magnetic resonance elastography of skeletal muscle deep tissue injury

The current state‐of‐the‐art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial–temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T₂‐weighted, and T₂‐mapping measurements were performed before, directly after indentation, and at several timepoints during a 14‐day follow‐up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T₂ was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T₂. Whereas T₂ showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage‐inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T₂. Since T₂ elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T₂ for localization of the actual damaged area.     

Magnetic resonance elastography of the lumbar back muscles: A preliminary study

Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness identified by manual palpation and strain elastography. Recently, magnetic resonance elastography (MRE) has allowed the stiffness of muscle to be characterized noninvasively in vivo, providing quantitative 3D stiffness maps (elastograms). The aim of this study was to characterize the stiffness (shear modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the lumbar region was performed on seven adults in supine position. MRE was acquired in three muscular states: relaxed with outstretched legs, stretched with passive pelvis flexion, and contracted with outstretched legs and tightened trunk muscles. The mean SM was measured within a region of interest manually defined in the multifidus, erector spinae, and the entire paraspinal compartment. The intermuscular difference and the effects of stretching and contraction were assessed by ANOVA and t‐tests. At rest, the mean SM of the paraspinal compartment was 1.6 ± 0.2 kPa. It increased significantly with stretching to 1.65 ± 0.3 kPa, and with contraction to 2.0 ± 0.7 kPa. Irrespective of muscular state, the erector spinae was significantly stiffer than the multifidus. The multifidus underwent proportionally higher stiffness changes from rest to contraction and stretching. MRE can be used to measure the stiffness of the LPM in different muscular states. We hypothesize that, irrespective of posture, the erector spinae behaves as semi‐rigid beam, and ensures permanent stiffness of the spine. The multifidus behaves as an adaptable muscle that provides segmental flexibility to the spine and tunes the spine stiffness. Clin. Anat. 31:514–520, 2018. © 2018 Wiley Periodicals, Inc.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

In vivo brain viscoelastic properties measured by magnetic resonance elastography

Magnetic resonance elastography (MRE) is a non-invasive imaging technique used to visualise and quantify mechanical properties of tissue, providing information beyond what can be currently achieved with standard MR sequences and could, for instance, provide new insight into pathological processes in the brain. This study uses the MRE technique at 3 T to extract the complex shear modulus for in vivo brain tissue utilizing a full three-dimensional approach to reconstruction, removing contributions of the dilatational wave by application of the curl operator. A calibrated phantom is used to benchmark the MRE measurements, and in vivo results are presented for healthy volunteers. The results provide data for in vivo brain storage modulus (G'), finding grey matter (3.1 kPa) to be significantly stiffer than white matter (2.7 kPa). The first in vivo loss modulus (G') measurements show no significant difference between grey matter (2.5 kPa) and white matter (2.5 kPa).     

Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity

MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli mu(1) = 0.84 +/- 0.22 (1.36 +/- 0.31) kPa, mu(2) = 2.03 +/- 0.19 (1.86 +/- 0.34) kPa and one shear viscosity of eta = 6.7 +/- 1.3 (5.5 +/- 1.6) Pa s (interindividual mean +/- SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for mu(1) and eta (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver.     

Single-cell RNA sequencing of human prostate basal epithelial cells reveals zone-specific cellular populations and gene expression signatures

Despite evidence of genetic signatures in normal tissue correlating with disease risk, prospectively identifying genetic drivers and cell types that underlie subsequent pathologies has historically been challenging. The human prostate is an ideal model to investigate this phenomenon because it is anatomically segregated into three glandular zones (central, peripheral, and transition) that develop differential pathologies: prostate cancer in the peripheral zone (PZ) and benign prostatic hyperplasia (BPH) in the transition zone (TZ), with the central zone (CZ) rarely developing disease. More specifically, prostatic basal cells have been implicated in differentiation and proliferation during prostate development and regeneration; however, the contribution of zonal variation and the critical role of basal cells in prostatic disease etiology are not well understood. Using single-cell RNA sequencing of primary prostate epithelial cultures, we elucidated organ-specific, zone-specific, and cluster-specific gene expression differences in basal cells isolated from human prostate and seminal vesicle (SV). Aggregated analysis identified ten distinct basal clusters by Uniform Manifold Approximation and Projection. Organ specificity compared gene expression in SV with the prostate. As expected, SV cells were distinct from prostate cells by clustering, gene expression, and pathway analysis. For prostate zone specificity, we identified two CZ-specific clusters, while the TZ and PZ populations clustered together. Despite these similarities, differential gene expression was identified between PZ and TZ samples that correlated with gene expression profiles in prostate cancer and BPH, respectively. Zone-specific profiles and cell type-specific markers were validated using immunostaining and bioinformatic analyses of publicly available RNA-seq datasets. Understanding the baseline differences at the organ, zonal, and cellular level provides important insight into the potential drivers of prostatic disease and guides the investigation of novel preventive or curative treatments. Importantly, this study identifies multiple prostate basal cell populations and cell type-specific gene signatures within prostate basal epithelial cells that have potential critical roles in driving prostatic diseases. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

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.