Improved quantification of tumor adhesion in meningiomas using MR elastography-based slip interface imaging.

Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p<0.001). The improved technique demonstrated superior discriminatory ability in identifying tumor adhesion patterns compared to the previously described algorithm, with an AUC of 0.86 vs. 0.72 for distinguishing complete adhesion from others (p = 0.037), and an AUC of 0.72 vs. 0.67 for non-adherent and others. Aggressive tumors exhibiting atypical features showed significantly higher adhesion percentages in recurrence group compared to non-recurrence group (p = 0.042). This study validates the efficacy of the improved SII technique in quantifying meningioma adhesions and demonstrates its potential to affect clinical decision-making. The reliability of the technique, coupled with potential to help predict meningioma recurrence, particularly in aggressive tumor subsets, highlights its promise in guiding treatment strategies.

MR elastography-based slip interface imaging (SII) for functional assessment of myofascial interfaces: A feasibility study.

PURPOSE: Abnormal adherence at functional myofascial interfaces is hypothesized as an important phenomenon in myofascial pain syndrome. This study aimed to investigate the feasibility of MR elastography (MRE)-based slip interface imaging (SII) to visualize and assess myofascial mobility in healthy volunteers. METHODS: SII was used to assess local shear strain at functional myofascial interfaces in the flexor digitorum profundus (FDP) and thighs. In the FDP, MRE was performed at 90 Hz vibration to each index, middle, ring, and little finger. Two thigh MRE scans were performed at 40 Hz with knees flexed and extended. The normalized octahedral shear strain (NOSS) maps were calculated to visualize myofascial slip interfaces. The entropy of the probability distribution of the gradient NOSS was computed for the two knee positions at the intermuscular interface between vastus lateralis and vastus intermedius, around rectus femoris, and between vastus intermedius and vastus medialis. RESULTS: NOSS map depicted distinct functional slip interfaces in the FDP for each finger. Compared to knee flexion, clearer slip interfaces and larger gradient NOSS entropy at the vastus lateralis-vastus intermedius interface were observed during knee extension, where the quadriceps are not passively stretched. This suggests the optimal position for using SII to visualize myofascial slip interface in skeletal muscles is when muscles are not subjected to any additional force. CONCLUSION: The study demonstrated that MRE-based SII can visualize and assess myofascial interface mobility in extremities. The results provide a foundation for investigating the hypothesis that myofascial pain syndrome is characterized by changes in the mobility of myofascial interfaces.

Association Between Anatomic and Clinical Indicators of Injury Severity After Moderate-Severe Traumatic Brain Injury: A Pilot Study Using Multiparametric Magnetic Resonance Imaging.

This study sought to identify whether an anatomical indicator of injury severity as measured by multiparametric magnetic resonance imaging (MRI) including magnetic resonance elastography (MRE), is predictive of a clinical measure of injury severity after moderate-severe traumatic brain injury (TBI). Nine individuals who were admitted to acute inpatient rehabilitation after moderate-to-severe TBI completed a comprehensive MRI protocol prior to discharge from rehabilitation, which included conventional MRI with diffusion tensor imaging (DTI). Of those, five of nine also underwent brain MRE to measure the brain parenchyma stiffness. Clinical severity of injury was measured by the length of post-traumatic amnesia (PTA). MRI-assessed non-hemorrhage contusion score and hemorrhage score, DTI-measured white matter fractional anisotropy, and MRE-measured lesion stiffness were all assessed. A higher hemorrhagic score was significantly associated with a longer length of PTA (p = 0.026). Participants with a longer PTA tended to have a higher non-hemorrhage contusion score and softer contusion lesions than the contralateral control side, although the small sample size did not allow for assessment of a significant association. To our knowledge, this is the first report applying MRI/MRE imaging protocol to quantitate altered brain anatomy after moderate-severe TBI and its association with PTA, a known clinical predictor of post-acute outcome. Future larger studies could lead to the development of prediction models that integrate clinical data with anatomical (MRI), structural (DTI), and mechanical (MRE) changes caused by TBI, to inform prognosis and care planning.

SWENet: A Physics-Informed Deep Neural Network (PINN) for Shear Wave Elastography.

Shear wave elastography (SWE) enables the measurement of elastic properties of soft materials in a non-invasive manner and finds broad applications in various disciplines. The state-of-the-art SWE methods rely on the measurement of local shear wave speeds to infer material parameters and suffer from wave diffraction when applied to soft materials with strong heterogeneity. In the present study, we overcome this challenge by proposing a physics-informed neural network (PINN)-based SWE (SWENet) method. The spatial variation of elastic properties of inhomogeneous materials has been introduced in the governing equations, which are encoded in SWENet as loss functions. Snapshots of wave motions have been used to train neural networks, and during this course, the elastic properties within a region of interest illuminated by shear waves are inferred simultaneously. We performed finite element simulations, tissue-mimicking phantom experiments, and ex vivo experiments to validate the method. Our results show that the shear moduli of soft composites consisting of matrix and inclusions of several millimeters in cross-section dimensions with either regular or irregular geometries can be identified with excellent accuracy. The advantages of the SWENet over conventional SWE methods consist of using more features of the wave motions and enabling seamless integration of multi-source data in the inverse analysis. Given the advantages of SWENet, it may find broad applications where full wave fields get involved to infer heterogeneous mechanical properties, such as identifying small solid tumors with ultrasound SWE, and differentiating gray and white matters of the brain with magnetic resonance elastography.

Wavelet MRE: Imaging propagating broadband acoustic waves with wavelet-based motion-encoding gradients.

PURPOSE: To demonstrate a novel MR elastography (MRE) technique, termed here wavelet MRE. With this technique, broadband motion sensitivity is achievable. Moreover, the true tissue displacement can be reconstructed with a simple inverse transform. METHODS: A wavelet MRE sequence was developed with motion-encoding gradients based on Haar wavelets. From the phase images' displacement was estimated using an inverse transform. Simulations were performed using a frequency sweep and a transient as ground-truth motions. A PVC phantom was scanned using wavelet MRE and standard MRE with both transient (one and 10 cycles of 90-Hz motion) and steady-state dual-frequency motion (30 and 60 Hz) for comparison. The technique was tested in a human brain, and motion trajectories were estimated for each voxel. RESULTS: In simulation, the displacement information estimated from wavelet MRE closely matched the true motion. In the phantom test, the MRE phase data generated from the displacement information derived from wavelet MRE agreed well with standard MRE data. Testing of wavelet MRE to assess transient motion waveforms in the brain was successful, and the tissue motion observed was consistent with a previous study. CONCLUSION: The uniform and broadband frequency response of wavelet MRE makes it a promising method for imaging transient, multifrequency motion, or motion with unknown frequency content. One potential application is measuring the response of brain tissue undergoing low-amplitude, transient vibrations as a model for the study of traumatic brain injury.

Effects of extreme drought events on vegetation activity from the perspectives of meteorological and soil droughts in southwestern China.

Under climate warming, extreme drought events (EDEs) in southwestern China have become more frequent and severe and have had significant impacts on vegetation growth. Clarifying the influence of soil and meteorological droughts on the vegetation photosynthetic rate (PHR) and respiration rate (RER) can help policymakers to anticipate the impacts of drought on vegetation and take measures to reduce losses. In this study, the frequency and features of EDEs from 1990 to 2021 were analyzed using the standardized precipitation evapotranspiration index, and the longest-lasting and most severe EDE was chosen to assess the effects of drought on vegetation activity. Then, a land surface model was used to simulate the vegetation PHR and RER. Finally, the effects of the EDE on the vegetation PHR and RER were analyzed from the perspectives of soil and meteorological droughts. The results revealed that from 1990 to 2021, a total of 11 EDEs were observed in southwestern China, and the longest-lasting and most severe EDE occurred in 2009-2010 (EDE2009/2010). EDE2009/2010 significantly reduced the monthly mean PHR and RER by 9.82 g C m-2 month-1 and 0.80 g C m-2 month-1, respectively, causing a cumulative reduction of approximately 5.61 × 1013 g C. Soil and meteorological droughts had a driving force of 39 % on the PHR changes and an explanatory force of 42 % on the RER reduction. In particular, the soil drought had an average explanatory force of 25 % on the PHR and made a contribution of 24 % to the RER. The drought affected different types of vegetation differently, and crops were more susceptible than grassland and forests on the monthly time scale. The vegetation exhibited resilience to drought, returning to normal PHR and RER levels 2 months after the end of EDE2009/2010. This research contributes to understanding and predicting the impact of EDEs on vegetation growth in southwestern China.

Magnetic Resonance Elastography-Based Technique to Assess the Biomechanics of the Skull-Brain Interface: Repeatability and Age-Sex Characteristics.

Increasing concerns have been raised about the long-term negative effects of subconcussive repeated head impact (RHI). To elucidate RHI injury mechanisms, many efforts have studied how head impacts affect the skull-brain biomechanics and have found that mechanical interactions at the skull-brain interface dampen and isolate brain motions by decoupling the brain from the skull. Despite intense interest, in vivo quantification of the functional state of the skull-brain interface remains difficult. This study developed a magnetic resonance elastography (MRE) based technique to non-invasively assess skull-brain mechanical interactions (i.e., motion transmission and isolation function) under dynamic loading. The full MRE displacement data were separated into rigid body motion and wave motion. The rigid body motion was used to calculate the brain-to-skull rotational motion transmission ratio (Rtr) to quantify skull-brain motion transmissibility, and the wave motion was used to calculate the cortical normalized octahedral shear strain (NOSS) (calculated based on a partial derivative computing neural network) to evaluate the isolation capability of the skull-brain interface. Forty-seven healthy volunteers were recruited to investigate the effects of age/sex on Rtr and cortical NOSS, and 17 of 47 volunteers received multiple scans to test the repeatability of the proposed techniques under different strain conditions. The results showed that both Rtr and NOSS were robust to MRE driver variations and had good repeatability, with intraclass correlation coefficient (ICC) values between 0.68 and 0.97 (fair to excellent). No age or sex dependence were observed with Rtr, whereas a significant positive correlation between age and NOSS was found in the cerebrum, frontal, temporal, and parietal lobes (all p < 0.05), but not in the occipital lobe (p = 0.99). The greatest change in NOSS with age was found in the frontal lobe, one of the most frequent locations of traumatic brain injury (TBI). Except for the temporal lobe (p = 0.0087), there was no significant difference in NOSS between men and women. This work provides motivation for utilizing MRE as a non-invasive tool for quantifying the biomechanics of the skull-brain interface. It evaluated the age and sex dependence and may lead to a better understanding of the protective role and mechanisms of the skull-brain interface in RHI and TBI, as well as improve the accuracy of computational models in simulating the skull-brain interface.

The Safety and Efficacy of Low-Dose Naltrexone in Patients with Fibromyalgia: A Systematic Review.

Fibromyalgia (FM) is a chronic pain sensitivity syndrome characterized by diffuse musculoskeletal pain and many other systemic manifestations. Low-dose naltrexone (LDN) has been increasingly used as an off-label treatment option in FM. However, current evidence on the safety and efficacy of LDN in patients with FM is not well known. To systematically assess the current evidence on the safety and efficacy of LDN use in the treatment of FM. A comprehensive bibliographic search was conducted on EBM Reviews - Cochrane Central Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic, Embase, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions and Scopus databases in September 2022. Inclusion criteria were articles that were published in English, focusing on clinical trials involving LDN for the treatment of FM. Two reviewers independently screened and extracted the data. A qualitative analysis was used due to the high methodological heterogeneity between studies. The electronic search produced 805 articles. After applying the inclusion criteria, 9 articles (one RCT, two case reports, two case series, and four pilot trials) were selected for evaluation. LDN intervention protocols, study designs, and follow-up periods were different among the included studies. Overall, LDN was found to be effective in the symptomatic management of FM, and of the 78% of included studies that evaluated for safety, no severe adverse events were reported. Proving the efficacy and safety of low-dose naltrexone is a future possibility based on current study data, but the level of scientific evidence is limited. Future well-designed trials with large sample sizes are required.

Use of magnetic resonance elastography to gauge meningioma intratumoral consistency and histotype.

OBJECTIVE: To determine whether tumor shear stiffness, as measured by magnetic resonance elastography, corresponds with intratumoral consistency and histotype. MATERIALS AND METHODS: A total of 88 patients with 89 meningiomas (grade 1, 74 typical [13 fibroblastic, 61 non-fibroblastic]; grade 2, 12 atypical; grade 3, 3 anaplastic) were prospectively studied, each undergoing preoperative MRE in conjunction with T1-, T2- and diffusion-weighted imaging. Contrast-enhanced T1-weighted sequences were also obtained. Tumor consistency was evaluated as heterogeneous or homogenous, and graded on a 5-point scale intraoperatively. MRE-determined shear stiffness was associated with tumor consistency by surgeon's evaluation and whole-slide histologic analyses. RESULTS: Mean tumor stiffness overall was 3.81+/-1.74 kPa (range, 1.57-12.60 kPa), correlating well with intraoperative scoring (r = 0.748; p = 0.001). MRE performed well as a gauge of tumor consistency (AUC = 0.879, 95 % CI: 0.792-0.938) and heterogeneity (AUC = 0.773, 95 % CI: 0.618-0.813), significantly surpassing conventional MR techniques (DeLong test, all p < 0.001 after Bonferroni adjustment). Shear stiffness was independently correlated with both fibrous content (partial correlation coefficient = 0.752; p < 0.001) and tumor cellularity (partial correlation coefficient = 0.547; p < 0.001). MRE outperformed other imaging techniques in distinguishing fibroblastic meningiomas from other histotypes (AUC = 0.835 vs 0.513 âˆ¼ 0.634; all p < 0.05), but showed limited ability to differentiate atypical or anaplastic meningiomas from typical meningiomas (AUC = 0.723 vs 0.616 âˆ¼ 0.775; all p > 0.05). Small (<2.5 cm, n = 6) and intraventricular (n = 2) tumors displayed inconsistencies between MRE and surgeon's evaluation. CONCLUSIONS: The results of this prospective study provide substantial evidence that preoperative evaluation of meningiomas with MRE can reliably characterize tumor stiffness and spatial heterogeneity to aid neurosurgical planning.

Probing the Mechanical Properties of Large Arteries by Measuring Their Deformation In Vivo with Ultrasound.

Aging and cardiovascular diseases (CVDs) may alter the microstructures of arteries and hence their mechanical properties. Therefore, the measurement of intrinsic artery mechanical properties in vivo can provide valuable information in understanding aging and CVDs and is of clinical significance. The accuracy of advanced ultrasound imaging techniques in measuring the deformation of large arteries under blood pressure is good. However, the assessment of arterial stiffness in vivo remains a challenge. An inverse method to infer the constitutive parameters of arteries in vivo from the blood pressure-arterial radius relationship (P-r curve) is proposed here. The stability analysis reveals that a key constitutive parameter, bθ, which measures the circumferential hardening of an artery, can be reliably identified. An in vivo experiment was performed on the common carotid arteries of 41 healthy volunteers (age: 37 ± 17 y). The value of bθ varies significantly (from 0.55 ± 0.15 for the young group to 0.93 ± 0.29 for the older group, p < 0.01) and is positively correlated with age (r = 0.673, p < 0.01). Furthermore, our theoretical analysis and experimental study have revealed a strong correlation between the clinic-used stiffness index ß and bθ. This study shows that the arterial material parameter bθ can be measured in vivo, which makes it promising as a new biomarker in the diagnosis of CVDs.

MR Elastography-Based Shear Strain Mapping for Assessment of Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVES: To evaluate the potential of MR elastography (MRE)-based shear strain mapping to noninvasively predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: Fifty-nine histopathology-proven HCC patients with conventional 60-Hz MRE examinations (+/-MVI, n = 34/25) were enrolled retrospectively between December 2016 and October 2019, with one subgroup comprising 29/59 patients (+/-MVI, n = 16/13) who also underwent 40- and 30-Hz MRE examinations. Octahedral shear strain (OSS) maps were calculated, and the percentage of peritumoral interface length with low shear strain (i.e., a low-shear-strain length, pLSL, %) was recorded. For OSS-pLSL, differences between the MVI (+) and MVI (-) groups and diagnostic performance at different MRE frequencies were analyzed using the Mann-Whitney test and area under the receiver operating characteristic curve (AUC), respectively. RESULTS: The peritumor OSS-pLSL was significantly higher in the MVI (+) group than in the MVI (-) group at the three frequencies (all p < 0.01). The AUC of peritumor OSS-pLSL for predicting MVI was good/excellent in all frequency groups (60-Hz: 0.73 (n = 59)/0.80 (n = 29); 40-Hz: 0.84; 30-Hz: 0.90). On further analysis of the 29 cases with all frequencies, the AUCs were not significantly different. As the frequency decreased from 60-Hz, the specificity of OSS increased at 40-Hz (53.8-61.5%) and further increased at 30-Hz (53.8-76.9%), and the sensitivity remained high at lower frequencies (100.0-93.8%) (all p > 0.05). CONCLUSIONS: MRE-based shear strain mapping is a promising technique for noninvasively predicting the presence of MVI in patients with HCC, and the most recommended frequency for OSS is 30-Hz. KEY POINTS: • MR elastography (MRE)-based shear strain mapping has the potential to predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma preoperatively. • The low interface shear strain identified at tumor-liver boundaries was highly correlated with the presence of MVI.

Predicting pituitary adenoma consistency with preoperative magnetic resonance elastography.

OBJECTIVE: Pituitary adenoma is one of the most common primary intracranial neoplasms. Most of these tumors are soft, but up to 17% may have a firmer consistency. Therefore, knowing the tumor consistency in the preoperative setting could be helpful. Multiple imaging methods have been proposed to predict tumor consistency, but the results are controversial. This study aimed to evaluate the efficacy of MR elastography (MRE) in predicting tumor consistency and its potential use in a series of patients with pituitary adenomas. METHODS: Thirty-eight patients with pituitary adenomas (≥ 2.5 cm) were prospectively evaluated with MRI and MRE before surgery. Absolute MRE stiffness values and relative MRE stiffness ratios, as well as the relative ratio of T1 signal, T2 signal, and diffusion-weighted imaging apparent diffusion coefficient (ADC) values were determined prospectively by calculating the ratio of those values in the tumor to adjacent left temporal white matter. Tumors were classified into three groups according to surgical consistency (soft, intermediate, and firm). Statistical analysis was used to identify the predictive value of the different radiological parameters in determining pituitary adenoma consistency. RESULTS: The authors included 32 (84.21%) nonfunctional and 6 (15.79%) functional adenomas. The mean maximum tumor diameter was 3.7 cm, and the mean preoperative tumor volume was 16.4 cm3. Cavernous sinus invasion was present in 20 patients (52.63%). A gross-total resection was possible in 9 (23.68%) patients. The entire cohort's mean absolute tumor stiffness value was 1.8 kPa (range 1.1-3.7 kPa), whereas the mean tumor stiffness ratio was 0.66 (range 0.37-1.6). Intraoperative tumor consistency was significantly correlated with absolute and relative tumor stiffness (p = 0.0087 and 0.007, respectively). Tumor consistency alone was not a significant factor for predicting gross-total resection. Patients with intermediate and firm tumors had more complications compared to patients with soft tumors (50.00% vs 12.50%, p = 0.02) and also had longer operative times (p = 0.0002). CONCLUSIONS: Whereas other MRI sequences have proven to be unreliable in determining tumor consistency, MRE has been shown to be a reliable tool for predicting adenoma consistency. Preoperative knowledge of tumor consistency could be potentially useful for surgical planning, counseling about potential surgical risks, and estimating the length of operative time.

Multiparametric magnetic resonance imaging/magnetic resonance elastography assesses progression and regression of steatosis, inflammation, and fibrosis in alcohol-associated liver disease.

BACKGROUND: Magnetic resonance imaging (MRI) and MRI-based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol-associated liver disease (ALD). METHODS: We utilized four different preclinical mouse models in our study: Model 1-mice were fed a fast-food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2-mice were fed chronic-binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin-22 at different time points to induce disease regression; Model 3-mice were administered CCl4 for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4-mice were administered EtOH plus CCl4 for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions. RESULTS: Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three-parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression (r = 0.84, p < 0.0001) and regression (r = 0.79, p < 0.0001) as measured by collagen content in livers. CONCLUSION: This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.

A new method for quantification and 3D visualization of brain tumor adhesion using slip interface imaging in patients with meningiomas.

OBJECTIVES: To develop an objective quantitative method to characterize and visualize meningioma-brain adhesion using MR elastography (MRE)-based slip interface imaging (SII). METHODS: This retrospective study included 47 meningiomas (training dataset: n = 35; testing dataset: n = 12) with MRE/SII examinations. Normalized octahedral shear strain (NOSS) values were calculated from the acquired MRE displacement data. The change in NOSS at the tumor boundary (ΔNOSSbdy) was computed, from which a 3D ΔNOSSbdy map of the tumor surface was created and the probability distribution of ΔNOSSbdy over the entire tumor surface was calculated. Statistical features were calculated from the probability histogram. After eliminating highly correlated features, the capability of the remaining feature for tumor adhesion classification was assessed using a one-way ANOVA and ROC analysis. RESULTS: The magnitude and location of the tumor adhesion can be visualized by the reconstructed 3D ΔNOSSbdy surface map. The entropy of the ΔNOSSbdy histogram was significantly different between adherent tumors and partially/completely non-adherent tumors in both the training (AUC: 0.971) and testing datasets (AUC: 0.900). Based on the cutoff values obtained from the training set, the ΔNOSSbdy entropy in the testing dataset yielded an accuracy of 0.83 for distinguishing adherent versus partially/non-adherent tumors, and 0.67 for distinguishing non-adherent versus completely/partially adherent tumors. CONCLUSIONS: SII-derived ΔNOSSbdy values are useful for quantification and classification of meningioma-brain adhesion. The reconstructed 3D ΔNOSSbdy surface map presents the state and location of tumor adhesion in a "clinician-friendly" manner, and can identify meningiomas with a high risk of adhesion to adjacent brain parenchyma. KEY POINTS: • MR elastography (MRE)-based slip interface imaging shows promise as an objective tool to preoperatively discriminate meningiomas with a high risk of intraoperative adhesion. • Measurement of the change of shear strain at meningioma boundaries can provide quantitative metrics depicting the state of adhesion at the tumor-brain interface. • The surface map of tumor adhesion shows promise in assisting precise adhesion localization, using a comprehensible, "clinician-friendly" 3D visualization.

Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer.

PURPOSE: To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS: The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0 T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram. RESULTS: PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60 Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90 Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60 Hz]; 0.975 vs. 0.904, P = 0.060 [90 Hz], respectively). CONCLUSIONS: MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis.

Circulating extracellular vesicles (EVs) are a novel and emerging biomarker for nonalcoholic steatohepatitis (NASH). It has been demonstrated that total circulating EVs and hepatocyte-derived EVs are elevated in male mice with diet-induced NASH. How hepatocyte-derived EVs change over time and other cellular sources of EVs in NASH have not been determined. Our objective was to define the quantitative evolution of hepatocyte-derived, macrophage-derived, neutrophil-derived, and platelet-derived EVs in male and female mice with dietary NASH. Fluorescently labeled antibodies and a nanoscale flow cytometer were used to detect plasma levels of EVs. Asialoglycoprotein receptor 1 (ASGR1) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1) are markers of hepatocyte-derived EVs; galectin 3 is a marker of macrophage-derived EVs; common epitope on lymphocyte antigen 6 complex, locus G/C1 (Ly-6G and Ly-6C) is a marker of neutrophil-derived EVs; and clusters of differentiation 61 (CD61) is a marker of platelet-derived EVs. Nonalcoholic fatty liver disease activity score (NAS) was calculated using hematoxylin and eosin-stained liver sections, and magnetic resonance imaging (MRI) was used for measurement of the fat fraction and elastography. Hepatocyte-derived EVs increased in both male and female mice at 12 and 10 weeks of feeding, respectively, and remained elevated at 24 weeks in both male and female mice and at 48 weeks in male mice and 36 weeks in female mice. Macrophage- and neutrophil-derived EVs were significantly elevated at 24 weeks of dietary feeding concomitant with the histologic presence of inflammatory foci in the liver. In fat-, fructose-, and cholesterol- (FFC) fed male mice, platelet-derived EVs were elevated at 12, 24, and 48 weeks, whereas in female mice, platelet derived EVs were significantly elevated at 24 weeks. Hepatocyte-, macrophage- and neutrophil-derived EVs correlated well with the histologic NAS. Conclusion: Circulating cell-type-specific EVs may be a novel biomarker for NASH diagnosis and longitudinal follow up.

Prediction of nonalcoholic fatty liver disease (NAFLD) activity score (NAS) with multiparametric hepatic magnetic resonance imaging and elastography.

OBJECTIVES: To investigate the use of MR elastography (MRE)-derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. METHODS: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. RESULTS: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between "not-NASH" and "definite-NASH." "Borderline-NASH" prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. CONCLUSION: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. KEY POINTS: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80-92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Stiffness and Beyond: What MR Elastography Can Tell Us About Brain Structure and Function Under Physiologic and Pathologic Conditions.

Brain magnetic resonance elastography (MRE) was developed on the basis of a desire to "palpate by imaging" and is becoming a powerful tool in the investigation of neurophysiological and neuropathological states. Measurements are acquired with a specialized MR phase-contrast pulse sequence that can detect tissue motion in response to an applied external or internal excitation. The tissue viscoelasticity is then reconstructed from the measured displacement. Quantitative characterization of brain viscoelastic behaviors provides us an insight into the brain structure and function by assessing the mechanical rigidity, viscosity, friction, and connectivity of brain tissues. Changes in these features are associated with inflammation, demyelination, and neurodegeneration that contribute to brain disease onset and progression. Here, we review the basic principles and limitations of brain MRE and summarize its current neuroanatomical studies and clinical applications to the most common neurosurgical and neurodegenerative disorders, including intracranial tumors, dementia, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury. Going forward, further improvement in acquisition techniques, stable inverse reconstruction algorithms, and advanced numerical, physical, and preclinical validation models is needed to increase the utility of brain MRE in both research and clinical applications.

In vivo characterization of 3D skull and brain motion during dynamic head vibration using magnetic resonance elastography.

PURPOSE: To introduce newly developed MR elastography (MRE)-based dual-saturation imaging and dual-sensitivity motion encoding schemes to directly measure in vivo skull-brain motion, and to study the skull-brain coupling in volunteers with these approaches. METHODS: Six volunteers were scanned with a high-performance compact 3T-MRI scanner. The skull-brain MRE images were obtained with a dual-saturation imaging where the skull and brain motion were acquired with fat- and water-suppression scans, respectively. A dual-sensitivity motion encoding scheme was applied to estimate the heavily wrapped phase in skull by the simultaneous acquisition of both low- and high-sensitivity phase during a single MRE exam. The low-sensitivity phase was used to guide unwrapping of the high-sensitivity phase. The amplitude and temporal phase delay of the rigid-body motion between the skull and brain was measured, and the skull-brain interface was visualized by slip interface imaging (SII). RESULTS: Both skull and brain motion can be successfully acquired and unwrapped. The skull-brain motion analysis demonstrated the motion transmission from the skull to the brain is attenuated in amplitude and delayed. However, this attenuation (%) and delay (rad) were considerably greater with rotation (59 ± 7%, 0.68 ± 0.14 rad) than with translation (92 ± 5%, 0.04 ± 0.02 rad). With SII the skull-brain slip interface was not completely evident, and the slip pattern was spatially heterogeneous. CONCLUSION: This study provides a framework for acquiring in vivo voxel-based skull and brain displacement using MRE that can be used to characterize the skull-brain coupling system for understanding of mechanical brain protection mechanisms, which has potential to facilitate risk management for future injury.

Pancreatic stiffness response to an oral glucose load in obese adults measured by magnetic resonance elastography.

BACKGROUND: To test the feasibility of magnetic resonance elastography (MRE) for assessing changes in pancreatic stiffness of obese adults administered an oral glucose load. METHODS: MRE scans were performed on 21 asymptomatic obese volunteers (BMI ≥ 27 kg/m2) before and after receiving a 75-g oral glucose load, and repeated in 7 days without a glucose load. Shear waves at 40 and 60 Hz were introduced into the upper abdomen by a pneumatic drum driver (diameter of 12 cm). Two radiologists subjectively graded the overall quality of the wave images of the pancreas using a scale from 1 to 4, in which suboptimal image quality was considered to be scores of 1 and 2. RESULTS: Good inter-observer agreement was found for image quality at both frequencies (kappa = 0.805 for 40 Hz and 0.762 for 60 Hz). The median overall image quality score was significantly higher in 40 Hz than that of 60 Hz (4 versus 2). At 40 Hz, pancreatic stiffness in response to oral glucose had a decrease of 6.7% (pre vs post: 1.17 ±â€¯0.13 kPa vs 1.08 ±â€¯0.12 kPa; P < 0.001), whereas the change in stiffness was not significant at 60 Hz (pre vs post: 2.01 ±â€¯0.21 kPa vs 2.02 ±â€¯0.24 kPa; P = 0.695). Excellent intersession agreement was found for MRE acquisitions at 40 Hz with an overall intraclass correlation coefficient = 0.947 (95% confidence interval: 0.913-0.967). CONCLUSION: MRE at 40 Hz provides good-quality wave images and high sensitivity to changes in the mechanical properties of pancreatic tissue in obese volunteers after an oral glucose load.