MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS

A novel MRE adaptive seismic isolator using curvelet transform identification

Magnetorheological elastomeric (MRE) material is a novel type of material that can adap-tively change the rheological property rapidly, continuously, and reversibly when subjected to real-time external magnetic field. These new type of MRE materials can be developed by employing various schemes, for instance by mixing carbon nanotubes or acetone contents during the curing process which produces functionalized multiwall carbon nanotubes (MWCNTs). In order to study the mechanical and magnetic effects of this material, for potential application in seismic isolation, in this paper, different mathematical models of magnetorheological elastomers are analyzed and modified based on the reported studies on traditional magnetorheological elastomer. In this regard, a new feature identification method, via utilizing curvelet analysis, is proposed to make a multi-scale constituent analysis and subsequently a comparison between magnetorheological elastomer nanocomposite and traditional magnetorheological elastomers in a microscopic level. Furthermore, by using this “smart” material as the laminated core structure of an adaptive base isolation system, magnetic circuit analysis is numerically conducted for both complete and incomplete designs. Magnetic distribution of different laminated magnetorheological layers is discussed when the isolator is under compressive preloading and lateral shear loading. For a proof of concept study, a scaled building structure is established with the proposed isolation device. The dynamic performance of this isolated structure is analyzed by using a newly developed reaching law sliding mode control and Radial Basis Function (RBF) adaptive sliding mode control schemes. Transmissibility of the structural system is evaluated to assess its adaptability, controllability and nonlinearity. As the findings in this study show, it is promising that the structure can achieve its optimal and adaptive performance by designing an isolator with this adaptive material whose magnetic and mechanical properties are functionally enhanced as compared with traditional isolation devices. The adaptive control algorithm presented in this research can transiently suppress and protect the structure against non-stationary disturbances in the real time

비알코올성 지방간 환자에서 정량적 초음파 영상 지표의 개발 및 지방간 진단능 평가

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 이정민.Purpose: To investigate the diagnostic performance of quantitative ultrasound (QUS) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Materials and methods: In this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. Participants underwent ultrasound (US) examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, attenuation coefficient (AC) at tissue attenuation imaging (TAI) and scatter-distribution coefficient (SC) at tissue scatter-distribution imaging (TSI) were measured. Correlation between the QUS parameters (AC and SC) and MRI-PDFF was evaluated using Pearson correlation coefficients. Diagnostic performance of AC at TAI and SC at TSI for detecting hepatic steatosis (MRI-PDFF ≥5%) and hepatic fat content ≥10% (MRI-PDFF ≥10%) were assessed by receiver operating characteristic (ROC) analysis. Significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis. Results: Participants were classified with MRI-PDFF <5% (n=38), 5-10% (n=23), and ≥10% (n=59). AC at TAI and SC at TSI were significantly correlated with MRI-PDFF (r=0.659 and 0.727, P<0.001 for both). For detecting hepatic steatosis and hepatic fat content ≥10%, the area under the ROC curves (AUCs) of AC at TAI were 0.861 (95% confidence interval [CI]: 0.786-0.918) and 0.835 (95% CI: 0.757-0.897), and of SC at TSI were 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972), respectively. In multivariate linear regression analysis, MRI-PDFF was an independent determinant of AC at TAI and SC at TSI. Conclusion: AC at TAI and SC at TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.배경 및 목적: 본 연구에서는 비알코올성 지방간 환자에서 지방간 정도를 평가하기 위한 정량적 초음파 지표를 개발하고, 자기공명영상 양성자밀도 지방분율을 기준으로 하여 정량적 초음파 지표의 지방간 진단능을 평가하고자 한다. 재료 및 방법: 본 단일센터 전향적 연구에서는 2019년 3월부터 2020년 1월까지 임상적으로 비알코올성 지방간이 의심되는 환자와 간이식 공여자를 포함한 총 120명의 참가자가 등록되었다. 참가자들은 무선주파수 (radiofrequency, RF) 데이터를 얻기 위한 초음파 검사와 자기공명영상 양성자밀도 지방분율(Magnetic resonance imaging proton density fat fraction, MRI-PDFF) 검사를 시행하였다. 초음파 RF 데이터를 분석하여, 조직감쇠영상(tissue attenuation imaging, TAI)에서의 감쇠계수 (attenuation coefficient, AC)와 조직 산란분포 영상(tissue scatter-distribution imaging, TSI)에서의 산란분포계수 (scatter-distribution coefficient, SC)를 획득하였다. 이 두 정량적 초음파 지표 (AC, SC)와 자기공명영상 양성자밀도 지방분율(MRI-PDFF) 사이의 연관성을 피어슨 상관계수를 통해 분석하였다. 정량적 초음파 지표들이 MRI-PDFF ≥5% 와 MRI-PDFF ≥10%의 지방간을 진단하는 진단능을 Receiver operating characteristics (ROC) 분석을 통해 확인하였다. 또한, 다변량 회귀분석(multivariate linear regression analysis)을 통해, 두 정량적 초음파 지표에 영향을 주는 임상 또는 영상적 지표를 확인하였다. 결과: 참가자는 지방간 정도에 따라 세 단계로 구분되었다 (MRI-PDFF <5% (n=38), 5-10% (n=23), and ≥10% (n=59)). 감쇠계수 (AC at TAI)와 산란분포계수 (SC at TSI)는 자기공명영상 양성자밀도 지방분율과 강한 상관관게를 보였다 (r=0.659 and 0.727, P<0.001 for both). 지방간 유무 진단 (MRI-PDFF ≥5%)과 MRI-PDFF ≥10%의 지방간진단에 있어 감쇠계수의 진단능은 0.861 (95% confidence interval [CI]: 0.786-0.918) 과 0.835 (95% CI: 0.757-0.897)이었고, 산란분포계수의 진단능은 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972) 이었다. 다변량회귀분석에서 지방분율이 정량적 초음파 지표와 연관성을 보이는 유일한 독립적인 인자로 확인되었다. 결론: 본 연구에서 감쇠계수 (AC at TAI)와 산란분포계수 (SC at TSI)는 자기공명영상 양성자 지방분율과 높은 상관성을 보였고, 지방간의 진단과 그 정도를 확인하는데 있어 높은 진단능을 보였다.Abstract -----------------------1 Contents -----------------------3 List of Tables -----------------4 List of Figures -----------------5 Introduction -----------------6 I. Pilot study -----------------8 Materials and Methods ---- 8 Results ----------------------13 II. Main study ----------------15 Materials and Methods --- 15 Results ----------------------22 Discussion ----------------25 References ----------------30 Tables ----------------------35 Figures ----------------------43 Appendix --------------- 46 Abstract in Korean --------- 49Docto

Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish

Purpose: The zebrafish (Danio rerio) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness of the role of biomechanical properties in tumor progression and neuronal development has led to an increasing interest in the noninvasive mapping of the viscoelastic properties of zebrafish by elastography methods applicable to bulky and nontranslucent tissues. Methods: Microscopic multifrequency MR elastography is introduced for mapping shear wave speed (SWS) and loss angle (φ) as markers of stiffness and viscosity of muscle, brain, and neuroblastoma tumors in postmortem zebrafish with 60 µm in-plane resolution. Experiments were performed in a 7 Tesla MR scanner at 1, 1.2, and 1.4 kHz driving frequencies. Results: Detailed zebrafish viscoelasticity maps revealed that the midbrain region (SWS = 3.1 ± 0.7 m/s, φ = 1.2 ± 0.3 radian [rad]) was stiffer and less viscous than telencephalon (SWS = 2.6 ± 0. 5 m/s, φ = 1.4 ± 0.2 rad) and optic tectum (SWS = 2.6 ± 0.5 m/s, φ = 1.3 ± 0.4 rad), whereas the cerebellum (SWS = 2.9 ± 0.6 m/s, φ = 0.9 ± 0.4 rad) was stiffer but less viscous than both (all p < .05). Overall, brain tissue (SWS = 2.9 ± 0.4 m/s, φ = 1.2 ± 0.2 rad) had similar stiffness but lower viscosity values than muscle tissue (SWS = 2.9 ± 0.5 m/s, φ = 1.4 ± 0.2 rad), whereas neuroblastoma (SWS = 2.4 ± 0.3 m/s, φ = 0.7 ± 0.1 rad, all p < .05) was the softest and least viscous tissue. Conclusion: Microscopic multifrequency MR elastography-generated maps of zebrafish show many details of viscoelasticity and resolve tissue regions, of great interest in neuromechanical and oncological research and for which our study provides first reference values

Mechanical stiffness and anisotropy measured by MRE during brain development in the minipig

The relationship between brain development and mechanical properties of brain tissue is important, but remains incompletely understood, in part due to the challenges in measuring these properties longitudinally over time. In addition, white matter, which is composed of aligned, myelinated, axonal fibers, may be mechanically anisotropic. Here we use data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) to estimate anisotropic mechanical properties in six female Yucatan minipigs at ages from 3 to 6 months. Fiber direction was estimated from the principal axis of the diffusion tensor in each voxel. Harmonic shear waves in the brain were excited by three different configurations of a jaw actuator and measured using a motion-sensitive MR imaging sequence. Anisotropic mechanical properties are estimated from displacement field and fiber direction data with a finite element- based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. TI-NLI finds spatially resolved TI material properties that minimize the error between measured and simulated displacement fields. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal at all four ages. These maps show that white matter is more dissipative and anisotropic than gray matter, and reveal significant effects of brain development on brain stiffness and structural anisotropy. Changes in brain mechanical properties may be a fundamental biophysical signature of brain development

Physiology and cell biology of acupuncture observed in calcium signaling activated by acoustic shear wave

This article presents a novel model of acupuncture physiology based on cellular calcium activation by an acoustic shear wave (ASW) generated by the mechanical movement of the needle. An acupuncture needle was driven by a piezoelectric transducer at 100 Hz or below, and the ASW in human calf was imaged by magnetic resonance elastography. At the cell level, the ASW activated intracellular Ca 2+ transients and oscillations in fibroblasts and endothelial, ventricular myocytes and neuronal PC-12 cells along with frequency-amplitude tuning and memory capabilities. Monitoring in vivo mammalian experiments with ASW, enhancement of endorphin in blood plasma and blocking by Gd 3+ were observed; and increased Ca 2+ fluorescence in mouse hind leg muscle was imaged by two-photon microscopy. In contrast with traditional acupuncture models, the signal source is derived from the total acoustic energy. ASW signaling makes use of the anisotropy of elasticity of tissues as its waveguides for transmission and that cell activation is not based on the nervous system. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Changes in Liver Mechanical Properties and Water Diffusivity During Normal Pregnancy Are Driven by Cellular Hypertrophy

During pregnancy, the body's hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 ± 15%, p < 0.001), (ii) increased liver stiffness (12 ± 15%, p = 0.012), (iii) decreased viscosity (-23 ± 14%, p < 0.001), and (iv) increased water diffusivity (12 ± 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context

Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience