Quantifying uniaxial prestress and waveguide effects on dynamic elastography estimates for a cylindrical rod.

Dynamic elastography attempts to reconstruct quantitative maps of the viscoelastic properties of materials by noninvasively measuring mechanical wave motion in them. The target motion is typically transversely-polarized relative to the wave propagation direction, such as bulk shear wave motion. In addition to neglecting waveguide effects caused by small lengths in one dimension or more, many reconstruction strategies also ignore nonzero, non-isotropic static preloads. Significant anisotropic prestress is inherent to the functional role of some biological materials of interest, which also are small in size relative to shear wavelengths in one or more dimensions. A cylindrically shaped polymer structure with isotropic material properties is statically elongated along its axis while its response to circumferentially-, axially-, and radially-polarized vibratory excitation is measured using optical or magnetic resonance elastography. Computational finite element simulations augment and aid in the interpretation of experimental measurements. We examine the interplay between uniaxial prestress and waveguide effects. A coordinate transformation approach previously used to simplify the reconstruction of un-prestressed transversely isotropic material properties based on elastography measurements is adapted with partial success to estimate material viscoelastic properties and prestress conditions without requiring advanced knowledge of either.

Longitudinal study of sub-regional cerebral viscoelastic properties of 5XFAD Alzheimer's disease mice using multifrequency MR elastography.

PURPOSE: To study sub-regional, longitudinal changes occurring inside brains of 5XFAD mice, an Alzheimer's disease (AD) model, based on viscoelastic parameters derived using MR elastography and their spatial variation. METHODS: Female 5XFAD and non-transgenic B6SJLF1/J mice as controls (n = 9 for both groups) were used for the study. Scans were performed inside a 9.4T preclinical MRI scanner using SampLe Interval Modulation-magnetic resonance elastography (SLIM-MRE). Experiments were performed at ages 2, 4, and 6 mo, and by using three actuation frequencies: 900, 1000, and 1100 Hz. Multifrequency dual elasto-visco (MDEV) reconstruction was used to combine 3D multifrequency MRE data and calculate magnitude G∗ , and phase angle φ, of the complex shear modulus G∗ . Mean values were measured for the overall brain and sub-regions associated with the early onset of AD, to check for the effect of aging and mouse model. Spatial coefficient of variation (CV) of both parameters across different age-groups were analyzed. RESULTS: G∗ and φ values reduced with age for overall brain in 5XFAD mice with significant difference in mean G∗ between 5XFAD and control mice at 6 mo (P = .029). Analyzing values from the hippocampal region highlighted drop in mean G∗ and φ values. The CV of G∗ inside hippocampus enabled differentiation at 4 mo with it being significantly lower in 5XFAD mice (P = .0007). CONCLUSION: Multifrequency 3D MRE revealed longitudinal viscoelastic changes in 5XFAD mice and the CV of G∗ in brain sub-regions may qualify as biomarker for early diagnosis of AD.

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T.

PURPOSE: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. METHODS: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. RESULTS: The mean G' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. CONCLUSION: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method.

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis.

OBJECTIVES: To determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen. METHODS: This prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness. RESULTS: For compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels. CONCLUSION: Tomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine. KEY POINTS: • Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. • Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis. • Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

Concurrent 3D acquisition of diffusion tensor imaging and magnetic resonance elastography displacement data (DTI-MRE): Theory and in vivo application.

PURPOSE: To introduce a newly developed technique (DTI-MRE) for the simultaneous acquisition of diffusion tensor imaging (DTI) and 3D-vector field magnetic resonance elastography (MRE) data, and to demonstrate its feasibility when applied in vivo to the mouse brain. METHODS: In DTI-MRE, simultaneous encoding is achieved by using a series of diffusion/motion-sensitizing gradients (dMSGs) with specific timing and directions. By adjusting the duration of the dMSGs with the diffusion time and with the mechanical vibration frequency, the shear wave motion and diffusion are encoded into the MR phase and MR magnitude signals, respectively. The dMSGs are applied in a noncollinear and noncoplanar manner that optimizes the capture of both the DTI signal attenuation and the three-dimensional MRE displacements. In this work, the feasibility of the DTI-MRE technique was demonstrated on in vivo mouse brains (n=3) using a 9.4T animal MRI scanner. The DTI-MRE derived parameters (MD, mean diffusivity; FA, fractional anisotropy; MRE displacement fields; and shear modulus |G|) were compared with those acquired using conventional, separate MRE and diffusion methods. RESULTS: The averaged (MD, FA, and |G|) values for three mice are (0.580 ± 0.050 µm2 /ms, 0.43 ± 0.02, and 4.80 ± 0.06 kPa) and (0.583 ± 0.035 µm2 /ms, 0.46 ± 0.02, and 4.91 ± 0.19 kPa) for DTI-MRE, and conventional DTI and 3D-vector field MRE measurements, respectively. All derived parameters (MD, FA, |G|, and displacement) obtained using the combined DTI-MRE method and conventional methods were significantly correlated with P < 0.05. CONCLUSION: Simultaneous acquisition of DTI and 3D-vector field MRE is feasible in vivo and reduces the scan time by up to 50% compared with conventional, separate acquisitions, while providing an immediate co-registration of maps of diffusion properties and stiffness. Magn Reson Med 77:273-284, 2017. © 2016 Wiley Periodicals, Inc.

Cardiac MR elastography of the mouse: Initial results.

PURPOSE: Many cardiovascular diseases are associated with abnormal function of myocardial contractility or dilatability, which is related to elasticity changes of the myocardium over the cardiac cycle. The mouse is a common animal model in studies of the progression of various cardiomyopathies. We introduce a novel noninvasive approach using microscopic scale MR elastography (MRE) to measure the myocardium stiffness change during the cardiac cycle on a mouse model. METHODS: A harmonic mechanical wave of 400 Hz was introduced into the mouse body. An electrocardiograph-gated and respiratory-gated fractional encoding cine-MRE pulse sequence was applied to encode the resulting oscillatory motion on a short-axis slice of the heart. Five healthy mice (age range, 3-13.5 mo) were examined. The weighted summation effective stiffness of the left ventricle wall during the cardiac cycle was estimated. RESULTS: The ratio of stiffness at end diastole and end systole was 0.5-0.67. Additionally, variation in shear wave amplitude in the left ventricle wall throughout the cardiac cycle was measured and found to correlate with estimates of stiffness variation. CONCLUSION: This study demonstrates the feasibility of implementing cardiac MRE on a mouse model. Magn Reson Med 76:1879-1886, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous, multidirectional acquisition of displacement fields in magnetic resonance elastography of the in vivo human brain.

BACKGROUND: To implement a multidirectional motion encoding scheme for magnetic resonance elastography (MRE) of the human brain with reduced acquisition time, and investigate its performance relative to a conventional MRE scheme. METHODS: The sample interval modulation (SLIM) scheme was implemented in a multishot, variable density spiral MRE sequence. The brains of seven healthy volunteers were investigated with both SLIM-MRE and conventional MRE acquisitions in a single imaging session on a clinical 3 Tesla MRI scanner with 50 Hz vibration. Following extraction of displacement fields, complex shear modulus property maps were estimated for each encoding concept. RESULTS: The SLIM-MRE and conventional MRE acquisitions produced deformation fields that were nearly identical and exhibited an average correlation coefficient of 0.95 (all p < 0.05). Average properties of white matter differed between the two acquisitions by less than 5% for all volunteers, which is better than reproducibility estimates for conventional MRE alone. CONCLUSION: The use of SLIM provides very similar quantitative property estimates compared with the conventional MRE encoding scheme. The SLIM acquisition is 2.5 times faster than the conventional acquisition, and may speed the adoption of MRE in clinical settings.

Simultaneous MR elastography and diffusion acquisitions: diffusion-MRE (dMRE).

PURPOSE: To present a new technique for concurrent MR elastography (MRE) and diffusion MRI: diffusion-MRE (dMRE). METHODS: In dMRE, shear wave motion and MR signal decay due to diffusion are encoded into the phase and magnitude components of the MR signal by using a pair of bipolar gradients for both motion-sensitization and diffusion encoding. The pulse sequence timing is adjusted so that the bipolar gradients are sensitive to both coherent and incoherent intravoxel motions. The shape, number, and duration of the gradient lobes can be adjusted to provide flexibility and encoding efficiency. In this proof-of-concept study, dMRE was validated using a tissue phantom composed of a gel bead embedded in a hydrated mixture of agarose and gelatin. The apparent diffusion coefficient (ADC) and shear stiffness measured using dMRE were compared with results obtained from separate, conventional spin-echo (SE) diffusion and SE-MRE acquisitions. RESULTS: The averaged ADC values (n = 3) for selected ROIs in the beads were (1.75 ± 0.16) µm(2) /ms and (1.74 ± 0.16) µm(2) /ms for SE-diffusion and dMRE methods, respectively. The corresponding shear stiffness values in the beads were (2.45 ± 0.23) kPa and (2.42 ± 0.20) kPa. CONCLUSION: Simultaneous MRE and diffusion acquisition is feasible and can be implemented with no observable interference between the two methods.

1-Norm waveform analysis for MR elastography-based quantification of inhomogeneity: Effects of the freeze-thaw cycle and Alzheimer's disease.

BACKGROUND: Despite its success in the mechanical characterization of biological tissues, magnetic resonance elastography (MRE) uses ill-posed wave inversions to estimate tissue stiffness. 1-Norm has been recently introduced as a mathematical measure for the scattering of mechanical waves due to inhomogeneities based on an analysis of the delineated contours of wave displacement. PURPOSE: To investigate 1-Norm as an MRE-based quantitative biomarker of mechanical inhomogeneities arising from microscopic structural tissue alterations caused by the freeze-thaw cycle (FTC) or Alzheimer's disease (AD). METHODS: In this proof-of-concept study, we prospectively investigated excised porcine kidney (n = 6), liver (n = 6), and muscle (n = 6) before vs. after the FTC at 500-2000 Hz and excised murine brain of healthy controls (n = 3) vs. 5xFAD species with AD (n = 3) at 1200-1800 Hz using 0.5 T tabletop MRE. 1-Norm analysis was compared with conventional wave inversion. RESULTS: While the FTC reduced both stiffness and inhomogeneity in kidney, liver, and muscle tissue, AD led to lower brain stiffness but more pronounced mechanical inhomogeneity. CONCLUSION: Our preliminary results show that 1-Norm is sensitive to tissue mechanical inhomogeneity due to FTC and AD without relying on ill-posed wave inversion techniques. 1-Norm has the potential to be used as an MRE-based diagnostic biomarker independent of stiffness to characterize abnormal conditions that involve changes in tissue mechanical inhomogeneity.

In vivo measurement of volumetric strain in the human brain induced by arterial pulsation and harmonic waves.

Motion-sensitive phase contrast magnetic resonance imaging and magnetic resonance elastography are applied for the measurement of volumetric strain and tissue compressibility in human brain. Volumetric strain calculated by the divergence operator using a biphasic effective-medium model is related to dilatation and compression of fluid spaces during harmonic stimulation of the head or during intracranial passage of the arterial pulse wave. In six volunteers, phase contrast magnetic resonance imaging showed that the central cerebrum expands at arterial pulse wave to strain values of (2.8 ± 1.9)·10(-4). The evolution of volumetric strain agrees well with the magnitude of the harmonic divergence measured in eight volunteers by magnetic resonance elastography using external activation of 25 Hz vibration frequency. Intracranial volumetric strain was proven sensitive to venous pressure altered by abdominal muscle contraction. In eight volunteers, an increase in volumetric strain due to abdominal muscle contraction of approximately 45% was observed (P = 0.0001). The corresponding compression modulus in the range of 9.5-13.5 kPa demonstrated that the compressibility of brain tissue at 25 Hz stimulation is much higher than that of water. This pilot study provides the background for compression-sensitive magnetic resonance imaging with or without external head stimulation. Volumetric strain may be sensitive to fluid flow abnormalities or pressure imbalances between vasculature and parenchyma as seen in hydrocephalus.

Decoupling Uniaxial Tensile Prestress and Waveguide Effects From Estimates of the Complex Shear Modulus in a Cylindrical Structure Using Transverse-Polarized Dynamic Elastography.

Dynamic elastography, whether based on magnetic resonance, ultrasound, or optical modalities, attempts to reconstruct quantitative maps of the viscoelastic properties of biological tissue, properties altered by disease and injury, by noninvasively measuring mechanical wave motion in the tissue. Most reconstruction strategies that have been developed neglect boundary conditions, including quasi-static tensile or compressive loading resulting in a nonzero prestress. Significant prestress is inherent to the functional role of some biological tissues currently being studied using elastography, such as skeletal and cardiac muscle, arterial walls, and the cornea. In the present article a configuration, inspired by muscle elastography but generalizable to other applications, is analytically and experimentally studied. A hyperelastic polymer phantom cylinder is statically elongated in the axial direction while its response to transverse-polarized vibratory excitation is measured. We examine the interplay between uniaxial prestress and waveguide effects in this muscle-like tissue phantom using computational finite element simulations and magnetic resonance elastography measurements. Finite deformations caused by prestress coupled with waveguide effects lead to results that are predicted by a coordinate transformation approach that has been previously used to simplify reconstruction of anisotropic properties using elastography. Here, the approach estimates material viscoelastic properties that are independent of the nonhomogeneous prestress conditions without requiring advanced knowledge of those stress conditions.

Vibration-synchronized magnetic resonance imaging for the detection of myocardial elasticity changes.

Vibration synchronized magnetic resonance imaging of harmonically oscillating tissue interfaces is proposed for cardiac magnetic resonance elastography. The new approach exploits cardiac triggered cine imaging synchronized with extrinsic harmonic stimulation (f = 22.83 Hz) to display oscillatory tissue deformations in magnitude images. Oscillations are analyzed by intensity threshold-based image processing to track wave amplitude variations over the cardiac cycle. In agreement to literature data, results in 10 volunteers showed that endocardial wave amplitudes during systole (0.13 ± 0.07 mm) were significantly lower than during diastole (0.34 ± 0.14 mm, P < 0.001). Wave amplitudes were found to decrease 117 ± 40 ms before myocardial contraction and to increase 75 ± 31 ms before myocardial relaxation. Vibration synchronized magnetic resonance imaging improves the temporal resolution of magnetic resonance elastography as it overcomes the use of extra motion encoding gradients, is less sensitive to susceptibility artifacts, and does not suffer from dynamic range constraints frequently encountered in phase-based magnetic resonance elastography.

Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus.

INTRODUCTION: Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. METHODS: In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 ± 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters µ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue. RESULTS: The viscoelastic parameters µ and α were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, α increased after shunt placement (P < 0.001) to almost normal values whereas µ remained symptomatically low. CONCLUSION: The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded.

Tabletop MR elastography for investigating effects of the freeze-thaw cycle on the mechanical properties of biological tissues.

PURPOSE: We aimed at characterizing the effects of the freeze-thaw cycle (FTC) on ex vivo specimens of porcine muscle, liver, kidney, and brain using tabletop magnetic resonance elastography (MRE) combined with rheological modeling. While frozen tissue banks potentially facilitate access to large amounts of well-preserved biospecimens, the impact of the FTC on their viscoelastic properties remains elusive. METHODS: In this proof-of-concept study, fresh specimens from porcine lumbar muscle (n = 6), liver (n = 6), kidney (n = 6), and brain (n = 6) were examined before and after the FTC using 0.5T tabletop MRE at 500 Hz, 1000 Hz, 1500 Hz, and 2000 Hz. Seven standard rheological models (Maxwell, Springpot, Voigt, Zener, Jeffrey, fractional Voigt, fractional Zener) were employed to calculate frequency independent viscoelastic parameters. RESULTS: The Zener rheological model showed the best fit quality for tissues before and after FTC in the investigated frequency range. Global rheological behavior after the FTC was softer for all tissues. Differences in mechanical parameters between tissues were preserved after the FTC and showed similar trends as before the FTC. Moreover, rheological fit quality improved after the FTC - a result that will be beneficial in investigating frozen tissue bank samples. CONCLUSION: Multifrequency tabletop MRE allows rheological characterization of tissue samples before and after the FTC. Our results encourage further biomechanical characterization of frozen tissue bank samples, which may provide valuable information on the diagnostic potential of elastographic methods.

Investigating the heterogeneity of viscoelastic properties in prostate cancer using MR elastography at 9.4T in fresh prostatectomy specimens.

PURPOSE: To quantify the heterogeneity of viscoelastic tissue properties in prostatectomy specimens from men with prostate cancer (PC) using MR elastography (MRE) with histopathology as reference. METHODS: Twelve fresh prostatectomy specimens were examined in a preclinical 9.4T MRI scanner. Maps of the complex shear modulus (|G*| in kPa) with its real and imaginary part (G' and G" in kPa) were calculated at 500 Hz. Prostates were divided into 12 segments for segment-wise measurement of viscoelastic properties and histopathology. Coefficients of variation (CVs in %) were calculated for quantification of heterogeneity. RESULTS: Group-averaged values of cancerous vs. benign segments were significantly increased: |G*| of 12.13 kPa vs. 6.14 kPa, G' of 10.84 kPa vs. 5.44 kPa and G" of 5.45 kPa vs. 2.92 kPa, all p < 0.001. In contrast, CVs were significantly increased for benign segments: 23.59% vs. 26.32% (p = 0.014) for |G*|, 27.05% vs. 37.84% (p < 0.003) for G', and 36.51% vs. 50.37% (p = 0.008) for G". DISCUSSION: PC is characterized by a stiff yet homogeneous biomechanical signature, which may be due to the unique nondestructive growth pattern of PC with intervening stroma, providing a rigid scaffold in the affected area. In turn, increased heterogeneity in benign prostate segments may be attributable to the presence of different prostate zones with involvement by specific nonmalignant pathology.

Optical coherence elastography for assessing the influence of intraocular pressure on elastic wave dispersion in the cornea.

The cornea is a highly specialized organ that relies on its mechanical stiffness to maintain its aspheric geometry and refractive power, and corneal diseases such as keratoconus have been linked to abnormal tissue stiffness and biomechanics. Dynamic optical coherence elastography (OCE) is a clinically promising non-contact and non-destructive imaging technique that can provide measurements of corneal tissue stiffness directly in vivo. The method relies on the concepts of elastography where shear waves are generated and imaged within a tissue to obtain mechanical properties such as tissue stiffness. The accuracy of OCE-based measurements is ultimately dependent on the mathematical theories used to model wave behavior in the tissue of interest. In the cornea, elastic waves propagate as guided wave modes which are highly dispersive and can be mathematically complex to model. While recent groups have developed detailed theories for estimating corneal tissue properties from guided wave behavior, the effects of intraocular pressure (IOP)-induced prestress have not yet been considered. It is known that prestress alone can strongly influence wave behavior, in addition to the associated non-linear changes in tissue properties. This present study shows that failure to account for the effects of prestress may result in overestimations of the corneal shear moduli, particularly at high IOPs. We first examined the potential effects of IOP and IOP-induced prestress using a combination of approximate mathematical theories describing wave behavior in thin plates with observations made from data published in the OCE literature. Through wave dispersion analysis, we deduce that IOP introduces a tensile hoop stress and may also influence an elastic foundational effect that were observable in the low-frequency components of the dispersion curves. These effects were incorporated into recently developed models of wave behavior in nearly incompressible, transversely isotropic (NITI) materials. Fitting of the modified NITI model with ex vivo porcine corneal data demonstrated that incorporation of the effects of IOP resulted in reduced estimates of corneal shear moduli. We believe this demonstrates that overestimation of corneal stiffness occurs if IOP is not taken into consideration. Our work may be helpful in separating inherent corneal stiffness properties that are independent of IOP; changes in these properties and in IOP are distinct, clinically relevant issues that affect the cornea health.

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus.

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease-related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (µ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25-62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease-related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH-related ventricular expansions and clinical symptoms.

Concurrent OCT and OCT angiography of retinal neurovascular degeneration in the 5XFAD Alzheimer's disease mice.

Significance: As one part of the central nervous system, the retina manifests neurovascular defects in Alzheimer's disease (AD). Quantitative imaging of retinal neurovascular abnormalities may promise a new method for early diagnosis and treatment assessment of AD. Previous imaging studies of transgenic AD mouse models have been limited to the central part of the retina. Given that the pathological hallmarks of AD frequently appear in different peripheral quadrants, a comprehensive regional investigation is needed for a better understanding of the retinal degeneration associated with AD-like pathology. Aim: We aim to demonstrate concurrent optical coherence tomography (OCT) and OCT angiography (OCTA) of retinal neuronal and vascular abnormalities in the 5XFAD mouse model and to investigate region-specific retinal degeneration. Approach: A custom-built OCT system was used for retinal imaging. Retinal thickness, vessel width, and vessel density were quantitatively measured. The artery and vein (AV) were classified for differential AV analysis, and trilaminar vascular plexuses were segmented for depth-resolved density measurement. Results: It was observed that inner and outer retinal thicknesses were explicitly reduced in the dorsal and temporal quadrants, respectively, in 5XFAD mice. A significant arterial narrowing in 5XFAD mice was also observed. Moreover, overall capillary density consistently showed a decreasing trend in 5XFAD mice, but regional specificity was not identified. Conclusions: Quadrant- and layer-specific neurovascular degeneration was observed in 5XFAD mice. Concurrent OCT and OCTA promise a noninvasive method for quantitative monitoring of AD progression and treatment assessment.

Measuring viscoelastic parameters in Magnetic Resonance Elastography: a comparison at high and low magnetic field intensity.

Magnetic Resonance Elastography (MRE) is a non-invasive imaging technique which involves motion-encoding MRI for the estimation of the shear viscoelastic properties of soft tissues through the study of shear wave propagation. The technique has been found informative for disease diagnosis, as well as for monitoring of the effects of therapies. The development of MRE and its validation have been supported by the use of tissue-mimicking phantoms. In this paper we present our new MRE protocol using a low magnetic field tabletop MRI device at 0.5 T and sinusoidal uniaxial excitation in a geometrical focusing condition. Results obtained for gelatin are compared to those previously obtained using high magnetic field MRE at 11.7 T. A multi-frequency investigation is also provided via a comparison of commonly used rheological models: Maxwell, Springpot, Voigt, Zener, Jeffrey, fractional Voigt and fractional Zener. Complex shear modulus values were comparable when processed from images acquired with the tabletop low field scanner and the high field scanner. This study serves as a validation of the presented tabletop MRE protocol and paves the way for MRE experiments on ex-vivo tissue samples in both normal and pathological conditions.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis vs. viral hepatitis assessed by MR elastography.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis (PSC) in comparison to viral hepatitis was assessed as a potential new biomarker using MR elastography (MRE). In this proof-of-concept study, we hypothesized a rather increased heterogeneity in PSC and a rather homogeneous distribution in viral hepatitis. Forty-six consecutive subjects (PSC: n = 20, viral hepatitis: n = 26) were prospectively enrolled between July 2014 and April 2017. Subjects underwent multifrequency MRE (1.5 T) using drive frequencies of 35-60 Hz and generating shear-wave speed (SWS in m/s) maps as a surrogate of stiffness. The coefficient of variation (CV in %) was determined to quantify fibrosis heterogeneity. Mean SWS and CV were 1.70 m/s and 21% for PSC, and 1.84 m/s and 18% for viral hepatitis. Fibrosis heterogeneity was significantly increased for PSC (P = 0.04) while no difference was found for SWS of PSC and viral hepatitis (P = 0.17). Global hepatic stiffness was similar in PSC and viral hepatitis groups, but spatial heterogeneity may reveal spatial patterns of stiffness changes towards enhanced biophysics-based diagnosis by MRI.