Waveguide effects and implications for cardiac magnetic resonance elastography: A finite element study.

Magnetic resonance elastography (MRE) is increasingly being applied to thin or small structures in which wave propagation is dominated by waveguide effects, which can substantially bias stiffness results with common processing approaches. The purpose of this work was to investigate the importance of such biases and artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries with one or more dimensions that are small relative to the shear wavelength; and (ii) a realistic cardiac geometry. Finite element models were created using simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry, and simulated displacements acquired by MRE from harmonic excitations from 60 to 220 Hz across a range of frequencies. The displacement wave fields were inverted with direct inversion of the Helmholtz equation with and without the application of bandpass filtering and/or the curl operator to the displacement field. In all geometries considered, and at all frequencies considered, strong biases and artifacts were present in inversion results when the curl operator was not applied. Bandpass filtering without the curl was not sufficient to yield accurate recovery. In the 3D geometries, strong biases and artifacts were present in 2D inversions even when the curl was applied, while only 3D inversions with application of the curl yielded accurate recovery of the complex shear modulus. These results establish that taking the curl of the wave field and performing a full 3D inversion are both necessary steps for accurate estimation of the shear modulus both in simple thin-walled or small structures and in a realistic cardiac geometry when using simple inversions that neglect the hydrostatic pressure term. In practice, sufficient wave amplitude, signal-to-noise ratio, and resolution will be required to achieve accurate results.

MR Elastography Analysis of Glioma Stiffness and IDH1-Mutation Status.

BACKGROUND AND PURPOSE: Our aim was to noninvasively evaluate gliomas with MR elastography to characterize the relationship of tumor stiffness with tumor grade and mutations in the isocitrate dehydrogenase 1 (IDH1) gene. MATERIALS AND METHODS: Tumor stiffness properties were prospectively quantified in 18 patients (mean age, 42 years; 6 women) with histologically proved gliomas using MR elastography from 2014 to 2016. Images were acquired on a 3T MR imaging unit with a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected contralateral white matter, across tumor grade, and by IDH1-mutation status. The performance of the use of tumor stiffness to predict tumor grade and IDH1 mutation was evaluated with the Wilcoxon rank sum, 1-way ANOVA, and Tukey-Kramer tests. RESULTS: Gliomas were softer than healthy brain parenchyma, 2.2 kPa compared with 3.3 kPa (P < .001), with grade IV tumors softer than grade II. Tumors with an IDH1 mutation were significantly stiffer than those with wild type IDH1, 2.5 kPa versus 1.6 kPa, respectively (P = .007). CONCLUSIONS: MR elastography demonstrated that not only were gliomas softer than normal brain but the degree of softening was directly correlated with tumor grade and IDH1-mutation status. Noninvasive determination of tumor grade and IDH1 mutation may result in improved stratification of patients for different treatment options and the evaluation of novel therapeutics. This work reports on the emerging field of "mechanogenomics": the identification of genetic features such as IDH1 mutation using intrinsic biomechanical information.

Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid.

Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients.

MR Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals. MATERIALS AND METHODS: MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20). CONCLUSIONS: This study demonstrates increased brain stiffness in patients with normal pressure hydrocephalus compared with age- and sex-matched healthy controls; these findings should motivate future studies investigating the use of MR elastography for this condition and the efficacy of shunt therapy.

Effects of advanced paternal age on trajectories of social behavior in offspring.

Our study is the first investigation of the effects of advanced paternal age (APA) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between APA and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (C57BL/6J) across postnatal development (N = 104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a de novo origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between APA, age-related changes in the paternal sperm DNA and neurodevelopmental disorders in their offspring.

Semi-automated vectorial analysis of anorectal motion by magnetic resonance defecography in healthy subjects and fecal incontinence.

BACKGROUND: Inter-observer variability limits the reproducibility of pelvic floor motion measured by magnetic resonance imaging (MRI). Our aim was to develop a semi-automated program measuring pelvic floor motion in a reproducible and refined manner. METHODS: Pelvic floor anatomy and motion during voluntary contraction (squeeze) and rectal evacuation were assessed by MRI in 64 women with fecal incontinence (FI) and 64 age-matched controls. A radiologist measured anorectal angles and anorectal junction motion. A semi-automated program did the same and also dissected anorectal motion into perpendicular vectors representing the puborectalis and other pelvic floor muscles, assessed the pubococcygeal angle, and evaluated pelvic rotation. KEY RESULTS: Manual and semi-automated measurements of anorectal junction motion (r = 0.70; P < 0.0001) during squeeze and evacuation were correlated, as were anorectal angles at rest, squeeze, and evacuation; angle change during squeeze or evacuation was less so. Semi-automated measurements of anorectal and pelvic bony motion were also reproducible within subjects. During squeeze, puborectalis injury was associated (P ≤ 0.01) with smaller puborectalis but not pelvic floor motion vectors, reflecting impaired puborectalis function. The pubococcygeal angle, reflecting posterior pelvic floor motion, was smaller during squeeze and larger during evacuation. However, pubococcygeal angles and pelvic rotation during squeeze and evacuation did not differ significantly between FI and controls. CONCLUSION & INFERENCES: This semi-automated program provides a reproducible, efficient, and refined analysis of pelvic floor motion by MRI. Puborectalis injury is independently associated with impaired motion of puborectalis, not other pelvic floor muscles in controls and women with FI.

Calculation of shear stiffness in noise dominated magnetic resonance elastography data based on principal frequency estimation.

Magnetic resonance elastography (MRE) is a non-invasive phase-contrast-based method for quantifying the shear stiffness of biological tissues. Synchronous application of a shear wave source and motion encoding gradient waveforms within the MRE pulse sequence enable visualization of the propagating shear wave throughout the medium under investigation. Encoded shear wave-induced displacements are then processed to calculate the local shear stiffness of each voxel. An important consideration in local shear stiffness estimates is that the algorithms employed typically calculate shear stiffness using relatively high signal-to-noise ratio (SNR) MRE images and have difficulties at an extremely low SNR. A new method of estimating shear stiffness based on the principal spatial frequency of the shear wave displacement map is presented. Finite element simulations were performed to assess the relative insensitivity of this approach to decreases in SNR. Additionally, ex vivo experiments were conducted on normal rat lungs to assess the robustness of this approach in low SNR biological tissue. Simulation and experimental results indicate that calculation of shear stiffness by the principal frequency method is less sensitive to extremely low SNR than previously reported MRE inversion methods but at the expense of loss of spatial information within the region of interest from which the principal frequency estimate is derived.

Nonconvex prior image constrained compressed sensing (NCPICCS): theory and simulations on perfusion CT.

PURPOSE: To present and evaluate a new image reconstruction method for dynamic CT based on a nonconvex prior image constrained compressed sensing (NCPICCS) algorithm. The authors systematically compared the undersampling potential, functional information recovery, and solution convergence speed of four compressed sensing (CS) based image reconstruction methods using perfusion CT data: Standard l1-based CS, nonconvex CS (NCCS), and l1-based and nonconvex CS, including an additional constraint based on a prior image (PICCS and NCPICCS, respectively). METHODS: The Shepp-Logan phantom was modified such that its uppermost ellipses changed attenuation through time, simulating both an arterial input function (AIF) and a homogeneous tissue perfusion region. Data were simulated with and without Poisson noise added to the projection data and subsequently reconstructed with all four CS-based methods at four levels of undersampling: 20, 12, 6, and 4 projections. Root mean squared (RMS) error of reconstructed images and recovered time attenuation curves (TACs) were assessed as well as convergence speed. The performance of both PICCS and NCPICCS methods were also evaluated using a kidney perfusion animal experiment data set. RESULTS: All four CS-based methods were able to reconstruct the phantoms with 20 projections, with similar results on the RMS error of the recovered TACs. NCCS allowed accurate reconstructions with as few as 12 projections, PICCS with as few as six projections, and NCPICCS with as few as four projections. These results were consistent for noise-free and noisy data. NCPICCS required the fewest iterations to converge across all simulation conditions, followed by PICCS, NCCS, and then CS. On animal data, at the lowest level of undersampling tested (16 projections), the image quality of NCPICCS was better than PICCS with fewer streaking artifacts, while the TAC accuracy on the selected region of interest was comparable. CONCLUSIONS: The authors have presented a novel method for image reconstruction using highly undersampled dynamic CT data. The NCPICCS method takes advantage of the information provided by a prior image, as in PICCS, but employs a more general nonconvex sparsity measure [such as the l(p)-norm (0 < p < or = 1)] rather than the conventional convex l1-norm. Despite the lack of guarantees of a globally optimal solution, the proposed nonconvex extension of PICCS consistently allowed for image reconstruction from fewer samples than the analogous l1-based PICCS method. Both nonconvex sparsity measures as well as prior image information (when available) significantly reduced the number of iterations required for convergence, potentially providing computational advantages for practical implementation of CS-based image reconstruction techniques.

Gastric motor disturbances in patients with idiopathic rapid gastric emptying.

BACKGROUND: The mechanisms of 'idiopathic' rapid gastric emptying, which are associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. METHODS: Fasting and postprandial (300kcal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; seven had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. KEY RESULTS: While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (P=0.002) body mass index than normal gastric emptying. MRI visualized propagating contractions at ∼3cpm in healthy people and patients. Compared with controls (0.32±0.04, Mean±SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2-14.0) in patients with rapid (0.48±0.06), but not normal gastric emptying (0.20±0.06). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. CONCLUSIONS & INFERENCES: MRI provides a non-invasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia.

Shear modulus decomposition algorithm in magnetic resonance elastography.

Magnetic resonance elastography (MRE) is an imaging modality capable of visualizing the elastic properties of an object using magnetic resonance imaging (MRI) measurements of transverse acoustic strain waves induced in the object by a harmonically oscillating mechanical vibration. Various algorithms have been designed to determine the mechanical properties of the object under the assumptions of linear elasticity, isotropic and local homogeneity. One of the challenging problems in MRE is to reduce the noise effects and to maintain contrast in the reconstructed shear modulus images. In this paper, we propose a new algorithm designed to reduce the degree of noise amplification in the reconstructed shear modulus images without the assumption of local homogeneity. Investigating the relation between the measured displacement data and the stress wave vector, the proposed algorithm uses an iterative reconstruction formula based on a decomposition of the stress wave vector. Numerical simulation experiments and real experiments with agarose gel phantoms and human liver data demonstrate that the proposed algorithm is more robust to noise compared to standard inversion algorithms and stably determines the shear modulus.

Magnetic resonance elastography of the lung: technical feasibility.

Magnetic resonance elastography (MRE) is a phase-contrast technique that can spatially map shear stiffness within tissue-like materials. To date, however, MRE of the lung has been too technically challenging-primarily because of signal-to-noise ratio (SNR) limitations and phase instability. We describe an approach in which shear wave propagation is not encoded into the phase of the MR signal of a material, but rather from the signal arising from a polarized noble gas encapsulated within. To determine the feasibility of the approach, three experiments were performed. First, to establish whether shear wave propagation within lung parenchyma can be visualized with phase-contrast MR techniques, MRE was performed on excised porcine lungs inflated with room air. Second, a phantom consisting of open-cell foam filled with thermally polarized (3)He gas was imaged with MRE to determine whether shear wave propagation can be encoded by the gas. Third, preliminary evidence of the feasibility of MRE in vivo was obtained by using a longitudinal driver on the chest of a normal volunteer to generate shear waves in the lung. The results suggest that MRE in combination with hyperpolarized noble gases is potentially useful for noninvasively assessing the regional elastic properties of lung parenchyma, and merits further investigation.

Semi-automated digital image analysis of joint space width in knee radiographs.

OBJECTIVE: To design a semi-automated program to measure the minimum tibiofemoral joint space width (JSW) of knee radiographs. DESIGN: Bilateral knee radiographs were obtained twice within a 2 week period from 34 asymptomatic research participants. Radiographic images were analyzed to report both the variability of the image analysis program and the reproducibility of JSW measurements within a 2 week period. In addition, the results were compared with minimum JSW measurements read manually by an experienced musculoskeletal radiologist. RESULTS: The variability of the image analysis program was shown to be within one pixel. The results showed that reproducibility was better with the automated method. In addition, the manual method measured a greater minimum JSW than the automated method. There was no significant difference in between-day measurements. There was a significant difference reported between the automated and manual minimum JSW measurements. CONCLUSION: A novel semi-automated method for measurement of JSW has been developed.

Spatio-temporal directional filtering for improved inversion of MR elastography images.

Dynamic magnetic resonance elastography can visualize and measure propagating shear waves in tissue-like materials subjected to harmonic mechanical excitation. This allows the calculation of local values of material parameters such as shear modulus and attenuation. Various inversion algorithms to perform such calculations have been proposed, but they are sensitive to areas of low displacement amplitude (and hence low SNR) that result from interference patterns due to reflection and refraction. A spatio-temporal directional filter applied as a pre-processing step can separate interfering waves so they can be processed separately. Weighted combinations of inversions from such directionally separated data sets can significantly improve reconstructions of shear modulus and attenuation.

Magnetic resonance elastography: non-invasive mapping of tissue elasticity.

Magnetic resonance elastography (MRE) is a phase-contrast-based MRI imaging technique that can directly visualize and quantitatively measure propagating acoustic strain waves in tissue-like materials subjected to harmonic mechanical excitation. The data acquired allows the calculation of local quantitative values of shear modulus and the generation of images that depict tissue elasticity or stiffness. This is significant because palpation, a physical examination that assesses the stiffness of tissue, can be an effective method of detecting tumors, but is restricted to parts of the body that are accessible to the physician's hand. MRE shows promise as a potential technique for 'palpation by imaging', with possible applications in tumor detection (particularly in breast, liver, kidney and prostate), characterization of disease, and assessment of rehabilitation (particularly in muscle). We describe MRE in the context of other recent techniques for imaging elasticity, discuss the processing algorithms for elasticity reconstruction and the issues and assumptions they involve, and present recent ex vivo and in vivo results.

FLAIR histogram segmentation for measurement of leukoaraiosis volume.

The purposes of this study were to develop a method to measure brain and white matter hyperintensity (leukoaraiosis) volume that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery (FLAIR) images and to assess the accuracy and reproducibility of the method. Whole-head synthetic image phantoms with manually introduced leukoaraiosis lesions of varying severity were constructed. These synthetic image phantom sets incorporated image contrast and anatomic features that mimicked leukoaraiosis found in real life. One set of synthetic image phantoms was used to develop the segmentation algorithm (FLAIR-histoseg). A second set was used to measure its accuracy. Test retest reproducibility was assessed in 10 elderly volunteers who were imaged twice. The mean absolute error of the FLAIR-histoseg method was 6.6% for measurement of leukoaraiosis volume and 1.4% for brain volume. The mean test retest coefficient of variation was 1.4% for leukoaraiosis volume and 0.3% for brain volume. We conclude that the FLAIR-histoseg method is an accurate and reproducible method for measuring leukoaraiosis and whole-brain volume in elderly subjects.

Complex-valued stiffness reconstruction for magnetic resonance elastography by algebraic inversion of the differential equation.

Noninvasive quantitation of the mechanical properties of tissue could improve early detection of pathology. Previously a method for detecting displacement from propagating shear waves using a phase-contrast MRI technique was developed. In this work it is demonstrated how a collection of data representing the full vector displacement field could be used to potentially estimate the full complex stiffness tensor. An algebraic inversion approach useful for piece-wise homogeneous materials is described in detail for the general isotropic case, which is then specialized to incompressible materials as a model for tissue. Results of the inversion approach are presented for simulated and experimental phantom data that show the technique can be used to obtain shear wave-speed and attenuation in regions where there is sufficient signal-to-noise ratio in the displacement and its second spatial derivatives. The sensitivity to noise is higher in the attenuation estimates than the shear wave-speed estimates. Magn Reson Med 45:299-310, 2001.

Autocorrection of three-dimensional time-of-flight MR angiography of the Circle of Willis.

OBJECTIVE: The purpose of this study was to investigate the efficacy of a retrospective adaptive motion correction technique known as autocorrection for reducing motion-induced artifacts in high-resolution three-dimensional time-of-flight MR angiography of the circle of Willis. MATERIALS AND METHODS: Ten consecutive volunteers were imaged with an unenhanced gradient-recalled echo three-dimensional time-of-flight MR angiography sequence of the circle of Willis. Each volunteer was asked to rotate approximately 2 degrees after completion of one third and one half of the acquisition in the axial, sagittal, and oblique planes (45 degrees to the axial and sagittal planes). A single static data set was also acquired for each volunteer. Unprocessed and autocorrected maximum-intensity-projection images were reviewed as blinded image pairs by six radiologists and were compared on a five-point image quality scale. RESULTS: Mean improvement in image quality after autocorrection was 1.4 (p < 0.0001), 1.1 (p < 0.0001), and 0.2 (p = 0.003) observer points (maximum value, 2.0), respectively, for examinations corrupted by motion in the axial, oblique, and sagittal planes. All three axes had statistically significant improvement in image quality compared with the uncorrected images. Changes in image quality after the application of the autocorrection algorithm to static angiogram data were not statistically significant (mean change in score = -0.13 points; p = 0.29). CONCLUSION: Autocorrection can reduce artifacts in motion-corrupted MR angiography of the circle of Willis without distorting motion-free examinations.

Magnetic resonance elastography of skeletal muscle.

While the contractile properties of skeletal muscle have been studied extensively, relatively little is known about the elastic properties of muscle in vivo. Magnetic resonance elastography (MRE) is a phase contrast-based method for observing shear waves propagating in a material to determine its stiffness. In this work, MRE is applied to skeletal muscle under load to quantify the change in stiffness with loading. A mathematical model of muscle is developed that predicts a linear relationship between shear stiffness and muscle load. The MRE technique was applied to bovine muscle specimens (N = 10) and human biceps brachii in vivo (N = 5). Muscle stiffness increased linearly for both passive tension (14.5 +/- 1.77 kPa/kg) and active tension, in which the increase in stiffness was dependent upon muscle size, as predicted by the model. A means of noninvasively assessing the viscoelastic pro-perties of skeletal muscle in vivo may provide a useful method for studying muscle biomechanics in health and disease.

Autocorrection in MR imaging: adaptive motion correction without navigator echoes.

A technique for automatic retrospective correction of motion artifacts on magnetic resonance (MR) images was developed that uses only the raw (complex) data from the MR imager and requires no knowledge of patient motion during the acquisition. The algorithm was tested on coronal images of the rotator cuff in a series of 144 patients, and the improvements in image quality were similar to those achieved with navigator echoes. The results demonstrate that autocorrection can significantly reduce motion artifacts in a technically demanding MR imaging application.

An investigation of the effects of mammographic acquisition parameters on a semiautomated quantitative measure of breast cancer risk.

The aim of this work was to investigate the effect of mammographic acquisition parameter variations on the estimation of percent density (PD) produced by a particular semiautomated algorithm. The PD algorithm requires the user to specify a threshold pixel value segmenting breast tissue of greater and lesser density. A whole breast specimen was imaged using a variety of acquisition techniques, and the image data were processed as prescribed by the PD algorithm. PD estimates for all possible values of the user threshold were calculated for all the images. The image data were normalized so that PD varied between 30% and 80% over a fixed threshold range of 23, and a PD value of 50% was obtained for a threshold value of 195. PD differences between all the images and a baseline standard mammographic acquisition technique were calculated. We also estimated PD differences caused by small (3%) variations in operator selection of the threshold value. We found that the largest differences in PD involved changes in the density control of the mammography unit, and changes in the detector (either film type or computed radiography). The maximum PD differences due to technique were all less than 10%, with root-mean-square (RMS) variations less than 4%. PD differences due to operator variation were 24% (maximum) and 6.1% (RMS). These findings suggest that PD differences due to mammographic technique will be considerably less than those inherent to the technique, due to operator variation. All of these estimates are likely larger than differences seen in practice since optimization of the threshold by the operator was not considered in this analysis.