Multi-Excitation Magnetic Resonance Elastography of the Brain: Wave Propagation in Anisotropic White Matter.

Magnetic resonance elastography (MRE) has emerged as a sensitive imaging technique capable of providing a quantitative understanding of neural microstructural integrity. However, a reliable method for the quantification of the anisotropic mechanical properties of human white matter is currently lacking, despite the potential to illuminate the pathophysiology behind neurological disorders and traumatic brain injury. In this study, we examine the use of multiple excitations in MRE to generate wave displacement data sufficient for anisotropic inversion in white matter. We show the presence of multiple unique waves from each excitation which we combine to solve for parameters of an incompressible, transversely isotropic (ITI) material: shear modulus, µ, shear anisotropy, ϕ, and tensile anisotropy, ζ. We calculate these anisotropic parameters in the corpus callosum body and find the mean values as µ = 3.78 kPa, ϕ = 0.151, and ζ = 0.099 (at 50 Hz vibration frequency). This study demonstrates that multi-excitation MRE provides displacement data sufficient for the evaluation of the anisotropic properties of white matter.

The"Newcastle Nomogram"-Statistical modelling predicts malignant transformation in potentially malignant disorders.

BACKGROUND: Nomograms are graphical calculating devices used to predict risk of malignant transformation (MT) or response to treatment during cancer management. To date, a nomogram has not been used to predict clinical outcome during oral potentially malignant disorder (PMD) treatment. The aim of this study was to create a nomogram for use by clinicians to predict the probability of MT, thereby facilitating accurate assessment of risk and objective decision-making during individual patient management. METHODS: Clinico-pathological data from a previously treated cohort of 590 newly presenting PMD patients were reviewed and clinical outcomes categorized as disease free, persistent PMD or MT. Multiple logistic regression was used to predict the probability of MT in the cohort using age, gender, lesion type, site and incision biopsy histopathological diagnoses. Internal validation and calibration of the model was performed using the bootstrap method (n = 1000), and bias-corrected indices of model performance were computed. RESULTS: Potentially malignant disorders were predominantly leukoplakias (79%), presenting most frequently at floor of mouth and lateral tongue sites (51%); 99 patients (17%) developed oral squamous cell carcinoma during the study period. The nomogram performed well when MT predictions were compared with patient outcome data, demonstrating good bias-corrected discrimination and calibration (Dxy  = 0.58; C = 0.790), with a sensitivity of 87% and specificity 63%, and a positive predictive value of 32% and negative predictive value 96%. CONCLUSION: The "Newcastle Nomogram" has been developed to predict the probability of MT in PMD, based on an internally validated statistical model. Based upon readily available and patient-specific clinico-pathological data, it provides clinicians with a pragmatic diagrammatic aid for clinical decision-making during diagnosis and management of PMD.

A Self-Assembling Whole-Cell Vaccine Antigen Presentation Platform.

Diarrhea is the most common infection in children under the age of 5 years worldwide. In spite of this, only a few vaccines to treat infectious diarrhea exist, and many of the available vaccines are sparingly and sporadically administered. Major obstacles to the development and widespread implementation of vaccination include the ease and cost of production, distribution, and delivery. Here we present a novel, customizable, and self-assembling vaccine platform that exploits the Vibrio cholerae bacterial biofilm matrix for antigen presentation. We use this technology to create a proof-of-concept, live-attenuated whole-cell vaccine that is boosted by spontaneous association of a secreted protein antigen with the cell surface. Sublingual administration of this live-attenuated vaccine to mice confers protection against V. cholerae challenge and elicits the production of antigen-specific IgA in stool. The platform presented here enables the development of antigen-boosted vaccines that are simple to produce and deliver, addressing many of the obstacles to vaccination against diarrheal diseases. This may also serve as a paradigm for the development of broadly protective biofilm-based vaccines against other mucosal infections.IMPORTANCE Diarrheal disease is the most common infection afflicting children worldwide. In resource-poor settings, these infections are correlated with cognitive delay, stunted growth, and premature death. With the development of efficacious, affordable, and easily administered vaccines, such infections could be prevented. While a major focus of research on biofilms has been their elimination, here we harness the bacterial biofilm to create a customizable platform for cost-effective, whole-cell mucosal vaccines that self-incorporate secreted protein antigens. We use this platform to develop a sublingually administered live-attenuated prototype vaccine based on Vibrio cholerae This serves not only as a proof of concept for a multivalent vaccine against common bacterial enteric pathogens but also as a paradigm for vaccines utilizing other bacterial biofilms to target mucosal infections.

Potentially malignant disorders revisited-The lichenoid lesion/proliferative verrucous leukoplakia conundrum.

BACKGROUND: Clinically identifiable potentially malignant disorders (PMD) precede oral squamous cell carcinoma development. Oral lichenoid lesions (OLL) and proliferative verrucous leukoplakia (PVL) are specific precursor lesions believed to exhibit both treatment resistance and a high risk of malignant transformation (MT). METHODS: A retrospective review of 590 PMD patients treated in Northern England by CO2 laser surgery between 1996 and 2014 was carried out. Lesions exhibiting lichenoid or proliferative verrucous features were identified from the patient database and their clinicopathological features and outcome post-treatment determined at the study census date of 31 December 2014. RESULTS: One hundred and 98 patients were identified as follows: 118 OLL and 80 PVL, most frequently leukoplakia at ventrolateral tongue and floor of mouth sites, equally distributed between males and females. Most exhibited dysplasia on incision biopsy (72% OLL; 85% PVL) and were treated by laser excision rather than ablation (88.1% OLL; 86.25% PVL). OLL were more common in younger patients (OLL 57.1 year; PVL 62.25 years; P = .008) and more likely than PVL to present as erythroleukoplakia (OLL 15.3%; PVL 2.5%; P = .003). Whilst no significant difference was seen between OLL and PVL achieving disease-free status (69.5% and 65%, respectively; P = .55), this was less than the overall PMD cohort (74.2%). MT was identified in 2 OLL (1.7%) and 2 PVL (2.5%) during follow-up. CONCLUSION: One-third of PMD cases showed features of OLL or PVL, probably representing a disease presentation continuum. Post-treatment disease-free status was less common in OLL and PVL, although MT was infrequent.

The Effect of the 2009 USPSTF breast cancer screening recommendations on breast cancer in Michigan: A longitudinal study.

In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended against routine screening mammography for women age 40-49 years and against teaching self-breast examinations (SBE). The aim of this study was to analyze whether breast cancer method of presentation changed following the 2009 USPSTF screening recommendations in a large Michigan cohort. Data were collected on women with newly diagnosed stage 0-III breast cancer participating in the Michigan Breast Oncology Quality Initiative (MiBOQI) registry at 25 statewide institutions from 2006 to 2015. Data included method of detection, cancer stage, treatment type, and patient demographics. In all, 30 008 women with breast cancer detected via mammogram or palpation with an average age of 60.1 years were included. 38% of invasive cancers were identified by palpation. Presentation with palpable findings decreased slightly over time, from 34.6% in 2006 to 28.9% in 2015 (P < .001). Over the 9-year period, there was no statistically significant change in rate of palpation-detected tumors for women age <50 years or ≥50 years (P = .27, .30, respectively). Younger women were more likely to present with palpable tumors compared to older women in a statewide registry. This rate did not increase following publication of the 2009 USPSTF breast cancer screening recommendations.

In situ proteolysis of the Vibrio cholerae matrix protein RbmA promotes biofilm recruitment.

The estuarine gram-negative rod and human diarrheal pathogen Vibrio cholerae synthesizes a VPS exopolysaccharide-dependent biofilm matrix that allows it to form a 3D structure on surfaces. Proteins associated with the matrix include, RbmA, RbmC, and Bap1. RbmA, a protein whose crystallographic structure suggests two binding surfaces, associates with cells by means of a VPS-dependent mechanism and promotes biofilm cohesiveness and recruitment of cells to the biofilm. Here, we show that RbmA undergoes limited proteolysis within the biofilm. This proteolysis, which is carried out by the hemagglutinin/protease and accessory proteases, yields the 22-kDa C-terminal polypeptide RbmA*. RbmA* remains biofilm-associated. Unlike full-length RbmA, the association of RbmA* with cells is no longer VPS-dependent, likely due to an electropositive surface revealed by proteolysis. We provide evidence that this proteolysis event plays a role in recruitment of VPS(-) cells to the biofilm surface. Based on our findings, we propose that association of RbmA with the matrix reinforces the biofilm structure and leads to limited proteolysis of RbmA to RbmA*. RbmA*, in turn, promotes recruitment of cells that have not yet initiated VPS synthesis to the biofilm surface. The assignment of two functions to RbmA, separated by a proteolytic event that depends on matrix association, dictates an iterative cycle in which reinforcement of recently added biofilm layers precedes the recruitment of new VPS(-) cells to the biofilm.

A cross-sectional examination of the relationship between approaches to learning and perceived stress among medical students in Malaysia.

Background: Learning approaches have been proposed to affect the experience of psychological stress among tertiary students in recent years. This relationship becomes important in stressful environments such as medical schools. However, the relationship between stress and learning approaches is not well understood, and often studies done cannot be generalized due to different sociocultural differences. In particular, no study in Malaysia has looked at learning approaches among medical students. Aims: To address this gap, we examined the relationship between perceived stress and learning approaches by considering sources of stress. Methodology: The Perceived Stress Scale (PSS-10), Medical Student Stressor Questionnaire, and the Revised Two-Factor Study Process Questionnaire were answered by the preclinical and final-year students studying MBBS in a Malaysian campus of British University. Results: Deep learning was positively and surface learning negatively associated with perception of coping with stress. In this study, neither approaches were associated with psychological stress as opposed to previous reports. We found surface learners to report higher level of stress associated with social stressors. We found students' self-perception of feeling incompetent and feeling they need to do well to be significant sources of stress. Discussion: Deep learning promotes psychological resilience. This is of paramount importance in learning environments where stress is highly prevalent such as medical school. Promotion of deep learning among medical students is required at earlier stages as they tend to solidify their approach through their university years and carry that approach beyond school into their workplace.

Addressing uncertainty in adaptation planning for agriculture.

We present a framework for prioritizing adaptation approaches at a range of timeframes. The framework is illustrated by four case studies from developing countries, each with associated characterization of uncertainty. Two cases on near-term adaptation planning in Sri Lanka and on stakeholder scenario exercises in East Africa show how the relative utility of capacity vs. impact approaches to adaptation planning differ with level of uncertainty and associated lead time. An additional two cases demonstrate that it is possible to identify uncertainties that are relevant to decision making in specific timeframes and circumstances. The case on coffee in Latin America identifies altitudinal thresholds at which incremental vs. transformative adaptation pathways are robust options. The final case uses three crop-climate simulation studies to demonstrate how uncertainty can be characterized at different time horizons to discriminate where robust adaptation options are possible. We find that impact approaches, which use predictive models, are increasingly useful over longer lead times and at higher levels of greenhouse gas emissions. We also find that extreme events are important in determining predictability across a broad range of timescales. The results demonstrate the potential for robust knowledge and actions in the face of uncertainty.

The transcription factor Mlc promotes Vibrio cholerae biofilm formation through repression of phosphotransferase system components.

The phosphoenol phosphotransferase system (PTS) is a multicomponent signal transduction cascade that regulates diverse aspects of bacterial cellular physiology in response to the availability of high-energy sugars in the environment. Many PTS components are repressed at the transcriptional level when the substrates they transport are not available. In Escherichia coli, the transcription factor Mlc (for makes large colonies) represses transcription of the genes encoding enzyme I (EI), histidine protein (HPr), and the glucose-specific enzyme IIBC (EIIBC(Glc)) in defined media that lack PTS substrates. When glucose is present, the unphosphorylated form of EIIBC(Glc) sequesters Mlc to the cell membrane, preventing its interaction with DNA. Very little is known about Vibrio cholerae Mlc. We found that V. cholerae Mlc activates biofilm formation in LB broth but not in defined medium supplemented with either pyruvate or glucose. Therefore, we questioned whether V. cholerae Mlc functions differently than E. coli Mlc. Here we have shown that, like E. coli Mlc, V. cholerae Mlc represses transcription of PTS components in both defined medium and LB broth and that E. coli Mlc is able to rescue the biofilm defect of a V. cholerae Δmlc mutant. Furthermore, we provide evidence that Mlc indirectly activates transcription of the vps genes by repressing expression of EI. Because activation of the vps genes by Mlc occurs under only a subset of the conditions in which repression of PTS components is observed, we conclude that additional inputs present in LB broth are required for activation of vps gene transcription by Mlc.

Diabetic retinopathy among the elderly with type 2 diabetes: A Nationwide longitudinal registry study.

PURPOSE: To investigate the prevalence, incidence and risk factors of DR in elderly people living with type 2 diabetes. METHODS: Individuals >80 years, in the Swedish National Diabetes Register (NDR) between 2008 and 2017, were included. Prevalence and incidence were calculated and stratified by age. Estimates were assessed by longitudinal binary logistic regression models. RESULTS: One hundred forty-one thousand, one hundred fifty-eight individuals with type 2 diabetes were included, median age 83 years, 53.3% females and with a median HbA1c 52 mmol/mol. The DR prevalence was stable at 336.2 cases/1000 patients in 2008 (95% CI, 330.2-342.3), with no significant changes during the 10-year period. Crude DR incidence rate: 88.5 cases/1000 patient years (95% CI, 87.6-89.4). The incidence rate was lower at higher ages. The effect of age on incident DR varied by sex, with females having an increasingly higher risk than males from 83 years of age, OR 1.25 (1.11-1.42) at age 90 years. The risk of incident DR with longer diabetes duration increased more rapidly at worse glycaemic control. CONCLUSION: The growing population of elderly with type 2 diabetes shows a stable proportion of DR and proposes an increased need for DR screening and eye care. Established risk factors for DR, such as diabetes duration and level of glycaemic control, are also important in the elderly; however, age and sex should be considered.

Automated quantitative assessment of bone contusions and overlying articular cartilage following anterior cruciate ligament injury.

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post-anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty-five patients (54% female, 26.4 ± 11.8 days post-injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury.

Mechanical Properties of White Matter Tracts in Aging Assessed via Anisotropic MR Elastography.

Magnetic resonance elastography (MRE) is a promising neuroimaging technique to probe tissue microstructure, which has revealed widespread softening with loss of structural integrity in the aging brain. Traditional MRE approaches assume mechanical isotropy. However, white matter is known to be anisotropic from aligned, myelinated axonal bundles, which can lead to uncertainty in mechanical property estimates in these areas when using isotropic MRE. Recent advances in anisotropic MRE now allow for estimation of shear and tensile anisotropy, along with substrate shear modulus, in white matter tracts. The objective of this study was to investigate age-related differences in anisotropic mechanical properties in human brain white matter tracts for the first time. Anisotropic mechanical properties in all tracts were found to be significantly lower in older adults compared to young adults, with average property differences ranging between 0.028-0.107 for shear anisotropy and between 0.139-0.347 for tensile anisotropy. Stiffness perpendicular to the axonal fiber direction was also significantly lower in older age, but only in certain tracts. When compared with fractional anisotropy measures from diffusion tensor imaging, we found that anisotropic MRE measures provided additional, complementary information in describing differences between the white matter integrity of young and older populations. Anisotropic MRE provides a new tool for studying white matter structural integrity in aging and neurodegeneration.

Altered brain functional connectivity in the frontoparietal network following an ice hockey season.

Sustaining sports-related head impacts has been reported to result in neurological changes that potentially lead to later-life neurological disease. Advanced neuroimaging techniques have been used to detect subtle neurological effects resulting from head impacts, even after a single competitive season. The current study used resting-state functional magnetic resonance imaging to assess changes in functional connectivity of the frontoparietal network, a brain network responsible for executive functioning, in collegiate club ice hockey players over one season. Each player was scanned before and after the season and wore accelerometers to measure head impacts at practices and home games throughout the season. We examined pre- to post-season differences in connectivity within the frontoparietal and default mode networks, as well as the relationship between the total number of head impacts sustained and changes in connectivity. We found a significant interaction between network region of interest and time point (p = .016), in which connectivity between the left and right posterior parietal cortex seed regions increased over the season (p < .01). Number of impacts had a significant effect on frontoparietal network connectivity, such that more impacts were related to greater connectivity differences over the season (p = .042). Overall, functional connectivity increased in ice hockey athletes over a season between regions involved in executive functioning, and sensory integration, in particular. Furthermore, those who sustained more impacts had the greatest changes in connectivity. Consistent with prior findings in resting-state sports-related head impact literature, these findings have been suggested to represent brain injury.Highlights Functional connectivity of the frontoparietal network significantly increased between the pre- and post-season, which may be a compensatory mechanism driven by neural tissue injury caused by repetitive head impacts.Changes in frontoparietal network connectivity are related to head impact exposure, measured as the number of head impacts sustained in a single season.Functional connectivity of the default mode network did not change over an ice hockey season.

Individual Muscle Force Estimation in the Human Forearm Using Multi-Muscle MR Elastography (MM-MRE).

OBJECTIVE: To establish the sensitivity of magnetic resonance elastography (MRE) to active muscle contraction in multiple muscles of the forearm. METHODS: We combined MRE of forearm muscles with an MRI-compatible device, the MREbot, to simultaneously measure the mechanical properties of tissues in the forearm and the torque applied by the wrist joint during isometric tasks. We measured shear wave speed of thirteen forearm muscles via MRE in a series of contractile states and wrist postures and fit these outputs to a force estimation algorithm based on a musculoskeletal model. RESULTS: Shear wave speed changed significantly upon several factors, including whether the muscle was recruited as an agonist or antagonist (p = 0.0019), torque amplitude (p = <0.0001), and wrist posture (p = 0.0002). Shear wave speed increased significantly during both agonist (p = <0.0001) and antagonist (p = 0.0448) contraction. Additionally, there was a greater increase in shear wave speed at greater levels of loading. The variations due to these factors indicate the sensitivity to functional loading of muscle. Under the assumption of a quadratic relationship between shear wave speed and muscle force, MRE measurements accounted for an average of 70% of the variance in the measured joint torque. CONCLUSION: This study shows the ability of MM-MRE to capture variations in individual muscle shear wave speed due to muscle activation and presents a method to estimate individual muscle force through MM-MRE derived measurements of shear wave speed. SIGNIFICANCE: MM-MRE could be used to establish normal and abnormal muscle co-contraction patterns in muscles of the forearm controlling hand and wrist function.

In vivoestimation of anisotropic mechanical properties of the gastrocnemius during functional loading with MR elastography.

Objective.In vivoimaging assessments of skeletal muscle structure and function allow for longitudinal quantification of tissue health. Magnetic resonance elastography (MRE) non-invasively quantifies tissue mechanical properties, allowing for evaluation of skeletal muscle biomechanics in response to loading, creating a better understanding of muscle functional health.Approach. In this study, we analyze the anisotropic mechanical response of calf muscles using MRE with a transversely isotropic, nonlinear inversion algorithm (TI-NLI) to investigate the role of muscle fiber stiffening under load. We estimate anisotropic material parameters including fiber shear stiffness (µ1), substrate shear stiffness (µ2), shear anisotropy (ϕ), and tensile anisotropy (ζ) of the gastrocnemius muscle in response to both passive and active tension.Main results. In passive tension, we found a significant increase inµ1,ϕ,andζwith increasing muscle length. While in active tension, we observed increasingµ2and decreasingϕandζduring active dorsiflexion and plantarflexion-indicating less anisotropy-with greater effects when the muscles act as agonist.Significance. The study demonstrates the ability of this anisotropic MRE method to capture the multifaceted mechanical response of skeletal muscle to tissue loading from muscle lengthening and contraction.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

Relationships between aggression, sensation seeking, brain stiffness, and head impact exposure: Implications for head impact prevention in ice hockey.

OBJECTIVES: The objectives of this study were to (1) examine the relationship between the number of head impacts sustained in a season of men's collegiate club ice hockey and behavioral traits of aggression and sensation seeking, and (2) explore the neural correlates of these behaviors using neuroimaging. DESIGN: Retrospective cohort study. METHODS: Participants (n = 18) completed baseline surveys to quantify self-reported aggression and sensation-seeking tendencies. Aggression related to playing style was quantified through penalty minutes accrued during a season. Participants wore head impact sensors throughout a season to quantify the number of head impacts sustained. Participants (n = 15) also completed baseline anatomical and magnetic elastography neuroimaging scans to measure brain volumetric and viscoelastic properties. Pearson correlation analyses were performed to examine relationships between (1) impacts, aggression, and sensation seeking, and (2) impacts, aggression, and sensation seeking and brain volume, stiffness, and damping ratio, as an exploratory analysis. RESULTS: Number of head impacts sustained was significantly related to the number of penalty minutes accrued, normalized to number of games played (r = .62, p < .01). Our secondary, exploratory analysis revealed that number of impacts, sensation seeking, and aggression were related to stiffness or damping ratio of the thalamus, amygdala, hippocampus, and frontal cortex, but not volume. CONCLUSIONS: A more aggressive playing style was related to an increased number of head impacts sustained, which may provide evidence for future studies of head impact prevention. Further, magnetic resonance elastography may aid to monitor behavior or head impact exposure. Researchers should continue to examine this relationship and consider targeting behavioral modification programs of aggression to decrease head impact exposure in ice hockey.

Mapping heterogenous anisotropic tissue mechanical properties with transverse isotropic nonlinear inversion MR elastography.

The white matter tracts of brain tissue consist of highly-aligned, myelinated fibers; white matter is structurally anisotropic and is expected to exhibit anisotropic mechanical behavior. In vivo mechanical properties of tissue can be imaged using magnetic resonance elastography (MRE). MRE can detect and monitor natural and disease processes that affect tissue structure; however, most MRE inversion algorithms assume locally homogenous properties and/or isotropic behavior, which can cause artifacts in white matter regions. A heterogeneous, model-based transverse isotropic implementation of a subzone-based nonlinear inversion (TI-NLI) is demonstrated. TI-NLI reconstructs accurate maps of the shear modulus, damping ratio, shear anisotropy, and tensile anisotropy of in vivo brain tissue using standard MRE motion measurements and fiber directions estimated from diffusion tensor imaging (DTI). TI-NLI accuracy was investigated with using synthetic data in both controlled and realistic settings: excellent quantitative and spatial accuracy was observed and cross-talk between estimated parameters was minimal. Ten repeated, in vivo, MRE scans acquired from a healthy subject were co-registered to demonstrate repeatability of the technique. Good resolution of anatomical structures and bilateral symmetry were evident in MRE images of all mechanical property types. Repeatability was similar to isotropic MRE methods and well within the limits required for clinical success. TI-NLI MRE is a promising new technique for clinical research into anisotropic tissues such as the brain and muscle.

A Weighted Head Accelerator Mechanism (WHAM) for visualizing brain rheology using magnetic resonance imaging.

BACKGROUND: A device for moving the head during MR imaging, called a Weighted Head Accelerator Mechanism (WHAM), rotates the head of a supine subject within programmable rotation limits and acceleration profiles. The WHAM can be used with custom MRI sequences to visualize the deformation and recoil of in vivo brain parenchyma with high temporal resolution, allowing element-wise calculation of strain and shear forces in the brain. Unlike previous devices, the WHAM can be configured to provide a wide range of motion and acceleration profiles. NEW METHOD: The WHAM was calibrated using a high-speed camera on a laboratory bench and in 1.5 Tesla and 3.0 Tesla MRI scanners using gel phantoms and human subjects. The MR imaging studies employed a spatial spin-saturation tagging sub-sequence, followed by serial image acquisition. In these studies, 256 images were acquired with a temporal resolution of 2.56 ms. Deformation of the brain was quantified by following the spatial tags in the images. RESULTS: MR imaging showed that the WHAM drove quantifiable brain motions using g forces less than those typically observed in day-to-day activities, with peak accelerations of ∼250 rad/sec2. COMPARISON WITH EXISTING METHODS: The peak pre-contact accelerations and velocities achieved by the WHAM device in this study are both higher than devices used in previous studies, while also allowing for modification of these factors. CONCLUSIONS: MR imaging performed with the WHAM provides a direct method to visualize and quantify "brain slosh" in response to rotational acceleration. Consequently, this approach might find utility in evaluating strategies to protect the brain from mild traumatic brain injury (mTBI).