Evaluation of cerebral cortex viscoelastic property estimation with nonlinear inversion magnetic resonance elastography

Objective. Magnetic resonance elastography (MRE) of the brain has shown promise as a sensitive neuroimaging biomarker for neurodegenerative disorders; however, the accuracy of performing MRE of the cerebral cortex warrants investigation due to the unique challenges of studying thinner and more complex geometries. Approach. A series of realistic, whole-brain simulation experiments are performed to examine the accuracy of MRE to measure the viscoelasticity (shear stiffness, μ, and damping ratio, ξ) of cortical structures predominantly effected in aging and neurodegeneration. Variations to MRE spatial resolution and the regularization of a nonlinear inversion (NLI) approach are examined. Main results. Higher-resolution MRE displacement data (1.25 mm isotropic resolution) and NLI with a low soft prior regularization weighting provided minimal measurement error compared to other studied protocols. With the optimized protocol, an average error in μ and ξ was 3% and 11%, respectively, when compared with the known ground truth. Mid-line structures, as opposed to those on the cortical surface, generally display greater error. Varying model boundary conditions and reducing the thickness of the cortex by up to 0.67 mm (which is a realistic portrayal of neurodegenerative pathology) results in no loss in reconstruction accuracy. Significance. These experiments establish quantitative guidelines for the accuracy expected of in vivo MRE of the cortex, with the proposed method providing valid MRE measures for future investigations into cortical viscoelasticity and relationships with health, cognition, and behavior

Aging brain mechanics: Progress and promise of magnetic resonance elastography

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development

Change in prevalence of post-traumatic stress disorder in the two years following trauma:a meta-analytic study

Background: Understanding the course of post-traumatic stress disorder (PTSD) and the factors that impact this is essential to inform decisions about when and for whom screening and intervention are likely to be beneficial. Objective: To provide meta-analytic evidence of the course of recovery from PTSD in the first year following trauma, and the factors that influence that recovery. Method: We conducted a meta-analysis of observational studies of adult PTSD prevalence which included at least two assessments within the first 12 months following trauma exposure, examining prevalence statistics through to 2 years post-trauma. We examined trauma intentionality (intentional or non-intentional), PTSD assessment method (clinician or self-report), sample sex distribution, and age as moderators of PTSD prevalence over time. Results: We identified 78 eligible studies including 16,484 participants. Pooled prevalence statistics indicated that over a quarter of individuals presented with PTSD at 1 month post-trauma, with this proportion reducing by a third between 1 and 3 months. Beyond 3 months, any prevalence changes were detected over longer intervals and were small in magnitude. Intentional trauma, younger age, and female sex were associated with higher PTSD prevalence at 1 month. In addition, higher proportions of females, intentional trauma exposure, and higher baseline PTSD prevalence were each associated with larger reductions in prevalence over time. Conclusions: Recovery from PTSD following acute trauma exposure primarily occurs in the first 3 months post-trauma. Screening measures and intervention approaches offered at 3 months may better target persistent symptoms than those conducted prior to this point. HIGHLIGHTS: PTSD rates in the immediate aftermath of trauma exposure decline from 27% at 1 month to 18% at 3 months post-trauma, showing significant spontaneous recovery.Problems appear to stabilize after 3 months.Screening/intervention for PTSD at 3 months post-trauma is indicated

Sex-based contributors to and consequences of post-traumatic stress disorder

Purpose of Review Women are twice as likely to develop post-traumatic stress disorder (PTSD) compared to men after a traumatic experience. The purpose of this mini review was to explore recent research on biological contributors to this sex difference. Recent Findings We identified 51 studies published since 2019. Studies found that beyond the influence of sex on the prevalence and symptoms of PTSD, there is evidence for and against sex-based differences in genetic and epigenetic factors (n = 8), brain structure and function (n = 11), neuroendocrine and inflammatory responses (n = 5), and in the role of sleep on emotional memory processing (n = 1). Sex differences were also observed in recovery and during PTSD treatment (n = 16). Finally, there is emerging evidence of sex-differentiated risk for medical and psychiatric comorbidities in PTSD (n = 10). Summary Rapid advances are being made using integrated multidisciplinary approaches to understand why females are at a heightened risk for developing PTSD

Network analysis of canine brain morphometry links tumour risk to oestrogen deficiency and accelerated brain ageing.

Structural 'brain age' is a valuable but complex biomarker for several brain disorders. The dog is an unrivalled comparator for neurological disease modeling, however canine brain morphometric diversity creates computational and statistical challenges. Using a data-driven approach, we explored complex interactions between patient metadata, brain morphometry, and neurological disease. Twenty-four morphometric parameters measured from 286 canine brain magnetic resonance imaging scans were combined with clinical parameters to generate 9,438 data points. Network analysis was used to cluster patients according to their brain morphometry profiles. An 'aged-brain' profile, defined by a small brain width and volume combined with ventriculomegaly, was revealed in the Boxer breed. Key features of this profile were paralleled in neutered female dogs which, relative to un-neutered females, had an 11-fold greater risk of developing brain tumours. Boxer dog and geriatric dog groups were both enriched for brain tumour diagnoses, despite a lack of geriatric Boxers within the cohort. Our findings suggest that advanced brain ageing enhances brain tumour risk in dogs and may be influenced by oestrogen deficiency-a risk factor for dementia and brain tumours in humans. Morphometric features of brain ageing in dogs, like humans, might better predict neurological disease risk than patient chronological age

Acute effects of high-intensity exercise on brain mechanical properties and cognitive function

Previous studies have shown that engagement in even a single session of exercise can improve cognitive performance in the short term. However, the underlying physiological mechanisms contributing to this effect are still being studied. Recently, with improvements to advanced quantitative neuroimaging techniques, brain tissue mechanical properties can be sensitively and noninvasively measured with magnetic resonance elastography (MRE) and regional brain mechanical properties have been shown to reflect individual cognitive performance. Here we assess brain mechanical properties before and immediately after engagement in a high-intensity interval training (HIIT) regimen, as well as one-hour post-exercise. We find that immediately after exercise, subjects in the HIIT group had an average global brain stiffness decrease of 4.2% (p < 0.001), and an average brain damping ratio increase of 3.1% (p = 0.002). In contrast, control participants who did not engage in exercise showed no significant change over time in either stiffness or damping ratio. Changes in brain mechanical properties with exercise appeared to be regionally dependent, with the hippocampus decreasing in stiffness by 10.4%. We also found that one-hour after exercise, brain mechanical properties returned to initial baseline values. The magnitude of changes to brain mechanical properties also correlated with improvements in reaction time on executive control tasks (Eriksen Flanker and Stroop) with exercise. Understanding the neural changes that arise in response to exercise may inform potential mechanisms behind improvements to cognitive performance with acute exercise

Calibration of a heterogeneous brain model using a subject-specific inverse finite element approach

Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models. In this study, the CAB-20MSym template model was developed, calibrated, and extensively verified. To implement material heterogeneity, a magnetic resonance elastography (MRE) template image was leveraged to define the relative stiffness gradient of the brain model. A multi-stage inverse FE (iFE) approach was used to calibrate the material parameters that defined the underlying non-linear deviatoric response by minimizing the error between model-predicted brain displacements and experimental displacement data. This process involved calibrating the infinitesimal shear modulus of the material using low-severity, low-deformation impact cases and the material non-linearity using high-severity, high-deformation cases from a dataset of in situ brain displacements obtained from cadaveric specimens. To minimize the geometric discrepancy between the FE models used in the iFE calibration and the cadaveric specimens from which the experimental data were obtained, subject-specific models of these cadaveric brain specimens were developed and used in the calibration process. Finally, the calibrated material parameters were extensively verified using independent brain displacement data from 33 rotational head impacts, spanning multiple loading directions (sagittal, coronal, axial), magnitudes (20–40 rad/s), durations (30–60 ms), and severity. Overall, the heterogeneous CAB-20MSym template model demonstrated good biofidelity with a mean overall CORA score of 0.63 ± 0.06 when compared to in situ brain displacement data. Strains predicted by the calibrated model under non-injurious rotational impacts in human volunteers (N = 6) also demonstrated similar biofidelity compared to in vivo measurements obtained from tagged magnetic resonance imaging studies. In addition to serving as an anatomically accurate model for further investigations of TBI biomechanics, the MRE-based framework for implementing material heterogeneity could serve as a foundation for incorporating subject-specific material properties in future models

Standard‐space atlas of the viscoelastic properties of the human brain

Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18–35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons

5-HTTLPR-environment interplay and its effects on neural reactivity in adolescents

It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11 years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity