Intrauterine exposure to SARS-CoV-2 infection and early newborn brain development.

Epidemiologic studies suggest that prenatal exposures to certain viruses may influence early neurodevelopment, predisposing offspring to neuropsychiatric conditions later in life. The long-term effects of maternal COVID-19 infection in pregnancy on early brain development, however, remain largely unknown. We prospectively enrolled infants in an observational cohort study for a single-site study in the Washington, DC Metropolitan Area from June 2020 to November 2021 and compared these infants to pre-pandemic controls (studied March 2014-February 2020). The primary outcomes are measures of cortical morphometry (tissue-specific volumes), along with global and regional measures of local gyrification index, and sulcal depth. We studied 210 infants (55 infants of COVID-19 unexposed mothers, 47 infants of COVID-19-positive mothers, and 108 pre-pandemic healthy controls). We found increased cortical gray matter volume (182.45 ± 4.81 vs. 167.29 ± 2.92) and accelerated sulcal depth of the frontal lobe (5.01 ± 0.19 vs. 4.40 ± 0.13) in infants of COVID-19-positive mothers compared to controls. We found additional differences in infants of COVID-19 unexposed mothers, suggesting both maternal viral exposures, as well as non-viral stressors associated with the pandemic, may influence early development and warrant ongoing follow-up.

Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture.

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.

Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse outcomes in offspring. The potential effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 without known COVID-19 exposures during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5 T MRI Scanner. Volumes of six brain tissue types were calculated. Cortical folding measures, including brain surface area, local gyrification index, and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety, and depression scales. Generalized estimating equations were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Results: Stress and depression scores are significantly higher in the pandemic cohort, compared to the pre-pandemic cohort. Fetal white matter, hippocampal, and cerebellar volumes are decreased in the pandemic cohort. Cortical surface area and local gyrification index are also decreased in all four lobes, while sulcal depth is lower in the frontal, parietal, and occipital lobes in the pandemic cohort, indicating delayed brain gyrification. Conclusions: We report impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies, in the setting of heightened maternal psychological distress. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies merit further study.

Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months.

Importance: Prenatal maternal psychological distress is associated with disturbances in fetal brain development. However, the association between altered fetal brain development, prenatal maternal psychological distress, and long-term neurodevelopmental outcomes is unknown. Objective: To determine the association of fetal brain development using 3-dimensional magnetic resonance imaging (MRI) volumes, cortical folding, and metabolites in the setting of maternal psychological distress with infant 18-month neurodevelopment. Design, Setting, and Participants: Healthy mother-infant dyads were prospectively recruited into a longitudinal observational cohort study from January 2016 to October 2020 at Children's National Hospital in Washington, DC. Data analysis was performed from January 2016 to July 2021. Exposures: Prenatal maternal stress, anxiety, and depression. Main Outcomes and Measures: Prenatal maternal stress, anxiety, and depression were measured using validated self-report questionnaires. Fetal brain volumes and cortical folding were measured from 3-dimensional, reconstructed T2-weighted MRI scans. Fetal brain creatine and choline were quantified using proton magnetic resonance spectroscopy. Infant neurodevelopment at 18 months was measured using Bayley Scales of Infant and Toddler Development III and Infant-Toddler Social and Emotional Assessment. The parenting stress in the parent-child dyad was measured using the Parenting Stress Index-Short Form at 18-month testing. Results: The cohort consisted of 97 mother-infant dyads (mean [SD] maternal age, 34.79 [5.64] years) who underwent 184 fetal MRI visits (87 participants with 2 fetal studies each) with maternal psychological distress measures between 24 and 40 gestational weeks and completed follow-up infant neurodevelopmental testing. Prenatal maternal stress was negatively associated with infant cognitive performance (ß = -0.51; 95% CI, -0.92 to -0.09; P = .01), and this association was mediated by fetal left hippocampal volume. In addition, prenatal maternal anxiety, stress, and depression were positively associated with all parenting stress measures at 18-month testing. Finally, fetal cortical local gyrification index and sulcal depth were negatively associated with infant social-emotional performance (local gyrification index: ß = -54.62; 95% CI, -85.05 to -24.19; P < .001; sulcal depth: ß = -14.22; 95% CI, -23.59 to -4.85; P = .002) and competence scores (local gyrification index: ß = -24.01; 95% CI, -40.34 to -7.69; P = .003; sulcal depth: ß = -7.53; 95% CI, -11.73 to -3.32; P < .001). Conclusions and Relevance: In this cohort study of 97 mother-infant dyads, fetal cortical local gyrification index and sulcal depth were associated with infant 18-month social-emotional and competence outcomes, and fetal left hippocampal volume mediated the association between prenatal maternal stress and infant cognitive outcome. These findings suggest that altered prenatal brain development in the setting of elevated maternal distress has adverse infant sociocognitive outcomes, and identifying early biomarkers associated with long-term neurodevelopment may assist in early targeted interventions.

In Utero MRI Identifies Impaired Second Trimester Subplate Growth in Fetuses with Congenital Heart Disease.

The subplate is a transient brain structure which plays a key role in the maturation of the cerebral cortex. Altered brain growth and cortical development have been suggested in fetuses with complex congenital heart disease (CHD) in the third trimester. However, at an earlier gestation, the putative role of the subplate in altered brain development in CHD fetuses is poorly understood. This study aims to examine subplate growth (i.e., volume and thickness) and its relationship to cortical sulcal development in CHD fetuses compared with healthy fetuses by using 3D reconstructed fetal magnetic resonance imaging. We studied 260 fetuses, including 100 CHD fetuses (22.3-32 gestational weeks) and 160 healthy fetuses (19.6-31.9 gestational weeks). Compared with healthy fetuses, CHD fetuses had 1) decreased global and regional subplate volumes and 2) decreased subplate thickness in the right hemisphere overall, in frontal and temporal lobes, and insula. Compared with fetuses with two-ventricle CHD, those with single-ventricle CHD had reduced subplate volume and thickness in right occipital and temporal lobes. Finally, impaired subplate growth was associated with disturbances in cortical sulcal development in CHD fetuses. These findings suggested a potential mechanistic pathway and early biomarker for the third-trimester failure of brain development in fetuses with complex CHD. SIGNIFICANCE STATEMENT: Our findings provide an early biomarker for brain maturational failure in fetuses with congenital heart disease, which may guide the development of future prenatal interventions aimed at reducing neurological compromise of prenatal origin in this high-risk population.

Normative placental structure in pregnancy using quantitative Magnetic Resonance Imaging.

INTRODUCTION: To characterize normative morphometric, textural and microstructural placental development by applying advanced and quantitative magnetic resonance imaging (qMRI) techniques to the in-vivo placenta. METHODS: We enrolled 195 women with uncomplicated, healthy singleton pregnancies in a prospective observational study. Women underwent MRI between 16- and 40-weeks' gestation. Morphometric and textural metrics of placental growth were calculated from T2-weighted (T2W) images, while measures of microstructural development were calculated from diffusion-weighted images (DWI). Normative tables and reference curves were constructed for each measured index across gestation and according to fetal sex. RESULTS: Data from 269 MRI studies from 169 pregnant women were included in the analyses. During the study period, placentas undergo significant increases in morphometric measures of volume, thickness, and elongation. Placental texture reveals increasing variability with advancing gestation as measured by grey level non uniformity, run length non uniformity and long run high grey level emphasis. Placental microstructure did not vary with gestational age. Placental elongation was the only metric that differed significantly between male and female fetuses. DISCUSSION: We report quantitative metrics of placental morphometry, texture and microstructure in a large cohort of healthy controls during the second and third trimesters of pregnancy. These measures can serve as normative references of in-vivo placental development to better understand placental function in high-risk conditions and allow for the early detection of placental mal-development.

The Financial Burden of Cancer on Families in the United States.

This study examined the relationship between a diagnosis of cancer and the likelihood of having any out-of-pocket costs (OOPC) and medical debt, and the amounts of OOPC and medical debt, at the household level. We used the 2013 Panel Study of Income Dynamics, a continuous, representative panel survey that collects demographic, economic, and social data in the United States. The analytic sample included head of households and their spouse (if married), 18-64 years old. Two-part models were used. The first part consisted of logistic regression models and the second part consisted of generalized linear models with logarithmic link and a gamma distribution. Logistic regression results showed odds of 2.13 (CI: 1.27, 3.57, p < 0.01) for any OOPC and odds of 1.55 (CI: 0.93, 2.58, p < 0.1) for any medical debt for households in which either the head or spouse (if married) reported a diagnosis of cancer compared to those that did not report a diagnosis of cancer. Likewise, results from the second part of the model for households with a positive amount of OOPC showed an exponentiated coefficient of 1.73 (CI: 1.33, 2.25, p < 0.01) for households in which either the head or spouse (if married) reported a diagnosis of cancer compared to households without a diagnosis of cancer. This study shows that a diagnosis of cancer places a financial burden on families, particularly with all types of debt, in the United States even after controlling for differences between households with a diagnosis of cancer and those without a diagnosis of cancer.

Association Between Socioeconomic Status and In Utero Fetal Brain Development.

Importance: Children raised in settings with lower parental socioeconomic status are at increased risk for neuropsychological disorders. However, to date, the association between socioeconomic status and fetal brain development remains poorly understood. Objective: To determine the association between parental socioeconomic status and in vivo fetal brain growth and cerebral cortical development using advanced, 3-dimensional fetal magnetic resonance imaging. Design, Setting, and Participants: This cohort study of fetal brain development enrolled 144 healthy pregnant women from 2 low-risk community obstetrical hospitals from 2012 through 2019 in the District of Columbia. Included women had a prenatal history without complications that included recommended screening laboratory and ultrasound studies. Exclusion criteria were multiple gestation pregnancy, known or suspected congenital infection, dysmorphic features of the fetus, and documented chromosomal abnormalities. T2-weighted fetal brain magnetic resonance images were acquired. Each pregnant woman was scanned at up to 2 points in the fetal period. Data were analyzed from June through November 2020. Exposures: Parental education level and occupation status were documented. Main Outcomes and Measures: Regional fetal brain tissue volume (for cortical gray matter, white matter, cerebellum, deep gray matter, and brainstem) and cerebral cortical features (ie, lobe volume, local gyrification index, and sulcal depth) in the frontal, parietal, temporal, and occipital lobes were calculated. Results: Fetal brain magnetic resonance imaging studies were performed among 144 pregnant women (median [interquartile range] age, 32.5 [27.0-36.1] years) with gestational age from 24.0 to 39.4 weeks; 75 fetuses (52.1%) were male, and 69 fetuses (47.9%) were female. Higher parental education level was associated with significantly increased volume in the fetal white matter (mothers: ß, 2.86; 95% CI, 1.26 to 4.45; P = .001; fathers: ß, 2.39; 95% CI, 0.97 to 3.81; P = .001), deep gray matter (mothers: ß, 0.16; 95% CI, 0.002 to 0.32; P = .048; fathers: ß, 0.16; 95% CI, 0.02 to 0.31; P = .02), and brainstem (mothers: ß, 0.06; 95% CI, 0.02 to 0.10; P = .01; fathers: ß, 0.04; 95% CI, 0.004 to 0.08; P = .03). Higher maternal occupation status was associated with significantly increased volume in the fetal white matter (ß, 2.07; 95% CI, 0.88 to 3.26; P = .001), cerebellum (ß, 0.17; 95% CI, 0.04 to 0.29; P = .01), and brainstem (ß, 0.03; 95% CI, 0.001 to 0.07; P = .04), and higher paternal occupation status was associated with significantly increased white matter volume (ß, 1.98; 95% CI, 0.71 to 3.25; P < .01). However, higher socioeconomic status was associated with significantly decreased fetal cortical gray matter volume (mothers: ß, -0.11; 95% CI, -0.18 to -0.03; P = .01; fathers: ß, -0.10; 95% CI, -0.18 to -0.03; P = .01). Higher parental socioeconomic status was associated with increased volumes of 3 brain lobes of white matter: frontal lobe (mothers: ß, 0.07; 95% CI, 0.02 to 0.13; P = .01; fathers: ß, 0.06; 95% CI, 0.01 to 0.11; P = .03), parietal lobe (mothers: ß, 0.07; 95% CI, 0.03 to 0.11; P < .001; fathers: ß, 0.06; 95% CI, 0.03 to 0.10; P = .001), and temporal lobe (mothers: ß, 0.04; 95% CI, 0.02 to 0.07; P < .001; fathers: ß, 0.04; 95% CI, 0.02 to 0.07; P < .001), and maternal SES score was associated with significantly decreased volume in the occipital lobe (ß, 0.02; 95% CI, 0.002 to 0.04; P = .03). Higher parental socioeconomic status was associated with decreased cortical local gyrification index (for example, for the frontal lobe, mothers: ß, -1.1; 95% CI, -1.9 to -0.3; P = .01; fathers: ß, -0.8; 95% CI, -1.6 to -0.1; P = .03) and sulcal depth, except for the frontal lobe (for example, for the parietal lobe, mothers: ß, -9.5; 95% CI, -13.8 to -5.3; P < .001; fathers: ß, -8.7; 95% CI, -13.0 to -4.4; P < .001). Conclusions and Relevance: This cohort study found an association between parental socioeconomic status and altered in vivo fetal neurodevelopment. While being born and raised in a lower socioeconomic status setting is associated with poorer neuropsychological, educational, and socioeconomic outcomes in children, these findings suggest that altered prenatal programming may be associated with these outcomes and that future targeted prenatal interventions may be needed.

Association of Prenatal Maternal Psychological Distress With Fetal Brain Growth, Metabolism, and Cortical Maturation.

IMPORTANCE: Prenatal maternal stress is increasingly associated with adverse outcomes in pregnant women and their offspring. However, the association between maternal stress and human fetal brain growth and metabolism is unknown. OBJECTIVE: To identify the association between prenatal maternal psychological distress and fetal brain growth, cortical maturation, and biochemical development using advanced 3-dimensional volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively recruited pregnant women from low-risk obstetric clinics in Washington, DC, from January 1, 2016, to April 17, 2019. Participants were healthy volunteers with a normal prenatal medical history, no chronic or pregnancy-induced physical or mental illnesses, and normal results on fetal ultrasonography and biometry studies. Fetal brain MRI studies were performed at 2 time points between 24 and 40 weeks' gestation. EXPOSURES: Prenatal maternal stress, anxiety, and depression. MAIN OUTCOMES AND MEASURES: Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and hippocampus were measured from 3-dimensional reconstructed T2-weighted MRI scans. Cortical folding measurements included local gyrification index, sulcal depth, and curvedness. Fetal brain N-acetylaspartate, creatine, and choline levels were quantified using 1H-MRS. Maternal stress, depression, and anxiety were measured with the Perceived Stress Scale (PSS), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State Anxiety Inventory (SSAI), and Spielberger Trait Anxiety Inventory (STAI). RESULTS: A total of 193 MRI studies were performed in 119 pregnant women (67 [56%] carrying male fetuses and 52 [44%], female fetuses; maternal mean [SD] age, 34.46 [5.95] years) between 24 and 40 gestational weeks. All women were high school graduates, 99 (83%) were college graduates, and 100 (84%) reported professional employment. Thirty-two women (27%) had positive scores for stress, 31 (26%) for anxiety, and 13 (11%) for depression. Maternal trait anxiety was associated with smaller fetal left hippocampal volume (STAI score: -0.002 cm3; 95% CI, -0.003 to -0.0008 cm3; P = .004). Maternal anxiety and stress were associated with increased fetal cortical gyrification in the frontal lobe (ß for SSAI score: 0.004 [95% CI, 0.001-0.006; P = .002]; ß for STAI score: 0.004 [95% CI, 0.002-0.006; P < .001]; ß for PSS score: 0.005 [95% CI, 0.001-0.008; P = .005]) and temporal lobe (ß for SSAI score: 0.004 [95% CI, 0.001-0.007; P = .004]; ß for STAI score: 0.004 [95% CI, 0.0008-0.006; P = .01]). Elevated maternal depression was associated with decreased creatine (EPDS score: -0.04; 95% CI, -0.06 to -0.02; P = .005) and choline (EPDS score: -0.03; 95% CI, -0.05 to -0.01; P = .02) levels in the fetal brain. CONCLUSIONS AND RELEVANCE: This study found that the prevalence of maternal psychological distress in healthy, well-educated, and employed pregnant women was high, underappreciated, and associated with impaired fetal brain biochemistry and hippocampal growth as well as accelerated cortical folding. These findings appear to support the need for routine mental health surveillance for all pregnant women and targeted interventions in women with elevated psychological distress.

In vivo estimates of axonal stretch and 3D brain deformation during mild head impact.

The rapid deformation of brain tissue in response to head impact can lead to traumatic brain injury. In vivo measurements of brain deformation during non-injurious head impacts are necessary to understand the underlying mechanisms of traumatic brain injury and compare to computational models of brain biomechanics. Using tagged magnetic resonance imaging (MRI), we obtained measurements of three-dimensional strain tensors that resulted from a mild head impact after neck rotation or neck extension. Measurements of maximum principal strain (MPS) peaked shortly after impact, with maximal values of 0.019-0.053 that correlated strongly with peak angular velocity. Subject-specific patterns of MPS were spatially heterogeneous and consistent across subjects for the same motion, though regions of high deformation differed between motions. The largest MPS values were seen in the cortical gray matter and cerebral white matter for neck rotation and the brainstem and cerebellum for neck extension. Axonal fiber strain (Ef) was estimated by combining the strain tensor with diffusion tensor imaging data. As with MPS, patterns of Ef varied spatially within subjects, were similar across subjects within each motion, and showed group differences between motions. Values were highest and most strongly correlated with peak angular velocity in the corpus callosum for neck rotation and in the brainstem for neck extension. The different patterns of brain deformation between head motions highlight potential areas of greater risk of injury between motions at higher loading conditions. Additionally, these experimental measurements can be directly compared to predictions of generic or subject-specific computational models of traumatic brain injury.

Inequalities in Poverty and Income between Single Mothers and Fathers.

BACKGROUND: The American family structure has changed in the past few decades due to a rise in the divorce rate and unmarried women with children. Research suggests a salary disparity between men and women, especially for those women after pregnancy. However, these studies were confined to individuals within traditional families, and there is a lack of information of income disparity and poverty status between single mothers and fathers. The current study explored the disparities in single-parent families based on the household income and the poverty status using a set of nationwide censor data. METHODS: The current study used data from the 2011 and 2013 Panel Study of Income Dynamics (N = 1135). Multivariate regression models were used in the analysis. RESULTS: The demographic characteristics of the weighted population showed that taxable income, total income, and poverty status were higher for single fathers than mothers, while non-work income was higher for single mothers than fathers. Single mothers were much more likely to be at the crisis category than single fathers. Multivariate analyses showed that gender, age, marital status, years of experience, and geographic region had effects on taxable income, and only gender, marital status, and region had effects on poverty status. CONCLUSIONS: The results suggest that vulnerable group of single mothers was acknowledged according to income and poverty status. Age, marital status, years of experience, and region would be the critical factors for predicting the income and poverty status for single parenthood.

3-D Measurements of Acceleration-Induced Brain Deformation via Harmonic Phase Analysis and Finite-Element Models.

OBJECTIVE: To obtain dense spatiotemporal measurements of brain deformation from two distinct but complementary head motion experiments: linear and rotational accelerations. METHODS: This study introduces a strategy for integrating harmonic phase analysis of tagged magnetic resonance imaging (MRI) and finite-element models to extract mechanically representative deformation measurements. The method was calibrated using simulated as well as experimental data, demonstrated in a phantom including data with image artifacts, and used to measure brain deformation in human volunteers undergoing rotational and linear acceleration. RESULTS: Evaluation methods yielded a displacement error of 1.1 mm compared to human observers and strain errors between [Formula: see text] for linear acceleration and [Formula: see text] for rotational acceleration. This study also demonstrates an approach that can reduce error by 86% in the presence of corrupted data. Analysis of results shows consistency with 2-D motion estimation, agreement with external sensors, and the expected physical behavior of the brain. CONCLUSION: Mechanical regularization is useful for obtaining dense spatiotemporal measurements of in vivo brain deformation under different loading regimes. SIGNIFICANCE: The measurements suggest that the brain's 3-D response to mild accelerations includes distinct patterns observable using practical MRI resolutions. This type of measurement can provide validation data for computer models for the study of traumatic brain injury.

Statistical Characterization of Human Brain Deformation During Mild Angular Acceleration Measured In Vivo by Tagged Magnetic Resonance Imaging.

Understanding of in vivo brain biomechanical behavior is critical in the study of traumatic brain injury (TBI) mechanisms and prevention. Using tagged magnetic resonance imaging, we measured spatiotemporal brain deformations in 34 healthy human volunteers under mild angular accelerations of the head. Two-dimensional (2D) Lagrangian strains were examined throughout the brain in each subject. Strain metrics peaked shortly after contact with a padded stop, corresponding to the inertial response of the brain after head deceleration. Maximum shear strain of at least 3% was experienced at peak deformation by an area fraction (median±standard error) of 23.5±1.8% of cortical gray matter, 15.9±1.4% of white matter, and 4.0±1.5% of deep gray matter. Cortical gray matter strains were greater in the temporal cortex on the side of the initial contact with the padded stop and also in the contralateral temporal, frontal, and parietal cortex. These tissue-level deformations from a population of healthy volunteers provide the first in vivo measurements of full-volume brain deformation in response to known kinematics. Although strains differed in different tissue type and cortical lobes, no significant differences between male and female head accelerations or strain metrics were found. These cumulative results highlight important kinematic features of the brain's mechanical response and can be used to facilitate the evaluation of computational simulations of TBI.

Statistical shape analysis of the human spleen geometry for probabilistic occupant models.

Statistical shape models are an effective way to create computational models of human organs that can incorporate inter-subject geometrical variation. The main objective of this study was to create statistical mean and boundary models of the human spleen in an occupant posture. Principal component analysis was applied to fifteen human spleens in order to find the statistical modes of variation, mean shape, and boundary models. A landmark sliding approach was utilized to refine the landmarks to obtain a better shape correspondence and create a better representation of the underlying shape contour. The first mode of variation was found to be the overall volume, and it accounted for 69% of the total variation. The mean model and boundary models could be used to develop probabilistic finite element (FE) models which may identify the risk of spleen injury during vehicle collisions and consequently help to improve automobile safety systems.

Modeling the biomechanical and injury response of human liver parenchyma under tensile loading.

The rapid advancement in computational power has made human finite element (FE) models one of the most efficient tools for assessing the risk of abdominal injuries in a crash event. In this study, specimen-specific FE models were employed to quantify material and failure properties of human liver parenchyma using a FE optimization approach. Uniaxial tensile tests were performed on 34 parenchyma coupon specimens prepared from two fresh human livers. Each specimen was tested to failure at one of four loading rates (0.01s(-1), 0.1s(-1), 1s(-1), and 10s(-1)) to investigate the effects of rate dependency on the biomechanical and failure response of liver parenchyma. Each test was simulated by prescribing the end displacements of specimen-specific FE models based on the corresponding test data. The parameters of a first-order Ogden material model were identified for each specimen by a FE optimization approach while simulating the pre-tear loading region. The mean material model parameters were then determined for each loading rate from the characteristic averages of the stress-strain curves, and a stochastic optimization approach was utilized to determine the standard deviations of the material model parameters. A hyperelastic material model using a tabulated formulation for rate effects showed good predictions in terms of tensile material properties of human liver parenchyma. Furthermore, the tissue tearing was numerically simulated using a cohesive zone modeling (CZM) approach. A layer of cohesive elements was added at the failure location, and the CZM parameters were identified by fitting the post-tear force-time history recorded in each test. The results show that the proposed approach is able to capture both the biomechanical and failure response, and accurately model the overall force-deflection response of liver parenchyma over a large range of tensile loadings rates.

A statistical geometrical description of the human liver for probabilistic occupant models.

Realistic numerical assessments of liver injury risk for the entire occupant population require incorporating inter-subject variations into numerical models. Statistical shape models of the abdominal organs have been shown to be useful tools for the investigation of the organ variations and could be applied to the development of statistical computational models. The main objective of this study was to establish a standard procedure to quantify the shape variations of a human liver in a seated posture, and construct three-dimensional (3D) statistical shape boundary models. Statistical shape analysis was applied to construct shape models of 15 adult human livers. Principal component analysis (PCA) was then utilized to obtain the modes of variation, the mean model, and a set of statistical boundary shape models, which were constructed using the q-hyper-ellipsoid approach. The first five modes of a human liver accounted for the major anatomical variations. The modes were highly correlated to the height, thickness, width, and curvature of the liver, and the concavity of the right lobe. The mean model and the principal components were utilized to construct four boundary models of human liver. The statistical boundary model approach presented in this study could be used to develop probabilistic finite element (FE) models. In the future, the probabilistic liver models could be used in FE simulations to better understand the variability in biomechanical responses and abdominal injuries under impact loading.

Effect of storage on tensile material properties of bovine liver.

Cadaveric tissue models play an important role in the assessment and optimization of novel restraint systems for reducing abdominal injuries. However, the effect of tissue preservation by means of freezing on the material properties of abdominal tissues remains unknown. The goal of this study was to investigate the influence of frozen storage time on the material responses of the liver parenchyma in tensile loading. Specimens from ten bovine livers were equally divided into three groups: fresh, 30-day frozen storage, and 60-day frozen storage. All preserved specimens were stored at -12°C. Dog-bone specimens from each preservation group were randomly assigned to one of three strain rates (0.01s(-1), 0.1s(-1), and 1.0s(-1)) and tested to failure in tensile loading. The local material response recorded at the tear location and the global material response of the whole specimen of the liver parenchyma specimens were investigated based on the experimental data and optimized analytical material models. The local and global failure strains decreased significantly between fresh specimens and specimens preserved for 30 days (p<0.05), and between fresh specimens and specimens preserved for 60 days (p<0.05) for all three loading rates. Changes on the material model parameters were also observed between fresh and preserved specimens. Preservation by means of frozen storage was found to affect both the material and failure response of bovine liver parenchyma in tensile loading. The stiffness of the tissue increased with increased preservation time and increased strain rate. In summary, significant changes (p<0.05) between the failure strain of previously frozen liver parenchyma samples and fresh samples were demonstrated at both global and local levels in this study. In addition, nonlinear and viscoelastic characteristics of the liver parenchyma were observed in tension for both fresh and preserved samples.

Statistical shape analysis of clavicular cortical bone with applications to the development of mean and boundary shape models.

During car collisions, the shoulder belt exposes the occupant's clavicle to large loading conditions which often leads to a bone fracture. To better understand the geometric variability of clavicular cortical bone which may influence its injury tolerance, twenty human clavicles were evaluated using statistical shape analysis. The interior and exterior clavicular cortical bone surfaces were reconstructed from CT-scan images. Registration between one selected template and the remaining 19 clavicle models was conducted to remove translation and rotation differences. The correspondences of landmarks between the models were then established using coordinates and surface normals. Three registration methods were compared: the LM-ICP method; the global method; and the SHREC method. The LM-ICP registration method showed better performance than the global and SHREC registration methods, in terms of compactness, generalization, and specificity. The first four principal components obtained by using the LM-ICP registration method account for 61% and 67% of the overall anatomical variation for the exterior and interior cortical bone shapes, respectively. The length was found to be the most significant variation mode of the human clavicle. The mean and two boundary shape models were created using the four most significant principal components to investigate the size and shape variation of clavicular cortical bone. In the future, boundary shape models could be used to develop probabilistic finite element models which may help to better understand the variability in biomechanical responses and injuries to the clavicle.