Deformation-based Morphometry Research Articles

Cognitive and motor correlates of grey and white matter pathology in Parkinson’s disease

IntroductionPrevious studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinson’s disease (PD). Here we investigate these relationships in a sample of PD patients and age-matched healthy controls. MethodsData included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer’s disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition. ResultsSubstantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p < 0.05). Hippocampal SNIPE scores were associated with cognitve decline in both PD and controls (p < 0.01). WMH burden was significantly associated with cognitive decline and increased motor deficits in the PD group, and gait deficits in both PD and controls (p < 0.03). ConclusionWhile substantia nigra atrophy and WMH burden were significantly associated with additional motor deficits, WMH burden and hippocampal atrophy were associated with cognitive deficits in PD patients. These results suggest an additive contribution of both grey and white matter damage to the motor and cognitive deficits in PD.

White matter hyperintensities and neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease

Neuropsychiatric symptoms (NPS), such as apathy, irritability and depression, are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease is common among AD patients and can be detected on MRI as white matter hyperintensities (WMH). In this longitudinal study, the relative contribution of WMH burden and GM atrophy to NPS was evaluated in a cohort of mild cognitive impairment (MCI), AD and normal controls. This study included 121 AD, 315 MCI and 225 normal control subjects from the Alzheimer’s Disease Neuroimaging Initiative. NPS were assessed using the Neuropsychiatric Inventory and grouped into hyperactivity, psychosis, affective and apathy subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry (DBM) was used to measure atrophy of grey matter regions. Linear mixed-effects models found focal grey matter atrophy and WMH volume both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. This study could provide a better understanding of the pathophysiology of NPS in AD and support the monitoring and control of vascular risk factors.

Spatial Patterning of Tissue Volume Loss in Schizophrenia Reflects Brain Network Architecture

BackgroundThere is growing recognition that connectome architecture shapes cortical and subcortical gray matter atrophy across a spectrum of neurological and psychiatric diseases. Whether connectivity contributes to tissue volume loss in schizophrenia in the same manner remains unknown. MethodsHere, we relate tissue volume loss in patients with schizophrenia to patterns of structural and functional connectivity. Gray matter deformation was estimated in a sample of 133 individuals with chronic schizophrenia (48 women, mean age 34.7 ± 12.9 years) and 113 control subjects (64 women, mean age 23.5 ± 8.4 years). Deformation-based morphometry was used to estimate cortical and subcortical gray matter deformation from T1-weighted magnetic resonance images. Structural and functional connectivity patterns were derived from an independent sample of 70 healthy participants using diffusion spectrum imaging and resting-state functional magnetic resonance imaging. ResultsWe found that regional deformation is correlated with the deformation of structurally and functionally connected neighbors. Distributed deformation patterns are circumscribed by specific functional systems (the ventral attention network) and cytoarchitectonic classes (limbic class), with an epicenter in the anterior cingulate cortex. ConclusionsAltogether, the present study demonstrates that brain tissue volume loss in schizophrenia is conditioned by structural and functional connectivity, accounting for 25% to 35% of regional variance in deformation.

Age-dependent brain volume and neuropsychological changes after chemotherapy in breast cancer patients.

This study investigated volumetric brain changes and cognitive performance in premenopausal and postmenopausal patients treated for early-stage breast cancer. Participants underwent elaborate neurocognitive assessments (neuropsychological testing, cognitive failure questionnaire, and high-resolution T1-weighted structural MRI) before and after chemotherapy. Volumetric brain changes were estimated, using longitudinal deformation-based morphometry, and correlated with cognitive changes. In total, 180 women participated in this study, of whom 72 patients with breast cancer had received adjuvant chemotherapy (C+), 49 patients did not receive chemotherapy (C-), and 59 healthy controls (HC). The population was categorized into two age groups: A young group who were premenopausal and younger than 52 years at baseline (n = 55C+/32C-/41HC), and an older group who were postmenopausal and older than 60 years (n = 17C+/17C-/18HC). Cognitive impairment occurred after chemotherapy in both young and older patients, although older patients showed more decline in processing speed (Trail making test b). White matter volume expansion was observed after chemotherapy, only significantly present in the younger subgroup of patients. In patients not treated with chemotherapy, diffuse gray and white matter volume reduction was observed. Less white matter expansion concurred with more cognitive decline (r > .349, p < .05). In conclusion, we found age-dependent cognitive decline and white matter volume changes in patients with breast cancer after chemotherapy, which could possibly be linked to neuroinflammatory processes. White matter expansion after chemotherapy, more pronounced in premenopausal patients, correlated with less cognitive decline. This suggests such expansion to be age-dependent, possibly caused by a protective response in the younger brain to chemotherapy-induced neurotoxicity.

Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described. A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs. We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p= .002 at the cluster level, p= .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b= 0.069, 95% CI= 0.04-0.1, p=2× 10-16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI= 0.0004-0.01, p= .026). We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

Progressive neuroanatomical changes caused by Grin1 loss-of-function mutation

NMDA receptor dysfunction is central to the encephalopathies caused by missense mutations in the NMDA receptor subunit genes. Missense variants of GRIN1, GRIN2A, and GRIN2B cause similar syndromes with varying severity of intellectual impairment, autism, epilepsy, and motor dysfunction. To gain insight into possible biomarkers of NMDAR hypofunction, we asked whether a loss-of-function variant in the Grin1 gene would cause structural changes in the brain that could be detected by MRI. We also studied the developmental trajectory of these changes to determine whether structural changes coincided with reported cognitive impairments in the mice. We performed magnetic resonance imaging in male Grin1−/− knockdown mice (GluN1KD) that were three, six, or twelve weeks old. Deformation-based morphometry was used to assess neuroanatomical differences. Volumetric reductions were detected in substantia nigra and striatum of GluN1KD mice at all ages. Changes in limbic structures were only evident at six weeks of age. Reductions in white matter volumes were first evident at three weeks, and additional deficits were detected at six and twelve weeks. FluoroJade immunofluorescence revealed degenerating neurons in twelve-week old GluN1KD mice. We conclude that Grin1 loss-of-function mutations cause volume reductions in dopaminergic structures early in development, while changes to limbic and white matter structures are delayed and are more pronounced in post-adolescent ages. The evidence of degenerating neurons in the mature brain indicates an ongoing process of cell loss as a consequence of NMDAR hypofunction.

C.03 Deformation-based morphometry analysis of longitudinal low-grade glioma growth

Background: Diffuse low-grade gliomas (LGGs) are primary brain tumours with infiltrative, anisotropic growth related to surrounding white and grey matter structures. Deformation-based morphometry (DBM) is a simple and objective image analysis method that can identify areas of local volume change over time. In this study, we illustrate the use of DBM to study the local expansion patterns of LGGs monitored by serial magnetic resonance imaging (MRI). Methods: We developed an image processing pipeline optimized for the study of LGG growth involving the fusion of follow-up MRIs for a given patient into an average template space using nonlinear registration. The displacement maps derived from nonlinear registration were converted to Jacobian maps, which estimate local tissue expansion and contraction over time. Results: Our results demonstrate that neoplastic growth occurs primarily around the edges of the tumour while the lesion core and areas adjacent to obstacles, such as the skull, show no significant expansion. Regions of normal brain tissue surrounding the lesion show slight contraction over time, representing compression due to mass effect of the tumour. Conclusions: DBM is a useful tool to understand the long-term clinical course of individual tumours and identify areas of rapid growth, which may explain the current presentation and/or predict future symptoms.

Neurologic Examination Findings Associated With Small Cerebellar Volumes After Prematurity

To help clinicians understand what to expect from small cerebellar volumes after prematurity, this study aims to characterize the specific impacts of small cerebellar volumes on the infant neurologic examination. A prospective cohort of preterm newborns (<32 weeks' gestational age) had brain magnetic resonance imaging (MRI) studies at term-equivalent age. Cerebellar volumes were compared with neurologic examination findings in follow-up, adjusting for severity of intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage. Deformation-based analyses delineated regional morphometric differences in the cerebellum associated with these findings. Of 119 infants with MRI scans, 109 (92%) had follow-up at 19.0±1.7 months corrected age. Smaller cerebellar volume at term was associated with increased odds of truncal hypotonia, postural instability on standing, and patellar hyperreflexia (P < .03). Small cerebellar volume defined as <19 cm3 by 40 weeks was associated with 7.5-fold increased odds of truncal hypotonia (P < .001), 8.9-fold odds postural instability (P < .001), and 9.7-fold odds of patellar hyperreflexia (P < .001). Voxel-based deformation-based morphometry showed postural instability associated with paravermian regions. Small cerebellar volume is associated with specific abnormalities on neurologic examination by 18 months of age, including truncal tone, reflexes, and postural stability.

Brain Morphometry Methods for Feature Extraction in Random Subspace Ensemble Neural Network Classification of First-Episode Schizophrenia.

Machine learning (ML) is a growing field that provides tools for automatic pattern recognition. The neuroimaging community currently tries to take advantage of ML in order to develop an auxiliary diagnostic tool for schizophrenia diagnostics. In this letter, we present a classification framework based on features extracted from magnetic resonance imaging (MRI) data using two automatic whole-brain morphometry methods: voxel-based (VBM) and deformation-based morphometry (DBM). The framework employs a random subspace ensemble-based artificial neural network classifier-in particular, a multilayer perceptron (MLP). The framework was tested on data from first-episode schizophrenia patients and healthy controls. The experiments differed in terms of feature extraction methods, using VBM, DBM, and a combination of both morphometry methods. Thus, features of different types were available for model adaptation. As we expected, the combination of features increased the MLP classification accuracy up to 73.12%-an improvement of 5% versus MLP-based only on VBM or DBM features. To further verify the findings, other comparisons using support vector machines in place of MLPs were made within the framework. However, it cannot be concluded that any classifier was better than another.

A deformation-based approach for characterizing brain asymmetries at different spatial scales of resolution

BackgroundStructural cerebral asymmetries are hypothesized to provide an architectural foundation for functional asymmetries and behavioral lateralities. Studies of structural asymmetries typically focus on gray matter measures that are influenced by gross deformation fields used for normalization, and thus characterize a combination of different morphologic influences on structural asymmetries. New methodA deformation-based morphometry approach was developed to characterize structural asymmetries at different spatial scales of resolution, which can provide relatively more specific inference about the morphologic reason(s) for structural asymmetries, using a dataset of 347 typically developing children (7.00–12.92 years). ResultsSignificant structural asymmetries were observed for a larger lobar spatial scale (e.g., frontal petalia) and for a smaller gyral/sulcal spatial scale of resolution (e.g., marginal sulcus). Total intracranial volume was significantly associated with asymmetries at the larger spatial scale of normalization, while age was significantly associated with asymmetries at the smaller scale of normalization. There were no significant anti- or fluctuating asymmetry effects based on Hartigan Dip Tests and Bonnett Tests, respectively. Comparison with existing method(s)While spatially similar asymmetries were observed in both gray matter and deformation field data (e.g., medial planum temporale/Heschl’s gyrus), the deformation approach characterizes asymmetries based on three iterations of successively smaller scales of normalization. ConclusionsStructural asymmetries can be identified in normalization deformations with a procedure that is tailored for sensitivity to structures at different spatial scales of resolution where there may be different mechanisms for the expression of asymmetry.

Left temporal plane growth predicts language development in newborns with congenital heart disease.

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age.

Cervical vertebral body growth and emergence of sexual dimorphism: a developmental study using computed tomography.

The size and shape of human cervical vertebral bodies serve as a reference for measurement or treatment planning in multiple disciplines. It is therefore necessary to understand thoroughly the developmental changes in the cervical vertebrae in relation to the changing biomechanical demands on the neck during the first two decades of life. To delineate sex-specific changes in human cervical vertebral bodies, 23 landmarks were placed in the midsagittal plane to define the boundaries of C2 to C7 in 123 (73M; 50F) computed tomography scans from individuals, ages 6months to 19years. Size was calculated as the geometric area, from which sex-specific growth trend, rate, and type for each vertebral body were determined, as well as length measures of local deformation-based morphometry vectors from the centroid to each landmark. Additionally, for each of the four pubertal-staged age cohorts, sex-specific vertebral body wireframes were superimposed using generalized Procrustes analysis to determine sex-specific changes in form (size and shape) and shape alone. Our findings reveal that C2 was unique in achieving more of its adult size by 5years, particularly in females. In contrast, C3-C7 had a second period of accelerated growth during puberty. The vertebrae of males and females were significantly different in size, particularly after puberty, when males had larger cervical vertebral bodies. Male growth outpaced female growth around age 10years and persisted until around age 19-20years, whereas females completed growth earlier, around age 17-18years. The greatest shape differences between males and females occurred during puberty. Both sexes had similar growth in the superoinferior height, but males also displayed more growth in anteroposterior depth. Such prominent sex differences in size, shape, and form are likely the result of differences in growth rate and growth duration. Female vertebrae are thus not simply smaller versions of the male vertebrae. Additional research is needed to further quantify growth and help improve age- and sex-specific guidance in clinical practice.

Brain atrophy in Parkinson's disease with polysomnography-confirmed REM sleep behavior disorder.

We aimed to investigate cortical and subcortical brain alterations in people with Parkinson's disease with polysomnography-confirmed rapid eye movement (REM) sleep behavior disorder (RBD). Thirty people with Parkinson's disease, including 15 people with RBD, were recruited and compared with 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. People with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared with people without RBD. Compared with controls, people with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, people without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson's disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson's disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in people with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in people with Parkinson's disease with RBD.

A surface-in gradient of thalamic damage evolves in pediatric multiple sclerosis.

ObjectiveCentral nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface‐in" process of injury suggesting progressive biology may begin.MethodsWe focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation‐based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods.ResultsTwenty‐seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow‐up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface‐in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44–4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12–0.54, p = 0.0021).InterpretationOur results suggest that a multiple sclerosis disease‐specific surface‐in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340–351.

Neural correlates of distinct cognitive phenotypes in early Parkinson's disease

ObjectiveCognitive decline is common in Parkinson's disease (PD), but changes can occur in a variety of cognitive domains. The lack of a single cognitive phenotype complicates diagnosis and tracking. In an earlier study we used a data-driven approach to identify distinct cognitive phenotypes of early PD. Here we identify the morphometric brain differences between those different phenotypes compared with cognitively normal PD participants. MethodsSix different cognitive classes were included (Weak, Typical, Weak-Visuospatial/Strong-Memory, Weak-Visuospatial, Amnestic, Strong). Structural differences between each class and the Typical class were assessed by deformation-based morphometry. ResultsThe different groups evidenced different patterns of atrophy. Weak class had frontotemporal and insular atrophy; Weak-Visuospatial/Strong-Memory class had frontotemporal, insular, parietal, and putamen atrophy; Weak-Visuospatial class had Rolandic operculum; Amnestic class had left frontotemporal, occipital, parietal and insular atrophy when compared to the Typical class. The Strong class did not have any atrophy but had significant differences in left temporal cortex in comparison to the Typical class. ConclusionsStructural neuroimaging differences are evident in PD patients with distinct cognitive phenotypes even very early in the disease process prior to the emergence of frank cognitive impairment. Future studies will elucidate whether these have prognostic value in identifying trajectories toward dementia, or if they represent groups sensitive to different treatments.

Radiologic changes in the aging nasal cavity

With an aging population, it is important to understand age-related anatomic changes in the nasal cavity and cribriform plate (CP) that may have clinical implications. Computed tomography (CT) scans obtained for non-rhinologic conditions were divided into a young cohort (N=35, 18-34 years old) and an older adult cohort (N=32, 80-99 years old). Intranasal airspace volumes and bony anatomy of the CP were manually segmented using OsiriX software. The CP was assessed for mean Hounsfield Units (HU) and percentage of olfactory foramina. Deformation based morphometry (DBM) was then performed on the same cohort and correlated with manual measurements. Individual nasal cavity volumes increased 17-75% with age. Regression analysis of all scans revealed age to be the predominant variable influencing intranasal volume differences when controlling for sex and head size. Mean HU of the CP negatively correlated with age. No age-related differences in bone stenosis of olfactory foramina were identified. Automated DBM measurements of intranasal volumes, as well as CP and zygoma mean HU correlated with manual measurements. Older subjects have a global increase in intranasal volumes and diffuse bone density loss in the CP. The clinical impact of age-related anatomic changes in the nasal cavity and CP requires further investigation.

Deformation based morphometry study of longitudinal MRI changes in behavioral variant frontotemporal dementia.

To objectively quantify how cerebral volume loss could assist with clinical diagnosis and clinical trial design in the behavioural variant of frontotemporal dementia (bvFTD). We applied deformation-based morphometric analyses with robust registration to precisely quantify the magnitude and pattern of atrophy in patients with bvFTD as compared to cognitively normal controls (CNCs), to assess the progression of atrophy over one year follow up and to generate clinical trial sample size estimates to detect differences for the structures most sensitive to change. This study included 203 subjects - 70 bvFTD and 133 CNCs - with a total of 482 timepoints from the Frontotemporal Lobar Degeneration Neuroimaging Initiative. Deformation based morphometry (DBM) revealed significant atrophy in the frontal lobes, insula, medial and anterior temporal regions bilaterally in bvFTD subjects compared to controls with outstanding subcortical involvement. We provide detailed information on regional changes per year. In both cross-sectional analysis and over a one-year follow-up period, ventricle expansion was the most prominent differentiator of bvFTD from controls and a sensitive marker of disease progression. Automated measurement of ventricular expansion is a sensitive and reliable marker of disease progression in bvFTD to be used in clinical trials for potential disease modifying drugs, as well as possibly to implement in clinical practice. Ventricular expansion measured with DBM provides the lowest published estimated sample size for clinical trial design to detect significant differences over one and two years.

Mild traumatic brain injury: The effect of age at trauma onset on brain structure integrity.

Mounting evidence suggests that mild traumatic brain injuries (mTBI) have long-term effects that interact with the aging process to precipitate cognitive decline. This line of research predicts that early exposure to brain trauma is particularly detrimental to long-term brain integrity. However, a second line of research into the effects of age at trauma onset predict that older brains are more vulnerable to the effects of mTBI than younger brains. We sought to determine whether patients who sustain a mTBI earlier in life fare better than patients who sustain a mTBI at an older age. We conducted a multi-cohort, case-control study, with participants randomly sampled from a population of patients with a history of mTBI. We recruited two cohorts of aging participants (N = 74, mean [SD] = 61.16 [6.41]) matched in age and education levels that differed in only one respect: age at mTBI onset. One cohort sustained their concussion in their early twenties (24.60 [6.34] y/o), the other in their early sixties (61.05 [4.90] y/o). Each mTBI cohort had its own matched control group. Participants underwent high-resolution MRI at 3 Tesla for T1 and diffusion-weighted images (DWI) acquisition. Images were processed and analyzed using Deformation-Based Morphometry and DWI Tract-Based Spatial Statistics to identify group differences in a 2 × 2 ANOVA design. Results showed a significant interaction on DWI measures of white matter integrity indicating larger anomalies in participants who sustained a mTBI at a younger age (F1,70, P < .05, FDR corrected). These findings suggest that mTBI initiates a lifelong neurodegeneration process that outweighs the risks associated with sustaining a mTBI at an older age. Implications are important for young athletes' populations exposed to the risk of mTBI in the practice of their sports and for retired athletes aging with a history of concussions sustained at a younger age.

Deformation-based Morphometry MRI Reveals Brain Structural Modifications in Living Mu Opioid Receptor Knockout Mice.

Mu opioid receptor (MOR) activation facilitates reward processing and reduces pain, and brain networks underlying these effects are under intense investigation. Mice lacking the MOR gene (MOR KO mice) show lower drug and social reward, enhanced pain sensitivity and altered emotional responses. Our previous neuroimaging analysis using Resting-state (Rs) functional Magnetic Resonance Imaging (fMRI) showed significant alterations of functional connectivity (FC) within reward/aversion networks in these mice, in agreement with their behavioral deficits. Here we further used a structural MRI approach to determine whether volumetric alterations also occur in MOR KO mice. We acquired anatomical images using a 7-Tesla MRI scanner and measured deformation-based morphometry (DBM) for each voxel in subjects from MOR KO and control groups. Our analysis shows marked anatomical differences in mutant animals. We observed both local volumetric contraction (striatum, nucleus accumbens, bed nucleus of the stria terminalis, hippocampus, hypothalamus and periacqueducal gray) and expansion (prefrontal cortex, amygdala, habenula, and periacqueducal gray) at voxel level. Volumetric modifications occurred mainly in MOR-enriched regions and across reward/aversion centers, consistent with our prior FC findings. Specifically, several regions with volume differences corresponded to components showing highest FC changes in our previous Rs-fMRI study, suggesting a possible function-structure relationship in MOR KO-related brain differences. In conclusion, both Rs-fMRI and volumetric MRI in live MOR KO mice concur to disclose functional and structural whole-brain level mechanisms that likely drive MOR-controlled behaviors in animals, and may translate to MOR-associated endophenotypes or disease in humans.

Age-related differences in olfactory cleft volume in adults: A computational volumetric study.

There is a growing need to understand the underlying mechanisms of age-related olfactory dysfunction with the increasing proportion of older adults over the next 20 years. Despite the importance of olfactory cleft (OC) volumes on odorant deposition and olfactory function, little is known about age-related changes to OC volume. The goal of this study was to use automated techniques in a cross-sectional design to investigate the extent to which OC volumes vary with age and determine the spatial specificity of any age-related effects. Retrospective cross-sectional study. Deformation-based morphometry was utilized to measure OC and sinus volumes in two independent samples of 101 (Medical University of South Carolina [MUSC] sample) and 95 (Hammersmith sample) healthy adults who underwent T1-weighted magnetic resonance imaging, with the Hammersmith sample serving as a replication sample. The mean age of the MUSC and Hammersmith samples were 54.9 ± 17.0 years and 52.1 years ± 15.7 years, respectively. In both samples, there was a significant positive association between age and OC volume that occurred at a constant rate across the lifespan (Cohen's f2 of 0.065 in the MUSC sample and 0.110 in the Hammersmith sample). Age-associated OC volume increases occurred in conjunction with decreases in sinus volumes as well as increases in non-OC nasal cavity volumes. In this cross-sectional study, there is an increase in OC volume with increasing age that occurs in the context of broad age-associated differences in sinonasal anatomy. Future studies should investigate the impact of age-associated differences in intranasal anatomy on nasal airflow, odorant deposition, and olfactory function. 4 Laryngoscope, 129:E55-E60, 2019.