Cortical Microstructure Research Articles

Frontoinsular cortical microstructure is linked to life satisfaction in young adulthood.

Life satisfaction is a component of subjective well-being that reflects a global judgement of the quality of life according to an individual's own needs and expectations. As a psychological construct, it has attracted attention due to its relationship to mental health, resilience to stress, and other factors. Neuroimaging studies have identified neurobiological correlates of life satisfaction; however, they are limited to functional connectivity and gray matter morphometry. We explored features of gray matter microstructure obtained through compartmental modeling of multi-shell diffusion MRI data, and we examined cortical microstructure in frontoinsular cortex in a cohort of 807 typical young adults scanned as part of the Human Connectome Project. Our experiments identified the orientation dispersion index (ODI), and analogously fractional anisotropy (FA), of frontoinsular cortex as a robust set of anatomically-specific lateralized diffusion MRI microstructure features that are linked to life satisfaction, independent of other demographic, socioeconomic, and behavioral factors. We further validated our findings in a secondary test-retest dataset and found high reliability of our imaging metrics and reproducibility of outcomes. In our analysis of twin and non-twin siblings, we found basic microstructure in frontoinsular cortex to be strongly genetically determined. We also found a more moderate but still very significant genetic role in determining microstructure as it relates to life satisfaction in frontoinsular cortex. Our findings suggest a potential linkage between well-being and microscopic features of frontoinsular cortex, which may reflect cellular morphology and architecture and may more broadly implicate the integrity of the homeostatic processing performed by frontoinsular cortex as an important component of an individual's judgements of life satisfaction.

Computational implementation of nonuniform orthotropic directions in the femoral diaphysis based on cortical bone microstructure to build a constitutive model

Computational implementation of nonuniform orthotropic directions in the femoral diaphysis based on cortical bone microstructure to build a constitutive model

Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multicenter structural magnetic resonance imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male), and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. Increases were observed in different brain regions in males and females, with larger effect sizes in females. BSC correlated with ADOS-2 Calibrated Severity Score in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared with cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

Apolipoprotein E homozygous ε4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample

Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation to APOE, sporadic recent findings have questioned the specificity of the hippocampus and instead suggested more global effects on the brain. With the present study we aimed to investigate associations between homozygous APOE ε4 status and cortical gray matter structure as well as white matter microstructure. In our study, we contrasted n = 31 homozygous APOE ε4 carriers (age=34.47 years, including a subsample of n = 12 subjects with depression) with a demographically matched sample without an ε4 allele (resulting total sample: N = 62). Morphometry analyses included a) Freesurfer based cortical segmentations of thickness and surface area measures and b) tract based spatial statistics of DTI measures. We found pronounced and widespread reductions in cortical surface area of ε4 homozygotes in 57 out of 68 cortical brain regions. In contrast, no differences in cortical thickness were observed. Furthermore, APOE ε4 homozygous carriers showed significantly lower fractional anisotropy in the corpus callosum, the right internal and external capsule, the left corona radiata and the right fornix. The present findings support a global rather than regionally specific effect of homozygous APOE ε4 allele status on cortical surface area and white matter microstructure. Future studies should aim to delineate the clinical implications of these findings.

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.

Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery.NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.

Abstract PS9-23: Second-generation HR-pQCT analysis of bone mineral density and microstructure in women with breast cancer who underwent adjuvant endocrine therapy

Abstract Background: Adjuvant endocrine therapy for 5-10 years reduces breast cancer (BC) mortality in women with hormone receptor-positive BC. However, aromatase inhibitors (AIs) decrease bone mineral density (BMD), and increase fractures, joint stiffness, and joint pain. Although dual energy X-ray absorptiometry (DXA) is widely used to assess BMD, it is a two-dimensional method and thus cannot analyze trabecular and cortical bone microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows in vivo analysis of peripheral bone microarchitecture with high spatial resolution and low radiation exposure. We used HR-pQCT to evaluate changes in volumetric bone density and microstructure consisting of trabecular and cortical bone associated with AI treatment in patients with early BC. Methods: This was a prospective single-center observational study of nonosteoporotic, postmenopausal women with hormone receptor-positive BC, whose baseline DXA lumber spine and femoral neck T-scores were > −2.5. All patients were scheduled to receive DXA and HR-pQCT at baseline and at 6 and 12 months after starting AI therapy. The primary endpoint was to examine changes in total volumetric BMD (Tt. vBMD), trabecular volumetric BMD (Tb. vBMD), cortical volumetric BMD (Ct. vBMD) change at the distal radius and the distal radius between baseline and 6 and 12 months after starting endocrine therapy. Results: Of the 20 women in the study (median age: 57.5 years; range: 55-72 years), 8 had undergone chemotherapy before registration. Their mean change in Tt. vBMD between baseline and 1 year were distal radius: −5.7% (SD: 2.5%, P<0.01); distal tibia: −3.8% (SD: 1.8%, P<0.01), Tb. vBMD distal radius: −4.0% (SD: 3.9%, P<0.01); distal tibia: −0.9% (SD: 2.4%, P<0.05), Ct. vBMD distal radius: −3.1% (SD: 1.6%, P<0.01); distal tibia: −2.9% (SD: 1.7%, P<0.01). Furthermore, at 1 year in trabecular bone, mean trabecular bone volume fraction (p<0.01), trabecular thickness (p<0.05), and trabecular number (p<0.01) were significantly decreased, and trabecular separation (p<0.01) increased, in both the distal radius and tibia. At 1 year in cortical bone, mean changes in cortical thickness (p<0.01) and cortical bone area (p<0.01) were significantly decreased in both the distal radius and tibia; however, the endocortical perimeter of cortical bone did not significantly change and cortical porosity (p<0.05) was significantly greater than that at baseline. At 1 year, DXA decreased at the total hip (−4.4%, P<0.01) and femoral neck (−0.6%, P=0.03) compared with baseline. However, no significant difference was seen in median values for lumbar spine BMD at 1 year, or for tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (PINP). Conclusion: Postmenopausal women who took AIs for early BC experience volumetric bone density decline and both trabecular and cortical bone deterioration. A decade of AI treatment is a standard treatment for early BC; however, healthcare professionals should monitor bone health during and after these treatments. Citation Format: Sayaka Kuba, Konosuke Watanabe, Megumi Matsumoto, Ko Chiba, Kosho Yamanouchi, Ayako Fukushima, Michi Morita, Ryota Otsubo, Hiroshi Yano, Kengo Kanetaka, Makoto Osaki, Takeshi Nagayasu, Susumu Eguchi. Second-generation HR-pQCT analysis of bone mineral density and microstructure in women with breast cancer who underwent adjuvant endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-23.

Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT).

The aim of this study was to examine the effects of period-specific and cumulative fluoride (F) intake on bone at the levels of cortical and trabecular bone microstructural outcomes at early adulthood using emerging multi-row detector computed tomography (MDCT)-based novel techniques. Ultra-high resolution MDCT distal tibia scans were collected at age 19 visits under the Iowa Bone Development Study (IBDS), and cortical and trabecular bone microstructural outcomes were computed at the distal tibia using previously validated methods. CT scans of a tissue characterization phantom were used to calibrate CT numbers (Hounsfield units) into bone mineral density (mg/cc). Period-specific and cumulative F intakes from birth up to the age of 19years were assessed for IBDS participants through questionnaire, and their relationships with MDCT-derived bone microstructural outcomes were examined using bivariable and multivariable analyses, adjusting for height, weight, maturity offset (years since age of peak height velocity (PHV)), physical activity (questionnaire for adolescents (PAQ-A)), healthy eating index version 2010 (HEI-2010) scores, and calcium and protein intakes. MDCT distal tibia scans were acquired for 324 participants from among the total of 329 participants at age 19 visits. No motion artifacts were observed in any MDCT scans, and all images were successfully processed to measure cortical and trabecular bone microstructural outcomes. At early adulthood, males were observed to have stronger trabecular bone microstructural features, as well as thicker cortical bone (p<0.01), as compared to age-similar females; however, females were found to have less cortical bone porosity as compared to males. Among participants with available F intake estimates (75 to 91% of the 324 with MDCT scans, depending on the period-specific F intake measure), no statistically significant associations were detected between any period-specific or cumulative F intake and bone microstructural outcomes of the tibia at the p<0.01 level. Only for females, statistically suggestive associations (p<0.05) were found between recent F intake (from 14 to 19years) and trabecular mean plate width and trabecular thickness at the tibia. Those associations became somewhat weaker, but still statistically suggestive, for trabecular thickness in fully adjusted analysis with height, weight, PHV, calcium and protein intake, and HEI-2010 and PAQ-A scores as covariates. The findings show that the effects of lifelong or period-specific F intake from combined sources for adolescents typical to the United States Midwest region are not strongly associated with bone microstructural outcomes at age 19years. These findings are generally consistent with previously reported results of IBDS analyses, which further confirms that effects of lifelong or period-specific F intake on skeletons in early adulthood are absent or weak, even at the levels of cortical and trabecular bone microstructural details.

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01years) of the participants was higher than their mean chronological age (10.77years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .

Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions

Cortical bone microstructure deficits may increase fracture risk in individuals with cardiovascular disease and diabetes. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo microstructure characterization but is limited in its ability to visualize important biological features. We conducted histological analyses and HR-pQCT imaging of distal tibia bone samples from 6 donors with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). Histology but not HR-pQCT identified previously undocumented morphopathological deficits that may contribute to cortical bone fragility. These observations may provide guidance for improved HR-pQCT microstructural characterization as well as insight into mechanisms of cortical bone degradation.

White matter fascicles and cortical microstructure predict reading-related responses in human ventral temporal cortex

Reading-related responses in the lateral ventral temporal cortex (VTC) show a consistent spatial layout across individuals, which is puzzling, since reading skills are acquired during childhood. Here, we tested the hypothesis that white matter fascicles and gray matter microstructure predict the location of reading-related responses in lateral VTC. We obtained functional (fMRI), diffusion (dMRI), and quantitative (qMRI) magnetic resonance imaging data in 30 adults. fMRI was used to map reading-related responses by contrasting responses in a reading task with those in adding and color tasks; dMRI was used to identify the brain's fascicles and to map their endpoint densities in lateral VTC; qMRI was used to measure proton relaxation time (T1), which depends on cortical tissue microstructure. We fit linear models that predict reading-related responses in lateral VTC from endpoint density and T1 and used leave-one-subject-out cross-validation to assess prediction accuracy. Using a subset of our participants (N=10, feature selection set), we find that i) endpoint densities of the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), and vertical occipital fasciculus (VOF) are significant predictors of reading-related responses, and ii) cortical T1 of lateral VTC further improves the predictions of the fascicle model. In the remaining participants (N=20, validation set), we show that a linear model that includes T1, AF, ILF and VOF significantly predicts i) the map of reading-related responses across lateral VTC and ii) the location of the visual word form area, a region critical for reading. Overall, our data-driven approach reveals that the AF, ILF, VOF and cortical microstructure have a consistent spatial relationship with an individual's reading-related responses in lateral VTC.

Diffusion-MRI-based regional cortical microstructure at birth for predicting neurodevelopmental outcomes of 2-year-olds.

Cerebral cortical architecture at birth encodes regionally differential dendritic arborization and synaptic formation. It underlies behavioral emergence of 2-year-olds. Brain changes in 0-2 years are most dynamic across the lifespan. Effective prediction of future behavior with brain microstructure at birth will reveal structural basis of behavioral emergence in typical development and identify biomarkers for early detection and tailored intervention in atypical development. Here we aimed to evaluate the neonate whole-brain cortical microstructure quantified by diffusion MRI for predicting future behavior. We found that individual cognitive and language functions assessed at the age of 2 years were robustly predicted by neonate cortical microstructure using support vector regression. Remarkably, cortical regions contributing heavily to the prediction models exhibited distinctive functional selectivity for cognition and language. These findings highlight regional cortical microstructure at birth as a potential sensitive biomarker in predicting future neurodevelopmental outcomes and identifying individual risks of brain disorders.

Contrasting alterations between cortical and subcortical myelin across age, AD diagnosis, and amyloid and tau pathology as assessed by quantitative R1 mapping

AbstractBackgroundAccumulation of pathology in cortical tissue are early pathological hallmarks of Alzheimer’s disease. High resolution T1w/T2w ratio maps from structural MRI may reflect tissue microstructure with sensitivity to myelin, iron, and dendritic density. Few studies have investigated this in AD with conflicting reports of directionality of T1w/T2w ratios in individuals with AD diagnosis and pathology. However, these ratios will be sensitive to pulse sequences, protocols and bias field inhomogeneities, limiting their utility in clinical and research contexts. Here we employ R1 (=1/T1) relaxometry mapping, a quantitative imaging measure that is sensitive to myelin, to investigate relationships between cortical and subcortical tissue microstructure, age, AD diagnosis, and amyloid and tau pathology.MethodParticipants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent 3T MRI with whole‐brain, 1mm isotropic MPnRAGE T1 relaxometry with motion correction (Kecskemeti et al., 2016) (N=605/CN, 39/AD; age = 65.49 +/‐ 7.89 yrs) with a subset undergoing lumbar puncture for CSF Aß42/Tau biomarker classification (N = 141/A‐T‐, 26/A+T‐, 22/A‐T+, 18/A+T+). T1‐weighted images were processed using ANTS and CAT12, and transformation warps were applied to produce subcortical R1 maps in MNI space (6mm smoothing) and cortical R1 surface meshes (164k mesh, 5mm smoothing). Vertex‐wise (GM) and voxel‐wise (WM) ANCOVA were performed (p&lt;0.05 FWE corrected). Covariates included age, sex, study protocol, and AD diagnosis in model 1, and age, sex, years between CSF collection and MRI, study protocol, and A/T biomarker group in model 2.ResultSignificant associations between R1 and age, clinical AD diagnosis, and A/T pathology were found (Figure 1A‐C). Post‐hoc tests revealed increased R1 due to A/T pathology driven by A+T+ individuals. In contrast, significant widespread decreases in subcortical R1 were found with age and AD diagnosis (Figure 1D&amp;E), with no significant alterations in subcortical R1 due to biomarker status.ConclusionCortical and subcortical tissue exhibit differential tissue microstructural changes in response to aging, AD diagnosis and pathology. Importantly, increases in cortical R1 in unimpaired A+T+ individuals may reflect increased remyelination prior to the development of cognitive impairment. Future research will assess longitudinal relationships of R1 with age, cognition and markers of neurodegeneration.

Bone Deterioration in Response to Chronic High-Altitude Hypoxia Is Attenuated by a Pulsed Electromagnetic Field Via the Primary Cilium/HIF-1α Axis.

Chronic high-altitude hypoxia induces irreversible abnormalities in various organisms. Emerging evidence indicates that hypobaric hypoxia markedly suppresses bone mass and bone strength. However, few effective means have been identified to prevent such bone deficits. Here, we assessed the potential of pulsed electromagnetic fields (PEMFs) to noninvasively resist bone deterioration induced by hypobaric hypoxia. We observed that exogenous PEMF treatment at 15 Hz and 20 Gauss (Gs) improved the cancellous and cortical bone mass, bone microstructure, and skeletal mechano-properties in rats subjected to chronic exposure of hypobaric hypoxia simulating an altitude of 4500 m for 6 weeks by primarily modulating osteoblasts and osteoblast-mediated bone-forming activity. Moreover, our results showed that whereas PEMF stimulated the functional activity of primary osteoblasts in hypoxic culture in vitro, it had negligible effects on osteoclasts and osteocytes exposed to hypoxia. Mechanistically, the primary cilium was found to function as the major electromagnetic sensor in osteoblasts exposed to hypoxia. The polycystins PC-1/PC-2 complex was identified as the primary calcium channel in the primary cilium of hypoxia-exposed osteoblastic cells responsible for the detection of external PEMF signals, and thereby translated these biophysical signals into intracellular biochemical events involving significant increase in the intracellular soluble adenylyl cyclase (sAC) expression and subsequent elevation of cyclic adenosine monophosphate (cAMP) concentration. The second messenger cAMP inhibited the transcription of oxygen homeostasis-related hypoxia-inducible factor 1-alpha (HIF-1α), and thus enhanced osteoblast differentiation and improved bone phenotype. Overall, the present study not only advances our understanding of bone physiology at high altitudes, but more importantly, proposes effective means to ameliorate high altitude-induced bone loss in a noninvasive and cost-effective manner. © 2023 American Society for Bone and Mineral Research (ASBMR).

Characterization of Baboon Cortical Bone Microstructural Changes by Low Field NMR and Correlation of Bone Mechanical Properties

A NMR spin-spin (T2) relaxation technique has been described for determining the porosity, mobile and the bound water distribution in baboon cortical bone and correlate to their mechanical properties. The technique of low-field proton NMR involves spin-spin relaxation and free induction decay (FID) measurements, and the computational inversion methods for decay data analysis. The advantages of using NMR T2 relaxation techniques for bone water distribution are illustrated. The CPMG T2 relaxation data can be inverted to T2 relaxation distribution and this distribution then can be transformed to a pore size distribution with the longer relaxation times corresponding to larger pores. The FID T2 relaxation data can be inverted to T2 relaxation distribution and this distribution then can be transformed to bound and mobile water distribution with the longest relaxation time corresponding to mobile water and the middle relaxation time corresponding to bound water. The technique is applied to quantify apparent changes in porosity, bound and mobile water in cortical bone. Overall bone porosity is determined using the calibrated NMR fluid volume from the proton relaxation data divided by overall bone volume. The NMR porosity, bound and mobile water components are determined from cortical bone specimens obtained from baboon donors of different ages, and the results are correlated to bone mechanical properties.

A multi-scale cortical wiring space links cellular architecture and functional dynamics in the human brain.

The vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here, we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico-cortical wiring established by postmortem anatomical studies and capitalises on cutting-edge in vivo neuroimaging and machine learning. The new model expands the currently prevailing diffusion magnetic resonance imaging (MRI) tractography approach by incorporation of additional features of cortical microstructure and cortico-cortical proximity. Studying several datasets and different parcellation schemes, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior-posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics based on resting-state functional magnetic resonance imaging (rs-fMRI) and human intracranial electroencephalography (EEG) coherence. Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals.

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study.

To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment. Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12months (mean 18.6months) received sequential therapy with 1mg/month intravenous ibandronate for 12months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12months after beginning administration. At 12months after beginning sequential therapy, the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6months after treatment initiation. Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment.

Cortical morphology at birth reflects spatiotemporal patterns of gene expression in the fetal human brain.

Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.

Detection of Alzheimer's Disease using cortical diffusion tensor imaging.

The aim of this research was to test a novel in‐vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer's Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the “Discovery” cohort, the second as the “Test” cohort and the last “ATN” (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADNI 3 cohort, comparing to amyloid and Tau PET. The method can detect altered quality of cortical grey matter in AD patients, providing an additional tool to assess AD, distinguishing between these and healthy controls with an accuracy range between good and excellent. These new measurements could be used within the “ATN” framework as an index of cortical microstructure quality and a marker of Neurodegeneration. Further development may aid diagnosis, patient selection, and quantification of the “Neurodegeneration” component in response to therapies in clinical trials.

Trace element distribution in human cortical bone microstructure: the potential for unravelling diet and social status in archaeological bones

Variation in the trace element chemistry of cortical bone microstructure is delineated for interred and non-interred human femora. This was done to investigate the range of element concentrations that might occur within single bones, specifically the original laminar bone and later osteons, and its potential for investigating chemical life histories. To do so, femora were chosen from individuals who experienced quite different ways of life over the past two millennia. The distributions of Sr, Ba, Cu, and Pb, mostly in partial (early) and complete (late) osteons, in cross-sections of proximal femora were characterized through Laser Ablation Inductively Coupled Plasma Mass Spectrometry. Absolute calibrations of these data were obtained using solution Inductively Coupled Plasma Mass Spectrometry on adjacent dissolved bulk samples. Chemical life histories were approximated by classifying bone microstructure into four categories: laminar bone and 1st, 2nd, and 3rd generation osteons. This four-part sequence, on average, charts the temporal dimension of an individual’s life. Consistent with recent studies of medieval bones, Sr and Ba are thought to be mainly responsive to diet, presumably related to the consumption of mostly locally produced food, while Cu and Pb do the same for heavy metal exposure often attributable to social status or occupation. No systematic differences in these elements were found between interred and non-interred individuals. The effect of diagenesis on interpretations of life histories based on archaeological bone, therefore, are minimized by plotting element concentrations across cortical bone cross-sections.