Non-invasive evaluation of blood oxygen saturation and hematocrit from T and T relaxation times: In-vitro validation in fetal blood.

Purpose: We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO ) from measurements of its T and T relaxation times.

Theory: Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO in terms of R and R . Resulting solutions for Hct and sO are the roots of cubic polynomials.

Widespread Volumetric Brain Changes following Tooth Loss in Female Mice.

Tooth loss is associated with altered sensory, motor, cognitive and emotional functions. These changes vary highly in the population and are accompanied by structural and functional changes in brain regions mediating these functions. It is unclear to what extent this variability in behavior and function is caused by genetic and/or environmental determinants and which brain regions undergo structural plasticity that mediates these changes.

Imaging sex/gender and autism in the brain: Etiological implications.

The male preponderance in autism prevalence has brought together the disparate topics of sex/gender and autism research. Two directions of neuroimaging studies on the relationships between sex/gender and autism may inform male-specific risk mechanisms and female-specific protective mechanisms of autism. First, we review how sex/gender moderates autism-related brain changes and how this informs general models of autism etiology.

Effects of voluntary exercise on structure and function of cortical microvasculature.

Aerobic activity has been shown highly beneficial to brain health, yet much uncertainty still surrounds the effects of exercise on the functioning of cerebral microvasculature. This study used two-photon fluorescence microscopy to examine cerebral hemodynamic alterations as well as accompanying geometric changes in the cortical microvascular network following five weeks of voluntary exercise in transgenic mice endogenously expressing tdTomato in vascular endothelial cells to allow visualization of microvessels irrespective of their perfusion levels. We found a diminished microvascular response to a hypercapnic challenge (10% FiCO) in running mice when compared to that in nonrunning controls despite commensurate increases in transcutaneous CO tension.

High-throughput discovery of novel developmental phenotypes.

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts.

MINC 2.0: A Flexible Format for Multi-Modal Images.

It is often useful that an imaging data format can afford rich metadata, be flexible, scale to very large file sizes, support multi-modal data, and have strong inbuilt mechanisms for data provenance. Beginning in 1992, MINC was developed as a system for flexible, self-documenting representation of neuroscientific imaging data with arbitrary orientation and dimensionality. The MINC system incorporates three broad components: a file format specification, a programming library, and a growing set of tools.

Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry.

Ex vivo magnetic resonance imaging (MRI) requires chemical fixation to preserve tissue during storage or extended imaging sessions. Although it is commonly understood that fixation may alter tissue volume and shape, the potential confounding effects of fixation and storage on morphometric analyses have not been well characterized. With increasing use of ex vivo MRI for mouse brain phenotying and opportunities for inter-study comparisons, we sought to characterize how changes in fixation and/or storage times affected tissue volume, and how this might impact phenotyping results.

Quantification of Gestational Changes in the Uteroplacental Vascular Tree Reveals Vessel Specific Hemodynamic Roles During Pregnancy in Mice.

The purpose of this study was to establish the time course and hemodynamic significance of de novo formed and enlarged uteroplacental arteries during pregnancy. Using x-ray microcomputed tomography (n = 4-7 placentas from 2-4 dams/gestational group), uteroplacental arterial vascular dimensions were measured at individual implantation sites. Dimensions and topology were used to compute total and vessel-specific resistances and cross-sectional areas.

Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature.

Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes.

Comparing homologous microscopic sections from multiple embryos using HREM.

• 3D HREM embryo images can be registered. • Homologous microscopic sections can be obtained from multiple embryos. • Anatomical phenotypes can be analyzed by computer.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model.

The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy.

Introduction: This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort.

Methods: One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm.

Relaxation properties of human umbilical cord blood at 1.5 Tesla.

Purpose: To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla.

Methods: Relaxometry measurements were performed on cord blood specimens (N = 88, derived from six caesarean deliveries) spanning a broad range of hematocrits (Hct = 0.

Variability of brain anatomy for three common mouse strains.

The way in which brain structures express different morphologies is not fully understood. Here we investigate variability in brain anatomy using ex vivo MRI of three common laboratory mouse strains: in two inbred strains (C57BL/6 and 129S6) and one outbred strain (CD-1). We use Generalised Procrustes Analysis (GPA) to estimate modes of anatomical variability.

Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods, in particular magnetic resonance imaging (MRI), have helped reveal alterations in the brain structure, metabolism, and function of patients and in groups at risk of developing AD, yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology.

Reduced cerebrovascular reserve is regionally associated with cortical thickness reductions in children with sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder which adversely affects cerebrovascular health. Previous studies have demonstrated regional cortical thinning in SCD. However, the reason behind regional reductions in cortical thickness remains unclear.

Prenatal β-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors.

Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a β-catenin/Brn2/Tbr2 transcriptional cascade.

Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.

Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). FMR1-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models.

Alterations in Functional and Structural Connectivity in Pediatric-Onset Multiple Sclerosis.

Background: Reduced white matter (WM) integrity is a fundamental aspect of pediatric multiple sclerosis (MS), though relations to resting-state functional MRI (fMRI) connectivity remain unknown. The objective of this study was to relate diffusion-tensor imaging (DTI) measures of WM microstructural integrity to resting-state network (RSN) functional connectivity in pediatric-onset MS to test the hypothesis that abnormalities in RSN reflects changes in structural integrity.

Methods: This study enrolled 19 patients with pediatric-onset MS (mean age = 19, range 13-24 years, 14 female, mean disease duration = 65 months, mean age of disease onset = 13 years) and 16 age- and sex-matched healthy controls (HC).

Longitudinal cerebellar growth following very preterm birth.

Purpose: To measure cerebellar growth in a longitudinal cohort of very preterm infants to identify early predictors of subsequent brain growth. Although the cerebellum grows rapidly during late gestation, the rate and variability of growth following premature birth, and the effects of associated injury, are largely unknown.

Materials And Methods: In all, 105 very-preterm born infants (24-32 weeks GA) were imaged using magnetic resonance imaging (MRI) at birth, term-equivalent, 2, and 4 years of age.

Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature.

Background: Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.

4D atlas of the mouse embryo for precise morphological staging.

After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages.

Neuroanatomic Differences Associated With Stress Susceptibility and Resilience.

Background: We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging and diffusion tensor imaging to determine neuroanatomic differences between stress-susceptible and resilient mice. We also examined synchronized anatomic differences between brain regions to gain insight into the plasticity of neural networks underlying stress susceptibility.

Methods: C57BL/6 mice underwent 10 days of social defeat stress and were subsequently tested for social avoidance.

Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP.

Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology.

Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects.