Loss of age-related laminar differentiation of intracortical myelin in bipolar disorder.

Age-related changes of intracortical myelin in bipolar disorder (BD) have been observed to deviate from the quadratic age curve observed in healthy controls (HC), but it is unclear if this holds at varying cortical depths. From BD (n = 44; age range = 17.6-45.5 years) and HC (n = 60; age range = 17.1-45.8 years) participants, we collected 3T T1-weighted (T1w) images with strong intracortical contrast. Signal values were sampled from 3 equivolume cortical depths. Linear mixed models were used to compare age-related changes in the T1w signal between depths and between groups at each depth. In HC, the age-related changes were significantly different between the superficial one-fourth depth and the deeper depths in the right ventral somatosensory (t = -4.63; FDRp = 0.00025), left dorsomedial somatosensory (t = -3.16; FDRp = 0.028), left rostral ventral premotor (t = -3.16; FDRp = 0.028), and right ventral inferior parietal cortex (t = -3.29; FDRp = 0.028). BD participants exhibited no differences in the age-related T1w signal between depths. Illness duration was negatively correlated with the T1w signal at the one-fourth depth in the right anterior cingulate cortex (rACC; rho = -0.50; FDRp = 0.029). Physiological age-related and depth-specific variation in the T1w signal were not observed in BD. The T1w signal in the rACC may reflect lifetime disease burden in the disorder.

Empirical transmit field bias correction of T1w/T2w myelin maps.

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.

Network properties of intracortical myelin associated with psychosocial functioning in bipolar I disorder.

OBJECTIVE: Psychosocial functioning in bipolar disorder (BD) persists even during euthymia and has repeatedly been associated with illness progression and cognitive function. Its neurobiological correlates remain largely unexplored. Using a structural covariance approach, we explored whole cortex intracortical myelin (ICM) and psychosocial functioning in 39 BD type I and 58 matched controls. METHOD: T1 -weighted images (3T) optimized for ICM measurement were analyzed using a surface-based approach. The ICM signal was sampled at cortical mid-depth using the MarsAtlas parcellation, and psychosocial functioning was measured via the Functioning Assessment Short Test (FAST). Following construction of structural covariance matrices, graph theoretical measures were calculated for each subject. Within BD and HC groups separately, correlations between network measures and FAST were explored. After accounting for multiple comparisons, significant correlations were tested formally using rank-based regressions accounting for sex differences. RESULTS: In BD only, psychosocial functioning was associated with global efficiency (ß = -0.312, pcorr  = 0.03), local efficiency in the right rostral dorsolateral prefrontal cortex (ß = 0.545, pcorr  = 0.001) and clustering coefficient in this region (ß = 0.497, pcorr  = 0.0002) as well as in the right ventromedial prefrontal cortex (ß = 0.428, pcorr  = 0.002). All results excepting global efficiency remained significant after accounting for severity of depressive symptoms. In contrast, no significant associations between functioning and network measures were observed in the HC group. CONCLUSION: These results uncovered a novel brain-behaviour relationship between intracortical myelin signal changes and psychosocial functioning in BD.

Exercise and microstructural changes in the motor cortex of older adults.

Exercise has been shown to counteract age-related volume decreases in the human brain, and in this imaging study, we ask whether the same holds true for the microstructure of the cortex. Healthy older adults (n = 47, 65-90 years old) either exercised three times a week on a stationary bike or maintained their usual physical routine over a 12-week period. Quantitative longitudinal relaxation rate (R1 ) magnetic resonance imaging (MRI) maps were made at baseline and after the 12-week intervention. R1 is commonly taken to reflect cortical myelin density. The change in R1 (ΔR1 ) was significantly increased in a region of interest (ROI) in the primary motor cortex containing motor outputs to the leg musculature in the exercise group relative to the control group (p = .04). The change in R1 in this ROI correlated with an increase in oxygen consumption at the first ventilatory threshold (VT1) (p = .04), a marker of improvement in submaximal aerobic performance. An exploratory analysis across the cortex suggested that the correlation was predominately confined to the leg representation in the motor cortex. This study suggests that microstructural declines in the cortex of older adults may be staved off by exercise.

Age-related deficits in intracortical myelination in young adults with bipolar disorder type I

Background: Previous studies have implicated white-matter-related changes in the pathophysiology of bipolar disorder. However, most of what is known is derived from in vivo subcortical white-matter imaging or postmortem studies. In this study, we investigated whole-brain intracortical myelin (ICM) content in people with bipolar disorder type I and controls. Methods: Between Sept. 1, 2014, and Jan. 31, 2017, we used a 3 T General Electric scanner to collect T1-weighted images in 45 people with bipolar disorder type I and 60 controls aged 17 to 45 years using an optimized sequence that was sensitive to ICM content. We analyzed images using a surfacebased approach. We used general linear models with quadratic age terms to examine the signal trajectory of ICM across the age range. Results: In healthy controls, the T1-weighted signal followed an inverted-U trajectory over age; in people with bipolar disorder type I, the association between ICM and age followed a flat trajectory (p < 0.05, Bonferroni corrected). Exploratory analyses showed that ICM signal intensity was associated with duration of illness, age of onset, and anticonvulsant and antipsychotic use in people with bipolar disorder type I (p < 0.05, uncorrected). Limitations: Because of the cross-sectional nature of the study, we were unable to comment on whether the effects were due to dysmyelination or demyelination in bipolar disorder. Conclusion: This foundational study is, to our knowledge, the first to show global age-related deficits in ICM maturation throughout the cortex in bipolar disorder. Considering the impact of myelination on the maintenance of neural synchrony and the integrity of neural connections, this work may help us better understand the cognitive and behavioural deficits seen in bipolar disorder.

Functional magnetic resonance imaging of auditory cortical fields in awake marmosets.

The primate auditory cortex is organized into a network of anatomically and functionally distinct processing fields. Because of its tonotopic properties, the auditory core has been the main target of neurophysiological studies ranging from sensory encoding to perceptual decision-making. By comparison, the auditory belt has been less extensively studied, in part due to the fact that neurons in the belt areas prefer more complex stimuli and integrate over a wider frequency range than neurons in the core, which prefer pure tones of a single frequency. Complementary approaches, such as functional magnetic resonance imaging (fMRI), allow the anatomical identification of both the auditory core and belt and facilitate their functional characterization by rapidly testing a range of stimuli across multiple brain areas simultaneously that can be used to guide subsequent neural recordings. Bridging these technologies in primates will serve to further expand our understanding of primate audition. Here, we developed a novel preparation to test whether different areas of the auditory cortex could be identified using fMRI in common marmosets (Callithrix jacchus), a powerful model of the primate auditory system. We used two types of stimulation, band pass noise and pure tones, to parse apart the auditory core from surrounding secondary belt fields. In contrast to most auditory fMRI experiments in primates, we employed a continuous sampling paradigm to rapidly collect data with little deleterious effects. Here we found robust bilateral auditory cortex activation in two marmosets and unilateral activation in a third utilizing this preparation. Furthermore, we confirmed results previously reported in electrophysiology experiments, such as the tonotopic organization of the auditory core and regions activating preferentially to complex over simple stimuli. Overall, these data establish a key preparation for future research to investigate various functional properties of marmoset auditory cortex.

Age-related mapping of intracortical myelin from late adolescence to middle adulthood using T1 -weighted MRI.

Magnetic resonance imaging (MRI) studies in humans have reported that the T1 -weighted signal in the cerebral cortex follows an inverted "U" trajectory over the lifespan. Here, we investigated the T1 -weighted signal trajectory from late adolescence to middle adulthood in humans to characterize the age range when mental illnesses tend to present, and efficacy of treatments are evaluated. We compared linear to quadratic predictors of age on signal in 67 healthy individuals, 17-45 years old. We investigated », ½, and ¾ depths in the cortex representing intracortical myelin (ICM), in the superficial white matter (SWM), and in a reference deep white matter tract. We found that the quadratic fit was superior in all regions of the cortex, while signal in the SWM and deep white matter showed no global dependence on age over this range. The signal trajectory in any region followed a similar shape regardless of cortical depth. The quadratic fit was analyzed in 70 cortical regions to obtain the age of maximum signal intensity. We found that visual, cingulate, and left ventromedial prefrontal cortices peak first around 34 years old, whereas motor and premotor areas peak latest at ∼38 years. Our analysis suggests that ICM trajectories over this range can be modeled well in small cohorts of subjects using quadratic functions, which are amenable to statistical analysis, thus suitable for investigating regional changes in ICM with disease. This study highlights a novel approach to map ICM trajectories using an age range that coincides with the onset of many mental illnesses. Hum Brain Mapp 38:3691-3703, 2017. © 2017 Wiley Periodicals, Inc.

Early regional cuprizone-induced demyelination in a rat model revealed with MRI.

The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum. In this study, we acquired high-resolution, three-dimensional images of the whole brain every 2 weeks, using a T1 -weighted magnetization-prepared rapid acquisition gradient echo imaging sequence, optimized for myelin contrast, in order to assess myelination across the entire rat brain over a period of 8 weeks on a 1% cuprizone diet. We observed a consistent pattern of demyelination, beginning in the cerebellum by 4 weeks and involving more rostral regions of the brain by 8 weeks on the cuprizone diet, with validation using Luxol fast blue histology. This imaging technique permits the effects of cuprizone-induced demyelination to be followed longitudinally in a single animal, over the entire brain. In turn, this may facilitate the establishment of the cuprizone model of demyelination in the rat.

Altered intracortical myelin staining in the dorsolateral prefrontal cortex in severe mental illness.

Imaging and postmortem studies into the severe mental illnesses of major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) have revealed deficiencies in the myelination of deep white matter tracts of the brain. Recent studies have further suggested that deficits could extend to myelinated fibers running through the cortex in those illnesses. Disruptions in this intracortical myelin may underlie functional symptomology in MDD, BD, and SZ; thus, in this study, we hypothesized that individuals with these illnesses may have reduced myelin staining relative to controls in the cerebral cortex. We stained 60 sections of dorsolateral prefrontal cortex for myelin with Luxol® fast blue in four groups: 15 BD, 15 MDD, 15 SZ, and 15 controls with no psychiatric illness. We digitally measured optical tissue attenuation reflecting the amount of myelin staining across six cortical depths in the middle frontal gyrus (MFG), in superficial white matter in the crown of the MFG, and in deep white matter. We found that a diagnosis of MDD or SZ meant that optical tissue attenuation was significantly reduced in the shallowest depths of the cortex. Furthermore, there was a trend toward reduced optical tissue attenuation in all illnesses across all myelinated regions we studied. These results encourage future studies into potential reductions in intracortical myelin in severe mental illness.

Functional mapping of face-selective regions in the extrastriate visual cortex of the marmoset.

The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset (Callithrix jacchus), a species of growing interest as a primate model in neuroscience. To address this question, we measured selective neural responses in the brain of four awake marmosets trained to fix their gaze upon images of faces, bodies, objects, and control patterns. In two of the subjects, we measured high gamma-range field potentials from electrocorticography arrays implanted over a large portion of the occipital and inferotemporal cortex. In the other two subjects, we measured BOLD fMRI responses across the entire brain. Both techniques revealed robust, regionally specific patterns of category-selective neural responses. We report that at least six face-selective patches mark the occipitotemporal pathway of the marmoset, with the most anterior patches showing the strongest preference for faces over other stimuli. The similar appearance of these patches to previous findings in macaques and humans, including their apparent arrangement in two parallel pathways, suggests that core elements of the face processing network were present in the common anthropoid primate ancestor living ∼35 million years ago. The findings also identify the marmoset as a viable animal model system for studying specialized neural mechanisms related to high-level social visual perception in humans.

Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination.

A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1 = 1/T1 and R2 = 1/T2 , at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.55 ± 0.08 s (-1) and R2 was found to be 15 ± 1 s(-1) , revealing significantly lower R1 and R2 in les white matter relative to wild-type (wt: R1 = 0.69 ± 0.05 s(-1) and R2 = 18 ± 1 s(-1) ). These deviated from the expected ΔR1 and ΔR2 values, given a complete lack of myelin in the les white matter, derived from the literature using values of myelin relaxivity, and we suspect that metals could play a significant role. The absolute concentrations of the paramagnetic transition metals iron (Fe) and manganese (Mn) were measured by a micro-synchrotron radiation X-ray fluorescence (µSRXRF) technique, with significantly greater Fe and Mn in les white matter than in wt (in units of µg [metal]/g [wet weight tissue]: les: Fe concentration,19 ± 1; Mn concentration, 0.71 ± 0.04; wt: Fe concentration,10 ± 1; Mn concentration, 0.47 ± 0.04). These changes in Fe and Mn could explain the deviations in R1 and R2 from the expected values in white matter. Although it was found that the influence of myelin still dominates R1 and R2 in wt rats, there were non-negligible changes in the contribution of the metals to relaxation. Although there are already problems with the estimation of myelin from R1 and R2 changes in disease models with pathology that also affects the relaxation rate constants, this study points to a specific pitfall in the estimation of changes in myelin in diseases or models with disrupted concentrations of paramagnetic transition metals. Copyright © 2016 John Wiley & Sons, Ltd.

Functional MRI of visual responses in the awake, behaving marmoset.

The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species' cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500 µm in-plane resolution in a 30 cm horizontal bore at 7 T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution.

Transcriptomics reveal a unique phago-mixotrophic response to low nutrient concentrations in the prasinophyte Pterosperma cristatum.

Constitutive mixoplankton-plastid-bearing microbial eukaryotes capable of both phototrophy and phagotrophy-are ubiquitous in marine ecosystems and facilitate carbon transfer to higher trophic levels within aquatic food webs, which supports enhanced sinking carbon flux. However, the regulation of the relative contribution of photosynthesis and prey consumption remains poorly characterized. We investigated the transcriptional dynamics behind this phenotypic plasticity in the prasinophyte green alga Pterosperma cristatum. Based on what is known of other mixoplankton species that cannot grow without photosynthesis (obligate phototrophs), we hypothesized that P. cristatum uses phagotrophy to circumvent the restrictions imposed on photosynthesis by nutrient depletion, to obtain nutrients from ingested prey, and to maintain photosynthetic carbon fixation. We observed an increase in feeding as a response to nutrient depletion, coinciding with an upregulation of expression for genes involved in essential steps of phagocytosis including prey recognition, adhesion and engulfment, transport and maturation of food vacuoles, and digestion. Unexpectedly, genes involved in the photosynthetic electron transfer chain, pigment biosynthesis, and carbon fixation were downregulated as feeding increased, implying an abatement of photosynthesis. Contrary to our original hypothesis, our results therefore suggest that depletion of inorganic nutrients triggered an alteration of trophic behavior from photosynthesis to phagotrophy in P. cristatum. While this behavior distinguishes P. cristatum from other groups of constitutive mixoplankton, its physiological response aligns with recent discoveries from natural microbial communities. These findings indicate that mixoplankton communities in nutrient-limited oceans can regulate photosynthesis against bacterivory based on nutrient availability.

Optimizing T1-weighted imaging of cortical myelin content at 3.0 T.

With increases in the sensitivity and resolution of anatomical MRI for the brain, methods for mapping the organization of the cerebral cortex by imaging its myelin content have emerged. This identifies major sensory and motor regions and could be used in studies of cortical organization, particularly if patterns of myelination can be visualized over the cortical surface robustly in individual subjects. The imaging problem is difficult, however, because of the relative thinness of the cerebral cortex and the low intracortical tissue contrast. In this paper, we optimize the contrast of T(1)-weighted MRI to help better visualize patterns of myelination. We measure a small but statistically significant difference in T(1) of 171 ± 40 ms between cortical regions with low and high myelin contents in the human cortex at 3T, and then perform simulations to choose parameters for an inversion-recovery pulse sequence that utilizes this T(1) difference to increase contrast within the cortex. We show that lengthening the delay between signal acquisition and the next inversion pulse in the sequence increases intracortical contrast more effectively than does image averaging. Using the optimized sequence, we show that major myelinated regions that are relatively thick, such as the primary motor and auditory regions, can be visualized well in individuals at 3T using whole-cortex 3D images made at 1mm isotropic resolution, while thinner regions, such as the primary visual cortex, can be visualized using targeted 3D images made at 0.5mm isotropic resolution. Our findings demonstrate that patterns of myelination can be better visualized in individual subjects when the imaging is optimized to highlight intracortical contrast and can help to pave the way for the creation of matched maps of microanatomy and function in the cortex of living individual humans.

Altered transition metal homeostasis in mice following manganese injections for manganese-enhanced magnetic resonance imaging.

In manganese-enhanced magnetic resonance imaging (MEMRI), the paramagnetic divalent ion of manganese (Mn(2+)) is injected into animals to generate tissue contrast, typically at much higher exposures than have been previously used in studies of Mn toxicity. Here we investigate the effect of these injections on the homeostasis of the transition metals iron and copper in mice to see if there are disruptions which should be considered in MEMRI studies. Manganese shares transport proteins with other transition metals including iron and copper, so it is possible that changes in manganese levels in tissue following injections of the metal may affect other metal levels too. This in turn may affect MRI contrast or the investigation of disease processes in the animal models being imaged. In this study, we measured manganese, iron, and copper concentrations in the blood, kidney, liver and in brain regions in mice treated with four injections of 30 mg/kg MnCl(2) 4H(2)O (dry chemical weight/body weight)-a common dose used in MEMRI. In addition to the expected increases in manganese in tissues, we noted a statistically significant reduction in copper in the kidney and liver. Also, we noted a statistically significant decrease in concentration of iron in the thalamus of the brain. These findings suggest that the high doses of manganese injected in MEMRI studies can disrupt the homeostasis of other transition metals in mice.

Rapid high-resolution three-dimensional mapping of T1 and age-dependent variations in the non-human primate brain using magnetization-prepared rapid gradient-echo (MPRAGE) sequence.

The use of quantitative T(1) mapping in neuroscience and neurology has raised strong interest in the development of T(1)-mapping techniques that can measure T(1) in the whole brain, with high accuracy and precision and within short imaging and computation times. Here, we present a new inversion-recovery (IR) based T(1)-mapping method using a standard 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence. By varying only the inversion time (TI), but keeping other parameters constant, MPRAGE image signals become linear to exp(-TI/T(1)), allowing for accurate T(1) estimation without flip angle correction. We also show that acquiring data at just 3 TIs, with the three different TI values optimized, gives maximum T(1) precision per unit time, allowing for new efficient approaches to measure and compute T(1). We demonstrate the use of our method at 7 T to obtain 3D T(1) maps of the whole brain in common marmosets at 0.60mm resolution and within 11 min. T(1) maps from the same individuals were highly reproducible across different days. Across subjects, the peak of cerebral gray matter T(1) distribution was 1735±52 ms, and the lower edge of cerebral white matter T(1) distribution was 1270±43 ms. We found a significant decrease of T(1) in both gray and white matter of the marmoset brain with age over a span of 14 years, in agreement with previous human studies. This application illustrates that MPRAGE-based 3D T(1) mapping is rapid, accurate and precise, and can facilitate high-resolution anatomical studies in neuroscience and neurological diseases.

Experimental identification and in silico prediction of bacterivory in green algae.

While algal phago-mixotrophs play a major role in aquatic microbial food webs, their diversity remains poorly understood. Recent studies have indicated several species of prasinophytes, early diverging green algae, to be able to consume bacteria for nutrition. To further explore the occurrence of phago-mixotrophy in green algae, we conducted feeding experiments with live fluorescently labeled bacteria stained with CellTracker Green CMFDA, heat-killed bacteria stained with 5-(4,6-dichlorotriazin-2-yl) aminofluorescein (DTAF), and magnetic beads. Feeding was detected via microscopy and/or flow cytometry in five strains of prasinophytes when provided with live bacteria: Pterosperma cristatum NIES626, Pyramimonas parkeae CCMP726, Pyramimonas parkeae NIES254, Nephroselmis pyriformis RCC618, and Dolichomastix tenuilepis CCMP3274. No feeding was detected when heat-killed bacteria or magnetic beads were provided, suggesting a strong preference for live prey in the strains tested. In parallel to experimental assays, green algal bacterivory was investigated using a gene-based prediction model. The predictions agreed with the experimental results and suggested bacterivory potential in additional green algae. Our observations underline the likelihood of widespread occurrence of phago-mixotrophy among green algae, while additionally highlighting potential biases introduced when using prey proxy to evaluate bacterial ingestion by algal cells.

Localization and Identification of Brain Microstructural Abnormalities in Paediatric Concussion.

In the United States, approximately 2.53 million people sustain a concussion each year. Relative to adults, youth show greater cognitive deficits following concussion and a longer recovery. An accurate and reliable imaging method is needed to determine injury severity and symptom resolution. The primary objective of this study was to characterize concussions with diffusion tensor imaging (DTI). This was performed through a normative Z-scoring analysis of DTI metrics, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), to quantify patient-specific injuries and identify commonly damaged brain regions in paediatric concussion patients relative to healthy controls. It was hypothesized that personalizing the detection analysis through normative Z-scoring would provide an understanding of trauma-induced microstructural damage. Concussion patients were volunteers recruited from the Emergency Department of the McMaster Children's Hospital with a recent concussion (n = 26), 9 males and 17 females, mean age 14.22 ± 2.64, while healthy paediatric brain DTI datasets (25 males and 24 females, mean age 13.52 ± 1.03) were obtained from an MRI data repository. Significant abnormalities were commonly found in the longitudinal fasciculus, fronto-occipital fasciculus, and corticospinal tract, while unique abnormalities were localized in a number of other areas reflecting the individuality of each child's injury. Total injury burden, determined by the number of regions containing outliers per DTI metric per patient, was used as the metric to quantify the overall injury severity of each patient. The primary outcome of this analysis found that younger patients experienced a significantly greater injury burden when measured using fractional anisotropy (p < 0.001). These results show that DTI was able to detect microstructural changes caused by concussion, on a per-person basis, and has the potential to be a useful tool for improving diagnostic accuracy and prognosis of a concussion.

Temporal profiling of therapy resistance in human medulloblastoma identifies novel targetable drivers of recurrence.

Medulloblastoma (MB) remains a leading cause of cancer-related mortality among children. The paucity of MB samples collected at relapse has hindered the functional understanding of molecular mechanisms driving therapy failure. New models capable of accurately recapitulating tumor progression in response to conventional therapeutic interventions are urgently needed. In this study, we developed a therapy-adapted PDX MB model that has a distinct advantage of generating human MB recurrence. The comparative gene expression analysis of MB cells collected throughout therapy led to identification of genes specifically up-regulated after therapy, including one previously undescribed in the setting of brain tumors, bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4). Subsequent functional validation resulted in a markedly diminished in vitro proliferation, self-renewal, and longevity of MB cells, translating into extended survival and reduced tumor burden in vivo. Targeting endothelial nitric oxide synthase, a downstream substrate of BPIFB4, impeded growth of several patient-derived MB lines at low nanomolar concentrations.

Manganese-enhanced MRI visualizes V1 in the non-human primate visual cortex.

MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl(2) . 4H(2)O in the tail vein. We found a statistically significant decrease in T(1) in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T(1) shortening in V1 (DeltaT(1) = 640 ms) relative to V2 (DeltaT(1) = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T(1)-weighted MRI. Furthermore, the dorso-medial (DM) and middle-temporal (MT) areas of the visual pathway could be identified by their T(1)-weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese-enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non-destructive localization of cortical regions to guide in the implementation of functional techniques.