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Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28–49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ( 1 H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's “reward” system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients. [ABSTRACT FROM AUTHOR]

Abstract: Galantamine, a drug used to treat Alzheimer''s disease, has recently emerged as a potential medical countermeasure against the toxicity of organophosphorus (OP) compounds, including the nerve agent soman. Here, magnetic resonance imaging (MRI) was used to characterize the neurotoxic effects of soman and the ability of galantamine to prevent these effects in guinea pigs, the best non-primate model to predict the effectiveness of antidotes against OP toxicity in humans. The brains of treated and untreated guinea pigs were imaged using a clinical 3.0 Tesla MRI scanner at 48h before and 6–7h, 48h and 7 days after their challenge with 1.0xLD50 soman (26.6μg/kg, sc). Significant brain atrophy was observed among all untreated animals at 7 days after their challenge with soman. In mildly intoxicated animals, significant shortening of spin–spin relaxation times (T2) was observed in the thalamus and amygdala at 7h after the challenge. In severely intoxicated animals, T2 values and T2-weighted signal intensities increased significantly in the piriform cortex, hippocampus, thalamus and amygdala; in most regions, changes were long-lasting. Voxel-based morphometric analysis of the images revealed that other brain regions were also damaged in these animals. Neuronal loss was confirmed histopathologically. In animals that were treated with galantamine (8mg/kg, im) 30min prior to the exposure to soman, T2, T2-weighted signal intensities, and CSF volumes were largely unaffected. It is, therefore, concluded that galantamine can effectively prevent the structural brain damage induced by an acute exposure to soman. [Copyright &y& Elsevier]

The perivascular space (PVS) is important to brain waste clearance and brain metabolic homeostasis. Enlarged PVS (ePVS) becomes visible on magnetic resonance imaging (MRI) and is best appreciated on T2-weighted (T2w) images. However, quantification of ePVS is challenging because standard-of-care T1-weighted (T1w) and T2w images are often obtained via two-dimensional (2D) acquisition, whereas accurate quantification of ePVS normally requires high-resolution volumetric three-dimensional (3D) T1w and T2w images. The purpose of this study was to investigate the use of a deep-learning-based super-resolution (SR) technique to improve ePVS quantification from 2D T2w images for application in patients with traumatic brain injury (TBI). We prospectively recruited 26 volunteers (age: 31 ± 12 years, 12 male/14 female) where both 2D T2w and 3D T2w images were acquired along with 3D T1w images to validate the ePVS quantification using SR T2w images. We then applied the SR method to retrospectively acquired 2D T2w images in 41 patients with chronic TBI (age: 41 ± 16 years, 32 male/9 female). ePVS volumes were automatically quantified within the whole-brain white matter and major brain lobes (temporal, parietal, frontal, occipital) in all subjects. Pittsburgh Sleep Quality Index (PSQI) scores were obtained on all patients with TBI. Compared with the silver standard (3D T2w), in the validation study, the SR T2w provided similar whole-brain white matter ePVS volume (r = 0.98, p < 0.0001), and similar age-related ePVS burden increase (r = 0.80, p < 0.0001). In the patient study, patients with TBI with poor sleep showed a higher age-related ePVS burden increase than those with good sleep. Sleep status is a significant interaction factor in the whole brain (p = 0.047) and the frontal lobe (p = 0.027). We demonstrate that images produced by SR of 2D T2w images can be automatically analyzed to produce results comparable to those obtained by 3D T2 volumes. Reliable age-related ePVS burden across the whole-brain white matter was observed in all subjects. Poor sleep, affecting the glymphatic function, may contribute to the accelerated increase of ePVS burden following TBI. [ABSTRACT FROM AUTHOR]

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v 1 (2004–2009) and v 2 (2009–2013) plasma NfL exposure and ancillary sMRI data at v scan (2011–2015, n = 179, mean v 1 to v scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL (v1) was associated with larger WMLV (both Log e transformed), after 5–6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv 2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL bayes). Among African American adults, NfL v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults. [ABSTRACT FROM AUTHOR]

This article offers methods and ideas for interference on fMR images, with particular application to identifying and testing for theories on working memory utilization. The BOLD contrast referred to in the article uses the difference in MR signals between oxyhemoglobin and deoxyhemoglobin levels that are caused by the excess inflow of blood due to neural activation. It comments on the slice perception used in the article. In general, one needs to register the slices before analyzing the fMR data. The sets of image slices are translated and rotated in all three planes to obtain the best match between the corresponding voxels. One criterion for such a match is minimization of the least-squares differences in voxel intensity values. Other comment pertains to the presence of motion artifacts in the fMR images. The author corrects data for motions effects and performs registration using the public-domain software package FIASCO. Another comment addresses the issue of visualizing the activation maps.

Background: Children with fetal alcohol spectrum disorders (FASD) often have deficits associated with multisensory processing. Because ethanol (EtOH) disrupts activity‐dependent neuronal plasticity, a process that is essential for refining connections during cortical development, we hypothesize that early alcohol exposure results in alterations in multisensory cortical networks, which could explain the multisensory processing deficits seen in FASD. Here, we use a gyrencephalic animal model to test the prediction that early alcohol exposure alters the functional connectivity and microstructural features of the rostral posterior parietal cortex (PPr), a visual‐tactile integrative area. Methods: Ferrets were exposed to moderate doses of EtOH during the brain growth spurt period. Functional connectivity and microstructural features were assessed using resting‐state functional magnetic resonance imaging and ex vivo diffusion kurtosis imaging (DKI), respectively, when the animals reached juvenile age and adulthood, respectively. Results: While the whole brain volume was smaller in alcohol‐treated animals, the relative size of the frontal brain area was larger when compared to control animals. Altered functional connectivity was observed in alcohol‐treated animals, where increased connectivity was observed between PPr and the region that provides its major visual inputs (the caudal portion of the parietal cortex), but not with the region that provides its major somatosensory inputs (tertiary somatosensory cortex). DKI revealed reduced microstructural tissue complexity in all investigated sensory areas of alcohol‐treated animals. Conclusions: In this study, we observed alterations in cortical functional connectivity and microstructural integrity in a cortical area involved in multisensory processing in a ferret FASD model. These findings indicate an alteration in cortical networks that may be related to the multisensory processing deficiencies observed in FASD. [ABSTRACT FROM AUTHOR]

Objectives: Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2–8 weeks following mild TBI. Methods: Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years). Results: We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network. Conclusions: Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population. [ABSTRACT FROM AUTHOR]

Data from diffusion magnetic resonance imaging (dMRI) can be used to reconstruct fiber tracts, for example, in muscle and white matter. Estimation of fiber orientations (FOs) is a crucial step in the reconstruction process and these estimates can be corrupted by noise. In this paper, a new method called Fiber Orientation Reconstruction using Neighborhood Information (FORNI) is described and shown to reduce the effects of noise and improve FO estimation performance by incorporating spatial consistency. FORNI uses a fixed tensor basis to model the diffusion weighted signals, which has the advantage of providing an explicit relationship between the basis vectors and the FOs. FO spatial coherence is encouraged using weighted ℓ 1 -norm regularization terms, which contain the interaction of directional information between neighbor voxels. Data fidelity is encouraged using a squared error between the observed and reconstructed diffusion weighted signals. After appropriate weighting of these competing objectives, the resulting objective function is minimized using a block coordinate descent algorithm, and a straightforward parallelization strategy is used to speed up processing. Experiments were performed on a digital crossing phantom, ex vivo tongue dMRI data, and in vivo brain dMRI data for both qualitative and quantitative evaluation. The results demonstrate that FORNI improves the quality of FO estimation over other state of the art algorithms. [ABSTRACT FROM AUTHOR]

Plasma neurofilament light chain (NfL)'s link to dementia may be mediated through white matter integrity (WMI). In this study, we examined plasma NfL's relationships with diffusion tensor magnetic resonance imaging markers: global and cortical white matter fractional anisotropy (FA) and trace (TR). Plasma NfL measurements at 2 times (v 1 : 2004–2009 and v 2 : 2009–2013) and ancillary dMRI (v scan : 2011–2015) were considered (n = 163, mean time v 1 to v scan = 5.4 years and v 2 to v scan : 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfL v1 was associated with greater global TR (β ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (β ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (β ± SE: + 0.0000767 ± 0.000021, b ± 0.31, p < 0.001, q = 0.0093). These associations were mainly among males and White adults. Among African American adults only, NfL v2 was associated with greater left temporal lobe TR. "Tracking high" in NfL was associated with reduced left frontal FA (Model 2, body mass index-adjusted: β ± SE:-0.01084 ± 0.00408, p = 0.009). Plasma NfL is a promising biomarker predicting future brain white matter integrity (WMI) in middle-aged adults. [ABSTRACT FROM AUTHOR]

Objectives: Rotator cuff (RC) tear is common among adults =60 years, with supraspinatus tear most common. Intramuscular fatty infiltration (FI) on imaging is predictive of long-term outcomes following RC tear. Physical therapists routinely diagnose RC tear only by clinical examination since most do not order imaging studies. Thus, there is limited knowledge about FI in older populations receiving physical therapy (PT) for initial management of RC tear. The primary objective of our pilot study is to determine longitudinal differences in supraspinatus FI over time among older adults receiving PT (PT cohort) for initial management of RC tear relative to older adult volunteers (control cohort), and with secondary objective to evaluate longitudinal self-reported shoulder function over time. Material and Methods: This was a prospective longitudinal cohort study. Forty adults, 60-85 years, were enrolled at baseline; one follow-up visit at =6 months. Shoulder magnetic resonance imaging and clinical screening for Charlson comorbidity index (CCI), body mass index (BMI), and American Shoulder and Elbow Surgeon (ASES) score were completed at baseline and follow-up visits. Supraspinatus FI was evaluated by 6-point Dixon fat fraction and Goutallier grade. PT (n = 15) and control (n = 25) cohorts were stratified by supraspinatus status: Intact (no tear), partial-thickness tear (PTT), and full-thickness tear (FTT). Comparisons within cohort were performed by Kruskal-Wallis test and between cohorts by Mann-Whitney U-test. Interobserver reliability was performed for Dixon fat fraction and Goutallier grade. Results: PT cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for FTT by Goutallier grade (no tear, 0.5 ± 0.5; PTT, 1.1 ± 0.2; and FTT, 1.5 ± 0.5; P = 0.033) and by Dixon fat fraction (no tear, 4.6% ± 1.4%; PTT, 6.1% ± 1.9%; and FTT, 6.7% ± 2.5%; P = 0.430). Control cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for supraspinatus FTT by Dixon fat fraction (no tear, 5.8% ± 1.2%; PTT, 7.1% ± 6.3%; and FTT, 21.4% ± 10.4%; P = 0.034) and by Goutallier grade (no tear, 0.8 ± 0.5; PTT, 1.0 ± 0.6; and FTT, 2.4 ± 1.7; P = 0.141). No difference between similar PT and control cohort subgroups at baseline except no tear groups for ASES score (PT cohort, 58.9 ± 8.2; control cohort, 84.0 ± 21.9; P = 0.049). No differences were identified for Δ-Dixon fat fraction and Δ-Goutallier grade over time in the PT and control cohorts. PT cohort no tear subgroup showed significant improvement (P = 0.042) for Δ-ASES score over time relative to PTT and FTT subgroups; no difference for Δ-ASES score over time in the control cohort. Conclusion: Full-thickness RC tear showed higher levels of FI relative to PTT or no tear at baseline. Our pilot study's trend suggested that older adults receiving PT for initial management of RC tear have full-thickness RC tear for shorter duration based on relative lower levels of FI at baseline as compared to older adult volunteers with full-thickness RC tear. Our pilot study also found that older adults in the PT cohort with no tear had superior shoulder functional recovery by ASES score over time relative to full-thickness and PTTs. [ABSTRACT FROM AUTHOR]

Aeromedical evacuation-relevant hypobaria after traumatic brain injury (TBI) leads to increased neurological injury and death in rats relative to those maintained under normobaria. Applicability of rodent brain injury research to humans may be limited, however, by differences in neuroanatomy. Therefore, we developed a model in which ferrets are exposed to polytrauma consisting of controlled cortical impact TBI and hemorrhagic shock subjected 24 h later to 6 h of hypobaria or normobaria. Our objective was to determine whether the deleterious effects of hypobaria observed in rats, with lissencephalic brains, are also present in a species with a human-like gyrencephalic brain. While no deaths were observed, magnetic resonance spectroscopy (MRS) results obtained two days post-injury indicated reduced cortical creatine, N-acetylaspartate, gamma-aminobutyric acid, myo-inositol, and glutamate that were not affected by hypobaria. T2-weighted magnetic resonance imaging quantification revealed increased hyperintensity volume representing cortical edema at the site of impact after polytrauma. Hypobaria did not exacerbate this focal edema but did lead to overall reductions in total cortical volume. Both normobaric and hypobaric ferrets exhibited impaired spatial memory six days post-injury on the Object Location Test, but no differences were noted between groups. Finally, cortical lesion volume was not exacerbated by hypobaria exposure on day 7 post-injury. Results suggest that air travel 24 h after polytrauma is associated with structural changes in the ferret brain. Future studies should investigate secondary injury from hypobaria after polytrauma in greater detail including alternative outcome measures, time points, and exposure to multiple flights. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study is to validate the muscle architecture derived from both ex vivo and in vivo diffusion-weighted magnetic resonance imaging (dMRI) of the human tongue with histology of an ex vivo tongue. Method: dMRI was acquired with a 200-direction high angular resolution diffusion imaging (HARDI) diffusion scheme for both a postmortem head (imaged within 48 hr after death) and a healthy volunteer. After MRI, the postmortem head was fixed and the tongue excised for hematoxylin and eosin (H&E) staining and histology imaging. Structure tensor images were generated from the stained images to better demonstrate muscle fiber orientations. The tongue muscle fiber orientations, estimated from dMRI, were visualized using the tractogram, a novel representation of crossing fiber orientations, and compared against the histology images of the ex vivo tongue. Results: Muscle fibers identified in the tractograms showed good correspondence with those appearing in the histology images. We further demonstrated tongue muscle architecture in in vivo tractograms for the entire tongue. Conclusion: The study demonstrates that dMRI can accurately reveal the complex muscle architecture of the human tongue and may potentially benefit planning and evaluation of oral surgery and research on speech and swallowing. [ABSTRACT FROM AUTHOR]

Introduction: Bidirectional effects between cognition and pain have been extensively reported. Although brain regions involved in cognitive and pain processing seem to partly overlap, it is unknown what specific brain regions are involved in the interaction between pain and cognition. Furthermore, the role of gonadal hormones on these interacting effects has not been examined. This study investigated brain activation patterns of the interaction between pain and cognition over different phases of the naturally occurring menstrual cycle. Methods: Fifteen healthy normally cycling females were examined over the course of 4 different cycle phases. Sensory stimulation was applied using electrical pulses and cognitive performance was assessed using the Multi‐Source Interference Task. Brain imaging consisted of functional magnetic resonance imaging using a repeated measures ANOVA group analysis approach. Results: Sensory stimulation was found to interact with task performance in the left precuneus, left posterior cingulate cortex and right inferior parietal lobule. No effects of cycle phase were observed to interact with main effects of stimulation, task or interaction effects between task performance and sensory stimulation. Conclusion: Potential neural correlates of shared resources between pain and cognition were demonstrated providing further insights into the potential mechanisms behind cognitive performance difficulties in pain patients and opening avenues for new treatment options including targeting specific cognitive factors in pain treatment such as cognitive interference. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic encephalopathy (HIE) is the result of global hypoxic-ischemic brain injury in neonates due to asphyxia during birth and is one of the most common causes of severe, long-term neurologic deficits in children. Methods: Resting state fMRI (rs-fMRI) was used to assess potential functional disruptions in the primary and association motor areas in HIE neonates (n = 16) compared to healthy controls (n = 11). Results demonstrate reduced intra-hemispheric resting state functional connectivity (rs-FC) between primary motor regions (upper extremity and facial motor regions) as well as reduced inter-hemispheric rs-FC in the HIE group. In addition, HIE neonates demonstrated increased rs-FC between motor regions and frontal, temporal and parietal cortices but decreased rs-FC with the cerebellum. These preliminary results provide initial evidence for the disruption of functional communication with the motor network in neonates with HIE. Further studies are necessary to both validate these findings in a larger dataset as well as to determine if rs-fMRI measurements collected at birth may have the potential to serve as a prognostic marker in addition to the traditional combination of clinical measurements and conventional MRI. [ABSTRACT FROM AUTHOR]

High-force lengthening contractions are associated with muscle damage and pain, and the muscle-tendon junction is commonly cited as the primary area where myofiber damage occurs. We induced injury in the rat tibialis anterior muscle and acquired magnetic resonance imaging (MRI) images postinjury. We also assayed membrane damage and quantified the number of centrally nucleated myofibers throughout the injured muscles. Results suggest that myofiber injury occurs primarily in the middle portion of the muscle, with interstitial edema in the middle and distal portions. Muscle Nerve, 2009 [ABSTRACT FROM AUTHOR]

Recent research strongly indicates that phonological tasks activate a subregion of the inferior frontal gyrus. The purpose of the present f MRI study was to investigate the extent to which activation of this region during phonological processing is due to speech processes per se such as articulatory recoding or to other cognitive task demands such as working memory. Thus, we compared activation patterns during segmentation of speech and tone sequences to a tone discrimination task. In particular, participants performed same/different judgments on pairs of words, pseudowords, and tone sequences that required segmentation of a continuous acoustic signal as well as tone pairs that did not require segmentation. Accuracy and reaction time data showed that speech and tone sequence segmentation conditions patterned more similarly to each other than to tone discrimination pairs. Analyses of group data revealed strong activation of the region at the border of the left inferior and middle frontal gyrus for all three segmentation conditions compared to tone discrimination, but no consistent differences were observed when word and pseudoword segmentation were directly contrasted. Analyses of individual subjects indicated that a large number of participants activated a small area of the middle frontal gyrus during the speech conditions compared to the sequences. These results suggest that a significant portion of active frontal areas is recruited for extracting acoustic information and maintaining it in memory for decision. However, some regions at the border of the inferior/middle frontal gyrus may be unique to speech segmentation. [ABSTRACT FROM AUTHOR]

The National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH-NINDS) Traumatic Brain Injury (TBI) Imaging Common Data Elements (CDEs) are standardized definitions for pathological intracranial lesions based on their appearance on neuroimaging studies. The NIH-NINDS TBI Imaging CDEs were designed to be as consistent as possible with the U.S. Food and Drug Administration (FDA) definition of biomarkers as "an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention." However, the FDA qualification process for biomarkers requires proof of reliable biomarker test measurements. We determined the interrater reliability of TBI Imaging CDEs on subacute brain magnetic resonance imaging (MRI) performed on 517 mild TBI patients presenting to 11 U.S. level 1 trauma centers. Three U.S. board-certified neuroradiologists independently evaluated brain MRI performed 2 weeks post-injury for the following CDEs: traumatic axonal injury (TAI), diffuse axonal injury (DAI), and brain contusion. We found very high interrater agreement for brain contusion, with prevalence- and bias-adjusted kappa (PABAK) values for pairs of readers from 0.92 [95% confidence interval, 0.88–0.95] to 0.94 [0.90–0.96]. We found intermediate agreement for TAI and DAI, with PABAK values of 0.74–0.78 [0.70–0.82]. The near-perfect agreement for subacute brain contusion is likely attributable to the high conspicuity and distinctive appearance of these lesions on T1-weighted images. Interrater agreement for TAI and DAI was lower, because signal void in small vascular structures, and artifactual foci of signal void, can be difficult to distinguish from the punctate round or linear areas of slight hemorrhage that are a common hallmark of TAI/DAI on MRI. [ABSTRACT FROM AUTHOR]

• Greater RDW v1 was associated with poorer WMI, among males only, particularly in terms of lower mean global fractional anisotropy (FA). • No such associations were found for anemia and δRDW (overall or sex-specific), or for RDW exposures among females and the non-anemic group. Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v 1 ; 2004–2009) and/or v 2 (2009–2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v scan : 2011–2015, n = 214, mean follow-up from v 1 ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW (v1) was linked with lower global mean fractional anisotropy (standardized effect size b = −0.30, p = 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males. [ABSTRACT FROM AUTHOR]

A neurological truism is that each side of the brain controls movements on the opposite side of the body. Yet some left hemisphere brain lesions cause bilateral impairment of complex motor function and/or ideomotor apraxia. We report that the left dorsal premotor cortex of normal right-handed people plays a fundamental role in sequential movement of both right and left hands. Subjects performed sequential finger movements during functional magnetic resonance imaging of the motor cortices. In right-handed subjects, the volume of activated dorsal premotor cortex showed a left hemispheric predominance during hand movements. We suggest that the observed left premotor dominance contributes to the lateralization found in lesion studies. [Copyright &y& Elsevier]

Purpose: Prostate brachytherapy (PB) entails the placement of radioactive sources throughout the entire prostate gland to treat localized cancer. Typically, the target volume in PB encompasses the entire prostate gland because of the inability to localize the cancer and the multifocal nature of this malignancy. However, because of the unique biochemical nature of the prostate gland, recent advances in magnetic resonance spectroscopic imaging (MRSI) of the prostate have allowed precise delineation of the cancer location within the prostate gland. This report reveals our initial experience of MRSI-guided PB.Methods: An MRSI study was obtained in 15 favorable-risk (prostate-specific antigen level ≤10 ng/mL, Gleason score ≤6, and clinical Stage ≤T2a) patients before their scheduled PB. The results of this study were used to internally map 7 × 7 × 9-mm volumes of prostate tissue to assign cancerous areas a higher dose of radiation. Such tumor-bearing areas had a low citrate/(choline+creatine) ratio consistent with cancer. On the basis of the anatomic MRI and MRSI correlation, three-dimensional coordinates were assigned to the locations of MRSI-defined cancer. The entire target volume was treated to 145 Gy using 125I. Abnormal citrate regions, termed the biologic tumor volume, were prescribed a dose of 130% of the target volume dose (188 Gy) to dose escalate in the abnormal citrate regions while respecting the normal radiation tolerances of the surrounding areas. Three-dimensional treatment planning was used to perform the implant.Results: Of the 15 prostate cancer patients evaluated, all had successful three-dimensional MRSI acquisition before their scheduled PB procedure. In 14 of the 15 patients planned with MRSI, the data were successfully incorporated into their treatment planning and were used to increase the radiation dose prescription to 130% in the MRSI-defined volumes. In 1 patient, MRSI revealed significant multifocal disease that made focal boosts impractical. Postimplant dosimetry confirmed a median V100 of 95% (range 89–98%) in the 15 evaluated patients for the prescription dose of 145 Gy to the target volume. Furthermore, the median BTV100 for the abnormal citrate region was 90% (range 80–100%) as determined by postimplant dosimetry. Urethral and rectal dose-volume histograms were within normal limits. Morbidity was comparable with that for conventionally treated patients.Conclusion: MRSI offers a promising new approach for the delivery of ionizing radiation in PB. Although this series was small and with a short follow-up, MRSI-guided implants are feasible and warrant further investigation as a means of improving the therapeutic ratio in PB. [Copyright &y& Elsevier]

Objective: To investigate early brain volumetric changes from acute to 6 months following mild traumatic brain injury (mTBI) in deep gray matter regions and their association with patient 6-month outcome. Methods: Fifty-six patients with mTBI underwent MRI and behavioral evaluation at acute (<10 days) and approximately 1 and 6 months post injury. Regional volume changes were investigated in key gray matter regions: thalamus, hippocampus, putamen, caudate, pallidum, and amygdala, and compared with volumes from 34 healthy control subjects. In patients with mTBI, we further assessed associations between longitudinal regional volume changes with patient outcome measures at 6 months including postconcussive symptoms, cognitive performance, and overall satisfaction with life. Results: Reduction in thalamic and hippocampal volumes was observed at 1 month among patients with mTBI. Such volume reduction persisted in the thalamus until 6 months. Changes in thalamic volumes also correlated with multiple symptom and functional outcome measures in patients at 6 months. Conclusion: Our results indicate that the thalamus may be differentially affected among patients with mTBI, resulting in both structural and functional deficits with subsequent post-concussive sequelae and may serve as a biomarker for the assessment of efficacy of novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms.Objective: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5-6 years later.Methods: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004-2009) and v2 (2009-2013) exposures and ancillary sMRI data at vscan (2011-2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values.Results: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q < 0.05), without significant sex differences. RDWv1 was related to smaller select regional cortical brain gray and white matter volumes in hematological measure-adjusted models; anemiav1 was associated with larger WML volumes only among whites.Conclusion: In summary, baseline anemia and RDW were consistently associated with smaller bilateral hippocampal volumes, particularly among females, while anemia was linked to larger WML volume among Whites. In hematological measure-adjusted models, baseline RDW was linked to smaller regional gray and white matter volumes. Pending studies with sMRI repeats, randomized controlled trials are needed, demonstrating associations of anemia and elevated RDW with reduced brain volumes and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: People with fetal alcohol spectrum disorder (FASD) often have structural or functional alterations of the central nervous system, including changes in brain network organization. These have been associated with neuropsychological deficits, but outcomes are not consistent across studies. We used a rat model of FASD to assess brain network alterations in males and females following ethanol exposure during a prenatal period similar to the first half of gestation in humans. Methods: Pregnant Long Evans rats were given an ethanol‐containing or isocaloric non‐ethanol diet from gestation day 6 to 20. Resting‐state functional magnetic resonance imaging was performed on offspring in young adulthood. Graph theoretical analysis was used to assess properties associated with the whole brain network organization, with a focus on segregation, integration, and small‐world organization—a feature which allows specialized local information processing (segregation) and simultaneously efficient global information sharing (integration). Results: Ethanol‐exposed females showed a significant decrease in small‐worldness compared with control females or with ethanol‐exposed males. Compared to control females, the proportion of animals with atypically high path length (1 standard deviation higher than the grand average) was significantly higher in ethanol‐exposed females, indicating that the alteration in small‐world organization is driven by decreased network integration. No significant effects were seen in males. Conclusion: The results revealed that prenatal ethanol exposure disrupts the balance between network segregation and integration in young adult female rats. The whole brain network is less integrated after ethanol exposure in the females, suggesting wide‐spread reduction of long‐range regional communication. [ABSTRACT FROM AUTHOR]

Pronounced spin phase artifacts appear in diffusion-weighted imaging (DWI) with only minor subject motion. While DWI data corruption is often identified as signal drop out in diffusion-weighted (DW) magnitude images, DW phase images may have higher sensitivity for detecting subtle subject motion. This article describes a novel method to return a metric of subject motion, computed using an image texture analysis of the DW phase image. This Phase Image Texture Analysis for Motion Detection in dMRI (PITA-MDD) method is computationally fast and reliably detects subject motion from diffusion-weighted images. A threshold of the motion metric was identified to remove motion-corrupted slices, and the effect of removing corrupted slices was assessed on the reconstructed FA maps and fiber tracts. Using a motion-metric threshold to remove the motion-corrupted slices results in superior fiber tracts and fractional anisotropy maps. When further compared to a state-of-the-art magnitude-based motion correction method, PITA-MDD was able to detect comparable corrupted slices in a more computationally efficient manner. In this study, we evaluated the use of DW phase images to detect motion corruption. The proposed method can be a robust and fast alternative for automatic motion detection in the brain with multiple applications to inform prospective motion correction or as real-time feedback for data quality control during scanning, as well as after data is already acquired. [ABSTRACT FROM AUTHOR]

This study sought to examine the interactive relations of socioeconomic status and race to corticolimbic regions that may play a key role in translating stress to the poor health outcomes overrepresented among those of lower socioeconomic status and African American race. Participants were 200 community-dwelling, self-identified African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN study. Brain volumes were derived using T1-weighted MP-RAGE images. Socioeconomic status by race interactions were observed for right medial prefrontal cortex (B = .26, p = .014), left medial prefrontal cortex (B = .26, p = .017), left orbital prefrontal cortex (B = .22, p = .037), and left anterior cingulate cortex (B = .27, p = .018), wherein higher socioeconomic status Whites had greater volumes than all other groups. Additionally, higher versus lower socioeconomic status persons had greater right and left hippocampal (B = -.15, p = .030; B = -.19, p = .004, respectively) and amygdalar (B = -.17, p = .015; B = -.21; p = .002, respectively) volumes. Whites had greater right and left hippocampal (B = -.17, p = .012; B = -.20, p = .003, respectively), right orbital prefrontal cortex (B = -.34, p < 0.001), and right anterior cingulate cortex (B = -.18, p = 0.011) volumes than African Americans. Among many factors, the higher levels of lifetime chronic stress associated with lower socioeconomic status and African American race may adversely affect corticolimbic circuitry. These relations may help explain race- and socioeconomic status-related disparities in adverse health outcomes. [ABSTRACT FROM AUTHOR]

Background: Quantification of rotator cuff intramuscular fatty infiltration is important for clinical decision-making in patients with rotator cuff tear. The semi-quantitative Goutallier classification system is the most commonly used method, but has limited reliability. Therefore, we sought to test a freely available fuzzy C-means segmentation software program for reliability of the quantification of shoulder intramuscular fatty infiltration on T1-weighted MR images and for correlation with fat fraction by six-point Dixon MRI.Materials and Methods: We performed a prospective cross-sectional study to measure visible intramuscular fat area percentage on oblique sagittal T1 MR images by fuzzy C-means segmentation and fat fraction maps by six-point Dixon MRI for 42 shoulder muscles. Intra- and inter-observer reliability were determined. Correlative analysis for fuzzy C-means and six-point Dixon intramuscular fatty infiltration measures was also performed.Results: We found that inter-observer reliability for the quantification of visible intramuscular fat area percentage by fuzzy C-means segmentation and fat fraction by six-point Dixon MRI was 0.947 and 0.951 respectively. The intra-observer reliability for the quantification of visible intramuscular fat area percentage by fuzzy C-means segmentation and fat fraction by six-point Dixon MRI was 0.871 and 0.979 respectively. We found a strong correlation between fuzzy C-means segmentation and six-point Dixon techniques; r = 0.850, p < 0.001 by individual muscle; and r = 0.977, p < 0.002 by study subject.Conclusion: Quantification of intramuscular fatty infiltration by fuzzy C-means segmentation on T1-weighted sequences demonstrates excellent reliability and strong correlation with fat fraction by six-point Dixon MRI. Quantitative fuzzy C-means segmentation is a viable alternative to the semi-quantitative Goutallier classification system. [ABSTRACT FROM AUTHOR]

Brain tumor, be it primary or metastatic, is usually life threatening for a person of any age. Primary surgical resection is one of the most effective ways of treating brain tumors and can have a tremendously increased success rate if the appropriate imaging modality is used for complete tumor resection. Magnetic resonance imaging (MRI) is the imaging modality of choice for brain tumor imaging because of its excellent soft-tissue contrast. MRI combined with continuum soft robotics has immense potential to be the next major technological breakthrough in the field of brain cancer diagnosis and therapy. In this paper, we present the design, kinematic, and force analysis of a flexible spring-based minimally invasive neurosurgical intracranial robot. It is comprised of an interconnected inner spring and an outer spring and is connected to actively cooled shape memory alloy (SMA) spring actuators via tendon driven mechanism. Our robot has three serially connected 2-DoF segments, which can be independently controlled due to the central tendon routing configuration. The kinematic and force analysis of the robot and the independent segment control were verified by experiments. Robot motion under forced cooling of SMA springs was evaluated as well as the MRI compatibility of the robot and its motion capability in brain-like gelatin environment. [ABSTRACT FROM PUBLISHER]

There are no reliable neuroimaging biomarkers to predict long-term outcome after spinal cord injury. This prospective longitudinal study evaluates diffusion tensor imaging (DTI) in predicting long-term outcome after cervical spinal cord injury (CSCI). We investigate the admission DTI parameters measured in 30 patients with CSCI, with 16 of them followed up to one year, and 15 volunteers serving as controls. All magnetic resonance imaging examinations were performed within 24 h of injury. The DTI parameters were measured in patients and controls, avoiding areas of hemorrhage in patients and at corresponding upper/middle/lower regions of the spinal cord in controls. Stepwise regression analysis was performed to find relevant parameters (normalized DTI values, age, sex, hemorrhagic contusion [HC or non-HC]) that correlated with two primary outcome measures: patient International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and Spinal Cord Independence Measure (SCIM III) scores at one year. Among all DTI measures, axial diffusivity (AD) most strongly correlated with both motor (r2 = 0.76, p < 0.01) and SCIM III scores (r2 = 0.77, p < 0.01) at one year. Further stepwise regression indicated that including AD ( p = 0.0001) and presence of HC ( p < 0.0001) in the regression model provided the best model fit for one year ISNCSCI (r2 = 0.93). The AD is a more specific parameter for axonal injury than radial diffusivity; this may indicate that axonal injury in the cord is the main factor affecting patient recovery. Our study demonstrates DTI measurement at the CSCI is a potential neuroimaging biomarker in predicting long-term neurological and functional outcome in blunt CSCI. [ABSTRACT FROM AUTHOR]

Organophosphorus ( OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase ( AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine ( ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the . [ABSTRACT FROM AUTHOR]

Blast-related traumatic brain injury (bTBI) resulting from improvised explosive devices is the hallmark injury of recent wars, and affects many returning veterans who experienced either direct or indirect exposure. Many of these veterans have long-term neurocognitive symptoms. However, there is very little evidence to show whether blast-induced acceleration alone, in the absence of secondary impacts, can cause mild TBI. In this study, we examine the effect of under-vehicle blast-induced hyperacceleration (uBIH) of ∼1700 g on the biochemical and microstrucutral changes in the brain using diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Two groups of adult male Sprague-Dawley (SD) rats were subjected to a sham procedure and uBIH, respectively. Axonal and neurochemical alterations were assessed using in vivo DTI and MRS at 2 h, 24 h, and 7 days after uBIH. Significant reduction in mean diffusivity, axial diffusivity, and radial diffusivity were observed in the hippocampus, thalamus, internal capsule, and corpus callosum as early as 2 h, and sustained up to 7 days post-uBIH. Total creatine (Cr) and glutamine (Gln) were reduced in the internal capsule at 24 h post-uBIH. The reductions in DTI parameters, Cr and Gln in vivo suggest potential activation of astrocytes and diffuse axonal injury following a single underbody blast, confirming previous histology reports. [ABSTRACT FROM AUTHOR]

Severe and moderate traumatic brain injury (sTBI) often results in long-term cognitive deficits such as reduced processing speed and attention. The intraparietal sulcus (IPS) is a neocortical structure that plays a crucial role in the deeply interrelated processes of multi-sensory processing and top down attention. Therefore, we hypothesized that disruptions in the functional and structural connections of the IPS may play a role in the development of such deficits. To examine these connections, we used resting state magnetic resonance imaging (rsfMRI and diffusion kurtosis imaging (DKI) in a cohort of 27 patients with sTBI (29.3 ± 8.9 years) and 27 control participants (29.8 ± 10.3 years). Participants were prospectively recruited and received rsfMRI and neuropsychological assessments including the Automated Neuropsychological Assessment Metrics (ANAM) at greater than 6 months post-injury. A subset of participants received a DKI scan. Results suggest that patients with sTBI performed worse than control participants on multiple subtests of the ANAM suggesting reduced cognitive performance. Reduced resting state functional connectivity between the IPS and cortical regions associated with multi-sensory processing and the dorsal attention network was observed in the patients with sTBI. The patients also showed reduced structural integrity of the superior longitudinal fasciculus (SLF), a key white matter tract connecting the IPS to anterior frontal areas, as measured by reduced mean kurtosis (MK) and fractional anisotropy (FA) and increased mean diffusivity (MD). Further, this reduced structural integrity of the SLF was associated with a reduction in overall cognitive performance. These findings suggest that disruptions in the structural and functional connectivity of the IPS may contribute to chronic cognitive deficits experienced by these patients. [ABSTRACT FROM AUTHOR]

• Parabrachial-periaqueductal gray FC correlates with subsequent pain. • Subgenual anterior cingulate cortex-PAG FC correlates with tonic pain. • PAG- and amydalocortical networks at rest correlate with subsequent tonic pain. • Cortical FC of PAG supports additional targets of neuromodulation to control pain. Resting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN). In 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN. Of all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t =-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction We demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions. [ABSTRACT FROM AUTHOR]

Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1–14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14–19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS. [ABSTRACT FROM AUTHOR]

This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (25 mg/kg, s.c.) or vehicle (peanut oil) once per day for 10 consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris water maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T 2 -weighted anatomical scans and diffusion kurtosis imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of prenatal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. [ABSTRACT FROM AUTHOR]

Primary objective: To investigate longitudinal diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) changes in white and grey matter in patients with mild traumatic brain injury (mTBI). Research design: A prospective case-control study. Methods and procedures: DKI data was obtained from 24 patients with mTBI along with cognitive assessments within 10 days, 1 month and 6 months post-injury and compared with age-matched control ( n = 24). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusion ( λr), mean kurtosis (MK) and radial kurtosis (K r) were extracted from the thalamus, internal capsule and corpus callosum. Main outcomes and results: Results demonstrate reduced Kr and MK in the anterior internal capsule in patients with mTBI across the three visits, and reduced MK in the posterior internal capsule during the 10 day time point. Correlations were observed between the change in MK or Kr between 1-6 months and the improvements in cognition between the 1 and 6 month visits in the thalamus, internal capsule and corpus callosum. Conclusions: These data demonstrate that DKI may be sensitive in tracking pathophysiological changes associated with mTBI and may provide additional information to conventional DTI parameters in evaluating longitudinal changes following TBI. [ABSTRACT FROM AUTHOR]

In the majority of patients with mild traumatic brain injury (mTBI), brain tissue impairment is undetectable by computed tomography and/or structural magnetic resonance imaging. Even in confirmed cases of head injury, conventional neuroimaging methods lack sensitivity in predicting neuropsychological outcomes of patients. The objectives of this study were to (1) cross-sectionally determine deviations in the neurometabolic profile of patients with mTBI from healthy controls at different stages of mTBI using tightly controlled examination windows, and (2) determine associations between acute neurometabolic markers of mTBI and chronic neurocognitive performance. Patients were examined at the early subacute ( n=43; 5.44±3.15 days post-injury (DPI)), late subacute ( n=33; 37.00±12.26 DPI) and chronic ( n=27; 195.30±19.60 DPI) stages of mTBI. Twenty-one neurologically intact subjects were used as controls. Proton magnetic resonance spectroscopy imaging (1H-MRSI) was used to obtain metabolic measurements from different brain regions. The Automated Neuropsychological Assessment Metrics (ANAM) was used for cognitive evaluation of patients at the chronic stage of mTBI. Measurements in the thalamus and centrum semiovale (CSV) emerged as the most indicative of injury and were used to predict neurocognitive outcome. The major findings of this study are (1) decreases in Cho/Cre (choline-to-creatine ratio) measured in the thalamus ( p=0.042) and CSV ( p=0.017) at the late subacute stage of mTBI; (2) positive associations of early subacute Cre measurements in the CSV with chronic ANAM scores measuring performance in delayed (r=0.497, p=0.019) and immediate (r=0.391, p=0.072) code substitution. These findings show that metabolic measurements in the thalamus and CSV can potentially serve as diagnostic and prognostic markers of mTBI. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) provides superior soft-tissue contrast in cancer diagnosis compared to other imaging modalities. However, the strong magnetic field inside the MRI bore along with limited scanner bore size poses significant challenges. Since current approaches in breast biopsy using MR images are primarily blind targeting approaches, it is necessary to develop an MRI-compatible robot that can avoid multiple needle insertions into the breast tissue. This MRI-compatible robotic system could potentially lead to improvement in the targeting accuracy and reduce sampling errors. A master–slave surgical system has been developed comprising a MRI-compatible slave robot which consists of one piezo motor and five pneumatic cylinders connected by long pneumatic transmission lines. The slave robot follows the configuration of the master robot, which provides an intuitive manipulation interface for the physician and operates inside the MRI bore to adjust the needle position and orientation and perform needle insertion tasks. Based on the MRI experiments using the slave robot, there was no significant distortion in the images, and hence the slave robot can be safely operated inside the MRI with minimal loss in signal-to-noise ratio (SNR). Ex vivo and in vivo experiments have been conducted to evaluate the performance of the master–slave surgical system. [ABSTRACT FROM AUTHOR]

Abstract: In this study we investigated the functional connectivity in 23 Mild TBI (mTBI) patients with and without memory complaints using resting state fMRI in the sub-acute stage of injury as well as a group of control participants. Results indicate that mTBI patients with memory complaints performed significantly worse than patients without memory complaints on tests assessing memory from the Automated Neuropsychological Assessment Metrics (ANAM). Altered functional connectivity was observed between the three groups between the default mode network (DMN) and the nodes of the task positive network (TPN). Altered functional connectivity was also observed between both the TPN and DMN and nodes associated with the Salience Network (SN). Following mTBI there is a reduction in anti-correlated networks for both those with and without memory complaints for the DMN, but only a reduction in the anti-correlated network in mTBI patients with memory complaints for the TPN. Furthermore, an increased functional connectivity between the TPN and SN appears to be associated with reduced performance on memory assessments. Overall the results suggest that a disruption in the segregation of the DMN and the TPN at rest may be mediated through both a direct pathway of increased FC between various nodes of the TPN and DMN, and through an indirect pathway that links the TPN and DMN through nodes of the SN. This disruption between networks may cause a detrimental impact on memory functioning following mTBI, supporting the Default Mode Interference Hypothesis in the context of mTBI related memory deficits. [Copyright &y& Elsevier]

Highlights: [•] We developed an automatic rat brain extraction algorithm, called the Rat Brain Deformable model method (RBD). [•] RBD is based on the deformable surface model. [•] RBD outperformed the existing rat brain extraction methods. [•] RBD achieved a higher accuracy of >92% volume overlap for brain extraction. [•] RBD was also robust against signal inhomogeneity in the images. [Copyright &y& Elsevier]

Abstract: This study was designed to test the hypothesis that in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6×LD50 or 300mg/kg, sc) or peanut oil (vehicle; 0.5ml/kg, sc) at 35–40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol. [Copyright &y& Elsevier]

Sex differences in pain sensitivity have been consistently found, but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy women, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in 4 test sessions during their menstrual, midfollicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during functional magnetic resonance imaging scans. However, lower pressure pain thresholds were found for follicular compared with other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and middle insula, midcingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum, and several frontal regions showed interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects. [ABSTRACT FROM AUTHOR]

Abstract: Sex differences in pain sensitivity have been consistently found, but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy women, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in 4 test sessions during their menstrual, midfollicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during functional magnetic resonance imaging scans. However, lower pressure pain thresholds were found for follicular compared with other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and middle insula, midcingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum, and several frontal regions showed interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects. [Copyright &y& Elsevier]

We develop a novel platform based on a tele-operated robot to perform high-resolution optical coherence tomography (OCT) imaging under continuous large field-of-view magnetic resonance imaging (MRI) guidance. Intra-operative MRI (iMRI) is a promising guidance tool for high-precision surgery, but it may not have sufficient resolution or contrast to visualize certain small targets. To address these limitations, we develop an MRI-compatible OCT needle probe, which is capable of providing microscale tissue architecture in conjunction with macroscale MRI tissue morphology in real time. Coregistered MRI/OCT images on ex vivo chicken breast and human brain tissues demonstrate that the complementary imaging scales and contrast mechanisms have great potential to improve the efficiency and the accuracy of iMRI procedure. [ABSTRACT FROM AUTHOR]

Fragile X syndrome ( FXS) is the most common form of inherited mental retardation and is studied in the Fmr1 knockout ( KO) mouse, which models both the anatomical and behavioral changes observed in FXS patients. In vitro studies have shown many alterations in synaptic plasticity and increased density of immature dendritic spines in the hippocampus, a region involved in learning and memory. In this study, magnetic resonance imaging ( MRI) and 1H magnetic resonance spectroscopy ( MRS) were used to determine in vivo longitudinal changes in volume and metabolites in the hippocampus during the critical period of early myelination and synaptogenesis at post-natal days ( PND) 18, 21, and 30 in Fmr1 KO mice compared with wild-type (WT) controls. MRI demonstrated an increase in volume of the hippocampus in the Fmr1 KO mouse compared with controls. MRS revealed significant developmental changes in the ratios of hippocampal metabolites N-acetylaspartate ( NAA), myo-inositol (Ins), and taurine to total creatine ( tCr) in Fmr1 KO mice compared with WT controls. Ins was decreased at PND 30, and taurine was increased at all ages studied in Fmr1 KO mice compared with controls. An imbalance of brain metabolites in the hippocampus of Fmr1 KO mice during the critical developmental period of synaptogenesis and early myelination could have long-lasting effects that adversely affect brain development and contribute to ongoing alterations in brain function. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) pain is a debilitating chronic condition that is severe and unrelenting. Despite decades of extensive research, the neuropathological mechanisms responsible for the development of this devastating condition remain largely unknown, hindering our ability to develop effective treatments. Because several lines of evidence implicate abnormalities of the thalamus and cortex in the etiology of SCI pain, we hypothesized that SCI pain results from abnormal functional connectivity of brain areas heavily implicated in pain processing. We performed a longitudinal study in a rat model of SCI (SCI group, n = 8; sham-operated group, n = 6) and acquired resting-state functional magnetic resonance imaging scans before spinal surgery and 3,7,14, and 21 (SCI only) days after surgery in the same animals. Functional connectivity was decreased between the ventroposterior lateral thalamus (VPL) and primary somatosensory cortex (SI) 7 d after SCI. This reduction preceded an increase in connectivity between SI and other cortical areas involved in nociceptive processing. In addition, VPL had increased connectivity to contralateral thalamus at 7 and 14 d after injury. The temporal pattern of the increase in functional connectivity within the thalamus and between cortical areas (particularly SI and retrosplenial cortex) had a striking resemblance to the temporal pattern for the development of a “below-level” mechanical hypersensitivity in the same animals. Our findings suggest that below-level hypersensitivity is associated with functional disconnection (asynchrony) between the thalamus and cortical areas involved in nociceptive processing. [ABSTRACT FROM AUTHOR]

Measuring the 3D motion of muscular tissues, e.g., the heart or the tongue, using magnetic resonance (MR) tagging is typically carried out by interpolating the 2D motion information measured on orthogonal stacks of images. The incompressibility of muscle tissue is an important constraint on the reconstructed motion field and can significantly help to counter the sparsity and incompleteness of the available motion information. Previous methods utilizing this fact produced incompressible motions with limited accuracy. In this paper, we present an incompressible deformation estimation algorithm (IDEA) that reconstructs a dense representation of the 3D displacement field from tagged MR images and the estimated motion field is incompressible to high precision. At each imaged time frame, the tagged images are first processed to determine components of the displacement vector at each pixel relative to the reference time. IDEA then applies a smoothing, divergence-free, vector spline to interpolate velocity fields at intermediate discrete times such that the collection of velocity fields integrate over time to match the observed displacement components. Through this process, IDEA yields a dense estimate of a 3D displacement field that matches our observations and also corresponds to an incompressible motion. The method was validated with both numerical simulation and in vivo human experiments on the heart and the tongue. [ABSTRACT FROM PUBLISHER]

Abstract: Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2h) and the sub-acute (7days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p <0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p <0.0005), hippocampus (p =0.014), corpus callosum (p =0.031) and contralateral external capsule (p =0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p <0.0005; external capsule: p =0.003; hippocampus: p =0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p =0.032; hippocampus: p =0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult. [Copyright &y& Elsevier]

Abstract: An important question remains as to how the brain differentially processes first (pricking) pain mediated by Aδ-nociceptors versus second (burning) pain mediated by C-nociceptors. In the present cross-over randomized, within-subjects controlled study, brain activity patterns were examined with event-related fMRI while pricking and burning pain were selectively evoked using a diode laser. Stimuli evoking equivalent pain intensities were delivered to the dorsum of the left foot. Different laser parameters were used to elicit pricking (60ms pulse duration) and burning (2.0s pulse duration) pain. Whole brain group analysis showed that several brain areas were commonly activated by pricking and burning pain, including bilateral thalamus, bilateral anterior insula, bilateral posterior parietal lobule, contralateral dorsolateral prefrontal cortex, ipsilateral cerebellum, and mid anterior cingulate cortex. These findings show that pricking and burning pain were associated with activity in many of the same nociceptive processing brain regions. This may be expected given that Aδ-and C-nociceptive signals converge to a great extent at the level of the dorsal horn. Other brain regions showed differential processing. Stronger activation in the pricking pain condition was found in the ipsilateral hippocampus, bilateral parahippocampal gyrus, bilateral fusiform gyrus, contralateral cerebellum and contralateral cuneus/parieto-occipital sulcus. Stronger activation in the burning pain condition was found in the ipsilateral dorsolateral prefrontal cortex. These differential activation patterns suggest preferential importance of Aδ-fiber signals versus C-fiber signals for these specific brain regions. [Copyright &y& Elsevier]

Functional magnetic resonance imaging (fMRI) was used to compare cortical nociceptive responses to painful contact heat in healthy young (ages 22–30, n= 7) and older (ages 56–75, n= 7) subjects. Compared to young subjects, older subjects had significantly smaller pain-related fMRI responses in anterior insula (aINS) ( P < 0.04), primary somatosensory cortex (S1) ( P= 0.03), and supplementary motor area ( P= 0.02). Gray matter volumes in S1 and aINS were significantly smaller for the older group ( P= 0.02 and 0.0001, respectively), suggesting reduced processing capacity in these regions that might account for smaller pain-related fMRI responses. [ABSTRACT FROM AUTHOR]