Analysis of Intervertebral Disc Degeneration Induced by Endplate Drilling or Needle Puncture in Complement C6-Sufficient and C6-Deficient Rabbits.

Previous studies indicate an implication of the terminal complement complex (TCC) in disc degeneration (DD). To investigate the functional role of TCC in trauma-induced DD in vivo, the model of endplate (EP) drilling was first applied in rabbits using a C6-deficient rabbit strain in which no TCC formation was possible. In parallel the model of needle puncture was investigated. Using a minimally invasive surgical intervention, lumbar rabbit intervertebral discs (IVDs) were treated with EP drilling or needle puncture. Degenerative effects of both surgical interventions were assessed by Pfirrmann grading and T2 quantification of the IVDs based on high-resolution MRI (11.7 T), as well as radiographic determination of disc height index. Pfirrmann grading indicated significant degenerative effects after EP drilling. Contrary to our assumption, no evidence was found that the absence of TCC formation in C6-deficient rabbits reduces the development of DD compared to C6-sufficient animals. EP drilling was proven to be suitable for application in rabbits. However, results of the present study do not provide clear evidence of a central functional role of TCC within DD and suggest that TCC deposition in DD patients may be primarily considered as a marker of complement activation during DD progression.

Anatomic and functional masseter muscle adaptation following orthognathic surgery-MRI analysis in 3 years of follow-up.

BACKGROUND: Orthodontic and surgical technical advances in recent years have resulted in treatment opportunities for a whole range of craniofacial skeletal disorders either in the adolescent or adult patient. In the growing child, these can include myofunctional orthodontic appliance therapy or distraction osteogenesis procedures, while in the adult, the mainstay approach revolves around orthognathic surgery. The literature agrees that for a change in craniofacial morphology to remain stable, the muscles acting upon the facial skeleton must be capable of adaptation in their structure and, therefore, their function. Failure of the muscles to adapt to the change in their length or orientation will place undesirable forces on the muscle attachments leading to potential instability of the skeleton. Adaptation can occur through various processes including those within the neuromuscular feedback mechanism, through changes within muscle structure or through altered muscle physiology, and through changes at the muscle/bone interface. It is now accepted that because there is no single method of assessing masticatory function, several measures should be taken, and whenever possible, simultaneously. METHODS: This investigation was designed to apply several, newly developed and more sophisticated methods of measuring muscle structure and function to a situation where adaptation of muscle is pivotal to the success of a therapeutic approach. Patients attending the combined orthodontic/orthognathic surgery clinic at the Clitrofa - Centro Médico, Dentário e Cirúrgico, in Trofa, Portugal, were screened. Ten patients scheduled for a bimaxillary osteotomy involving a combination of maxillary Le Fort I impaction procedure coupled with a sagittal split advancement of the mandible were selected to form the study group. The patients have MRI of the masseter muscle to evaluate the masseter muscle volume and fibre orientation changes. This exam was taken before surgery (T0), 6 to 12 months after surgery (T1), and 3 years after surgery (T2), by two independent observers, according to the protocol jointly developed between the Eastman Dental Institute - University of London and the MRI Centre - Department of Radiology at John Radcliffe Hospital - University of Oxford. RESULTS: Significant differences (p < 0.05) have been identified between Time 0 (pre-op) and Time 1 (6-12 months post-op) regarding the masseter area (mm2). The differences against Time 0 (pre-op) seem to disappear at Time 2 (3 years post-op). CONCLUSIONS: MRI therefore seems to be a valid tool for measuring differences in the masseter muscle area and volume associated with high-severity occlusal deformities, although showing not to be as efficient in detecting the same differences in cases of low-severity occlusal deformities.

Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging.

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study.

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds.

Purpose: Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions. Methods: Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.org; NCT00715533). We built a fully automated lesion segmentation algorithm using a fixed ADC threshold (≤620 × 10-6 mm2/s) to delineate the baseline DWI lesion and analyzed its performance compared to manual assessments. Diagnostic capabilities of best possible ADC thresholds were investigated using receiver operating characteristic curves. Influential patient factors on ADC thresholding techniques' performance were studied by conducting multiple linear regression. Results: 108 acute ischemic stroke patients were selected for analysis. The median Dice coefficient for the algorithm was 0.43 (IQR 0.20-0.64). Mean ADC values in the DWI lesion (ß = -0.68, p < 0.001) and DWI lesion volumes (ß = 0.29, p < 0.001) predicted performance. Optimal individual ADC thresholds differed between subjects with a median of ≤691 × 10-6 mm2/s (IQR ≤660-750 × 10-6 mm2/s). Mean ADC values in the DWI lesion (ß = -0.96, p < 0.001) and mean ADC values in the brain parenchyma (ß = 0.24, p < 0.001) were associated with the performance of individual thresholds. Conclusion: The performance of ADC thresholds for delineating acute stroke lesions varies substantially between patients. It is influenced by factors such as lesion size as well as lesion and parenchymal ADC values. Considering the inherent noisiness of ADC maps, ADC threshold-based automated delineation of very small lesions is not reliable.

Protocol for the Systematic Fixation, Circuit-Based Sampling, and Qualitative and Quantitative Neuropathological Analysis of Human Brain Tissue.

Human brain tissue has long been a critical resource for neuroanatomy and neuropathology, but with the advent of advanced imaging and molecular sequencing techniques, it has become possible to use human brain tissue to study, in great detail, the structural, molecular, and even functional underpinnings of human brain disease. In the century following the first description of Alzheimer's disease (AD), numerous technological advances applied to human tissue have enabled novel diagnostic approaches using diverse physical and molecular biomarkers, and many drug therapies have been tested in clinical trials (Schachter and Davis, Dialogues Clin Neurosci 2:91-100, 2000). The methods for brain procurement and tissue stabilization have remained somewhat consistently focused on formalin fixation and freezing. Although these methods have enabled research protocols of multiple modalities, new, more advanced technologies demand improved methodologies for the procurement, characterization, stabilization, and preparation of both normal and diseased human brain tissues. Here, we describe our current protocols for the procurement and characterization of fixed brain tissue, to enable systematic and precisely targeted diagnoses, and describe the novel, quantitative molecular, and neuroanatomical studies that broadly expand the use of formalin-fixed, paraffin-embedded (FFPE) tissue that will further our understanding of the mechanisms underlying human neuropathologies.

Ocular Dimensions, Refractive Error, and Body Stature in Young Chinese Children with Myopia in Kuala Lumpur, Malaysia.

Purpose: Eyeball shape varies with refraction and body stature. Nevertheless, there are few reports on three-dimensional measurements of eyeball shape in children. The aim of this cross-sectional observational study was to investigate the associations between three-dimensional measurements of ocular dimensions, refractive error, and body stature in young Chinese children with myopia in Kuala Lumpur. Materials and Methods: Thirty-five female and 35 male school children aged 8-9 years old were recruited in this study. Cycloplegic spherical equivalent (SE) and visual acuity (VA) were determined using a logarithm of the minimum angle of resolution (logMAR) chart. Body mass index (BMI), body height, and head circumference were ascertained. Three ocular dimensions, that is, longitudinal axial length (LAL), horizontal width (HW), and vertical height (VH), were determined using magnetic resonance imaging (MRI). Results: There were significant differences among the ocular dimensions in the myopic children. Bonferroni-corrected pairwise t-tests showed that LAL was significantly longer (mean difference, 0.318 mm) than VH, which was in turn significantly longer (mean difference, 0.245 mm) than HW. Body height was significantly correlated with LAL (p < 0.001) and SE (p < 0.001), and multivariate linear regression confirmed that longer LAL and more myopic SE were associated with increased body height (p < 0.001 for both) but not BMI (p = 0.894 and p = 0.413) or head circumference (p = 0.305 and p = 0.226). Conclusion: This study confirms previous reports that changes in ocular dimensions are associated with body height in young children. Axial elongation (forming a prolate profile) occurs in myopic children of both genders at a young age.

Making Visible the Invisible: Automatically Measured Global and Regional Brain Volume Is Associated with Cognitive Impairment and Fatigue in Multiple Sclerosis.

In multiple sclerosis (MS), the transition from relapsing-remitting to the secondary-progressive phase is characterized by a progression independent of relapse activity (PIRA), resulting in physical disability accumulation and invisible symptoms, i.e., fatigue and cognitive impairment (CI). These symptoms are related to neurodegenerative processes and have been correlated with MRI measures of brain atrophy only at a group level; however, the application in clinical practice of atrophy-based measurements for single-patient evaluation is yet to be fully investigated. In the present study, we aimed to evaluate the association between brain atrophy, measured with easy-to-use automatic software, and the "invisible" MS symptoms of cognition and fatigue. A total of 69 MS patients were included in the study; cognitive impairment and fatigue (FSS) (in addition to neurological disability, EDSS) were assessed and correlated with brain volumes calculated using the automated software QyScore® which is validated for single-patient use in the clinical setting. Results showed that the cognitive status was accurately reflected by measures of atrophy, with a sensitivity of up to 90%. CI patients showed a lower volume compared to cognitively normal patients in the whole brain (p = 0.017), gray matter (p = 0.042), insula (p = 0.035), cerebellum (p = 0.008), and limbic lobe (p = 0.049). FSS was associated with temporal lobe (r = -0.37, p = 0.013) and insular (r = -0.36, p = 0.019) volumes. The volumes of the same regions were also associated with EDSS. The global/regional atrophy results, assessed with automatic and easy-to-use software, correlated with cognitive and fatigue symptoms, thus supporting the clinical application in routine patient management.

Health Economic Impact of Software-Assisted Brain MRI on Therapeutic Decision-Making and Outcomes of Relapsing-Remitting Multiple Sclerosis Patients-A Microsimulation Study.

AIM: To develop a microsimulation model to assess the potential health economic impact of software-assisted MRI in detecting disease activity or progression in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We develop a simulated decision analytical model based on a hypothetical cohort of RRMS patients to compare a baseline decision-making strategy in which only clinical evolution (relapses and disability progression) factors are used for therapy decisions in MS follow-up, with decision-making strategies involving MRI. In this context, we include comparisons with a visual radiologic assessment of lesion evolution, software-assisted lesion detection, and software-assisted brain volume loss estimation. The model simulates clinical (EDSS transitions, number of relapses) and subclinical (new lesions and brain volume loss) disease progression and activity, modulated by the efficacy profiles of different disease-modifying therapies (DMTs). The simulated decision-making process includes the possibility to escalate from a low efficacy DMT to a high efficacy DMT or to switch between high efficacy DMTs when disease activity is detected. We also consider potential error factors that may occur during decision making, such as incomplete detection of new lesions, or inexact computation of brain volume loss. Finally, differences between strategies in terms of the time spent on treatment while having undetected disease progression/activity, the impact on the patient's quality of life, and costs associated with health status from a US perspective, are reported. RESULTS: The average time with undetected disease progression while on low efficacy treatment is shortened significantly when using MRI, from around 3 years based on clinical criteria alone, to 2 when adding visual examination of MRI, and down to only 1 year with assistive software. Hence, faster escalation to a high efficacy DMT can be performed when MRI software is added to the radiological reading, which has positive effects in terms of health outcomes. The incremental utility shows average gains of 0.23 to 0.37 QALYs over 10 and 15 years, respectively, when using software-assisted MRI compared to clinical parameters only. Due to long-term health benefits, the average annual costs associated with health status are lower by $1500-$2200 per patient when employing MRI and assistive software. CONCLUSIONS: The health economic burden of MS is high. Using assistive MRI software to detect and quantify lesions and/or brain atrophy has a significant impact on the detection of disease activity, treatment decisions, health outcomes, utilities, and costs in patients with MS.

Cerebral Microstructural Alterations in Patients With Early Parkinson's Disease Detected With Quantitative Magnetic Resonance Measurements.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. In early stages of PD, patients typically display normal brain magnet resonance imaging (MRI) in routine screening. Advanced imaging approaches are necessary to discriminate early PD patients from healthy controls. In this study, microstructural changes in relevant brain regions of early PD patients were investigated by using quantitative MRI methods. Methods: Cerebral MRI at 3T was performed on 20 PD patients in early stages and 20 age and sex matched healthy controls. Brain relative proton density, T1, T2, and T2' relaxation times were measured in 14 regions of interest (ROIs) in each hemisphere and compared between patients and controls to estimate PD related alterations. Results: In comparison to matched healthy controls, the PD patients revealed decreased relative proton density in contralateral prefrontal subcortical area, upper and lower pons, in ipsilateral globus pallidus, and bilaterally in splenium corporis callosi, caudate nucleus, putamen, thalamus, and mesencephalon. The T1 relaxation time was increased in contralateral prefrontal subcortical area and centrum semiovale, putamen, nucleus caudatus and mesencephalon, whereas T2 relaxation time was elevated in upper pons bilaterally and in centrum semiovale ipsilaterally. T2' relaxation time did not show significant changes. Conclusion: Early Parkinson's disease is associated with a distinct profile of brain microstructural changes which may relate to clinical symptoms. The quantitative MR method used in this study may be useful in early diagnosis of Parkinson's disease. Limitations of this study include a small sample size and manual selection of the ROIs. Atlas-based or statistical mapping methods would be an alternative for an objective evaluation. More studies are necessary to validate the measurement methods for clinical use in diagnostics of early Parkinson's disease.

Automatic linear measurements of the fetal brain on MRI with deep neural networks.

PURPOSE: Timely, accurate and reliable assessment of fetal brain development is essential to reduce short and long-term risks to fetus and mother. Fetal MRI is increasingly used for fetal brain assessment. Three key biometric linear measurements important for fetal brain evaluation are cerebral biparietal diameter (CBD), bone biparietal diameter (BBD), and trans-cerebellum diameter (TCD), obtained manually by expert radiologists on reference slices, which is time consuming and prone to human error. The aim of this study was to develop a fully automatic method computing the CBD, BBD and TCD measurements from fetal brain MRI. METHODS: The input is fetal brain MRI volumes which may include the fetal body and the mother's abdomen. The outputs are the measurement values and reference slices on which the measurements were computed. The method, which follows the manual measurements principle, consists of five stages: (1) computation of a region of interest that includes the fetal brain with an anisotropic 3D U-Net classifier; (2) reference slice selection with a convolutional neural network; (3) slice-wise fetal brain structures segmentation with a multi-class U-Net classifier; (4) computation of the fetal brain midsagittal line and fetal brain orientation, and; (5) computation of the measurements. RESULTS: Experimental results on 214 volumes for CBD, BBD and TCD measurements yielded a mean [Formula: see text] difference of 1.55 mm, 1.45 mm and 1.23 mm, respectively, and a Bland-Altman 95% confidence interval ([Formula: see text] of 3.92 mm, 3.98 mm and 2.25 mm, respectively. These results are similar to the manual inter-observer variability, and are consistent across gestational ages and brain conditions. CONCLUSIONS: The proposed automatic method for computing biometric linear measurements of the fetal brain from MR imaging achieves human-level performance. It has the potential of being a useful method for the assessment of fetal brain biometry in normal and pathological cases, and of improving routine clinical practice.

Footprint size matters: wider coronal greater tuberosity width is associated with increased rates of healing after rotator cuff repair.

BACKGROUND: The purpose of this study was to determine whether greater tuberosity morphology (1) could be measured reliably on magnetic resonance imaging (MRI), (2) differed between patients with rotator cuff tears (RCTs) compared with those without tears or glenohumeral osteoarthritis, or (3) differed between patients with rotator cuff repairs (RCR) who healed and those that did not. METHODS: This is a retrospective comparative study. (1) We measured greater tuberosity width (coronal and sagittal), lateral offset, and angle on MRI corrected into the plane of the humerus. To determine reliability, these measurements were made by two observers and intraclass correlation coefficients were calculated. (2) We compared these measurements between patients with a full-thickness RCT and patients aged >50 years without evidence of a RCT or glenohumeral osteoarthritis. (3) We then compared these measurements between those patients with healed RCRs and those with evidence of retear on MRI. In this portion, we only included patients with both a preoperative and postoperative MRI at least 1 year from RCR. Postoperative MRIs were obtained to assess healing rates, not because of concern for failure. Those without tendon defects were considered healed. RESULTS: (1) In a validation cohort of 50 patients with MRI, all inter-rater intraclass correlation coefficients were greater than 0.75. (2) There were no differences between our RCT group of 110 patients and our comparison group of 100 patients in tuberosity coronal width, sagittal width, or lateral offset. The RCT group had a significantly smaller greater tuberosity angle (63 ± 4° vs 65 ± 5°, P = .003). (3) In our group of 110 RCRs, postoperative MRI scans were obtained at a mean follow-up of 23.6 ± 15.7 months showing 84 (76%) patients had healed RCRs. Larger coronal tuberosity width was associated with healing (1.3 ± 0.2 vs 1.2 ± 0.2 cm, P = .032), as was smaller tear width (P < .001), and retraction (P < .001). When coronal width was dichotomized, there was a significantly higher healing rate with a width over 1.2 cm (85 vs 66%, P = .02). No other greater tuberosity morphological characteristics were associated with RCR or postoperative healing. CONCLUSION: RCTs do not appear to be associated with greater tuberosity morphology. Postoperative rotator cuff healing based on MRI is 76%. Higher rates of healing occur with a wider coronal tuberosity width (ie, rotator cuff tendon footprint). Consideration could be given to widening the footprint intraoperatively in an effort to improve healing rates although this remains to be validated.

Dual-task performance is associated with brain MRI Morphometry in individuals with mild cognitive impairment.

BACKGROUND AND PURPOSE: Cognitive impairment is a critical health problem in the elderly population. Research has shown that patients with mild cognitive impairment (MCI) may develop dementia in later years. Therefore, early identification of MCI could allow for interventions to help delay the progression of this devastating disease. Our objective in this study was to detect the early presence of MCI in elderly patients via neuroimaging and dual-task performance. METHODS: Brain MRI scans from 21 older adult volunteers, including cognitively healthy adults (HA, n = 9, age = 68-79 years) and mild cognitively impaired (MCI, n = 12, age = 66-92 years) were analyzed using automatic segmentation techniques. Regional volume, surface area, and thickness measures were correlated with simultaneous performance of motor and cognitive tasks (dual-task) within a novel upper-extremity function (UEF) test, using multivariate analysis of variance models. RESULTS: We found significant associations of dual-task performance with volume of five cortical brain regions (P ≤ .048) and thickness of 13 regions (P ≤ .043) within the frontal, temporal, and parietal lobes. There was a significant interaction effect of cognitive group on dual-task score for the inferior temporal gyrus volume (P ≤ .034), and the inferior parietal lobule, inferior temporal gyrus, and middle temporal gyrus average thickness (P ≤ .037). CONCLUSIONS: This study highlighted the potential of dual-tasking and MRI morphometric changes as a simple and accurate tool for early detection of cognitive impairment among community-dwelling older adults. The strong interaction effects of cognitive group on UEF dual-task score suggest higher association between atrophy of these brain structures and compromised dual-task performance among the MCI group.

Deep learning-based thigh muscle segmentation for reproducible fat fraction quantification using fat-water decomposition MRI.

BACKGROUND: Time-efficient and accurate whole volume thigh muscle segmentation is a major challenge in moving from qualitative assessment of thigh muscle MRI to more quantitative methods. This study developed an automated whole thigh muscle segmentation method using deep learning for reproducible fat fraction quantification on fat-water decomposition MRI. RESULTS: This study was performed using a public reference database (Dataset 1, 25 scans) and a local clinical dataset (Dataset 2, 21 scans). A U-net was trained using 23 scans (16 from Dataset 1, seven from Dataset 2) to automatically segment four functional muscle groups: quadriceps femoris, sartorius, gracilis and hamstring. The segmentation accuracy was evaluated on an independent testing set (3 × 3 repeated scans in Dataset 1 and four scans in Dataset 2). The average Dice coefficients between manual and automated segmentation were > 0.85. The average percent difference (absolute) in volume was 7.57%, and the average difference (absolute) in mean fat fraction (meanFF) was 0.17%. The reproducibility in meanFF was calculated using intraclass correlation coefficients (ICCs) for the repeated scans, and automated segmentation produced overall higher ICCs than manual segmentation (0.921 vs. 0.902). A preliminary quantitative analysis was performed using two-sample t test to detect possible differences in meanFF between 14 normal and 14 abnormal (with fat infiltration) thighs in Dataset 2 using automated segmentation, and significantly higher meanFF was detected in abnormal thighs. CONCLUSIONS: This automated thigh muscle segmentation exhibits excellent accuracy and higher reproducibility in fat fraction estimation compared to manual segmentation, which can be further used for quantifying fat infiltration in thigh muscles.

Volume Change in Frontal Cholinergic Structures After Traumatic Brain Injury and Cognitive Outcome.

The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI (n = 114) and controls with acute orthopedic injuries (n = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, p < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.

Structural plasticity of the bilateral hippocampus in glioma patients.

This study investigates the structural plasticity and neuronal reaction of the hippocampus in glioma patient pre-surgery. Ninety-nine glioma patients without bilateral hippocampus involvement (low-grade, n=52; high-grade, n=47) and 80 healthy controls with 3D T1 images and resting-fMRI were included. Hippocampal volume and dynamic amplitude of low-frequency fluctuation (dALFF) were analyzed among groups. Relationships between hippocampal volume and clinical characteristics were assessed. We observed remote hippocampal volume increases in low- and high-grade glioma and a greater response of the ipsilateral hippocampus than the contralesional hippocampus. The bilateral hippocampal dALFF was significantly increased in high-grade glioma. Tumor-associated epilepsy and the IDH-1 mutation did not affect hippocampal volume in glioma patients. No significant relationship between hippocampal volume and age was observed in high-grade glioma. The Kaplan-Meier curve and log-rank test revealed that large hippocampal volume was associated with shorter overall survival (OS) compared with small hippocampal volume (p=0.007). Multivariate Cox regression analysis revealed that large hippocampal volume was an independent predictor of unfavorable OS (HR=3.597, 95% CI: 1.160-11.153, p=0.027) in high-grade glioma. Our findings suggest that the hippocampus has a remarkable degree of plasticity in response to pathological stimulation of glioma and that the hippocampal reaction to glioma may be related to tumor malignancy.

Acromial morphology is not associated with rotator cuff tearing or repair healing.

BACKGROUND: The purposes of this study were to determine whether acromial morphology (1) could be measured accurately on magnetic resonance images (MRIs) as compared to computed tomographs (CTs) as a gold standard, (2) could be measured reliably on MRIs, (3) differed between patients with rotator cuff tears (RCTs) and those without evidence of RCTs or glenohumeral osteoarthritis, and (4) differed between patients with rotator cuff repairs (RCRs) that healed and those that did not. METHODS: This is a retrospective comparative study. We measured coronal, axial, and sagittal acromial tilt; acromial width, acromial anterior and posterior coverage, and glenoid version and inclination on MRI corrected into the plane of the glenoid. We determined accuracy by comparison with CT via intraclass correlation coefficients (ICCs). To determine reliability, these same measurements were made on MRI by 2 observers and ICCs calculated. We compared these measurements between patients with a full-thickness RCT and patients aged >50 years without evidence of an RCT or glenohumeral osteoarthritis. We then compared these measurements between those patients with healed RCRs and those with a retorn rotator cuff on MRI. In this portion, we only included patients with both a preoperative MRI and a postoperative MRI at least 1 year from RCR. Only those patients without tendon defects on postoperative MRIs were considered to be healed. In these patients, we also radiographically measured the critical shoulder angle. RESULTS: In a validation cohort of 30 patients with MRI and CT, all ICCs were greater than 0.86. In these patients, the inter-rater ICCs of the MRI measurements were >0.53. In our RCT group of 110 patients, there was greater acromial width [mean difference (95% confidence interval) = 0.1 (0, 0.2) mm, P = .012] and significantly less sagittal acromial tilt [9° (5°-12°), P < .001] than in our comparison group of 107 patients. A total of 110 RCRs were included. Postoperative MRI scans were obtained at a mean follow-up of 24.2 ± 15.8 months, showing 84 patients (76%) had healed RCRs. Aside from acromial width, which was 0.2 mm different and thus did not have clinical significance, there was no association between healing and any of the measured morphologic characteristics. Patients with healed repairs had significantly smaller tears in terms of both width (P < .001) and retraction (P < .001). CONCLUSION: Although the acromion is wider in RCTs, the difference of 0.1 mm likely has no clinical significance. The acromion is more steeply sloped from posteroinferior to anterosuperior in those with RCTs. These findings call into question subacromial impingement due to native acromial morphology as a cause of rotator cuff tearing. Acromial morphology, critical shoulder angle, and glenoid inclination were not associated with healing after RCR. This study does not support lateral acromioplasty.

The effects of dual plating on the vascularity of the distal femur.

AIMS: Dual plating of distal femoral fractures with medial and lateral implants has been performed to improve construct mechanics and alignment, in cases where isolated lateral plating would be insufficient. This may potentially compromise vascularity, paradoxically impairing healing. This study investigates effects of single versus dual plating on distal femoral vascularity. METHODS: A total of eight cadaveric lower limb pairs were arbitrarily assigned to either 1) isolated lateral plating, or 2) lateral and medial plating of the distal femur, with four specimens per group. Contralateral limbs served as matched controls. Pre- and post-contrast MRI was performed to quantify signal intensity enhancement in the distal femur. Further evaluation of intraosseous vascularity was done with barium sulphate infusion with CT scan imaging. Specimens were then injected with latex medium and dissection was completed to assess extraosseous vasculature. RESULTS: Quantitative MRI revealed a mean reduction of 21.2% (SD 1.3%) of arterial contribution in the lateral plating group and 25.4% (SD 3.2%) in the dual plating group (p = 0.051); representing a mean decrease in arterial contribution of 4.2%. The only significant difference found between both experimental groups was regionally, at the lateral aspect of the distal femur with a mean drop in arterial contribution in the lateral plating group of 18.9% (SD 2.6%) versus 24.0% (SD 3.2%) in the dual plating group (p = 0.048), representing a mean decrease in arterial contribution of 5.1%. Gross dissection revealed complete destruction of periosteal vessels underneath either medial or lateral plates in both groups. The network of genicular branches contributing to the posterior and distal femoral condyles was preserved in all specimens. A medial vascular pedicle was found dividing from the superficial femoral artery at a mean 12.7 cm (SD 1.7) proximal to the medial epicondyle and was undisrupted in the dual plating group. CONCLUSION: Lateral locking-plate application resulted in mean 21.2% reduction in distal femur vascularity. Addition of medial plates did not further markedly decrease vascularity. As such, the majority of the vascular insult occurred with lateral plating alone. Supplemental medially based fixation did not lead to marked devascularization of the distal femur, and should therefore be considered in the setting of comminution and poor bone stock in distal femoral fractures. Further clinical research is required to confirm the results of this study. Cite this article: Bone Joint J 2020;102-B(4):530-538.

Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses.

Chronic stress can impair the health of human brains. An important strategy that may prevent the accumulation of stress may be the consumption of functional foods. When senescence-accelerated mice prone 10 (SAMP10), a stress-sensitive strain, were loaded with stress using imposed male mouse territoriality, brain volume decreased. However, in mice that ingested theanine (6 mg/kg), the main amino acid in tea leaves, brain atrophy was suppressed, even under stress. On the other hand, brain atrophy was not clearly observed in a mouse strain that aged normally (Slc:ddY). The expression level of the transcription factor Npas4 (neuronal PAS domain protein 4), which regulates the formation and maintenance of inhibitory synapses in response to excitatory synaptic activity, decreased in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but increased in mice that ingested theanine. Lipocalin 2 (Lcn2), the expression of which increased in response to stress, was significantly high in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but not in mice that ingested theanine. These data suggest that Npas4 and Lcn2 are involved in the brain atrophy and stress vulnerability of SAMP10 mice, which are prevented by the consumption of theanine, causing changes in the expression of these genes.

Anatomical and Functional Characterization in Children With Unilateral Cerebral Palsy: An Atlas-Based Analysis.

Background. Variability in hand function among children with unilateral cerebral palsy (UCP) might reflect the type of brain injury and resulting anatomical sequelae. Objective. We used atlas-based analysis of structural images to determine whether children with periventricular (PV) versus middle cerebral artery (MCA) injuries might exhibit unique anatomical characteristics that account for differences in hand function. Methods. Forty children with UCP underwent structural brain imaging using 3-T magnetic resonance imaging. Brain lesions were classified as PV or MCA. A group of 40 typically developing (TD) children served as comparison controls. Whole brains were parcellated into 198 structures (regions of interest) to obtain volume estimates. Dexterity and bimanual hand function were assessed. Unbiased, differential expression analysis was performed to determine volumetric differences between PV and MCA groups. Principal component analysis (PCA) was performed and the top 3 components were extracted to perform regression on hand function. Results. Children with PV had significantly better hand function than children with MCA. Multidimensional scaling analysis of volumetric data revealed separate clustering of children with MCA, PV, and TD children. PCA extracted anatomical components that comprised the 2 types of brain injury. In the MCA group, reductions of volume were concentrated in sensorimotor structures of the injured hemisphere. Models using PCA predicted hand function with greater accuracy than models based on qualitative brain injury type. Conclusions. Our results highlight unique quantitative differences in children with UCP that also predict differences in hand function. The systematic discrimination between groups found in our study reveals future questions about the potential prognostic utility of this approach.