Resting and Functional Magnetic Resonance Spectroscopy of Glutamate in Schizophrenia at 7 Tesla

Schizophrenia is a debilitating disease that affects about 1% of the population. Current therapeutic interventions mostly target dopaminergic neurotransmission but are not effective in treating all symptoms. There is growing evidence to support involvement of glutamatergic neurotransmission, which may better account for the symptomatology of schizophrenia. Glutamate concentrations can be measured in vivo using magnetic resonance spectroscopy (MRS). Stronger MRIs provide benefits for MRS, but they also present challenges. Simulations were designed to examine how MRI field strength influences metabolite quantification. Glutamate and its metabolic precursor, glutamine, were more reliably and independently quantified with higher MRI field strengths, showing a clear benefit for MRS. Using a 7T MRI, voxels were placed within the dorsal anterior cingulate cortex (dACC) and thalamus of volunteers with schizophrenia, a psychiatric control group of volunteers with major depressive disorder (MDD), and healthy controls. Glutamine and glycine, both involved in glutamate neurotransmission, were lower in the thalamus in schizophrenia relative to healthy controls, whereas dACC glutamate concentrations were higher, demonstrating glutamatergic abnormalities in schizophrenia at rest. Prior MRS studies of schizophrenia have been in resting conditions. In a proof of concept study with healthy controls, it was shown that the Stroop Task was able elicit a significant glutamate increase in the dACC when in a functional state (glutamate fMRS) relative to resting conditions using the 7T MRI. This was then explored in the same schizophrenic and MDD subjects as the resting MRS study. Healthy controls significantly increased glutamate concentrations, but the schizophrenic and MDD groups did not significantly. The schizophrenic group had a slower glutamatergic response followed by a slower recovery, and, was the only group to demonstrate significant glutamine increases when activated, indicating potential abnormalities in glutamate dynamics. Using a 7T MRI, glutamate was explored in resting and activated conditions in schizophrenia. Glycine was demonstrated to be lower in schizophrenia using MRS for the first time, and the first functional MRS study was performed in a psychiatric population. The studies were made stronger by inclusion of a psychiatric control group. Future studies of schizophrenia with glutamate fMRS should focus on the delayed glutamatergic response to functional activation and abnormal recovery

A Portable Optical CT Scanner for Interactive Teaching of Medical Imaging Principles

Computed Tomography (CT) is widely used as a diagnostic imaging tool in modern medicine. The traditional method of teaching CT principles involves classroom lectures, with demonstrations on a clinical system that can only be accessed during off-hours. The x-ray and ‘black-box’ nature of a clinical system, and the lag time between lectures and demonstrations severely limit the teaching efficiency. A scaled-down portable imaging system that does not use x-rays would be ideal for an interactive classroom or laboratory session. We therefore developed a system using visible light rays instead of x-rays, so that experiments can be conducted immediately and safely with no high-voltage or radiation hazards. Educators at the University of Western Ontario will collaborate with industry to manufacture the scanner (http://www.deskcat.com/) to meet educational objectives, such as those specified by the Commission on the Accreditation of Medical Physics Education Programs (CAMPEP). The table-top CT imaging device will come with a “kit” of experimental modules and specialized software that demonstrate radiography and CT image reconstruction. Image quality is characterized by \u27live\u27 measurements of spatial resolution, contrast resolution, and optical attenuation coefficients using plastic specimens or liquids. We expect that a low-cost portable system (\u3c $15,000 CDN) will enrich the students\u27 learning experience and improve the long-term retention of fundamental imaging concepts. This teaching package should prove attractive to universities with Physics, Biophysics, or Biomedical Engineering Departments, as well as Medical Schools with residency training programs (Radiology, Nuclear Medicine, Medical Imaging, Radiation Oncology). The scanner will be demonstrated at the poster

Medial Prefrontal and Anterior Insular Connectivity in Early Schizophrenia and Major Depressive Disorder: A Resting Functional MRI Evaluation of Large-Scale Brain Network Models

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls

Threats to freshwater fisheries in the United States: perspectives and investments of state fisheries administrators and Agricultural Experiment Station directors

Freshwater fisheries provide human benefits (e.g., food, recreation) but are increasingly threatened by climate change, invasive species, and other stressors. Our purpose was to survey fisheries administrators from state fisheries agencies and Agricultural Experiment Stations (AESs) about their perceptions of, and resource investment toward threats to freshwater fisheries in the United States. Our rationale for studying these two types of fisheries administrators simultaneously was to inform state fisheries professionals about the fisheries relevance of AESs, elevate the profile of fisheries within AESs, and promote mutually beneficial state agency–AES partnerships. Survey respondents generally agreed that recreational, socioeconomic, and ecological services of fisheries were more important than nutritional and commercial benefits. The greatest perceived fisheries threats were water quality/quantity impairment, land‐use change, and invasive species—but, interestingly, not climate change. State fisheries agencies invested more personnel and finances into issues rated as less important but more controllable (e.g., fish production, habitat management) than issues rated as more important but larger in scale and more difficult to control (e.g., water quality/quantity, invasive species). Our research underscores the importance of ensuring that state agencies can address long‐term, socio‐ecologically critical management issues (e.g., climate change) amid budgetary constraints. We call for state agencies to collaborate with new partners (e.g., AESs) to mitigate fisheries threats by expanding fisheries management to more fully encompass terrestrial and human systems; promoting receptiveness to novel research/management ideas; actively predicting, monitoring, and planning for future stressors; and enhancing fisheries social‐ecological resilience

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = −0.02, p < 0.001) and frontal white matter Glx (z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies

Local Governance & Economic Development

This fourth panel at the 2018 Rural Healthcare Symposium at the University of Georgia School of Law focused on the intersection of rural healthcare and rural economic development

Stochastic Model-Informed Cognitive Neuroscience of Stroop-Performance in Schizophrenia

Functional magnetic resonance imaging at 7.0 Tesla was undertaken among Schizophrenia participants (Sz), and clinical (major mood disorder; MDD) and healthy controls (HC), during performance of the Stoop task. Stroop conditions included congruent and incongruent word color items, color-only items, and word-only items. Previous modeling results extended to this most widely used selective-attention task. All groups executed item-encoding operations (subprocesses of the item encoding process) at the same rate (performance accuracy being similarly high throughout), thus displaying like processing capacity; Sz participants, however, employed more subprocesses for item completions than did the MDD participants, who in turn used more subprocesses than the HC group. The reduced efficiency in deploying cognitive-workload capacity among the Sz participants was paralleled by more diffuse neuroconnectivity (Blood-Oxygen-Level-Dependent co-activation) with the anterior cingulate cortex (Broadman Area 32), spreading away from this encoding-intensive region; and by less evidence of network dissociation across Stroop conditions. Estimates of cognitive work done to accomplish item completion were greater for the Sz participants, as were estimates of entropy in both the modeled trial-latency distribution, and its associated neuro-circuitry. Findings are held to be symptom and assessment significant, and to have potential implications for clinical interventio

The Clinical and Genotypic Spectrum of Scoliosis in Multiple Pterygium Syndrome: A Case Series on 12 Children

Background: Multiple pterygium syndrome (MPS) is a genetically heterogeneous rare form of arthrogryposis multiplex congenita characterized by joint contractures and webbing or pterygia, as well as distinctive facial features related to diminished fetal movement. It is divided into prenatally lethal (LMPS, MIM253290) and nonlethal (Escobar variant MPS, MIM 265000) types. Developmental spine deformities are common, may present early and progress rapidly, requiring regular fo llow-up and orthopedic management. Methods: Retrospective chart review and prospective data collection were conducted at three hospital centers. Molecular diagnosis was confirmed with whole exome or whole genome sequencing. Results: This case series describes the clinical features and scoliosis treatment on 12 patients from 11 unrelated families. A molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient. The remaining 11 patients spanned the spectrum between mild (curve ≤ 25°) and malignant scoliosis (≥50° curve before 4 years of age); the two patients with MYH3 mutations presented with malignant scoliosis. Bracing and serial spine casting appear to be beneficial for a few years; non-fusion spinal instrumentation may be needed to modulate more severe curves during growth and spontaneous spine fusions may occur in those cases. Conclusions: Molecular diagnosis and careful monitoring of the spine is needed in children with MPS

[ \u3csup\u3e18\u3c/sup\u3e F]-DCFPyL Positron Emission Tomography/Magnetic Resonance Imaging for Localization of Dominant Intraprostatic Foci: First Experience

An ongoing prospective study is acquiring preoperative imaging data for men with prostate cancer (PCa) using the molecular imaging agent [ F]-DCFPyL targeted against prostate-specific membrane antigen (PSMA). To date, six men (of a planned accrual of 24) with clinically localized, biopsy-proven PCa have undergone preoperative [ F]-DCFPyL positron emission tomography (PET) imaging and multiparametric magnetic resonance imaging acquired using a hybrid PET/MRI system. Lesions identified by [ F]-DCFPyL uptake on PET/MRI were characterized in terms of maximum standardized uptake value (SUV ) and volume using a boundary threshold of 40% SUV . Following surgery, all prostatectomy specimens were processed using a whole-mount technique for accurate deformable co-registration and correlation with PCa foci defined on digitized pathology images. Well-defined intraprostatic dominant lesions were identified by [ F]-DCFPyL PET/MRI (mean SUV 11.4 ± 8.25; mean volume 2.2 ± 2.4 cm ) in all six men. Co-registered digitized whole-mount pathology for the first case revealed that intense [ F]-DCFPyL uptake (SUV 27 ± 1.1 cm ) and multiparametric MRI changes (Prostate Imaging Reporting and Data System score of 4) were highly correlated with a 0.5-cm dominant (largest) lesion with Gleason pattern 4 PCa in the right mid peripheral zone. A smaller focus (0.01 cm ) of lower-grade PCa (Gleason pattern 3) had much lower uptake (SUV 2.7). These early prospective data show that dominant intraprostatic lesions could be identified in all six men using [ F]-DCFPyL as an imaging probe. Trial accrual will continue to quantify in terms of spatial concordance the ability of [ F]-DCFPyL to identify the location and characterize the grade of intraprostatic cancer foci in clinically localized PCa. Patient summary: Positron emission tomography using a novel probe called [ F]-DCFPyL directed against the prostate-specific membrane antigen protein was able to identify locations of prostate cancer in the prostate glands of men undergoing imaging before surgery. In the future, such imaging may allow better targeting of treatment to the portion of the prostate containing the most aggressive components of cancer rather than treating the whole prostate in a uniform fashion. [ F]-DCFPyL positron emission tomography/magnetic resonance imaging shows promise for identifying high-grade intraprostatic foci of prostate cancer in a spatially accurate fashion to facilitate targeted biopsy and treatment. 18 18 18 18 3 18 3 3 3 18 18 18 18 max max max ma

Threats to freshwater fisheries in the United States: perspectives and investments of state fisheries administrators and Agricultural Experiment Station directors

Freshwater fisheries provide human benefits (e.g., food, recreation) but are increasingly threatened by climate change, invasive species, and other stressors. Our purpose was to survey fisheries administrators from state fisheries agencies and Agricultural Experiment Stations (AESs) about their perceptions of, and resource investment toward threats to freshwater fisheries in the United States. Our rationale for studying these two types of fisheries administrators simultaneously was to inform state fisheries professionals about the fisheries relevance of AESs, elevate the profile of fisheries within AESs, and promote mutually beneficial state agency–AES partnerships. Survey respondents generally agreed that recreational, socioeconomic, and ecological services of fisheries were more important than nutritional and commercial benefits. The greatest perceived fisheries threats were water quality/quantity impairment, land‐use change, and invasive species—but, interestingly, not climate change. State fisheries agencies invested more personnel and finances into issues rated as less important but more controllable (e.g., fish production, habitat management) than issues rated as more important but larger in scale and more difficult to control (e.g., water quality/quantity, invasive species). Our research underscores the importance of ensuring that state agencies can address long‐term, socio‐ecologically critical management issues (e.g., climate change) amid budgetary constraints. We call for state agencies to collaborate with new partners (e.g., AESs) to mitigate fisheries threats by expanding fisheries management to more fully encompass terrestrial and human systems; promoting receptiveness to novel research/management ideas; actively predicting, monitoring, and planning for future stressors; and enhancing fisheries social‐ecological resilience.This is a manuscript of an article published as Carlson, Andrew K., William W. Taylor, Michael T. Kinnison, S. Mažeika P. Sullivan, Michael J. Weber, Richard T. Melstrom, Paul A. Venturelli et al. "Threats to freshwater fisheries in the United States: perspectives and investments of state fisheries administrators and Agricultural Experiment Station directors." Fisheries (2019). doi: 10.1002/fsh.10238. Posted with permission.</p