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Introduction There is evidence that the concentrations of the main inhibitory neurotransmitter (GABA) may be altered in schizophrenia. The purpose of this study is to find the changes in the GABA concentration in the area of anterior and posterior cingulate cortex of patients with early-stage schizophrenia using the spectral-edited magnetic resonance spectroscopy. Objectives To measure the cerebral concentrations of the gamma-aminobutyric acid in schizophrenia patients at early stage. Methods Thirty-one subject, 18 controls (11m+7f, 29.6±5.7 y.o.) and 13 schizophrenia patients (F20.0, 8m+5f, 27.5±3.1 y.o.). Philips Achieva dStream 3T MRI scanner, standard head coil. The 3D T1w head images and MEGA-PRESS GABA spectra in ACC and PCC areas were acquired with the following parameters: 50x25x25 mm, TR = 2 s, TE = 64 ms, 180-editing pulses applied at 1.9 ppm and 7.6 ppm, NSA = 288 (acq.time ~10 min). GABA spectra were processed in Gannet program. The intensities of the GABA, Glutamate+glutamine (Glx), creatine (Cr) and unsuppressed water signals were acquired. T-test was used in search for between-group differences. Results In ACC region, significant reduction of the GABA/Water was observed (by ~15%, p=0.02) as well as a trend to a decrease in GABA/Cr (by ~10%, p=0.07) in schizophrenia. In PCC, no significant GABA/Water or GABA/Cr differences were observed. Glx/Water and Glx/Cr in both areas were also unchanged. Image: Image 2: Conclusions This study provides insight into neurotransmitter alterations at early-stage schizophrenia. The results demonstrate the region-specific changes in the balance of the main neurotransmitters. Since this balance is crucial for the normal cerebral functioning, the results may facilitate better understanding of the dynamics of the pathological process and provide additional information for understanding the biological mechanisms of the schizophrenia development. Disclosure of Interest None Declared

Introduction There is evidence that cerebral myelination is impaired in schizophrenia. The purpose of this study is to find the myelin content changes in the brain structures of patients with early-stage schizophrenia using the macromolecular proton fraction (MPF) method, and also to evaluate the differences in the myelination of these structures. Objectives To measure MPF in the brain structures of schizophrenia patients Methods Forty-five subjects, 22 controls (10m+12f, 31.6±9.7 y.o.) and 23 schizophrenia patients (F20.0, 11m+12f, 31.5±5.1 y.o.). Philips Achieva dStream 3T MRI scanner, standard head coil. The magnetization transfer (TR=20 ms, TE=4.60 ms, FA=10°), T1-weighted (TR=20 ms, TE=4.60 ms, FA=20°) and PD-weighted (TR=20 ms, TE=4.60 ms, FA=4°) were acquired. The MPF maps were reconstructed using home-made software. In FSL, non-brain structures were removed and MPF maps were registered to a standard MNI152 1 mm atlas. Harvard Oxford Cortical and Subcortical atlases were used to select areas of interest. T-test was used in search for between-group differences. Results A 3% decrease in myelination in schizophrenia was observed in whole cerebral cortex p = 0.03) and cerebral white matter (p=0.02). Trends to cortical demyelination were found: paracingular cortex (p=0.06), anterior (p=0.1) and posterior cingulate cortex (p=0.07). No myelination disorders were detected in the cerebellum. Image: Image 2: Image 3: Conclusions To our knowledge, the absence of cerebellar myelination disorders in patients at an early-stage schizophrenia is reported for the first time, while the observed decrease in cerebrum myelination in schizophrenia is consistent with the previous findings. The difference in myelination between cerebellum and cerebrum may help to characterize the dynamics of the pathological process and provide additional information for understanding the biological mechanisms of the development of schizophrenia. Grant RSF 20-15-00299 (partially). Disclosure of InterestNone Declared

Introduction Endogenous psychoses, e.g. schizophrenia, are a pressing problem of modern medicine and biology. Among various neurobiological models of schizophrenia,much attention is paid to disturbances in the brain neural activity and metabolism. Objectives The aim of this study was to analyze dynamics of motor cortex metabolites in the norm and in early stage of schizophrenia in period of BOLD response to event related single stimulus using MRI methods (fMRI and NMR). Methods Study was performed on clinical Phillips Achieva 3.0 T MRI scanner. Volume of interest in motor cortex was localized on the base of fMRI study (EPI FFE, TR = 3000 ms, TE = 30 ms) as the zone of activation (Fig 1) caused by bottom push with the forefinger in response to single auditory stimuli transmitted with the 18 s periodicity. The BOLD signal was measured each 3 sec. 1Н МR spectra (PRESS, TE = 30 ms TR = 3000 ms) were run; FID signals for time points t = 0, 3, 6, 9, 12, 15, 18 s after stimulus were summarized (Fig 2). Thus, the synchronization of BOLD and metabolic responses to single stimulus was achieved. The same method was applied for spectra accumulation in resting state. For FID processing custom made software was used (with apodization filtering (LB = 20, GB = -5), FT and manual phase correction). NAA, Cho, Cr signal intensities for each time point were normalized to their values at t = 0 and to the volume of activated cells containing in the voxel (segmented manually). Intergroup difference and time points differences were estimated using Mann-Whitney criterion with the level of significance p

Introduction The corpus callosum (CC) is one of the important structures responsible for communication between the brain hemispheres. Its role is particularly important in cognitive tasks performance, information processing, concentration of attention, in mnestic processes. The corresponding dysfunctions are the major symptoms of schizophrenia, and hence, structural characteristics of CC in schizophrenics are in the focus of attention. Objectives The aim of the study was to analyze the microstructural and metabolic features of the corpus callosum in recently onset schizophrenia. Methods The study was carried out in 13 men with juvenile endogenous paroxysmal psychosis (disease standing ≤ 5 years after first manifestation) aged 17-27 years (median 22.0±3.1 years). The studies were carried out during unfolding remission or in remission. Control group consisted of 15 mentally healthy young men (18-28 years). MRI and 1H-MRS studies were carried out on Achieva 3T MRI scanner device (Phillips). Diffuse tensor images were obtained in the axial plane using echo-planar pulse sequence. Diffuse gradients were applied in 32 noncolinear vectors. The spectra were recorded by single voxel 1H-MRS. The spectroscopic voxel (2×1×1 cm) was placed in the CC genu region. The PRESS sequence was used (TR/TE=1500/40 msec). Results Statistical analysis showed no abnormal diffusion values in the CC splenium in the patients. Significant changes in the parameters were found in the CC genu. The values of ADC and RD increased, while FA coefficient decreased in the CC genu of patients with the initial stage of schizophrenia; PD values were normal. The increase of RD in the presence of unchanged PD indicated a decrease of water diffusion velocity and anisotropy in the direction perpendicular to the axon orientation. A typical 1H-MRS of the CC genu was presented in Figure 1. The results of statistical analysis of metabolite signal intensities in the CC genu of patients and normal subjects were presented in Figure 2. NAA level was reduced significantly in the patients. No appreciable changes in Cho values in the CC genu were detected in the patients vs. normal subjects. Image: Image 2: Conclusions The increase of RD could be caused by several factors: impairment of myelin membranes, axon damage because of impairment of axon cytoskeleton, and changed organization of fibrils. Our results showed that RD increase in patients with early schizophrenia did not conform to active demyelination, which was proven by the normal level of Cho, while axon damage, shown by low level of NAA, did not lead to PD reduction. The decrease of NAA level detected in our study indicated axonal damage in the CC genu of patients in the early stage of schizophrenia. The increase of RD in the presence of normal Cho level seemed to indicate disorders in the axon cytoskeleton damage, but not active demyelination. Disclosure of Interest None Declared

Background: In most cases, lateral patellar dislocation (LPD) is accompanied by chondral injury and may initiate gradual degeneration of patellar cartilage, which might be detected with a T 2 mapping, a well-established method for cartilage lesions assessment., Purpose: To examine short-term consequences of single first-time LPD in teenagers by T 2 mapping of the patellar-cartilage state., Study Type: Prospective., Population: 95 patients (mean age: 15.1 ± 2.3; male/female: 46/49) with first-time, complete, traumatic LPD and 51 healthy controls (mean age: 14.7 ± 2.2, male/female: 29/22)., Field Strength/sequence: 3.0 T; axial T 2 mapping acquired using a 2D turbo spin-echo sequence., Assessment: MRI examination was conducted 2-4 months after first LPD. T 2 values were calculated in manually segmented cartilage area via averaging over three middle level slices in six cartilage regions: deep, intermediate, superficial layers, and medial lateral parts., Statistical Tests: ANOVA analysis with Tukey's multiple comparison test, one-vs.-rest logistic regression analysis. The threshold of significance was set at P < 0.05., Results: In lateral patellar cartilage, a significant increase in T 2 values was found in deep and intermediate layers in both patient groups with mild (deep: 34.7 vs. 31.3 msec, intermediate: 38.7 vs. 34.6 msec, effect size = 0.55) and severe (34.8 vs. 31.3 msec, 39.1 vs. 34.6 msec, 0.55) LPD consequences as compared to controls. In the medial facet, only severe cartilage damage showed significant prolongation of T 2 times in the deep layer (34.3 vs. 30.7 msec, 0.55). No significant changes in T 2 values were found in the lateral superficial layer (P = 0.99), whereas mild chondromalacia resulted in a significant decrease of T 2 in the medial superficial layer (41.0 vs. 43.8 msec, 0.55)., Data Conclusion: The study revealed substantial difference in T 2 changes after LPD between medial and lateral areas of patellar cartilage., Evidence Level: 2 TECHNICAL EFFICACY STAGE: 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: To find a possible quantitative relation between activation-induced fast (< 10 s) changes in the γ-aminobutyric acid (GABA) level and the amplitude of a blood oxygen level-dependent contrast (BOLD) response (according to magnetic resonance spectroscopy [MRS] and functional magnetic resonance imaging [fMRI])., Materials and Methods: fMRI data and MEGA-PRESS magnetic resonance spectra [echo time (TE)/repetition time (TR) = 68 ms/1500 ms] of an activated area in the visual cortex of 33 subjects were acquired using a 3 T MR scanner. Stimulation was performed by presenting an image of a flickering checkerboard for 3 s, repeated with an interval of 13.5 s. The time course of GABA and creatine (Cr) concentrations and the width and height of resonance lines were obtained with a nominal time resolution of 1.5 s. Changes in the linewidth and height of n-acetylaspartate (NAA) and Cr signals were used to determine the BOLD effect., Results: In response to the activation, the BOLD-corrected GABA + /Cr ratio increased by 5.0% (q = 0.027) and 3.8% (q = 0.048) at 1.6 and 3.1 s, respectively, after the start of the stimulus. Time courses of Cr and NAA signal width and height reached a maximum change at the 6th second (~ 1.2-1.5%, q < 0.05)., Conclusion: The quick response of the observed GABA concentration to the short stimulus is most likely due to a release of GABA from vesicles followed by its packaging back into vesicles., (© 2023. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Objective: To measure N-acetyl aspartyl glutamate (NAAG) and N-acetyl aspartate (NAA) concentrations in visual cortex activated by a continuous stimulation in a 3 T field., Methods: NAAG and NAA spectra were obtained with MEGA-PRESS pulse sequence (TE/TR = 140/2000 ms; δ ON NAAG /δ OFF NAAG  = 4.61/4.15 ppm; δ ON NAA /δ OFF NAA  = 4.84/4.38 ppm) in 14 healthy volunteers at rest and upon stimulation by a radial checkerboard flickering at a frequency of 8 Hz. Spectra of all subjects were frequency and phase aligned and then averaged. Additionally, to obtain the time-dependency data, spectra were divided into time sections of 64 s each. The intensities of NAA, NAAG and lactate + macromolecular (Lac + MM) signals were defined by integration of the real part of spectra. The heights of the central resonance of NAAG and NAA signals were measured., Results: The NAAG and NAA concentrations, measured with 2.5% and 0.5% error, respectively, were unaffected by visual activation. A significant increase in the Lac + MM signal by ~ 12% is clearly observed. No stimulation-induced time dependency was found for NAAG or NAA, while the increase in Lac + MM was gradual. The concentration values in visual cortex are in good agreement with the 7 T MRS measurements: [NAAG] = 1.55 mM, [NAA] = 11.95 mM., Conclusion: The MEGA-PRESS pulse sequence together with the spectral preprocessing techniques allowed to demonstrate that the concentrations of NAAG and NAA in the visual cortex remain constant during continuous visual stimulation within the margin of error. An increase in the lactate signal intensity signifies the activation of the anaerobic glycolysis in activated visual cortex., (© 2021. European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Purpose: To separately measure N-acetyl aspartul glutamate (NAAG), N-acetyl aspartate (NAA), aspartate (Asp), and glutamate (Glu) concentrations in white matter (WM) using J-editing techniques in patients with mild traumatic brain injury (mTBI) in the acute phase., Methods: Twenty-four patients with closed concussive head injury and 29 healthy volunteers were enrolled in the current study. For extended 1 H MRS examination, patients and controls were equally divided into two subgroups. In subgroup 1 (12 patients/15 controls), NAAG and NAA concentrations were measured in WM separately with MEGA-PRESS (echo time/repetition time [TE/TR] = 140/2000 ms; δ ON NAA / δ OFF NAA = 4.84/4.38 ppm, δ ON NAAG / δ OFF NAAG = 4.61/4.15 ppm). In subgroup 2 (12 patients/14 controls), Asp and Glu concentrations were acquired with MEGA-PRESS (TE/TR = 90/2000 ms; δ ON Asp / δ OFF Asp = 3.89/5.21 ppm) and TE-averaged PRESS (TE from 35 ms to 185 ms with 2.5-ms increments; TR = 2000 ms) pulse sequences, respectively., Results: tNAA and NAAG concentrations were found to be reduced, while NAA concentrations were unchanged, after mild mTBI. Reduced Asp and elevated myo-inositol (mI) concentrations were also found., Conclusion: The main finding of the study is that the tNAA signal reduction in WM after mTBI is associated with a decrease in the NAAG concentration rather than a decrease in the NAA concentration, as was thought previously. This finding highlights the importance of separating these signals, at least for WM studies, to avoid misinterpretation of the results. NAAG plays an important role in selectively activating mGluR3 receptors, thus providing neuroprotective and neuroreparative functions immediately after mTBI. NAAG shows potential for the development of new therapeutic strategies for patients with injuries of varying severity., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: To measure the transverse relaxation rate (T 2 ) of aspartate (Asp) from Asp-edited MEGA-PRESS spectra and use the measured T 2 values to estimate the Asp concentrations in gray matter (GM)- and white matter (WM)-dominant brain regions., Methods: Since Asp-edited MEGA-PRESS spectra contain non-overlapped Asp signals, TE-dependence arising from J-evolution can be considered using phantom MEGA-PRESS spectra acquired with the same parameters as in vivo spectra. Four TE values (90, 115, 140, and 150 ms) were selected from numeric analyses for effective detection of the edited Asp multiplet at ~2.71 ppm. The T 2 relaxation time was measured in the anterior cingulate cortex (ACC) of 16 healthy volunteers. Absolute cerebral Asp concentrations were measured with Asp-edited MEGA-PRESS in the ACC and left centrum semiovale (CS) of 44 healthy volunteers at TEs of 90, 115, 140, and 150 ms., Results: The in vivo and phantom T 2 values of the edited Asp signals were 165 ± 37 ms and 313 ± 27 ms, respectively. The cortical GM concentration quantified was significantly greater than the WM concentration (2.80 ± 0.31 mM vs. 1.01 ± 0.18 mM)., Conclusion: MEGA-PRESS is the most common editing method used for low-concentration metabolites detection. Estimation of the absolute Asp concentrations has potential in many research applications, such as studying the processes underlying the reduction of N-acetyl aspartate as well as studying mitochondrial diseases etc. The T 2 measurement method described has been successfully applied for edited Asp signals. This method can also be used for other strongly J-coupled signals., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group., Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide., Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset., Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)