Age-related differences of cerebellar cortex and nuclei: MRI findings in healthy controls and its application to spinocerebellar ataxia (SCA6) patients.

Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 - 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 - 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.

Clinical relevance of total choline (tCho) quantification in suspicious lesions on multiparametric breast MRI.

PURPOSE: To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5). METHODS: One hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (1H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results. RESULTS: One hundred three patients with 74 malignant and 29 benign lesions had full 1H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels < 2.4 mmol/l, no metastatic lymph nodes were found. CONCLUSION: Quantitative tCho evaluation from 1H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management. KEY POINTS: • Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment. • Quantitative tCho levels are associated with lymph node status in breast cancer. • Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.

Comparison of metabolic adaptations between endurance- and sprint-trained athletes after an exhaustive exercise in two different calf muscles using a multi-slice 31 P-MR spectroscopic sequence.

Measurements of exercise-induced metabolic changes, such as oxygen consumption, carbon dioxide exhalation or lactate concentration, are important indicators for assessing the current performance level of athletes in training science. With exercise-limiting metabolic processes occurring in loaded muscles, 31 P-MRS represents a particularly powerful modality to identify and analyze corresponding training-induced alterations. Against this background, the current study aimed to analyze metabolic adaptations after an exhaustive exercise in two calf muscles (m. soleus - SOL - and m. gastrocnemius medialis - GM) of sprinters and endurance athletes by using localized dynamic 31 P-MRS. In addition, the respiratory parameters VO2 and VCO2 , as well as blood lactate concentrations, were monitored simultaneously to assess the effects of local metabolic adjustments in the loaded muscles on global physiological parameters. Besides noting obvious differences between the SOL and the GM muscles, we were also able to identify distinct physiological strategies in dealing with the exhaustive exercise by recruiting two athlete groups with opposing metabolic profiles. Endurance athletes tended to use the aerobic pathway in the metabolism of glucose, whereas sprinters produced a significantly higher peak concentration of lactate. These global findings go along with locally measured differences, especially in the main performer GM, with sprinters revealing a higher degree of acidification at the end of exercise (pH 6.29 ± 0.20 vs. 6.57 ± 0.21). Endurance athletes were able to partially recover their PCr stores during the exhaustive exercise and seemed to distribute their metabolic activity more consistently over both investigated muscles. In contrast, sprinters mainly stressed Type II muscle fibers, which corresponds more to their training orientation preferring the glycolytic energy supply pathway. In conclusion, we were able to analyze the relation between specific local metabolic processes in loaded muscles and typical global adaptation parameters, conventionally used to monitor the training status of athletes, in two cohorts with different sports orientations.

The pH heterogeneity in human calf muscle during neuromuscular electrical stimulation.

PURPOSE: The aim of the study was to examine pH heterogeneity during fatigue induced by neuromuscular electrical stimulation (NMES) using phosphorus magnetic resonance spectroscopy (31 P-MRS). It is hypothesized that three pH components would occur in the 31 P-MRS during fatigue, representing three fiber types. METHODS: The medial gastrocnemius of eight subjects was stimulated within a 3-Tesla whole body MRI scanner. The maximal force during stimulation (Fstim ) was examined by a pressure sensor. Phosphocreatine (PCr), adenosintriphosphate, inorganic phosphate (Pi), and the corresponding pH were estimated by a nonvolume-selective 31 P-MRS using a small loop coil at rest and during fatigue. RESULTS: During fatigue, Fstim and PCr decreased to 27% and 33% of their initial levels, respectively. In all cases, the Pi peak increased when NMES was started and split into three different peaks. Based on the single Pi peaks during fatigue, an alkaline (6.76 ± 0.08), a medium (6.40 ± 0.06), and an acidic (6.09 ± 0.05) pH component were observed compared to the pH (7.02 ± 0.02) at rest. CONCLUSION: It is suggested that NMES is able to induce pH heterogeneity in the medial gastrocnemius, and that the single Pi peaks represent the different muscle fiber types of the skeletal muscle. Magn Reson Med 77:2097-2106, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy.

In vivo(1)H MR spectroscopic detection of pain associated metabolic changes in the human brain may allow for an objective evaluation of the perceived pain intensity and assessment of the involved neurotransmitters. Ultimately, it may lead to a deeper understanding of the mechanisms that underlie neuronal pain processing. The present study reports results of time-resolved measurements of acute heat pain induced changes of the excitatory (Glx) and inhibitory (GABA+) neurotransmitter turnover in the anterior cingulate cortex (ACC) and occipital cortex (OC) by using (1)H MEGA-PRESS spectroscopy. In ACC and OC, the ratio Glx/tCr increased by median values of 21.5% (p < 0.001) and 15.7% (p < 0.001), respectively. At the same time, GABA+/tCr decreased by median values of 15.1% (p = 0.114) in ACC and 12.7% (p < 0.001) in OC. To our knowledge, this study demonstrates for the first time the possibility of quantifying pain-induced neurotransmitter changes in the brain by using functional (1)H MEGA-PRESS. The increase of Glx/tCr may be ascribed to an elevated glutamatergic turnover, while the decrease of GABA+/tCr may reflect reduced activity of the inhibitory system in ACC and OC during pain processing.

Interrelations of muscle functional MRI, diffusion-weighted MRI and (31) P-MRS in exercised lower back muscles.

Exercise-induced changes of transverse proton relaxation time (T2 ), tissue perfusion and metabolic turnover were investigated in the lower back muscles of volunteers by applying muscle functional MRI (mfMRI) and diffusion-weighted imaging (DWI) before and after as well as dynamic (31) P-MRS during the exercise. Inner (M. multifidus, MF) and outer lower back muscles (M. erector spinae, ES) were examined in 14 healthy young men performing a sustained isometric trunk-extension. Significant phosphocreatine (PCr) depletions ranging from 30% (ES) to 34% (MF) and Pi accumulations between 95% (left ES) and 120%-140% (MF muscles and right ES) were observed during the exercise, which were accompanied by significantly decreased pH values in all muscles (∆pH ≈ -0.05). Baseline T2 values were similar across all investigated muscles (approximately 27 ms at 3 T), but revealed right-left asymmetric increases (T2 ,inc ) after the exercise (right ES/MF: T2 ,inc = 11.8/9.7%; left ES/MF: T2 ,inc = 4.6/8.9%). Analyzed muscles also showed load-induced increases in molecular diffusion D (p = .007) and perfusion fraction f (p = .002). The latter parameter was significantly higher in the MF than in the ES muscles both at rest and post exercise. Changes in PCr (p = .03), diffusion (p < .01) and perfusion (p = .03) were strongly associated with T2,inc , and linear mixed model analysis revealed that changes in PCr and perfusion both affect T2,inc (p < .001). These findings support previous assumptions that T2 changes are not only an intra-cellular phenomenon resulting from metabolic stress but are also affected by increased perfusion in loaded muscles.

Remote operation of cross-sectional imaging devices as a new form of teleoperation: Structural, technical, regulatory, and qualification aspects in Germany.

BACKGROUND: There is a significant shortage of radiographers in Germany and this shortage is expected to increase. Thus, it is becoming increasingly difficult for radiological facilities to adequately provide their services for the required period of time. Teleradiology has already been established for electronic transmission of diagnostic radiographic imaging examinations between two geographical locations for diagnostic reporting. Recently, the concept of teleoperating radiological devices has become increasingly attractive. METHOD: We examined the potential of teleoperating magnetic resonance imaging (MRI) in radiological facilities within the German regulatory framework in order to address the shortage of qualified personnel. To this end, we are introducing the concept of remote scanning, the structural foundations, the technical requirements associated with it, as well as the legal and educational qualifications of the relevant professional groups. Furthermore, suggestions regarding nomenclature and necessary standard operating procedures to efficiently integrate teleoperation into a clinical workflow adhering to high patient safety standards are provided. RESULTS: Companies provide technical solutions or even experienced radiographers as a service on demand for teleoperating radiological imaging devices remotely from a distance. There should be a comprehensive on-site strategy to effectively embed remote scanning into clinics. Local information technology and data security institutions should be involved in implementation. In order to guarantee that the remote operation workflow is able to provide health care services in line with regulative and legal standards, it is essential to implement standardized personal and institutional training, certifications, and accreditation procedures. Standard operating procedures (SOPs) and checklists for the involved staff, which are adapted to the local workflow in the participating facilities, are beneficial. CONCLUSION: Remote MRI scanning is an evolving technology that further expands the concept of teleradiology to include teleoperations and provides flexibility with respect to the staffing of MRI operators. Careful consideration and dedicated expertise of all involved parties are required to ensure patient safety, meet regulations, and successfully integrate teleoperations into clinics. KEY POINTS: · Remote MRI scanning expands the concept of teleradiology.. · Remote scanning provides flexibility regarding the staffing of MRI operators.. · IT and data security institutions should be involved when implementing remote scanning.. · Comprehensible SOPs and checklists should be established for remote MRI scanning.. · Radiation protection legislation does not allow purely remote CT scanning..

Standardization of a CT Protocol for Imaging Patients with Suspected COVID-19-A RACOON Project.

CT protocols that diagnose COVID-19 vary in regard to the associated radiation exposure and the desired image quality (IQ). This study aims to evaluate CT protocols of hospitals participating in the RACOON (Radiological Cooperative Network) project, consolidating CT protocols to provide recommendations and strategies for future pandemics. In this retrospective study, CT acquisitions of COVID-19 patients scanned between March 2020 and October 2020 (RACOON phase 1) were included, and all non-contrast protocols were evaluated. For this purpose, CT protocol parameters, IQ ratings, radiation exposure (CTDIvol), and central patient diameters were sampled. Eventually, the data from 14 sites and 534 CT acquisitions were analyzed. IQ was rated good for 81% of the evaluated examinations. Motion, beam-hardening artefacts, or image noise were reasons for a suboptimal IQ. The tube potential ranged between 80 and 140 kVp, with the majority between 100 and 120 kVp. CTDIvol was 3.7 ± 3.4 mGy. Most healthcare facilities included did not have a specific non-contrast CT protocol. Furthermore, CT protocols for chest imaging varied in their settings and radiation exposure. In future, it will be necessary to make recommendations regarding the required IQ and protocol parameters for the majority of CT scanners to enable comparable IQ as well as radiation exposure for different sites but identical diagnostic questions.

Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany - A cross sectional study from the German Network University Medicine (NUM).

BACKGROUND: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. METHODS: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. RESULTS: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. CONCLUSIONS: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.

Effects of olanzapine on 31P MRS metabolic markers in schizophrenia.

Antipsychotic drug action might include mechanisms related to normalising phospholipid and high-energy metabolism. We applied brain metabolic imaging with (31)P magnetic resonance spectroscopy ((31)P MRS) and two-dimensional chemical shift imaging to assess changes of metabolism of phospholipids and high-energy phosphates in schizophrenia patients at baseline (four antipsychotic-naïve and three off antipsychotics) and at follow-up, after 6 weeks of treatment with olanzapine. Results indicate a significant increase of adenosine-triphosphate (ATP) in the right inferior temporal cortex and a trend towards ATP decrease in the left cerebellum. This suggests a shift in high-energy phosphates (rather than phospholipids), possibly related to normalisation of functioning in these areas.

Reorganization and Plasticity of the Language Network in Patients with Cerebral Gliomas.

Language is organized in large-scale networks in the human brain that show a strong potential for flexible interactions and adaptation. Neuroplasticity is the central mechanism that allows such dynamic modulation to changing conditions across the life span and is particularly important for network reorganization after brain lesions. Most studies on language reorganization focused on language recovery after stroke. Yet, a strong degree of adaptive neuroplasticity can also be observed in patients with brain tumors in language-eloquent brain areas. This review discusses key mechanisms for neural reorganization in patients with brain tumors. Our main aim is to elucidate the underlying mechanisms for intra- and interhemispheric plasticity in the language network in these patients. The following reorganization patterns are discussed: 1) Persisting function within the tumor; 2) Reorganization in perilesional regions; 3) Reorganization in a distributed network of the affected hemisphere; 4) Reorganization to the contralesional hemisphere. In this context, we shed light on language-related reorganization patterns in frontal and temporo-parietal areas and discuss their functional relevance. We also address tumor-related changes in structural and functional connectivity between eloquent brain regions. Thereby, we aim to expand the general understanding of the plastic potential of the neural language network and facilitate clinical decision-making processes for effective, function-preserving tumor treatment.

Ultra-short echo time (UTE) MR imaging: A brief review on technical considerations and clinical applications.

BACKGROUND: With the availability of MRI sequences with ultrashort echo times (UTE sequences), a signal can be gained from tissue, which was formerly only indirectly accessible. While already extensively employed in various research settings, the widespread transition of UTE imaging to clinical practice is just starting. METHODS: Based on a systematic literature search as well as knowledge gained through annual participation in conferences dedicated to advances in MRI, this review aims to give a brief overview of technical considerations and challenges of UTE imaging and summarizes the major areas of application of UTE imaging. RESULTS: UTE is already employed in clinical practice for structural lung imaging as well as the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. In specific contexts it can replace CT examinations with ionizing radiation and is especially attractive for pediatric patients and longitudinal monitoring of disease progression and treatment. CONCLUSION: UTE imaging provides an interesting and very valuable tool for various clinical purposes and promises a multitude of new insights into tissue properties. While some challenges remain, ongoing adoption in the clinical routine can be expected, as UTE approaches provide a new contrast and capture a signal in tissue formerly invisible on MR imaging. KEY POINTS: · UTE imaging gains relevance in clinical settings. · UTE imaging is employed for the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. · UTE imaging is employed in the clinical routine for structural lung imaging. · UTE imaging promises a multitude of new insights into tissue properties.

Optimized Whole-Body PET MRI Sequence Workflow in Pediatric Hodgkin Lymphoma Patients.

18F-FDG PET/MRI might be the diagnostic method of choice for Hodgkin lymphoma patients, as it combines significant metabolic information from PET with excellent soft-tissue contrast from MRI and avoids radiation exposure from CT. However, a major issue is longer examination times than for PET/CT, especially for younger children needing anesthesia. Thus, a targeted selection of suitable whole-body MRI sequences is important to optimize the PET/MRI workflow. Methods: The initial PET/MRI scans of 84 EuroNet-PHL-C2 study patients from 13 international PET centers were evaluated. In each available MRI sequence, 5 PET-positive lymph nodes were assessed. If extranodal involvement occurred, 2 splenic lesions, 2 skeletal lesions, and 2 lung lesions were also assessed. A detection rate was calculated dividing the number of visible, anatomically assignable, and measurable lesions in the respective MRI sequence by the total number of lesions. Results: Relaxation time-weighted (T2w) transverse sequences with fat saturation (fs) yielded the best result, with detection rates of 95% for nodal lesions, 62% for splenic lesions, 94% for skeletal lesions, and 83% for lung lesions, followed by T2w transverse sequences without fs (86%, 49%, 16%, and 59%, respectively) and longitudinal relaxation time-weighted contrast-enhanced transverse sequences with fs (74%, 35%, 57%, and 55%, respectively). Conclusion: T2w transverse sequences with fs yielded the highest detection rates and are well suited for accurate whole-body PET/MRI in lymphoma patients. There is no evidence to recommend the use of contrast agents.

Effect of contrast agent on the results of in vivo ¹H MRS of breast tumors - is it clinically significant?

Choline (Cho) signal identification and quantification in (1)H MRS are used in breast cancer diagnosis. However, an influence of the gadolinium-based contrast agent on the Cho amplitude has been reported experimentally. This study aims to identify the impact of gadolinium-based contrast agents on Cho detection and quantification in postcontrast breast MRS. Consecutive patients were recruited prospectively and randomly allocated to two groups. Group A received a neutral (gadolinium diethylenetriaminepentaacetic acid bis-methylamide) and group B an ionic (gadolinium diethylenetriaminepentaacetic acid) contrast agent, each at a dosage of 0.1 mmol/kg. First, the presence of Cho was identified visually. Then, the normalized Cho intensity in malignant lesions was quantified. Multivariate analysis was applied to identify independent influencing factors on Cho. Sixty-three lesions were investigated [A, n = 34; B, n = 29; 43 malignant (one bilaterally malignant), 20 benign]. Cho was identified visually in 14 of 20 malignant tumors in group A and 12 of 22 malignant tumors in group B (p = 0.477). Normalized Cho differed significantly (p = 0.001) between groups A (mean, 26.8 ± 6.0 AU) and B (mean, 18.2 ± 12.5 AU). No linewidth differences were identified (p > 0.05). Multivariate analysis revealed only group membership (A versus B) as an independent predictor of Cho (p = 0.017). The results suggest stronger negative effects of an ionic relative to a neutral gadolinium-based contrast agent on breast tumor MRS in vivo. These results should be considered when conducting and comparing quantitative Cho measurements in the breast.

Absolute quantitation of brain metabolites with respect to heterogeneous tissue compositions in (1)H-MR spectroscopic volumes.

OBJECT: Referencing metabolite intensities to the tissue water intensity is commonly applied to determine metabolite concentrations from in vivo (1)H-MRS brain data. However, since the water concentration and relaxation properties differ between grey matter, white matter and cerebrospinal fluid (CSF), the volume fractions of these compartments have to be considered in MRS voxels. MATERIALS AND METHODS: The impact of partial volume correction was validated by phantom measurements in voxels containing mixtures of solutions with different NAA and water concentrations as well as by analyzing in vivo (1)H-MRS brain data acquired with various voxel compositions. RESULTS: Phantom measurements indicated substantial underestimation of NAA concentrations when assuming homogeneously composed voxels, especially for voxels containing solution, which simulated CSF (error: ≤ 92%). This bias was substantially reduced by taking into account voxel composition (error: ≤ 10%). In the in vivo study, tissue correction reduced the overall variation of quantified metabolites by up to 35% and revealed the expected metabolic differences between various brain tissues. CONCLUSIONS: Tissue composition affects extraction of metabolite concentrations and may cause misinterpretations when comparing measurements performed with different voxel sizes. This variation can be reduced by considering the different tissue types by means of combined analysis of spectroscopic and imaging data.

Functional connectivity and neurotransmitter impairments of the salience brain network in chronic low back pain patients: a combined resting-state functional magnetic resonance imaging and 1 H-MRS study.

ABSTRACT: Functional reorganisation of the salience network (SN) has been proposed as one of the key pathomechanisms associated with central nociceptive processing in the chronic pain state. Being associated with an altered functional connectivity within the SN, these processes have been hypothesized to result from a loss of inhibitory function leading to node hyperexcitability and spontaneous pain. Combined resting-state BOLD functional magnetic resonance imaging (MRI) and 1 H-MR spectroscopy was applied to chronic back pain patients and healthy subjects to assess deviations from functional integrity (weighted closeness centrality [wCC], derived from resting-state functional MRI), oscillatory BOLD characteristics (spectral power), and neurotransmitter levels (GABA + , glutamate+glutamine) in 2 key SN nodes, anterior insular (aIns R ) and anterior mid-cingulate cortices. In addition, examinations were repeated in chronic back pain patients after a 4-week interdisciplinary multimodal pain treatment and in healthy subjects after 4 weeks to explore longitudinal, treatment-mediated changes in target variables. The aIns R and, to a lesser extent, the anterior mid-cingulate of patients exhibited significantly reduced wCC accompanied by a spectral power shift from a lower to a higher frequency band, indicating a desynchronization of their neuronal activity within the SN, possibly because of increased spontaneous activations. Without revealing neurotransmitter differences, patients alone showed significant positive associations between local GABA + levels and wCC in aIns R , suggesting a stronger dependence of node synchronization on the inhibitory tone in the chronic pain state. However, this needs to be explored in the future using magnetic resonance spectroscopy techniques that are more sensitive to detecting subtle neurotransmitter changes and also allow multifocal characterization of neurotransmitter tone.

Neurometabolic patterns of an "at risk for mental disorders" syndrome involve abnormalities in the thalamus and anterior midcingulate cortex.

BACKGROUND: The ultra-high risk (UHR) paradigm allows the investigation of individuals at increased risk of developing psychotic or other mental disorders with the aim of making prevention and early intervention as specific as possible in terms of the individual outcome. METHODS: Single-session 1H-/31P-Chemical Shift Imaging of thalamus, prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices was applied to 69 UHR patients for psychosis and 61 matched healthy controls. N-acetylaspartate (NAA), glutamate/glutamine complex (Glx), energy (PCr, ATP) and phospholipid metabolites were assessed, analysed by ANOVA (or ANCOVA [with covariates]) and correlated with symptomatology (SCL-90R). RESULTS: The thalamus showed decreased NAA, inversely correlated with self-rated aggressiveness, as well as increased PCr, and altered phospholipid breakdown. While the aMCC showed a pattern of NAA decrease and PCr increase, the DLPFC showed PCr increase only in the close-to-psychosis patient subgroup. There were no specific findings in transition patients. CONCLUSION: The results do not support the notion of a specific pre-psychotic neurometabolic pattern, but likely reflect correlates of an "at risk for mental disorders syndrome". This includes disturbed neuronal (mitochondrial) metabolism in the thalamus and aMCC, with emphasis on left-sided structures, and altered PL remodeling across structures.

1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain.

Reliable detection of metabolic changes in the brain in vivo induced by chronic low back pain may provide improved understanding of neurophysiological mechanisms underlying the manifestation of chronic pain. In the present study, absolute concentrations of N-acetyl-aspartate (NAA), creatine (Cr), total choline (tCho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln) were measured in three different pain processing cortical regions (anterior insula, anterior cingulate cortex, and thalamus) of ten patients with non-specific chronic low back pain by means of proton MR spectroscopy ((1)H-MRS) and compared to matched healthy controls. Significant decrease of Glu was observed in the anterior cingulate cortex of patients. Patients also revealed a trend of decreasing Gln concentrations in all investigated brain areas. Reductions of NAA were observed in the patient group in anterior insula and in anterior cingulated cortex, whereas mI was reduced in anterior cingulated cortex and in thalamus of patients. Reduced concentrations of Glu and Gln may indicate disordered glutamatergic neurotransmission due to prolonged pain perception, whereas decrease of NAA and mI may be ascribed to neuron and glial cell loss. No significant changes were found for Cr. The morphological evaluation of anatomic brain data revealed a significantly decreased WM volume of 17% (p<0.05) as well as a non significant trend for GM volume increase in the anterior insula of patients.

Alterations of neurometabolism in the dorsolateral prefrontal cortex and thalamus in transition to psychosis patients change under treatment as usual - A two years follow-up 1H/31P-MR-spectroscopy study.

BACKGROUND: The ultra-high risk (UHR) paradigm allows early contact with patients developing acute psychosis and the study of treatment effects on the underlying pathology. METHODS: 29 patients with first acute psychosis according to CAARMS criteria (transition patients, TP) (T0) and thereof 22 patients after two-year follow-up (mean 788 d) (T1) underwent 1H-/31P-MR spectroscopy of the prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices and the thalamus. N-acetylaspartate (NAA), glutamate (Glu, Glx), energy (PCr, ATP) and phospholipid metabolites (PME, PDE) were compared to 27 healthy controls by ANCOVA and correlated with patients' symptom ratings (BPRS-E, SCL-90R). For longitudinal analysis, linear mixed model (LMM) and ANCOVA for repeated measures were used. RESULTS: DLPFC: In patients, NAA and PME were decreased bilaterally and Glu on the left side at T0. Left-sided Glu and NAA (trend) and bilateral Glx increased during follow-up. Thalamus: In TP, bilateral NAA, left-sided Glu and right-sided Glx were decreased at T0; bilateral NAA and left-sided Glx increased during follow-up. aMCC: In TP, bilateral NAA, right-sided Glu, and bilateral PME and PDE were decreased, while left-sided PCr was increased at T0. No changes were observed during follow-up. CONCLUSION: Regardless of the long-term diagnosis, the psychotic state of illness includes disturbed neuronal function in the DLPFC, thalamus and aMCC. Treatment-as-usual (TAU), including antipsychotic/antidepressant medication and supportive psychotherapy, had an effect on the thalamo-frontal area but not or less pronounced on the neurometabolic deficits of the aMCC.