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Defying the COVID-19 pandemic required restriction measures of unprecedented scale, that may induce and exacerbate psychiatric symptoms across the population. We aimed to assess in vivo dynamic effects of mitigation strategies on human brain neurobiology, neuroplastic as well as psychometric parameters. Three structural magnetic resonance imaging measurements, serum brain-derived neurotrophic factor (sBDNF) analyses, and psychometric assessments (Beck Depression Inventory-II and Perceived Stress Questionnaire-20) were performed in healthy individuals and patients with a recurrent major depressive disorder in the period from September 2020 to July 2021. Group differences and changes over time in structural imaging, neuroplastic and psychometric parameters were assessed with linear mixed models. Analysis of data from 18 patients with a recurrent major depressive disorder and 28 healthy individuals showed clinically relevant scores for depression and stress in the patient group as well as significant cross-sectional differences in depression scores (F = 30.89, p < 0.001) and three subscales of the Perceived Stress Questionnaire (Worries: F = 19.19, p < 0.001, Tension: F = 34.44, p < 0.001, Joy: F = 12.05, p = 0.001). Linear mixed models revealed no significant changes over time in cortical thickness of the prefrontal cortex, anterior cingulate cortex, hippocampus, and amygdala (F = 0.29, p > 0.1) and no interaction with group (F = 0.28, p > 0.1). Further, analysis revealed no main effect of time and no interaction of time x group in depressive symptoms, perceived stress subscales, and sBDNF (all p > 0.1). Despite the limited sample size, the strength of this investigation lies in the multimodal assessment of peri-pandemic lockdown effects. Nine months of varying restrictions measures did not result in observable changes in brain morphology nor impact depressive symptoms in either psychiatric patients with a recurrent major depressive disorder or healthy individuals. While these neurobiological and psychometric data stand in contrast to initial expectations about the effects of restriction measures, they might inform future investigations of longitudinal effects of restriction measures on mental health.
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COVID-19 , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/psicología , Pandemias , Psicometría , Estudios Transversales , Neurobiología , Control de Enfermedades Transmisibles , Depresión/patologíaRESUMEN
Self-reported sexual orientation of transgender individuals occasionally changes over transition. Using functional magnetic resonance imaging, we tested the hypothesis that neural and behavioral patterns of sexual arousal in transgender individuals would shift from the assigned to the experienced gender (e.g., trans women's responses becoming more dissimilar to those of cis men and more similar to those of cis women). To this aim, trans women (N = 12) and trans men (N = 20) as well as cisgender women (N = 24) and cisgender men (N = 14) rated visual stimuli showing male-female, female-female or male-male intercourse for sexual arousal before and after four months of gender-affirming hormone therapy. A Bayesian framework allowed us to incorporate previous behavioral findings. The hypothesized changes could indeed be observed in the behavioral responses with the strongest results for trans men and female-female scenes. Activation of the ventral striatum supported our hypothesis only for female-female scenes in trans women. The respective application or depletion of androgens in trans men and trans women might partly explain this observation. The prominent role of female-female stimuli might be based on the differential responses they elicit in cis women and men or, in theory, the controversial concept of autogynephilia. We show that correlates of sexual arousal in transgender individuals might change in the direction of the experienced gender. Future investigations should elucidate the mechanistic role of sex hormones and the cause of the differential neural and behavioral findings.The study was registered at ClinicalTrials.gov (NCT02715232), March 22, 2016.
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Teorema de Bayes , Disforia de Género , Imagen por Resonancia Magnética , Excitación Sexual , Personas Transgénero , Humanos , Masculino , Femenino , Adulto , Disforia de Género/psicología , Disforia de Género/tratamiento farmacológico , Personas Transgénero/psicología , Conducta Sexual/efectos de los fármacos , Conducta Sexual/psicología , Adulto Joven , Estriado Ventral/efectos de los fármacos , Estriado Ventral/diagnóstico por imagenRESUMEN
BACKGROUND: Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity. METHODS: Individuals with gender dysphoria and cisgender controls underwent 2 MRI measurements, with a median interval of 145 days (interquartile range [IQR] 128.25-169.75 d, mean 164.94 d) between the first and second MRI. Transgender women (TW) and transgender men (TM) underwent the first MRI before GHT and the second MRI after approximately 4.5 months of GHT, which comprised estrogen and anti-androgen therapy in TW or testosterone therapy in TM. Hypothalamic volumes were segmented using FreeSurfer, and effects of GHT were tested using repeated-measures analysis of covariance. RESULTS: The final sample included 106 participants: 38 TM, 15 TW, 32 cisgender women (CW) and 21 cisgender men (CM). Our analyses revealed group × time interaction effects for total, left and right hypothalamus volume, and for several subunits (left and right inferior tubular, left superior tubular, right anterior inferior, right anterior superior, all p corr < 0.01). In TW, volumes decreased between the first and second MRI in these regions (all p corr ≤ 0.01), and the change from the first to second MRI in TW differed significantly from that in CM and CW in several subunits (p corr < 0.05). LIMITATIONS: We did not address the influence of transition-related psychological and behavioural changes. CONCLUSION: Our results suggest a subunit-specific effect of GHT on hypothalamus volumes in TW. This finding is in accordance with previous reports of positive and negative effects of androgens and estrogens, respectively, on cerebral volumes.
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Emociones , Disforia de Género , Masculino , Femenino , Humanos , Disforia de Género/diagnóstico por imagen , Disforia de Género/tratamiento farmacológico , Hipotálamo/diagnóstico por imagen , TestosteronaRESUMEN
INTRODUCTION: Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6'-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2H MRSI (DMI) and 1H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. METHODS: Five volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6'-2H2]-glucose administration using time-resolved 3D 2H FID-MRSI with elliptical phase encoding at 7T and 3D 1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. RESULTS: One hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2H DMI and 3T 1H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2H and 1H data points a weak to moderate negative correlation was observed for Glx4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc6 data GM (r=-0.61, p<0.001) and WM (r=-0.70, p<0.001). CONCLUSION: This study demonstrates that indirect detection of deuterium labeled compounds using 1H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Deuterio/metabolismo , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Glucosa/metabolismoRESUMEN
Introduction: Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6'- 2 H 2 ]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2 H MRSI (DMI) and 1 H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. Methods: Five volunteers (4m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8g/kg oral [6,6'- 2 H 2 ]-glucose administration using time-resolved 3D 2 H FID-MRSI with elliptical phase encoding at 7T and 3D 1 H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. Results: One hour after oral tracer administration regionally averaged deuterium labeled Glx 4 concentrations and the dynamics were not significantly different over all participants between 7T 2 H DMI and 3T 1 H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc 6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2 H and 1 H data points a weak to moderate negative correlation was observed for Glx 4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc 6 data GM (r=- 0.61, p<0.001) and WM (r=-0.70, p<0.001). Conclusion: This study demonstrates that indirect detection of deuterium labeled compounds using 1 H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2 H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.
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Impaired glucose metabolism in the brain has been linked to several neurological disorders. Positron emission tomography and carbon-13 magnetic resonance spectroscopic imaging (MRSI) can be used to quantify the metabolism of glucose, but these methods involve exposure to radiation, cannot quantify downstream metabolism, or have poor spatial resolution. Deuterium MRSI (2H-MRSI) is a non-invasive and safe alternative for the quantification of the metabolism of 2H-labelled substrates such as glucose and their downstream metabolic products, yet it can only measure a limited number of deuterated compounds and requires specialized hardware. Here we show that proton MRSI (1H-MRSI) at 7 T has higher sensitivity, chemical specificity and spatiotemporal resolution than 2H-MRSI. We used 1H-MRSI in five volunteers to differentiate glutamate, glutamine, γ-aminobutyric acid and glucose deuterated at specific molecular positions, and to simultaneously map deuterated and non-deuterated metabolites. 1H-MRSI, which is amenable to clinically available magnetic-resonance hardware, may facilitate the study of glucose metabolism in the brain and its potential roles in neurological disorders.
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Encéfalo , Glucosa , Humanos , Glucosa/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Neurotransmisores/metabolismoRESUMEN
OBJECTIVES: Noninvasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies, for example, cancer, dementia, and depression. A novel approach to map glucose metabolism noninvasively in the human brain has been presented recently on ultrahigh-field magnetic resonance (MR) scanners (≥7T) using indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine, and lactate. The aim of this study was to demonstrate the feasibility to noninvasively detect deuterium-labeled downstream glucose metabolites indirectly in the human brain via 3-dimensional (3D) proton ( 1 H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. MATERIALS AND METHODS: This prospective, institutional review board-approved study was performed in 7 healthy volunteers (mean age, 31 ± 4 years, 5 men/2 women) after obtaining written informed consent. After overnight fasting and oral deuterium-labeled glucose administration, 3D metabolic maps were acquired every â¼4 minutes with â¼0.24 mL isotropic spatial resolution using real-time motion-, shim-, and frequency-corrected echo-less 3D 1 H-MR spectroscopic Imaging on a clinical routine 3T MR system. To test the interscanner reproducibility of the method, subjects were remeasured on a similar 3T MR system. Time courses were analyzed using linear regression and nonparametric statistical tests. Deuterium-labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1 H MR spectra due to exchange of labeled and unlabeled molecules. RESULTS: Sixty-five minutes after deuterium-labeled glucose administration, glutamate + glutamine (Glx) signal intensities decreased in gray/white matter (GM/WM) by -1.63 ± 0.3/-1.0 ± 0.3 mM (-13% ± 3%, P = 0.02/-11% ± 3%, P = 0.02), respectively. A moderate to strong negative correlation between Glx and time was observed in GM/WM ( r = -0.64, P < 0.001/ r = -0.54, P < 0.001), with 60% ± 18% ( P = 0.02) steeper slopes in GM versus WM, indicating faster metabolic activity. Other nonlabeled metabolites showed no significant changes. Excellent intrasubject repeatability was observed across scanners for static results at the beginning of the measurement (coefficient of variation 4% ± 4%), whereas differences were observed in individual Glx dynamics, presumably owing to physiological variation of glucose metabolism. CONCLUSION: Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware, offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for noninvasive imaging of glucose and neurotransmitter metabolism in the human brain.
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Glucosa , Glutamina , Masculino , Humanos , Femenino , Adulto , Deuterio/metabolismo , Glutamina/metabolismo , Glucosa/metabolismo , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios de Factibilidad , Protones , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Glutamatos/metabolismo , Neurotransmisores/metabolismoRESUMEN
Background: Serotonergic agents affect brain plasticity and reverse stress-induced dendritic atrophy in key fronto-limbic brain areas associated with learning and memory. Objectives: The aim of this study was to investigate effects of the antidepressant escitalopram on gray matter during relearning in healthy individuals to inform a model for depression and the neurobiological processes of recovery. Design: Randomized double blind placebo control, monocenter study. Methods: In all, 76 (44 females) healthy individuals performed daily an associative learning task with emotional or non-emotional content over a 3-week period. This was followed by a 3-week relearning period (randomly shuffled association within the content group) with concurrent daily selective serotonin reuptake inhibitor (i.e., 10 mg escitalopram) or placebo intake. Results: Via voxel-based morphometry and only in individuals that developed sufficient escitalopram blood levels over the 21-day relearing period, an increased density of the left dorsolateral prefrontal cortex was found. When investigating whether there was an interaction between relearning and drug intervention for all participants, regardless of escitalopram levels, no changes in gray matter were detected with either surfaced-based or voxel-based morphometry analyses. Conclusion: The left dorsolateral prefrontal cortex affects executive function and emotional processing, and is a critical mediator of symptoms and treatment outcomes of depression. In line, the findings suggest that escitalopram facilitates neuroplastic processes in this region if blood levels are sufficient. Contrary to our hypothesis, an effect of escitalopram on brain structure that is dependent of relearning content was not detected. However, this may have been a consequence of the intensity and duration of the interventions. Registration: ClinicalTrials.gov Identifier: NCT02753738; Trial Name: Enhancement of learning associated neural plasticity by Selective Serotonin Reuptake Inhibitors; URL: https://clinicaltrials.gov/ct2/show/NCT02753738.
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Background: Theta burst stimulation (TBS) belongs to one of the biological antidepressant treatment options. When applied bilaterally, excitatory intermittent TBS (iTBS) is commonly targeted to the left and inhibitory continuous TBS (cTBS) to the right dorsolateral prefrontal cortex. TBS was shown to influence neurotransmitter systems, while iTBS is thought to interfere with glutamatergic circuits and cTBS to mediate GABAergic neurotransmission. Objectives: We aimed to expand insights into the therapeutic effects of TBS on the GABAergic and glutamatergic system utilizing 3D-multivoxel magnetic resonance spectroscopy imaging (MRSI) in combination with a novel surface-based MRSI analysis approach to investigate changes of cortical neurotransmitter levels in patients with treatment-resistant depression (TRD). Methods: Twelve TRD patients (five females, mean age ± SD = 35 ± 11 years) completed paired MRSI measurements, using a GABA-edited 3D-multivoxel MEGA-LASER sequence, before and after 3 weeks of bilateral TBS treatment. Changes in cortical distributions of GABA+/tNAA (GABA+macromolecules relative to total N-acetylaspartate) and Glx/tNAA (Glx = mixed signal of glutamate and glutamine), were investigated in a surface-based region-of-interest (ROI) analysis approach. Results: ANCOVAs revealed a significant increase in Glx/tNAA ratios in the left caudal middle frontal area (p corr. = 0.046, F = 13.292), an area targeted by iTBS treatment. Whereas, contralateral treatment with cTBS evoked no alterations in glutamate or GABA concentrations. Conclusion: This study demonstrates surface-based adaptions in the stimulation area to the glutamate metabolism after excitatory iTBS but not after cTBS, using a novel surface-based analysis of 3D-MRSI data. The reported impact of facilitatory iTBS on glutamatergic neurotransmission provides further insight into the neurobiological effects of TBS in TRD.
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An essential core function of one's cognitive flexibility is the use of acquired knowledge and skills to adapt to ongoing environmental changes. Animal models have highlighted the influence serotonin has on neuroplasticity. These effects have been predominantly demonstrated during emotional relearning which is theorized as a possible model for depression. However, translation of these mechanisms is in its infancy. To this end, we assessed changes in effective connectivity at rest and during associative learning as a proxy of neuroplastic changes in healthy volunteers. 76 participants underwent 6 weeks of emotional or non-emotional (re)learning (face-matching or Chinese character-German noun matching). During relearning participants either self-administered 10 mg/day of the selective serotonin reuptake inhibitor (SSRI) escitalopram or placebo in a double-blind design. Associative learning tasks, resting-state and structural images were recorded before and after both learning phases (day 1, 21 and 42). Escitalopram intake modulated relearning changes in a network encompassing the right insula, anterior cingulate cortex and right angular gyrus. Here, the process of relearning during SSRI intake showed a greater decrease in effective connectivity from the right insula to both the anterior cingulate cortex and right angular gyrus, with increases in the opposite direction when compared to placebo. In contrast, intrinsic connections and those at resting-state were only marginally affected by escitalopram. Further investigation of gray matter volume changes in these functionally active regions revealed no significant SSRI-induced structural changes. These findings indicate that the right insula plays a central role in the process of relearning and SSRIs further potentiate this effect. In sum, we demonstrated that SSRIs amplify learning-induced effective connections rather than affecting the intrinsic task connectivity or that of resting-state.
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Aprendizaje por Asociación , Conectoma , Corteza Insular , Red Nerviosa , Plasticidad Neuronal , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Adulto , Aprendizaje por Asociación/efectos de los fármacos , Aprendizaje por Asociación/fisiología , Citalopram/farmacología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiología , Humanos , Corteza Insular/diagnóstico por imagen , Corteza Insular/efectos de los fármacos , Corteza Insular/fisiología , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/efectos de los fármacos , Lóbulo Parietal/fisiología , Descanso , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto JovenRESUMEN
Learning-induced neuroplastic changes, further modulated by content and setting, are mirrored in brain functional connectivity (FC). In animal models, selective serotonin reuptake inhibitors (SSRIs) have been shown to facilitate neuroplasticity. This is especially prominent during emotional relearning, such as fear extinction, which may translate to clinical improvements in patients. To investigate a comparable modulation of neuroplasticity in humans, 99 healthy subjects underwent three weeks of emotional (matching faces) or non-emotional learning (matching Chinese characters to unrelated German nouns). Shuffled pairings of the original content were subsequently relearned for the same time. During relearning, subjects received either a daily dose of the SSRI escitalopram or placebo. Resting-state functional magnetic resonance imaging was performed before and after the (re-)learning phases. FC changes in a network comprising Broca's area, the medial prefrontal cortex, the right inferior temporal and left lingual gyrus were modulated by escitalopram intake. More specifically, it increased the bidirectional connectivity between medial prefrontal cortex and lingual gyrus for non-emotional and the connectivity from medial prefrontal cortex to Broca's area for emotional relearning. The context dependence of these effects together with behavioral correlations supports the assumption that SSRIs in clinical practice improve neuroplasticity rather than psychiatric symptoms per se. Beyond expanding the complexities of learning, these findings emphasize the influence of external factors on human neuroplasticity.
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Escitalopram/farmacología , Aprendizaje/efectos de los fármacos , Imagen por Resonancia Magnética/métodos , Plasticidad Neuronal/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Adulto , Austria , Método Doble Ciego , Emociones/efectos de los fármacos , Femenino , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Masculino , Recuerdo Mental/efectos de los fármacos , Modelos EstadísticosRESUMEN
The accurate segmentation of in vivo magnetic resonance imaging (MRI) data is a crucial prerequisite for the reliable assessment of disease progression, patient stratification or the establishment of putative imaging biomarkers. This is especially important for the hippocampal formation, a brain area involved in memory formation and often affected by neurodegenerative or psychiatric diseases. FreeSurfer, a widely used automated segmentation software, offers hippocampal subfield delineation with multiple input options. While a single T1-weighted (T1) sequence is regularly used by most studies, it is also possible and advised to use a high-resolution T2-weighted (T2H) sequence or multispectral information. In this investigation it was determined whether there are differences in volume estimations depending on the input images and which combination of these deliver the most reliable results in each hippocampal subfield. 41 healthy participants (age = 25.2 years ± 4.2 SD) underwent two structural MRIs at three Tesla (time between scans: 23 days ± 11 SD) using three different structural MRI sequences, to test five different input configurations (T1, T2, T2H, T1 and T2, and T1 and T2H). We compared the different processing pipelines in a cross-sectional manner and assessed reliability using test-retest variability (%TRV) and the dice coefficient. Our analyses showed pronounced significant differences and large effect sizes between the processing pipelines in several subfields, such as the molecular layer (head), CA1 (head), hippocampal fissure, CA3 (head and body), fimbria and CA4 (head). The longitudinal analysis revealed that T1 and multispectral analysis (T1 and T2H) showed overall higher reliability across all subfields than T2H alone. However, the specific subfields had a substantial influence on the performance of segmentation results, regardless of the processing pipeline. Although T1 showed good test-retest metrics, results must be interpreted with caution, as a standard T1 sequence relies heavily on prior information of the atlas and does not take the actual fine structures of the hippocampus into account. For the most accurate segmentation, we advise the use of multispectral information by using a combination of T1 and high-resolution T2-weighted sequences or a T2 high-resolution sequence alone.
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PURPOSE: Recently, a 3D-concentric ring trajectory (CRT)-based free induction decay (FID)-MRSI sequence was introduced for fast high-resolution metabolic imaging at 7 T. This technique provides metabolic ratio maps of almost the entire brain within clinically feasible scan times, but its robustness has not yet been thoroughly investigated. Therefore, we have assessed quantitative concentration estimates and their variability in healthy volunteers using this approach. METHODS: We acquired whole-brain 3D-CRT-FID-MRSI at 7 T in 15 min with 3.4 mm nominal isometric resolution in 24 volunteers (12 male, 12 female, mean age 27 ± 6 years). Concentration estimate maps were calculated for 15 metabolites using internal water referencing and evaluated in 55 different regions of interest (ROIs) in the brain. Data quality, mean metabolite concentrations, and their inter-subject coefficients of variation (CVs) were compared for all ROIs. RESULTS: Of 24 datasets, one was excluded due to motion artifacts. The concentrations of total choline, total creatine, glutamate, myo-inositol, and N-acetylaspartate in 44 regions were estimated within quality thresholds. Inter-subject CVs (mean over 44 ROIs/minimum/maximum) were 9%/5%/19% for total choline, 10%/6%/20% for total creatine, 11%/7%/24% for glutamate, 10%/6%/19% for myo-inositol, and 9%/6%/19% for N-acetylaspartate. DISCUSSION: We defined the performance of 3D-CRT-based FID-MRSI for metabolite concentration estimate mapping, showing which metabolites could be robustly quantified in which ROIs with which inter-subject CVs expected. However, the basal brain regions and lesser-signal metabolites in particular remain as a challenge due susceptibility effects from the proximity to nasal and auditory cavities. Further improvement in quantification and the mitigation of B0 /B1 -field inhomogeneities will be necessary to achieve reliable whole-brain coverage.