Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS).

Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model.

Background And Hypothesis: Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited.

Study Design: We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs).

Baroreflex sensitivity is associated with markers of hippocampal gliosis and dysmyelination in patients with psychosis.

Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups.

Patient-reported exposures and outcomes link the gut-brain axis and inflammatory pathways to specific symptoms of severe mental illness.

Unlabelled: We developed a "gut-brain-axis questionnaire" (GBAQ) to obtain standardized person-specific "review of systems" data for microbiome-gut-brain-axis studies. Individual items were compared to PANSS symptom measures using dimensional, transdiagnostic and traditional categorical approaches.

Method: Forty psychotic participants, independent of diagnoses, and 42 without psychosis (18 nonpsychotic affective disorders, 24 healthy controls) completed the GBAQ and underwent research diagnostic and symptom assessments.

An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth.

Unlabelled: The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented.

Fast, regional three-dimensional hybrid (1D-Hadamard 2D-rosette) proton MR spectroscopic imaging in the human temporal lobes.

H-MRSI is commonly performed with gradient phase encoding, due to its simplicity and minimal radio frequency (RF) heating (specific absorption rate). Its two well-known main problems-(i) "voxel bleed" due to the intrinsic point-spread function, and (ii) chemical shift displacement error (CSDE) when slice-selective RF pulses are used, which worsens with increasing volume of interest (VOI) size-have long become accepted as unavoidable. Both problems can be mitigated with Hadamard multislice RF encoding.

MR spectroscopic imaging at 3 T and outcomes in surgical epilepsy.

For the spectroscopic assessment of brain disorders that require large-volume coverage, the requirements of RF performance and field homogeneity are high. For epilepsy, this is also challenging given the inter-patient variation in location, severity and subtlety of anatomical identification and its tendency to involve the temporal region. We apply a targeted method to examine the utility of large-volume MR spectroscopic imaging (MRSI) in surgical epilepsy patients, implementing a two-step acquisition, comprised of a 3D acquisition to cover the fronto-parietal regions, and a contiguous parallel two-slice Hadamard-encoded acquisition to cover the temporal-occipital region, both with T /T = 2000/40 ms and matched acquisition times.

Global brain volume and N-acetyl-aspartate decline over seven decades of normal aging.

We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.

Quantitative multivoxel proton MR spectroscopy for the identification of white matter abnormalities in mild traumatic brain injury: Comparison between regional and global analysis.

Background: 3D brain proton MR spectroscopic imaging ( H MRSI) facilitates simultaneous metabolic profiling of multiple loci, at higher, sub-1 cm , spatial resolution than single-voxel H MRS with the ability to separate tissue-type partial volume contribution(s).

Purpose: To determine if: 1) white matter (WM) damage in mild traumatic brain injury (mTBI) is homogeneously diffuse, or if specific regions are more affected; 2) partial-volume-corrected, structure-specific H MRSI voxel averaging is sensitive to regional WM metabolic abnormalities.

Study Type: Retrospective cross-sectional cohort study.

Whole brain neuronal abnormalities in focal epilepsy quantified with proton MR spectroscopy.

Objective: To test the hypothesis that localization-related epilepsy is associated with widespread neuronal dysfunction beyond the ictal focus, reflected by a decrease in patients' global concentration of their proton MR spectroscopy (H-MRS) observed marker, N-acetyl-aspartate (NAA).

Methods: Thirteen patients with localization-related epilepsy (7 men, 6 women) 40±13 (mean±standard-deviation)years old, 8.3±13.

Quantitative Proton Spectroscopy of the Testes at 3 T: Toward a Noninvasive Biomarker of Spermatogenesis.

Objectives: The aim of this study was to compare testicular metabolite concentrations between fertile control subjects and infertile men.

Materials And Methods: Single voxel proton magnetic resonance spectroscopy (H-MRS) was performed in the testes with and without water suppression at 3 T in 9 fertile control subjects and 9 infertile patients (8 with azoospermia and 1 with oligospermia). In controls only, the T1 and T2 values of water and metabolites were also measured.

Global brain metabolic quantification with whole-head proton MRS at 3 T.

Total N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS ( H-MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%-65% of the brain. Here we wish to demonstrate that non-localized, whole-head (WH) H-MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.

Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging.

Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume. Within 10 patients with relapsing-remitting course, there were 180 regions-of-interest consisting of up to seven semi-annual follow-ups of normal-appearing white matter (NAWM, n = 10), pre-lesional tissue giving rise to acute lesions which resolved (n = 3) or persisted (n = 3), and of moderately (n = 9) and severely hypointense (n = 6) chronic lesions.

Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the Era of Volumetric MR Imaging.

Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient.

Quantifying global-brain metabolite level changes with whole-head proton MR spectroscopy at 3T.

Background And Purpose: To assess the sensitivity of non-localized, whole-head H-MRS to an individual's serial changes in total-brain NAA, Glx, Cr and Cho concentrations - metabolite metrics often used as surrogate markers in neurological pathologies.

Materials And Methods: In this prospective study, four back-to-back (single imaging session) and three serial (successive sessions) non-localizing, ~3min H-MRS (TE/TR/TI=5/10/940ms) scans were performed on 18 healthy young volunteers: 9 women, 9 men: 29.9±7.

MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update.

Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first-line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques.

Prefrontal neuronal integrity predicts symptoms and cognition in schizophrenia and is sensitive to genetic heterogeneity.

Schizophrenia is a genetically complex syndrome with substantial inter-subject variability in multiple domains. Person-specific measures to resolve its heterogeneity could focus on the variability in prefrontal integrity, which this study indexed as relative rostralization within the anterior cingulate cortex (ACC). Twenty-two schizophrenia cases and 11 controls underwent rigorous diagnostic procedures, symptom assessments (PANSS, Deficit Syndrome Scale) and intelligence testing.

N-acetyl-aspartate levels correlate with intra-axonal compartment parameters from diffusion MRI.

Diffusion MRI combined with biophysical modeling allows for the description of a white matter (WM) fiber bundle in terms of compartment specific white matter tract integrity (WMTI) metrics, which include intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De||), extra-axonal radial diffusivity (De┴), axonal water fraction (AWF), and tortuosity (α) of extra-axonal space. Here we derive these parameters from diffusion kurtosis imaging to examine their relationship to concentrations of global WM N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myo-Inositol (mI), as measured with proton MR spectroscopy ((1)H-MRS), in a cohort of 25 patients with mild traumatic brain injury (MTBI). We found statistically significant (p<0.

Hypo-metabolism of the rostral anterior cingulate cortex associated with working memory impairment in 18 cases of schizophrenia.

Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions.

Automated whole-brain N-acetylaspartate proton MRS quantification.

Concentration of the neuronal marker, N-acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole-head proton ((1) H)-MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole-brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency-range peak integration approach previously employed. MRI and whole-head (1) H-MRS from 18 healthy young adults were examined.

Global N-acetylaspartate in normal subjects, mild cognitive impairment and Alzheimer's disease patients.

Background: Mild cognitive impairment (MCI) is an intermediary state on the way to Alzheimer's disease (AD). Little is known about whole brain concentration of the neuronal marker, N-acetylaspartate (NAA) in MCI patients.

Objective: To test the hypothesis that since MCI and AD are both neurodegenerative, quantification of the NAA in their whole brain (WBNAA) could differentiate them from cognitively-intact matched controls.

Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation.

Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.

Spectroscopic localization by simultaneous acquisition of the double-spin and stimulated echoes.

Purpose: To design a proton MR spectroscopy ((1) H-MRS) localization sequence that combines the signal-to-noise-ratio (SNR) benefits of point resolved spectroscopy (PRESS) with the high pulse bandwidths, low chemical shift displacements (CSD), low specific absorption rates (SAR), short echo times (TE), and superior radiofrequency transmit field (B1+) immunity of stimulated echo acquisition mode (STEAM), by simultaneously refocusing and acquiring both the double-spin and stimulated echo coherence pathways from the volume of interest.

Theory And Methods: We propose a family of (1)H-MRS sequences comprising three orthogonal spatially selective pulses with flip angles 90° < α, β, γ < 128°. The stimulated and double-spin echo are refocused in-phase simultaneously by altering the pulses' phases, flip angles and timing, as well as the interpulse gradient spoiling moments.