Neuromelanin-sensitive MRI for mechanistic research and biomarker development in psychiatry.

Neuromelanin-sensitive MRI is a burgeoning non-invasive neuroimaging method with an increasing number of applications in psychiatric research. This MRI modality is sensitive to the concentration of neuromelanin, which is synthesized from intracellular catecholamines and accumulates in catecholaminergic nuclei including the dopaminergic substantia nigra and the noradrenergic locus coeruleus. Emerging data suggest the utility of neuromelanin-sensitive MRI as a proxy measure for variability in catecholamine metabolism and function, even in the absence of catecholaminergic cell loss.

Altered Hierarchical Gradients of Intrinsic Neural Timescales in Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the United States. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit.

Neuromelanin-Sensitive MRI as Candidate Marker for Treatment Resistance in First-Episode Schizophrenia.

Objective: Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders.

Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [F]-VAT.

Background: Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition.

Methods: A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [F]-VAT.

Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals.

Importance: The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist.

Objective: To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity.

Design, Setting, And Participants: This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample).

Altered hierarchical gradients of intrinsic neural timescales in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of older adults in the US and worldwide. Resting-state functional magnetic resonance imaging (rs-fMRI) has become a widely used neuroimaging tool to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of intrinsic neural signals using rs-fMRI, is thought to quantify the duration that neural information is stored in a local cortical circuit.

Probing midbrain dopamine function in pediatric obsessive-compulsive disorder via neuromelanin-sensitive magnetic resonance imaging.

Obsessive-compulsive disorder (OCD) is an impairing psychiatric condition, which often onsets in childhood. Growing research highlights dopaminergic alterations in adult OCD, yet pediatric studies are limited by methodological constraints. This is the first study to utilize neuromelanin-sensitive MRI as a proxy for dopaminergic function among children with OCD.

Gradient boosting decision-tree-based algorithm with neuroimaging for personalized treatment in depression.

Introduction: Pretreatment positron emission tomography (PET) with 2-deoxy-2-[F]fluoro-D-glucose (FDG) and magnetic resonance spectroscopy (MRS) may identify biomarkers for predicting remission (absence of depression). Yet, no such image-based biomarkers have achieved clinical validity. The purpose of this study was to identify biomarkers of remission using machine learning (ML) with pretreatment FDG-PET/MRS neuroimaging, to reduce patient suffering and economic burden from ineffective trials.

Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial.

Previous proton magnetic resonance spectroscopy (H-MRS) studies suggest a perturbation in glutamate and/or GABA in Major Depressive Disorder (MDD). However, no studies examine the ratio of glutamate and glutamine (Glx) to GABA (Glx/GABA) as it relates to depressive symptoms, which may be more sensitive than either single metabolite. Using a within-subject design, we hypothesized that reduction in depressive symptoms correlates with reduction in Glx/GABA in the anterior cingulate cortex (ACC).

Standardized Data Acquisition for Neuromelanin-sensitive Magnetic Resonance Imaging of the Substantia Nigra.

The dopaminergic system plays a crucial role in healthy cognition (e.g., reward learning and uncertainty) and neuropsychiatric disorders (e.

Individual Differences in Cerebral Perfusion as a Function of Age and Loneliness.

Loneliness is defined as the subjective feeling that one's social needs are not satisfied by both quantity and quality of one's social relationships. Loneliness has been linked to a broad range of adverse physical and mental health consequences. There is an interest in identifying the neural and molecular processes by which loneliness adversely affects health.

Cross-Scanner Harmonization of Neuromelanin-Sensitive MRI for Multisite Studies.

Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a validated measure of neuromelanin concentration in the substantia nigra-ventral tegmental area (SN-VTA) complex and is a proxy measure of dopaminergic function with potential as a noninvasive biomarker. The development of generalizable biomarkers requires large-scale samples necessitating harmonization approaches to combine data collected across sites.

Purpose: To develop a method to harmonize NM-MRI across scanners and sites.

Distinct hierarchical alterations of intrinsic neural timescales account for different manifestations of psychosis.

Hierarchical perceptual-inference models of psychosis may provide a holistic framework for understanding psychosis in schizophrenia including heterogeneity in clinical presentations. Particularly, hypothesized alterations at distinct levels of the perceptual-inference hierarchy may explain why hallucinations and delusions tend to cluster together yet sometimes manifest in isolation. To test this, we used a recently developed resting-state fMRI measure of intrinsic neural timescale (INT), which reflects the time window of neural integration and captures hierarchical brain gradients.

Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression.

Late-life depression (LLD) is a prevalent and disabling condition in older adults that is often accompanied by slowed processing and gait speed. These symptoms are related to impaired dopamine function and sometimes remedied by levodopa (L-DOPA). In this study, we recruited 33 older adults with LLD to determine the association between a proxy measure of dopamine function-neuromelanin-sensitive magnetic resonance imaging (NM-MRI)-and baseline slowing measured by the Digit Symbol test and a gait speed paradigm.

Abnormal blood-brain barrier water exchange in chronic multiple sclerosis lesions: A preliminary study.

Relapsing-remitting multiple sclerosis (RRMS) is associated with persistent blood-brain barrier (BBB) dysfunction. The impact of this persistent dysfunction in both active and chronic MS lesions has yet to be investigated due to technological challenges associated with invasive assessment of BBB water transportation (e.g.

Reproducibility assessment of neuromelanin-sensitive magnetic resonance imaging protocols for region-of-interest and voxelwise analyses.

Neuromelanin-sensitive MRI (NM-MRI) provides a noninvasive measure of the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). NM-MRI has been validated as a measure of both dopamine neuron loss, with applications in neurodegenerative disease, and dopamine function, with applications in psychiatric disease. Furthermore, a voxelwise-analysis approach has been validated to resolve substructures, such as the ventral tegmental area (VTA), within midbrain dopaminergic nuclei thought to have distinct anatomical targets and functional roles.

Abbreviated quantitative UTE imaging in anterior cruciate ligament reconstruction.

Background: Existing ultrashort echo time magnetic resonance imaging (UTE MRI) methods require prohibitively long acquisition times (~ 20-40 min) to quantitatively assess the clinically relevant fast decay T* component in ligaments and tendons. The purpose of this study was to evaluate the feasibility and clinical translatability of a novel abbreviated quantitative UTE MRI paradigm for monitoring graft remodeling after anterior cruciate ligament (ACL) reconstruction.

Methods: Eight patients who had Graftlink™ hamstring autograft reconstruction were recruited for this prospective study.

In vivo evaluation of human patellar tendon microstructure and microcirculation with diffusion MRI.

Background: Patellar tendon (PT) microstructure integrity and microcirculation status play a crucial role in the progression of tendinopathy and tendon repair.

Purpose: To assess the feasibility and robustness of stimulated-echo based diffusion-weighted MRI with readout-segmented echo-planar imaging (ste-RS-EPI) for noninvasive assessment of microstructure and microcirculation of human PT.

Study Type: Prospective.

MRI biomarkers in osseous tumors.

Although radiography continues to play a critical role in osseous tumor assessment, there have been remarkable advances in cross-sectional imaging. MRI has taken a lead in this assessment due to high tissue contrast and spatial resolution, which are well suited for bone lesion assessment. More recently, although somewhat lagging other organ systems, quantitative parameters have shown promising potential as biomarkers for osseous tumors.

3D MRI of whole-brain water permeability with intrinsic diffusivity encoding of arterial labeled spin (IDEALS).

This work proposes a novel MRI method - Intrinsic Diffusivity Encoding of Arterial Labeled Spin (IDEALS) - for the whole-brain mapping of water permeability in the human brain without an exogenous contrast agent. Quantitative separation of the intravascular and extravascular labeled water MRI signal was achieved in arterial spin labeling experiments with segmented 3D-GRASE acquisition by modulating the relative sensitivity between relaxation, true diffusion, and pseudodiffusion. The intrinsic diffusivity encoding in k-space created different broadening of the image-domain point spread functions for intravascular and extravascular labeled spins, from which blood-brain barrier (BBB) water extraction fraction (E) and water permeability surface area product (PS) were estimated.