A data-driven algorithm to determine H-MRS basis set composition.

Purpose: Metabolite amplitude estimates derived from linear combination modeling of MR spectra depend on the precise list of constituent metabolite basis functions used (the "basis set"). The absence of clear consensus on the "ideal" composition or objective criteria to determine the suitability of a particular basis set contributes to the poor reproducibility of MRS. In this proof-of-concept study, we demonstrate a novel, data-driven approach for deciding the basis-set composition using Akaike information criteria (AIC).

Gradient scheme optimization for PRESS-localized edited MRS using weighted pathway suppression.

This study aimed to design and implement an optimized gradient scheme for PRESS-localized edited magnetic resonance spectroscopy (MRS) to enhance suppression of out-of-voxel (OOV) artifacts. These artifacts, which originate from insufficient crushing of unwanted coherence transfer pathways (CTPs), are particularly challenging in editing schemes for metabolites like gamma-aminobutyric acid (GABA) and glutathione (GSH). To address this, a volume-based likelihood model was developed to guide gradient scheme optimization, prioritizing suppression of CTPs based on likelihood.

Benchmarking the Impact of Anatomical Segmentation on In Vivo Magnetic Resonance Spectroscopy.

Purpose: Estimation of metabolite concentrations in brain magnetic resonance spectroscopy (MRS) requires correction for differences in tissue water content, relaxation properties, and the proportions of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Accurate knowledge of the relative proportions of these tissue classes within the volume of interest is therefore essential for reliable quantification. Commonly used brain segmentation tools differ in their algorithms, priors, and implementation, potentially introducing variability in MRS-derived concentration estimates.

MRS-BIDS, an extension to the Brain Imaging Data Structure for magnetic resonance spectroscopy.

The Brain Imaging Data Structure (BIDS) is an increasingly adopted standard for organizing scientific data and metadata. It facilitates easier and more straightforward data sharing and reuse. BIDS currently encompasses several biomedical imaging and non-imaging techniques, and as more research groups begin to use it, additional experimental techniques are being incorporated into the standard, allowing diverse experimental methods to be stored within the same cohesive structure.

Identifying out-of-voxel echoes in edited MRS with phase cycle inversion.

Purpose: To identify the origin of out-of-voxel (OOV) signals based on the coherence transfer pathway (CTP) formalism using signal phase conferred by the acquisition phase cycling scheme. Knowing the CTP driving OOV artifacts enables optimization of crusher gradients to improve their suppression without additional data acquisition.

Theory And Methods: A phase cycle systematically changes the phase of RF pulses across the transients of an experiment, encoding phase shifts into the data that can be used to suppress unwanted CTPs.

GABA, Glx, and GSH in the cerebellum: their role in motor performance and learning across age groups.

Introduction: The cerebellum is essential for motor control and learning, relying on structural and functional integrity. Age-related atrophy leads to Purkinje cell loss, but subtle neurochemical changes in GABA, Glx (glutamate + glutamine), and glutathione (GSH) may precede degeneration and contribute to motor decline.

Methods: 25 younger (YA) and 25 older adults (OA) were included in this study.

Comparison of test-retest repeatability of DESPOT and 3D-QALAS for T and T mapping.

Background: Relaxometry, specifically T and T mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimate T and T relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy of T and T measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the magnetic resonance imaging (MRI) hardware, and the image reconstruction.

Reproducibility Made Easy: A Tool for Methodological Transparency and Efficient Standardized Reporting Based on the Proposed MRSinMRS Consensus.

Recent expert consensus publications have highlighted the issue of poor reproducibility in magnetic resonance spectroscopy (MRS) studies, mainly due to the lack of standardized reporting criteria, which affects their clinical applicability. To combat this, guidelines for minimum reporting standards (MRSinMRS) were introduced to aid journal editors and reviewers in ensuring the comprehensive documentation of essential MRS study parameters. Despite these efforts, the implementation of MRSinMRS standards has been slow, attributed to the diverse nomenclature used by different vendors, the variety of raw MRS data formats, and the absence of appropriate software tools for identifying and reporting necessary parameters.

MRS-Sim: Open-Source Framework for Simulating In Vivo-like Magnetic Resonance Spectra.

Realistic, in vivo-like synthetic data is increasingly needed to develop and validate methods in magnetic resonance spectroscopy. MRS-Sim is a powerful, open-source framework for simulating such data while providing known ground truth values. Its modularity enables modeling the complexities of MRS data for various in vivo scenarios.

Diagnostic and theranostic opportunities in Neuro-oncology.

Theranostics, the interlinking of diagnostic and therapeutic procedures, can be particularly valuable in neuro-oncology, addressing the challenges posed by the blood-brain and brain-tumor barriers. While it is traditionally associated with nuclear medicine, advances in MR imaging techniques have opened new theranostic frontiers. This review covers the present challenges in neuro-oncology and how these could be overcome utilizing radioligand-based molecular radiotherapy as well as how label-free theranostics employing methods such as chemical exchange saturation transfer (CEST) and MR spectroscopy could advance the field.

Pitfalls in 2HG detection with TE-optimized MRS at 3T.

Background And Purpose: In-vivo magnetic resonance spectroscopy (MRS) of 2-hydroxyglutarate (2HG) may provide diagnostic and monitoring biomarkers in isocitrate dehydrogenase (IDH)-mutated glioma. A previous meta-analysis has shown good diagnostic accuracy of TE-optimized PRESS for IDH-mutated glioma, but most studies feature IDH-wildtype glioma as a comparison. However, when considering newly identified brain lesions that may mimic glioma, full characterization of its diagnostic utility should also consider the accuracy of 2HG measurement in non-tumor tissue.

Age dependency of neurometabolite T relaxation times.

Purpose: To measure T relaxation times of metabolites at 3 T in a healthy aging population and investigate age dependence.

Methods: A cohort of 101 healthy adults was recruited with approximately 10 male and 10 female participants in each "decade" band: 18 to 29, 30 to 39, 40 to 49, 50 to 59, and 60+ years old. Inversion-recovery PRESS data (TE/TR: 30/2000 ms) were acquired at 8 inversion times (TIs) (300, 400, 511, 637, 780, 947, 1148, and 1400 ms) from voxels in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC).

A Water Relaxation Atlas for Age- and Region-Specific Metabolite Concentration Correction at 3 T.

Metabolite concentration estimates from magnetic resonance spectroscopy (MRS) are typically quantified using water referencing, correcting for relaxation-time differences between metabolites and water. One common approach is to correct the reference signal for differential relaxation within three tissue compartments (gray matter, white matter, and cerebrospinal fluid) using fixed literature values. However, water relaxation times (T and T) vary between brain locations and with age.

Metabolite T relaxation times decrease across the adult lifespan in a large multi-site cohort.

Purpose: Relaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo MRS. However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T and age in a large, multi-site cohort.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

A data-driven algorithm to determine H-MRS basis set composition.

Purpose: Metabolite amplitude estimates derived from linear combination modeling of MR spectra depend upon the precise list of constituent metabolite basis functions used (the "basis set"). The absence of clear consensus on the "ideal" composition or objective criteria to determine the suitability of a particular basis set contributes to the poor reproducibility of MRS. In this proof-of-concept study, we demonstrate a novel, data-driven approach for deciding the basis-set composition using Akaike information criteria (AIC).

Comparison of test-retest reproducibility of DESPOT and 3D-QALAS for water and mapping.

Purpose: Relaxometry, specifically and mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimate and relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy of and measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction.

Association between Inhibitory-Excitatory Balance and Brain Activity Response during Cognitive Flexibility in Young and Older Individuals.

Cognitive flexibility represents the capacity to switch among different mental schemes, providing an adaptive advantage to a changing environment. The neural underpinnings of this executive function have been deeply studied in humans through fMRI, showing that the left inferior frontal cortex (IFC) and the left inferior parietal lobule (IPL) are crucial. Here, we investigated the inhibitory-excitatory balance in these regions by means of γ-aminobutyric acid (GABA+) and glutamate + glutamine (Glx), measured with magnetic resonance spectroscopy, during a cognitive flexibility task and its relationship with the performance level and the local task-induced blood oxygenation level-dependent (BOLD) response in 40 young (18-35 years; 26 female) and 40 older (18-35 years; 21 female) human adults.

Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone.

Model-based frequency-and-phase correction of H MRS data with 2D linear-combination modeling.

Purpose: Retrospective frequency-and-phase correction (FPC) methods attempt to remove frequency-and-phase variations between transients to improve the quality of the averaged MR spectrum. However, traditional FPC methods like spectral registration struggle at low SNR. Here, we propose a method that directly integrates FPC into a 2D linear-combination model (2D-LCM) of individual transients ("model-based FPC").

Metabolite T relaxation times decrease across the adult lifespan in a large multi-site cohort.

Purpose: Relaxation correction is crucial for accurately estimating metabolite concentrations measured using magnetic resonance spectroscopy (MRS). However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T and age in a large, multi-site cohort.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for advanced MRS.

Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study.

Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions.

GABA-edited MEGA-PRESS at 3 T: Does a measured macromolecule background improve linear combination modeling?

Purpose: The J-difference edited γ-aminobutyric acid (GABA) signal is contaminated by other co-edited signals-the largest of which originates from co-edited macromolecules (MMs)-and is consequently often reported as "GABA+." MM signals are broader and less well-characterized than the metabolites, and are commonly approximated using a Gaussian model parameterization. Experimentally measured MM signals are a consensus-recommended alternative to parameterized modeling; however, they are relatively under-studied in the context of edited MRS.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for Advanced MRS.

Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study.

Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions.