Showing papers by "Jamie Near published in 2019"
TL;DR: Assessment of the validity of MRS measures of human brain metabolite concentrations by comparing multiple M RS measures acquired using different MRS acquisition sequences.
Abstract: Purpose In vivo magnetic resonance spectroscopy (MRS) is the only technique capable of non-invasively assessing metabolite concentrations in the brain. The lack of alternative methods makes validation of MRS measures challenging. The aim of this study is to assess the validity of MRS measures of human brain metabolite concentrations by comparing multiple MRS measures acquired using different MRS acquisition sequences. Methods Single-voxel SPECIAL and MEGA-PRESS MR spectra were acquired from both the dorsolateral prefrontal cortex and primary motor cortices in 15 healthy subjects. The SPECIAL spectrum, as well as both the edit-off and difference spectra of MEGA-PRESS were each analyzed in LCModel to obtain estimates of the absolute concentrations of total choline (TCh; glycerophosphocholine + phosphocholine), total creatine (TCr; creatine + phosphocreatine), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), NAA + NAAG, glutamate (Glu), glutamine (Gln), Glu + Gln, scyllo-inositol (Scyllo), myo-inositol (Ins), glutathione (GSH), γ-aminobutyric acid (GABA), lactate (Lac) and aspartate (Asp). Then, having obtained up to three independent measures of each metabolite per brain region per subject, correlations between the different measures were assessed. Results The degree of correlation between measures varied greatly across both the metabolites and sequences tested. As expected, metabolites with the most prominent spectral peaks (TCh, TCr, NAA + NAAG, Ins and Glu) had the most well-correlated measures between methods, while metabolites with less prominent spectral peaks (Lac, Gln, GABA, Asp, and NAAG) tended to have poorly-correlated measures between methods. Some metabolites with relatively less prominent spectral peaks (GSH, Scyllo) had fairly well-correlated measures between some methods. Combining metabolites improved the agreement between methods for measures of NAA + NAAG, but not for Glu + Gln. Conclusions Given that the ground truth for in vivo MRS measures is never known, the method proposed here provides a promising means to assess the validity of in vivo MRS measures, which has not yet been explored widely.
41 citations
TL;DR: An effort to develop a new universal MEGA‐PRESS sequence with HERMES functionality for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and timings is described.
39 citations
TL;DR: This study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression, and observed a significant decrease in NAA levels following ECT, due to neuronal loss or a transient dysfunction in prefrontal cortex.
Abstract: Objective Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS). Methods In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures. Results No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035. Conclusions Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.
29 citations
TL;DR: Cerebral glutathione, a marker of oxidative stress, has been quantified in neurodegenerative diseases and psychiatric disorders using proton magnetic resonance spectroscopy using a reproducible MRS technique.
Abstract: BACKGROUND Cerebral glutathione (GSH), a marker of oxidative stress, has been quantified in neurodegenerative diseases and psychiatric disorders using proton magnetic resonance spectroscopy (MRS). Using a reproducible MRS technique is important, as it minimizes the impact of measurement technique variability on the study results and ensures that other studies can replicate the results. HYPOTHESIS We hypothesized that very short echo time (TE) acquisitions would have comparable reproducibility to a long TE MEGA-PRESS acquisition, and that the short TE PRESS acquisition would have the poorest reproducibility. STUDY TYPE Prospective. SUBJECTS/PHANTOMS Ten healthy adults were scanned during two visits, and six metabolite phantoms containing varying concentrations of GSH and metabolites with resonances that overlap with GSH were scanned once. FIELD STRENGTH/SEQUENCE At 3T we acquired MRS data using four different sequences: PRESS, SPECIAL, PR-STEAM, and MEGA-PRESS. ASSESSMENT Reproducibility of each MRS sequence across two visits was assessed. STATISTICAL TESTS Mean coefficients of variation (CV) and mean absolute difference (AD) were used to assess reproducibility. Linear regressions were performed on data collected from phantoms to examine the agreement between known and quantified levels of GSH. RESULTS Of the four techniques, PR-STEAM had the lowest mean CV and AD (5.4% and 7.5%, respectively), implying excellent reproducibility, followed closely by PRESS (5.8% and 8.2%) and SPECIAL (8.0 and 10.1%), and finally by MEGA-PRESS (13.5% and 17.1%). Phantom data revealed excellent fits (R2 ≥ 0.98 or higher) using all methods. DATA CONCLUSION Our data suggest that GSH can be quantified reproducibly without the use of spectral editing. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:176-183.
24 citations
TL;DR: The Gln concentrations in PCC (mean of two measurements) were positively correlated with GlN concentrations in plasma (p < 0.01, r = 0.72), however, the Glu concentrations in the two regions were not correlated with those in plasma.
Abstract: Both glutamine (Gln) and glutamate (Glu) are known to exist in plasma and brain. However, despite the assumed relationship between brain and plasma, no studies have clarified the association between them. Proton magnetic resonance spectroscopy (MRS) was sequentially performed twice, with a 60-min interval, on 10 males and 10 females using a 3T scanner. Blood samples for liquid chromatography–mass spectrometry (LC/MS) to measure Gln and Glu concentrations in plasma were collected during the time interval between the two MRS sessions. MRS voxels of interest were localized at the posterior cingulate cortex (PCC) and cerebellum (Cbll) and measured by the SPECIAL sequence. Spearman’s correlation coefficient was used to examine the association between brain and plasma metabolites. The Gln concentrations in PCC (mean of two measurements) were positively correlated with Gln concentrations in plasma (p < 0.01, r = 0.72). However, the Glu concentrations in the two regions were not correlated with those in plasma. Consideration of the different dynamics of Gln and Glu between plasma and brain is crucial when addressing the pathomechanism and therapeutic strategies for brain disorders such as Alzheimer’s disease and hepatic encephalopathy.
15 citations
TL;DR: The included studies provide inconclusive support for glutamatergic elevations within frontal brain regions in patients with schizophrenia and the key benefit of employing 1H-MRSI to examine schizophrenia pathophysiology appears to be its broader spatial coverage.
8 citations
TL;DR: Special MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters, which is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.
Abstract: Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.
6 citations
TL;DR: The Fischer 344 atlas as discussed by the authors is a high-resolution 3D MRI atlas of the Fischer 344 adult rat brain, which consists of 256 coronal slices with 98 manually delineated structures and substructures.
Abstract: This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 μm isotropic image volume composed of 256 coronal slices with 98 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats. Slices in the average brain image were then digitally segmented, individually and bilaterally, on the basis of image contrast in conjunction with Paxinos and Watson’s (2007) stereotaxic rat brain atlas. Summary statistics (mean and standard deviation of regional volumes) are reported for each brain region across the sample used to generate the atlas, and a statistical comparison of a chosen subset of regional brain volumes between male and female rats is presented. On average, the coefficient of variation of regional brain volumes across all rats in our sample was 5%, with no individual brain region having a coefficient of variation greater than 14%. A full description of methods used, as well as the atlas, the template that the atlas was derived from, and a masking file, can be found at https://www.nearlab.xyz/fischer344atlas. To our knowledge, this is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain. Graphical HIGHLIGHTS Open-access high-resolution anatomical MRI template for Fischer 344 rat brain. Segmented atlas of 98 regions for use as a tool in Fischer 344 preclinical research paradigms. Analysis of population variability of regional brain volumes. Analysis of sex-differences in regional brain volumes
2 citations
TL;DR: This is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain, and will be a source of inspiration for future studies of Fischer 344 preclinical research paradigms.
Abstract: This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 μm isotropic image volume composed of 256 coronal slices with 71 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats. Slices in the average brain image were then manually segmented, individually and bilaterally, on the basis of image contrast in conjunction with Paxinos and Watson’s (2007) stereotaxic rat brain atlas. Summary statistics (mean and standard deviation of regional volumes) are reported for each brain region across the sample used to generate the atlas, and a statistical comparison of a chosen subset of regional brain volumes between male and female rats is presented. On average, the coefficient of variation of regional brain volumes across all rats in our sample was 4%, with no individual brain region having a coefficient of variation greater than 13%. A full description of methods used, as well as the atlas, the template that the atlas was derived from, and a masking file, can be found at Zenodo at https://doi.org/10.5281/zenodo.3555556. To our knowledge, this is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain. HIGHLIGHTS ⍰ Open-access high-resolution anatomical MRI template for Fischer 344 rat brain. ⍰ Segmented atlas of 71 regions for use as a tool in Fischer 344 preclinical research paradigms. ⍰ Analysis of population variability of regional brain volumes. ⍰ Analysis of sex-differences in regional brain volumes KEYWORDS: Fischer 344; Structural MRI; Segmentation; Rat brain template; Digital brain atlas; Sex-differences;