scholarly journals The Macromolecular MR Spectrum in Healthy Aging

2021 ◽  
Author(s):  
Steve C.N. Hui ◽  
Tao Gong ◽  
Helge J. Zöllner ◽  
Yulu Song ◽  
Saipavitra Murali-Manohar ◽  
...  
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Basis Set ◽  
Basis Sets ◽  
Water Suppression ◽  
List Type ◽  
Reduced Basis ◽  
Inversion Time ◽  
One Way Anova ◽  
Age And Sex

AbstractPurposeMobile macromolecules (MMs) from amino acids, cytosolic proteins and mobile lipids contribute a significant spectral background underlying the metabolite signals in the MR spectrum. A recent consensus recommends that MM contributions should be removed or included in modeling basis sets for determination of metabolite concentrations and/or metabolite ratios. The purpose of this study was to acquire the MM spectrum from healthy participants at a range of ages, and to investigate changes in the signals with age and sex groups.MethodsInversion time (TI) series were acquired to determine an optimal inversion time to null the metabolite signals. Experiments were carried out using a single adiabatic hyperbolic-secant inversion pulse. After the preliminary experiment, 102 volunteers (49M/53F) between 20 and 69 years were recruited for in vivo data acquisition in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). The protocol consisted of a T1-weighted MPRAGE for structural images, followed by PRESS localization using a voxel size of 30 × 26 × 26 mm3 with pre-inversion (TR/TI 2000/600 ms) and CHESS water suppression. Metabolite-nulled spectra were modeled using a reduced basis set (NAA, Cr, Cho, Glu) and a flexible spline baseline (0.1 ppm knot spacing) followed by subtraction of the modeled metabolite signals to yield a ‘clean’ MM spectrum, using the Osprey software. Pearson’s correlation coefficient was calculated between integrals and age for the 14 MM signals between 0.9–4.2 ppm. One-way ANOVA was performed to determine differences between age groups. An independent t-test was carried out to determine differences between sexes. Relationships between brain tissues with age and sex groups were also measured.ResultsMM spectra were successfully acquired in 99 (CSO) and 96 (PCC) of 102 subjects. No significant correlations were seen between age and MM integrals. One-way ANOVA also suggested no age-group differences for any MM peak (all p > 0.004). No differences were observed between sex groups. The voxels were segmented as 80 ± 4% white matter, 18 ± 4% gray matter, and 2 ± 1% CSF for CSO and 28 ± 4% white matter, 61 ± 4% gray matter and 11 ± 1% CSF for PCC. WM and GM showed a significant (p < 0.05) negative linear association with age in the WM-predominant CSO (R = −0.29) and GM-predominant PCC regions (R = −0.57) respectively while CSF increased significantly with age in both regions.ConclusionOur findings indicate that the MM spectrum is stable across a large age range and between sexes, suggesting a pre-defined MM basis function can be used for linear combination modeling of metabolite data from different age and sex groups.HighlightsA large publicly available MM-aging dataset is presented.Macromolecule signals do not change with age between 20 and 70.There is no sex difference for macromolecule integrals.

scholarly journals Blood–brain barrier leakage is more widespread in patients with cerebral small vessel disease

Neurology ◽  
2016 ◽  
Vol 88 (5) ◽  
pp. 426-432 ◽  
Author(s):  
C. Eleana Zhang ◽  
Sau May Wong ◽  
Harm J. van de Haar ◽  
Julie Staals ◽  
Jacobus F.A. Jansen ◽  
...  
Keyword(s):  
White Matter ◽  
Blood Brain Barrier ◽  
Gray Matter ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Leakage Rate ◽  
Brain Barrier ◽  
Dce Mri ◽  
Vessel Disease ◽  
Age And Sex

Objective:As blood–brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)–MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage.Methods:We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter.Results:Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions.Conclusion:We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.

Imaging of neuroinflammation in adult Niemann-Pick type C disease

Neurology ◽  
2020 ◽  
Vol 94 (16) ◽  
pp. e1716-e1725
Author(s):  
Mark Walterfang ◽  
Maria A. Di Biase ◽  
Vanessa L. Cropley ◽  
Andrew M. Scott ◽  
Graeme O'Keefe ◽  
...  
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Structural Mri ◽  
Matter Volume ◽  
Pet Scanning ◽  
Type C ◽  
Niemann Pick ◽  
The Brain ◽  
Age And Sex

ObjectiveTo test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls.MethodWe scanned all participants with the PET radioligand 11C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA).ResultsWe found increased binding of 11C-(R)-PK-11195 in total white matter compared to controls (p < 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus (p < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls (p < 0.001). A significant correlation between 11C-(R)-PK11195 binding and FA was shown (p = 0.002), driven by the NPC patient group.ConclusionsOur findings suggest that neuroinflammation—particularly in white matter—may underpin some structural and degenerative changes in patients with NPC.

MR signal intensity of gray matter/white matter contrast and intracranial fat: effects of age and sex

2002 ◽  
Vol 114 (3) ◽  
pp. 149-161 ◽  
Author(s):  
Dennis M. Kim ◽  
Stavra A. Xanthakos ◽  
Larry A. Tupler ◽  
Daniel P. Barboriak ◽  
H.Cecil Charles ◽  
...  
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Signal Intensity ◽  
Age And Sex

FT-IR microspectroscopic analysis of diseased white matter brain tissues

1995 ◽  
Vol 53 ◽  
pp. 968-969
Author(s):  
Steven M. Le Vine ◽  
David L. Wetzel
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Twitcher Mouse ◽  
Grid Pattern ◽  
Marked Contrast ◽  
Spatially Resolved ◽  
Ft Ir ◽  
Ir Microspectroscopy ◽  
Chemical Evidence

In situ FT-IR microspectroscopy has allowed spatially resolved interrogation of different parts of brain tissue. In previous work the spectrrscopic features of normal barin tissue were characterized. The white matter, gray matter and basal ganglia were mapped from appropriate peak area measurements from spectra obtained in a grid pattern. Bands prevalent in white matter were mostly associated with the lipid. These included 2927 and 1469 cm-1 due to CH2 as well as carbonyl at 1740 cm-1. Also 1235 and 1085 cm-1 due to phospholipid and galactocerebroside, respectively (Figs 1and2). Localized chemical changes in the white matter as a result of white matter diseases have been studied. This involved the documentation of localized chemical evidence of demyelination in shiverer mice in which the spectra of white matter lacked the marked contrast between it and gray matter exhibited in the white matter of normal mice (Fig. 3).The twitcher mouse, a model of Krabbe’s desease, was also studied. The purpose in this case was to look for a localized build-up of psychosine in the white matter caused by deficiencies in the enzyme responsible for its breakdown under normal conditions.

A Systematic DFT Study of Two Elementary Steps Involving Hydrogen Peroxide and the Hydroxyl Radical in the Fenton Reaction

2018 ◽  
Author(s):  
Danilo Carmona ◽  
David Contreras ◽  
Oscar A. Douglas-Gallardo ◽  
Stefan Vogt-Geisse ◽  
Pablo Jaque ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Hydroxyl Radical ◽  
Ab Initio ◽  
Fenton Reaction ◽  
Basis Set ◽  
Basis Sets ◽  
Dft Methods ◽  
Elementary Steps ◽  
Oxygen Oxygen ◽  
Complete Basis Set

The Fenton reaction plays a central role in many chemical and biological processes and has various applications as e.g. water remediation. The reaction consists of the iron-catalyzed homolytic cleavage of the oxygen-oxygen bond in the hydrogen peroxide molecule and the reduction of the hydroxyl radical. Here, we study these two elementary steps with high-level ab-initio calculations at the complete basis set limit and address the performance of different DFT methods following a specific classification based on the Jacob´s ladder in combination with various Pople's basis sets. Ab-initio calculations at the complete basis set limit are in agreement to experimental reference data and identified a significant contribution of the electron correlation energy to the bond dissociation energy (BDE) of the oxygen-oxygen bond in hydrogen peroxide and the electron affinity (EA) of the hydroxyl radical. The studied DFT methods were able to reproduce the ab-initio reference values, although no functional was particularly better for both reactions. The inclusion of HF exchange in the DFT functionals lead in most cases to larger deviations, which might be related to the poor description of the two reactions by the HF method. Considering the computational cost, DFT methods provide better BDE and EA values than HF and post--HF methods with an almost MP2 or CCSD level of accuracy. However, no systematic general prediction of the error based on the employed functional could be established and no systematic improvement with increasing the size in the Pople's basis set was found, although for BDE values certain systematic basis set dependence was observed. Moreover, the quality of the hydrogen peroxide, hydroxyl radical and hydroxyl anion structures obtained from these functionals was compared to experimental reference data. In general, bond lengths were well reproduced and the error in the angles were between one and two degrees with some systematic trend with the basis sets. From our results we conclude that DFT methods present a computationally less expensive alternative to describe the two elementary steps of the Fenton reaction. However, choice of approximated functionals and basis sets must be carefully done and the provided benchmark allows a systematic validation of the electronic structure method to be employed

DFT Benchmark Study of the O--O Bond Dissociation Energy in Peroxides Validated with High-Level Ab-Initio Calculations

2019 ◽  
Author(s):  
Danilo Carmona ◽  
Pablo Jaque ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Reference Value ◽  
Basis Set ◽  
Basis Sets ◽  
Mean Deviation ◽  
Bond Dissociation ◽  
Dissociation Energies ◽  
The Mean ◽  
Experimental Values ◽  
High Level ◽  
Almost All

<div><div><div><p>Peroxides play a central role in many chemical and biological pro- cesses such as the Fenton reaction. The relevance of these compounds lies in the low stability of the O–O bond which upon dissociation results in radical species able to initiate various chemical or biological processes. In this work, a set of 64 DFT functional-basis set combinations has been validated in terms of their capability to describe bond dissociation energies (BDE) for the O–O bond in a database of 14 ROOH peroxides for which experimental values ofBDE are available. Moreover, the electronic contributions to the BDE were obtained for four of the peroxides and the anion H2O2− at the CBS limit at CCSD(T) level with Dunning’s basis sets up to triple–ζ quality provid- ing a reference value for the hydrogen peroxide anion as a model. Almost all the functionals considered here yielded mean absolute deviations around 5.0 kcal mol−1. The smallest values were observed for the ωB97 family and the Minnesota M11 functional with a marked basis set dependence. Despite the mean deviation, order relations among BDE experimental values of peroxides were also considered. The ωB97 family was able to reproduce the relations correctly whereas other functionals presented a marked dependence on the chemical nature of the R group. Interestingly, M11 functional did not show a very good agreement with the established order despite its good performance in the mean error. The obtained results support the use of similar validation strategies for proper prediction of BDE or other molecular properties by DF Tmethods in subsequent related studies.</p></div></div></div>

Benchmark of Simplified Time-Dependent Density Functional Theory for UV-Vis Spectral Properties of Porphyrinoids

2019 ◽  
Author(s):  
Kamal Batra ◽  
Stefan Zahn ◽  
Thomas Heine
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Large Scale ◽  
Absolute Error ◽  
Time Dependent ◽  
Basis Set ◽  
Basis Sets ◽  
Functional Theory ◽  
Framework Materials ◽  
Dependent Density

<p>We thoroughly benchmark time-dependent density- functional theory for the predictive calculation of UV/Vis spectra of porphyrin derivatives. With the aim to provide an approach that is computationally feasible for large-scale applications such as biological systems or molecular framework materials, albeit performing with high accuracy for the Q-bands, we compare the results given by various computational protocols, including basis sets, density-functionals (including gradient corrected local functionals, hybrids, double hybrids and range-separated functionals), and various variants of time-dependent density-functional theory, including the simplified Tamm-Dancoff approximation. An excellent choice for these calculations is the range-separated functional CAM-B3LYP in combination with the simplified Tamm-Dancoff approximation and a basis set of double-ζ quality def2-SVP (mean absolute error [MAE] of ~0.05 eV). This is not surpassed by more expensive approaches, not even by double hybrid functionals, and solely systematic excitation energy scaling slightly improves the results (MAE ~0.04 eV). </p>

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