Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain

Instrella, Ronald; Juchem, Christoph

doi:10.1002/mrm.29903

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…Because it is not feasible to measure metabolite T1 and T2 times in a subject-specific manner due to the lengthy nature of these experiments, it is typical to choose an estimate T1 and T2 (such the average T1 and T2 for NAD + found in this study) to use as correction factors when calculating metabolite absolute concentrations. Doing so means that the uncertainty of the parameter estimates, described by the standard deviation of the measurements, propagates through to the final concentration estimate (30). This study thus additionally investigated the propagation of uncertainty for the T1 and T2 measurements for the H2 NAD + proton.…”

Section: Discussionmentioning

confidence: 99%

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Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Swago,

Wilson,

Elliott

et al. 2024

Preprint

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Introduction The purpose of this study was to use a single-slice spectrally-selective sequence to measure T1and T2relaxation times of NAD+ proton resonances in the downfield1H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD+quantification. Methods Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T2relaxation, and saturation recovery data were to measure T1relaxation. The downfield acquisition used a spectrally-selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially-selective Shinnar-Le Roux refocusing pulse for localization. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation. Results The mean ± standard deviation of T1relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T2relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R2of the H2 and H6 T1fits were 0.98. The mean R2of the H4 proton T1fit was 0.96. The mean R2of the T2fits of the H2 and H4 proton resonances were 0.98, while the mean R2of the T2fits of the H4 proton was 0.93. The relative uncertainty in NAD+ concentration due to relaxation time uncertainty was 8.5%-11%. Conclusion Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD+T1and T2relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

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Section: Discussionmentioning

confidence: 99%

“…The partial derivatives of [NAD] with respect to T1NAD and T2NAD were derived by Instrella and Juchem (30):…”

Section: Uncertainty Propagation Analysismentioning

confidence: 99%

Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Swago,

Wilson,

Elliott

et al. 2024

Preprint

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Toward quantitative CEST imaging of glutamate in the mouse brain using a multi‐pool exchange model calibrated by ¹H‐MRS

Maguin,

Mougel,

Valette

et al. 2024

Magnetic Resonance in Med

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PurposeTo develop a CEST quantification model to map glutamate concentration in the mouse brain at 11.7 T, overcoming the limitations of conventional glutamate‐weighted CEST (gluCEST) contrast (magnetization transfer ratio with asymmetric analysis).Methods1H‐MRS was used as a gold standard for glutamate quantification to calibrate a CEST‐based quantitative pipeline. Joint localized measurements of Z‐spectra at B1 = 5 μT and quantitative 1H‐MRS were carried out in two voxels of interest in the mouse brain. A six‐pool Bloch‐McConnell model was found appropriate to fit experimental data. Glutamate exchange rate was estimated in both regions with this dedicated multi‐pool fitting model and using glutamate concentration determined by 1H‐MRS.ResultsGlutamate exchange rate was estimated to be ˜1300 Hz in the mouse brain. Using this calibrated value, maps of glutamate concentration in the mouse brain were obtained by pixel‐by‐pixel fitting of Z‐spectra at B1 = 5 μT. A complementary study of simulations, however, showed that the quantitative model has high sensitivity to noise, and therefore, requires high‐SNR acquisitions. Interestingly, fitted [Glu] seemed to be overestimated compared to 1H‐MRS measurements, although it was estimated with simulations that the model has no intrinsic fitting bias with our experimental level of noise. The hypothesis of an unknown proton‐exchanging pool contributing to gluCEST signal is discussed.ConclusionHigh‐resolution mapping of glutamate in the brain was made possible using the proposed calibrated quantification model of gluCEST data. Further studying of the in vivo molecular contributions to gluCEST signal could improve modeling.

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Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression

Swanberg,

Prinsen,

Averill

et al. 2024

NMR in Biomedicine

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Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (1H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD‐associated 1H‐MRS‐visible brain metabolite abnormalities. Here we employ 7 T 1H MRS to examine concentrations of glutamate, glutamine, GABA, and glutathione in the medial prefrontal cortex (mPFC) of PTSD patients with MDD (PTSD+MDD+; N = 6) or without MDD (PTSD+MDD−; N = 5), as well as trauma‐unmatched controls without PTSD but with MDD (PTSD−MDD+; N = 9) or without MDD (PTSD−MDD−; N = 18). Participants with PTSD demonstrated decreased ratios of GABA to glutamine relative to healthy PTSD−MDD− controls but no single‐metabolite abnormalities. When comorbid MDD was considered, however, MDD but not PTSD diagnosis was significantly associated with increased mPFC glutamine concentration and decreased glutamate:glutamine ratio. In addition, all participants with PTSD and/or MDD collectively demonstrated decreased glutathione relative to healthy PTSD−MDD− controls. Despite limited findings in single metabolites, patterns of abnormality in prefrontal metabolite concentrations among individuals with PTSD and/or MDD enabled supervised classification to separate them from healthy controls with 80+% sensitivity and specificity, with glutathione, glutamine, and myoinositol consistently among the most informative metabolites for this classification. Our findings indicate that MDD can be an important factor in mPFC glutamate metabolism abnormalities observed using 1H MRS in cohorts with PTSD.

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Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain

Cited by 3 publications

References 66 publications

Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Toward quantitative CEST imaging of glutamate in the mouse brain using a multi‐pool exchange model calibrated by ¹H‐MRS

Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression

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Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain

Cited by 3 publications

References 66 publications

Quantification of NAD+T1and T2relaxation times using downfield1H MRS at 7 T in human brain in vivo

Quantification of NAD+T1and T2relaxation times using downfield1H MRS at 7 T in human brain in vivo

Toward quantitative CEST imaging of glutamate in the mouse brain using a multi‐pool exchange model calibrated by 1H‐MRS

Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression

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Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Quantification of NAD⁺T₁and T₂relaxation times using downfield¹H MRS at 7 T in human brain in vivo

Toward quantitative CEST imaging of glutamate in the mouse brain using a multi‐pool exchange model calibrated by ¹H‐MRS