20 research outputs found
Neurotransmitter measurements in the human brain at 3 Tesla and 7 Tesla
No full textMagnetic Resonance Spectroscopy (MRS) is a powerful technique that can potentially be used to measure metabolite concentrations in the brain non-invasively. However, the available signal-to-noise ratios (SNR) of MR spectra are limited because metabolites are present in low (millimolar or less) concentrations, and different resonances overlap in frequency. These challenges have led to the use of specialized pulse sequences and increasingly higher static magnetic field strengths. The emergence of higher fields presents opportunities for making more precise measurements of metabolites and for acquisitions from smaller volumes or in faster times.
First, this thesis addresses the need to re-evaluate the optimal measurement and sequence parameters to be used at ultra-high field (7 Tesla) for detecting specific brain metabolites. By calculating theoretical Cramer-Rao Lower Bound (CRLB) values for a set of 17 metabolites that are above or near the detection threshold, the optimal PRESS sequence timings for acquisitions have been designed. The advantage of this approach is that calculation of CRLBs is versatile and may be used to evaluate optimal parameters for other pulse sequences. Second, this thesis includes a quantitative comparison of measurements of the neurotransmitter GABA made using MEGA-PRESS between 3 Tesla and 7 Tesla, and defines the bandwidth requirements for making measurements with higher precision at higher fields. Third, the thesis also evaluates and demonstrates the potential of novel event-related functional spectroscopic acquisitions and investigates changes in metabolite profiles as a function of neuronal activity with relatively high temporal resolution. The transient changes in metabolites that occur following short periods of stimulation of visual cortex have been quantified
GABA and glutamate in the preterm neonatal brain: In-vivo measurement by magnetic resonance spectroscopy
No full textCognitive and behavioral disabilities in preterm infants, even without obvious brain injury on conventional neuroimaging, underscores a critical need to identify the subtle underlying microstructural and biochemical derangements. The gamma-aminobutyric acid (GABA) and glutamatergic neurotransmitter systems undergo rapid maturation during the crucial late gestation and early postnatal life, and are at-risk of disruption after preterm birth. Animal and human autopsy studies provide the bulk of current understanding since non-invasive specialized proton magnetic resonance spectroscopy (1H-MRS) to measure GABA and glutamate are not routinely available for this vulnerable population due to logistical and technical challenges. We review the specialized 1H-MRS techniques including MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS), special challenges and considerations needed for interpretation of acquired data from the developing brain of preterm infants. We summarize the limited in-vivo preterm data, highlight the gaps in knowledge, and discuss future directions for optimal integration of available in-vivo approaches to understand the influence of GABA and glutamate on neurodevelopmental outcomes after preterm birth
Clinical Course of a Fetus with Hypoplastic Left Heart Syndrome and Premature Ductal Constriction.
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Third Trimester Cerebellar Metabolite Concentrations are Decreased in Very Premature Infants with Structural Brain Injury.
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Non-invasive measurement of biochemical profiles in the healthy fetal brain.
No full text© 2020 The Author(s) Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy. Objective: To investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy. Study design: We prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18–39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ms and analyzed in LCModel. Results: We successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%–20% increased the mean metabolite concentrations and decreased the number of observations available for analysis. Conclusion: We report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus
Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants
No full text© 2020, The Author(s). Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy (1H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated 1H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury
