GABA Increase Revealed during Deep Hypothermic Circulatory Arrest using Short TE 1H MR Spectroscopy
Poster No:
1962
Submission Type:
Late-Breaking Abstract Submission
Authors:
Meng Gu1, Ralph Hurd1, Daniel Spielman1
Institutions:
1Stanford University, Stanford, CA
First Author:
Co-Author(s):
Late Breaking Reviewer(s):
Introduction:
Deep hypothermic circulatory arrest (DHCA) is a widely used strategy for brain protection during cardiac surgery. (Hameed et al., 2020) It is of great interest to study brain metabolism during surgery using magnetic resonance spectroscopy (MRS) as it has profound implications in patient recovery. As a major neural inhibitor, Gamma-aminobutyric-acid (GABA) increase has been discovered in brain tissue after DHCA using high frequency 13C MRS. (Kajimoto et al., 2016) However, GABA dynamics has not been investigated during circulatory arrest.
At 3T, short-TE 1H MRS offers the advantage of acquiring signals from a rich set of metabolites with short scan times and minimal signal loss from T2 relaxation and thus is a unique approach to study in-vivo GABA dynamics during circulatory arrest. However, LCModel quantification of GABA using short TE spectra was not widely used due to poor spectral quality and high Cramer-Rao lower bound of estimation, hampering investigation of brain metabolism. As a result, GABA was conventionally quantified using editing techniques such as MEGA-PRESS with long minimum scan times. (Mescher, Merkle, Kirsch, Garwood, & Gruetter, 1998)
In this study, neonatal pigs were used to study brain metabolism in DHCA during cardiac surgery. High quality short-TE single-voxel spectra with low line-width were continuously obtained that resulted in acceptable Cramer-Rao lower bound of GABA estimation. Using this method, LCModel quantification revealed that GABA level increases during circulatory arrest before gradually decreases toward baseline.
At 3T, short-TE 1H MRS offers the advantage of acquiring signals from a rich set of metabolites with short scan times and minimal signal loss from T2 relaxation and thus is a unique approach to study in-vivo GABA dynamics during circulatory arrest. However, LCModel quantification of GABA using short TE spectra was not widely used due to poor spectral quality and high Cramer-Rao lower bound of estimation, hampering investigation of brain metabolism. As a result, GABA was conventionally quantified using editing techniques such as MEGA-PRESS with long minimum scan times. (Mescher, Merkle, Kirsch, Garwood, & Gruetter, 1998)
In this study, neonatal pigs were used to study brain metabolism in DHCA during cardiac surgery. High quality short-TE single-voxel spectra with low line-width were continuously obtained that resulted in acceptable Cramer-Rao lower bound of GABA estimation. Using this method, LCModel quantification revealed that GABA level increases during circulatory arrest before gradually decreases toward baseline.
Methods:
Three two-week old piglets were put on a cardiopulmonary bypass pump and placed in a GE MR750 3T scanner (GE Healthcare, Waukesha, WI) to study brain metabolism. Single-voxel MRS data were acquired from a 12 x 12 x 15 mm3 right midbrain voxel continuously for approximately four hours using sLASER with TE/TR=30ms/2s and 64 averages for each acquisition. The brain temperature was measured as soon as each acquisition completed using the chemical shift difference between the water and the 2-ppm NAA resonances and used as a reference to keep the brain temperature at 28°C. After the brain temperature equilibrated at 28°C, pump was turned off for about 50 minutes of circulatory arrest. The pump was then restarted and heating initiated until the brain temperature reached 37°C for a 2-hour recovery period. (Spielman et al., 2022)
Original spectra were reconstructed with eddy-current correction, zero-order phasing, coil-combination and pure water spectrum subtraction and quantified using the LCModel with 23 phantom-measured metabolite basis and a fixed-spline-knots dkntmn=0.02 for improved baseline estimation.
Original spectra were reconstructed with eddy-current correction, zero-order phasing, coil-combination and pure water spectrum subtraction and quantified using the LCModel with 23 phantom-measured metabolite basis and a fixed-spline-knots dkntmn=0.02 for improved baseline estimation.
Results:
Representative in-vivo spectra from one of the three studies and their LCModel fits at baseline, during circulatory arrest and at the end of the recovery were shown in Figure 1. Prominent lactate peak can be seen during circulatory arrest at 1.3ppm as shown in Figure 1c, due to lack of blood supply to the brain. The lactate peak dropped toward the baseline level after resumption of the blood supply during the recovery as demonstrated in Figure 1d. The dynamics of the brain temperature, estimated lactate to total creatine ratio (Lac/tCr) and GABA to total creatine ratio (GABA/tCr) were shown in Figure 2. The error bar of the Lac/tCr and GABA/tCr were calculated by multiplying the quantified values by the %SD estimated using the LCModel. The average %SD for Lac and GABA were 10% and 25% respectively.
Conclusions:
High quality single voxel 1H MR spectra were obtained from neonatal pig brains in the study of deep hypothermic circulatory arrest. Using LCModel, lactate and GABA were quantified with acceptable Creamer Rao lower bounds. Quantified dynamics showed lactate and GABA levels started increasing at the onset of the circulatory arrest and stayed at elevated levels before dropping toward the baseline after the resumption of the blood supply in the recovery period.
Brain Stimulation:
Invasive Stimulation Methods Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Receptors 2
Cerebral Metabolism and Hemodynamics
Novel Imaging Acquisition Methods:
MR Spectroscopy 1
Keywords:
Acquisition
GABA
Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
Neurotransmitter
Pediatric Disorders
1|2Indicates the priority used for review
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Provide references using APA citation style.
Kajimoto, M., Ledee, D. R., Olson, A. K., Isern, N. G., Robillard-Frayne, I., Des Rosiers, C., & Portman, M. A. (2016). Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion. J Cereb Blood Flow Metab, 36(11), 1992-2004. doi:10.1177/0271678X16666846
Mescher, M., Merkle, H., Kirsch, J., Garwood, M., & Gruetter, R. (1998). Simultaneous in vivo spectral editing and water suppression. NMR Biomed, 11(6), 266-272. doi:10.1002/(sici)1099-1492(199810)11:6<266::aid-nbm530>3.0.co;2-j
Spielman, D. M., Gu, M., Hurd, R. E., Riemer, R. K., Okamura, K., & Hanley, F. L. (2022). Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery. NMR Biomed, 35(9), e4752. doi:10.1002/nbm.4752