Brain-metabolite transverse relaxation times in magnetic resonance spectroscopy increase as adenosine triphosphate depletes during secondary energy failure following acute hypoxia-ischaemia in the newborn piglet

Cady, Ernest B.; Lorek, A; Penrice, J; Wylezińska, M; Cooper, Chris E.; Brown, Guy C.; Owen-Reece, H; Kirkbride, Vincent; Wyatt, John; Osmund, E.; Reynolds, Robert N.

doi:10.1016/0304-3940(94)90797-8

Cited by 35 publications

(23 citation statements)

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“…Although the changes observed in this work occurred during a secondary cerebral energy failure (in contradistinction to the primary transient hypoxic-ischemic episode), it is likely that the ADC changes observed during SEF similarly reflect cytotoxic edema resulting from loss of osmoregulation. This conclusion may be supported by a possible increase in the apparent transverse relaxation times of intracellular 'H metabolites during a similar time period for this = 0.05 model, presumed to reflect enhanced metabolite mobility as the intracellular water fraction increased (21).…”

Section: Discussionmentioning

confidence: 60%

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Thornton

Ordidge

Penrice

et al. 1998

Magnetic Resonance in Med

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Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.

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Section: Discussionmentioning

confidence: 60%

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Thornton

Ordidge

Penrice

et al. 1998

Magnetic Resonance in Med

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“…The predictive value of TE 136 ms was slightly better than using a TE of 272 ms. Differences in T2 values of metabolites and the effects of brain hypoxia-ischemia on these T2 values might change metabolite ratios (9,10). Therefore, differences in ratios between neonates with a good or a poor outcome may be more prominent at certain TE.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, T2 values for NAA, Cho, and Cr differ (8,9), and thereby differences in NAA/Cho or NAA/Cr ratios between good outcome and poor outcome groups might be more prominent at certain TE. In addition, T2 values may change following cerebral hypoxia-ischemia (10). Therefore, differences in metabolite ratios might be more prominent at longer TE.…”

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confidence: 99%

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

2001

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Previous studies have shown altered brain metabolism after cerebral hypoxia-ischemia, using magnetic resonance spectroscopy with echo times (TE) of 272 and 136 ms, based on peak-area or peak-height ratios. The present study examined the additional value of proton magnetic resonance spectroscopy with a short TE (31 ms) to predict a poor outcome in neonates with brain hypoxia-ischemia. Studies were performed in 21 full-term neonates with perinatal asphyxia in a 1.5 tesla magnetic field. Proton magnetic resonance spectroscopy was performed in a single volume of interest including the basal ganglia. TE of 272, 136 and 31 ms were used. After curve-fitting procedures, peakareas as well as peak-height ratios of different brain metabolites were calculated, comparing patients with a poor versus a good outcome. Seven neonates out of 21 had a poor outcome. Neonates with a poor outcome showed a significantly lower Nacetylaspartate/choline (NAA/Cho) and a significantly raised lactate/NAA (Lac/NAA) ratio using TE of 272 and 136 ms. Using a TE of 31 ms, no differences were found in glutamate/ NAA (Glx/NAA), Glx/Cho, myo-inositol/NAA (mI/NAA), and mI/Cho ratios between neonates with a good and those with a poor outcome. Highest predictive values could be achieved for NAA/Cho with a TE of 136 ms. We conclude that low NAA/Cho and high Lac/NAA ratios predict a poor outcome in neonates with cerebral hypoxia-ischemia. Previous studies have shown changes in the cerebral metabolism of human neonates and of animals following hypoxiaischemia (1-5). Using 1 H-MRS, decreases in NAA/Cho and NAA/Cr ratios were noted to predict poor neurodevelopment (1). An increased brain Lac, which, under normal circumstances, is present in only very small amounts in the neonatal brain and is hardly detectable by 1 H-MRS at term age, also predicts a poor outcome (3, 6). These studies used TE of 272 or 136 ms (1, 2, 4, 6). Using a TE of 272 ms, the peak at 1.33 ppm represents Lac. Using a TE of 136 ms, the Lac peak will be inverted, thereby distinguishing between Lac and lipids or macromolecules. Due to coupling effects, the amplitude of the Lac peak is expected to be smaller at TE 136 ms compared with TE 272 ms (7). Secondly, T2 values for NAA, Cho, and Cr differ (8, 9), and thereby differences in NAA/Cho or NAA/Cr ratios between good outcome and poor outcome groups might be more prominent at certain TE. In addition, T2 values may change following cerebral hypoxia-ischemia (10). Therefore, differences in metabolite ratios might be more prominent at longer TE. In fact, a recent study demonstrated a better predictive value for a long TE (270 ms) versus a short TE (20 ms) in occipital gray matter of young children (11).With shorter TE, e.g. 30 ms, lipids and macromolecules can be identified. Especially in ischemic brain areas, these metabolites with resonances of 0.9 -1.3 ppm will be elevated massively, thereby complicating the detection of lactate at 1.33 ppm (12

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“…Previous studies in infants with NE at Ͻ1 wk of age (median, 1.8 d) concur with our findings (34); studies conducted in infants with NE at Ն1 wk of age have demonstrated a decrease in NAA/Cr (19) and NAA/Cho (53) ratios in infants with a poor neurodevelopmental outcome. This delay in reduction in NAA/Cr or NAA/Cho may indicate that neuronal loss occurred during a prolonged time or that a reduced NAA concentration may be masked by increased metabolite T 2 values during secondary energy failure (54).…”

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confidence: 99%

Early Increases in Brain myo-Inositol Measured by Proton Magnetic Resonance Spectroscopy in Term Infants with Neonatal Encephalopathy

et al. 2001

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Our aim was to assess brain myo-inositol/creatine plus phosphocreatine (Cr) in the first week in term infants with neonatal encephalopathy using localized short echo time proton magnetic resonance spectroscopy and to relate this to measures of brain injury, specifically lactate/Cr in the first week, basal ganglia changes on magnetic resonance imaging (MRI), and neurodevelopmental outcome at 1 y. Fourteen term infants with neonatal encephalopathy of gestational age (mean Ϯ SD) 39.6 Ϯ 1.6 wk, birth weight 3270 Ϯ 490 g, underwent MRI and magnetic resonance spectroscopy at 3.5 Ϯ 2.1 d. Five infants were entered in a pilot study of treatment with moderate whole-body hypothermia for neonatal encephalopathy; two were being cooled at the time of the scan. T 1 -and T 2 -weighted transverse magnetic resonance images were graded as normal or abnormal according to the presence or absence of the normal signal intensity of the posterior limb of the internal capsule and signal intensity changes in the basal ganglia. Localized proton magnetic resonance spectroscopy data were obtained from an 8-cm 3 voxel in the basal ganglia using echo times of 40 and 270 ms, and the peak area ratios of myo-inositol/Cr and lactate/Cr were measured. Outcome was scored using Griffith's development scales and neurodevelopmental examination at 1 y. MRI and outcome were normal in six infants and abnormal in eight. myo-Inositol/Cr and lactate/Cr were higher in infants with abnormal MRI and outcome (p Ͻ 0.01, p Ͻ 0.01, respectively). myo-Inositol/Cr and lactate/Cr were correlated (p Ͻ 0.01) and were both correlated to the Griffith's developmental scales (p Ͻ 0.01, p Ͻ 0.01, respectively). In conclusion, these preliminary data suggest that early increases in brain basal ganglia myo-inositol/Cr in infants with neonatal encephalopathy are associated with increased lactate/Cr, MRI changes of severe injury, and a poor neurodevelopmental outcome at 1 y. (Pediatr Res 50: 692-700, 2001) Abbreviations MRS, magnetic resonance spectroscopy HI, hypoxia-ischemia MRI, magnetic resonance imaging TE, echo time PLIC, posterior limb of the internal capsule Cr, creatine plus phosphocreatine NAA, N-acetyl-aspartate NE, neonatal encephalopathy SMIT, Na ϩ /myo-inositol cotransporter MR, magnetic resonance OS, optimality score SI, signal intensity PRESS, point-resolved spectroscopy Cho, choline-containing compounds DQ, development quotient Cellular adaptation to osmotic stress is a vital process that protects cells from the effects of dehydration or edema. To maintain homeostasis cells produce osmolytes, molecules designed to create osmolality without compromising other cell functions (1).Osmolytes appear to be especially important in the brain as alterations in ion composition would affect excitability. myoInositol is one of the major osmolytes present in the CNS; others include sorbitol, taurine, betaine, and glycerophosphocholine.myo-Inositol transport inside cells comprises uptake, which is selective and actively driven by SMIT (2), and efflux, which is nonselective and...

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Brain-metabolite transverse relaxation times in magnetic resonance spectroscopy increase as adenosine triphosphate depletes during secondary energy failure following acute hypoxia-ischaemia in the newborn piglet

Cited by 35 publications

References 14 publications

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic‐ischemic injury: Relationships to cerebral energy metabolism

Value of 1H-MRS Using Different Echo Times in Neonates with Cerebral Hypoxia-Ischemia

Early Increases in Brain myo-Inositol Measured by Proton Magnetic Resonance Spectroscopy in Term Infants with Neonatal Encephalopathy

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