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In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR).

Simões RV, Muñoz-Moreno E, Carbajo RJ, González-Tendero A, Illa M, Sanz-Cortés M, Pineda-Lucena A, Gratacós E - PLoS ONE (2015)

Bottom Line: Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma.Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury).Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.

View Article: PubMed Central - PubMed

Affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

ABSTRACT

Background: Intrauterine growth restriction (IUGR) is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI) and spectroscopy (MRS), to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.

Methods: IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i) absolute metabolite quantifications, using linear fitting; (ii) local temperature estimations, based on the water chemical shift; and (iii) classification, using spectral pattern analysis.

Results: Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury). Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.

Conclusions: IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

No MeSH data available.


Related in: MedlinePlus

In vivo MRI with brain atlas registration and MRS voxel positions.(A) semi-automatic atlas registration on coronal T2-w image–legend: blue, cingulated cortex; orange and brown (outer), parietal cortex; purple, temporal cortex; grey, entorhinal cortex; red, subcortical white matter; green, hippocampus; orange and brown (inner), thalamus; yellow, corpus callosum; light orange, diencephalon. (B) MRS voxel positions on reference coronal T2-w MR images–from left to right: cortex, hippocampus, striatum.
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pone.0131310.g001: In vivo MRI with brain atlas registration and MRS voxel positions.(A) semi-automatic atlas registration on coronal T2-w image–legend: blue, cingulated cortex; orange and brown (outer), parietal cortex; purple, temporal cortex; grey, entorhinal cortex; red, subcortical white matter; green, hippocampus; orange and brown (inner), thalamus; yellow, corpus callosum; light orange, diencephalon. (B) MRS voxel positions on reference coronal T2-w MR images–from left to right: cortex, hippocampus, striatum.

Mentions: In one of the litters, one IUGR newborn died before starting the MR study. Thus, a total of six controls and five IUGR newborns from three litters underwent MR examination within the first 8 h after delivery. The body weights of this subcohort (6 controls, 50–62g; 5 IUGRs, 29–36g) were representative of the main cohort (Table 1), and the relative positions of those fetuses in the respective horn were not significantly different between IUGRs (0.5±0.2) and controls (0.7±0.3, p = 0.279). IUGR pups were significantly smaller than controls (-44% body weight) and had smaller placentas (-43% weight) (Table 1). The registration of in vivo MRI data with the digital atlas of the rabbit brain showed differences in the estimated average volumes of the total brain and specific brain tissues investigated (Fig 1A). These parameters were all significantly smaller compared to controls: total brain, -18%; cortex, -19%; hippocampus, -23%; and striatum, -21% (Table 1). The estimated contribution of each tissue studied to the respective MRS voxel (Fig 1B) was always >50%, although some significant differences were noticed in cortex and hippocampus due to overall smaller sizes in IUGR (Table 1). Specifically in the cortex region, the average relative composition of cortical tissue in the voxel was: cingulate cortex, 60%; frontal cortex, 6%; medial frontal cortex, 4%; and parietal cortex, 9%. Moreover, the animal body (rectal) temperatures remained constant throughout the MR studies, and were identical in both groups (around 35°C). However, the estimated brain temperatures in the three brain regions studied were consistently lower than the body temperature (around 31–32°C). Also, estimated local temperatures in IUGR brains were slightly lower than in controls, reaching significance only in the cortex region (Table 1).


In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR).

Simões RV, Muñoz-Moreno E, Carbajo RJ, González-Tendero A, Illa M, Sanz-Cortés M, Pineda-Lucena A, Gratacós E - PLoS ONE (2015)

In vivo MRI with brain atlas registration and MRS voxel positions.(A) semi-automatic atlas registration on coronal T2-w image–legend: blue, cingulated cortex; orange and brown (outer), parietal cortex; purple, temporal cortex; grey, entorhinal cortex; red, subcortical white matter; green, hippocampus; orange and brown (inner), thalamus; yellow, corpus callosum; light orange, diencephalon. (B) MRS voxel positions on reference coronal T2-w MR images–from left to right: cortex, hippocampus, striatum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514800&req=5

pone.0131310.g001: In vivo MRI with brain atlas registration and MRS voxel positions.(A) semi-automatic atlas registration on coronal T2-w image–legend: blue, cingulated cortex; orange and brown (outer), parietal cortex; purple, temporal cortex; grey, entorhinal cortex; red, subcortical white matter; green, hippocampus; orange and brown (inner), thalamus; yellow, corpus callosum; light orange, diencephalon. (B) MRS voxel positions on reference coronal T2-w MR images–from left to right: cortex, hippocampus, striatum.
Mentions: In one of the litters, one IUGR newborn died before starting the MR study. Thus, a total of six controls and five IUGR newborns from three litters underwent MR examination within the first 8 h after delivery. The body weights of this subcohort (6 controls, 50–62g; 5 IUGRs, 29–36g) were representative of the main cohort (Table 1), and the relative positions of those fetuses in the respective horn were not significantly different between IUGRs (0.5±0.2) and controls (0.7±0.3, p = 0.279). IUGR pups were significantly smaller than controls (-44% body weight) and had smaller placentas (-43% weight) (Table 1). The registration of in vivo MRI data with the digital atlas of the rabbit brain showed differences in the estimated average volumes of the total brain and specific brain tissues investigated (Fig 1A). These parameters were all significantly smaller compared to controls: total brain, -18%; cortex, -19%; hippocampus, -23%; and striatum, -21% (Table 1). The estimated contribution of each tissue studied to the respective MRS voxel (Fig 1B) was always >50%, although some significant differences were noticed in cortex and hippocampus due to overall smaller sizes in IUGR (Table 1). Specifically in the cortex region, the average relative composition of cortical tissue in the voxel was: cingulate cortex, 60%; frontal cortex, 6%; medial frontal cortex, 4%; and parietal cortex, 9%. Moreover, the animal body (rectal) temperatures remained constant throughout the MR studies, and were identical in both groups (around 35°C). However, the estimated brain temperatures in the three brain regions studied were consistently lower than the body temperature (around 31–32°C). Also, estimated local temperatures in IUGR brains were slightly lower than in controls, reaching significance only in the cortex region (Table 1).

Bottom Line: Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma.Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury).Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.

View Article: PubMed Central - PubMed

Affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

ABSTRACT

Background: Intrauterine growth restriction (IUGR) is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI) and spectroscopy (MRS), to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.

Methods: IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i) absolute metabolite quantifications, using linear fitting; (ii) local temperature estimations, based on the water chemical shift; and (iii) classification, using spectral pattern analysis.

Results: Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury). Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.

Conclusions: IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

No MeSH data available.


Related in: MedlinePlus