Brain Volume and Metabolism in Fetuses With Congenital Heart Disease Evaluation With Quantitative Magnetic Resonance Imaging and Spectroscopy

Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Circulation (Impact Factor: 14.43). 12/2009; 121(1):26-33. DOI: 10.1161/CIRCULATIONAHA.109.865568
Source: PubMed


Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity.
Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral N-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25 1/7 to 37 1/7 weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age-adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (P<0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (P<0.001).
Third-trimester fetuses with some forms of CHD have smaller gestational age- and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development.

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    • "Cerebral changes characterized by reduced brain volume and altered metabolism have been demonstrated using magnetic resonance imaging (MRI) and spectroscopy as early as the third trimester in fetuses with cyanotic CHD. The exact mechanisms leading to these findings are not precisely characterized but are likely, in part, a consequence of reduced cerebral blood flow (Limperopoulos et al., 2010; Clouchoux et al., 2012). Reduced oxygen saturations have been found to strongly correlate with reduced frontal GM volume in infants (Watanabe et al., 2009). "
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    ABSTRACT: Background Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized. Hypothesis We hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes. Methods Ten adults with chronic cyanosis from CHD (40 ± 4 years) and mean oxygen saturations of 82 ± 2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects. Results Five of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8 ± 2). Quantitative MRI revealed evidence of extensive generalized WM and GM volumetric loss: Global GM volume was reduced in cyanosed subjects (630 ± 16 vs: 696 ± 14 mL in controls, p = 0.01). Global WM was also reduced (471 ± 10 vs: 564 ± 18 mL, p = 0.003). Ventricular CSF volume was increased (35 ± 10 vs: 26 ± 5 mL, p = 0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p ≤ 0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R = − 0.89, p = 0.009), high sensitivity C-reactive protein (R = − 0.964, p < 0.0001) and asymmetric dimethylarginine (R = − 0.75, p = 0.026) but not with oxygen saturations, packed cell volume or viscosity. Conclusions We present the first comprehensive analysis of brain structure in adults with chronic neurocyanosis due to congenital heart disease. We demonstrate clear evidence for marked macro- and microvascular injury. Cyanotic patients show global evidence for reduced brain volume as well as specific foci of cortical thickness reduction. The GM volume loss correlated with hsCRP, BNP and ADMA suggesting that inflammation, neurohormonal activation and endothelial dysfunction may have important roles in its pathogenesis.
    Clinical neuroimaging 01/2014; 4. DOI:10.1016/j.nicl.2013.12.011 · 2.53 Impact Factor
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    • "Children with HLHS have reduced IQ and a variety of deficits of neurocognitive function [47]. While some of this is likely to be due to neurologic insults occurring during cardiac surgery and the post-operative period, recent studies have suggested that newborns with HLHS have brain abnormalities at birth [10] and that their brain growth and metabolism are abnormal towards the end of gestation [48]. One possible etiology is inadequate cerebral perfusion due to abnormal fetal hemodynamics. "
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    ABSTRACT: The distribution of blood flow in fetuses with congenital heart disease (CHD) is likely to influence fetal growth, organ development, and postnatal outcome, but has previously been difficult to study. We present the first measurements of the distribution of the fetal circulation in left-sided CHD made using phase contrast cardiac magnetic resonance (CMR). Twenty-two fetuses with suspected left-sided CHD and twelve normal controls underwent fetal CMR and echocardiography at a mean of 35 weeks gestation (range 30--39 weeks). Fetuses with left-sided CHD had a mean combined ventricular output 19% lower than normal controls (p < 0.01). In fetuses with left-sided CHD with pulmonary venous obstruction, pulmonary blood flow was significantly lower than in those with left-sided CHD without pulmonary venous obstruction (p < 0.01). All three fetuses with pulmonary venous obstruction had pulmonary lymphangectasia by fetal CMR and postnatal histology. Fetuses with small but apex forming left ventricles with left ventricular outflow tract or aortic arch obstruction had reduced ascending aortic and foramen ovale flow compared with normals (p < 0.01). Fetuses with left-sided CHD had more variable superior vena caval flows than normal controls (p < 0.05). Six fetuses with CHD had brain weights at or below the 5th centile for gestational age, while none of the fetuses in the normal control group had brain weights below the 25th centile. Measurement of the distribution of the fetal circulation in late gestation left-sided CHD is feasible with CMR. We demonstrated links between fetal blood flow distribution and postnatal course, and examined the relationship between fetal hemodynamics and lung and brain development. CMR enhances our understanding of pathophysiology of the fetal circulation and, with more experience, may help with the planning of perinatal management and fetal counselling.
    Journal of Cardiovascular Magnetic Resonance 07/2013; 15(1):65. DOI:10.1186/1532-429X-15-65 · 4.56 Impact Factor
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    • "Future developments will include the application of our automatic tissue segmentation to clinical scans with diagnosed abnormalities, such as ventriculomegaly, to describe how brain volume deviates regionally in altered development (e.g. Kazan-Tannus et al., 2007; Limperopoulos et al., 2010). Further application of our atlas-based tissue segmentation to in utero imaging later in the third trimester may improve the understanding for normal fetal brain development by comparison to imaging studies of premature brains (Huppi et al., 1998). "
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    ABSTRACT: In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 08/2011; 29(5):529-36. DOI:10.1016/j.ijdevneu.2011.04.001 · 2.58 Impact Factor
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