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: 14.95). 12/2009; 121(1):26-33. DOI: 10.1161/CIRCULATIONAHA.109.865568
Source: PubMed

ABSTRACT 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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    • "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 · 2.92 Impact Factor
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    • "Based on severe CHDs and immune deficiency, death occurs during the first year of life in up to 95% of cases, mostly affecting males [1] [2] [4] [6]. Although periventricular cysts (possibly ischemic) were found in only one fetus, individuals with CHDs, including those with heterotaxy, may also present with brain developmental abnormalities, as recently demonstrated by fetal MRI [17]. Prenatal MRI with its multiplanar capabilities seems useful in the visualization of multiple spleens and in confirming splenic absence, which might be related to poor survival outcomes. "
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    ABSTRACT: Situs anomalies refer to an abnormal organ arrangement, which may be associated with severe errors of development. Due regard being given to prenatal magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US), this study sought to demonstrate the in utero visualization of situs anomalies on MRI, compared to US. This retrospective study included 12 fetuses with situs anomalies depicted on fetal MRI using prenatal US as a comparison modality. With an MRI standard protocol, the whole fetus was assessed for anomalies, with regard to the position and morphology of the following structures: heart; venous drainage and aorta; stomach and intestines; liver and gallbladder; and the presence and number of spleens. Situs inversus totalis was found in 3/12 fetuses; situs inversus with levocardia in 1/12 fetuses; situs inversus abdominis in 2/12 fetuses; situs ambiguous with polysplenia in 3/12 fetuses, and with asplenia in 2/12 fetuses; and isolated dextrocardia in 1/12 fetuses. Congenital heart defects (CHDs), vascular anomalies, and intestinal malrotations were the most frequent associated malformations. In 5/12 cases, the US and MRI diagnoses were concordant. Compared to US, in 7/12 cases, additional MRI findings specified the situs anomaly, but CHDs were only partially visualized in six cases. Our initial MRI results demonstrate the visualization of situs anomalies and associated malformations in utero, which may provide important information for perinatal management. Using a standard protocol, MRI may identify additional findings, compared to US, which confirm and specify the situs anomaly, but, with limited MRI visualization of fetal CHDs.
    European journal of radiology 06/2011; 81(4):e495-501. DOI:10.1016/j.ejrad.2011.06.016 · 2.16 Impact Factor
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