Near-infrared frequency-domain optical spectroscopy and magnetic resonance imaging: a combined approach to studying cerebral maturation in neonatal rabbits

Abstract

The neonatal rabbit brain shows prolonged postnatal development both structurally and physiologically. We use noninvasive near-IR frequency-domain optical spectroscopy (NIRS) and magnetic resonance imaging (MRI) to follow early developmental changes in cerebral oxygenation and anatomy, respectively. Four groups of animals are measured: NIRS in normals, MRI in normals, and both NIRS and MRI with hypoxia-ischemia (HI) (diffusion MRI staging). NIRS and/or MRI are performed from P3 (postnatal day=P) up to P76. NIRS is performed on awake animals with a frequency-domain tissue photometer. Absolute values of oxyhemoglobin concentration ([HbO 2 ]), deoxyhemoglobin concentration ([HbR]), total hemoglobin concentration (HbT), and hemoglobin saturation (StO 2 ) are calculated. The brains of all animals appeared to be maturing as shown in the diffusion tensor MRI. Mean optical coefficients (reduced scattering) remained unchanged in all animals throughout. StO 2 increased in all animals (40% at P9 to 65% at P43) and there are no differences between normal, HI controls, and HI brains. The measured increase in StO 2 is in agreement with the reported increase in blood flow during the first 2 months of life in rabbits. HbT, which reflects blood volume, peaked at postnatal day P17, as expected since the capillary density increases up to P17 when the microvasculature matures.

Functional correlates of central white matter maturation in perinatal period in rabbits

“…3), similar to changes reported for neonatal rabbits (D'Arceuil et al, 2005; D'Arceuil et al, 2008; Drobyshevsky et al, 2005), rodents (Calabrese and Johnson, 2013), kittens (Baratti et al, 1999) and humans (Mukherjee et al, 2001). It has long been established that myelination is not a prerequisite to the origin of diffusion anisotropy in WM (Beaulieu, 2002), and WM tracts are substantially anisotropic on diffusion weighted images even in fetuses and neonates much before the onset of myelination (Drobyshevsky et al, 2005; Wimberger et al, 1995).…”

“…This period of development in rabbits is characterized by reaching important behavioral milestones: eye opening, increase of locomotive abilities, hopping and first exploratory behavior. Maturation of DTI indices continues is rabbits during at least four postnatal weeks (D'Arceuil et al, 2005). Similar, rapid phase of FA change between P12 and P24 coincides with the onset of active myelination in rats (Calabrese and Johnson, 2013; Jito et al, 2008).…”

Three-Dimensional High-Resolution Diffusion Tensor Imaging and Tractography of the Developing Rabbit Brain

“…It is known that all white matter structures show increasing FA with age and this has been published for in vivo rabbit brain [D'Arceuil et al, 2005], for human brain [Neil et al, 1998Prayer et al, 2001;Wolf et al, 2001;Forbes et al, 2002;Mukherjee et al, 2002;Schmithorst et al, 2002;Schneider et al, 2004;Ben Bashat et al, 2005;Gupta et al, 2005;Snook et al, 2005;Dubois et al, 2006] and for other animal brains [Mori et al, 2001;Kroenke et al, 2005;Zhang et al, 2005]. The structural coherence of the cerebral white matter (in perfusionfixed tissue) is known to be preserved postmortem [Sun et al, 2003[Sun et al, , 2005 and we have shown increased FA in all major white matter structures with increasing postnatal age in our postmortem, perfusion-fixed brains.…”

“…The rabbits' brains are lissencephalic, i.e., there is no cortical folding, and the average cortical thickness, measured on in vivo T 2 -weighted magnetic resonance images, increases at least up to the 6th postnatal week. In addition, myelination continues in the corpus callosum, internal capsule and the centrum semiovale up to at least the 4th week postpartum [D'Arceuil et al, 2005]. In comparison, the brains of human neonates continue to myelinate postnatally, in particular the corticospinal (CST) and corticobulbar (CBT) tracts continue to myelinate until 2 years of age [Sarnat, 1989].…”

“…FA increases during myelination, i.e., during brain maturation and is decreased in certain disease states [Okuda, 1994;Huppi et al, 1998;Neil et al, 1998;Klingberg et al, 1999Klingberg et al, , 2000Woolley et al, 2000;Guo et al, 2001Guo et al, , 2002Wolf et al, 2001;Forbes et al, 2002;Snook et al, 2005]. A previous in vivo DTI study in rabbits has shown that FA increases in the major white matter structures within the first postnatal month [D'Arceuil et al, 2005]. In postmortem tissue, which is perfused fixed or fixed directly after death , diffusion anisotropy is preserved [Sun et al, 2003[Sun et al, , 2005 and this allows the acquisition of very-high-resolution DTI of fixed tissue which can reveal submillimeter tissue structure, particularly in the gray matter, which is difficult to measure in the in vivo images [Mori et al, 2001;Kroenke et al, 2005;Zhang et al, 2005] because of the very long imaging times required for these scans ( 6 5 h) .…”