Drobyshevsky Alexander, Jiang Rugang, Derrick Matthew, Luo Kehuan, Tan Sidhartha
Department of Pediatrics, NorthShore University HealthSystem Research Institute, Evanston, IL, USA.
Department of Pediatrics, NorthShore University HealthSystem Research Institute, Evanston, IL, USA.
Exp Neurol. 2014 Nov;261:76-86. doi: 10.1016/j.expneurol.2014.06.021. Epub 2014 Jul 2.
Anisotropy indices derived from diffusion tensor imaging (DTI) are being increasingly used as biomarkers of central WM structural maturation, myelination and even functional development. Our hypothesis was that the rate of functional changes in central WM tracts directly reflects rate of changes in structural development as determined by DTI indices. We examined structural and functional development of four major central WM tracts with different maturational trajectories, including internal capsule (IC), corpus callosum (CC), fimbria hippocampi (FH) and anterior commissure (AC). Rabbits were chosen due to perinatal brain development being similar to humans, and four time points were studied: P1, P11, P18 and adults. Imaging parameters of structural maturation included fractional anisotropy (FA), mean and directional diffusivities derived from DTI, and T2 relaxation time. Axonal composition and degree of myelination were confirmed on electron microscopy. To assess functional maturation, conduction velocity was measured in myelinated and non-myelinated fibers by electrophysiological recordings of compound action potential in perfused brain slices. Diffusion indices and T2 relaxation time in rabbits followed a sigmoid curve during development similar to that for humans, with active changes even at premyelination stage. The shape of the developmental curve was different between the fiber tracts, with later onset but steeper rapid phase of development in IC and FH than in CC. The structural development was not directly related to myelination or to functional development. Functional properties in projection (IC) and limbic tracts (FH) matured earlier than in associative and commissural tracts (CC and AC). The rapid phase of changes in diffusion anisotropy and T2 relaxation time coincided with the development of functional responses and myelination in IC and FH between the second and third weeks of postnatal development in rabbits. In these two tracts, MRI indices could serve as surrogate markers of the early stage of myelination. However, the discordance between developmental change of diffusion indices, myelination and functional properties in CC and AC cautions against equating DTI index changes as biomarkers for myelination in all tracts.
源自扩散张量成像（DTI）的各向异性指数正越来越多地被用作中枢白质结构成熟、髓鞘形成乃至功能发育的生物标志物。我们的假设是，中枢白质束功能变化的速率直接反映了由DTI指数所确定的结构发育变化的速率。我们研究了具有不同成熟轨迹的四条主要中枢白质束的结构和功能发育，包括内囊（IC）、胼胝体（CC）、海马伞（FH）和前连合（AC）。选择兔子是因为其围产期脑发育与人类相似，并研究了四个时间点：出生后第1天（P1）、第11天（P11）、第18天（P18）和成年期。结构成熟的成像参数包括分数各向异性（FA）、源自DTI的平均扩散率和方向扩散率，以及T2弛豫时间。通过电子显微镜确认轴突组成和髓鞘形成程度。为了评估功能成熟，通过对灌注脑片复合动作电位的电生理记录来测量有髓和无髓纤维的传导速度。兔子在发育过程中的扩散指数和T2弛豫时间遵循与人类相似的S形曲线，甚至在髓鞘形成前期也有活跃变化。纤维束之间发育曲线的形状不同，IC和FH的发育起始较晚但快速发育阶段比CC更陡峭。结构发育与髓鞘形成或功能发育没有直接关系。投射束（IC）和边缘束（FH）的功能特性比联合束和连合束（CC和AC）成熟得更早。兔子出生后第二至第三周期间，IC和FH中扩散各向异性和T2弛豫时间的快速变化阶段与功能反应和髓鞘形成的发育相吻合。在这两条束中，MRI指数可作为髓鞘形成早期阶段的替代标志物。然而，CC和AC中扩散指数、髓鞘形成和功能特性的发育变化之间的不一致警示我们，不要将DTI指数变化等同于所有束中髓鞘形成的生物标志物。
