Quantitative MRI of Microstructure and Iron Homeostasis in ADHD Brain

注意缺陷/多动障碍是儿童精神病学中研究最多的疾病，反映了其高患病率和显著的终身损害。尽管在记录这种疾病的生物学基础方面取得了进展，但我们仍然缺乏有用的病理生理学模型。与许多其他精神疾病类似，ADHD被认为是分布式神经回路完整性受损的结果，然而，ADHD的神经基础仍然不够明确。患有多动症的儿童也普遍出现皮质套厚度下降，这在前额叶上部和内侧皮层区域最为明显。除了净体积缺陷外，患有多动症的儿童还表现出额叶皮质发育轨迹的严重延迟，这通常发生在儿童晚期和青少年早期。一般来说，脑组织的微观结构和神经生理学与其潜在的功能密切相关，众所周知，铁通过其在髓鞘形成中的重要作用对正常的大脑发育很重要。尽管有几项研究表明血清铁异常与多动症之间存在联系，但尚未直接研究脑铁稳态的参与及其对多动症的影响。所有这些发现都强调了解决非特异性形态学发现的生物物理和神经生理基础的重要性。

Attention-Deficit/Hyperactivity Disorder is the most studied condition in child psychiatry, reflecting its high prevalence and significant lifelong impairment. Despite progress in documenting the biological bases for the disorder, we still lack useful models of pathophysiology. Similar to many other psychiatric illnesses, ADHD is believed to result from compromises in the integrity of distributed neural circuits, however, the neural bases of ADHD remain insufficiently specified. Children with ADHD also have globally decreased thickness of the cortical mantle, which is regionally most pronounced in superior and medial prefrontal cortex. Besides this net volumetric deficit, children with ADHD also exhibit profoundly delayed developmental trajectories of the frontal cortical sculpting that normally takes place over late childhood and early adolescence. In general, both the microstructure and the neurophysiology of brain tissues are closely associated with their underlying function and it is well known that iron is important for normal brain development through its essential role in myelination. Although several studies have suggested a link between serum iron abnormalities and ADHD, the involvement of brain iron homeostasis and its effects on ADHD have not been studied directly. All of these findings highlight the importance of addressing the biophysical and neurophysiological foundation of otherwise non-specific morphologic findings. The goal of this proposal is to investigate the relationship between brain iron homeostasis and tissue microstructure in normal and ADHD children with particular focus on the medial frontal-parietal circuits. Specifically, we are interested in whether altered brain iron homeostasis and tissue microstructure are correlated with age, gender and disease severity. To investigate this, we will conduct a cross-sectional study in both typically developing and ADHD children using well established MRI techniques (T2, T2* and diffusion tensor imaging) along with two new quantitative MRI techniques; Magnetic Field Correlation (MFC) imaging and Diffusional Kurtosis Imaging (DKI). This approach will lead to a better understanding of the disease process and, potentially, to a means of monitoring therapy