Quantitative MRI of Microstructure and Iron Homeostasis in ADHD Brain

注意力缺陷/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严重的终生损害。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。ADHD儿童的皮质外套膜厚度也在全球范围内减少，这在区域内最明显的是前额叶上皮质和内侧皮质。除了这一净体积缺陷，ADHD儿童还表现出严重延迟的额叶皮质雕刻的发育轨迹，这通常发生在儿童后期和青春期早期。总的来说，脑组织的微结构和神经生理学都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而对正常的大脑发育起重要作用。尽管一些研究表明血清铁异常与ADHD之间存在联系，但尚未直接研究脑铁稳态的参与及其对ADHD的影响。所有这些发现都突显了解决其他非特异性形态发现的生物物理和神经生理学基础的重要性。 这项建议的目的是研究正常儿童和ADHD儿童脑铁稳态与组织微结构之间的关系，特别关注额顶内侧环路。具体地说，我们感兴趣的是，改变的脑铁稳态和组织微结构是否与年龄、性别和疾病严重程度相关。为了研究这一点，我们将使用成熟的MRI技术(T2、T2*和扩散张量成像)以及两种新的定量MRI技术：磁场相关成像(MFC)和弥散峰度成像(DKI)，对典型发育中的儿童和ADHD儿童进行横断面研究。这种方法将导致对疾病过程的更好的了解，并有可能成为监测治疗的手段。

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