Neuroimaging Core

结构和功能成像方法 先进的成像技术提供了一个详细的了解改变大脑功能的发育障碍，以及一种手段，以测试治疗。分子生物学革命揭示了影响大脑发育的无数基因型。神经影像学使我们能够表征与特定突变相关的表型。多种成像模式的组合- MRI、MEG、CT、PET和SPECT -提供了独特的疾病区域分析。成像有几个明显的优势： 1.成像是非侵入性的。 2.成像提供脑组织的结构、生理、功能和生化方面的区域（空间定位）评估。虽然单一的模式不能提供这种广泛的特征， MRI、CT、SPECT和PET信息的空间配准集成可以提供“成像” 表型或概况。结合脑磁图的时间和光谱信息，这种“表型”可以扩展到5维。 3.它允许全身筛查潜在的毒性和副作用以及非局部传播。 4.“成像”表型可以在其每个域中定量，以提供疾病进展和对治疗的反应的客观指标。这样的定量可以是体积的（例如区域大小）、形态的（例如包裹性与浸润性、星状肿瘤）或沿生理轴的参数沿着（例如分形组织血容量、微血管渗透性或葡萄糖代谢速率）。 5.使用成像标准作为临床前（以及通过扩展临床）试验的“入选标准”将提高样本群体的同质性，并加快药物评价过程，以及为患者分层/治疗选择提供客观标准或一组标准。 6.成像是平移的。MRI、CT、SPECT和PET可在人体临床前和临床试验中进行。 与在动物模型中建立的生物标志物相同的生物标志物可用于人类。此外，成像可以提供生物反应的早期证据。相反，可以在早期阶段识别无反应的患者，并且可以改变管理。 7.临床前成像在伦理上是适当的，因此最大限度地减少了实验室动物的使用。临床前成像可以使用连续设计。这具有许多优点：（i）通过使用每只小鼠作为其自身的“对照”，不需要知道疾病进展的精确速率。因此，可以在不假设队列平均值的情况下识别队列响应的小差异。（ii）统计功效得到改善。例如，配对t检验可用于筛选治疗后的肿瘤体积。（iii）非侵入性成像揭示了肿瘤学发作之前的疾病，（iv）可研究群组内的个体差异，从而 反映了患者的可变性。

Structural and Functional imaging approaches Advanced imaging technology affords a detailed understanding of altered brain function in the developmental disabilities as well as a means with which to test therapies. The molecular biology revolution has revealed a myriad of genotypes that affect brain development. Neuroimaging permits us to characterize phenotypes that associate with particular mutations. The combination of multiple imaging modalities - MRI, MEG, CT, PET and SPECT - offers a unique regional profiling of disease. Imaging has several distinct advantages: 1. Imaging is non-invasive. 2. Imaging offers regional (spatially-localized) assessment of structural, physiological, functional and biochemical aspects of brain tissue. Although a single modality cannot offer this broad characterization, spatially registered integration of MRI, CT, SPECT and PET information can provide an "imaging" phenotype, or profile. Combined with the temporal and spectral informafion from MEG, this "phenotype" can be extended to 5-dimensions. 3. It allows whole-body screening for potential toxicifies and side effects as well as non-local spread. 4.The "Imaging" phenotype can be quantified in each of its domains to provide objective indices of disease progression and response to therapy. Such quantificafion may be volumetric (e.g. region size), morphologic (e.g. encapsulated vs. infiltrative, stellate tumor) or parametric along physiological axes (such as fracfional tissue blood volume, microvascular permeability or rate of glucose metabolism). 5. Use of imaging criteria as "inclusion criteria" for preclinical (and by extension clinical) trials will improve the homogeneity of the sample populafion and speed up the drug evaluafion process as well as providing an objective criterion or set of criteria for patient stratification/selection for treatment. 6.Imaging is translational. MRI, CT, SPECT and PET can be performed in human preclinical and clinical trials. The same biomarkers can be used in humans as were established in the animal models. Furthermore, imaging may provide eariy evidence of biological response. Conversely a non-responding patient can be identified at an eariier stage and management can be altered. 7. Preclinical imaging is ethically appropriate, thus minimizing use of laboratory animals. Preclinical imaging can use a serial design. This has many advantages: (i) By using each mouse as its own "control", it is not necessary to know the precise rate of disease progression. Consequently, small differences in the response of a cohort can be identified without assuming a cohort mean, (ii) Statistical power is Improved. For example, a paired t test can be used to screen for tumor volume post-treatment, (ili) Non-invasive imaging discloses disease prior to onset of symptomatology, (iv) individual differences within a cohort can be studied, thereby reflecting patient variability.