Neuroimaging Core

结构和功能成像方法 先进的成像技术提供了对发育障碍患者大脑功能变化的详细了解，并为测试治疗方法提供了一种手段。分子生物学革命揭示了无数影响大脑发育的基因类型。神经成像使我们能够确定与特定突变相关的表型。多种成像方式的组合--MRI、MEG、CT、PET和SPECT--为疾病提供了独特的地区性特征。成像有几个明显的优势： 1.影像是无创的。 2.成像提供对脑组织结构、生理、功能和生化方面的区域性(空间局部化)评估。尽管单一的形态不能提供这种广泛的表征， MRI、CT、SPECT和PET信息的空间注册集成可以提供“成像” 表型，或特征。结合脑磁图的时间和光谱信息，这种“表型”可以扩展到5个维度。 3.它允许全身筛查潜在的毒物和副作用以及非局部传播。 4.“影像”表型可以在其每个领域中进行量化，以提供疾病进展和治疗反应的客观指标。这种定量可以是体积(如区域大小)、形态(如包裹性与浸润性、星状肿瘤)或沿生理轴线的参数(如裂隙组织血容量、微血管通透性或葡萄糖代谢率)。 5.使用影像标准作为临床前(以及临床)试验的“纳入标准”，将改善样本人群的均质性，加快药物评估过程，并为患者分层/选择治疗提供客观标准或一套标准。 6.成像是翻译的。MRI、CT、SPECT和PET可以在人类临床前和临床试验中进行。 与在动物模型中建立的一样，同样的生物标记物也可以用于人类。此外，成像可能提供生物反应的早期证据。相反，无反应的患者可以在更早的阶段被识别出来，并且可以改变治疗方法。 7.临床前成像在伦理上是适当的，因此最大限度地减少了对实验室动物的使用。临床前成像可以使用系列化设计。这有很多优点：(I)通过使用每只小鼠作为自己的“对照”，不需要知道疾病进展的准确速度。因此，可以在不假定队列平均值的情况下确定队列反应的微小差异：(2)统计能力得到改善。例如，配对t检验可用于筛选治疗后的肿瘤体积，(ILI)非侵入性成像可在症状出现之前发现疾病，(Iv)可研究队列中的个体差异，从而 反映了患者的变异性。

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.