Neuroimaging Core

神经影像核心

• 批准号: 8038879
• 负责人: Timothy P Roberts
• 金额: $ 21.9万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038879
• 关键词: Achievement; Adolescent; Adverse effects; Affect; Aftercare; Anatomy; Animal Model; Behavioral; Biochemical; Biological; Biological Markers; Blood Volume; Brain; Child; Clinical Trials; Data; Development; Developmental Disabilities; Dimensions; Disease; Disease Progression; Encapsulated; Experimental Designs; Functional Imaging; Genotype; Goals; Human; Image; Image Analysis; Imaging technology; Individual Differences; Laboratory Animals; Life; Magnetic Resonance Imaging; Microvascular Permeability; Modality; Molecular Biology; Mus; Mutation; Neurosciences Research; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Physiological; Positron-Emission Tomography; Process; Resolution; Rodent; Sampling; Screening procedure; Selection for Treatments; Speed; Staging; Stratification; Technology; Testing; Tissues; Tumor Volume; base; brain tissue; cohort; design; glucose metabolism; imaging modality; improved; in vivo; inclusion criteria; indexing; neuroimaging; pre-clinical; response; single photon emission computed tomography; tumor

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.

结构和功能成像方法 先进的成像技术对发育障碍中大脑功能的改变以及测试疗法的手段有了详细的了解。分子生物学革命揭示了无数影响大脑发育的基因型。神经影像允许我们表征与特定突变相关的表型。多种成像方式（MRI，MEG，CT，PET和SPECT）的组合提供了独特的疾病区域分析。成像具有几个不同的优势： 1。成像是无创的。 2。成像提供了脑组织的结构，生理，功能和生化方面的区域（空间定位）评估。尽管单一模式无法提供这种广泛的特征，但 MRI，CT，SPECT和PET信息的空间注册集成可以提供“成像” 表型或配置文件。结合MEG的时间和光谱信息，该“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本地扩散。 4.可以在其每个领域中量化“成像”表型，以提供疾病进展和对治疗反应的客观指标。这种量化可以是体积的（例如区域大小），形态学（例如，封装的与浸润性，星状肿瘤）或沿生理轴的参数（例如，微血管血容量，微血管渗透性或葡萄糖代谢率））。 5。将成像标准用作临床前（和扩展临床）试验的“包容性标准”将改善样本人群的同质性，并加快药物评估过程，并提供客观的标准或一组患者分层/选择治疗的标准。 6.成像是翻译。 MRI，CT，SPECT和PET可以在人类临床前和临床试验中进行。 与动物模型中建立的相同的生物标志物可以在人类中使用。此外，成像可能会提供生物学反应的eariy证据。相反，可以在较高的阶段识别出无反应的患者，并且可以改变管理。 7。临床前成像在道德上是适当的，因此最大程度地减少了实验动物的使用。临床前成像可以使用串行设计。这具有许多优势：（i）通过将每只小鼠用作自己的“控制”，就不必知道疾病进展的确切速度。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，（ii）统计能力得到改善。例如，配对的t检验可用于筛查治疗后肿瘤体积，（ILI）非侵入性成像在症状发作前揭示了疾病，（iv）可以研究组中的个体差异，从而研究，从而研究疾病。 反映患者的变异性。