Project description:Imaging biomarkers play a wide-ranging role in clinical trials for neurological disorders. This includes selecting the appropriate trial participants, establishing target engagement and mechanism-related pharmacodynamic effect, monitoring safety, and providing evidence of disease modification. In the early stages of clinical drug development, evidence of target engagement and/or downstream pharmacodynamic effect-especially with a clear relationship to dose-can provide confidence that the therapeutic candidate should be advanced to larger and more expensive trials, and can inform the selection of the dose(s) to be further tested, i.e., to "de-risk" the drug development program. In these later-phase trials, evidence that the therapeutic candidate is altering disease-related biomarkers can provide important evidence that the clinical benefit of the compound (if observed) is grounded in meaningful biological changes. The interpretation of disease-related imaging markers, and comparability across different trials and imaging tools, is greatly improved when standardized outcome measures are defined. This standardization should not impinge on scientific advances in the imaging tools per se but provides a common language in which the results generated by these tools are expressed. PET markers of pathological protein aggregates and structural imaging of brain atrophy are common disease-related elements across many neurological disorders. However, PET tracers for pathologies beyond amyloid β and tau are needed, and the interpretability of structural imaging can be enhanced by some simple considerations to guard against the possible confound of pseudo-atrophy. Learnings from much-studied conditions such as Alzheimer's disease and multiple sclerosis will be beneficial as the field embraces rarer diseases.
Project description:Background: The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their relevance to DNAm profiles from pediatric samples. Given that DNAm patterns in early life undergo rapid changes and have been linked to a wide range of health outcomes and environmental exposures, direct investigations of tissue-specific DNAm variation in pediatric samples may help inform the design and interpretation of DNAm analyses from early life cohorts. In this study, we present a systematic comparison of genome-wide DNAm patterns between matched pediatric buccal epithelial cells (BECs) and peripheral blood mononuclear cells (PBMCs), two of the most widely used peripheral tissues in human epigenetic studies. Specifically, we assessed DNAm variability, cross-tissue DNAm concordance and genetic determinants of DNAm across two independent early life cohorts encompassing different ages. Results: BECs had greater inter-individual DNAm variability compared to PBMCs and highly variable CpGs were more likely to be positively correlated between the matched tissues compared to less variable CpGs. These sites were enriched for CpGs under genetic influence, suggesting that a substantial proportion of DNAm co-variation between tissues can be attributed to genetic variation. Finally, we demonstrated the relevance of our findings to human epigenetic studies by categorizing CpGs from published DNAm association studies of pediatric BECs and peripheral blood. Conclusions: Taken together, our results highlight a number of important considerations and practical implications in the design and interpretation of EWAS analyses performed in pediatric peripheral tissues.
Project description:Selecting the best available preventive and therapeutic measures to avoid disability and death is an important goal for all health care practitioners. To achieve this goal, we need to perform studies that determine the value of these measures. In this article, we discuss the possible study designs that can be used for evaluating new approaches to prevention and treatment. The gold standard study design is a randomized, controlled, double-blind trial. In many instances, a randomized controlled trial may not be ethically or practically feasible. Other study types, such as case series, case-control studies, cohort studies, cross-sectional studies, crossover designs, and open-label studies, may be required to hypothesize and evaluate the link between an exposure or predictor variable and an outcome variable. Various study types pertaining to neonatal-perinatal medicine are reviewed in this article.
Project description:The goal of the study was to identify transcriptional correlates of SLE disease activity both at the cohort and at the individual levels. To do so, we longitudinally profiled the whole blood transcriptomes of 158 SLE patients by microarray for up to 4 years, yielding 924 SLE samples and 48 matched pediatric healthy samples. The transcriptional data are complemented by demographic, laboratory and clinical data.
Project description:In the last decade, several radiopharmaceuticals have been developed and investigated for imaging in vivo of pediatric brain tumors with the aim of exploring peculiar metabolic processes as glucose consumption, amino-acid metabolism, and protein synthesis with nuclear medicine techniques. Although the clinical shreds of evidence are limited, preliminary results are encouraging. In this review, we performed web-based and desktop research summarizing the most relevant findings of the literature published to date on this topic. Particular attention was given to the wide spectrum of nuclear medicine advances and trends in pediatric neurooncology and neurosurgery. Furthermore, the role of somatostatin receptor imaging through single-photon emission computed tomography (SPECT) and positron emission tomography (PET) probes, with reference to their potential therapeutic implications, was examined in the peculiar context. Preliminary results show that functional imaging in pediatric brain tumors might lead to significant improvements in terms of diagnostic accuracy and it could be of help in the management of the disease.
Project description:BACKGROUND:Structural and functional brain images are essential imaging modalities for medical experts to study brain anatomy. These images are typically visually inspected by experts. To analyze images without any bias, they must be first converted to numeric values. Many software packages are available to process the images, but they are complex and difficult to use. The software packages are also hardware intensive. The results obtained after processing vary depending on the native operating system used and its associated software libraries; data processed in one system cannot typically be combined with data on another system. OBJECTIVE:The aim of this study was to fulfill the neuroimaging community’s need for a common platform to store, process, explore, and visualize their neuroimaging data and results using Neuroimaging Web Services Interface: a series of processing pipelines designed as a cyber physical system for neuroimaging and clinical data in brain research. METHODS:Neuroimaging Web Services Interface accepts magnetic resonance imaging, positron emission tomography, diffusion tensor imaging, and functional magnetic resonance imaging. These images are processed using existing and custom software packages. The output is then stored as image files, tabulated files, and MySQL tables. The system, made up of a series of interconnected servers, is password-protected and is securely accessible through a Web interface and allows (1) visualization of results and (2) downloading of tabulated data. RESULTS:All results were obtained using our processing servers in order to maintain data validity and consistency. The design is responsive and scalable. The processing pipeline started from a FreeSurfer reconstruction of Structural magnetic resonance imaging images. The FreeSurfer and regional standardized uptake value ratio calculations were validated using Alzheimer’s Disease Neuroimaging Initiative input images, and the results were posted at the Laboratory of Neuro Imaging data archive. Notable leading researchers in the field of Alzheimer’s Disease and epilepsy have used the interface to access and process the data and visualize the results. Tabulated results with unique visualization mechanisms help guide more informed diagnosis and expert rating, providing a truly unique multimodal imaging platform that combines magnetic resonance imaging, positron emission tomography, diffusion tensor imaging, and resting state functional magnetic resonance imaging. A quality control component was reinforced through expert visual rating involving at least 2 experts. CONCLUSIONS:To our knowledge, there is no validated Web-based system offering all the services that Neuroimaging Web Services Interface offers. The intent of Neuroimaging Web Services Interface is to create a tool for clinicians and researchers with keen interest on multimodal neuroimaging. More importantly, Neuroimaging Web Services Interface significantly augments the Alzheimer’s Disease Neuroimaging Initiative data, especially since our data contain a large cohort of Hispanic normal controls and Alzheimer’s Disease patients. The obtained results could be scrutinized visually or through the tabulated forms, informing researchers on subtle changes that characterize the different stages of the disease.
Project description:This article reviews dual X-ray absorptiometry (DXA) technique and interpretation with emphasis on the considerations unique to pediatrics. Specifically, the use of DXA in children requires the radiologist to be a "clinical pathologist" monitoring the technical aspects of the DXA acquisition, a "statistician" knowledgeable in the concepts of Z-scores and least significant changes, and a "bone specialist" providing the referring clinician a meaningful context for the numeric result generated by DXA. The patient factors that most significantly influence bone mineral density are discussed and are reviewed with respect to available normative databases. The effects the growing skeleton has on the DXA result are also presented. Most important, the need for the radiologist to be actively involved in the technical and interpretive aspects of DXA is stressed. Finally, the diagnosis of osteoporosis should not be made on DXA results alone but should take into account other patient factors.
Project description:ObjectiveTo review progress in understanding pediatric obsessive-compulsive disorder (OCD). The focus is on the frontal-striatal-thalamic model of OCD, neurobiological and genetic studies of the disorder, and their influence on recent advances in treatment.MethodComputerized literature searches were conducted with the key words "obsessive-compulsive disorder" in conjunction with "pediatric," "genetics," and "imaging."ResultsNeuroimaging studies find evidence to support the frontal-striatal-thalamic model. Genetic and neurochemical studies also implicate glutamate in the pathological finding of OCD. This has led to the application of glutamate-modulating agents to treat OCD.ConclusionsStudies of pediatric OCD have led to a refined frontal-striatal-thalamic model of pathogenesis and are having an evidence-based impact on treatment. Despite this progress, fully explanatory models are still needed that would allow for accurate prognosis and the development of targeted and efficacious treatments.