Basic question: Can an entire-body positron emission tomography (PET) scanner be exploited to improve evaluation, monitoring and measurement of both peripheral and central demyelination in multiple sclerosis (MS) patients? We assume here that demyelination outside the brain may involve the spinal cord if not also possibly some of the larger peripheral nerves outside the spinal column in a manner that may be detected with the greater sensitivity and resolution of the most recent state-of-the-art PET scanners.
Initial approach: Adopt a cost-effective and reduced-risk approach initially for an exploratory study by using commercially available and already FDA-approved PET amyloid imaging radiopharmaceuticals that also bind to myelin to follow radiotracer uptake in white matter, thereby tracking demyelination versus remyelination for MS patients in comparison with normal healthy subjects. This initial approach with the greater sensitivity and resolution of modern entire-body PET scanners when used for amyloid/myelin imaging should hypothetically enable monitoring of increased versus decreased activity in both the peripheral nervous system (PNS) and the central nervous system (CNS), rather than only imaging the brain as performed in most conventional imaging evaluations for MS patients.
Future approach: Investigate other possible radiotracers (including those not yet FDA approved) that may be useful for monitoring demyelination, neuroinflammation and/or microglial activation in both the PNS and CNS of MS patients. In addition, PET myelin imaging by PET-CT scanners will be compared with analogous imaging by PET-MR scanners.
Significance: Improved molecular imaging with new entire-body PET scanners that provide improved detection sensitivity and spatial resolution for quantitative measurement of demyelination and remyelination will support better decision-making for patient care with more robust outcome measures for monitoring therapeutic drugs evaluated in clinical trials for the treatment of multiple sclerosis.
The PORTAL-DOORS Project (PDP) has been pursued to develop the Nexus-PORTAL-DOORS-Scribe (NPDS) cyberinfrastructure as a distributed network system of data repositories to manage lexical and semantic data and metadata from and/or about online and offline resources. Designed with the Hierarchically Distributed Mobile Metadata (HDMM) architectural style in a manner analogous to IRIS-DNS, the NPDS cyberinfrastructure provides distributed multilevel metadata management as an open, flexible, and extensible networked system of independent community customizable who-what-where registries, directories, and diristries for identifying, describing, locating, and linking things on the internet, web and grid. In the current work reported here, we combined our original principles from PDP, HDMM, and NPDS together with additional principles for scientific reproducibility and social engineering related to our family of quantitative metrics with acronym FAIR for Fair Attribution to Indexed Reports and Fair Acknowledgment of Information Records.We call this new consolidated collection of principles the DREAM principles with acronym DREAM for the phrase Discoverable Data with Reproducible Results for Equivalent Entities with Accessible Attributes and Manageable Metadata . To codify these DREAM principles as a concrete artifact for the semantic web, and thus to operationalize their use, we developed an OWL 2.0 ontology that we named the PDP-DREAM ontology.
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