SPARC - FOA Priorities

This webpage serves as the official list of Priorities for SPARC. Please revisit in January 2020 when we anticipate providing information on a potential new funding opportunity associated with our current priorities. If you have any questions, or if you have suggestions for future Priorities, please email NIH-CF_SPARC@mail.nih.gov  


 

CURRENT Priorities

(Pending available funding mechanism)

These priorities were posted December 2, 2019.

The NIH SPARC program intends to open a funding announcement in FY20 to support critical program needs. Similar to the process used for RM17-009, applications will be required to be directly responsive to a specific currently active program priority. To allow teams to begin forming and planning, we are activating the below priority in advance of the associated funding announcement, which will be posted here.

Priority: Interoperable, extensible, and personalizable simulations on the o2S2PARC platform to inform bioelectronic medicine development, with particular focus on diseases and conditions that impact the stomach, colon, lungs, heart, or lower urinary tract.

Additional information:

Despite the vast amounts of data and software tools being generated by autonomic/enteric/peripheral neuroscience researchers inside and outside of SPARC, the field currently lacks a comprehensive effort to incorporate anatomical and physiological data into interactive multiscale, multiphysics models capable of predicting how modulation of a given neural target will impact organ functional responses. A range of challenges has so far limited the number and utility of existing computational models:

  • Few existing organ models explicitly consider the role of the autonomic nervous system and electrophysiological signaling in function.
  • With some exceptions, experimentation and interactive computational model development are performed by different groups, without attention to the potential advantages of coordination.
  • With some exceptions, the collection of experimental data is not driven by the parameter needs of model developers.
  • The technical and conceptual heterogeneity of existing computational models renders integration difficult, particularly across species, spatial and temporal scales, and organs.
  • Existing neuroscience knowledgebases and computational resources are underutilized.

 

The NIH SPARC program has supported the development of a framework capable of addressing these challenges, and now seeks to populate this framework by supporting the development of interoperable components to power advanced predictive simulations of neuromodulation interventions for a range of diseases and conditions. These components should be built on the online computational platform o2S2PARC and should leverage at least in part, existing experimental data/knowledge. Components might include:

  • Interoperable interactive numerical simulations;
  • Software to identify parameters from existing data in an unsupervised fashion;
  • Models that account for variability and uncertainty across species, individuals, and sexes;
  • Models that are capable of predicting off-target effects;
  • Techniques for identifying underdetermined parameter ranges where future experimental and computational data collection efforts would be most impactful;
  • Approaches that encompass collaborative efforts between modelers, experimentalists, and/or physician-scientists that generally support:
    • Generation of computational models from experimental information,
    • Integration of heterogeneous computational models, and
    • Extension beyond individual computational models.

Relevant Background and Resources

 


ARCHIVED Priorities

RFA-RM-16-003 (previous FOA) 
These Priorities are archived for reference purposes only.

These priorities were posted February 8, 2016.

  • Modification of technologies, such as those previously developed to understand neural circuits in the Central Nervous System, to understand neural circuits in the Peripheral Nervous System; or technology used to understand neural circuits controlling one organ which can be modified for use with another target organ or multiple other organs
  • Sensing techniques for relevant biomarkers to inform closed-loop response systems in organs (e.g., biomolecule sampling/measuring)
  • Technologies for cell-class specific targeting and manipulation in peripheral nerves and ganglia, appropriate for animal models with clinical relevance (e.g., optogenetics)
  • Activity sensors and associated imaging technologies suitable for peripheral nerve and end-organ monitoring (e.g., voltage probes)
  • Reliable, wireless, high density technologies capable of simultaneous recording/stimulation of all neural signals going to and coming from a targeted organ; and or to facilitate functional mapping between multiple organs and nerves
  • Biomimetic or biologically-active interfaces for chronic implants of electrodes and sensors that enhance our ability to chronically study the function of a target organ
  • Invasive and non-invasive technologies for tunable stimulation/inhibition/block of nerve activity (e.g., ultrasound, magnetic fields, etc.)
  • Tools for non-invasive tracing and functional imaging to facilitate minimally invasive surgeries in humans and anatomical mapping
  • Computational platforms and predictive models that generate testable hypotheses of autonomic nervous system control of organs

RFA-RM-17-009 (previous FOA)
These Priorities are archived for reference purposes only.

These priorities were posted March, June and September, 2017.

  • Imaging and targeting:
    • Quantitative imaging and analysis techniques for PNS and/or organ tissue
    • Contrast agents to identify variability due to individual subject differences in either neuroanatomy or neurophysiology
    • Whole-body imaging of neural tracts (in vivo or ex vivo); the ex-vivo approaches may be destructive or non-destructive to the tissue
    • Fascicular tracing/targeting (i.e., methods to increase contrast, biochemical, surgical, and/or viral)
    • Fiber type targeting (i.e., methods to ligate an imaging agent, biochemical, surgical, and/or viral); this includes plexi, unbundled nerves, and/or vascular nerves
    • Methods to assess blood flow within microvasculature of nerves and ganglia. Of particular interest are methods that can observe blood flow under electrodes
    • Non-invasive imaging tools to locate and characterize isolated ganglia and/or nerve branches
    • Organ preparation and/or methods to image neural junctions/terminals in an organ of interest
    • Phantoms to support development of new imaging technologies for neuroanatomy
    • Real-time localized sensing and/or imaging of neurotransmitter release and/or uptake in the PNS
    • Adaptation of stitching, segmenting, and tracing software to PNS and organ datasets
    • Adaptation of biomechanical, biochemical, and bioelectrical models of organ function for use in studying the impact of neuromodulation on organ function
    • Computational models to assess safety limits of stimulation and/or blocking of neural activity (e.g. biophysics and regulatory science for neural interfaces)
    • Biophysical models of electrical neuromodulation that predict selective activation or block specific fiber types and locations. These computational models should be predictive of side effects (i.e. other fibers that may be activated or blocked)
    • Methods to enhance spatial resolution and/or selectivity for fiber types, fascicles, plexi, or ganglia that do not rely on genetic manipulation or transfer (e.g., methods to ligate an imaging agent, enhance contrast, or selectively activate nerve components without genetic manipulation or transfer)
  • Modeling and simulation:
    • Computational models to assess safety limits of stimulation and/or blocking of neural activity (e.g. biophysics and regulatory science for neural interfaces) with or without model validation in vivo
    • Computational models of neuromodulation that incorporate variability due to individual subject differences
    • Biophysical models of electrical, infrared, or ultrasonic neuromodulation that predict selective activation or block specific fiber types and locations. These computational models should be predictive of side effects (i.e. other fibers that may be activated or blocked)
    • Adaptation of stitching, segmenting, and tracing software to PNS and organ datasets
    • Adaptation of biomechanical, biochemical, and bioelectrical models of organ function for use in studying the impact of neuromodulation on organ function
    • Computational models for non-invasive nerve stimulation technologies (e.g., TENS) to provide higher spatial resolution and/or fiber-type specificity. Models must be validated in vivo
  • Surgical:
    • Surgical tools to safely find and/or access nerves, fascicles, and/or ganglia/plexi (e.g. imaging, protocols, etc)
    • Surgical phantoms
    • Real-time in-vivo methods to determine if the PNS is damaged during surgery
    • Methods to repair PNS damage after implant of a neural interface
    • Surgical tools to safely find, access, and/or attach interfaces to nerves, fascicles, and/or ganglia/plexi (e.g. imaging, protocols, etc)
  • Interfacing:
    • New approaches to neuromodulate the PNS that are inherently safe, have high specificity (temporal, spatial, fiber type), and are minimally or non-invasive. 
    • Blocking must be reversible. 
    • Potential approaches might include biologically derived methods to interface with the PNS in vivo, such as artificial biologic constructs, hydrogel-encapsulated cells, or engineered tissue grafts
    • Multi-modal (e.g. optogenetic and electrical) neural interfaces that provide greater specificity than a single-mode interface
    • Adaptation of signals engineering approaches to increase spatial and temporal precision of existing multichannel neuromodulation technologies. For example, applying inverse transform or phased array methods to an existing nerve cuff 
    • Distribution of existing neuromodulation systems to the SPARC consortium. While some adaptation may be required to build interfaces for SPARC1 or SPARC3 investigators, the emphasis of this priority is on the manufacture, distribution, training, and support for these technologies and the associated surgical methods to implant them in nerves, ganglia, or plexi 
    • Adaptation and safety testing of existing systems for use in large animal models or humans. Systems should provide high-specificity neuromodulation of the PNS or assess end-organ function 
    • Biosensors to detect end-organ function biomarkers
    • Methods to identify and understand chronic PNS tissue damage after implant of a neural interface
    • Surgical tools to safely find, access, and/or attach interfaces to nerves, fascicles, plexi, and/or ganlgia (e.g., imaging, surgical protocols, etc.) - This Priority only supports development of surgical tooling and methods, not development of new interfaces
    • Methods for performing electrophysiological recordings during MR imaging
    • Enhancement of FDA-cleared or approved non-invasive nerve stimulation technologies (e.g., TENS) to provide higher spatial resolution and/or fiber-type specificity
  • Sample preparation priorities:
    • Transgenic large animal models to facilitate imaging/targeting or interfacing with peripheral nerves and/or end organs
    • Methods for accessing and patch clamping ganglia, plexi, and small nerves. This may include techniques for enzymatic digestion or robotic automation of access to dissociated ganglia
    • Optimization of techniques to label human peripheral nerves and/or end organs. This may include new antibodies, fluorophores, or image processing algorithms to improve immunohistochemical analysis of small nerves or nerve-organ junctions
    • Organ preparation and/or methods to image neural junctions/terminals in an organ of interest
  • Services provided to all SPARC consortium members:
    • Large-scale high-resolution image capture of ex vivo specimens (e.g. TEM, X-ray, or light sheet)
    • Device testing (e.g., mechanical, electrochemical, toxicity, accelerated life, ISO 10993 or equivalent)
    • ASIC design, development, and validation
    • Packaging and encapsulation, or interconnects suitable for >6 month animal trials or human use
    • Genetics services (e.g., RNA-seq, viral vector development, and transgenic line generation)
    • Distribution of existing neuromodulation systems to the SPARC consortium. While some adaptation may be required to build interfaces for SPARC1 or SPARC3 investigators, the emphasis of this priority is on the manufacture, distribution, training, and support for these technologies and the associated surgical methods to implant them in nerves, ganglia, or plexi 
  • Animal and tissue preparation priorities:
    • Genetic approaches for large animals to facilitate imaging/targeting or interfacing with peripheral nerves and/or end organs (e.g., transgenic models, viral vectors, etc.)
    • Methods for accessing and patch clamping ganglia, plexi, and small nerves. This may include techniques for enzymatic digestion or robotic automation of access to dissociated ganglia
    • Optimization of techniques to label human peripheral nerves and/or end organs. This may include new fluorophores or image processing algorithms to improve immunohistochemical analysis of small nerves or nerve-organ junctions

This page last reviewed on March 17, 2020