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Improved Technologies and Ligands for Non-invasive Brain Imaging (R43/R44)



A continuing impediment to the understanding and diagnosis of brain disorders is our limited ability to non-invasively visualize viruses, proteins, metabolites, and other molecules in the brain in vivo. Existing technology, such as Positron Emission Tomography (PET), Magnetic Resonance Spectroscopy (MRS), and Single-photon emission computed tomography (SPECT), are currently optimal only for a limited range of molecules. For example, there is currently no ligand available for non-invasive imaging of latent HIV in the human brain, which would be valuable for treatment of HIV/AIDS, or for detection of metabolites and signaling molecules associated with multiple glial cell types, which could shed light on the involvement of glial cell activity in substance use disorders (SUD). Further, there are considerable limitations to many of the currently available imaging ligands, including poor selectivity, high cost, or risks from radiation exposure in the case of pediatric populations. As an example of imprecision in targeting molecules, an MRS protocol may be unable to distinguish neuronal neurotransmitter concentrations from non-neuronal, with deep ramifications for the interpretation of such findings. More research is needed to improve the ability of existing imaging ligands and technologies (e.g., analytical programs) for non-invasive imaging of brain function such that changes from disease or other insults to the brain can be better tracked, and the response to pharmacological interventions can be better interpreted.

Research Objectives

The proposed SBIR concept will support small business efforts that address challenges in the realm of brain imaging including: 1. the further development and commercialization of in vivo imaging technologies, 2. the development of ligands or imaging technologies to enable visualization of latent or replicating HIV viruses within the brain, 3. the development of imaging ligands for visualizing changes in receptors or other brain proteins relevant to substance abuse and co-occurring psychiatric disorders (e.g., anxiety, depression), 4. the development of imaging ligands for visualizing neuronal and/or glial retrograde/signaling molecules (e.g., glutamine, anandamide).

If the innovative tool to be commercialized will be developed via a partnership of ideas between a small business and an academic/non-profit research institution, the program director/principal investigator should consider applying using the STTR mechanism (R41/R42).  Applicants are encouraged to contact NIH Scientific/Research staff for more detailed guidance. 

Specific Areas of Research Interest

This initiative will support small business development of research-enabling tools, technologies, or products such as (but not limited to):

  • The development of new or improved ligands for imaging brain structure and function, including for neuronal or glial retrograde/signaling molecules, neurotransmitters and associated receptors, metabolites, proteins, and/or other molecules
  • The development of ligands for visualizing replicating or latent HIV in the brain
  • The development of ligands targeting specific glial cells (e.g., oligodendrocytes, astrocytes, microglia) or markers for state of activation (e.g., resting vs. activated microglia)
  • The development and optimization of ligands for the detection of epigenomic or epitranscriptomic readers, writers, and erasers that function in the brain and/or in HIV regulation
  • The development of new or improved MRI protocols for chemical imaging (e.g., MRS)
  • The development of new or improved software (e.g., MR sequence), devices, or analytical tools for imaging brain structure and function or for identification of latent or replicating viruses in the brain
  • The development of improved software or devices for non-invasive imaging in the service of diagnosis and monitoring treatment of SUDs, pain, or HIV/AIDS


See Section VIII. Other Information for award authorities and regulations.

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