Purpose. This funding opportunity announcement (FOA) invites Small Business Innovation Research (SBIR) grant applications that propose research and development of probes useful in imaging the structure and function of the brain and other parts of the nervous system, with award duration and amounts greater than those routinely allowed under the SBIR programs. Specifically this FOA invites SBIR applications that propose research and development of probes that generate signals detectable by one or more imaging modality. Such probes should indicate the structure or function of molecules or subcellular elements of neurons or other cells of the nervous system. Of special interest are applications that propose research and development of novel probes, although significant enhancements of already existing probes are also invited. Grant applications may propose projects that will result in probes solely intended for use in research or probes that might have clinical utility. It is expected that this initiative will require expertise from a variety of disciplines, including neuroscience, biology, chemistry, physics, engineering, biotechnology, and bioengineering. Moreover, it is anticipated that these types of expertise will be brought together in various combinations in individual proposed projects. Mechanism of Support. This FOA will utilize the SBIR (R43/R44) grant mechanisms for Phase I, Phase II, and Fast-Track applications. Funds Available and Anticipated Number of Awards.Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received. Budget and Project Period. Phase I awards normally may not exceed $100,000 total for a period normally not to exceed 6 months. Phase II awards normally may not exceed $750,000 total for a period normally not to exceed 2 years. For this funding opportunity, budgets up to $350,000 total costs per year for up to two years may be requested for Phase I. Budgets up to $600,000 total costs per year and up to three years may be requested for Phase II. Eligible Institutions/Organizations: Only United States SBCs are eligible to receive SBIR applications. A SBC is one that, on the date of award for both Phase I and Phase II funding agreements, meets ALL of the criteria as described in Section III. Eligible Project Directors/Principal Investigators: Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. On an SBIR application, the PD/PI must have his/her primary employment (more than 50%) with the SBC at the time of award and for the duration of the project. Number of Applications: Applicant SBCs may submit more than one application, provided each application is scientifically distinct. Resubmissions:Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications will be permitted only a single amendment (A1).See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016Original new and competing renewal applications that were submitted prior to January 25, 2009 will be permitted two amendments (A1 and A2).For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date. Number of PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be designated on the application.