Fellowships, grants, & awards.

Novel Technologies for In Vivo Imaging (SBIR/STTR)

The National Cancer Institute (NCI), the NIEHS, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite applications for the development and delivery of novel image acquisition or enhancement technology and methods for biomedical imaging and image-guided interventions and therapy, which may incorporate limited pilot or clinical feasibility evaluations using either preclinical models or clinical studies. This initiative is intended to facilitate the proof of feasibility, development, and delivery of novel imaging technologies for early detection, screening, diagnosis, image-guided interventions, and treatment of various diseases, and secondarily to facilitate limited evaluation studies to show proof of concept and functionality.

The overarching research objectives of this program announcement (PAR) are to stimulate discovery, development, optimization, and delivery of novel imaging technologies and methods to capture, process, validate, present, interpret, or understand in vivo imaging data that support the missions of the NCI, NIEHS, NIBIB, or NIDDK. This initiative is intended to facilitate the development of novel imaging technologies for risk assessment, early detection, screening, diagnosis, or image-guided treatment of cancer and other diseases and to facilitate clinical evaluation and optimization studies that are specifically limited to proof of concept and pilot data on clinical functionality of the development. Clinical trials for clinical validation of emerging imaging technologies are beyond the scope and not responsive to this PAR.

The interests of the NCI focus on imaging in vivo for cancer preconditions, cancer screening, diagnosis, progression, treatment monitoring, recurrence, and surrogate end points. NCI interests also include the discovery, development, and delivery of imaging technologies that are cancer-specific, and optimization and validation of imaging technologies for cancer applications. The scope includes system integration, contrast agents, pre- and postprocessing algorithms and software for imaging, image understanding, and related informatics that are cancer-specific. The interests of the NIBIB focus on the discovery, development, and delivery of imaging platforms and related component technologies, contrast agents, image processing, and related informatics that can be applied to disease and injury. The interests of the NIEHS focus on detection, screening, and diagnosis of tissue and organ toxicity related to exposures to environmental agents. These include initiation of toxicity or exacerbation of disease or dysfunction resulting from toxic exposure, treatment, and recovery. NIDDK interests focus on diabetes and digestive and kidney diseases.

This PAR is directed toward the discovery, development, optimization, and delivery of innovative image acquisition and enhancement methods, including high-risk, high-gain research on technologies, as follows: 1) novel single and multimodality molecular imaging systems, methods, agents, and related software and informatics, including the integration of these technologies with emerging biomedical imaging methods for more effective health care delivery for cancer and other diseases; 2) novel single and multimodality anatomical and functional imaging systems, methods, agents, and related software and informatics for more effective health care delivery for cancer and other diseases; and 3) research partnerships among academic investigators in device and drug industries, which are encouraged in order to more rapidly translate and deliver completed imaging system developments.

Significant advances in medical imaging technologies have been made over the past 25 years in such areas as magnetic resonance imaging, computed tomography, nuclear medicine, ultrasound, and optical imaging. These advances have largely focused on structural or anatomical imaging at the organ or tissue level. Now there is an opportunity to stimulate the development and integration of novel imaging technologies that exploit our current knowledge of the genetic and molecular bases of various diseases. Molecular biological discoveries have great implications for prevention, detection, and targeted therapy. It would be very useful to have imaging technologies that are able to provide cellular and molecular information--in vivo molecular imaging--similar to that currently available from histological or microarray techniques in vitro.

The advances made in molecular methods pose new requirements for the performance of conventional biomedical imaging systems. For example, molecular imaging systems may need to be optimized for a molecular probe or probes as well as anatomical imaging. The integration of molecular imaging methods into multimodality systems will affect data acquisition, processing, reduction, display, and archiving. Therefore, there is a need to support advances in methods for both molecular and conventional anatomical and functional imaging.

The need to encourage and support biomedical imaging and imaging technology development by academic and industrial researchers was stressed by participants at several NIH- and NCI-supported forums over the past few years. The needs include 1) promoting the development of novel, high-risk, high-gain technologies; 2) supporting them to maturation, dissemination, and full exploitation; 3) integrating new technologies into commercially available imaging systems for targeted applications; 4) harmonizing imaging methods across versions of a single platform or across multiple platforms to permit the image-based surrogate outcome metrics of the kind required for multisite preclinical and clinical investigations; 5) funding a small number of copies of integrated system prototypes for placement, as required, for off-site research and clinical feasibility studies; and 6) improving technology transfer, delivery, and dissemination by promoting early-stage partnerships between academia and industry to encourage sharing of research resources, including data sharing and validation studies necessary to meet federal regulatory requirements. Thus, the aims of this initiative and the support mechanism are also directed at encouraging the discovery, development, and delivery of imaging tools to support biomedical imaging in general for applications in oncology and other specialties.

Developments of novel imaging technologies usually require multidisciplinary approaches and teams with broad expertise in a variety of research areas. Such varied expertise might include imaging physics, chemistry, molecular and cellular biology, signal and image processing, computer vision, informatics and biostatistics, and clinical sciences. The coordination and collaboration of investigators with the necessary variety of disciplines to demonstrate the utility and applicability of new imaging methods is encouraged.

Studies with preclinical models and clinical studies to demonstrate the feasibility of developments are encouraged, including multisite evaluations, where appropriate. Methods that establish "ground truth" are required at appropriate levels of resolution to validate these emerging imaging methods (e.g., imaging excised tissue using protocols similar to those used in vivo; correlation of molecular imaging results with microarray library analyses). Developments of molecular probes or targeted contrast agents are considered important approaches to detection of molecular changes in vivo to take better advantage of many technologies with potential for molecular imaging.

The following topics would make appropriate proposed projects. This list is not meant to be all-inclusive.

1) Early disease detection. Developments may address innovative high-resolution imaging methods, with a particular intent to identify and characterize abnormalities or other early changes, including molecular events on the path to disease. Possible topics include novel solutions for in vivo microscopic imaging systems, or microscopic implanted devices with high spatial and/or temporal resolution, which may use either intrinsic or exogenous contrast agents.

2) Disease screening. These methods may include, but are not limited to, development and optimization of efficient imaging systems for screening, with the intent of achieving improved sensitivity and specificity for disease detection. Applications could address innovative improvements to current imaging methods, including hardware and/or software upgrades, or emerging imaging sensors and methods.

Research topics of interest include finding a means to significantly reduce imaging time or effects of motion, use of novel contrast agents or imaging probes, use of technologies that reduce or that do not involve ionizing radiation, or use of novel contrast agents and imaging probes. System integration and software methods could include a variety of image processing and data reduction techniques including temporal analysis of serial studies, close-to-real-time image processing, novel image display methods, and related imaging informatics for more cost-effective solutions for screening.

3) Imaging for diagnosis, staging, or monitoring the effects of therapy. This initiative encourages, but is not limited to, the development of novel imaging methods such as functional or molecular imaging or spectroscopy methods that would significantly improve the specificity of diagnosis of cancer and other diseases, that would allow deterministic methods or patient-specific staging, or that would measure early effects of therapy. Examples of system integration would include multimodality imaging, image fusion or registration of the different modalities employed, development of software methods that would estimate the probability of malignancy or other specific disease identification, quantitative information for monitoring the effects of therapy, and close-to-real-time image analysis.

4) Image-guided biopsy (IGB), image-guided therapy (IGT), and image-guided interventional (IGI) procedures. This initiative encourages novel approaches using imaging technologies to significantly improve specificity, to identify lesion extent and microscopic involvement, and to minimize tissue damage accompanying biopsy and therapy. Of particular interest are innovative approaches to IGB, IGT, or IGI methods that include novel imaging systems that provide molecular target information or information at the cellular or molecular level sufficient for image guidance and treatment. Some examples of system integration that are of interest include, but are not limited to, multimodality imaging, navigational systems, registration methods, real-time feedback mechanisms for controlling therapy (including radiation therapy), and the use of methods that are adaptive or that allow patient-specific optimization of treatment and computer-assisted surgery.

5) Copies of prototype imaging systems. Support may be requested to make one or more copies of the prototype for placement in collaborating facilities for preclinical or clinical feasibility investigations, including harmonization across versions of a single platform or across multiple platforms to enable multicenter comparison studies. Collaboration with NCI-funded centers may be possible, as in the NCI Network for Translational Research in Optical Imaging (http://grants.nih.gov/grants/guide/rfa-files/ RFA-CA-03-002.html) or the Lung Image Database Consortium (http://www3.cancer.gov/ bip/steercom.htm). Investigators who anticipate needing funds for these purposes are advised to contact program staff.

6) Research resources. The development of research resources that facilitate a consensus process for optimization and validation of emerging imaging technologies is encouraged. Examples include the development of open-source software; image processing software; and related informatics that can be ported onto different platforms; methods and image databases required for validation of software performance; and other hardware or informatics methods that assist in more efficient delivery of imaging technologies for screening, diagnosis, and treatment for cancer and other diseases. Investigators interested in development of research resources and related research are advised to contact program staff.

This solicitation utilizes the Small Business Innovation Research (SBIR R43 and R44) and Small Business Technology Transfer (STTR R41 and R42) mechanisms, and runs in parallel with a program announcement of identical scope (PAR-03-124) that utilizes the Phased Innovation Award (R21/33) mechanism for exploratory and developmental studies and that is open to a broad range of organizations.

Applications are subject to cost and duration guidelines that are expanded over those stated in the Omnibus Solicitation of the NIH (PHS 2003-2). This PAR must be read in conjunction with the current Omnibus Solicitation of the NIH, the Centers for Disease Control and Prevention, and the Food and Drug Administration for SBIR and STTR grant applications. The solicitation (see http://grants.nih.gov/grants/ funding/sbirsttr1/index.pdf) contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. All of the instructions within the current SBIR/STTR Omnibus Solicitation apply, with the following exceptions: special receipt dates, initial review convened by the NCI Division of Extramural Activities, special time and budget limitations, and additional review considerations.

This PAR uses just-in-time concepts described in the current SBIR/STTR Omnibus Solicitation. Follow the instructions for nonmodular research grant applications. Applications may be submitted for Phase I STTR (R41) or Phase I SBIR (R43) grant support; Phase II STTR (R42) or Phase II SBIR (R44) grant support; or as a pair of Phase I and II applications under the SBIR/STTR Fast Track option described in the Omnibus Solicitation. Phase II applications in response to this PAR will be accepted only as competing continuations of previously funded NIH Phase I SBIR/STTR awards. The Phase II application must be a logical extension of the Phase I research, but the Phase I project does not need to have been supported in response to this announcement.

Fast Track applications will benefit from expedited evaluation of progress following Phase I feasibility work for faster transition to Phase II funding for development work, with minimal or no funding gap between the Phase I and Phase II work. This PAR has features intended to enhance success rates for Fast Track applications.

The SBIR/STTR Omnibus Solicitation describes statutory guidelines on levels of funding support and periods of project duration for SBIR and STTR Phase I and Phase II awards. Guidelines for this PAR are up to $100,000 total costs per Phase I year and time periods up to two years. Phase II applications submitted to this PAR have no budget limitations and may request up to four years of support. For a Phase I-Phase II pair of Fast Track applications, the total duration of support cannot exceed five years.

NCI grantees who have successfully completed their Phase II aims may submit a competitive renewal of their Phase II project requesting support up to an additional three years for research activities that must include steps necessary to meet federal regulatory requirements (e.g., good practice requirements, validation, early stage clinical safety, efficacy and feasibility studies, premarketing approval, investigational device exception, etc.). All Phase II provisions stated in this PAR apply to a competing continuation application.

The deadline for receipt of letters of intent is 22 October 2003, with 19 November 2003 the deadline for receipt of applications. Complete information on this PAR is located online at http://grants1.nih.gov/grants/guide/pa-files/ PAR-03-125.html.

Contact: NCI--Houston Baker, Guoying Liu, or Keyvan Farahani, Biomedical Imaging Program, or James A. Deye, Radiation Research Program, NCI, 6130 Executive Plz, Ste 6000, Bethesda, MD 20892-7412 USA, 301-496-9531 for BIP, 301496-6111 for RRP, fax: [phone], e-mail: [e-mail], [e-mail], [e-mail], [e-mail]; NIEHS--Jerrold J. Heindel, Organs and Systems Toxicology Branch, Division of Extramural Research and Training, NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA, 919-541-0781, fax: [phone], e-mail: heindelj@ niehs.nih.gov; NIBIB--John W. Hailer, NIBIB, 6707 Democracy Blvd, Ste 200, Bethesda, MD 20892-5469 USA, 301-451-4780, fax: [phone], e-mail: [e-mail]; NIDDK--Judith Podskalny, Training and Career Development, Digestive Diseases Centers, and SBIR/STTR, NIDDK, 6707 Democracy Blvd, Ste 667, Bethesda, MD 20892-5450 USA, 301-594-8876, fax: [phone], e-mail: [e-mail]. Reference: PA No. PAR-03-123