Comments and Perspectives

Roderic Pettigrew

Rapid and revolutionary changes in the world of biomedical research are moving the field of “personalized medicine” from concept to reality. Although still in its infancy, the use of custom-tailored tools, technologies, and therapies to diagnose and treat diseases before symptom onset is increasing.

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) plays a crucial role in furthering the tools and technologies needed for personalized medicine. Established in December 2000, this institute at the National Institutes of Health (NIH) is unique in that its mission is to improve human health by leading the development and accelerating the application of biomedical technologies. The institute is dedicated to integrating physical and engineering sciences with life sciences to advance basic research and medical care.

The current NIBIB grant portfolio is robust and includes a diverse mix of scientific topics. So far in fiscal year 2004, NIBIB has funded approximately 704 research and training grants totaling $205,459,000. In biomedical imaging, NIBIB supports grants in scientific areas such as nuclear medicine, optical imaging, molecular and cellular imaging, ultrasound, CT, MRI, biovisualization, and image-guided, robotic-assisted interventions.

Scientific growth in cellular and molecular imaging is critical to realizing the vision of personalized medicine. Thus, NIBIB is actively supporting this promising field, funding molecular imaging projects totaling $25 million in 2003. Although many challenges lie ahead, NIBIB-funded investigators are reporting progress.

Recent advances in molecular imaging come from intense efforts toward developing nanometer-scale target-specific homing and signaling systems and fusion gene reporter systems that allow for direct imaging of gene expression. These reporter systems can be used with multiple modalities, such as nuclear, optical, and MRI, to exploit their respective unique advantages. The systems offer the potential to study important biologic or pathologic events that are controlled by expressions of multiple genes, thereby potentially providing a more specific understanding of the basis of disease and normal physiology.

Additional advances in molecular imaging are derived from the accelerated development of novel small molecular agents that target specific biomarkers, as well as successful efforts to conjugate these to contrast agents. Recent developments in genomics and proteomics have provided a challenging but target-rich environment. Specific targeting ability of these small molecular agents will no doubt lead to in vivo imaging of cellular-level communications and interactions and thus help decipher many mysteries of intracellular function.

An example of the practical benefit of imaging at the cellular level is the remarkable demonstration that multiphoton microscopy can detect and characterize complicated macromolecular structures in cells and tissues. In particular, multiphoton scattering can quantify microtubules in regenerating axons in the central nervous system and detect collagen in vascular smooth muscle and growing bone. In addition, multiphoton fluorescence can show neurofibrillary tangles from Alzheimer’s disease patients.

Realizing both the basic research and practical health care potential of molecular imaging, however, requires improvement in the overall sensitivity and specificity of techniques by a factor of 1,000. Major advances in molecular probe construct, performance, and detection are necessary to meet the specific goal of time-resolved monitoring of single molecular events. To this end, initiatives in cellular and molecular imaging have been included in the NIH Roadmap, announced in 2003 as a set of trans-NIH initiatives to accelerate fundamental and cross-cutting research discoveries and their translation from bench to bedside (and vice versa). The Roadmap focuses on 3 major areas: new pathways to discovery, research teams of the future, and reengineering of the clinical research enterprise.

One key focus is the “Molecular Libraries and Imaging” group of initiatives under new pathways to discovery. The first of these initiatives to fund applications was “Development of High-Resolution Probes for Cellular Imaging.” This initiative will facilitate generation of novel probes with substantially improved performance. Eventually, the information gained will help realize the long-term goal of treatments tailored to individuals based on physiologic profiling of cell function with molecular monitoring of targeted therapeutics.

For additional information, visit http://www.nibib.nih.gov.