From left, Roderic I. Pettigew,PhD,MD; Donna J. Dean, PhD; and William J. Heetderks, PhD,MD.

With 800 active grants in its portfolio, the National Institute of Biomedical Imaging and Bioengineering is intent on refining the diagnostic and treatment processes that will propel medicine into the 21st century.

Disease expresses itself in ways that differ from one person to the next, depending on the individual patient’s gene structure. This explains why the diagnostic process is not foolproof, and why treatment works well in some cases, and barely adequately or not at all in others.

With that understanding, researchers believe that someday the optimal method of attacking any given illness will involve tailoring the therapeutic intervention to each patient’s unique genetic makeup. And radiologists will be the ones bearing routine clinical responsibility for identifying the expression of patients’ gene characteristics as well as for identifying the molecular-level targets where microscopic devices carrying disease-fighting agents will be delivered with pinpoint accuracy. This is the belief of the man at the helm of the relatively new federal institute supporting a remarkable compendium of research selected to develop the tools and techniques critical to this mission – the National Institute of Biomedical Imaging and Bioengineering (NIBIB) in Bethesda, Md.

“This and everything else we do here at NIBIB pertains to the future of radiologic imaging and bioengineering,” says NIBIB Director Roderic Ivan Pettigrew, PhD, MD. “Right now we are helping develop the clinical techniques of tomorrow. We’re constantly in the process of mapping out a path to this vision of individualized medicine. Among other things this involves the merger of diagnosis and therapy in order to be patient specific  and more efficient in the way we manage, treat, and ultimately prevent disease.

“One place we are headed is personalized molecular medicine, which may even involve the ability to initiate successful preemptive strikes against disease, long before the disease becomes a problem and the treatment is made more complicated. These are things radiologists need to begin thinking about because the radiologist of the future will have an active role in molecular medicine. Radiologists will help define on a person-by-person basisif not on a lesion-by-lesion basisthe genetic profiles that allow us to very specifically tailor diagnosis and treatment to the individual patient. The NIBIB is supporting research that will get us to that place. We’re developing the tools for that tomorrow today.”


The NIBIB – the newest among the 27 entities comprising the National Institutes of Health – was established by an act of Congress in late December 2000 and opened for business with $112 million on its books in January 2001, when its first budget was approved. Today, just entering its third fiscal year, the NIBIB operates on a budget of approximately $280 million and is charged with administering a portfolio of more than 800 active grants covering such projects as molecular imaging; novel gene- and drug-delivery systems; image-guided intervention; optical imaging techniques; contrast development; minimally invasive therapies; improvements to x-ray, CT, ultrasound, and MRI; small-animal imaging systems; tissue engineering; medicinal nanotechnology; bioinformatics; and research infrastructure development.

“In a nutshell, we are an institute that is innovative and technology-based, that seeks to merge the quantitative and physical sciences with the biological and health care sciences for the benefit of mankind and to help address the nation’s health care agenda,” says Pettigrew. “The mission of the NIBIB is to focus on supporting the development of emerging and breakthrough technologies that enable fundamental new discoveries in medicine and  new applications of existing technologies with regard to the diagnosis, treatment, and prevention of disease. We try to help identify areas where technological innovation needs to happen and in ways that researchers and clinicians end up with the tools they need. We also try to help create new things to improve, fundamentally, processes, to advance technology in general, as well as to gain new insights into human physiology and disease.

“So, as an institute, a basic mode of operation is to pursue research that will provide information, understanding, and developments that would not have occurred otherwise.”


The work of the NIBIB is highly collaborative, embracing a number of medical and scientific communities. Among them are the fields of physics, engineering, statistics, chemistry, cell and molecular biology, behavioral biology, and computer science. Overwhelmingly, though, the communities most key to the NIBIB’s efforts are radiologists and biomedical engineerstwo groups with different styles and cultures, but two groups with much to gain through collaboration, says C. Douglas Maynard, MD, retired professor of radiology at Wake Forrest University School of Medicine, who was instrumental in the launch of NIBIB.

“What started this whole thing was a growing awareness that the biomedical imaging and biomedical engineering communities were trying to achieve the same things, but neither felt adequately represented at the NIH from the standpoint of having access to money for research in their respective areas,” Maynard explains.

Maynard was president of the Academy of Radiology Research (ARR) at the time Congress was considering a bill to authorize creation of the NIBIB. It was Maynard’s own representative in the House of Representatives who introduced that proposed legislation at Maynard’s behest.

The ARR for quite some time had been advocating formation of such an institute and was joined in that ambition by the American Institute for Medical and Biological Engineering (AIMBE). So, when Congress voted to form the NIBIB in response to lobbying by the ARR and the AIMBE, those two organizations were prepared to help craft a mission statement for the new institute.

“Both organizations and their respective communities were enthusiastic about NIBIB because it opened the door to opportunities for them to collaborate with one another, something seldom if ever done by them before,” says Donna J. Dean, PhD, deputy director of the NIBIB. Dean served as its acting director from inception until September 2002, when Pettigrew came aboard as permanent director. “We had radiologists marveling at their ability to collaborate for the first time ever with, for example, a materials scientistand vice versa.”

Cultural Commonalities

Although radiology and bioengineering are worlds apart, Pettigrew finds the two have far more commonalities than they do differences.

“Both communities understand science from a holistic standpoint with a more integrative, synergistic view,” he says. “When I speak to radiologists and give presentations, they are essentially the same presentations I’ll give later when I speak to engineers. That’s because I don’t think in terms of differences between these two areas. I never have. On my first day here, I thought about our mission and mandate and how to achieve itin particular, how to achieve it with the communities we were created to support. This involves collaboration among these and all other communities that address health care challenges.”

Pettigrew says he found that easy to do because he was formally trained as an engineer before entering medical school to become a nuclear physician and radiologist with a specialized interest in MRI research and clinical applications.

“My background allows me to stand astride both those worlds,” says the former Emory University professor. “That is without doubt a major reason why I was selected for this position.”

To facilitate a spirit of collaboration, Pettigrew reorganized the NIBIB soon after he arrived. “The initial organization consisted of a Division of Biomed-

ical Imaging and a Division of Bioengineering,” he reports. “That ceased to exist officially in May of this year. The reorganization did away with those two divisions and replaced them with a Division of Discovery Science and Technology, a Division of Applied Science and Technology, and a Division of Interdisciplinary Training. We did this because we wanted to achieve a more integrated multidisciplinary scientific approach that really reflects how science is being done today and how it will be done in the remainder of the 21st century, and where the scientific community as a whole is moving, which is toward interdisciplinary, crosscutting, transdiscipline approaches to problem solving.

“I am a big believer in the idea that, if you bring the best of multiple disciplines together to focus on a single problem, you stand a much better chance of getting not only a solution but an optimal solution. You cannot get that if you have just a single discipline focusing on it. So, I thought our institute should be out front on that. I thought our structure should reflect that belief and vision.

“One of the things I feel good about is the fact that we have made significant progress in getting the extramural community to think less of their individual areas of expertise and focus more in terms of an interdisciplinary team science approach.”


Implicit in the NIBIB’s mission statement is a call not only to bring together diverse medical and scientific fields but also to help other NIH entities become more effective in meeting their own missions and mandates, Pettigrew explains.

“One of the things we need to do is understand where the areas of need are within the various institutes,” he says. “We’re constantly asking, what are the problems that they’re facing where technology can be helpful? What are the gaps where they don’t have adequate capabilities and technological tools?’

Some answers are set forth in a process known within the NIH as “the roadmap”. Essentially, these roadmaps are far-reaching initiatives too ambitious to be achieved by any one NIH enterprise alone.

A major roadmap project currently under way within the NIH involves the development of molecular libraries and molecular imaging.

“This offers tremendous potential for developing technologies to improve not only the understanding of human physiology and disease but also the management, treatment andone dayprevention of same,” says Pettigrew. “With molecular libraries, the goals are to screen hundreds of thousands of small molecules in an effort to identify those that have natural affinity for specific targets, such as protein expressed on the surface of cells or specific molecular markers of disease, which could then lead to a basis for new therapeutic interventions and a basis for new probes with which to image these new drugs, and determine the spatial distribution, the temporal behavior, and the toxicologic profiles of these new agents.”

In this, as with other roadmap activities, the NIBIB is but one player. However, the bandleader nevertheless happens to be a radiologistElias Zerhouni, MD, director of the NIH.

“Having a radiologist in the top position at the NIH is advantageous only in the sense that we at the NIBIB speak the same language as he does,” says Pettigrew. “When we make a presentation to Dr Zerhouni and it involves radiology, we don’t have to be concerned about the possibility that our ideas will be lost in the translation, since no translating is required. But, apart from that, Dr Zerhouni’s background does not favor the NIBIB. He is scrupulously fair and evenhanded in his considerations toward each and every one of the institutes that comprise the NIH.”

The Research

Much of the research insight being accumulated by the NIBIB originates with projects that the institute underwrites at various molecular imaging centers around the country. These are located at the University of California at Los Angeles; Massachusetts General Hospital in Boston; University of Michigan in Ann Arbor; and Washington University in St. Louis; and Memorial Sloan-Ketering Cancer Center in New York City. More are currently being added.

Additionally, the NIBIB soon will initiate an NIH-sponsored intramural research program. “The complete makeup of the intramural program has not yet been decided but will likely reflect in large part the type of expertise we’re able to recruit and bring to the NIH in areas such as nanotechnology, tissue engineering, or platform technologies,” Pettigrew explains. “As part of this program, we’re also planning on leveraging the resources of other federal agencies – one in particular is the National Institute of Standards and Technology [NIST], which is in a great position to have a synergistic relationship with us. The NIST – about a 30-minute drive from here – has a number of labs. We, on the other hand, do not  yet have laboratory space. We are negotiating a memorandum of understanding where we will utilize some of their laboratory space and also work synergistically with some of their scientists in areas of mutual interest, while we in exchange provide some of the intellectual capital.”

There even is a role for vendors in all this, for partnering with industry has been a goal of Pettigrew’s since almost his first day at the NIBIB.

“As financial resources become more precious, we have to look for creative ways to be efficient and effective,” he says, adding that partnership would be good for industry, too. “There are areas of need, gaps that have not been addressed, that are perhaps too big or complicated or challenging for either of us to do alone but could be done as partners. There are areas of opportunity that business might not have wanted to explore because they are too risky, and in their business model, it doesn’t make sense to take that risk. But from a scientific standpoint, the risk-taking is warranted because the pay-off, if successful, could be so huge. That’s where we can step

in and help by shouldering some of

that risk.”

The NIBIB plans in December to host an industry-based workshop as a means of attracting more participation among vendors.

“We’re inviting representatives from the major manufacturers across multiple industrial disciplines – including equipment, pharmaceuticals, biomaterials, medical devices, and more – in an effort to explore areas of commonality and synergy between this public institute and the private sector,” says Pettigrew “We’ll try to identify problems that are not now being addressed by either the public or private sector, but that could be addressed by a public-private partnership.”


High on the list of NIBIB goals has been a call to establish centers for research training. To date, the institute has helped organize and fund 15 training centers, including programs at the University of Ohio, Cincinnati; Harvard University, Boston; the University of Chicago; the University of Arizona, Tucson; Vanderbilt University, Nashville, Tenn; Duke University, Durham, NC; the University of Iowa, Iowa City; the University of California at Los Angeles; and the University of Florida, Gainesville.

“This is just a start,” promises William J. Heetderks, PhD, MD, associate director for science programs, one of the fewer than 50 federal employees who work at the NIBIB (compared to the 17,000 total NIH labor force).

Like Pettigrew, Heetderks possess both a PhD and an MD – many more staffers have one or the other. These highly credentialed employees serve as grant program portfolio managers, stewards of the grants peer-review process, policy officers, and as liaison to trans-NIH initiatives.

“This is a wonderful, hard-working group of people who are energized by the vision of the institute,” says Dean.

However, a problem for the NIBIB at the moment is money – the budget for fiscal year 2004 (which started October 1) has as of this writing yet to be authorized by Congress. The overdue FY 2004 budget includes an increase for the NIBIB of about $4 million.

“We still have funds to operate,” Dean assures. “Congress may not have approved a new budget, but at least

we’re getting continuing resolutions from them.”

A continuing resolution, she explains, is a stop-gap measure that authorizes funds to be released to keep government operating in the absence of a new budget. The catch for entities like the NIBIB is that the amount allotted is the same as that contained in the expired budget. Continuing resolutions are usually good for a period of 30 days; if Congress cannot agree on a new budget, it simply keeps passing continuing resolutions until agreement is reached. Last time around, it was 6 months into the new fiscal year before a budget was finally adopted.

Reshuffling The Deck

Dean expects the NIBIB will nonetheless be able to award at least $30 million to $40 million in new grants this current fiscal year, even with the limitation of having to live within the means of the old budget, which no one expects. The number of grants in the NIBIB portfolio is quite an accomplishment for such a young institute, and how that came to be is itself a fascinating tale.

“Of the 800 active grants in our portfolio, approximately 300 were transferred to us from other NIH enterprises,” Dean explains. The transfers began in FY 2002. Candidates for transfer were identified by each of the NIH institutes,  relying on the NIBIB’s mission statement for guidance.

“We told the other institutes that we did not want their big center grants, just their research project grants that might be broadly applicable to biomedical imaging and biomedical engineering,” Dean says. “In FY 2002, the grant transfer candidates were worth a total of $67 million. It was a comparatively small amount, but it gave the NIBIB a foundation.”

Adding the allotments from the NIBIB’s own FY 2002 budget to that sum, the institute ended up awarding more than $100 million in grants during the first year of operation. However, the ARR and AIMBE – in their capacities of nurturing associations for the NIBIB – were not satisfied that the other NIH institutes had been fully forthcoming in identifying transfer candidates. They complained to Congress, which responded by including a provision in the NIH’s FY 2003 budget to require that $150 million in existing project grants be moved to the auspices of the NIBIB, reports Dean.

Some of the institutes objected on grounds that, in complying with the Congressional directive, “they would be giving away pieces considered integral to their own biomedical imaging programs that they needed to retain control over in order to accomplish their individual missions,” says Dean.

The solution for some of these NIH entities was to transfer fewer grants than expected but then make up the difference with a cash payment – an arrangement the NIBIB found perfectly acceptable. “We had to be sensitive to the activities and wishes of these other institutes,” says Dean.

Maynard, the former ARR president, indicates that the objections some institutes had to funds being shifted to the NIBIB centered around a desire simply to continue the tradition of having grant money allocated for disease- or organ-specific research, not the much broader type of endeavors contemplated by the mandate of the new institute.

“It was never the intent of the NIBIB to raid the grants of other NIH entities,” he clarifies. “It wasn’t until people saw that there weren’t going to be any raids did they believe such would not be the case. But any time you take money from one place to another, there are going to be people who at least initially will feel that’s not the thing to do.”

The total of cash payments made to NIBIB that year was about $50 million, or one third of the requisite sum, says Dean. That $50 million enabled NIBIB to issue requests-for-applications on 10 brand-new areas of research interest, which brought forth a combined total of more than 1,100 responses – an overwhelming number, in Dean’s calculus. “The money gave us a real jump-start, and the outpouring of applications confirmed for us that there are communities out there very interested in the work of the NIBIB,” she says.

The $150 million received from the other institutes brought the total

of NIBIB’s budget in FY 2003 to $280



During NIBIB’s formative period, a list of about 18 varied research goals was offered by the AAR and AIMBE. Those goals were adopted, but it is not clear just how they have been prioritized by the NIBIB. “Since our mandate is broad and the nature of our work is groundbreaking and dynamic, it would be unfair to give you a prioritized line-up. However, there are always several key focus areas,” says Pettigrew.

Heetderks also allows that those near the top of the list include molecular imaging, image-guided surgery, optical imaging, and functional MR. “In all fairness, we don’t pick an area and make it a priority at the expense of everything else,” Heetderks notes. “We only have so much money to go around, and we can’t possibly fund everything. At least not yet.”

An example of a worthy project the NIBIB has chosen to fund is entitled “Live Tissue Intrinsic Emission Microscopy Using Multi-Photon Excited Native Fluorescence and Second-Harmonic Generation.” As Heetderks describes, “The goal of this project is to be able to do histopathologic imaging in living tissue. The conventional way you evaluate tissue is with a biopsy. The tissue is then stained and examined under the microscope in a pathology laboratory. What the investigator is doing here is looking at the ways that cells autofluoresce under suitable light so that high-contrast images can be achieved in situ. This native fluorescence is not seen using conventional illumination because the reflection and diffusion of the incident light washes out the fluorescence signal much like sunlight washes out the light from stars in the daytime. To avoid this washout, the investigators are

exciting fluorescence with two-photon microscopy. So far they’ve gotten some fairly dramatic images, which is offering the potential of one day doing living biopsies in other words, doing the biopsy right as you’re doing the surgery.”

From Pettigrew’s vantage point, that project – along with all of the others supported by the NIBIB – offers much hope for a brighter, healthier future.

“Technological innovation is the engine that drives scientific progress in general and medical advancement in particular, and we’re here to facilitate that,” he says. “We’re here to, among other things, focus the imaging and bioengineering world – people and resources both towards realizing such advancement.”

Rich Smith is a contributing writer for Decisions in Axis Imaging News.