“Biomedical imaging science is not just for the practice of radiology or clinical diagnosis today,” says Calum Avison, professor at Vanderbilt University. “It is a coherent and multidisciplinary science.”

Prior to 1895 when the most rudimentary x-rays were developed, this science was non-existent. Since there was no way to view inside the body, blind clinical diagnoses were based solely on physical symptoms. The advent of x-rays changed the practice of clinical medicine and continues to have an impact as a powerful tool to image bones and detect foreign objects. The promise of the x-rays led to increased exploration in finding ways to obtain structural information about the interior of the body. Ultrasound machines were invented in 1950 and have improved from large, cumbersome machines to the advanced, portable systems being used today.

The next technological advances which provided greater image clarity were computed tomography, or CT scanning, and nuclear imaging, such as positron emission tomography (PET) scanning. Nuclear imaging represented a shift away from anatomy to examining the biochemistry and function of the underlying tissue. The PET scanning can be used to measure the metabolic rate of the brain, map the distribution of receptors within the brain, and determine how chemical levels vary with certain disease states or drug reactions.

Magnetic resonance imaging (MRI) is the most recent innovation in clinical imaging technology, improving from low magnetic fields of 0.15 Tesla in 1984 to 7 Tesla today.

Today’s Art of Imaging

Major improvements have been made in all of the imaging modalities as a result of advances in technology. High-tech imaging and advanced computer algorithms enable physicians to see exquisite details of bones, tissues, organs, and vascular systems with high spatial resolutions. For example, a CT scan can pinpoint something as small as calcifications in coronary arteries, and 7 Tesla MRI provides superb anatomical views with high spatial resolution.

Imaging today extends beyond traditional radiology, complementing and expanding upon advances in other scientific fields, such as genomics, proteomics, and molecular biology. Building upon the trends of the last five years, imaging is now used to study function rather than just anatomy.

Molecular imaging allows physicians to target specific processes, quantitative imaging provides objective data, and animal studies can be done using imaging to test such variables as drug interaction and reaction.

“We have a new class of multidisciplinary imaging scientists who are experts in relating image-based measurements to pathology, physiology, proteomics, genomics, and metabolism,” says Avison. “One critical distinction between radiologists and imaging scientists is that radiologists are experts in relating imaging science to pathology.”

Imaging science is recognized as an important field for the development and application as an investigative tool in biology and medicine. The most recently formed institute within the National Institutes of Health is the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The institute coordinates with biomedical imaging and bioengineering programs of other agencies and NIH projects to support imaging and engineering research with potential medical applications.

Why Image?

Non-invasive imaging can detect, characterize, and monitor disease; assess the effects of drugs on metabolism, blood flow, and neural activity; detect and map the distribution of drugs; provide three-dimensional, undistorted views; and be sensitive to biological processes. It can provide information on spatial heterogeneity of tissues and details about structure and morphology, such as bone loss and size of tumors.

The Institute of Imaging Science (IIS) at Vanderbilt University uses micro-CT systems to examine bone development and erosion, as well as the growth of tumors. Specialized imaging systems for animals are consolidated at the IIS, enabling information from multiple sources to be integrated.

“We can compare the growth in animal models that are untreated with animals that are treated,” says Avison. “An important aspect of these imaging technologies is that animals are not sacrificed. You are also using fewer animals so it is a more efficient and more cost-effective way to do research studies.”

Imaging also provides precise information on tissue composition and biophysical characteristics. A single imaging session can give clinicians specifics about tissue parameters and other measures that reflect vascular function and assist in developing multi-parametric characterizations of tumors that may lead to improved diagnosis and treatment without the need for a biopsy. Neural activity, cardiac mechanics, blood perfusion, and rate of oxygen usage can be traced using sophisticated MRIs.

Molecular imaging using nuclear and optical methods is beneficial when looking at certain biochemical and molecular biological processes. This type of imaging can show the effect of abnormalities, such as cocaine abuse, Alzheimer’s disease, or psychiatric disorders, on the brain based on the distribution and density of neuroreceptors.

Different imaging systems may be appropriate to answer different questions. For instance, very high resolution imaging may be necessary to do brain mapping and multiple modalities, including the high field vertical MRI system to study the behavior of monkeys. A 9.4 or 11.7 Tesla MRI may be needed to image mice, while a 4.7 Tesla may be better for larger animals.

A micro-PET, which is good for imaging small animals, requires cyclotron and radiochemistry synthesis and provides a resolution of 1.5 mm. Optical imaging requires light produced from within small animals either by fluorescence after excitation by a light source or by bioluminescence from cells containing luciferase.

“Animal studies, especially of mice and primates, will push techniques in the future and these may then affect human imaging studies,” notes Avison. “Imaging science represents the marriage of technology with chemistry, pharmacology, and molecular biology to provide powerful new probes.”

Facility Planning Issues

“It is important for architects and facilities planners to have a basic understanding of what is going on in the science world in order to design appropriate facilities,” says Jerry Percifield, principal at Lord, Aeck & Sargent.

Facility planning issues include safety, emerging science strategies, site selection, equipment planning, support services, patient requirements, and regulations. The imaging industry is regulated at the local, state, and federal levels by the Nuclear Regulatory Commission (NRC), the American Association of Laboratory Animal Certification (AALAC), U.S. Department of Agriculture, Institutional Animal Care & Use Committee (IACUC), and the American Association of Physicists in Medicine (AAPM).

“It is very important as you design facilities to understand the regulations,” stresses Percifield. “If you are doing both research and clinical programs like those taking place at Vanderbilt, there are separate regulatory issues associated with patients, patient rights, and privacy. When you do research and clinical work, there are serious implications about how you overlap requirements for patient work and animal work.”

Patient issues are regulated by the Health Insurance Portability and Accountability Act (HIPAA), the Clinical Laboratories Improvement Act (CLIA), the Institutional Review Board (IRB), and the Human Investigation Committee (HIC).

In addition to the regulations, the design planning must also consider issues associated with shared resources, time allocation, and funding to pay for the machines. An interdisciplinary approach to problem solving is helpful when dealing with multidisciplinary uses of a facility.

Site Selection Issues

It is important to select a quiet site where sensitive imaging equipment will not be disturbed by vibrations, noise, electromagnetic interference, or radio frequency interference. Building a facility near a bus line or other sources of heavy traffic or noise would not be a good idea.

The location of the facility should provide easy accessibility for patients, researchers, staff members, and visitors. It should also be easy to transport animals and equipment in and out of the building.

The location of the IIS at Vanderbilt’s Medical Center North Complex facilitates easy intra-institutional collaboration between other departments, schools, and centers located on campus. Real estate is sparse at Vanderbilt, so vertical building additions are often used to maximize space.

“One of the key aspects to getting funded was to have intra-institutional collaborations,” says Howard Wertheimer, principal at Lord, Aeck & Sargent. “It’s important to develop links to other researchers who can share the investment.”

Vanderbilt also maintains inter-institutional collaborations with the National Center for Toxicology Research, the University of Alabama, the University of Texas, Meharry Medical College, and Wayne State University.

“There is no substitute for collaboration and you can be far more competitive in these times of dire funding,” says Avison. “The people make it work, so it is important to build a facility that makes sure people are brought together.”

Equipment Planning

Using high-tech equipment requires the necessary support services and utilities. The machines require a tremendous amount of surge-protected electrical power with a backup source of electricity in case of an emergency. The facility must be able to accommodate the high demand for power and other utility services. Therefore, the design and construction must be based on the scientific equipment that will be used in the facility and the type of collaboration that will occur. It is important to understand what type of equipment will be used at the beginning of the planning stages in order to define space requirements based on size and weight.

The type of equipment to be used will dictate the safety considerations and shielding requirements that will be built into the design.

When Lord, Aeck & Sargent designed the IIS at Vanderbilt, plans took into account a 7 Tesla human magnet, which did not yet exist anywhere in the world. The two-story magnet is located on the lower level, but extends through a hole in the slab up to the first floor. Considering the gauss lines and necessary shielding to protect building occupants is important.

The design also features plenty of space on the first floor for interaction between scientists. The IIS houses approximately $20 million worth of imaging equipment, but a $2,000 cappuccino machine located in the seminar room is viewed as one of the most important pieces of equipment to facilitate collaboration.

The second floor of the IIS houses ultrasound and micro-CT and PET equipment, as well as magnets for animal imaging. A removable floor slab and overhead hoist beam enables equipment to be transported in and out of the building.

“It is really important to think about how you move these pieces of equipment because it is not an easy task,” says Wertheimer. “Part of the design and construction process is having the rigging companies involved.”

Challenges

Designing and operating a facility that houses imaging equipment is not without challenges. The cost of the equipment can be prohibitive and it is becoming increasingly difficult to find funding sources, making it critical to justify the need for inter- and intra-disciplinary programs.

“I suspect this concept of a dedicated resource is going to be dead in a few years. Nobody is going to be able to afford to have these dedicated, single-use facilities,” says Percifield. “The idea of how to share them will become part of the design process.”

It is vital to plan for the next generation because the technology is changing rapidly. Although it is difficult to predict what type of equipment will be available in the future, it is crucial to incorporate a comprehensive infrastructure into the design to accommodate tomorrow’s machines. Special facility requirements must be factored into the design to accommodate space requirements for large equipment and to meet the technical need for shielding.

The blending of clinical and research activities from a regulatory standpoint can be troublesome.

“Making sure both the human and animal models are dealt with fairly and humanely are critical components and continue to be looked at because the blending of the clinical aspects and the research is fairly new,” says Percifield.

By Tracy Carbasho