Innovation detects disease earlier

Calibration technique promises improved diagnostics for patients

The emergence of advanced medical imaging technologies has had a profound effect on the modern world. They have enabled scientists and doctors to study cells and determine abnormalities that signal disease. Optical imaging devices can produce much higher resolution images than magnetic resonance imaging (MRI)—the gold standard in diagnostic imaging—but they are generally inferior for applications that require higher depth penetrations. However, a number of recent advancements in optical imaging techniques are able to improve the ability of light to propagate through tissues with diffraction-limited beam qualities. New optical imaging systems thus have the potential to provide higher resolution depth measurements of biological tissue than previously possible.

Dr. Robert Chang

Dr. Robert Chang of the Department of Mechanical Engineering at Stevens Institute of Technology is working to advance this promising technology with a standard calibration tool so that new optical imaging devices can be applied to measure depth with precision in clinical settings. He has been awarded a grant from the National Institute of Standards and Technology (NIST) to develop a standard calibration tool for depth-resolving optical imaging modalities.

“Early diagnosis can make a tremendous difference in the effectiveness of treatment for many diseases,” says Dr. Michael Bruno, Dean of the Charles V. Schaefer, Jr. School of Engineering and Science. “The standardization and proliferation of medical imaging technology that improves diagnostic capabilities can thus have an impact on the health of millions.”

"Providing accurate depth resolution standards will ensure confidence in high resolution medical imaging modalities capable of detecting tumors at much earlier stages of development," says Dr. Frank Fisher, Interim Director of the Department of Mechanical Engineering. "These standards are crucial for the establishment of cross-validated optical measurements necessary for future technological innovation in the screening and diagnosis of many human disease states."

Just as there is a need to routinely zero a scale for quantitative weight measurements, scientists need to calibrate microscopes so that they can produce accurate and precise spatial measurements. The most widely accepted benchmark for testing the quality and resolving power of optical imaging systems in the lateral dimension is the United States Air Force resolution test chart, which consists of a fine chrome film pattern of three bars or alternating dark/bright line pairs deposited on glass. Researchers determine the limitations of the device’s lateral resolving power by finding the largest bar or line pairs that it fails to discern.

This established standard has made lateral optical imaging devices extremely precise, widely accepted clinical tools, but axial (depth) optical imaging devices like optical coherence tomography (OCT) and near-IR fluorescence imaging have no widely accepted standard. Dr. Chang has therefore proposed the design and fabrication of a tissue phantom (or tissue-simulating object) to serve as a test target for the calibration of these burgeoning optical imaging technologies. The test target would be highly reproducible, stable, independently characterized for physical dimensions, and mimic the light-scattering properties of normal tissue heterogeneity. It would be an essential tool for assessing the alignment, sensitivity, resolution, and contrast of various prototypes of optical devices in development and in various stages of preclinical and clinical testing.

The establishment of a calibration standard is crucial for fields like ophthalmology, in which OCT is used to generate optical biopsies of the retinal layers and to delineate corneal layers. Doctors can use OCT systems to get a cross-sectional image of retina and look for microstructural abnormalities down to the micron scale, with depth penetration of 2mm. Quantitative thickness measurements of these reflective tissue layers can aid the diagnosis and treatment of numerous diseases of the eye. Doctors can also check the size and shape of the corena to determine if a patient is a good candidate for Lasik surgery.

Micron-scale depth imaging can also help in the study of certain cancers. Materials have different refractive indexes and scatter light differently. Doctors know how cancer cells and healthy cells differ in reflective index, so they can use OCT to detect cancerous cells. For instance, endoscopic-based OCT has been used to study the invasion of mucosal layers into submucosal layers of the gastrointestinal lining, which can be an early indicator of colon cancer. The same principle can also be applied for earlier detection of atherosclerosis, a risk factor for heart attacks in which fatty material accumulates on blood vessel walls. The fatty materials begin to cause protrusions at minute scales, and OCT can detect these abnormalities at early stages.

Despite numerous promising applications, it has been difficult to apply OCT technology in clinical settings. In the absence of a calibration tool to standardize measurement, existing OCT systems measuring a retina provide measurements disparate enough that they represent the difference between a normal and abnormal cornea. This imprecision currently undermines their value as a clinical tool, and Dr. Chang’s Biomodeling and Biomeasurement Lab’s development of a standardizable testing method and tissue phantom promises to help realize the potential of depth-resolving optical imaging.

Robert Chang received his B.S. from The University of Pennsylvania and Ph.D. in Mechanical Engineering from Drexel University with a research focus in computer-aided tissue engineering. His doctoral dissertation centered on the development of biofabrication systems to create reproducible, biomimetic 3D micro-organs as a high-throughput in vitro radiation/drug model for NASA's exploration in planetary environments.

He received a National Research Council (NRC) Research Fellowship to work as a biomechanical engineer in the Physical Measurement Laboratory at the National Institute of Standards and Technology (NIST) where he has engineered novel tissue models towards the validation of depth-resolving optical modalities including optical coherent tomography (OCT) and confocal microscopy for dimensional metrology as well as hyperspectral imaging for wound healing applications and surgical scenes. Robert is currently an Assistant Professor in the Mechanical Engineering Department at Stevens where his research interests are in biofabrication, biomodeling, and measurement of biotissues.

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