Optical Coherence Tomography Laboratory

Director:

Mark Brezinski, MD, PhD

Current Team:

Bin Liu PhD, Christopher Vercollone BS, Shiyi Zan BS, James Maddison, Sherry Hall, Elyse Tufts, Denise Johnson, Christopher Rashidifard

Collaborators:

Michael Brenner MD, Kathy Jenkins MD, MPH, Amy Juraszek MD, Phillip Lang MD, MBA, Robert Langer PhD, Maria Rupnick MD, PhD

Note: Dr. Brezinski would like to recognize his close collaborations in the first decade with Professor James Fujimoto of MIT and Eric Swanson MS of Lincoln Labs

In addition: Neil Weissman MD, James Southern MD, PhD, the late 'Chip' Gold MD, PhD, as well as many other talented team members who have contributed previously.

Optical Coherence Tomography:

Optical Coherence Tomography (OCT) is the first new imaging technology since MRI. We are the pioneering team that developed it and it is FDA approved in Ophthalmology and Cardiology (2010). In both fields it has regulatory approval in at least 30 other countries. Since 2000 we have been developing and are studying the technology for musculoskeletal disease, and have the vast majority of publications in this field. Of particular use has been polarization sensitive OCT (PS-OCT) which allows us to detect collagen breakdown long before gross changes occur in tissue. Clinical studies underway include early detection of osteoarthritis before cartilage breakdown, improving outcomes of rotator cuff repair, and guiding treatment decision in rheumatoid arthritis.

Our lab is also one of the world leaders in quantum biology. This has been a goal of science since the time of Einstein. This is large scale objects like cells being driven by principles which previously only affected structures on the order of atoms and molecules. The work can potentially lead to paradigm shifts in therapeutics such as the use of quantum entanglement in therapeutics, which has been achieved with leukemic cells.

Areas of Research:

Optical Coherence Tomography (OCT): The development, theory, application, and examination of physical principles of optical coherence tomography, principally in nontransparent tissue.

2010 marked FDA approval and sales of OCT for intravascular imaging. OCT is analogous to ultrasound, measuring the back reflection of infrared light rather than acoustical waves. The greatest current advantage of OCT over existing technology is its resolution, which is up to 25x higher than anything available in clinical medicine. Additional advantages are its acquisition rates at video speed, catheters/endoscopes as small as 0.017 inches, and its ability to combine with a range of spectroscopic techniques. OCT is a true bench to bedside success, from an idea to lifesaving patient imaging systems and well over 10,000 US jobs.

Major studies:

1. OCT arthroscopy in comparison to MRI and conventional arthroscopy for assessing early OA markers

2. Assessing shoulder tendon, euthesis, and bone in the rotator cuff repair to prevent re-rupture.

3. Early markers of rheumatoid arthritis from aggressive preventative therapy.

3. Second order (quantum) OCT imaging for tissue characterization

4. Development of new models of rat OA.

5. OCT technology development

6. Quantitative polarization sensitive OCT (PS-OCT) for assessing (tissue) tissue collagen

7. Fully quantized OCT

Quantum Biology:

There can be minimal controversy that the understanding and control of macroscopic quantum systems (MQS) would represent more than just an intellectual pursuit, but if attainable, would have a paradigm shifting impact on a broad spectrum of fields. MQS, long referred to as ‘Schrodinger's cat-like states’, will be defined here as the situation where macroscopic properties are governed by quantum mechanics rather than classical mechanics. Our objective is to control (and understand the mechanism behind).

In an earlier paper we laid down several foundations (both theoretically and experimentally) for the work in the current paper through a study examining the nonlocal nature of quantum correlations between a spatially separated grating and target (various media separated by two reflectors). Experimental design was critical in identifying macroscopic quantum phenomena in the large scale system. In that paper, both the target and grating represented the distal ends of the Michelson interferometer arms irradiated with a thermal source of broad bandwidth and the light had low purity with respect to second order correlations (which we demonstrated to have quantum mechanical properties unlike first order correlations). It was the demonstration that second order correlations exhibited quantum mechanical effects that drew the most attention at the time, an observation that has important implications in quantum imaging. However, it was both the macroscopic superposition within the target and its ability to be 'altered' nonlocally by the grating that were the actual focus. Alterations in the grating angle, due to the experimental design, led nonlocally to varying degrees of macroscopic superposition in the target.

In the experimental portion of the current paper we demonstrate nonlocal (remote) interactions between leukemic cell lines (HL-60 cells) physically separated in Euclidean space. Induction of apoptosis (programmed cell death) in cells at one location led to correlations in cell death rates (and apoptosis markers) in their entangled pair (vehicle treated) at a remote location occurring through mechanisms consistent with quantum principles. The differences were statistically significant from controls both in terms cell death rates and apoptotic enzymes. Cell death rates were not significantly different between the treated cultures and their entangled pairs. The results do not necessarily mean the quantum interactions are between entire cells as low purity correlated mesoscopic subsystems within cells can macroscopically alter overall function remotely.

Relevant Papers:

Brezinski ME, Tearney GJ, Bouma BE, Izatt JA, Hee MR, Swanson EA, Southern JF, Fujimoto JG. Optical coherence tomography for optical biopsy. Properties and demonstration of vascular pathology. Circulation. 1996 Mar 15;93(6):1206-13.

Tearney GJ, Brezinski ME, Bouma BE, Boppart SA, Pitris C, Southern JF, Fujimoto JG. In vivo endoscopic optical biopsy with optical coherence tomography. Science 1997, 276:2037-2039.

Herrmann JM, Pitris C, Bouma BE, Boppart SA, Jesser CA, Stamper DL, Fujimoto JG, Brezinski ME. High resolution imaging of normal and osteoarthritic cartilage with optical coherence tomography. J Rheumatol. 1999 Mar; 26(3):627-35.

Drexler W, Stamper D, Jesser C, Li X, Pitris C, Saunders K, Martin S, Lodge MB, Fujimoto JG, Brezinski ME. Correlation of collagen organization with polarization sensitive imaging of in vitro cartilage: implications for osteoarthritis. J Rheumatol. 2001 Jun; 28(6):1311-8.

Schenck J, Brezinski ME. Ultrasound induced improvement in optical coherence tomography. Proceeding of the National Academy of Science 2002; 99: 9761-9764.

Liu B, Harman M, Brezinski ME. Variables affecting polarization-sensitive optical coherence tomography imaging examined through the modeling of birefringent phantoms. J Opt Soc Am A Opt Image Sci Vis. 2005 Feb; 22(2):262-71.

Li X, Martin S, Pitris C, Ghanta R, Stamper DL, Harman M, Fujimoto JG, Brezinski ME. High-resolution optical coherence tomographic imaging of osteoarthritic cartilage during open knee surgery. Arthritis Res Ther. 2005; 7(2): R318-23.

Huang C, Liu B, Brezinski ME. Ultrasound-enhanced optical coherence tomography: improved penetration and resolution. J Opt Soc Am A Opt Image Sci Vis. 2008 Apr;25(4):938-46.

Adams SB, Herz PR, Stamper DL, Roberts MJ, Bourquin S, Patel NA, Schneider K, Martin SD, Shortkroff S, Fujimoto JG, Brezinski ME. High resolution imaging of progressive articular cartilage degeneration. in a rat. J Orthop Res, 2006; 24: 708-715.

Liu B, Harman M, Giattina S, Stamper DL, Demakis C, Chilek M, Raby S and Brezinski ME. Characterizing of tissue microstructure with single detector polarization sensitive optical coherence tomography. Applied Optics. 2006; 45: 4464-4479.

Brezinski ME and Liu B. Nonlocal quantum macroscopic superposition in a high-thermal low-purity state. Physical Review A (Atomic, Molecular, and Optical Physics) 2008, 78:063824.

Liu B, Azimi E, Brezinski ME. Improvement in dynamic range limitation of swept source optical coherence tomography by true logarithmic amplification. J Opt Soc Am A Opt Image Sci Vis. 2010 Mar 1;27(3):404-14.

Zheng K, Martin SD, Rashidifard CH, Liu B, Brezinski ME. In vivo micron-scale arthroscopic imaging of human knee osteoarthritis with optical coherence tomography: comparison with magnetic resonance imaging and arthroscopy. Am J Orthop 2010 39(3):122-125.

Brezinski, MD, PhD. Current capabilities of optical coherence tomography as a high impact cardiovascular imaging modality circulation. (in press)

Brezinski, MD, PhD. A quantum field approach to optical coherence tomography. Insights into potential new advances of the technology. (in press)

Book:

Brezinski ME. Optical Coherence Tomography: Principles and Applications. Academic Press, 2006, (Note: second addition being written)

Grant Support:

5 R01 AR044812-11 Brezinski (PI)

NIH/NIAMS

Mechanism & Efficacy of Assessing Osteoarthritis by OCT

The long term objective of the program is to develop optical coherence tomography for high resolution imaging of early osteoarthritis

5 R01 EB002638-08 Brezinski (PI)

NIH/NIBIB

Identification and Treatment of Unstable Plaque with OCT

Using a rabbit model of atherosclerosis to improve the ability of OCT to identify unstable plaque.

5 R01 AR046996-07 Brezinski (PI)

NIH/NIAMS

Advanced Techniques for Assessing Osteoarthritis in Rats

Developed animal models for assessing osteoarthritis.

5 R01 EB00419-04 Brezinski (PI)

NIH/NIBIB

Optical Coherence Tomography for Microsurgical Guidance

The program focused on improving OCT imaging for the assessment of pulmonary hypertension and guidance of pulmonary ablation.

5 R01 HL55686-10 Brezinski (PI)

NIH/NHLBI

Optical Coherence Tomography for the Evaluation of Pulmonary Circulation

The program focused on improving OCT imaging for the assessment of pulmonary hypertension and guidance of pulmonary ablation.