Real-Time Intra-Operative Infrared Parathyroid Visualization System

NCIIA Grant Proposal

Vanderbilt University

29 October 2009

Isaac Pence Contact Information

Team: Principal Investigator Isaac Pence Anita Mahadevan-Jansen [email protected] [email protected] 502-403-7209 615-343-4787 Box 350748 Sta B Box 351631 Sta B

Graduate Advisor Administrative contact Dean Paras Mary H Judd [email protected] [email protected] 216-310-2026 615-322-4229 Box 1631 Sta B

Title Real-Time Intra-Operative Infrared Parathyroid Visualization System

Abstract

Complications from incomplete or accidental removal of the parathyroid glands are a major concern associated with endocrine surgery. Current localization techniques are primarily preoperative and only applicable in select surgeries. The proximity of the various tissues encountered in the neck during surgery and the tendency of these tissues to blend together serve as confounding factors for surgeons. There is a need for a sensitive, real-time, intra-operative diagnostic tool to assist with anatomical guidance. Previous studies have shown the ability of near-infrared (NIR) autofluorescence to differentiate between the parathyroid and the surrounding tissue based on the intrinsic optical properties. The parathyroid exhibits stronger fluorescence than all other tissues in the neck. Near-infrared imaging would provide spatial context as a more intuitive approach for the surgeon. Here we present the first application of an autofluorescence-based imaging system for real-time intra-operative use in endocrine surgery. A 785nm diode laser is used to excite the tissue and a converter tube is employed to detect the NIR fluorescence and render it in the visible wavelengths. The image is then captured by CCD and processed to apply a false color gradient for distinction between tissue types. We demonstrate the utility of the NIR fluorescence imaging system in vivo and in vitro. Preliminary results indicate that imaging is able to capture the higher level of autofluorescence exhibited by the parathyroid differentiating it from the surrounding tissue. The specific aims are:  modification of existing infrared visualization system,  optimization of design specifications for integration into a surgical setting,  verification of designed system both in vitro and in vivo.

Project Description

The parathyroid glands are small endocrine glands within the neck that regulate levels of calcium in the blood through production of parathyroid hormone. The ability to consistently regulate calcium is of great importance due to the vital role that it plays as a neurotransmitter in the conduction of nerve signals. Without close regulation, the body would not retain the ability to generate action potentials and therefore could not cause muscle contractions. The strength and density of bones is also essential and reliant upon these glands.

When thyroid or parathyroid disease affects a patient, primary hyperparathyroidism affecting 100,000 new patients a year (Zanocco), if treatment by other methods is not possible, physicians must often resort to surgical excision of the diseased tissue. Due to the close proximity and similarity in appearance of the tissues, visual distinction, especially of the parathyroid, is often difficult, complicating excision. Further difficulties include the small size and variable location of the parathyroid organs within the neck. The reliance of surgeons on visual inspection of the tissues to differentiate between them are subjective and often inconclusive. Inadequate excision during parathyroidectomy or accidental removal of or damage to the parathyroid glands during thyroidectomy are two of the serious complications associated with endocrine surgery.

Hypoparathyroidism is a condition resulting from abnormally low secretion of parathyroid hormone. Some of the complications from this problem are paresthesias, muscle aches, cramps, and spasms, fatigue, anxiety, depression, memory problems, loss of consciousness, impaired kidney function, heart arrhythmias, cataracts, calcium deposits in the brain, stunted growth, or slow mental development in children. The most prevalent form of this condition is acquired or iatrogenic hypoparathyroidism, due to errors during head or neck surgery. Up to 11% of thyroid surgery patients suffer from permanent hypoparathyroidism (McHenry), 6.4% of these due to inadvertent resection of the parathyroid glands (Sippel). Another complication of endocrine surgery is the incomplete resection of the thyroid pathology, causing up to 6% of patients undergoing reoperation (Rosato). As these surgeries cost $4986 each, repeat surgeries lead to high medical costs (Zanocco). To avoid this complication, there is a need for a sensitive, real-time, intra-operative diagnostic tool to assist with anatomical guidance. Existing methods for localization of the parathyroid glands are either preoperative imaging or postoperative histopathology, limiting the intra-operative performance. Previous studies have shown the ability of near-infrared (NIR) autofluorescence to differentiate between the parathyroid and the surrounding tissue based on the intrinsic optical properties. The parathyroid exhibits stronger autofluorescence than all other tissues in the neck. Near-infrared imaging would provide spatial context as a more intuitive approach for the surgeon. By completing this design project, the need for a real-time intra-operative localization tool is fulfilled, spanning a gap in current endocrine surgery technology.

History and Context

Optical spectroscopy has shown the ability to differentiate between tissue archetecture and biochemical differences. Pararthyroid tissue has been found to exhibit autofluorescence in the NIR wavelengths. This project represents the first use of NIR autofluorescence as a diagnostic tool for intra-operative imaging.

This project is a continuation from the previous year's design course. A team last year developed a working prototype and tested it's applicability in vitro with human parathyroid tissue. Integration into the surgical setting as well as optimizing both the physical and optical elements is yet to be solved. The project currently needs further technical improvements; a prototype exists, requiring further development.

Team Isaac Pence is doing this project alone to simplify development. Along with having already completed the undergraduate Biomedical optics curriculum, he has experience with the systems and in the optics lab. By beginning the research prior to the start of the semester, it would have been more difficult to bring other seniors up to speed. Isaac is also presenting this project at the SPIE Photonics West conference in San Francisco in January 2010. Isaac is experienced with the required programming in both LabView and MATLAB, and has a sufficient background in the hardware required for modification of the IR viewer system.

Outside advisors for this project are Dean Paras, a graduate student, and Dr. Mahadevan- Jansen, both of the Biomedical Optics department. The knowledge, experience and expertise of both of these individuals will be paramount in designing, optimizing and testing the system. Use of Dr. Mahadevan-Jansen's optics lab will serve as the primary working facility. Dr. James Broome is a member of the Vanderbilt Endocrine Surgery Center and will help facilitate system testing, data collection, and give insight into most useful methods for completion of this project.

Work Plan and Outcomes

In completing this project, I hope to gain a better understanding of the design process, optics and the applications of a new system. I hope to gain experience in interacting with professionals within the medical community as well as learning how to best fulfill their needs. I hope to develop a useful tool that can improve the efficiency of endocrine surgery and reduce likelihood of adverse effects due to this treatment method. I hope to gain a better understanding of the difficulties associated with a design process to be able to use these skills in my future career. At the end of the period, the finished system will hopefully be available for continue use within the surgical department, or pursued by future design groups to further optimize and integrate the design.

Evaluation and Sustainability Plan:

The resulting system from this design project will be tested in vitro and in vivo for evaluation of clinical applicability and efficacy. By obtaining feedback on attainable image clarity and aiding within the surgical setting, the system may be evaluated as successful. Potential verification of system accuracy will be evaluated based upon histopathology of samples ex vivo. If this system is effective in differentially locating and imaging the parathyroid in real- time during surgery, it will be considered a success.

Appendix

Project Timeline

ID Task Name Duration Start Finish Predecessors 1 NCIIA Proposal Due 1 day 29-Oct 29-Oct 2 Written/Oral Report 1 day 4-Nov 4-Nov 3 Evaluation of lens system 7 days 5-Nov 12-Nov 4 Written/Oral report 1 day 11-Nov 11-Nov 5 Preliminary redesign of viewer 10 days 12-Nov 22-Nov 6 Written/Oral report 1 day 18-Nov 18-Nov 7 Begin eletronic reference pages 1 day 19-Nov 19-Nov 8 IWB w/conflict map and expansion 1 day 8-Dec 8-Dec 9 Current tecnhique observation 10 days 8-Dec 18-Dec 10 Preliminary Design of Device/lens 5 days 13-Jan 18-Jan 5 11 Preliminary Testing of device 3 days 19-Jan 22-Jan 5,10 12 Present at SPIE Conference 1 day 25-Jan 25-Jan 9, 10, 11 13 Analysis of status 5 days 1-Feb 6-Feb 12 14 Advisor meeting to discuss improvements 4 days 7-Feb 11-Feb 12,13 15 Redesign/update of device 20 days 12-Feb 4-Mar 13,14 16 Testing of new design, data collection 35 days 4-Mar 8-Apr 15 17 Finalize report days 8-Apr ? 16 18 Final project due 1 day ? ? 17

Budget Funding for alterations to existing viewer (machine shop) (~10 hours) $200 Funding for creation/purchase of improved lens setup (machine shop) (~15-30 hours) $300-800 Total anticipated expenses $500-1000

Reference:

McHenry CR, Patient Volumes and Complications in Thyroid surgery. Br. J. Surj. 2002(89) 821- 823

Rosato L, Avenia N, Bernante P, Palma M, Gulino G, Nasi PG, Pelizzo MR, Pezzullo L, Complications of Thyroid Surgery: Analysis of a Multicentric Study on 14,934 Patients Operated on in Italy over 5 Years. World J. Surg. 2004(28) 271-276

Sippel RS, Ozgul O, Hartig GK, Mack EA, Chen H, Risks and Consequences of Incidental Parathyroidectomy during Thyroid Resection. ANZ J. Surg. 2007(77) 33-36.

Zanocco K, Angelos P, Sturgeon C, Cost-effectiveness analysis of parathyroidectomy for asymptomatic primary hyperparathyroidism, Surgery 140(6) 874-882.