Real-Time Intra-Operative Infrared
Parathyroid Visualization System
NCIIA Grant Proposal
Vanderbilt University
29 October 2009
Isaac Pence
Contact Information
Team:
Isaac Pence
isaac.j.pence@vanderbilt.edu
502-403-7209
Box 350748 Sta B
Principal Investigator
Anita Mahadevan-Jansen
anita.mahadevan-jansen@Vanderbilt.Edu
615-343-4787
Box 351631 Sta B
Graduate Advisor
Dean Paras
constantine.a.paras@vanderbilt.edu
216-310-2026
Administrative contact
Mary H Judd
mary.judd@Vanderbilt.Edu
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. MahadevanJansen, 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 realtime during surgery, it will be considered a success.
Appendix
Project Timeline
ID Task Name
1 NCIIA Proposal Due
Duration Start
Finish Predecessors
1 day
29-Oct 29-Oct
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Written/Oral Report
Evaluation of lens system
Written/Oral report
Preliminary redesign of viewer
Written/Oral report
Begin eletronic reference pages
IWB w/conflict map and expansion
Current tecnhique observation
Preliminary Design of Device/lens
Preliminary Testing of device
Present at SPIE Conference
Analysis of status
Advisor meeting to discuss improvements
Redesign/update of device
Testing of new design, data collection
Finalize report
Final project due
1 day
7 days
1 day
10 days
1 day
1 day
1 day
10 days
5 days
3 days
1 day
5 days
4 days
20 days
35 days
days
1 day
4-Nov
5-Nov
11-Nov
12-Nov
18-Nov
19-Nov
8-Dec
8-Dec
13-Jan
19-Jan
25-Jan
1-Feb
7-Feb
12-Feb
4-Mar
8-Apr
?
4-Nov
12-Nov
11-Nov
22-Nov
18-Nov
19-Nov
8-Dec
18-Dec
18-Jan
22-Jan
25-Jan
6-Feb
11-Feb
4-Mar
8-Apr
?
?
5
5,10
9, 10, 11
12
12,13
13,14
15
16
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) 821823
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.