Copyright © 2011 by ASME 1

INTRODUCTION In current clinical practice, a patient usually undergoes a diagnostic computer tomography (CT) scan for evaluation of specific presenting symptoms. The presence of cancer is then confirmed by a diagnostic biopsy or at surgical exploration by histopathologic analysis. Suspicious finding on the diagnostic CT scan may be followed by an 18F FDG (Fluorodeoxyglucose radiolabeled with 18F) positron emission tomography (PET) scan. In a majority of cases, these pre-operative CT and PET scans are used to identify the approximate location of the tumor(s) before surgical intervention. Surgery remains the most effective means of treating solid malignancies despite advances in chemotherapy and radiation therapy [1]. During surgery, the surgeon relies on these pre-operative imaging modalities, sight, and palpation to attempt to locate the tumor(s). At the discretion of the surgeon, a tiny fraction (typically less than 1% of the surgically extracted tissue and only 0.1%-0.2% of the volume of the tissue sample submitted for study) is analyzed by frozen section analysis to confirm the presence of cancer and/or determine the surgical resection margins. Assessment of margins is generally not available until as much as one week after surgery. Additionally, the margin assessment is not necessarily complete since the entire excised tissue specimen cannot be practically examined under the optical microscope. This is significant since it has been shown previously that accurate assessments of surgical margins and intraoperative detection of occult tumors improve long term patient outcomes [2]. Clearly, techniques and tools that enable surgeons to make informed real-time decisions based on accurate assessment of surgical margins could lead to better patient outcomes and dramatically impact diagnosis, staging of the disease, and post-operative treatment. In this paper, a new method for cancer detection is presented. The method

relies upon differences in the characteristics of eddy currents induced in tissue containing tumor(s) and normal tissue. The eddy currents are induced by an electromagnetic (EM) probe, comprising a pair of concentrically wound coils of wire and resembling a transformer. A time varying voltage is imposed on the primary coil, which induces a current and voltage in the secondary (detector) coil. This induced voltage on the detector coil is altered when the EM probe is brought in the vicinity of a partially conducting specimen such as biological tissue. EXPERIMENTAL SETUP AND METHODS A phase-lock technique is used to measure variations in the voltage on the detector coil with respect to the voltage on the primary coil. Measurements of amplitude of voltage on the detector coil at a fixed phase relative to that on the primary coil are performed using a lock-in amplifier. The surgically excised tissue specimens are interrogated by placing the tissue sample directly beneath the probe. Using a precision stage, the probe is brought into full contact with the sample. At this point, the stage is zeroed to establish an origin by bringing it 10 mm above the surface of the tissue. An automated program then commands the stage to bring the probe into contact with the tissue three successive times while recording changes in voltage at a fixed phase, Vφ. The change in detector coil voltage is recorded for each trial, the high, low and average of these touches calculated, and finally the trial is plotted with error bars representing the variation between each time the probe makes contact with the sample. This process is repeated for various locations on a given tissue sample, based upon the geometry, suspected tumor location, and any other known markers such as tissue cauterization or scar tissue. Ex vivo eddy current measurements are performed on surgically excised tissue specimens from human patients

EDDY CURRENT DETECTION OF CANCER IN SURGICALLY EXCISED TISSUE

Emily K. Sequin, Jennifer McFerran-Brock, Joseph West, Vish Subramaniam

Department of Mechanical Engineering The Ohio State University

Columbus, OH 43210 USA

School of Engineering University of Alaska - Anchorage

Anchorage, AK 99508 USA

Proceedings of the ASME 2011 Summer Bioengineering Conference SBC2011

June 22-25, 2011, Farmington, Pennsylvania, USA

SBC2011-53021

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Copyright © 2011 by ASME 2

under a protocol approved by the OSU Human Subjects Review Board. In an attempt to understand the nature of the eddy currents induced in the biological tissue, similar measurements are made for simulated eddy current domain sizes using copper loops of various known diameters of wire. These experiments are conducted with the wire loop located directly beneath the EM probe such that the center axis of the ring is along the same line as the center axis of the probe. Again, changes in Vφ are recorded as the EM probe is brought in the vicinity of the wire loop. RESULTS AND DISCUSSION Ex Vivo Measurements on Surgically Excised Tissue Tissue samples obtained from human subjects with different cancers were subjected to point-wise measurements with the EM probe. Measurements on a case involving a liver resection from a hepatic cancer metastatic case are presented here. The resection samples comprise two pieces as shown in Fig. 1. The specimen shown in Fig. 1A contains tumor, cauterized tissue, and some normal tissue. The specimen in Fig. 1B contains only normal tissue and cauterized tissue. There are three key details to observe in the measured detector coil voltages at fixed phase shown in Fig. 2. First, the difference in signal between the tumor and normal regions of the specimen are substantial, suggesting that the EM probe can distinguish between normal tissue and tumor. Second, the data in the vicinity of the tumor suggests that the probe can be used to assess surgical margins. Finally, measurements on the cauterized tissue show a distinct difference from both the normal tissue and tumor Measurements on Closed Wire Loops Measurements similar to those on surgically excised tissue were conducted on closed wire loops of 1.024 mm thickness and various diameters. These loops represent eddy current domains of various sizes and the results are summarized in Fig. 3. As can be seen, the absolute detector coil voltage at a fixed phase is smallest when the eddy current loop diameter is comparable to that of the EM probe. Conversely, the voltage difference from the null condition (indicated by the dotted line in Fig. 3) is largest when the eddy current domain size is comparable to that of the EM probe. The null condition represents Vφ in the absence of eddy currents (i.e. no sample). Also, Vφ approaches the null condition as the loop diameter becomes smaller. Likewise, with increasing wire loop diameter Vφ approaches the null condition (i.e. no loop) case. The results of Fig. 3 also identify the minimum detectable eddy current domain size (~ 4 mm) and the fact that eddy current domains as large as ~40 mm are detectable with the current EM probe. CONCLUSIONS Eddy current measurements of surgically excised tissue using an EM probe have been shown to successfully distinguish between cancer and normal tissue. Using phase-sensitive techniques, the presence of eddy currents in biological tissue is detected using an EM probe consisting of a primary (driver) coil and detector coil. Accompanying measurements on closed wire loops serve to identify limits of detection of the present probe as well as to determine the approximate sizes of the eddy current domains. The exact mechanisms that affect the characteristics and formation of eddy currents in biological tissue are not known, but their characteristics are expected to depend both on tissue structure and electrical conductivity. This method appears promising for assessing surgical margins by ex vivo measurements on excised tissue and may be useful in intraoperative detection of cancer.

REFERENCES [1] Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R,

Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2007/, based on November 2009 SEER data submission, posted to the SEER web site, 2010.

[2] Bertsch, D.J., Burak Jr., W.E., Young, D.C., Arnold, M.W., Martin, E.W., 1995, “Radioimmunoguided Surgery System Improves Survival for Patients with Recurrent Colorectal Cancer,” Surgery, (118), pp. 634-639

[3] V. V. Subramaniam, J. D. West, J. L. McFerran, E. K. Sequin, D. Sun, and P. Zou “Electromagnetic System and Method”, International PCT WO2010/093479 A2 published on August 19, 2010.

Figure 1. Location of eddy current measurements on liver resection specimen

Figure 2. Voltages at a fixed phase measured with the EM probe

Figure 3. EM Measurements on closed wire loops used to

simulate eddy currents in tissue

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