1. Electrical Resistivity of K12/TRb Tumors vs. Normal Liver Tissue
Dieter Haemmerich
S. Tyler Staelin
Supan Tungjitkusolmun
Jang-Zern Tsai
Omer R. Ozkan
David Mahvi
John G. Webster
This research has been supported by NIH grant #1R01 HL

2. Motivation
Liver is second most common site of metastases next to lymph nodes
Usage of resistivity data:
Detect tumors via bio-impedance measurements
Radio Frequency ablation as treatment:
Determine distribution of absorbed electromagnetic energy
No known studies on in-vivo tumor resistivity at audio and radiofrequencies
We tried to model liver metastases in animal (rat)
Explain RF ablation: catheter is inserted into tissue; current flows from catheter to groundpad (placed on back) -> surrounding tissue is heated.
Dieter Haemmerich, Univ. Wisconsin-Madison

3. Experimental Details
K12/TRb is a colon cancer line with histologic characteristics similar to human colon cancer
Liver tumors were initiated in 40 rats by injecting 106 cells intrahepatically (n=20) or 8·106 cells intraspleenically (n=20)
Rats were opened 6 – 9 weeks after injections
24 tumors in 18 rats were measured
Cell line used to model liver metastases
Intraspleenic injections -> metastases developed in liver
Dieter Haemmerich, Univ. Wisconsin-Madison

4. Tumor resistivity was measured over 4 weeks in 1-week intervals
Tumors were 1cm – 2 cm in diameter
Normal liver tissue was measured for control
Animals were sacrificed after measurement
Tumor volume was estimated
Histologic slides were created of each tumor
% Necrosis and % Fibrosis were estimated at measurement site
Dieter Haemmerich, Univ. Wisconsin-Madison

5. Current-to-voltage converter
Experiment Setup
Tissue
Function RS232 generator
Amplifier
Current-to-voltage converter
Channel 1
RS232
Oscilloscope
Channel 2
Computer
Probe
4-terminal method minimizes errors from electrode polarization
Probe has silver electrodes, 0.38 mm diameter, 1.5 mm apart, 5 mm long, covered with AgCl
We measured at 8 frequencies from 1 Hz to 1 MHz
Dieter Haemmerich, Univ. Wisconsin-Madison

6. Resistivity: Tumor vs. Normal
Dieter Haemmerich, Univ. Wisconsin-Madison

7. Current paths in tissue
Current paths at DC and low frequencies
Current paths at high frequencies
It is generally agreed upon…
Applies to most types of tissue
Why different in tumor? I’ll come back to that later.
Dieter Haemmerich, Univ. Wisconsin-Madison

8. Approximation Equation
Resistivity curves approximated by:
A Resistivity at low frequencies
Q = A / (1+eB)... Resistivity at high frequencies
C Controls rate of decrease
Parameters A, Q, C were fit for each tumor and control
Dieter Haemmerich, Univ. Wisconsin-Madison

9. Sample Tumor Resistivity Data and Approximation
A = 397, Q = 211, C = -1.01
Dieter Haemmerich, Univ. Wisconsin-Madison

10. Spearman`s correlation coefficients were determined between each of the parameters (A, Q, C) and:
Tumor Volume
Tumor Age
% Necrosis at measurement site
% Fibrosis at measurement site
How did we know where measurement site is?
Dieter Haemmerich, Univ. Wisconsin-Madison

11. Probe tracts
-> measurement site can be determined
Dieter Haemmerich, Univ. Wisconsin-Madison

12. Typical Tumor
Compared to normal liver cells:
Cells are very unordered, very diverse, not well differentiated, multiple nuclei
Dieter Haemmerich, Univ. Wisconsin-Madison

13. Tumor-Liver Interface
Ordered vs. unordered
Liver parenchyma compressed at border
Very few blood vessels inside tumor
Dieter Haemmerich, Univ. Wisconsin-Madison

14. Necrosis and Fibrosis
Tumor gets blood support from tumor-liver-boundary
As tumor grows, inner regions get depleted of nutrients and waste products accumulate
This leads to necrosis (cell death), preferably at the tumor center
After cells die, (tumor) tissue gets replaced with fibroblastic tissue
Blood brings nutrients to the cells and carries metabolic waste products away from cells
Fibrosis depends on regenerative capabilities of cell type
Dieter Haemmerich, Univ. Wisconsin-Madison

15. Tumor with Necrosis & Fibrosis
Dieter Haemmerich, Univ. Wisconsin-Madison

16. Central Necrosis
Dieter Haemmerich, Univ. Wisconsin-Madison

17. Significance Probabilities (P-values)
Tumor Parameters
Age
Volume
Fibrosis
Necrosis A
0.2085
0.0161
0.3527
0.0031 
0.900
0.1815
0.9198
0.0018 C
0.5355
0.3416
0.2748
0.0116
Significance probabilities calculated from Spearman’s Correlation Coefficients
P-values are underlined where significance is reached
Dieter Haemmerich, Univ. Wisconsin-Madison

18. Parameter A vs. Necrosis
Dieter Haemmerich, Univ. Wisconsin-Madison

19. Parameter Q vs. Necrosis
Dieter Haemmerich, Univ. Wisconsin-Madison

20. Conclusions
Results strongly support theory that necrosis is responsible for drop in resistivity:
When cells are intact, current is restricted to extracellular room at low frequencies
During cell necrosis cell membrane loses integrity. Resistivity drops.
Difference in resistivity at frequencies below 100 kHz can be exploited to increase efficacy of electromagnetic tumor heating (RF ablation)
Currently RF ablation uses frequ. Around 500 kHz
Dieter Haemmerich, Univ. Wisconsin-Madison

21. Model Geometry
Dieter Haemmerich, Univ. Wisconsin-Madison

22. Temp. distribution Current density
Parameter
Case 1
Case 2
Case 3
Liver resistivity
102.7 cm
308.0 cm
924.0 cm
Tumor resistivity
Total energy
574 J
974 J
1732 J
Red: 50C-boundary
Dieter Haemmerich, Univ. Wisconsin-Madison

23. Acknowledgements Web Site
Glen Leverson
Thomas F. Warner
Web Site
Acknowledge two people who had significant contribution to study
Dieter Haemmerich, Univ. Wisconsin-Madison