# Patent

## Title
Method for ablation volume determination and geometric reconstruction

## Abstract

A method for determining a volume of ablated tissue is provided. The method includes the steps of: supplying energy to tissue to create an ablation volume therein; excising one or more slices of the tissue having a portion of the ablation volume therein; and subjecting at least a portion of the slice to a first contrast agent for a predetermined period of time, wherein the contrast agent is configured to color dead cells within the ablation volume.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of priority to U.S. Provisional Application Ser. No. 61/084,489 entitled “METHOD FOR ABLATION VOLUME DETERMINATION AND GEOMETRIC RECONSTRUCTION” filed Jul. 29, 2008 by Prakash Manley, which is incorporated by reference herein.


BACKGROUND
1. Technical Field
The present disclosure relates to electrosurgical apparatuses, systems and methods. More particularly, the present disclosure is directed to a system and method for determining the volume of an ablation lesion after a tissue ablation procedure utilizing electrosurgical electrodes.
2. Background of Related Art
Energy-based tissue treatment is well known in the art. Various types of energy (e.g., electrical, ultrasonic, microwave, cryogenic, heat, laser, etc.) are applied to tissue to achieve a desired result. Electrosurgery involves application of high radio frequency electrical current to a surgical site to cut, ablate, coagulate or seal tissue. In monopolar electrosurgery, a source or active electrode delivers radio frequency energy from the electrosurgical generator to the tissue and a return electrode carries the current back to the generator. In monopolar electrosurgery, the source electrode is typically part of the surgical instrument held by the surgeon and applied to the tissue to be treated. A patient return electrode is placed remotely from the active electrode to carry the current back to the generator.
In the case of tissue ablation, radiofrequency electrical current or microwave energy is applied to a targeted tissue site to create an ablation volume. The resulting ablation volume may then be observed and various ablation metrics may be measured and recorded. Conventional methods of obtaining ablation metrics include recording the small diameter, large diameter, and height of the ablated tissue to calculate the volume. Typically, these three parameters are input for the equation for ellipsoidal volume to calculate an approximate ablation volume. Conventional methods such as this often provide inexact measurements, inconsistent recordings, as well as inaccurate reporting of achieved volumes. Further, conventional methods of volumetric calculation lack evaluative tools such as determining the effect of adjacent structures on the ablation volume, qualifying the completeness of the ablation volume, predicting specific volumes and/or shapes based on a given energy applicator configuration.
SUMMARY
The present disclosure relates to a method for determining a volume of an ablation lesion. The method includes the steps of: supplying energy to tissue to create an ablation volume therein; excising one or more slices of the tissue having a portion of the ablation volume therein; and subjecting at least a portion of the slice to a first contrast agent for a predetermined period of time, wherein the contrast agent is configured to color dead cells within the ablation volume.
A method for determining a volume of an ablation lesion is also contemplated by the present disclosure. The method includes the steps of: supplying energy to tissue to create an ablation volume therein; excising one or more slices of the tissue having a portion of the ablation volume therein; subjecting at least a portion of the slice to a first contrast agent for a predetermined period of time, wherein the contrast agent is configured to color dead cells within the ablation volume. The method also includes the steps of rinsing the slice with a rinse solution to remove any superficial attachment of contrast agent from live cells and drying the slice to remove the rinse solution and the first contrast agent.



BRIEF DESCRIPTION OF THE DRAWINGS
Various embodiments of the present disclosure are described herein with reference to the drawings wherein:
FIG. 1 shows an embodiment of an electrosurgical system for tissue ablation, measuring ablation volume, and displaying image scan data;
FIG. 2 shows an electrode defining a path through tissue for heating ablation;
FIG. 3 shows a sliced segment of the tissue of FIG. 2; and
FIG. 4 illustrates a method for determining an ablation volume according to embodiments of the present disclosure.



DETAILED DESCRIPTION
Particular embodiments of the present disclosure are described hereinbelow with reference to the accompanying drawings. In the following description, well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail.
The present disclosure provides for a system and method for determining a volume of an ablation lesion and providing a geometric reconstruction of the ablation volume. The ablation lesion may be created by applying any suitable energy, such as radiofrequency (“RF”), microwave, electrical, ultrasound, heat, cryogenic, and laser. For the purposes of illustration, the following description discusses formation of the ablation use via the application of RF energy and corresponding electrosurgical ablation electrodes to create ablation lesions in accordance with embodiments of the present disclosure. Those skilled in the art will appreciate that corresponding instruments may have to be utilized based on the type of suitable energy being utilized.
Size and shape of ablation volumes is primarily dependent on the thermal spread and energy flow patterns. In addition, ablation volume is also dependent on the type of tissue being ablated as well as tissue's inherent conductivity and dielectric properties, which govern the thermal spread and energy flow therethrough. The type of energy being used in ablation (e.g., RF, microwave, etc.) may also have a bearing on the patterns of cell death and apoptosis. Thermal injury begins at 41° C. with time of the heat exposure required for complete cell death exponentially decreasing above 42.5° C. (See Dickson J. A., Caldewood S. K., Temperature Range and Selective Sensitivity of Tumors to Hyperthermia: A Critical Review, Ann. N. Y. Acad. Sci., 1980, Vol. 335, pp. 180-205, Rhee J. G., Song C. W., Thermotolerance of Organized Tissues and Tumors. In: Henle K J, ed., Thermotolerance. Vol. 1, Boca Raton, Fla.; CRC Press Inc., 1987, pp. 73-95.) Apoptosis may be seen at temperature below 46° C. with necrosis beyond this threshold. (See Liu F. F., Wilson B. C., Hyperthermia and Photodynamic Therapy. In: Tannock I F, Hill R P, eds., The Basic Science of Oncology, New York, N.Y.; McGraw-Hill Book Co.; 1998; pp. 443-453.). Correlating an accurately modeled temperature profile or tissue property profile with viability and apoptosis assays for determining ablation volume may be used for instantaneous real-time determination of ablation volume.
Referring to FIG. 1, an ablation electrode 100 is shown having an insulated shaft 102 and an electrically exposed tip 103. Electrode 100 may be, for example, a high frequency or RF thermo-ablation electrode configured to be placed in the body of a patient (not explicitly shown) so that the tip 103 is near a target tissue “T”, such as a cancerous tumor or other tissue structure within the body. A hub or junction connector element illustrated schematically by 106 may be any suitable type of connection device, such as jacks, hoses, ports, etc. that connect the RF electrode to a power source, such as a radiofrequency (RF) or microwave generator 107. The generator 107, according to embodiments of the present disclosure, can perform monopolar and bipolar electrosurgical procedures, including tissue ablation procedures (e.g., RF or microwave). Further, the generator may include suitable electronic circuitry configured for generating radio frequency power specifically suited for ablation, as well as other electrosurgical modes (e.g., cutting, blending, division, etc.) and procedures (e.g., monopolar, bipolar, vessel sealing, tissue ablation).
With reference to FIG. 2, the electrode 100 is shown being inserted through the tissue “T” at a trajectory or path 131. Electrode 100 is used to create an ablation lesion defined by an ablation volume 125 within the tissue “T” by heating tissue via application of energy from the generator 107 to the tissue. Path 131 may also be defined as an axis of electrode 100 through ablation volume 125. Path 131 of electrode 100 through volume 125 provides a trajectory reference or point 135 from which volumetric calculations may be made for volume 125, as will be discussed in further detail below.
Once the ablation volume 125 is created, a segment of the tissue “T” encompassing the ablation volume 125 is excised. Volume 125 may be deconstructed into a plurality of slices, depicted here as 125a, 125b, 125c, and 125d, for analyzing the boundaries of the ablation volume 125. This enables volumetric determination of volume 125 and, further, graphical representation on a display (not explicitly shown). FIG. 3 shows a cross-sectional view of any slice 125n of the plurality of slices 125a-125d indicated by line 3-3 in FIG. 2. Each of the plurality of slices 125n defines a cross-sectional perimeter 140n generally concentric about trajectory point 135n.
In certain situations, the boundary between destroyed tissue of the ablation volume 125 and viable tissue along the sectional perimeter 140n of the surrounding tissue T is defined poorly. Thus, the present disclosure provides for a method to provide added contrast between the ablated tissue and the viable to better define the boundary between the ablation volume 125 and the tissue T. In one embodiment, after the ablation volume 125 is excised and one or more cross-sectional slices 125n thereof are obtained, a stain, a dye or another type of a cytometric contrast agent is applied to the slice.
Suitable contrast agents for use as a stain include nitro-blue tetrazolium, hematoxylin and eosin stains, reduced dihydro-pyridine nucleotide, fluorescent dyes such as calcein AM and ethidium homodimer, available from Invitrogen Corp. of Carlsbad, Calif., which may be used with an anti-fading agent such as ProLong® Gold Antifade Reagent also available from Invitrogen Corp. of Carlsbad, Calif. In one embodiment, the contrast agent may be trypan blue, which is a suitable viability marker that stains dead cells a blue color useful for ablation boundary demarcation.
Contrast agents are difficult to use with three-dimensional arrangement of parenchymal tissue due to the fact that irrelevant background material such as extra-cellular matrix, collagen and serum are also stained by the contrast agents. The present disclosure provides for a method which allows for use of contrast agents with parenchymal tissue (e.g., liver) to identify the ablation volume 125. The stain is applied to one or more cross-sectional slices of the tissue “T” enclosing the ablation volume 125. The magnitude of background staining is controlled by limiting the staining period to a predetermined period of time and thereafter rinsing the contrast agents from the slices of the tissue “T.” The contrast agents stain the dead tissue, while the viable tissue is unstained after the rinse. The rinsed slices are then dried to further remove any residual stain from the viable tissue to obtain a clear demarcation between ablated stained tissue and viable unstained tissue. As a result, the tissue within the ablated volume 125 appears a different color (e.g., blue) from the natural tissue color of surrounding viable tissue (e.g., red). Due to rapid deterioration of tissue and staining contrast, the stained slices may be imaged immediately (e.g., photographed, scanned, etc.) to capture the demarcation of the ablation volume 125 for later analysis.
A method for volumetric determination of boundaries of the ablation volume 125 according to embodiments of the present disclosure will now be described with reference to FIG. 4 in conjunction with FIGS. 2 and 3. In step 300, electrosurgical energy is supplied from the RF generator 107 to the electrode 100. As illustrated in FIG. 2, electrode 100 is used to create an ablation lesion by heating volume 125 via application of RF energy from the generator 107 to volume 125.
In step 310, ablation volume 125 is excised from the tissue “T” and is cut or “sliced” substantially perpendicular to trajectory point 135 into a plurality of slices 125a-125d. The slices may be of any desired thickness. In one embodiment, the slices may be about 0.5 cm thick to allow for the slices to be placed on plate scanner to obtain a digital image thereof.
In step 320, one or more of the slices 125a-125d are stained by a contrast agent to demarcate the boundary between the dead cells of the ablation volume 125 and the viable cells of the surrounding tissue “T.” Staining may be performed by submerging the slice 125n in a contrast agent solution for a predetermined period of time form about 1 minute to about 5 minutes. The contrast agent penetrates cellular walls of dead cells of the ablation volume 125 while having no effect on viable tissue surrounding the ablation volume, thereby coloring the ablation volume 125 a color (e.g., blue) different from the viable tissue. This provides a clear contrast between the ablation volume 125 and the remaining viable tissue.
To prevent the coloring of the viable tissue, in step 330, the slice 125n is rinsed by a solution (e.g., a phosphate buffered saline solution) to remove any superficial attachment of the contrast agent from the cells. In addition, the slice 125n is dried to remove the rinse solution and the contrast agent. This may be accomplished by using an absorbent material (e.g., cloth, paper towel, etc.) to remove the solutions from the slice 125n. 
In step 340, the contrasted slice 125n is imaged, by scanning, by photographing, etc., to capture the colored ablation volume 125. This allows for subsequent evaluation of the ablation volume 125, such as depth, size, etc. More specifically, with reference to FIG. 2, a thickness, indicated in FIG. 2 as “A,” and a cross-sectional perimeter 140a-140d for each of the plurality of slices 125a-125d may be determined. Cross-sectional perimeters 140a-140d for each of the plurality of slices 125a-125d are derived based on the contrasted image of the ablation zone.
The volume of each of the plurality of slices 125a-125d may also be determined. Any suitable method for determining volume may be used, such as, for example, the contour or perimeter method. In addition, the volume of the ablation volume 125 may be determined based on volumetric data of each of the slices 125n individually and then modeled to obtain the shape of the volume as defined on each slice. Cross sectional perimeter 140a-140d for each slice 125a-125d may be used to determine the volume. Alternatively, for each slice 125n, thickness “A” may be multiplied by the perimeter area of that particular slice to determine the slice volume. This determination is carried out for each of the plurality of slices 125a-125d. The volume determinations derived for each of the plurality of slices 125a-125d are then summed to yield an ablation volume. In this manner, an accurate volumetric determination is made rather than approximated calculations yielded by conventional and/or presently competing volumetric calculation methods.
EXAMPLE
Trypan blue staining. An ablation lesion was created in porcine liver tissue. The ablation lesion was then excised and sliced into cross-sectional slices. A staining solution of trypan blue (0.4% trypan blue, 0.81% sodium chloride, 0.06% potassium phosphate dibasic) from Sigma-Aldrich of St. Louis, Mo. was placed in a beaker placed under a fume hood. The slice, with a pertinent surface containing a segment of the ablation volume was exposed to the solution in the beaker for approximately 5 minutes. The slice was then removed and was washed vigorously in a rinsing solution of 1× phosphate buffered saline solution. The rinsed and stained slice was then dried by absorbing the staining and rinsing solutions. The dried slice was then imaged by scanning the slice. The staining procedure was repeated for each of the slices of the ablated lesion.
While several embodiments of the disclosure have been shown in the drawings and/or discussed herein, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of particular embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

## Claims

1. A method for determining a volume of ablated tissue comprising the steps of:
inserting an electrode into tissue, a longitudinal axis of the electrode defining a path of the electrode;
supplying energy via the electrode to tissue to create an ablation volume therein;
excising a plurality of slices of the tissue having at least a portion of the ablation volume therein, each of the plurality of slices having a thickness, a cross-sectional perimeter, and a trajectory point defined by the path of the electrode;
subjecting the plurality of the slices to a first contrast agent for a predetermined period of time, wherein the contrast agent is configured to color dead cells within the ablation volume;
rinsing the plurality of the slices with a rinse solution to remove any superficial attachment of the contrast agent from live cells of the tissue;
drying the plurality of the slices to remove the rinse solution and the first contrast agent;
determining a volume of each of the plurality of slices based on the trajectory point, the cross-sectional perimeter, and the thickness of each slice of the tissue; and
summing the volumes from each of the plurality of slices to obtain the volume of ablated tissue.

2. The method according in claim 1, wherein the energy of the supplying step is selected from the group consisting of radio frequency and microwave.

3. The method according in claim 1, wherein the energy of the supplying step is supplied to at least one electrode.

4. The method according to claim 1, further comprising the step of:
forming a solution having the contrast agent; and
submerging at least a portion of each of the plurality of the slices to the solution.

5. The method according to claim 1, wherein the rinse solution of the rinsing step is 1× phosphate buffered saline solution.

6. The method according to claim 1, wherein the first contrast agent of the subjecting step is trypan blue.

7. The method according to claim 1, wherein the predetermined period of the subjecting step is about 5 minutes.

8. A method for determining a volume of ablated tissue comprising the steps of:
inserting an electrode into tissue, a longitudinal axis of the electrode defining a path of the electrode;
supplying energy to tissue to create an ablation volume therein;
excising a plurality of slices of the tissue having at least a portion of the ablation volume therein, each of the plurality of slices having a thickness, a cross-sectional perimeter, and a trajectory point defined by the path of the electrode;
controlling a magnitude of background staining of at least a portion of the slice in order to identify a boundary of the volume of ablated tissue by limiting a staining period of time with respect to a contrast agent applied to the at least a portion of the slice to a predetermined period of time and thereafter rinsing the contrast agent from the at least a portion of the slice; and
determining a volume of each of the plurality of slices based on the trajectory point, the cross-sectional perimeter, and the thickness of each slice of the tissue; and
summing the volumes from each of the plurality of slices to obtain the volume of ablated tissue.