CA2441489A1 - Inducing and contouring ice formation - Google Patents
Inducing and contouring ice formation Download PDFInfo
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- CA2441489A1 CA2441489A1 CA 2441489 CA2441489A CA2441489A1 CA 2441489 A1 CA2441489 A1 CA 2441489A1 CA 2441489 CA2441489 CA 2441489 CA 2441489 A CA2441489 A CA 2441489A CA 2441489 A1 CA2441489 A1 CA 2441489A1
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- freezing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/02—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques
Abstract
Chemicals and associated technique for sculpturing ice formation, increasing the difference in freezing rate between targeted and non-targeted tissue, inducing ice nucleation at temperature higher than cells' normal freezing temperature and optimizing cryodestruction.
Description
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tonal August 20, 2003 Page 3 of 12 References Cited jReferenced i3y]
U.S. F~atent Documents 5139496 Aug., 1992 Hed 606/23.
5160313 Nov.. 1992 Carpenter et al. 600136.
5658276 Aug., 1997 Griswold 606/24.
5358931 Oct.. 1994 Rubinsky et al. 514/12.
5654279 Aug., 1997 Rubinsky 5906209 May, 1999 Tortai 12 Other References 14 [1 ] David I. Lee, David E. McGinnis, Rick Feld and Stephen E. Strup Retroperitoneal laparoscopic cryoablation of small renal tumors: intermediate results, 16 Urology, Volume 67, Issue 7, January 2003, Pages 83-88 .
18 [2] John C. Saliken, Bryan J. Donnelly & John C. Rewcastle The evolution & state of the modern technology for prostate crosurgery Urology, Volume 60, Issue 2 Supplement , Augusf 2002, Pages 26-33.
22 [3] Bruce L. Daniel and Kim Butts The use of view angle tilting to reduce distortions in MRI of Cryosurgery 24 Magnetic Resonance Imaging, Vol.18, Issue 3, April 2000, pages 289-286.
26 [4] Fahy et al., "Ultrastructure-Function . . . Rat Heart", Cryobiology, vol. 14, pp. 418-427, 1977.
[5] Vinas et al., "Early Hemodynamic . . . Cryogenic Injury'°, Neurol Res, vol. 17, pp. 465-468, 1995.
32 [6] (Onik GM, Cohen JK, Reyes GD, et al. Percutaneous radical cryosurgical ablation of the prostate under transrectal ultrasound guidance. Cancer 1993; 72: 1291-1299) and 34 (Lee F, Bahn 36 [7] DK, Mc Hugh TA, et al. Ultrasound- guided percutaneous cryoablation of prostate cancer. Radiology 1994; 192:769-776.).
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 4 of 12 REVIEW OF RELATED LITERATURE
Carpenter et al (US Patent 5160313 discusses the use of diluent or eluent e.g.
4 ethylsulfoxide, glycerol, propanediol and other compounds to a transplantable tissue which has been cryopreserved with an intracellular cryoprotectant to reduce the level of 6 cryoprotectant in the cells to a substantially non-toxic level. It is not stipulated nor it is the purpose of the said invention to sculpture ice formation and increase the freezing 8 rate difference between cells and cause further damage to targeted tissue as proposed in this patent application.
Rubinsky et al (US Patent 5358931 disclosed property thermal hysteresis proteins from 12 certain fish oils in polar regions in protecting cells and their membranes from damage from cold temperature. The purpose is to increase the water crystallization in the 14 intracellular spaces between targeted cells while decreasing crystallization in the cells.
The intracellular ice packets should pierce the targeted cell's membrane, killing the 16 tissue by Koushafar and Rubinsky [9]. However, in this technique freezing of normal tissue was observed. This is a reverse of our proposed technique and methodology.
Hed (US Patent 5139496) disclosed the use of ultrasound waves to initiate ice nucleation within targeted cells. While it is also one of the aims of this proposed invention to induce ice formation prior to normal freezing rate, this invention is using 22 osmotic and nucleatic chemicals and not energies such as ultrasound.
24 Griswold (US Patent 5,658,276) describes the use of wire warmerslheaters to protect critical organs and provide means of melting the ice during the thawing cycles. The 26 proposed invention does not apply external heat to prevent unwanted freezing but alter the cells freezing rate through introduction of chemicals.
CROSS REFERENCE TO RELATED APPLICATIONS: -RIGHTS TO INVENTIONS MADE UNDER FEDERALLY-SPONSORED RESEARCH
32 AND DEVELOPMENT: None 36 This invention relates to the use of chemicals in cryosurgical treatment.
Invention comprises of chemicals and associated technique for sculpturing ice formation, increasing the difference in freezing rate between targeted and non-targeted tissue, 42 inducing ice nucleation at temperature higher than cells' normal freezing temperature.
44 The chemicals are chosen among nucleatic and osmotic agents.
46 The technique involves the injection of nucleatic and osmotic chemicals to the targeted tissue prior to cryosurgical freezing. Then the injection of water prior to freezing of 48 tissues.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tonal August 20, 2003 Page 5 of 12 The main drawback in cryosurgery is unwanted freezing of nearby critical organs) 4 andlor non-targeted tissues.
6 A means to counteract this adverse effect is the use of a urethra) warmer in prostate cryosurgery. Warm water is circulated through a catheter inserted into the urethra to 8 prevent urethra) fistula and impotence. Other adjacent non-targeted and surrounding tissues are still at risk of freezing.
Another attempt is by means of a magnetostrictive polymer tube positioned nearest to 12 the probe's tip where thermal exchange happens. It shuts off at a set temperature or is shut manually to block incoming cold supply instantly. This however, does not address 14 the tissues' response to already supplied cold temperature. Ice formed in tissues extend uncontrollably from the targeted location.
Moreover, preventing unwanted freezing is dependent on the surgeon's skill to 18 accurately positioned the cryosurgical probes to the exact location of targeted tumor and at minimum contact with critical organs throughout the freezing. Still, ice formation expands uncontrollably at cryogenic temperatures.
22 It is therefore the object of this invention to provide a reproducible technique to sculpture ice formation during cryosurgery and means to instantly control ice formation.
By doing 24 so, provide a more reliable freezing treatment.
26 The above objective is accomplished effectively by manipulating the response of cells to cold supply instead.
Response of cells is manipulated effectively in this invention by introducing nucleatic and osmotic agents to the targeted tissue. The chemicals are chosen among polyhydric alcohols such as glycerols and mannitol; carbohydrates such as trehalose and sucrose;
32 free amino acids and their derivates, including proline, taurine and beta-alanine; urea and ethylene amines such as trimethyl amone oxide (TMAO) and betaine together and 34 are bio-compatibles.
36 These chemicals induce ice formation at temperature higher than the normal temperature of cells. Thus, create great difference in the rate of ice formation between 38 targeted and non-targeted tissues. Non-targeted tissues can then greatly be spared from freezing. Moreover, these chemicals induce greater production of destructive ice within targeted cells.
42 Concentrations of the above chemicals vary from 0.5M to 2.5M. Concentration that yield the maximum water absorption and rate of ice formation for each of the said chemicals 44 vary for each chemical.
46 The preferred chemical specification: 2.5M L-Proline 99+°!°, 2.5M of Glycerol 99+% , 2.5M of Taurine 99%, 1.5M Beta-Aianine 99+%, 1.5M of Betaine 98%, 1.5M Sucrose 48 98%, 1.5M D-mannitol 98%, 0.5M D-Trehalose dihydrate, 1.5M or 2.5M of Urea 99+%.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 6 of 12 2 Associated Technique:
For each chemical, the volume is about 10% of the tumor volume. The chemicals are 4 injected to targeted tumor volume prior to freezing. Vllater is injected after the chemical is injected, ten minutes later.
The added water counteracts any adverse effects of water displacing from non-targeted 8 areas as caused by the chemicals and provide greater cellular strain.
Freezing zone can be extended to a desired distance from the margin of the tumor or targeted tissue by also injecting the chemical to this area.
Cryosurgical freezing should be started after another ten minutes.
The injection to the tumor is guided by ultrasound as for subcutaneous targets. Ice 16 formation is monitored using ultrasound and open MRI.
18 Tissue temperature is monitored using thermocouples placed within the target volume, critical organs and non-targeted nearby tissues.
Established lethal temperatures range from -25°C such as in prostate cryosurgery to -22 40°C e.g. in breast cryosurgery. Thus, freezing is stopped when this temperature is reached.
The combined hastening of ice formation and creation of greater cellular strain within the 26 targeted tissue results to optimum cellular destruction even prior to reaching the lethal temperatures.
Biopsies and MRI images will be taken before and after the cryosurgical procedure when ice is melted to ensure maximum cellular destruction to point of rupture has been achieved in the procedure, and unwanted freezing of non-targeted tissue has been 32 minimized.
34 Experiments and studies performed for this invention showed a more remarkable destruction of targeted tissues injected with the chemicals than those not injected.
Rates of ice formation and water absorption of sample tissues treated with the various 38 chemicals show tremendous increase.
BEST MODE FOR CARRYINC9 OIJT THE IN!/ENTION
Preparing the Chemicals:
44 To produce:
46 1 ) 2.5M of L-Proline 99+% (Molecular weight = 115.13):
48 Dissolve 287.82 grams of L-Proline 99+% in one liter of water.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 7 of 12 2 2) 2.5M of Glycerol 99+%
4 Dissolve 230.22 grams of Glycerol 99+% in one liter of water.
6 3) 2.5M of Taurine 99%
8 Dissolve 315.38 grams of Taurine 99% in one liter of water.
4) 1.5M Beta-Alanine 99+%
12 Dissolve 133.64 grams of Beta-Alanine 99% in one liter of water.
14 5) 1.5M of Betaine 98%
16 Dissolve 175.72 grams of Betaine 98% in one liter of water.
18 6) 1.5M Sucrose 98%
Dissolve 513.45 grams of Sucrose 98% in one liter of water.
7) 1.5M D-mannitol 98%
Dissolve 273.26 grams of D-mannitol 98% in one liter of water.
8) 0.5M D-Trehalose dihydrate 99%
Dissolve 189.15 grams of D-Trehalose dihydrate 99% in one liter of water.
9) 1.5M or 2.5M of Urea 99+%.
For 1.5M Urea: Dissolve 90.09 grams of Urea 99+% in one liter of 34 water.
36 For 2.5M Urea: Dissolve 150.15 grams of Urea 99+% in one liter of water.
Volume of chemicals above is about 10% of the tumor volume.
To administer the correct amount of chemical throughout the targeted volume for ice 42 sculpturing, it is crucial to determine the volume and exact location of the targeted tumor.
44 The current method that yields the best estimate of prostate tumor volume is serum Prostate Specific Antigen (PSA) with 0.5 Pearson Correlation Coefficient.
Tumor volume estimates for other subcutaneous tumors are done by first taking a 48 Computed Topography (CT) scan or MRI image. The image is then entered to a Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tonal August 20, 2003 Page 8 of 12 computer for calculation. The computer reconstructs the image in three-dimension and 2 performs voxel counting, trapezoid approximation technique and area summation calculation.
The most accurate biopsy and imaging technique should be used in determining the 6 stage and location of targeted tumor and its exact location. Such as to date, for prostate cancer, Transrectal Ultrasound (TRUS) biopsies as described by Onik could be used.
Technique for Administering the Chemicals and Maximizing the Effects:
For subcutaneous tumors, the injection of the chemicals and the insertion of cryosurgical 12 probe should be guided by ultrasound with sector scan transducer. Doppler ultrasound that display colored images should give clear distinction of tumor boundary and normal 14 tissues. Ultrasound must operate at higher frequency for better imaging of various tissues and organs such as at least 5 or 7.5MHz.
Targeted gland such as prostate can be shrieked using androgen deprivation technique 18 prior to injecting the chemicals) and performing cryosurgery. Shrinking the gland ensures better absorption and distribution of the chemicals. Moreover, shrinking the gland decreases the risk of freezing the rectum since the other effect of this method is increasing the space between the rectum and the prostate capsule due to the effect of 22 increasing the amount of fat in the Denonvilliers fascia region [Onik, "Percutaneous Prostate Cryoablation].
Injecting water in the targeted tissue counteracts any adverse effects of water displacing from 26 non-targeted areas due to the chemical injected, and creates greater cellular strain. Water of volume approximately 50% of the tumor volume should be sufficient. Water can be injected 10 28 minutes after the injection of the chemical.
Freezing of tissues using cryosurgical probe can begin 10 minutes after injection of chemicals and/or after the injection of water. Diameter and shape of probe tip depend on the diameter, 32 shape and desired extent of ice formation.
34 For sculpturing ice formation, it is critical to monitor the temperatures and ice formation of targeted tissue, critical organs and extended freezing areas. Thus, thermocouples are 36 placed in these areas.
38 Diameter of ice ball and extent of ice crystals formed outside of tumor volume should be measured using linear array ultrasound or open MRI during the entire procedure.
Diameter of ice ball should be graphed with respect to time and temperature.
Rate of ice ball formation will then be calculated. This is to monitor if treatment plan was followed in 42 the procedure performed.
44 MRI images will be taken before and after the cryosurgical procedure when ice is melted to ensure maximum cellular destruction to point of rupture has been achieved in the procedure, 46 and unwanted freezing of non-targeted tissue has been minimized.
48 Several cryoprobes are imbedded within the substance of the tumor. Number of cryoprobes and Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 9 of 12 distances between them depend on the size and shape of tumor. The established lethal 2 temperature that causes cellular necrosis is at least -25 for prostate cancer, and -40°C as in the case of breast carcinoma. In this proposed technique, we expect higher temperature 4 destructive freezing since we have induced faster rate and maximum amount of ice formation at much higher tissue temperature. We already observed greater tissue damage at less than 6 20°C.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 shows the injection of chemical to the targeted tissue A.
Figure 2 shows the injection of chemical to adjacent normal tissue B as represented by 14 broken curve lines if ice ball formation should be slightly be extended beyond targeted tissue.
Tonal August 20, 2003 Page 3 of 12 References Cited jReferenced i3y]
U.S. F~atent Documents 5139496 Aug., 1992 Hed 606/23.
5160313 Nov.. 1992 Carpenter et al. 600136.
5658276 Aug., 1997 Griswold 606/24.
5358931 Oct.. 1994 Rubinsky et al. 514/12.
5654279 Aug., 1997 Rubinsky 5906209 May, 1999 Tortai 12 Other References 14 [1 ] David I. Lee, David E. McGinnis, Rick Feld and Stephen E. Strup Retroperitoneal laparoscopic cryoablation of small renal tumors: intermediate results, 16 Urology, Volume 67, Issue 7, January 2003, Pages 83-88 .
18 [2] John C. Saliken, Bryan J. Donnelly & John C. Rewcastle The evolution & state of the modern technology for prostate crosurgery Urology, Volume 60, Issue 2 Supplement , Augusf 2002, Pages 26-33.
22 [3] Bruce L. Daniel and Kim Butts The use of view angle tilting to reduce distortions in MRI of Cryosurgery 24 Magnetic Resonance Imaging, Vol.18, Issue 3, April 2000, pages 289-286.
26 [4] Fahy et al., "Ultrastructure-Function . . . Rat Heart", Cryobiology, vol. 14, pp. 418-427, 1977.
[5] Vinas et al., "Early Hemodynamic . . . Cryogenic Injury'°, Neurol Res, vol. 17, pp. 465-468, 1995.
32 [6] (Onik GM, Cohen JK, Reyes GD, et al. Percutaneous radical cryosurgical ablation of the prostate under transrectal ultrasound guidance. Cancer 1993; 72: 1291-1299) and 34 (Lee F, Bahn 36 [7] DK, Mc Hugh TA, et al. Ultrasound- guided percutaneous cryoablation of prostate cancer. Radiology 1994; 192:769-776.).
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 4 of 12 REVIEW OF RELATED LITERATURE
Carpenter et al (US Patent 5160313 discusses the use of diluent or eluent e.g.
4 ethylsulfoxide, glycerol, propanediol and other compounds to a transplantable tissue which has been cryopreserved with an intracellular cryoprotectant to reduce the level of 6 cryoprotectant in the cells to a substantially non-toxic level. It is not stipulated nor it is the purpose of the said invention to sculpture ice formation and increase the freezing 8 rate difference between cells and cause further damage to targeted tissue as proposed in this patent application.
Rubinsky et al (US Patent 5358931 disclosed property thermal hysteresis proteins from 12 certain fish oils in polar regions in protecting cells and their membranes from damage from cold temperature. The purpose is to increase the water crystallization in the 14 intracellular spaces between targeted cells while decreasing crystallization in the cells.
The intracellular ice packets should pierce the targeted cell's membrane, killing the 16 tissue by Koushafar and Rubinsky [9]. However, in this technique freezing of normal tissue was observed. This is a reverse of our proposed technique and methodology.
Hed (US Patent 5139496) disclosed the use of ultrasound waves to initiate ice nucleation within targeted cells. While it is also one of the aims of this proposed invention to induce ice formation prior to normal freezing rate, this invention is using 22 osmotic and nucleatic chemicals and not energies such as ultrasound.
24 Griswold (US Patent 5,658,276) describes the use of wire warmerslheaters to protect critical organs and provide means of melting the ice during the thawing cycles. The 26 proposed invention does not apply external heat to prevent unwanted freezing but alter the cells freezing rate through introduction of chemicals.
CROSS REFERENCE TO RELATED APPLICATIONS: -RIGHTS TO INVENTIONS MADE UNDER FEDERALLY-SPONSORED RESEARCH
32 AND DEVELOPMENT: None 36 This invention relates to the use of chemicals in cryosurgical treatment.
Invention comprises of chemicals and associated technique for sculpturing ice formation, increasing the difference in freezing rate between targeted and non-targeted tissue, 42 inducing ice nucleation at temperature higher than cells' normal freezing temperature.
44 The chemicals are chosen among nucleatic and osmotic agents.
46 The technique involves the injection of nucleatic and osmotic chemicals to the targeted tissue prior to cryosurgical freezing. Then the injection of water prior to freezing of 48 tissues.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tonal August 20, 2003 Page 5 of 12 The main drawback in cryosurgery is unwanted freezing of nearby critical organs) 4 andlor non-targeted tissues.
6 A means to counteract this adverse effect is the use of a urethra) warmer in prostate cryosurgery. Warm water is circulated through a catheter inserted into the urethra to 8 prevent urethra) fistula and impotence. Other adjacent non-targeted and surrounding tissues are still at risk of freezing.
Another attempt is by means of a magnetostrictive polymer tube positioned nearest to 12 the probe's tip where thermal exchange happens. It shuts off at a set temperature or is shut manually to block incoming cold supply instantly. This however, does not address 14 the tissues' response to already supplied cold temperature. Ice formed in tissues extend uncontrollably from the targeted location.
Moreover, preventing unwanted freezing is dependent on the surgeon's skill to 18 accurately positioned the cryosurgical probes to the exact location of targeted tumor and at minimum contact with critical organs throughout the freezing. Still, ice formation expands uncontrollably at cryogenic temperatures.
22 It is therefore the object of this invention to provide a reproducible technique to sculpture ice formation during cryosurgery and means to instantly control ice formation.
By doing 24 so, provide a more reliable freezing treatment.
26 The above objective is accomplished effectively by manipulating the response of cells to cold supply instead.
Response of cells is manipulated effectively in this invention by introducing nucleatic and osmotic agents to the targeted tissue. The chemicals are chosen among polyhydric alcohols such as glycerols and mannitol; carbohydrates such as trehalose and sucrose;
32 free amino acids and their derivates, including proline, taurine and beta-alanine; urea and ethylene amines such as trimethyl amone oxide (TMAO) and betaine together and 34 are bio-compatibles.
36 These chemicals induce ice formation at temperature higher than the normal temperature of cells. Thus, create great difference in the rate of ice formation between 38 targeted and non-targeted tissues. Non-targeted tissues can then greatly be spared from freezing. Moreover, these chemicals induce greater production of destructive ice within targeted cells.
42 Concentrations of the above chemicals vary from 0.5M to 2.5M. Concentration that yield the maximum water absorption and rate of ice formation for each of the said chemicals 44 vary for each chemical.
46 The preferred chemical specification: 2.5M L-Proline 99+°!°, 2.5M of Glycerol 99+% , 2.5M of Taurine 99%, 1.5M Beta-Aianine 99+%, 1.5M of Betaine 98%, 1.5M Sucrose 48 98%, 1.5M D-mannitol 98%, 0.5M D-Trehalose dihydrate, 1.5M or 2.5M of Urea 99+%.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 6 of 12 2 Associated Technique:
For each chemical, the volume is about 10% of the tumor volume. The chemicals are 4 injected to targeted tumor volume prior to freezing. Vllater is injected after the chemical is injected, ten minutes later.
The added water counteracts any adverse effects of water displacing from non-targeted 8 areas as caused by the chemicals and provide greater cellular strain.
Freezing zone can be extended to a desired distance from the margin of the tumor or targeted tissue by also injecting the chemical to this area.
Cryosurgical freezing should be started after another ten minutes.
The injection to the tumor is guided by ultrasound as for subcutaneous targets. Ice 16 formation is monitored using ultrasound and open MRI.
18 Tissue temperature is monitored using thermocouples placed within the target volume, critical organs and non-targeted nearby tissues.
Established lethal temperatures range from -25°C such as in prostate cryosurgery to -22 40°C e.g. in breast cryosurgery. Thus, freezing is stopped when this temperature is reached.
The combined hastening of ice formation and creation of greater cellular strain within the 26 targeted tissue results to optimum cellular destruction even prior to reaching the lethal temperatures.
Biopsies and MRI images will be taken before and after the cryosurgical procedure when ice is melted to ensure maximum cellular destruction to point of rupture has been achieved in the procedure, and unwanted freezing of non-targeted tissue has been 32 minimized.
34 Experiments and studies performed for this invention showed a more remarkable destruction of targeted tissues injected with the chemicals than those not injected.
Rates of ice formation and water absorption of sample tissues treated with the various 38 chemicals show tremendous increase.
BEST MODE FOR CARRYINC9 OIJT THE IN!/ENTION
Preparing the Chemicals:
44 To produce:
46 1 ) 2.5M of L-Proline 99+% (Molecular weight = 115.13):
48 Dissolve 287.82 grams of L-Proline 99+% in one liter of water.
Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 7 of 12 2 2) 2.5M of Glycerol 99+%
4 Dissolve 230.22 grams of Glycerol 99+% in one liter of water.
6 3) 2.5M of Taurine 99%
8 Dissolve 315.38 grams of Taurine 99% in one liter of water.
4) 1.5M Beta-Alanine 99+%
12 Dissolve 133.64 grams of Beta-Alanine 99% in one liter of water.
14 5) 1.5M of Betaine 98%
16 Dissolve 175.72 grams of Betaine 98% in one liter of water.
18 6) 1.5M Sucrose 98%
Dissolve 513.45 grams of Sucrose 98% in one liter of water.
7) 1.5M D-mannitol 98%
Dissolve 273.26 grams of D-mannitol 98% in one liter of water.
8) 0.5M D-Trehalose dihydrate 99%
Dissolve 189.15 grams of D-Trehalose dihydrate 99% in one liter of water.
9) 1.5M or 2.5M of Urea 99+%.
For 1.5M Urea: Dissolve 90.09 grams of Urea 99+% in one liter of 34 water.
36 For 2.5M Urea: Dissolve 150.15 grams of Urea 99+% in one liter of water.
Volume of chemicals above is about 10% of the tumor volume.
To administer the correct amount of chemical throughout the targeted volume for ice 42 sculpturing, it is crucial to determine the volume and exact location of the targeted tumor.
44 The current method that yields the best estimate of prostate tumor volume is serum Prostate Specific Antigen (PSA) with 0.5 Pearson Correlation Coefficient.
Tumor volume estimates for other subcutaneous tumors are done by first taking a 48 Computed Topography (CT) scan or MRI image. The image is then entered to a Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tonal August 20, 2003 Page 8 of 12 computer for calculation. The computer reconstructs the image in three-dimension and 2 performs voxel counting, trapezoid approximation technique and area summation calculation.
The most accurate biopsy and imaging technique should be used in determining the 6 stage and location of targeted tumor and its exact location. Such as to date, for prostate cancer, Transrectal Ultrasound (TRUS) biopsies as described by Onik could be used.
Technique for Administering the Chemicals and Maximizing the Effects:
For subcutaneous tumors, the injection of the chemicals and the insertion of cryosurgical 12 probe should be guided by ultrasound with sector scan transducer. Doppler ultrasound that display colored images should give clear distinction of tumor boundary and normal 14 tissues. Ultrasound must operate at higher frequency for better imaging of various tissues and organs such as at least 5 or 7.5MHz.
Targeted gland such as prostate can be shrieked using androgen deprivation technique 18 prior to injecting the chemicals) and performing cryosurgery. Shrinking the gland ensures better absorption and distribution of the chemicals. Moreover, shrinking the gland decreases the risk of freezing the rectum since the other effect of this method is increasing the space between the rectum and the prostate capsule due to the effect of 22 increasing the amount of fat in the Denonvilliers fascia region [Onik, "Percutaneous Prostate Cryoablation].
Injecting water in the targeted tissue counteracts any adverse effects of water displacing from 26 non-targeted areas due to the chemical injected, and creates greater cellular strain. Water of volume approximately 50% of the tumor volume should be sufficient. Water can be injected 10 28 minutes after the injection of the chemical.
Freezing of tissues using cryosurgical probe can begin 10 minutes after injection of chemicals and/or after the injection of water. Diameter and shape of probe tip depend on the diameter, 32 shape and desired extent of ice formation.
34 For sculpturing ice formation, it is critical to monitor the temperatures and ice formation of targeted tissue, critical organs and extended freezing areas. Thus, thermocouples are 36 placed in these areas.
38 Diameter of ice ball and extent of ice crystals formed outside of tumor volume should be measured using linear array ultrasound or open MRI during the entire procedure.
Diameter of ice ball should be graphed with respect to time and temperature.
Rate of ice ball formation will then be calculated. This is to monitor if treatment plan was followed in 42 the procedure performed.
44 MRI images will be taken before and after the cryosurgical procedure when ice is melted to ensure maximum cellular destruction to point of rupture has been achieved in the procedure, 46 and unwanted freezing of non-targeted tissue has been minimized.
48 Several cryoprobes are imbedded within the substance of the tumor. Number of cryoprobes and Canadian Intellectual Property INDUCING AND CONTOURING ICE FORMATION
Tortal August 20, 2003 Page 9 of 12 distances between them depend on the size and shape of tumor. The established lethal 2 temperature that causes cellular necrosis is at least -25 for prostate cancer, and -40°C as in the case of breast carcinoma. In this proposed technique, we expect higher temperature 4 destructive freezing since we have induced faster rate and maximum amount of ice formation at much higher tissue temperature. We already observed greater tissue damage at less than 6 20°C.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 shows the injection of chemical to the targeted tissue A.
Figure 2 shows the injection of chemical to adjacent normal tissue B as represented by 14 broken curve lines if ice ball formation should be slightly be extended beyond targeted tissue.
Claims (23)
1. Chemicals for sculpturing ice formation in cryosurgery.
2. Chemicals for creating or increasing the difference in the rate of freezing/ice formation between targeted and non-targeted tissues.
3. Chemicals for inducing ice nucleation within targeted cells.
4. A technique for ice sculpturing using chemicals.
5. A technique for creating or increasing the difference in the rate of freezing/ice formation between targeted and non-targeted tissues.
6. A technique for inducing ice nucleation within targeted cells.
7. Chemicals such as in Claim 1 that are nucleatic agents.
8. Chemicals used in freezing of tissues that are both nucleatic and osmotic agents.
9. Chemicals used in freezing of tissues that are osmotic agents.
10. A technique for freezing of tissues wherein nucleatic agent(s) is/are introduced into targeted tissue prior to freezing.
11. A technique for freezing of tissues wherein chemicals of both osmotic and nucleatic agent(s) is/are introduced to a targeted tissue.
12. A technique for freezing of tissues wherein chemicals of osmotic agent(s) is/are introduced to a targeted tissue.
13. The technique of using chemicals to manipulate the response of cells to freezing.
14. Chemicals for manipulating the response of cells to freezing.
15. Chemicals for minimizing unwanted freezing.
16. Technique for minimizing unwanted freezing using chemical(s).
17. Chemical(s) to induce cellular strain during freezing.
18. Chemical(s) that optimize(s) cellular strain during freezing.
19. A technique for inducing cellular strain during freezing.
20. A technique that optimize(s) cellular strain during freezing.
21. Chemical(s) for sculpturing ice formation.
22. A technique for sculpturing ice formation in tissues using chemicals.
23. The use of chemicals in cryosurgery.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2441489 CA2441489A1 (en) | 2003-09-12 | 2003-09-12 | Inducing and contouring ice formation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2441489 CA2441489A1 (en) | 2003-09-12 | 2003-09-12 | Inducing and contouring ice formation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2441489A1 true CA2441489A1 (en) | 2005-03-12 |
Family
ID=34230784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2441489 Abandoned CA2441489A1 (en) | 2003-09-12 | 2003-09-12 | Inducing and contouring ice formation |
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| Country | Link |
|---|---|
| CA (1) | CA2441489A1 (en) |
Cited By (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US9375345B2 (en) | 2006-09-26 | 2016-06-28 | Zeltiq Aesthetics, Inc. | Cooling device having a plurality of controllable cooling elements to provide a predetermined cooling profile |
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-
2003
- 2003-09-12 CA CA 2441489 patent/CA2441489A1/en not_active Abandoned
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