WO2002034297A2 - Endoscopic vascular visualisation, diagnostic and/or surgical procedure - Google Patents
Endoscopic vascular visualisation, diagnostic and/or surgical procedure Download PDFInfo
- Publication number
- WO2002034297A2 WO2002034297A2 PCT/EP2001/012416 EP0112416W WO0234297A2 WO 2002034297 A2 WO2002034297 A2 WO 2002034297A2 EP 0112416 W EP0112416 W EP 0112416W WO 0234297 A2 WO0234297 A2 WO 0234297A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- blood
- cavity
- fluorocarbon
- oxygen carrier
- liquid
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
Definitions
- the present invention relates to a method for performing an endoscopic, in particular an endovascular visualisation, diagnostic and/or surgical procedure wherein a structure in or of a cavity, which is normally filled with blood, is made visible, and to a method of producing a pharmaceutical composition for use in such a procedure.
- the present invention in particular relates to a method for performing an endoscopic, in particular an endovascular visualisation procedure.
- these problems are solved by replacing the blood in said cavity at least partially by a fluorocarbon-based oxygen carrier in the form of a liquid, in particular a liquid emulsion, which is more transparent than blood and by making said structure visible through the liquid present in said cavity by means of a camera, working in particular in the visible and/or infrared range, or by means of a sonic or ultrasonic visualisation device.
- a fluorocarbon-based oxygen carrier in the form of a liquid, in particular a liquid emulsion, which is more transparent than blood and by making said structure visible through the liquid present in said cavity by means of a camera, working in particular in the visible and/or infrared range, or by means of a sonic or ultrasonic visualisation device.
- a camera working in the visible and/or infrared range
- the used camera comprises preferably means for enhancing the contrast to achieve a clearer image of the structure.
- a fluorocarbon-based oxygen carrier in the form of a liquid which is more transparent than blood.
- the transparent liquid is usually an emulsion so that the visibility therethrough by the bare eye is limited.
- contrast enhancing means Since the camera and the contrast enhancing means are known per se, they will not be described further into detail in the present specification.
- Use can for example be made of a CCD camera or a CMOS camera.
- a light source is preferably provided, in particular a light source emitting light in the visible or in the (near) infrared range which can be detected by the camera.
- At least 50 vol.%, more preferably at least 80 vol. % and most preferably at least 90 vol. % of the blood in the cavity at the location of the structure which has to be made visible is replaced by the transparent liquid to improve the visibility in that cavity.
- This visibility depends amongst others on the amount of red blood cells present in the blood.
- at least 97 vol. %, and most preferably substantially all of the blood is replaced in the cavity.
- the transparent liquid may comprise one or more oxygen carrying fluorocarbons, in particular perfluorocarbons like perfluorodecalin and/or perfluoromethylcyclohexylpiperidin.
- it comprises water and salts, preferably in an amount to provide an osmotic pressure of between 200 and 400 mOsm and more preferably of between 280 and 340 mOsm.
- the liquid is an emulsion, it further comprises one or more emulsifiers, such as Proxanol-268.
- the replacement of the blood can be done in different ways. First of all it is possible to maintain the normal flow of blood through the cavity and to inject or infuse the transparent liquid into this flow, either in or upstream of the cavity. When the transparent liquid flows through the cavity, the structure in or of this cavity can be made visible. In this embodiment, it is possible to interrupt the normal blood stream upstream the location where the transparent liquid is injected or infused. In that way, a higher concentration of transparent liquid can be achieved, and this for a longer period of time, with a particular amount of transparent liquid. Although a rather high amount of the transparent liquid may be introduced in the blood stream, it is preferable to introduce as less as possible of this liquid in the blood stream.
- Perftoran When use is made of Perftoran, up to 80 % of the total blood volume may for example be replaced. As an example, it is possible to flush during a short time the cardiac cavity with Perftoran (or another oxygen carrying solution) which is clear and could replace the blood during the visualisation or intervention time.
- Perftoran or another oxygen carrying solution
- the amount of Perftoran clears the view to take the necessary images or and, if used for a surgical operation, to enable the surgeon to perform the operation under good visual conditions during short periods of time.
- the method according to the present invention enables thus in particular an intracardiac visualisation of structures in the beating heart (e.g. deformed mitral valve, intracardiac clots or tumors (if combined with an aortic filter), subvalvular aortic stenoses, assistance for endovascular treatment of mitral valve stenosis and possibly even endovascular valve replacement, etc.).
- structures in the beating heart e.g. deformed mitral valve, intracardiac clots or tumors (if combined with an aortic filter), subvalvular aortic stenoses, assistance for endovascular treatment of mitral valve stenosis and possibly even endovascular valve replacement, etc.
- the transparent liquid can be circulated through the organ in a separate closed circuit with a pump and oxygen is added to the oxygen carrying transparent liquid to ensure an adequate oxygen supply into the organ during the intervention. While the organ is flushed with the transparent liquid one has a clear view of the intervention site either to take images or to perform a surgical operation. At the end of the procedure the separate perfusion loop of the transparent liquid is removed and the general blood flow through the target organ is restored. The Perftoran or similar transparent artificial blood remaining in the body is harmless.
- Perftoran is a good oxygen carrier, it restores the energetic needs of the organ and has been widely used as emergency replacement perfusion in trauma emergency situations.
Abstract
The invention relates to a method for performing an endoscopic, in particular an endovascular visualisation, diagnostic and/or surgical procedure wherein a structure in or of a cavity, which is normally filled with blood, is made visible. In order to increase the visibility in the cavity, the blood in this cavity is at least partially replaced by a fluorocarbon-based oxigen carrier in the form of a liquid which is more transparent than blood. The structure can then be made visible through the liquid present in the cavity by means of a camera, working in particular in the visible and/or infrared range, or by means of a sonic or ultrasonic visualisation device. The invention also relates to the use of a fluorocarbon-based oxygen carrier for producing a pharmaceutical composition in the form of a liquid, which is more transparent than blood, such a for example Perftoran or Perflubron, for use in an endoscopic, in partiular an endovascular, visualisation, diagnostic and/or surgical procedure.
Description
"Method and composition for performing an endoscopic vascular visualisation, diagnostic and/or surgical procedure"
The present invention relates to a method for performing an endoscopic, in particular an endovascular visualisation, diagnostic and/or surgical procedure wherein a structure in or of a cavity, which is normally filled with blood, is made visible, and to a method of producing a pharmaceutical composition for use in such a procedure. The present invention in particular relates to a method for performing an endoscopic, in particular an endovascular visualisation procedure.
The general trend in modern surgery is to resort to minimal invasive interventions whenever possible, in particular to endovascular procedures. The obvious benefits are shorter interventions, less traumatic impact for the patient, shorter recovery times and better utilisation of operating rooms.
Invasive heart surgery is still very problematic when minimal invasive techniques are planned. The main reason is that the cavity can only be accessed by resorting to extra corporal circulation shunting the heart and allowing to open the cavities.
It is possible to introduce minimal invasive surgery tools in the heart without having to stop the heart in theory but the issue is then to be able to see the intravascular, in particular the intracardiac, structures to be operated upon. This is also true when having to perform a surgical operation in other organs.
The problems of making intravascular structures visible due to the presence of blood therein do not only arise when performing surgical operations but also when the vascular structure is to be
visualised for example for making a diagnosis or for any other purpose, for example for teaching purposes.
In the method according to the present invention, these problems are solved by replacing the blood in said cavity at least partially by a fluorocarbon-based oxygen carrier in the form of a liquid, in particular a liquid emulsion, which is more transparent than blood and by making said structure visible through the liquid present in said cavity by means of a camera, working in particular in the visible and/or infrared range, or by means of a sonic or ultrasonic visualisation device. According to the invention, it has been found that by replacing at least a portion of the blood in the cavity, the structure of or in the cavity can be seen by means of a camera working in the visible and/or infrared range. The used camera comprises preferably means for enhancing the contrast to achieve a clearer image of the structure. As fluorocarbon-based oxygen carrier different so-called artificial bloods can be used, especially Perftoran and Perflubron have been found very effective. These compositions have already been used to provide organs with oxygen when being removed from the body but they do not have been used to increase the visibility in internal body cavities which are normally filled with blood, such as in particular the different heart chambers and the lumen of veins and arteries.
The composition of Perftoran and some properties thereof are given in the following table:
In the method according to the invention, use is made of a fluorocarbon-based oxygen carrier in the form of a liquid which is more transparent than blood. Like Perftoran, Perflubron and most other artificial kinds of blood, the transparent liquid is usually an emulsion so that the visibility therethrough by the bare eye is limited. However, the present inventors have found that by means of a camera, or by means of a sonic or ultrasonic visualisation device, it is possible to achieve a clear view through such emulsions, in particular when the camera is provided with contrast enhancing means. Since the camera and the contrast enhancing means are known per se, they will not be described further into detail in the present specification. Use can for example be made of a CCD camera or a CMOS camera. To provide light in the cavity to achieve a better image of the structure, a light source is preferably provided, in particular a light source emitting light in the visible or in the (near) infrared range which can be detected by the camera.
In the method according to the invention, preferably at least 50 vol.%, more preferably at least 80 vol. % and most preferably at least 90 vol. % of the blood in the cavity at the location of the structure which has to be made visible is replaced by the transparent liquid to improve the visibility in that cavity. This visibility depends amongst others on the amount of red blood cells present in the blood. In order to
achieve the best visibility, at least 97 vol. %, and most preferably substantially all of the blood is replaced in the cavity.
For providing the required oxygen carrying properties, the transparent liquid may comprise one or more oxygen carrying fluorocarbons, in particular perfluorocarbons like perfluorodecalin and/or perfluoromethylcyclohexylpiperidin. In addition, it comprises water and salts, preferably in an amount to provide an osmotic pressure of between 200 and 400 mOsm and more preferably of between 280 and 340 mOsm. When the liquid is an emulsion, it further comprises one or more emulsifiers, such as Proxanol-268.
The replacement of the blood can be done in different ways. First of all it is possible to maintain the normal flow of blood through the cavity and to inject or infuse the transparent liquid into this flow, either in or upstream of the cavity. When the transparent liquid flows through the cavity, the structure in or of this cavity can be made visible. In this embodiment, it is possible to interrupt the normal blood stream upstream the location where the transparent liquid is injected or infused. In that way, a higher concentration of transparent liquid can be achieved, and this for a longer period of time, with a particular amount of transparent liquid. Although a rather high amount of the transparent liquid may be introduced in the blood stream, it is preferable to introduce as less as possible of this liquid in the blood stream. When use is made of Perftoran, up to 80 % of the total blood volume may for example be replaced. As an example, it is possible to flush during a short time the cardiac cavity with Perftoran (or another oxygen carrying solution) which is clear and could replace the blood during the visualisation or intervention time. The amount of Perftoran clears the view to take the necessary images or and, if used for a surgical operation, to enable the
surgeon to perform the operation under good visual conditions during short periods of time.
If a longer intervention is required one must shunt the total circulation of the heart with extracorporal circulation with a heart-lung pump, and perfuse the heart with the transparent oxygen carrying liquid with a second pump in order to see clearly the intracavital structures. This would allow minimal invasive surgery of the heart in situ, but with the heart-lung pump for extracorporal circulation. The method according to the present invention enables thus in particular an intracardiac visualisation of structures in the beating heart (e.g. deformed mitral valve, intracardiac clots or tumors (if combined with an aortic filter), subvalvular aortic stenoses, assistance for endovascular treatment of mitral valve stenosis and possibly even endovascular valve replacement, etc.). For almost all other organs, in particular also for inspecting the inner wall of the lumen of veins or arteries, it is possible to replace the blood circulation through the cavity in the organ locally by the oxygen carrying transparent liquid during the intervention with the help of a pump. By temporarily bypassing the bloodstream of the organ, the main bloodstream can be maintained. Once an amount of transparent liquid has been passed through the cavity in the organ to make it free of blood, the transparent liquid can be circulated through the organ in a separate closed circuit with a pump and oxygen is added to the oxygen carrying transparent liquid to ensure an adequate oxygen supply into the organ during the intervention. While the organ is flushed with the transparent liquid one has a clear view of the intervention site either to take images or to perform a surgical operation. At the end of the procedure the separate perfusion loop of the transparent liquid is removed and the general blood flow through the target organ is
restored. The Perftoran or similar transparent artificial blood remaining in the body is harmless.
In the method according to the invention, use is preferably made of Perftoran or of Perflubron as oxygen carrying transparent emulsion, although other oxygen transporting liquids can be used provided they show the required transparency to enable to look therethrough by means of a camera. Perftoran is a good oxygen carrier, it restores the energetic needs of the organ and has been widely used as emergency replacement perfusion in trauma emergency situations.
Claims
1. A method of producing a pharmaceutical composition for use in an endoscopic, in particular an endovascular, visualisation, diagnostic and/or surgical procedure wherein a structure in or of a cavity, which is normally filled with blood, is made visible, characterised in that use is made of a fluorocarbon-based oxygen carrier in the form of a liquid which is more transparent than blood for preparing said composition, which is a pharmaceutical composition for replacing at least partially the blood in said cavity wherein said procedure is to be carried out to increase the visibility by means of electromagnetic or sonic or ultrasonic waves therein, in particular by means of visible or infrared light waves.
2. A method according to claim 1 , characterised in that said fluorocarbon-based oxygen carrier is in the form of a liquid emulsion.
3. A method according to claim 1 or 2, characterised in that said fluorocarbon-based oxygen carrier contains water and salts, in particular chlorides.
4. A method according to any one of the claims 1 to 3, characterised in that said fluorocarbon-based oxygen carrier has an osmotic pressure of between 200 and 400 mOsm, preferably between 280 and 340 mOsm.
5. A method according to any one of the claims 1 to 4, characterised in that the fluorocarbon-based oxygen carrier comprises perfluorodecalin.
6. A method according to any one of the claims 1 to 5, characterised in that the fluorocarbon-based oxygen carrier comprises perfluoromethylcyclohexylpiperidin.
7. A method according to any one of the claims 1 to 6, characterised in that the fluorocarbon-based oxygen carrier comprises Perftoran.
8. A method according to any one of the claims 1 to 6, characterised in that the fluorocarbon-based oxygen carrier comprises
Perflubron.
9. A method for performing an endoscopic, in particular an endovascular visualisation, diagnostic and/or surgical procedure wherein a structure in or of a cavity, which is normally filled with blood, is made visible, characterised in that the blood in said cavity is at least partially replaced by a fluorocarbon-based oxygen carrier in the form of a liquid which is more transparent than blood, in particular a liquid emulsion, and said structure is made visible through the liquid present in said cavity by means of a camera, working in particular in the visible and/or infrared range, or by means of a sonic or ultrasonic visualisation device.
10. A method according to claim 9, characterised in that at least 50 vol. %, preferably at least 80 vol. % and most preferably at least 90 vol. % of the blood is replaced by the transparent liquid in the cavity at the location of said structure.
1 1. A method according to claim 10, characterised in that at least 97 vol. % of the blood is replaced by the transparent liquid in the cavity at the location of said structure.
12. A method according to any one of the claims 9 to 11 , characterised in that said transparent liquid is circulated through the cavity, the flow of blood through the cavity being preferably bypassed.
13. A method according to any one of the claims 9 to 1 1 , characterised in that a predetermined amount of said transparent liquid is fed in the blood flowing through the cavity and when this transparent liquid passes the structure, it is made visible by means of the camera or by means of the sonic or ultrasonic visualisation device.
14. A method according to any one of the claims 8 to 12, characterised in that said camera is an electronic camera, comprising preferably contrast enhancing means.
15. A method according to any one of the claims 9 to 14, characterised in that said fluorocarbon-based oxygen carrier has a composition as claimed in any one of the claims 2 to 8.
16. A method according to any one of the claims 9 to 15, characterised in that it is a method for performing an endoscopic, in particular an endovascular visualisation procedure in a cavity which is normally filled with blood wherein a structure in or of the cavity is made visible by means of a camera after having replaced at least part of the blood present in the cavity with a fluorocarbon-based oxygen carrier in the form of a liquid which is more transparent than blood.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2002223652A AU2002223652A1 (en) | 2000-10-24 | 2001-10-24 | Endoscopic vascular visualisation, diagnostic and/or surgical procedure |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00870242.5 | 2000-10-24 | ||
| EP00870242 | 2000-10-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2002034297A2 true WO2002034297A2 (en) | 2002-05-02 |
| WO2002034297A3 WO2002034297A3 (en) | 2002-12-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2001/012416 WO2002034297A2 (en) | 2000-10-24 | 2001-10-24 | Endoscopic vascular visualisation, diagnostic and/or surgical procedure |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2002223652A1 (en) |
| WO (1) | WO2002034297A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1354868A1 (en) * | 2000-12-29 | 2003-10-22 | Otkrytoe Aktsionernoe Obchestvo Nauchno-Proizvodstvennaya Firma "Perftoran" | Perfluoronated cycle-containing tertiary amines used as a basis for gas-conveying emulsions and device for the production thereof |
| US7794699B2 (en) | 2005-01-05 | 2010-09-14 | Michigan Molecular Institute | Nano-structured blood substitutes |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021301A1 (en) * | 1993-03-16 | 1994-09-29 | Holmes, Michael, John | Improvements in or relating to contrast agents |
| WO1996023524A1 (en) * | 1995-02-02 | 1996-08-08 | Nycomed Imaging A/S | Contrast media for in vivo imaging based on light transmission on reflection |
| WO1997025978A1 (en) * | 1996-01-15 | 1997-07-24 | BELOYARTSEV, Arkady Felixovich | Method of obtaining perfluorocarbon emulsions for medical purposes |
-
2001
- 2001-10-24 AU AU2002223652A patent/AU2002223652A1/en not_active Abandoned
- 2001-10-24 WO PCT/EP2001/012416 patent/WO2002034297A2/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994021301A1 (en) * | 1993-03-16 | 1994-09-29 | Holmes, Michael, John | Improvements in or relating to contrast agents |
| WO1996023524A1 (en) * | 1995-02-02 | 1996-08-08 | Nycomed Imaging A/S | Contrast media for in vivo imaging based on light transmission on reflection |
| WO1997025978A1 (en) * | 1996-01-15 | 1997-07-24 | BELOYARTSEV, Arkady Felixovich | Method of obtaining perfluorocarbon emulsions for medical purposes |
Non-Patent Citations (3)
| Title |
|---|
| MATTREY R F ET AL: "Perfluorochemicals as liver- and spleen-seeking ultrasound contrast agents." JOURNAL OF ULTRASOUND IN MEDICINE: OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE. UNITED STATES APR 1983, vol. 2, no. 4, April 1983 (1983-04), pages 173-176, XP008007732 ISSN: 0278-4297 * |
| MAZZONI M ET AL: "Dose monitoring in Partial Liquid Ventilation by infrared measurement of expired perfluorochemicals." BIOMEDICAL INSTRUMENTATION & TECHNOLOGY / ASSOCIATION FOR THE ADVANCEMENT OF MEDICAL INSTRUMENTATION. UNITED STATES 1999 JUL-AUG, vol. 33, no. 4, July 1999 (1999-07), pages 356-364, XP008007827 ISSN: 0899-8205 * |
| MCDONAGH, PAUL ET AL: "Perflubron Emulsion Reduces Inflammation during Extracorporeal Circulation" JOURNAL OF SURGICAL RESEARCH (2001), 99(1), 7-16 , XP002212940 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1354868A1 (en) * | 2000-12-29 | 2003-10-22 | Otkrytoe Aktsionernoe Obchestvo Nauchno-Proizvodstvennaya Firma "Perftoran" | Perfluoronated cycle-containing tertiary amines used as a basis for gas-conveying emulsions and device for the production thereof |
| EP1354868A4 (en) * | 2000-12-29 | 2004-09-29 | Otkrytoe Aktsionernoe Obchestv | Perfluoronated cycle-containing tertiary amines used as a basis for gas-conveying emulsions and device for the production thereof |
| US7794699B2 (en) | 2005-01-05 | 2010-09-14 | Michigan Molecular Institute | Nano-structured blood substitutes |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002034297A3 (en) | 2002-12-12 |
| AU2002223652A1 (en) | 2002-05-06 |
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