Ultrasound contact fluid

Abstract

An aqueous ultrasound contact fluid includes a pharmaceutical grade triglyceride and a pharmaceutically acceptable emulsifier and the use of the ultrasound contact fluid in an intraoperative or interventional ultrasound imaging procedure. A method for intraoperative ultrasound imaging includes filling an aqueous ultrasound contact fluid into a body cavity. The aqueous ultrasound contact fluid is a composition comprising a pharmaceutical grade triglyceride and a pharmaceutically acceptable emulsifier and optionally a pharmaceutically acceptable humectant, and the triglyceride content is in the range of 8-240 g/1000 ml composition contact fluid and the amount of emulsifier is 0.4-18 g/1000 ml composition contact fluid, and optionally a humectant in the amount of 1.2-30 g/1000 ml. The method further includes obtaining an ultrasound image of a body region that comprises at least part of the body cavity filled with the aqueous ultrasound contact fluid. The aqueous ultrasound contact fluid reduces image artifacts associated with the body cavity.

Claims

1. A method for intraoperative ultrasound imaging, comprising: filling a body cavity with an aqueous ultrasound contact fluid, wherein the aqueous ultrasound contact fluid is a composition comprising a pharmaceutical grade triglyceride and a pharmaceutically acceptable emulsifier and optionally a pharmaceutically acceptable humectant, wherein the triglyceride content is in the range of 8-240 g/1000 ml contact fluid and the amount of emulsifier is 0.4-18 g/1000 ml contact fluid, and optionally a humectant in the amount of 1.2-30 g/1000 ml; and obtaining an ultrasound image of a body region that comprises at least part of the body cavity filled with the aqueous ultrasound contact fluid, wherein the aqueous ultrasound contact fluid reduces image artifacts associated with the body cavity.

2. The method according to claim 1, wherein the amount of triglyceride is in the range of 10-200 g/1000 ml contact fluid, and wherein the amount of emulsifier is 0.5-15 g/1000 ml contact fluid and optionally a humectant in the amount of 1.2-25 g/1000 ml contact fluid.

3. The method according to claim 1, wherein the amount of triglyceride is 50-110 g/1000 ml contact fluid, the amount of emulsifier is 2-10 g/1000 ml contact fluid, and optionally a humectant in the amount of 5-15 g/1000 ml contact fluid.

4. The method according to claim 1, wherein said triglyceride is vegetable oil.

5. The method according to claim 4, wherein said vegetable oil is selected from the group consisting of soybean oil, olive oil, palm oil, and copra oil.

6. The method according to claim 1, wherein said emulsifier is selected from the group consisting of lecithin, egg yolk lecithin, soy lecithin, emulsifying wax, cetearyl alcohol, polysorbate 20, and ceteareth 20.

7. The method according to claim 1, wherein the humectant is selected from the group consisting of glycerol, lactic acid, polyols, propylene glycol, and sorbitol.

8. The method according to claim 1, wherein the ultrasound contact fluid comprises a pH adjusting additive.

9. The method according to claim 8, wherein an amount of the pH adjusting additive is added to set the pH in the range of 6 to 8.

10. The method according to claim 9, wherein the pH is set to 7.

11. The method according to claim 1, wherein the ultrasound contact fluid comprises 90 g soybean oil, 5.5 g lecithin and 10 g glycerol and physiological saline to obtain 1000 ml.

12. The method according to claim 1, wherein the ultrasound contact fluid has an attenuation coefficient α>0.066.

13. The method according to claim 12, wherein the attenuation coefficient α is in the range of 0.20 to 1.10.

14. The method according to claim 13, wherein the attenuation coefficient α is 0.80.

15. The method according to claim 1, wherein said triglyceride is an animal fat.

16. The method according to claim 15, wherein said animal fat is selected from the group consisting of milk fats, fish oils, and fish liver oils.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows reformatted image slices from 3D ultrasound volumes acquired intraoperatively as displayed on a navigation system. In the left image we observe a high intensity region at the bottom left cavity wall, introduced by waves transmitted through the low attenuation water filled cavity. In the right image the position of the ultrasound probe has been changed to the left of the operating channel, and we observe that the bright rim, or the apparent enhanced echo, is now observed in the bottom right cavity wall.

(2) FIG. 2 shows ultrasound imaging of a cavity with dipping reflector when filled with A) NaCl (0.9%) fluid which is representative for fluids applied during brain surgery and B) fluid with attenuation as defined according to the invention.

(3) FIG. 3 shows comparison of images of resection cavity in piglet brain using physiological saline (a) and contact fluid according to the present invention (b).

SUMMARY OF THE INVENTION

(4) The present invention is concerned with an aqueous ultrasound contact fluid comprising a pharmaceutical grade triglyceride and a pharmaceutically acceptable emulsifier and optionally a pharmaceutically acceptable humectant as defined in the Patent claims.

DETAILED DESCRIPTION OF THE INVENTION

(5) The term ultrasound contact fluid as used herein means a medium used to exclude air between the ultrasound probe and the tissue, hence the main purpose is to provide acoustic coupling between the ultrasound transducer/probe and the tissue to be investigated. The term is synonymous with terms like “contact fluid”, “contact agent”, “coupling fluid”, “acoustic fluid”, “acoustic coupling fluid” and “acoustic coupling agent”.

(6) An object of the current invention is to solve the problem encountered in ultrasound imaging, where a difference in signal intensity is observed because the ultrasound is at least partly propagating in media with different attenuation. This results in an ultrasound image in which there are substantial regional differences in signal intensity. This problem makes it difficult to interpret the images and it is difficult to adjust the acquisition parameters to balance the regional differences in signal intensity.

(7) It is another object of the present invention is to solve the problem encountered when inserting a fluid to a body cavity, and there is observable a difference in intensity dependent on whether or not the ultrasound waves have at least partly been propagating in the organ or cavity in which the fluid has been administered.

(8) A further object of the current invention is to solve the problem encountered when inserting a fluid to a body cavity or the cardiac system to enable ultrasound imaging, and the ultrasound images have a highly different intensity at the fluid filled cavity wall and beyond compared to the signal intensities of the tissue adjacent to the cavity.

(9) The present invention concerns an aqueous ultrasound contact fluid which can be use in body cavities or resection cavities during ultrasound imaging, particularly when said ultrasound imaging is carried out during surgery. The composition of the fluid according to the present invention provides attenuation of the acoustic waves equal to the tissue to be examined.

(10) In an embodiment of the invention an aqueous ultrasound contact fluid is provided comprising a pharmaceutical grade triglyceride, a pharmaceutically acceptable emulsifier and optionally a pharmaceutically acceptable humectant wherein triglyceride content is in the range of 8-240 g/1000 ml contact fluid and the amount of emulsifier is 0.4-18 g/1000 ml contact fluid and optionally an humectant in the amount of 1.2-30 g/1000 ml contact fluid.

(11) In another embodiment of the invention an ultrasound contact fluid is provided wherein the triglyceride content is in the range of 10-200 g/1000 ml contact fluid, the amount of emulsifier is 0.5-15 g/1000 ml contact fluid and the optional amount of humectant is 1-25 g/1000 ml contact fluid.

(12) In a further embodiment of the invention an ultrasound contact fluid is provided wherein the amount of triglyceride is 50-110 g/1000 ml contact fluid, the amount of emulsifier is 2-10 g/1000 ml contact fluid and optionally an humectant in the amount of 5-15 g/1000 ml contact fluid.

(13) The pharmaceutical grade triglyceride used may be selected from vegetable oils or animal fats. Vegetable oils may preferably be selected from the group consisting of soybean oil, olive oil, palm oil and copra oil. Examples of animal fats that may be used are milk fats, fish oils and fish liver oils.

(14) The pharmaceutically acceptable emulsifier used may be selected from the group consisting of lecithin (e.g. egg yolk lecithin, soy lecithin), emulsifying wax, cetearyl alcohol, polysorbate 20, and ceteareth 20.

(15) The pharmaceutically acceptable humectant may be selected from the group consisting of glycerol, lactic acid, polyols, propylene glycol, and sorbitol.

(16) For an ultrasound contact fluid to be used in body and resection cavities a pH in the physiological range is necessary, and the pH in the fluid can be adjusted to a pH level suitable for the intended clinical use, for example in the range 6 to 8, preferably about 7, by use of means generally known in the art. Further the fluid according to the invention is a biocompatible and sterile fluid for acoustic examinations/imaging of cavities.

(17) Adjustment of osmolality and salinity of fluids to physiological acceptable values are generally known in the art and such adjustments means are applicable for the present invention.

(18) In a particular embodiment of the present invention the ultrasound contact fluid according to the invention comprises 90 g soybean oil, 5.5 g lecithin and 10 g glycerol and physiological saline water to obtain 1000 ml.

(19) The present invention concerns an aqueous ultrasound contact fluid that can be administered to patients (human or animals) before or during ultrasound examination, which is biocompatible, sterile and has an attenuation coefficient α that is at least a factor 30 larger than the attenuation coefficient for water, (i.e. α>0.066.). In an embodiment of the invention the attenuation coefficient α is in the range of 0.20 to 1.10, preferably 0.80. In an embodiment of the invention the contact fluid has an attenuation coefficient α targeted at 0.80 dB/(MHz.Math.cm), which is in the same order as α of the adult human brain.

(20) The effect of the invention is shown in FIG. 2A (prior art) in which a phantom with a cavity is filled with NaCl (0.9%) and a high intensity signal is seen at and below the bottom of the fluid filled cavity. This high intensity signal is partly masking the structures below the bottom of the cavity, and this is also frequently encountered in a clinical situation. In FIG. 2B (present invention) the cavity is filled with a fluid according to the present invention that provides attenuation of the acoustic waves according to the criteria of the invention. It is observed that the dipping structure in the cavity has at least the same intensity as seen in FIG. 2A, while the intensity at the bottom cavity and beyond is reduced in amplitude and more similar to the intensity of the adjacent media

EXAMPLES

Example 1

(21) The imaging properties of the contact fluid according to the invention have been evaluated on a phantom (FIG. 2) and on fresh piglet cadavers (FIG. 3).

(22) Phantom

(23) In the phantom a needle is inserted in a cavity made in oasis and imaged by a flat linear array (Vingmed Ultrasound System FiVe). Images were made with a regular saline shown to the left (A) in FIG. 2 and with a contact fluid according to the invention with a higher attenuation shown to the right (B) in FIG. 2. The same acquisition parameters were used, but the global gain was adjusted in each case to provide the “best image” as defined by an experienced ultrasound operator. The bright region below the bottom of the cavity in (A) is almost completely vanished in (B). Thus the image made using a contrast fluid with attenuation in accordance with the present invention gives a more accurate picture without artefacts present in (A).

(24) Piglet Brain

(25) Newly destroyed piglets were used in an experiment comparing imaging quality using saline or a contact fluid according to the present invention. Resection cavity (marked with arrows in FIG. 3) made in a fresh piglet brain imaged using physiological saline to fill the resection cavity (a) and imaged using a contact fluid according to the invention (b). The acquisition parameters are identical in both cases. The dominating signal enhancements in the deeper part of the images are caused by strong reflection from the scull base. The difference in intensity below the resection cavity in the two images (a and b) is pronounced. Even if the slice orientation is not perfectly identical in the images, it is apparent that there is no artificial signal enhancement directly below the bottom of the resection cavity in b. The differences in signal intensity can also be seen in the deeper bone reflections in a and b.

Example 2

(26) An animal study assessing safety of the ultrasound contact fluid according to the invention have been carried out.

(27) 8 rats and 6 pigs were included in the study. The rats were included for intraparechymal injection into the brain, and the pigs were included with injection of the contrast fluid into the subarachnoid space. Animal behaviour, EEG registrations, histopathology and immunohistochemistry were evaluated.

(28) In this safety study in rats and pigs no adverse clinical events of the contact fluid according to the present invention for improving image quality in ultrasound-guided operations were detected. Hence, the ultrasound contact fluid according to the invention appears safe under the tested circumstances.