WO2023132810A1 - Liquid skin marker - Google Patents
Liquid skin marker Download PDFInfo
- Publication number
- WO2023132810A1 WO2023132810A1 PCT/TR2023/050007 TR2023050007W WO2023132810A1 WO 2023132810 A1 WO2023132810 A1 WO 2023132810A1 TR 2023050007 W TR2023050007 W TR 2023050007W WO 2023132810 A1 WO2023132810 A1 WO 2023132810A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- liquid skin
- skin marker
- polyvinyl pyrrolidone
- barium sulphate
- ultrasound gel
- Prior art date
Links
- 239000003550 marker Substances 0.000 title claims abstract description 36
- 239000007788 liquid Substances 0.000 title claims abstract description 35
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims abstract description 28
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 20
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 20
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 20
- 238000002604 ultrasonography Methods 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims description 5
- 239000008240 homogeneous mixture Substances 0.000 claims description 4
- 238000002591 computed tomography Methods 0.000 description 26
- 239000000463 material Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 238000001959 radiotherapy Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZJNLYGOUHDJHMG-UHFFFAOYSA-N 1-n,4-n-bis(5-methylhexan-2-yl)benzene-1,4-diamine Chemical compound CC(C)CCC(C)NC1=CC=C(NC(C)CCC(C)C)C=C1 ZJNLYGOUHDJHMG-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000679 solder Inorganic materials 0.000 description 2
- 229940100555 2-methyl-4-isothiazolin-3-one Drugs 0.000 description 1
- 229940100484 5-chloro-2-methyl-4-isothiazolin-3-one Drugs 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229920003082 Povidone K 90 Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920006328 Styrofoam Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- DHNRXBZYEKSXIM-UHFFFAOYSA-N chloromethylisothiazolinone Chemical compound CN1SC(Cl)=CC1=O DHNRXBZYEKSXIM-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- BEGLCMHJXHIJLR-UHFFFAOYSA-N methylisothiazolinone Chemical compound CN1SC=CC1=O BEGLCMHJXHIJLR-UHFFFAOYSA-N 0.000 description 1
- 239000008261 styrofoam Substances 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0404—X-ray contrast preparations containing barium sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
- A61K31/79—Polymers of vinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
Definitions
- the invention relates to a liquid skin marker developed for use in the field of medicine in general, and specifically in the field of radiation oncology, where radiation is used to examine the internal structure of the human body, and any application where marking of the outer surface of the body is required during this process.
- Anatomical image data must be obtained in order to make three-dimensional (3D) treatment planning of patients for whom a radiotherapy (RT) treatment is decided.
- three-dimensional anatomical image data is obtained from the patients with the help of a Computed Tomography (CT) device.
- Markers (rifle shot, solder wire, commercial marker, etc.) are used on the skin before CT scanning so that some parts of the patients can be easily found on CT images. While skin markers help easily locate the desired area on CT images, they cause artifacts (anomalies usually caused by software and hardware defects). These artifacts are observed on CT images as high Hounsfield Unit (HU) changes at short distances.
- HU Hounsfield Unit
- Artifacts have some negative effects on the RT treatment planning process. One of them is that it can make it difficult to distinguish organ separations when introducing organs to the computer (contouring) on patient CT images. The other is that the artifacts formed on the CT images of the patients cause incorrect dose calculations while planning the 3D treatment. Therefore, in terms of the accuracy of the treatment given to the patient, it is necessary to reduce artifacts on CT images.
- Commercial products in the form of low-density solid spheres and wires are used during CT scanning in order to reduce artifacts on CT images. These commercial markers reduce artifacts and dose calculation errors in CT images relative to rifle shot and solder wire. However, dose calculation errors are still high. In addition, the use of these commercial products during CT scanning should be more practical.
- the commercial product used should provide convenience for both the patient and the personnel. If the area to be marked will be marked with a solid sphere, it takes a lot of time to attach many solid spheres one by one and to remove them after scanning. Likewise, it takes time to cut the commercial product in the form of wire, attach and remove it.
- the present invention relates to a liquid skin marker comprising ultrasound gel, Barium Sulphate and Polyvinyl Pyrrolidone, which fulfills the above-mentioned requirements, eliminates all disadvantages and provides some additional advantages.
- the primary objective of the invention is to develop a skin marker that is recognizable on CT images, which produces optimum HU and causes the least possible artifact, resulting in a much lower dose calculation error than other commercial products.
- the area to be marked on the patient's skin can be easily drawn in the form of dots or in the form of a cylinder, with the help of an apparatus like an injector during CT scanning, and can be easily wiped with a paper towel after the scanning. This shortens the processing time.
- the objective of the invention is to develop liquid markers with high viscosity in contrast to the physically solid structure of commercially used markers.
- the liquid skin marker of the invention With the liquid skin marker of the invention, it is provided that it is recognizable on CT images, the product produces optimum HU and causes the least possible artifact. It can be reduced from Maximum or 3000 HU to approximately 200 HU. In the study, the electron dose calculation error in the Radiotherapy Eclipse Treatment Planning System can be reduced from about -12% to about 3%. It allows a more reliable treatment planning in the treatments of patients.
- liquid skin marker of the invention is produced from materials used in medicine and applied from outside the body, the possibility of allergy and side effects is low.
- Figure 1 The effect of liquid skin marker and other materials on the number of CT images (Philips Brilliance CT) is shown.
- the carrier Styrofoam was carved in 2 mm dimensions and filled with different materials and computed tomography was performed.
- the CT image and materials are Rifle shot, Liquid Skin marker and Ultrasound gel, from top to bottom, respectively.
- the invention comprises a liquid skin marker, 80-85% ultrasound gel, 10% Barium Sulphate and 5-10% Polyvinyl Pyrrolidone by volume. Minor changes can be made between 85% ultrasound gel and 5% Polyvinyl Pyrrolidone responsible for viscosity increase, provided that 10% Barium Sulphate, which acts as a radiopaque substance, remains constant. For example, 10% Barium Sulphate + 84% ultrasound gel + 6% Polyvinyl Pyrrolidone.
- the liquid skin marker of the invention preferably comprises 85% ultrasound gel, 10% Barium Sulphate and 5% Polyvinyl Pyrrolidone (PVP) by volume.
- PVP K90 is preferably used in the invention as Polyvinyl Pyrrolidone (PVP).
- Barium Sulphate is included as a radiopaque substance and absorbs X-rays in proportion to its concentration.
- ultrasound gel helps to adjust Barium Sulphate concentration and ultrasound gel generally comprises substances such as deionized water, carbomer, Triethanol amine, Mono Propylene glycol, Methylchloroisothiazolinone and Methylisothiazolinone.
- PVP ensures that the viscosity is kept at a certain level.
- the increase of the PVP substance in the liquid increases the viscosity.
- the preparation method of liquid skin marker comprises the following steps:
- the liquid skin marker of the invention is in the form of a cream and no viscosity measurement was made. It can be easily used in skin marker applications for radiotherapy with a PVP ratio of 5% - 10%, but in the mixtures where PVP is greater than 10%, difficulties may be experienced in application due to the increase in viscosity.
- liquid skin marker is planned to be applied to the patient in the form of a sphere or cylinder (for marking in the form of dots and lines as it appears on the patient) by pouring it out of a small opening of a closed volume like an injector. Having a geometric diameter of 1-2 mm creates an ideal image.
- spherical shape it should be 1-2 mm in diameter.
- cylindrical shape it can be formed with 1-2 mm diameter and desired length.
- the visibility of the liquid skin marker on CT images and the HUmax value increase proportionally with increasing the size of the applied shape.
- the optimum liquid skin marker should be sufficiently visible (when processing CT images, the window / level settings of the computer screen are adjusted to (W/L:-500HU/1000HU) values) and have the lowest HUmax value as possible.
- Table 1 The number of CT images produced by liquid skin marker and several different materials
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Inorganic Chemistry (AREA)
- Apparatus For Radiation Diagnosis (AREA)
Abstract
The invention relates to a liquid skin marker comprising ultrasound gel, Barium Sulphate and Polyvinyl Pyrrolidone. The liquid skin marker comprises 85% ultrasound gel, 10% Barium Sulphate and 5% Polyvinyl Pyrrolidone by volume.
Description
LIQUID SKIN MARKER
Technical Field
The invention relates to a liquid skin marker developed for use in the field of medicine in general, and specifically in the field of radiation oncology, where radiation is used to examine the internal structure of the human body, and any application where marking of the outer surface of the body is required during this process.
State of the Art (Background)
Anatomical image data must be obtained in order to make three-dimensional (3D) treatment planning of patients for whom a radiotherapy (RT) treatment is decided. For this purpose, three-dimensional anatomical image data is obtained from the patients with the help of a Computed Tomography (CT) device. Markers (rifle shot, solder wire, commercial marker, etc.) are used on the skin before CT scanning so that some parts of the patients can be easily found on CT images. While skin markers help easily locate the desired area on CT images, they cause artifacts (anomalies usually caused by software and hardware defects). These artifacts are observed on CT images as high Hounsfield Unit (HU) changes at short distances.
Artifacts have some negative effects on the RT treatment planning process. One of them is that it can make it difficult to distinguish organ separations when introducing organs to the computer (contouring) on patient CT images. The other is that the artifacts formed on the CT images of the patients cause incorrect dose calculations while planning the 3D treatment. Therefore, in terms of the accuracy of the treatment given to the patient, it is necessary to reduce artifacts on CT images. Commercial products in the form of low-density solid spheres and wires are used during CT scanning in order to reduce artifacts on CT images. These commercial markers reduce artifacts and dose calculation errors in CT images relative to rifle shot and solder wire. However, dose calculation errors are still high. In addition, the use of these commercial products during CT scanning should be more practical. The commercial product used should provide convenience for both the patient and the personnel. If the area to be marked will be marked with a solid sphere, it takes a lot of time to attach many solid
spheres one by one and to remove them after scanning. Likewise, it takes time to cut the commercial product in the form of wire, attach and remove it.
Brief Summary and Objectives of the Invention
The present invention relates to a liquid skin marker comprising ultrasound gel, Barium Sulphate and Polyvinyl Pyrrolidone, which fulfills the above-mentioned requirements, eliminates all disadvantages and provides some additional advantages.
The primary objective of the invention is to develop a skin marker that is recognizable on CT images, which produces optimum HU and causes the least possible artifact, resulting in a much lower dose calculation error than other commercial products.
With the liquid skin marker of the invention, the area to be marked on the patient's skin can be easily drawn in the form of dots or in the form of a cylinder, with the help of an apparatus like an injector during CT scanning, and can be easily wiped with a paper towel after the scanning. This shortens the processing time.
The objective of the invention is to develop liquid markers with high viscosity in contrast to the physically solid structure of commercially used markers. With the liquid skin marker of the invention, it is provided that it is recognizable on CT images, the product produces optimum HU and causes the least possible artifact. It can be reduced from Maximum or 3000 HU to approximately 200 HU. In the study, the electron dose calculation error in the Radiotherapy Eclipse Treatment Planning System can be reduced from about -12% to about 3%. It allows a more reliable treatment planning in the treatments of patients.
Since the liquid skin marker of the invention is produced from materials used in medicine and applied from outside the body, the possibility of allergy and side effects is low.
Definitions of Drawings Illustrating the Invention
The figures and related explanations necessary for a better understanding of the liquid marker subject to the invention are as follows.
Figure 1: The effect of liquid skin marker and other materials on the number of CT images (Philips Brilliance CT) is shown. The carrier Styrofoam was carved in 2 mm dimensions and filled with different materials and computed tomography was performed. In the sagittal plane,
the CT image and materials are Rifle shot, Liquid Skin marker and Ultrasound gel, from top to bottom, respectively.
Detailed Description of the Invention
In this detailed description, the invention is explained in such a way that content of the liquid skin marker, method of preparation and method of application do not have any limiting effect.
The invention comprises a liquid skin marker, 80-85% ultrasound gel, 10% Barium Sulphate and 5-10% Polyvinyl Pyrrolidone by volume. Minor changes can be made between 85% ultrasound gel and 5% Polyvinyl Pyrrolidone responsible for viscosity increase, provided that 10% Barium Sulphate, which acts as a radiopaque substance, remains constant. For example, 10% Barium Sulphate + 84% ultrasound gel + 6% Polyvinyl Pyrrolidone.
The liquid skin marker of the invention preferably comprises 85% ultrasound gel, 10% Barium Sulphate and 5% Polyvinyl Pyrrolidone (PVP) by volume. PVP K90 is preferably used in the invention as Polyvinyl Pyrrolidone (PVP).
In the liquid skin marker, Barium Sulphate is included as a radiopaque substance and absorbs X-rays in proportion to its concentration.
In liquid skin marker, ultrasound gel helps to adjust Barium Sulphate concentration and ultrasound gel generally comprises substances such as deionized water, carbomer, Triethanol amine, Mono Propylene glycol, Methylchloroisothiazolinone and Methylisothiazolinone.
In the liquid skin marker, PVP ensures that the viscosity is kept at a certain level. The increase of the PVP substance in the liquid increases the viscosity.
In the preparation of liquid skin marker, firstly the concentration must be adjusted and then the viscosity must be adjusted. Mixing times are proportional to the total amount of mixture to be prepared.
The preparation method of liquid skin marker comprises the following steps:
• Mixing 85% Ultrasound gel and 10% Barium Sulphate by volume until a homogeneous mixture is obtained,
• Then adding 5% Polyvinyl Pyrrolidone by volume,
• Mixing at room temperature until a homogeneous mixture is obtained.
Ultrasound gel viscosities are generally = 10 Kcps and it is estimated that they will reach ~ 100 Kcps when 5% PVP is used to prepare the liquid skin marker. The liquid skin marker of the invention is in the form of a cream and no viscosity measurement was made. It can be easily used in skin marker applications for radiotherapy with a PVP ratio of 5% - 10%, but in the mixtures where PVP is greater than 10%, difficulties may be experienced in application due to the increase in viscosity. Because the application of the liquid skin marker is planned to be applied to the patient in the form of a sphere or cylinder (for marking in the form of dots and lines as it appears on the patient) by pouring it out of a small opening of a closed volume like an injector. Having a geometric diameter of 1-2 mm creates an ideal image.
For spherical shape, it should be 1-2 mm in diameter.
For cylindrical shape, it can be formed with 1-2 mm diameter and desired length.
The visibility of the liquid skin marker on CT images and the HUmax value increase proportionally with increasing the size of the applied shape. The optimum liquid skin marker should be sufficiently visible (when processing CT images, the window / level settings of the computer screen are adjusted to (W/L:-500HU/1000HU) values) and have the lowest HUmax value as possible. HUmax ranges from ~ 400 HU to =1000 HU. This value varies in relation to the section thickness of the liquid skin marker on CT images.
Table 1: The number of CT images produced by liquid skin marker and several different materials
The number of CT images produced by CT in the experiment with liquid skin marker and several different materials is shown in Table 1 and the comparison regarding its visibility is shown in Figure 1. While comparing the visibility in Figure 1, adequate separation of the image of the materials from the surface must be possible. In Figure 1, the visibility of the liquid skin marker is the most convenient among the materials.
Claims
1. A liquid skin marker, characterized in that it comprises ultrasound gel, Barium Sulphate and Polyvinyl Pyrrolidone.
2. Liquid skin marker according to claim 1, characterized in that it comprises 80-85% ultrasound gel, 10% Barium Sulphate and 5-10% Polyvinyl Pyrrolidone by volume.
3. Liquid skin marker according to claim 2, characterized in that it comprises 85% ultrasound gel, 10% Barium Sulphate and 5% Polyvinyl Pyrrolidone by volume.
4. A method for preparing a liquid skin marker according to claim 3, characterized in that it comprises the following steps:
• Mixing 85% Ultrasound gel and 10% Barium Sulphate by volume until a homogeneous mixture is obtained,
• Then adding 5% Polyvinyl Pyrrolidone by volume,
• Mixing at room temperature until a homogeneous mixture is obtained.
5
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2022/000142 TR2022000142A1 (en) | 2022-01-06 | LIQUID SKIN MARKER | |
| TR2022000142 | 2022-01-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023132810A1 true WO2023132810A1 (en) | 2023-07-13 |
Family
ID=87074093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2023/050007 WO2023132810A1 (en) | 2022-01-06 | 2023-01-05 | Liquid skin marker |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2023132810A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060088476A1 (en) * | 2004-10-25 | 2006-04-27 | Polyzenix Gmbh | Loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same |
| US20120059244A1 (en) * | 2009-05-08 | 2012-03-08 | University Of Ulster | Skin marker |
-
2023
- 2023-01-05 WO PCT/TR2023/050007 patent/WO2023132810A1/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060088476A1 (en) * | 2004-10-25 | 2006-04-27 | Polyzenix Gmbh | Loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same |
| US20120059244A1 (en) * | 2009-05-08 | 2012-03-08 | University Of Ulster | Skin marker |
Non-Patent Citations (1)
| Title |
|---|
| ÖZGÜVEN YILDIRAY, YÜCEL BIRSEN, ÖZYÜREK BETÜL, KARAKUŞ GÜLDEREN, ÖZGÜVEN YÜCEL: "Concentration modulated skin marker for radiotherapy treatment planning process", PHYSICA MEDICA, ACTA MEDICA EDIZIONI E CONGRESSI, ROME, IT, vol. 29, no. 2, 1 March 2013 (2013-03-01), IT , pages 196 - 203, XP093078914, ISSN: 1120-1797, DOI: 10.1016/j.ejmp.2012.03.004 * |
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