KR20130073823A - Contrast medium composition comprising high concentrated contrast agent having contrast enhancement effect - Google Patents

Abstract

PURPOSE: A contrast composition using higher concentration iodine is provided to enhance contrast effect and to obtain an image with excellent definition and identification. CONSTITUTION: A contrast composition contains 360-450 mgI/ml of an aqueous contrast agent selected from the group consisting of iopentol, iotrolan, iohexol, ioversol, ioxilan, iodixanol, and iobitridol. The aqueous contrast agent is iohexol. The concentration of the aqueous contrast is 380-420 mgI/ml. The contrast composition further contains an aqueous buffer solution, a sterilized injection solution, a chelating agent, and a pH adjusting agent. [Reference numerals] (AA) Iodine content mg I/ml

Description

CONTRAST MEDIUM COMPOSITION COMPRISING HIGH CONCENTRATED CONTRAST AGENT HAVING CONTRAST ENHANCEMENT EFFECT}

The present invention relates to a contrast agent composition for use in imaging, and more particularly to a contrast agent composition exhibiting a high contrast enhancement effect, including a high concentration of contrast agent.

Computed tomography (CT) is a method in which a target area of the human body is irradiated from various directions to collect the transmitted X-rays with a detector, and the computer reconstructs the difference in absorption of the X-rays to the site using mathematical techniques. Talk about shooting techniques. The basic principle of CT is that the X-ray tube is irradiated with X-ray beam as it travels around a section of the human body, and the detector collects each intensity and the computer calculates the absorption intensity of each part based on the data. Therefore, the image is reconstructed and displayed on the monitor.

CT has excellent resolution and contrast in distinguishing blood, cerebrospinal fluid, white matter, gray matter, and tumors compared to conventional X-ray images, and can represent minute differences in absorption. .

The main feature of CT is the use of X-rays, and structures with similar densities are difficult to distinguish by X-ray examination alone. Short-wavelength X-rays are effective for imaging bone-dense structures, but sharpness decreases for imaging soft tissues, so X-rays alone are limited in distinguishing between tissue and surrounding areas. Thus, contrast agents are needed to artificially provide contrast between the organ being examined and the surrounding tissue. That is, unlike gastrointestinal radiographic diagnosis, urography and angiography X-rays require intravenous administration of a safe, water-soluble, radiopaque contrast agent.

Currently, iodine-based contrast agents are the most widely used, and in particular, the development of non-ionic triiodobenzoic acid derivatives such as iopamidol, iohexelol and ioversol in the field of X-ray contrast agents based on triiodobenzene Significantly developed.

Iomeprol {C ₁₇ H ₂₂ I ₃ N ₃ O ₈ ; N, N'-bis (2,3-dihydroxypropyl) -5-[(hydroxyacetyl) methylamino] -2,4,6-triiodo-1,3-benzenedicarboxamide; CAS [ RN] [78649-41-9]},

Iopromide {C ₁₈ H ₂₄ I ₃ N ₃ O ₈ ; N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodo-5-[(methoxyacetyl) amino] -N-methyl-1,3-benzenedicarboxamide ; CAS [RN] [73334-07-3]},

Iobersol {C ₁₈ H ₂₄ I ₃ N ₃ O ₉ ; N, N'-bis (2,3-dihydroxypropyl) -5-[(hydroxyacetyl) (2-hydroxyethyl) amino] -2,4,6-triiodo-1,3-benzene Dicarboxamide; CAS [RN] [87771-40-2]},

Iohexol {C ₁₉ H ₂₆ I ₃ N ₃ O ₉ ; 5- [acetyl (2,3-dihydroxypropyl) amino] -N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodo-1,3-benzenedica Boxamide; CAS [RN] [66108-95-0]},

Iopenpentol (C ₂₀ H ₂₈ I ₃ N ₃ O ₉ ; 5- [acetyl (2-hydroxy-3-methoxypropyl) amino] -N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodo-1,3- Benzenedicarboxamide, CAS [RN] [89797-00-2]},

Iopamidol {C ₁₇ H ₂₂ I ₃ N ₃ O ₈ ; 5-[(2-hydroxy-1-oxopropyl) amino] -N, N'-bis (2-hydroxy-1- (hydroxymethyl) ethyl) -2,4,6-triiodo-1 , 3-benzenedicarboxamide, CAS [RN] [60166-93-0]},

Iovitridol {C ₂₀ H ₂₈ I ₃ N ₃ O ₉ ; N, N'-bis (2,3-dihydroxypropyl) -5-[[3-hydroxy-2- (hydroxymethyl) -1-oxopropyl] amino] -2,4,6-triio Fig-N, N'-dimethyl-1,3-benzenedicarboxamide; CAS [RN] [136949-58-1]}

The reason for using iodine as a contrast agent is because the density of iodine is large and the absorption degree to X-rays is large, so that the contrast enhancement effect is excellent. That is, when X-rays come in contact with iodine contained in the contrast agent, X-rays are absorbed by iodine and appear white on CT, so the organ to be diagnosed looks bright.

The rate of infusion of the contrast agent and the iodine concentration of the contrast agent are selected from various types according to the test purpose. In particular, Iohexol is clinically licensed for use in concentrations of 140 mgI / mL, 180 mgI / mL, 240 mgI / mL, 300 mgI / mL, and up to 350 mgI / mL for conventional CT contrast enhancement. .

However, it is difficult to meet the demand for more precise and accurate diagnosis of imaging with conventionally approved composition of contrast agent for explosive demand and expectation (early diagnosis and precise diagnosis) of medical market for medical technology development and diagnosis. In order to achieve high quality imaging, new contrast composition comprising a high concentration of contrast agent exhibiting contrast enhancement effect is needed.

The present invention aims to provide a new contrast agent composition having a high concentration of contrast agent and / or low Hounsfield value in order to solve the above problems of the prior art.

The present invention is to solve the above problems Iopentol, Iotrolan, Iohexol, Iohexol, Ioversol, Ioxilan, Iodixanol and Iodixanol Provided is a contrast agent composition comprising an aqueous contrast agent selected from the group consisting of vitridol (Iobitridol) at a concentration of 360 mgI / mL to 450 mgI / mL.

In the present invention, the contrast agent composition containing the aqueous contrast agent at a concentration of 360 mgI / mL to 450 mgI / mL means that 360 mg to 450 mg of iodine atoms are contained per 1 ml of the contrast agent composition.

In the present invention, the aqueous contrast agent is characterized in that iohexol. Iohexol is known to contain 6 -OH groups in the molecule to show high hydrophilicity, which is generally lower in chemical and neurotoxicity than other nonionic contrast agents. Iopromide is highly neurotoxic and cannot be used for spinal cord imaging, while Iobersol has no indication of celiac and spinal cord contrast, while Iohexol has a wide range of adaptation. It is sold a lot.

In the present invention, the concentration of the iohexol in the contrast agent composition is 360 mgI / mL to 450 mgI / mL, preferably 380 mgI / mL, 400 mgI / mL, which is higher than the conventionally used concentration of 350 mgI / mL. Or 420 mgI / mL. In the present invention, when the concentration of the iohexol of the contrast composition is 3360 mgI / mL to 450 mgI / mL, the contrast enhancement effect can be obtained in both portal vein and arterial phase when the contrast composition is used for liver CT imaging. have.

In the present invention, the contrast agent composition is characterized in that it further comprises an aqueous buffer, sterile water for injection, chelating agent, and pH adjusting agent.

In the present invention, the aqueous buffer is characterized in that tromethamine. In the present invention, the aqueous buffer comprises 2-amino-2- (hydroxymethyl) -1,3-propanediol known as tromethamine. Tromethamine is toxicologically acceptable and described in U.S. Pharmacopoeia XXI, U. S. Pharmacopeial Convention, Rockville, MD1985 (U.S.P XXI). Tromethamine (chemical name 2-amino-2-hydroxymethyl-1,3-propanediol) also contains trimethyl as described in Merck Index (11th edition, Merck Co. Inc. Laway, New Jersey (1989)). Aminomethane; Tris (hydroxymethyl) aminomethane; Trisamine; Tris buffer; Tromethamol; Tromethane; THAM; TRIS; Talatrol; Tris amino; Tris-steryl; It is known by the names Trisma. The tromethamine and its salts are known to act as buffers in the pH 6-9 range.

In the present invention, the chelating agent is characterized in that at least one selected from ethylenediamine, calcium disodium edate and disodium edate.

The chelating agent of the present invention can be used without limitation as long as it is a pharmaceutically acceptable chelating agent, but ethylene diamine, calcium disodium edetate or disodium edetate is preferred. Of these, disodium edetate is more preferable. The concentration of the chelating agent is preferably 0.01 to 1 mg / mL, in particular 0.05 to 0.5 mg / mL. When the amount of the chelating agent is less than the above range, the stabilizing action of the contrast agent containing the iohexole or the like is not sufficient. If the amount of the chelating agent exceeds the above range, the stabilizing action by the chelating agent reaches its upper limit and further such amount is not desirable with regard to safety.

The pH adjusting agent of the contrast agent composition of the present invention is a pharmaceutically acceptable agent for injectables such as hydrochloric acid or salts thereof, citric acid or salts thereof, phosphoric acid or salts thereof, acetic acid or salts thereof, etc. Buffers may be used and the pH of the composition is preferably adjusted to 7.0 to 8.0 with such a pH adjuster.

Other necessary pharmaceutically acceptable isotonic agents, preservatives and the like may be added to prepare the injectables of the present invention.

In the present invention, CEA and CEP of the contrast agent composition containing the aqueous contrast agent at a concentration of 360 mgI / mL to 450 mgI / mL are CEA ₃₅₀ and the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml. It satisfies the following relationship with CEP ₃₅₀ .

CEA> CEA _{350 ,} CEP> CEP ₃₅₀

The CEA is a contrast enhancement value in arterial phase, which measures a Hounsfield Unit (HU) of the abdominal aorta at the level at which the celiac artery is visible in the artery during liver CT imaging. The CEP is a contrast enhancement value in portal phase, and represents a result of measuring a hounsfield unit (HU) of a portal vein at a level at which a portal portal vein is seen.

That is, in the case of the present invention, by using the iohexol at a higher concentration than 350 mgI / ml, which is conventionally used clinically, CEA and CEP are improved in the arterial and portal vein in liver CT imaging.

In the present invention, CEA ₃₈₀ and CEP ₃₈₀ of the contrast medium composition containing the aqueous contrast agent at a concentration of 380 mgI / mL CEA ₃₅₀ and CEP ₃₅₀ of the contrast medium composition containing the aqueous contrast agent at a concentration of 350 mgI / ml and Characterized by satisfying the relationship.

1.7 ≥ CEA ₃₈₀ / CEA ₃₅₀ ≥ 1.1 

1.7 ≥ CEP ₃₈₀ / CEP ₃₅₀ ≥ 1.1

In the present invention, CEA ₄₀₀ , and CEP ₄₀₀ of the contrast medium composition containing the aqueous contrast medium at a concentration of 400 mgI / mL and CEA ₃₈₀ and CEP ₃₈₀ of the contrast medium composition containing the aqueous contrast medium at a concentration of 350 mgI / ml and The following relationship is satisfied.

1.7 ≥ CEA ₄₀₀ / CEA ₄₀₀ ≥ 1.1 

1.7 ≥ CEP ₄₀₀ / CEP ₃₅₀ ≥ 1.1

In the present invention, CEA ₄₂₀ , and CEP ₄₂₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 420 mgI / mL and CEA ₃₈₀ and CEP ₃₈₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml and The following relationship is satisfied.

1.7 ≥ CEA ₄₂₀ / CEA ₃₅₀ ≥ 1.1 

1.7 ≥ CEP ₄₂₀ / CEP ₃₅₀ ≥ 1.05

In the present invention, the contrast composition is generally used for liver CT imaging.

The contrast agent composition according to the present invention uses an amount of iodine to contrast action at a higher concentration than conventionally used concentrations, it is possible to obtain an image with excellent contrast enhancement effect and excellent contrast contrast in the CT image. In particular, in liver CT imaging, both the arterial and portal vein show contrast enhancement effects.

Figure 1 shows the results of the liver CT image after the rabbit 380 mgI / ml iohexole injection formulation prepared according to an embodiment of the present invention to the rabbit.
Figure 2 shows the results of taking a liver CT image after administering to the rabbit 400 mgI / ml iohexol injection formulation prepared according to an embodiment of the present invention.
Figure 3 shows the results of taking a liver CT image after administering a 420 mgI / ml iohexole injectable formulation prepared in accordance with an embodiment to the rabbit.
Figure 4 shows the results of the liver CT image after the administration of a 350 mgI / ml iohexole injectable formulation prepared by a comparative example of the present invention to the rabbit.
5 illustrates changes in CEA and CEP values, which are contrast enhancement effects in liver CT images, according to the amount of iodine used in embodiments of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the scope of the present invention is not limited by the following examples.

< Example  1> 380 mgI Of ml  Concentration Iohexol  Injectable formulation

To bring the concentration of Iohexol in the contrast composition to 380 mgI / ml At room temperature (RT) 819.71 g of Iohexol, 1.31 g Tromethamine, 0.11 g Edetate Calcium Disodium were mixed until completely dissolved in 75 ml water for injection (WFI). The pH was adjusted to 7.79 with 1N hydrochloric acid solution and the final dose of the formulation was 1 L using WFI. Then, sterile filtration through a micro filter. The solution so obtained was filled in 100 mL vials. The vial was then sealed with a rubber stopper and an aluminum cap to obtain an injection.

< Example  2> 400 mgI Of ml  Concentration Iohexol  Injectable formulation

To make the concentration of Iohexol 400 mgI / ml Injections were obtained by a method similar to Example 1 except that 862.80 g and 1.38 g of tromethamine were used in the amount of iohexol.

< Example  3> 420 mgI Of ml  Concentration Iohexol  Injectable formulation

To make the concentration of Iohexol 420 mgI / ml Injections were obtained by a method similar to Example 1, except that 905.88 g and 1.45 g of tromethamine were used in the amount of iohexol.

< Example  4> 450 mgI Of ml  Concentration Iohexol  Injectable formulation

To make the concentration of Iohexol 450 mgI / ml An injection was obtained by a method similar to Example 1 except that 970.5 g and 1.55 g of tromethamine were used in the amount of iohexol.

Comparative Example 1 350 mgI Of ml  Concentration Iohexol  Injectable Formulations:

Injectables were obtained by a similar method as in Example 1, except that 755.0 g and 1.21 g of tromethamine were used to prepare 350 mgI / ml of the previously approved dose of iohexol. .

< Test Example  1> viscosity, osmotic pressure and pH  Measure

For the injection composition of Examples 1 to 3 and Comparative Example 1 pH was measured before and after adjusting the viscosity, osmotic pressure and pH, the results are shown in Table 1 below.

division Iodine concentration Viscosity Osmotic pressure pH Example 1 380 mgI / ml 19 905 7.79 Example 2 360 mgI / ml 10 810 7.75 Example 3 400 mgI / ml 37.5 1034 7.80 Example 4 420 mgI / ml 45.0 1096 7.79 Example 5 450 mgI / ml 71 1204 7.85 Comparative Example 1 350 mgI / ml 19 748 7.55

It can be seen that the viscosity and the osmotic pressure increase gradually as the concentration of iodine increases. In the case of pH, it adjusted to the range of 7.5-8.0.

< Test Example  2> Example  1,380 mgI Of ml Iohexol  In liver tissue with an injectable formulation CT  Image measurement and HU ( Hounsfield Unit ) Measure

The 380 mgI / ml iohexol injectable formulation prepared in Example 1 was administered to seven rabbits, liver CT images were taken, and the results are shown in FIG. 1.

CT imaging method: After performing anesthesia of a target animal, using Definition (64 MDCT, Siemens, Germany), a 22 G IV catheter was installed in the auricular vein of a rabbit and connected to a power injector using a connector. The contrast agent prepared in 1 (6.4-6.5 mL) was injected at a rate of 1.4 ml / sec, and CT images were acquired at timed intervals. CT scan parameters were set as follows. (100 mAs; 80 kVp table speed).

In the image of FIG. 1, the left side is an image in the arterial phase, and the result of measuring Hounsfield Unit (HU) of the abdominal aorta at the level at which the celiac artery is visible The Hounsfield Unit (HU) at this time was referred to as a Hounsfield Unit (HU), ie, CEA ₃₈₀ (contrast enhancement value in arterial phase).

In the image of FIG. 1, the right side is an image in a portal phase, and represents a result of measuring a hounsfield unit (HU) of a portal vein at a level where a portal portal (main portal vein) is seen. The contrast enhancement value was set as Hounsfield Unit (HU), that is, CEP ₃₈₀ (contrast enhancement value in portal phase), and the results are shown in Table 2 as in the CEA ₃₈₀ .

ID CEA ₃₈₀ CEP ₃₈₀ 708 2157 531 709 1835 402 701 1358 538 702 1975 720 703 2323 633 704 2542 802 503 2115 691 average 2043.6 616.7 standard deviation 379.2 135.7

Test Example 3 Image Measurement and Hounds (Houndsfield Unit) Measurement in Liver Tissues Using the 400 mgI / ml Iohexol Injection Formulation of Example 5

Using the 400 mgI / ml Iohexol injectable formulation prepared in Example 5, the image was taken in the same manner as in Test Example 2 for three rabbits and the results are shown in FIG. The results of measuring CEA ₄₀₀ and CEP ₄₀₀ for the image of FIG. 2 are shown in Table 3 below.

ID CEA ₄₀₀ CEP ₄₀₀ 1005 2526 667 1006 2412 641 1007 1850 504 Average 2262.7 604.0 standard deviation 361.9 87.6

<Test Example 4> Image measurement and HV measurement in liver tissue using the stock formulation of 420 mg I / ml iohexol of Example 4

Using the 420 mgI / ml Iohexol injection formulation prepared in Example 4, the image was taken in the same manner as in Test Example 2 and the results are shown in FIG. The results of measuring CEA ₄₂₀ and CEP ₄₂₀ of the image of FIG. 3 are shown in Table 4 below.

ID CEA ₄₂₀ CEP ₄₂₀ 1009 2574 552

Experimental Example 5 Image Measurement and HV Measurement in Liver Tissue Using 350 mgI / ml Iohexol Injectable Formulation of Comparative Example

Using the 350 mgI / ml Iohexol injection formulation prepared in Comparative Example, the image was taken in the same manner as in Test Example 2 and the results are shown in FIG. The results of measuring CEA ₃₅₀ and CEP ₃₅₀ for the image of FIG. 4 are shown in Table 5 below.

ID CEA ₃₅₀ CEP ₃₅₀ 608 1971 493 610 1557 461 702 1872 553 703 1701 497 704 1521 623 705 1278 421 707 1959 473 Average 1694.1 503 Standard deviation 258.3 66.4

CEA and CEP of Examples and Comparative Examples measured in Test Examples 2 to 5 are shown in FIG. 5 according to respective iodine concentrations.

In the concentration of iodine in the range of 360 to 450 mgI / ml in Figure 5 the CEA value increases to show the contrast enhancement effect in the arterial phase (Arterial phase), the CEP value increases and decreases in the portal phase (Portal phase) contrast enhancement effect It can be seen that increases and decreases.

In addition, it can be seen that when the concentration of iodine is 460 mgI / ml or more, the CEA value decreases, and the CEP value decreases from the iodine concentration 350 mgI / mL of the comparative example.

Therefore, in the contrast agent composition according to the present invention, the concentration of iodine can be in the range of 350 to 450 mgI / ml in which the contrast enhancement effect in the arterial phase during CT imaging of the liver, the contrast enhancement effect in both the arterial and portal vein 380 It can be seen that to 420 mgI / ml is more preferred.

In addition, CT scans of the liver at 380, 400, and 420 mgI / ml iodine concentrations are performed using the Hounsfield Unit (HU) and iodine concentrations of 350 mgI / ml at the arterial and portal phases. When comparing the Hounsfield values (Hounsfield Unit, HU) in the arterial and portal vein is shown in Table 7 below.

CEA _/ CEA ₃₅₀ CEP _/ CEP ₃₅₀ 380 mgI / ml CEA _{380 /} CEA ₃₅₀ = 1.206 CEP _{380 /} CEP ₃₅₀ = 1.226 400 mgI / ml CEA _{400 /} CEA ₄₀₀ = 1.335 CEP _{400 /} CEP ₄₀₀ = 1.201 420 mgI / ml CEA _{420 /} CEA ₄₀₀ = 1.519 CEP _{420 /} CEP ₄₂₀ = 1.097

As shown in Table 7, as the concentration of iodine increases, the ratio of Hounsfield Unit (HU) in the artery is increased and the Hounsfield value in the venous is higher than that of 350 mgI / ml. The ratio of Hounsfield Unit (HU) decreases, and Hounsfield Unit (HU) at an iodine concentration of 350 mgI / ml, which is conventionally used in both arteries and portal vein, when the iodine concentration is 380-420 mgI / ml. Increased.

Claims (15)

Select from the group consisting of Iopentol, Iotrolan, Iohexol, Iohexol, Ioversol, Ioxilan, Iodixanol and Iobitridol Contrast agent composition comprising an aqueous contrast agent at a concentration of 360 mgI / mL to 450 mgI / mL.
The method of claim 1,
The contrast agent composition, characterized in that the aqueous contrast agent is iohexol
The method of claim 2,
Contrast agent composition comprising the aqueous contrast agent at a concentration of 380 mgI / mL to 420 mgI / mL.
The method of claim 2,
Contrast agent composition comprising the aqueous contrast agent at a concentration of 380 mgI / mL.
The method of claim 2,
Contrast agent composition comprising the aqueous contrast medium at a concentration of 400 mgI / mL
The method of claim 2,
Contrast agent composition comprising the aqueous contrast agent at a concentration of 420 mgI / mL.
The method of claim 1,
The contrast medium composition further comprises an aqueous buffer, sterile water for injection, chelating agent, and pH adjusting agent.
The method of claim 7, wherein
Said aqueous buffer is tromethamine.
The method of claim 7, wherein
The chelating agent is a contrast agent composition, characterized in that at least one selected from ethylene diamine, calcium disodium edate and disodium edate.
The method of claim 1,
Contrast composition having a pH of 7-8.
The method of claim 3,
CEA and CEP of the contrast agent composition containing the aqueous contrast agent at a concentration of 360 mgI / mL to 450 mgI / mL are related to CEA ₃₅₀ and CEP ₃₅₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml. Contrast composition, characterized in that to satisfy.
CEA> CEA _{350 ,} CEP> CEP ₃₅₀
5. The method of claim 4,
CEA ₃₈₀ and CEP ₃₈₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 380 mgI / mL satisfy the following relationship with CEA ₃₅₀ and CEP ₃₅₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml. Contrast agent composition.
1.7 ≥ CEA ₃₈₀ / CEA ₃₅₀ ≥ 1.1 
1.7 ≥ CEP ₃₈₀ / CEP ₃₅₀ ≥ 1.1
The method of claim 5,
When the aqueous contrast agent is contained at a concentration of 400 mgI / mL, CEA ₄₀₀ and CEP ₄₀₀ of the contrast agent composition satisfy the following relationship with CEA ₃₈₀ and CEP ₃₈₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml. Contrast agent composition, characterized in that.
1.7 ≥ CEA ₄₀₀ / CEA ₃₅₀ ≥ 1.1 
1.7 ≥ CEP ₄₀₀ / CEP ₃₅₀ ≥ 1.1
The method according to claim 6,
CEA ₄₂₀ and CEP ₄₂₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 420 mgI / mL satisfy the following relationship with CEA ₃₈₀ and CEP ₃₈₀ of the contrast agent composition containing the aqueous contrast agent at a concentration of 350 mgI / ml. Contrast agent composition.
1.7 ≥ CEA ₄₂₀ / CEA ₃₅₀ ≥ 1.1 
1.7 ≥ CEP ₄₂₀ / CEP ₃₅₀ ≥ 1.05
The method of claim 1,
The contrast agent composition is characterized in that the contrast medium is used for CT imaging

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