Determination of the mass attenuation coefficient for the contrast agent Iohexol using 662 kev photons from a Cesium-137 source.

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1 Determination of the mass attenuation coefficient for the contrast agent Iohexol using 662 kev photons from a Cesium-137 source. Elizabeth Cañipa *1, 2, Eric Farías 1, 2, Oscar Hernández 1, 3, Echevarria 1, 4 Claudio 1 Programa de Magister en Biofísica médica, Universidad de Chile. 2 Hospital Clínico Universidad de Chile. 3 Universidad del Norte, Barranquilla, Colombia. 4 Universidad Diego Portales, Chile. Abstract: Iohexol is an iodinated chemical compound (C 19 H 26 I 3 N 3 O 9 ) which is currently used as a contrast agent in x-ray radiography. Due to its composition including iodine has the property to enhance the attenuation of photons in the biological material in which has been injected. This work is part of a more extensive study to determine the optimal dilution of Omnipaque (Iohexol) in serum providing good images with minimal toxic effects and less radiation dose to individuals. Here, results of an experimental determination of its mass attenuation coefficient at dilutions of 50% and 100 % performed at energies of 662 kev provided by a Cs-137 source, and 59.5 kev from an Am-241, are presented. Measurements were performed using calibrated gamma sources and a standard gamma spectroscopy system available at the nuclear physics laboratory of the Faculty of Sciences, University of Chile. As quality control the attenuation coefficient for water was determined at both energies finding an agreement with accepted values within 2 %. The system was also checked at 662 kev with lead sheets obtaining similar agreement with values in tables and computer codes. For a dilution to 50% of Iohexol the attenuation coefficient is reduced to 61 % at the energy of 59.5 kev. Calculations made with the computer code XCOM for Omnipaque at 100% at both energies were close the experimental values within 2 %. KEYWORDS: attenuation; Iohexol; mass attenuation coefficient; Am-241 radiographic contrast; Cs-137, 1. Introduction Radiological contrast substances allow us to visualize internal structures of organisms that are not generally visible through the X ray (Rx). Usually in the radiological exploration some structures as bones or lungs have different opacity, but there are other organs (heart, kidney, brain) and conduits (blood vessel, alimentary canal, ureters) that are not possible to observe unless a contrast medium is used. Attenuation of X ray radiation by an element depends mainly on the atomic number Z, begins larger for high Z values, like it happens in lead and mercury, which are very toxic and therefore impedes its utility in medicine. However, iodine has high attenuation coefficient and is part of our endocrine system being tolerated by our organism in physiologic doses. The organic compounds used as contrast agent are acid with three or six atoms of iodine that confer the opacity character [1]. Among the combinations of iodine organic compound there is a hydrosoluble group used in urinary and vascular radiology. Chemically they are constituted by a bencenic ring in with an atom of iodine in positions 2, 4 and 6. In position 1 has a group COOH partially responsible of the solubility of the product. In positions 3 and 5 they have two radicals which are responsible for their toxicity and tolerance. Among these compounds we find Iohexol Fig.1, a molecule soluble in water and not ionic, with 46.36% of iodine in their composition [2]. *Elizabeth Cañipa Zuleta, ecanipa@gmail.com 1

2 Figure 1: Chemical structures of Iohexol. Molecule Toxicity of these compounds presents a great problem for medical use, and their effects are in direct relation between the injected (ml) quantity and the patient weight [3, 4]. Since Omnipaque (Iohexol) is of frequent use in medicine [5], our study is oriented to determine its radiation attenuation characteristic, in diluted form to minimize its urologic effect, thus contributing to a possible decrease in the doses of RX received by the patients without altering the image quality. This work was performed through spectroscopy of photons emitted by a radio-active source. In order to determine the mass attenuation coefficient (µ m ), we used a radioactive source of Cesium -137 (Amersham, kbq) that emits 662 kev photons and another source of Americium- 241(Amersham, x 10 5 kbq) which emit gamma photons of 59.5 kev (35.78%), which has similar energy to those used in radiodiagnostic. The measurements were carried out in the nuclear physics laboratory of the Faculty of Sciences, University of Chile. 2.Theoretical Considerations The attenuation of electromagnetic radiation (gammas and X rays) is produced mainly by the photoelectric and Compton effects. The intensity of the incoming radiation I 0 decrease according to the thickness x of the material following the exponential Law [6]: I (x) = I o e (-μ x) (1) Where, I (x) is the intensity of the radiation after passing through the absorber the thickness x, the intensity of the incoming radiation I 0 decreases according thickness x, I o is the incident intensity and μ correspond to the lineal attenuation coefficient. Equation (1) can be transformed to: ln (I (x) / I o ) = - µx (2) One can observe that, if the thickness is expressed in cm, µ is given in cm -1. If the lineal coefficient is divided by the density the mass attenuation coefficient is obtained: µ m = µ / ρ (3) Which is expressed in cm 2 /g, if the density is given in g/cm 3. In general, a high density material requires less thickness than low density material for equivalent attenuation. It is for this reason that heavy absorbent materials are occupied in radiological protection, for example lead. In table 1 the elements used in this study are indicated with their respective densities. 2

Table 1: Density of Lead, Water, serum, Omnipaque 50% and Omnipaque 100%. Density (g/cm 3 ) Lead Water Serum Omnipaque Omnipaque 50% 100% 11.39 1.00 1.009 1.184 1.359 3. Experimental Method 3.

3 Table 1: Density of Lead, Water, serum, Omnipaque 50% and Omnipaque 100%. Density (g/cm 3 ) Lead Water Serum Omnipaque Omnipaque 50% 100% Experimental Method 3.1 Equipment and Instruments: The spectroscopic system Fig. 2 is constituted by a scintillator detector (Canberra) NaI (Tl), 2 "x 2" connected to a photomultiplier tube (Ortec 266), pulse preamplifier (Ortec 113), power supply (Ortec 556), pulse amplifier (Canberra 2020), oscilloscope (Digital EZ Co OS-5020) and a multichannel MCA with software "Maestro" which to visualize the spectrum and to store the information provided by the detector. 3.2 General setup Figure 2: Diagram of the experimental setup: S (radioactive source), absorbers, PS (power supply), D (Detector), PM (photomultiplier), PA (Preamplifier), A (Amplifier), MCA (Multichannel analyzer). 3.3 Materials: Absorbers: Omnipaque 300 mg I / ml: it is a sterile solution of Iohexol diluted in water for injection that without preserving antimicrobial. The ph of the solution is between 6.8 at 7.7. with an osmolality of 709 mosm / kg of water. Description: Iohexol C 19 H 26 I 3 N 3 O 9 (647,1 mg / ml), 5 - [acetyl (2,3-dihydroxipropil) amino] -N.N' bis (2,3 dihydropropil) -2,4,6-triodine-1,3-benzendicarboxiamide, is a contrast radiographic material nonionic, water soluble, with 46.36%. In watery solution each molecule triodine molecule remains without being dissociated. It also contains: Trometamol C 4 H 11 NO 3 (1.2 mg / ml), Edetate of Sodium Calcium C 10 H 12 CaN 2 Na 2 O 8 (0.1 mg / ml) and H 2 O (710.6 mg / ml) dilutes. The substance in study was diluted in physiologic serum: NaCl to 0.9%. 3

3.3.2 Omnipaque containers: Twenty two cylinders of Polyvinyl chloride (PVC), 5 cm. of diameter, with two circular disc of cellulose triacetate, 0.020 cm.

4 3.3.2 Omnipaque containers: Twenty two cylinders of Polyvinyl chloride (PVC), 5 cm. of diameter, with two circular disc of cellulose triacetate, cm. thickness were made to contain the liquid materials Fig. 3. The width of the cylinders varied from to cm, including the sheets of cellulose triacetate (C 24 H 32 OR 16 ). Liquid was injected through a hole of 0.2 cm. diameter. The triacetate cellulose was chosen by its uniformity and a measured attenuation of less than 0.1% Figure 3: Photographic representation of one of the containers used for determine the attenuation coefficient of Omnipaque PVC Beam of photons (I 0 ) ( I ) Detector Sheets of Triacetate Radioactives sources: Cs Radioactive source Am Lead sheets thickness between 0.10 and 0.12 cm of Digital caliper (Helio 102) accuracy of 0.01 mm which was used to measure the containers Precipitate glass of 100 ml, graduate in millimeters Physiologic serum: NaCl 0.9%. 3.4 Measurements Calibration in energy of the spectroscopy system was made with a set of radioactives sources of energies and well-known intensities that were provided by the International Agency of Energy atomic (IAEA): Measurements with 662 kev photons from Cs-137 source The experimental set up is shown in figure 4, where source and detector were lined up in a vertical axis. Sheets of lead were positioned in between the source and detector varying the thickness from cm to cm, and the corresponding gamma intensity for each thickness, I(x), was measured for periods of 300 seconds, while I o was measured initially. In the case of liquids, a glass flask was used and I 0 was determined with no liquid in it. Controlled amounts of water were added up to 8.5 cm. The same procedure was used for Omnipaque (Iohexol). 4

Figure 4: Experimental assembly for measurements carried out with Cs-137. 3.4.3 Measurements with 59.5 kev photons from Am-241 source The experimental setup is the one described in figure 5.

The liquid thickness was given by the separation of the acetate windows which varied from 0.217 cm to 3.084 cm.

5 Figure 4: Experimental assembly for measurements carried out with Cs Measurements with 59.5 kev photons from Am-241 source The experimental setup is the one described in figure 5. Eighteen containers filled with the liquid were irradiated in time periods adjusted to have a statistical un certainties of 1 %, or less in the number of I(x) photons collected. The liquid thickness was given by the separation of the acetate windows which varied from cm to cm.. The measurements were performed in the following order: first was water, next was serum and finally Omnipaque in concentrations of 50 % and 100 %. This sequence was chosen because Omnipaque has high viscosity and may crystallize being difficult to remove from the container. I 0 was measured with an empty container. Water was used for quality control of the experimental method. Figure 5. A picture of the experimental setup for the Am-241 source is shown. 5

6 ln(io/i) 4. Results and analysis 4.1 Determination of the linear attenuation coefficient with 662 kev Results for Pb, water and Omnipaque are represented in figure 6.- and given in Table 2. The slopes of the curves in figure 6 indicate the different linear attenuation coefficients of the materials studied in this work. Clearly, at this energy the liquid materials, water and Omnipaque, have less capability to reduce the intensity of the photon beam as compared with Pb. Figure 6: linear attenuation coefficient of the Lead, water and Omnipaque.. ln(io/i) v/s thickness 0,9 0,8 0,7 0,6 0,5 0,4 0,3 H 2 O Omnipaque Pb 0,2 0, thickness 4.2 Determination of the linear attenuation coefficient with 59.5 kev Experimental results for the linear attenuation coefficients for the four liquids: water, serum, Omnipaque 50%, and Omnipaque 100 %, are represented in Fig.7. It is observed the similarity of attenuation capability of water and serum at this energy, as compared with Omnipaque, showing the advantage of this liquid to differentiate doped tissues in medical images. 6

7 LN(Io/I) Figure 7: Linear attenuation coefficient of water, serum, Omnipaque 50% and Omnipaque 100% 8 7 LN(Io/I) v/s Thickness H 2 O Serum Omnipaque 50% Omnipaque Thickness (cm) In addition to the experimental values, calculations obtained by the use of the computer code XCOM are given in Table (2), (3) for both energies. A significant agreement was obtained, within experimental uncertainties, between the values given by the experiment and the computer code. No calculations were done by XCOM [7] in the case when Omnipaque was diluted at 50 %. It is interest to mention that at 59.5 kev the linear attenuation for water is about 2.5 times the value at 662 kev, while in the case of Omnipaque the increment is about 24 times. This explain the advantage of setting the voltage in X ray tubes at values less than 100 kv when using radiopaque substances for radiographic examinations Table 2 : Mass attenuation coefficients (cm 2 /g) calculations obtained by the use of the computer code XCOM for 59.5 kev (Am-241) and 662 kev (Cs-137) compared with experimentals values. Experimental XCOM Energy (kev) µ mh2o (cm 2 /g) µ momnipaque 100% (cm 2 /g) µ momnipaque 50% (cm 2 /g) µ mpb (cm 2 /g) µ m serum (cm2/g)

8 Table 3: Results of the linear and mass attenuation coefficient with their overall errors for 59.5 kev and 662 kev. Sustances µ(cm -1 ) µ m (cm 2 / gm) Relative error.% 59.5keV Water ± Serum ± Omnipaque al 50% 1.40 ± Omnipaque al 100% 2.58 ± keV Water ± Omnipaque al 100% ± Lead ± Acknowledgements To Dr. José Roberto Morales, Dr. Pedro Miranda and nuclear physics laboratory of the Faculty of Sciences, University of Chile. REFERENCES [1] Grainger RG. Intravascular contrast media- the past, the present and the future. Br. J. Radiology 1992;55:1-18 [2] GE health care product Omnipaque 300 mg, medical information, April 2002 [3] Rudnick MR, Goldfarb S, Wexler L, Ludbrook PA, Murphy MJ, Halpern EF et al. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study. Kidney Int 1995; 47(1): Bettman MA, Heeren T, Greenfield A, Goudin C. Adverse Events with Radiographic Contrast Agents: Results of SCVIR Contrast Agent Registry. Radiology 1997;. [4] FLasser EC, Lyon SG, Berry, CC. Contrast Media Reactions: Analysis of Data from Reports to the US FDA. Radiology 1997; 203:605. Frequency of use of contrast agents. [5] Sorenson, J., Physics in Nuclear medicine, second Edition, W.B. Saunder Company, [6] Hubbell, J.H., Tables of X-ray mass attenuation coefficients and mass energy--- absorption coefficients. National Institute of Standards and Technology, Gaithersburg. 8

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