Skyscan 1076 in vivo scanning: X-ray dosimetry

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1 Skyscan 1076 in vivo scanning: X-ray dosimetry

2 DOSIMETRY OF HIGH RESOLUTION IN VIVO RODENT MICRO-CT IMAGING WITH THE SKYSCAN 1076 An important distinction is drawn between local tissue absorbed dose in milligrays, and the weighted whole body effective dose equivalent in millisieverts. Details of the conversion from local dose to effective dose equivalent are given in Appendix 1. Effective dose equivalent is calculated using ICRP (International Commission of Radiological Protection) tissue specific weighting factors (International Commission of Radiological Protection Publication 60, 1990) based on the difference in radiation sensitivity of different body tissues. Note that in the absence of a fully worked out dosimetry system for the rodent, it is necessary to employ tissue dose weighting factors from the human. It should be noted that in the Skyscan 1076 scanner the x-ray beam is directed and the non-selected regions of the animal shielded, so that radiation dose to the non-selected part of the animal is minimal, for example when the knee region is scanned the knee only is irradiated. If the whole rodent is scanned (a procedure requiring several sequential autospliced scans) dosimetry is simplified, and the effective dose equivalent is then the same as the absorbed dose in Grays (since the radiation quality factor for x-rays is 1). For all scans imaging less than the whole body, effective dose equivalent will be less than the absorbed dose. In a single rotation scan in the 1076, a region 1.7 cm long only is scanned (width 3.5 or 6.8 cm), and scanning longer regions with multiple sequential scans does not increase the local absorbed dose at any location. An important feature of irradiation by x-rays typical of micro-ct ( kv) is that the smaller the diameter of animal tissue scanned, the larger the dose; this is because at these relatively low energies (and considering the spread of energies from microfocus x-ray sources) there is considerable absorption of the lower energy x-rays at the skin, resulting in a relatively high skin dose. However the skin and fur, comprising a layer about 2mm thick, are not radiation sensitive. Where the scanned tissue diameter is greater, average dose across the whole diameter is reduced. It should be borne in mind that in the in vivo micro-ct imaging of rodents, when considering multiple sequential scans of the same animal, repeated general anaesthesia, a cause of stress and weight curtailment, is probably a welfare issue of at least as great significance as radiation doses of the magnitude reported here. Page 2 of 10

3 METHOD Dosimetry measurements were carried out by the Department of Medical Physics and Radiation Protection, Faculty of Medicine, University of Ghent, Belgium. An ionisation chamber was employed. A full range of measurements with different filters and settings was carried out on 29 April, 2003, on the Skyscan 1076 scanner at the Skyscan head office, Aartselaar, Belgium. The following are the specifications of the dosimetry performed by Ghent University, 2003: The CT chamber used was the PTW W30009 s/n The electrometer was the NE Farmer 2670 s/n 151. The dose in air at the rotation axis D air is defined as : D air = 1/h N a M where h = slice thickness in cm, N a = calibration factor for the conversion to dose length product (DLP): 8.862E+7 Gy.cm/C M = display reading in C. The percentage depth dose at depth for the used beam qualities are taken from: The Physics of Radiology, 3rd. Ed., HE Johns and JR Cunningham, CC Thomas Publisher, Illinois, Page 3 of 10

4 RESULTS Table 1. Mouse dosimetry (50 kv, 200 µa x-ray, 1mm Al filter) Anatomical site scanned Width of animal tissue scanned Combined tissue weighting factor (converts Gy to Sv) Local absorbed dose rate, Gy/min Local absorbed dose from 10 minute scan, Gy Whole body effective dose equivalent rate, Sv/min Hindlimb knee 10 mm Thorax 30 mm Abdomen 30 mm Head 17 mm Table 2. Rat dosimetry (80 kv, 124 µa x-ray, 1mm Al filter) Anatomical site scanned Width of animal tissue scanned Combined tissue weighting factor (converts Gy to Sv) Local absorbed dose rate, Gy/min Local absorbed dose from 10 minute scan, Gy Whole body effective dose equivalent rate, Sv/min Hindlimb knee 15 mm Thorax 60 mm Abdomen 60 mm Head 25 mm Page 4 of 10

5 APPENDIX 1: EFFECTIVE DOSE EQUIVALENT In the absence of detailed dosimetry factors for rodents, we can obtain estimates of effective dose equivalents to rodents by using human tissue weighting factors published by the International Commission on Radiological Protection (ICRP). We have to take into account the varying biological effects of radiation on a particular tissue (or body part) type, T. The same radiation exposure to different parts of the body can have very different results. That is, if the entire body were irradiated with a uniform beam of a single type of radiation, some parts of the body would react more sensitively than others. To take this effect into account, the ICRP has published list of tissue weighting factors, denoted W T, for a number of organs and tissues that most significantly contribute to overall biological damage to the body (ICRP Publication 60, 1990). Table 3 below gives the values of the tissue weighting factor W T from ICRP 60. The ICRP went on to define the integrated effective human-equivalent dose, or effective dose equivalent denoted H E, for the determination of the whole-body biological damage due to various forms of radiation exposure in different parts of the body. This effective dose equivalent is given as follows: H E W H T T T (1) where W T is the ICRP s tissue weighting factor for the type of tissue or body part T, and H T is the dose equivalent for tissue T defined in Equation (1). The units of H E are sieverts, Sv, the same as those of H T. Essentially the effective dose equivalent indicates the radiation probabilistic harm caused by irradiation of a restricted part of the body, expressed as the dose of low LET radiation given uniformly to the whole body that would cause the same degree of radiation probabilistic harm. Tissue weighted effective dose equivalents are shown in table 3 for four typical rodent micro-ct scan scenarios, head, upper body, lower body and knee. Tissue fractions have been calculated by reference to ICRP publication 70 (1995), Radiation protection basic anatomical and physiological data. As an example for interpreting these data, a dose in mgy received by the knee should be multiplied by the weighting factor of to calculate an effective dose equivalent in msv that is, the dose (low LET) delivered uniformly to the whole body of the rodent, that would cause the same radiation harm as the dose delivered to the rodent knee only. Page 5 of 10

6 Table 3. Tissue weighted dosimetry of the rodent for SKYSCAN 1076 in vivo micro-ct Tissue ICRP Tissue weighting factor H T Fraction of tissue, head scan H T head Fraction of tissue, upper body scan H T upper body Fraction of tissue, lower body scan H T lower body Fraction of tissue, knee H T knee Gonads Bone Marrow Colon Lung Stomach Bladder Breast Liver Esophagus Thyroid Skin Bone Surface Remainder Total: Adrenals, brain, upper large intestine, small intestine, kidney, muscle, pancreas, spleen, thymus, and uterus.

7 APPENDIX 2: CALCULATION OF DOSE TO MICE IN THE SKYSCAN 1076 SCANNER, BASED ON X-RAY EXPOSURE FROM THE SOURCE 15 June 2005 Dose calculations to mice in the Skyscan 1076 in vivo scanner are intended to supplement the measurement of doses by ionisation chamber. Both the calculations from source exposure and measurements by ionisation chamber inside the scanner, require correction for depth in tissue. 1. The measured exposure rate at a distance of one foot (300 mm) from the microfocus x-ray source is 11 Roentgens (R) per minute. This relates to a source applied voltage of 100 kv, current 100 µa i.e. 10 W of power. To reduce dose to mice during in vivo scanning, source applied voltage is reduced to 50 kv (200 µa). This reduces exposure to about 60% of the value for 100 kv. Furthermore, a 1 mm aluminium filter is applied to the x-ray beam. The filter reduces x-ray exposure by five times (i.e. to 20% of the unfiltered value) due to removal of the dominant 10keV x-ray peak from the tungsten target. As a result, scanning at 50 kv (200 µa) and with 1 mm Al filter, reduces the exposure at 30 cm to the value: = 1.32 R/min Source sample distance correction: In the 1076 scanner the distance from source to sample midline is not 300 mm but 121 mm. Due to the inverse square law the x-ray exposure therefore increases by: Exposure = 6.15 times (1) = 8.12 R A more modern unit for exposure is the X unit, of coulombs per kilogram one X unit is 1 C / kg of ionisation charge generated in air, and equals 3881 R Therefore 8.12 R corresponds to 2.09 E-3 X units (C / kg) of exposure

8 2. Exposure-dose relationship The dose to biological tissue per mass (g) is slightly different from the dose from air due to a different atomic composition and mean atomic number. If one assumes tissue to have the following composition: Hydrogen 5.98 E22 atoms / g Oxygen 2.75 E22 atoms / g Nitrogen E22 atoms / g Carbon 6.02 E22 atoms / g then the electronic density for tissue is 3.28 E23 electrons / g (Cember 1988). For air the electron density is 3.01 E23 electrons / g. Thus, the ratio of x-ray energy absorption of biological tissue to air is given: (2) X unit (C / kg) of exposure in air corresponds to an absorbed dose in air of 34 Gy (joules / kg) This is derived as follows: 1 X unit = 1C kg ion in air C ev ion J ev Gy 1 J / kg = 34 Gy (3) (Cember 1988) Note that exposure is an integrated unit of charge deposited in air, and thus is independent of the time over which exposure occurs. The strength of a radiation field is usually expressed as the exposure rate, in C/kg/seconds or minutes. As a result, the ratio of exposure in air (C/kg) to dose in biological tissue (Gy) refer to equation 2 is given: = 37 Consequently, an exposure rate at the midline of the Skyscan 1076 scanner of 8.12 R/min, equals 2.09 E-3 C/kg/min, and this corresponds to a dose rate of 2.09 E-3 37 = Gy / minute This dose rat needs to be corrected for depth in tissue According to data published in Johns and Cunningham (1983) depth corrections for an x-ray beam similar to that in the Skyscan 1076 microct scanner, are: Mouse leg depth 5 mm depth factor Mouse body depth 15 mm depth factor Multiplying the dose rat by the depth factors we obtain: Dose rate to the mouse hindlimb Dose rate to the mouse body = Gy / min = Gy / min Page 8 of 10

9 These fairly simple calculations are reasonably close to the dose rates calculated to the mouse hindlimb and body from ionisation chamber measurements. The dose rate values obtained from ionisation chamber measurements (see the accompanying dosimetry report) are compared to the calculated values in table 4, below. Table 4. Dose rates to the mouse hindlimb and body in the Skyscan 1076 in vivo scanner, measured by ionisation chamber and calculated from the x-ray exposure rate of the micro-focus source. In vivo scanned site Depth of tissue Dose rate calculated from x-ray source exposure (Gy / min) Dose rate calculated from ionisation chamber measurement, (Gy / min) Mouse hindlimb 5 mm Mouse body 15 mm The average of the dose values obtained from ionisation chamber measurement and from calculation from the source exposure measurement, was used in the dose calculations given in tables 1 and 2. REFERENCES Cember H (1988) Introduction to Health Physics. Pergamon Press, 2 nd edition. International Commission on Radiological Protection (1991) Publication 60, 1990 Recommendations of the ICRP Ann. ICRP Vol. 21 No. 1/3, Pergamon Press, Oxford, UK. International Commission on Radiological Protection (1995) Publication 70, Radiation protection basic anatomical and physiological data. Ann. ICRP vol. 25 (2), Report of the task group of the committee. Pergamon Press, Oxford, UK. Johns HE, Cunningham JR, The Physics of Radiology, 3rd. Ed., CC Thomas Publisher, Illinois, Page 9 of 10

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