The software of GAMOS version 5.1.0 can read DICOM RTSTRUCT file to calculate the dose or energy deposited in a structure. Before being used, they have to be converted into the list of CT voxels that belong to each structure. One of the tools that can be used to draw structures on a CT image file is Carimas.
JOURNAL OF MEDICAL RESEARCH ORGAN SEGMENTATION AND ABSORBED DOSE CALCULATION Nguyen Thi Phuong Thao1, Nguyen Thien Trung2 Vietnam Atomic Energy Institute, 2Techbase-Yahoo Japan The software of GAMOS version 5.1.0 can read DICOM RTSTRUCT file to calculate the dose or energy deposited in a structure Before being used, they have to be converted into the list of CT voxels that belong to each structure One of the tools that can be used to draw structures on a CT image file is Carimas We have developed a tool that could identify the CT voxels that belong to the structures drawn by Carimas and could write this information in a file usable by GAMOS As a first check of the tool, A geometrical comparison of the areas calculated with Carimas with those calculated by GAMOS using the converted file has been made In a second step, using a source of F - 18 placed in the water volumes of the NEMA phantom and comparing the absorbed dose on a disintegration in the drawn structures calculated by Carimas with those calculated by GAMOS have been implemented After validating the tool, using the CT images of adult male patients, drawing in Carimas the structures defining several structures, i.e kidney and spleen, and calculating the self-absorbed and cross-absorbed dose with GAMOS were made A patient to patient variability of up to 41.75% (spleen → kidney) was found Keywords: DICOM RTSTRUCT, GAMOS, Geant4, Carimas, voxel phantom I INTRODUCTION The information on the anatomy, the software packages can now be used to draw activity, and the dose distributions in different the structures on a CT image [2] and allow for parts of human body (whether corresponding the reading of those structures and calculation to real organs or to simulation issues) is crucial of the activities and deposited doses of for medical staff to determine the appropriate treatments [3] The volume of interest can be nuclear medicine or radiotherapy treatment, drawn by many contours on each z slice, or as well as to understand the treatment effects even in three-dimensional consideration For One of the tasks that need this information is instance, 3D Slicer is an open source software the assessment of the possible side effects of platform for medical image informatics, image internal exposure to radionuclide on the organs processing, and three-dimensional visualization and tissues that strongly affect to the health of [4] It is appreciated for its easy use Similarly, patients [1] These features are imbedded and ITK - SNAP is a software used to segment enable to be extracted from the CT image structures in 3D medical images with many Currently, plenty of different commercial utilities [5] They can link cursors for seamless 3D navigation with manual segmentation in Corresponding author: Nguyen Thi Phuong Thao, three orthogonal planes at once The software Vietnam Atomic Energy Institute supports many different 3D image formats, Email: nguyen.thi.phuong.thao.8488@gmail.com including NIfTI and DICOM Compared to Received: 27/11/2018 other larger, open-source image analysis tools, Accepted: 12/03/2019 JMR 118 E4 (2) - 2019 113 JOURNAL OF MEDICAL RESEARCH ITK-SNAP design focuses specifically on the this structure on the voxel map after reading problem of image segmentation It was written the structural information from a DICOM only for 64 bit modes Developed for both CT RTSTRUCT file and PET images, Carimas is a general medical In this report, we develop a tool that uses imaging processing platform developed in the drawing on CT images (VRML file) of Turku PET Centre, Finland [2] Carimas can Carimas for specifying the structure to which read only uncompressed images and run only the image voxels belong The information of on Windows After loading the PET/CT images these voxels can be converted to structure to Carimas, it allows users to define a structure text format of GAMOS in order to calculate by drawing a volume or a set of contours on the absorbed dose on a disintegration (the S each slice Information about coordinates of value) at voxel level points forming the structure can be saved as a VRML file Most of the software can measure area, mean, standard deviation, and max II METHODS Study setting of selection or entire image, measure lengths In this section, a procedure to segment a and angles, generate histograms and profile structure and extract the information from CT plots, calculate the activity or HU values on the images is proposed Such information is vital drawing for calculation of absorbed dose at voxel level However, the general drawback of these software is that they not support the feature of outputting data to indicate which voxels belong to a volume Besides, there is no free available software that can be used to draw the structures on a CT image, identify to which structures each of the CT image voxel belongs, and calculate the absorbed dose in them by using the Monte Carlo simulation method proved to be the most precise way to such calculations GAMOS is an easy-to-use Monte Carlo simulation tool built on the top of the Geant4 toolkit [6] Besides image processing and 3D visualization, GAMOS can make use of DICOM CT structures to compute the absorbed using GAMOS Materials and methods Firstly, the desired structures have to be obviously indicated and embedded in the CT images This step is straightforwardly resolved using the Carimas program [2] Once Carimas inputs the DICOM CT images, the images are displayed as both 2D and 3D images The users can use the default shapes of Carimas such as sphere, cylinder, tube, and cube Subsequently, the editing functions of Carimas enable one to modify the Volume of Interest (VOI) for getting the desired shape as illustrated in Figure The VOI is then saved as a VRML file, containing the coordinates of the points on dose or energy deposit in each structure, a the surface of the VOI The information on the very important task in nuclear medicine To coordinates of these points are used to figure this, GAMOS offers a simple text format out which voxels belong to the VOI in the next to list the structures that each image voxel stage using the so-called flood-fill algorithm as belongs to, plus a robust mechanism to identify described in the following [7 - 8] 114 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Figure Arbitrary structures drawn by Carimas on top of CT images The closed, blurred pink shape indicates the desired VOI The flood-fill algorithm is widely used but not for such purposes In this article, we adopted this algorithm to precisely indicate which voxels belong to a structure taken from the previous phase of procedure A box called the World Volume (WV) is firstly created The WV adequately contains the VOI as presented in Figure in which the black circles covered by the pink square is our desired structures All appropriate voxels of the CT images in WV are then figured out including their coordinate information Note that such a performance is straightforward due to the available minimum and maximum values of x, y, z coordinates saved in the VRML files The coordinates of all the voxel vertices in the WV are used to specify all the voxels containing the points locating on the surface of the VOI It is also noted that those voxels cannot cover the surface of the VOI In the VRML file, the points on the surface of the VOI are listed line-by-line Each line corresponds to the points located on the same JMR 118 E4 (2) - 2019 plane, three of them are arbitrarily chosen to create a pediment On each pediment, each edge is divided into several segments so that the dimension of each part is smaller than that of the voxel Then each vertex is connected to its neighbors on the same pediment to look for all voxels on that line The loop is repeated for all pediments and planes to get a voxel net covering the surface of the VOI After covering the VOI, a “prototype” voxel is embraced and set free to flood in the VOI until it touches the VOI’s surface All voxels that are in contact with that prototype one are then chosen Similarly, all of the chosen voxels are again moved until they fill the whole VOI The information of those specified voxels in the VOI is saved to the second VRML file which can later be recalled by Carimas The geometry of the treated volume is then compared to the original VOI for validating results The smaller the voxel size is, the more consistent the treated volume is to the shape of the VOI 115 JOURNAL OF MEDICAL RESEARCH Figure Illustration of specification of the WV strictly covering the VOI The upper left, upper right, and lower left panels are the WV in (Oy, Oz), (Ox, Oz), and (Ox, Oy) plains, respectively The lower right panel shows three dimensional WV Once the information of structures is fully disintegrations occurring in all source structures available, it has to be transformed to GAMOS and (2) the S values of absorbed dose per format The structures from a DICOM file unit cumulated activity (mGy(Bqs) - 1) The S of RTSTRUCT modality can be converted values depend on the absorbed fraction, which to the simple text format of GAMOS For are computed by the phantom with a Monte that purpose, one adds the name of the Carlo transport method: DICOM in the metadata file containing the information of the DICOM CT images used by the DICOM2G4 command After reading the structure’s information from the RTSTRUCT S(target←source) = ∑ ∆i ∅i (target←source) mtarget Where mtarget is the target tissue mass, ∆i file, GAMOS identifies on each (Ox, Oy) plain is the equilibrium dose constant for particles of of the CT image which voxels belong to each a particular type and energy, here indicated by structure provided that they are surrounded by i, and ϕ_i represents the absorbed fraction of the structure energy for target structure for particle i emitted From this step, GAMOS is consistently in the source structure From the CT images, used for calculating the S values As presented GAMOS can calculate the dose or energy in MIRD 11 [9], to estimate the absorbed dose deposit in each voxel With DICOM RT structure to a structure, the following two components in the g4dcm file, GAMOS can calculate the are necessary: (1) the time-integrated activities dose/energy/S value of each structure The S (Bqs) which correspond to the number of values are calculated for the phantom and for 116 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH the specific patient In this article the S values indicated by this algorithm including the shape, for the patients are calculated for kidney and spleen position, and volume of the voxel set are The S values are calculated for both NEMA by Carimas CT images of an adult male are phantoms [10] and adult male patients The used in which the VOIs represent a spherical three water spheres with the radii of 6.20mm, tumor, left kidney, right kidney, and spleen 7.82mm, 13.36mm are filled with F-18 These The selected sizes of each voxel are: 5mm, spheres not overlap With each sphere, the 3mm, 2mm and 1.5mm Figure shows the CT images are cropped to get a cube which depiction of the mentioned structures by sets is appropriate to contain the sphere The voxel of appropriate voxels determined by flood fill dimensions are equal to 1/20, 1/40 and 1/60 of algorithm firstly compared with those directly obtained the diameter of the spheres, respectively The Figure indicates that the shape and the S values and the difference in volume of each location of the structures are relatively well sphere are compared with those of OLINDA/ reflected by the sets of voxels, especially within EXM [11] In real situation, the CT images of the area constrained by solid curve showing adult male patients (on Siemens scanners) the boundary of the structures However, at are converted to GAMOS text files (g4dcm) to the border, the voxelization of these structures get the S values for kidneys and spleen The creates an inevitable difference in shape This voxel dimension on three axes are 0.97mm, difference is quantitatively interpreted by their 0.97mm, and 2mm Note that the sources are volumes and stems from the size of individual assumed to be uniform distributed by F-18 voxel and can efficiently be reduced as the size In all calculation, the number of events is of voxels decreases as shown in Table Here 100 million, the data of the isotopes is taken the volumes of voxel sets are compared with from the LUND database The S values of those of structures given by Carimas as the the patients will then be used to calculate the size of voxel is curtailed from 5mm to 1.5mm biggest variability from patient to patient As decreasing the size of voxels, the volume Research ethics differences are also remarkably reduced by Following the research ethics, the study is based on PET / CT images of patients, provided by Cho Ray Hospital Research has no effect on patients’ health and patient information is kept strictly confidential around a factor of ten For smallest voxel size III RESULTS it is the smaller structure and has a perfectly To evaluate the applicability and validity of established algorithm, all crucial quantities JMR 118 E4 (2) - 2019 of 1.5mm, such differences are less than 5% for all examined cases Note that the case of tumor sphere exhibits the highest deviation This feature is easily understandable since rounded shape, which challenges the interpretation when using square voxels 117 JOURNAL OF MEDICAL RESEARCH Figure Several representative human structures indicated by sets of appropriate voxels Table The comparison of volumes of the structures and the voxel set for difference size of voxel Structure Voxel dimension (mm) Volume of structure (mm3) Right kidney Left kidney Spleen Sphere tumor 252250 19.54 232767 10.31 221296 4.87 1.5 215861 2.30 274500 21.04 248373 9.52 237032 4.52 1.5 231096 1.90 286000 33.08 247050 14.96 230168 7.10 1.5 222594 3.58 48125 43.69 39042 16.57 36304 8.40 34742 3.74 3 3 1.5 118 Volume of Difference (%) the voxel set |Vset of voxel -Vstructure | (mm3) Vstructure 211006 226776 214906 33491 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH The voxel size can alternatively be reduced to the resolution of the CT image (less than 0.5mm), which may well reflect the shape and volume of the volume of interest To determine which voxel belongs to a structure, it is based on the voxel center position If the center of a voxel is in a structure, the whole voxel belonging to this structure will be considered This method has a crucial drawback in application to very thin organs such as skin and mucosa due to large deviations as shown in Table for a spherical tumor The consideration of S values will be carried out below, firstly for NEMA phantom - S values of NEMA phantom The dose for water spheres calculated by GAMOS and OLINDA/EXM is presented in Table F - 18 is assumed to be uniformly distributed in the water sphere, emitting isotropic radiation The comparison of the self-dose of the sphere will be done, when directly calculated with the spherical model using the OLINDA/EXM software and when calculated from the dose of each voxel calculated by GAMOS In all case, the greater the volume difference, the greater the difference in S value The difference in S value is less than 5% when the difference in volume is less than 10% and when the voxel size is equal to 1/20 of the phantom's diameter Table The S values (mGy/MBq) for water spheres of NEMA phantom filled with F - 18 Mass (g) m=1 m=2 m = 10 Difference of volume (%) VGAMOS -VOLINDA⁄EXM VOLINDA⁄EXM Difference of S value (%) SGAMOS -SOLINDA⁄EXM SOLINDA⁄EXM 10.03 - 4.66 3.86E - 7.17 - 2.12 2448.68 1.75E - 18.85 - 13.32 2210.93 1.93E - 10.12 - 4.40 121703 2139.05 1.98E - 7.11 - 1.93 1.34 4966 11948.71 3.66E - 15.58 - 14.12 0.67 37003 11129.13 4.03E - 9.36 - 5.62 0.45 118499 10798.22 4.10E - 6.59 - 3.98 Voxel Size (mm) Number of voxel in sphere 0.62 5136 0.31 37248 0.21 Volume of the sphere (mm3) Volume of the group of voxels (mm3) S value calculated by GAMOS 1224.05 3.41E - 1109.66 3.76E - 116123 1075.41 0.78 5160 0.39 37272 0.26 1000 2000 10000 S value calculated by OLINDA 18.44 3.944E - 2.019E - 4.27E - - 13.53 The difference of this dose is due to the difference at the surface of the sphere A voxel at the surface of the sphere has a part of volume inside the sphere Taking the energy and the volume of whole surface-voxel will cause differences when calculating the average dose for the sphere - The S value for the organs of patients Using the established tool and GAMOS software to calculate the S values for the four important organs of five adult patients is carried out (Table and Table 4) We assume that the JMR 118 E4 (2) - 2019 119 JOURNAL OF MEDICAL RESEARCH radiopharmaceutical is uniformly distributed and isotropic in the source organ The S value is calculated by the Monte Carlo method with the number of event so that the statistical error is kept below 5% We see the results of the different patients are varied The biggest differences (patient to patient) in radiation exposure in these cases are up to 41.75% for cross-dose and 22.14 % for self-dose Table S values for the kidneys and spleen in the adult male patients for F - 18 assumed to be uniformly distributed in kidney (mGy/MBq) The biggest difference (%) The S value (mGy/MBq) Target structure Patient1 Patient2 Patient3 Patient4 Patient5 Kidney 1.78E - 1.65E - 1.82E - 1.49E - 1.72E - 22.14 Spleen 4.120E - 4.66E - 3.59E - 3.99E - 4.07E - 29.81 Smax -Smin Smin Table S values for the kidneys and spleen in the adult male patients for F - 18 assumed to be uniformly distributed in the spleen (mGy/MBq) The S value (mGy/MBq) Target structure The biggest difference (%) Smax -Smin Smin Patient1 Patient2 Patient3 Patient4 Patient5 Kidney 5.33E - 5.43E - 4.00E - 5.03E - 5.67E - 41.75 Spleen 2.76E - 2.81E - 2.99E - 3.02E - 2.82E - 9.42 IV DISCUSSION In the Figure and Table 1, the shape and the congregation of the voxels present the shape and the position of the structures well The smaller the voxel size, the closer the shape and the volume of the voxel set is to the shape and volume of the structure From the S value of the water spheres of the NEMA phantom, seeing that in the selected voxel dimensions, the S value calculated by GAMOS is always smaller than the result calculated by OLINDA/EXM The smaller the size of the voxel, the smaller the difference between the results obtained by GAMOS and 120 OLINDA/EXM With a voxel size of 1/60 the diameter of the sphere, the difference of S value is less than 5% when the difference of volume is less than 10% With the S values of the adult male patients, seeing that with all pairs of source-target organs, the S values of different patients are different In these cases that have the biggest difference, the source and the target are not the same A patient to patient, variability of up to 41.75% has been found when the S values are spleen → kidney This is caused by differences in the anatomy and the distance between the structures JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Many geometric phantoms as well as voxel phantoms are used to represent the anatomy of human subjects The S values for the phantom will be used along with the residence time of the pharmaceutical in the body to calculate the accumulate dose for the patients Besides, some authors assumed that the S value from structure A to structure B is equal to the one of the structure B to A (S(A←B) = S(B←A)) [11] Based on the above results, it is found out that, the above expect cannot be achieved Therefore, this assumption for calculating the S values for these pairs of structures cannot be used In fact, the distribution of radioactivity and density in a body is very complex; it may cause an even bigger difference in the dose distribution Therefore, it is very important to calculate the dose for each patient This has not been done in Vietnam and many countries in the world To estimate the absorbed dose for a patient, it can use PET/CT images It can help to calculate the absorbed dose for each voxel And the last step is determining which voxel belongs to a structure, in order to best estimate the average dose that each structure receives V CONCLUSION Because the distribution of radioactive pharmaceuticals in the body and the anatomy of patient is very complex, it is important to calculate the absorbed dose for each patient GAMOS is the free and easy to use It can use PET/CT images to calculate the absorbed dose at voxel level for patients First, it needs to convert both DICOM PET and CT images to the GAMOS format The PET image gives the source distribution and CT images give anatomical information of each structure Then the tool helps find out which voxels belong to JMR 118 E4 (2) - 2019 an organ to calculate the dose for each organ The dose value on each of these structures is sum of self-dose and cross dose This can be used to estimate the risk for vital organs and the effect of treatment in order to extend the life of the patient Acknowledgements Many thanks for the support from Mr Nguyen Tan Chau (PET/CT Department-Cho Ray Hospital), Dr Pham Nguyen Thanh Vinh (Ho Chi Minh City University of Education) and Dr Nguyen Khanh Toan REFERENCE Helal N (2012) Patient organs dose calculations in nuclear medicine J Med Signals Sens, 24, 231 – 234 Sergey V Nesterov, Chunlei Han & Maija Mäki et al (2009) Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas) Eur J Nucl Med Mol Imaging, 36,1594 – 1602 Antoine Rosset, Luca Spadola, Osman Ratib et al (2004) OsiriX: An Open-Source Software for Navigating in Multidimensional DICOM Images Journal of Digital Imaging, 17, 205 - 216 Alexander K., Pinter C., Fichtinger G (2018) Streamlined open-source gel dosimetry analysis in 3D slicer Biomedical Physics & Engineering Express, 4, 041 - 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1023 JMR 118 E4 (2) - 2019 ... 2019 an organ to calculate the dose for each organ The dose value on each of these structures is sum of self -dose and cross dose This can be used to estimate the risk for vital organs and the... done in Vietnam and many countries in the world To estimate the absorbed dose for a patient, it can use PET/CT images It can help to calculate the absorbed dose for each voxel And the last step... complex, it is important to calculate the absorbed dose for each patient GAMOS is the free and easy to use It can use PET/CT images to calculate the absorbed dose at voxel level for patients First,