Assessment of Uncertainty in Volume Estimation of Non-Static Target: A Phantom Study using Racemosa Wood.

INTRODUCTION: CT information of the target undergoing motion/movement during its scanning has been questioned by many researchers for its preciseness as well as accuracy. The present study was taken with aim to validate the racimosa wood as lung equivalent and to assess the uncertainty in volume estimation during virtual simulation of non-static target of known dimension such as in lung cancer radiotherapy. MATERIALS AND METHODS: The racemosa wood was validated as lung equivalent material with the help of two methods. Wood insert with tumor model was put into the hollow cylinder space of dimension 6.4 cm in diameter provided in CIRS phantom. First CT image of rest position was taken and given name "No Movement". Subsequently the tumor was shifted +/-5mm, +/-15mm and +/-25 mm with respect to "Rest Position". CT images of the CIRS phantom containing tumor in wood cylinder were acquired after each movement given to wood cylinder. RESULTS: The relative electron density of racemosa wood corresponding to HU value -724 was found to be 0.275 gm/cm3. The true volume of the target was 7.8.cm3 however variation up to 9.5 cm3 was observed in CT produced volume of the target over the range of different movements. DISCUSSION: The racemosa wood was found to be having range of density (- 850 HU to - 400 HU) similar to real human lung density variation. Various studies have been performed using uniform density lung structures in their experimental setups to assess the accuracy in lung cancer radiation delivery. However, in the present work approximately real clinical setting was reproduced by putting the wood cylinder with density variation from 0.2 gm/cm3- 4.5 gm/cm3in hollow space provided in one lung structure the phantom used in this study. CONCLUSIONS: The racemosa wood was found to be lung equivalent which is available locally and cost-effective as well. Overestimation in the target volume (by CT imaging) showed a trend of increase with 3 directional movement amplitudes. The results of this study can be utilised in lung cancer radiotherapy as the same were derived from setup having clinical settings in terms of lung density variation, shape, compositions of the phantom maximally as found during the real patient radiotherapy.

Evaluation of Electron Specific Absorbed Fractions in Organs of Digimouse Voxel Phantom Using Monte Carlo Simulation Code FLUKA.

BACKGROUND: For preclinical evaluations of radiopharmaceuticals, most studies are carried out on mice. Electron specific absorbed fractions (SAF) values have had vital role in the assessment of absorbed dose. In past studies, electron SAFs were given for limited source target pairs using older reports of human organ compositions. OBJECTIVE: Electron specific absorbed fraction values for monoenergetic electrons of energies 15, 50, 100, 500, 1000 & 4000 keV were evaluated for the Digimouse voxel phantom incorporated in Monte Carlo code FLUKA. From the latest report (International Commission on Radiological Protection ICRP) 110, organ compositions and densities were adopted. MATERIAL AND METHODS: We have used the Digimouse voxel phantom which was incorporated in Monte Carlo code FLUKA. Simulation studies were performed using FLUKA. The organ sources considered in this study were lungs, skeleton, heart, bladder, testis, stomach, spleen, pancreas, liver, kidney, adrenal, eye and brain. The considered target organs were lungs, skeleton, heart, bladder, testis, stomach, spleen, pancreas, liver, kidney, adrenal and brain. Eye and brain were considered as target organs only for eye and brain as source organs. RESULTS: The electron SAF values for self-irradiation decreases with increasing electron energy. The electron SAF values for cross-irradiation are also found to be dependent on the electron energy and the geometries of source and target. Organ masses and electron SAF values are presented in tabular form. CONCLUSION: The results of this study will be useful in evaluating the absorbed dose to various organs of mice similar in size to the present study.

Evaluation of Volumetric Doses of Organs at Risk in Carcinoma Cervix Patients with HDR Intracavitary Brachytherapy and Comparison of CT-based and Conventional Plans.

BACKGROUND: Brachytherapy treatment planning in cervix carcinoma patients using two dimensional (2D) orthogonal images provides only point dose estimates while CT-based planning provides volumetric dose assessment helping in understanding the correlation between morbidity and the dose to organs at risk (OARs) and treatment volume. OBJECTIVE: Aim of present study is to compare International Commission on Radiation Units and Measurements Report 38 (ICRU 38) reference point doses to OARs with volumetric doses using 2D images and CT images in patients with cervical cancer. MATERIAL AND METHODS: In this prospective study, 20 patients with cervical cancer stages (IIB-IIIB) were planned for a brachytherapy dose of 7Gy per fraction for three fractions using 2D image-based treatment plan and CT-based plan. ICRU 38 points for bladder and rectum were identified on both 2D image-based plan and CT-based plan and doses (DICRU) at these points were compared to the minimum dose to 2cc volume (D2cc) of bladder and rectum receiving the highest dose. RESULTS: D2cc bladder dose was 1.60 (±0.67) times more than DICRUb bladder dose whereas D2cc rectum dose was 1.13±0.40 times DICRUr. Significant difference was found between DICRUb and D2cc dose for bladder (p=.0.016) while no significant difference was seen between DICRUr and D2cc dose for rectum (p=0.964). CONCLUSION: The study suggests that ICRU 38 point doses are not the true representation of maximum doses to OARs. CT-based treatment planning is more a reliable tool for OAR dose assessment than the conventional 2D radiograph-based plan.

Validation of the Gel & Wax Boluses and Comparison of their Dosimetric Performance with Virtual Bolus.

BACKGROUND: In general, radiotherapy treatment planning is performed using the virtual bolus. It is necessary to investigate physical bolus in comparison to virtual one. OBJECTIVES: In the present study, first, radiological properties of superflab Gel bolus and Paraffin wax bolus was investigated in terms of their relative electron density. Then, dosimetric performance of both the bolus (i.e. Gel and Parafin wax) was compared with Virtual bolus. MATERIAL AND METHODS: In This experimental study, the radiological property of Wax and Gel boluses was investigated using two methods. In one, the relative electron density of both the Gel and Wax boluses was calculated by measuring their linear attenuation coefficient where in another method relative electron density was calculated by recording their CT No directly from their CT scan. Later CT scan of solid water slab phantom (dimension 30x30x15 cm3), with physical boluses (i.e. Gel and Wax bolus) of appropriate thicknesses required to deliver a dose of 200 cGy at Dmax using 4 MV, 6 MV and 15 MV photon beams, was taken. These CT data sets were retrieved to TPS. A plan was done to deliver a dose of 200 cGy at Dmax using Single 4 MV, 6 MV and 15 MV photon beams. Dose at depths Dmax, 1 cm, 2 cm, 3 cm, 4 cm and 5 cm was recorded. Using this similar method, doses at depths viz Dmax, 1 cm, 2 cm, 3 cm, 4 cm and 5 cm was recorded for the Gel and Wax boluses. The differences in dose of gel and wax bolus from virtual bolus were recorded for comparison of their dosimetric performance. RESULTS: The measured (calculated) relative electron density of wax and Gel bolus was found to be 0.958 (0.926) and 0.923 (0.907), respectively. Variation in dosimetric performance of Gel and Wax with reference to Virtual bolus was studied. However, on average, Gel bolus was more consistent with virtual bolus. CONCLUSION: To avoid any dose difference between, delivered (using physical bolus) and planned (using virtual bolus), the physical boluses should be investigated for their dosimetric performance in comparison to virtual bolus. The results obtained and methodology used in this study can be applied in routine radiotherapy practices.

Evaluation of AAA and XVMC Algorithms for Dose Calculation in Lung Equivalent Heterogeneity in Photon Fields: A Comparison of Calculated Results with Measurements.

AIMS: The aims of the present work are (1) to evaluate dose calculation accuracy of two commonly used algorithms for 15 MV small photon fields in a medium encompassing heterogeneity and (2) to compare them with measured results obtained from gafchromic film EBT2. MATERIALS AND METHODS: Authors employed kailwood (Pinus Wallichiana) to mimic lung. Briefly, seven Kailwood plates, each measuring 25x25 cm2 of varying thicknesses totaling 13 cm equivalent to the mean thickness of an adult human lung, were sandwiched between 5 cm tissue equivalent material from top and 10 cm below. Physical measurements were performed using Radiochromic film EBT2. The field sizes of 1x1, 2x2, 5x5 and 10x10 cm2 were selected at 100 cm SSD. Simulations were performed using EGSnrc/DOSRZnrc Monte Carlo code. The dose variation inside the inhomogeneity and near the interface was calculated using AAA & XVMC algorithm. RESULTS: Preliminary results show that there is large variation of dose inside inhomogeneity. The maximum variation of dose inside the inhomogeneity for 1x1 cm2 was found 40% by AAA and 4.5% by XVMC compared to measured/simulated results. For the field size of 2x2 cm2, these figures were 27% by AAA & 3.5% by XVMC. For 5x5 cm2 field size, the variation is small which becomes insignificant for larger fields. CONCLUSION: The results presented in this work indicate that for smaller fields, XVMC algorithm gives more realistic prediction, while there is the need for caution on using AAA algorithm for dose calculations involving small area irradiation encompassing heterogeneities and low-density media.

Performance Evaluation of Algorithms in Lung IMRT: A comparison of Monte Carlo, Pencil Beam, Superposition, Fast Superposition and Convolution Algorithms.

BACKGROUND: Inclusion of inhomogeneity corrections in intensity modulated small fields always makes conformal irradiation of lung tumor very complicated in accurate dose delivery. OBJECTIVE: In the present study, the performance of five algorithms via Monte Carlo, Pencil Beam, Convolution, Fast Superposition and Superposition were evaluated in lung cancer Intensity Modulated Radiotherapy planning. MATERIALS AND METHODS: Treatment plans for ten lung cancer patients previously planned on Monte Carlo algorithm were re-planned using same treatment planning indices (gantry angel, rank, power etc.) in other four algorithms. RESULTS: The values of radiotherapy planning parameters such as Mean dose, volume of 95% isodose line, Conformity Index, Homogeneity Index for target, Maximum dose, Mean dose; %Volume receiving 20Gy or more by contralateral lung; % volume receiving 30 Gy or more; % volume receiving 25 Gy or more, Mean dose received by heart; %volume receiving 35Gy or more; %volume receiving 50Gy or more, Mean dose to Easophagous; % Volume receiving 45Gy or more, Maximum dose received by Spinal cord and Total monitor unit, Volume of 50 % isodose lines were recorded for all ten patients. Performance of different algorithms was also evaluated statistically. CONCLUSION: MC and PB algorithms found better as for tumor coverage, dose distribution homogeneity in Planning Target Volume and minimal dose to organ at risks are concerned. Superposition algorithms found to be better than convolution and fast superposition. In the case of tumors located centrally, it is recommended to use Monte Carlo algorithms for the optimal use of radiotherapy.

Estimation of Photon Specific Absorbed Fractions in Digimouse Voxel Phantom using Monte Carlo Simulation Code FLUKA.

BACKGROUND: Most preclinical studies are carried out on mice. For internal dose assessment of a mouse, specific absorbed fraction (SAF) values play an important role. In most studies, SAF values are estimated using older standard human organ compositions and values for limited source target pairs. OBJECTIVE: SAF values for monoenergetic photons of energies 15, 50, 100, 500, 1000 and 4000 keV were evaluated for the Digimouse voxel phantom incorporated in Monte Carlo code FLUKA. The organ sources considered in this study were lungs, skeleton, heart, bladder, testis, stomach, spleen, pancreas, liver, kidney, adrenal, eye and brain. The considered target organs were lungs, skeleton, heart, bladder, testis, stomach, spleen, pancreas, liver, kidney, adrenal and brain. Eye was considered as a target organ only for eye as a source organ. Organ compositions and densities were adopted from International Commission on Radiological Protection (ICRP) publication number 110. RESULTS: Evaluated organ masses and SAF values are presented in tabular form. It is observed that SAF values decrease with increasing the source-to-target distance. The SAF value for self-irradiation decreases with increasing photon energy. The SAF values are also found to be dependent on the mass of target in such a way that higher values are obtained for lower masses. The effect of composition is highest in case of target organ lungs where mass and estimated SAF values are found to have larger differences. CONCLUSION: These SAF values are very important for absorbed dose calculation for various organs of a mouse.

Linking radiosilver to monoclonal antibodies reduced by ascorbic acid. Comparison of results with stable silver using gravimetric technique and silver 110-M using radiotracer technique.

Radiosilver-111 and Radiogold-199 were proposed by us (1) as suitable isotopes for radioimmunotherapy in areas such as India by reason of their suitable half-lives and B-emissions (Ag-111 T1/2 = 7.45 d and Au-199 T1/2 = 3.15 d). Since silver is monovalent, it is difficult to link to conventional bifunctional chelates. We therefore explored the use of sulfur-based linkers (2). Encouraged by the Thakur and De Fulvio Technique (3) of linking technetium to disulfide groups in antibodies reduced by ascorbic acid that is eminently biocompatible, we have explored the linkage of silver to immunoglobulin reduced by ascorbic acid. The linkage of silver was assessed with stable Ag-108 using dialysis to quantify the free silver after the reaction of silver and reduced immunoglobulins in various molar ratios (1:1, 1:2, 1:5, 1:10). The silver quantity was estimated gravimetrically after precipitation as chloride. It was observed that using these molar ratios there was negligible silver efflux into the dialysate, suggesting stable linkage. We also assessed the linkage using Ag-110M as radiotracer. The comparative results with the two techniques are described.

Removal of endotoxin from antibody preparations for clinical use. Assessment of polymyxin-sepharose CNBr affinity chromatography.

Despite attempts to maintain asepsis, good manufacturing practices, and the use of terminal sterilization by millipore filtration, the nuclear practitioner is always worried about the possibility of endotoxin contamination. Methods, such as ion-exchange chromatography, have been tried for removing endotoxins during the preparation of radiolabeled antibodies, and so on. As suggested by Stevenson (1990), we evaluated the Issekutz technique (1) of endotoxin removal by affinity chromatography using a polymyxin cyanogen bromide (CNBr) Sepharose column. The endotoxin content of millipore filtrates of heat killed/sonicated suspensions of Pseudomonas pyocyaneus, E. coli were measured using a Sigma (St. Louis, MO) Endotoxin Assay Kit before and after filtration through such columns and compared with the results obtained using gel exclusion and ion-exchange columns of the same length and diameter. Reduction of endotoxin content to undetectable levels by the polymyxin column was observed. The use of such columns for terminal endotoxin removal analogous to terminal sterilization is advocated especially when developing a radiopharmaceutical such as radiolabeled antibodies for in house use.