Toxoplasmosis epidemic in a population of urbanised allied rock-wallabies (Petrogale assimilis) on Magnetic Island (Yunbenun), North Queensland.

A mortality event involving 23 allied rock-wallabies (Petrogale assimilis) displaying neurological signs and sudden death occurred in late April to May 2021 in a suburban residential area directly adjacent to Magnetic Island National Park, on Magnetic Island (Yunbenun), North Queensland, Australia. Three allied rock-wallabies were submitted for necropsy, and in all three cases, the cause of death was disseminated toxoplasmosis. This mortality event was unusual because only a small, localised population of native wallabies inhabiting a periurban area on a tropical island in the Great Barrier Reef World Heritage Area were affected. A disease investigation determined the outbreak was likely linked to the presence of free-ranging feral and domesticated cats inhabiting the area. There were no significant deaths of other wallabies or wildlife in the same or other parts of Magnetic Island (Yunbenun) at the time of the outbreak. This is the first reported case of toxoplasmosis in allied rock-wallabies (Petrogale assimilis), and this investigation highlights the importance of protecting native wildlife species from an infectious and potentially fatal parasitic disease.

A novel alphaherpesvirus and concurrent respiratory cryptococcosis in a captive koala (Phascolarctos cinereus).

A novel alphaherpesvirus was detected in a captive adult, lactating, female koala (Phascolarctos cinereus) admitted to James Cook University Veterinary Emergency Teaching & Clinical Hospital in March 2019, showing signs of anorexia and severe respiratory disease. Postmortem examination revealed gross pathology indicative of pneumonia. Histopathology demonstrated a chronic interstitial pneumonia, multifocal necrotising adrenalitis and hepatitis. Intranuclear inclusion bodies were detected by light microscopy in the respiratory epithelium of the bronchi, bronchioles, alveoli, and hepatocytes, biliary epithelium and adrenal gland associated with foci of necrosis. Cryptococcus gattii was isolated from fresh lung on necropsy, positively identified by PCR, and detected histologically by light microscopy, only in the lung tissue. A universal viral family-level PCR indicated that the virus was a member of the Herpesviruses. Sequence analysis in comparison to other known and published herpesviruses, indicated the virus was a novel alphaherpesvirus, with 97% nucleotide identity to macropodid alphaherpesvirus 1. We provisionally name the novel virus phascolarctid alphaherpesvirus 3 (PhaHV-3). Further research is needed to determine the distribution of this novel alphaherpesvirus in koala populations and establish associations with disease in this host species.

Image guidance doses delivered during radiotherapy: Quantification, management, and reduction: Report of the AAPM Therapy Physics Committee Task Group 180.

BACKGROUND: With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. AIMS: This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. MATERIALS & METHODS: We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. RESULTS: We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. DISCUSSION: Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. CONCLUSION: Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

Monte Carlo computed machine-specific correction factors for reference dosimetry of TomoTherapy static beam for several ion chambers.

PURPOSE: To determine k(Q(msr),Q(o) ) (f(msr),f(o) ) correction factors for machine-specific reference (msr) conditions by Monte Carlo (MC) simulations for reference dosimetry of TomoTherapy static beams for ion chambers Exradin A1SL, A12; PTW 30006, 31010 Semiflex, 31014 PinPoint, 31018 microLion; NE 2571. METHODS: For the calibration of TomoTherapy units, reference conditions specified in current codes of practice like IAEA∕TRS-398 and AAPM∕TG-51 cannot be realized. To cope with this issue, Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)] described a new formalism introducing msr factors k(Q(msr),Q(o) ) (f(msr),f(o) ) for reference dosimetry, applicable to static TomoTherapy beams. In this study, those factors were computed directly using MC simulations for Q(0) corresponding to a simplified (60)Co beam in TRS-398 reference conditions (at 10 cm depth). The msr conditions were a 10 × 5 cm(2) TomoTherapy beam, source-surface distance of 85 cm and 10 cm depth. The chambers were modeled according to technical drawings using the egs++ package and the MC simulations were run with the egs_chamber user code. Phase-space files used as the source input were produced using PENELOPE after simulation of a simplified (60)Co beam and the TomoTherapy treatment head modeled according to technical drawings. Correlated sampling, intermediate phase-space storage, and photon cross-section enhancement variance reduction techniques were used. The simulations were stopped when the combined standard uncertainty was below 0.2%. RESULTS: Computed k(Q(msr),Q(o) ) (f(msr),f(o) ) values were all close to one, in a range from 0.991 for the PinPoint chamber to 1.000 for the Exradin A12 with a statistical uncertainty below 0.2%. Considering a beam quality Q defined as the TPR(20,10) for a 6 MV Elekta photon beam (0.661), the additional correction k(Q(msr,)Q) (f(msr,)f(ref) ) to k(Q,Q(o) ) defined in Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)] formalism was in a range from 0.997 to 1.004. CONCLUSION: The MC computed factors in this study are in agreement with measured factors for chamber types already studied in literature. This work provides msr correction factors for additional chambers used in reference dosimetry. All of them were close to one (within 1%).

On proton CT reconstruction using MVCT-converted virtual proton projections.

PURPOSE: To describe a novel methodology of converting megavoltage x-ray projections into virtual proton projections that are otherwise missing due to the proton range limit. These converted virtual proton projections can be used in the reconstruction of proton computed tomography (pCT). METHODS: Relations exist between proton projections and multispectral megavoltage x-ray projections for human tissue. Based on these relations, these tissues can be categorized into: (a) adipose tissue; (b) nonadipose soft tissues; and (c) bone. These three tissue categories can be visibly identified on a regular megavoltage x-ray computed tomography (MVCT) image. With an MVCT image and its projection data available, the x-ray projections through heterogeneous anatomy can be converted to the corresponding proton projections using predetermined calibration curves for individual materials, aided by a coarse segmentation on the x-ray CT image. To show the feasibility of this approach, mathematical simulations were carried out. The converted proton projections, plotted on a proton sinogram, were compared to the simulated ground truth. Proton stopping power images were reconstructed using either the virtual proton projections only or a blend of physically available proton projections and virtual proton projections that make up for those missing due to the range limit. These images were compared to a reference image reconstructed from theoretically calculated proton projections. RESULTS: The converted virtual projections had an uncertainty of ±0.8% compared to the calculated ground truth. Proton stopping power images reconstructed using a blend of converted virtual projections (48%) and physically available projections (52%) had an uncertainty of ±0.86% compared with that reconstructed from theoretically calculated projections. Reconstruction solely from converted virtual proton projections had an uncertainty of ±1.1% compared with that reconstructed from theoretical projections. If these images are used for treatment planning, the average proton range uncertainty is estimated to be less than 1.5% for an imaging dose in the milligray range. CONCLUSIONS: The proposed method can be used to convert x-ray projections into virtual proton projections. The converted proton projections can be blended with existing proton projections or can be used solely for pCT reconstruction, addressing the range limit problem of pCT using current therapeutic proton machines.

Poster - Thur Eve - 46: The upcoming international code of practice for small static photon field dosimetry.

The increased use of small photon fields in stereotactic and intensity-modulated radiotherapy has raised the need for standardizing the dosimetry of such fields using procedures consistent with those for conventional radiotherapy. An international working group, established by the IAEA in collaboration with AAPM and IPEM, is finalising a Code of Practice for the dosimetry of small static photon fields. Procedures for reference dosimetry in nonstandard machine specific reference (msr) fields are provided following the formalism of Alfonso et al. (Med. Phys. 35: 5179; 2008). Reference dosimetry using ionization chambers in machines that cannot establish a conventional 10 cm × 10 cm reference field is based on either a direct calibration in the msr field traceable to primary standards, a calibration in a reference field and a generic correction factor or the product of a correction factor for a virtual reference field and a correction factor for the difference between the msr and virtual fields. For the latter method, procedures are provided for determining the beam quality in non-reference conditions. For the measurement of field output factors in small fields, procedures for connecting large field measurements using ionization chambers to small field measurements using high-resolution detectors such as diodes, diamond, liquid ion chambers, organic scintillators and radiochromic film are given. The Code of Practice also presents consensus data on correction factors for use in conjunction with measured, detector-specific output factors. Further research to determine missing data according to the proposed framework will be strongly encouraged by publication of this document.

Monte Carlo-based simulation of dynamic jaws tomotherapy.

PURPOSE: Original TomoTherapy systems may involve a trade-off between conformity and treatment speed, the user being limited to three slice widths (1.0, 2.5, and 5.0 cm). This could be overcome by allowing the jaws to define arbitrary fields, including very small slice widths (<1 cm), which are challenging for a beam model. The aim of this work was to incorporate the dynamic jaws feature into a Monte Carlo (MC) model called TomoPen, based on the MC code PENELOPE, previously validated for the original TomoTherapy system. METHODS: To keep the general structure of TomoPen and its efficiency, the simulation strategy introduces several techniques: (1) weight modifiers to account for any jaw settings using only the 5 cm phase-space file; (2) a simplified MC based model called FastStatic to compute the modifiers faster than pure MC; (3) actual simulation of dynamic jaws. Weight modifiers computed with both FastStatic and pure MC were compared. Dynamic jaws simulations were compared with the convolution∕superposition (C∕S) of TomoTherapy in the "cheese" phantom for a plan with two targets longitudinally separated by a gap of 3 cm. Optimization was performed in two modes: asymmetric jaws-constant couch speed ("running start stop," RSS) and symmetric jaws-variable couch speed ("symmetric running start stop," SRSS). Measurements with EDR2 films were also performed for RSS for the formal validation of TomoPen with dynamic jaws. RESULTS: Weight modifiers computed with FastStatic were equivalent to pure MC within statistical uncertainties (0.5% for three standard deviations). Excellent agreement was achieved between TomoPen and C∕S for both asymmetric jaw opening∕constant couch speed and symmetric jaw opening∕variable couch speed, with deviations well within 2%∕2 mm. For RSS procedure, agreement between C∕S and measurements was within 2%∕2 mm for 95% of the points and 3%∕3 mm for 98% of the points, where dose is greater than 30% of the prescription dose (gamma analysis). Dose profiles acquired in transverse and longitudinal directions through the center of the phantom were also compared with excellent agreement (2%∕2 mm) between all modalities. CONCLUSIONS: The combination of weights modifiers and interpolation allowed implementing efficiently dynamic jaws and dynamic couch features into TomoPen at a minimal cost in terms of efficiency (simulation around 8 h on a single CPU).

State of the art on dose prescription, reporting and recording in Intensity-Modulated Radiation Therapy (ICRU report No. 83).

The International Commission on Radiation Units and Measurements (ICRU) report No. 83 provides the information necessary to standardize techniques and procedures and to harmonize the prescribing, recording, and reporting of intensity modulated radiation therapy. Applicable concepts and recommendations in previous ICRU reports concerning radiation therapy were adopted, and new concepts were elaborated. In particular, additional recommendations were given on the selection and delineation of the targets volumes and the organs at risk; concepts of dose prescription and dose-volume reporting have also been refined.

Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy.

With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D(98%), D(50%) and D(2%) values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.

A robust procedure for verifying TomoTherapy Hi-Art™ source models for small fields.

The dosimetric measurement and modeling of small radiation treatment fields (<2 × 2 cm2) are difficult to perform and prone to error. Measurements of small fields are often adversely influenced by the properties of the detectors used to make them. The dosimetric properties of small fields have been difficult to accurately model due to the effects of source occlusion caused by the collimating jaws. In this study, small longitudinal slice widths (SWs) of the TomoTherapy® Hi-Art® machine are characterized by performing dosimetric measurements topographically. By using a static gantry, opening the central 16 MLC leaves during the irradiations, and symmetrically scanning detectors 10 cm through each longitudinal SW, integral doses to a 'TomoTherapy equivalent' 10 × 10 cm2 area are topographically measured. To quantify the effects of source occlusion for TomoTherapy, a quantity referred to as the integral scanned dose to slice width ratio (D/SW) is introduced. (D/SW) ratios are measured for SWs ranging from 0.375 to 5 cm in size using ion chambers and a radiographic film. The measurements of the (D/SW) ratio are shown to be insensitive to the detectors used in this study. The (D/SW) ratios for TomoTherapy have values of unity in the range of SW sizes from 5 cm to approximately 2 cm. For SWs smaller than 2 cm in size, the source-occlusion effect substantially reduces the measured machine output and the value of the (D/SW) ratios. The topographic measurement method presented provides a way to directly evaluate the accuracy of the small-field source model parameters used in dose calculation algorithms. As an example, the electron source spot size of a Penelope Monte Carlo (MC) model of TomoTherapy was varied to match computed and measured (D/SW) ratios. It was shown that the MC results for small SW sizes were sensitive to that particular parameter.

On the relationships between electron spot size, focal spot size, and virtual source position in Monte Carlo simulations.

PURPOSE: Every year, new radiotherapy techniques including stereotactic radiosurgery using linear accelerators give rise to new applications of Monte Carlo (MC) modeling. Accurate modeling requires knowing the size of the electron spot, one of the few parameters to tune in MC models. The resolution of integrated megavoltage imaging systems, such as the tomotherapy system, strongly depends on the photon spot size which is closely related to the electron spot. The aim of this article is to clarify the relationship between the electron spot size and the photon spot size (i.e., the focal spot size) for typical incident electron beam energies and target thicknesses. METHODS: Three electron energies (3, 5.5, and 18 MeV), four electron spot sizes (FWHM = 0, 0.5, 1, and 1.5 mm), and two tungsten target thicknesses (0.15 and 1 cm) were considered. The formation of the photon beam within the target was analyzed through electron energy deposition with depth, as well as photon production at several phase-space planes placed perpendicular to the beam axis, where only photons recorded for the first time were accounted for. Photon production was considered for "newborn" photons intersecting a 45 x 45 cm2 plane at the isocenter (85 cm from source). Finally, virtual source position and "effective" focal spot size were computed by back-projecting all the photons from the bottom of the target intersecting a 45 x 45 cm2 plane. The virtual source position and focal spot size were estimated at the plane position where the latter is minimal. RESULTS: In the relevant case of considering only photons intersecting the 45 x 45 cm2 plane, the results unambiguously showed that the effective photon spot is created within the first 0.25 mm of the target and that electron and focal spots may be assumed to be equal within 3-4%. CONCLUSIONS: In a good approximation photon spot size equals electron spot size for high energy X-ray treatments delivered by linear accelerators.

Bragg peak prediction from quantitative proton computed tomography using different path estimates.

This paper characterizes the performance of the straight-line path (SLP) and cubic spline path (CSP) as path estimates used in reconstruction of proton computed tomography (pCT). The GEANT4 Monte Carlo simulation toolkit is employed to simulate the imaging phantom and proton projections. SLP, CSP and the most-probable path (MPP) are constructed based on the entrance and exit information of each proton. The physical deviations of SLP, CSP and MPP from the real path are calculated. Using a conditional proton path probability map, the relative probability of SLP, CSP and MPP are calculated and compared. The depth dose and Bragg peak are predicted on the pCT images reconstructed using SLP, CSP, and MPP and compared with the simulation result. The root-mean-square physical deviations and the cumulative distribution of the physical deviations show that the performance of CSP is comparable to MPP while SLP is slightly inferior. About 90% of the SLP pixels and 99% of the CSP pixels lie in the 99% relative probability envelope of the MPP. Even at an imaging dose of ∼0.1 mGy the proton Bragg peak for a given incoming energy can be predicted on the pCT image reconstructed using SLP, CSP, or MPP with 1 mm accuracy. This study shows that SLP and CSP, like MPP, are adequate path estimates for pCT reconstruction, and therefore can be chosen as the path estimation method for pCT reconstruction, which can aid the treatment planning and range prediction of proton radiation therapy.

Proof of principle of ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT-treated and 2D-treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D-RT.

On the use of a proton path probability map for proton computed tomography reconstruction.

PURPOSE: To describe a method to estimate the proton path in proton computed tomography (pCT) reconstruction, which is based on the probability of a proton passing through each point within an object to be imaged. METHODS: Based on multiple Coulomb scattering and a semianalytically derived model, the conditional probability of a proton passing through each point within the object given its incoming and exit condition is calculated in a Bayesian inference framework, employing data obtained from Monte Carlo simulation using GEANT4. The conditional probability at all of the points in the reconstruction plane forms a conditional probability map and can be used for pCT reconstruction. RESULTS: From the generated conditional probability map, a most-likely path (MLP) and a 90% probability envelope around the most-likely path can be extracted and used for pCT reconstruction. The reconstructed pCT image using the conditional probability map yields a smooth pCT image with minor artifacts. pCT reconstructions obtained using the extracted MLP and the 90% probability envelope compare well to reconstructions employing the method of cubic spline proton path estimation. CONCLUSIONS: The conditional probability of a proton passing through each point in an object given its entrance and exit condition can be obtained using the proposed method. The extracted MLP and the 90% probability envelope match the proton path recorded in the GEANT4 simulation well. The generated probability map also provides a benchmark for comparing different path estimation methods.

Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic energy from 250 to 200 MeV decreases the total neutron energy fluence produced by stopping a monoenergetic pencil beam in a water phantom by a factor of 2.3. It is possible to significantly lower the requirements on the maximum kinetic energy of a compact proton accelerator if the ability to treat a small percentage of patients with rotational therapy is sacrificed. This decrease in maximum kinetic energy, along with the corresponding decrease in neutron production, could lower the cost and ease the engineering constraints on a compact proton accelerator treatment facility.

A new formalism for reference dosimetry of small and nonstandard fields.

The use of small fields in radiotherapy techniques has increased substantially, in particular in stereotactic treatments and large uniform or nonuniform fields that are composed of small fields such as for intensity modulated radiation therapy (IMRT). This has been facilitated by the increased availability of standard and add-on multileaf collimators and a variety of new treatment units. For these fields, dosimetric errors have become considerably larger than in conventional beams mostly due to two reasons; (i) the reference conditions recommended by conventional Codes of Practice (CoPs) cannot be established in some machines and (ii) the measurement of absorbed dose to water in composite fields is not standardized. In order to develop standardized recommendations for dosimetry procedures and detectors, an international working group on reference dosimetry of small and nonstandard fields has been established by the International Atomic Energy Agency (IAEA) in cooperation with the American Association of Physicists in Medicine (AAPM) Therapy Physics Committee. This paper outlines a new formalism for the dosimetry of small and composite fields with the intention to extend recommendations given in conventional CoPs for clinical reference dosimetry based on absorbed dose to water. This formalism introduces the concept of two new intermediate calibration fields: (i) a static machine-specific reference field for those modalities that cannot establish conventional reference conditions and (ii) a plan-class specific reference field closer to the patient-specific clinical fields thereby facilitating standardization of composite field dosimetry. Prior to progressing with developing a CoP or other form of recommendation, the members of this IAEA working group welcome comments from the international medical physics community on the formalism presented here.