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Background This article is a summary of the quantitative imaging subgroup of the 2017 AAPM Practical Big Data Workshop (PBDW-2017) on progress and challenges in big data applied to cancer treatment and research supplemented by a draft white paper following an American Association of Physicists in Medicine FOREM meeting on Imaging Genomics in 2014. Aims The goal of PBDW-2017 was to close the gap between theoretical vision and practical experience with encountering and solving challenges in curating and analyzing data. Conclusions Recommendations based on the meetings are summarized.

A modular implementation of a scanning multi-source X-ray tube is designed for the increasing number of multi-source imaging applications in computed tomography (CT). An electron beam array coupled with an oscillating magnetic deflector is proposed as a means for producing an X-ray focal spot at any position along a line. The preliminary multi-source model includes three thermionic electron guns that are deflected in tandem by a slowly varying magnetic field and pulsed according to a scanning sequence that is dependent on the intended imaging application. Particle tracking simulations with particle dynamics analysis software demonstrate that three 100 keV electron beams are laterally swept a combined distance of 15 cm over a stationary target with an oscillating magnetic field of 102 G perpendicular to the beam axis. Beam modulation is accomplished using 25 μ s pulse widths to a grid electrode with a reverse gate bias of −500 V and an extraction voltage of +1000 V. Projected focal spot diameters are approximately 1 mm for 138 mA electron beams and the stationary target stays within thermal limits for the 14 kW module. This concept could be used as a research platform for investigating high-speed stationary CT scanners, for lowering dose with virtual fan beam formation, for reducing scatter radiation in cone-beam CT, or for other industrial applications.

Uranyl nitrate hexahydrate [UO2(NO3)2 · 6H2O] (UNH) holds interest as a potential nuclear reactor fuel for manufacturing the key medical isotope 99mTc through the production and subsequent decay of...

A semi-automatic image segmentation method, called SAMBAS, based on workflow familiar to clinical radiologists is described. The user initializes 3D segmentation by drawing a long axis on a multi-plane reformat (MPR). As the user draws, a 2D segmentation updates in real-time for interactive feedback. When necessary, additional long axes, short axes, or other editing operations may be drawn on one or more MPR planes. The method learns probability distributions from the drawing to perform the MPR segmentation, and in turn, it learns from the MPR segmentation to perform the 3D segmentation. As a preliminary experiment, a batch simulation was performed where long and short axes were automatically drawn on each of 285 multispectral MR brain scans of glioma patients in the 2018 BraTS Challenge training data. Average Dice coefficient for tumor core was 0.86, and the Hausdorff-95% distance was 4.4 mm. As another experiment, a convolution neural network was trained on the same data, and applied to the BraTS validation and test data. Its outputs, computed offline, were integrated into the interactive method. Ten volunteers used the interface on the BraTS validation and test data. On the 66 scans of the validation data, average Dice coefficient for core tumor improved from 0.76 with deep learning alone, to 0.82 as an interactive system.

The central goal of this design is to meet U.S. demand for the medical isotope 99Mo with a water-cooled critical reactor featuring discrete, cladded fuel elements. 99Mo is produced within the solid fuel that is powering the fission reaction. The fuel is a low-enriched uranyl nitrate hexahydrate crystal, chosen to take advantage of a flexible uranium recovery process. The low melting temperature of the fuel material has required utilizing an annular fuel pin geometry. Preliminary heat transfer calculations and MCNP modeling have demonstrated the capability of such a design to produce the desired quantities of 99Mo.

Universities and society benefit from academic entrepreneurship. Unfortunately, policies and procedures often have the effect of discouraging entrepreneurship by academics. While the culture of entrepreneurship is changing in university leadership and among faculty and students there are many administration policies which hamper entrepreneurial engagement with society. This chapter examines how academic entrepreneurship can be better managed by universities.

Intensity modulated radiation therapy (IMRT) is performed on a regular basis in the clinic to create complex radiation fields to treat cancer, but it has not been implemented in microradiotherapy (mRT) for preclinical systems. A multileaf collimator (MLC) is an integral part of a radiotherapy system that allows IMRT application. Presented here is the development of a key component of an open source mRT system for preclinical research. We have designed and fabricated a binary micro multileaf collimator (bmMLC) for mRT that can provide 1 mm or better resolution at isocenter and attenuate over 98% of a 250 kVp X-ray beam. This is the smallest collimator system designed for RT systems, with 20 brass leaves, each 0.5 mm thick, creating a physical field opening of 1 cm × 1 cm. The mode of actuation for the leaves was rotational, rather than linear, which is typical in larger clinical RT systems. The design presented here met the identified design requirements and represents a rigorous design process, during which several less successful designs were investigated and eventually discarded. After the fabrication of the design, dosimetric characteristics were tested and requirements were met. The final bmMLC designs and technical documents are made available as open-source.

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.

Background Three-dimensional (3D) printing has become a useful method of fabrication for many clinical applications. It is also a technique that is becoming increasingly accessible, as the price of the necessary tools and supplies decline. One emerging, and unreported, application for 3D printing is to aid in the visualization of 3D imaging data by creating physical models of select structures of interest. Methods Presented here are three physical models that were fabricated from three different 3D microscopy datasets. Different methods of fabrication and imaging techniques were used in each case. Results Each model is presented in detail. This includes the imaging modality used to capture the raw data, the software used to create any computer models and the 3D printing tools used to create each model. Despite the differences in their creation, these examples follow a simple common workflow that is also detailed. Conclusions Following these approaches, one can easily make 3D printed models from 3D microscopy datasets utilizing off the shelf commercially available software and hardware.

This work builds on a suite of studies related to the ‘interplay’, or lack thereof, for respiratory motion with helical tomotherapy (HT). It helps explain why HT treatments without active motion management had clinical outcomes that matched positive expectations. An analytical calculation is performed to illuminate the frequency range for which interplay‐type dose errors could occur. Then, an experiment is performed which completes a suite of tests. The experiment shows the potential for a stable motion probability distribution function (PDF) with HT and respiratory motion. This PDF enables one to use a motion‐robust or probabilistic optimization to intrinsically include respiratory motion into the treatment planning. The reason why HT is robust to respiratory motion is related to the beam modulation sampling of the tumor motion. Because active tracking‐based motion management is more complicated for a variety of reasons, HT optimization that is robust to motion is a useful alternative for those many patients that cannot benefit from active motion management. PACS number: 87.55.‐x, 87.56.‐v

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 [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 60Co 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 60Co 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 kQ, Q o defined in Alfonso [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%).

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 (

Purpose To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials A total of 18 non–small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.

Rapid development in imaging techniques, including functional imaging, have fueled the drive to implement new methods of delivering 3D radiation therapy, such as intensity-modulated radiation therapy, with unprecedented accuracy. The International Commission on Radiation Units and Measurements (ICRU) Report 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 other International Commission on Radiation Units and Measurements reports concerning radiation therapy were adopted, and new concepts and recommendations were elaborated. In particular, additional recommendations were given on the selection and delineation of the target volumes and the organs at risk; concepts of dose prescription and dose-volume reporting have also been refined.

The purpose of this study was to determine the maximum proton kinetic energy required to treat a given percentage of patients eligible for stereotactic radiosurgery (SRS) with coplanar arc‐based proton therapy, contingent upon the number and location of gantry angles used. Treatment plans from 100 consecutive patients treated with SRS at the University of Wisconsin Carbone Cancer Center between June of 2007 and March of 2010 were analyzed. For each target volume within each patient, in‐house software was used to place proton pencil beam spots over the distal surface of the target volume from 51 equally‐spaced gantry angles of up to 360°. For each beam spot, the radiological path length from the surface of the patient to the distal boundary of the target was then calculated along a ray from the gantry location to the location of the beam spot. This data was used to generate a maximum proton energy requirement for each patient as a function of the arc length that would be spanned by the gantry angles used in a given treatment. If only a single treatment angle is required, 100% of the patients included in the study could be treated by a proton beam with a maximum kinetic energy of 118 MeV. As the length of the treatment arc is increased to 90°, 180°, 270°, and 360°, the maximum energy requirement increases to 127, 145, 156, and 179 MeV, respectively. A very high percentage of SRS patients could be treated at relatively low proton energies if the gantry angles used in the treatment plan do not span a large treatment arc. Maximum proton kinetic energy requirements increase linearly with size of the treatment arc. PACS numbers: 87.55.‐x, 87.53.Ly, 87.53.Bn

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., thefocal 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 × 45 cm 2 plane at the isocenter (85 cm from source). Finally, virtual source position and “effective” focal spot size were computed by backprojecting all the photons from the bottom of the target intersecting a 45 × 45 cm 2 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 × 45 cm 2 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.

The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water™ phantom was used to simulate a moving lung tumor inside of the LUNGMAN™ anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT™ film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA™ software was used to verify the delivery performed on a TomoTherapy Hi-Art II™ device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.

Purpose To assess patient setup corrections based on daily megavoltage CT (MVCT) imaging for four anatomic treatment sites treated on tomotherapy. Method and Materials Translational and rotational setup corrections, based on registration of daily MVCT to planning CT images, were analyzed for 1,179 brain and head and neck (H&N), 1,414 lung, and 1,274 prostate treatment fractions. Frequencies of three-dimensional vector lengths, overall distributions of setup corrections, and patient-specific distributions of random and systematic setup errors were analyzed. Results Brain and H&N had lower magnitude positioning corrections and smaller variations in translational setup errors but were comparable in roll rotations. Three-dimensional vector translational shifts of larger magnitudes occurred more frequently for lung and prostate than for brain and H&N treatments, yet this was not observed for roll rotations. The global systematic error for prostate was 4.7 mm in the vertical direction, most likely due to couch sag caused by large couch extension distances. Variations in systematic errors and magnitudes of random translational errors ranged from 1.6 to 2.6 mm for brain and H&N and 3.2 to 7.2 mm for lung and prostate, whereas roll rotational errors ranged from 0.8° to 1.2° for brain and H&N and 0.5° to 1.0° for lung and prostate. Conclusions Differences in setup were observed between brain, H&N, lung, and prostate treatments. Patient setup can be improved if daily imaging is performed. This analysis can assess the utilization of daily image guidance and allows for further investigation into improved anatomic site-specific and patient-specific treatments.

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.

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.

Organ motion and injury to adjacent structures limit curative treatment of intraabdominal tumors with external beam radiotherapy. We evaluated the use of Laparoscopically Implanted Tissue Expander Radiotherapy (LITE-RT) to exclude critical structures during irradiation of the urinary bladder in two dogs with transitional cell carcinoma (TCC) using helical tomotherapy. Dogs had histologically confirmed bladder TCC with no metastasis. A custom-shaped tissue expander was placed between the colon and bladder laparoscopically in one dog and during laparotomy in the other. The prescribed radiation dose was 45 Gy to 98% volume of the bladder in 18 fractions of 2.5 Gy. Tumor response and normal tissue effects were monitored with cystoscopy and colonic biopsies before treatment and 3, 6, and 15 months after treatment. Based on treatment plans from inflated vs. deflated tissue expander CT images, there was a mean dose reduction to the colon of 53% and 31% for the two dogs. Interfractional target repositioning was possible by using volumetric megavoltage computed tomography helical tomotherapy. Both dogs had no clinical signs of chronic colitis but did experience mild cystitis during treatment. Tissue expanders became detached, requiring an additional surgery for reattachment, in both dogs. One dog developed a fibrous adhesion resulting in bladder rupture during inflation, which necessitated early device removal. One dog was euthanized for tumor-associated ureteral obstruction at 8 months while the other is alive at 21 months. We conclude that LITE-RT shows promise in treatment of canine bladder TCC due to lack of acute colitis and enteritis.

It has been suggested for quality assurance purposes that linac output variations for helical tomotherapy (HT) be within +/-2% of the long-term average. Due to cancellation of systematic uncertainty and averaging of random uncertainty over multiple beam directions, relative uncertainties in the dose distribution can be significantly lower than those in linac output. The sensitivity of four HT cases with respect to linac output uncertainties was assessed by scaling both modeled and measured systematic and random linac output uncertainties until a dose uncertainty acceptance criterion failed. The dose uncertainty acceptance criterion required the delivered dose to have at least a 95% chance of being within 2% of the planned dose in all of the voxels in the treatment volume. For a random linac output uncertainty of 5% of the long-term mean, the maximum acceptable amplitude of the modeled, sinusoidal, systematic component of the linac output uncertainty for the four cases was 1.8%. Although the measured linac output variations represented values that were outside of the +/-2% tolerance, the acceptance criterion did not fail for any of the four cases until the measured linac output variations were scaled by a factor of almost three. Thus, the +/-2% tolerance in linac output variations for HT is a more conservative tolerance than necessary.

Feasibility of delivering a simultaneously integrated boost to canine nasal tumors using helical tomotherapy to improve tumor control probability (TCP) via an increase in total biological equivalent uniform dose (EUD) was evaluated. Eight dogs with varying size nasal tumors (5.8-110.9 cc) were replanned to 42 Gy to the nasal cavity and integrated dose boosts to gross disease of 45.2, 48.3, and 51.3 Gy in 10 fractions. EUD values were calculated for tumors and mean normalized total doses (NTD(mean)) for organs at risk (OAR). Normal Tissue Complication Probability (NTCP) values were obtained for OARs, and estimated TCP values were computed using a logistic dose-response model and based on deliverable EUD boost doses. Significant increases in estimated TCP to 54%, 74%, and 86% can be achieved with 10%, 23%, and 37% mean relative EUD boosts to the gross disease, respectively. NTCP values for blindness of either eye and for brain necrosis were < 0.01% for all boosts. Values for cataract development were 31%, 42%, and 46% for studied boost schemas, respectively. Average NTD(mean) to eyes and brain for mean EUD boosts were 10.2, 11.3, and 12.1 Gy3, and 7.5, 7.2, and 7.9 Gy2, respectively. Using helical tomotherapy, simultaneously integrated dose boosts can be delivered to increase the estimated TCP at 1-year without significantly increasing the NTD(mean) to eyes and brain. Delivery of these treatments in a prospective trial may allow quantification of a dose-response relationship in canine nasal tumors.

To evaluate the feasibility of using tomotherapy to deliver whole brain radiotherapy with hippocampal avoidance, hypothesized to reduce the risk of memory function decline, and simultaneously integrated boost to brain metastases to improve intracranial tumor control.Ten patients treated with radiosurgery and whole brain radiotherapy underwent repeat planning using tomotherapy with the original computed tomography scans and magnetic resonance imaging-computed tomography fusion-defined target and normal structure contours. The individually contoured hippocampus was used as a dose-limiting structure (6 Gy); the whole brain dose was prescribed at 32.25 Gy to 95% in 15 fractions, and the simultaneous boost doses to individual brain metastases were 63 Gy to lesionsor=2.0 cm in the maximal diameter and 70.8 Gy to lesions2.0 cm. The plans were generated with a field width (FW) of 2.5 cm and, in 5 patients, with a FW of 1.0 cm. The plans were compared regarding conformation number, prescription isodose/target volume ratio, target coverage, homogeneity index, and mean normalized total dose.A 1.0-cm FW compared with a 2.5-cm FW significantly improved the dose distribution. The mean conformation number improved from 0.55 +/- 0.16 to 0.60 +/- 0.13. Whole brain homogeneity improved by 32% (p0.001). The mean normalized total dose to the hippocampus was 5.9 +/- 1.3 Gy(2) and 5.8 +/- 1.9 Gy(2) for 2.5- and 1.0-cm FW, respectively. The mean treatment delivery time for the 2.5- and 1.0-cm FW plans was 10.2 +/- 1.0 and 21.8 +/- 1.8 min, respectively.Composite tomotherapy plans achieved three objectives: homogeneous whole brain dose distribution equivalent to conventional whole brain radiotherapy; conformal hippocampal avoidance; and radiosurgically equivalent dose distributions to individual metastases.

The purpose of this study was to measure and compare the loss of buildup to the skin of the breast in the prone position due to 2 different positioning systems during tangential external beam irradiation. Two experiments were performed; one with a standard nylon-covered foam support and another with a novel helium-filled Mylar bag support. The choice of helium-filled Mylar was to reduce the contamination to as low as possible. The experiments were designed to allow a surface dose measurement and a depth dose profile with the pads placed in the path of the beam in front of the detector. All measurements were taken using a Capintec PS-033 thin-window parallel plate ionization chamber. The standard nylon-covered foam pad caused the surface dose to rise as it got closer to the skin. When the pad was directly touching the surface, the surface dose increased by 300% compared to the result when no pad was present. This loss of buildup to the surface was similar to that of a custom bolus material. The opposite effect occurred with the use of the helium-filled Mylar bag, namely the surface dose gradually decreased as the pad got closer to the phantom. When the Mylar pad was directly touching the phantom, the surface dose was decreased by 7% compared to when no pad was present. The use of a foam pad could potentially result in a significant higher dose to the skin, resulting in an enhanced acute skin reaction. Therefore, special care should be taken in this clinical scenario and further investigation of an air- or helium-based mylar support pad should be investigated in the context of definitive breast radiation treatment.

Tomotherapy is the delivery of intensity modulated radiation therapy using rotational delivery of a fan beam in the manner of a CT scanner. In helical tomotherapy the couch and gantry are in continuous motion akin to a helical CT scanner. Helical tomotherapy is inherently capable of acquiring CT images of the patient in treatment position and using this information for image guidance. This review documents technological advancements of the field concentrating on the conceptual beginnings through to its first clinical implementation. The history of helical tomotherapy is also a story of technology migration from academic research to a university-industrial partnership, and finally to commercialization and widespread clinical use.

Background: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose × tissue volume) received by normal tissue (NTID) was calculated from dose–volume histograms. Results: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20 MV beam plans resulted in 7.7%–11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. Conclusions: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.

In image-guided radiation therapy, megavoltage computerized tomography (MVCT) delivers higher dose to the patient for lower image quality than diagnostic kilovoltage CT (kVCT). One way to reduce the mean imaging dose is to reduce the imaging volume, which is often sufficient for registration and dosimetry purposes. The filtered back projection using truncated data causes artefacts that degrade the image quality. Those artefacts can be effectively reduced by wavelet-based multi-resolution analysis (WMRA), in which the detail and approximate information are reconstructed separately to bypass the non-locality of filtered back projection. In this study, WMRA was used to reconstruct local images from both very low-dose kVCT scans from a bench-top tomotherapy unit and MVCT scans from helical tomotherapy. Results show that mean imaging dose can be significantly reduced by imaging a small region of interest. In simulation, the root-mean-square error brought by the truncation is smaller than 1-2% and depends on the level of dose reduction. On the other hand, the same mean dose that would have been delivered by a low-quality global CT can be conformed to a smaller volume to improve the visibility of low-contrast organs and fine structures using WMRA. Organs at risk can be avoided during repeated daily CT imaging when irregular-shaped reconstruction areas are used. WMRA does not involve computationally expensive iterations and is suitable for image-guided radiation therapy where imaging speed is essential. Compared with extrapolation methods, errors are further reduced to improve the detection of low contrast and fine structures.

Current dosimetric protocols based on the absorbed dose (AAPM TG-51 and IAEA TRS-398 protocols) require calibration measurements under reference conditions. For some radiotherapy systems, this requirement cannot be met, and calibration has to be performed under nonreference experimental conditions. In order to solve this problem, both protocols can be extended by inclusion of the measured-to-reference conversion factor, k(mr). In order to determine this factor, basic dosimetric quantities, like stopping power ratios, mass attenuation coefficients and chamber correction factors have to be calculated. If measurements are not feasible, accurate Monte Carlo modeling is required. The extension of the protocols is illustrated using the case of the helical tomotherapy radiation unit, where the typical calibration measurement conditions are the 10 x 5 cm2 field size and the 85 cm surface source distance, limited by the system design. It was calculated that the k(mr) factor for this conditions is close to unity (0.997+/-0.001). In addition, the deviation of the measurement conditions from the reference conditions results in the change of the quality conversion factor (approximately 0.995-0.998, depending on the ionization chamber used). This change is the same regardless of the used calibration protocol. For smaller field sizes the corrections become more significant, resulting in the total correction factor compared to the reference conditions of up to 1.5% for the smallest considered field size of 2 x 2 cm2.

Purpose To evaluate the utility of relatively low-dose megavoltage computed tomography (MVCT) images from a clinical helical tomotherapy system for setup verification purposes. Methods and materials Cross-sectional kilovolt computed tomography (kVCT) images were obtained for treatment planning purposes on a diagnostic third-generation CT scanner, followed by MVCT images from a helical tomotherapy system in 8 pet dogs with spontaneously occurring tumors. The kVCT and MVCT images were aligned for setup verification purposes, allowing repositioning before treatment delivery. Results Tumors are readily visualized on the MVCT images. At a dose of 2–3 cGy, the MVCT images are of sufficient quality for verification of treatment setup, but soft-tissue contrast is inferior to that with conventional kVCT. The MV and kVCT images were successfully aligned. When necessary, patients undergoing helical tomotherapy were repositioned before treatment. Conclusions Megavoltage CT image quality is sufficient for tumor identification and three-dimensional setup verification in dogs with spontaneous tumors. The MVCT images can be aligned with the planning kVCT to ensure proper patient registration before treatment. Image alignment was successful in these canine patients, despite no skin markings defining patient positioning between the two scans. MVCT images facilitate setup verification, and their tomographic nature offers improvements over conventional portal imaging.

A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during C T. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. “Hot spots” (≥150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

Similar to conventional conformal radiotherapy, during lung tomotherapy, a motion margin has to be set for respiratory motion. Consequently, large volume of normal tissue is irradiated by intensive radiation. To solve this problem, we have developed a new motion mitigation method by incorporating target motion into treatment optimization. In this method, the delivery-breathing correlation is determined prior to treatment plan optimization. Beamlets are calculated by using the CT images at the corresponding breathing phases from a dynamic (four-dimensional) image sequence. With the displacement vector fields at different breathing phases, a set of deformed beamlets is obtained by mapping the dose to the primary phase. Optimization incorporating motion is then performed by using the deformed beamlets obtained by dose mapping. During treatment delivery, the same breathing-delivery correlation can be reproduced by instructing the patient to breathe following a visually displayed guiding cycle. This method was tested using a computer-simulated deformable phantom and a real lung case. Results show that treatment optimization incorporating motion achieved similar high dose conformality on a mobile target compared with static delivery. The residual motion effects due to imperfect breathing tracking were also analyzed.

Daily imaging during the course of a fractionated radiotherapy treatment has the potential for frequent intervention and therefore effective adaptation of the treatment to the individual patient. The treatment information gained from such images can be analysed and updated daily to obtain a set of patient individualized parameters. However, in many situations, the uncertainty with which these parameters are estimated cannot be neglected. In this work this methodology is applied to the adaptive estimation of setup errors, the derivation of a daily optimal pre-treatment correction strategy, and the daily update of the treatment margins after application of these corrections. For this purpose a dataset of 19 prostate cancer patients was analysed retrospectively. The position of the prostate was measured daily with an optically guided 3D ultrasound localization system. The measurement uncertainty of this system is approximately 2 mm. The algorithm finds the most likely position of the target maximizing an a posteriori probability given the set of measurements. These estimates are used for the optimal corrections applied to the target volume. The results show that the application of the optimal correction strategy allows a reduction in the treatment margins in a systematic way with increasing progression of the treatment. This is not the case using corrections based only on the measured values that do not take the measurement uncertainty into account.

The Monte Carlo method is the most accurate method for radiotherapy dose calculations, if used correctly. However, any Monte Carlo dose calculation is burdened with statistical noise. In this paper, denoising of Monte Carlo dose distributions with a three-dimensional adaptive anisotropic diffusion method was investigated. The standard anisotropic diffusion method was extended by changing the filtering parameters adaptively according to the local statistical noise. Smoothing of dose distributions with different noise levels in an inhomogeneous phantom, a conventional and an IMRT treatment case is shown. The resultant dose distributions were analysed using several evaluating criteria. It is shown that the adaptive anisotropic diffusion method can reduce statistical noise significantly (two to five times, corresponding to the reduction of simulation time by a factor of up to 20), while preserving important gradients of the dose distribution well. The choice of free parameters of the method was found to be fairly robust.

Under various clinical situations, it is desirable to modify the original treatment plan to better suit the clinical goals. In this work, a method to help physicians modify treatment plans based on their clinical preferences is proposed. The method uses a weighted quadratic dose objective function. The commonly used organ-/ROI-based weighting factors are expanded to a set of voxel-based weighting factors in order to obtain greater flexibility in treatment plan modification. Two different but equivalent modification schemes based on Rustem's quadratic programming algorithms--modification of a weighting matrix and modification of prescribed doses--are presented. Case studies demonstrated the effectiveness of the two methods with regard to their capability to fine-tune treatment plans.

Patient motion, especially respiratory motion, results in various artefacts such as blurring and streaks in tomographic images. The interplay of the movement of the beam aperture and variations of organ anatomy during delivery can create 'hot' and 'cold' spots throughout the field in intensity-modulated radiation therapy (IMRT). Detection and correction of patient motion is extremely important in tomographic imaging and IMRT. Tomographic projection data (sinogram) encode not only the patient anatomy information, but also the intra-scanning motion information. In this paper, we developed an algorithm to detect and correct the in-plane respiratory motion directly in sinogram space. The respiratory motion is modelled as time-varying scaling along the x and y directions. Its effects on the sinogram are discussed. Based on the traces of some nodal points in the sinogram, the intra-scanning motion is determined. The motion correction is also implemented in sinogram space. The motion-corrected sinogram is used for reconstruction by the filtered back-projection (FBP) method. Computer simulations validate the motion detection and correction algorithm. The reconstructed images from the motion-corrected sinogram eliminate the majority of the artefacts. The method could be applied to projection data used in CT and ECT, as well as in tomotherapy delivery modification and dose reconstruction.

Multi-modal imaging approaches of tumor metabolism that provide improved specificity, physiological relevance and spatial resolution would improve diagnosing of tumors and evaluation of tumor progression. Currently, the molecular probe FDG, glucose fluorinated with (18)F at the 2-carbon, is the primary metabolic approach for clinical diagnostics with PET imaging. However, PET lacks the resolution necessary to yield intratumoral distributions of deoxyglucose, on the cellular level. Multi-modal imaging could elucidate this problem, but requires the development of new glucose analogs that are better suited for other imaging modalities. Several such analogs have been created and are reviewed here. Also reviewed are several multi-modal imaging studies that have been performed that attempt to shed light on the cellular distribution of glucose analogs within tumors. Some of these studies are performed in vitro, while others are performed in vivo, in an animal model. The results from these studies introduce a visualization gap between the in vitro and in vivo studies that, if solved, could enable the early detection of tumors, the high resolution monitoring of tumors during treatment, and the greater accuracy in assessment of different imaging agents.

For any radiotherapy verification technique, it is desirable that issues with the accelerator, multileaf collimator and patient position be detected. In previous works, an effective method for this level of verification was presented. This paper identifies second-order issues affecting the part of the process in which the incident energy fluence is verified. These problems will affect any rotational intensity-modulated radiotherapy delivery that divides each rotation or arc into projections: however the solutions offered in this paper are specific to the method previously developed. The issues affecting the energy fluence verification method include leaf bouncing. delivery implementation and leaf latency. All three matters were found to introduce small errors in the verified energy fluence values for a small fraction of leaf states. The overall effect on the deposited dose over the course of a rotational delivery involving thousands of beam pulses per rotation is negligible. Regardless, effective correction strategies are presented; these are utilized in order to characterize both the delivered energy fluence and deposited dose as accurately as possible.

An integrated tomotherapy system allows for improved radiotherapy verification by enabling the collection of megavoltage computed tomography (MVCT) images before or after treatment delivery. In this investigation, the possibility of collecting MV tomographic data and reconstructing images during a tomotherapy treatment is examined. By overcoming difficulties with the normalization of modulated treatment data and with the incompleteness of treatment data, it is possible to use data collected during tomotherapeutic treatments for MVCT reconstruction. The benefits of these techniques include potential increases in patient throughput, reductions in imaging dose, visualization of the patient in the treatment position and improvements in image contrast.

This paper will present the results of an investigation into three iterative approaches to inverse treatment planning. These techniques have been examined in the hope of developing an optimization algorithm suitable for the large-scale problems that are encountered in tomotherapy. The three iterative techniques are referred to as the ratio method, iterative least-squares minimization and the maximum-likelihood estimator. Our results indicate that each of these techniques can serve as a useful tool in tomotherapy optimization. As compared with other mathematical programming techniques, the iterative approaches can reduce both memory demands and time requirements. In this paper, the results from small- and large-scale optimizations will be analysed. It will also be demonstrated that the flexibility of the iterative techniques can be greatly enhanced through the use of dose-volume histogram based penalty functions and/or through the use of weighting factors assigned to each region of the patient. Finally, results will be presented from an investigation into the stability of the iterative techniques.

A technique for 2D or 3D image/patient registration, PFPM (projection based Fourier phase matching method), is proposed. This technique provides image/patient registration directly from sequential tomographic projection data. The method can also deal with image files by generating 2D Radon transforms slice by slice. The registration in projection space is done by calculating a Fourier invariant (FI) descriptor for each one-dimensional projection datum, and then registering the FI descriptor by the Fourier phase matching (FPM) method. The algorithm has been tested on both synthetic and experimental data. When dealing with translated, rotated and uniformly scaled 2D image registration, the performance of the PFPM method is comparable to that of the IFPM (image based Fourier phase matching) method in robustness, efficiency, insensitivity to the offset between images, and registration time. The advantages of the former are that subpixel resolution is feasible, and it is more insensitive to image noise due to the averaging effect of the projection acquisition. Furthermore, the PFPM method offers the ability to generalize to 3D image/patient registration and to register partial projection data. By applying patient registration directly from tomographic projection data, image reconstruction is not needed in the therapy set-up verification, thus reducing computational time and artefacts. In addition, real time registration is feasible. Registration from partial projection data meets the geometry and dose requirements in many application cases and makes dynamic set-up verification possible in tomotherapy.

Multileaf collimators (MLCs) have advanced past their original design purpose as a replacement for field shaping cerrobend blocks. Typically, MLCs incorporate an interlocking tongue-and-groove design between adjacent leaves to minimize leakage between leaves. They are beginning to be used to provide intensity modulation for conformal three-dimensional radiation therapy. It is possible that a critical target volume may receive an underdose due to the region of overlap if adjacent leaves are allowed to alternate between the open and closed positions, as they might if intensity modulation is employed. This work demonstrates the magnitude of that effect for a commercially available one-dimensional temporally modulated MLC. The magnitude of the transmission between leaves as a function of leaf separation was also studied, as well as the transmission as a function of leaf rotation away from the source. The results of this work were used for the design of a tomotherapy MLC. The radiation leakage considerations for a tomotherapy MLC are discussed.

Patient registration, a technique to ensure dose conformity, is an essential part of tomographic radiotherapy. A new six parameter (three translational and three angular) algorithm to implement this technique has been developed. The method is stable, accurate, and most importantly uses sinogram data as input, obviating image reconstruction. A sinogram, an array of Radon transforms, is derived directly from the raw data, which are photon transmission fluences from either a diagnostic or a megavoltage X-ray source. The algorithm uses properties of the Radon and Fourier transforms, such as the central slice theorem and Fourier shift theorem, to decouple translational and angular offsets. The theoretical underpinnings of this algorithm are presented here, whereas numerical verification using synthetic and experimental data is presented elsewhere.

Stopping-power ratios are a function of field size and vary with accelerators. To investigate how these variations affect relative output factor measurements made using ion chambers for electron beams, especially for small fields, (L/rho)air(water) is calculated using the Monte Carlo technique for different field sizes, beam energies, and accelerators and is compared to the data in TG-21 or TG-25, which are for mono-energetic broad beams. For very small field sizes defined by cutouts, if the change in (L/rho)air(water) with dmax is ignored (i.e., TG-25 is not carefully followed), there is an overestimate of relative output factors by up to 3%. Ignoring the field-size effect on stopping-power ratio adds an additional overestimate of up to one-half percent, and using mono-energetic stopping-power ratio data instead of realistic beam data gives another error, but in the opposite direction, of up to 0.7%. Due to the cancellation of these latter two errors, following TG-25 with (L/rho)air(water) data for broad mono-energetic beams will give the correct answer for the ROF measurement within 0.4% compared to using (L/rho)air(water) data for which the field-size effect is considered for realistic electron beams.

The objective of this study was to document the utility of computed tomography (CT) and a three-dimensional (3-D) radiotherapy treatment planning system for assessing the development of acute radiation pneumonitis in a canine model. Fourteen dogs were randomly assigned to a nonirradiated control group or one of three radiation dose groups receiving a single fraction of either 12, 15, or 18 Gy delivered to two-thirds of the right hemithorax. CT and survey radiographs were performed in all dogs prior to and at defined intervals for up to 13 weeks following irradiation. All images were subjectively evaluated for development of radiation pneumonitis and CT images were quantitatively analyzed. Radiation pneumonitis was detected earlier with CT images than with radiographs. Quantitatively, functional lung volume and radiation pneumonitis lesion volume on CT images changed over time in all irradiated dogs. However, there was no statistically significant difference between the three radiation dose groups, but a marked difference between irradiated dogs and nonirradiated controls. These data suggest that CT is superior to survey radiography for the evaluation and quantification of acute radiation pneumonitis in this canine model. Quantification of acute radiation pneumonitis suggests future promise for evaluating the efficacy of modifiers to lessen the effects of irradiating normal lung tissue in this canine model.

Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS) are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.