bluuebunny/crossref_metadata_2025 huggingface dataset:
TU‐E‐BRB‐01: Is AcurosXBTM Equivalent in Accuracy to Monte Carlo for Complex IMRT and VMAT Dose Calculations?
Authors: Ansbacher W , Bush K , Gagne I , Zavgorodni S , Beckham W
Published: November 2011

Purpose: To assess the accuracy of a new algorithm, a deterministic solution of the Boltzmann Transport Equations (AcurosXB,TM, Varian Medical Systems), in intensity‐modulated (IMRT) and volumetric‐modulated (VMAT) planning against a benchmark Monte Carlo system and a standard clinical algorithm (AAA, Varian Medical Systems) Method and Materials: Four sites were chosen: prostate, lung, oropharynx and nasopharynx, each exhibiting characteristic challenges for planning. CT‐based plans using 6MV IMRT and VMAT delivery were developed for each site and calculated as dose‐to‐water using Acuros v. 11 and AAA v. 10. Plans were exported to and calculated on a 36‐CPU implementation of the EGSnrc‐BEAMnrc MonteCarlo code with better than 1% statistical uncertainty. Dose and DVH differences were evaluated in the Varian‐Eclipse environment for the target PTVs and relevant critical OARs. Results: Dosimetric differences between Acuros and MonteCarlo were in general much smaller than between AAA and MonteCarlo. For Acuros, the greatest differences occurred in low density lung (densities < 0.1 g/cc) or in air cavities, and were less than 5% of the target dose, extending over regions no greater than 5mm. Corresponding AAA differences were as high as 7% and extended for up to 10mm into higher‐density tissues. As a result, the mean lung PTV dose difference was less than 0.5% for Acuros, but 1.7% for AAA. For the other three sites, the Acuros dose differences were within 3% over more than 97% of a representative volume defined by the 60% isodose contours. AAA dose differences were within 3% over 94% of the volume. Conclusions: Within normal tissue‐like materials (densities up to 1.6g/cc) and in complex clinical planning scenarios involving dynamic beam modulation, Acuros and MonteCarlo generally agreed within the statistical precision of the MonteCarlo dose calculations. Small discrepancies beyond this level could be attributed to differences in treatment head and MLC modelling between Eclipse and BEAMnrc.

Partial funding provided through a research agreement with Varian Medical Systems
TU‐E‐BRB‐07: Feasibility of a Dedicated Breast CT Platform for Orthovoltage Rotational External Beam Radiation Therapy: A Simulation Study
Authors: Prionas N , McKenney S , Boone J
Published: November 2011

Purpose: To evaluate the feasibility of a dedicated breast computed tomography (bCT) platform to deliver therapeutic dose distributions, specifically for partial breast irradiation (PBI), whole breast irradiation (WBI), and dose painting, through orthovoltage rotational external beam radiation therapy (EBRT).Methods: Rotational EBRT using the geometry of a prototype bCT platform was evaluated by means of MCNPX Monte Carlo simulator. A 178 keV monoenergetic photon source was used to approximate 320 kVp photons filtered by 4 mm of copper, as validated by depth‐dose characteristics in polyethylene. The source was rotated around a 14 cm voxelized polyethylene disk (0.1 cm tall) or cylinder (9 cm tall) to simulate primary and primary + scattered photon interactions, respectively. Simulations were also performed using bCT patient images. Beam collimation was varied in the x‐y plane of rotation (1–14 cm) and in the z‐direction (0.1–10 cm).Results: As x‐y collimation narrowed, 2D dose profiles shifted from a cupped profile with high edge dose (14 cm beam) to an increasingly peaked central dose. A 1 cm beam had a center‐to‐cylinder edge dose ratio of 14.8. Similar distributions were observed experimentally. Dose painting for multiple foci, a line distribution, and a ring distribution was demonstrated using multiple rotations with varying collimation. A homogeneous dose distribution (<5% fluctuation) with skin sparing was demonstrated by weighted summation of four dose profiles. Using 2 cm z‐collimation, scatter tails decreased exponentially towards the cylinder top/bottom to 3% of maximum dose. Simulations using patient bCT images demonstrated the potential for treatment planning and image‐guided therapy. Conclusions: A bCT platform can feasibly deliver orthovoltage rotational EBRT for the treatment of breast cancer. A variety of dose distributions can be generated allowing for PBI to a single focus, dose painting, and WBI with skin sparing. Dedicated bCT is a potential platform for image‐guided radiation therapy.

One author is a consultant to Varian Imaging Systems (Palo Alto, Calif) and Artemis (Erlangen, Germany) and receives funding from Varian Imaging Systems, Fuji Medical Systems (Stamford, Conn), and Hologic (Bedford, Mass).
TU‐E‐BRC‐10: Selecting Training Data to Optimize Accuracy of Respiratory Surrogate‐Based Tumor Displacement Models
Authors: Malinowski K , McAvoy T , George R , Dieterich S , DˈSouza W
Published: November 2011

Purpose: Accuracy of respiratory surrogate models of tumor displacement is influenced by selection of appropriate training data, the simultaneous tumor localizations and respiratory surrogate measurements used to create the model. The object of this study was to explore ways in which (1) varying timing and (2) selectively discarding samples of training data can improve surrogate model accuracy. Methods: Motion from 125 lung, 10 liver, and 47 pancreas SBRT treatment fractions from 92 patients was analyzed. Each treatment fraction dataset included radiographically measured tumor positions, positions of three surrogate markers affixed to the torso, and tumor positions predicted by a commercial tumor tracking system from marker measurements. Partial‐least‐squares regression models of tumor position were trained on samples from 26 Hz position data. Low‐frequency (0.05–0.10 Hz) and high‐frequency (26 Hz) training datasets 5–150 seconds in duration were created. The effect of discarding samples with the highest leverage (as measured by Hotellingˈs T,2 statistic) was evaluated. Tumor localization errors were measured over 20 minutes. Results: The baseline tumor localization error (mean +/− standard deviation) in training data was 1.9 +/− 1.7 mm. Mean errors for high‐frequency training data were 4.7–4.9 mm and did not differ significantly with number (1–2), timing, or duration (5–30 sec) of acquisitions. Mean +/− standard deviation errors for low‐frequency training data varied from 4.4 +/− 2.7 mm (0.10 Hz, 2.5‐min acquisition) to 6.6 +/− 16.1 mm (0.05 Hz, 45‐sec acquisition). Removal of high‐leverage samples reduced tumor localization errors for high‐frequency‐derived models by 4–7% but did not reduce errors for low‐frequency data. Conclusions: Lengthening training data acquisitions improves models derived from low‐frequency but not high‐frequency training data. Conversely, removing high‐leverage training samples benefits high‐frequency data only. Training sample selection involves interplay between sampling rate, acquisition duration, and number of training samples.

This work was supported in part by grant # CA124766 from the NIH/NCI and by the Achievement Rewards for College Scientists (ARCS) scholarship.
TU‐E‐110‐03: Inverse Geometry X‐Ray Fluoroscopy Using Scanning‐Beam Digital X‐Ray Technology
Authors: Speidel M
Published: November 2011

Scanning‐beam digital x‐ray (SBDX) is an inverse geometry x‐ray fluoroscopic system using a sequentially illuminated array of focal spot positions, CdTe photon‐counting detector array, and real‐time image reconstructor. The system design substantially improves the dose efficiency of fluoroscopy by minimizing image degrading x‐ray scatter, maintaining high primary detection efficiency at high kVp, and increasing entrance field area. SBDX also has a unique real‐time tomosynthesis capability that enables 3D catheter tracking, fiducial tracking, and 3D vessel dimension analysis during procedures. Recently, image intensity equalization via adaptive reduction of beam‐on time in more transmissive patient regions has been investigated.

These advanced fluoroscopic capabilities stem from a radically different x‐ ray source design. SBDX has a large‐area transmission‐style tungsten target bonded to a water‐cooled beryllium plate. A multihole collimator positioned beyond the target defines a series of narrow overlapping x‐ray beams. As the focal spot is electronically deflected from one collimator hole to the next, detector images are simultaneously acquired. Images of the scanning field‐of‐view are reconstructed in real time at up to 30 Hz. Design challenges include achieving sufficient x‐ray source output, fast readout rates in the detector, and the need for real‐time image reconstruction.

This lecture will present the principles of the SBDX system and inverse geometry fluoroscopy. Applications of SBDX tomosynthesis and techniques used to increase signal‐to‐noise ratio and reduce heat loading in the x‐ray source will be discussed.

This research was supported by NIH Grant R01 HL084022, NovaRay Medical, Inc., and Triple Ring Technologies, Inc.

Learning Objectives:

1. Understand how inverse geometry x‐ray fluoroscopy design improves dose efficiency

2. Understand the operating principles of the scanning‐beam digital x‐ray system

3. Understand applications of real‐time tomosynthesis in fluoroscopically‐guided procedures
TU‐E‐220‐01: Physical Principles for the Best Detection of Breast Cancer by Ultrasound
Authors: Kelly K
Published: November 2011

The methods of 2D screening ultrasound image gathering and review were analyzed, and improvements were made to increase the cancer yield compared with handheld ultrasound breast screening. It was important to understand that recognition of an unexpected finding is made easier when the finding is in motion or appears to be in motion. It is a natural feature of ultrasound to be able to create this sense, since image generation is quick, harmless, and inexpensive. Thousands of images can be created and reviewed as a cine loop during the detection process by looking for an abnormality of motion. Once that abnormality is detected, the still images of that region can be reviewed for their diagnostic content. A number of problems were identified that potentially decrease the changes of recognizing subtle findings indicative of possible cancer: the speed and randomness of scanning, distraction of the reader by patient interaction, ambient lighting, impermanence of images, image spacing, image size, and contrast. These problems were mitigated by computer control of the scanning to ensure image generation every 0.8 mm and full coverage of both breasts with craniocaudad rows overlapping 7 mm, permanently recorded images allowing offline review in a darkened, non‐distracting environment, a decrease of image size with high‐resolution monitors, and expansion of the gray scale steps in the region of fat and cancer. A study of 6425 dense‐ breasted women with screening mammograms showed a doubling of cancer detection and a tripling of ▭ 1 cm invasive cancers with the addition of automated ultrasound with these improvements compared with screening mammography alone. The ACRIN 6666 study of handheld screening ultrasound found a 60% increase of cancer detection.
TU‐E‐220‐03: 3D Ultrasound Guided Minimally Invasive Prostate Therapy and Biopsy
Authors: Fenster A
Published: November 2011

The prostate biopsy procedure is plagued by high false negative rates (up to 34%) as early‐stage prostate cancer (PCa) is generally not visible on ultrasound. As a result, a negative biopsy does not rule out a diagnosis of PCa, as many tumors are missed on initial biopsy. In such circumstances, patients will undergo multiple repeat prostate biopsy (RPBx) to find undetected PCa. In a repeat biopsy, the physician must either avoid previously biopsied tissue (in cases of prior negative biopsy) or target the same anatomical site for patients with non‐diagnostic, atypical small acinar proliferations (ASAP).

3D TRUS is hypothesized to be superior to 2D TRUS for accurate guidance and recording of the prostate biopsy procedure. Patients undergoing RPBx might benefit most from the hypothesized improvements, as previous Bx core locations can be viewed in 3D and used to guide a RPBx. Accuracy is also important when suspicious findings exist on other diagnostic imaging modalities, such as MRI or PET, are used to direct a TRUS‐guided biopsy. In this paper, we describe a new method to guide prostate biopsy procedures using 3D ultrasound. This new approach allows us to guide the biopsy to specific 3D targets in the prostate, record the biopsy locations in 3D, and register the intra‐biopsy procedural 3D ultrasound image with an MR image to guide the biopsy to specific locations in the prostate.

Learning Objectives

1. Understanding the limitations of conventional 2D ultrasound guided prostate biopsy

2. Understanding the issues related to performing the prostate biopsy procedure with 3D US guidance

3. Understanding the issues related to the use of MR in conjunction with 3D US to guide the prostate biopsy procedure
TU‐G‐BRA‐04: Biological Optimization in Carbon Therapy
Authors: Oelfke U
Published: November 2011

The application of high linear energy transfer (LET) radiation in modern radiation oncology, like carbon‐ion therapy, requires different concepts of treatment plan optimization when compared RT‐planning for photon beams. Although, by far not perfect, the standard strategy employs the concept of relative biological effectiveness (RBE), which converts the delivered physical particle dose into a radio‐biologically equivalent dose of low LET beams. In order to introduce the respective RBE models into the inverse planning process of particle therapy one directly aims to optimize the biological effect, mostly expressed in terms of a linear quadratic model (LQM) for a dose‐effect relationship.

We will first introduce the general framework of biological optimization for inverse planning of intensity modulated particle therapy (IMPT). The effects of the intrinsic radiation quality on the design of treatment plans will be demonstrated for various forms of dose delivery methods, like spread‐out Bragg peaks (SOBP), distal edge‐tracking (DET) or 3D‐spot scanning and different clinical treatment sites. So far, the employed models only account for the most important radiobiological factor, the anticipated local LET distribution, while other additional factors like the oxygen enhancement ratio or the influence of different fractionation schemes are not considered explicitly.

Finally, another important issue will be briefly mentioned, the robustness of biologically optimized treatment plans versus uncertainties in the dose delivery process or even the limited knowledge of the biological input parameters of the employed models that are predicting the biological effect. Some results in the framework of the worst‐case optimization will be discussed.

Learning Objectives:

1. To review the framework of biological inverse planning of carbon therapy

2. To understand the potential and inherent limitations of the optimization approach
TU‐G‐BRB‐05: Dosimetric Characterization of Motion Effect in Delivering Uniform Target Dose Distribution Using Scanning Proton Beams
Authors: Tsunashima Y , Poenisch F , Li H , Zhu X , Balter P , Umezawa M , Sahoo N , Mohan R , Dong L
Published: November 2011

Purpose: The purpose of this study is to evaluate the impact of motion on scanning beam delivery in synchrotron‐based spot‐scanning proton therapy.Methods: A MatriXX 2D ion chamber array detector was placed on a moving platform with 19 cm of solid water for buildup. The platform was moved perpendicular to the beam direction in a simulated breathing pattern using a computer controlled stepping motor. A 10×10cm2 uniform field was delivered using a 173.7MeV beam with an approximately 20 mm spot size (FWHM in water) and 8 mm spot spacing. The delivery time was 1.2 sec/paint, 1–4 repaints were studied. The treatment field was delivered at different motion amplitudes: A=0 (reference), 3, 5, 10 and 20 mm and motion cycles T=3s and 5s. We also tested the starting phase effect by starting the beam at different phases of the motion cycle. In each case the dose distributions under motion were compared to the reference. Results: In the presence of motion, the delivered dose pattern to a moving phantom is typically skewed and non‐uniform. However, if the motion amplitude was less than 5mm, there was less dosimetric impact (<1% difference in homogeneity) regardless of motion cycle, number of repainting, and the beam starting phase conditions. However there were 6.9% and 27.9% dose difference in homogeneity compared to the reference for 10mm and 20mm motion amplitudes. We found that the starting phase had an impact on the shape of the delivered dose pattern. Multiple repainting minimized but not eliminated the dose pattern distortion caused by different starting phases. Conclusions: Delivered dose pattern can be distorted by the interplay effect of patient motion and scanning beam delivery. However, when the spot size (20mm FWHM) and spacing (8mm) are appropriate, the delivered dose pattern can tolerate non‐anticipated motion up to 5mm.
TU‐G‐BRB‐07: Evaluation of Tissue‐Equivalent 3D Polymer Gel Dosimeters as Phantoms for PET/CT Verification of Proton Beam Deliveries
Authors: Lopatiuk‐Tirpak O , Su Z , Li Z , Hsi W , Meeks S , Zeidan O
Published: November 2011

Purpose: to investigate the potential of polymer gel dosimeters for concurrent measurements of three‐dimensional positron emission activity and dose distributions; to evaluate the ability of this technique to identify dosimetric errors due to delivery uncertainties, including those due to range modification and target motion.Methods: three BANG3‐Pro2 gel dosimeters irradiated by proton beams were imaged in a PET/CT scanner, starting within 3 minutes after irradiation. The radiation was delivered as a pristine beam under static conditions, as well as an SOBP, with and without phantom motion. The motion trace was defined by a sinusoidal curve with 2 cm peak‐to‐peak amplitude and the frequency of 0.25 Hz. The dose was read out using an established optical CT scanning procedure. PET/CT images of activated gels were validated against analytical calculations of activity and correlated to measured dose. The effects of target motion on activity and dose distributions were evaluated by volumetric gamma analysis against the treatment plan. Results: The profiles of positron emission activity along the central beam axis were found to be consistent with analytical calculations. Temporal dependence of activity decay suggests that the observed PET signal is due mainly to decay of 15O and 11C. Lateral profiles were found to exhibit good spatial correlation throughout the beam range. This allowed using a modified gamma analysis method to compare the signatures of target motion in PET and dose images. Mean gamma for static PET and dose datasets was 0.07 and 0.11, respectively. For the motion delivery, the mean gamma value increased to 0.63 for both datasets. The spatial distributions of the gamma criterion for PET and dose datasets were qualitatively similar. Conclusions: Polymer gels can accurately capture both dosimetric and activation information. Dosimetric errors due to target motion can be quantified by PET/CT using a novel method of analysis.

This work was supported by the Bankhead‐Coley Florida Biomedical Research Program under Grant No. 1BD10‐34212.
TU‐G‐BRC‐01: JUNIOR INVESTIGATOR WINNER: 4D Planning over the Full Course of Fractionation: Assessment of the Benefit of Tumor Trailing
Authors: McQuaid D , Bortfeld T
Published: November 2011

Purpose: Tumor trailing techniques have been proposed as a method of reducing the problem of intrafraction motion in radiotherapy. However the dosimetric assessment of trailing strategies is complicated by the requirement to study dose deposition over a full fraction delivery. Common 4D planning strategies allowing assessment of dosimetric motion effects study a single cycle acquired with 4DCT. In this paper a methodology to assess dose deposited over an entire treatment course is advanced and used to assess the potential benefit of tumor trailing strategies for lung cancer patients. Methods: A digital phantom mimicking patient anatomy was programmed to follow the tumor respiratory trajectory observed from 33 lung cancer patients. The phantom consisted of a human torso with an implanted centrally located lung lesion segmented from a patient CT. Motion margins required to obtain CTV coverage by 95% of the prescription dose to 90% of the available cases were computed for a standard treatment strategy and a trailing treatment strategy. The accumulated dose from the full multi‐fraction delivery was then calculated for each both alternative treatment delivery strategies. Results: The trailing strategy facilitated a reduction in the required motion margin of over 30% relative to the conventional delivery. When the dose was computed across the entire delivery for the 33 cases the trailing strategy was found to significantly reduce the underdoseage to the outlier cases and the reduced margin trailing margin facilitated a 15% reduction for the mean lung dose and 7% reduction for the mean esophagus dose. Conclusions: The target trailing delivery strategy facilitated margin reduction leading to reduced normal tissue dose while at the same time improving the robustness of the target dose to possible outlier tumor motion trajectories.
TU‐G‐BRC‐04: The Dosimetric Impact of Prostate Rotations during Electromagnetically Guided External Beam Radiation Therapy
Authors: Amro H , Hadley S , McShan D , Hamstra D , Sandler H , Vineberg K , Litzenberg D
Published: November 2011

Purpose: To measure the dose decrement to the prostate caused by daily prostate motion and to correlate target coverage with prostate rotations to establish individualized rotational tolerances and PTV margins. Methods: Real—time tracking data for 26 patients were obtained during RT and used to calculate “average” prostate rotations and translations. For each patient, IMRT treatment plans meeting RTOG0126 dosimetric criteria were created with 0, 2, 3, and 5 mm PTV margins. Daily translations and rotations were used to calculate prostate delivered (dynamic) dose from the planned (static) dose. Dose volume histograms, D95, and V79 are computed from the dynamic dose to evaluate the coverage and the adequacy of PTV margins under measured target motion. The intra‐fractional effective rotations of the prostate (rotations weighted by rotation lever arm and prostate geometrical shape) were obtained for each patient. Results: Large variations in dosimetric coverage were seen among patients. Adequate coverage to target was met in 39%, 65%, and 84% of the patients for plans with 2, 3, and 5 mm PTV margins, respectively. This dosimetric coverage could not be correlated with measured rotations for any of the PTV margins. Prostate shape and the length of rotation lever‐arm were parameterized and used to obtain effective rotations from the measured rotations. Clear correlations were seen between effective rotations and the prostate delivered dose. Conclusions: Prostate rotations, if left unmanaged, could cause significant underdosing to the target even if daily translational tolerances applied and a 5 mm PTV margin is used. Unlike translations, effective management of prostate rotations requires individualized rotational tolerances due to variations in prostate shape and rotation lever‐arm length among patients. Consequently, individualized rotational tolerances enable PTV margins to be individualized.
TU‐G‐BRC‐05: Daily Respiratory Gating Window Adjustment Is Necessary for Abdominal Radiation Therapy Patients: A Retrospective Analysis with Simulation 4DCT and Daily Fluoroscopy
Authors: Ge J , Santanam L , Noel C , Parikh P
Published: November 2011

Purpose: To evaluate the need for adjusting the respiratory gating window on a daily basis due to variability of intrafraction motion of abdominal tumors treated with stereotactic and conventional fractionated radiotherapy. Methods: Thirteen patients (8 with liver cancer and 5 with pancreatic cancer) were implanted with visicoil fiducials and treated with amplitude based respiratory gated (RPM) radiation therapy on a Varian Trilogy linear accelerator (Varian Medical, Inc.). A total of 225 fluoroscopic movies were recorded using an Intrafraction Motion Review Software (Varian Medical, Inc.) over 106 fractions with an average length of ∼15s each. Intrafraction tumor motion was represented by the amplitude (peak‐to‐trough) of the fiducial motion trace extracted from each fluoroscopic movie. The superior‐inferior motion over the course of radiotherapy was compared to the maximum motion from 4D‐Computed Tomography (4DCT). Results: All patients showed predominant motion in superior‐inferior direction ranging from 1mm to 29 mm. The motion varied on a day to day basis, with changes of amplitude up to 6.7±5.4 mm for liver‐SBRT patients and 7.8±2.0 mm for pancreas‐fractionated patients. The maximum motion from 4DCT was compared to individual fractions for all patients. For liver‐SBRT patients, 4DCT overestimated the motion on 5/ 27 fractions (average 6.4 mm); and underestimated motion on 11/27 fractions (average 6.8 mm). For pancreas‐fractionated patients, 4DCT overestimated the motion on 60/79 fractions (average 13.6mm); and underestimated the motion on 16/79 fractions (average 7.9 mm). Conclusions: Observed intrafraction motion range varied from fraction to fraction and majority of treatment fractions (88%) were either overestimated or underestimated by 4DCT. These results suggest the need for daily respiratory gating window adjustment for a more accurate and efficient delivery.
TU‐G‐BRC‐09: A Comparison of Step‐And‐Shoot and DMLC IMRT‐Delivery for Real‐Time Tumor Tracking
Authors: Hofmann K , Krauss A , Nill S , Oelfke U
Published: November 2011

Purpose: The dose distributions of static and dynamically delivered IMRT fields for real‐time target tracking were evaluated to determine which methods work best for the compensation of breathing‐induced organ motion.Methods: A single IMRT beam of a clinical plan was applied with the step‐and‐shoot delivery technique and the sliding‐window technique with the research Siemens 160MLC in order to account for a two‐dimensional, sinusoidal target motion and for a real patient breathing‐curve. For the sliding‐window dose delivery, two different maximum leaf speeds, as well as synchronized and non‐synchronized leaf trajectories were employed. All fields were delivered without and with tracking of the target using three electromagnetic transponders of the Calypso‐System. The dose distributions were measured with radio‐chromic films in a water equivalent phantom in 5cm depth and were compared to the step‐and‐shoot delivery for a non‐moving phantom. For the dose comparison a gamma criterion of 2%/2mm was utilized.Results: For both motions tracking improved the gamma‐index by 13%–32%. For the dynamic delivery no significant advantage was observed between unsynchronized and synchronized leaf trajectories. Moreover no remarkable differences were found by comparing results obtained with different maximum leaf speeds. For both target motions the step‐and‐shoot delivery shows a better dose distribution using the tracking approach: For the 2D‐motion a gamma‐passing rate of 86.3% can be achieved using step‐and‐shoot compared to 78.2% on average for the dynamic dose delivery. For the patient breathing‐motion 83.3% compared to an average of 77.1% were obtained. When comparing the results of both motion patterns, slightly higher passing rates were found with the periodic 2D‐sinusoidal motion. Conclusions: Only small differences were observed for different IMRT dose delivery modes with organ motion tracking, except for the tracked step‐and‐shoot delivery. However, more experiments have to be performed to investigate other IMRT plans and explicit dependencies on the field modulation.

Supported by Siemens Healthcare/CR
TU‐G‐214‐02: Imaging the Biological Effect of Dose in the Liver Normal Tissue
Authors: Cao Y
Published: November 2011

The potential clinical value of in vivo functional and physiological imaging for assessment of dose response of the liver parenchyma has been explored in recent years. Conventional NTCP models are based upon physics parameters (dose, volume). While providing guidance for treatment planning and permitting safe delivery of higher doses than having previously been possible, they do not account for the broad range of individual patient biological radiosensitivity. Early monitoring of the biological effect of dose in the liver normal tissue via functional and physiological imaging can potentially select patients with pre‐clinical signs of hepatic function changes prior to the onset of symptomatic radiation‐induced injury. In addition, mapping regional distributions of hepatic function and its response to dose would permit re‐arrangement of the dose distribution to preserve functional subunits in the liver. Care must be taken, however, to understand the limits of these imaging techniques, including reproducibility, and to validate the biomarker with adequate endpoints.

This lecture will provide an overview on functional imaging for developing a dose‐response model of the liver for individualized therapy. The limitations of these techniques will also be discussed.

Learning objectives:

1. Understand functional imaging as a biomarker for normal tissue response in the liver;

2. Understand the influence of imaging parameters and image quality on quantitative metrics and uncertainty in the dose‐response model of the liver.

3. Understand clinical applications and limitations.
TU‐G‐110‐05: Efficacy of Fixed Filtration for Rapid KVp‐Switching Dual Energy X‐Ray Systems
Authors: Yao Y , Wang A , Pelc NJ
Published: November 2011

Purpose: Dose efficiency of dual kVp imaging can be improved if the beams are filtered to remove photons in the common part of their spectra, thereby increasing spectral separation. While there are a number of advantages to rapid kVp‐switching for dual energy, it may not be feasible to have two different filters for the two spectra. Therefore, we are interested in whether a fixed added filter can improve the dose efficiency of kVp‐switching dual energy x‐ray systems.Methods: Simulations were done to decompose known phantoms into basis materials of aluminum and water, using 80 and 140 kVp x‐ray spectra. Precision of the decomposition was evaluated based on the propagation of the Poisson noise in the detected intensities through the decomposition function. We hypothesized that a K‐edge filter would provide the energy selectivity needed to remove overlap of the spectra and hence increase the precision at constant dose. When optimizing the filter design, we considered filtration material (Z), filter thickness, and the relative power allocated to the two beams. We imposed a constraint of <50% loss of x‐ray output due to filtration while maintaining constant entrance dose. The detector absorption efficiency of a CsI screen was also included in the simulation. Results: An improvement in precision of >30% at fixed dose (or lower dose for the same precision) was achieved with optimal filtration. The optimal filter material depends somewhat on the phantom composition and ranges across the lanthanide series. Increasing filtration thickness increases the average spectral separation. When ignoring tube power limitations, the precision improvement with increasing filtration continues increasing, although sublinearly. Conclusions: This study demonstrates the potential of fixed filtration to improve the dose efficiency and material decomposition precision for rapid kVp‐switching dual energy systems.

GE Healthcare
TU‐G‐110‐06: Detection of Contrast Agents with a CdTe Semiconductor Detector Intended for Small Animal Imaging
Authors: Schulze J , Koenig T , Zuber M , Zwerger A , Fauler A , Nill S , Fiederle M , Oelfke U
Published: November 2011

Purpose: The objective of this study was to find out if a spectroscopic semiconductor detector from the Medipix2 family is capable to simultaneously resolve the K‐edges of iodine and gadolinium contrast agents present in a phantom at various concentrations. Employing a pixel pitch comparable to the range of X‐ray fluorescences generated in the CdTe sensor, the energy response function (ERF) of the detector system employed is heavily biased. Therefore, its detection limits prior to any corrections were determined in this work.Methods: The detector used delivers spectroscopic information by means of an adjustable energy window. The sensor of the detector is made of 1 mm thick cadmium telluride (CdTe) that has an active area of 4.2cm × 2.8cm and features a pixel pitch of 165um. The X‐ray source employed was operated at 70kVp that corresponds to a mean photon energy of roughly 40keV. A phantom containing six different concentrations (11.8umol/ml, 23.6umol/ml, 47.3ummol/ml, 118.2umol/ml, 236.4umol/ml and 472.8umol/ml) of iodine (Imeron300) and gadolinium (Multihance 0.5M) contrast agents was employed, containing capillary tubes with diameters of 1.6mm and 0.8mmin order to mimic blood vessels.Results: The K‐edges of iodine (33.2keV) and of gadolinium (50.2keV) could easily be detected for the 3 highest concentrations: 118.2umol/ml, 236.4umol/ml and 472.8umol/ml. With these concentrations the reconstructed absorption coefficients increased significantly between the energy windows 25–30keV and 35–40keV for iodine and between 42–47keV and 52–57keV for gadolinium. Conclusions: A pixel pitch of 165um is large enough to detect the absorption edges of iodine and gadolinium using a single tube voltage. However, quantitative measurements require the reconstruction of the acquired spectra by a precise knowledge of the ERFs of all photon energies involved.
TU‐G‐211‐05: Assessment of Partial Volume Effect after Applying Four Reconstruction Algorithms for SPECT Oncology Scans: Simulation Study
Authors: Shcherbinin S , Celler A
Published: November 2011

Purpose: We investigated the severity of partial volume effects (PVE) in SPECT oncology studies when images are reconstructed by four different algorithms. Methods: We simulated an oncology SPECT scan with three spherical objects (diameter of 4.4cm, volume of 61mL) representing tumors. These objects were filled with different activities and positioned inside a large cylinder imitating the human body. Our tumor‐like objects were not only surrounded by low‐activity tissues, but also placed next to some organ (for example, liver) with variable activity. We simulated a typical oncology SPECT scan with 60 camera stops over a 360 degree rotation. In total, four methods with increasing complexity were employed to reconstruct images. The first algorithm, M1, included corrections for attenuation and resolution loss and imitated techniques conventionally used in clinics. Method M2 additionally incorporated model‐based scatter correction. Methods M3 and M4 employed the known (from structural imaging modalities) boundaries of tumor(s) and corrected activity inside tumor(s) for spill‐out only (simplified technique M3) or iteratively updated both tumor(s) and background accounting for both spill‐in and spill‐out (advanced technique M4). Results: Incorporation of model‐based scatter correction (method M2) improved the quantification for all tumor‐like objects. Method M1 underestimated tumor activities by 20–25%, whereas method M2 underestimated these activities by only 12–15%. Both PVE corrections M3 and M4 led to substantially better activity estimations with errors of 0–5%. In addition, method M4 provided the best activity distribution in regions encompassing tumors. The relative error of the voxelized activity distribution in that surrounding region was 20–27% for method M1, 19–25% for method M2, 15–18% for method M3, and 12–13% for method M4. Conclusions: The SPECT‐generated activity distribution can be considerably improved by using template‐based corrections for PVE. Correspondingly, the quality of procedures such as tumor staging, estimating response to treatment, and patient‐specific dosimetry can be enhanced.
TU‐G‐211‐08: A Multi‐Vendor Phantom Study Comparing the Image Quality Produced from Three State‐Of‐The‐Art SPECT‐CT Systems
Authors: Hughes T , Celler A
Published: November 2011

Purpose: Ongoing advancements in SPECT‐CT hardware and software raise important questions regarding the relative performances of various cameras and their respective image‐processing software. This phantom study compares images produced from three state‐of‐the‐art cameras using four figures‐of‐merit (FOM) to assess image quality. Methods: A thorax phantom modeling the spine, lungs, a healthy heart and 2 tumours (cylindrical bottles) was scanned with the following SPECT‐CT systems: Philipsˈ Precedence (PP), GEˈs Infinia‐Hawkeye (GH), and Siemensˈ Symbia‐T6 (SS). For each scan, Tc‐99m solutions were injected into the heart (120mL), two bottles (33mL) and thorax (7000mL) to yield activity concentration ratios of roughly 6:1 and 8:1 for heart:thorax and tumour:thorax, respectively. The processing was performed using the reconstruction software available on the cameras; namely, Evolution, Astonish and Flash3D for GH, PP, and SS, respectively. Additionally, all sets of data were reconstructed using our in‐house (MIRG) software. Mean values of activity error, uniformity, signal to noise ratio (SNR) and image contrast were used as FOM for the three objects of interest in each image (heart and 2 bottles). Two‐tailed paired t‐tests were used to test significance between means, considering p<0.05 as significant. Results: No significant differences were observed for all FOM between MIRG reconstructions using PP, GH and SS acquisition data. Mean activity errors for the PP reconstructions were significantly closer to the truth relative to GH and SS reconstructions and contrast measurements were significantly better for PP relative to SS. However, PP uniformity was significantly lower than GH and SS. No significant differences were found between GH and SS for all FOM. Conclusions: When reconstructing the data with the same algorithm, no significant differences were observed for any FOM; however, when using the respective vendor algorithms, PP yielded more accurate activity and contrast measurements, yet lower uniformity relative to GH and SS images.
TU‐G‐220‐02: Quantitative Ultrasound Imaging: A Historical Persective
Authors: Hall TJ
Published: November 2011

Quantitative ultrasound (QUS) analysis attempts to gain further understanding of tissue pathology through analysis of the underlying echo signals. QUS is effectively as old as medical ultrasound imaging. A notable example is the initial application of ultrasound to breast tissue. The developers concurrently attempted to differentiate between benign and malignant tissues through an analysis of the echo signals they saw.

There have been a many “successes” and a few “failures” during QUS development, but there has been a great deal of progress in QUS methods. Although Lord Rayleigh described the basics of acoustics in the late 1800ˈs, tissue classification with QUS requires a more detailed analysis of wave propagation in tissue. Modern methods more accurately model the interaction of an acoustic wave propagating in inhomogeneous media (like tissue) and more use more sophisticated models of tissue.

We (the UW‐Madison Ultrasound Group) and our collaborators (at the University of Illinois, University of Iowa, Intrermountain Healthcare, Duke, Boston University, and Rensselaer Polytechnic Institute), as well as many others around the world, are actively developing QUS methods. The goals of this presentation are to provide a description of some of the key underlying physical principles involved in QUS, some of the key successes and notable failures. From this, it is clear that a rigorous understanding of both the underlying physical principles and basic biology are necessary for maximizing the potential of QUS techniques. Further, the motivation for system‐independent QUS parameter descriptions of tissue will be presented.

The prospects for the future development and application of QUS methods are very encouraging. Current clinical ultrasound systems provide higher center frequency, broader bandwidth, and lower noise echo signals, and these lead to improved QUS accuracy and precision. Some of those developments will also be highlighted.

Learning Objectives:

1. Understand the basic concept of quantitative ultrasound (QUS) analysis

2. Understand the range of QUS parameters that describe tissue properties

3. Understand the desire for system‐independent QUS

4. Begin to appreciate the prospects for clinical application of QUS
WE‐A‐BRA‐01: Commissioning and Implementation of New Equipment or Treatment Paradigms
Authors: Soen J , Pankuch M
Published: November 2011

A fundamental responsibility of the Clinical Medical Physics is to assist in the project management and commissioning of new equipment. The undertaking of such responsibilities may appear overwhelming when added to the routine clinical physics responsibilities of an operational center. In addition, the unique challenge of effective implementation requires extensive collaborative efforts from the entire staff, including physicians, therapists, nursing and administration. Methods for successful cooperation typically fall outside the realm of formal training programs. It is the responsibility of the onsite medical physicist to first understand the functionality, the capabilities, and the limitation of their new equipment and then to productively pass this information along to the clinical staff.

Several simple strategies can be considered before, during and after the commissioning duties. These include creating a clear, well defined plan with transparent expectations of the physicians, the clinical staff and administration. While this is obvious, it is not always clear how this is accomplished and what pitfalls one may encounter in the process. A new modality often requires the use of the latest, possibly less familiar tools. The physicist must ensure proper access and appropriate training for these tools often leading to unanticipated problems and unfamiliar results. A key component is to realistically estimate the amount of time it will require and to communicate that to the whole team. A comprehensive awareness of the complete system by entire planning team must be a fundamental beginning product of the project and should be permitted to be flexible enough to process unexpected complications exposed in the commissioning process.

The use of these tactics will be discussed in two clinical cases: 1) The implementation of 4‐D CT in a proton therapy environment and 2) the commissioning of an Elekta accelerator for both CMS‐XIO and CMS Monaco. While specific vendors will be used in the examples, the tactics discussed will be generally applicable to any vendor or equipment.

Learning Objective:

1. Understand basic strategies, processes and techniques employed in safe and effective execution of a project plan.

2. Examine the described strategies used by the speakers in two actual clinical examples.

3. Understand organizational issues that one may have to address prior to and during the commissioning and implementation of new equipment.
WE‐A‐BRB‐02: Gold Nanoparticle‐Aided Brachytherapy with Vascular Dose Painting: Estimation of Dose Enhancement to the Endothelial Cell Nucleus
Authors: Ngwa W , Makrigiorgos M , Berbeco R
Published: November 2011

Purpose: Microdosimetry is employed to estimate dose enhancement to endothelial cell nuclei, caused by radiation‐induced photo/Auger electrons originating from gold nanoparticles (AuNP) targeting the tumor endothelium, during brachytherapy. Methods: A tumor vascular endothelial cell (EC) is modeled as a slab of 2μm (thickness) × 10μm (length) × 10μm (width). The EC nucleus is centrally located with 5μm diameter and thickness of 0.5 – 1μm, corresponding to nucleus size 5 – 10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNP attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the non‐uniform distribution of AuNPs, with significantly higher local concentration expected near the EC. Four brachytherapy sources were investigated, I‐125, Pd‐103, Yb‐169, as well as 50kVp x‐rays. Results: For nucleus size 10 % of cellular volume, Pd‐103,I‐125, 50kVp, and Yb‐169 yielded total nDEF values: 5.55 – 73.00, 4.81 – 58.29, 4.73 – 56.59, and 3.19 – 25.84, respectively over local concentration range of 7 – 140 mg/g. Meanwhile, for nucleus size 5 % of cellular volume, Pd‐103,I‐125, 50kVp, and Yb‐169 yielded nDEF values of 6.38 – 89.49, 5.48 – 71.65, 5.39 – 69.87, and 3.51 – 32.31, respectively over similar concentration range. Conclusions: The results predict that substantial dose enhancement to the sensitive nucleus of endothelial cells can be achieved by applying tumor vasculature‐targeted AuNPs as adjuvants to brachytherapy, with low energy sources. Such magnitude dose enhancement may cause severe biological damage to tumor endothelial cells, without increased toxicity to healthy tissues not containing AuNPs.
WE‐A‐BRB‐03: X‐Ray Guided Targeting of Nanoparticles to Cancer
Authors: Ferraro D , Hallahan D
Published: November 2011

Purpose: X‐irradiation induces the expression of novel receptors on the surface of cancer cells. Peptide ligands that bind specifically to these receptors are now used to retarget liposomes and nanoparticles containing chemotherapy for cancer. Here we show that radiolabeling of nanoparticles will be used to image the spatial and temporal distribution of nanoparticles targeted to radiation inducible receptors during planned clinical trials. Methods: Biodegradable nanoparticles were manufactured by use of cross linking reagents with nanoparticle albumin. Peptide ligands that target radiation inducible receptors, HVGGSSV and GIRLRG were conjugated to nanoparticles using bifunctional PEG linkers. Radiolabeling with radioiodine was conjugated to nanoparticles by use of iodigen while Zr86 was conjugated by use of DFO as a chelator. Near infrared imaging was also used when Alexafluor750 fluorophore was conjugated to nanoparticles. Radiolabeled nanoparticles were injected by tail vein into mice bearing irradiated cancers. The biodistribution was imaged by PET, SPECT and NIR imaging. Results: Cancer specific binding of targeted nanoparticle was achieved by both the HVGGSSV and GIRLRG peptide ligands that bind to radiation inducible TIP‐1 and GRP‐78 receptors respectively. PEGylated nanoparticles have a circulation time greater than 24 hours which necessitated internal emitters with long half lives. Radiolabeled nanoparticles imaged by PET and gamma camera maintained cancer specific binding in mouse models of cancer. Nanoparticles and liposomes that were targeted to radiation inducible proteins bind selectively and for 7 to 9 days respectively. Anti‐cancer drugs including doxorubicin in liposomes and paclitaxel in nanoparticle enhanced radiation‐induced tumor control in mouse models of cancer. Conclusions: Radiation inducible receptors on cancer are suitable for targeted drug delivery. Long half lived radionuclides are needed to monitor the biodistribution in these PEGylated nanoparticles. PET and SPECT imaging are planned for upcoming clinical trials.

National Cancer Institute R01 and R21 grants.