Volume 35, Issue 6, June 2008
Index of content:
- Joint Imaging/Therapy Scientific Session: Room 352
- Innovative Frontiers in Medical Physics
TU‐D‐352‐01: Beyond the Limits of Active Matrix Flat‐Panel Imagers: A Comparative Performance Assessment of X‐Ray Converter Enhancement Versus Innovative Active Pixel Sensor Architectures35(2008); http://dx.doi.org/10.1118/1.2962559View Description Hide Description
Purpose: Despite the many advantages of Active Matrix Flat‐Panel Imagers (AMFPIs), these devices suffer from modest system gain relative to additive noise, as well as restrictions on maximum frame rates and charge trapping. A quantitative comparison of the performance of two of the strategies being developed to overcome these limitations is presented. One strategy employs significant enhancement of direct detection converter properties while the other employs complex, polycrystallinesilicon (poly‐Si) pixel circuits to form active pixel sensor (APS) architectures. Method and Materials:Theoretical upper limits for DQE and for other metrics that determine maximum frame rate and charge trapping effects were computed under fluoroscopic and radiographic conditions using a combination of cascaded systems analysis and circuit simulation. The cascaded systems calculations employed empirical measurements, published data and analytical calculations, while the simulations used representative a‐Si:H and poly‐Si transistor models. Results: The potential of high sensitivity photoconductors, such as , to offer up to a factor of 10 increase in system gain results in significant improvement to DQE performance under conditions of low exposures and/or for very small pixel sizes. Poly‐Si APS designs are capable of equivalent, or even greater DQE improvement through a combination of gain provided by in‐pixel amplifiers, along with correlated double sampling of the pixel signal. Furthermore, APS circuit designs allow substantially higher frame rates as well as reduction in charge trapping effects such as ghosting. Conclusion: While both approaches offer substantial improvements in DQE, and thus imaging performance, under conditions of low exposure and/or for small pixel pitches, converter enhancement offers the potential advantage of compatibility with existing AMFPI array designs. Conversely, poly‐Si APS architectures offer flexibility of design, function and operation, providing for the possibility of variable gain as well as addressing frame rate limitations and charge trapping issues.
TU‐D‐352‐02: Magnetic Resonance Imaging to Track Mesenchymal Stem Cells (MSCs) in a Murine Myocardial Infarction Model35(2008); http://dx.doi.org/10.1118/1.2962560View Description Hide Description
Purpose: To track the migration and engraftment of the mesenchymal stem cells (MSCs) with micrometer‐sized particles of iron oxide (MPIO) labeling into myocardial infarcted site using MRI in mice. Method and Materials: MSCs with GFP fluorescence were labeled with MPIO. Mice were irradiated with a dose of 8 Gy and received rescuing bone marrow transplantation 24 hrs later. The labeled MSCs (∼3–7×105cells) were then transplanted into the tibial modullary space of mice. The mice were randomly divided into two groups. At 14 days post‐MSCs transplantation, one group underwent myocardial infarction (MI; n=4; open chest with ligation of the left anterior descending coronary artery (LAD)) and the other group underwent sham‐operated surgery (Sham; n=2; open chest without ligating the LAD). MRI was performed at baseline, 3 days (D3), 7 days (D7) and 14 days (D14) post‐surgery. Short‐axis cardiac images were acquired using T2*‐weighted imaging and T2 mapping technique. The results were confirmed by fluorescent microscopy. The contrast‐to‐noise ratio (CNR) at the MI zone was calculated. For the Sham group, a CNR at a region of interest (ROI) designated in the left ventricular anterior wall was also calculated and compared with the MI group. Results: Pronounced signal intensity attenuation at the MI zone was observed by MRI at D7 and D14, potentially due to the accumulation of MPIO labeled stem cells. Both accumulation of stem cells with GFP signal and MPIO deposition in the heart were detected in the fluorescent microscopic images. The CNR were significantly different between the MI and Sham groups at D7 and D14 (p<0.05). Conclusion: Hypointense signal was observed at the MI zone in MRI, suggesting the infiltration of labeled MSCs. Current study may support a potential approach in cell therapy to noninvasive monitor migration of labeled cells post myocardial injury.
35(2008); http://dx.doi.org/10.1118/1.2962561View Description Hide Description
Purpose: To design a Compton camera to image gamma‐ray emission during the treatment of proton therapy as a possible method to verify dose delivering.Method and Materials The pixilated (Ce) crystal was investigated as both scattering and absorbing detectors. In this design each crystal module used in front layer has the size of 2.5cm × 2.5cm × 0.5cm that was segmented into 4mm × 4mm × 2mm on its top to enhance the spatial resolution based on the differential response of PSPMT that receives scintillation light. Each detector in the rear layer has the size of 2.5cm × 2.5cm × 3.0cm and was segmented into 4mm × 4mm × 10mm. The position resolution in locating interaction is about 2mm laterally and 2.5mm vertically in the front detectors while the resolutions are 2mm and 15 mm in the rear detectors. The efficiency and angular uncertainty of this Compton camera was investigated based on numerical calculation. The geometry of the detectors and distance between detectors were optimized to achieve high efficiency or high angular resolution.Results: Angular uncertainty of ∼0.1 radians was the low limit for us to image 511 keV gamma rays because of the Doppler broadening. However, the angular uncertainty below 0.05 radians was achievable by observing the scattered photons at about 25°–60° scattering angle for 10 cm distance between detectors.Conclusion: Based on numerical calculation, we proposed a Compton camera with two layers. The potential angular resolution in imaging 511 keV gamma rays was about 0.3 radians while it was 0.05 radians or less from gamma rays above 2 MeV. The angular uncertainty is relevant to resolution, but higher resolution can potentially be achieved with proper image reconstruction algorithms that will be developed and evaluated in future.
TU‐D‐352‐04: Novel Decision Aid for IMRT Treatment Plans Generated Using Multiobjective Optimization35(2008); http://dx.doi.org/10.1118/1.2962562View Description Hide Description
Purpose: To develop the decision making component of a multiobjective IMRT optimization procedure for prostate cancer that incorporates disparate sources of information used in clinical decision making, the uncertain outcomes inherent in radiation therapy and the preferences of the patient. Method and Materials: Currently, many IMRT plans are developed for each patient without indication of which plan provides the optimal balance between tumor control and complication probability. Coupled with the typical number of objectives, plan selection is difficult. We chose a Bayesian Network (BN) coupled with a MarkovModel (MM) and utility theory to calculate Quality Adjusted Life Expectancy (QALE) for IMRTtreatment of prostate cancer. The BN was constructed with the advice of experts; conditional probabilities were obtained from research and clinical trial publications and expert opinion. Local, regional, and distant control were included as were complications to bladder and rectum. The MM relied on transition probabilities derived from the BN, published clinical trials and life expectancy tables. Utilities were obtained from the literature. Plan ranking was based on QALE or any of the components, e.g. local control or complications. Results: Probabilities of local and distant control as a function of disease state matched published values well, as did life expectancies. Sensitivity analyses highlighted the critical nodes in the network. Analysis of outcomes versus probability of lymph node involvement provided a basis for decisions regarding pelvic irradiation. A BN is well‐suited to handle rigorously conditional probabilities and the disparate nature of clinical variables. QALE provides a method for ranking plans based on clinically relevant criteria that incorporates the probabilistic nature of the outcome. Conclusion: A decision aid was constructed using a Bayesian Network coupled to a MarkovModel. This resulted in the ability to rank competing plans based either on QALE or specific outcomes.
TU‐D‐352‐05: The Effect of Magnetic Interference On a Coupled MR‐Linac System: 3D Modeling of RF in a Linac35(2008); http://dx.doi.org/10.1118/1.2962563View Description Hide Description
Purpose: In order to provide real‐time Image Guided Radiotherapy(IGRT), the coupling of a 0.2T bi‐planar Magnetic ResonanceImager(MRI) and medicallinear accelerator(linac) is proposed. This integration forces the linac to be within the fringe fields of the bi‐planar magnets causing magnetic interference. Appropriate shielding must be designed and optimized in order to reduce the fringe field magnitudes to a point where a clinically useful radiation beam is produced. Method and Materials: A first step to designing shielding is the full 3D radio‐frequency (rf) modeling of the linac waveguide using the Finite Element Method(FEM). The main accelerating cavities were modeled in 3D using COMSOL Multiphysics and compared to the widely used program Poisson Superfish. The full waveguide was then modeled in 3D and the coupling coefficients were determined. Results: A comparison of linac important parameters (i.e. resonant frequency, power dissipation, stored energy, Q value, shunt impedance and transit time factor) were made between the 3D model in COMSOL and that of Poisson Superfish. All values were found to be within 0.8% where the differences are attributed to differences in meshing between the two programs. A linac model consisting of 5 and one half accelerating cavities with 5 coupling cavities was then generated. A 3D instead of a 2D model was used since it is more accurate in determining the coupling coefficients between the accelerating and coupling cavities. Conclusion: This work is the first step to determining the magnetic shielding required in producing a clinically useful radiation beam from a coupled MR‐Linac system. The extracted parameters from the 3D model were found to be less than 1% different from the benchmarked program Poisson Superfish. This 3D model is however inherently more accurate since the full modeling of coupling between accelerating and coupling cavities has been achieved.
TU‐D‐352‐06: Modeling the Effect of Different Oxygenation Levels On Radiation Therapy Response Using Kinetic Parameters Derived From PET/CT Imaging35(2008); http://dx.doi.org/10.1118/1.2962564View Description Hide Description
Purpose: Although tumor hypoxia is frequently related to increased radioresistance, the interplay between hypoxia and the time course of tumor response is not well understood. This study investigates effects of different oxygenation levels on therapeutic response using an imaging‐basedtumor simulation model.Method and Materials: A multiscale tumormodel was developed employing cell‐line‐specific input variables and kinetic parameters derived from pre‐therapy and PET/CT scans, which provided information on cellularproliferation and tumor hypoxia. For each tumor voxel, stochastic simulations were performed by modelingcellulargrowth and therapeutic response based on the linear quadratic formalism including the oxygen enhancement ratio. Model parameters were fitted to published in‐vitro and animal models of head and neck squamous cellcarcinoma (HNSCC) cells. Using the obtained parameters, the model was applied to a human HNSCC case to investigate effects of different uniform and non‐uniform oxygenation levels. Resulting virtual images were compared for treatment efficacy under various hypoxic conditions. Results: Simulating cell cycle redistribution of cultured cells among the phases of the cell cycle after a single irradiation event yielded excellent agreement (within 3.8 %) with in‐vitro data, showing complete redistribution after 50 hours. In comparison to growth and response curves obtained in experiments with murine HNSCC xenografts, the model quantitatively and qualitatively reproduced macroscopic tumor behavior within experimental uncertainties. Simulations of the clinical case showed increased radioresistance with decreasing oxygen levels. Consideration of the uptake resulted in heterogeneous tumor response, featuring pronounced radioresistance below 2.5 mmHg pO2. Conclusion: Our results suggest that hypoxia adversely affects tumor response, especially when applying uniform dose prescriptions to heterogeneous tumors. The developed model is a valuable prospective tool for transforming voxel‐based information into patient‐specific parameters for outcome modeling and investigating biologically based non‐uniform dose prescriptions, thus helping to identify a biologically optimized treatment regimen.
TU‐D‐352‐07: Enhanced Energy Transfer From Mega‐Voltage Radiation to the Tumor Cell Killing Singlet Oxygen by Semiconductive Nanoparticles35(2008); http://dx.doi.org/10.1118/1.2962565View Description Hide Description
Purpose: To investigate a novel energy transfer pathway from 6 MV therapeutic X‐rays to Quantum dots(QDs), which further activates Photofrin to produce reactive singlet oxygen species by a process known as Foster Resonance Energy Transfer, and subsequently enhances cell kill. Method and Materials: The photon emission efficiency of QDs upon excitation by 6 MV X‐rays was measured as a function of the dose rate from 100 cGy/min to 600 cGy/min. A conjugate was synthesized based on the conjugation of Photofrin and QDs. The quenching of the photon emission was measured with the conjugate. The energy transferred to the photofrin was calculated based on the principle of Foster Resonance Energy Transfer (FRET) that the energy transfer efficiency is proportional to the degree of quenching. The cell kill enhancement with the conjugates was studied using A549 human lungcarcinoma cells and an optical density based assay. The cellular distribution of the conjugates was imaged by a confocal microscope.Results:QDs were found to be excited by the 6 MV radiation and the number of visible photons generated from QD depended linearly on the radiationdose rate. The FRET efficiency increases as the number of Photofrin molecules conjugated to the quantum dots increases. The conjugate resulted in a statistical significant 34% increased cell kill at 24 pmol/ml conjugate concentration compared to radiation alone with minimal toxicity in non‐irradiated controls. Fluorescence microscopy revealed that the conjugates were distributed within the cytoplasm. Conclusion: This conjugate shows distinct properties as a novel media for generating singlet oxygen and enhanced tumor cell killing, which is achieved synergistically with radiation through a physical and linear interaction between QDs and X‐ray; the conjugate itself shows minimal dark toxicity at nM concentration, thus can be readily targeted by conformal radiotherapy with high geometrical specificity.
35(2008); http://dx.doi.org/10.1118/1.2962566View Description Hide Description
Purpose: Most current diagnostic and therapeutic X‐ray techniques use nonspecific, broadband continuum radiation. By taking advantage of resonant absorption complexes in heavy‐element‐tagged nanoparticles or contrast agents delivered to disease sites, we can use tunable, narrow energy bands for both therapy and diagnosis (theranostics) that is extremely efficient and minimizes radiation exposure to neighboring tissue. Method and Materials: We use an electron beamion trap (EBIT) as the source of tunable, monochromatic X‐rays for imaging and therapy and a cryogenic x‐ray microcalorimeter to form spectroscopically resolved images. The high resolving power (E/ΔE > 2000) and low background of the microcalorimeter are essential for verifying the resonant absorption signatures predicted by our relativistic R‐matrix calculations. The microcalorimeter is used to tune the X‐ray emission from the EBIT plasma to the band of resonant absorption lines in the tagged nanoparticles. The unprecedented signal to noise of the microcalorimeter means that it can identify line emission with less than 20 counts per energy resolution element, making the eventual dose necessary for diagnosticimaging potentially very low. Results: We describe the EBIT and the microcalorimeter with emphasis on the X‐ray energy range required by cancer theranostics. Preliminary studies with the microcalorimeter demonstrate that it can image atomic fingerprints of heavy‐element uptake such as goldnanoparticles that can be embedded in malignant tissue. Conclusion: We discuss two key component technologies for atomic level theranostics : The electron beamion trap is a smart x‐ray source capable of generating monoenergetic resonant X‐rays that maximally interact with the matching high‐Z contrast agent or nanoparticles; the spectroscopic microcalorimeter is a “zero‐background” detector by design and can discriminate resonant signatures with 10 times better resolution than any other X‐ray spectrometer, thus providing very high sensitivity for detailed mapping of elemental distributions such as goldnanoparticles and platinum‐based chemotherapeutic compounds.
TU‐D‐352‐09: Development of a Carbon‐Nanotube Field Emission Based Multi‐Pixel Microbeam Cellular Irradiation System35(2008); http://dx.doi.org/10.1118/1.2962567View Description Hide Description
Purpose: High spatial and temporal resolution cellular microbeam irradiation is important in studying dynamic radiation response at the cellular level. Existing systems include charged particle, x‐ray, and electron single beamirradiators. We have proposed a multi‐pixel electron microbeam array irradiator based on carbon nanotube(CNT)field emission with individually controllable beams to irradiate cellular scale regions in a Petri dish under real time microscope observation. Method and Materials: We have developed and tested a prototype single pixel 30keV electron irradiator utilizing a CNTfield emissioncathode. The cathode is temporally modulated to deliver a calibrated electron dose to the target. Microfabrication methods are used to develop beamcollimators of fine aperture. Dosimetry is performed using GAFCHROMIC film, and system feasibility is demonstrated via Rat‐1 cell line irradiation. A multi‐pixel system with a cathode chip and electron transparent window has been built, and the multi‐pixel method has been demonstrated via field emissiontesting.Results: Preliminary data show the CNT electron microbeam irradiator is capable of 100 Gy/sec dose rate and 23um beam diameter. An “L” shaped irradiation pattern was used in feasibility demonstration using plated Rat‐1 cells. Irradiation was visualized via Gamma‐H2AX fluorescence marking of DNA damage. The multi‐pixel microbeam concept has been demonstrated through fabrication and testing of a 5×5 microbeam array cathode. A 2.5mA field emission current was achieved with all pixels emitting. Conclusion: We have demonstrated the feasibility of a carbon nanotubefield emission based single microbeam cellular irradiation system as well as the cathode fabrication for the multi‐pixel microbeam prototype system still under development. The CNT microbeam irradiator is capable of delivering radiation over a large dynamic dose rate range with high temporal resolution. The eventual CNT based cellular irradiator is expected to be compact and made available for broad application.