Honors & Awards
Member, Canadian College of Medical Physicists (CCPM) (2000)
M.Sc., Bulgarian National University, Physics (1992)
PhD, McGill University, Medical Physics (1998)
Development and integration of X-ray, MRI and US imaging technologies for radiation therapy guidance; Design of synergistic approaches to radiation therapy delivery; Treatment planning optimization and modeling.
Primary Objective: The primary objectives of this prospective pilot study is to: 1. determine the feasibility and reproducibility of 3D contrast enhanced ultrasound imaging in liver cancer patients undergoing Stereotactic Ablative Radiotherapy and 2. evaluate whether there are treatment induced early changes in imaging metrics derived from 3D contrast enhanced ultrasound. This study will provide valuable insight as to the potential of baseline and/or early post-treatment 3D ultrasound perfusion characteristics (measurements of blood-flow) of primary and metastatic liver tumors to predict tumor response to Stereotactic Ablative Radiotherapy. The investigators' underlying goal is to assess whether early perfusion changes at 1-7 days after SABR initiation can be used as a non-invasive early biomarker for treatment response assessment. Secondary Objectives: Evaluate the feasibility of contrast-enhanced ultrasound-to-CT fusion by assisting three-dimensional (3D) perfusion ultrasound (US) imaging with optical and electromagnetic tracking of the ultrasound probe on patients with liver cancer that will undergo CT for treatment planning and/or response evaluation.
Stanford is currently not accepting patients for this trial. For more information, please contact Kevin Smith, 650-725-4099.
SPECIFIC STUDY AIMS 1. To evaluate congruence between pelvic anatomical structures segmented on MRI and/or CT scans co-registered with transperineal US scans acquired with an optically and/or electromagnetically tracked matrix array ultrasound transducer. 2. To estimate the achievable accuracy of anatomy tracking based on 3D US matrix-array transducer imaging and grey-level based image registration algorithms.
Patients are invited to participate in a research study of liver perfusion (how blood flows to the liver over time). Researchers hope to learn whether perfusion characteristics of liver metastases may be predictive of response to treatment and whether liver perfusion characteristics can be used to follow response to treatment. Patients were selected as a possible participant in this study because they are identified as having liver metastases
To develop planning and delivery capabilities for linear accelerator-based nonisocentric trajectory modulated arc therapy (TMAT) and to evaluate the benefit of TMAT for accelerated partial breast irradiation (APBI) with the patient in prone position.An optimization algorithm for volumetrically modulated arc therapy (VMAT) was generalized to allow for user-defined nonisocentric TMAT trajectories combining couch rotations and translations. After optimization, XML scripts were automatically generated to program and subsequently deliver the TMAT plans. For 10 breast patients in the prone position, TMAT and 6-field noncoplanar intensity modulated radiation therapy (IMRT) plans were generated under equivalent objectives and constraints. These plans were compared with regard to whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose.For TMAT APBI, nonisocentric collision-free horizontal arcs with large angular span (251.5 ± 7.9°) were optimized and delivered with delivery time of ∼4.5 minutes. Percentage changes of whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose for TMAT relative to IMRT were -10.81% ± 6.91%, -27.81% ± 7.39%, -14.82% ± 9.67%, and 39.40% ± 10.53% (P≤.01).This is a first demonstration of end-to-end planning and delivery implementation of a fully dynamic APBI TMAT. Compared with IMRT, TMAT resulted in marked reduction of the breast tissue volume irradiated at high doses.
View details for DOI 10.1016/j.ijrobp.2015.04.034
View details for Web of Science ID 000357900600037
View details for PubMedID 26050608
External beam radiation therapy (EBRT) is included in the treatment regimen of the majority of cancer patients. With the proliferation of hypofractionated radiotherapy treatment regimens, such as stereotactic body radiation therapy (SBRT), interfractional and intrafractional imaging technologies are becoming increasingly critical to ensure safe and effective treatment delivery. Ultrasound (US)-based image guidance systems offer real-time, markerless, volumetric imaging with excellent soft tissue contrast, overcoming the limitations of traditional X-ray or computed tomography (CT)-based guidance for abdominal and pelvic cancer sites, such as the liver and prostate. Interfractional US guidance systems have been commercially adopted for patient positioning but suffer from systematic positioning errors induced by probe pressure. More recently, several research groups have introduced concepts for intrafractional US guidance systems leveraging robotic probe placement technology and real-time soft tissue tracking software. This paper reviews various commercial and research-level US guidance systems used in radiation therapy, with an emphasis on hardware and software technologies that enable the deployment of US imaging within the radiotherapy environment and workflow. Previously unpublished material on tissue tracking systems and robotic probe manipulators under development by our group is also included.
View details for DOI 10.7759/cureus.280
View details for PubMedID 26180704
We sought to assess the feasibility and reproducibility of 3-dimensional ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression in tumor angiogenesis using a clinical matrix array transducer and a clinical grade VEGFR2-targeted contrast agent in a murine model of human colon cancer.Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice with human colon cancer xenografts (n = 33) were imaged with a clinical ultrasound system and transducer (Philips iU22; X6-1) after intravenous injection of either clinical grade VEGFR2-targeted microbubbles or nontargeted control microbubbles. Nineteen mice were scanned twice to assess imaging reproducibility. Fourteen mice were scanned both before and 24 hours after treatment with either bevacizumab (n = 7) or saline only (n = 7). Three-dimensional USMI data sets were retrospectively reconstructed into multiple consecutive 1-mm-thick USMI data sets to simulate 2-dimensional imaging. Vascular VEGFR2 expression was assessed ex vivo using immunofluorescence.Three-dimensional USMI was highly reproducible using both VEGFR2-targeted microbubbles and nontargeted control microbubbles (intraclass correlation coefficient, 0.83). The VEGFR2-targeted USMI signal significantly (P = 0.02) decreased by 57% after antiangiogenic treatment compared with the control group, which correlated well with ex vivo VEGFR2 expression on immunofluorescence (ρ = 0.93, P = 0.003). If only central 1-mm tumor planes were analyzed to assess antiangiogenic treatment response, the USMI signal change was significantly (P = 0.006) overestimated by an average of 27% (range, 2%-73%) compared with 3-dimensional USMI.Three-dimensional USMI is feasible and highly reproducible and allows accurate assessment and monitoring of VEGFR2 expression in tumor angiogenesis in a murine model of human colon cancer.
View details for DOI 10.1097/RLI.0000000000000128
View details for PubMedID 25575176
To clinically evaluate an iterative metal artifact reduction (IMAR) algorithm prototype in the radiation oncology clinic setting by testing for accuracy in CT number retrieval, relative dosimetric changes in regions affected by artifacts, and improvements in anatomical and shape conspicuity of corrected images.A phantom with known material inserts was scanned in the presence/absence of metal with different configurations of placement and sizes. The relative change in CT numbers from the reference data (CT with no metal) was analyzed. The CT studies were also used for dosimetric tests where dose distributions from both photon and proton beams were calculated. Dose differences and gamma analysis were calculated to quantify the relative changes between doses calculated on the different CT studies. Data from eight patients (all different treatment sites) were also used to quantify the differences between dose distributions before and after correction with IMAR, with no reference standard. A ranking experiment was also conducted to analyze the relative confidence of physicians delineating anatomy in the near vicinity of the metal implants.IMAR corrected images proved to accurately retrieve CT numbers in the phantom study, independent of metal insert configuration, size of the metal, and acquisition energy. For plastic water, the mean difference between corrected images and reference images was -1.3 HU across all scenarios (N = 37) with a 90% confidence interval of [-2.4, -0.2] HU. While deviations were relatively higher in images with more metal content, IMAR was able to effectively correct the CT numbers independent of the quantity of metal. Residual errors in the CT numbers as well as some induced by the correction algorithm were found in the IMAR corrected images. However, the dose distributions calculated on IMAR corrected images were closer to the reference data in phantom studies. Relative spatial difference in the dose distributions in the regions affected by the metal artifacts was also observed in patient data. However, in absence of a reference ground truth (CT set without metal inserts), these differences should not be interpreted as improvement/deterioration of the accuracy of calculated dose. With limited data presented, it was observed that proton dosimetry was affected more than photons as expected. Physicians were significantly more confident contouring anatomy in the regions affected by artifacts. While site specific preferences were detected, all indicated that they would consistently use IMAR corrected images.IMAR correction algorithm could be readily implemented in an existing clinical workflow upon commercial release. While residual errors still exist in IMAR corrected images, these images present with better overall conspicuity of the patient/phantom geometry and offer more accurate CT numbers for improved local dosimetry. The variety of different scenarios included herein attest to the utility of the evaluated IMAR for a wide range of radiotherapy clinical scenarios.
View details for DOI 10.1118/1.4906245
View details for PubMedID 25735272
To investigate the variation of imaging dose with tube potential in variable pitch body CT perfusion (CTp) protocols using the TG111 dosimetric formalism.TG111 recommendations were followed in choosing the phantom, dosimetric equipment, and methodology. Specifically, equilibrium doses (D(eq)) were measured centrally and peripherally in a long PMMA phantom. Reference planar average equilibrium doses were determined for each tube potential, for a reference set of exposure parameters (collimation, pitch, filtration) on a Siemens Definition CT scanner. These reference values were utilized to predict the imaging dose during perfusion scans using interpretations of the TG111 formalism. As a gold reference, the midscan average planar perfusion doses (D(CTp)) were obtained directly from central and peripheral D(eq) measurements for body CTp scans (144 and 271 mm) using variable pitch acquisition. Measurement-based D(CTp) values obtained using a thimble chamber were compared to the TG111-predicted values, and to CTDI(vol) reported at the console.Reference planar average equilibrium dose values measured for reference uniform pitch helical scans were consistently higher than console-reported or measured values for CTDI(vol). The measurement-based perfusion dose D(CTp) was predicted accurately by the reported CTDI(vol) for the 144 mm scan. The 271 mm scans delivered systematically larger dose than reported. The TG111-based dose estimates were proven to be conservative, as they were systematically higher than both the measured and the reported imaging doses.Upon successful implementation of TG111 formalism, standard imaging dose was measured for a body CTp protocol using the variable pitch helical acquisition. The TG111 formalism is not directly applicable to this type of acquisition. Measurement of dose for all variable pitch protocols is strongly suggested.
View details for DOI 10.1118/1.4876377
View details for Web of Science ID 000337106300030
View details for PubMedID 24877823
External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide-angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast.A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeam™ STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom.The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V50% and V100% parameters that have been correlated with EBRT toxicity.The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose-volume parameters correlated with toxicity.
View details for DOI 10.1016/j.radonc.2013.10.031
View details for Web of Science ID 000329482000027
View details for PubMedID 24231240
Many real time ultrasound (US) guided therapies can benefit from management of motion-induced anatomical changes with respect to a previously acquired computerized anatomy model. Spatial calibration is a prerequisite to transforming US image information to the reference frame of the anatomy model. We present a new method for calibrating 3D US volumes using intramodality image registration, derived from the 'hand-eye' calibration technique. The method is fully automated by implementing data rejection based on sensor displacements, automatic registration over overlapping image regions, and a self-consistency error metric evaluated continuously during calibration. We also present a novel method for validating US calibrations based on measurement of physical phantom displacements within US images. Both calibration and validation can be performed on arbitrary phantoms. Results indicate that normalized mutual information and localized cross correlation produce the most accurate 3D US registrations for calibration. Volumetric image alignment is more accurate and reproducible than point selection for validating the calibrations, yielding <1.5 mm root mean square error, a significant improvement relative to previously reported hand-eye US calibration results. Comparison of two different phantoms for calibration and for validation revealed significant differences for validation (p = 0.003) but not for calibration (p = 0.795).
View details for DOI 10.1088/0031-9155/58/21/7481
View details for Web of Science ID 000326377100004
View details for PubMedID 24099806
View details for Web of Science ID 000347163501106
Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy.We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume ?12 mL) received multifraction regimens with BED ?100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2).The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02).A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.
View details for DOI 10.1016/j.ijrobp.2011.10.071
View details for Web of Science ID 000308061900060
View details for PubMedID 22381907
Emerging prolonged, hypofractionated radiotherapy regimens rely on high-dose conformality to minimize toxicity and thus can benefit from image guidance systems that continuously monitor target position during beam delivery. To address this need we previously developed, as a potential add-on device for existing linear accelerators, a novel telerobotic ultrasound system capable of real-time, soft-tissue imaging. Expanding on this capability, the aim of this work was to develop and characterize an image-based technique for real-time detection of prostate displacements.Image processing techniques were implemented on spatially localized ultrasound images to generate two parameters representing prostate displacements in real time. In a phantom and five volunteers, soft-tissue targets were continuously imaged with a customized robotic manipulator while recording the two tissue displacement parameters (TDPs). Variations of the TDPs in the absence of tissue displacements were evaluated, as was the sensitivity of the TDPs to prostate translations and rotations. Robustness of the approach to probe force was also investigated.With 95% confidence, the proposed method detected in vivo prostate displacements before they exceeded 2.3, 2.5, and 2.8 mm in anteroposterior, superoinferior, and mediolateral directions. Prostate pitch was detected before exceeding 4.7° at 95% confidence. Total system time lag averaged 173 ms, mostly limited by ultrasound acquisition rate. False positives (FPs) (FP) in the absence of displacements did not exceed 1.5 FP events per 10 min of continuous in vivo imaging time.The feasibility of using telerobotic ultrasound for real-time, soft-tissue-based monitoring of target displacements was confirmed in vivo. Such monitoring has the potential to detect small clinically relevant intrafractional variations of the prostate position during beam delivery.
View details for DOI 10.1016/j.ijrobp.2011.10.049
View details for Web of Science ID 000306128100062
View details for PubMedID 22285664
In external-beam radiation therapy, existing on-board x-ray imaging chains orthogonal to the delivery beam cannot recover 3D target trajectories from a single view in real-time. This limits their utility for real-time motion management concurrent with beam delivery. To address this limitation, the authors propose a novel concept for on-board imaging based on the inverse-geometry Scanning-Beam Digital X-ray (SBDX) system and evaluate its feasibility for single-view 3D intradelivery fiducial tracking.A chest phantom comprising a posterior wall, a central lung volume, and an anterior wall was constructed. Two fiducials were placed along the mediastinal ridge between the lung cavities: a 1.5 mm diameter steel sphere superiorly and a gold cylinder (2.6 mm length × 0.9 mm diameter) inferiorly. The phantom was placed on a linear motion stage that moved sinusoidally. Fiducial motion was along the source-detector (z) axis of the SBDX system with ±10 mm amplitude and a programmed period of either 3.5 s or 5 s. The SBDX system was operated at 15 frames per second, 100 kVp, providing good apparent conspicuity of the fiducials. With the stage moving, detector data were acquired and subsequently reconstructed into 15 planes with a 12 mm plane-to-plane spacing using digital tomosynthesis. A tracking algorithm was applied to the image planes for each temporal frame to determine the position of each fiducial in (x,y,z)-space versus time. A 3D time-sinusoidal motion model was fit to the measured 3D coordinates and root mean square (RMS) deviations about the fitted trajectory were calculated.Tracked motion was sinusoidal and primarily along the source-detector (z) axis. The RMS deviation of the tracked z-coordinate ranged from 0.53 to 0.71 mm. The motion amplitude derived from the model fit agreed with the programmed amplitude to within 0.28 mm for the steel sphere and within -0.77 mm for the gold seed. The model fit periods agreed with the programmed periods to within 7%.Three dimensional fiducial tracking with approximately 1 mm or better accuracy and precision appears to be feasible with SBDX, supporting its use to guide radiotherapy.
View details for DOI 10.1118/1.3697529
View details for Web of Science ID 000302371900045
View details for PubMedID 22482637
Metal artifacts can degrade computed tomographic (CT) simulation imaging and impair accurate delineation of tumors for radiation treatment planning purposes. We investigated a Digital Imaging and Communications in Medicine-based metal artifact reduction technique in tonsillar cancer delineation.Eight patients with significant artifact and tonsil cancer were evaluated. Each patient had a positron emission tomography (PET)-CT and a contrast-enhanced CT obtained at the same setting during radiotherapy simulation. The CTs were corrected for artifact using the metal deletion technique (MDT). Two radiation oncologists independently delineated primary gross tumor volumes (GTVs) for each patient on native (CTnonMDT), metal corrected (CTMDT), and reference standard (CTPET/nonMDT) imaging, 1 week apart. Mixed effects models were used to determine if differences among GTVs were statistically significant. Two diagnostic radiologists and 2 radiation oncologists independently qualitatively evaluated CTs for each patient. Ratings were on an ordinal scale from -3 to +3, denoting that CTMDT was markedly, moderately, or slightly worse or better than CTnonMDT. Scores were compared with a Wilcoxon signed-rank test.The GTVPET/nonMDT were significantly smaller than GTVnonMDT (P = .004) and trended to be smaller than GTVMDT (P = .084). The GTVnonMDT and GTVMDT were not significantly different (P = .93). There was no significant difference in the extent to which GTVnonMDT or GTVMDT encompassed GTVPET/nonMDT (P = .33). In the subjective assessment of image quality, CTMDT did not significantly outperform CTnonMDT. In the majority of cases, the observer rated the CTMDT equivalent to (53%) or slightly superior (41%) to the corresponding CTnonMDT.The MTD modified images did not produce GTVMDT that more closely reproduced GTVPET/nonMDT than did GTVnonMDT. Moreover, the MTD modified images were not judged to be significantly superior when compared to the uncorrected images in terms of subjective ability to visualize the tonsilar tumors. This study failed to demonstrate value of the adjunctive use of a CT corrected for artifacts in the tumor delineation process. Artifacts do make tumor delineation challenging, and further investigation of other body sites is warranted.
View details for DOI 10.1016/j.prro.2011.06.004
View details for PubMedID 24674033
An integrated Overhauser-enhanced MRI-Prepolarized MRI system was developed to obtain radiobiological information that could be accurately coregistered with diagnostic quality anatomic images. EPR and NMR images were acquired through the double resonance technique and field cycling of the main magnetic field from 5 mT to 0.5 T. Dedicated EPR and NMR coils were devised to minimize radiofrequency power deposition with high signal-to-noise ratio. Trityl and nitroxide radicals were used to characterize oxygen and redox sensitivities of multispin echo Overhauser-enhanced MRI. Oxygen resolution of 3 mmHg was obtained from 2 mM deoxygenated trityl phantoms. Trityl radicals were stable in reducing environments and did not alter the redox-sensitive decaying rate of the nitroxide signals. Nitroxide radicals had a compounding effect for the trityl oximetry. Tumor oxygenation and redox status were acquired with anatomical images by injecting trityl and nitroxide probes subsequently in murine tumors. The Overhauser-enhanced MRI-Prepolarized MRI system is ready for quantitative longitudinal imaging studies of tumor hypoxia and redox status as radiotherapy prognostic factors.
View details for DOI 10.1002/mrm.22732
View details for Web of Science ID 000289760800027
View details for PubMedID 21500268
To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.
View details for DOI 10.1016/j.ijrobp.2010.05.015
View details for Web of Science ID 000288471500036
View details for PubMedID 20801584
The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance.A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active.Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as would be enabled by real-time imaging, gross tumor volume coverage was identical while notable reductions of bladder and rectal volumes exposed to large doses were possible. The quality of U.S. images obtained during beam operation was not appreciably degraded by radiofrequency interference and 2D tracking of a phantom object in U.S. images obtained with the beam on/off yielded no significant differences.Remotely controlled robotic U.S. imaging is feasible in the radiotherapy environment and for the first time may offer real-time volumetric soft-tissue guidance concurrent with radiotherapy delivery.
View details for DOI 10.1118/1.3515457
View details for Web of Science ID 000285849400027
View details for PubMedID 21302793
A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.
View details for DOI 10.1136/jnis.2009.001941
View details for Web of Science ID 000281357900019
View details for PubMedID 21990637
To design and evaluate a magnetic resonance imaging (MRI) protocol to be incorporated in the simulation process for external beam accelerated partial breast irradiation.An imaging protocol was developed based on an existing breast MRI technique with the patient in the prone position on a dedicated coil. Pulse sequences were customized to exploit T1 and T2 contrast mechanisms characteristic of lumpectomy cavities. A three-dimensional image warping algorithm was included to correct for geometric distortions related to nonlinearity of spatially encoding gradients. Respiratory motion, image distortions, and susceptibility artifacts of 3.5-mm titanium surgical clips were examined. Magnetic resonance images of volunteers were acquired repeatedly to analyze residual setup deviations resulting from breast tissue deformation.The customized sequences generated high-resolution magnetic resonance images emphasizing lumpectomy cavity morphology. Respiratory motion was negligible with the subject in the prone position. The gradient-induced nonlinearity was reduced to less than 1 mm in a region 15 cm away from the isocenter of the magnet. Signal-void regions of surgical clips were 4 mm and 8 mm for spin echo and gradient echo images, respectively. Typical residual repositioning errors resulting from breast deformation were estimated to be 3 mm or less.MRI guidance for accelerated partial breast irradiation with the patient in the prone position with adequate contrast, spatial fidelity, and resolution is possible.
View details for DOI 10.1016/j.ijrobp.2009.03.063
View details for Web of Science ID 000269328700045
View details for PubMedID 19632067
Quantitative reconstruction of cone beam X-ray computed tomography (CT) datasets requires accurate modeling of scatter, beam-hardening, beam profile, and detector response. Typically, commercial imaging systems use fast empirical corrections that are designed to reduce visible artifacts due to incomplete modeling of the image formation process. In contrast, Monte Carlo (MC) methods are much more accurate but are relatively slow. Scatter kernel superposition (SKS) methods offer a balance between accuracy and computational practicality. We show how a single SKS algorithm can be employed to correct both kilovoltage (kV) energy (diagnostic) and megavoltage (MV) energy (treatment) X-ray images. Using MC models of kV and MV imaging systems, we map intensities recorded on an amorphous silicon flat panel detector to water-equivalent thicknesses (WETs). Scattergrams are derived from acquired projection images using scatter kernels indexed by the local WET values and are then iteratively refined using a scatter magnitude bounding scheme that allows the algorithm to accommodate the very high scatter-to-primary ratios encountered in kV imaging. The algorithm recovers radiological thicknesses to within 9% of the true value at both kV and megavolt energies. Nonuniformity in CT reconstructions of homogeneous phantoms is reduced by an average of 76% over a wide range of beam energies and phantom geometries.
View details for DOI 10.1109/TMI.2008.928922
View details for Web of Science ID 000261364900011
View details for PubMedID 19033095
A calculation model for the quantitative prediction of primary intensity fluence distributions obtained by the Bragg diffraction focusing of kilovoltage radiation by cylindrical x-ray lenses is presented. The mathematical formalism describes primary intensity distributions from cylindrically-symmetric x-ray lenses, with a planar isotropic radiation source located in a plane perpendicular to the lens axis. The presence of attenuating medium inserted between the lens and the lens focus is accounted for by energy-dependent attenuation. The influence of radiation scattered within the media is ignored. Intensity patterns are modeled under the assumption that photons that are not interacting with the lens are blocked out at any point of interest. The main characteristics of the proposed calculation procedure are that (i) the application of vector formalism allows universal treatment of all cylindrical lenses without the need of explicit geometric constructs; (ii) intensity distributions resulting from x-ray diffraction are described by a 3D generalization of the mosaic spread concept; (iii) the calculation model can be immediately coupled to x-ray diffraction simulation packages such as XOP and Shadow. Numerical simulations based on this model are to facilitate the design of focused orthovoltage treatment (FOT) systems employing cylindrical x-ray lenses, by providing insight about the influence of the x-ray source and lens parameters on quantities of dosimetric interest to radiation therapy.
View details for DOI 10.1088/0031-9155/53/3/001
View details for Web of Science ID 000252792700001
View details for PubMedID 18199899
View details for Web of Science ID 000258805302049
In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO(2)-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO(2)-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO(2) Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO(2)-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.
View details for DOI 10.1088/0031-9155/51/19/012
View details for Web of Science ID 000241083800012
View details for PubMedID 16985278
Siemens Medical Solutions, Oncology Care Systems Group (SMSOCSG) is supporting the development of several technologies that enable image acquisition and decision making processes required for IGRT in various clinical settings. Four such technologies are presented including: (i) the integration of a traditional multi-slice computed tomography (CT) scanner "on rails" with a C-arm gantry linear accelerator; (ii) the development of a high sensitivity, fast, megavoltage (MV) electronic portal imaging device capable of clinical MV Conebeam CT (MVCBCT) reconstruction and fluoroscopy mounted on a C-arm gantry linear accelerator; (iii) the modification of a mobile C-arm with flat panel kilovoltage (kV) diagnostic imager; and (iv) the development of an in-line megavoltage and kilovoltage flat panel imaging system that has the potential to image both anatomical and dosimetric information in "real-time" utilizing the traditional C-arm gantry linear accelerator geometry. Each method of IGRT has unique as well as complementary qualities which are discussed from both a clinical and technical perspective.
View details for DOI 10.1016/j.meddos.2005.12.013
View details for Web of Science ID 000236687500003
View details for PubMedID 16551525
Kilovolt x-rays are clearly suboptimal compared to MV photon beams for radiotherapy of deep-seated tumours because of the increased attenuation in tissue, causing a rapid dose fall-off. This picture could change drastically when tumours can be labelled with contrast medium, containing high atomic number elements. This causes a significant dose enhancement to the tumour by exploiting the high cross sections for the photo-electric effect for kV x-rays. In this work, we have investigated the dosimetric and microdosimetric characteristics of kV contrast-enhanced radiation therapy (CERT) for different photon energies, contrast-medium concentrations and types (I and Gd). Two idealized patient treatment plans (head and lung) for irradiation with CT-arc beams were calculated. It is shown that the dose enhancement in tumours can be highly significant (up to about sixfold for realistic 80-120 kVp x-ray spectra and an iodine concentration of 50 mg ml-1) but that dose homogeneity in the tumour depends on photon energy, contrast-medium concentration and type, and irradiation scheme. An attempt to optimize the irradiation scheme is discussed. The microdosimetric study of the dose mean lineal energy shows that radiation quality changes in the contrast-medium-labelled region compared to homogeneous tissue are fairly small and limited to 10%. It is concluded that kV-CERT is a promising radiotherapy technique, provided contrast medium can be delivered reliably to tumours.
View details for DOI 10.1088/0031-9155/50/15/005
View details for Web of Science ID 000231321600005
View details for PubMedID 16030382
Energy modulated electron beam therapy with conventional clinical accelerators has lagged behind photon IMRT despite its potential to achieve highly conformal dose distributions in superficial targets. One of the reasons for this is the absence of an automated collimating device that allows for the flexible delivery of a series of variable field openings. Electron-specific multileaf collimators attached to the bottom of the applicator require the use of a large number of motors and suffer from being relatively bulky and impractical for head and neck sites. In this work, we investigate the treatment planning aspects of a proposed 'few-leaf' electron collimator (FLEC) that consists of four motor-driven trimmer bars at the end of the applicator. The device is designed to serve as an accessory to standard equipment and allows for the shaping of any irregular field by combination of rectangular fieldlets. Using a Monte Carlo model of the FLEC, dose distributions are optimized using a simulated annealing (SA) inverse planning algorithm based on a limited number of Monte Carlo pre-generated, realistic phantom-specific dose kernels and user-specified dose-volume constraints. Using a phantom setup with an artificial target enclosed by organs at risk (OAR) as well as using a realistic patient case, we demonstrate that highly conformal distributions can be generated. Estimates of delivery times are made and show that a full treatment fraction can be kept to 15 min or less.
View details for DOI 10.1088/0031-9155/50/5/009
View details for Web of Science ID 000227886900010
View details for PubMedID 15798259
The objective of this work was to demonstrate the feasibility of acquiring low-exposure megavoltage cone-beam CT (MV CBCT) three-dimensional (3D) image data of sufficient quality to register the CBCT images to kilovoltage planning CT images for patient alignment and dose verification purposes.A standard clinical 6-MV Primus linear accelerator, operating in arc therapy mode, and an amorphous-silicon (a-Si) flat-panel electronic portal-imaging device (EPID) were employed. The dose-pulse rate of 6-MV Primus accelerator beam was windowed to expose an a-Si flat panel by using only 0.02 to 0.08 monitor unit (MUs) per image. A triggered image-acquisition mode was designed to produce a high signal-to-noise ratio without pulsing artifacts. Several data sets were acquired for an anthropomorphic head phantom and frozen sheep and pig cadaver head, as well as for a head-and-neck cancer patient on intensity-modulated radiotherapy (IMRT). For each CBCT image, a set of 90 to 180 projection images incremented by 1 degree to 2 degrees was acquired. The two-dimensional (2D) projection images were then synthesized into a 3D image by use of cone-beam CT reconstruction. The resulting MV CBCT image set was used to visualize the 3D bony anatomy and some soft-tissue details. The 3D image registration with the kV planning CT was performed either automatically by application of a maximization of mutual information (MMI) algorithm or manually by aligning multiple 1D slices.Low-noise 3D MV CBCT images without pulsing artifacts were acquired with a total delivered dose that ranged from 5 to 15 cGy. Acquisition times, including image readout, were on the order of 90 seconds for 180 projection images taken through a continuous gantry rotation of 180 degrees. The processing time of the data required an additional 90 seconds for the reconstruction of a 256(3) cube with 1.0-mm voxel size. Implanted gold markers (1 mm x 3 mm) were easily visible or all exposure levels without artifacts. In general, the presence of high Z materials such as tooth fillings or implanted markers did not result in visible streak artifacts. The registration of structures such as the spinal canal and the nasopharynx in the MV CBCT and kV CT data sets was possible with millimeter and degree accuracy as assessed by displacement simulations and subsequent visual evaluation.We believe that the quality of these images, along with the rapid acquisition and reconstruction times, demonstrates that MV CBCT performed by use of a standard linear accelerator equipped with a flat-panel imager can be applied clinically for patient alignment.
View details for DOI 10.1016/j.ijrobp.2004.10.011
View details for Web of Science ID 000226700200032
View details for PubMedID 15736320
We present a novel method for rapid removal of patient scatter from cone beam (CB) projection images that requires no scatter measurement, physical modeling or strong assumptions regarding the spatial smoothness of the scatter distribution. Method: A modulator grid is placed between the imaged distribution and the detector that differentially frequency modulates primary and scattered photons. When photons travel through the grid, photons that originate directly from the CB source are modulated by a higher frequency than scattered photons that have more proximal, diffusely distributed sources. We employ non-linear Fourier domain filtering to attenuate the contribution of scatter to the image spectrum. The theoretical validity of the method is verified using linear analysis of planar sources and its performance is evaluated using a simulator based on this analytical model. Results: Simulation experiments with an ideal modulator indicate that even unrealistically large amounts of scatter are almost entirely removed by this method. The recovered images are devoid of major artifacts and exhibit an RMS error of 10%. Conclusions: We have verified the theoretical validity of scatter removal via spatial frequency modulation. A disadvantage of the technique is that it will always produce a filtered image having at best 0.41 of the maximum detector resolution when maximum scatter rejection is desired. This is not a major consideration in most medical X-ray CB imaging applications using contemporary detector technology, especially since scatter often significantly reduces useful resolution.
View details for Web of Science ID 000238998401210
View details for PubMedID 17282580
In the current state-of-the art of clinical inverse planning, the design of clinically acceptable IMRT plans is predominantly based on the optimization of physical rather than biological objective functions. A major impetus for this trend is the unproven predictive power of radiobiological models, which is largely due to the scarcity of data sets for an accurate evaluation of the model parameters. On the other hand, these models do capture the currently known dose-volume effects in tissue dose-response, which should be accounted for in the process of optimization. In order to incorporate radiobiological information in clinical treatment planning optimization, we propose a hybrid physico-biological approach to inverse treatment planning based on the application of a continuous penalty function method to the constrained minimization of a biological objective. The objective is defined as the weighted sum of normal tissue complication probabilities evaluated with the Lyman normal-tissue complication probability model. Physical constraints specify the admissible minimum and maximum target dose. The continuous penalty function method is then used to find an approximate solution of the resulting large-scale constrained minimization problem. Plans generated by our approach are compared to ones produced by a commercial planning system incorporating physical optimization. The comparisons show clinically negligible differences, with the advantage that the hybrid technique does not require specifications of any dose-volume constraints to the normal tissues. This indicates that the proposed hybrid physico-biological method can be used for the generation of clinically acceptable plans.
View details for DOI 10.1118/1.1617411
View details for Web of Science ID 000186596900012
View details for PubMedID 14655942
The influence of organ volume sampling, lateral scatter inclusion, and the selection of objectives and constraints on the inverse treatment planning process with a commercial treatment planning system is investigated and suitable parameters are identified for an inverse treatment planning replacement of a clinical forward planning technique for prostate cancer. For the beam geometries of the forward technique, a variable set of parameters is used for the calculation of dose from pencil beams. An optimal set is identified after the evaluation of optimized plans that correspond to different sets of pencil-beam parameters. This set along with a single, optimized set of objectives and constraints is used to perform inverse planning on ten randomly selected patients. The acceptability of the resulting plans is verified by comparisons to the clinical ones calculated with the forward techniques. For the particular commercial treatment planning system, the default values of the pencil beam parameters are found adequate for inverse treatment planning. For all ten patients, the optimized, single set of objectives and constraints results in plans with target coverage comparable to that of the forward plans. Furthermore inverse treatment planning reduces the overall mean rectal and bladder doses by 4.8% and 5.8% of the prescription dose respectively. The study indicates that (i) inverse treatment planning results depend implicitly on the sampling of the dose distribution, (ii) inverse treatment planning results depend on the method used by the dose calculation model to account for scatter, and (iii) for certain sites, a single set of optimization parameters can be used for all patient plans.
View details for PubMedID 12132941
A method that allows a straightforward implementation of dose-volume constraints in gradient algorithms for inverse treatment planning is presented. The method is consistent with the penalty function approach, which requires the formulation of an objective function with penalty terms proportional to the magnitudes of constraint violations. Dose constraints with respect to minimum and maximum target dose levels are incorporated in quadratic, dose-penalty terms. Analogously, quadratic volume-penalty terms in the objective function reflect the violation of dose-volume constraints imposing limits on the fractions of healthy organ volumes that can be irradiated above specified dose levels. It has been demonstrated that within the framework of this formulation neither modified objective functions nor finite difference gradient calculations are necessary for the incorporation of gradient minimization algorithms. As an example, a simple steepest descent algorithm is presented along with its application to illustrate prostate and lung cases.
View details for DOI 10.1118/1.1469629
View details for Web of Science ID 000175675000023
View details for PubMedID 12033581
View details for Web of Science ID 000166896300423
A method for three-dimensional verification of anatomy setup that uses the correlation of portal images and reference megavoltage digitally reconstructed radiographs (MDRRs) is presented. Prior to a treatment, an orthogonal pair of portal images is acquired from which subimages containing anatomical features are selected. These subimages are consequently matched to MDRRs that represent different rotations of the anatomy around axes going through the treatment isocenter. The Pearson correlation coefficient is employed for the matching since it is invariant with respect to global scaling and shifting of the image intensities. Furthermore, it does not require feature extraction or point-pair identification. The greatest value of the correlation coefficient corresponds to the proper rotational alignment of the anatomy and the location of the correlation maximum in each view indicates the translational shifts of the anatomy. The mean accuracy of translation and rotation registrations tests were a fraction of a millimeter and a fraction of a degree, respectively, for MDRR-to-MDRR matching. For portal-to-MDRR matching, the mean translation registration error is on the order of 1 mm and the mean error in radial displacement is of the order of 2.7 mm.
View details for Web of Science ID 000083775800030
View details for PubMedID 10587227
Conventional inverse treatment planning attempts to calculate dose distributions that may not be feasible given the specified dose levels to various anatomical structures. A technique for inverse treatment planning has been developed that uses only target dose levels which are easily selectable to be feasible. A nonlinear constrained minimization problem is formulated to reflect the goal of sparing critical organs as much as possible while delivering a certain target dose within specified uniformity. The objective function is the squared dose delivered to critical organs. The constraints require the delivery of certain target dose within specified uniformity and non-negative pencil beam weights. A continuous penalty function method is introduced as a method for solving the large-scale constrained minimization problem. The performance of the continuous penalty function method is optimized by numerical investigation of few numerical integration schemes and a pair of weighting functions which influence the utility of the method. Clinical examples are presented that illustrate several features of the technique. The properties of the continuous penalty function method suggest that it may be a viable alternative to conventional inverse treatment planning.
View details for Web of Science ID 000072063400010
View details for PubMedID 9507482
An active set algorithm for optimization of radiation therapy dose planning by intensity modulated beams has been developed. The algorithm employs a conjugate-gradient routine for subspace minimization in order to achieve a higher rate of convergence than the widely used constrained steepest-descent method at the expense of a negligible amount of overhead calculations. The performance of the new algorithm has been compared to that of the constrained steepest-descent method for various treatment geometries and two different objectives. The active set algorithm is found to be superior to the constrained steepest descent, both in terms of its convergence properties and the residual value of the cost functions at termination. Its use can significantly accelerate the design of conformal plans with intensity modulated beams by decreasing the number of time-consuming dose calculations.
View details for Web of Science ID A1997XV90400010
View details for PubMedID 9304574
An algorithm for automatic registration of pairs of portal images based on image correlation is presented. It uses a fast-Fourier-transform-based cross-correlation operator to find the optimal registration, accounting for both in-plane translations and rotations. Different cross-correlation operators have been tested: the Pearson linear correlation coefficient has been implemented by fast Fourier transform and its performance has been compared to that of the more conventional normalized cross-correlation. A sequential approach has been applied to speed up the registration considerably without degrading the performance of the algorithm. The algorithm has also been applied to the automatic registration of portal images to digitally reconstructed radiographs (DRRs), which have been modified to resemble megavoltage images. The results are indicative of the feasibility of this approach to the inspection of patient setup in radiation therapy.
View details for Web of Science ID A1996TR49900009
View details for PubMedID 8700035