Treatment plan adaptation for MRI-guided radiotherapy using solely MRI data: a CT-based simulation study.

An integrated MRI-accelerator system provides MRI images before and during irradiation. Our purpose is to investigate the feasibility of treatment plan adaptation using solely MRI data, which lack density information. In this study we used CT data to quantify the tissue density effect. Treatment planning was performed for five prostate cancer patients. We simulated correction of a 3, 5, 7 and 10 mm prostate shift relative to the body contour in the anterior, posterior, superior and inferior directions. We applied the original treatment plan to each corrected prostate shift and recalculated the dose distribution using the same monitor units (MU). We calculated the dose differences with and without density information. The latter mimics geometrically correct MRI data. Physical path lengths, available in MRI data, are used to perform MU rescaling per beam and are shown to be of more importance than tissue densities for treatment plan adaptation in prostate cancer. As the change in the physical path length of the central beam axis is representative of the entire beam, MU rescaling based on central beam axis information works fine. In conclusion, MRI data could be used for treatment plan adaptation in prostate cancer provided that the images are geometrically correct.

Real-time profiling of respiratory motion: baseline drift, frequency variation and fundamental pattern change.

To precisely ablate tumor in radiation therapy, it is important to locate the tumor position in real time during treatment. However, respiration-induced tumor motions are difficult to track. They are semi-periodic and exhibit variations in baseline, frequency and fundamental pattern (oscillatory amplitude and shape). In this study, we try to decompose the above-mentioned components from discrete observations in real time. Baseline drift, frequency (equivalently phase) variation and fundamental pattern change characterize different aspects of respiratory motion and have distinctive clinical indications. Furthermore, smoothness is a valid assumption for each one of these components in their own spaces, and facilitates effective extrapolation for the purpose of estimation and prediction. We call this process 'profiling' to reflect the integration of information extraction, decomposition, processing and recovery. The proposed method has three major ingredients: (1) real-time baseline and phase estimation based on elliptical shape tracking in augmented state space and Poincaré sectioning principle; (2) estimation of the fundamental pattern by unwarping the observation with phase estimate from the previous step; (3) filtering of individual components and assembly in the original temporal-displacement signal space. We tested the proposed method with both simulated and clinical data. For the purpose of prediction, the results are comparable to what one would expect from a human operator. The proposed approach is fully unsupervised and data driven, making it ideal for applications requiring economy, efficiency and flexibility.

Inference of hysteretic respiratory tumor motion from external surrogates: a state augmentation approach.

It is important to monitor tumor movement during radiotherapy. Respiration-induced motion affects tumors in the thorax and abdomen (in particular, those located in the lung region). For image-guided radiotherapy (IGRT) systems, it is desirable to minimize imaging dose, so external surrogates are used to infer the internal tumor motion between image acquisitions. This process relies on consistent correspondence between the external surrogate signal and the internal tumor motion. Respiratory hysteresis complicates the external/internal correspondence because two distinct tumor positions during different breathing phases can yield the same external observation. Previous attempts to resolve this ambiguity often subdivided the data into inhale/exhale stages and restricted the estimation to only one of these directions. In this study, we propose a new approach to infer the internal tumor motion from external surrogate signal using state augmentation. This method resolves the hysteresis ambiguity by incorporating higher-order system dynamics. It circumvents the segmentation of the internal/external trajectory into different phases, and estimates the inference map based on all the available external/internal correspondence pairs. Optimization of the state augmentation is investigated. This method generalizes naturally to adaptive on-line algorithms.

Real-time prediction of respiratory motion based on local regression methods.

Recent developments in modulation techniques enable conformal delivery of radiation doses to small, localized target volumes. One of the challenges in using these techniques is real-time tracking and predicting target motion, which is necessary to accommodate system latencies. For image-guided-radiotherapy systems, it is also desirable to minimize sampling rates to reduce imaging dose. This study focuses on predicting respiratory motion, which can significantly affect lung tumours. Predicting respiratory motion in real-time is challenging, due to the complexity of breathing patterns and the many sources of variability. We propose a prediction method based on local regression. There are three major ingredients of this approach: (1) forming an augmented state space to capture system dynamics, (2) local regression in the augmented space to train the predictor from previous observation data using semi-periodicity of respiratory motion, (3) local weighting adjustment to incorporate fading temporal correlations. To evaluate prediction accuracy, we computed the root mean square error between predicted tumor motion and its observed location for ten patients. For comparison, we also investigated commonly used predictive methods, namely linear prediction, neural networks and Kalman filtering to the same data. The proposed method reduced the prediction error for all imaging rates and latency lengths, particularly for long prediction lengths.

Automated generation of a four-dimensional model of the liver using warping and mutual information.

The use of mutual information (MI) based alignment to map changes in liver shape and position from exhale to inhale was investigated. Inhale and exhale CT scans were obtained with intravenous contrast for six patients. MI based alignment using thin-plate spine (TPS) warping was performed between each inhale and exhale image set. An expert radiation oncologist identified corresponding vessel bifurcations on the exhale and inhale CT image and the transformation for identified points was determined. This transformation was then used to determine the accuracy of the MI based alignment. The reproducibility of the vessel bifurcation identification was measured through repeat blinded vessel bifurcation identification. Reproducibility [standard deviation (SD)] in the L/R, A/P, and I/S directions was 0.11, 0.09, and 0.14 cm, respectively. The average absolute difference between the transformation obtained using MI based alignment and the vessel bifurcation in the L/R, A/P, and I/S directions was 0.13 cm (SD=0.10 cm), 0.15 cm (SD=0.12 cm), and 0.15 cm (SD-0.14 cm), respectively. These values are comparable to the reproducibility of bifurcation identification, indicating that MI based alignment using TPS warping is accurate to within measurement error and is a reliable tool to aid in describing deformation that the liver undergoes from the exhale to inhale state.

Inclusion of organ deformation in dose calculations.

A previously described system for modeling organ deformation using finite element analysis has been extended to permit dose calculation. Using this tool, the calculated dose to the liver during radiotherapy can be compared using a traditional static model (STATIC), a model including rigid body motion (RB), and finally a model that incorporates rigid body motion and deformation (RBD). A model of the liver, consisting of approximately 6000 tetrahedral finite elements distributed throughout the contoured volume, is created from the CT data obtained at exhale. A deformation map is then created to relate the liver in the exhale CT data to the liver in the inhale CT data. Six intermediate phase positions of each element are then calculated from their trajectories. The coordinates of the centroid of each element at each phase are used to determine the dose received. These intermediate dose values are then time weighted according to a population-modeled breathing pattern to determine the total dose to each element during treatment. This method has been tested on four patient datasets. The change in prescribed dose for each patient's actual tumor as well as a simulated tumor of the same size, located in the superior, intermediate, and inferior regions of the liver, was determined using a normal tissue complication model, maintaining a predicted probability of complications of 15%. The average change in prescribed dose from RBD to STATIC for simulated tumors in the superior, intermediate, and inferior regions are 4.0 (range 2.1 to 5.3), -3.6 (range -5.0 to -2.2), and -14.5 (range -27.0 to -10.0) Gy, respectively. The average change in prescribed dose for the patient's actual tumor was -0.4 Gy (range -4.1 to 1.7 Gy). The average change in prescribed dose from RBD to RB for simulated tumors in the superior, intermediate, and inferior regions are -0.04 (range -2.4 to 2.2), 0.2 (range -1.5 to 1.9), and 3.9 (range 0.8 to 7.3) Gy, respectively. The average change in the prescribed dose for the patient's actual tumor was 0.7 Gy (range 0.2 to 1.1 Gy). This patient sampling indicates the potential importance of including deformation in dose calculations.

Technical note: creating a four-dimensional model of the liver using finite element analysis.

Finite element analysis and two liver CT scans were used to construct a four-dimensional (4D) model of the liver during breathing. A linear elastic, small deformation mechanical model was applied to one patient to obtain intermediate organ position and shape between exhale and inhale. Known transformations between anatomically defined subsections of the exhale and inhale liver surfaces were applied as constraints to the exhale CT liver model. Intermediate states were then calculated and time weighted to determine a 4D model of the liver as it deforms during the breathing cycle. This model can be used to calculate a more accurate dose distribution during radiotherapy.

Determination of ventilatory liver movement via radiographic evaluation of diaphragm position.

PURPOSE: To determine the accuracy of estimation of liver movement inferred by observing diaphragm excursion on radiographic images. METHODS AND MATERIALS: Eight patients with focal liver cancer had platinum embolization microcoils implanted in their livers during catheterization of the hepatic artery for delivery of regional chemotherapy. These patients underwent fluoroscopy, during which normal breathing movement was recorded on videotape. Movies of breathing movement were digitized, and the relative projected positions of the diaphragm and coils were recorded. For 6 patients, daily radiographs were also acquired during treatment. Retrospective measurements of coil position were taken after the diaphragm was aligned with the superior portion of the liver on digitally reconstructed radiographs. RESULTS: Coil movement of 4.9 to 30.4 mm was observed during normal breathing. Diaphragm position tracked inferior-superior coil displacement accurately (population sigma 1.04 mm) throughout the breathing cycle. The range of coil movement was predicted by the range of diaphragm movement with an accuracy of 2.09 mm (sigma). The maximum error observed measuring coil movement using diaphragm position was 3.8 mm for a coil 9.8 cm inferior to the diaphragm. However, the distance of the coil from the top of the diaphragm did not correlate significantly with the error in predicting liver excursion. Analysis of daily radiographs showed that the error in predicting coil position using the diaphragm as an alignment landmark was 1.8 mm (sigma) in the inferior-superior direction and 2.2 mm in the left-right direction, similar in magnitude to the inherent uncertainty in alignment. CONCLUSIONS: This study demonstrated that the range of ventilatory movement of different locations within the liver is predicted by diaphragm position to an accuracy that matches or exceeds existing systems for ventilatory tracking. This suggests that the diaphragm is an acceptable anatomic landmark for radiographic estimation of liver movement in anterior-posterior projections for most patients.

Clinical use of electronic portal imaging: report of AAPM Radiation Therapy Committee Task Group 58.

AAPM Task Group 58 was created to provide materials to help the medical physicist and colleagues succeed in the clinical implementation of electronic portal imaging devices (EPIDs) in radiation oncology. This complex technology has matured over the past decade and is capable of being integrated into routine practice. However, the difficulties encountered during the specification, installation, and implementation process can be overwhelming. TG58 was charged with providing sufficient information to allow the users to overcome these difficulties and put EPIDs into routine clinical practice. In answering the charge, this report provides; comprehensive information about the physics and technology of currently available EPID systems; a detailed discussion of the steps required for successful clinical implementation, based on accumulated experience; a review of software tools available and clinical use protocols to enhance EPID utilization; and specific quality assurance requirements for initial and continuing clinical use of the systems. Specific recommendations are summarized to assist the reader with successful implementation and continuing use of an EPID.

Technical note: acquisition of CT models for radiotherapy applications with reduced tube heating.

The potential or changing computed tomography (CT) protocols to provide data sets that generate high quality digitally reconstructed radiographs (DRRs) from scans with very low tube currents is demonstrated. DRRs were generated from CT data acquired with slice thickness of 1, 3, and 5 mm, using high current to reduce noise in axial images. These DRRs were compared to one generated from a CT scan acquired using 1 mm aperture and very low (10 mA) current. The DRR generated via this technique is comparable to that generated with high current and 1 mm aperture, and higher resolution than from the 3 and 5 mm CT scans.

A feasibility study of mutual information based setup error estimation for radiotherapy.

We have investigated a fully automatic setup error estimation method that aligns DRRs (digitally reconstructed radiographs) from a three-dimensional planning computed tomography image onto two-dimensional radiographs that are acquired in a treatment room. We have chosen a MI (mutual information)-based image registration method, hoping for robustness to intensity differences between the DRRs and the radiographs. The MI-based estimator is fully automatic since it is based on the image intensity values without segmentation. Using 10 repeated scans of an anthropomorphic chest phantom in one position and two single scans in two different positions, we evaluated the performance of the proposed method and a correlation-based method against the setup error determined by fiducial marker-based method. The mean differences between the proposed method and the fiducial marker-based method were smaller than 1 mm for translational parameters and 0.8 degree for rotational parameters. The standard deviations of estimates from the proposed method due to detector noise were smaller than 0.3 mm and 0.07 degree for the translational parameters and rotational parameters, respectively.

A comparison of ventilatory prostate movement in four treatment positions.

PURPOSE: To ensure target coverage during radiotherapy, all sources of geometric uncertainty in target position must be considered. Movement of the prostate due to breathing has not traditionally been considered in prostate radiotherapy. The purpose of this study is to report the influence of patient orientation and immobilization on prostate movement due to breathing. METHODS AND MATERIALS: Four patients had radiopaque markers implanted in the prostate. Fluoroscopy was performed in four different positions: prone in alpha cradle, prone with an aquaplast mold, supine on a flat table, and supine with a false table under the buttocks. Fluoroscopic movies were videotaped and digitized. Frames were analyzed using 2D-alignment software to determine the extent of movement of the prostate markers and the skeleton for each position during normal and deep breathing. RESULTS: During normal breathing, maximal movement of the prostate markers was seen in the prone position (cranial-caudal [CC] range: 0.9-5.1 mm; anterior-posterior [AP] range: up to 3.5 mm). In the supine position, prostate movement during normal breathing was less than 1 mm in all directions. Deep breathing resulted in CC movements of 3.8-10.5 mm in the prone position (with and without an aquaplast mold). This range was reduced to 2.0-7.3 mm in the supine position and 0.5-2.1 mm with the use of the false table top. Deep breathing resulted in AP skeletal movements of 2.7-13.1 mm in the prone position, whereas AP skeletal movements in the supine position were negligible. CONCLUSION: Ventilatory movement of the prostate is substantial in the prone position and is reduced in the supine position. The potential for breathing to influence prostate movement, and thus the dose delivered to the prostate and normal tissues, should be considered when positioning and planning patients for conformal irradiation.

Stereotactic radiosurgery of cerebral arteriovenous malformations with a multileaf collimator and a single isocenter.

OBJECTIVE: To prospectively demonstrate the safety and efficacy of stereotactic radiosurgery for arteriovenous malformations (AVMs) of the brain with a linear accelerator fitted with a multileaf collimator. METHODS: A novel radiosurgery system was developed at the University of Michigan Medical Center with a standard multileaf collimator and a computer-controlled radiotherapy system. Data were accumulated prospectively on all patients undergoing treatment with this system since treatment began in 1995. RESULTS: Thirty-six patients with 37 AVMs have undergone treatment to date. At more than 3 years since treatment, 15 of 16 AVMs with a volume of less than 10 cc were proven to be obliterated by angiography or magnetic resonance imaging, and one was considered a treatment failure. At more than 24 months since therapy, all four AVMs with a volume of 10 to 25 cc were obliterated. Four patients with AVMs with a volume of more than 25 cc have undergone staged therapy, treating the entire volume to 10 Gy twice, but none has been followed long enough to demonstrate a final outcome. There were four transient and no permanent complications. CONCLUSION: Our early data indicate that stereotactic radiosurgery of cerebral AVMs with a linear accelerator and a multileaf collimator is safe and effective. Large AVMs may be especially suitable for this mode of therapy. Staged treatment of very large AVMs seems to be a promising addition to standard treatment, but longer follow-up is necessary to confirm that complete obliteration can be achieved.

Quantization of setup uncertainties in 3-D dose calculations.

Random setup errors can lead to erroneous prediction of the dose distribution calculated for a patient using a static computed tomography (CT) model. Multiple recomputations of the dose distribution covering the range of expected patient positions provides a way to estimate a course of treatment. However, due to the statistical nature of the setup uncertainties, many courses of treatment must be simulated to calculate a distribution of average dose values delivered to a patient. Thus, direct simulation methods can be time consuming and may be impractical for routine clinical treatment planning applications. Methods have been proposed to efficiently calculate the distribution of average dose values via a convolution of the dose distribution (calculated on a static CT model) with a probability distribution function (generally Gaussian) that describes the nature of the uncertainty. In this paper, we extend the convolution-based calculation to calculate the standard deviation of potential outcomes sigmaD(x,y,z) about the distribution of average dose values, and we characterize the statistical significance of this quantity using the central limit theorem. For an example treatment plan based on a treatment protocol in use at our institution, we found that there is a 68% probability that the actual dose delivered to any point (x,y,z) will be within 3% of the average dose value at that point. The standard deviation also yields confidence limits on the dose distribution, and these may be used to evaluate treatment plan stability.

A method for incorporating organ motion due to breathing into 3D dose calculations.

A method is proposed that incorporates the effects of intratreatment organ motion due to breathing on the dose calculations for the treatment of liver disease. Our method is based on the convolution of a static dose distribution with a probability distribution function (PDF) which describes the nature of the motion. The organ motion due to breathing is assumed here to be one-dimensional (in the superior-inferior direction), and is modeled using a periodic but asymmetric function (more time spent at exhale versus inhale). The dose distribution calculated using convolution-based methods is compared to the static dose distribution using dose difference displays and the effective volume (Veff) of the uninvolved liver, as per a liver dose escalation protocol in use at our institution. The convolution-based calculation is also compared to direct simulations that model individual fractions of a treatment. Analysis shows that incorporation of the organ motion could lead to changes in the dose prescribed for a treatment based on the Veff of the uninvolved liver. Comparison of convolution-based calculations and direct simulation of various worst-case scenarios indicates that a single convolution-based calculation is sufficient to predict the dose distribution for the example treatment plan given.

The treatment planning of segmental, conformal stereotactic radiosurgery utilizing a standard multileaf collimator.

Over a period of approximately 3 years, our institution has implemented and refined a system of Stereotactic Radiosurgery (SRS) which utilizes the standard multi leaf collimator (MLC) of the Scanditronix MM50 Racetrack Microtron and treats in an arrangement of segmental "pseudo-arcs." This system employs a commercial BRW based stereotactic frame which is mounted to the treatment table. With the exception of the table-mounted frame hardware there have been no modifications to the treatment machine to accommodate these treatments. By use of standard evaluation parameters (e.g., treatment time, planning time, dose conformance and dose heterogeneity ratios) this system compares quite favorably with reported data from institutions treating SRS with either a GammaKnife or a standard linear accelerator with tertiary collimators.

A mathematical model for correcting patient setup errors using a tilt and roll device.

An algorithm is presented for determining how to adjust the actuators of a tilt and roll table. The algorithm is based on a geometrical model of the table, which was designed with six degrees of freedom. This design and algorithm allows complete translational and rotational corrections to be applied to the target volume position on a daily basis.

A tilt and roll device for automated correction of rotational setup errors.

A tilt and roll device has been developed to add two additional degrees of freedom to an existing treatment table. This device allows computer-controlled rotational motion about the inferior-superior and left-right patient axes. The tilt and roll device comprises three supports between the tabletop and base. An automotive type universal joint welded to the end of a steel pipe supports the center of the table. Two computer-controlled linear electric actuators utilizing high accuracy stepping motors support the foot of table and control the tilt and roll of the tabletop. The current system meets or exceeds all pre-design specifications for precision, weight capacity, rigidity, and range of motion.

Improvement of CT-based treatment-planning models of abdominal targets using static exhale imaging.

PURPOSE: CT-based models of the patient that do not account for the motion of ventilation may not accurately predict the shape and position of critical abdominal structures. Respiratory gating technology for imaging and treatment is not yet widely available. The purpose of the current study is to explore an intermediate step to improve the veracity of the patient model and reduce the treated volume by acquiring the CT data with the patients holding their breath at normal exhale. METHODS AND MATERIALS: The ventilatory time courses of diaphragm movement for 15 patients (with no special breathing instructions) were measured using digitized movies from the fluoroscope during simulation. A subsequent clinical protocol was developed for treatment based on exhale CT models. CT scans (typically 3.5-mm slice thickness) were acquired at normal exhale using a spiral scanner. The scan volume was divided into two to three segments, to allow the patient to breathe in between. Margins were placed about intrahepatic target volumes based on the ventilatory excursion inferior to the target, and on only the reproducibility of exhale position superior to the target. RESULTS: The average patient's diaphragm remained within 25% of the range of ventilatory excursion from the average exhale position for 42% of the typical breathing cycle, and within 25% of the range from the average inhale position for 15% of the cycle. The reproducibility of exhale position over multiple breathing cycles was 0.9 mm (2sigma), as opposed to 2.6 mm for inhale. Combining the variation of exhale position and the uncertainty in diaphragm position from CT slices led to typical margins of 10 mm superior to the target, and 19 mm inferior to the target, compared to margins of 19 mm in both directions under our prior protocol of margins based on free-breathing CT studies. For a typical intrahepatic target, these smaller volumes resulted in a 3.6% reduction in Veff for the liver. Analysis of portal films shows proper target coverage for patients treated based on exhale modeled plans. CONCLUSIONS: Modeling abdominal treatments at exhale, while not realizing all the gains of gated treatments, provides an immediate reduction in the volume of normal tissue treated, and improved reliability of patient data for NTCP modeling, when compared to current "free breathing" CT models of patients.