Validation of biomechanical deformable image registration in the abdomen, thorax, and pelvis in a commercial radiotherapy treatment planning system.

PURPOSE: The accuracy of deformable image registration tools can vary widely between imaging modalities and specific implementations of the same algorithms. A biomechanical model-based algorithm initially developed in-house at an academic institution was translated into a commercial radiotherapy treatment planning system and validated for multiple imaging modalities and anatomic sites. METHODS: Biomechanical deformable registration (Morfeus) is a geometry-driven algorithm based on the finite element method. Boundary conditions are derived from the model-based segmentation of controlling structures in each image which establishes a point-to-point surface correspondence. For each controlling structure, material properties and fixed or sliding interfaces are assigned. The displacements of internal volumes for controlling structures and other structures implicitly deformed are solved with finite element analysis. Registration was performed for 74 patients with images (mean vector resolution) of thoracic and abdominal 4DCT (2.8 mm) and MR (5.3 mm), liver CT-MR (4.5 mm), and prostate MR (2.6 mm). Accuracy was quantified between deformed and actual target images using distance-to-agreement (DTA) for structure surfaces and the target registration error (TRE) for internal point landmarks. RESULTS: The results of the commercial implementation were as follows. The mean DTA was ≤ 1.0 mm for controlling structures and 1.0-3.5 mm for implicitly deformed structures on average. TRE ranged from 2.0 mm on prostate MR to 5.1 mm on lung MR on average, within 0.1 mm or lower than the image voxel sizes. Accuracy was not overly sensitive to changes in the material properties or variability in structure segmentations, as changing these inputs affected DTA and TRE by ≤ 0.8 mm. Maximum DTA > 5 mm occurred for 88% of the structures evaluated although these were within the inherent segmentation uncertainty for 82% of structures. Differences in accuracy between the commercial and in-house research implementations were ≤ 0.5 mm for mean DTA and ≤ 0.7 mm for mean TRE. CONCLUSIONS: Accuracy of biomechanical deformable registration evaluated on a large cohort of images in the thorax, abdomen and prostate was similar to the image voxel resolution on average across multiple modalities. Validation of this treatment planning system implementation supports biomechanical deformable registration as a versatile clinical tool to enable accurate target delineation at planning and treatment adaptation.

Utility and validation of biomechanical deformable image registration in low-contrast images.

PURPOSE: The application of a biomechanical deformable image registration algorithm has been demonstrated to overcome the potential limitations in the use of intensity-based algorithms on low-contrast images that lack prominent features. Because validation of deformable registration is particularly challenging on such images, the dose distribution predicted via a biomechanical algorithm was evaluated using the measured dose from a deformable dosimeter. METHODS AND MATERIALS: A biomechanical model-based image registration algorithm registered computed tomographic (CT) images of an elastic radiochromic dosimeter between its undeformed and deformed positions. The algorithm aligns the external boundaries of the dosimeter, created from CT contours, and the internal displacements are solved by modeling the physical material properties of the dosimeter. The dosimeter was planned and irradiated in its deformed position, and subsequently, the delivered dose was measured with optical CT in the undeformed position. The predicted dose distribution, created by applying the deformable registration displacement map to the planned distribution, was then compared with the measured optical CT distribution. RESULTS: Compared with the optical CT distribution, biomechanical image registration predicted the position and size of the deformed dose fields with mean errors of ≤1 mm (maximum, 3 mm). The accuracy did not differ between cross sections with a greater or lesser deformation magnitude despite the homogenous CT intensities throughout the dosimeter. The overall 3-dimensional voxel passing rate of the predicted distribution was γ3%/3mm = 91% compared with optical CT. CONCLUSIONS: Biomechanical registration accurately predicted the deformed dose distribution measured in a deformable dosimeter, whereas previously, evaluations of a commercial intensity-based algorithm demonstrated substantial errors. The addition of biomechanical algorithms to the collection of adaptive radiation therapy tools would be valuable for dose accumulation, particularly in feature-poor images such as cone beam CT and organs such as the liver.

Dose escalated liver stereotactic body radiation therapy at the mean respiratory position.

PURPOSE: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. METHODS AND MATERIALS: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. RESULTS: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. CONCLUSIONS: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

Simplified strategies to determine the mean respiratory position for liver radiation therapy planning.

PURPOSE: Establishing the time-weighted mean respiratory position in the liver is challenging due to poor tumor contrast on 4-dimensional (4D) imaging. The purpose of this study is to validate simplified strategies in determining the mean position of liver tumors for radiation therapy planning, and quantify the potential for planning target volume (PTV) reduction. METHODS AND MATERIALS: Full, 10-phase 4D computed tomography (CT) data sets from 10 liver radiation therapy patients were analyzed to compare 2 techniques. First, a mid-ventilation CT was chosen from the initial reconstruction of the 4DCT. This was based on the minimum displacement of the diaphragm at each phase relative to its mean respiratory position, calculated using rigid registration over all 4DCT phases. Second, the exhale 4DCT was deformed to the inhale 4DCT using biomechanical-based deformable registration. The diaphragm's mean cranio-caudal position in the respiratory cycle (normalized as a percentage relative to exhale) was applied to the exhale-to-inhale deformation map assuming a linear trajectory to reconstruct a mid-position CT. These strategies were compared with the time-weighted mean respiratory position, calculated with deformable registration over all 10 4DCT phases. PTVs incorporating respiratory motion were then compared for 2 planning strategies: exhale 4DCT using the internal target volume (ITV), or mid-position CT using dose-probability margins. RESULTS: Compared with the mean respiratory tumor position, the mid-ventilation CT and mid-position CT had mean (maximum) tumor vector errors of 1.0 ± 0.5 (2.1) mm and 0.6 ± 0.3 (1.4) mm, respectively, within the image resolution. Compared with ITV-based PTV, dose-probability PTV reduced the irradiated volume by 34% ± 7% on average, up to 43%. CONCLUSIONS: Simplified strategies to select a mid-ventilation CT or reconstruct a mid-position CT for the liver were validated with respect to the mean respiratory position. These data sets require significantly smaller PTVs, potentially allowing for dose-escalated liver stereotactic body radiation therapy to improve local control.

Individualized 3D reconstruction of normal tissue dose for patients with long-term follow-up: a step toward understanding dose risk for late toxicity.

PURPOSE: Understanding the relationship between normal tissue dose and delayed radiation toxicity is an important component of developing more effective radiation therapy. Late outcome data are generally available only for patients who have undergone 2-dimensional (2D) treatment plans. The purpose of this study was to evaluate the accuracy of 3D normal tissue dosimetry derived from reconstructed 2D treatment plans in Hodgkin's lymphoma (HL) patients. METHODS AND MATERIALS: Three-dimensional lung, heart, and breast volumes were reconstructed from 2D planning radiographs for HL patients who received mediastinal radiation therapy. For each organ, a reference 3D organ was modified with patient-specific structural information, using deformable image processing software. Radiation therapy plans were reconstructed by applying treatment parameters obtained from patient records to the reconstructed 3D volumes. For each reconstructed organ mean dose (Dmean) and volumes covered by at least 5 Gy (V5) and 20 Gy (V20) were calculated. This process was performed for 15 patients who had both 2D and 3D planning data available to compare the reconstructed normal tissue doses with those derived from the primary CT planning data and also for 10 historically treated patients with only 2D imaging available. RESULTS: For patients with 3D planning data, the normal tissue doses could be reconstructed accurately using 2D planning data. Median differences in Dmean between reconstructed and actual plans were 0.18 Gy (lungs), -0.15 Gy (heart), and 0.30 Gy (breasts). Median difference in V5 and V20 were less than 2% for each organ. Reconstructed 3D dosimetry was substantially higher in historical mantle-field treatments than contemporary involved-field mediastinal treatments: average Dmean values were 15.2 Gy vs 10.6 Gy (lungs), 27.0 Gy vs 14.3 Gy (heart), and 8.0 Gy vs 3.2 Gy (breasts). CONCLUSIONS: Three-dimensional reconstruction of absorbed dose to organs at risk can be estimated accurately many years after exposure by using limited 2D data. Compared to contemporary involved-field treatments, normal tissue doses were significantly higher in historical mantle-field treatments. These methods build capacity to quantify the relationship between 3D normal tissue dose and observed late effects.

A novel technique to enable experimental validation of deformable dose accumulation.

PURPOSE: To propose a novel technique to experimentally validate deformable dose algorithms by measuring 3D dose distributions under the condition of deformation using deformable gel dosimeters produced by a novel gel fabrication method. METHOD: Five gel dosimeters, two rigid control gels and three deformable gels, were manufactured and treated with the same conformal plan that prescribed 400 cGy to the isocenter. The control gels were treated statically; the deformable gels were treated while being compressed by an actuation device to simulate breathing motion (amplitude of compression = 1, 1.5, and 2 cm, respectively; frequency = 16 rpm). Comparison between the dose measured by the control gels and the corresponding static dose distribution calculated in the treatment planning system (TPS) has determined the intrinsic dose measurement uncertainty of the gel dosimeters. Doses accumulated using MORFEUS, a biomechanical model-based deformable registration and dose accumulation algorithm, were compared with the doses measured by the deformable gel dosimeters to verify the accuracy of MORFEUS using dose differences at each voxel as well as the gamma index test. Flexible plastic wraps were used to contain and protect the deformable gels from oxygen infiltration, which inhibits the gels' dose sensitizing ability. Since the wraps were imperfect oxygen barrier, dose comparison between MORFEUS and the deformable gels was performed only in the central region with a received dose of 200 cGy or above to exclude the peripheral region where oxygen penetration had likely affected dose measurements. RESULTS: Dose measured with the control gels showed that the intrinsic dose measurement uncertainty of the gel dosimeters was 11.8 cGy or 4.7% compared to the TPS. The absolute mean voxel-by-voxel dose difference between the accumulated dose and the dose measured with the deformable gels was 4.7 cGy (SD = 36.0 cGy) or 1.5% (SD = 13.4%) for the three deformable gels. The absolute mean vector distance between the 250, 300, 350, and 400 cGy isodose surfaces on the accumulated and measured distributions was 1.2 mm (SD < 1.5 mm). The gamma index test that used the dose measurement precision of the control gels as the dose difference criterion and 2 mm as the distance criterion was performed, and the average pass rate of the accumulated dose distributions for all three deformable gels was 92.7%. When the distance criterion was relaxed to 3 mm, the average pass rate increased to 96.9%. CONCLUSION: This study has proposed a novel technique to manufacture deformable volumetric gel dosimeters. By comparing the doses accumulated in MORFEUS and the doses measured with the dosimeters under the condition of deformation, the study has also demonstrated the potential of using deformable gel dosimetry to experimentally validate algorithms that include deformations into dose computation. Since dose less than 200 cGy was not evaluated in this study, future investigations will focus more on low dose regions by either using bigger gel dosimeters or prescribing a lower dose to provide a more complete experimental validation of MORFEUS across a wider dose range.

Navigator channel adaptation to reconstruct three dimensional heart volumes from two dimensional radiotherapy planning data.

BACKGROUND: Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients. METHODS: Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient. RESULTS: The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62). CONCLUSIONS: The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects.

Accumulated dose in liver stereotactic body radiotherapy: positioning, breathing, and deformation effects.

PURPOSE: To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic body radiotherapy (SBRT) and investigate their geometric causes. METHODS AND MATERIALS: Thirty previously treated liver cancer patients were retrospectively evaluated. Stereotactic body radiotherapy was planned on the static exhale CT for 27-60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning four-dimensional (4D) CT (predicted breathing dose) and also over each fraction's respiratory-correlated cone-beam CT (accumulated treatment dose). The contribution of different geometric errors to changes between the accumulated and predicted breathing dose were quantified. RESULTS: Twenty-one patients (70%) had accumulated dose deviations relative to the planned static prescription dose >5%, ranging from -15% to 5% in tumors and -42% to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4D CT-predicted dose, which were similar in magnitude. Thirty-two tissues in these 16 patients had deviations >5% relative to the 4D CT-predicted dose, and residual setup errors (n = 17) were most often the largest cause of the deviations, followed by deformations (n = 8) and breathing variations (n = 7). CONCLUSION: The majority of patients had accumulated dose deviations >5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in more than half the patients, commonly owing to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose escalation, adaptive SBRT, and aid in correlation with clinical outcomes.

Rectal motion in patients receiving preoperative radiotherapy for carcinoma of the rectum.

PURPOSE: To assess the movement of rectum, mesorectum, and rectal primary during a course of preoperative chemoradiotherapy. METHODS AND MATERIALS: Seventeen patients with Stage II or III rectal cancer had a planning CT scan with rectal contrast before commencement of preoperative chemoradiation. The scan was repeated during Weeks 1, 3, and 5 of chemoradiation. The rectal primary (gross tumor volume), rectum, mesorectum, and bladder were contoured on all four scans. An in-house biomechanical model-based deformable image registration technique, Morfeus, was used to measure the three-dimensional spatial change in these structures after bony alignment. The required planning target volume margin for this spatial change, after bone alignment, was also calculated. RESULTS: Rectal contrast was found to introduce a systematic error in the position of all organs compared with the noncontrast state. The largest change in structures during radiotherapy was in the anterior and posterior directions for the mesorectum and rectum and in the superior and inferior directions for the gross tumor volume. The planning target volume margins required for internal movement for the mesorectum based on the three scans acquired during treatment are 4 mm right, 5 mm left, 7 mm anterior, and 6 mm posterior. For the rectum, values were 8 mm right, 8 mm left, 8 mm anterior, and 9 mm posterior. The greatest movement of the rectum occurred in the upper third. CONCLUSIONS: Contrast is no longer used in CT simulation. Assuming bony alignment, a nonuniform margin of 8 mm anteriorly, 9 mm posteriorly, and 8 mm left and right is recommended.

Effect of breathing motion on radiotherapy dose accumulation in the abdomen using deformable registration.

PURPOSE: To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration. METHODS AND MATERIALS: Twenty-one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale computed tomography (CT) for 27-60 Gy in six fractions, were included. A biomechanical model-based deformable image registration algorithm retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified. RESULTS: Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was -1 (-14 to 8) to minimum tumor, -4 (-15 to 0) to maximum bowel, -4 (-25 to 1) to maximum duodenum, 2 (-1 to 9) to maximum esophagus, -2 (-13 to 4) to maximum stomach, 0 (-3 to 4) to mean liver, and -1 (-5 to 1) and -2 (-7 to 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues. CONCLUSION: Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases as a result of breathing motion. These changes may not be accurately accounted for with rigid motion.

Interfraction liver shape variability and impact on GTV position during liver stereotactic radiotherapy using abdominal compression.

PURPOSE: For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. METHODS AND MATERIALS: Evaluable patients were treated in a Research Ethics Board-approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCT scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house-developed finite-element model-based deformable registration (MORFEUS). RESULTS: We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left-right (LR), anterior-posterior (AP), and superior-inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left-right, anterior-posterior, and superior-inferior directions, respectively. CONCLUSIONS: Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver registrations on respiratory sorted CBCT scans were small in most patients (<5 mm).

Evaluating the extent of cell death in 3D high frequency ultrasound by registration with whole-mount tumor histopathology.

PURPOSE: High frequency ultrasound imaging, 10-30 MHz, has the capability to assess tumor response to radiotherapy in mouse tumors as early as 24 h after treatment administration. The advantage of this technique is that the image contrast is generated by changes in the physical properties of dying cells. Therefore, a subject can be imaged before and multiple times during the treatment without the requirement of injecting specialized contrast agents. This study is motivated by a need to provide metrics of comparison between the volume and localization of cell death, assessed from histology, with the volume and localization of cell death surrogate, assessed as regions with increased echogeneity from ultrasound images. METHODS: The mice were exposed to radiation doses of 2, 4, and 8 Gy. Ultrasound images ivere collected from each tumor before and 24 h after exposure to radiation using a broadband 25 MHz center frequency transducer. After radiotherapy, tumors exhibited hyperechoic regions in ultrasound images that corresponded to areas of cell death in histology. The ultrasound and histological images were rigidly registered. The tumors and regions of cell death were manually outlined on histological images. Similarly, the tumors and hyperechoic regions were outlined on the ultrasound images. Each set of contours was converted to a volumetric mesh in order to compare the volumes and the localization of cell death in histological and ultrasound images. RESULTS: A shrinkage factor of 17 +/- 2% was calculated from the difference in the tumor volumes evaluated from histological and ultrasound images. This was used to correct the tumor and cell death volumes assessed from histology. After this correction, the average absolute difference between the volume of cell death assessed from ultrasound and histological images was 11 +/- 14% and the volume overlap was 70 +/- 12%. CONCLUSIONS: The method provided metrics of comparison between the volume of cell death assessed from histology and that assessed from ultrasound images. It was applied here to evaluate the capability of ultrasound imaging to assess early tumor response to radiotherapy in mouse tumors. Similarly, it can be applied in the future to evaluate the capability of ultrasound imaging to assess early tumor response to other modalities of cancer treatment. The study contributes to an understanding of the capabilities and limitation of ultrasound imaging at noninvasively detecting cell death. This provides a foundation for future developments regarding the use of ultrasound in preclinical and clinical applications to adapt treatments based on tumor response to cancer therapy.

Reconstruction of 3D lung models from 2D planning data sets for Hodgkin's lymphoma patients using combined deformable image registration and navigator channels.

PURPOSE: Late complications (cardiac toxicities, secondary lung, and breast cancer) remain a significant concern in the radiation treatment of Hodgkin's lymphoma (HL). To address this issue, predictive dose-risk models could potentially be used to estimate radiotherapy-related late toxicities. This study investigates the use of deformable image registration (DIR) and navigator channels (NCs) to reconstruct 3D lung models from 2D radiographic planning images, in order to retrospectively calculate the treatment dose exposure to HL patients treated with 2D planning, which are now experiencing late effects. METHODS: Three-dimensional planning CT images of 52 current HL patients were acquired. 12 image sets were used to construct a male and a female population lung model. 23 "Reference" images were used to generate lung deformation adaptation templates, constructed by deforming the population model into each patient-specific lung geometry using a biomechanical-based DIR algorithm, MORFEUS. 17 "Test" patients were used to test the accuracy of the reconstruction technique by adapting existing templates using 2D digitally reconstructed radiographs. The adaptation process included three steps. First, a Reference patient was matched to a Test patient by thorax measurements. Second, four NCs (small regions of interest) were placed on the lung boundary to calculate 1D differences in lung edges. Third, the Reference lung model was adapted to the Test patient's lung using the 1D edge differences. The Reference-adapted Test model was then compared to the 3D lung contours of the actual Test patient by computing their percentage volume overlap (POL) and Dice coefficient. RESULTS: The average percentage overlapping volumes and Dice coefficient expressed as a percentage between the adapted and actual Test models were found to be 89.2 +/- 3.9% (Right lung = 88.8%; Left lung = 89.6%) and 89.3 +/- 2.7% (Right = 88.5%; Left = 90.2%), respectively. Paired T-tests demonstrated that the volumetric reconstruction method made a statistically significant improvement to the population lung model shape (p < 0.05). The error in the results were also comparable to the volume overlap difference observed between inhale and exhale lung volumes during free-breathing respiratory motion (POL: p = 0.43; Dice: p = 0.20), which implies that the accuracies of the reconstruction method are within breathing constraints and would not be the confining factor in estimating normal tissue dose exposure. CONCLUSIONS: The result findings show that the DIR-NC technique can achieve a high degree of reconstruction accuracy, and could be useful in approximating 3D dosimetric representations of historical 2D treatment. In turn, this could provide a better understanding of the biophysical relationship between dose-volume exposure and late term radiotherapy effects.

Accuracy and sensitivity of finite element model-based deformable registration of the prostate.

PURPOSE: Evaluate the accuracy and the sensitivity to contour variation and model size of a finite element model-based deformable registration algorithm for the prostate. METHODS AND MATERIALS: Two magnetic resonance images (MRIs) were obtained for 21 prostate patients with three implanted markers. A single observer contoured the prostate and markers and performed blinded recontouring of the first MRI. A biomechanical-model based deformable registration algorithm, MORFEUS, was applied to each dataset pair, deforming the second image (B) to the first image (A). The residual error was calculated by comparing the center of mass (COM) of the markers with the predicted COM. Sensitivity to contour variation was calculated by deforming B to the repeat contour of A (A2). The sensitivity to the model size was calculated by reducing the number of nodes (B', A', A2') and repeating the analysis. RESULTS: The average residual error of the registration for B to A and B to A2 was 0.22 cm (SD: 0.08 cm) and 0.24 cm (SD: 0.09 cm), respectively. The average residual error of the registration of B' to A' and B' to A2' was 0.22 cm (SD: 0.10 cm) and 0.25 cm (SD: 0.10 cm), respectively. The average time to run MORFEUS on the standard and reduced model was 3606 s (SD: 7788 s) and 56 s (SD: 16 s), respectively. CONCLUSIONS: The accuracy of the algorithm, equal to the image voxel size, is not affected by intraobserver contour variability or model size. Reducing the model size significantly increases algorithm efficiency.

Improving image-guided target localization through deformable registration.

PURPOSE: To quantify the improvements in online target localization using kV cone beam CT (CBCT) with deformable registration. METHODS AND MATERIAL: Twelve patients treated under a 6 fraction liver cancer radiation therapy protocol were imaged in breath hold using kV CBCT at each treatment fraction. The images were imported into the treatment planning software and rigidly registered by fitting the liver, identified on the daily kV CBCT image, into the liver contours, previously drawn on the planning CT. The liver was then manually contoured on each CBCT image. Deformable registration was automatically performed, aligning the CT liver to the liver on each CBCT image using MORFEUS, a biomechanical model based deformable registration algorithm. The tumor, defined on planning CT, was mapped onto the CBCT, through MORFEUS. The center of mass (COM) displacement of the tumor was computed. RESULTS: The mean (SD) displacement magnitude (absolute value) of the COM following deformable registration was 0.08 (0.07), 0.10 (0.11), and 0.10 (0.17) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COM was 0.34, 0.65, and 0.97 cm in the LR, AP, and SI directions, respectively. Fifteen percent of the treatment fractions had a COM displacement of greater than 0.3 cm and 33% of patients had at least 1 fraction with a displacement of greater than 0.3 cm. The deformable registration, excluding the manual contouring of the liver, was performed in less than 1 minute, on average. DISCUSSION: Rigid registration of the liver volume between planning CT and verification kV CBCT localizes the tumor to within 0.3 cm for the majority (66%) of patients; however, larger offsets in tumor position can be observed due to liver deformation.

Adapting population liver motion models for individualized online image-guided therapy.

Respiratory motion varies on a daily basis in abdominal cancer patients, affecting the ability to successfully deliver local therapy and requiring increased treatment margins to account for this variation. Deformable registration techniques can accurately describe respiratory motion, however, online application can be limited by long computational times and user intervention. A technique has been developed to quickly quantify patient breathing motion from respiratory-sorted volumetric images by calculating 1D shifts in image intensities between spatially corresponding regions of interest (navigator channels) on patient's images. The 1D motion at the superior, inferior, anterior, and posterior liver edges was detected and applied to adapt a population liver respiratory motion model. For validation, deformable registration was performed for each patient using a validated technique, MORFEUS, for relative validation, and vessel bifurcations, identified on patient's inhale and exhale images, for absolute validation. The accuracy of the adapted-population model to describe the patient respiratory motion was (absolute mean +/- SD) 0.26 +/- 0.11 cm and 0.30 +/- 0.21 cm in the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The accuracy of predicting the tumor COM motion was 0.30 +/- 0.22 cm, and 0.34 +/- 0.31, while the absolute validation, based on bifurcations was 0.26 +/- 0.16 cm and 0.13 +/- 0.04 cm in the SI and AP directions, respectively. This technique was developed to complement and quickly adapt a full 3D biomechanical based deformable registration technique, MORFEUS, to be applied in the online setting.

Development of multiorgan finite element-based prostate deformation model enabling registration of endorectal coil magnetic resonance imaging for radiotherapy planning.

PURPOSE: Endorectal coil (ERC) magnetic resonance imaging (MRI) provides superior visualization of the prostate compared with computed tomography at the expense of deformation. This study aimed to develop a multiorgan finite element deformable method, Morfeus, to accurately co-register these images for radiotherapy planning. METHODS: Patients with prostate cancer underwent fiducial marker implantation and computed tomography simulation for radiotherapy planning. A series of axial MRI scans were acquired with and without an ERC. The prostate, bladder, rectum, and pubic bones were manually segmented and assigned linear elastic material properties. Morfeus mapped the surface of the bladder and rectum between two imaged states, calculating the deformation of the prostate through biomechanical properties. The accuracy of deformation was measured as fiducial marker error and residual surface deformation between the inferred and actual prostate. The deformation map was inverted to deform from 100 cm(3) to no coil. RESULTS: The data from 19 patients were analyzed. Significant prostate deformation occurred with the ERC (mean intrapatient range, 0.88 +/- 0.25 cm). The mean vector error in fiducial marker position (n = 57) was 0.22 +/- 0.09 cm, and the mean vector residual surface deformation (n = 19) was 0.15 +/- 0.06 cm for deformation from no coil to 100-cm(3) ERC, with an image vector resolution of 0.22 cm. Accurately deformed MRI scans improved soft-tissue resolution of the anatomy for radiotherapy planning. CONCLUSIONS: This method of multiorgan deformable registration enabled accurate co-registration of ERC-MRI scans with computed tomography treatment planning images. Superior structural detail was visible on ERC-MRI, which has potential for improving target delineation.