M Fatyga

How does CT image noise affect 3D deformable image registration for image-guided radiotherapy planning?

PURPOSE To measure the sensitivity of deformable image registration to image noise. Deformable image registration can be used to map organ contours and other treatment planning data from one CT to another. These CT studies can be acquired with either conventional fan-beam CT systems or more novel cone-beam CT techniques. However, cone-beam CT images can have higher noise levels than fan-beam CT, which might reduce registration accuracy. We have investigated the effect of image quality differences on the deformable registration of fan-beam CTs and CTs with simulated cone-beam noise. METHOD Our study used three CT studies for each of five prostate patients. Each CT was contoured by three experienced radiation oncologists. For each patient, one CT was designated the source image and the other two were target images. A deformable image registration process was used to register each source CT to each target CT and then transfer the manually drawn treatment planning contours from the source CT to the target CTs. The accuracy of the automatically transferred contours (and thus of the deformable registration process) was assessed by comparing them to the manual contours on the target CTs, with the differences evaluated with respect to interobserver variability in the manual contours. Then each of the target CTs was modified to include increased noise characteristic of cone-beam CT and the tests were repeated. Changes in registration accuracy due to increased noise were detected by monitoring changes in the automatically transferred contours. RESULTS We found that the additional noise caused no significant loss of registration accuracy at magnitudes that exceeded what would normally be found in an actual cone-beam CT. SUMMARY We conclude that noise levels in cone-beam CTs that might reduce manual contouring accuracy do not reduce image registration and automatic contouring accuracy.

Improving IMRT dose accuracy via deliverable Monte Carlo optimization for the treatment of head and neck cancer patients

The purpose of this work is to investigate the effect of dose-calculation accuracy on head and neck (H&N) intensity modulated radiation therapy (IMRT) plans by determining the systematic dose-prediction and optimization-convergence errors (DPEs and OCEs), using a superposition/convolution (SC) algorithm. Ten patients with locally advanced H&N squamous cell carcinoma who were treated with simultaneous integrated boost IMRT were selected for this study. The targets consisted of gross target volume (GTV), clinical target volume (CTV), and nodal target volumes (CTV nodes). The critical structures included spinal cord, parotid glands, and brainstem. For all patients, three IMRT plans were created: A: an SC optimized plan (SCopt), B: an SCopt plan recalculated with Monte Carlo [MC(SCopt)], and C: an MC optimized plan (MCopt). For each structure, DPEs and OCEs were estimated as DPE(SC)=D(B)-D(A) and OCE(SC)=D(C)-D(B) where A, B, and C stand for the three different optimized plans as defined above. Deliverable optimization was used for all plans, that is, a leaf-sequencing step was incorporated into the optimization loop at each iteration. The range of DPE(SC) in the GTV D98 varied from -1.9% to -4.9%, while the OCE(SC) ranged from 0.9% to 7.0%. The DPE(SC) in the contralateral parotid D50 reached 8.2%, while the OCE(SC) in the contralateral parotid D50 varied from 0.91% to 6.99%. The DPE(SC) in cord D2 reached -3.0%, while the OCE(SC) reached to -7.0%. The magnitude of the DPE(SC) and OCE(SC) differences demonstrate the importance of using the most accurate available algorithm in the deliverable IMRT optimization process, especially for the estimation of normal structure doses.

A Deliverable Four-Dimensional Intensity-Modulated Radiation Therapy-Planning Method for Dynamic Multileaf Collimator Tumor Tracking Delivery

PURPOSE To develop a deliverable four-dimensional (4D) intensity-modulated radiation therapy (IMRT) planning method for dynamic multileaf collimator (MLC) tumor tracking delivery. METHODS AND MATERIALS The deliverable 4D IMRT planning method involves aligning MLC leaf motion parallel to the major axis of target motion and translating MLC leaf positions by the difference in the target centroid position between respiratory phases of the 4D CT scan. This method ignores nonlinear respiratory motion and deformation. A three-dimensional (3D) optimal method whereby an IMRT plan on each respiratory phase of the 4D CT scan was independently optimized was used for comparison. For 12 lung cancer patient 4D CT scans, individual phase plans and deformable dose-summed 4D plans using the two methods were created and compared. RESULTS For each of the individual phase plans, the deliverable method yielded similar isodose distributions and dose-volume histograms. The deliverable and 3D optimal methods yielded statistically equivalent dose-volume metrics for both individual phase plans and 4D plans (p > 0.05 for all metrics compared). The deliverable method was affected by 4D CT artifacts in one case. Both methods were affected by high vector field variations from deformable registration. CONCLUSIONS The deliverable method yielded similar dose distributions for each of the individual phase plans and statistically equivalent dosimetric values compared with the 3D optimal method, indicating that the deliverable method is dosimetrically robust to the variations of fractional time spent in respiratory phases on a given 4D CT scan. Nonlinear target motion and deformation did not cause significant dose discrepancies.

Dose escalation for locally advanced lung cancer using adaptive radiation therapy with simultaneous integrated volume-adapted boost.

PURPOSE To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. METHODS AND MATERIALS Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). RESULTS The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. CONCLUSIONS The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy

PURPOSE To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). METHODS AND MATERIALS One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms-small deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)-were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. RESULTS For day-to-day registrations, the mean DSC was 0.75 ± 0.09 with SICLE, 0.70 ± 0.12 with DEMONS, 0.66 ± 0.12 with rigid-tumor registration, and 0.60 ± 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. CONCLUSIONS Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.

A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: A radiobiological modeling study

A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.

Quantification of the impact of MLC modeling and tissue heterogeneities on dynamic IMRT dose calculations

This study quantifies the dose prediction errors (DPEs) in dynamic IMRT dose calculations resulting from (a) use of an intensity matrix to estimate the multi-leaf collimator (MLC) modulated photon fluence (DPE(IGfluence) instead of an explicit MLC particle transport, and (b) handling of tissue heterogeneities (DPE(hetero)) by superposition/convolution (SC) and pencil beam (PB) dose calculation algorithms. Monte Carlo (MC) computed doses are used as reference standards. Eighteen head-and-neck dynamic MLC IMRT treatment plans are investigated. DPEs are evaluated via comparing the dose received by 98% of the GTV (GTV D 98%), the CTV D 95%, the nodal D 90%, the cord and the brainstem D 02%, the parotid D 50%, the parotid mean dose (D (Mean)), and generalized equivalent uniform doses (gEUDs) for the above structures. For the MC-generated intensity grids, DPE(IGfluence) is within +/- 2.1% for all targets and critical structures. The SC algorithm DPE(hetero) is within +/- 3% for 98.3% of the indices tallied, and within +/- 3.4% for all of the tallied indices. The PB algorithm DPE(hetero) is within +/- 3% for 92% of the tallied indices. Statistical equivalence tests indicate that PB DPE(hetero) requires a +/- 3.6% interval to state equivalence with the MC standard, while the intervals are < 1.5% for SC DPE(hetero) and DPE(IGfluence). Overall, these results indicate that SC and MC IMRT dose calculations which use MC-derived intensity matrices for fluence prediction do not introduce significant dose errors compared with full Monte Carlo dose computations; however, PB algorithms may result in clinically significant dose deviations.

BIOLOGICAL OPTIMIZATION IN VOLUMETRIC MODULATED ARC RADIOTHERAPY FOR PROSTATE CARCINOMA

PURPOSE To investigate the potential benefits achievable with biological optimization for modulated volumetric arc (VMAT) treatments of prostate carcinoma. METHODS AND MATERIALS Fifteen prostate patient plans were studied retrospectively. For each case, planning target volume, rectum, and bladder were considered. Three optimization schemes were used: dose-volume histogram (DVH) based, generalized equivalent uniform dose (gEUD) based, and mixed DVH/gEUD based. For each scheme, a single or dual 6-MV, 356° VMAT arc was used. The plans were optimized with Pinnacle(3) (v. 9.0 beta) treatment planning system. For each patient, the optimized dose distributions were normalized to deliver the same prescription dose. The quality of the plans was evaluated by dose indices (DIs) and gEUDs for rectum and bladder. The tallied DIs were D(1%), D(15%), D(25%), and D(40%), and the tallied gEUDs were for a values of 1 and 6. Statistical tests were used to quantify the magnitude and the significance of the observed differences. Monitor units and treatment times for each optimization scheme were also assessed. RESULTS All optimization schemes generated clinically acceptable plans. The statistical tests indicated that biological optimization yielded increased organs-at-risk sparing, ranging from ~1% to more than ~27% depending on the tallied DI, gEUD, and anatomical structure. The increased sparing was at the expense of longer treatment times and increased number of monitor units. CONCLUSIONS Biological optimization can significantly increase the organs-at-risk sparing in VMAT optimization for prostate carcinoma. In some particular cases, however, the DVH-based optimization resulted in superior treatment plans.

Lung dose for minimally moving thoracic lesions treated with respiration gating.

PURPOSE To evaluate incidental doses to benign lung tissue for patients with minimally moving lung lesions treated with respiratory gating. METHODS AND MATERIALS Seventeen lung patient plans were studied retrospectively. Tumor motion was less than 5 mm in all cases. For each patient, mid-ventilation (MidVen) and mid-inhalation (MidInh) breathing phases were reconstructed. The MidInh phase was centered on the end-of-inhale (EOI) phase within a 30% gating window. Planning target volumes, heart, and spinal cord were delineated on the MidVen phase and transferred to the MidInh phase. Lungs were contoured separately on each phase. Intensity-modulated radiotherapy plans were generated on the MidVen phases. The plans were transferred to the MidInh phase, and doses were recomputed. The evaluation metric was based on dose indices, volume indices, generalized equivalent uniform doses, and mass indices for targets and critical structures. Statistical tests were used to establish the significance of the differences between the reference (MidVen) and compared (MidInh) dose distributions. RESULTS Statistical tests demonstrated that the indices evaluated for targets, cord, and heart differed by within 2.3%. The index differences in the lungs, however, are in excess of 6%, indicating the potentially achievable lung sparing and/or dose escalation. CONCLUSIONS Respiratory gating is a clinical option for patients with minimally moving lung lesions treated at EOI. Gating will be more beneficial for larger tumors, since dose escalation in those cases will result in a larger increase in the tumor control probability.

A Voxel-by-Voxel Comparison of Deformable Vector Fields Obtained by Three Deformable Image Registration Algorithms Applied to 4DCT Lung Studies

Background: Commonly used methods of assessing the accuracy of deformable image registration (DIR) rely on image segmentation or landmark selection. These methods are very labor intensive and thus limited to relatively small number of image pairs. The direct voxel-by-voxel comparison can be automated to examine fluctuations in DIR quality on a long series of image pairs. Methods: A voxel-by-voxel comparison of three DIR algorithms applied to lung patients is presented. Registrations are compared by comparing volume histograms formed both with individual DIR maps and with a voxel-by-voxel subtraction of the two maps. When two DIR maps agree one concludes that both maps are interchangeable in treatment planning applications, though one cannot conclude that either one agrees with the ground truth. If two DIR maps significantly disagree one concludes that at least one of the maps deviates from the ground truth. We use the method to compare 3 DIR algorithms applied to peak inhale-peak exhale registrations of 4DFBCT data obtained from 13 patients. Results: All three algorithms appear to be nearly equivalent when compared using DICE similarity coefficients. A comparison based on Jacobian volume histograms shows that all three algorithms measure changes in total volume of the lungs with reasonable accuracy, but show large differences in the variance of Jacobian distribution on contoured structures. Analysis of voxel-by-voxel subtraction of DIR maps shows differences between algorithms that exceed a centimeter for some registrations. Conclusion: Deformation maps produced by DIR algorithms must be treated as mathematical approximations of physical tissue deformation that are not self-consistent and may thus be useful only in applications for which they have been specifically validated. The three algorithms tested in this work perform fairly robustly for the task of contour propagation, but produce potentially unreliable results for the task of DVH accumulation or measurement of local volume change. Performance of DIR algorithms varies significantly from one image pair to the next hence validation efforts, which are exhaustive but performed on a small number of image pairs may not reflect the performance of the same algorithm in practical clinical situations. Such efforts should be supplemented by validation based on a longer series of images of clinical quality.