Kristy K. Brock

Accuracy of finite element model-based multi-organ deformable image registration.

As more pretreatment imaging becomes integrated into the treatment planning process and full three-dimensional image-guidance becomes part of the treatment delivery the need for a deformable image registration technique becomes more apparent. A novel finite element model-based multi-organ deformable image registration method, MORFEUS, has been developed. The basis of this method is twofold: first, individual organ deformation can be accurately modeled by deforming the surface of the organ at one instance into the surface of the organ at another instance and assigning the material properties that allow the internal structures to be accurately deformed into the secondary position and second, multi-organ deformable alignment can be achieved by explicitly defining the deformation of a subset of organs and assigning surface interfaces between organs. The feasibility and accuracy of the method was tested on MR thoracic and abdominal images of healthy volunteers at inhale and exhale. For the thoracic cases, the lungs and external surface were explicitly deformed and the breasts were implicitly deformed based on its relation to the lung and external surface. For the abdominal cases, the liver, spleen, and external surface were explicitly deformed and the stomach and kidneys were implicitly deformed. The average accuracy (average absolute error) of the lung and liver deformation, determined by tracking visible bifurcations, was 0.19 (s.d.: 0.09), 0.28 (s.d.: 0.12) and 0.17(s.d.:0.07)cm, in the LR, AP, and IS directions, respectively. The average accuracy of implicitly deformed organs was 0.11 (s.d.: 0.11), 0.13 (s.d.: 0.12), and 0.08(s.d.:0.09)cm, in the LR, AP, and IS directions, respectively. The average vector magnitude of the accuracy was 0.44(s.d.:0.20)cm for the lung and liver deformation and 0.24(s.d.:0.18)cm for the implicitly deformed organs. The two main processes, explicit deformation of the selected organs and finite element analysis calculations, require less than 120 and 495s, respectively. This platform can facilitate the integration of deformable image registration into online image guidance procedures, dose calculations, and tissue response monitoring as well as performing multi-modality image registration for purposes of treatment planning.

The reproducibility of organ position using active breathing control (ABC) during liver radiotherapy

PURPOSE To evaluate the intrafraction and interfraction reproducibility of liver immobilization using active breathing control (ABC). METHODS AND MATERIALS Patients with unresectable intrahepatic tumors who could comfortably hold their breath for at least 20 s were treated with focal liver radiation using ABC for liver immobilization. Fluoroscopy was used to measure any potential motion during ABC breath holds. Preceding each radiotherapy fraction, with the patient setup in the nominal treatment position using ABC, orthogonal radiographs were taken using room-mounted diagnostic X-ray tubes and a digital imager. The radiographs were compared to reference images using a 2D alignment tool. The treatment table was moved to produce acceptable setup, and repeat orthogonal verification images were obtained. The positions of the diaphragm and the liver (assessed by localization of implanted radiopaque intra-arterial microcoils) relative to the skeleton were subsequently analyzed. The intrafraction reproducibility (from repeat radiographs obtained within the time period of one fraction before treatment) and interfraction reproducibility (from comparisons of the first radiograph for each treatment with a reference radiograph) of the diaphragm and the hepatic microcoil positions relative to the skeleton with repeat breath holds using ABC were then measured. Caudal-cranial (CC), anterior-posterior (AP), and medial-lateral (ML) reproducibility of the hepatic microcoils relative to the skeleton were also determined from three-dimensional alignment of repeat CT scans obtained in the treatment position. RESULTS A total of 262 fractions of radiation were delivered using ABC breath holds in 8 patients. No motion of the diaphragm or hepatic microcoils was observed on fluoroscopy during ABC breath holds. From analyses of 158 sets of positioning radiographs, the average intrafraction CC reproducibility (sigma) of the diaphragm and hepatic microcoil position relative to the skeleton using ABC repeat breath holds was 2.5 mm (range 1.8-3.7 mm) and 2.3 mm (range 1.2-3.7 mm) respectively. However, based on 262 sets of positioning radiographs, the average interfraction CC reproducibility (sigma) of the diaphragm and hepatic microcoils was 4.4 mm (range 3.0-6.1 mm) and 4.3 mm (range 3.1-5.7 mm), indicating a change of diaphragm and microcoil position relative to the skeleton over the course of treatment with repeat breath holds at the same phase of the respiratory cycle. The average population absolute intrafraction CC offset in diaphragm and microcoil position relative to skeleton was 2.4 mm and 2.1 mm respectively; the average absolute interfraction CC offset was 5.2 mm. Analyses of repeat CT scans demonstrated that the average intrafraction excursion of the hepatic microcoils relative to the skeleton in the CC, AP, and ML directions was 1.9 mm, 0.6 mm, and 0.6 mm respectively and the average interfraction CC, AP, and ML excursion of the hepatic microcoils was 6.6 mm, 3.2 mm, and 3.3 mm respectively. CONCLUSION Radiotherapy using ABC for patients with intrahepatic cancer is feasible, with good intrafraction reproducibility of liver position using ABC. However, the interfraction reproducibility of organ position with ABC suggests the need for daily on-line imaging and repositioning if treatment margins smaller than those required for free breathing are a goal.

INTER- AND INTRAFRACTION VARIABILITY IN LIVER POSITION IN NON-BREATH- HOLD STEREOTACTIC BODY RADIOTHERAPY

PURPOSE The inter- and intrafraction variability of liver position was assessed in patients with liver cancer treated with kilovoltage cone-beam computed tomography (CBCT)-guided stereotactic body radiotherapy. METHODS AND MATERIALS A total of 314 CBCT scans obtained in the treatment position immediately before and after each fraction were evaluated from 29 patients undergoing six-fraction, non-breath-hold stereotactic body radiotherapy for unresectable liver cancer. Off-line, the CBCT scans were sorted into 10 bins, according to the phase of respiration. The liver position (relative to the vertebral bodies) was measured using rigid alignment of the exhale CBCT liver with the exhale planning CT liver, following the alignment of the vertebrae. The interfraction liver position change was measured by comparing the pretreatment CBCT scans, and the intrafraction change was measured from the CBCT scans obtained immediately before and after each fraction. RESULTS The mean amplitude of liver motion for all patients was 1.8 mm (range, 0.1-5.7), 8.0 mm (range, 0.1-18.8), and 4.3 mm (range 0.1-12.1) in the medial-lateral (ML), craniocaudal (CC), and anteroposterior (AP) directions, respectively. The mean absolute ML, CC, and AP interfraction changes in liver position were 2.0 mm (90th percentile, 4.2), 3.5 mm (90th percentile, 7.3), and 2.3 mm (90th percentile, 4.7). The mean absolute intrafraction ML, CC, and AP changes were 1.3 mm (90th percentile, 2.9), 1.6 mm (90th percentile, 3.6), and 1.5 mm (90th percentile, 3.1), respectively. The interfraction changes were significantly larger than the intrafraction changes, with a CC systematic error of 2.9 and 1.1 mm, respectively. The intraobserver reproducibility (sigma, n = 29 fractions) was 1.3 mm in the ML, 1.4 mm in the CC, and 1.6 mm in the AP direction. CONCLUSION Interfraction liver position changes relative to the vertebral bodies are an important source of geometric uncertainty, providing a rationale for prefraction soft-tissue image guidance. The intrafraction change in liver position from the beginning to the end of each fraction was small for most patients.

Pelvic Radiotherapy for Cancer of the Cervix: Is What You Plan Actually What You Deliver?

PURPOSE Whole pelvic intensity-modulated radiotherapy (IMRT) is increasingly being used to treat cervix cancer and other gynecologic tumors. However, tumor and normal organ movement during treatment can substantially detract from the benefits of this approach. This study explored the effect of internal anatomic changes on the dose delivered to the tumor and organs at risk using a strategy integrating deformable soft-tissue modeling with simulated dose accumulation. METHODS AND MATERIALS Twenty patients with cervix cancer underwent baseline and weekly pelvic magnetic resonance imaging during treatment. Interfraction organ motion and delivered (accumulated) dose was modeled for three treatment scenarios: four-field box, large-margin whole pelvic IMRT (20-mm planning target volume, but 10 mm inferiorly) and small-margin IMRT (5-mm planning target volume). RESULTS Individually, the planned dose was not the same as the simulated delivered dose; however, when taken as a group, this was not statistically significant for the four-field box and large-margin IMRT plans. The small-margin IMRT plans yielded adequate target coverage in most patients; however, significant target underdosing occurred in 1 patient who displayed excessive, unpredictable internal target movement. The delivered doses to the organs at risk were significantly reduced with the small-margin plan, although substantial variability was present among the patients. CONCLUSION Simulated dose accumulation might provide a more accurate depiction of the target and organ at risk coverage during fractionated whole pelvic IMRT for cervical cancer. The adequacy of primary tumor coverage using 5-mm planning target volume margins is contingent on the use of daily image-guided setup.

Contact surface and material nonlinearity modeling of human lungs

A finite element model has been developed to investigate the effect of contact surfaces and hyperelastic material properties on the mechanical behavior of human lungs of one lung cancer patient. The three-dimensional model consists of four parts, namely the left lung, right lung, tumor in the left lung and chest wall. The interaction between the lungs and chest wall was modeled using frictionless surface-based contact. Hyperelastic material properties of the lungs are used in the model. The effect of the two parameters is investigated by tracking the tumor movement, and by comparing the analytical results to the patient bifurcation points: 45 points in each lung and 18 points around the tumor. The accuracy of the model is improved by including the contact surface and hyperelastic material properties. The average error and the standard deviation (SD) in modeling the displacement in the SI direction are reduced from 0.68 (SD = 0.34) cm in the elastic model to 0.09 (0.21) cm in the contact-hyperelastic model. Similarly, the average error (SD) of tumor location decreases from 0.71 (0.21) cm in the elastic material without contact to -0.03 (0.24) cm in the hyperelastic material with contact model.

Three-Dimensional Motion of Liver Tumors Using Cine-Magnetic Resonance Imaging

PURPOSE To measure the three-dimensional motion of liver tumors using cine-magnetic resonance imaging (MRI) and compare it to the liver motion assessed using fluoroscopy. METHODS AND MATERIALS Liver and liver tumor motion were investigated in the first 36 patients with primary (n = 20) and metastatic (n = 16) liver cancer accrued to our Phase I stereotactic radiotherapy study. At simulation, all patients underwent anteroposterior fluoroscopy, and the maximal diaphragm excursion in the craniocaudal (CC) direction was observed. Cine-MRI using T(2)-weighted single shot fast spin echo sequences were acquired in three orthogonal planes during free breathing through the centroid of the most dominant liver tumor. ImageJ software was used to measure the maximal motion of the tumor edges in each plane. The intra- and interobserver reproducibility was also quantified. RESULTS The average CC motion of the liver at fluoroscopy was 15 mm (range, 5-41). On cine-MRI, the average CC tumor motion was 15.5 mm (range, 6.9-35.4), the anteroposterior motion was 10 mm (range, 3.7-21.6), and the mediolateral motion was 7.5 mm (range, 3.8-14.8). The fluoroscopic CC diaphragm motion did not correlate well with the MRI CC tumor motion (r = 0.25). The mean intraobserver error was <2 mm in the CC, anteroposterior, and mediolateral directions, and 90% of measurements between observers were within 3 mm. CONCLUSIONS The results of our study have shown that cine-MRI can be used to directly assess liver tumor motion in three dimensions. Tumor motion did not correlate well with the diaphragm motion measured using kilovoltage fluoroscopy. The tumor motion data from cine-MRI can be used to facilitate individualized planning target volume margins to account for breathing motion.

Interfraction and Intrafraction Changes in Amplitude of Breathing Motion in Stereotactic Liver Radiotherapy

PURPOSE Interfraction and intrafraction changes in amplitude of liver motion were assessed in patients with liver cancer treated with kV cone beam computed tomography (CBCT)-guided stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS A total of 314 CBCTs obtained with the patient in the treatment position immediately before and after each fraction, and 29 planning 4DCTs were evaluated in 29 patients undergoing six-fraction SBRT for unresectable liver cancer, with (n = 15) and without (n = 14) abdominal compression. Offline, the CBCTs were sorted into 10 bins, based on phase of respiration. Liver motion amplitude was measured using liver-to-liver alignment from the end-exhale and end-inhale CBCT and four-dimensional CT reconstructions. Inter- and intrafraction amplitude changes were measured from the difference between the pre-SBRT CBCTs relative to the planning four-dimensional CT, and from the pre-SBRT and post-SBRT CBCTs, respectively. RESULTS Mean liver motion amplitude for all patients (range) was 1.8 (0.1-7.0), 8.0 (0.1-18.8), and 4.3 (0.1-12.1) mm in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) directions, respectively. Mean absolute inter- and intrafraction liver motion amplitude changes were 1.0 (ML), 1.7 (CC), and 1.6 (AP) mm and 1.3 (ML), 1.6 (CC), and 1.9 (AP) mm, respectively. No significant correlations were found between intrafraction amplitude change and intrafraction time (range, 4:56-25:37 min:sec), and between inter- and intrafraction amplitude changes and liver motion amplitude. Intraobserver reproducibility (sigma, n = 29 fractions) was 1.3 (ML), 1.4 (CC), and 1.4 (AP) mm. CONCLUSIONS For the majority of liver SBRT patients, the change in liver motion amplitude was minimal over the treatment course and showed no apparent relationships with the magnitude of liver motion and intrafraction time.

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).

Automated Weekly Replanning for Intensity-Modulated Radiotherapy of Cervix Cancer

PURPOSE The adoption of intensity-modulated radiotherapy (IMRT) to treat cervical malignancies has been limited in part by complex organ and tumor motion during treatment. This study explores the limits of a highly adaptive, small-margin treatment scenario to accommodate this motion. In addition, the dosimetric consequences of organ and tumor motion are modeled using a combination of deformable registration and fractional dose accumulation techniques. METHODS AND MATERIALS Thirty-three cervix cancer patients had target volumes and organs-at-risk contoured on fused, pretreatment magnetic resonance-computed tomography images and weekly magnetic resonance scans taken during treatment. The dosimetric impact of interfraction organ and target motion was compared for two hypothetical treatment scenarios: a 3-mm margin plan with no replanning, and a 3-mm margin plan with an automated replan performed on the updated weekly patient geometry. RESULTS Of the 33 patients, 24 (73%) met clinically acceptable target coverage (98% of the clinical target volume receiving at least 95% of the prescription dose) using the 3-mm margin plan without replanning. The range in dose to 98% of the clinical target volume across all patients was 7.9% of the prescription dose if no replanning was performed. After weekly replanning, this range was tightened to 2.6% of the prescription dose and all patients met clinically acceptable target coverage while maintaining organ-at-risk dose sparing. CONCLUSIONS The dosimetric impact of anatomical motion underscores the challenges of applying IMRT to treat cervix cancer. An appropriate adaptive strategy can ensure target coverage for small-margin IMRT treatments and maintain favorable organ-at-risk dose sparing.