[en] Purpose/Objective: Radiation therapy (XRT) is an effective cancer treatment. A goal of therapy is minimization of side effects. Bone growth after XRT of children is one limiting normal tissue tolerance. The goal of the current experiment is to identify the possible protective effect of hyperbaric oxygen (HBO) and basic fibroblast growth factor (FGF) on bone growth after lower extremity radiation. Material and Methods: 170 five weeks old female C3H mice were divided into 17 study groups. Groups 1-4 are controls which received XRT at 0, 10, 20, and 30 Gy single fraction without subsequent HBO. Groups 5-7 had XRT at 10 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 8-10 had XRT at 20 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 11-13 had XRT at 30 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 14-17 had XRT at 30 Gy and iv FGF with or without HBO at weeks 1-4 (groups 14, 15), and at weeks 5-8 (groups 16, 17) after XRT. Using fluoroscopy, the animals were positioned so that the beam was directed to irradiate the entire right hindlimb, including the majority of the femur. Dosimetry was confirmed by TLD in mouse phantoms. HBO treatments were given 5 days per week for 4 weeks to each study group using 2 ATA (max. 15 PSI) of 100% oxygen for 3 hours/day. FGF was given intravenously at 6 μg twice a week for 4 weeks. X-ray films were taken to measure the leg (tibia and femur) length of animals before and 18 weeks after radiation. The acute and chronic side effects of skin in the irradiated area were checked daily according to standard criteria. The leg bones and soft tissue were collected at the end of experiment for histologic study. Result: HBO significantly reduces the retardation of bone growth induced by XRT for 10 and 20 Gy groups. For example, at the 18th week, leg length discrepancy is 0.0±1.6% for control, 4.2±1.3% for 10 Gy, and 8.2±1.8% for 20 Gy. HBO in 10 Gy groups decreased these discrepancies to 2.2±1.8% (P=0.013) in weeks 1-4, 1.9±1.9% (P=0.004) in weeks 5-8, and 2.4±1.3% (P=0.007) in weeks 9-12. In the 20 Gy groups, HBO decreased these discrepancies to 7.0±2.3% (P=0.20) in weeks 1-4, 5.0±1.6% (P=0.003) in weeks 5-8, and 4.0±2.4% (P=0.001) in weeks 9-12. Interestingly HBO delayed till weeks 9-12 still had substantial benefit. At the highest radiation dose (30 Gy), HBO did not have any measurable protective effect at any time period. Leg length discrepancy was 10.7±3.0% at 30 Gy without any treatment. Interestingly, FGF did improve leg length discrepancy with or without HBO. With HBO, leg length discrepancy was 6.5±1.8% (P=0.009) in weeks 1-4 group, and 7.3±2.1% (P=0.005) in weeks 5-8 group. In the groups that had FGF without HBO, leg length discrepancy was 6.8±1.4% (P=0.009) in weeks 1-4 group, and 7.6±1.4% (P=0.007) in weeks 5-8 group. HBO did not show any protective effect on acute and chronic skin reactions. In group 15, 50-75% of the irradiated area showed epilation after FGF treatment (given at 1-4 week after 30 Gy XRT). All other groups which received 30 Gy XRT showed close to 100% epilation in the irradiated area. Conclusion: HBO raises normal tissue oxygen level and both HBO and FGF can stimulates neovasculature. These effects might, in turn, counteract radiation induced anti-angiogenesis. The current experiment shows that radiation induced normal tissue damage can be significant reduced by HBO and FGF treatment. Planed preventive therapies such as HBO or FGF may make bone growth retardation less severe in pediatric patients requiring high dose bone irradiation

[en] Purpose: The goal of the current experiment is to test for protective effect of hyperbaric oxygen (HBO) and basic fibroblast growth factor (bFGF) on bone growth. Methods and Materials: Control C3H mice received hind leg irradiation at 0, 10, 20, or 30 Gy. HBO-treated groups received radiation 1, 5, or 9 weeks before beginning HBO. The remaining groups began bFGF ± HBO 1 or 5 weeks after 30 Gy. HBO treatments were given 5 days per week for 4 weeks at 2 ATA for 3 h/day. bFGF was given intravenously at 6 μg twice a week for 4 weeks. Results: HBO improved bone growth after radiation in the 10 and 20 Gy groups. At 18 weeks control tibia length discrepancy is 0.0, 4.2, 8.2, and 10.7% after 0, 10, 20, and 30 Gy, respectively. HBO beginning in week 1, 5, or 9 following 10 Gy decreased these discrepancies to 2.0% (p < 0.05), 1.8% (p < 0.05), and 2.4% (p < 0.05), respectively. After 20 Gy, HBO decreased these discrepancies to 7.0% (p = ns), 4.9% (p < 0.05), and 3.6% (p < 0.05), respectively. At 30 Gy, HBO alone had no effect on bone shortening. bFGF improved tibia length discrepancy with or without HBO. At 18 weeks length discrepancies were 6.5% (p < 0.05) and 7.3 (p < 0.05), and after bFGF alone were 6.8% (p < 0.05) and 7.3% (p < 0.05) for treatment beginning in week 1 or 5, respectively. Tibial growth at 18 and 33 weeks following radiation were similar. Conclusion: Radiation effects on bone growth can be significant reduced by HBO after 10 or 20 Gy, but not after 30 Gy. At 30 Gy bFGF still significantly reduced the degree of bone shortening, but HBO provided no added benefit to bFGF therapy

[en] Purpose: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. Methods and Materials: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. Results: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between features in both DRR-MRI and portal image. Moreover, target volume could be accurately visualized in the DRR-MRI and mapped over to the corresponding portal image for treatment verification. The accuracy of DRR-MRI was also examined by comparing it to the corresponding simulation image. The matching results indicated that the maximum deviation of anatomical features was less than 2.5 mm. Conclusion: A method for MR image-guided portal verification of brain treatment field was developed. Although the radiographic appearance in the DRR-MRI is different from that in the portal image, DRR-MRI provides essential anatomical features (landmarks and target volume) as well as their relative locations to be used as references for computerized portal verification

[en] An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in cine mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 ± 0.005, p < 0.0001) as well as a linear relationship (slope = 1.027 ± 0.061, R² = 0.980) without phase shift. The AVC was also compared to the spirometric tidal volumes, showing a similar linearity (slope = 1.030 ± 0.092, R² = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 ± 0.44 and 0.82 ± 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

[en] An analytical approach to predict respiratory diaphragm motion should have advantages over a correlation-based method, which cannot adapt to breathing pattern changes without re-calibration for a changing correlation and/or linear coefficient. To quantitatively calculate the diaphragm motion, a new expandable 'piston' respiratory (EPR) model was proposed and tested using 4DCT torso images of 14 patients. The EPR model allows two orthogonal lung motions (with a few volumetric constraints): (1) the lungs expand (ΔV_EXP) with the same anterior height variation as the thoracic surface, and (2) the lungs extend (ΔV_EXT) with the same inferior distance as the volumetrically equivalent 'piston' diaphragm. A volume conservation rule (VCR) established previously (Li et al 2009 Phys. Med. Biol. 54 1963-78) was applied to link the external torso volume change (TVC) to internal lung volume change (LVC) via lung air volume change (AVC). As the diaphragm moves inferiorly, the vacant space above the diaphragm inside the rib cage should be filled by lung tissue with a volume equal to ΔV_EXT (=LVC-ΔV_EXP), while the volume of non-lung tissues in the thoracic cavity should conserve. It was found that ΔV_EXP accounted for 3-24% of the LVC in these patients. The volumetric shape of the rib cage, characterized by the variation of cavity volume per slice over the piston motion range, deviated from a hollow cylinder by -1.1% to 6.0%, and correction was made iteratively if the variation is >3%. The predictions based on the LVC and TVC (with a conversion factor) were compared with measured diaphragm displacements (averaged from six pivot points), showing excellent agreements (0.2 ± 0.7 mm and 0.2 ± 1.2 mm, respectively), which are within clinically acceptable tolerance. Assuming motion synchronization between the piston and points of interest along the diaphragm, point motion was estimated but at higher uncertainty (∼10% ± 4%). This analytical approach provides a patient-independent technique to calculate the patient-specific diaphragm motion, using the anatomical and respiratory volumetric constraints.

[en] Purpose: To provide more clinically useful image registration with improved accuracy and reduced time, a novel technique of three-dimensional (3D) volumetric voxel registration of multimodality images is developed. Methods and Materials: This technique can register up to four concurrent images from multimodalities with volume view guidance. Various visualization effects can be applied, facilitating global and internal voxel registration. Fourteen computed tomography/magnetic resonance (CT/MR) image sets and two computed tomography/positron emission tomography (CT/PET) image sets are used. For comparison, an automatic registration technique using maximization of mutual information (MMI) and a three-orthogonal-planar (3P) registration technique are used. Results: Visually sensitive registration criteria for CT/MR and CT/PET have been established, including the homogeneity of color distribution. Based on the registration results of 14 CT/MR images, the 3D voxel technique is in excellent agreement with the automatic MMI technique and is indicatory of a global positioning error (defined as the means and standard deviations of the error distribution) using the 3P pixel technique: 1.8 deg ± 1.2 deg in rotation and 2.0 ± 1.3 (voxel unit) in translation. To the best of our knowledge, this is the first time that such positioning error has been addressed. Conclusion: This novel 3D voxel technique establishes volume-view-guided image registration of up to four modalities. It improves registration accuracy with reduced time, compared with the 3P pixel technique. This article suggests that any interactive and automatic registration should be safeguarded using the 3D voxel technique

[en] We sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM). With the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers. The mean and median intra-observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or inter-observer error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm. We have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging

[en] Purpose: To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. Methods and materials: Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. Results: We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of <5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of <2% (mean 0.54%). Conclusion: Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints in our procedure reduced uncertainty in planning and treatment