Deformable registration of abdominal kilovoltage treatment planning CT and tomotherapy daily megavoltage CT for treatment adaptation.

In adaptive radiation therapy the treatment planning kilovoltage CT (kVCT) images need to be registered with daily CT images. Daily megavoltage CT (MVCT) images are generally noisier than the kVCT images. In addition, in the abdomen, low image contrast, differences in bladder filling, differences in bowel, and rectum filling degrade image usefulness and make deformable image registration very difficult. The authors have developed a procedure to overcome these difficulties for better deformable registration between the abdominal kVCT and MVCT images. The procedure includes multiple image preprocessing steps and a two deformable registration steps. The image preprocessing steps include MVCT noise reduction, bowel gas pockets detection and painting, contrast enhancement, and intensity manipulation for critical organs. The first registration step is carried out in the local region of the critical organs (bladder, prostate, and rectum). It requires structure contours of these critical organs on both kVCT and MVCT to obtain good registration accuracy on these critical organs. The second registration step uses the first step results and registers the entire image with less intensive computational requirement. The two-step approach improves the overall computation speed and works together with these image preprocessing steps to achieve better registration accuracy than a regular single step registration. The authors evaluated the procedure on multiple image datasets from prostate cancer patients and gynecological cancer patients. Compared to rigid alignment, the proposed method improves volume matching by over 60% for the critical organs and reduces the prostate landmark registration errors by 50%.

The validation of tomotherapy dose calculations in low-density lung media.

The dose-calculation accuracy of the tomotherapy Hi-Art II(R) (Tomotherapy, Inc., Madison, WI) treatment planning system (TPS) in the presence of low-density lung media was investigated. In this evaluation, a custom-designed heterogeneous phantom mimicking the mediastinum geometry was used. Gammex LN300 and balsa wood were selected as two lung-equivalent materials with different densities. Film analysis and ionization chamber measurements were performed. Treatment plans for esophageal cancers were used in the evaluation. The agreement between the dose calculated by the TPS and the dose measured via ionization chambers was, in most cases, within 0.8%. Gamma analysis using 3% and 3 mm criteria for radiochromic film dosimetry showed that 98% and 95% of the measured dose distribution had passing gamma values < or =1 for LN300 and balsa wood, respectively. For a homogeneous water-equivalent phantom, 95% of the points passed the gamma test. It was found that for the interface between the low-density medium and water-equivalent medium, the TPS calculated the dose distribution within acceptable limits. The phantom developed for this work enabled detailed quality-assurance testing under realistic conditions with heterogeneous media.

Estimation of setup uncertainty using planar and MVCT imaging for gynecologic malignancies.

PURPOSE: This prospective study investigates gynecologic malignancy online treatment setup error corrections using planar kilovoltage/megavoltage (KV/MV) imaging and helical MV computed tomography (MVCT) imaging. METHODS AND MATERIALS: Twenty patients were divided into two groups. The first group (10 patients) was imaged and treated using a conventional linear accelerator (LINAC) with image-guidance capabilities, whereas the second group (10 patients) was treated using tomotherapy with MVCT capabilities. Patients treated on the LINAC underwent planar KV and portal MV imaging and a two-dimensional image registration algorithm was used to match these images to digitally reconstructed radiographs (DRRs). Patients that were treated using tomotherapy underwent MVCT imaging, and a three-dimensional image registration algorithm was used to match planning CT to MVCT images. Subsequent repositioning shifts were applied before each treatment and recorded for further analysis. To assess intrafraction motion, 5 of the 10 patients treated on the LINAC underwent posttreatment planar imaging and DRR matching. Based on these data, patient position uncertainties along with estimated margins based on well-known recipes were determined. RESULTS: The errors associated with patient positioning ranged from 0.13 cm to 0.38 cm, for patients imaged on LINAC and 0.13 cm to 0.48 cm for patients imaged on tomotherapy. Our institutional clinical target volume-PTV margin value of 0.7 cm lies inside the confidence interval of the margins established using both planar and MVCT imaging. CONCLUSION: Use of high-quality daily planar imaging, volumetric MVCT imaging, and setup corrections yields excellent setup accuracy and can help reduce margins for the external beam treatment of gynecologic malignancies.

Helical tomotherapy planning for left-sided breast cancer patients with positive lymph nodes: comparison to conventional multiport breast technique.

PURPOSE: To evaluate the feasibility of using helical tomotherapy for locally advanced left-sided breast cancer. METHODS AND MATERIALS: Treatment plans were generated for 10 left-sided breast cancer patients with positive lymph nodes comparing a multiport breast (three-dimensional) technique with the tomotherapy treatment planning system. The planning target volumes, including the chest wall/breast, supraclavicular, axillary, and internal mammary lymph nodes, were contoured. The treatment plans were generated on the tomotherapy treatment planning system to deliver 50.4 Gy to the planning target volume. To spare the contralateral tissues, directional blocking was applied to the right breast and right lung. The optimization goals were to protect the lungs, heart, and right breast. RESULTS: The tomotherapy plans increased the minimal dose to the planning target volume (minimal dose received by 99% of target volume = 46.2 +/- 1.3 Gy vs. 27.9 +/- 17.1 Gy) while improving the dose homogeneity (dose difference between the minimal dose received by 5% and 95% of the planning target volume = 7.5 +/- 1.8 Gy vs. 37.5 +/- 26.9 Gy). The mean percentage of the left lung volume receiving >or=20 Gy in the tomotherapy plans decreased from 32.6% +/- 4.1% to 17.6% +/- 3.5%, while restricting the right-lung mean dose to <5 Gy. However, the mean percentage of volume receiving >or=5 Gy for the total lung increased from 25.2% +/- 4.2% for the three-dimensional technique to 46.9% +/- 8.4% for the tomotherapy plan. The mean volume receiving >or=35 Gy for the heart decreased from 5.6% +/- 4.8% to 2.2% +/- 1.5% in the tomotherapy plans. However, the mean heart dose for tomotherapy delivery increased from 7.5 +/- 3.4 Gy to 12.2 +/- 1.8 Gy. CONCLUSION: The tomotherapy plans provided better dose conformity and homogeneity than did the three-dimensional plans for treatment of left-sided breast tumors with regional lymph node involvement, while allowing greater sparing of the heart and left lung from doses associated with increased complications.

Enhanced efficiency in helical tomotherapy quality assurance using a custom-designed water-equivalent phantom.

Tomotherapy is an image-guided, intensity-modulated radiation therapy system that delivers highly conformal dose distributions in a helical fashion. This system is also capable of acquiring megavoltage computed-tomography images and registering them to the planning kVCT images for accurate target localization. Quality assurance (QA) of this device is time intensive, but can be expedited by improved QA tools and procedures. A custom-designed phantom was fabricated to improve the efficiency of daily QA of our Tomotherapy machine. The phantom incorporates ionization chamber measurement points, plugs of different densities and slide-out film cartridges. The QA procedure was designed to verify in less than 30 min the vital components of the tomotherapy system: static beam quality and output, image quality, correctness of image registration and energy of the helical dose delivery. Machine output, percent depth dose and off-axis factors are simultaneously evaluated using a static 5 x 40 cm(2) open field. A single phantom scan is used to evaluate image quality and registration accuracy. The phantom can also be used for patient plan-specific QA. The QA results over a period of 6 months are reported in this paper. The QA process was found to be simple, efficient and capable of simultaneously verifying several important parameters.

Dosimetric consequences of uncorrected setup errors in helical Tomotherapy treatments of breast-cancer patients.

BACKGROUND AND PURPOSE: The Tomotherapy Hi-Art II system allows acquisition of pre-treatment MVCT images to correct patient position. This work evaluates the dosimetric impact of uncorrected setup errors in breast-cancer radiation therapy. MATERIALS AND METHODS: Breast-cancer patient-positioning errors were simulated by shifting the patient computed-tomography (CT) dataset relative to the planned photon fluence and re-computing the dose distributions. To properly evaluate the superficial region, film measurements were compared against the Tomotherapy treatment planning system (TPS) calculations. A simulation of the integrated dose distribution was performed to evaluate the setup error impact over the course of treatment. RESULTS: Significant dose differences were observed for 11-mm shifts in the anterolateral and 3-mm shifts in the posteromedial directions. The results of film measurements in the superficial region showed that the TPS overestimated the dose by 14% at a 1-mm depth, improving to 3% at depths >or=5mm. Significant dose reductions in PTV were observed in the dose distributions simulated over the course of treatment. CONCLUSIONS: Tomotherapy's rotational delivery provides sufficient photon fluence extending beyond the skin surface to allow an up to 7-mm uncorrected setup error in the anterolateral direction. However, the steep dose falloff that conforms to the lung surface leads to compromised dose distributions with uncorrected posteromedial shifts. Therefore, daily image guidance and consequent patient repositioning is warranted for breast-cancer patients.

Prospective clinical trial of positron emission tomography/computed tomography image-guided intensity-modulated radiation therapy for cervical carcinoma with positive para-aortic lymph nodes.

PURPOSE: To describe a more aggressive treatment technique allowing dose escalation to positive para-aortic lymph nodes (PALN) in patients with cervical cancer, by means of positron emission tomography (PET)/computed tomography (CT)-guided intensity-modulated radiation therapy (IMRT). Here, we describe methods for simulation and planning of these treatments and provide objectives for target coverage as well as normal tissue sparing to guide treatment plan evaluation. METHODS AND MATERIALS: Patients underwent simulation on a PET/CT scanner. Treatment plans were generated to deliver 60.0 Gy to the PET-positive PALN and 50.0 Gy to the PALN and pelvic lymph node beds. Treatment plans were optimized to deliver at least 95% of the prescribed doses to at least 95% of each target volume. Dose-volume histograms were calculated for normal structures. RESULTS: The plans of 10 patients were reviewed. Target coverage goals were satisfied in all plans. Analysis of dose-volume histograms indicated that treatment plans involved irradiation of approximately 50% of the bowel volume to at least 25.0 Gy, with less than 10% receiving at least 50.0 Gy and less than 1% receiving at least 60.0. With regard to kidney sparing, approximately 50% of the kidney volume received at least 16.0 Gy, less than 5% received at least 50.0 Gy, and less than 1% received at least 60.0 Gy. CONCLUSIONS: We have provided treatment simulation and planning methods as well as guidelines for the evaluation of target coverage and normal tissue sparing that should facilitate the more aggressive treatment of cervical cancer.

Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in the zebrafish hindbrain.

Failure of Notch signaling in zebrafish mind bomb (mib) mutants results in a neurogenic phenotype where an overproduction of early differentiating neurons is accompanied by the loss of later-differentiating cell types. We have characterized in detail the hindbrain phenotype of mib mutants. Hindbrain branchiomotor neurons (BMNs) are reduced in number but not missing in mib mutants. In addition, BMN clusters are frequently fused across the midline in mutants. Mosaic analysis indicates that the BMN patterning and fusion defects in the mib hindbrain arise non-cell autonomously. Ventral midline signaling is defective in the mutant hindbrain, in part due to the differentiation of some midline cells into neural cells. Interestingly, while early hindbrain patterning appears normal in mib mutants, subsequent rhombomere-specific gene expression is completely lost. The defects in ventral midline signaling and rhombomere patterning are accompanied by an apparent loss of neuroepithelial cells in the mutant hindbrain. These observations suggest that, by regulating the differentiation of neuroepithelial cells into neurons, Notch signaling preserves a population of non-neuronal cells that are essential for maintaining patterning mechanisms in the developing neural tube.