Output factor comparison of Monte Carlo and measurement for Varian TrueBeam 6 MV and 10 MV flattening filter-free stereotactic radiosurgery system.

The dose measurements of the small field sizes, such as conical collimators used in stereotactic radiosurgery (SRS), are a significant challenge due to many factors including source occlusion, detector size limitation, and lack of lateral electronic equilibrium. One useful tool in dealing with the small field effect is Monte Carlo (MC) simulation. In this study, we report a comparison of Monte Carlo simulations and measurements of output factors for the Varian SRS system with conical collimators for energies of 6 MV flattening filter-free (6 MV) and 10 MV flattening filter-free (10 MV) on the TrueBeam accelerator. Monte Carlo simulations of Varian's SRS system for 6 MV and 10 MV photon energies with cones sizes of 17.5 mm, 15.0 mm, 12.5 mm, 10.0 mm, 7.5 mm, 5.0 mm, and 4.0 mm were performed using EGSnrc (release V4 2.4.0) codes. Varian's version-2 phase-space files for 6 MV and 10 MV of TrueBeam accelerator were utilized in the Monte Carlo simulations. Two small diode detectors Edge (Sun Nuclear) and Small Field Detector (SFD) (IBA Dosimetry) were applied to measure the output factors. Significant errors may result if detector correction factors are not applied to small field dosimetric measurements. Although it lacked the machine-specific kfclin,fmsrQclin,Qmsr correction factors for diode detectors in this study, correction factors were applied utilizing published studies conducted under similar conditions. For cone diameters greater than or equal to 12.5 mm, the differences between output factors for the Edge detector, SFD detector, and MC simulations are within 3.0% for both energies. For cone diameters below 12.5 mm, output factors differences exhibit greater variations.

Accuracy of 3D volumetric image registration based on CT, MR and PET/CT phantom experiments.

Registration is critical for image-based treatment planning and image-guided treatment delivery. Although automatic registration is available, manual, visual-based image fusion using three orthogonal planar views (3P) is always employed clinically to verify and adjust an automatic registration result. However, the 3P fusion can be time consuming, observer dependent, as well as prone to errors, owing to the incomplete 3-dimensional (3D) volumetric image representations. It is also limited to single-pixel precision (the screen resolution). The 3D volumetric image registration (3DVIR) technique was developed to overcome these shortcomings. This technique introduces a 4th dimension in the registration criteria beyond the image volume, offering both visual and quantitative correlation of corresponding anatomic landmarks within the two registration images, facilitating a volumetric image alignment, and minimizing potential registration errors. The 3DVIR combines image classification in real-time to select and visualize a reliable anatomic landmark, rather than using all voxels for alignment. To determine the detection limit of the visual and quantitative 3DVIR criteria, slightly misaligned images were simulated and presented to eight clinical personnel for interpretation. Both of the criteria produce a detection limit of 0.1 mm and 0.1 degree. To determine the accuracy of the 3DVIR method, three imaging modalities (CT, MR and PET/CT) were used to acquire multiple phantom images with known spatial shifts. Lateral shifts were applied to these phantoms with displacement intervals of 5.0+/-0.1 mm. The accuracy of the 3DVIR technique was determined by comparing the image shifts determined through registration to the physical shifts made experimentally. The registration accuracy, together with precision, was found to be: 0.02+/-0.09 mm for CT/CT images, 0.03+/-0.07 mm for MR/MR images, and 0.03+/-0.35 mm for PET/CT images. This accuracy is consistent with the detection limit, suggesting an absence of detectable systematic error. This 3DVIR technique provides a superior alternative to the 3P fusion method for clinical applications.

Craniospinal irradiation with spinal IMRT to improve target homogeneity.

PURPOSE: To report a new technique for the spinal component of craniospinal irradiation (CSI) in the supine position, to describe a verification procedure for this method, and to compare this technique with conventional plans. METHODS AND MATERIALS: Twelve patients were treated between 1998 and 2006 with CSI using a novel technique. Sixteen children were treated with a conventional field arrangement. All patients were followed for outcomes and toxicity. CSI was delivered using a posteroanterior (PA) intensity-modulated radiation therapy (IMRT) spinal field matched to conventional, opposed lateral cranial fields. Treatment plans were generated for each patient using the IMRT technique and a standard PA field technique. The resulting dosimetry was compared to determine target homogeneity, maximum dose to normal tissues, and total monitor units delivered. RESULTS: Evaluation of the spinal IMRT technique compared with a standard PA technique reveals a 7% reduction in the target volume receiving > or =110% of the prescribed dose and an 8% increase in the target volume receiving > or =95% of the prescribed dose. Although target homogeneity was improved, the maximum dose delivered in the paraspinal muscles was increased by approximately 8.5% with spinal IMRT compared to the PA technique. Follow-up evaluations revealed no unexpected toxicity associated with the IMRT technique. CONCLUSIONS: A new technique of spine IMRT is presented in combination with a quality assurance method. This method improves target dose uniformity compared to the conventional CSI technique. Longer follow-up will be required to determine any benefit with regard to toxicity and disease control.

Brain tumor segmentation using holistically nested neural networks in MRI images.

PURPOSE: Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. METHODS: Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. RESULTS: The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of 0.83 and 0.85 were achieved. A quantitative comparison indicated that the proposed method outperforms the popular fully convolutional network (FCN) method. In terms of efficiency, the proposed method took around 10 h for training with 50,000 iterations, and approximately 30 s for testing of a typical MRI image in the BRATS 2013 dataset with a size of 160 × 216 × 176, using a DELL PRECISION workstation T7400, with an NVIDIA Tesla K20c GPU. CONCLUSIONS: An effective brain tumor segmentation method for MRI images based on a HNN has been developed. The high level of accuracy and efficiency make this method practical in brain tumor segmentation. It may play a crucial role in both brain tumor diagnostic analysis and in the treatment planning of radiation therapy.

A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma.

PURPOSE: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. METHODS AND MATERIALS: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. RESULTS: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). CONCLUSIONS: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.

A novel 3D volumetric voxel registration technique for volume-view-guided image registration of multiple imaging modalities.

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 multi-modalities 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 degrees +/- 1.2 degrees 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 safe-guarded using the 3D voxel technique.

Parameters favorable to intraprostatic radiation dose escalation in men with localized prostate cancer.

PURPOSE: To identify , within the framework of a current Phase I trial, whether factors related to intraprostatic cancer lesions (IPLs) or individual patients predict the feasibility of high-dose intraprostatic irradiation. METHODS AND MATERIALS: Endorectal coil MRI scans of the prostate from 42 men were evaluated for dominant IPLs. The IPLs, prostate, and critical normal tissues were contoured. Intensity-modulated radiotherapy plans were generated with the goal of delivering 75.6 Gy in 1.8-Gy fractions to the prostate, with IPLs receiving a simultaneous integrated boost of 3.6 Gy per fraction to a total dose of 151.2 Gy, 200% of the prescribed dose and the highest dose cohort in our trial. Rectal and bladder dose constraints were consistent with those outlined in current Radiation Therapy Oncology Group protocols. RESULTS: Dominant IPLs were identified in 24 patients (57.1%). Simultaneous integrated boosts (SIB) to 200% of the prescribed dose were achieved in 12 of the 24 patients without violating dose constraints. Both the distance between the IPL and rectum and the hip-to-hip patient width on planning CT scans were associated with the feasibility to plan an SIB (p = 0.002 and p = 0.0137, respectively). CONCLUSIONS: On the basis of this small cohort, the distance between an intraprostatic lesion and the rectum most strongly predicted the ability to plan high-dose radiation to a dominant intraprostatic lesion. High-dose SIB planning seems possible for select intraprostatic lesions.

Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas.

BACKGROUND: FLAIR and T2 weighted MRIs are used based on institutional preference to delineate high grade gliomas and surrounding edema for radiation treatment planning. Although these sequences have inherent physical differences there is limited data on the clinical and dosimetric impact of using either or both sequences. METHODS: 40 patients with high grade gliomas consecutively treated between 2002 and 2008 of which 32 had pretreatment MRIs with T1, T2 and FLAIR available for review were selected for this study. These MRIs were fused with the treatment planning CT. Normal structures, clinical tumor volume (CTV) and planning tumor volume (PTV) were then defined on the T2 and FLAIR sequences. A Venn diagram analysis was performed for each pair of tumor volumes as well as a fractional component analysis to assess the contribution of each sequence to the union volume. For each patient the tumor volumes were compared in terms of total volume in cubic centimeters as well as anatomic location using a discordance index. The overlap of the tumor volumes with critical structures was calculated as a measure of predicted toxicity. For patients with MRI documented failures, the tumor volumes obtained using the different sequences were compared with the recurrent gross tumor volume (rGTV). RESULTS: The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p < 0.0001 and p = 0.0001 respectively). Based on the discordance index, the abnormality identified using the different sequences also differed in location. Fractional component analysis showed that the intersection of the tumor volumes as defined on both T2 and FLAIR defined the majority of the union volume contributing 63.6% to the CTV union and 82.1% to the PTV union. T2 alone uniquely identified 12.9% and 5.2% of the CTV and PTV unions respectively while FLAIR alone uniquely identified 25.7% and 12% of the CTV and PTV unions respectively. There was no difference in predicted toxicity to normal structures using T2 or FLAIR. At the time of analysis, 26 failures had occurred of which 19 patients had MRIs documenting the recurrence. The rGTV correlated best with the FLAIR CTV but the percentage overlap was not significantly different from that with T2. There was no statistical difference in the percentage overlap with the rGTV and the PTVs generated using either T2 or FLAIR. CONCLUSIONS: Although both T2 and FLAIR MRI sequences are used to define high grade glial neoplasm and surrounding edema, our results show that the volumes generated using these techniques are different and not interchangeable. These differences have bearing on the use of intensity modulated radiation therapy (IMRT) and highly conformal treatment as well as on future clinical trials where the bias of using one technique over the other may influence the study outcome.

A dosimetric comparison of four treatment planning methods for high grade glioma.

BACKGROUND: High grade gliomas (HGG) are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D) conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma. METHODS: Three dimensional conformal (3D), sequential boost IMRT, integrated boost (IB) IMRT and Tomotherapy (TOMO) treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. RESULTS: The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID) to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans. CONCLUSION: No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH) of the normal brain and may not be a good indicator of delayed radiation toxicity.

Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers.

BACKGROUND: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of a cardiac prevention and rehabilitation programme for all patients at first presentation with coronary artery disease.

BACKGROUND: A cardiac prevention and rehabilitation (CP&R) programme was established for patients following their first clinical episode of coronary heart disease and 1-year outcomes were evaluated against British targets for coronary prevention. METHODS: Patients were evaluated 1 year after participation and outcomes compared with patients in the same health district registered with a random half of general practitioners not eligible for the programme (internal reference group) and patients identified in other English centres which participated in the EUROASPIRE II survey (external reference group). RESULTS: Three hundred and eighteen patients (76% of 417 incident cases) attended for 1-year screening. Of those who participated in the programme 96/113 (85%) attended (Group 1); 152/194 (78%) attended from all those eligible for the programme (Group 2); 166/223 (74%) attended from those receiving usual care in the same health district (Group 3 - internal reference group). In the EUROASPIRE II survey (Group 4 - external reference group) 362/744 (58%) patients were screened. Current smoking at follow-up was Group 1, 8%, Group 2, 11%, Group 3, 13% and Group 4, 18%. Proportions with a BMI < 25 kg/m were 29%, 25%, 32%, 18%; BP < 140/90 mmHg 58%, 56%, 49%, 48%; total cholesterol < 5.0 mmol/l 60%, 54%, 43%, 46%; antiplatelet therapy 88%, 87%, 86%, 81%; beta-blocker therapy 48%, 46%, 46%, 44%; and lipid lowering therapy 56%, 51%, 36%, 69% respectively. CONCLUSIONS: A CP&R programme was associated with a majority of coronary patients, whether attending the programme or not, achieving the Joint British Society's recommended prevention targets within the same health district. Specifically, a higher proportion of programme patients reached the cholesterol target of <5.0 mmol/l compared with both usual care and other centres elsewhere. This was achieved by using more lipid lowering therapy compared with usual care in the same health district, but less than other centres outside the health district. The overall results for the whole health district show a higher standard of preventive care compared with contemporary EUROASPIRE II results from other health districts in England.