Lung sparing in MR-guided non-adaptive SBRT treatment of peripheral lung tumors.

Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.

Using Smartphone Chatbot for Postoperative Care after Intravitreal Injection during COVID-19 Period: A Retrospective Cohort Study.

BACKGROUND: During COVID-19 pandemic period, it was difficult for the patients regular and scheduled follow-up in outpatient department, especially when lock-down. However, early detection of patients with initial infection or other serious conditions after ocular surgeries, such as intravitreous injection (IVI) for age-related macular degeneration (AMD). OBJECTIVE: We accessed a postoperative care chatbot system (PCCS) in smartphone for patients to self-report postoperative symptoms/signs with an instant bidirectional feedback system. METHODS: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patient to report and grade six ocular symptoms/signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days postoperatively to assess their symptoms/signs per day after receiving an alert. The data automatically collected using a cloud computer system judged the grade and sent messages to medical staff for further medical assistance. User's satisfaction questionnaire was collected on the 7th day. RESULTS: One hundred and eighty-five patients participated in this study. There were 26 reports (3.03%) of symptom grade deterioration (increased blurred vision, eye swelling, nausea, and floater/flash) in 12 patients (6.5%). No gender difference for the earlier medical consultation. One case occurred endophthalmitis and improved after 2 times prompt IVI antibiotics. 87% of patients were satisfied or very satisfied to communicate their symptoms instantly with the app, willing to use it again and considered it could improve quality of care. The incidence of earlier medical consultation is 3.8% (7/185) and the incidence of endophthalmitis is 0.5% (1/185). CONCLUSIONS: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing early medical consultation without gender differences in AMD patients who receiving intravitreal injections. It achieves satisfactory response from patients.

Stereotactic Magnetic Resonance-guided Adaptive Radiation Therapy for Localized Kidney Cancer: Early Outcomes from a Prospective Phase 1 Trial and Supplemental Cohort.

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13-20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was -1.8 ml/min/1.73 m2 (95% confidence interval or CI [-6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was -0.20 cm (95% CI [-0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. PATIENT SUMMARY: For patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance--guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.

Comparison of MR-soft tissue based versus biliary stent based alignment for image guidance in pancreatic SBRT.

PURPOSE: The role of biliary stents in image-guided localization for pancreatic cancer has been inconclusive. To date, stent accuracy has been largely evaluated against implanted fiducials on cone beam computed tomography. We aim to use magnetic resonance (MR) soft tissue as a direct reference to examine the geometric and dosimetric impacts of stent-based localization on the newly available MR linear accelerator. METHODS: Thirty pancreatic cancer patients (132 fractions) treated on our MR linear accelerator were identified to have a biliary stent. In our standard adaptive workflow, patients were set up to the target using soft tissue for image registration and structures were re-contoured on daily MR images. The original plan was then projected on treatment anatomy and dose predicted, followed by plan re-optimization and treatment delivery. These online predicted plans were soft tissue-based and served as reference plans. Retrospective image registration to the stent was performed offline to simulate stent-based localization and the magnitude of shifts was taken as the geometric accuracy of stent localization. New predicted plans were generated based on stent-alignment for dosimetric comparison. RESULTS: Shifts were within 3 mm for 90% of the cases (mean = 1.5 mm); however, larger shifts up to 7.2 mm were observed. Average PTV coverage dropped by 1.1% with a maximum drop of 26.8%. The mean increase in V35Gy was 0.15, 0.05, 0.02, and 0.02 cc for duodenum, stomach, small bowel and large bowel, respectively. Stent alignment was significantly worse for all metrics except for small bowel (p = 0.07). CONCLUSIONS: Overall discrepancy between stent- and soft tissue-alignment was modest; however, large discrepancies were observed for select cases. While PTV coverage loss may be compensated for by using a larger margin, the increase in dose to gastrointestinal organs at risk may limit the role of biliary stents in image-guided localization.

Synthetic CT generation for MRI-guided adaptive radiotherapy in prostate cancer.

Current MRI-guided adaptive radiotherapy (MRgART) workflows require fraction-specific electron and/or mass density maps, which are created by deformable image registration (DIR) between the simulation CT images and daily MR images. Manual density overrides may also be needed where DIR-produced results are inaccurate. This approach slows the adaptive radiotherapy workflow and introduces additional dosimetric uncertainties, especially in the presence of the magnetic field. This study investigated a method based on a conditional generative adversarial network (cGAN) with a multi-planar method to generate synthetic CT images from low-field MR images to improve efficiency in MRgART workflows for prostate cancer. Fifty-seven male patients, who received MRI-guided radiation therapy to the pelvis using the ViewRay MRIdian Linac, were selected. Forty-five cases were randomly assigned to the training cohort with the remaining twelve cases assigned to the validation/testing cohort. All patient datasets had a semi-paired DIR-deformed CT-sim image and 0.35T MR image acquired using a true fast imaging with steady-state precession (TrueFISP) sequence. Synthetic CT images were compared with deformed CT images to evaluate image quality and dosimetric accuracy. To evaluate the dosimetric accuracy of this method, clinical plans were recalculated on synthetic CT images in the MRIdian treatment planning system. Dose volume histograms for planning target volumes (PTVs) and organs-at-risk (OARs) and dose distributions using gamma analyses were evaluated. The mean-absolute-errors (MAEs) in CT numbers were 30.1 ± 4.2 HU, 19.6 ± 2.3 HU and 158.5 ± 26.0 HU for the whole pelvis, soft tissue, and bone, respectively. The peak signal-to-noise ratio was 35.2 ± 1.7 and the structural index similarity measure was 0.9758 ± 0.0035. The dosimetric difference was on average less than 1% for all PTV and OAR metrics. Plans showed good agreement with gamma pass rates of 99% and 99.9% for 1%/1 mm and 2%/2 mm, respectively. Our study demonstrates the potential of using synthetic CT images created with a multi-planar cGAN method from 0.35T MRI TrueFISP images for the MRgART treatment of prostate radiotherapy. Future work will validate the method in a large cohort of patients and investigate the limitations of the method in the adaptive workflow.

A framework for automated and streamlined kV cone beam computed tomography image quality assurance: a multi-institutional study.

The purpose of this study was to develop and evaluate a framework to support automated standardized testing and analysis of Cone Beam Computed Tomography (CBCT) image quality QA across multiple institutions. A survey was conducted among the participating institutions to understand the variability of the CBCT QA practices. A commercial, automated software platform was validated by seven institutions participating in a consortium dedicated to automated quality assurance. The CBCT image analysis framework was used to compare periodic QA results among 23 linear accelerators (linacs) from seven institutions. The CBCT image quality metrics (geometric distortion, spatial resolution, contrast, HU constancy, uniformity and noise) data are plotted as a function of means with the upper and lower control limits compared to the linac acceptance criteria and AAPM recommendations. For example, mean geometric distortion and HU constancy metrics were found to be 0.13 mm (TG142 recommendation: ≤2 mm) and 13.4 respectively (manufacturer acceptance specification: ≤±50).Image upload and analysis process was fully automated using a MATLAB-based platform. This analysis enabled a quantitative, longitudinal assessment of the performance of quality metrics which were also compared across 23 linacs. For key CBCT parameters such as uniformity, contrast, and HU constancy, all seven institutions used stricter goals than what would be recommended based on the analysis of the upper and lower control limits. These institutional goals were also found to be stricter than that found in AAPM published guidance. This work provides a reference that could be used to machine-specific optimized tolerance of CBCT image maintenance via control charts to monitor performance we well as the sensitivity of different tests in support of a broader quality assurance program. To ensure the daily image quality needed for patient care, the optimized statistical QA metrics recommended to using along with risk-based QA.

Comprehensive Patient-Specific Intensity-Modulated Radiation Therapy Quality Assurance Comparing Mobius3D/FX to Conventional Methods of Evaluation.

Purpose To determine the appropriateness of implementing Mobius3D/FX (Varian Medical Systems, Inc., Palo Alto, CA, USA) as not only a pretreatment secondary check but as an alternative to measurement-based patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods Mobius3D/FX was commissioned and stock beam models were tweaked so that an independent recalculated 3D dose distribution can be obtained. Then, 50 patient-specific treatment plans for various indications were delivered across a 2D ion chamber array, radiochromic film setup, and electronic portal imager and analyzed with MobiusFX and gamma analysis. The concordance of plans scored as passing between MobiusFX and the conventional methods of QA was determined. Results All analyzed treatment plans passed with a gamma passing rate >90% across all conventional QA methods, most commonly using a 3%/3mm gamma criterion except for film measurements where a 5%/3mm criterion was applied. There was good agreement and concordance between MobiusFX and conventional methods when using a 3%/3mm criteria for MobiusFX, whereas a 2%/2mm criteria appeared too stringent as it failed treatment plans deemed clinically acceptable using conventional methods. Conclusions Using a 50-sample subset of clinically delivered treatment plans this non-inferiority-type comparison shows Mobius3D/FX based on log file analysis to be a suitable alternative to conventional QA methods when utilizing the 3%/3mm gamma criterion. Methods based on log file analysis can provide an opportunity for resource sparing, improving the efficiency, and workflow for evaluating IMRT treatment plans.

A technique to generate synthetic CT from MRI for abdominal radiotherapy.

PURPOSE: To investigate a method to classify tissues types for synthetic CT generation using MRI for treatment planning in abdominal radiotherapy. METHODS: An institutional review board approved volunteer study was performed on a 3T MRI scanner. In-phase, fat and water images were acquired for five volunteers with breath-hold using an mDixon pulse sequence. A method to classify different tissue types for synthetic CT generation in the abdomen was developed. Three tissue clusters (fat, high-density tissue, and spine/air/lungs) were generated using a fuzzy-c means clustering algorithm. The third cluster was further segmented into three sub-clusters that represented spine, air, and lungs. Therefore, five segments were automatically generated. To evaluate segmentation accuracy using the method, the five segments were manually contoured on MRI images as the ground truth, and the volume ratio, Dice coefficient, and Hausdorff distance metric were calculated. The dosimetric effect of segmentation accuracy was evaluated on simulated targets close to air, lungs, and spine using a two-arc volumetric modulated arc therapy (VMAT) technique. RESULTS: The volume ratio of auto-segmentation to manual segmentation was 0.88-2.1 for the air segment and 0.72-1.13 for the remaining segments. The range of the Dice coefficient was 0.24-0.83, 0.84-0.93, 0.94-0.98, 0.93-0.96, and 0.76-0.79 for air, fat, lungs, high-density tissue, and spine, respectively. The range of the mean Hausdorff distance was 3-29.1 mm, 0.5-1.3 mm, 0.4-1 mm, 0.7-1.6 mm, and 1.2-1.4 mm for air, fat, lungs, high-density tissue, and spine, respectively. Despite worse segmentation accuracy in air and spine, the dosimetric effect was 0.2% ± 0.2%, with a maximum difference of 0.8% for all target locations. CONCLUSION: A method to generate synthetic CT in the abdomen was developed, and segmentation accuracy and its dosimetric effect were evaluated. Our results demonstrate the potential of using MRI alone for treatment planning in the abdomen.

The irregular breathing effect on target volume and coverage for lung stereotactic body radiotherapy.

The major challenge in treating a mobile target is obtaining the temporal and spatial information imaging and treatment details. This phantom study quantitatively evaluates the geometric and dosimetric effects of various treatment techniques under different respiratory patterns. The regular motion model was a sinusoidal waveform with a longitudinal range of ±1.5 cm and a period of 4 sec, while irregular motion models were generated by extracting signals from clinical cases. Helical CT for a static target and 4D CT with retrospective sorting were acquired. Phase bin, maximum, and average intensity projection (MIP and AIP) CT datasets were reconstructed. RapidArc and IMRT plans were generated on static and moving target CT datasets with different motion patterns using the phase-based gating and nongating treatment. Dose measurements were performed using EBT3 films. Dose profile and gamma analysis (±3%/1 mm criteria) were used for dose comparisons. For the irregular motions, internal target volume variations between AIP and MIP datasets (AIP/MIP) had slight differences (-6.2% to -7.7%) for gated plans, and larger differences (-12.3% to -15.2%) for nongated plans. Dosimetric measurements showed a high gamma passing rate (>98.5%) for the static plan in the target region, while the AIP and MIP gated plans had average passing rates of 92.2% ± 5.7% and 85.8% ± 9.5%, respectively. Nongated plans had significantly lower and deviated passing rates, while the AIP and MIP plans had passing rates of 43.6% ± 22.2% and 66.7% ± 28.2%, respectively (p < 0.05). Lung stereotactic body radiotherapy treatment delivered with the gated technique did not compromise the gross tumor volumes coverage, and was insensitive to the breathing irregularities and plan techniques. Adequate margins should be accounted to cover the mis-gating effect when using the phase-based gating under irregular motion.

A simple method for determining dosimetric leaf gap with cross-field dose width for rounded leaf-end multileaf collimator systems.

PURPOSE: The dosimetric leaf gap (DLG) and multileaf collimator (MLC) transmission are two important systematic parameters used to model the rounded MLC leaf ends effect when commissioning an Eclipse treatment planning system (TPS). Determining the optimal DLG is a time consuming process. This study develops a simple and reliable method for determining the DLG using the cross-field dose width. METHODS AND MATERIALS: A Varian TrueBeam linac with 6 MV, 10 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photon beams and equipped with the 120 Millennium MLC and the Eclipse™ TPS was used in this study. Integral sliding fields and static slit MLC field doses with different gap widths were measured with an ionization chamber and GAFCHROMIC EBT3 films, respectively. Measurements were performed for different beam energies and at depths of 5 and 10 cm. DLGs were derived from a linear extrapolation to zero dose and intercepting at the gap width axis. In the ion chamber measurements method, the average MLC leaf transmission to the gap reading for each gap (RgT) were calculated with nominal and cross-field dose widths, respectively. The cross-field dose widths were determined according to the dose profile measured with EBT3 films. Additionally, the optimal DLG values were determined using plan dose measurements, as the value that produced the closest agreement between the planned and measured doses. DLGs derived from the nominal and cross-field dose width, the film measurements, and the optimal process, were obtained and compared. RESULTS: The DLG values are insensitive to the variations in depth (within 0.07 mm). DLGs derived from nominal gap widths showed a significantly lower values (with difference about 0.5 mm) than that from cross-field dose widths and from film measurements and from plan optimal values. The method in deriving DLGs by correcting the nominal gap widths to the cross-field dose widths has shown good agreements to the plan optimal values (with difference within 0.21 mm). CONCLUSIONS: The DLG values derived from the cross-field dose width method were consistent with the values derived from film measurements and from the plan optimal process. A simple and reliable method to determine DLG for rounded leaf-end MLC systems was established. This method provides a referable DLG value required during TPS commissioning.

Towards abdominal MRI-based treatment planning using population-based Hounsfield units for bulk density assignment.

This study investigates the dosimetric impact of using population-based Hounsfield units (HUs) and ICRU-based HUs as a function of the number of tissue segments for bulk density assignment toward MRI-based treatment planning in the abdomen. To avoid potential geometric differences between CT and MR images, CT images rather than MR images were chosen to simulate an MRI-only planning scenario. A retrospective study was performed utilizing 18 patients that had previously undergone stereotactic body radiation therapy for liver or pancreas cancer. HU values in the CT datasets were collected for various tissue types, and compared with the HUs derived from ICRU report 46. Doses were recalculated using the fluence obtained from clinical plans and with (1) homogeneous assignment, (2) ICRU-based HU assignment and (3) population-based HU assignment using three, four, five, nine or ten tissue segments. Dose-volume metrics for targets and organs-at-risk for all scenarios were compared with those obtained using the clinical CT. For the planning target volume (PTV) D99.9%, the mean differences from clinical CT plans were -2.1% ± 3.9%, -0.6% ± 0.3% and -0.1% ± 0.3% for homogeneity, ICRU-HUs and population-HUs using ten tissue segments, respectively. The population-HU method resulted in better dosimetric accuracy compared to the ICRU-HU method (p-value < 0.05). The dosimetric accuracy of homogeneity plans was comparable to that of both ICRU-HU and population-HU plans when targets were far from the lungs but deteriorated when targets were close to the lungs. As the number of tissue segments decreased, the dosimetric accuracy for PTV D99.9% reduced for the population-HU method, from -0.1% for ten tissue segments to -0.4% for three tissue segments, while no such dependence was observed for the ICRU-HU method. Hence, to generate a clinically acceptable plan when using MRI to synthesize CT in the abdomen for treatment planning, it might be sufficient for electron density assignment with either the population-HU or ICRU-HU method to only use three tissue segments.

Mass production of C50 carotenoids by Haloferax mediterranei in using extruded rice bran and starch under optimal conductivity of brined medium.

Microbial carotenoids have potentially healthcare or medical applications. Haloferax mediterranei was difficult to economically grow into a large quantities as well as producing a valuable pigment of carotenoids. This study reports a novel investigation into the optimal conductivity on the mass production of carotenoids from H. mediterranei. The major component at about 52.4% in the extracted red pigment has been confirmed as bacterioruberin, a C50 carotenoids, by liquid chromatography separation and mass spectrometry analysis. By maintaining higher conductivity of 40 S/m in the brined medium, the cell concentration attained to 7.73 × 10(9) cells/L with low pigments concentration of 125 mg/L. When the conductivity was controlled at about 30 S/m, we obtained the highest cell concentration to 1.29 × 10(10) cells/L with pigments of 361.4 mg/L. When the conductivity was maintained at optimal 25 S/m, the pigments can be increased to maximum value of 555.6 mg/L at lower cell concentration of 9.22 × 10(9) cells/L. But conductivity below 20 S/m will cause the significant decrease in cell concentration as well as pigments due to the osmotic stress around the cells. Red pigment of carotenoids from an extremely halophilic archaebacterium could be efficiently produced to a high concentration by applying optimal conductivity control in the brined medium with extruded low-cost rice bran and corn starch.

Quantitative characterizations of ultrashort echo (UTE) images for supporting air-bone separation in the head.

Accurate separation of air and bone is critical for creating synthetic CT from MRI to support Radiation Oncology workflow. This study compares two different ultrashort echo-time sequences in the separation of air from bone, and evaluates post-processing methods that correct intensity nonuniformity of images and account for intensity gradients at tissue boundaries to improve this discriminatory power. CT and MRI scans were acquired on 12 patients under an institution review board-approved prospective protocol. The two MRI sequences tested were ultra-short TE imaging using 3D radial acquisition (UTE), and using pointwise encoding time reduction with radial acquisition (PETRA). Gradient nonlinearity correction was applied to both MR image volumes after acquisition. MRI intensity nonuniformity was corrected by vendor-provided normalization methods, and then further corrected using the N4itk algorithm. To overcome the intensity-gradient at air-tissue boundaries, spatial dilations, from 0 to 4 mm, were applied to threshold-defined air regions from MR images. Receiver operating characteristic (ROC) analyses, by comparing predicted (defined by MR images) versus 'true' regions of air and bone (defined by CT images), were performed with and without residual bias field correction and local spatial expansion. The post-processing corrections increased the areas under the ROC curves (AUC) from 0.944 ± 0.012 to 0.976 ± 0.003 for UTE images, and from 0.850 ± 0.022 to 0.887 ± 0.012 for PETRA images, compared to without corrections. When expanding the threshold-defined air volumes, as expected, sensitivity of air identification decreased with an increase in specificity of bone discrimination, but in a non-linear fashion. A 1 mm air mask expansion yielded AUC increases of 1 and 4% for UTE and PETRA images, respectively. UTE images had significantly greater discriminatory power in separating air from bone than PETRA images. Post-processing strategies improved the discriminatory power of air from bone for both UTE and PETRA images, and reduced the difference between the two imaging sequences. Both post-processed UTE and PETRA images demonstrated sufficient power to discriminate air from bone to support synthetic CT generation from MRI data.

Investigation of a method for generating synthetic CT models from MRI scans of the head and neck for radiation therapy.

Magnetic resonance (MR) images often provide superior anatomic and functional information over computed tomography (CT) images, but generally are not used alone without CT images for radiotherapy treatment planning and image guidance. This study aims to investigate the potential of probabilistic classification of voxels from multiple MRI contrasts to generate synthetic CT ('MRCT') images. The method consists of (1) acquiring multiple MRI volumes: T1-weighted, T2-weighted, two echoes from a ultra-short echo time (UTE) sequence, and calculated fat and water image volumes using a Dixon method, (2) classifying tissues using fuzzy c-means clustering with a spatial constraint, (3) assigning attenuation properties with weights based on the probability of individual tissue classes being present in each voxel, and (4) generating a MRCT image volume from the sum of attenuation properties in each voxel. The capability of each MRI contrast to differentiate tissues of interest was investigated based on a retrospective analysis of ten patients. For one prospective patient, the correlation of skull intensities between CT and MR was investigated, the discriminatory power of MRI in separating air from bone was evaluated, and the generated MRCT image volume was qualitatively evaluated. Our analyses showed that one MRI volume was not sufficient to separate all tissue types, and T2-weighted images was more sensitive to bone density variation compared to other MRI image types. The short echo UTE image showed significant improvement in contrasting air versus bone, but could not completely separate air from bone without false labeling. Generated MRCT and CT images showed similar contrast between bone and soft/solid tissues. These results demonstrate the potential of the presented method to generate synthetic CT images to support the workflow of radiation oncology treatment planning and image guidance.

Formulation design and evaluation of quantum dot-loaded nanostructured lipid carriers for integrating bioimaging and anticancer therapy.

AIM: The authors studied the bioimaging and delivery of drug-entrapped, nanostructured lipid carriers with quantum dots (QDs), called QDNLCs, for integrating imaging and therapy. MATERIALS & METHODS: Nanostructured lipid carriers consisting of QDs, including lipophilic QDs, carboxyl-function QDs or PEG QDs were prepared. Application of the nanocarriers was evaluated by cytotoxicity, cell migration, cellular uptake, in vivo real-time tumor monitoring and drug accumulation in tumors. RESULTS: All QDNLCs exhibited a size of 245 nm with camptothecin encapsulation of >99%. Cytotoxicity of the nanoparticles against melanoma cells was superior to that of free camptothecin. Carboxylic acid-conjugated QDNLCs (C-QDNLCs) showed the highest cell internalization and in vivo fluorescence labeling compared with the other carriers. Real-time bioimaging demonstrated that C-QDNLCs maintained signaling in tumors for at least 24 h. The camptothecin accumulation in melanomas increased by 6.4-fold after incorporation into C-QDNLCs. CONCLUSION: For the first time, nanostructured lipid carriers were coordinated with QDs and an anticancer drug to provide efficient tumor imaging and drug delivery. Original submitted 1 May 2012; Revised submitted 30 August 2012; Published online 5 February 2013.

Contralateral breast dose after whole-breast irradiation: an analysis by treatment technique.

PURPOSE: To investigate the contralateral breast dose (CBD) across a continuum of breast-conservation therapy techniques. METHODS AND MATERIALS: An anthropomorphic phantom was CT-simulated, and six treatment plans were generated: open tangents, tangents with an external wedge on the lateral beam, tangents with lateral and medial external wedges, a simple segment plan (three segments per tangent), a complex segmental intensity-modulated radiotherapy (IMRT) plan (five segments per tangent), and a beamlet IMRT plan (>100 segments). For all techniques, the breast on the phantom was irradiated to 5000 cGy. Contralateral breast dose was measured at a uniform depth at the center and each quadrant using thermoluminescent detectors. RESULTS: Contralateral breast dose varied with position and was 50 ± 7.3 cGy in the inner half, 24 ± 4.1 cGy at the center, and 16 ± 2.2 cGy in the outer half for the open tangential plan. Compared with an average dose of 31 cGy across all points for the open field, the average doses were simple segment 32 cGy (range, 99-105% compared with open technique), complex segment 34 cGy (range, 103-117% compared with open technique), beamlet IMRT 34 cGy (range, 103-124% compared with open technique), lateral wedge only 46 cGy (range, 133-175% compared with open technique), and medial and lateral wedge 96 cGy (range, 282-370% compared with open technique). CONCLUSIONS: Single or dual wedge techniques resulted in the highest CBD increases compared with open tangents. To obtain the desired homogeneity to the treated breast while minimizing CBD, segmental and IMRT techniques should be encouraged over external physical compensators.

Analysis of variation in calibration curves for Kodak XV radiographic film using model-based parameters.

Film calibration is time-consuming work when dose accuracy is essential while working in a range of photon scatter environments. This study uses the single-target single-hit model of film response to fit the calibration curves as a function of calibration method, processor condition, field size and depth. Kodak XV film was irradiated perpendicular to the beam axis in a solid water phantom. Standard calibration films (one dose point per film) were irradiated at 90 cm source-to-surface distance (SSD) for various doses (16-128 cGy), depths (0.2, 0.5, 1.5, 5, 10 cm) and field sizes (5 × 5, 10 × 10 and 20 × 20 cm²). The 8-field calibration method (eight dose points per film) was used as a reference for each experiment, taken at 95 cm SSD and 5 cm depth. The delivered doses were measured using an Attix parallel plate chamber for improved accuracy of dose estimation in the buildup region. Three fitting methods with one to three dose points per calibration curve were investigated for the field sizes of 5 × 5, 10 × 10 and 20 × 20 cm². The inter-day variation of model parameters (background, saturation and slope) were 1.8%, 5.7%, and 7.7% (1 σ) using the 8-field method. The saturation parameter ratio of standard to 8-field curves was 1.083 ± 0.005. The slope parameter ratio of standard to 8-field curves ranged from 0.99 to 1.05, depending on field size and depth. The slope parameter ratio decreases with increasing depth below 0.5 cm for the three field sizes. It increases with increasing depths above 0.5 cm. A calibration curve with one to three dose points fitted with the model is possible with 2% accuracy in film dosimetry for various irradiation conditions. The proposed fitting methods may reduce workload while providing energy dependence correction in radiographic film dosimetry. This study is limited to radiographic XV film with a Lumisys scanner.

Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug.

Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

Dose discrepancies in the buildup region and their impact on dose calculations for IMRT fields.

PURPOSE: Dose accuracy in the buildup region for radiotherapy treatment planning suffers from challenges in both measurement and calculation. This study investigates the dosimetry in the buildup region at normal and oblique incidences for open and IMRT fields and assesses the quality of the treatment planning calculations. METHODS: This study was divided into three parts. First, percent depth doses and profiles (for 5 x 5, 10 x 10, 20 x 20, and 30 x 30 cm2 field sizes at 0 degrees, 45 degrees, and 70 degrees incidences) were measured in the buildup region in Solid Water using an Attix parallel plate chamber and Kodak XV film, respectively. Second, the parameters in the empirical contamination (EC) term of the convolution/ superposition (CVSP) calculation algorithm were fitted based on open field measurements. Finally, seven segmental head-and-neck IMRT fields were measured on a flat phantom geometry and compared to calculations using gamma and dose-gradient compensation (C) indices to evaluate the impact of residual discrepancies and to assess the adequacy of the contamination term for IMRT fields. RESULTS: Local deviations between measurements and calculations for open fields were within 1% and 4% in the buildup region for normal and oblique incidences, respectively. The C index with 5%/1 mm criteria for IMRT fields ranged from 89% to 99% and from 96% to 98% at 2 mm and 10 cm depths, respectively. The quality of agreement in the buildup region for open and IMRT fields is comparable to that in nonbuildup regions. CONCLUSIONS: The added EC term in CVSP was determined to be adequate for both open and IMRT fields. Due to the dependence of calculation accuracy on (1) EC modeling, (2) internal convolution and density grid sizes, (3) implementation details in the algorithm, and (4) the accuracy of measurements used for treatment planning system commissioning, the authors recommend an evaluation of the accuracy of near-surface dose calculations as a part of treatment planning commissioning.

Physicochemical characterization and drug release of thermosensitive hydrogels composed of a hyaluronic acid/pluronic f127 graft.

Pluronic F127 (PF127) is a copolymer which forms thermosensitive hydrogels. Hyaluronic acid (HA) was grafted to PF127 to form a new hydrogel matrix (HP) for delivery of cisplatin and carboplatin. The physicochemical properties and drug delivery of the graft were examined in this study. HP system (20% HP copolymer in water) exhibited a similar sol-gel transition temperature (28.3 degrees C) as PF127 system (20% PF127 copolymer in water) but with a shorter gelling process. A stronger structure was obtained by HP system according to scanning electron microscopic (SEM) images and viscosity kinetics. In vitro release test showed the sustained-release characteristics of hydrogels entrapped with cisplatin and carboplatin. The drug release rate from HP hydrogel was slower than that from PF127 hydrogel. The reduction of drug release by HP system as compared to the control solution was more significant for cisplatin than for carboplatin. Such a thermosensitive hydrogel may be advantageous as an injectable therapeutic formulation for anticancer treatment.