Inter-observer variability in library plan selection on iterative CBCT and synthetic CT images of cervical cancer patients.

INTRODUCTION: In the Library-of-Plans (LoP) approach, correct plan selection is essential for delivering radiotherapy treatment accurately. However, poor image quality of the cone-beam computed tomography (CBCT) may introduce inter-observer variability and thereby hamper accurate plan selection. In this study, we investigated whether new techniques to improve the CBCT image quality and improve consistency in plan selection, affects the accuracy of LoP selection in cervical cancer patients. MATERIALS AND METHODS: CBCT images of 12 patients were used to investigate the inter-observer variability of plan selection based on different CBCT image types. Six observers were asked to individually select a plan based on clinical X-ray Volumetric Imaging (XVI) CBCT, iterative reconstructed CBCT (iCBCT) and synthetic CTs (sCT). Selections were performed before and after a consensus meeting with the entire group, in which guidelines were created. A scoring by all observers on the image quality and plan selection procedure was also included. For plan selection, Fleiss' kappa (κ) statistical test was used to determine the inter-observer variability within one image type. RESULTS: The agreement between observers was significantly higher on sCT compared to CBCT. The consensus meeting improved the duration and inter-observer variability. In this manuscript, the guidelines attributed the overall results in the plan selection. Before the meeting, the gold standard was selected in 76% of the cases on XVI CBCT, 74% on iCBCT, and 76% on sCT. After the meeting, the gold standard was selected in 83% of the cases on XVI CBCT, 81% on iCBCT, and 90% on sCT. CONCLUSION: The use of sCTs can increase the agreement of plan selection among observers and the gold standard was indicated to be selected more often. It is important that clear guidelines for plan selection are implemented in order to benefit from the increased image quality, accurate selection, and decrease inter-observer variability.

Anatomical evaluation of deep-learning synthetic computed tomography images generated from male pelvis cone-beam computed tomography.

Background and purpose: To improve cone-beam computed tomography (CBCT), deep-learning (DL)-models are being explored to generate synthetic CTs (sCT). The sCT evaluation is mainly focused on image quality and CT number accuracy. However, correct representation of daily anatomy of the CBCT is also important for sCTs in adaptive radiotherapy. The aim of this study was to emphasize the importance of anatomical correctness by quantitatively assessing sCT scans generated from CBCT scans using different paired and unpaired dl-models. Materials and methods: Planning CTs (pCT) and CBCTs of 56 prostate cancer patients were included to generate sCTs. Three different dl-models, Dual-UNet, Single-UNet and Cycle-consistent Generative Adversarial Network (CycleGAN), were evaluated on image quality and anatomical correctness. The image quality was assessed using image metrics, such as Mean Absolute Error (MAE). The anatomical correctness between sCT and CBCT was quantified using organs-at-risk volumes and average surface distances (ASD). Results: MAE was 24 Hounsfield Unit (HU) [range:19-30 HU] for Dual-UNet, 40 HU [range:34-56 HU] for Single-UNet and 41HU [range:37-46 HU] for CycleGAN. Bladder ASD was 4.5 mm [range:1.6-12.3 mm] for Dual-UNet, 0.7 mm [range:0.4-1.2 mm] for Single-UNet and 0.9 mm [range:0.4-1.1 mm] CycleGAN. Conclusions: Although Dual-UNet performed best in standard image quality measures, such as MAE, the contour based anatomical feature comparison with the CBCT showed that Dual-UNet performed worst on anatomical comparison. This emphasizes the importance of adding anatomy based evaluation of sCTs generated by dl-models. For applications in the pelvic area, direct anatomical comparison with the CBCT may provide a useful method to assess the clinical applicability of dl-based sCT generation methods.

Influence of daily setup measurements and corrections on the estimated delivered dose during IMRT treatment of prostate cancer patients.

PURPOSE: To evaluate the impact of marker-based position verification, using daily imaging and an off-line correction protocol, by calculating the delivered dose to prostate, rectum and bladder. METHODS: Prostate cancer patients (n=217) were treated with IMRT, receiving 35 daily fractions. Plans with five beams were optimized taking target coverage (CTV, boost) and organs-at-risk (rectum and bladder) into account. PTV margins were 8mm. Prostate position was verified daily using implanted fiducial gold markers by imaging the first segment of all the five beams on an EPID. Setup deviations were corrected off-line using an adapted shrinking-action-level protocol. The estimated delivered dose, including daily organ movements, was calculated using a version of PLATO's dose engine, enabling batch processing of large numbers of patients. The dose was calculated +/- inclusion of setup corrections, and was evaluated relative to the original static plan. The marker-based measurements were considered representative for all organs. RESULTS: Daily organ movements would result in an underdosage of 2-3Gy to CTV and boost volume relative to the original plan, which was prevented by daily setup corrections. The dose to rectum and bladder was on average unchanged, but a large spread was introduced by organ movements, which was reduced by including setup corrections. CONCLUSIONS: Without position verification and setup corrections, margins of 8mm would be insufficient to account for position uncertainties during IMRT of prostate cancer. With the daily off-line correction protocol, the remaining variations are accommodated adequately.

Charge modification of the endothelial surface layer modulates the permeability barrier of isolated rat mesenteric small arteries.

We hypothesized that modulation of the effective charge density of the endothelial surface layer (ESL) results in altered arterial barrier properties to transport of anionic solutes. Rat mesenteric small arteries (diameter approximately 190 microm) were isolated, cannulated, perfused, and superfused with MOPS-buffered physiological salt solutions. MOPS-solutions were of normal ionic strength (162 mM, MOPS), low ionic strength (81 mM, LO-MOPS), or high ionic strength (323 mM, HI-MOPS), to modulate ESL charge density (normal, high, or low ESL charge, respectively). Osmolarity of MOPS, LO-MOPS, and HI-MOPS was kept constant at 297 mosmol/l, using additional glucose when necessary. Perfusate solutions were supplemented with 1% BSA. Arteries were cannulated with a double-barreled theta-pipet on the inlet side and a regular pipet on the outlet side. After infusion of FITC-labeled dextran of 50 kDa (FITC-Delta50) and the endothelial membrane dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate, the dynamics of arterial dye filling were determined with confocal microscopy. ESL thickness, as determined from the initial exclusion zone for FITC-Delta50 on the luminal endothelial surface, was 6.3 +/- 1.4 microm for LO-MOPS, 2.7 +/- 1.0 microm for MOPS, and 1.1 +/- 1.3 microm for HI-MOPS. At low ionic strength, FITC-Delta50 permeated into the ESL with a total ESL permeation time (tauESL) of 26 min, and at normal ionic strength with a tauESL of 20 min. No apparent exclusion of FITC-Delta50 from the ESL could be observed at high ionic strength. In conclusion, we demonstrate that the modulation of solvent ionic strength influences the thickness and barrier properties of the ESL.

Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy.

Endothelial cells are covered by a surface layer of membrane-associated proteoglycans, glycosaminoglycans, glycoproteins, glycolipids, and associated plasma proteins. This layer may limit transendothelial solute transport. We determined dimension and transport properties of this endothelial surface layer (ESL) in isolated arteries. Rat mesenteric small arteries (diameter approximately 150 microm) were isolated and cannulated with a double-barreled -pipette on the inlet side and a regular pipette on the outlet side. Dynamics and localization of intra-arterial fluorescence by FITC-labeled dextrans (FITC-Deltas) and the endothelial membrane dye DiI were determined with confocal microscopy. Large FITC-Delta (148 kDa) filled a core volume inside the arteries within 1 min but was excluded from a 2.6 +/- 0.5-microm-wide region on the luminal side of the endothelium during 30 min of dye perfusion. Medium FITC-Delta (50.7 kDa) slowly penetrated this ESL within 30 min but did not permeate into the arterial wall. Small FITC-Delta (4.4 kDa) quickly passed the ESL and accumulated in the arterial wall. Prolonged luminal fluorochrome illumination with a bright mercury lamp destroyed the approximately 3-microm exclusion zone for FITC-Delta 148 within a few minutes. This study demonstrates the presence of a thick ESL that contributes to the permeability barrier to solutes. The layer is sensitive to phototoxic stress, and its damage could form an early event in atherosclerosis.