Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control. A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. All calculations and measurements are normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions. Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an overestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.

Towards improvement of autonomous glider navigation accuracy through the use of regional ocean models

Autonomous underwater gliders are robust and widely-used ocean sampling platforms that are characterized by their endurance, and are one of the best approaches to gather subsurface data at the appropriate spatial resolution to advance our knowledge of the ocean environment. Gliders generally do not employ sophisticated sensors for underwater localization, but instead dead-reckon between set waypoints. Thus, these vehicles are subject to large positional errors between prescribed and actual surfacing locations. Here, we investigate the implementation of a large-scale, regional ocean model into the trajectory design for autonomous gliders to improve their navigational accuracy. We compute the dead-reckoning error for our Slocum gliders, and compare this to the average positional error recorded from multiple deployments conducted over the past year. We then compare trajectory plans computed on-board the vehicle during recent deployments to our prediction-based trajectory plans for 140 surfacing occurrences.

Improving accuracy and intelligibility of decisions

Intelligible and accurate risk-based decision-making requires a complex balance of information from different sources, appropriate statistical analysis of this information and consequent intelligent inference and decisions made on the basis of these analyses. Importantly, this requires an explicit acknowledgement of uncertainty in the inputs and outputs of the statistical model. The aim of this paper is to progress a discussion of these issues in the context of several motivating problems related to the wider scope of agricultural production. These problems include biosecurity surveillance design, pest incursion, environmental monitoring and import risk assessment. The information to be integrated includes observational and experimental data, remotely sensed data and expert information. We describe our efforts in addressing these problems using Bayesian models and Bayesian networks. These approaches provide a coherent and transparent framework for modelling complex systems, combining the different information sources, and allowing for uncertainty in inputs and outputs. While the theory underlying Bayesian modelling has a long and well established history, its application is only now becoming more possible for complex problems, due to increased availability of methodological and computational tools. Of course, there are still hurdles and constraints, which we also address through sharing our endeavours and experiences.

Early osteogenic response of osteoprogenitor cells on modified titanium implant surfaces leads to improved osteogenesis

Background: Implant surface micro-roughness and hydrophilicity are known to improve the osteogenic differentiation potential of osteoprogenitor cells. This study was aimed to determine whether topographically and chemically modified titanium implant surfaces stimulate an initial osteogenic response in osteoprogenitor cells, which leads to their improved osteogenesis. ----- ----- Methods: Statistical analysis of microarray gene expression profiling data available from studies (at 72 hours) on sand-blasted, large grit acid etched (SLA) titanium surfaces was performed. Subsequently, human osteoprogenitor cells were cultured on SLActive (hydrophilic SLA), SLA and polished titanium surfaces for 24 hours, 3 days and 7 days. The expression of BMP2, BMP6, BMP2K, SP1, ACVR1, FZD6, WNT5A, PDLIM7, ITGB1, ITGA2, OCN, OPN, ALP and RUNX2 were studied using qPCR. ----- ----- Results: Several functional clusters related to osteogenesis were highlighted when genes showing statistically significant differences (from microarray data at 72 hours) in expression on SLA surface (compared with control surface) were analysed using DAVID (online tool). This indicates that differentiation begins very early in response to modified titanium surfaces. At 24 hours, ACVR1 (BMP pathway), FZD6 (Wnt pathway) and SP1 (TGF-β pathway) were significantly up-regulated in cultures on the SLActive surface compared to the other surfaces. WNT5A and ITGB1 also showed higher expression on the modified surfaces. Gene expression patterns on Day 3 and Day 7 did not reveal any significant differences.----- ----- Conclusion: These results suggest that the initial molecular response of osteoprogenitor cells to modified titanium surfaces may be responsible for an improved osteogenic response via the BMP and Wnt signalling pathways.

Quantification of the accuracy of MRI generated 3D models of long bones compared to CT generated 3D models

Orthopaedic fracture fixation implants are increasingly being designed using accurate 3D models of long bones based on computer tomography (CT). Unlike CT, magnetic resonance imaging (MRI) does not involve ionising radiation and is therefore a desirable alternative to CT. This study aims to quantify the accuracy of MRI-based 3D models compared to CT-based 3D models of long bones. The femora of five intact cadaver ovine limbs were scanned using a 1.5T MRI and a CT scanner. Image segmentation of CT and MRI data was performed using a multi-threshold segmentation method. Reference models were generated by digitising the bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and CT-derived models were validated against the reference models. The results demonstrated that the CT-based models contained an average error of 0.15mm while the MRI-based models contained an average error of 0.23mm. Statistical validation shows that there are no significant differences between 3D models based on CT and MRI data. These results indicate that the geometric accuracy of MRI based 3D models was comparable to that of CT-based models and therefore MRI is a potential alternative to CT for generation of 3D models with high geometric accuracy.

The reliability, accuracy and minimal detectable difference of a multi-segment kinematic model of the foot-shoe complex

Kinematic models are commonly used to quantify foot and ankle kinematics, yet no marker sets or models have been proven reliable or accurate when wearing shoes. Further, the minimal detectable difference of a developed model is often not reported. We present a kinematic model that is reliable, accurate and sensitive to describe the kinematics of the foot–shoe complex and lower leg during walking gait. In order to achieve this, a new marker set was established, consisting of 25 markers applied on the shoe and skin surface, which informed a four segment kinematic model of the foot–shoe complex and lower leg. Three independent experiments were conducted to determine the reliability, accuracy and minimal detectable difference of the marker set and model. Inter-rater reliability of marker placement on the shoe was proven to be good to excellent (ICC = 0.75–0.98) indicating that markers could be applied reliably between raters. Intra-rater reliability was better for the experienced rater (ICC = 0.68–0.99) than the inexperienced rater (ICC = 0.38–0.97). The accuracy of marker placement along each axis was <6.7 mm for all markers studied. Minimal detectable difference (MDD90) thresholds were defined for each joint; tibiocalcaneal joint – MDD90 = 2.17–9.36°, tarsometatarsal joint – MDD90 = 1.03–9.29° and the metatarsophalangeal joint – MDD90 = 1.75–9.12°. These thresholds proposed are specific for the description of shod motion, and can be used in future research designed at comparing between different footwear.

Next generation low-cost motion capture systems can provide comparable spatial accuracy to high-end systems

The objective quantification of three-dimensional kinematics during different functional and occupational tasks is now more in demand than ever. The introduction of new generation of low-cost passive motion capture systems from a number of manufacturers has made this technology accessible for teaching, clinical practice and in small/medium industry. Despite the attractive nature of these systems, their accuracy remains unproved in independent tests. We assessed static linear accuracy, dynamic linear accuracy and compared gait kinematics from a Vicon MX20 system to a Natural Point OptiTrack system. In all experiments data were sampled simultaneously. We identified both systems perform excellently in linear accuracy tests with absolute errors not exceeding 1%. In gait data there was again strong agreement between the two systems in sagittal and coronal plane kinematics. Transverse plane kinematics differed by up to 3 at the knee and hip, which we attributed to the impact of soft tissue artifact accelerations on the data. We suggest that low-cost systems are comparably accurate to their high-end competitors and offer a platform with accuracy acceptable in research for laboratories with a limited budget.