Waiting in Pain II: An Updated Review of the Provision of Persistent Pain Services in Australia.

OBJECTIVE: To provide an update on Australian persistent pain services (number, structure, funding, wait times, activity). METHODS: An updated national search was conducted. Of those identified, 74 persistent pain services provided detailed responses between July 2016 and February 2018 (64 adult, seven pediatric, two pelvic pain, and one cancer pain). A similar structure to the original Waiting in Pain (WIP) survey was used, and participants chose online or telephone completion. RESULTS: Pediatric pain services had more than doubled but remained limited. Adult services had also increased, with a concurrent decrease in median wait times and an increase in the number of new referrals seen each year. Despite this, some lengthy wait times (≥3 years) persisted. Wait times were longest at clinics using public or combined funding models and offering pain management group programs (PMGPs). Although clinical activity had increased, medical staffing had not, suggesting that clinics were operating differently. Privately funded clinics performed more procedures than publicly funded services. Use of PMGPs had increased, but program structure remained diverse. CONCLUSIONS: Specialist pain services have expanded since the original WIP survey, facilitating treatment access for many. However, wait time range suggested that the most disadvantaged individuals still experienced the longest wait times, often far exceeding the recommended 6-month maximum wait. More needs to be done. Numerous developments (e.g., National Strategic Action Plan for Pain Management, health system changes as a result of the COVID-19 pandemic) will continue to influence the delivery of pain services in Australia, and repeated analysis of service structures and wait times will optimize our health system response to the management of this condition.

Rapid Fabrication of Custom Microfluidic Devices for Research and Educational Applications.

Microfluidic devices allow for the manipulation of fluids, particles, cells, micro-sized organs or organisms in channels ranging from the nano to submillimeter scales. A rapid increase in the use of this technology in the biological sciences has prompted a need for methods that are accessible to a wide range of research groups. Current fabrication standards, such as PDMS bonding, require expensive and time consuming lithographic and bonding techniques. A viable alternative is the use of equipment and materials that are easily affordable, require minimal expertise and allow for the rapid iteration of designs. In this work we describe a protocol for designing and producing PET-laminates (PETLs), microfluidic devices that are inexpensive, easy to fabricate, and consume significantly less time to generate than other approaches to microfluidics technology. They consist of thermally bonded film sheets, in which channels and other features are defined using a craft cutter. PETLs solve field-specific technical challenges while dramatically reducing obstacles to adoption. This approach facilitates the accessibility of microfluidics devices in both research and educational settings, providing a reliable platform for new methods of inquiry.

A 3D printed modular phantom for quality assurance of image-guided small animal irradiators: Design, imaging experiments, and Monte Carlo simulations.

PURPOSE: The goal of this work was to develop and test a cylindrical tissue-equivalent quality assurance (QA) phantom for micro computed tomography (microCT) image-guided small animal irradiators that overcomes deficiencies of existing phantoms due to its mouse-like dimensions and composition. METHODS: The 8.6-cm-long and 2.4-cm-diameter phantom was three-dimensionally (3D) printed out of Somos NeXt plastic on a stereolithography (SLA) printer. The modular phantom consisted of four sections: (a) CT number evaluation section, (b) spatial resolution with slanted edge (for the assessment of longitudinal resolution) and targeting section, (c) spatial resolution with hole pattern (for the assessment of radial direction) section, and (d) uniformity and geometry section. A Python-based graphical user interface (GUI) was developed for automated analysis of microCT images and evaluated CT number consistency, longitudinal and radial modulation transfer function (MTF), image uniformity, noise, and geometric accuracy. The phantom was placed at the imaging isocenter and scanned with the small animal radiation research platform (SARRP) in the pancake geometry (long axis of the phantom perpendicular to the axis of rotation) with a variety of imaging protocols. Tube voltage was set to 60 and 70 kV, tube current was set to 0.5 and 1.2 mA, voxel size was set to 200 and 275 µm, imaging times of 1, 2, and 4 min were used, and frame rates of 6 and 12 frames per second (fps) were used. The phantom was also scanned in the standard (long axis of the phantom parallel to the axis of rotation) orientation. The quality of microCT images was analyzed and compared to recommendations presented in our previous work that was derived from a multi-institutional study. Additionally, a targeting accuracy test with a film placed in the phantom was performed. MicroCT imaging of the phantom was also simulated in a modified version of the EGSnrc/DOSXYZnrc code. Images of the resolution section with the hole pattern were acquired experimentally as well as simulated in both the pancake and the standard imaging geometries. The radial spatial resolution of the experimental and simulated images was evaluated and compared to experimental data. RESULTS: For the centered phantom images acquired in the pancake geometry, all imaging protocols passed the spatial resolution criterion in the radial direction (>1.5 lp/mm @ 0.2 MTF), the geometric accuracy criterion (<200 µm), and the noise criterion (<55 HU). Only the imaging protocol with 200-µm voxel size passed the criterion for spatial resolution in the longitudinal direction (>1.5 lp/mm @ 0.2 MTF). The 70-kV tube voltage dataset failed the bone CT number consistency test (<55 HU). Due to cupping artifacts, none of the imaging protocols passed the uniformity test of <55 HU. When the phantom was scanned in the standard imaging geometry, image uniformity and longitudinal MTF were satisfactory; however, the CT number consistency failed the recommended limit. A targeting accuracy of 282 and 251 µm along the x- and z-direction was observed. Monte Carlo simulations confirmed that the radial spatial resolution for images acquired in the pancake geometry was higher than the one acquired in the standard geometry. CONCLUSIONS: The new 3D-printed phantom presents a useful tool for microCT image analysis as it closely mimics a mouse. In order to image mouse-sized animals with acceptable image quality, the standard protocol with a 200-µm voxel size should be chosen and cupping artifacts need to be resolved.

The Role of Oxygen in Avascular Tumor Growth.

The oxygen status of a tumor has significant clinical implications for treatment prognosis, with well-oxygenated subvolumes responding markedly better to radiotherapy than poorly supplied regions. Oxygen is essential for tumor growth, yet estimation of local oxygen distribution can be difficult to ascertain in situ, due to chaotic patterns of vasculature. It is possible to avoid this confounding influence by using avascular tumor models, such as tumor spheroids, a much better approximation of realistic tumor dynamics than monolayers, where oxygen supply can be described by diffusion alone. Similar to in situ tumours, spheroids exhibit an approximately sigmoidal growth curve, often approximated and fitted by logistic and Gompertzian sigmoid functions. These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation. This work examines the oxygen dynamics of spheroids and demonstrates that this growth can be derived mechanistically with cellular doubling time and oxygen consumption rate (OCR) being key parameters. The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement. Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.

Feasibility testing of a pre-clinical coded aperture phase contrast imaging configuration using a simple fast Monte Carlo simulator.

A simple method of simulating possible coded aperture phase contrast X-ray imaging apparatus is presented. The method is based on ray tracing, with the rays treated ballistically within a voxelized sample and with the phase-shift-induced angular deviations and absorptions applied at a plane in the middle of the sample. For the particular case of a coded aperture phase contrast configuration suitable for small animal pre-clinical imaging we present results obtained using a high resolution voxel array representation of a mathematically-defined 'digital' mouse. At the end of the article a link to the software is supplied.

A novel respiratory motion compensation strategy combining gated beam delivery and mean target position concept --a compromise between small safety margins and long duty cycles.

PURPOSE: To evaluate a novel respiratory motion compensation strategy combining gated beam delivery with the mean target position (MTP) concept for pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Four motion compensation strategies were compared for 10 targets with motion amplitudes between 6mm and 31mm: the internal target volume concept (plan(ITV)); the MTP concept where safety margins were adapted based on 4D dose accumulation (plan(MTP)); gated beam delivery without margins for motion compensation (plan(gated)); a novel approach combining gating and the MTP concept (plan(gated&MTP)). RESULTS: For 5/10 targets with an average motion amplitude of 9mm, the differences in the mean lung dose (MLD) between plan(gated) and plan(MTP) were <10%. For the other 5/10 targets with an average motion amplitude of 19mm, gating with duty cycles between 87.5% and 75% reduced the residual target motion to 12mm on average and 2mm safety margins were sufficient for dosimetric compensation of this residual motion in plan(gated&MTP). Despite significantly shorter duty cycles, plan(gated) reduced the MLD by <10% compared to plan(gated&MTP). The MLD was increased by 18% in plan(MTP) compared to that of plan(gated&MTP). CONCLUSIONS: For pulmonary targets with motion amplitudes >10-15mm, the combination of gating and the MTP concept allowed small safety margins with simultaneous long duty cycles.

Multiple breath-hold CBCT for online image guided radiotherapy of lung tumors: simulation with a dynamic phantom and first patient data.

BACKGROUND AND PURPOSE: Computer controlled breath-hold effectively reduces organ motion for image-guided precision radiotherapy of lung tumors. However, the acquisition time of 3D cone-beam-CT (CBCT) exceeds maximum breath-hold times. We have developed an approach enabling online verification using CBCT image acquisition with ABC®-based breath-hold. METHODS: Patient CBCT images were acquired with ABC®-based repeat breath-hold. The clinical situation was also simulated with a Motion Phantom. Reconstruction of patient and phantom images with selection of free-breathing and breath-hold projections only was performed. RESULTS: CBCT-imaging in repeat breath-hold resulted in a precisely spherical appearance of a tumor-mimicking structure in the phantom. A faint "ghost" structure (free-breathing phases) can be clearly discriminated. Mean percentage of patient breath-hold time was 66%. Reconstruction based on free-breathing-only shows blurring of both tumor and diaphragm, reconstruction based on breath-hold projections only resulted in sharp contours of the same structures. From the phantom experiments, a maximal repositioning error of 1mm in each direction can be estimated. DISCUSSION AND CONCLUSION: CBCT during repetitive breath hold provides reliable soft-tissue-based positioning. Fast 3D-imaging during one breath-hold is currently under development and has the potential to accelerate clinical linac-based volume imaging.

Feasibility of the use of the Active Breathing Co ordinator (ABC) in patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC).

INTRODUCTION: One method to overcome the problem of lung tumour movement in patients treated with radiotherapy is to restrict tumour motion with an active breathing control (ABC) device. This study evaluated the feasibility of using ABC in patients receiving radical radiotherapy for non-small cell lung cancer. METHODS: Eighteen patients, median (range) age of 66 (44-82) years, consented to the study. A training session was conducted to establish the patient's breath hold level and breath hold time. Three planning scans were acquired using the ABC device. Reproducibility of breath hold was assessed by comparing lung volumes measured from the planning scans and the volume recorded by ABC. Patients were treated with a 3-field coplanar beam arrangement and treatment time (patient on and off the bed) and number of breath holds recorded. The tolerability of the device was assessed by weekly questionnaire. Quality assurance was performed on the two ABC devices used. RESULTS: 17/18 patients completed 32 fractions of radiotherapy using ABC. All patients tolerated a maximum breath hold time >15s. The mean (SD) patient training time was 13.8 (4.8)min and no patient found the ABC very uncomfortable. Six to thirteen breath holds of 10-14 s were required per session. The mean treatment time was 15.8 min (5.8 min). The breath hold volumes were reproducible during treatment and also between the two ABC devices. CONCLUSION: The use of ABC in patients receiving radical radiotherapy for NSCLC is feasible. It was not possible to predict a patient's ability to hold breath. A minimum tolerated breath hold time of 15 s is recommended prior to commencing treatment.

Obtaining breathing patterns from any sequential thoracic x-ray image set.

A technique is presented to allow a breathing pattern to be obtained from any multi-slice CT, cone-beam or other series of sequential chest x-ray image sets. The technique requires no extra signals to be recorded and does not need specific external or internal oscillating structures to be visible in the field of view. The breathing pattern is instead acquired from analysing the variation in pixel values between projection images. For cone-beam image sets, slowly varying changes, due to an angular attenuation dependence, must be corrected before the breathing trace analysis can begin. All the results of the new technique were checked visually and were in good agreement. If the studied image set could be analysed using the existing 'Amsterdam shroud' technique, then the results it provided were also used for comparison. In cases that allowed comparison by both techniques, the results were in agreement. The new technique was also shown to provide a usable signal when applied to cardiac motion.

Evidence for strong Breit interaction in dielectronic recombination of highly charged heavy ions.

Resonant strengths have been measured for dielectronic recombination of Li-like iodine, holmium, and bismuth using an electron beam ion trap. By observing the atomic number dependence of the state-resolved resonant strength, clear experimental evidence has been obtained that the importance of the generalized Breit interaction (GBI) effect on dielectronic recombination increases as the atomic number increases. In particular, it has been shown that the GBI effect is exceptionally strong for the recombination through the resonant state [1s2s(2)2p(1/2)](1).