An international survey on the clinical use of rigid and deformable image registration in radiotherapy.

OBJECTIVES: Rigid image registration (RIR) and deformable image registration (DIR) are widely used in radiotherapy. This project aims to capture current international approaches to image registration. METHODS: A survey was designed to identify variations in use, resources, implementation, and decision-making criteria for clinical image registration. This was distributed to radiotherapy centers internationally in 2018. RESULTS: There were 57 responses internationally, from the Americas (46%), Australia/New Zealand (32%), Europe (12%), and Asia (10%). Rigid image registration and DIR were used clinically for computed tomography (CT)-CT registration (96% and 51%, respectively), followed by CT-PET (81% and 47%), CT-CBCT (84% and 19%), CT-MR (93% and 19%), MR-MR (49% and 5%), and CT-US (9% and 0%). Respondent centers performed DIR using dedicated software (75%) and treatment planning systems (29%), with 84% having some form of DIR software. Centers have clinically implemented DIR for atlas-based segmentation (47%), multi-modality treatment planning (65%), and dose deformation (63%). The clinical use of DIR for multi-modality treatment planning and accounting for retreatments was considered to have the highest benefit-to-risk ratio (69% and 67%, respectively). CONCLUSIONS: This survey data provides useful insights on where, when, and how image registration has been implemented in radiotherapy centers around the world. DIR is mainly in clinical use for CT-CT (51%) and CT-PET (47%) for the head and neck (43-57% over all use cases) region. The highest benefit-risk ratio for clinical use of DIR was for multi-modality treatment planning and accounting for retreatments, which also had higher clinical use than for adaptive radiotherapy and atlas-based segmentation.

Comparison of automatic image registration uncertainty for three IGRT systems using a male pelvis phantom.

A series of phantom images using the CIRS Virtual Human Male Pelvis was acquired across available dose ranges for three image-guided radiotherapy (IGRT) imaging systems: Elekta XVI CBCT, Varian TrueBeam CBCT, and TomoTherapy MV CT. Each image was registered to a fan-beam CT within the XVI software 100 times with random initial offsets. The residual registration error was analyzed to assess the role of imaging hardware and reconstruction in the uncertainty of the IGRT process. Residual translation errors were similar for all systems and < 0.5 mm. Over the clinical dose range for prostate IGRT images (10-25 mGy), all imaging systems provided acceptable matches in > 90% of registrations when incorporating residual rotational error using a dual quaternion derived distance metric. Outside normal dose settings, large uncertainties were observed at very low and very high dose levels. No trend between initial offset and residual registration error was observed. Patient images may incur higher uncertainties than this phantom study; however, these results encourage automatic matching for standard dose settings with review by treatment staff.

Comprehensive characterisation of the IBA myQA SRS for SRS and SBRT patient specific quality assurance.

The myQA SRS (IBA) is a new to market 2D complementary metal oxide semiconductor detector array with an active area 140 × 120 mm2 and 0.4 mm resolution, making it a potential real-time dosimetry alternative to radiochromic film for stereotactic plan verification. Characterisation of the device was completed to assess performance. The dosimetric properties of the device were assessed for 6FF and 6FFF beams from a Varian TrueBeam STx with high definition multileaf collimator. Clinical suitability of the device for Patient Specific Quality Assurance was verified using ten SRS/SBRT plans, compared against other detectors, as well as multi leaf collimator (MLC) tests including picket fence and chair. Gamma analysis was performed using myQA software with criteria of 4%/1 mm. The device demonstrated compliance with recommended specifications for basic tests. After the required warm-up period, the maximum deviation in detector signal from initial readings was 0.2%. Short-term and long-term reproducibility was 0.1% (6FF) and 1.0% (6FFF), respectively. Dose linearity was within 0.3% (6FF) and 0.7% (6FFF) and dose-rate dependence within 1.7% (6FF) and 2.9% (6FFF) and were verified with a Farmer type ionization chamber (PTW 30013). Angular dependence was quantified for coplanar and non-coplanar situations. Output factors and beam profiles measured on the device showed agreement within 1% of baseline RAZOR diode (IBA) and CC04 ionisation chamber (IBA) measurements for field sizes 1 × 1 to 10 × 10 cm2. The minimum gamma (4%/1 mm) pass rates for MLC-pattern tests were 96.5% and 98.1% for the myQA SRS and film, respectively. The average gamma (4%/1 mm) pass rates for SBRT and SRS plans were 98.8% and 99.8% respectively. This work represents one of the first studies performed on the commissioning and performance characterisation of this novel device, demonstrating its accuracy and reliability, making it highly useful as a film alternative in stereotactic treatment plan verification.

ACPSEM position paper: pre-treatment patient specific plan checks and quality assurance in radiation oncology.

The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) has not previously made recommendations outlining the requirements for physics plan checks in Australia and New Zealand. A recent workforce modelling exercise, undertaken by the ACPSEM, revealed that the workload of a clinical radiation oncology medical physicist can comprise of up to 50% patient specific quality assurance activities. Therefore, in 2022 the ACPSEM Radiation Oncology Specialty Group (ROSG) set up a working group to address this issue. This position paper authored by ROSG endorses the recommendations of the American Association of Physicists in Medicine (AAPM) Task Group 218, 219 and 275 reports with some contextualisation for the Australia and New Zealand settings. A few recommendations from other sources are also endorsed to complete the position.

Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

Orientation dependent far-infrared terahertz absorptions in single crystal pentaerythritol tetranitrate (PETN) using terahertz time-domain spectroscopy.

Terahertz time-domain spectroscopy (THZ-TDS) has been used to measure the absorption spectra in the range 7-100 cm(-1) (0.2-3 THz) of single crystal pentaerythritol tetranitrate (PETN). Absorption was measured in transmission mode as a function of incident polarization with the incident and transmitted wave vectors oriented along the crystallographic directions [100], <10(a/c)(2)>, and <110>. Samples were rotated with respect to the incident polarization while absorption was measured at both 300 and 20 K. Comparatively minor differences were observed among the three orientations. Two broad absorptions at 72 and >90 cm(-1), and several weaker absorptions at 36, 55, 80, and 82 cm(-1), have been observed at cryogenic temperatures.

The adaptation and investigation of cone-beam CT reconstruction algorithms for horizontal rotation fixed-gantry scans of rabbits.

Fixed-gantry radiation therapy has been proposed as a low-cost alternative to the conventional rotating-gantry radiation therapy, that may help meet the rising global treatment demand. Fixed-gantry systems require gravitational motion compensated reconstruction algorithms to produce cone-beam CT (CBCT) images of sufficient quality for image guidance. The aim of this work was to adapt and investigate five CBCT reconstruction algorithms for fixed-gantry CBCT images. The five algorithms investigated were Feldkamp-Davis-Kress (FDK), prior image constrained compressed sensing (PICCS), gravitational motion compensated FDK (GMCFDK), motion compensated PICCS (MCPICCS) (a novel CBCT reconstruction algorithm) and simultaneous motion estimation and iterative reconstruction (SMEIR). Fixed-gantry and rotating-gantry CBCT scans were acquired of 3 rabbits, with the rotating-gantry scans used as a reference. Projections were sorted into rotation bins, based on the angle of rotation of the rabbit during image acquisition. The algorithms were compared using the structural similarity index measure root mean square error, and reconstruction time. Evaluation of the reconstructed volumes showed that, when compared with the reference rotating-gantry volume, the conventional FDK algorithm did not accurately reconstruct fixed-gantry CBCT scans. Whilst the PICCS reconstruction algorithm reduced some motion artefacts, the motion estimation reconstruction methods (GMCFDK, MCPICCS and SMEIR) were able to greatly reduce the effect of motion artefacts on the reconstructed volumes. This finding was verified quantitatively, with GMCFDK, MCPICCS and SMEIR reconstructions having RMSE 17%-19% lower and SSIM 1% higher than a conventional FDK. However, all motion compensated fixed-gantry CBCT reconstructions had a 56%-61% higher RMSE and 1.5% lower SSIM than FDK reconstructions of conventional rotating-gantry CBCT scans. The results show that motion compensation is required to reduce motion artefacts for fixed-gantry CBCT reconstructions. This paper further demonstrates the feasibility of fixed-gantry CBCT scans, and the ability of CBCT reconstruction algorithms to compensate for motion due to horizontal rotation.

Reducing 4D CT imaging artifacts at the source: first experimental results from the respiratory adaptive computed tomography (REACT) system.

Breathing variations during 4D CT imaging often manifest as geometric irregularities known as respiratory-induced image artifacts and ultimately effect radiotherapy treatment efficacy. To reduce such image artifacts we developed Respiratory Adaptive Computed Tomography (REACT) to trigger CT acquisition during periods of regular breathing. For the first time, we integrate REACT with clinical hardware and hypothesize that REACT will reduce respiratory-induced image artifacts ≥ 4 mm compared to conventional 4D CT. 4D image sets were acquired using REACT and conventional 4D CT on a Siemens Somatom scanner. Scans were taken for 13 respiratory traces (12 patients) that were reproduced on a lung-motion phantom. Motion was observed by the Varian RPM system and sent to the REACT software where breathing irregularity was evaluated in real-time and used to trigger the imaging beam. REACT and conventional 4D CT images were compared to a ground truth static-phantom image and compared for absolute geometric differences within the region-of-interest. Breathing irregularity during imaging was retrospectively assessed using the root-mean-square error of the RPM measured respiratory signal during beam on (RMSE_Beam_on) for each phase of the respiratory cycle. REACT significantly reduced the average frequency of respiratory-induced image artifacts ≥ 4 mm by 70% for the tumor (p = 0.003) and 76% for the lung (p = 0.0002) compared to conventional 4D CT. Volume reductions of 10% to 6% of the tumor and 2% to 1% of the lung compared to conventional 4D CT were seen. Breathing irregularity during imaging (RMSE_Beam_on) was significantly reduced by 27% (p = 0.013) using the REACT method. For the first time, REACT was successfully integrated with clinical hardware. Our findings support the hypothesis that REACT significantly reduced respiratory-induced image artifacts compared to conventional 4D CT. These experimental results provide compelling evidence for further REACT investigation, potentially providing clearer images for clinical use.

Deforming to Best Practice: Key considerations for deformable image registration in radiotherapy.

Image registration is a process that underlies many new techniques in radiation oncology - from multimodal imaging and contour propagation in treatment planning to dose accumulation throughout treatment. Deformable image registration (DIR) is a subset of image registration subject to high levels of complexity in process and validation. A need for local guidance to assist in high-quality utilisation and best practice was identified within the Australian community, leading to collaborative activity and workshops. This report communicates the current limitations and best practice advice from early adopters to help guide those implementing DIR in the clinic at this early stage. They are based on the state of image registration applications in radiotherapy in Australia and New Zealand (ANZ), and consensus discussions made at the 'Deforming to Best Practice' workshops in 2018. The current status of clinical application use cases is presented, including multimodal imaging, automatic segmentation, adaptive radiotherapy, retreatment, dose accumulation and response assessment, along with uptake, accuracy and limitations. Key areas of concern and preliminary suggestions for commissioning, quality assurance, education and training, and the use of automation are also reported. Many questions remain, and the radiotherapy community will benefit from continued research in this area. However, DIR is available to clinics and this report is intended to aid departments using or about to use DIR tools now.

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) for lung cancer is a modality of treatment that has improved outcomes for lung cancer patients. However, radiotherapy for lung cancer is underutilized and fewer than half of elderly patients with non-small cell lung cancer (NSCLC) receive active treatment. The purpose of this study is to report on a collaboration in implementing an NSCLC SABR (stereotactic ablative body radiation) program safely, efficiently, and uniformly across several centers, including regional sites. The first aim of this paper is to detail the collaboration and implementation that started in 2013 and is ongoing. The second aim of this paper is to document early toxicities and quality of life outcomes. METHOD: A tripartite approach was used to develop the protocol and networks required for the implementation of SABR across multiple sites in NSW. Departments starting the programmes were supported and physics credentialing with central site submission was required before commencing the treatment. Additional ongoing support was available via an email discussion group involving all members of the collaboration. RESULTS: Between July 22, 2013 and February 22, 2016, 41 patients were enrolled with 34 patients in active follow up. The toxicity profile so far is similar to those of published studies with no appreciable effect on quality of life outcomes. CONCLUSION: The collaboration formed an effective framework in facilitating the implementation of SABR across several sites in NSW and could be used as a model for the safe and uniform implementation of new technologies in Australia.

Cone-beam CT reconstruction with gravity-induced motion.

Fixed-gantry cone-beam computed tomography (CBCT), where the imaging hardware is fixed while the subject is continuously rotated 360° in the horizontal position, has implications for building compact and affordable fixed-gantry linear accelerators (linacs). Fixed-gantry imaging with a rotating subject presents a challenging image reconstruction problem where the gravity-induced motion is coupled to the subject's rotation angle. This study is the first to investigate the feasibility of fixed-gantry CBCT using imaging data of three live rabbits in an ethics-approved study. A novel data-driven motion correction method that combines partial-view reconstruction and motion compensation was developed to overcome this challenge. Fixed-gantry CBCT scans of three live rabbits were acquired on a standard radiotherapy system with the imaging beam fixed and the rabbits continuously rotated using an in-house programmable rotation cradle. The reconstructed images of the thoracic region were validated against conventional CBCT scans acquired at different cradle rotation angles. Results showed that gravity-induced motion caused severe motion blur in all of the cases if unaccounted for. The proposed motion correction method yielded clinically usable image quality with <1 mm gravity-induced motion blur for rabbits that were securely immobilized on the rotation cradle. Shapes of the anatomic structures were correctly reconstructed with <0.5 mm accuracy. Translational motion accounted for the majority of gravity-induced motion. The motion-corrected reconstruction represented the time-averaged location of the thoracic region over a 360° rotation. The feasibility of fixed-gantry CBCT has been demonstrated. Future work involves the validation of imaging accuracy for human subjects, which will be useful for emerging compact fixed-gantry radiotherapy systems.

A CBCT study of the gravity-induced movement in rotating rabbits.

Fixed-beam radiotherapy systems with subjects rotating about a longitudinal (horizontal) axis are subject to gravity-induced motion. Limited reports on the degree of this motion, and any deformation, has been reported previously. The purpose of this study is to quantify the degree of anatomical motion caused by rotating a subject around a longitudinal axis, using cone-beam CT (CBCT). In the current study, a purpose-made longitudinal rotating was aligned to a Varian TrueBeam kV imaging system. CBCT images of three live rabbits were acquired at fixed rotational offsets of the cradle. Rigid and deformable image registrations back to the original position were used to quantify the motion experienced by the subjects under rotation. In the rotation offset CBCTs, the mean magnitude of rigid translations was 5.7 ± 2.7 mm across all rabbits and all rotations. The translation motion was reproducible between multiple rotations within 2.1 mm, 1.1 mm, and 2.8 mm difference for rabbit 1, 2, and 3, respectively. The magnitude of the mean and absolute maximum deformation vectors were 0.2 ± 0.1 mm and 5.4 ± 2.0 mm respectively, indicating small residual deformations after rigid registration. In the non-rotated rabbit 4DCBCT, respiratory diaphragm motion up to 5 mm was observed, and the variation in respiratory motion as measured from a series of 4DCBCT scans acquired at each rotation position was small. The principle motion of the rotated subjects was rigid translational motion. The deformation of the anatomy under rotation was found to be similar in scale to normal respiratory motion. This indicates imaging and treatment of rotated subjects with fixed-beam systems can use rigid registration as the primary mode of motion estimation. While the scaling of deformation from rabbits to humans is uncertain, these proof-of-principle results indicate promise for fixed-beam treatment systems.

A survey of modulated radiotherapy use in Australia & New Zealand in 2015.

A survey of radiation oncology medical physics departments across Australia and New Zealand was conducted to assess the usage, commissioning and quality assurance of modulated radiotherapy techniques such as IMRT and VMAT. Survey responses were collected in April-May 2015 to snapshot current practice and historical implementation. The survey asked 142 questions, and is the most detailed survey of its kind published to date. Analysis of results at overall department level, as well as sub-analysis for different equipment and techniques in use, was performed. Results show a high prevalence of IMRT and VMAT in use, and demonstrate the large heterogeneity in clinical practice and experience across the region.

Structural changes in self-assembled monolayers initiated by ultraviolet light.

Self-assembled monolayers of 2-anthracenethiol and 2-naphthalenethiol on gold (111) were irradiated with low-power UV light. Scanning tunneling microscope images recorded in situ show unusual structural changes. In the case of 2-anthracenethiol, structures measuring 4-7 nm wide and 30-40 nm in length are formed. Images taken 10 min after irradiation ceased to show further surface reorganization. With 2-naphthalenethiol SAMs, smaller structures form upon irradiation, which subsequently revert to resemble the original structure after time.

Identifying Raman and Infrared Vibrational Motions of Erythritol Tetranitrate.

The vibrational bands of erythritol tetranitrate (ETN) were measured experimentally with both Raman spectroscopy and attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy. Seventy-two (3N-6) vibrational modes were predicted for ETN using density functional theory calculations performed using the B3LYP/6-31G* density functional basis set and geometry optimization. Raman spectroscopy and ATR FT-IR were used to measure observable Raman and IR signatures between 140 and 3100 wavenumbers (cm(-1)). Within this spectral range, 32 Raman bands and 21 IR bands were measured and identified by their predicted vibrational motion. The spectroscopic and theoretical analysis of ETN performed will advance the detection and identification capabilities of field measuring instruments for this explosive.

Adapting Raman spectra from laboratory spectrometers to portable detection libraries.

Raman spectral data collected with high-resolution laboratory spectrometers are processed into a format suitable for importing as a user library on a 1064 nm DeltaNu first generation, field-deployable spectrometer prototype. The two laboratory systems used are a 1064 nm Bruker Fourier transform (FT)-Raman spectrometer and a 785 nm Kaiser dispersive spectrometer. The steps taken to adapt for device-dependent spectral resolution, wavenumber shifts between instruments, and relative intensity response are described. Effects due to the differing excitation laser wavelengths were found to be minimal, indicating--at least for the near-infrared (NIR)--that data can be ported between different systems, so long as certain measures are taken with regard to the reference and field spectra.

Evidence for the production of N4 via the N2 A3Sigma(u)+ + N2 A3Sigma(u)+ energy pooling reaction.

We report mass spectrometric evidence supporting our proposed mechanistic pathway for the production of N4 through the energy pooling reaction N2 A3Sigma(u)+ + N2 A3Sigma(u)+. N2 A3Sigma(u)+ is generated from the quenching of resonantly excited xenon in a mixture of xenon, 15N2, and 14N2 that is illuminated with xenon resonant lamps (147 nm). Mass spectra are periodically taken of the mixture. Over time, we observe significant isotopic scrambling of the 15N2 and 14N2, generating 15N14N in concentrations approaching 10% (approximately 2 Torr) of the initial 15N2 concentration. Though we do not observe the direct formation of N4, the isotopic ratios indicate that an excited complex (15N2(14)N2) exists long enough so that scrambling of the nitrogen atoms can occur, offering a possible route to the formation of tetrahedral nitrogen (1Td N4).

Anharmonic vibrational properties of explosives from temperature-dependent Raman.

Raman spectra from 50 to 3500 cm(-1) and 4-296 K are analyzed for molecular crystal powders of the explosives pentaerythritol tetranitrate (PETN), beta-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and the inert naphthalene. Temperature-dependent Raman spectroscopy is utilized for its sensitivity to anharmonic couplings between thermally populated phonons and higher frequency vibrations relevant to shock up-pumping. The data are analyzed with anharmonic perturbation theory, which is shown to have significant fundamental limitations in application to real data. Fitting to perturbation theory revealed no significant differences in averaged anharmonicities among the three explosives, all of which exhibited larger averaged anharmonicities than naphthalene by a factor of 3. Calculations estimating the multiphonon densities of states also failed to correlate clearly with shock sensitivity. However, striking differences in temperature-dependent lifetimes were obvious: PETN has long lived phonons and vibrons, HMX has long lived phonons but short lived vibrons, while TATB has short lived phonons and vibrons at low temperature. Naphthalene, widely used as a model system, has significantly different anharmonicities and density of states from any of the explosives. The data presented suggest the further hypothesis that hindered vibrational energy transfer in the molecular crystals is a significant factor in shock sensitivity.

Temperature-dependent far-infrared spectra of single crystals of high explosives using terahertz time-domain spectroscopy.

Survey spectra of single-crystal HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine), and PETN (pentaerythritol tetranitrate) were acquired in the region from 10 to 80 cm(-1) using terahertz time-domain spectroscopy. The spectra were taken at temperatures ranging from 8.4 to 300 K. Generally, the spectra show multiple absorption peaks in the range 50-80 cm(-1), with PETN (110) showing strong absorption features at room temperature. RDX (210) is the most notable in the region 10-40 cm(-1), showing multiple spectral features, while HMX (010) shows a very broad absorption at 47.8 cm(-1) with a fwhm of 37.3 cm(-1). Future plans include polarization-dependent investigations for multiple crystallographic orientations over an increased spectral range and higher-level theoretical calculations.