A phantom assessment of achievable contouring concordance across multiple treatment planning systems

In this paper, the highest level of inter- and intra-observer conformity achievable with different treatment planning systems (TPSs), contouring tools, shapes, and sites have been established for metrics including the Dice similarity coefficient (DICE) and Hausdorff Distance. High conformity values, e.g. DICEBreast_Shape = 0.99 ± 0.01, were achieved. Decreasing image resolution decreased contouring conformity

Comparison of magnetic resonance imaging and computed tomography for breast target volume delineation in prone and supine positions

Purpose To\ua0determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57\ua0(95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52\ua0(95% CI 0.48-0.56) for MRI supine, 0.56\ua0(95% CI 0.53-0.59) for CT prone and 0.55\ua0(95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41\ua0(95% CI 0.36-0.46) for supine and 0.38\ua0(0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Terahertz Applications in Medicine, the Environment and Optics

Current and future applications for Terahertz (1012 Hz) have been obtained from within the existing literature. Terahertz spectroscopy techniques and analysis tools for; Terahertz Time Domain Spectroscopy (THz-TDS), Continuous Wave (CW) Spectroscopy, and Terahertz Imaging, have been developed to explore optical, environmental and medical applications. Two Nematic Liquid crystals have been characterised for future optical applications. Fiber Drawn metamaterials have also been explored using THz-TDS and CW spectroscopy for their optical applications. Spectroscopy differentiated various Biochars and sought their possible constituents to aid in enhancing soil fertility. The use of Terahertz spectroscopy in radiation dosimetry using two detection methods: Film and radiosensitive gel, were found to not be feasible. Various x-ray and Terahertz imaging systems have been compared. Nematic Liquid crystals, E7 and K15, optical properties have been investigated by THz- TDS. The birefringence of K15 was found to be 0.103 ± 0.004, whilst E7 was 0.144 ± 0.004 between (0.15-1.00) THz. Spectroscopy has been used to characterise Fiber Drawn Metamaterials. Fiber Drawn metamaterials were shown to have resonances between (0.1-0.4) THz at their theoretically established frequency under Transverse Magnetic polarisation. This resonance may be tailored by selecting the appropriate orientation of the slotted resonators in the spooling production process. The resonance frequency may also be increased by increasing the incident angle for longitudinally invariant metamaterials. This shift in frequency to higher frequencies due to an increase in incident angle may be overcome by patterning. Both sputtered and direct fiber drawn metamaterials were shown to have negative magnetic permeability in the Terahertz region, with negative effective permeability near the resonance frequency. Stacking and drawing of two dimensional direct drawn metamaterials resulted in 3 dimensional layered structures with magnetic resonances. The resonances increase with increasing layers and care must be taken to keep Bragg peaks from interfering with this resonance. These three dimensional structures may be extended into development of sub-wavelength waveguides. Biochar has been analysed by THz-TDS which can discriminate between Biochar types to aid in field detection, from their absorption and refractive index differences. BMC5 Biochar has the same index of refraction (N=1.29) as its constituents of dried chicken manure and Saligna Biochar. Terahertz frequency “fingerprints” may be used to determine Biochars constituents from pelletised samples if a quantitative analysis is performed. This is a complex structure and any insight into its mechanics is highly sought after. THz-TDS cannot distinguish between chemically treated Biochar, or thermal and biological prepared Biochars compared to unprepared Biochars. THz-TDS has been explored in radiation dosimetry, to better understand dosimeters (Film and radiosensitive gel) and in an attempt to determine if THz techniques could be used for dosimetry readout. Terahertz radiation could not establish the dose of EBT2 Gafchromic Film or PAGAT gel. The only possible application from this is a dual THz/X-ray system as the Terahertz radiation cannot read out the Film but does have a negligible effect. Terahertz imaging has been explored on both broadband and CW systems, and directly compared to X-rays. The literature has established that Terahertz radiation has many advantages over other frequencies, some examples include having less scatter than higher frequencies, being non-ionising and non-destructive. The same test phantom has been used to determine X-ray On-Board Imager and Terahertz Broadband Confocal Imaged resolutions of 1.25 lp/mm and 0.56 lp/mm respectively. X-rays have a higher spatial resolution than the Terahertz techniques used here. X-rays and THz have different contrast mechanisms. Despite the resolution difference Terahertz radiation may image lower atomic number samples better than X-rays, including water and plastics. Terahertz imaging applications include security screening, medical imaging and material imaging for quality assurance

Atlas-based segmentation technique incorporating inter-observer delineation uncertainty for whole breast

Accurate, efficient auto-segmentation methods are essential for the clinical efficacy of adaptive radiotherapy delivered with highly conformal techniques. Current atlas based auto-segmentation techniques are adequate in this respect, however fail to account for inter-observer variation. An atlas-based segmentation method that incorporates inter-observer variation is proposed. This method is validated for a whole breast radiotherapy cohort containing 28 CT datasets with CTVs delineated by eight observers. To optimise atlas accuracy, the cohort was divided into categories by mean body mass index and laterality, with atlas\u27 generated for each in a leave-one-out approach. Observer CTVs were merged and thresholded to generate an auto-segmentation model representing both inter-observer and inter-patient differences. For each category, the atlas was registered to the left-out dataset to enable propagation of the auto-segmentation from atlas space. Auto-segmentation time was recorded. The segmentation was compared to the gold-standard contour using the dice similarity coefficient (DSC) and mean absolute surface distance (MASD). Comparison with the smallest and largest CTV was also made. This atlas-based auto-segmentation method incorporating inter-observer variation was shown to be efficient (\u3c4min) and accurate for whole breast radiotherapy, with good agreement (DSC\u3e0.7, MASD \u3c9.3mm) between the auto-segmented contours and CTV volumes

THz-TDS of filter paper at differing humidities

Characterisation of filter paper using Terahertz Time Domain Spectroscopy (THz-TDS) is given at different humidities. This is achieved using saturated salt solutions. The absorption coefficient of filter paper increases with frequency and relative humidity

Defining and assessing an anisotropic delineation margin for modern radiotherapy

Purpose: Uncertainty in target volume delineation for modern radiotherapy impacts dosimetry and patient outcomes. Delineation uncertainty is generally overlooked in practice as a source of error, potentially since historically, other uncertainties have been the main focus. This work defined and assessed an anisotropic delineation margin in both polar and spherical coordinate systems in order to account for the spatially varying nature of this uncertainty using a whole breast radiotherapy cohort as a proof of concept. Methods: A cohort of 21 whole breast radiotherapy patient datasets with clinical target volumes delineated by eight independent observers was utilized. Patients were divided into categories based on target volume and laterality. An anisotropic delineation margin for each category was determined by multiplying the average standard deviation in observer contours in each category by a factor of two. Standard deviation was determined in both polar and spherical coordinates at angular increments. This anisotropic approach was compared to a conventional clinical approach, where the delineation margin was applied in the cardinal directions only. The assessment of the delineation margin was undertaken by comparing the encompassment of the observer volumes by the target volume with added margin. The extra, presumed healthy tissue included in the margin and the malignant tissue missed by the margin were determined. Results: The proposed delineation margin is effective at accounting for inter-observer variation, producing \u3e95% coverage of all CTVs for polar, spherical, and Cartesian margins in 82%, 79%, and 92% of cases, respectively. Additionally, \u3c1% malignant tissue was missed for 65%, 70%, and 91% of cases and \u3c37% healthy tissue was included in 95%, 89%, and 97% of cases. A conventional delineation margin approach is most appropriate for small and gold standard target volumes. However, for large target volumes, an anisotropic margin is necessary, producing significantly greater coverage of CTVs, including significantly less presumed healthy tissue and missing significantly less malignant tissue. Conclusions: All delineation margin methods that account for target volume and laterality proved to be adequate, with appropriate encompassment of interobserver variation and minimal inclusion of extra excess healthy tissue and exclusion of possible malignant tissue. The anisotropic approach was found to be superior to a conventional approach for target volumes \u3e1400 cm3 only with significantly greater encompassment of interobserver variation, less missed malignant tissue and less included healthy tissue. This methodology has been validated for a whole breast radiotherapy cohort as a proof of concept, however could be applied to other anatomical sites

Pre-treatment verification of lung SBRT VMAT plans with delivery errors: Toward a better understanding of the gamma index analysis

Purpose To study the sensitivity of the ArcCHECK in detecting delivery errors for lung stereotactic body radiotherapy (SBRT) using the Volumetric Modulated Arc Therapy (VMAT) technique and to evaluate the sensitivity of eight global and local gamma tolerances with different cut-off percentages. Methods Baseline VMAT plans were generated for 15 lung SBRT patients. We delivered the smallest errors(gantry, collimator, and multileaf collimator MLC) which had ≥ ±2% dose difference in the modified treatment plans compared to the baseline plan (the clinical significance of those errors were assessed in our previous study. A total of 100 plan in which 15 baseline plans were measured using the ArcCheck detector along with ion chamber measurements. The sensitivity of the global and local gamma-index method using criteria of 1%/1 mm, 2%/1 mm, 2%/2 mm, and 3%/3 mm was investigated. Results The gamma (γ) pass rates for these plans exhibited considerable spread. The majority of simulated errors were not detected. Broadly similar detection levels were achieved with the different gamma criteria and cut-offs. Combining ion chamber measurements with ArcCHECK did not improve error detection. Conclusions Commonly adopted gamma criteria are not sensitive enough to validate lung SBRT VMAT plans at the 2% dose difference level. The error detection levels are fairly consistent despite changes in gamma criteria and cut-offs. The choice of gamma criteria was not significant and there was no clear benefit in tightening the gamma criteria