Medicine

Examining differences among opioid agonist treatment clients in regional and metropolitan settings of New South Wales, Australia

Wed, 01 Jan 2025 00:00:00 GMT

Examining differences among opioid agonist treatment clients in regional and metropolitan settings of New South Wales, Australia Winter, Daniel T; Monds, Lauren A; Lintzeris, Nicholas; Haber, Paul S; Day, Carolyn A Objective: Whilst prior studies have examined characteristics and barriers for opioid agonist treatment (OAT) clients in regional settings, there are limited studies examining these differences in relation to metropolitan OAT clients. This study aimed to examine key characteristics, including sedating medication and substance use, transport and driving behaviours and differences between OAT clients within regional and metropolitan areas of New South Wales, Australia. Design: Cross-sectional survey of OAT clients. Setting: Fifteen public OAT clinics across New South Wales, Australia, between January 2020 and June 2021. Participants: Survey was completed by 482 people currently receiving OAT. Main outcome measures: Self-reported sample characteristics, self-reported sedating medication use and substance use, transportation and driving histories. Results: Significant differences in OAT pharmacotherapies prescribed between regional and metropolitan participants were noted (aOR = 2.42, 95% CI = 1.42-4.11). Methadone was the most commonly prescribed OAT in both settings (74.1% and 54.4%, respectively). Nearly half (45.6%) of regional participants received OAT from a private dispensary compared to 4.7% in metropolitan areas. While few differences in past-month substance use were noted, reported heroin use was lower (aOR = 0.27; 95% CI = 0.09-0.78) in regional areas. Regional participants were more likely than metropolitan participants to drive a vehicle to dosing (aOR = 2.89, 95% CI = 1.12-7.46) and less likely to take public transport (aOR = 0.41, 95% CI = 0.18-0.93) or active transport (aOR = 3.75, 95% CI = 1.50-9.40). Few differences regarding driving offences, based on geography, were noted. Conclusions: Key differences with treatment, substance use, transport and driving were noted within this study. It is evident that regional OAT clients more often rely on motor vehicles to complete daily activities. Such challenges related to OAT should be addressed by informed policy and regulatory changes that ensure access and equity of treatment and safety, regardless of location.

A mentally healthy framework to guide employers and policy makers

Mon, 01 Jan 2024 00:00:00 GMT

A mentally healthy framework to guide employers and policy makers Glozier, Nick Mobile health (mHealth) apps have the potential to expand access to evidence-based interventions for mental health conditions, including depression. HeadGear was developed to prevent depression and improve well-being among the working population and was associated with significant positive effects in an efficacy trial. This study presents the results from a naturalistic trial intended to evaluate real-world usage of the app. We examined the naturalistic use of HeadGear between March 2019 and March 2022, using app analytic data, in-app event data, and surveys assessing depressive symptoms, well-being, and work performance repeated at 30-day intervals over 5-month app usage. During the observation period, HeadGear was widely disseminated to the public, and downloaded 26,455 times. Of those who downloaded the app, 12,995 completed baseline. The mean age of users was 38.23 (SD = 12.39) and 60% were women. Approximately one in four met criteria for probable depression at baseline. Depressive symptoms showed consistent improvement at all time points (Cohen’s d ranging from 0.24 at 1 month to 0.13 at 5 months). A similar pattern emerged for well-being. Work performance showed improvement to 2-month follow-up only. The strongest change was found for those with greater symptom severity at baseline, and those with high app engagement. Attrition at follow-up points was high. Findings regarding the real-world use of HeadGear are promising and highlight the use of such apps among those with higher symptom severity (despite the intended use of the app as a prevention tool). Further work is required to tailor mHealth apps to reach their full potential through an enhanced understanding of the utility of individual features for effectiveness and engagement.

Trends in Effectiveness of Organizational eHealth Interventions in Addressing Employee Mental Health: Systematic Review and Meta-analysis

Sat, 01 Jan 2022 00:00:00 GMT

Trends in Effectiveness of Organizational eHealth Interventions in Addressing Employee Mental Health: Systematic Review and Meta-analysis Stratton, Elizabeth; Lampit, Amit; Choi, Isabella; Gavelin, Hanna Malmberg; Aji, Melissa; Taylor, Jennifer; Calvo, Rafael; Harvey, Samuel; Glozier, Nick Background: Mental health conditions are considered the leading cause of disability, sickness absence, and long-term work incapacity. eHealth interventions provide employees with access to psychological assistance. There has been widespread implementation and provision of eHealth interventions in the workplace as an inexpensive and anonymous way of addressing common mental disorders. Objective: This updated review aimed to synthesize the literature on the efficacy of eHealth interventions for anxiety, depression, and stress outcomes in employee samples in organizational settings and evaluate whether their effectiveness has improved over time. Methods: Systematic searches of relevant articles published from 2004 to July 2020 of eHealth intervention trials (app- or web-based) focusing on the mental health of employees were conducted. The quality and bias of all studies were assessed. We extracted means and SDs from publications by comparing the differences in effect sizes (Hedge g) in standardized mental health outcomes. We meta-analyzed these data using a random-effects model. Results: We identified a tripling of the body of evidence, with 75 trials available for meta-analysis from a combined sample of 14,747 articles. eHealth interventions showed small positive effects for anxiety (Hedges g=0.26, 95% CI 0.13-0.39; P<.001), depression (Hedges g=0.26, 95% CI 0.19-0.34; P<.001), and stress (Hedges g=0.25, 95% CI 0.17-0.34; P<.001) in employees’ after intervention, with similar effects seen at the medium-term follow-up. However, there was evidence of no increase in the effectiveness of these interventions over the past decade. Conclusions: This review and meta-analysis confirmed that eHealth interventions have a small positive impact on reducing mental health symptoms in employees. Disappointingly, we found no evidence that, despite the advances in technology and the enormous resources in time, research, and finance devoted to this area for over a decade, better interventions are being produced. Hopefully, these small effect sizes do not represent optimum outcomes in organizational settings.

Relapse Prevention, Aftercare, and Long-Term Follow-Up

Fri, 01 Jan 2021 00:00:00 GMT

Relapse Prevention, Aftercare, and Long-Term Follow-Up Haber, Paul S This chapter provides an overview of relapse prevention and strategies to long-term patient follow-up (aftercare programs), including approaches to working with alcohol-dependent patients who resume heavy alcohol use. Negotiating goals of treatment has already been discussed (Chapter 4) recognizing that abstinence is not the only option. Indeed, many patients are not ready to engage in treatment that sets a goal of abstinence but may accept the need to reduce drinking. Recent research has confirmed that substantial reductions in drinking may be associated with sustained clinical improvements. The World Health Organisation (WHO) has defined four drinking risk levels (veryhigh-,high-, moderate-, and low-risk) and clinical benefit has been associated with reduction of at least two risk levels reaching low-risk drinking or moderate-risk for those who were initially drinking at very-high-risk levels.

Cognitive Impairment

Fri, 01 Jan 2021 00:00:00 GMT

Cognitive Impairment Monds, Lauren; Ridley, Nicole; Logge, Warren; Withall, Adrienne This chapter provides an overview of treatment options and approaches for patients with cognitive impairment. The prevalence of cognitive impairment (CI) in people seeking treatment for alcohol use disorder (AUD) is high (up to two thirds with some form of impairment). Impaired cognitive functioning is related to poorer treatment retention and increased risk of relapse. Early assessment and ongoing monitoring of cognitive status is therefore essential for appropriate treatment planning and to maximise likelihood of treatment success.

Aboriginal and Torres Strait Islander Peoples

Fri, 01 Jan 2021 00:00:00 GMT

Aboriginal and Torres Strait Islander Peoples Assan, Robert; Zheng, Catherine; Wilson, Scott; Freeburn, Bradley; Boffa, John; Purcell-Khodr, Gemma; Doyle, Michael; Conigrave, Kate This chapter provides guidance on managing unhealthy alcohol use among Aboriginal and Torres Strait Islander peoples. This includes care of those who are drinking above recommended limits, whether or not there is an alcohol use disorder present. Content of this chapter is based on both consultation with Aboriginal and Torres Strait Islander health professionals and communities and on published research. Much of the published research on treatment approaches among Aboriginal and Torres Strait Islander peoples has been qualitative in nature.

Pharmacotherapies

Fri, 01 Jan 2021 00:00:00 GMT

Pharmacotherapies Morley, Kirsten; Rombouts, Susan; Jamshidi, Nazila; Haber, Paul S Pharmacotherapy should be considered for all patients with moderate to severe alcohol use disorder (AUD) following detoxification. They are best used in conjunction with psychosocial support. For some, medication is associated with a critical period of abstinence, during which the patient can learn to maintain abstinence or reduce drinking. For patients who are motivated to take the medication, it can be a potential tool for reducing the core symptoms of AUD. In Australia, there is a requirement for pharmacotherapies to be part of a comprehensive treatment program to gain Pharmaceutical Benefits Scheme (PBS) subsidy. Trials of pharmacotherapies have typically included some form of psychosocial support. Thus, it is recommended that pharmacotherapy should be considered in association with psychosocial supports as part of an after-care treatment plan.

Alcohol Withdrawal

Fri, 01 Jan 2021 00:00:00 GMT

Alcohol Withdrawal Haber, Paul S; Lintzeris, Nicholas Alcohol withdrawal is a syndrome occurring in people with longstanding high risk drinking who either stop or substantially decrease alcohol consumption. The symptoms include adrenergic overactivity, central nervous system (CNS) excitation and gastrointestinal disturbance. The risk of withdrawal is greater with higher levels of alcohol use, previous episodes of withdrawal and concurrent health problems including cessation of other drugs. Withdrawal ranges in severity from trivial to life-threatening, tending to greater severity with successive episodes.

Brief e-Health Interventions for Alcohol Use and Related-Problems

Fri, 01 Jan 2021 00:00:00 GMT

Brief e-Health Interventions for Alcohol Use and Related-Problems Riordan, Benjamin C; Cunningham, John; Kay-Lambkin, Frances This chapter provides a description of brief e-health interventions and their role in addressing alcohol use and related problems. The chapter describes common components of e-health interventions and the current evidence base and provides references for current e-health interventions. Brief in-person Interventions are an effective and cost-effective way to reduce alcohol use problems. Despite this, most Australians who experience an alcohol use disorder (AUD) will never receive treatment, and for those who do, the average delay from emergence of AUD to first treatment contact is 18 years. Several barriers may prevent the implementation of Brief Interventions for alcohol use problems, such as: time, access to health professionals trained in brief intervention, lack of resources, cost, and the stigma associated with seeking treatment for problematic alcohol use. But brief e-health interventions (interventions delivered via internet, mobile phone, or computer) reduce several barriers to treatment.

An Introduction to the Guidelines for the Treatment of Alcohol Problems

Fri, 01 Jan 2021 00:00:00 GMT

An Introduction to the Guidelines for the Treatment of Alcohol Problems Haber, Paul S; Riordan, Benjamin C The Guidelines for the Treatment of Alcohol Problems have been periodically developed over the past 25 years. In 1993, the first version of these guidelines, titled: ‘An outline for the management of alcohol problems: Quality assurance in the treatment of drug dependence project’ was published (Mattick & Jarvis 1993). The Australian Government commissioned an update a decade later (Shand et al. 2003) and a further edition in 2009 to integrate the Guidelines with the Australian Guidelines to Reduce Health Risks from Drinking Alcohol (National Health and Medical Research Council, NHMRC 2009; Haber et al., 2009). The present version of the Guidelines was also commissioned by the Commonwealth of Australia to remain current and integrated with the updated NHMRC consumption guidelines (2020).

Prevalence of Alcohol Consumption and Related Harms in Australia

Fri, 01 Jan 2021 00:00:00 GMT

Prevalence of Alcohol Consumption and Related Harms in Australia Riordan, Benjamin C; Winter, Daniel T; Haber, Paul S Alcohol offers a mixed legacy to our society, having long been used in a broad range of social, cultural, and religious contexts; some societies routinely permit alcohol use while others frown upon or ban consumption. Reasons for consuming alcohol include relaxation, enjoyment, or as part of a celebration, or in response to boredom, sorrow, sadness or trauma. Frequent consumption can often lead to a habit or compulsive use of alcohol, with a dose-dependent relationship existing between alcohol use and related harms. Such harms include chronic and acute harms to the self, harms to others, along with boarder socioeconomic consequences from alcohol consumption.

Guidelines for the Treatment of Alcohol Problems

Fri, 01 Jan 2021 00:00:00 GMT

Guidelines for the Treatment of Alcohol Problems Haber, Paul S.; Riordan, Benjamin C. The Guidelines for the Treatment of Alcohol Problems have been periodically developed over the past 25 years. These guidelines provide up-to-date, evidence-based information to clinicians on available treatments for people with alcohol problems and are largely directed towards individual clinicians in practice, such as primary care physicians (general practitioners, nursing staff), specialist medical practitioners, psychologists and other counsellors, and other health professionals.

'That thing in his head': Aboriginal and non-Aboriginal Australian caregiver responses to neurodevelopmental disability diagnoses

Wed, 01 Jan 2020 00:00:00 GMT

'That thing in his head': Aboriginal and non-Aboriginal Australian caregiver responses to neurodevelopmental disability diagnoses Hamilton, Sharynne; Maslen, Sarah; Watkins, Rochelle; Conigrave, Katherine; Freeman, Jacinta; O'Donnell, Melissa; Mutch, Raewyn; Bower, Carol Little is known about the significance of cultural differences to how caregivers receive a diagnosis of neurodevelopmental disability. As part of a Fetal Alcohol Spectrum Disorder prevalence study among sentenced, detained youth, our qualitative study explored the experiences of diagnostic assessment among detained young people and their caregivers. We present findings from the perspectives of caregivers. In conversation with the sociology of diagnosis literature, we present vignettes of three Aboriginal and two non-Aboriginal caregivers’ experiences of the diagnostic assessment process. We found that Aboriginal caregivers conceptualised their children’s diagnosis and ongoing management in the context of their family networks and community. In contrast, non-Aboriginal caregivers focused on how the diagnosis would affect their child and interactions with various institutions including healthcare systems and schools. Caregivers’ engagement with diagnostic reports and resources also followed cultural lines. Reflections on intergenerational drinking were voiced by Aboriginal caregivers, who expressed shame at receiving diagnosis. These findings advance our appreciation of cultural difference in receiving a diagnosis, the examination of which is in its nascent stages. We also suggest ways to mitigate harm from a stigmatising diagnosis and soften the well-established effects of medical dominance over the process of defining a person’s capacity and status.

Asking young Aboriginal people who use illicit drugs about their healthcare preferences using audio-computer-assisted self-interviewing

Tue, 01 Jan 2019 00:00:00 GMT

Asking young Aboriginal people who use illicit drugs about their healthcare preferences using audio-computer-assisted self-interviewing Dowsett, Marianne; Ganora, Christopher; Day, Carolyn; Lee, Kylie; Dawson, Angela; Joseph, Telphia; White, Ann; Freeburn, Bradley; Conigrave, Katherine Introduction and Aims Substance use significantly contributes to increasing the disease burden experienced by young Aboriginal and Torres Strait Islander (Aboriginal) Australians. Little is known about the primary healthcare needs of young Aboriginal people who use drugs. The aim of this study was to pilot Audio Computer Assisted Self-Interviewing (ACASI) as a method of asking young Aboriginal people who use illicit drugs about their health concerns and service preferences, in inner-Sydney, New South Wales. Design and Methods We employed a sequential mixed methods exploratory study design. Qualitative data was collected using a focus group and in-depth interviews. These findings informed the development of the ACASI survey, which asked questions on substance use, health concerns, health service usage, barriers and preferences for services. Recruitment sites included youth and health services. Qualitative results were analysed thematically, and survey results using descriptive statistics. Results Eight people participated in the focus group and two in in-depth interviews. Of the 38 survey respondents, 68% reported illicit drug use. Reported barriers to service access included waiting time and services seeming unfriendly or not understanding Aboriginal people. Participants expressed preferences for Aboriginal-friendly health services that provide internet access, literacy skill development and opportunities to learn about Aboriginal culture. Participants found the ACASI survey user-friendly. Discussion and Conclusions This is the first report describing health concerns and service preferences of young Aboriginal people who use illicit drugs. The ACASI survey appears to be an appropriate and efficient approach to giving a voice to young Aboriginal people.

Coming of age: 21 years providing opioid substitution treatment within an Aboriginal community-controlled primary health service

Fri, 01 Jan 2021 00:00:00 GMT

Coming of age: 21 years providing opioid substitution treatment within an Aboriginal community-controlled primary health service Freeburn, Bradley; Loggins, Summer; Lee, Kylie; Conigrave, Katherine In Australia, Aboriginal and Torres Strait Islander community controlled health services have been established since 1971 to provide accessible, quality and culturally-appropriate primary healthcare. The first of these services, the Aboriginal Medical Service Cooperative Redfern (‘the AMS’), created its own Drug and Alcohol Unit (‘the Unit’) in 1999. The Unit initially prescribed opioid substitution treatment (OST) and its coordinator, Bradley Freeburn, a Bundjalung man, provided counselling. Soon afterwards, the Unit started dispensing OST. It now cares for around 150 individuals, each of whom is understood in the context of family, community and culture. The Unit is on the same site as the AMS's primary care service, specialised medical and mental health clinics, and dental clinic. This allows for integrated physical and mental health care. The Unit contributes to drug and alcohol workforce development for other AMS staff, state-wide and nationally. Several Aboriginal and Torres Strait Islander community controlled health services around Australia now offer OST prescription, and a small number administer slow-release buprenorphine. We are not aware of others that dispense Suboxone. In the USA and Canada, over the last 10 years, First Nations communities have also responded to lack of treatment access, by creating standalone OST clinics. We were not able to find examples of Māori-controlled OST clinics in Aotearoa, New Zealand. The feasibility of this model of readily accessible OST, situated within a holistic, culturally-grounded primary health-care service recommends it for consideration and evaluation, for Indigenous or non-Indigenous communities.

Indigenous Australian drinking patterns

Fri, 01 Jan 2021 00:00:00 GMT

Indigenous Australian drinking patterns Zheng, Catherine; Conigrave, James; Conigrave, Katherine; Wilson, Scott; Perry, Jimmy; Chikritzhs, Tanya; Fitts, Michelle; Lee, K S Kylie Background Measuring self-reported alcohol use is challenging in any population, including when episodic drinking may be common. Drinking among Indigenous Australians has been shown to vary greatly within and between communities. However, most survey methods assume ‘regular’ patterns of drinking. National estimates have also been shown to underestimate alcohol use among this group. This paper describes drinking patterns in two representative community samples (urban and remote). Methods Indigenous Australians (aged 16+ years) in two South Australian sites were recruited to complete the Grog Survey App. The App is a validated, interactive tablet-based survey tool, designed to help Indigenous Australians describe their drinking. Drinking patterns were described using medians and interquartile ranges; gender and remoteness were compared using Wilcoxon rank-sum tests. Spearman correlations explored the relationship between drinking patterns and age. Logistic regressions tested if beverage or container preference differed by remoteness or gender. Results Three-quarters of participants (77.0%, n=597/775) were current drinkers. Median standard drinks quarters of current drinkers (73.7%) reported a period without drinking (median: 60 days). Remote drinkers were more likely to drink beer. Improvised containers were used by 40.5% of drinkers. Conclusions Episodic drinking with extended ‘dry’ periods and from non-standard drinking containers was common in this representative sample of Indigenous Australians. The diversity of container use and beverage preference, by gender and remoteness, illustrates nuances in drinking patterns between communities. It shows the importance of community-level data to inform local strategies addressing alcohol misuse.

Assessment of inter-laboratory differences in SARS-CoV-2 consensus genome assemblies between public health laboratories in Australia

Fri, 01 Jan 2021 00:00:00 GMT

Assessment of inter-laboratory differences in SARS-CoV-2 consensus genome assemblies between public health laboratories in Australia Foster, Charles S.P.; Stelzer-Braid, Sacha; Deveson, Ira W.; Bull, Rowena A.; Yeang, Malinna; Phan-Au, Jane; Silva, Mariana Ruiz; van Hal, Sebastiaan J.; Rockett, Rebecca J.; Sintchenko, Vitali; Kim, Ki Wook; Rawlinson, William D. Abstract Whole-genome sequencing of viral isolates is critical for informing transmission patterns and ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences in consensus genome assemblies of 72 matched SARS-CoV-2-positive specimens sequenced at different laboratories in Sydney, Australia. Raw sequence data were assembled using two different bioinformatics pipelines in parallel, and resulting consensus genomes were compared to detect laboratory-specific differences. Matched genome sequences were predominantly concordant, with a median pairwise identity of 99.997%. Identified differences were predominantly driven by ambiguous site content. Ignoring these produced differences in only 2.3% (5/216) of pairwise comparisons, each differing by a single nucleotide. Matched samples were assigned the same Pango lineage in 98.2% (212/216) of pairwise comparisons, and were mostly assigned to the same phylogenetic clade. However, epidemiological inference based only on single nucleotide variant distances may lead to significant differences in the number of defined clusters if variant allele frequency thresholds for consensus genome generation differ between laboratories. These results underscore the need for a unified, best-practices approach to bioinformatics between laboratories working on a common outbreak problem.

A catalogue of tools and variables from crisis and routine care to support decision-making about allocation of intensive care beds and ventilator treatment during pandemics: Scoping review

Fri, 01 Jan 2021 00:00:00 GMT

A catalogue of tools and variables from crisis and routine care to support decision-making about allocation of intensive care beds and ventilator treatment during pandemics: Scoping review Cardona, Magnolia; Dobler, Claudia C; Koreshe, Eyza; Heyland, Daren K; Nguyen, Rebecca H; Sim, Joan P Y; Clark, Justin; Psirides, Alex PURPOSE: This scoping review sought to identify objective factors to assist clinicians and policy-makers in making consistent, objective and ethically sound decisions about resource allocation when healthcare rationing is inevitable. MATERIALS AND METHODS: Review of guidelines and tools used in ICUs, hospital wards and emergency departments on how to best allocate intensive care beds and ventilators either during routine care or developed during previous epidemics, and association with patient outcomes during and after hospitalisation. RESULTS: Eighty publications from 20 countries reporting accuracy or validity of prognostic tools/algorithms, or significant correlation between prognostic variables and clinical outcomes met our eligibility criteria: twelve pandemic guidelines/triage protocols/consensus statements, twenty-two pandemic algorithms, and 46 prognostic tools/variables from non-crisis situations. Prognostic indicators presented here can be combined to create locally-relevant triage algorithms for clinicians and policy makers deciding about allocation of ICU beds and ventilators during a pandemic. No consensus was found on the ethical issues to incorporate in the decision to admit or triage out of intensive care. CONCLUSIONS: This review provides a unique reference intended as a discussion starter for clinicians and policy makers to consider formalising an objective a locally-relevant triage consensus document that enhances confidence in decision-making during healthcare rationing of critical care and ventilator resources.

Opioid agonist treatment and patient outcomes during the COVID_19 pandemic in south east Sydney, Australia

Fri, 01 Jan 2021 00:00:00 GMT

Opioid agonist treatment and patient outcomes during the COVID_19 pandemic in south east Sydney, Australia Lintzeris, Nicholas; Deacon, Rachel M.; Hayes, Victoria; Cowan, Tracy; Mills, Llewellyn; Parvaresh, Laila; Dodds, Lucy Harvey; Jansen, Louisa; Dojcinovic, Raelene; Leung, Man Cho; Demirkol, Apo; Finch, Therese; Mammen, Kristie Introduction In early 2020, many services modified their delivery of opioid treatment in response to the COVID-19 pandemic, to limit viral spread and maintain treatment continuity. We describe the changes to treatment and preliminary analysis of the association with patients' substance use and well-being. Methods A pre-post comparison of treatment conditions and patient self-reported outcomes using data extracted from electronic medical records in the 5 months before (December 2019–April 2020) and after (May 2020–September 2020) changes were implemented in three public treatment services in South Eastern Sydney Local Health District. Results Data are available for 429/460 (93%) patients. Few (21, 5%) dropped out of treatment. In the ‘post’ period there was significantly more use of depot buprenorphine (12–24%), access to any take-away doses (TAD; 24–69%), access to ≥6 TAD per week (7–31%), pharmacy dosing (24–52%) and telehealth services. There were significant reductions in average opioid and benzodiazepine use, increases in cannabis use, with limited group changes in social conditions, or quality of life, psychological and physical health. At an individual level, 22% of patients reported increases in their use of either alcohol, opioids, benzodiazepines or stimulants of ≥4 days in the past 4 weeks. Regression analysis indicates increases in substance use were associated with higher levels of supervised dosing. Discussion and Conclusions These preliminary findings suggest that the modified model of care continued to provide safe and effective treatment, during the pandemic. Notably, there was no association between more TAD and significant increases in substance use. Limitations are discussed and further evaluation is needed.

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

Wed, 01 Jan 2020 00:00:00 GMT

Reducing 4D CT imaging artifacts at the source: first experimental results from the respiratory adaptive computed tomography (REACT) system Morton, Natasha; Sykes, Jonathan; Barber, Jeffrey; Hofmann, Christian; Keall, Paul; O'Brien, Ricky 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.

Real-Time Image Guided Ablative Prostate Cancer Radiation Therapy: Results From the TROG 15.01 SPARK Trial

Wed, 01 Jan 2020 00:00:00 GMT

Real-Time Image Guided Ablative Prostate Cancer Radiation Therapy: Results From the TROG 15.01 SPARK Trial Keall, Paul; Nguyen, Doan Trang; O'Brien, Ricky; Hewson, Emily; Ball, Helen; Poulsen, Per; Booth, Jeremy; Greer, Peter; Hunter, Perry; Wilton, Lee; Bromley, Regina; Kipritidis, John; Eade, Thomas; Kneebone, Andrew; Hruby, George; Moodie, Trevor; Hayden, Amy; Turner, Sandra; Arumugam, Sankar; Sidhom, Mark; Harcastle, Nick; Siva, Shankar; Tai, Keen-Hun; Gebski, Val; Martin, Jarad Purpose: Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy. Methods and materials: Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity. Results: Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities. Conclusions: Real-time IGRT is clinically effective for prostate cancer SABR.

Evaluating reconstruction algorithms for respiratory motion guided acquisition

Wed, 01 Jan 2020 00:00:00 GMT

Evaluating reconstruction algorithms for respiratory motion guided acquisition Dillon, Owen; Keall, Paul; Shieh, Chun-Chien; O'Brien, Ricky Conventional thoracic 4DCBCT scans take 1320 projections over 4 min. This paper investigates which reconstruction algorithms best leverage Respiratory-Motion-Guided (RMG) acquisition in order to reduce scan time and dose while maintaining image quality. We investigated a 200 projection, on average 1 min RMG acquisition. RMG acquisition ensures even angular separation between projections at each respiratory phase by adjusting the imaging gantry rotation to the patient respiratory signal in real time. Conventional 1320 projection data and RMG 200 projection data were simulated from 4DCT volumes of 14 patients. Each patient had an initial 4DCT reconstruction, treated as a planning 4DCT, and a 4DCT reconstruction acquired later, used for 4DCBCT data simulation and evaluation. Reconstructions were computed using the Feldkamp-David-Kress (FDK), McKinnon-Bates (MKB), RecOnstructiOn using Spatial and TEmporal Regularization (ROOSTER), and Motion Compensated FDK (MCFDK) algorithms. We also introduced and evaluated a novel MCMKB algorithm. Image quality was evaluated with Root-Mean-Square Error (RMSE), Structural SIMilarity index (SSIM) and Tissue Interface Sharpness (TIS). Rigid registration of the tumor volume regions between the reconstruction and the ground truth was used to evaluate geometric accuracy. Relative to conventional 4DCBCT acquisition, the RMG acquisition delivered 80% less dose and was on average 70% faster. The conventional-acquisition 4DFDK-reconstruction volumes had mean RMSE, SSIM, TIS and geometric error of 94, 0.9987, 2.69 and 1.19 mm respectively. The RMG-acquisition MCFDK-reconstruction volumes had mean RMSE, SSIM, TIS and geometric error of 113, 0.9986, 1.76 and 1.77 mm respectively with minimal increase in computational cost. These results suggest scan time and dose can be significantly reduced with minimal impact on reconstruction quality by implementing RMG acquisition and motion compensated reconstruction.

Is multileaf collimator tracking or gating a better intrafraction motion adaptation strategy? An analysis of the TROG 15.01 stereotactic prostate ablative radiotherapy with KIM (SPARK) trial

Wed, 01 Jan 2020 00:00:00 GMT

Is multileaf collimator tracking or gating a better intrafraction motion adaptation strategy? An analysis of the TROG 15.01 stereotactic prostate ablative radiotherapy with KIM (SPARK) trial Hewson, Emily; Nguyen, Doan Trang; O'Brien, Ricky; Poulsen, Per; Booth, Jeremy; Greer, Peter; Eade, Thomas; Kneebone, Andrew; Hruby, George; Moodie, Trevor; Hayden, Sandra; Hardcastle, Nicholas; Siva, Shankar; Tai, Keen-Hun; Martin, Jarad; Keall, Paul Purpose: Stereotactic Ablative Radiotherapy (SABR) has recently emerged as a favourable treatment option for prostate cancer patients. With higher doses delivered over fewer fractions, motion adaptation is a requirement for accurate delivery of SABR. This study compared the efficacy of multileaf collimator (MLC) tracking vs. gating as a real-time motion adaptation strategy for prostate SABR patients enrolled in a clinical trial. Methods: Forty-four prostate cancer patients treated over five fractions in the TROG 15.01 SPARK trial were analysed in this study. Forty-nine fractions were treated using MLC tracking and 166 fractions were treated using beam gating and couch shifts. A time-resolved motion-encoded dose reconstruction method was used to evaluate the dose delivered using each motion adaptation strategy and compared to an estimation of what would have been delivered with no motion adaptation strategy implemented. Results: MLC tracking and gating both delivered doses closer to the plan compared to when no motion adaptation strategy was used. Differences between MLC tracking and gating were small with differences in the mean discrepancy from the plan of -0.3% (CTV D98%), 1.4% (CTV D2%), 0.4% (PTV D95%), 0.2% (rectum V30Gy) and 0.0% (bladder V30Gy). On average, 0.5 couch shifts were required per gated fractions with a mean interruption duration of 1.8 ± 2.6 min per fraction treated using gating. Conclusion: Both MLC tracking and gating were effective strategies at improving the accuracy of the dose delivered to the target and organs at risk. While dosimetric performance was comparable, gating resulted in interruptions to treatment.

Toward improved 3D carotid artery imaging with Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT)

Wed, 01 Jan 2020 00:00:00 GMT

Toward improved 3D carotid artery imaging with Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT) Reynolds, Tess; Dillon, Owen; Prinable, Joseph; Whelan, Brendan; Keall, Paul Purpose: Interventional treatments of aneurysms in the carotid artery are increasingly being supplemented with three-dimensional (3D) x-ray imaging. The 3D imaging provides additional information on device sizing and stent malapposition during the procedure. Standard 3D x-ray image acquisition is a one-size fits all model, exposing patients to additional radiation and results in images that may have cardiac-induced motion blur around the artery. Here, we investigate the potential of a novel dynamic imaging technique Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT) to personalize image acquisition by adapting the gantry velocity and projection rate in real-time to changes in the patient's electrocardiogram (ECG) trace. Methods: We compared the total number of projections acquired, estimated carotid artery widths and image quality between ACROBEAT and conventional (single rotation fixed gantry velocity and acquisition rate, no ECG-gating) scans in a simulation study and a proof-of-concept physical phantom experimental study. The simulation study dataset consisted of an XCAT digital software phantom programmed with five patient-measured ECG traces and artery motion curves. The ECG traces had average heart rates of 56, 64, 76, 86, and 100 bpm. To validate the concept experimentally, we designed and manufactured the physical phantom from an 8-mm diameter silicon rubber tubing cast into Phytagel. An artery motion curve and the ECG trace with an average heart rate of 56 bpm was passed through the phantom. To implement ACROBEAT on the Siemens ARTIS pheno angiography system for the proof-of-concept experimental study, the Siemens Test Automation Control System was used. The total number of projections acquired and estimated carotid artery widths were compared between the ACROBEAT and conventional scans. As the ground truth was available for the simulation studies, the image quality metrics of Root Mean Square Error (RMSE) and Structural Similarity Index (SSIM) were also utilized to assess image quality. Results: In the simulation study, on average, ACROBEAT reduced the number of projections acquired by 63%, reduced carotid width estimation error by 65%, reduced RMSE by 11% and improved SSIM by 27% compared to conventional scans. In the proof-of-concept experimental study, ACROBEAT enabled a 60% reduction in the number of projections acquired and reduced carotid width estimation error by 69% compared to a conventional scan. Conclusion: A simulation and proof-of-concept experimental study was completed applying a novel dynamic imaging protocol, ACROBEAT, to imaging the carotid artery. The ACROBEAT results showed significantly improved image quality with fewer projections, offering potential applications to intracranial interventional procedures negatively affected by cardiac motion.

Experimental evaluation of the dosimetric impact of intrafraction prostate rotation using film measurement with a 6DoF robotic arm

Wed, 01 Jan 2020 00:00:00 GMT

Experimental evaluation of the dosimetric impact of intrafraction prostate rotation using film measurement with a 6DoF robotic arm Shi, Kehuan; Dipuglia, Andrew; Booth, Jeremy; Alnaghy, Saree; Kyme, Andre; Keall, Paul; Nguyen, Doan Trang Purpose: Tumor motion during radiotherapy can cause a reduction in target dose coverage and an increase in healthy tissue exposure. Tumor motion is not strictly translational and often exhibits complex six degree-of-freedom (6DoF) translational and rotational motion. Although the dosimetric impact of prostate tumor translational motion is well investigated, the dosimetric impact of 6DoF motion has only been studied with simulations or dose reconstruction. This study aims to experimentally quantify the dose error caused by 6DoF motion. The experiment was designed to test the hypothesis that 6DoF motion would cause larger dose errors than translational motion alone through gamma analyses of two-dimensional film measurements. Methods: Four patient-measured intrafraction prostate motion traces and four VMAT 7.25 Gy/Fx SBRT treatment plans were selected for the experiment. The traces represented typical motion patterns, including small-angle rotations (<4°), transient movement, persistent excursion, and erratic rotations (>6°). Gafchromic film was placed inside a custom-designed phantom, held by a high-precision 6DoF robotic arm for dose measurements in the coronal plane during treatment delivery. For each combination of the motion trace and treatment plan, two film measurements were made, one with 6DoF motion and the other with the three-dimensional (3D) translation components of the same trace. A gamma pass rate criteria of 2% relative dose/2 mm distance-to-agreement was used in this study and evaluated for each measurement with respect to the static reference film. Two test thresholds, 90% and 50% of the reference dose, were applied to investigate the difference in dose coverage for the PTV region and surrounding areas, respectively. The hypothesis was tested using a Wilcoxon signed-rank test. Results: For each of the 16 plan and motion trace pairs, a reduction in the gamma pass rate was observed for 6DoF motion compared with 3D translational motion. With 90% gamma-test threshold, the reduction was 5.8% ± 7.1% (P < 0.01). With 50% gamma-test threshold, the reduction was 4.1% ± 4.8% (P < 0.01). Conclusion: For the first time, the dosimetric impact of intrafraction prostate rotation during SBRT treatment was measured experimentally. The experimental results support the hypothesis that 6DoF tumor motion causes higher dose error than translation motion alone.

Optimising lung imaging for cancer radiation therapy

Wed, 01 Jan 2020 00:00:00 GMT

Optimising lung imaging for cancer radiation therapy Dunbar, Michelle; O'Brien, Ricky; Froyland, Gary Effective radiotherapy is dependent on being able to (i) visualise the tumour clearly, and (ii) deliver the correct dose to the cancerous tissue, whilst sparing the healthy tissue as much as possible. In the presence of tumour motion, both of these tasks become increasingly difficult to perform accurately. This increases the likelihood of an incorrect dose being delivered to cancerous tissue and exposure of healthy tissue to unnecessary radiation. For tumours in the lung and thoracic region subject to respiratory-induced motion, 4D Cone-Beam CT (4D-CBCT) is a novel approach for producing a sequence of 3D images of the patient’s anatomy throughout different phases of the respiratory cycle. However, current implementations involve sub-optimal heuristic approaches to acquire the imaging data required to account for tumour motion. This leads to undersampling of images for particular phases in the respiratory cycle (such as peak inhale and exhale), resulting in noisy or poorly reconstructed 3D images. In this paper we present a novel Mixed Integer Program (MIP) to optimise the timing and angles for the acquisition of imaging data. The result is greatly enhanced image quality for each image across the respiratory cycle, whilst minimising motion blur. Numerical experiments indicate that our approach universally improves over the conventional acquisition process by 93% and simultaneously reduces unnecessary dose to the patient and can be solved in under a minute.

Simulated multileaf collimator tracking for stereotactic liver radiotherapy guided by kilovoltage intrafraction monitoring: Dosimetric gain and target overdose trends

Wed, 01 Jan 2020 00:00:00 GMT

Simulated multileaf collimator tracking for stereotactic liver radiotherapy guided by kilovoltage intrafraction monitoring: Dosimetric gain and target overdose trends Poulsen, Per; Murtaza, Ghulam; Worm, Esben; Ravkilde, Thomas; O'Brien, Ricky; Grau, Cai; Hoyer, Morten; Keall, Paul Purpose: To investigate the potential benefit of multileaf collimator (MLC) tracking guided by kilovoltage intrafraction monitoring (KIM) during stereotactic body radiotherapy (SBRT) in the liver, and to understand trends of target overdose with MLC tracking. Methods: Six liver SBRT patients with 2-3 implanted gold markers received SBRT delivered with volumetric modulated arc therapy (VMAT) in three fractions using daily cone-beam CT setup. The CTV-to-PTV margins were 5 mm in the axial plane and 10 mm in the cranio-caudal directions, and the plans were designed to give minimum target doses of 95% (CTV) and 67% (PTV). The three-dimensional marker trajectory estimated by post-treatment analysis of kV fluoroscopy images acquired throughout treatment delivery was assumed to represent the tumor motion. MLC tracking guided by real-time KIM was simulated. The reduction in CTV D95 (minimum dose to 95% of the clinical target volume) relative to the planned D95 (ΔD95) was compared between actual non-tracking and simulated MLC tracking treatments. Results: MLC tracking maintained a high CTV dose coverage for all 18 fractions with ΔD95 (mean: 0.2 percentage points (pp), range: -1.7 to 1.9 pp) being significantly lower than for the actual non-tracking treatments (mean: 6.3 pp range: 0.6-16.0 pp) (p = 0.002). MLC tracking of large target motion perpendicular to the MLC leaves created dose artifacts with regions of overdose in the CTV. As a result, the mean dose in spherical volumes centered in the middle of the CTV was on average 2.4 pp (5 mm radius sphere) and 1.3 pp (15 mm radius sphere) higher than planned (p = 0.002). Conclusions: Intrafraction tumor motion can deteriorate the CTV dose of liver SBRT. The planned CTV dose coverage may be restored with KIM-guided MLC tracking. However, MLC tracking may have a tendency to create hotspots in the CTV.

Dual cardiac and respiratory gated thoracic imaging via adaptive gantry velocity and projection rate modulation on a linear accelerator: A Proof-of-Concept Simulation Study.

Tue, 01 Jan 2019 00:00:00 GMT

Dual cardiac and respiratory gated thoracic imaging via adaptive gantry velocity and projection rate modulation on a linear accelerator: A Proof-of-Concept Simulation Study. Reynolds, T; Shieh, C-C; Keall, P; O'Brien, R Purpose: Cardiac motion is typically not accounted for during pretreatment imaging for central lung and mediastinal tumors. However, cardiac induced tumor motion averages 5.8 mm for esophageal tumors and 3-5 mm for some lung tumors, which can result in positioning errors. Our aim is to reduce both cardiac- and respiratory-induced motion artifacts in thoracic cone beam computed tomography (CBCT) images through gantry velocity and projection rate modulation on a standard linear accelerator (linac). Methods: The acquisition of dual cardiac and respiratory gated CBCT thoracic images was simulated using the XCAT phantom with patient-measured respiratory and ECG traces. The gantry velocity and projection rate were modulated based on the cardiac and respiratory signals to maximize the angular consistency between adjacent projections in the gated cardiac-respiratory bin. The mechanical limitations of a gantry-mounted CBCT system were investigated. For our protocol, images were acquired during the 60%-80% window of cardiac phase and 20% displacement either side of peak exhale of the respiratory cycle. The comparator method was the respiratory-only gated CBCT acquisition with constant gantry speed and projection rate in routine use for respiratory correlated four-dimensional (4D) CBCT. All images were reconstructed using the Feldkamp-Davis-Kress (FDK) algorithm. The methods were compared in terms of image sharpness as measured using the edge response width (ERW) and contrast as measured using the contrast to noise ratio (CNR). The effects of the total number of projections acquired and magnitude of cardiac motion on scan time and image quality were also investigated. Results: Median total scan times with our protocol ranged from 117 s (40 projections) through to 296 s (100 projections), compared with 240 s for the conventional protocol (1320 projections). The scan times were dictated by the number of projections acquired, heart rate, length of the respiratory cycle and mechanical constraints of the CBCT system. Our protocol was able to provide between 8% and 43% decrease in the median value of the ERW in the anterior/posterior (AP) direction across the 17 traces when there was 0.5 cm of cardiac motion and between 35% and 64% decrease when there was 1.0 cm of cardiac motion over conventional acquisition. In the superior-inferior (SI) direction, our protocol was able to provide between 22% and 26% decrease in the median value of the ERW across the 17 traces when there was 0.5 cm of cardiac motion and between 30% and 35% decrease when there was 1.0 cm of cardiac motion over conventional acquisition. The magnitude of the cardiac motion did not have an observable effect on the median value of the CNR. Across all 17 traces, our adaptive protocol produced noticeably more consistent, albeit lower CNR values compared with conventional acquisition. Conclusion: For the first time, the potential of adapting CBCT image acquisition to changes in the patient's cardiac and respiratory rates simultaneously for applications in radiotherapy was investigated. This work represents a step towards thoracic imaging that reduces the effects of both cardiac and respiratory motion on image quality.

Technical Note: The first live treatment on a 1.0 Tesla inline MRI-linac.

Tue, 01 Jan 2019 00:00:00 GMT

Technical Note: The first live treatment on a 1.0 Tesla inline MRI-linac. Liney, G; Jelen, U; Byrne, H; Dong, B; Roberts, TL; Kuncic, Z; Keall, P Purpose: This work describes the first live imaging and radiation delivery performed on a prototype 1.0 T inline MRI-Linac system in a rat brain tumor model, which was conducted on 29 January 2019. Methods: A human scale 1.0 T MRI-Linac was adapted to be suitable for animal studies via a specially constructed open 6-channel receiver radiofrequency (RF) coil. A Fischer rat injected with 9L glioma cells in the right hemisphere was imaged and irradiated at day 11 post surgery as part of a larger cohort survival study. The rat was anesthetized and positioned at the iscocenter of the MRI-Linac. Imaging was used to localize the brain and confirm the presence of a tumor following the administration of a gadolinium nanoparticle contrast agent. A single dose of 10 Gy was delivered using a 2.25 cm × 2.90 cm radiation field covering the whole brain and verified with radiosensitive film in situ. Real-time imaging was used throughout the irradiation period to monitor the animal and target position. Results: The signal-to-noise ratio (SNR) measured in the rat brain was 38. Postcontrast imaging was able to demonstrate a tumor of 5 mm diameter in the upper right hemisphere of the brain approximately 45 min after administration of the nanoparticles. The radiation beam had no impact on SNR and images at the rate of 2 Hz were effective in monitoring both respiration and intrafractional motion. In vivo film dosimetry confirmed the intended dose delivery. The total procedure time was 35 min. Conclusions: We have successfully used MRI guidance to localize and subsequently deliver a radiation field to the whole brain of a rat with a right hemispheric tumor. Real-time imaging during beam on was of sufficient quality to monitor breathing and perform exception gating of the treatment. This represents the first live use of a high field inline MRI-Linac.

See, Think, and Act: Real-Time Adaptive Radiotherapy.

Tue, 01 Jan 2019 00:00:00 GMT

See, Think, and Act: Real-Time Adaptive Radiotherapy. Keall, P; Poulsen, P; Booth, J The world is embracing the information age, with real-time data at hand to assist with many decisions. Similarly, in cancer radiotherapy we are inexorably moving toward using information in a smarter and faster fashion, to usher in the age of real-time adaptive radiotherapy. The three critical steps of real-time adaptive radiotherapy, aligned with driverless vehicle technology are a continuous see, think, and act loop. See: use imaging systems to probe the patient anatomy or physiology as it evolves with time. Think: use current and prior information to optimize the treatment using the available adaptive degrees of freedom. Act: deliver the real-time adapted treatment. This paper expands upon these three critical steps for real-time adaptive radiotherapy, provides a historical context, reviews the clinical rationale, and gives a future outlook for real-time adaptive radiotherapy.

Dosimetric impact of intrafraction rotations in stereotactic prostate radiotherapy: A subset analysis of the TROG 15.01 SPARK trial.

Tue, 01 Jan 2019 00:00:00 GMT

Dosimetric impact of intrafraction rotations in stereotactic prostate radiotherapy: A subset analysis of the TROG 15.01 SPARK trial. Wolf, J; Nicholls, J; Hunter, P; Nguyen, DT; Keall, P; Martin, J Background and purpose: Accurate delivery of radiotherapy is critical to achieve optimal treatment outcomes. Interfraction translational IGRT is now standard, and intrafraction motion management is becoming accessible. Some platforms can report both translational and rotational movements in real time. This study aims to quantify the dosimetric impact of observed intrafraction rotation of the prostate measured using monitoring software. Materials and methods: A dose grid resampling algorithm was used to model the dosimetric impact of prostate rotations for 20 patients on a SBRT prostate clinical trial. Translations were corrected before and during treatment, but rotations were not. Real time rotation data were acquired using KIM and a cumulative histogram analysis performed. Prostate volumes were rotated by the range of observed angles and used to calculate DVH data. Results: The pitch axis had a higher range of observed rotations resulting in only 7 patients spending at least 90% of the beam on time across all fractions within rotation angles resulting in PTV D95% ≥36 Gy in this axis. The yaw and roll axes saw 17 and 15 patients respectively achieving this criterion. All but one of 20 patients exceeded CTV D98% ≥36 Gy for all observed rotation angles. Conclusions: Current CTV-PTV margins do not result in compromised CTV dose coverage due to inter and intrafraction prostate rotations in the absence of other uncertainties. Reduced PTV dosing is due to the extremely conformal treatment delivery but is unlikely to be clinically deleterious. Prostate standard IGRT should continue to focus on correcting any observed translational movements. Margin reduction could be explored in conjunction with other uncertainties.

Imaging of regional ventilation: Is CT ventilation imaging the answer? A systematic review of the validation data.

Tue, 01 Jan 2019 00:00:00 GMT

Imaging of regional ventilation: Is CT ventilation imaging the answer? A systematic review of the validation data. Hegi-Johnson, F; de Ruysscher, D; Keall, P; Hendriks, L; Vinogradskiy, Y; Yamamoto, T; Tahir, B; Kipritidis, J Computed Tomography Ventilation Imaging (CTVI) is an experimental imaging modality that derives regional lung function information from non-contrast respiratory-correlated CT datasets. Despite CTVI being extensively studied in cross-modality imaging comparisons, there is a lack of consensus on the state of its clinical validation in humans. This systematic review evaluates the CTVI clinical validation studies to date, highlights their common strengths and weaknesses and makes recommendations. We performed a PUBMED and EMBASE search of all English language papers on CTVI between 2000 and 2018. The results of these searches were filtered in accordance to a set of eligibility criteria and analysed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. One hundred and forty-four records were identified, and 66 full text records were reviewed. After detailed assessment, twenty-three full text papers met the selection criteria and were included in the final review. This included thirteen prospective studies, with 579 human subjects. Studies used diverse methodologies, with a large amount of heterogeneity between different studies in terms of the reference ventilation imaging modality (e.g. nuclear medicine, hyperpolarised gas MRI), imaging parameters, DIR algorithm(s) used, and ventilation metric(s) applied. The most common ventilation metrics used deformable image registration to evaluate the exhale-to-inhale motion field Jacobian determinant (DIR-Jac) or changes in air volume content based on Hounsfield Units (DIR-HU). The strength of correlation between CTVI and the reference ventilation imaging modalities was moderate to strong when evaluated at the lobar or global level, with the average ± S.D. (number of studies) linear regression correlation coefficients were 0.73 ± 0.25 (n = 6) and 0.86 ± 0.11 (n = 12) for DIR-Jac and DIR-HU respectively, and the SPC were 0.45 ± 0.31 (n = 6) and 0.41 ± 0.11 (n = 5) for DIR-Jac and DIR-HU respectively. We concluded that it is difficult to make a broad statement about the validity of CTVI due to the diverse methods used in the validation literature. Typically, CTVI appears to show reasonable cross-modality correlations at the lobar/whole lung level but poor correlations at the voxel level. Since CTVI is seeing new implementations in prospective trials, it is clear that refinement and standardization of the clinical validation methodologies are required. CTVI appears to be of relevance in radiotherapy planning, particularly in patients whose main pulmonary impairment is not a gas exchange problem but alternative imaging approaches may need to be considered in patients with other pulmonary diseases (i.e. restrictive or gas exchange problems).

SPARE: Sparse-view reconstruction challenge for 4D cone-beam CT from a 1-min scan.

Tue, 01 Jan 2019 00:00:00 GMT

SPARE: Sparse-view reconstruction challenge for 4D cone-beam CT from a 1-min scan. Shieh, C-C; Gonzalez, Y; Li, B; Jia, X; Rit, S; Mory, S; Riblett, M; Hugo, G; Zhang, Y; Jiang, Z; Liu, X; Ren, L; Keall, P Purpose: Currently, four-dimensional (4D) cone-beam computed tomography (CBCT) requires a 3-4 min full-fan scan to ensure usable image quality. Recent advancements in sparse-view 4D-CBCT reconstruction have opened the possibility to reduce scan time and dose. The aim of this study is to provide a common framework for systematically evaluating algorithms for 4D-CBCT reconstruction from a 1-min scan. Using this framework, the AAPM-sponsored SPARE Challenge was conducted in 2018 to identify and compare state-of-the-art algorithms. Methods: A clinically realistic CBCT dataset was simulated using patient CT volumes from the 4D-Lung database. The selected patients had multiple 4D-CT sessions, where the first 4D-CT was used as the prior CT, and the rest were used as the ground truth volumes for simulating CBCT projections. A GPU-based Monte Carlo tool was used to simulate the primary, scatter, and quantum noise signals. A total of 32 CBCT scans of nine patients were generated. Additional qualitative analysis was performed on a clinical Varian and clinical Elekta dataset to validate the simulation study. Participants were blinded from the ground truth, and were given 3 months to apply their reconstruction algorithms to the projection data. The submitted reconstructions were analyzed in terms of root-mean-squared-error (RMSE) and structural similarity index (SSIM) with the ground truth within four different region-of-interests (ROI) - patient body, lungs, planning target volume (PTV), and bony anatomy. Geometric accuracy was quantified as the alignment error of the PTV. Results: Twenty teams participated in the challenge, with five teams completing the challenge. Techniques involved in the five methods included iterative optimization, motion-compensation, and deformation of the prior 4D-CT. All five methods rendered significant reduction in noise and streaking artifacts when compared to the conventional Feldkamp-Davis-Kress (FDK) algorithm. The RMS of the three-dimensional (3D) target registration error of the five methods ranged from 1.79 to 3.00 mm. Qualitative observations from the Varian and Elekta datasets mostly concur with those from the simulation dataset. Each of the methods was found to have its own strengths and weaknesses. Overall, the MA-ROOSTER method, which utilizes a 4D-CT motion model for temporal regularization, had the best and most consistent image quality and accuracy. Conclusion: The SPARE Challenge represents the first framework for systematically evaluating state-of-the-art algorithms for 4D-CBCT reconstruction from a 1-min scan. Results suggest the potential for reducing scan time and dose for 4D-CBCT. The challenge dataset and analysis framework are publicly available for benchmarking future reconstruction algorithms.

Real-time direct diaphragm tracking using kV imaging on a standard linear accelerator.

Tue, 01 Jan 2019 00:00:00 GMT

Real-time direct diaphragm tracking using kV imaging on a standard linear accelerator. Hindley, N; Keall, P; Booth, J; Shieh, C-C Purpose: As the predominant driver of respiratory motion, the diaphragm represents a key surrogate for motion management during the irradiation of thoracic cancers. Existing approaches to diaphragm tracking often produce phase-based estimates, suffer from lateral side failures or are not executable in real-time. In this paper, we present an algorithm that continuously produces real-time estimates of three-dimensional (3D) diaphragm position using kV images acquired on a standard linear accelerator. Methods: Patient-specific 3D diaphragm models were generated via automatic segmentation on end-exhale four-dimensional-computed tomography (4D-CT) images. The estimated trajectory of diaphragmatic motion, referred to as the principal motion vector, was obtained by registering end-exhale to end-inhale 4D-CT images. Two-dimensional (2D) diaphragm masks were generated by forward-projecting 3D models over the complement of angles spanned during kV image acquisition. For each kV image, diaphragm position was determined by shifting angle-matched 2D masks along the principal motion vector and selecting the position of highest contrast on a vertical difference image. Retrospective analysis was performed using 22 cone beam CT (CBCT) image sequences for six lung cancer patients across two datasets. Given the current lack of objective ground truth for diaphragm position, our algorithm was evaluated by examining its ability to track implanted markers. Simple linear regression was used to construct 3D marker motion models and estimation errors were computed as the difference between estimated and ground truth marker positions. Additionally, Pearson correlation coefficients were used to characterize diaphragm-marker correlation. Results: The mean ± standard deviation of the estimation errors across all image sequences was -0.1 ± 0.7 mm, -0.1 ± 1.8 mm and 0.2 ± 1.4 mm in the LR, SI, and AP directions respectively. The 95th percentile of the absolute errors ranged over 0.5-3.1 mm, 1.6-6.7 mm, and 1.2-4.0 mm in the LR, SI, and AP directions, respectively. The mean ± standard deviation of diaphragm-marker correlations over all image sequences was -0.07 ± 0.57, 0.67 ± 0.49, and 0.29 ± 0.52 in the LR, SI, and AP directions, respectively. Diaphragm-marker correlation was observed to be highly dependent on marker position. Mean correlation along the SI axis ranged over 0.91-0.93 for markers situated in the lower lobes of the lung, while correlations ranging over -0.51-0.79 were observed for markers situated in the upper and middle lobes. Conclusion: This work advances a new approach to real-time direct diaphragm tracking in realistic treatment scenarios. By achieving continuous estimates of diaphragmatic motion, the proposed method has applications for both markerless tumor tracking and respiratory binning in 4D-CBCT.

Time-resolved Volumetric MRI in MRI-guided Radiotherapy: An in Silico Comparative Analysis

Tue, 01 Jan 2019 00:00:00 GMT

Time-resolved Volumetric MRI in MRI-guided Radiotherapy: An in Silico Comparative Analysis Paganelli, C; Portoso, S; Garau, N; Meschini, G; Via, R; Buizza, G; Keall, P; Riboldi, M; Baroni, G MRI-treatment units enable 2D cine-MRI centred in the tumour for motion detection in radiotherapy, but they lack 3D information due to spatio-temporal limits. To derive time-resolved 3D information, different approaches have been proposed in the literature, but a rigorous comparison among these strategies has not yet been performed. The goal of this study is to quantitatively investigate five published strategies that derive time-resolved volumetric MRI in MRI-guided radiotherapy: Propagation, out-of-plane motion compensation, Fayad model, ROI-based model and Stemkens model. Comparisons were performed using an MRI digital phantom generated with six different patient-derived motion signals and tumour-shapes. An average 4D cycle was generated as well as 2D cine-MRI data with corresponding 3D in-room ground truth. Quantitative analysis was performed by comparing the estimated 3D volume to the ground truth available for each 2D cine-MRI sample. A grouped patient statistical analysis was performed to evaluate the performance of the selected methods, in case of tumour tracking or motion estimation of the whole anatomy. Analyses were also performed based on patient characteristics. Quantitative ranking of the investigated methods highlighted that Propagation and ROI-based model strategies achieved an overall median tumour centre of mass 3D distance from the ground truth of 1.1 mm and 1.3 mm, respectively, and a diaphragm distance below 1.6 mm. Higher errors and variabilities were instead obtained for other methods, which lack the ability to compensate for in-room variations and to account for regional changes. These results were especially evident when further analysing patient characteristics, where errors above 2 mm/5 mm in tumour/diaphragm were found for more irregular breathing patterns in case of out-of-plane motion compensation, Fayad and Stemkens models. These findings suggest the potential of the proposed in silico framework to develop and compare strategies to estimate time-resolved 3DMRI in MRI-guided radiotherapy.

FLASH radiotherapy: Newsflash or flash in the pan?

Tue, 01 Jan 2019 00:00:00 GMT

FLASH radiotherapy: Newsflash or flash in the pan? Maxim, P; Keall, P; Cai, J No abstract. A point / counterpoint article on the merits of ultra-high dose rate radiation therapy.

Anatomical Deformation Due to Horizontal Rotation: Towards Gantry-Free Radiation Therapy

Tue, 01 Jan 2019 00:00:00 GMT

Anatomical Deformation Due to Horizontal Rotation: Towards Gantry-Free Radiation Therapy Buckley, J; Rai, R; Liney, G; Dowling, J; Holloway, L; Metcalfe, P; Keall, P Gantry-free radiation therapy systems may be simpler and more cost effective, particularly for MRI-guided photon or hadron therapy. This study aims to understand and quantify anatomical deformations caused by horizontal rotation with scan sequences sufficiently short to facilitate integration into an MRI-guided workflow. Rigid and non-rigid pelvic deformations due to horizontal rotation were quantified for a cohort of 8 healthy volunteers using a bespoke patient rotation system and a clinical MRI scanner. For each volunteer a reference scan was acquired at 0° followed by sequential faster scans in 45° increments through to 360°. All fast scans were registered to the 0° image via a three-step process: first, images were aligned using MR visible couch markers. Second, the scans were pre-processed then rigidly registered to the 0° image. Third, the rigidly registered scans were non-rigidly registered to the 0° image to assess soft tissue deformation. The residual differences after rigid and non-rigid registration were determined from the transformation matrix and the deformation vector field, respectively. The rigid registration yielded mean rotations of ⩽2.5° in all cases. The average 3D translational magnitudes range was 5.8 ± 2.9 mm-30.0 ± 11.0 mm. Translations were most significant in the left-right (LR) direction. Smaller translations were observed in the anterior-posterior (AP) and superior-inferior (SI) directions. The maximum deformation magnitudes range was: 10.0 ± 0.9 mm-28.0 ± 2.8 mm and average deformation magnitudes range: 2.3 ± 0.6 mm-7.5 ± 1.0 mm. Average non-rigid deformation magnitude was correlated with BMI (correlation coefficient 0.84, p = 0.01). Rigid pelvic deformations were most significant in the LR direction but could be accounted for with on-line adjustments. Non-rigid deformations can be significant and will need to be accounted for in order to facilitate the delivery of gantry-free therapy with an automated patient rotation system.

The Accuracy and Precision of the KIM Motion Monitoring System Used in the Multi-Institutional TROG 15.01 Stereotactic Prostate Ablative Radiotherapy With KIM (SPARK) Trial

Tue, 01 Jan 2019 00:00:00 GMT

The Accuracy and Precision of the KIM Motion Monitoring System Used in the Multi-Institutional TROG 15.01 Stereotactic Prostate Ablative Radiotherapy With KIM (SPARK) Trial Hewson, E; Nguyen, DT; O'Brien, R; Kim, J-H; Montanaro, T; Moodie, T; Greer, P; Hardcastle, N; Eade, T; Kneebone, A; Hruby, G; Hayden, A; Turner, S; Siva, S; Tai, K-H; Hunter, P; Sams, J; Poulsen, P; Booth, J; Martin, J; Keall, P Purpose: Kilovoltage intrafraction monitoring (KIM) allows for real-time image guidance for tracking tumor motion in six-degrees-of-freedom (6DoF) on a standard linear accelerator. This study assessed the geometric accuracy and precision of KIM used to guide patient treatments in the TROG 15.01 multi-institutional Stereotactic Prostate Ablative Radiotherapy with KIM trial and investigated factors affecting accuracy and precision. Methods: Fractions from 44 patients with prostate cancer treated using KIM-guided SBRT were analyzed across four institutions, on two different linear accelerator models and two different beam models (6 MV and 10 MV FFF). The geometric accuracy and precision of KIM was assessed from over 33 000 images (translation) and over 9000 images (rotation) by comparing the real-time measured motion to retrospective kV/MV triangulation. Factors potentially affecting accuracy, including contrast-to-noise ratio (CNR) of kV images and incorrect marker segmentation, were also investigated. Results: The geometric accuracy and precision did not depend on treatment institution, beam model or motion magnitude, but was correlated with gantry angle. The centroid geometric accuracy and precision of the KIM system for SABR prostate treatments was 0.0 ± 0.5, 0.0 ± 0.4 and 0.1 ± 0.3 mm for translation, and -0.1 ± 0.6°, -0.1 ± 1.4° and -0.1 ± 1.0° for rotation in the AP, LR and SI directions respectively. Centroid geometric error exceeded 2 mm for 0.05% of this dataset. No significant relationship was found between large geometric error and CNR or marker segmentation correlation. Conclusions: This study demonstrated the ability of KIM to locate the prostate with accuracy below other uncertainties in radiotherapy treatments, and the feasibility for KIM to be implemented across multiple institutions.

Technical Note: Experimental Characterization of the Dose Deposition in Parallel MRI-linacs at Various Magnetic Field Strengths

Tue, 01 Jan 2019 00:00:00 GMT

Technical Note: Experimental Characterization of the Dose Deposition in Parallel MRI-linacs at Various Magnetic Field Strengths Begg, J; Alnaghy, S; Causer, T; Alharthi, T; George, A; Glaubes, L; Dong, B; Goozee, G; Keall, P; Jelen, U; Liney, G; Holloway, L Purpose: Dose deposition measurements for parallel MRI-linacs have previously only shown comparisons between 0 T and a single available magnetic field. The Australian MRI-Linac consists of a magnet coupled with a dual energy linear accelerator and a 120 leaf Multi-Leaf Collimator with the radiation beam parallel to the magnetic field. Two different magnets, with field strengths of 1 and 1.5 T, were used during prototyping. This work aims to characterize the impact of the magnetic field at 1 and 1.5 T on dose deposition, possible by comparing dosimetry measured at both magnetic field strengths to measurements without the magnetic field. Methods: Dose deposition measurements focused on a comparison of beam quality (TPR20/10 ), PDD, profiles at various depths, surface doses, and field size output factors. Measurements were acquired at 0, 1, and 1.5 T. Beam quality was measured using an ion chamber in solid water at isocenter with appropriate TPR20/10 buildup. PDDs and profiles were acquired via EBT3 film placed in solid water either parallel or perpendicular to the radiation beam. Films at surface were used to determine surface dose. Output factors were measured in solid water using an ion chamber at isocenter with 10 cm solid water buildup. Results: Beam quality was within ±0.5% of the 0 T value for the 1 and 1.5 T magnetic field strengths. PDDs and profiles showed agreement for the three magnetic field strengths at depths beyond 20 mm. Deposited dose increased at shallower depths due to electron focusing. Output factors showed agreement within 1%. Conclusion: Dose deposition at depth for a parallel MRI-linac was not significantly impacted by either a 1 or 1.5 T magnetic field. PDDs and profiles at shallow depths and surface dose measurements showed significant differences between 0, 1, and 1.5 T due to electron focusing.

Harvest: an open-source tool for the validation and improvement of peptide identification metrics and fragmentation exploration

Fri, 01 Jan 2010 00:00:00 GMT

Harvest: an open-source tool for the validation and improvement of peptide identification metrics and fragmentation exploration McHugh, Leo C; Arthur, Jonathan W Background// Protein identification using mass spectrometry is an important tool in many areas of the life sciences, and in proteomics research in particular. Increasing the number of proteins correctly identified is dependent on the ability to include new knowledge about the mass spectrometry fragmentation process, into computational algorithms designed to separate true matches of peptides to unidentified mass spectra from spurious matches. This discrimination is achieved by computing a function of the various features of the potential match between the observed and theoretical spectra to give a numerical approximation of their similarity. It is these underlying “metrics” that determine the ability of a protein identification package to maximise correct identifications while limiting false discovery rates. There is currently no software available specifically for the simple implementation and analysis of arbitrary novel metrics for peptide matching and for the exploration of fragmentation patterns for a given dataset. Results// We present Harvest: an open source software tool for analysing fragmentation patterns and assessing the power of a new piece of information about the MS/MS fragmentation process to more clearly differentiate between correct and random peptide assignments. We demonstrate this functionality using data metrics derived from the properties of individual datasets in a peptide identification context. Using Harvest, we demonstrate how the development of such metrics may improve correct peptide assignment confidence in the context of a high-throughput proteomics experiment and characterise properties of peptide fragmentation. Conclusions// Harvest provides a simple framework in C++ for analysing and prototyping metrics for peptide matching, the core of the protein identification problem. It is not a protein identification package and answers a different research question to packages such as Sequest, Mascot, X!Tandem, and other protein identification packages. It does not aim to maximise the number of assigned peptides from a set of unknown spectra, but instead provides a method by which researchers can explore fragmentation properties and assess the power of novel metrics for peptide matching in the context of a given experiment. Metrics developed using Harvest may then become candidates for later integration into protein identification packages. Source code for Harvest 1.0