Improving the Quality of Care in Radiation Oncology using Artificial Intelligence.

Radiation therapy is a complex process involving multiple professionals and steps from simulation to treatment planning to delivery, and these procedures are prone to error. Additionally, the imaging and treatment delivery equipment in radiotherapy is highly complex and interconnected and represents another risk point in the quality of care. Numerous quality assurance tasks are carried out to ensure quality and to detect and prevent potential errors in the process of care. Recent developments in artificial intelligence provide potential tools to the radiation oncology community to improve the efficiency and performance of quality assurance efforts. Targets for artificial intelligence enhancement include the quality assurance of treatment plans, target and tissue structure delineation used in the plans, delivery of the plans and the radiotherapy delivery equipment itself. Here we review recent developments of artificial intelligence applications that aim to improve quality assurance processes in radiation therapy and discuss some of the challenges and limitations that require further development work to realise the potential of artificial intelligence for quality assurance.

Re-Validation of the COmprehensive Score for Financial Toxicity (COST): Assessing the Scale's Utility in Chronic Disease Populations.

OBJECTIVE: To report the psychometric properties of the COmprehensive Score for financial Toxicity (COST) patient-reported outcome measure (PROM), an 11-item scale previously validated among patients diagnosed with cancer and receiving chemotherapy. METHODS: Data come from a cross-sectional survey (n = 2755 response rate of 87%) of participants in a remote digital health coaching intervention collected between January 2017 and February 2019. RESULTS: COST demonstrated very good internal consistency (Cronbach's alpha = .89) and good convergent validity. Lower financial toxicity was associated with improved physical and mental well-being HRQOL measures after controlling for covariates (b = 0.13, P < .0001; b = 0.28, P < .0001, respectively). Supplemental analyses indicated that the COST instrument loaded on 2 factors. CONCLUSIONS: The COST measure of financial toxicity has good internal consistency and predictive validity in a sample of patients with chronic conditions. However, contrary to previous research examining the psychometric properties of COST in a sample of individuals with cancer, which found COST to be unidimensional, our analyses indicated that the COST measure of financial toxicity is multidimensional in a sample of individuals with chronic conditions. In particular, the items that asked about "general financial wellbeing" loaded on the second factor while "illness-related financial wellbeing" loaded on the first.

Two alternative methods for the retrieval of somatic cell populations from the mouse ovary.

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis, therefore, necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian samples. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both.

Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line.

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34-41 years of age; n=3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100nM ruxolitinib for 72h resulted in significant increases in STAT3 mRNA (P=0.034) and p-Y701-STAT1 protein (P=0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Constraints on Light Dark Matter Particles Interacting with Electrons from DAMIC at SNOLAB.

We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the DAMIC detector at SNOLAB of 2-6×10^{-22} A cm^{-2}. We evaluate the charge distribution of pixels that collect <10e^{-} for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c^{-2}. We also present new constraints on hidden-photon dark matter with masses in the range 1.2-30 eV c^{-2}.

An image-guided precision proton radiation platform for preclinical in vivo research.

There are many unknowns in the radiobiology of proton beams and other particle beams. We describe the development and testing of an image-guided low-energy proton system optimized for radiobiological research applications. A 50 MeV proton beam from an existing cyclotron was modified to produce collimated beams (as small as 2 mm in diameter). Ionization chamber and radiochromic film measurements were performed and benchmarked with Monte Carlo simulations (TOPAS). The proton beam was aligned with a commercially-available CT image-guided x-ray irradiator device (SARRP, Xstrahl Inc.). To examine the alternative possibility of adapting a clinical proton therapy system, we performed Monte Carlo simulations of a range-shifted 100 MeV clinical beam. The proton beam exhibits a pristine Bragg Peak at a depth of 21 mm in water with a dose rate of 8.4 Gy min-1 (3 mm depth). The energy of the incident beam can be modulated to lower energies while preserving the Bragg peak. The LET was: 2.0 keV µm-1 (water surface), 16 keV µm-1 (Bragg peak), 27 keV µm-1 (10% peak dose). Alignment of the proton beam with the SARRP system isocenter was measured at 0.24 mm agreement. The width of the beam changes very little with depth. Monte Carlo-based calculations of dose using the CT image data set as input demonstrate in vivo use. Monte Carlo simulations of the modulated 100 MeV clinical proton beam show a significantly reduced Bragg peak. We demonstrate the feasibility of a proton beam integrated with a commercial x-ray image-guidance system for preclinical in vivo studies. To our knowledge this is the first description of an experimental image-guided proton beam for preclinical radiobiology research. It will enable in vivo investigations of radiobiological effects in proton beams.

Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations.

PURPOSE: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. METHODS: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose-volume histogram. RESULTS: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 - 0.94, changes in patient body habitus, AUC = 0.67 - 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 - 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D99 change <7%]. Larger variations have even higher detectability. Displacements in the patient's position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D99 of the PTV changed by up to 57% for the patient position shifts considered here. CONCLUSIONS: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC's, and changes in the patient habitus. Shifts in the patient's position which can introduce large changes in the target dose coverage were not readily detected.

Validating FMEA output against incident learning data: A study in stereotactic body radiation therapy.

PURPOSE: Though failure mode and effects analysis (FMEA) is becoming more widely adopted for risk assessment in radiation therapy, to our knowledge, its output has never been validated against data on errors that actually occur. The objective of this study was to perform FMEA of a stereotactic body radiation therapy (SBRT) treatment planning process and validate the results against data recorded within an incident learning system. METHODS: FMEA on the SBRT treatment planning process was carried out by a multidisciplinary group including radiation oncologists, medical physicists, dosimetrists, and IT technologists. Potential failure modes were identified through a systematic review of the process map. Failure modes were rated for severity, occurrence, and detectability on a scale of one to ten and risk priority number (RPN) was computed. Failure modes were then compared with historical reports identified as relevant to SBRT planning within a departmental incident learning system that has been active for two and a half years. Differences between FMEA anticipated failure modes and existing incidents were identified. RESULTS: FMEA identified 63 failure modes. RPN values for the top 25% of failure modes ranged from 60 to 336. Analysis of the incident learning database identified 33 reported near-miss events related to SBRT planning. Combining both methods yielded a total of 76 possible process failures, of which 13 (17%) were missed by FMEA while 43 (57%) identified by FMEA only. When scored for RPN, the 13 events missed by FMEA ranked within the lower half of all failure modes and exhibited significantly lower severity relative to those identified by FMEA (p = 0.02). CONCLUSIONS: FMEA, though valuable, is subject to certain limitations. In this study, FMEA failed to identify 17% of actual failure modes, though these were of lower risk. Similarly, an incident learning system alone fails to identify a large number of potentially high-severity process errors. Using FMEA in combination with incident learning may render an improved overview of risks within a process.

Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults.

OBJECTIVE: To explore the associations between serum concentrations of vitamin D (25(OH)D) and all-cause mortality among US adults defined by lung function (LF) status, particularly among adults with obstructive LF (OLF). METHODS: Data from 10,795 adults aged 20-79 years (685 with restrictive LF (RLF) and 1309 with OLF) who participated in the Third National Health and Nutrition Examination Survey (1988-1994), had a spirometric examination, and were followed through 2006 were included. RESULTS: During 14.2 years of follow-up, 1792 participants died. Mean adjusted concentrations of 25(OH)D were 75.0 nmol/l (s.e. 0.7) for adults with normal LF (NLF), 70.4 nmol/l (s.e. 1.8) for adults with RLF, 75.5 nmol/l (s.e. 1.5) for adults with mild obstruction and 71.0 nmol/l (s.e. 1.9) among adults with moderate or worse obstruction (P=0.030). After adjustment for sociodemographic factors, lifestyle factors, clinical variables and prevalent chronic conditions, a concentration of <25 nmol/l compared with ⩾ 75 nmol//l was associated with mortality only among adults with NLF (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.03, 3.00). Among participants with OLF, adjusted HRs were 0.65 (95% CI 0.29, 1.48), 1.21 (95% CI 0.89, 1.66) and 0.97 (95% CI 0.78, 1.19) among those with concentrations <25, 25-<50 and 50-<75 nmol/l, respectively. CONCLUSIONS: Baseline concentrations of 25(OH)D did not significantly predict mortality among US adults with impaired LF.

The contribution of dynamic changes in photosynthesis to shade tolerance of two conifer species.

Generally 'shade tolerance' refers to the capacity of a plant to exist at low light levels but characteristics of shade can vary and must be taken into account in defining the term. We studied Abies amabilis Dougl. ex J.Forbes and Tsuga heterophylla (Raf.) Sarg. under a forest canopy in the northwest of the Olympic Peninsula, USA, which has low annual sunshine hours and frequent overcast days. Using BF3 sunshine sensors, we surveyed diffuse and total light received by saplings growing under a range of canopy openness up to 30%. We measured variation in photosynthetic capacity over the growing season and within days and estimated photosynthesis induction in relation to ambient light. Three components of shade tolerance are associated with variation in light climate: (i) Total light on the floor of an 88-year stand of naturally regenerated T. heterophylla was greater on overcast than clear days. Light on overcast days varied throughout the day sometimes with a cyclical pattern. (ii) Photosynthetic capacity, Amax, varied both through the growing season and within days. Amax was generally greater in the latter part of the growing season, being limited by temperature and stomatal conductance, gs, at times during the early part. Saplings in more shaded areas had lower Amax and in the latter part of the growing season Amax was found to decline from mid-afternoon. (iii) Two patterns of photosynthesis induction to increased light were found. In a mean ambient light of 139 µmol m(-2) s(-1), induction had a curvilinear response to a step increase in light with a mean time constant, τ, of 112.3 s. In a mean ambient light of 74 µmol m(-2) s(-1), induction had a two-part increase: one with τ1 of 11.3 s and the other with τ2 of 184.0 s. These are the smallest published values of τ to date. (iv) Both variation in photosynthetic capacity and induction are components of shade tolerance where light varies over time. Amax acclimates to seasonal and diurnal changes in light and varies between microenvironments. The rapid induction processes can cause a rapid response of photosynthesis to changes in diffuse or direct light.

The dynamic relationship between plant architecture and competition.

In this review, structural and functional changes are described in single-species, even-aged, stands undergoing competition for light. Theories of the competition process as interactions between whole plants have been advanced but have not been successful in explaining these changes and how they vary between species or growing conditions. This task now falls to researchers in plant architecture. Research in plant architecture has defined three important functions of individual plants that determine the process of canopy development and competition: (i) resource acquisition plasticity; (ii) morphogenetic plasticity; (iii) architectural variation in efficiency of interception and utilization of light. In this review, this research is synthesized into a theory for competition based on five groups of postulates about the functioning of plants in stands. Group 1: competition for light takes place at the level of component foliage and branches. Group 2: the outcome of competition is determined by the dynamic interaction between processes that exert dominance and processes that react to suppression. Group 3: species differences may affect both exertion of dominance and reaction to suppression. Group 4: individual plants may simultaneously exhibit, in different component parts, resource acquisition and morphogenetic plasticity. Group 5: mortality is a time-delayed response to suppression. Development of architectural models when combined with field investigations is identifying research needed to develop a theory of architectural influences on the competition process. These include analyses of the integration of foliage and branch components into whole-plant growth and precise definitions of environmental control of morphogenetic plasticity and its interaction with acquisition of carbon for plant growth.

Odor tracking flight of male Manduca sexta moths along plumes of different cross-sectional area.

Males of the hawkmoth, Manduca sexta, track wind-borne plumes of female sex pheromone by flying upwind, while continuously turning from side-to-side and changing altitude. Their characteristic "zigzagging" trajectory has long been thought to result from the interaction of two mechanisms, an odor-modulated orientation to wind and a built-in central nervous system turning program. An interesting and as of yet unanswered question about this tracking behavior is how the cross-section of an odor plume or its clean-air "edges" affects moths' odor tracking behavior. This study attempts to address this question by video recording and analyzing the behavior of freely flying M. sexta males tracking plumes from pheromone sources of different lengths and orientations with equal odor concentration per unit area. Our results showed that moths generated significantly wider tracks in wide plumes from the longest horizontally-oriented sources as compared to narrower point-source plumes, but had relatively unaltered tracks when orienting to plumes from the same length sources oriented vertically. This suggests that in addition to wind and the presence of pheromones, the area of the plume's cross section or its edges may also play an important role in the plume tracking mechanisms of M. sexta.

Monocular and binocular low-contrast visual acuity and optical coherence tomography in pediatric multiple sclerosis.

BACKGROUND: Low-contrast letter acuity and optical coherence tomography (OCT) capture visual dysfunction and axonal loss in adult-onset multiple sclerosis (MS), and have been proposed as secondary outcome metrics for therapeutic trials. Clinical trials will soon be launched in pediatric MS, but such outcome metrics have not been well-validated in this population. OBJECTIVES: To determine whether MS onset during childhood and adolescence is associated with measurable loss of visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such features are noted only in the context of clinical optic nerve inflammation (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve relapses, and to define the optimal methods for such detection. STUDY DESIGN: Cross-sectional study. METHODS: Monocular and binocular high- and low-contrast letter acuity and contrast sensitivity were assessed in a cross-sectional cohort of children (ages 5 to 17 years) with MS (N=22 patients, 44 eyes; 8 patients with a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three academic centers. Binocular summation was determined by calculating the number of letters correctly identified using the binocular score minus the better eye score for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3). Results were analyzed in terms of "eyes" as: MS ON+, MS ON-, and control eyes. Generalized estimating equation (GEE) regression models were used to compare patients to controls. RESULTS: Traditional high-contrast visual acuity scores did not differ between MS ON+, MS ON-, and controls eyes. MS ON+ eyes had decreased monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when comparing MS ON- and control eyes. The magnitude of binocular summation using low-contrast charts was similar for pediatric MS participants and controls and was not diminished in children with a history of ON. While the mean RNFL thickness for all MS eyes (103±17 µm) trended lower when compared to corresponding measures in control eyes (109±9 µm, p=0.085), we confirmed a highly significant reduction in mean RNFL thickness in MS eyes with a history of ON (86±22 µm, p<0.001). RNFL thickness of MS ON- eyes in pediatric MS patients (109±11 µm) did not differ from controls (p=0.994). CONCLUSIONS: Low-contrast letter acuity detects subtle visual loss in MS patients with prior ON, consistent with incomplete recovery, a finding further supported by RNFL loss in ON affected eyes. In MS patients with prior unilateral ON, binocular acuity is decreased; however, the magnitude of binocular summation is preserved, unlike adult-onset MS who exhibit a reduced capacity for visual compensation in the context of unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate RNFL thinning in ON- eyes of children and adolescents with MS. Further validation is required to confirm whether neurodegeneration of visual pathways occurs in the absence of relapse, and thus whether OCT will serve as a sensitive metric for such pathology in the pediatric and adolescent MS context.

Prevalence and risk factors for metabolic syndrome in Medellin and surrounding municipalities, Colombia, 2008-2010.

OBJECTIVE: We assessed the prevalence of and risk factors for metabolic syndrome (MetS) among adults 25-64 years of age from Medellin and surrounding municipalities, Colombia. METHOD: We used 2008-2010 data from the Antioquia STEPwise approach to Surveillance (STEPS), a multi-stage complex cross-sectional survey designed according to World Health Organization guidelines. The revised 2005 International Diabetes Federation definition of MetS was used. RESULTS: There were a total of 3000 participants. Of these, 21.4% had high blood pressure (HBP) and 64% had abdominal obesity (AO). In the subsample with serum data (n = 943), 19.8% had high fasting serum glucose, 43.9% had high triglycerides (HTG), and 56.6% had low HDL cholesterol (L-HDL). Among those with data to define MetS (n = 901), 41% had MetS. Older age was associated with MetS and all components except L-HDL. Female sex [odds ratio (OR) = 2.85, 95% confidence interval (CI): 2.20-3.70], being married (OR = 1.40, CI: 1.09-1.82), and high physical activity (OR = 0.59, CI: 0.39-0.91) were associated with AO, smoking with HTG (OR = 1.76, CI: 1.16-2.67) and L-HDL (OR = 1.67, CI: 1.10-2.51) and rural residence with HBP (OR = 3.42, CI: 1.83-6.37) and L-HDL (OR = 1.18, CI: 1.10-2.51). CONCLUSION: The prevalence of MetS and AO was high in this Colombian region. Targeted strategies for promoting healthy behaviors are needed.

Consensus recommendations for incident learning database structures in radiation oncology.

PURPOSE: Incident learning plays a key role in improving quality and safety in a wide range of industries and medical disciplines. However, implementing an effective incident learning system is complex, especially in radiation oncology. One current barrier is the lack of technical standards to guide users or developers. This report, the product of an initiative by the Work Group on Prevention of Errors in Radiation Oncology of the American Association of Physicists in Medicine, provides technical recommendations for the content and structure of incident learning databases in radiation oncology. METHODS: A panel of experts was assembled and tasked with developing consensus recommendations in five key areas: definitions, process maps, severity scales, causality taxonomy, and data elements. Experts included representatives from all major North American radiation oncology organizations as well as users and developers of public and in-house reporting systems with over two decades of collective experience. Recommendations were developed that take into account existing incident learning systems as well as the requirements of outside agencies. RESULTS: Consensus recommendations are provided for the five major topic areas. In the process mapping task, 91 common steps were identified for external beam radiation therapy and 88 in brachytherapy. A novel feature of the process maps is the identification of "safety barriers," also known as critical control points, which are any process steps whose primary function is to prevent errors or mistakes from occurring or propagating through the radiotherapy workflow. Other recommendations include a ten-level medical severity scale designed to reflect the observed or estimated harm to a patient, a radiation oncology-specific root causes table to facilitate and regularize root-cause analyses, and recommendations for data elements and structures to aid in development of electronic databases. Also presented is a list of key functional requirements of any reporting system. CONCLUSIONS: Incident learning is recognized as an invaluable tool for improving the quality and safety of treatments. The consensus recommendations in this report are intended to facilitate the implementation of such systems within individual clinics as well as on broader national and international scales.

In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques.

Macular optical coherence tomography (OCT) segmentation, enabling quantification of retinal axonal and neuronal subpopulations, may help elucidate the neuroretinal pathobiology of multiple sclerosis (MS). This study aimed to determine the agreement, reproducibility, and visual correlations of retinal layer thicknesses measured by different OCT segmentation techniques, on two spectral-domain OCT devices. Macular scans of 52 MS patients and 30 healthy controls from Spectralis OCT and Cirrus HD-OCT were segmented using fully manual (Spectralis), computer-aided manual (Spectralis and Cirrus), and fully automated (Cirrus) segmentation techniques. Letter acuity was recorded. Bland-Altman analyses revealed low mean differences across OCT segmentation techniques on both devices for ganglion cell + inner plexiform layers (GCIP; 0.76-2.43 µm), inner nuclear + outer plexiform layers (INL + OPL; 0.36-1.04 µm), and outer nuclear layers including photoreceptor segment (ONL + PR; 1.29-3.52 µm) thicknesses. Limits of agreement for GCIP and ONL + PR thicknesses were narrow. Results of fully manual and computer-aided manual segmentation were comparable to those of fully automated segmentation. MS patients demonstrated macular RNFL, GCIP, and ONL + PR thinning compared to healthy controls across OCT segmentation techniques, irrespective of device (p < 0.03 for all). Low-contrast letter acuity in MS correlated significantly and more strongly with GCIP than peripapillary RNFL thicknesses, regardless of the segmentation method or device. GCIP and ONL + PR thicknesses, measured by different OCT devices and segmentation techniques, are reproducible and agree at the individual and cohort levels. GCIP thinning in MS correlates with visual dysfunction. Significant ONL + PR thinning, detectable across OCT segmentation techniques and devices, strongly supports ONL pathology in MS. Fully automated, fully manual and computer-assisted manual OCT segmentation techniques compare closely, highlighting the utility of accurate and time-efficient automated segmentation outcomes in MS clinical trials.

Detection of clinical and subclinical retinal abnormalities in neurosarcoidosis with optical coherence tomography.

The aim of this work was to determine if neurosarcoidosis (NS) patients exhibit quantitative and/or qualitative in vivo evidence of retinal abnormalities on optical coherence tomography (OCT). Retinal imaging was performed using spectral-domain Cirrus HD-OCT in 20 NS patients (40 eyes) and 24 age-matched healthy controls (48 eyes). Study participants also underwent magnetic resonance imaging of the brain and spine, cerebrospinal fluid (CSF) analysis, and detailed neurological and ophthalmological evaluation. Quantitative OCT abnormalities of average macular thickness (AMT), peri-papillary retinal nerve fiber layer (RNFL) thickness, or both, were detectable in 60% of NS patients. Of NS patients with ocular symptomatology, 75% demonstrated quantitative OCT abnormalities, while only 25% had detectable abnormalities on detailed ophthalmological assessment. Furthermore, 33% of NS patients without ocular symptoms had quantitative OCT changes, while only 8% had abnormal ophthalmologic examination. RNFL and macular thinning and swelling were significant in the NS cohort compared to healthy controls (variance ratio testing; RNFL: p = 0.02, AMT: p = 0.006). AMT also correlated inversely with disease duration (r (s) = -0.65, p = 0.002). Patient proportions with OCT abnormalities did not differ according to NS subtype (myelopathic, meningeal, or encephalitic NS), CSF findings, or immunotherapy exposure. No qualitative OCT abnormalities were detected. Retinal abnormalities occur in all NS subtypes, and may be clinical or subclinical. Our findings suggest OCT may enable greater detection of retinal abnormalities in NS than ophthalmological assessment alone, and have implications for the assessment of ocular involvement in NS, and sarcoidosis in general. Longitudinal NS studies utilizing OCT are warranted.

Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis.

Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P < 0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P = 0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P < 0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.

MO-D-BRB-07: Failure-Mode and Effects Analysis Study for CyberKnife Stereotactic Radiosurgery.

PURPOSE: The purpose of this study is to conduct a Failure Modes and Effect Analysis (FMEA) for CyberKnife Stereotactic Radiosurgery to determine the sensitivity of existing QA procedures and determine in which areas new QA procedures needed to be implemented. METHODS: Members from each professional team providing service for CyberKnife radiosurgery (Medical Physicists, Nurses, Physicians, Radiation Therapists, and Administrators) were interviewed to gather potential failure modes. A patient flow chart was developed from patient consult to conclusion of last treatment. Failure modes were mapped to nodes in the flow charts to identify potential high-risk areas. A matrix was created to correlate existing QA procedures with failure modes to identify failure modes that were not covered by any QA as well as identify the sensitivity of QA procedures to prevent failures. RESULTS: 180 failure modes were identified. Current AAPM QA recommendations were found to focus preferentially on technical failure modes (15%), while the majority of failure modes found are process failures and human errors (85%). Creating a Venn diagram of CyberKnife and Gamma Knife failure modes revealed a large overlap area. The most effective QA checks are checklists for physics second chart review and pre- treatment time-out checklists. Existing checklists were modified and new checklists added to address high-ranked failure modes. New procedure guidelines, e.g. for contouring workflow and add-on simulations, were developed as QC to address clusters of failure modes. An ARIA-CyberKnife DICOM interface is being implemented to resolve failure modes centering around multiple fraction, multiple plan treatments and total dose tracking. CONCLUSIONS: This work is the first FMEA study for the CyberKnife stereotactic radiosurgery. It will facilitate medical physicists using the CyberKnife to deliver SRS/SBRT treatments to transition from experience-based technical QA to a comprehensive new quality paradigm including technical, process, and human safety aspects.