Radiation Exposure from the Patient Perspective: An Argument for the Inclusion of Dose History.

ABSTRACT: Patients in diagnostic imaging departments often ask about the risk of injury from x radiation. They are referred to wall posters or consent forms that declare (rightly) that the risk of harm from the proposed exam is very small and is far outweighed by the benefit. If a comparative risk value is provided, most likely it is based on a single exposure and derived from population estimates of cancer incidence and mortality. But is that information the most relevant for the patient? In a recent position statement, the AAPM recommends that only current exam risk should be considered, and that risk is independent of previous exams. We argue that if an exam carries risk of a negative event, the likelihood that a negative event occurred over all events increases with the number of exams. This cumulative risk, though still very small, must be a relevant consideration for health management.

Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning.

The COVID-19 pandemic has provided stiff challenges for planning and resourcing in health services in the UK and worldwide. Epidemiological models can provide simulations of how infectious disease might progress in a population given certain parameters. We adapted an agent-based model of COVID-19 to inform planning and decision-making within a healthcare setting, and created a software framework that automates processes for calibrating the model parameters to health data and allows the model to be run at national population scale on National Health Service (NHS) infrastructure. We developed a method for calibrating the model to three daily data streams (hospital admissions, intensive care occupancy, and deaths), and demonstrate that on cross-validation the model fits acceptably to unseen data streams including official estimates of COVID-19 incidence. Once calibrated, we use the model to simulate future scenarios of the spread of COVID-19 in England and show that the simulations provide useful projections of future COVID-19 clinical demand. These simulations were used to support operational planning in the NHS in England, and we present the example of the use of these simulations in projecting future clinical demand during the rollout of the national COVID-19 vaccination programme. Being able to investigate uncertainty and test sensitivities was particularly important to the operational planning team. This epidemiological model operates within an ecosystem of data technologies, drawing on a range of NHS, government and academic data sources, and provides results to strategists, planners and downstream data systems. We discuss the data resources that enabled this work and the data challenges that were faced.

Cell Surface Remodeling of Mycobacterium abscessus under Cystic Fibrosis Airway Growth Conditions.

Understanding the physiological processes underlying the ability of Mycobacterium abscessus to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of M. abscessus complex isolates points to amino acids being significant sources of carbon and energy for M. abscessus in both CF sputum and synthetic CF medium and to the bacterium undergoing an important metabolic reprogramming in order to adapt to this particular nutritional environment. Cell envelope analyses conducted on the same representative isolates further revealed unexpected structural alterations in major cell surface glycolipids known as the glycopeptidolipids (GPLs). Besides showing an increase in triglycosylated forms of these lipids, CF sputum- and synthetic CF medium-grown isolates presented as yet unknown forms of GPLs representing as much as 10% to 20% of the total GPL content of the cells, in which the classical amino alcohol located at the carboxy terminal of the peptide, alaninol, is replaced with the branched-chain amino alcohol leucinol. Importantly, both these lipid changes were exacerbated by the presence of mucin in the culture medium. Collectively, our results reveal potential new drug targets against M. abscessus in the CF airway and point to mucin as an important host signal modulating the cell surface composition of this pathogen.

COMP Report: A survey of radiation safety regulations for medical imaging x-ray equipment in Canada.

X-ray regulations and room design methodology vary widely across Canada. The Canadian Organization of Medical Physicists (COMP) conducted a survey in 2016/2017 to provide a useful snapshot of existing variations in rules and methodologies for human patient medical imaging facilities. Some jurisdictions no longer have radiation safety regulatory requirements and COMP is concerned that lack of regulatory oversight might erode safe practices. Harmonized standards will facilitate oversight that will ensure continued attention is given to public safety and to control workplace exposure. COMP encourages all Canadian jurisdictions to adopt the dose limits and constraints outlined in Health Canada Safety Code 35 with the codicil that the design standards be updated to those outlined in NCRP 147 and BIR 2012.

Evaluating a complex system-wide intervention using the difference in differences method: the Delivering Choice Programme.

OBJECTIVES: We report the use of difference in differences (DiD) methodology to evaluate a complex, system-wide healthcare intervention. We use the worked example of evaluating the Marie Curie Delivering Choice Programme (DCP) for advanced illness in a large urban healthcare economy. METHODS: DiD was selected because a randomised controlled trial was not feasible. The method allows for before and after comparison of changes that occur in an intervention site with a matched control site. This enables analysts to control for the effect of the intervention in the absence of a local control. Any policy, seasonal or other confounding effects over the test period are assumed to have occurred in a balanced way at both sites. Data were obtained from primary care trusts. Outcomes were place of death, inpatient admissions, length of stay and costs. RESULTS: Small changes were identified between pre- and post-DCP outputs in the intervention site. The proportion of home deaths and median cost increased slightly, while the number of admissions per patient and the average length of stay per admission decreased slightly. None of these changes was statistically significant. CONCLUSIONS: Effects estimates were limited by small numbers accessing new services and selection bias in sample population and comparator site. In evaluating the effect of a complex healthcare intervention, the choice of analysis method and output measures is crucial. Alternatives to randomised controlled trials may be required for evaluating large scale complex interventions and the DiD approach is suitable, subject to careful selection of measured outputs and control population.

Automated breast image classification using features from its discrete cosine transform.

PURPOSE: This work aimed to improve breast screening program accuracy using automated classification. The goal was to determine if whole image features represented in the discrete cosine transform would provide a basis for classification. Priority was placed on avoiding false negative findings. METHODS: Online datasets were used for this work. No informed consent was required. Programs were developed in Mathematica and, where necessary to improve computational performance ported to C++. The use of a discrete cosine transform to separate normal from cancerous breast tissue was tested. Features (moments of the mean) were calculated in square sections of the transform centered on the origin. K-nearest neighbor and naive Bayesian classifiers were tested. RESULTS: Forty-one features were generated and tested singly, and in combination of two or three. Using a k-nearest neighbor classifier, sensitivities as high as 98% with a specificity of 66% were achieved. With a naive Bayesian classifier, sensitivities as high as 100% were achieved with a specificity of 64%. CONCLUSION: Whole image classification based on discrete cosine transform (DCT) features was effectively implemented with a high level of sensitivity and specificity achieved. The high sensitivity attained using the DCT generated feature set implied that these classifiers could be used in series with other methods to increase specificity. Using a classifier with near 100% sensitivity, such as the one developed in this project, before applying a second classifier could only boost the accuracy of that classifier.

Automatic detection of anomalies in screening mammograms.

BACKGROUND: Diagnostic performance in breast screening programs may be influenced by the prior probability of disease. Since breast cancer incidence is roughly half a percent in the general population there is a large probability that the screening exam will be normal. That factor may contribute to false negatives. Screening programs typically exhibit about 83% sensitivity and 91% specificity. This investigation was undertaken to determine if a system could be developed to pre-sort screening-images into normal and suspicious bins based on their likelihood to contain disease. Wavelets were investigated as a method to parse the image data, potentially removing confounding information. The development of a classification system based on features extracted from wavelet transformed mammograms is reported. METHODS: In the multi-step procedure images were processed using 2D discrete wavelet transforms to create a set of maps at different size scales. Next, statistical features were computed from each map, and a subset of these features was the input for a concerted-effort set of naïve Bayesian classifiers. The classifier network was constructed to calculate the probability that the parent mammography image contained an abnormality. The abnormalities were not identified, nor were they regionalized.The algorithm was tested on two publicly available databases: the Digital Database for Screening Mammography (DDSM) and the Mammographic Images Analysis Society's database (MIAS). These databases contain radiologist-verified images and feature common abnormalities including: spiculations, masses, geometric deformations and fibroid tissues. RESULTS: The classifier-network designs tested achieved sensitivities and specificities sufficient to be potentially useful in a clinical setting. This first series of tests identified networks with 100% sensitivity and up to 79% specificity for abnormalities. This performance significantly exceeds the mean sensitivity reported in literature for the unaided human expert. CONCLUSIONS: Classifiers based on wavelet-derived features proved to be highly sensitive to a range of pathologies, as a result Type II errors were nearly eliminated. Pre-sorting the images changed the prior probability in the sorted database from 37% to 74%.

Temperature-driven plasticity in growth cessation and dormancy development in deciduous woody plants: a working hypothesis suggesting how molecular and cellular function is affected by temperature during dormancy induction.

The role of temperature during dormancy development is being reconsidered as more research emerges demonstrating that temperature can significantly influence growth cessation and dormancy development in woody plants. However, there are seemingly contradictory responses to warm and low temperature in the literature. This research/review paper aims to address this contradiction. The impact of temperature was examined in four poplar clones and two dogwood ecotypes with contrasting dormancy induction patterns. Under short day (SD) conditions, warm night temperature (WT) strongly accelerated timing of growth cessation leading to greater dormancy development and cold hardiness in poplar hybrids. In contrast, under long day (LD) conditions, low night temperature (LT) can completely bypass the short photoperiod requirement in northern but not southern dogwood ecotypes. These findings are in fact consistent with the literature in which both coniferous and deciduous woody plant species' growth cessation, bud set or dormancy induction are accelerated by temperature. The contradictions are addressed when photoperiod and ecotypes are taken into account in which the combination of either SD/WT (northern and southern ecotypes) or LD/LT (northern ecotypes only) are separated. Photoperiod insensitive types are driven to growth cessation by LT. Also consistent is the importance of night temperature in regulating these warm and cool temperature responses. However, the physiological basis for these temperature effects remain unclear. Changes in water content, binding and mobility are factors known to be associated with dormancy induction in woody plants. These were measured using non-destructive magnetic resonance micro-imaging (MRMI) in specific regions within lateral buds of poplar under SD/WT dormancing inducing conditions. Under SD/WT, dormancy was associated with restrictions in inter- or intracellular water movement between plant cells that reduces water mobility during dormancy development. Northern ecotypes of dogwood may be more tolerant to photoinhibition under the dormancy inducing LD/LT conditions compared to southern ecotypes. In this paper, we propose the existence of two separate, but temporally connected processes that contribute to dormancy development in some deciduous woody plant: one driven by photoperiod and influenced by moderate temperatures; the other driven by abiotic stresses, such as low temperature in combination with long photoperiods. The molecular changes corresponding to these two related but distinct responses to temperature during dormancy development in woody plants remains an investigative challenge.

Magnetic resonance microimaging indicates water diffusion correlates with dormancy induction in cultured hybrid poplar (Populus spp.) buds.

Water content and mobility, which are factors known to be associated with dormancy induction in woody plants on a tissue level, were measured using non-destructive magnetic resonance microimaging (MRMI). Two cultured poplar clones ('Okanese' - temperature-insensitive dormancy and 'Walker' - temperature-sensitive dormancy) were subjected to dormancy differentiating temperature regimes, 18.5/3.5 degrees C and 18.5/13.5 degrees C (day/night), under a short photoperiod. Apparent diffusion coefficient, an indicator of water mobility, correlated with dormancy development in the axillary bud and vascular bud trace regions. In contrast, T(1) relaxation time, an indicator of static biophysical water properties, did not correlate significantly with dormancy in the regions that were examined. Although MRMI studies using T(1) relaxation measurements have dominated the phytological field, our work indicates that water mobility is an important factor in studies examining water changes during dormancy induction in the critical tissues of woody plants.

Neuroimaging assessment of memory-related brain structures in a rat model of acute space-like radiation.

PURPOSE: To investigate the acute effects on the central nervous system (CNS) of (56)Fe radiation, a component of high-energy charged particles (HZE) in space radiation, using quantitative magnetic resonance imaging (MRI) noninvasively. MATERIALS AND METHODS: Sprague-Dawley rats were exposed to whole-brain (56)Fe (0, 1, 2, and 4 Gy). At 1 week postirradiation, MRI scans were made using T2-weighted (T2WI), diffusion-weighted (DWI), and contrast enhanced T1-(CET1) imaging. T2 relaxation time and apparent diffusion coefficient (ADC) values were obtained from memory-related brain regions of interest (ROIs). Histopathology was correlated using ex vivo tissues. RESULTS: No overt abnormalities were visualized using T2WI and DWI at 1 week postradiation. CET1 values did not differ significantly between the irradiated and control animals. Compared to 0 Gy, there were significant prolongations in T2 values and reductions in ADC after irradiation. In the absence of evident neuronal pathology, immunohistochemistry revealed astrocytic activation in 4 Gy animals. CONCLUSION: At 1 week after whole-brain (56)Fe exposure, T2 and ADC values can differentiate radiosensitivity in regions critical for hippocampal-related memory. MRI may provide noninvasive assessment of the initial molecular/cellular disturbances in vivo after HZE irradiation.

Nuclear magnetic resonance spectroscopy of bovine ovarian follicular fluid at four selected times of the oestrous cycle.

The objective of the study was to determine if nuclear magnetic resonance (NMR) spectral features of ovarian follicular fluid were correlated with the physiological status of follicles so that we could assess the feasibility of using NMR spectroscopy during assisted reproduction therapy. Thirty-five sexually mature, nullparious heifers were monitored by transrectal ultrasonography to assess their follicle wave status during the oestrous cycle. Ovariectomies were performed on Day 3 of wave 1 (D3W1, n = 10), Day 6 of wave 1 (D6W1, n = 9), Day 1 of wave 2 (D1W2, n = 9), or in the immediate preovulatory period of at least 17 days after ovulation (De17, n = 9). Follicle status was determined to be dominant or subordinate. Follicular fluid was extracted from the follicles and NMR spectra were collected. Principal components were extracted from ratios of line amplitudes and tested for effects of follicle status (dominant v. subordinate) and cycle time point (D1W3, D1W6, D1W2 and De17) using multivariate analysis of variance. For most line ratio combinations, main effects of status, time point and their interaction were found (P < 0.05). We concluded that NMR spectra may be used for the determination of ovarian follicle physiological status.

Automated search for arthritic patterns in infrared spectra of synovial fluid using adaptive wavelets and fuzzy C-means analysis.

Analysis of synovial fluid by infrared (IR) clinical chemistry requires expert interpretation and is susceptible to subjective error. The application of automated pattern recognition (APR) may enhance the utility of IR analysis. Here, we describe an APR method based on the fuzzy C-means cluster adaptive wavelet (FCMC-AW) algorithm, which consists of two parts: one is a FCMC using the features from an M-band feature extractor adopting the adaptive wavelet algorithm and the second is a Bayesian classifier using the membership matrix generated by the FCMC. A FCMC-cross-validated quadratic probability measure (FCMC-CVQPM) criterion is used under the assumption that the class probability density is equal to the value of the membership matrix. Therefore, both values of posterior probabilities and selection criterion MFQ can be obtained through the membership matrix. The distinctive advantage of this method is that it provides not only the 'hard' classification of a new pattern, but also the confidence of this classification, which is reflected by the membership matrix.

Neuroprotection from soman-induced seizures in the rodent: evaluation with diffusion- and T2-weighted magnetic resonance imaging.

Exposure to the organophosphate nerve agent soman produces seizures that in turn lead to neuropathology. This study describes the temporal and spatial evolution of brain pathology following soman-induced convulsions and the attenuation of these alterations after neuroprotective intervention with magnetic resonance imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and thalamus exhibited significant decreases (23%) in apparent diffusion coefficients (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements declined significantly at 12 h (37%) returning to near normal values by 24 h. Histopathological analyses confirmed moderate cell loss within the hippocampus and piriform cortex. Together these findings suggest that initial cell death was resolved through regional cellular remodeling. Pharmacological countermeasures were administered in the form of diazepam, a benzodiazepine anticonvulsant, or gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied immediately after soman exposure prevented acute ADC changes. However the presence of edema, using T2 measurements, was detected at 3 h within the retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34% below normal). GK-11 therapy appeared to prevent most of these changes. However at 7 days after soman, a decrease (17%) in ADC was observed in the piriform cortex. Pathology was confined to the piriform cortex suggesting that this region is more difficult to protect. This is the first report that provides temporal and spatial resolution using MRI with histological correlation of pharmacological interventions against soman-mediated seizure-induced neuropathology.

Reconsideration of pacemakers and MR imaging.

The presence of an implanted pacemaker is widely regarded as an absolute contraindication to magnetic resonance (MR) imaging; however, this viewpoint is based largely on safety concerns in the 1982-1996 period. Since 1996, changes in pacemaker electronics including decreased ferromagnetic content, increased sophistication of the circuitry, and onboard computer capabilities suggest that the absolute contraindication of MR imaging for pacemaker patients should be reconsidered. In addition, there are now data from prospective trials of 232 patients with demand pacemakers who underwent MR imaging at 0.5-1.5 T. Although a variety of pacemaker parameters were evaluated before, during, immediately after, and 3 months after MR imaging, no significant pacemaker changes were identified. No patients reported abnormal sensations such as pacemaker movement or irregular heartbeats even at direct questioning. These results suggest that peripheral locations such as the brain and knee may be considered for MR imaging. Thus, pacemaker patients should be assessed individually for their suitability for MR imaging, which may be performed safely under defined conditions.

Neuronal and glial cell populations in the piriform cortex distinguished by using an approximation of q-space imaging after status epilepticus.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy produces an injury cascade that includes neuronal loss and gliosis. The pilocarpine model reliably reproduces the symptoms of temporal lobe epilepsy and the resulting neuronal glial changes can be accurately depicted on diffusion-weighted images. The judicious choice of diffusion-encoding gradients can isolate multiple apparently isochromatic diffusing populations, but the assignment of these populations to specific tissue characteristics has been difficult. We sought to distinguish neuronal tissue from glial cell-infiltrated tissue by using signatures from unique spin populations obtained from an approximation of q-space imaging. METHODS: Ten male Sprague-Dawley rats received pilocarpine injections to induce seizures. All animals underwent diffusion-weighted imaging at 12 hours, 24 hours, and 7 days. At least two animals were selected for histologic analysis at each imaging time point. RESULTS: The results indicated that seizure-induced neurologic dysfunction may have been reflected in the emergence of new spin populations. In the piriform cortex-amygdala region of interest, the mean free diffusion path increased from 12 to 20 microm within 12 hours of seizure onset and persisted for at least 7 days. These results were temporally correlated with histologic evidence of necrotic changes. CONCLUSION: Our results suggest that even incomplete sampling of q space can provide useful physiologic information.

Magnetic resonance diffusion imaging of ovarian masses: a first experience with 12 cases.

OBJECTIVE: The objective of the study was to determine the feasibility of using apparent diffusion coefficient (ADC) measurement for the differential diagnosis of malignancy in ovarian masses. MATERIALS AND METHODS: Twelve cases involving ovarian masses were imaged using spin echo diffusion magnetic resonance imaging (MRI). Five cases involved malignant ovarian masses, on the basis of postoperative histologic examination, and the rest involved benign masses. The ovarian masses were imaged in vivo (10 cases) before surgery and ex vivo (8 cases) after surgical resection. Diffusion-weighted data were corrected for motion using the phase data from unweighted data in nine cases. Multifactorial analysis of variance was used to evaluate the effects of malignancy, location (in vivo versus ex vivo), and motion correction on the measurement of ADC intensity and texture. RESULTS: Motion correction caused an undesirable spatial smoothing of the ADC maps and a significant interaction (p=0.047) was found between location and motion correction. ADC value (p=0.028) and texture (p=0.001) differences were found between malignant and nonmalignant ovarian masses. CONCLUSION: Measurement of ADC intensity and texture has the potential to differentially diagnose malignancy in individual ovarian masses if the problem of image motion artifact can be eliminated through the use of faster imaging sequences.

Recurrent nonstatus generalized seizures alter the developing chicken brain.

PURPOSE: Noninvasive magnetic resonance imaging was used to assess the evolution of seizure-induced pathology in epileptic, carrier, and normal chickens. Our objective was to determine whether repetitively evoked seizures in an epileptic fowl model of generalized seizures resulted in altered brain development. METHODS: Data were obtained from seizure and control groups at 45, 90, and 180 days after hatching. RESULTS: At 180 days, apparent diffusion coefficient (ADC) values in the optic tectum and archistriatum of the stimulated epileptic chicks were reduced, whereas ADC values in the nonstimulated group remained unchanged. The mean brain volume of epileptic chickens from the stimulated group was smaller than that from the nonstimulated group at 90 and 180 days. CONCLUSIONS: These findings establish that recurrent seizures modify the brain matrix.

Water self-diffusion tensor changes in an avian genetic developmental model of epilepsy.

Diffusion tensor imaging (DTI) was used to investigate whether tissue anisotropy in the developing brain is modified by recurrent seizures in epileptic chickens. Twelve epileptic chickens were sorted equally into two experimental groups at 10 days old. Until the age of 180 days, one group was photically stimulated beginning at an age of 2 weeks and repeated every 2 days while the other group was not stimulated. The photic stimulation induced generalized tonic-clonic seizures, and the unstimulated group did not display seizures. Both treatment groups were imaged at three time points, 45 (juvenile), 90 (adolescent), and 180 (adult) days posthatching, and maps of major and minor elements of anisotropy (eta and epsilon), trace and fractional anisotropy (FA) were generated. The eta, epsilon, and trace values in the hyperstriatum, archistriatum, and optic tectum showed significant changes as a function of developmental time point. Differences and/or interactions due to seizures were seen in the archistriatum and optic tectum for eta, epsilon, and trace with the largest differences between the stimulated and unstimulated birds being seen for eta in juvenile birds in the archistriatum (38.1 x 10(-11) m(2)/s versus 18.0 x 10(-11) m(2)/s) and the optic tectum (53.9 x 10(-11) m(2)/s versus 27.1 x 10(-11) m(2)/s). With the DTI parameters being sensitive to microstructure in the brain, these results demonstrate that seizures produce measurable differences, over unstimulated chickens, in brain structure for juvenile chickens, but the differences disappear as the brain matures. In other words, while seizure activity appears to induce atypical biophysical change (relative to unseizing birds) in the brain at a young age, the change is apparently reversed as the brain matures.