Advanced automated PET image segmentation in radiation therapy

Manual segmentation of the metabolic tumour volume (MTV) in positron emission tomography (PET) imaging is subject to intra and inter-observer variability. Many PET based automatic segmentation algorithms (PETAS) have been proposed as solutions to this problem with machine-learned techniques showing promise for accurate MTV segmentation. However, no consensus has been reached on the optimal method for radiotherapy (RT) treatment planning, with the current American Association for Physcists in Medicine Task Group 211 and the International Atomic Energy Association advisory committees recommending that not one single PET-AS can be recommended for target volume delineation. This project, therefore, aimed to improve the MTV segmentation of a machine-learned PET-AS methodology called ATLAAS which has been proposed for standardised MTV segmentation by Berthon et al in Radiother Onc (2016). Berthon et al additionally validated the ATLAAS algorithm on diagnostic PET imaging in Radiother Onc (2017). However, it has not been validated externally or for the role of MTV segmentation during treatment. Intratreatment segmentation is challenging due to reduced metabolic uptake, tuiv mour to background ratio and reduced metabolic volume. Therefore, in this body of work, the performance of ATLAAS and 151 other PET-AS chosen from the literature, were evaluated for suitable MTV segmentation in PET imaging acquired after one cycle of neoadjuvant chemotherapy. This research resulted in the development of a new training dataset and demonstrated that ATLAAS can be used as a basis for adaptive radiotherapy and trained on imaging datasets outside of the original training cohort. However, this research still demonstrated that the performance of ATLAAS could be improved. Therefore, this led to an investigation into the inclusion of additional tumour characteristics in the development of the ATLAAS training model, in order to reduce the impact PET image resolution has on MTV segmentation. In this research, derived MTVs were compared to \ground truth" volumes derived from CT imaging. The results presented in this body of work, showed that interpolating PET imaging to the resolution of the CT image improved the performance of PET-AS segmentation and improved ATLAAS MTV segmentation by 19% and inclusion of one of the tumour features compactness one, compactness two or sphericity in the ATLAAS training model improved MTV segmentation by an additional 3%. As part of this body of work, the requirement for a standardised PET-AS method was demonstrated by developing prognostic models, using standardised imaging and tumour features, from the MTV derived by 9 PET-AS demonstrated by Berthon et al in Phys. Med. Biol (2017) to be promising for accurate MTV segmentation. This showed how segmentation of the MTV 120-80% Threshold in increments of 10%, Adaptive Thresholding, Region Growing, K-means Clustering with 2 and 3 clusters, Gaussian Fuzzy C-means with 3 and 4 clusters and Fuzzy-C means with 2 clusters v has a subsequent effect on patient risk stratification with patients changing risk stratification quartiles dependent upon the PET-AS used to derive the MTV

Explaining trends in alcohol-related harms in Scotland 1991–2011 (II): policy, social norms, the alcohol market, clinical changes and a synthesis

Objective: To provide a basis for evaluating post-2007 alcohol policy in Scotland, this paper tests the extent to which pre-2007 policy, the alcohol market, culture or clinical changes might explain differences in the magnitude and trends in alcohol-related mortality outcomes in Scotland compared to England & Wales (E&W). Study design: Rapid literature reviews, descriptive analysis of routine data and narrative synthesis. Methods: We assessed the impact of pre-2007 Scottish policy and policy in the comparison areas in relation to the literature on effective alcohol policy. Rapid literature reviews were conducted to assess cultural changes and the potential role of substitution effects between alcohol and illicit drugs. The availability of alcohol was assessed by examining the trends in the number of alcohol outlets over time. The impact of clinical changes was assessed in consultation with key informants. The impact of all the identified factors were then summarised and synthesised narratively. Results: The companion paper showed that part of the rise and fall in alcohol-related mortality in Scotland, and part of the differing trend to E&W, were predicted by a model linking income trends and alcohol-related mortality. Lagged effects from historical deindustrialisation and socio-economic changes exposures also remain plausible from the available data. This paper shows that policy differences or changes prior to 2007 are unlikely to have been important in explaining the trends. There is some evidence that aspects of alcohol culture in Scotland may be different (more concentrated and home drinking) but it seems unlikely that this has been an important driver of the trends or the differences with E&W other than through interaction with changing incomes and lagged socio-economic effects. Substitution effects with illicit drugs and clinical changes are unlikely to have substantially changed alcohol-related harms: however, the increase in alcohol availability across the UK is likely to partly explain the rise in alcohol-related mortality during the 1990s. Conclusions: Future policy should ensure that alcohol affordability and availability, as well as socio-economic inequality, are reduced, in order to maintain downward trends in alcohol-related mortality in Scotland

Impact of 18F-Choline PET scan acquisition time on delineation of GTV in prostate cancer [Poster Abstract]

Background: Dose painting radiotherapy requires accurate outlining of primary tumour volumes in the prostate. T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) is the best imaging method for defining the gross tumour volume (GTV). Choline positron emission tomography (PET) is currently a controversial tracer. The image acquisition differs significantly in published studies. Many used early static imaging. One study found that 18F-choline PET/CT with late image acquisition has superior accuracy to T2W MR and functional MR alone1. We investigate whether increasing 18F-Choline PET scan acquisition time from 60 (PET-60) to 90 (PET-90) minutes improves GTV TVD. Methods. Analysis was performed on 9 18F-Choline PET scans. Patients were injected with 370MBq of activity. Three clinicians (C1, C2 and C3) independently and without reference to each other contoured GTVs on each of the T2W-MRI, PET-60 and PET-90 scans at differing times. Scans were registered by a clinician using rigid co-registration. The treating clinicians MRI contour was used as a reference contour. The resulting PET and MRI GTVs were transferred to the PET-60 and PET-90 scans after image registration. The Dice Similarity Coefficient (DSC), Specificity (Sp) and Sensitivity (S) were calculated from contour mask voxel analysis. Results. Table 1 shows the mean and range DSC, S and Sp scores on MRI, PET-60 and PET-90 for C1, C2 and C3 in comparison to the treating clinicians contour on MRI (C1). A 2 sampled T-test (P < 0.01) showed, no significant difference in the Sp, S and DSC between GTVs on PET-60 and PET-90 scans. Further to this, as shown in Figure 1, variability in GTV delineation is significant between observers in a singular case as well as across imaging modalities. Conclusion. Compared to MRI delineated GTVs, 18F-Choline PET GTVs are significantly different. This study found however that increasing the PET scan acquisition time from 60 to 90 minutes did not improve the performance of GTV TVD in comparison to MRI delineated GTV

Assessing radiomic feature robustness to interpolation in 18F-FDG PET imaging

Radiomic studies link quantitative imaging features to patient outcomes in an effort to personalise treatment in oncology. To be clinically useful, a radiomic feature must be robust to image processing steps, which has made robustness testing a necessity for many technical aspects of feature extraction. We assessed the stability of radiomic features to interpolation processing and categorised features based on stable, systematic, or unstable responses. Here, 18F-fluorodeoxyglucose (18F-FDG) PET images for 441 oesophageal cancer patients (split: testing = 353, validation = 88) were resampled to 6 isotropic voxel sizes (1.5 mm, 1.8 mm, 2.0 mm, 2.2 mm, 2.5 mm, 2.7 mm) and 141 features were extracted from each volume of interest (VOI). Features were categorised into four groups with two statistical tests. Feature reliability was analysed using an intraclass correlation coefficient (ICC) and patient ranking consistency was assessed using a Spearman’s rank correlation coefficient (ρ). We categorised 93 features robust and 6 limited robustness (stable responses), 34 potentially correctable (systematic responses), and 8 not robust (unstable responses). We developed a correction technique for features with potential systematic variation that used surface fits to link voxel size and percentage change in feature value. Twenty-nine potentially correctable features were re-categorised to robust for the validation dataset, after applying corrections defined by surface fits generated on the testing dataset. Furthermore, we found the choice of interpolation algorithm alone (spline vs trilinear) resulted in large variation in values for a number of features but the response categorisations remained constant. This study attempted to quantify the diverse response of radiomics features commonly found in 18F-FDG PET clinical modelling to isotropic voxel size interpolation

Impact of co-located welfare advice in healthcare settings: prospective quasi-experimental controlled study

Background: Evaluations of primary healthcare co-located welfare advice services have been methodologically limited. Aims: To examine the impact and cost-consequences of co-located benefits and debt advice on mental health and service use. Method: Prospective, controlled quasi-experimental study in eight intervention and nine comparator sites across North Thames. Changes in the proportion meeting criteria for common mental disorder (CMD, 12-item General Health Questionnaire); well-being scores (Shortened Warwick and Edinburgh Mental Well-being Scale), 3-month GP consultation rate and financial strain were measured alongside funding costs and financial gains. Results: Relative to controls, CMD reduced among women (ratio of odds ratios (rOR) = 0.37, 95% CI 0.20–0.70) and Black advice recipients (rOR = 0.09, 95% CI 0.03–0.28). Individuals whose advice resulted in positive outcomes demonstrated improved well-being scores (β coefficient 1.29, 95% CI 0.25–2.32). Reductions in financial strain (rOR = 0.42, 95% CI 0.23–0.77) but no changes in 3-month consultation rate were found. Per capita, advice recipients received £15 per £1 of funder investment. Conclusions: Co-located welfare advice improves short-term mental health and well-being, reduces financial strain and generates considerable financial returns

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Machine-learned target volume delineation of 18F-FDG PET images after one cycle of induction chemotherapy

Biological tumour volume (GTVPET) delineation on 18F-FDG PET acquired during induction chemotherapy (ICT) is challenging due to the reduced metabolic uptake and volume of the GTVPET. Automatic segmentation algorithms applied to 18F-FDG PET (PET-AS) imaging have been used for GTVPET delineation on 18F-FDG PET imaging acquired before ICT. However, their role has not been investigated in 18F-FDG PET imaging acquired after ICT. In this study we investigate PET-AS techniques, including ATLAAS a machine learned method, for accurate delineation of the GTVPET after ICT. Twenty patients were enrolled onto a prospective phase I study (FiGaRO). PET/CT imaging was acquired at baseline and 3 weeks following 1 cycle of induction chemotherapy. The GTVPET was manually delineated by a nuclear medicine physician and clinical oncologist. The resulting GTVPET was used as the reference contour. The ATLAAS original statistical model was expanded to include images of reduced metabolic activity and the ATLAAS algorithm was re-trained on the new reference dataset. Estimated GTVPET contours were derived using sixteen PET-AS methods and compared to the GTVPET using the Dice Similarity Coefficient (DSC). The mean DSC for ATLAAS, 60% Peak Thresholding (PT60), Adaptive Thresholding (AT) and Watershed Thresholding (WT) was 0.72, 0.61, 0.63 and 0.60 respectively. The GTVPET generated by ATLAAS compared favourably with manually delineated volumes and in comparison, to other PET-AS methods, was more accurate for GTVPET delineation after ICT. ATLAAS would be a feasible method to reduce inter-observer variability in multi-centre trials

On the functional anatomy of the urge-for-action

Several common neuropsychiatric disorders (e.g., obsessive-compulsive disorder, Tourette syndrome (TS), autistic spectrum disorder) are associated with unpleasant bodily sensations that are perceived as an urge for action. Similarly, many of our everyday behaviors are also characterized by bodily sensations that we experience as urges for action. Where do these urges originate? In this paper, we consider the nature and the functional anatomy of “urges-for-action,” both in the context of everyday behaviors such as yawning, swallowing, and micturition, and in relation to clinical disorders in which the urge-for-action is considered pathological and substantially interferes with activities of daily living (e.g., TS). We review previous frameworks for thinking about behavioral urges and demonstrate that there is considerable overlap between the functional anatomy of urges associated with everyday behaviors such as swallowing, yawning, and micturition, and those urges associated with the generation of tics in TS. Specifically, we show that the limbic sensory and motor regions—insula and mid-cingulate cortex—are common to all of these behaviors, and we argue that this “motivation-for-action” network should be considered distinct from an “intentional action” network, associated with regions of premotor and parietal cortex, which may be responsible for the perception of “willed intention” during the execution of goal-directed actions