Deep Boosted Regression for MR to CT Synthesis

Attenuation correction is an essential requirement of positron emission tomography (PET) image reconstruction to allow for accurate quantification. However, attenuation correction is particularly challenging for PET-MRI as neither PET nor magnetic resonance imaging (MRI) can directly image tissue attenuation properties. MRI-based computed tomography (CT) synthesis has been proposed as an alternative to physics based and segmentation-based approaches that assign a population-based tissue density value in order to generate an attenuation map. We propose a novel deep fully convolutional neural network that generates synthetic CTs in a recursive manner by gradually reducing the residuals of the previous network, increasing the overall accuracy and generalisability, while keeping the number of trainable parameters within reasonable limits. The model is trained on a database of 20 pre-acquired MRI/CT pairs and a four-fold random bootstrapped validation with a 80:20 split is performed. Quantitative results show that the proposed framework outperforms a state-of-the-art atlas-based approach decreasing the Mean Absolute Error (MAE) from 131HU to 68HU for the synthetic CTs and reducing the PET reconstruction error from 14.3% to 7.2%.Comment: Accepted at SASHIMI201

Improved MR to CT synthesis for PET/MR attenuation correction using Imitation Learning

The ability to synthesise Computed Tomography images - commonly known as pseudo CT, or pCT - from MRI input data is commonly assessed using an intensity-wise similarity, such as an L2-norm between the ground truth CT and the pCT. However, given that the ultimate purpose is often to use the pCT as an attenuation map ($\mu$-map) in Positron Emission Tomography Magnetic Resonance Imaging (PET/MRI), minimising the error between pCT and CT is not necessarily optimal. The main objective should be to predict a pCT that, when used as $\mu$-map, reconstructs a pseudo PET (pPET) which is as close as possible to the gold standard PET. To this end, we propose a novel multi-hypothesis deep learning framework that generates pCTs by minimising a combination of the pixel-wise error between pCT and CT and a proposed metric-loss that itself is represented by a convolutional neural network (CNN) and aims to minimise subsequent PET residuals. The model is trained on a database of 400 paired MR/CT/PET image slices. Quantitative results show that the network generates pCTs that seem less accurate when evaluating the Mean Absolute Error on the pCT (69.68HU) compared to a baseline CNN (66.25HU), but lead to significant improvement in the PET reconstruction - 115a.u. compared to baseline 140a.u.Comment: Aceppted at SASHIMI201

Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2.

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society

Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. METHODS: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. RESULTS: 694 (276 younger (5-11 years), 418 older (12-17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2-9.75) with Alpha, 5 days (IQR 2-9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2-5) symptoms with Alpha, 4 (IQR 2-7) with Delta; in older children, 5 (IQR 3-8) symptoms with Alpha, 6 (IQR 3-9) with Delta infection ). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. CONCLUSIONS: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Construction of a device for magnetic separation of superparamagnetic iron oxide nanoparticles

Suspensions of iron oxide particles, so called ferrofluids, are successfully used in various technical, biochemical and medical applications. For example they find use in the area of sensor engineering, magnetic resonance imaging (MRI) and especially magnetic particle imaging (MPI). MPI is a new tomographic imaging technique that determines the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs). Besides a very high spatial and temporal resolution MPI provides quantitative realtime imageing. The nanoparticles cause a magnetization change that can be measured. As the particle size distribution has a huge impact on the magnetization behavior is an important parameter for optimization. While synthesizing, SPIONs particles with various dimensions are formed what necessitates a systematically separation by size. For this purpose a construction of a simple device for magnetic separation of SPIONs has been developed. First attemps of separation show the potential of this method

PET/MRI attenuation estimation in the lung:A review of past, present, and potential techniques

Positron emission tomography/magnetic resonance imaging (PET/MRI) potentially offers several advantages over positron emission tomography/computed tomography (PET/CT), for example, no CT radiation dose and soft tissue images from MR acquired at the same time as the PET. However, obtaining accurate linear attenuation correction (LAC) factors for the lung remains difficult in PET/MRI. LACs depend on electron density and in the lung, these vary significantly both within an individual and from person to person. Current commercial practice is to use a single-valued population-based lung LAC, and better estimation is needed to improve quantification. Given the under-appreciation of lung attenuation estimation as an issue, the inaccuracy of PET quantification due to the use of single-valued lung LACs, the unique challenges of lung estimation, and the emerging status of PET/MRI scanners in lung disease, a review is timely. This paper highlights past and present methods, categorising them into segmentation, atlas/mapping, and emission-based schemes. Potential strategies for future developments are also presented

Imitation learning for improved 3D PET/MR attenuation correction

The assessment of the quality of synthesised/pseudo Computed Tomography (pCT) images is commonly measured by an intensity-wise similarity between the ground truth CT and the pCT. However, when using the pCT as an attenuation map (μ-map) for PET reconstruction in Positron Emission Tomography Magnetic Resonance Imaging (PET/MRI) minimising the error between pCT and CT neglects the main objective of predicting a pCT that when used as μ-map reconstructs a pseudo PET (pPET) which is as similar as possible to the gold standard CT-derived PET reconstruction. This observation motivated us to propose a novel multi-hypothesis deep learning framework explicitly aimed at PET reconstruction application. A convolutional neural network (CNN) synthesises pCTs by minimising a combination of the pixel-wise error between pCT and CT and a novel metric-loss that itself is defined by a CNN and aims to minimise consequent PET residuals. Training is performed on a database of twenty 3D MR/CT/PET brain image pairs. Quantitative results on a fully independent dataset of twenty-three 3D MR/CT/PET image pairs show that the network is able to synthesise more accurate pCTs. The Mean Absolute Error on the pCT (110.98 HU ± 19.22 HU) compared to a baseline CNN (172.12 HU ± 19.61 HU) and a multi-atlas propagation approach (153.40 HU ± 18.68 HU), and subsequently lead to a significant improvement in the PET reconstruction error (4.74% ± 1.52% compared to baseline 13.72% ± 2.48% and multi-atlas propagation 6.68% ± 2.06%)

Short Acquisition Time PET/MR Pharmacokinetic Modelling Using CNNs

Standard quantification of Positron Emission Tomography (PET) data requires a long acquisition time to enable pharmacokinetic (PK) model fitting, however blood flow information from Arterial Spin Labelling (ASL) Magnetic Resonance Imaging (MRI) can be combined with simultaneous dynamic PET data to reduce the acquisition time. Due the difficulty of fitting a PK model to noisy PET data with limited time points, such ‘fixed- R1’ techniques are constrained to a 30 min minimum acquisition, which is intolerable for many patients. In this work we apply a deep convolutional neural network (CNN) approach to combine the PET and MRI data. This permits shorter acquisition times as it avoids the noise sensitive voxelwise PK modelling and facilitates the full modelling of the relationship between blood flow and the dynamic PET data. This method is compared to three fixed- R1PK methods, and the clinically used standardised uptake value ratio (SUVR), using 60 min dynamic PET PK modelling as the gold standard. Testing on 11 subjects participating in a study of pre-clinical Alzheimer’s Disease showed that, for 30 min acquisitions, all methods which combine the PET and MRI data have comparable performance, however at shorter acquisition times the CNN approach has a significantly lower mean square error (MSE) compared to fixed- R1PK modelling (p=0.001). For both acquisition windows, SUVR had a significantly higher MSE than the CNN method (p ࣘ 0.003). This demonstrates that combining simultaneous PET and MRI data using a CNN can result in robust PET quantification within a scan time which is tolerable to patients with dementia