Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Objective To assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection. Design Baseline findings from a prospective, observational cohort study. Setting Community-based individuals from two UK centres between 1 April and 14 September 2020. Participants Individuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls. Intervention Assessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI. Main outcome measures Severe post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation. Results 201 individuals (mean age 45, range 21–71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110–162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05). Conclusions In individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities. Trial registration number NCT04369807; Pre-results.

We propose a modification of Wells et al. technique for bias field estimation and segmentation of magnetic resonance (MR) images. We show that replacing the class other, which includes all tissue not modeled explicitly by Gaussians with small variance, by a uniform probability density, and amending the expectation-maximization (EM) algorithm appropriately, gives significantly better results. We next consider the estimation and filtering of high-frequency information in MR images, comprising noise, intertissue boundaries, and within tissue microstructures. We conclude that post-filtering is preferable to the prefiltering that has been proposed previously. We observe that the performance of any segmentation algorithm, in particular that of Wells et al. (and our refinements of it) is affected substantially by the number and selection of the tissue classes that are modeled explicitly, the corresponding defining parameters and, critically, the spatial distribution of tissues in the image. We present an initial exploration to choose automatically the number of classes and the associated parameters that give the best output. This requires us to define what is meant by "best output" and for this we propose the application of minimum entropy. The methods developed have been implemented and are illustrated throughout on simulated and real data (brain and breast MR).