Public Funding for Perspectum Ltd

Collaboration between the academic and commercial sectors will be vital for the future of healthcare. Increasingly we are moving towards using software tools that combine the results of many different measurements and tests. This creates a comprehensive, overall picture of disease in an individual patient. These sophisticated tools provide valuable support and information for healthcare professionals to make clinical and treatment decisions. Collaboration between the academic and commercial sectors is necessary to develop these tools as they rely on both cutting-edge academic research in the understanding of disease, and their translation to the clinic as regulated products. We will second the manager of the Live Tissue Facility (LTF) in the Department of Oncology, University of Oxford to Perspectum Ltd. The LTF is a dedicated laboratory facility for processing and analysing human tissue samples (e.g. blood samples, tumour biopsy specimens) to support research. Perspectum are world leaders in using sophisticated magnetic resonance imaging (MRI) techniques to detect markers of disease. The work that we do will develop and adapt the LTF to make it accessible to Perspectum and suitable for their research needs. This will mostly involve changes in procedures and processes and so we will be able to use existing LTF funds to achieve this. The result will be a facility that is suitable and accessible for both institutions. Using this facility Perspectum will work towards combining human tissue data with their cutting-edge imaging technology, genetic information and pathology data to create sophisticated and innovative new software tools. The secondee will bring knowledge to Perspectum of how to process and analyse human tissue and how to equip a laboratory so that it is suitable for this work. They will also gain valuable experience of doing research in the commercial sector and take this knowledge back to the University. Here, they will use the knowledge to improve the LTF so that it is more attractive to other companies that may want to use it. The secondee will also learn to identify opportunities to commercialise the services provided by the LTF. This will generate income for the LTF and allow it to grow and expand into bigger and more impactful research projects. This will help generate more collaborations between the academic and commercial sectors and lead to faster advances in health care research.

This project aims to improve the clinical care of patients with liver tumours. By developing state-of-the-art tools that integrate genetic, radiology and pathology information we expect to improve the diagnosis and characterisation of tumours, and inform the selection of therapeutic options. This has the potential to improve clinical outcomes for the patient and reduce costs for the healthcare system. Liver surgery is the treatment of choice for curing liver tumours. However, surgery has inherent risks which are exacerbated if liver health is already compromised. This is of particular concern with the rising prevalence of obesity-linked chronic liver disease and more aggressive pre-operative chemotherapy. A major opportunity for improving diagnosis and treatment of liver tumours is better characterisation of tumour tissue, liver health and patient physiology. While there have been huge scientific and technical innovations in the understanding of liver and cancer biology, the translation of these developments to bedside care to improve health outcomes for cancer patients has been limited. Perspectum span out of the University of Oxford to commercialise novel MRI technology for diagnosing liver disease. In this project, Perspectum will collaborate with leading experts at the University of Oxford and Hampshire Hospitals NHS Foundation Trust (HHFT) to deliver this project. Initially, we will establish the analytical validity and clinical validity of either whole tissue or single cell whole genome sequencing (WGS). We will then begin a prospective study, in which patients can be included, as part of their standard package of care. With this consent Perspectum will provide a detailed consolidated and actionable report containing quantitative MRI imaging, digital pathology and WGS. This report will then be provided to the physician to assess the value of these additional metrics and whether they would have influenced the physician in determining the most appropriate treatment pathway for the patient. This project will develop a combined WGS, digital pathology and imaging approach to understanding primary and secondary liver tumours in patients with suspected liver cancer. Combining advanced imaging, pathology and WGS is something not currently done in clinical practice. By utilising this integrated approach, we hope to demonstrate measurable improvement in clinical outcomes and substantial benefits for healthcare systems.

Liver disease is an epidemic with up to four in ten people having health problems from their liver not working properly. A proportion of these patients develop scarring that is most commonly picked up late but which can progress without stopping to complete liver failure. It is one of the UK's largest health challenges for which we do not have answers. At present we use a wide range of single tests. These pick up disease when it is really well established or worse but do not pinpoint early disease or pick out those patients who are destined for much worse. Our project will address this lack of answers by teaming up with companies to make software that stitches together a wide range of different tests to come up with much better, much earlier answers. This would be a big breakthrough from the current 'one-size-fits-all' approach which does not work. This will allow small companies, such as Jiva.ai and Perspectum, to grow by working with university researchers in Manchester and Nottingham under the umbrella of global companies like Roche Diagnostics and GE Healthcare. This mix of skills between universities, hospitals and companies is a great way to come up with exciting breakthroughs. The three precise areas where we hope to make big discoveries are picking up very early liver problems in the community (currently they get missed); pulling together a wide range of data to help MRI scans beat large needle biopsies of the liver (which can on occasion go very wrong, like major bleeding or even death); and picking up those patients very early who might get liver cancer (at the moment liver cancer is often a death sentence because it gets picked up so late when there are no good treatments). To make sure we are successful we have got specialists who know how to develop new products in the NHS, experts to make sure the patient voice is heard, advice on developing your company, experts in working out whether the money adds up for new tests or treatments and experts in making sure good things get taken up into daily practice in the NHS. A big marker of our success will be seeing the small and medium sized companies grow because we have created new ways of giving patients the care they need in liver disease.

To develop the economic analysis that will persuade clients to incorporate a new diagnostic tool into the clinical diagnostic pathway for liver disease.

Biliary diseases are hard to diagnose and monitor, resulting in patient anxiety. There is an increasing incidence of biliary diseases, due in part to increasing levels of obesity, leading to increasing incidence of mortality. To date, there are no biomarkers for biliary diseases. We aim to redress this situation via a novel quantitative imaging technology, MRCP+. Chronic inflammation of the biliary ducts leads to hardening, obstruction, and eventual destruction, particularly in primary sclerosing cholangitis (PSC), a chronic, immune-mediated biliary disease. Currently, liver transplantation is the only proven life-extending intervention. PSC is designated an "orphan" disease (low incidence), however drug development has proved unsuccessful to date due to a lack of a reliable clinical endpoint. Post-transplant biliary complications remain a major cause of morbidity and mortality for all liver transplantations (approximately 14,000 per year in US/Europe). Currently, an invasive endoscopic procedure, ERCP, is a recommended modality for assessment of biliary disease, though ERCP is invasive and associated with significant risks of morbidity. This has encouraged take-up of MRI-based MRCP, which is non-invasive. Unfortunately, the advantages of MRCP are frustrated by its current limitations, a situation that this project aims to transform. A position statement from the International PSC Study Group outlines areas of unmet need for imaging techniques in PSC, including (1) early detection of disease, (2) the determination of disease stage, activity and prognosis, (3) a clinically meaningful definition of dominant bile duct stenosis, and (4) the early detection of cholangiocarcinoma. A recent survey by PSC Support highlighted that patients experience significant anxiety due to the uncertainties surrounding the prognostics limitations. Thus, there is a clear need for effective, non-invasive staging and monitoring of disease progression in PSC and related biliary diseases. Perspectum was spun out of the University of Oxford with the express aim to develop and commercialise technology for liver disease applications and its flagship product, LiverMultiScan, has been successfully adopted worldwide. Its newer product, MRCP+, is the only image processing software to enhance and quantify MRCP images. We aim to gather evidence in support of MRCP+ to enable it to be deployed clinically throughout the world.

"There has been a surge in incidence of the metabolic syndrome, a cluster of conditions including obesity, increased blood pressure and Type 2 diabetes (T2D), which increase the risk of fatty liver disease, steatohepatitis, heart disease and stroke. Multiple interacting organs are involved, primarily the pancreas, liver, spleen, kidneys and heart. Though T2D occurs when the pancreas doesn't work properly, concentrating on a single organ (e.g. pancreas) to diagnose T2D, or to assess the risk of it developing, is insufficient because all of the organs interact as a complex system, and so not only do each contribute to the diagnosis, but so does their combination. Most diabetes cases are detected using circulating (blood, urine) biomarkers (e.g. creatinine, aspartate transaminase, HbA1c). However, these are not sufficiently organ-specific and would benefit from complementary imaging, in particular MRI with its excellent soft-tissue contrast. Once detected and diagnosed, T2D is typically treated with the drug Metformin. This has transformed diabetes care; but it has limitations. New drugs overcome many of these limitations, including the glucagon-like peptide (GLP-1) receptor agonist and immunotherapies. Unfortunately, these cost at least ten times more than Metformin, so prescribing to everyone with diabetes poses a major problem for the NHS. This proposal aims to develop a method to stratify those patients for whom Metformin is expected to be inadequate and who should be prescribed more advanced, more expensive therapies. The technique will be based on Perspectum's Liver_Multiscan_. Perspectum has developed a quantitative MRI method to detect and stage early liver disease. As well, it has pilot data demonstrating its utility in other organs, for example: its technology can be used to estimate portal hypertension from the spleen; that it can detect and measure pancreatitis and fatty pancreas; and can characterise the tissue of the kidneys. Furthermore, Perspectum's founders worked originally in heart MRI imaging. This proposal will extend Liver_Multiscan_ to the other organs and vessels -- pancreas, kidney, spleen, aorta -- involved in the metabolic syndrome. The technical developments by Perspectum will be complemented by the accumulation and analysis of clinical data, both circulating biomarkers, genotyping and imaging, at three diverse endocrinology centres (Liverpool, Oxford, London). There will be strong patient and clinician involvement. The enhanced multi-organ product will be commercialised by Perspectum. The data produced by the project will be made available to researchers throughout the UK who are working to advance our understanding of T2D and the metabolic syndrome."

"The London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare will improve NHS patient care and health outcomes, reduce healthcare costs and support the growth of companies, supporting the economy. It will do this by applying artificial intelligence technologies to medical imaging (for example MRI scans, CT scans PET scans and ultrasound). Artificial intelligence will enable faster and earlier diagnosis, automation of reporting, improved patient screening for disease, and identification of the best treatment for each person. We will create a powerful, dynamic Centre bringing together industry, small and medium sized enterprises (SMEs), world-leading researchers, healthcare professionals covering many areas of practice, and experts in data science/governance. The Centre is a collaboration between three excellent universities (King's, Imperial and QMUL), four leading NHS Trusts (Guy's & St Thomas', King's College Hospital, South London & the Maudsley and Barts Health), multinational industry (Siemens, NVIDIA, IBM, GSK), 10 UK-based SMEs and the Health Innovation Network. The Centre will have a physical hub embedded in St Thomas' Hospital, in the heart of one of the UK's top-performing NHS Trusts with specialist services and one of the UK's largest critical care units. It will be underpinned by the existing Wellcome/EPSRC Centre for Medical Engineering, a flagship investment in medical imaging. The Centre will deliver well-governed, controlled access to high-quality NHS imaging and patient data for academic researchers, SMEs and industry partners. This will be done while preserving patient privacy as the first requirement. We will add dedicated expertise in health economics & statistics, care pathway design and clinical implementation to create an environment where products can be created and tested. Recognising this is a new development in healthcare, patients, the wider public and policy makers will all have opportunities to input and shape priorities for the Centre. The Centre will drive progress through a selection of 12 exemplar projects, specifically chosen, with public input, to illustrate the breadth of opportunity-- covering early life (fetal diagnosis) to old age (dementia), various organ systems including heart, brain and lungs, and diseases such as heart failure, headache, congenital conditions and cancer. In addition to the direct benefits of the Centre, this activity will act as a beacon to attract multinational companies, venture capital investment and AI talent from across the world, creating jobs, broader economic benefit and contributing to the UK's prosperity."

"This project aims to improve the standard care of patients with Autoimmune Hepatitis (AIH). AIH is a chronic inflammatory disease of the liver of unknown cause that, if untreated, can lead to liver failure, and death. Whislt there is an effective treatment with steriods and medicines that supress the immune system, these are not perfect, with many patients experiencing relapses and undesired side effects (such as weight gain, sleep disturbance, osteoporosis, eye problems). Efforts are therefore made to reduce doses where possible. As a result AIH patients require lifelong treatment and monitoring. Liver biopsy is the gold standard for evaluating the health of the liver but is risky, imprecise, expensive and painful, and therefore not a favoured option for treatment monitoring. Blood tests can identify when the liver is inflammed, but are not sensitive enough to small changes that might indicate a patients condition is likely to worsen. Better treatment monitoring in AIH has the potential to reduce the negative consequences of a relapse or 'flare', to reduce the chances of progression to cirrhosis from undetected long-term inflammation and to inform treatment more effectively, potentially reducing side effects. It also has the potential to reduce the need to invasive painful and risky biopsies. Perspectum Diagnostics span out of the University of Oxford to commercialise MRI technology for diagnosing liver disease. Its flagship product, LiverMultiScan, is a non-invasive procedure that can quantify the health of liver in a simple 15-minute scan. LMS has been successfully adopted worldwide for clinical trials investiagating non-alcoholic fatty liver disease. In this project, Perspectum will join with the internationally-recognised experts in the field of AIH in the department of hepatology at Kings College Hospital NHS trust, to address the utility of MRI to quanitfy liver fibrosis and inflammation in AIH patients, aiming to improve patient care and reduce healthcare costs. The main aim of the project is to demonstrate how adding a LiverMultiScan into the standard care pathway for patients with AIH may allow better treatment and accurate dosing of steroids thus preventing liver failure and associated NHS costs."

"We have formed a consortium of collaborating hospitals and commercial companies with public and patient involvement and input from charities to enable us to work with the public and the NHS to best develop and test the use of Artificial Intelligence programmes to improve health care. We are working with university academics and NHS hospitals across the country, from the south-west into London and including the North of England and Scotland. Our programme includes predominantly UK based companies ranging in size from a few employees to hundreds. We aim to learn about the difficult areas of ethics and public acceptance for machine learning and decision making in health care, and the use of patient data by commercial companies. We will put in strict safeguards to ensure patients and all involved in health care are confident that their data is managed securely and in a manner that would meet with their approval. Our ambition is to develop a relationship with patients and the NHS that will enable improved development and use of Artificial Intelligence to enhance the delivery of safer, better care, with clinical and economic gains to the NHS. Our programme of work will include the analysis and testing of algorithms on data for which we already have patient consent, and the collection of new patient data for which we will gain consent. This data will be securely stored and made available under strict rules to our collaborating academics and universities, and to commercial companies. Once we have developed and tested the Artificial Intelligence algorithms we will then test them in the NHS following applications to, and approvals from Research Ethics Committees."

"PathLEAD (**Path**ology data **L**akes, **E**ducation, **A**nalytics and **D**iscovery) is a consortium of nationally leading experts from the teaching hospitals of Coventry, Belfast, Nottingham and Oxford, their associated Universities and Philips, the commercial partner. We will develop computer aided diagnostics for testing of pathology samples. Specialist doctors (called pathologists) currently carry out testing via visual examination of pathology specimens under the microscope, a process that is inherently subjective. A large proportion of tissue samples examined are normal and using specialist pathologist time to establish this is expensive. We believe this can be done by computers, and valuable pathologist time saved and used elsewhere. Therefore we will develop a computer programme that will recognise normal tissue so that the sample does not need to examined by the pathologist. Furthermore we know that pathologists' performance is variable and in some cases limited, particularly where the tasks they perform are complex or require extensive experience. This can mean patients with some forms of breast and prostate cancer do not get the best treatment. Our computer programmes will assist the pathologist and improve these decisions. The development of these tools requires thousands of image files obtained from scanning microscope slides. This is time consuming to collect so once this data has been produced it is a valuable resource. We aim to make this available to other research teams, our commercial partner Philips and UK-based companies developing tools to improve healthcare. The result will be greater knowledge, improved tools and better care for the future. We recognise that patients have the right not to allow their data to be used for this purpose, and will be using the recently launched NHS National Data Opt Out scheme to record patients wishes accurately. Patients and lay representatives on our ethical and management committee will help decide how this data should be used. We expect that some tools will become successful commercially and plan to exploit this success re-investing some of the income back into the NHS to benefit patients. Our ability to provide high quality data, expertise, access to top-grade computer equipment and knowledge of commercialising these tools, will percolate to UK companies, building the economy in this sector and lead to the UK becoming a global leader. Our expertise will provide education to the pathology and computer science communities to share the knowledge gained, gaining in quality and efficiency, and having patients' benefit as our ultimate goal."

This project aims to improve the surgical care of patients with primary and secondary liver cancer. It will do this by developing a new product that uses medical imaging to measure the health of a patient’s liver, helping doctors personalise their treatment plans to individual patients. Liver surgery is the treatment of choice for curing cancer in the liver with on-going advances making curative treatment is available to more patients. However, it is difficult to decide how best to treat patients with the ideal combination of surgery, chemotherapy or localised non-surgical treatments. The greater the extent of liver surgery, the greater the risk of complications, which can include death, particularly in patients with unhealthy livers. Surgeons consider the volume of liver that would remain after surgery, but there is a clear need to also consider the health of this liver to reduce complications. Perspectum Diagnostics span out of the University of Oxford to commercialise novel MRI technology for diagnosing liver disease. Its first product was successful in bringing this technology to the clinic worldwide. In this project, Perspectum will join with the University of Edinburgh and North Hampshire Hospital, both internationally-recognised pioneers in the field of liver surgery, to address this important clinical need with a new product 'Hepatica' aiming to improve patient care and reduce healthcare costs.

To develop new algorithms to create the vital bioinformatic and statistical platform for a novel MRI-based method to determine fat, iron, inflammation/fibrosis in the liver.

Awaiting Public Project Summary

Chronic liver disease has been termed “the silent killer”: It usually does not cause symtoms until it is too late and most of the liver has been destroyed, at which point life expectancy is short. Furthermore, unlike heart disease or cancer, chronic liver disease will become much more frequent over the next 20 years, mainly because many more people are becoming obese and diabetic, two illnesses which damage the liver. We therefore need better diagnostic tools to recognise patients with liver disease early, to accurately measure the degree of liver damage, and measure both, the progression of liver damage over time, and its improvement with treatment. Currently, the only reliable diagnostic method is biopsy, where liver tissue is obtained by inserting a needle and is then assessed under a microscope. Liver biopsy has serious limitations, is unwelcomed by patients, as it can be painful, and there is a risk of serious complications. Perspectum Diagnostics is a company founded by members of Oxford University, who have developed new magnetic resonance imaging (MRI) technology, LiverMultiscan™, to quickly, accurately and safely measure the degree and extent of liver damage without needles. We believe that our test could replace liver biopsy and become the best way to assess patients over time. We propose to develop our prototype technology into a robust diagnostic product, to be used routinely in patients within 2-3 years. Our vision is to fundamentally change the way liver disease is diagnosed and treated, because our new imaging method will provide risk-free, instant, and accurate assessment of the liver.