Title: Advanced computer diagnostics for whole body magnetic resonance imaging to improve management of patients with metastatic bone cancer
Funder: Department of Health and Social Care

Abstract: This project will create advanced image analysis software to be used with WB-MR to provide doctors with timely information to treat patients with bone disease from prostate cancer. The software will be commercialised and made available for potential adoption within the NHS. WB-MRI on its own can reveal bone disease across the body, but the MR scanners used to produce the images lack sophisticated software to measure all the disease demonstrated. Using our prototype software with WB-MRI, we can measure the total body bone disease volume (TDV) and also the total disese apparent diffusion coefficient (ADC), which reflects tumour cell density. We have proof of concept data that shows that TDV decreases whilst ADC values increase (reflecting reduction in tumour cell density) when bone disease responds to treatment, thus aiding the decision to continue, stop or change therapy. However, our software is scripted using interactive data language (IDL), which has limitations: (1) image processing is time consuming, (2) it lacks a user-friendly interface, (3) pre-processing steps are needed, and (4) visual selection by a doctor is required to define disease, which introduces inter-/intra-operator variability of 5%/12% for ADC/TDV estimations. We aim to deliver our invention for innovation by: Software development. We have forged a commercial/research collaboration with Mint Medical GmbH. The Company has an excellent image analysis and reporting platform used for assessing tumour response to treatment. We will develop a powerful software toolkit that will automate WB-MRI analysis, which will be integrated onto this platform. Specific innovations include: (1) Novel image processing (Noise-Corrected eDWI; patent filed) to improve/ automate disease identification and segmentation, (2) improved tools for measuring ADC/TDV statistics, (3) machine learning of imaging trial data to develop treatment response classifiers. Components (1) & (2) will be incorporated into a plugin for the widely used image-viewer (OsiriX) for testing in our multicentre imaging trial. We will roadmap a commercial version, which will include components (1), (2) & (3) for CE marking, in collaboration with Mint Medical GmbH. Imaging trial validation: We will evaluate our software toolkit in 96 patients with prostate bone disease included in a multicentre clinical trial [CTC-STOP] using a test-validation set design. We assume the response rate to chemotherapy is 30% and the sensitivity of WB-MRI for response assessment at 8-12 weeks after treatment is 86% [Blackledge M, 2014]. A sample size of 43 patients will have 90% power to show that the sensitivity of WB-MRI is > 50% at one-sided 5% significance level; an improvement from the Health Economics evaluation: We will evaluate the cost and cost-effectiveness to the NHS of WB-MRI plus the software versus conventional tests (CT, BS) for disease management in patients with prostate bone disease. This will include the cost of WB-MRI (including using the software), CT and BS tests. It will also include economic modelling to evaluate the cost-effectiveness of both options, accounting for the impact of the testing regime on subsequent treatment, as well as disease outcomes and treatment costs.

Lay abstract: Bone disease from cancer spread is an important cause of pain, fractures and death. Treatment of bone disease is changing because there are new but often-expensive drugs that can improve symptoms and prolong life. However, standard CT scan and bone scan (BS) in the NHS use harmful radiation and cannot reliably assess which patients are responding to cancer treatments. In contrast, whole body MRI (WB-MRI), which includes a special scan called diffusion-weighted imaging (DWI), does not use harmful radiation and can more accurately identify patients responding to treatment. WB-MRI can be performed across the NHS but is not currently used to measure treatment response of bone disease because there is no software to assess multiple sites of disease typically seen in these patients. The main aim of this project is to develop, test and evaluate new computer software, based on an existing prototype, to measure treatment response of bone cancer in patients. We want to show that using our software with WB-MRI can more reliably tell doctors whether treatment is effective compared with standard CT and BS, so that expensive ineffective treatment can be stopped or replaced. We will develop our software prototype to include more sophisticated analysis and a user-friendly interface in collaboration with our commercial partner. The software will be evaluated in 96 patients with prostate bone cancer undergoing WB-MRI before and at 8-12 weeks after treatment; and will be compared with CT and BS for ability to identify responders and non-responders to treatment. We will test the reliability of the software across 8-10 centres, and find out whether WB-MRI is cost-effective as a replacement test for CT and BS. Based on this, we will develop a sofware for commercialisation with our industrial partner, which will be CE marked containing enhanced tools for faster and more powerful analysis.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS