Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives

Eur Radiol DOI 10.1007/s00330-017-4972-z MAGNETIC RESONANCE Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives N. M. deSouza 1 & J. M. Winfield 1 & J. C. Waterton 2 & A. Weller 1 & M.-V. Papoutsaki 1 & S. J. Doran 1 & D. J. Collins 1 & L. Fournier 3 & D. Sullivan 4 & T. Chenevert 5 & A. Jackson 2 & M. Boss 6 & S. Trattnig 7 & Y. Liu 8 Received: 30 November 2016 / Revised: 24 May 2017 / Accepted: 28 June 2017 # The Author(s) 2017. This article is an open access publication Abstract For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials Contribution of NIST - not subject to copyright in the US * N. M. deSouza M. Boss J. M. Winfield S. Trattnig J. C. Waterton A. Weller Y. Liu 1 CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Surrey SM2 5PT, UK 2 Manchester Academic Health Sciences Institute, University of Manchester, Manchester, UK 3 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Radiology Department, Université Paris Descartes Sorbonne Paris Cité, Paris, France 4 Duke Comprehensive Cancer Institute, Durham, NC, USA 5 Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA 6 Applied Physics Division, National Institute of Standards and Technology (NIST), Boulder, CO, USA T. Chenevert 7 Department of Biomedical Imaging and Image guided Therapy, Medical University of Vienna, 1090 Vienna, Austria A. Jackson 8 European Organisation for Research and Treatment of Cancer, Headquarters, Brussels, Belgium M.-V. Papoutsaki S. J. Doran D. J. Collins L. Fournier D. Sullivan Eur Radiol involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multivendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology. Key Points • Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials. • Establishing Bprecision^ of the measurement in the multicentre context is essential. • A repository with traceable data of known provenance promotes further research. Keywords Diffusion-weighted MRI . Multicentre trials . Quality assurance . Quantitation . Standardization Essentials 1. When utilizing the Apparent Diffusion Coefficient (ADC) as an imaging biomarker in multicentre trials, processes that standardise data acquisition and analysis within a framework of Quality Assurance and Quality Control are mandatory. 2. Test-object and healthy volunteer studies should be used to develop an imaging protocol for multi-vendor, multi field-strength use and establish the precision of the ADC measurement within a multicentre trial context. 3. A streamlined workflow for data curation, archiving and analysis in a central repository ensures traceable data within the trial as well as its preservation for further research. 2. A standardised ADC measurement in longitudinal studies could be utilized as a prognostic biomarker in oncology and for stratifying patients for therapeutic interventions. Introduction Diffusion-weighted magnetic resonance imaging (DW-MRI) provides unique soft tissue contrast and is now used in tumour detection, staging and for monitoring response to treatment in a variety of tumour types [1–8]. It may be utilized qualitatively (binary, normal vs. abnormal), semi-quantitatively (scoring system, e.g., grade I-V) or quantitatively (continuum, derived numerical values). Qualitative assessments are quick and easy for the expert radiologist but are variable in interpretation. Objective semi-quantitative (scoring systems) or quantitative (numerical) assessments are more robust; the latter deliver information beyond visual perception. The apparent diffusion coefficient (ADC) derived from DW-MRI describes the diffusion of a water molecule proton (typically over 10-40 μm during 10-100 msec) and reflects tissue microstructure and its remodelling. This is interesting for drug developers as it sits in the Bpharmacologic audit trail^ [9] downstream of a target and its pathway (thereby uniting many therapy classes), but upstream of macroscopic disease modification (thus making it suitable for early readouts). Such quantitative measurements potentially offer earlier indicators of response than conventional size criteria, with ethical and economic benefits for sponsors and pharmaceutical companies as well as for patients and society in general. The implementation of DW-MRI, however, is variable across scanner platforms [10], tissue-type being studied and methods of interpretation and analysis. Consensus on image acquisition and analysis methods must be reached before embarking on a clinical trial and measures put in place to standardise the process across centres. Furthermore, the utility of quantitative ADC metrics as response biomarkers depends on the variability of the measurement, which must be established and minimized. This article reviews current knowledge of factors that require consideration (equipment, technical development, quality control, infrastructure, expertise and governance issues) when acquiring and analysing DW-MRI data prior to adopting ADC as a biomarker in multicentre trials. Data Acquisition Patient Impact Hardware and software considerations 1. A standardised ADC measurement would enable incorporation of an imaging biomarker of response as an early end-point in multicentre trials of cancer therapies. Over the last decade significant hardware improvements have enhanced data acquisition. Signal-to-noise ratio [SNR] Eur Radiol improvements have resulted from higher field strength (3T), improved (...truncated)