Multicentre imaging measurements for oncology and in the brain

Abstract

ABSTRACT. Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (,2-3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B 1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T 1 , diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. There have been many approaches to carrying out multicentre imaging studies. A common difficulty is a measurement made at one centre is often not reproducible at another centre and to pool measurements from several centres into a large trial reduces its statistical power. Yet there is a strong imperative to be able to carry out meaningful multicentre studies so clinical drug trials with a large number of subjects can take place in a reasonable time. Analysing the sources of intercentre variation, with insight into the MR physics aspects of the imaging process, and then reducing them where possible has allowed progress to be made. Measuring actual quantities, such as volume, relaxation time or transfer constant, has meant in principle we are able to obtain values independent of the scanner used and the particular way the measurement was carried out.Multicentre imaging studies are desirable for several reasons. 1. In clinical treatment trials, they are usually the only way of achieving the large number of patients needed to statistically power the study. 2. Measurement of good intercentre agreement demonstrates the imaging technique is good and the results of clinical or scientific research can be applied to other centres. 3. Good intercentre agreement also demonstrates that the physical factors involv...

Diffusion-weighted magnetic resonance imaging in cancer: Reported apparent diffusion coefficients,in-vitroandin-vivoreproducibility

“…Statistical significance is usually assessed at P < 0.05 [125,126] . "A good qualified biomarker should have three properties: Biological relevance to the disease process under study, sensitivity to the disease process and good reproducibility" [127] . In clinical trials questions revolve around whether changes in individual patients can be measured reliably and reproducibly and whether they predict important clinical outcomes in terms of monitoring response to therapy [5,128] .…”

“…In a serial single-centre study, to establish treatment effect, each subject will normally be scanned at the same centre at each time point and it is the within-subject variance measured at a given centre, over the duration of the study, which is important. If the study is to be multi-centre "then between-centre variance should also be controlled" [127] . The within-centre variance for a subject or repeatability is important and it is measured using the Bland-Altman analysis method [123] .…”

“…The within-centre variance for a subject or repeatability is important and it is measured using the Bland-Altman analysis method [123] . In single centre studies, "repeated measurements are usually made in pairs over a set of subjects (typically 5-20) to establish the difference between repeats and whether this depends on the mean value of the parameter being estimated" [127] . In multicentre studies, protocol matching is the simplest method of reducing measurement differences [127] although "differences in imaging hardware produced by different vendors may prevent identical protocols being used at every site".…”

“…In single centre studies, "repeated measurements are usually made in pairs over a set of subjects (typically 5-20) to establish the difference between repeats and whether this depends on the mean value of the parameter being estimated" [127] . In multicentre studies, protocol matching is the simplest method of reducing measurement differences [127] although "differences in imaging hardware produced by different vendors may prevent identical protocols being used at every site". ADC maps are quantitative imaging maps, which in principle are "independent of the particular imaging protocols used" [127] although in reality significant variations in ADC values of different anatomical regions have been reported both in single-centre and in multi-centre studies [126] .…”

“…In multicentre studies, protocol matching is the simplest method of reducing measurement differences [127] although "differences in imaging hardware produced by different vendors may prevent identical protocols being used at every site". ADC maps are quantitative imaging maps, which in principle are "independent of the particular imaging protocols used" [127] although in reality significant variations in ADC values of different anatomical regions have been reported both in single-centre and in multi-centre studies [126] . In the following discussions the words (Philips, Siemens, GE and Toshiba) refer to MR system vendors Philips (Philips Healthcare, Best, The Netherlands), Siemens (Siemens Healthcare, Erlangen, Germany), GE (GE Healthcare, Waukesha, WI) and Toshiba (Toshiba Medical Systems, Tokyo, Japan).…”