Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences

Tofts, PS; Steens, Stefan C. A.; Cercignani, Mara; Admiraal-Behloul, Faiza; Hofman, Paul; Osch, Matthias J.P. van; Teeuwisse, Wouter M.; Tozer, Daniel J.; Waesberghe, J.H.T.M. van; Yeung, Reuben Au; Barker, Gareth J.; Buchem, Mark A. van

doi:10.1007/s10334-006-0049-8

Cited by 42 publications

(60 citation statements)

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“…One of the largest contributors to MTR variability is B 1 field non uniformity. [18][19][20] To minimize the effect of MTR variations between different brains on MTR sensitivity to cortical demyelination, we normalized the mean MTR ctx of each region using the subject's overall mean WM MTR. The mean normMTR ctx in MM ctx spanned the range of values inferred from published values.…”

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confidence: 99%

Clinically feasible MTR is sensitive to cortical demyelination in MS

et al. 2013

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Objective: Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS.Methods: MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MM ctx ), mostly demyelinated (MD ctx ), or intermediately demyelinated (ID ctx ). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. Conclusions: This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS. Neurology â 2013;80:246-252 GLOSSARY CL 5 cortical demyelinated lesions; HSD 5 honestly significant difference; ID ctx 5 intermediately demyelinated; LSM 5 least-squares mean; MD ctx 5 mostly demyelinated; MM ctx 5 mostly myelinated; MR 5 magnetic resonance; MS 5 multiple sclerosis; MTR 5 magnetization transfer ratio; MTR ctx 5 mean cortical magnetization transfer ratio; normMTR ctx 5 normalized cortical magnetization transfer ratio; PLP 5 proteolipid protein; TE 5 echo time; TR 5 repetition time; T1W 5 T1-weighted; WM 5 white matter.Cortical demyelinated lesions (CL) have been detected in patients with multiple sclerosis (MS) for more than 5 decades.1,2 Postmortem studies have raised the possibility that CL may be more prevalent than white matter (WM) demyelination 3 and that intracortical and mixed cortical/ WM lesions together may account for .50% of all MS brain lesions. 4 Despite their detection on postmortem tissue, most CL are invisible on conventional MRI. 4,5 The double inversion recovery sequence improves detection but does not reveal most CL. 5,6 While nonquantitative imaging features low sensitivity to CL, the sensitivity of semiquantitative and quantitative MRI is unclear. Although one ex vivo imaging study performed at 1.5 T revealed that T1 and T2 relaxation rates (not magnetization transfer ratio [MTR]) are sensitive to CL, 7 a separate study performed at 9.4 T found MTR and T2 relaxation rate (not T1) to be most sensitive.

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confidence: 99%

Clinically feasible MTR is sensitive to cortical demyelination in MS

et al. 2013

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“…All image data collection procedures are potentially vulnerable to the following sources of variation [3,12]: MR acquisition is also vulnerable to the following effects:…”

Section: Image Data Collectionmentioning

confidence: 99%

“…N RF coil architecture, which affects the B 1 and hence FA distribution (whether head or body coil excitation is used). Body coil excitation is preferable [12], although there can still be differences between vendors, particularly at 3 T.…”

Section: Image Data Collectionmentioning

confidence: 99%

“…tumour outline) and to generate a histogram (if used) [12] N mode of operation of analysis software N changes in analysis software over time.…”

Section: Image Analysismentioning

confidence: 99%

“…The largest source of variation in measuring MTR values are sequence and pulse differences [62], and B 1 factors [12]. MTR values in normal white matter are in the range 30-60 pu (percent units), depending crucially on the sequence used [8,12,62,63].…”

Section: Magnetisation Transfer Ratiomentioning

confidence: 99%

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Multicentre imaging measurements for oncology and in the brain

Tofts

Collins²

2011

BJR

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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...

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Magnetization Transfer Ratio in Gray Matter

Khaleeli¹,

Altmann²,

Cercignani³

et al. 2008

Arch Neurol

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Background: Magnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS). Objectives: To investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS.

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Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences

Abstract: Body coil excitation is preferred for multi-centre studies. Analysis (segmentation and histogram generation) should ideally be carried out at a single site.

Cited by 42 publications

References 41 publications

Clinically feasible MTR is sensitive to cortical demyelination in MS

Clinically feasible MTR is sensitive to cortical demyelination in MS

Multicentre imaging measurements for oncology and in the brain

Magnetization Transfer Ratio in Gray Matter

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