Has your patient's multiple sclerosis lesion burden or brain atrophy actually changed?

Abstract

Changes in mean magnetic resonance imaging (MRI)-derived measurements between patient groups are often used to determine outcomes in therapeutic trials and other longitudinal studies of multiple sclerosis (MS). However, in day-to-day clinical practice the changes withinindividual patients may also be of interest. In this paper, we estimated the measurement error of an automated brain tissue quantification algorithm and determined the thresholds for statistically significant change of MRI-derived T2 lesion volume and brain atrophy in individual patients. Twenty patients with MS were scanned twice within 30 min. Brain tissue volumes were measured using the computer algorithm. Brain atrophy was estimated by calculation of brain parenchymal fraction. The threshold of change between repeated scans that represented statistically significant change beyond measurement error with 95% certainty was 0.65 mL for T2 lesion burden and 0.0056 for brain parenchymal fraction. Changes in lesion burden and brain atrophy below these thresholds can be safely (with 95% certainty) explained by measurement variability alone. These values provide clinical neurologists with a useful reference to interpret MRI-derived measures in individual patients.

Keywords

brain atrophy computer-assisted image processing magnetic resonance imaging multiple sclerosis

Get full access to this article

View all access options for this article.

References

Filippi M , Dousset V , McFarland HF , Miller DH , Grossman RI. Role of magnetic resonance imaging in the diagnosis and monitoring of multiple sclerosis: consensus report of the White Matter Study Group . J Magn Reson Imaging 2002; 15: 499-504 .

Fisher E , Rudick RA , Simon JH , Cutter G , Baier M , Lee JC et al. Eight-year follow-up study of brain atrophy in patients with MS . Neurology 2002; 59: 1412-1420 .

Warfield SK , Kaus M , Jolesz FA , Kikinis R. Adaptive, template moderated, spatially varying statistical classification . Med Image Anal 2000; 4: 43-55 .

Wei X , Warfield SK , Zou KH , Wu Y , Li X , Guimond A et al. Quantitative analysis of MRI signal abnormalities of brain white matter with high reproducibility and accuracy . J Magn Reson Imaging 2002; 15: 203-209 .

Hohol M , Guttmann C , Olek M , Cook S , Gjorstrup P , Linde A et al. Roquinimex (LinomideR) treatment in secondary progressive and relapsing remitting multiple sclerosis: results from 48 week randomized, double-blind, placebo-controlled pilot studies . Neurology 1997; 48: A174-A174 .

Guttmann CR , Kikinis R , Anderson MC , Jakab M , Warfield SK , Killiany RJ et al. Quantitative follow-up of patients with multiple sclerosis using MRI: reproducibility . J Magn Reson Imaging 1999; 9: 509-518 .

Collins DL , Montagnat J , Zijdenbos AP , Evans AC , Arnold DL. Automated estimation of brain volume in multiple sclerosis with BICCR . In Proceedings of the 17th International Conference on Information Processing in Medical Imaging, London. Springer-Verlag, 2001: 141-147 .

Ge Y , Grossman RI , Udupa JK , Wei L , Mannon LJ , Polansky M et al. Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis . Radiology 2000; 214: 665-670 .

Rudick RA , Fisher E , Lee JC , Simon J , Jacobs L. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group . Neurology 1999; 53: 1698-1704 .

10.

Caramanos Z , Arnold DL , Collins DL. Measuring brain volume in patients with multiple sclerosis: a comparison of three common approaches . Proc Int Soc Magn Reson Med 2003; 11: 922-922 .

11.

Bland JM , Altman DG. Measurement error . BMJ 1996; 313: 744-744 .

12.

Eliasziw M , Young SL , Woodbury MG , Fryday-Field K. Statistical methodology for the concurrent assessment of interrater and intrarater reliability: using goniometric measurements as an example . Phys Ther 1994; 74: 777-788 .

13.

Mitchell JR , Karlik SJ , Lee DH , Eliasziw M , Rice GP , Fenster A. The variability of manual and computer assisted quantification of multiple sclerosis lesion volumes . Med Phys 1996; 23: 85-97 .

14.

Jacobson NS , Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research . J Consult Clin Psychol 1991; 59: 12-19 .

15.

Bland JM , Altman DG. Measurement error proportional to the mean . BMJ 1996; 313: 106-106 .

16.

Mitchell JR , Karlik SJ , Lee DH , Fenster A. Computer-assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain . J Magn Reson Imaging 1994; 4: 197-208 .

17.

Kikinis R , Shenton ME , Gerig G , Martin J , Anderson M , Metcalf D et al. Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging . J Magn Reson Imaging 1992; 2: 619-629 .

18.

Weiner HL , Guttmann CR , Khoury SJ , Orav EJ , Hohol MJ , Kikinis R et al. Serial magnetic resonance imaging in multiple sclerosis: correlation with attacks, disability, and disease stage . J Neuroimmunol 2000; 104: 164-173 .

19.

Filippi M , Horsfield MA , Ader HJ , Barkhof F , Bruzzi P , Evans A et al. Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis . Ann Neurol 1998; 43: 499-506 .

20.

Kikinis R , Guttmann CR , Metcalf D , Wells WM , Ettinger GJ , Weiner HL et al. Quantitative follow-up of patients with multiple sclerosis using MRI: technical aspects . J Magn Reson Imaging 1999; 9: 519-530 .

21.

Warfield S , Dengler J , Zaers J , Guttmann CR , Wells WM, 3rd , Ettinger GJ et al. Automatic identification of gray matter structures from MRI to improve the segmentation of white matter lesions . J Image Guid Surg 1995; 1: 326-338 .

22.

Wells WM , Grimson WEL , Kininis R , Jolesz FA. Adaptive segmentation of MRI data . IEEE Trans Med Imaging 1996; 15: 419-442 .

23.

Molyneux PD , Tubridy N , Parker GJ , Barker GJ , MacManus DG , Tofts PS et al. The effect of section thickness on MR lesion detection and quantification in multiple sclerosis . AJNR Am J Neuroradiol 1998; 19: 1715-1720 .