Water diffusion is elevated in widespread regions of normal-appearing white matter in multiple sclerosis and correlates with diffusion in focal lesions

Abstract

Pathological changes in the normal-appearing white matter in multiple sclerosis are well recognised, but their relationship to pathology in focal lesions is not well understood. Magnetic resonance diffusion imaging is sensitive to abnormalities in the integrity, size and geometry of water spaces in brain tissue. This study investigated the anatomical distribution of normal-appearing white matter diffusion abnormalities and their relationship to diffusion in focal lesions in multiple sclerosis (MS). The average apparent diffusion coefficient (ADC_av) was measured by three-axis echoplanar diffusion imaging in normal-appearing white matter regions and lesions throughout the brain in 40 patients, and in white matter in 14 matched controls. The correlation between the ADC_av in normal-appearing white matter and lesions was determined. In controls and patients, diffusion was highest in the corpus callosum. Patients had a higher mean ADC_av than controls in widespread regions including the corpus callosum, cerebellar, temporal and occipital normal-appearing white matter. Mean normal-appearing white matter ADC_av correlated strongly with mean lesion ADC_av (r=0.67, P < 0.001). This study demonstrates that water diffusion is elevated in widespread areas of normal-appearing white matter in MS, and is correlated with diffusion in lesions. These findings suggest that the pathogenetic mechanisms causing tissue damage in lesions and normal-appearing white matter are at least partly linked.

Keywords

MRI multiple sclerosis brain diffusion pathophysiology

Get full access to this article

View all access options for this article.

References

Husted CA et al. (1994) Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging . Ann Neurol 36: 157-165 .

Dousset V et al. (1992) Experimental allergic encephalomyelitis and multiple sclerosis lesion characterization with magnetization transfer imaging . Radiology 182: 483-491 .

LeBihan D , Breton E. (1985) Imagerie de diffusion in vivo par resonance magnetique nucleaire . CR Acad Sc Paris 301: 1109-1112 .

Christiansen P et al. (1993) Increased water self-diffusion in chronic plaques and apparently normal white matter in patients with multiple sclerosis . Acta Neurol Scand 87: 195-199 .

Horsfield MA et al. (1996) Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance . Magn Reson Med 36: 393-400 .

Droogan AG et al. (1999) Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging . Magn Reson Imag 17: 653-661 .

Werring DJ et al. (1999) Diffusion tensor imaging of lesions and normal appearing white matter in multiple sclerosis . Neurology 52: 1626-1632 .

Filippi M et al. (2000) A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging . Arch Neurol 57: 1017-1021 .

Poser CM et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols . Ann Neurol 13: 227-231 .

10.

Lublin FD , Reingold SC. (1996) Defining the clinical course of multiple sclerosis: results of an international survey . Neurology 46: 907-911 .

11.

Kurtzke JF. (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) . Neurology 33: 1444-1152 .

12.

Barker GJ , Clark CA , Franconi F , Symms M. (1997) A CSF-suppressed, EPI based pulse sequence for diffusion tensor and apparent diffusion constant measurement in multiple sclerosis . Proc Int Soc Magn Reson 1: 223-223 (Abstract).

13.

Stejsjkal EO , Tanner JE. (1965) Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient . J Chem Phys 42: 288-292 .

14.

LeBihan D et al. (1996) MR imaging of intravoxel incoherent motions . Radiology 161: 401-407 .

15.

Hand D , Crowder M (1996) Practical longitudinal data analysis. Chapman and Hall: London .

16.

Falconer JC , Narayana PA. (1997) Cerebrospinal fluid-suppressed high-resolution diffusion imaging of human brain . Magn Reson Med 37: 119-123 .

17.

Pierpaoli C et al. (1996) Diffusion tensor MR imaging of the human brain . Radiology 210: 637-648 .

18.

Ulug AM , van Zijl PCM. (1999) Orientation-independent diffusion imaging without tensor diagonalisation: anisotropy definitions based on physical attributes of the diffusion ellipsoid . JMRI 9: 804-813 .

19.

Loevner LA et al. (1995) Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements . Radiology 196: 511-515 .

20.

Sarchielli P et al. (1999) Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients . Brain 122: 513-521 .

21.

Leary SM et al. (1999) Magnetization transfer of normal appearing white matter in primary progressive multiple sclerosis . Multiple Sclerosis 5: 313-316 .

22.

Brownell B , Hughes JT. (1962) The distribution of plaques in the cerebrum in multiple sclerosis . JNeurol Neurosurg Psychiatry 25: 315-320 .

23.

Narayanan S et al. (1997) Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions . Ann Neurol 41: 385-391 .

24.

Allen IV , McKeown SR. (1979) A histological, histo-chemical and biochemical study of the macroscopically normal white matter in multiple sclerosis . J Neurol Sci 41: 81-91 .

25.

Newcombe J , Cuzner ML , Roytta M , Frey H. (1980) White matter proteins in multiple sclerosis . J Neurochemistry 34: 700-708 .

26.

Tourtellotte WW , Parker JA. (1968) Some spaces and barriers in postmortem multiple sclerosis. In Lajtha A and Ford DH (eds.) Brain Barrier Systems. Progress in Brain Research. Vol. 29. Elsevier:Amsterdam , pp 493-525.

27.

Evangelou N et al. (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis . Ann Neurol 47: 391-395 .

28.

Trapp BD et al. (1998) Axonal transection in the lesions of multiple sclerosis . N Engl J Med 338: 278-285 .

29.

Ferguson B , Matyszak MK , Esiri MM , Perry VH. (1997) Axonal damage in acute multiple sclerosis lesions . Brain 120: 393-399 .

30.

De Stefano N et al. (1998) In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis . Brain 122: 1933-1939 .

31.

Moreau T et al. (1996) Cytokine release increases conduction block in partially demylinated pathways due to multiple sclerosis . Brain 119: 225-237 .

32.

Goodkin DE et al. (1998) A serial study of new MS lesions and the white matter from which they arise . Neurology 51: 1689-1697 .

33.

Filippi M et al. (1998) Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis . Ann Neurol 43: 809-814 .

34.

Pike GB et al. (1998) A longitudinal study of magnetisation transfer in multiple sclerosis . Proc Int Soc Magn Reson Med 1: 122-122 (Abstract).

35.

Werring DJ et al. (2000) The pathogenesis of lesions and normal-appearing white matter abnormalities in multiple sclerosis: A serial diffusion magnetic resonance imaging study . Brain 123: 1667-1676 .

36.

Nakashima I et al. (1999) Clinical and MRI study of brainstem and cerebellar involvement in Japanese patients with multiple sclerosis . J Neurol Neurosurg Psychiatry 67: 153-157 .

37.

Miller DH. (1999) Clinical and magnetic resonance imaging heterogeneity in multiple sclerosis . JNeurol Neurosurg Psychiatry 67: 139-139 .

38.

Luchinetti C et al. (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis. A study of 113 cases . Brain 122: 2279-2295 .