Elsevier

Academic Radiology

Volume 8, Issue 11, November 2001, Pages 1116-1126
Academic Radiology

Multiprotocol MR Image Segmentation in Multiple Sclerosis: Experience with Over 1,000 Studies

https://doi.org/10.1016/S1076-6332(03)80723-7Get rights and content

Abstract

Rationale and Objectives

Multiple sclerosis (MS) is an acquired disease of the central nervous system. Several clinical measures are commonly used to express the severity of the disease, including the Expanded Disability Status Scale and the ambulation index. These measures are subjective and may be difficult to reproduce. The aim of this research is to investigate the possibility of developing more objective measures derived from MR imaging.

Materials and Methods

Various magnetic resonance (MR) imaging protocols are being investigated for the study of MS. Seeking to replace the Expanded Disability Status Scale and ambulation index with an objective means to assess the natural course of the disease and its response to therapy, the authors have developed multiprotocol MR image segmentation methods based on fuzzy connectedness to quantify both macrosopic features of the disease (lesions, gray matter, white matter, cerebrospinal fluid, and brain parenchyma) and the microscopic appearance of diseased white matter. Over 1,000 studies have been processed to date.

Results

By far the strongest correlations with the clinical measures were demonstrated by the magnetization transfer ratio histogram parameters obtained for the various segmented tissue regions. These findings emphasize the importance of considering the microscopic and diffuse nature of the disease in the individual tissue regions. Brain parenchymal volume also demonstrated a strong correlation with clinical measures, which suggests that brain atrophy is an important disease indicator.

Conclusion

Fuzzy connectedness is a viable, highly reproducible segmentation method for studying MS.

Section snippets

T2-Weighted Imaging

The sensitivity of T2-weighted imaging in the detection of MS has long been recognized (5, 6). MS lesions appear hyperintense on T2-weighted images. The clinical course of MS is mainly defined by the baseline disability of the patient, also called the disease burden. The extent of lesions on T2-weighted images, usually expressed as the total volume of lesions (T2LV), is currently regarded as the MR imaging measure of this disease burden. Dual-echo T2-weighted and proton-density (PD)–weighted

T1-Weighted Imaging with Gadolinium Enhancement

In MS, gadolinium (gadopentetate dimeglumine) enhancement on MR images is characterized by transient blood-brain barrier abnormality and inflammation that represents the acute stage of the evolution of MS (17, 18). On enhanced T1-weighted images, gadolinium enhancement appears as a homogeneous, strongly hyperintense lesion or as a ring-shaped area of hyperintensity at the edge of chronic reactivated lesions. Enhancement is sensitive in demonstrating disease activity and may help distinguish

MT Imaging

MS is now believed to be a diffuse process that extensively involves the WM and is not restricted to the focal regions of disease activity visible as “lesions” on conventional T2-weighted, PD, and gadolinium-enhanced T1-weighted images. This notion came about mainly from MT image analysis (22) but is also supported by postmortem study (23) revealing microscopic disease characterized by edema, cellular infiltration, and demyelination in macroscopically normal-appearing WM. In MT imaging (24),

T1-Weighted Imaging

Another standard MR imaging technique routinely used in MS is T1-weighted imaging (spin echo), which often shows hypointense areas that have been suggested to represent areas of axonal loss and gliosis (28). In recent quantitative studies (29, 30), a significant correlation was reported between increase in disability and increase in the volume of these lesions. If hypointense lesions represent areas of severe demyelination, axonal loss, or gliosis (27, 28), then the higher rate of new lesions

Data Acquisition

The MR imaging protocols we have used are listed in the Table. Every patient recruited in our trial undergoes all acquisitions listed. Our image database currently consists of the following number of patient studies and three-dimensional volume images that have been processed by the methods described in this section: 690 T2-weighted imaging studies; 660 T1-weighted studies, each with and without contrast enhancement; and 670 MT studies. Altogether, the study included 100 patients and over 4,000

Validation

Any segmentation effort consists of (a) a theoretical or algorithmic framework, (b) considerable engineering effort to make the framework work in the application at hand, and (c) evaluation to establish the precision, accuracy, and efficiency of the method for the particular application. Precision here refers to the reproducibility of the segmentation results with all subjective actions taken into consideration, including how the patient is positioned in the imager and any operator input

Automation, Failure, and User Assistance

Any segmentation method can go wrong, and therefore will, if enough studies are analyzed in a routine clinical trial. Therefore, for quality assurance, it is important to have a knowledgeable human operator within the processing loop. Complete automation may therefore be an elusive goal, perhaps reachable after only a great deal of experience within the same imaging modality, protocol, and application setting. As researchers and developers, our aim should be to consider human interaction within

Acknowledgments

The authors are grateful to Mary A. Blue for typing the manuscript.

References (54)

  • RA Rudick et al.

    Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG)

    Neurology

    (1997)
  • KP Johnson et al.

    Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group

    Neurology

    (1998)
  • Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group

    Neurology

    (1995)
  • DH Miller et al.

    The role of magnetic resonance techniques in understanding and managing multiple sclerosis

    Brain

    (1998)
  • DW Paty et al.

    Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group

    Neurology

    (1993)
  • Y Miki et al.

    Relapsing-remitting multiple sclerosis: longitudinal analysis of MR images—lack of correlation between changes in T2 lesion volume and clinical findings

    Radiology

    (1999)
  • AJ Thompson et al.

    Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study

    Br Med J

    (1990)
  • AG Kermode et al.

    Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis: pathogenetic and clinical implications

    Brain

    (1990)
  • M Filippi et al.

    Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

    Neurology

    (1994)
  • RI Grossman et al.

    Multiple sclerosis: gadolinium enhancement in MR imaging

    Radiology

    (1986)
  • AG Kermode et al.

    Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement

    Neurology

    (1990)
  • DH Miller et al.

    Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis

    Brain

    (1993)
  • M Filippi et al.

    Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS

    Neurology

    (1996)
  • HJ Barratt et al.

    The site of the lesion causing deafness in multiple sclerosis

    Scand Audiol

    (1988)
  • V Dousset et al.

    Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging

    Radiology

    (1992)
  • SD Wolff et al.

    Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo

    Magn Reson Med

    (1989)
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    Supported in part by grants NS37172 and NS29029 from the National Institutes of Health.

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