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Quantitative Diffusion Measurements in Focal Multiple Sclerosis Lesions

Correlations with Appearance on TI-Weighted MR Images

¹ Department of Radiology, Mount Sinai School of Medicine, One Gustave L. Levy PI., New York, NY 10029.
² Present address: Department of Radiology, Rm. S-047, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA.

Received September 20, 1999; accepted after revision February 2, 2000.

 
Presented in part at the annual meeting of the American Society of Neuroradiology, Philadelphia, May 1998.

Address correspondence to S. W. Atlas.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. Relative hypointensity on T1-weighted MR imaging has been suggested as a putative disability marker. The purpose of our study was to determine if there are quantifiable diffusion differences among focal multiple sclerosis lesions that appear differently on conventional T1-weighted MR images. We hypothesized that markedly hypointense lesions on unenhanced T1-weighted images would have significantly increased diffusion compared with other lesions, and enhancing portions of lesions would have different diffusion compared with nonenhancing lesions.

SUBJECTS AND METHODS. Average apparent diffusion coefficient (ADC) was calculated for 107 lesions identified on T2-weighted images in 16 patients with multiple sclerosis and was compared with the ADC of normal white matter in 16 age- and sex-matched control subjects. Seventy-five nonenhancing lesions (29 isointense, 46 hypointense) and 32 enhancing lesions (6 isointense, 26 hypointense) were categorized on the basis of unenhanced T1-weighted MR imaging.

RESULTS. Hypointense and isointense nonenhancing lesions both showed significantly higher ADC than normal white matter (p < 0.0001). Hypointense nonenhancing lesions showed higher ADC values than isointense nonenhancing lesions (p < 0.0001). Diffusion in enhancing portions of enhancing lesions was decreased when compared with nonenhancing portions.

CONCLUSION. Quantitative diffusion data from MR imaging differ among multiple sclerosis lesions that appear different from each other on T1-weighted images. These quantitative diffusion differences imply microstructural differences, which may prove useful in documenting irreversible disease.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
MR imaging is widely used in multiple sclerosis, both to aid in the diagnosis and to evaluate and monitor disease activity. Although T2-weighted imaging has been generally regarded as sensitive in detecting multiple sclerosis plaques, it is nonspecific in determining the age of lesions and in distinguishing underlying histopathologic substrates because all lesions typically show high signal intensity. Moreover, the visible lesion load as determined on T2-weighted images does not correlate strongly with clinical disability [1].

The suboptimal correlation between clinical disability and visible lesion load on conventional MR imaging can be explained by several theories. One explanation is that focal lesions in multiple sclerosis that are visible on T2-weighted MR images may actually be markedly different histopathologically, even though they appear to be identical on T2-weighted MR images. This hypothesis has prompted the investigation of a variety of MR imaging techniques in an attempt to show histopathologic substrates of lesions on in vivo imaging. For instance, the relative intensity of focal lesions on unenhanced T1-weighted images has been correlated with clinical disability and hypothesized as a means of distinguishing different histopathologic substrates of multiple sclerosis lesions that may appear similar on T2-weighted images [2]. Studies using magnetization transfer MR imaging have revealed heterogeneity of focal multiple sclerosis lesions that have a similar appearance on T2-weighted images, with decreased magnetization transfer ratios thought to reflect a breakdown in macromolecular structure and to imply more demyelination [3, 4]. The signal intensity of multiple sclerosis plaques on T1-weighted images has also been correlated with the magnetization transfer ratio [5] and with microscopic disorders [6]. Increasing hypointensity of multiple sclerosis plaques on T1-weighted images has been shown to correspond to decreased magnetization transfer ratio values and increased demyelination on pathologic examination. In addition, contrast enhancement [7], reflecting transient abnormality of the blood-brain barrier, has also been used in an attempt to characterize "activity" of focal multiple sclerosis lesions that may otherwise be similar in appearance.

Although it is widely known that focal lesions in multiple sclerosis can display a variety of histopathologic substrates on microscopic examination [8], it has been recently hypothesized that axonal destruction represents the irreversible lesion of multiple sclerosis [9]. The recognition of such a pathologic change on imaging would clearly be important for many reasons, including prognosis, response to therapy, and monitoring disease activity, particularly when considering the dynamic nature of the disease. On imaging, relative hypointensity on T1-weighted MR imaging has been suggested as a marker of irreversible disease [2], but protocol-to-protocol variation using this nonquantitative finding makes this suboptimal as a putative disability marker.

Diffusion-weighted MR imaging can provide quantitative information regarding tissue structure based on the molecular motion of water [10, 11]. This MR imaging technique is made sensitive to molecular water diffusion by applying a pair of gradient pulses before and after the 180° radiofrequency pulse in a spin-echo sequence [12, 13]. Most MR imaging—visible water is either in axons or enclosed in myelin sheaths, so it is intuitive that either demyelination or axonal loss would lead to changes in measured diffusion in multiple sclerosis lesions. Therefore, diffusion-weighted MR imaging may yield insight into the biophysical nature of focal white matter lesions in multiple sclerosis patients and may provide important data for prognosis and treatment. Indeed, preliminary studies using diffusion-weighted imaging have reported abnormal diffusion characteristics in multiple sclerosis lesions [14,15,16,17,18].

The overall purpose of our study was to determine if there are quantifiable diffusion differences among focal multiple sclerosis lesions that appear qualitatively different on conventional T1-weighted MR images. On the basis of previous reports concerning the significance of relative signal intensity of focal multiple sclerosis lesions on T1-weighted MR imaging, we hypothesized that markedly hypointense lesions on unenhanced T1-weighted images would have significantly increased diffusion compared with other lesions, and that enhancing portions of lesions on T1-weighted images would have significantly different diffusion compared with nonenhancing lesions.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Sixteen patients with clinically defined multiple sclerosis and 16 age- and sex-matched healthy control subjects were studied. The patient population consisted of 13 females and three males who were 16-62 years old (mean, 33.4 years). The control subjects were healthy volunteers with no significant medical history or physical findings. Eleven patients were classified clinically as having relapsing-remitting multiple sclerosis, and five patients had secondary progressive disease.

Imaging was performed on a 1.5-T MR imaging system (Signa Horizon Echospeed; General Electric Medical Systems, Milwaukee, WI) modified with hardware for echoplanar imaging. All patients initially underwent conventional axial imaging, including axial T1-weighted spin-echo (TR/TE, 600/10), proton density-weighted fast spin-echo (TR/TE_eff, 2000/30; echo train length, four), and T2-weighted fast spin-echo (TR/TE_eff, 3600/95; echo train length, eight) imaging. These images used a 24-cm field of view, a 256 x 192 matrix, and 5-mm-thick sections with 2.5-mm spacing. A multislice single-shot spin-echo echo-planar diffusion-weighted imaging sequence with two square diffusion gradient pulses applied before and after the 180° pulse (TR/TE, 10000/99; 5-mm-thick sections with 2.5-mm spacing; 24-cm field of view; 128 x 128 matrix) was performed during the same session using a diffusion sensitivity of b = 1000 sec/mm². The diffusion gradients were applied sequentially in three orthogonal axes to generate three sets of axial diffusion-weighted MR images. Diffusion MR imaging parameters included of 35 msec and of 37 msec. All diffusion echoplanar images and conventional images were obtained at the same slice locations. All diffusion measurements were performed on data obtained before contrast administration. The patients received IV gadolinium dimeglumine at a standard dose (0.1 mmol/kg), and axial T1-weighted images were obtained immediately after injection and were compared with unenhanced axial T1-weighted images.

The raw diffusion data were reconstructed automatically on an offline workstation (Sparc 20; Sun Microsystems, Mountain View, CA) using software developed in IDL (Research Systems, Boulder, CO) and were returned to an independent console for display and determination of region-of-interest (ROI) measurements. The sizes of ROIs were chosen to be appropriate for each lesion, so that the maximum ROI was used without volume averaging. The mean apparent diffusion coefficient (ADC) (the average of the ADC in three orthogonal directions, or diffusion trace) was calculated from the three diffusion-weighted images [19]. ROI measurements were made on the mean ADC images after being carefully drawn on the echoplanar T2-weighted (b = 0) image obtained during the same acquisition; measurements were made both within the lesion and on frontal white matter in the control subjects. In all cases, special care was taken to avoid including either normal tissue or other regions of abnormal tissue in the ROI analysis. Note that ROI localization was performed by identification on the echoplanar T2-weighted images, which are acquired as part of the diffusion echoplanar acquisition. These T2-weighted images generally suffer the same distortions and have the same spatial resolution as the diffusion images. Moreover, these images are part of the same echoplanar sequence used for obtaining diffusion-weighted images, so this would also minimize concerns about patient motion between different MR imaging sequences. To further avoid problems with volume averaging of lesion and adjacent cerebral spinal fluid, lesions abutting sulci and lesions abutting the ventricular surface were excluded from this analysis. In addition, cases in which gross patient motion occurred between diffusion and conventional MR imaging sequences were excluded. This was assessed by a neuroradiologist who carefully noted any changes in relative positions of neuroanatomic landmarks such as the ventricular system relative to the deep white matter anatomy.

Classification of lesions for subsequent comparison of the mean ADC values was made by two experienced neuroradiologists in a consensus fashion on the basis of the appearance of the lesions on unenhanced and contrast-enhanced T1-weighted images. Enhancing lesions were analyzed separately from nonenhancing lesions. Separate ROI measurements were carefully drawn in the enhancing lesions in both the nonenhancing and enhancing portions of the lesions, within the entire enhancing lesions (homogeneous enhancement), and within the entire lesion in nonenhancing lesions. Additionally, both nonenhancing and enhancing lesions were classified as hypointense if the lesion was markedly hypointense on T1-weighted images and more hypointense than gray matter, and as isointense if the lesions were isointense or slightly hypointense on T1-weighted images and not hypointense to gray matter (Fig. 1).

View larger version (138K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1. —35-year-old woman with multiple sclerosis. Axial T1-weighted MR image shows left parietal focal lesions in periventricular white matter that were categorized as hypointense (solid arrow) because signal intensity is visibly lower than that of normal gray matter. Note other lesions that were categorized as isointense (open arrow) because signal intensity was isointense to that of normal gray matter.

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
One hundred seven focal multiple sclerosis lesions were identified on T2-weighted images. Eight of the 16 patients had enhancing lesions, for a combined total of 32 enhancing lesions; six lesions were classified as isointense and 26 were classified as hypointense to gray matter on axial unenhanced T1-weighted images. Of the 32 enhancing lesions, 29 were noted to have both an enhancing and a nonenhancing portion, and three lesions showed homogeneous enhancement. Seventy-five nonenhancing lesions were identified: 29 were isointense and 39 were entirely hypointense to gray matter on unenhanced T1-weighted images (seven additional hypointense lesions had thin peripheral rims of hyperintensity on T1-weighted images; these were excluded from further analysis). The mean ADC was calculated in the lesions and in the frontal white matter in the control subjects (Table 1). (Note: Diffusion measurements in tissues that are anisotropic, such as white matter, should ideally include the entire diffusion tensor, which reqquires at least seven measurements; however, measurements made on the mean ADC image, which is an average of the ADC in three orthogonal axes, have been shown to be adequate [19].) An unpaired t test was used for statistical analysis (Table 2). A p value of less than 0.05 indicated significance.

Nonenhancing Lesion Analysis
Overall, nonenhancing multiple sclerosis lesions showed significantly increased diffusion (isointense nonenhancing lesions, 1075 x 10^-6 mm²/sec; hypointense nonenhancing lesions, 1315 x 10^-6 mm²/sec) compared with normal white matter (752 x 10^-6 mm²/sec). However, mean ADC values of nonenhancing lesions varied according to their relative signal intensity on unenhanced T1-weighted images. Diffusion in hypointense nonenhancing lesions was significantly greater than diffusion in isointense nonenhancing lesions (p < 0.0001).

Enhancing Lesion Analysis
The diffusion in all isointense enhancing lesions (both the enhancing and nonenhancing portions) was statistically equivalent to that of normal white matter. The diffusion in all hypointense enhancing lesions (both the enhancing and the nonenhancing portions) was greater than that of normal white matter.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Conventional MR imaging is generally thought of as the most sensitive means of measuring lesion load and disease activity in multiple sclerosis and is commonly used as an outcome criterion in therapeutic trials [20, 21]. T2-weighted images are nonspecific in determining lesion age and cannot characterize the pathologic substrate of irreversible clinical disability defined by demyelination and axonal loss. Moreover, studies have failed to show a strong correlation between lesion load, as defined by T2-weighted images, and clinical disability. These facts have prompted studies using alternative imaging methods such as magnetization transfer imaging, and now diffusion-weighted imaging, in an attempt to quantify the extent of myelin loss in lesions in both the animal model and in patients [3,4,5].

Diffusion-weighted MR imaging has great potential for studying cerebral white matter diseases because of its inherent sensitivity to water diffusion, because white matter is a tissue with an extremely high level of structural organization that compartmentalizes and restricts motion of water. Destruction of the myelin sheath, axonal loss, or both would result in significant expansion of the extracellular space [22], which should correspond to a quantitative increase in diffusion or loss of anisotropy. Some prior studies have reported abnormal diffusion in multiple sclerosis lesions [14,15,16,17,18]. Reported findings have included an increase in the ADC in acute multiple sclerosis plaques (lesions < 3 months old as judged on serial MR imaging) as compared with chronic plaques [15] and an increase in multiple sclerosis plaques in patients with mild and marked clinical disability [16].

In our study, we analyzed diffusion quantitatively in multiple sclerosis lesions and correlated their measured mean ADCs with signal intensity on T1-weighted images. The rationale for this study design is based on prior studies that have attempted to correlate appearance on T1-weighted images with histopathology and with disability. Because the relative hypointensity of focal lesions can be a somewhat qualitative criterion that may vary with minor changes in imaging parameters, diffusion-weighted MR imaging offers a quantitative measure of in vivo biophysical states of tissues of interest.

Our study reports an overall analysis of all nonenhancing lesions showing increased mean ADC values as compared with normal white matter in control subjects. This finding is in concurrence with diffusion tensor data reported in both acute and chronic multiple sclerosis lesions in a study comparing focal multiple sclerosis with normal-appearing white matter in those same patients [23]. In our study, further analysis revealed that mean ADC values of these nonenhancing lesions varied with their signal intensities on the unenhanced T1-weighted images, and these categoric differences match up well with previous pathology literature comparing conventional T1-weighted MR imaging findings with histopathology. In our study, diffusion was significantly greater in the lesions that were hypointense than in the lesions that were isointense to normal gray matter on T1-weighted MR imaging. Tievsky et al. [23] reported no difference in diffusion measurements between acute and chronic multiple sclerosis lesions; however, that categorization was based on contrast enhancement rather than signal intensity on unenhanced T1-weighted images. Bruck et al. [6] correlated pathology from biopsy specimens of multiple sclerosis lesions with the T1-weighted images and found that increasing hypointensity of plaques in relation to normal white matter corresponded to increased demyelination, significant axon loss, and expansion of the extracellular space (i.e., more chronic lesions). Also, the hypointensity of lesions on T1-weighted images was directly related to the extent of axonal reduction and the amount of extracellular edema. Bruck et al. also reported that lesions that were isointense to white matter on T1-weighted images were lesions that showed cellular infiltrate with edema but relative preservation of axons on pathologic examination. Our data showing that markedly hypointense lesions had a significant increase in the mean ADC are consistent with the loss of the normal myelin structure, axonal loss, or subsequent expansion of the extracellular space as seen on pathologic examination.

Our data also showed that enhancing portions of lesions had relatively restricted diffusion compared with nonenhancing central portions of the same lesions. This finding concurs with diffusion tensor measurements reported in acute multiple sclerosis lesions as defined by contrast enhancement [23]. This relatively decreased diffusion may be the result of cellular infiltration [24]. Alternatively, restriction of diffusion may reflect remyelination, or relative preservation of structural integrity (e.g., preservation of axons). Although the precise histopathologic correlates of these various areas seen on MR imaging are uncertain, the data are consistent with the hypothesis that the presence of macromolecular structure (e.g., remyelination, proteins) is the common substrate in enhancing lesions.

Like previous MR imaging data derived from studies using magnetization transfer that were also designed to investigate alterations in tissue structure in multiple sclerosis [3,4,5, 25,26,27,28], our data provide further evidence that MR imaging may be useful as a sophisticated tool to investigate biophysical tissue states in these lesions. Similar to magnetization transfer studies, diffusion offers an objective, quantitative analysis of focal tissue changes that can be otherwise invisible on standard imaging. Intuitively, diffusion-weighted MR imaging is related to magnetization transfer MR imaging because both techniques provide information about tissue structure by way of measurement of water molecules and their relationship to macro-molecules. Magnetization transfer differentiates in a general sense bound water from nonbound water, thereby implying the presence or absence of macromolecules, such as proteins. Diffusion-weighted MR imaging investigates water motion that, in the presence of macromolecules such as cell membranes, can be restricted, although the precise mechanisms are incompletely understood. The restriction of water diffusion may or may not be caused by actual binding, whether transient or not. Certain types of macromolecules, even without binding, can present boundaries that restrict free water motion. It has been shown that the mere presence of impenetrable barriers to diffusion can alter ADC (the "edge effect") [29,30,31].

We recognize that our study has limitations. We have no histopathologic data from MR imaging-identified lesions that we analyzed. Such data are difficult to obtain in multiple sclerosis because these lesions are rarely biopsied. We did not measure the diffusion tensor, which may be even more sensitive to changes in diffusion because of its measurement of the directional component of diffusion. We also note that standard deviations of some of our measurements are relatively high. Our comparisons do clearly reach statistical significance, though, and our findings are consistent with previous reports and fit well with prior qualitative studies based on T1-weighted imaging. We did not test reproducibility of diffusion measurements, which would be an important goal of subsequent studies.

In conclusion, significant changes in measured mean ADC values occur on diffusion MR imaging in lesions that differ in appearance on T1-weighted MR imaging. These quantitative diffusion MR imaging data imply microstructural differences in these lesions. Although pathologic correlation is still forthcoming, quantitative diffusion-weighted MR imaging may prove to be useful in documenting irreversible disease. If so, these data may have significant implications for guiding patient management and patient selection for clinical drug trials.

References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Miki Y, Grossman R, Udupa J, 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;213:395 -399[Abstract/Free Full Text]
2. Truyen L, van Waesberghe J, van Walderveen M, et al. Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 1996;47:1469 -1476[Abstract/Free Full Text]
3. Dousset V, Grossman RI, Ramer KN, et al. Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology 1992; 182:483 -491[Abstract/Free Full Text]
4. Hiehle JF, Lenkinski RE, Grossman RI, et al. Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis. Magn Reson Med 1994;32:285 -293[Medline]
5. Loevner L, Grossman R, Cohen J, Lexa F, Kessler D, Kolson D. Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. Radiology 1995;196:511 -515[Abstract/Free Full Text]
6. Bruck W, Bitsch A, Kolenda H, Bruck Y, Stiefel M, Lassman H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol 1997;42:783 -793[Medline]
7. Grossman RI, Gonzalez-Scarano F, Atlas SW, Galetta S, Silberberg DH. Multiple sclerosis: gadolinium enhancement in MR imaging. Radiology 1986;161:721 -725[Abstract/Free Full Text]
8. Sobel R. The pathology of multiple sclerosis. Neurol Clin 1995;13:1 -21[Medline]
9. Trapp B, Peterson J, Ransohoff R, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278 -285[Abstract/Free Full Text]
10. Pierpaoli C, Basser P. Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 1996;36:893 -906[Medline]
11. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology 1996;201:637 -648[Abstract/Free Full Text]
12. Stejskal EO. Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys 1965;42:288 -292
13. Le Bihan D, Breton E, Lallemand D, et al. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 1986;161:401 -407[Abstract/Free Full Text]
14. Larsson H, Tomsen C, Frederiksen J, Stubgaard M, Henriksen O. In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis. Magn Reson Imaging 1992;10:7 -12[Medline]
15. Christiansen P, Gideon P, Thomsen C, Stubgaard M, Henrikson O, Larsson H. Increased water self-diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis. Acta Neurol Scand 1993;87:195 -199[Medline]
16. Horsfield M, Lai M, Webb S, et al. Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance. Magn Reson Med 1996;36:393 -400[Medline]
17. Horsfield M, Larsson H, Jones D, Gass A. Diffusion magnetic resonance imaging in multiple sclerosis. J Neurol Neurosurg Psychiatry 1998;64 [suppl 1]: S80-S84
18. Ernst T, Chang L, Walot I, Huff K. Physiologic MRI of a tumefactive multiple sclerosis lesion. Neurology 1998;51:1486 -1488[Abstract/Free Full Text]
19. Moseley ME, Cohen Y, Kucharczyk J, et al. Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 1990;176:439 -445[Abstract/Free Full Text]
20. Miller D, Albert P, Barkhof F, et al. Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. Ann Neurol 1996;39:6 -16[Medline]
21. Miller D, Grossman R, Reingold S, McFarland H. The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Brain 1998;121:3 -24[Abstract/Free Full Text]
22. Barnes D, Munro P, Youl B, Prineas J, McDonald W. The longstanding MS lesion: a quantitative MRI and electron microscopic study. Brain 1991;114:1271 -1280[Abstract/Free Full Text]
23. Tievsky A, Ptak T, Farkas J. Investigation of apparent diffusion coefficient and diffusion tensor anisotropy in acute and chronic multiple sclerosis lesions. AJNR 1999;20:1491 -1499[Abstract/Free Full Text]
24. Nesbit GM, Forbes GS, Scheithauer BW, Okazaki H, Rodriguez M. Multiple sclerosis: histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy. Radiology 1991;180:467 -474[Abstract/Free Full Text]
25. van Buchem M, Grossman R, Armstrong C, et al. Correlation of volumetric magnetization transfer imaging with clinical data in MS. Neurology 1998;50:1609 -1617[Abstract]
26. van Buchem M, McGowan J, Kolson D, Polansky M, Grossman R. Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden. Magn Reson Med 1996;36:632 -636[Medline]
27. Phillips M, Grossman R, Miki Y, et al. Comparison of T2 lesion volume and magnetization transfer ratio histogram analysis and of atrophy and measures of lesion burden in patients with multiple sclerosis. AJNR 1998;19:1055 -1060[Abstract]
28. Filippi M, Rocca M, Horsfield M, Comi G. A one year study of new lesions in multiple sclerosis using monthly gadolinium enhanced MRI: correlations with changes of T2 and magnetization transfer lesion loads. J Neurol Sci 1998;158:203 -208[Medline]
29. Putz B, Barsky D, Schulten K. Edge enhancement by diffusion in microscopic magnetic resonance imaging. J Magn Reson 1992;97:27 -53
30. Callaghan P, Coy A, Forde L, Rofe C. Diffusive relaxation and edge enhancement in NMR microscopy. J Magn Reson 1993;101:347 -350
31. Cho Z, Hong I, Ro Y. Some new observations on pulse sequence dependent diffusion related edge enhancement in MR microscopy. Magn Reson Med 1996;36:197 -203[Medline]

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