2006 IEEE International Symposium on Signal Processing and Information Technology

Optimal Filter Design for Multiple Sclerosis Lesions Segmentation from Regions of Interest in Brain MRI
Mohsen Ghazel, Post-Doctorate Fellow E &CE Department University of British Columbia Vancouver, B.C. V6T 1Z4 Anthony Traboulsee, MD, FRCPC, Division of Neurology Department of Medicine University of British Columbia Vancouver, B.C. V6T 1Z4 Rabab K. Ward, FRSC, FIEEE, FCAE, FEIC E &CE Department University of British Columbia Vancouver, B.C. V6T 1Z4

Abstract In this paper, we propose an optimal lter design strategy for the purpose of detecting and segmenting MS lesions in prescribed regions of interest within brain MRI data. Reliable segmentation of multiple sclerosis lesions in magnetic resonance brain imaging is important for at least three types of practical applications: pharmaceutical trials, decision making for drug treatment or surgery, and patient follow-up. Manual segmentation of the MS lesions in brain MRI by well qualied experts is usually preferred. However, manual segmentation is hard to reproduce and can be time consuming in the presence of large volumes of MRI data. On the other hand, automated segmentation methods are signicantly faster and yield reproducible results. However, these methods generally produce segmentation results that agree only partially with the ground truth segmentation provided by the expert. In this work, we propose a semiautomated MS lesion detection system that combines the knowledge of the expert with the computational capacity to produce faster and more reliable MS segmentation results. In particular, the user selects coarse regions of interest (ROIs) that enclose potential MS lesions and a sufcient background of healthy white matter tissues. Having this two-class classication problem, we propose a feature extraction method based on optimal lter design that aim for producing output texture features corresponding to the MS lesions and healthy tissues background which are maximally separable. If this is achieved, the two output features may be easily separated using simple thresholding operations. The method is applied on real MRI data and the results are qualitatively compared to a ground truth, which is manually segmented by a human expert.

Keywords: Multiple sclerosis, segmentation, texture lter design. I. I NTRODUCTION Multiple sclerosis (MS) is a common disease of young adults that primarily affects the white matter (MW) of the central nervous system. Magnetic resonance (MR) imaging is increasingly being used to assess the progression of the disease and to evaluate the effect of drug therapy, supplementing traditional neurological disability scales such as the extended disability status scale (EDSS) [12]. The analysis of MR images may be done qualitatively and/or quantitatively. Qualitative analysis is performed by visually estimating the diseases progress, classifying lesions in the scan as either new lesions, changing lesions or static lesions [9]. The most common quantitative parameter is the burden (or load) of the disease expressed in terms of the volume of the lesions. In clinical trials, the large number of MR images to be analyzed makes manual analysis by human experts extremely

time consuming. Furthermore, the intra- and inter-observer variability associated with manual delineations complicates the analysis of the results. High inter- and intra-observer variability has been demonstrated in several studies, where segmentations, performed by a group of experts, at different time points, were compared [8], [12]. Also, it is not clear how a human rater combines information from multiple images when multi-spectral MR data are examined. Therefore, there is a need for semi-automated or fully automated methods for MS lesion segmentation that can analyze large amounts of multispectral MR data in a reproducible way which correlates well with analysts. Over the past decade, a number of semi- and fullyautomated algorithms for the segmentation of multiple sclerosis lesions in MR images have been described. Various mathematical methods are at the core of these algorithms, for instance, neural networks [3] and fuzzy connectivity principles [13]. Works dealing with segmentation include van Leemput et al. [14] and Wareld et al. [15]. The two frameworks model brain images using the voxels intensity feature. In [14] intensity-based classication is used with a stochastic model for normal brain images. Regions that are found to be model outliers are labeled as potential MS lesions. Wareld et al. segment the lesions in the WM regions after the gray matter (GM) structures have been identied and removed [15]. Automated segmentation methods yield reproducible segmentation results and are signicantly faster than manual segmentation. However, to date, there still no state of the art fully automated segmentation methods for MS lesion that are capable to fully reproduce the segmentation results obtained by a qualied expert. Most automated segmentation techniques produce segmentation results that agree only partially with the ground truth segmentation provided by the experts. For instance the automated segmentation method proposed by Leemput et al. [14] produced segmentation results that spatially overlapped with those provided by the experts only about 50% of the time and failed to detect some of the MS lesions identied the experts (false-negatives)- which is a grave concern from a medical point of view. In this work, we propose a semi-automated method for MS lesion segmentation. The expert rst manually selects some regions of interest (ROIs) that he/she believes may potentially contain some MS pathologies, based on his/her

0-7803-9754-1/06/$20.002006 IEEE

expertise. Any potential MS lesions within these ROIs are then automatically detected and segmented, based on optimal ltering of the ROIs that results in maximal separations between the features and energies of the MS lesions from the surrounding normal white matter tissues, hence making the two classes more separable and distinguishable. Accordingly, our method combines the knowledge of the expert and the computational power of the automated system to yield more reliable and reproducible MS segmentation results. This paper is organized as follows: In section 2, the proposed lter design method is outlined. Some experimental results are presented in section 3 and concluding remarks are presented in section 4. II. M ETHOD In the eld of medical imaging, the term texture is applied to an homogeneous area in order to characterize its visual aspect. This basic denition implies three concepts: the rst is the identication or isolation, within an area, of an elementary unit also called primitive; the second is the repetition of the primitive which generates the image, and the third the relationship existing between the texture and of the material and its structure. This means, from a practical point of view, that analyzing the texture of the image of a given object can provide information about the nature and structure of this object. The texture is inevitably affected by pathologic changes occurring in a tissue. Magnetic resonance imaging (MRI) is known to be by far the best para-clinical test in MS, depicting abnormalities in 95% of patients [4]. Recently, texture analysis has been applied for the purpose of MS lesion quantication and classication. For example, Mathias et al. [7] applied texture analysis to quantify the pathological changes that occur within the spinal cord associated with MS. Gasperini, et al. [2], applied texture analysis to quantify cerebral normal appearing white matter (NAWM). Yu et al. [16], applied statistical texture analysis to standard MR images of patients with MS, in order to discriminate between active and non-active MS lesions. However, the application of texture analysis for the purpose of MS lesion detection and segmentation has been rather limited. In this work, we investigate the design of optimal lter that aim for achieving maximal textural features and energies separation between two classes (MS lesion and healthy tissues) and hence make them more distinguishable and easier to segment and separate from one another. A. ROIs Selection First, an expert selects a number of regions of interests (ROI) within the white matter of the brain that - based on his/her knowledge - may potentially contain one or more MS lesions. These ROIs dene clinically interesting tissue areas in the brain where potential MS lesions may be present. There is no restriction on the size or shape of these regions but it is desirable to enclose all the potential MS lesions within ROIs that contain a sufcient healthy white matter background in order to help the classier to distinguish between the lesion and non-lesion pixels and produce better segmentation results.

Enclosing the MS lesions within ROIs containing only two classes of pixels - lesion pixels and white matter healthy pixels - reduces the problem of MS lesion detection and segmentation to a two-class classication problem. Next, we outline how the MS lesions are then detected and segmented. 1) Characteristics of MS Lesions: As illustrated in Fig. 1, MS lesions appear as regions with an increased signal intensity of a PD-weighted MRI images. They also have a fairly uniform density. As illustrated in Fig. 1(a), we have drawn a line passing through an MS lesion. Fig. 1(b) shows the gray-level prole of pixels located on this line. An important observation from this prole is that abrupt changes in graylevel values occur in the transition between the MS lesion and the surrounding white matter tissues. Thus, the signicant texture features are the ones that are able to capture the structures within and outside the MS lesions as well as the highly variable transitional structures from the MS lesion to the surrounding healthy white matter tissues. B. Optimal Filter Design The design of an optimal ltering strategy was motivated by Laws texture lters [5]. Laws developed and described a method of texture analysis, particularly applicable to radiographic images, which seek to classify each pixel of an image. The laws method uses lter masks to extract secondary features from natural micro-structure characteristics of the image (level, edge, spot and ripple) which can then be used for segmentation and classication. However, it was experimentally observed that the Laws lters were not as effective for the purpose of MS lesion segmentation in MRI brain images. The proposed optimal lter exploits the characteristics of the MS lesions discussed above. In particular, in order to be effective in detecting the high-intensity MS abnormalities from the lower intensity background healthy tissues, the optimal lter for MS detection should produce a feature output image, where: the high-intensity MS lesions are transformed into brighter areas, and the low-intensity background pixels (healthy white matter tissues) are transformed to darker areas. In order words, the optimal texture lter should make highintensity MS lesions even brighter and the lower-intensity background and healthy tissues even darker. If this can be achieved, then the MS lesions can be segmented from their background using simple thresholding techniques. Fig. 2 illustrates a block diagram of the proposed lterbased feature extraction system. The pre-selected ROIs serve are the input of the lter with output y. In order for the output regions to be properly thresholded, a derived image is generated by calculating the localized energy, dened as E[y 2 ], over a small window centered about each pixel. This provides us with output images of texture energy. These texture energy images were then smoothed, to reinforce the difference between the various types of texture features produced by the lter by reducing the effects of noise and local variability within dissimilar regions. A moving window average was taken over the whole image using a weighted kernel. As

250

200

150

100

50

50

100

150 Distance along profile

200

250

300

Line the MS lesion and the surrounding white matter tissues.

Intensity prole along the line

Fig. 1. Intensity prole along a line through a few MS lesions: Note that abrupt change in gray-level values occur in the transition between

Fig. 2.

An overview of the proposed optimal lter for feature separation and MS lesion classication nd segmentation.

mentioned above, the aim of the optimal lter is the extraction of local frequencies in the ROIs where one of the textures has low signal energy and the other texture has high energy. If such an effective lter is designed, the smoothed texture energy images should be composed of mainly two distinguishable features: one corresponding to the high energy MS lesions and the other corresponding to the low energy healthy tissue background. These two features can then be separated using a simple thresholding strategy. C. Mathematical Derivations Given an input ROI consisting of two textures, x1 (m, n) and x2 (m, n), and the output for texture, xi (m, n), is the feature image vi (m, n), i = 1, 2.. The ltered image, yi (m, n), is given by: yi (m, n) = h(m, n) xi (m, n) If we dene h as the N N lter, then: yi (m, n) = hT xi (m, n). Similarly, the smoothing operation may be dened as: vi (m, n) = w zi (m, n),
T

where w(k, l) is an Nw Nw smoothing lter. The size of the localized energy window was not found to be critical, as similar effects were observed for sizes ranging from 5 5 to 9 9. However, the size of the smoothing lter represents a a tradeoff between accurate energy estimation and accurate edge preservation. For edge localization, high spatial resolution is desired, while for energy estimation, high spatial frequency resolution is desired. These conicting goals need to be balanced in the smoothing lter. For our purposes, we are more concerned with accurate energy estimation than sharp edge preservation. Besides, MRI data usually lacks high frequency content, such as edges. In order to achieve good feature separation we seek to maximize the following objective function: J(h) = (v1 v2 )2 , 2 2 v1 + v2 (4)

(1)

2 where vi and vi are the feature mean and variance, respectively. It can be shown that the feature mean is given by:

(2)

vi = hT Rxi xi h,

(5)

(3)

where Rxi xi = E[xi (m, n)xT (m, n)] [10]. Assuming that i the lter outputs, yi (m, n), have a Gaussian distribution, the

variance of the feature image, vi (m, n), is given by: vi = w Rzi zi w

T

2i , v

(6)

where Rzi zi = [?]. Finding the optimal lter, h, which maximizes J(h) entails solving the following equation: J(h) h =
v v 2 2 2(v1 v2 )( h1 h2 )(v1 + v2 ) 2 2 (v1 + v2 )2 v (v1 v2 )2 ( h1 2 2 (v1 + v2 )2

E[zi (m, n)zT (m, n)] i

2 v 2 h

= 0.

(7)

Solving Eq. (7) is not straightforward. In [10], two methods for the solution were proposed: 1) Since both J(h) and J(h) are known, a gradient search h may be performed. 2) Assuming that the lter output, yi (m, n) can be modeled as separable rst-order autoregressive (AR(1)) processes. Then the optimal lter h satises the following closed-form relationship: R1x2 Rx1 x1 h = h. x2 (8)

In other words, the optimal lter coefcient vector is designed by computing the eigenvectors of R1x2 Rx1 x1 x2 and selecting the one maximizing the criterion J(h). The main problem with the gradient search is the risk of converging to a local minimum. For many applications, the assumption in the last approach on the yi (m, n) to be separable AR(1) processes may be a crude approximation. However, in [10], [11], Randen and Husoy empirically demonstrated that no signicant improvements was observed on the classication performance when using the gradient search instead of the closed-form solution. Thus, in this work we have chosen the closed-form optimization method for estimating the optimal lter coefcients h. Next, some experimental results are presented and discussed. III. E XPERIMENTAL R ESULTS Fig. 3 illustrates some preliminary results obtained for one real PD-weighted MRI slice. The true MS lesions were manually traced by a human expert for comparative purposes. The user rst selected two ROIs that enclosed the potential MS lesions. These ROIs were then passed as input to the optimal feature separation lter. The segmentation obtained by the proposed semi-automated segmentation method are also presented and compared with the ground truth. In view of the presented sample experimental results, we make the following observations: Fig. 3(a) illustrates the system output obtained by applying the designed optimal feature extraction lter on the prescribed two-class ROIs. It appears that the designed lter has achieved its objective of separating the features of the two classes (MS lesions and normal white matter tissues). Note how the MS lesions have been transformed to brighter areas with increased intensity,

while the background (healthy white matter tissues) has been transformed to a darker area. The optimal lter has transformed the MS lesions and the healthy tissues background into two more distinguishable sub-regions and could now be easily separated from one another using simple thresholding operations. After applying the thresholding operations on the lter output images, the MS lesions where then detected and segmented from the healthy white matter tissues, as illustrated in Fig. 3 (b). The segmentation results obtained by the proposed optimal feature extraction lter can be can be qualitatively compared to the ground truth as obtained by an expert, as presented in Fig. 3(c). Note that the proposed lter-based classication and segmentation method was successful in detecting the presence of each and every true MS lesion lesion identied by the human expert. This is indeed very important as one of the most important reservations against most of the fully automated MS lesion segmentation methods lies in their failure to detect some of the true MS lesion. In practice, it is clear that failure to detect true MS lesions may have grave consequences from a medical perspective. However, it should also be noted that, for some of the MS lesions, the proposed scheme seems to under-segment the MS lesions. That is the sizes of some of the segmented MS lesions are smaller than the true sizes of these lesions, as segmented by the Expert. Some of the reasons behind this under-segmentation may include: the selection of the threshold value and the thresholding operator applied on the lter output, some of the questionable assumptions for the lter output and the estimation of its parameters, the selection of the smoothing lter support, and the assumption that the prescribed ROIs contain only two classes (MS lesions and normal white matter tissues) which may not be valid in practice due to partial volume effects. These issues and others are currently the subject of our work in progress. Our ultimate goal is to design a more optimal and effective lter that yields MS lesions segmentation results that spatially correlate with the ground truth results obtained by the experts. The results obtained so far, are encouraging. Note also that the proposed segmentation method has produced a few false positives consisting of small circular shaped lesions. These falsely identied lesions may be removed by applying morphological opening and closing. This can easily be achieved by removing any segmented region that cannot contain a disk with a pre-determined radius. The radius has to be chosen carefully so that only small false-positives are removed.

In order to provide a fair assessment of the performance of our proposed method, we recognize the need to perform a more extensive validation of the proposed segmentation method using a larger MRI data set. Only preliminary results were presented here but comparable results have been obtained so far using a few other MRI scans. A more extensive validation of the proposed method using a larger MRI data

Fig. 3. Segmentation of MS Lesions using optimal lter design: (a) Output of the optimal lter, (b) Segmentation results based on thresholding

the output of the optimal lter, (c) the ground truth: as obtained by an expert.

set is still work in progress. IV. C ONCLUSION In this work, we proposed a semi-automated MS lesion detection and segmentation method based on optimal lter design for maximal feature selection and separation. The method is based on designing an optimized lter that aims for separating the texture features and energies of the two main classes assumed to be within the prescribed ROIs - namely the MS lesions and the normal white matter. This has resulted in a system output where the MS lesions have been transformed to brighter areas with increased intensity, while the background (healthy white matter tissues) has been transformed to a darker area. Consequently, the MS lesions and the healthy tissues become more distinguishable at the output of the system than they were originally. In fact, they may even be separated from one another by applying a simple a thresholding operation. Some of our work in progress aiming to improve and validate the proposed optimal lter-based MS lesion segmentation method include: developing an approach for performing the ROIs selection automatically - hence resulting in a fully automated method, selecting alternative features and feature and space (i.e., in the wavelet or fractal domains), incorporating additional special considerations into the feature space, overcoming the consistent MS lesion under-segmentation produced by the proposed method, removing the small falsely identied lesions without affecting true lesions, and performing a more extensive testing and validation of the proposed method. R EFERENCES
[1] R. M. Haralick, K. Shanmugam, J. Dinstein, Textural features for image classication, IEEE Trans. Syst. Man. Cybern, vol. 6, pp. 610-621, 1973. [2] Gasperini C, Horseld MA, Thorpe JW, Kidd D, Barker GJ, Tofts PS, MacmManus DG, Thompson AJ, MacDonald WI, Miller EH, MRI texture in normal appearing white matter of MS patients: relationship to other quantitative MRI and clinical parameters, J. Magn. Reson Imag. 1994; 11:33-42. [3] Goldberg-Zimring, D., et al., Automated detection and chracterization of multiple sclerosis lesions in brain MR images, Magnetic Resonance Imaging, vol. 16(3), pp. 311-318, 1998.

[4] R. I. Grossman and J.C McGowan, Perspectives on Multiple Sclerosis, AJNR, 19:1251-1265, August 1998. [5] Laws K. T., Rapid texture identication, Image processing for missible guidance, SPIE, vol. 238, pp 376-380, 1980. [6] Lechtenberg, R., Multiple Sclerosis Fact Book, Second Edition, Philadelphia, 1995. [7] J. M. Mathias, P. S. Tofts, N. A. Losseff, Texture Analysis of Spinal Cord Pathology in Multiple Sclerosis, Magnhetic Resonance in Medicine, vol. 42, pp. 929-935, 1999. [8] Paty, D. W., and D. K. B. Li, Interferon Beta-1b is Effective in Relapsing- Remitting Multiple Sclerosis. II. MRI Analysis Results of a Multicenter, Randomized, Double-Blind, Placebo-controlled Trial, Neurology, vol. 43, pp. 662667, Apr. 1993. [9] Poser, C. M., et al., New Diagnostic Criteria for Multiple Sclerosis: Guidelines for Research Protocols, Annals of Neurology, vol. 13(3), pp. 227-231, Mar. 1983. [10] Randen T. and Husy J. H., Texture segmentation using lters with optimized energy separation, IEEE Trans. Image Processing, vol. 8, pp. 571582, Apr. 1999. [11] Randen T. and Husy J. H.,, Filtering for texture classication: A comparative study, IEEE Trans. Pattern Anal. Machine Intell., vol. 21, pp. 291310, Apr. 1999. [12] Thompson, A. J., C. Polman and R. Hohlfeld (editors), Multiple Sclerosis: Clinical Challenges and Controversies, Martin Dunitz, London, 1997. [13] Udupa, J. K., et al., Multiple Sclerosis Lesion Quantication Using Fuzzy-Connectedness Principles , IEEE Trans. on Medical Imaging, vol. 16(5), pp. 598-609, Oct. 1997. [14] Van Leemput, K., et al., Automated segmentation of multiple sclerosis lesions by model outlier detection, IEEE Trans. on Medical Imaging, vol. 20, pp. 677-688, Aug. 2001. [15] Wareld, S., et al., Automatic Identication of Grey Matter Structures from MRI to Improve the Segmentation of White Matter Lesions, J Image Guided Surgery, vol. 1(6), pp. 326-338, 1995. [16] O. Yu, Y. Mauss, G. Zollner, I.J. Namer, and J. Chambron, Distinct Patterns of Active and Non-active Plaque using Texture Analysis on Brain MRI Images in Multiple Sclerosis Patients: Preliminary Results, Magnetic Resonance Imaging, Vol. 17, No. 9, pp. 1261-1267, 1999.