Statistical Cerebrovascular Segmentation for Phase-Contrast MRA Data Mohamed Sabry 1, Charles B. Sites 1, Aly A. Farag 1, Stephen Hushek 2, Thomas Moriarty 2 1 Computer Vision and Image Processing Laboratory University of Louisville, Louisville, KY, 40292. {msabry, syschuck, farag}@cvip.Louisville.edu http://www.cvip.uofl.edu 2 Dept. of Neurological Surgery, University of Louisville, KY, 40292. Abstract-In this paper, we present a statistically based segmentation algorithm to extract vascular tree from Phase Contrast Magnetic Resonance Angiography, “PCMRA”. Classification is based on the intensity distribution of the tissues in the data volume, where voxels are classified as either vessels or non-vessels. Our algorithm is adaptive to reduce the bias field effect in the images by estimating the model parameters for each slice of the data volume using the Expectation Maximization, “EM” algorithm for finite mixture of densities. A connectivity filter is designed taking into account the topology of the vascular tree to remove nonvessel tissues that appear after statistical segmentation in the form of small islands. We also implemented the Maximum Intensity Projection algorithm, “MIP” to validate the results by projecting both the segmented and original data volumes at different angles. Hence, the resultant images from both volumes can be compared side by side, which facilitates the validation process. Finally, the segmented tree is visualized in 3D using Visualization Toolkit, “VTK”, which can be viewed on a stereo graphics workstation or in a virtual reality environment. The results are validated by our medical research team and successfully showed small MRA vessels down to the limit of the scanner resolution. Keywords - Statistical segmentation, Vascular Tree, PCMRA. is extracted based on the tubular shape of vessels [5]. Other approaches for MRA vessel segmentation is the manually defined seed locations for segmentation [6]. Validating the model is very tedious and difficult process since practitioners usually rotate the visualized 3D model by certain angles in order that the views at these angles agrees with the available 2-D images taken by digital subtraction angiography (DSA) or MIP. MIP algorithm is the most common way of displaying 3-D MRA although it is sensitive to high intensity values that obscure regions of slow flow. The MIP image is similar in appearance to traditional X-ray but has some characteristics that make it easy to process digitally. In this paper, we present an automatic statistically based segmentation algorithm to extract vascular system from phasecontrast MRA, where voxels are classified as either arteries or non-arteries. Our algorithm is adaptive to reduce MRA inhomogenities caused by the bias field by estimating the model parameters for each slice of the data volume using expectation maximization (EM). A connectivity metric (filter) is developed to authenticate the cerebrovascular tissues. Finally, we validated the results using the technique presented in [7]. II. RELATED WORK I. INTODUCTION The human cerebrovascular system is a complex threedimensional anatomical structure. Serious types of vascular diseases such as carotid stenosis, aneurysm, and vascular malformation may lead to brain stroke, which is the third leading cause of death and the number one cause of disability. An accurate model of the vascular system from MRA data volume is needed to detect these diseases at early stages and hence may prevent invasive treatments. A variety of methods have been developed for segmenting vessels within MRA. One class of methods is based on a statistical model, which classifies voxels within the image volume into either vascular or non-vascular class for time-of-flight MRA [1]. Another class of segmentation is based on intensity threshold where points are classified as either greater or less than a given intensity. This is the basis of the iso-intensity surface reconstruction method [2]–[4]. This method suffers from errors due to image inhomogenities in addition; the choice of the threshold level is subjective. An alternative to segmentation is axis detection known as skeletonization process, where the central line of the tree vessels The most frequently used methods of acquisition in MRA are the ‘bright blood’ sequences TOF (time-of-flight) and PCA (phase contrast angiography), which rely on suppression of background stationary tissue and increased vessel-to-soft-tissue contrast from the flow of moving spins. Wilson and Noble [1] showed that the histogram of TOF data volume could be classified into three intensity regions. The lowest intensity region corresponds mainly to cerebrospinal fluid (CSF) surrounding the brain tissue, bone and the background air. The middle intensity region corresponds to brain tissue, including both the gray and white matter. The high-intensity region consists of fat, which is found adjacent to the skin, and arteries. They modeled the low and middle intensity regions (CSF and brain tissues) by Gaussian distribution. The high intensity region (arteries) is modeled by a uniform distribution over the whole intensity range. Fig. 1, shows a typical TOF data volume histogram, where the dotted line, represent the actual data volume and the solid line represents the fit of two Gaussian and a uniform distribution. They estimated the distribution parameters using EM algorithm and classified voxels using Bayes classifier. Fig. 2. PCA volume histogram Fig. 1. TOF volume histogram III. STASTICAL CLASSIFICATION ANALYSIS In case of PCA, our studies showed that the situation is different. We analyzed different PCA data sets and found that the volume histogram always has one peak near the low intensity region, which is not surprising since PCA is known to have good suppression of stationary tissues over TOF. We proposed the following model; we will assume that our data volume consists of two classes, vessel and non-vessel. Non-vessel class includes both the low and middle intensity regions (CSF, WM, and GM) and is modeled by a Gaussian distribution. The vessel class includes arteries and is modeled by a uniform distribution. Fig. 2, shows a typical PCA data volume histogram, where the dotted line, represent the actual PCA data volume and the solid line represents the fit of a Gaussian and a uniform distribution. The total distribution of the PCA data can be expressed as a finite mixture of two classes; vessel and non-vessel. p( x) p( x | 1 ) P(1 ) p( x | 2 ) P(2 ) Where, p (x ) is the total distribution of PCA data, (1) x is the p( x | 1 ) is the posterior distribution of nonvessel class, p( x | 2 ) is the posterior distribution of vessel class, P(1 ) and P( 2 ) are the proportions of non-vessel and voxel intensity, vessel classes in data volume respectively. A Gaussian distribution models non-vessel class as follows: p( x | 1 ) ( x )2 exp 2 2 2 2 1 (2) p(x i|ω2 )P(ω2 ) p(x i|ω1 )P(ω1 ) ( x )2 exp i 2 P(ω1 ) 2 2 2 1 P(ω2 ) I 1 P(1 ) I xi* 2 ln P( 2 ) 2 we should estimate the parameters of each class distribution. Four parameters need to be estimated IV. PARAMETERS ESTIMATION EM is a general method of finding the maximum-likelihood estimate of the parameters of an underlying distribution from a given data set when the data is incomplete or has missing values [8]. The mixture-density parameter estimation problem is probably one of the most widely used applications of the EM algorithm in the computational pattern recognition community, where parameters are iteratively estimated by updating the initial estimates of the parameters. When the distribution is Gaussian, the parameters of the distribution can be directly estimated from the following equations. N new (3) p old i 1 N p N new 2 p i 1 old P(ω2 | xi ) P(ω1 | xi ) (4) (1 | xi ) xi old N p (8) (1 | xi ) (1 | xi )( xi new ) 2 i 1 vessel class if: , 2 , P(1 ) for non- vessel class and P( 2 ) for vessel class, which can be achieved by EM algorithm. i 1 Where, I is the maximum intensity in the data volume. According to Bayes classifier, a voxel x i is said to belong to (7) * A uniform distribution models vessel class as follows: 1 I (6) Where, x i is the decision level. Before classification takes place, p( x | 2 ) (5) old (1 | xi ) (9) 1 N P new (1 ) N p old i 1 (1 | xi ) P new ( 2 ) 1 P new (1 ) p old (10) Table 1, shows the initial and final estimates of the parameters estimated by EM for patient1 and patient2 respectively. (11) TABLE 1 RESULTS OF EM ALGORITHM FOR PATIENT1 AND PATIENT2. p old ( xi | k ) P( k ) (12) ( k | xi ) old p ( xi | 1 ) P(1 ) p old ( xi | 2 ) P( 2 ) N is the total number of voxels in the PCA volume and xi is the intensity of voxel i . Where, 0 Patient 1 Initial Final Est. Est. 19 25 Patient 2 Initial Final Est. Est. 4 16 2 168.5 223.9 35 128.78 P0 (1 ) 0.9 0.1 0.9812 0.0188 0.9 0.1 0.9224 0.0776 0 P0 ( 2 ) V. PARAMETERS INITIALIZATION Convergence of EM algorithm is critically dependent on the initial guess of the parameters. The mean 0 is chosen to be the Fig. 4 and Fig. 5, show the fit of a Gaussian and uniform distribution by EM algorithm versus the total distribution of the whole MRA volume for patient1 and patient2 respectively. intensity corresponding to the histogram maximum value as 02 can be estimated as follows: p( x) p( x | 1 ) P(1 ) p( x | 2 ) P(2 ) (13) shown in Fig 3. The variance p ( x) 1 2 02 ( x 0 )2 1 ) P0 (1 ) P0 ( 2 ) 2 2 0 I (14) P0 (1 ) (15) exp( p( 0 ) 2 0 2 2 0 P0 ( 2 ) I P02 (1 ) P ( ) 2 p( 0 ) 0 2 I 2 Fit of Mixture Dist. By EM PCA Volume Histogram (16) Fig. 4. Fit of a Gaussian and uniform distribution by EM algorithm versus the It is a fact that arteries constitute a small percentage of the human brain, hence the initial estimates for P0 ( 2 ) and P0 (1 ) are 0.1 and 0.9 respectively. EM steps are repeated iteratively until no further changes in the parameter values or difference between them is very small. EM is found to converge for many data sets after 15 iterations. We did not approximate the EM parameter estimation equations as in [1] to speed up the processing time. total distribution of the whole PCA volume for patient1. Fit of Mixture Dist. By EM PCA Volume Histogram Fig. 5. Fit of a Gaussian and uniform distribution by EM algorithm versus the total distribution of the whole PCA volume for patient2. VI. ADAPTIVE SEGMENTATION Segmenting the whole data volume based on a single decision level x * is not an accurate model and is prone to error. Fig. 3. Estimating 0 Fig. 6. Typical seed image Fig. 5. Dotted curve is the total volume histogram. Each solid line is a slice histogram. The histogram of each volume slice is studied independently. It is found that, having a single decision level for each slice to adapt the changes of arteries intensity from slice to another is a better model. The solid lines of Fig. 5, shows the independent histograms of the first four slices of the PCA volume. The dotted line represents the histogram of the whole data volume. Classifier parameters are then estimated for each slice independently and a new decision level is calculated for each slice. This adaptation will reduce the effect of MRA inhomogenities caused by bias field. As a generalization, the whole volume can be divided into n sub-volumes of m slices. Our case occurs when m equals one. VII. CONNECTIVITY FILTER Some non-cerebrovascular tissues appear in the final segmented volume. A connectivity metric (filter) is developed to authenticate the cerebrovascular tissues. The filter exploits the fact that the vascular system is a tree-like structure and makes use of the 3D computer graphics region-filling algorithm to extract the vascular tree. The algorithm needs for a start a point that belongs to the tree. That can be achieved by searching the data volume for the slice that has the largest brightest spots which corresponds to the carotid arteries cross section voxels. Those voxels are marked as parents, and are pushed into a stack data structure. Let vessel_array is a 3D empty array that will store the connected vessel tree extracted by the filter. Each parent voxel is popped from the stack and is inserted into vessel_array, then it is compared with the 26-adjacent neighbour voxels (children) that form a small cube whose center is the parent. If the child is adjacent to its parent, it is marked as parent too and is pushed into the stack. The process is repeated until the stack is empty. vessel_array now contains our connected tree. Since our algorithm investigates only those neighbours (children) surrounding the current voxel (parent), hence, we eliminate the possibility of having unconnected tissues in the final volume. Fig. 6 shows a typical seed image for carotid voxels, where arrows point to carotid cross sections. VIII. VALIDATION One of the crucial issues with 3D volumes generated from MRA scans is the validation with respect to the known structures. It is quite difficult to devise validation criteria because of the extent and complexity of the vascular tree. While basic arteries and veins are of known size and significance, the rest of the vascular tree does not have distinct landmarks to recognize. Basic evaluations of these models using phantoms can be employed but there exists no such phantom that mimics the complexity of the vascular tree especially those vessels whose diameters less than 1mm. Practitioners usually validate the resulting cerebrovascular volume by rotating the visualized 3-D model by certain angles in order that the views at these angles agree with the available 2-D images taken by DSA or MIP. In [7], we implemented the MIP algorithm such that we can generate any projection of the data volume at any angle. We applied the algorithm to both the original and segmented volumes. The generated projected images from all directions at different angles to both volumes can then be compared to each other side by side. This technique will help practitioners to evaluate visually the quality of the MRA results fast when compared with traditional methods. IX. RESULTS The MRA data sets were collected using GE MEDICAL SYSTEMS Genesis Signa MRI system. MRA data set consists of 256x256x117 axial slices from Nasal Cavity to the top of the skull with 1mm thickness. The first row of Fig. 7 and 8 show the MRA volume of patient1 and patient2, respectively, projected by the MIP algorithm at angles 0, 25, 45, 90 before segmentation, while the second row of both figures show the resultant images at the same angles after applying our segmentation technique. First row of Fig. 9 shows some selected row data slices numbered (1, 7, 98, 101, and 117) for patient1. The second row shows the segmented slices before applying the connectivity filter. The third row shows the segmented slices after the application of the connectivity filter. Note that the filter removed all the nonvessels that formed small islands in the data volume. The last column of the same figure shows the 3D visualization for each mentioned case. This patient suffers from a severe artery malformation, which is apparent in the images of second column from left. Left and Right images of Fig.10 show the 3-D visualization of patient1 and patient2 respectively. Fig. 11 shows the 3D volume of patient2 before and after applying the connectivity filter. Since stereo viewing is recommended for highly complex 3D vascular structure, we used VTK as a visualization toolkit because of its capability in rendering the results in stereo, besides it can be used with virtual reality display environments such as Immersa-Desk system, where our 3-D results are displayed. Speed wise, the proposed segmentation algorithm is very fast compared with other algorithms. 256x256x117 slices takes 2 minutes over Onyx-II supercomputer Fig. 7. First row shows the MIP images of the MRA volume of patient1 projected at angles 0, 25, 45, 90 respectively before segmentation. Second row shows the resultant MIP images generated at the same angles after applying our segmentation technique Fig. 8. First row shows the MIP images of the MRA volume of patient2 projected at angles 0, 25, 45, 90 respectively before segmentation. Second row shows the resultant MIP images generated at the same angles after applying our segmentation technique #1 #37 #98 #101 #117 Fig. 9. Patient1 (1st row) selected raw data slices numbered (1, 7, 98, 101, and 117). (2nd row) segmented slices by our algorithm before connectivity filter. (3rd row) segmented slices by our algorithm after connectivity filter. (last column) from top to bottom, 3D visualization for the un-segmented volume, segmented volume without connectivity filter, and segmented volume with connectivity filter. Fig. 10. 3-D visualization of patient1 and patient2 respectively. Fig. 11. 3-D visualization before and after applying connectivity filter for patient2. X. CONCLUSION We have presented a fast automatic statistically based segmentation algorithm to extract the cerebrovascular system from phase contrast MR angiography. Our algorithm is adaptive by finding an intensity decision level for each data slice to overcome MRA inhomogenities. We designed a parent/child connectivity filter to remove tissues that form small islands in the segmented volume. XI. FUTURE WORK Investigate the application of MRF to segmentation process to take into account the spatial distribution of voxels in data volume and also improve the statistical model by taking into account geometrical features beside the intensity level. ACKNOWLEDGMENT The Whitaker Foundation Research Grant No. 98-009 has funded this project. The generous support of Norton Healthcare Organization for our medical research through Grants 97-72 and 97-73 is greatly appreciated. REFERENCES [1] D. L. Wilson and J. A. Noble, “An adaptive segmentation algorithm for time-of-flight MRA data,” IEEE Trans on Med. Imaging, vol. 18, no. 10, pp. 938–945, 1999. [2] H. E. Cline, W. E. Lorensen, R. Kikinis, and R. Jolesz, “Threedimensional segmentation of MR images of the head using probability and connectivity,” Neurosurgery, vol. 14, pp. 1037–1045, 1990. [3] S. Nakajima, H. Atsumi, and A. H. Bhalerao, et al., “Computer-assisted surgical planning for cerebrovascular neurosurgery,” Neurosurgery, vol. 41, pp. 403–409, 1997. [4] H. E. Cline, W. E. Lorensen, S. P. Souza, F. A. Jolesz, R. Kikinis, G. Gerig, and T. E. Kennedy, “3D surface rendered MR images of the brain and its vasculature,” JCAT, vol. 15, pp. 344–351, 1991. [5] Peter J. Yim, Peter L. 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