Journal of Medical and Biological Engineering, 30(5): 283-288 283 Development of a Multi-scale Noise Reduction Algorithm for Cone-beam Micro-CT Using Fuzzy Logic-based Anisotropic Filter Zhiwei Tang Guangshu Hu* Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China Received 16 Sep 2009; Accepted 18 Nov 2009; doi: 10.5405/jmbe.30.5.03 Abstract In micro-CT, smaller voxels require much higher dose to achieve adequate signal-to-noise ratio compared to conventional CT, thus, necessitating a method to reduce statistical noise and then to improve dose efficiency. We developed a method for multi-scale filtration of micro-CT data before reconstruction. The study aims are to increase the signal-to-noise ratio (SNR) of image data while at the same time maintaining image quality, in particular spatial sharpness of the images. In our approach, each projection is decomposed into successive sub-bands representing different levels of resolution from coarse to fine. Within each sub-band, pixels are distinguished into high-contrast regions (edges) and smooth regions using a fuzzy logic operation. Anisotropic filters are then used to adaptively smooth the image data. The degree of smoothing is controlled by the factor obtained by fuzzy logic operation. Both the fuzzy membership function and fuzzy rules are defined in such a way that the performance is optimized in terms of its robustness to noise. The potential of our algorithm was evaluated using phantom and clinical data. It was shown that SNR could be improved by a factor of 4 at the same radiation dose without loss of sharpness or introduction of new image artifacts. Alternatively, on the basis of clinical performance, our method shows that the radiation dose can be significantly reduced while at the same time maintaining the noise level and the image sharpness. Additionally, our approach can be extended to other imaging methods as an efficient tool for edge-preserving noise reduction. Keywords: Micro-CT, Noise reduction, Multi-scale, Fuzzy logic, Anisotropic filter 1. Introduction Small-animal imaging has played a critical role in phenotyping and drug discovery, and provided a basic understanding of mechanism of disease. Among the newly developed small-animal imaging modalities, micro-CT, with its spatial resolution on the order of several microns, is believed to have great potential for accurate 3D imaging of anatomy in a minimally invasive way [1,2]. The signal-to-noise ratio (SNR) is a special concern for micro-CT, especially if longitudinal studies are required. The major source of measurement noise is the x-ray photon flux. The smaller voxels of micro-CT (usually less than 100 um) require much higher dose, since any voxel, independent of its size, must interact with a certain number of x-ray photons for adequate image quality. Therefore, in order to compensate for the reduction of the voxel size, the photon flow must be much larger in micro-CT to achieve a SNR comparable to that of clinical CT. If the photon noise (measured by its * Corresponding author: Guangshu Hu Tel: +86-10-62784568; Fax: +86-10-62784568 E-mail: [email protected] variance) is kept constant and the linear dimension of the voxel is reduced by 2 (i.e. a reduction of voxel volume by 8) the dose must be increased by up to 16 times [3,4]. Thus, although desirable, a high enough SNR for micro-CT is difficult to achieve, due to the associated increase in radiation dose risk. To improve noise characteristics or dose efficiency in micro-CT, the aim of this study is to develop an edge-preserving multi-scale filtering approach which treats the projection data used for reconstruction. In contrast to conventional filtering, our methods have the potential to reduce random noise while trying to keep the structure information in images [5]. By using fuzzy logic [6,7], we aim to define a confidence measure with respect to the existence of edge by adaptive judgment, where the judgment is adapted to the local gray-scale statistics and to the context spatial of the pixel. The anisotropic filters are subsequently used to filtering image on a multi-scale structure. The filter is numerically robust (choice of the parameters is not critical) and faster than robust statistics estimation smoothing. Additionally, it can be straightly integrated with fuzzy logic manner and multi-scale concept. J. Med. Biol. Eng., Vol. 30. No. 5 2010 284 0 xa BIG = B ( x ) xa 1 2. Methods 2.1 Fuzzy logic edge detector In previous studies, binary edge detector was usually introduced, which could distinguish only between edge and no edge. This edge detector was used to control the spatial filter by switching the filter on or off [8]. A disadvantage of this hard switching was that in the case of higher noise level, due to edge ambiguities, the filter introduced blurring and artifacts. Fuzzy logic is an extension of classical theory called binary logic. It handles the concept of partial membership (partial truth). In fuzzy logic theory, the membership degree can be taken as a value intermediate between zero and one. Fuzzy sets are generally represented by membership function, i.e., a mapping from the underlying universe into the unit interval [0, 1]. The membership function of the intersection of two fuzzy sets A and B (A∩B) is modeled by triangular norm, while the membership function of the union of two fuzzy sets A or B (A∪B) is modeled by triangular co-norm (see Table 1 for some examples) [7]. Additionally, we denote γA(ε) and γB(ε) as the corresponding membership in the fuzzy sets A and B, respectively, where ε is an element of universe U. Table 1. Common fuzzy operations. Fuzzy Intersection (A∩B) (γA(ε)∧γB(ε)) Algebraic product γA(ε)γB(ε) Fuzzy Union (A∪B) (γA(ε)∨γB(ε)) Algebraic sum γA(ε)+γB(ε)- γA(ε)γB(ε) In this study, we propose a fuzzy logic edge detector for denoising. The determined degree of the edge confidence is expressed as a real number between zero (no edge for sure) and one (edge for sure). The uncertainties at lower processing levels are combined in a specific way (using fuzzy rule) to obtain a meaningful result at a higher processing level. This provides more freedom for further processing tasks. We assume that when an edge-like structure extends the pixel (x, y) in a certain direction, it causes large derivative values perpendicular to the direction. Thus, we use the parameter θ(x, y) to measure whether an edge extends pixel (x, y). θ(x, y) is calculated as follows: θ(x, y) = σ - k∣Ip(x, y)- μ∣ if x a if a x b (2) if x b that is, the possibility where edge exists increases for higher γB value. Specifically, between x = a and x = b, the membership function increases linearly. Subsequently, γB of the specific neighbors from the 2-D window (3 × 3) are analyzed and combined in a meaningful way (defined by the fuzzy logic rule) to determine the edge confidence measure α(x, y) for each pixel (x, y). The degree of α(x, y) is expressed as a real number measuring the existence of edge between two extremes: zero (no edge for sure) and one (edge for sure). Considering the fact that when an edge extends a pixel(x, y), it will occupy a group of connected pixels, we design the fuzzy rule R (see Table 2) as there is an edge if γB of the central pixel is BIG and at least three neighboring pixels (x+i, y+j) (i, j = -1, 0, +1) in the 2-D window are also considered as BIG (see Figure 1 for some examples). The intersection (∧) of all combinations of γB(x, y) and three different neighboring BIG membership functions γB(x+i, y+j) (i, j = -1, 0, +1) are computed, where the algebraic product is used as the intersection operator. The results of these outcomes are summed, using the∨ operator, which is the algebraic sum (see Table 1) of all possible instances(see Table 2) to obtain the edge confidence α(x, y). The activation degree of R indicates to what degree α(x, y) can be considered as true. The edge confidence α(x, y) will be used to control the strength of smoothing in adaptive filtering as explained in next section. Table 2. Fuzzy rule description (∧: And; ∨: Or; : there exists). Subfact SF1 SF2 SF3 SF4 Rule R Fact γB(x,y) = BIG γB(x+i1,y+j1) = BIG γB(x+i2,y+j2) = BIG γB(x+i3,y+j3) = BIG Antecedent i1 , j2 ,i2 , j3 ,i4 , j4 ( SF1 SF2 SF3 SF4 ) Consequent There exists an edge at [(i1 , j1 ) (i2 , j2 ) (i3 , j3 )] (i1,2,3 , j1,2,3 ) (0, 0) (x,y). (1) 2 where Ip(x,y) is the pixel value at (x,y), σ and μ are the local variance and mean values in the neighborhood, and k is a constant coefficient usually between 1.5~2. If θ is big, it means that Ip(x, y) is close to its mean value of neighborhood and the local variances are probably generated by the edge-like structure. Contrariwise, the local variances may be probably produced by noise. Actually, there would be gradual transition from small θ value caused by noise to large θ caused by edge. To differentiate between noise and edge, we define the membership function BIG for the signal θ(x, y), i.e., the membership γB[θ(x, y)], as follows: Figure 1. Examples of fuzzy rule in a sliding window for fuzzy logic edge detector: B, big; X, unsure. 2.2 Fuzzy logic bilateral filter The anisotropic filter is a classic example of an edge-preserving noise reduction method. Bilateral filter is a special class of anisotropic filter, which obtains the pixel value Noise Reduction for Cone-Beam Micro-CT at location x with an average of nearby and similar pixel values by a combined domain (space) and range (similarity) filter [9,10]. A commonly used bilateral filter is the shift-invariant Gaussian filtering, in which both the domain (space) filter and the range (similarity) filter function are Gaussian functions [11]. For an image with value I(p) at pixel p, a bilateral Gaussian filtering operation is defined by: Gg ,h 1 I ( p) Np g ( p q ) h ( I ( p ) I ( q )) I ( q ) (3) qD where: Np g ( p q ) h ( I ( p ) I ( q )), m (t ) exp( qD t ) 2m 2 2 (5) The actual value of the statement “▽D(x, y) is SMALL” is FS[▽D , h]. Combining with domain filter, we defined the proposed fuzzy logic bilateral filtering in terms of the calculated fuzzy derivatives (fuzzy rule R1), for each of the eight neighbors, as follows: 1 I out ( x , y ) 1 g ( k , l ) wr ( x k , y l ) I p ( x k , y l ) k 1 l 1 1 (6) 1 k 1 l 1 g ( k , l ) wr ( x k , y l ) Table 3. Pixel positions involved in the calculation of derivatives. Direction D Neighboring derivative Central derivative DD ( x, y ) CD ( x, y ) NW D ( x 1, y 1) D ( x, y ) W D ( x 1, y ) D ( x, y ) SW D ( x 1, y 1) D ( x, y ) S D ( x, y 1) D ( x, y ) SE D ( x 1, y 1) D ( x, y ) E D ( x 1, y ) D ( x, y ) NE D ( x 1, y 1) D ( x, y ) N D ( x, y 1) D ( x, y ) (4) D denotes a sliding window of the neighboring pixels centered at the pixel p. g and h are filtering parameters measuring the width of φg and φh, respectively. The general idea behind our method is to integrate the edges feature orientations into bilateral filter while filtering the unstationary noise. Consider a 3 × 3 neighborhood of a pixel Ip(x, y). The derivative ▽ D(x, y) is defined as the absolute difference between the central pixel (x, y) and its neighbor in the direction D; D∈{NW,W,SW,S,SE,E,NE,N}. For example, ▽N(x, y) = ∣Ip(x, y-1)-Ip(x, y)∣. It is assumed that when an edge structure extends in a certain direction D, it causes large derivative values perpendicular to the direction D at the current pixel position (x, y) and its neighbor pixels as well. For example, if a edge extends in W to E direction, either ▽N(x, y) together with ▽N(x, y-1) or ▽S(x, y) with ▽S(x, y+1) are expected to be relatively large. In such a manner, by taking into account those derivative values for each direction and combining them in a fuzzy logic way, we determine the averaging weight for every neighboring pixel. We use the following logic rule R1 to determine the fuzzy derivative value for a certain direction D at (x, y) position. The rule R1 is C described as, if the derivative of central pixel D ( x, y ) is D SMALL and the derivative D ( x, y ) of neighboring pixel in direction D is also SMALL, we conclude that there is SMALL derivative value SDD(x, y) in direction D, i.e. a small edge magnitude along the direction perpendicular to D. In Table 3, we give an enumeration of the pixel positions that are involved in the calculation of central and neighboring derivatives. The intersection (and) operator is defined using algebraic product (see Table 1). The fuzzy membership function SMALL, decreases for larger▽D, is defined according to the Gaussian function: FS[▽D , h] = φh(▽D) 285 The weighting coefficient wr for neighboring pixel in D’ th direction, which will replace the range filter coefficient in regular Gaussian bilateral filtering, is defined as the output of the fuzzy controller fixed by rule R1, i.e., the weight for the D’ th direction is equal to SDD(x, y). The smaller the derivative CD ( x, y ) and DD ( x, y ) , the larger will be weighting coefficients wr, and hence the corresponding neighboring pixel values will be taken more into account for the filtering. Considering the edge confidence α(x, y) calculated in the last section, we can modify the filtering formula in order to control the amount of filtering as follows: I out ( x , y ) I p ( x , y ) (1 ( x , y )) 1 1 ( k 1 l 1 g ( k , l ) wr ( x k , y l ) I p ( x k , y l ) 1 1 g ( k , l ) wr ( x k , y l ) I p ( x , y )) (7) k 1 l 1 Currently, the smoothing parameter g and h are determined empirically. 2.3 Multi-scale analyzing and filtering Multi-scale methods decompose the image into multiple frequency bands and perform processing separately for each band. Edges and noise mainly belong to the high-frequency portion, and contrast information is conveyed primarily in the low-frequency. The proposed fuzzy logic-based analysis and filtering is integrated into a multi-scale structure to process micro-CT images. As shown in Figure 2, each image is decomposed into a succession of sub-bands using Laplacian Pyramid [12]. Within each sub-band, pixels are analyzed and segmented into highly textured region (edges) and weakly textured region using fuzzy logic edge detector. Highly anisotropic filtering is applied to the highly textured region using fuzzy logic-based bilateral kernels that are elongated along the edges and that will not blur in the direction perpendicular to these edges. In the weakly textured region, slight anisotropic filtering is applied to reduce high-frequency random noise. The result of the analysis phase is used to control the amount of the filtering. As the noise is mainly contained in the high-frequency levels, the low-frequency levels will be left unfiltered to maintain the coarser contrast information. Those operations are applied to each of the individual sub-bands before recomposing the pyramid, as indicated in the figure. 286 J. Med. Biol. Eng., Vol. 30. No. 5 2010 Low-pass and down-sample Fuzzy logic edge detector Anisotropic filtering Sum and up-sample Low-pass and down-sample Fuzzy logic edge detector Anisotropic filtering Sum and up-sample Low-pass and down-sample Up-sample Figure 2. Block diagram of multi-scale analyzing and filtering. 2.4 Experiments and data processing The algorithms were evaluated using measured projection data acquired with our micro-CT system. The system is a bench-based cone-beam computed tomography system with cone angle of 9.5º. The micro-CT system consists of a Hamamatsu flat panel detector, an Oxford micro-focal x-ray tube and a rotational bench. The x-ray tube can be operated with 0~50 kV, 0~1 mA anodic current, and 50-μm focal spot. The detector is a 50-mm Ti:CsI-CMOS device with 50-μm pixels. The radiological constants are 40 kVp, 0.2 mAs per frame. A 0.1 mm aluminum filter is placed between the source and the object. Projection images are reconstructed into a 3D volume (400 × 400 × 400) by the short-scan Feldkamp algorithms from images of 190 view angles. The pixel pitch of reconstructed volume is 0.1 mm. Projection image was first decomposed into a four-level Laplacian Pyramid by recursive low-pass filtering and subtraction. Since the random noise is mainly contained in high-frequency band, the lowest frequency level is left unfiltered. Each high-frequency level was first processed with fuzzy logic edge detector to obtain two-dimensional edge confidence data α(x, y). The parameter k in Eq. (1) was set as 1.8. The parameters a and b in Eq. (2) determine the slope of membership function. Note that a and b are adapted to depend on the global noise level σav, which is represented by extraction of average local variance of all pixels. The choices of a = 0 and b = 2.5σav were experimentally found to be best in terms of optimal division between noise and edge. Then the band image is smoothed with anisotropic filter. The parameter g of domain filter is chosen as 1 pixel to avoid unnecessary blurring of coarser structures. The parameter h is set according to the global noise level σav as h = 2σav. The resulting image is then recomposed from the filtered details and low-pass image. Figure 4 illustrates the reconstructed images from original data, linear Gaussian (5 × 5) filtered data and our multi-scale anisotropic filtered data. The result shows that our filter has effectively reduced noise and maintained structure information, in contrast to the loss of edge caused by the conventional linear Gaussian filter. For more quantitative comparison, we calculate the signal-noise-ratio (SNR) of a uniform area (marked with a square in Figure 4). The SNR is defined as the local mean divided by the local standard deviation (Stdv) of image densities in the selected area. Table 4 lists the Means, Stdvs, and SNRs of the uniform area. The SNR of the image reconstructed from multi-scale anistropic filter is almost the same as that of the images reconstructed from linear Gaussian filter, without removing intrinsic structure. Figure 3. PMMA-air phantom. (a) Original image (b) Gaussian filtering 3. Results To investigate the efficiency of our approach, a thorax-like phantom was scanned and tested. The phantom is a cylinder made of poly(methyl methacrylate) (PMMA) with two perforative air holes (see Figure 3). The high contrast between the air and PMMA region is well representative of the contrast between the lungs and soft tissue in the thorax. The image quality and the influence of our filtering algorithms can be judged best by regarding the image themselves and the difference images of the filtered data minus the original image. (c) Multi-scale anisotropic filtering Figure 4. Reconstructed slice of thorax-like phantom with filtered projection images (left), difference image between original and filtered one (right). Noise Reduction for Cone-Beam Micro-CT 287 Figure 5. Schematic plot of the method of on-line MTF calculation: (a) the cross section image of the air hole is used as a sharp edge; (b) the pixel values across the edge are used as to derive the LSF; (c) the Fourier transform of the LSF is then calculated to determine the MTF; (d) MTF. In order to quantify the spatial resolution of the processed image, we proposed an on-line modular transfer function (MTF) measurement method. The cross-sectional view of the air hole in the reconstructed image provides a sharp edge (Figure 5). The line spread function (LSF) can be obtained by derivative of the pixel values crossing the edge. Then, the MTF is calculated through the Fourier transform of the LSF (Figure 5). Using this method, the spatial resolution (quantified by MTF) of reconstructed images by different filtering methods was calculated. The MTF for various noise reduction algorithms are shown in Figure 6. In order to measure the improvement of dose efficiency, we reconstructed high-dose projections whose dose is 5 times higher than regular projections. The results indicate that the linear Gaussian filter produced a much lower spatial resolution, while our method provided almost the same spatial resolution as high-dose images. (a) Original image High dose Gaussian filter (b) Gaussian filtering Multi-scale anisotropic filter (c) Multi-scale anisotropic filtering Figure 6. MTF for various noise reduction algorithms. We also used our filtering algorithms with low-dose true rat data to demonstrate its applicability for clinic. The results are shown in Figure 7. Noise has been reduced about 75% without losing edge after fuzzy multi-scale anisotropic filtering. It can be clearly see that the overall image quality is greatly improved with our denoising method. 4. Discussion and conclusion The aim of this study was to improve the reconstructed-image quality of micro-CT, which is degraded Figure 7. Reconstructed slice of true rat with filtered projection images (left), different image subtracting original image (right). by the random noise caused by insufficient radiation dose. As described above, our filtering method effectively reduces noise without losing structure information. Averagely, noise can be typically reduced to 25% of its original level. Iterative reconstruction methods with Bayesian priors can also reduce noise without blurring noise, but need a large number of iterations to ensure convergence [13]. The fuzzy logic operation is entirely based on a series of multiplicative and additive operations which are computationally inexpensive and will therefore not increase the calculation time significantly. Our method contains several parameters to be tuned J. Med. Biol. Eng., Vol. 30. No. 5 2010 288 experimentally. However, for both high and low noise level, the fuzzy logic-based multi-scale bilateral filtering gives excellent results with the same parameters set. Therefore, the selection of parameters is not critical and the method is robust in use. For the speed and robustness, our filtering method combined with FBP reconstruction is suitable for the routine clinical use. We have demonstrated the fuzzy logic based multi-scale bilateral filtering is a sufficient way to reduce noise without losing structures information for micro-CT images. This new method has great potential in future micro-CT applications as an available tool to improve image quality and increase dose efficiency by means of data preprocessing. This will make micro-CT studies more feasible. [4] [5] [6] [7] [8] [9] [10] References [1] [2] [3] P. Ruegsegger, B. Koller and R. 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