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MAXIMUM LIKELIHOOD – EXPECTATION MAXIMUM RECONSTRUCTION WITH LIMITED DATASET FOR EMISSION TOMOGRAPHY A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Rahul Patel May, 2007 MAXIMUM LIKELIHOOD – EXPECTATION MAXIMUM RECONSTRUCTION WITH LIMITED DATASET FOR EMISSION TOMOGRAPHY Rahul Patel Thesis Approved: Accepted: ______________________________ Advisor Dr. Dale Mugler ______________________________ Department Chair Dr. Daniel Sheffer ______________________________ Co-Advisor Dr. Anthony Passalaqua ______________________________ Dean of the College Dr. George K. Haritos ______________________________ Committee Member Dr. Daniel Sheffer ______________________________ Dean of the Graduate School Dr. George R. Newcome ______________________________ Date ii ABSTRACT Medical Imaging provides a non-invasive technique to look at the structural and functional information of internal organs and structures. One of the most widely used Medical Imaging techniques is emission tomography, in which a radioisotope is given to a patient. Measurement of the radioactive distribution throughout the patient gives the physiological and patho-physiological information about the patient [2]. The two types of emission tomography are Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT). The image is reconstructed using the data acquired, also known as the projection data, by a mathematical technique known as Filtered Back Projection (FBP). In emission tomography, it is difficult to locate the exact location from which an emission originated. If the detectors are placed apart, the probability of scatter being detected as signal decreases. The main risk with this method is limited projection data due to the limited number of total number of detectors. The main purpose of this study is to verify whether or not we can reconstruct images with a limited dataset. This method will provide us a better estimate of the exact location of the radioactivity. Traditional reconstruction algorithms like FBP can not reconstruct an image with a limited dataset. Hence we work with an iterative algorithm, Maximum Likelihood – Expectation iii Maximum (ML-EM). This research uses the most commonly used Shepp – Logan head phantom. To test whether we can reconstruct the image using a limited dataset without any statistical difference, we use the Chi-Square Goodness of Fit test. Since it is an iterative approach, we also look at the line profile of the reconstructed images with a different number of iterations. The primary conclusion drawn from this testing was that no statistically significant differences exist between the images reconstructed from a limited dataset and the original image. We have proven that by using Modified ML-EM algorithm, we can reconstruct the image with limited dataset. iv ACKNOWLEDGEMENTS I would like to begin by thanking my parents for giving me the courage and strength I needed to complete my goals. Dr. Anthony Passalaqua: thank you for your guidance and valuable insights in the project. Dr. Dale Mugler, and Dr. Dan Sheffer: thank you for your advice and selfless concern for students. Finally thanks go out to my friends Manisha Shah, Ashish Jagtiani, Anand Parikh, Nikhil Shrirao, Rupesh Sawant and Saket Kharshikar for their valuable support. v TABLE OF CONTENTS Page LIST OF TABLES……………………………………………………………………..…ix LIST OF FIGURES………………………………………………………………………xi CHAPTER I. INTRODUCTION ………………………………………..………………………1 II. LITERATURE REVIEW………………………………………………....………3 III. 2.1 Basic Principles of PET...………………………………………....….…..3 2.2 Basic Principles of SPECT…………………………………....………….6 2.3 Radon Transform and Filtered Backprojection…………….………..…....8 2.4 Iterative Reconstruction Algorithms...………………………..…….……12 2.5 Practical Issues…………………………………………………………...14 METHOD…………………………………….....………………….….….……..16 3.1 Mathematics of ML-EM Algorithm.……………………….….…….…...16 3.2 Modified ML-EM Flowchart.……...……………………….….…….…..19 3.3 System Matrix………………………………………………………........23 3.4 Hypothesis and Statistical Testing……………………………………….25 3.5 Advantages and Disadvantages of Ml-EM Reconstruction Algorithm.....26 vi IV. V. RESULTS………………………………………………………….…………….30 4.1 FBP Reconstruction with limited dataset………………………………..30 4.2 Modified ML-EM Reconstruction on image..………….….…………….33 4.3 Effect of the number of iterations on the reconstruction………..……….35 4.4 Effect of the number of bins skipped on the reconstruction...….………..40 4.5 Reconstruction with a real SPECT image………………………….…….44 4.6 Reconstruction with a faulty detector…...……………………………….45 CONCLUSION………………………………………………………...……….48 BIBLIOGRAPHY………………………………………………………………………50 vii LIST OF TABLES Table 4.1 Page Detector Skipped and Resulting Chi-Square Error………..……………..40 viii LIST OF FIGURES Figure Page 2.1.1 Positron emission and annihilation……………….…………………...….4 2.1.2 Conceptual diagram of coincidence detection in a PET system………….5 2.1.3 Types of coincidence in PET……………………………………………..6 2.2.1 Gamma Camera…………………………………………………………..7 2.3.1 Object under reconstruction and its sinogram…………………………....8 2.3.2 Shepp-Logan phantom and its RadonTransform…………………………9 2.3.3 Demonstration of FBP Algorithm…………………………...…………...12 4.1.1 Original Shepp-Logan Head Phantom and FBP Reconstructed image with ½ dataset and 60 angles……….. ……………..……..……………..30 4.1.2 FBP Reconstructed image with ½ dataset and 1800 angles……………..31 4.1.3 FBP Reconstructed image with ¼ dataset and 1800 angles……………..31 4.1.4 FBP Reconstructed image with ¼ dataset and linear interpolation (a) 1800 angles (b) 360 angles (c) 180 angles d) 60 angles……………..32 4.2.1 Modified ML-EM Algorithm (a) Original Shepp-Logan phantom (b) Reconstructed image (c) Sinogram……………..……..……………..33 4.3.1 Chi-Square Goodness of Fit for Modified ML-EM algorithm…………..36 4.3.2 Reconstruction images at (a) 5 iterations (b) 15 iterations (c) 35 iterations (d) 50 iterations (e) 75 iterations (f) 100 iterations…….37 4.3.3 Line profile values at (a) 5 iterations (b) 15 iterations (c) 35 iterations (d) 50 iterations (e) 75 iterations (f) 100 iterations…….38 ix 4.4.1 Plot of number of detectors skipped V/S Chi-Square Error……………..41 4.4.2 Reconstructed images and their sinograms with (a) no detectors skipped (b) ½ detectors (c) 1/3 detectors (d) 1/5 detectors (e) 1/10 detectors……………………………………....41 4.5.1 Reconstruction with a real SPECT image (a) original image (b) no detectors skipped (c) ½ detectors (d) 1/3 detectors (e) 1/5 detectors (f) 1/10 detectors…………………………………….....44 4.6.1 Ring artifact in the image due to faulty detector…………………………46 4.6.2 Sinogram which shows that detector 16 is bad…………………………..46 4.6.3 Image reconstructed using ML-EM Recon Algorithm…………………..47 x CHAPTER I INTRODUCTION Recent advances in computer technology have brought a new revolution in the field of medical imaging. Now it is easy to acquire data and perform mathematical operations to reconstruct the data and provide emphasis on the required anatomical details. Medical Imaging provides a non-invasive technique to look at the functional and structural information of internal organs and structure [2]. There are many different types of modern medical imaging techniques, including Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) to name a few [10]. We will focus on two types of emission tomography: Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT). The basic principles of both techniques are outlined in Chapter 2. Traditionally, mathematical algorithms are used to reconstruct the image. The most famous reconstruction technique that relies heavily on the Fourier transform is Filtered Back Projection [10]. The basic principles of Filtered Back Projection are presented in Chapter 2. These conventional techniques are undoubtedly the most widely used algorithms for image reconstruction [10]. In the early 1980’s, new methods of image reconstruction in emission tomography emerged, which could overcome some of the 1 shortcoming of the conventional methods. These methods could take into account physical characteristics of emission tomography, the Poisson nature of photons, and many such other factors leading to better image reconstruction. We will concentrate on one of these iterative reconstruction techniques called Maximum Likelihood Expectation Maximum (ML-EM) reconstruction. The mathematics of this method is provided in Chapter 3. It has been observed that ML-EM reconstruction produces better images than filtered back projection algorithms. The main reason ML-EM has not been widely accepted is because the algorithm is computation intensive. We present a new method, which we call the “Modified MLEM”, which will reconstruct the image with a partial data set. In our method we place the detectors apart, hence decrease the number of detectors in the system, yet reconstruct the image without any artifacts and the same image sharpness. This new technique may not only potentially reduce the noise in the system due to photon scattering but will also reduce the cost of the system. The detailed discussion of this new technique is mentioned in Chapter 3. Images reconstructed are presented in Chapter 4. Our analysis suggests that the Modified ML-EM reconstruction algorithm produces an image with the same spatial and contrast resolution, with a possibility of reducing the scatter photons and with a better reconstructed image. An outline of possible future work is given in Chapter 5. 2 CHAPTER II LITERATURE REVIEW The goal of Emission Computer Tomography is to give accurate quantitative measurement of radioactivity distribution throughout the patient to extract physiological and patho-physiological information. It has been shown that quantitative measurement of Fluoro Deoxy Glucose (FDG) uptake in tumor is useful for grading diseases (Strauss and Conti 1991) [22]. Accurate myocardial blood flow has helped to identify triple vessel coronary artery disease and FDG uptake is useful in studies of cerebral metabolism [22]. In this section we present some of the basic concepts in SPECT and PET that may help us to understand the reconstruction method better. We also present the standard reconstruction algorithm, the Filtered Back Projection Algorithm, which is based on direct inversion of the Radon Transform. 2.1 Basic Principles of PET A proton-rich isotope, such as Carbon-11, Fluorine-18, Oxygen-15 or Nitrogen13, is given to the subject of a PET study and is placed in the field of view of a number of detectors. The radionuclide decays to produce a positron, neutron and neutrino. The 3 proton travels a short distance (~1 mm) within the body and gives up its kinetic energy due to interaction with the human tissue [22]. The positron annihilates with an electron to produce two 511 keV photons, traveling in opposite directions. Reference: http://depts.washington.edu/nucmed/IRL/pet_intro/ Figure 2.1.1: Positron emission and annihilation These photons may be detected by the detectors surrounding the subject. The detector electronics are linked to detect an emission due to the same annihilation. When a photon is registered at a detector, it generates a time pulse. The pulses are registered and called coincident only if the two detection events fall within a small time window generated by the coincidence circuitry [10]. These coincidence events are stored in arrays corresponding to projections through the patient which later contribute to the image. The conceptual diagram is shown in figure 2.1.2. 4 Reference: http://depts.washington.edu/nucmed/IRL/pet_intro/ Figure 2.1.2: Conceptual diagram of coincidence detection in a PET system. The coincidence events fall into 4 categories: true, scattered, random and multiple [22]. Pictorial views of the first three events are shown in figure 2.1.3. For a true coincidence to occur, both the photons occurring due to an annihilation event are detected within the coincidence time window. A scattered coincidence is one in which one of the detected photons has undergone a Compton scattering event, resulting in a wrong Line of Response (LOR) [22]. Random coincidence occurs when two photons not arising from the same annihilation are detected within the coincidence time window of the system. Random coincidence is proportional to the rate of single events measured [22]. Multiple coincidence occurs when more than two photons are detected in different detectors within the coincidence resolving time. In this event it is difficult to detect the LOR and the event is rejected. Scattered and Random coincidences contribute to the statistical noise in the image. 5 Reference: http://depts.washington.edu/nucmed/IRL/pet_intro/ Figure 2.1.3: Types of Coincidence in PET 2.2 Basic Principle of SPECT SPECT is Single Positron Emission Tomography. As the name suggests, single photon emissions are the source of emission rather than X-ray transmissions. Similar to PET, in SPECT the patient is injected with a harmless tracer chemical which will emit gamma rays, which also have short half lifes [10]. Unlike PET, in SPECT single photons are emitted. Note that in PET, the detectors are situated in a ring, and the nature of the positron annihilations combined with the shape of the PET scanner itself provides a selfcollimation. In SPECT, however, the detectors are set up in a strip, so the collimator is necessary to localize the site from which the photon was emitted [23]. 6 Reference: http://www.physics.ubc.ca/~mirg/home/tutorial/hardware.html Figure 2.2.1: Gamma Camera Once a tracer is injected, the gamma rays, which have the functional information, need to be detected. These gamma rays are detected using a gamma camera. The components making up the gamma camera are collimator, detector crystals, photomultipler tube array, position logistics controller and data analysis computer. The collimator allows only rays which are traveling in a straight direction to pass through. They are made of gamma rays absorbing material such as lead or tungsten [23]. The scintillation detector detects the gamma rays incident on it. For better image quality the detection efficiency of the scintillation detector should be very high. The gamma rays interact with the crystal by means of the Photoelectric effect or Compton scattering. The released electrons interact with the crystal lattice to produce light, in a process known as scintillation. The amount of signal given by the scintillation detector is then increased by passing through a Photomultiplier tube (PMT) [23]. At the end of PMT is a photocathode 7 which emits electrons proportional to the light photons. These electrons are then multiplied using a series of dynodes. The position circuit helps in locating the exact position of each scintillation event. The raw data is then passed to a computer to reconstruct an image using a reconstruction algorithm. 2.3 Radon Transform and Filtered Back Projection After acquiring the projection data, PET and SPECT reconstruction is done the same way. Traditionally the most common reconstruction algorithm used is the Filtered Back Projection algorithm. Gamma rays are released within the tissue. The line integrals represent the total amount of tracer in the tissues along the line [10]. Reference: http://depts.washington.edu/uwmip/Week_4/tomo_06_ho.pdf Figure 2.3.1: Object under reconstruction and its sinogram 8 The Radon transform of a distribution is always referred to as the sinogram of the image. Figure 2.3.1 shows how a sinogram is obtained. We have placed two tracers inside the object. As the gamma camera moves around the object we obtain the projections at different bins. All the projection data stacked up together gives us a sinogram. The Radon transform and its inverse provide the mathematical basics for the reconstruction of tomographic images. The Radon Transform of a distribution f(x,y) is given by [24] p (r , ) f ( x, y ) ( x cos y sin r )dxdy where is a delta function x, y – coordinates of a point in spatial domain r, - coordinates of the point in polar domain The most commonly used slice image used for reconstruction is the Shepp – Logan phantom. The phantom and its Radon transform are shown in figure 2.3.2. Reference: http://www.aapm.org/meetings/99AM/pdf/2806-57576.pdf Figure 2.3.2: Shepp – Logan phantom and its radon transform. 9 (2.1) Mathematically the backprojection is defined as f ( x, y ) p( x cos y sin , )d (2.2) 0 Due to the point spread function, the reconstructed image produced is blurred [24]. Filtered Back Projection rectifies this problem by including an additional filtering step. Hence the algorithm consists of two steps. First, the filtering step concerns the line integrals that make up the projection of the object. This filter makes the value zero outside of certain boundaries, leaving behind only the real object to be reconstructed. The second step is the backprojection algorithm. If f(x,y) is the unknown image to be reconstructed, the Fourier transform of the image is give by [10,24] F (u, v) f ( x, y )e 2i (ux vy ) dxdy (2.3) The Inverse Fourier transform of a point is given by f ( x, y ) F (u, v)e 2i ( ux vy ) dudv 2 f ( x, y ) P ( r , )e 2ir ( x cos y sin ) rdrd 0 0 Now we split the integral into two halves. f ( x, y ) P ( r , )e 2ir ( x cos y sin ) 0 0 f ( x, y ) P ( r , )e rdrd 2 P ( r , )e 2ir ( x cos y sin ) rdrd 0 2ir ( x cos y sin ) 0 0 rdrd P(r , )e 2ir ( x cos( ) y sin( )) rdrd (2.4) 0 0 One of the important properties of polar coordinates is P(r , ) P(r , ) (2.5) 10 Using equation 2.5 in equation 2.4 we get, f ( x, y ) P ( r , )e 2ir ( x cos y sin ) 0 rdrd P(r , )e 2ir ( x cos y sin ) ( r )drd 0 0 0 f ( x, y ) P(r , )e 2ir ( x cos y sin ) r drd 0 f ( x, y ) p 1 ( x cos y sin , )d (2.6) 0 where p ( , ) 1 P ( r , )e 2ir ( ) r drd p 1 ( , ) p ( , ) * b( ) (2.7) where b is a filter of magnitude |r|. Equation 2.6 shows that f(x,y) can be obtained by backprojection p 1 ( , ) which is the filtered sinogram [24]. The filter has a magnitude of |r|. The filtered backprojection is the most widely used reconstruction algorithm. 11 Original Image Filtered Backprojection Image Forward Back Projection Projection Ramp Filter Sinogram Filtered Sinogram Reference: http://www.aapm.org/meetings/99AM/pdf/2806-57576.pdf Figure 2.3.3: Demonstration of FBP Algorithm 2.4 Iterative Reconstruction Algorithms Iterative Reconstruction algorithms are based on a mathematical model of the physics of PET or SPECT. For mathematical computation we express a true trace distribution f(x,y), which is reconstructed as an image of LxL pixels, by a vector (b) (b 12 = 1,2,…,B, B = LxL). If we include N angles and M samples per projection, we represent the projected data by a 1-D vector n*(d) (d = 1, 2,…, D, D = MxN). The model that relates the above two factors is given by [2, 5, 6] B n * (d ) p (b, d ) (b) (2.8) b 1 where p(b,d) is the probability of the emission b to be detected by detector bin d so that p(b,d) ≥ 0 [2, 5]. These probabilities form a BxD matrix, which is commonly known as the system matrix. Thus the probability of an emission b being detected is given by D p (b) p (b, d ) 1 (2.9) d 1 In equation (2.8), if the system matrix p(b,d) and the projection data n*(d) are available, we are left with a set of linear equations for (b) . A typical SPECT image is of size 128x128 image (with 128 bins x 60 angles) making direct inversion for solving the linear equations difficult. Direct inversion is relatively slow and needs a lot of memory to store variables. To avoid numerical instabilities, an iterative approach is used. In the iterative approach we start off with an initial estimate of the image 0 (b) . The forward projection is then calculated from the intermediate estimate k (b) , then multiplying with the probability matrix p(b,d), to give a corresponding projection data represented by nk(d). [2, 5, 6] B n k (d ) p(b, d )k (b) j 1 This calculation is then compared, by division, with the true measured projection data n*(d). From this comparison we derive the correction term by backprojection and 13 updating the image to k 1 (b) [2, 3]. The next update of the forward projection nk+1(d) is closer to the true projection data n*(d). All iterative reconstruction algorithms use the same approach, but they differ in the way that the correction term is derived and the new update is calculated. Iterative reconstruction algorithms can again be divided into two categories. The first class contains conventional mathematical iterative methods like Algebraic Reconstruction Technique (ART) and Simultaneous Iterative Reconstruction Techniques (SIRT) [2, 3]. The second class contains an iterative statistical method, which generally maximizes a likelihood function. These statistical methods may include some a-priori information [2, 3]. One of the most commonly used pieces of a-priori information is the positive value constraint, since the activity distribution can never be negative. The best known example of a statistical algorithm is the ML-EM algorithm. 2.5 Practical issues In practical applications we do not always get a perfect sinogram and a perfect reconstructed image. Some of the practical problems are listed below. 1) Insufficient angular sampling Angular sampling is directly proportional to the scan time. Hence to reduce the scan time sometimes we reduce the angular samples in the system. 2) Incomplete or missing data set Metal implants within the patient block the radiation, leading to missing data in its shadow. 14 3) Motion artifacts Patient motions, such as respiration or heart beat, make it harder to reconstruct the image. 4) Noise Photon detection depends on the efficiency of the system. To get a better image with less noise we can increase the radiation dose or the exposure time. 5) Limited detector size Due to practical limitations the size of the detector is limited. Finite detector size limits the spatial resolution of the acquired data. 15 CHAPTER III ML-EM RECONSTRUCTION ALGORITHM One of the important issues in SPECT and PET is quantitative accuracy of radionuclide distribution and concentration. Image reconstruction falls broadly into two categories [3]. The single step Fourier transform methods are the most widely used methods due to its short reconstruction time. The other category, algebraic reconstruction techniques may take a longer time to reconstruct but may incorporate stochastic variations, thus yielding more accurate results. 3.1 Mathematics of ML-EM Algorithm In the ML-EM algorithm, the projection data collected plays an important role. In a SPECT scanner, the size of the projection data depends on both the number of detectors in the camera strip and the number of angles. If the camera has b number of detectors and we measure at a angles, then the total number of counts is the projection data is J = a*b. For ease of calculations, this vector is generally represented as a column vector. In PET, there is a ring of detectors around the patient which measures the annihilation event. As discussed in Chapter I, an event is recorded only if the two events 16 occur within a time window. If the detector ring has N detectors, the number of counts in projection data is given by J = N(N-1)/2 [10]. For computer reconstruction, the image to be reconstructed is digitized into a matrix x with nx rows and ny columns. Again for computational purposes, we represent the image as a column vector I with I = nx*ny elements. Physicists have proved that such emissions follow a Poisson model. So the unknown total number of emission events in the ith pixel, xˆ (i ) , represents a Poisson random variable, with mean x (i ) . We know that; the system matrix represents the probability distribution of the projection data. Hence elements of the system matrix p(i,j) represents the probability of emission i to be detected by detector j. The system matrix will be discussed in detail in later sections. It is possible to calculate the expected value of the projection data depending on the system matrix using the formula: [3, 5, 7, 10] I nˆ ( j ) E (n(i )) x(i ). p (i, j ) (3.1) i 1 The probability of the entire projection dataset is the product of individual counts, so the likelihood function is given by [3, 5, 7] J L( x) P(n x) j 1 e nˆ ( j ) nˆ ( j ) n ( j ) n( j )! To simplify the above equation we take the log on both sides: l ( x) log( L( x)) J l ( x) (log(e nˆ ( j ) ) log(nˆ ( j ) n ( j ) ) log(n( j )!)) j 1 J l ( x) ( nˆ ( j ) n( j ) log(nˆ ( j )) log(n( j )!)) j 1 17 Substituting equation 3.1 we arrive at the log-likelihood function: J I J I J j 1 i 1 j 1 l ( x) x(i ) p(i, j ) n( j ) log( x(i ) p(i, j )) log(n( j )!) j 1 i 1 It can be shown using the first and second derivatives of the log-likelihood function that the matrix of second derivatives is negative semidefinite and that l(x) is concave [6]. As a result, sufficient conditions for a vector x̂ to yield a maximum of l(x) are the KuhnTucker conditions [14]: 0 ( x(i ) J l ( x) n( j ) xˆ (i ) p (i, j ) ) xˆ (i ) I x(i ) j 1 xˆ (i' ) p(i', j) i ' 1 and l ( x) 0 if xˆ (i ) 0 x(i ) xˆ The algorithm requires an initial estimate x 0 , and using the maximization condition to iteratively improve the estimate. Researchers have used a variety of initial estimates to reach the results faster. The main formula for ML-EM algorithm is derived by solving the above maximization condition for xˆ (i ) . n( j ) p (i, j ) J x n 1 (i ) x n (i ) j 1 I x n (i ' ) p (i ' , j ) i '1 This can be written as x n 1 (i ) x n (i )x n (i ) Hence the sum is really a multiplicative coefficient that corrects the image at every step. As the number of iterations increase, the x n (i ) term gets closer and closer to 1. 18 3.3 Modified ML-EM Algorithm Given below is the simplified flowchart for the ML-EM algorithm [9]. Calculate Probability matrix Gij Start with initial image estimate (b) Forward Projection: B ni Gi , j kj j 1 Comparison: n ' i n *i / n i Back Projection: D x j Gi , j n' i i 1 Normalization: D x ' j x j / Gi , j i 1 Update: kj 1 kj * x' j 19 To better understand the working of the algorithm we consider a 4x4 image. 100 0 0 0 This image can be represented in a column matrix as 100 0 0 0 Now let us try to reconstruct this image using 4 reconstruction angles and 2 bins. The total number of projection data points is the product of number of angles and the number of bins. Hence in our example it is 8. The projection data points are represented below in yellow. The image is represented in blue. 7 8 6 100 0 1 5 0 0 2 4 3 At each point the value measured is the sum of all the pixel values that the bin can measure using line integral approach. Hence the projection data for our example is 20 100 0 0 100 n 0 100 100 0 Probability (G) matrix represents the probability of a pixel b being located at detector d. This makes the size of the matrix huge; generally BxD (where B represents the image size and D represents the projection data). Hence the size of the Probability (G) matrix in our example is 8x4. It is represented as 1 0 0 1 G 0 1 1 0 1 0 1 0 0 1 0 1 0 1 0 1 1 0 1 0 0 1 1 0 1 0 0 1 To reduce the number of iterations we start off with an initial estimate of the image with individual values equal to the average projection data. 25 25 25 25 B We perform forward projection ( ni Gi , j kj ) on this initial estimate. j 1 21 50 50 50 50 n 50 50 50 50 The comparison step is done in ML-EM by dividing the original projection data with the obtained projection data. 2 0 0 2 n 0 2 2 0 D Backprojection ( x j Gi , j n' i ) of the data gives us our correction term. This correction i 1 D term needs to be normalized ( x' j x j / Gi , j ) before we multiply it with the real image. i 1 2 1 x 1 0 We then multiply this matrix by the original image to get the first estimate of the image. 22 50 25 1 25 0 Performing similar iterations as shown above the second image correction terms are 4 / 3 2 / 3 x1 2 / 3 0 Hence the second estimate of the image is 66.66 16.66 2 16.66 0 As the number of iteration goes on increasing the estimated image approaches closer and closer to the real image. We know that; as the number of iterations goes on increasing, the error goes on decreasing. But if the number of iterations is too high, due to the Poisson nature of the data, the image may look a little noisy. Hence many researchers have suggested that 50 iterations give an acceptable result in real SPECT image. In our study too, we will consider 50 iterations. 3.4 System Matrix The system matrix is the most important part of the ML-EM algorithm. It contains the information of the geometry of the imaging system being used. It provides the model 23 of how detectors in the system see the emission event that takes place in the object being imaged. The ability to add various mathematical models like attenuation correction, scatter correction, interaction of photons with collimators and detectors, point spread function and filters make it a more sophisticated model. The size of the system matrix depends on both the size of the image and the number of points in the projection dataset. If we have an image with size lxl, then for computational purpose we represent the image by a column vector (b) (where b = 1,…,B, B=lxl). As discussed earlier, for PET the projection data is represented by a column vector n(d) (where d = 1,…,D, D=N*(N-1)/2) where N represents the number of detectors surrounding the object to be reconstructed. In SPECT the projection data is of size (na*nb) where na is the number of angles and nb represents the number of bins. Hence the total size of the system matrix is BxD. In other words the entire image is represented in each row and the entire projection data is represented by one column of the system matrix. Thus a fixed row in the system matrix corresponds to a particular detector at a particular angle. Since this matrix contains the probability of an emission at a particular point showing up at a particular detector at a particular angle, many elements within this matrix are zeros. Very few pixels in this matrix will have non-zero terms. This makes the system matrix very sparse. Let us consider an image with following parameters: Image size = 32x32, Number of angles = 60 Number of bins = 128 24 The size of the system matrix is 1024*7680 (7,864,320 elements). The number of nonzero elements in this matrix is just 173,586 i.e. 2.2073%. In addition to this, if we know that the image lies within a specific area of the digitized pixel grid, then a mask can be used. Pixels which lie outside this mask are made zeros which will not contribute to the final image. This makes the system matrix sparser. Different techniques are used to calculate the system matrix. The technique we used solely depends on the geometry of the imaging system. The values are calculated depending on the area of intersection of the ith pixel and the strip defined by the jth detector. Various constraints can be added to this matrix. For our Modified ML-EM algorithm, we add one more constraint to the system matrix. As discussed earlier, each row in the system matrix contributes to a particular detector pair. So to remove the detectors from the reconstruction algorithm, we can replace the value at that point by a zero. It is very important to modify the system matrix according to the system change or it may introduce artifacts in the image. The most common artifacts introduced due to improper sampling are the ring artifacts. This will make the system matrix sparser. 3.6 Hypothesis and Statistical Testing The null hypothesis of this research state that: The original image and image reconstructed by Modified ML-EM method will demonstrate no statistically significant difference. 25 To test our null hypothesis we will use the Chi-Square Goodness of Fit method. For a Chi-square goodness of fit computation, the data is divided into k bins and the test statistic is defined as k 2 (Oi Ei ) 2 / Ei i 1 where O is the observed result and E is the expected result. 3.6. Advantages and Disadvantages of ML-EM reconstruction algorithm There are several promising characteristics of the modified ML-EM algorithm that give it an advantage over conventional techniques such as Radon Transform or Filtered Back Projection. However there are some drawbacks which may avoid its use for practical purposes. Advantages: 1) Modeling of the measurement process The projection data are Poisson in nature with mean value equal to the line integrals, as discussed in Chapter 2. Filtered Back Projection works well if the number of counts is very high, since for higher count statistics, the mean value of the counts is close to the line integrals [10, 2, 7]. But for low count statistics, the measured data may have a large variation from the mean. ML-EM can use this information in the system matrix p(b,d) to give a better image. The ML-EM method 26 can also model the interaction of the photons with the body, the collimators and detectors. [2] 2) Modeling of image degrading factors The major problem that SPECT and PET face is the scatter of photons. Various models have been presented that can be incorporated in the system matrix p(b,d). A few of the most common methods mentioned in [2] are Scatter Correction done by the subtraction based method, Point Spread Function Recovery by convolution method, attenuation correction method, geometrical weighting of the point spread function, and Monte Carlo simulation. 3) Reduction of Cross Talk One of the problems with imaging reconstruction algorithms in PET is the cross talk between detectors. These detector crystals convert photons to a proportional amount of light energy produced. These crystals are coated with light reflecting material which forces the light to go in the downward direction. In spite of the light reflecting coat; some amount of light gets detected by the adjacent detectors, hence contributing to noise. By placing the detectors apart we reduce the possibility of cross talk between the detectors. 4) Reduction of cost of the system By placing the detectors apart, the system requires fewer detectors to cover the same area. This can reduce the overall cost of the system without affecting the image quality. 5) Reduction of storage space 27 The projection data acquired by the imaging system is huge. This projection data may be saved to evaluate the reconstruction algorithm. As the size of the image and the number of slices goes on increasing, the projection data size also increases. Hence to reduce the storage space required, the Modified ML-EM algorithm may be used. It can reduce the space requirement to 1/10th of the original size without affecting the spatial or contrast resolution of the reconstructed image. 6) Reconstruction with faulty detectors Sometimes the detectors in the camera strip malfunction. In this case the normal Filtered Back Projection may introduce ring artifacts in the image. There are special codes installed in the system which detect faulty detectors. To avoid artifacts due to this, the data can be interpolated. A better way to solve this problem will be to modify the system matrix. The corresponding values in the system matrix can be made zero to give a reconstructed image without artifacts. This point is explained in detail is section 4.6. Disadvantages: 1) Noisy Reconstruction with higher iterations As the number of iterations goes on increasing, the result in real images with noise initially converges to an acceptable image. For a higher number of iterations, the likelihood still increases but the resulting image becomes noisy. [2, 10] This is due to the Poisson nature of the variables. [2, 10] This can be avoided by using a fixed stopping rule depending on the error. A second approach is to use a smoothing filter after the image is reconstructed. The most common approach is the second one. 28 2) Longer Calculation Time Filtered Back Projection is a single step process whereas ML-EM uses an iterative approach. ML-EM may require from 10-100 iterations depending on the stopping rule used. Several methods have been suggested to decrease the calculation time in the ML-EM algorithm. The most common approach is the OS-EM method proposed by Hudson and Larkin in 1994. [2, 10] In this method, projection data is divided into subsets and uses only one subset for each iteration. OS-EM has proved to increase the reconstruction time by a factor of 6. [2, 10] 3) More iterations with fewer detectors As we decrease the number of detectors, the number of iterations required to reconstruct an acceptable image goes on increasing. Hence there is always a tradeoff between the number of detectors skipped and the reconstruction time. 29 CHAPTER IV RESULTS 4.1 FBP Reconstruction with limited dataset In this section, we test whether FBP can reconstruct images with a limited dataset. We use half the number of detectors to reconstruct the image. Figure 4.1.1 shows the original Shepp- Logan head phantom and the reconstructed image with ½ detectors and 60 angles. Figure 4.1.1 Original Shepp-Logan Head Phantom and FBP Reconstructed Image with 60 angles 30 To reconstruct the image, we can increase the number of angles to 1800. Figure 4.1.2 shows a reconstructed image with 1800 angles. In practical situations, it is impossible to increase the number of angles to such a huge number. Figure 4.1.2 FBP Reconstructed image with ½ dataset and 1800 angles Now we try to reconstruct the image with ¼ data points and 1800 angles. Figure 4.1.3 shows the reconstructed image. Hence we see that even with such high number of angles we can not reconstruct the image. Figure 4.1.3 FBP Reconstructed image with 1/4 dataset and 1800 angles. 31 Now, we try to interpolate the projection data between the original data points and then reconstruct the image using the modified projection data. Figure 4.1.4 represents reconstructed images. (a) 1800 angles (b) 360 angles (c) 180 angles (d) 60 angles Figure 4.1.4 FBP Reconstructed image with ¼ data points and linear interpolation (a) 1800 angles (b) 360 angles (c) 180 angles (d) 60 angles The image produced is good with a loss in resolution, which causes blurring at the edges. 32 4.2 Modified ML-EM Reconstruction on image In this section, we show the results for the Modified ML-EM algorithm. Through out the study we use a Shepp-Logan head phantom with the following parameters: 1) size = 32x32 2) angles = 60 angles 3) number of bins = 128 bins 4) number of iterations = 50. These parameters are the most commonly used parameters in the field. Many studies have suggested that 50 iterations produce an acceptable result in the medical field. Figure 4.2.1 shows a sample reconstructed image. (a) Original Shepp-Logan phantom Figure 4.2.1: Modified ML-EM Algorithm: (a) Original Shepp-Logan phantom (b) Reconstructed image (c) Sinogram 33 (b) Reconstructed image (c) Sinogram Figure 4.2.1: Modified ML-EM Algorithm: (a) Original Shepp-Logan phantom (b) Reconstructed image (c) Sinogram continued 34 4.3 Effect of the number of iterations on the reconstruction As mentioned earlier, ML-EM is an iterative algorithm. Therefore as the number of iterations goes on increasing, the error goes on decreasing. To calculate the error, we use the Chi-Square Goodness of Fit method. For a Chi-square goodness of fit computation, the data is divided into k bins and the test statistic is defined as k 2 (Oi Ei ) 2 / Ei i 1 where O is the observed result and E is the expected result. The number of pixels in the image is 1024 (32x32). So the degree of freedom is 1023. Assuming a significance level of 0.05, (20.05,1023) 124 . Figure 4.3.1 shows the plot of error with respect to the number of iterations. As the number of iterations increase the likelihood goes on increasing. 35 Figure 4.3.1: Chi-Square Goodness of fit for Modified ML-EM algorithm Figure 4.3.2 below represents images acquired at different number of iterations. As the number of iterations increase, the image quality gets better. The images are taken with the following parameters: 1) size = 32x32 2) angles = 60 angles 3) number of bins = 128 bins 36 (a) 5 iterations (b) 15 iterations (c) 35 iterations (d) 50 iterations Figure 4.3.2: Reconstructed image at (a) 5 iterations, (b) 15 iterations, (c) 35 iterations, (d) 50 iterations, (e) 75 iterations and (f) 100 iterations 37 (e) 75 iterations (f) 100 iterations Figure 4.3.2: Reconstructed image at (a) 5 iterations, (b) 15 iterations, (c) 35 iterations, (d) 50 iterations, (e) 75 iterations and (f) 100 iterations continued Figure 4.3.3 represents the values of a single horizontal line through the center of the image with respect to number of iterations. The red line represents the reconstructed image and blue represents the true values. We can see that as the number of iterations increase, the difference between the two plots goes on decreasing. (a) 5 iterations (b) 15 iterations Figure 4.3.3: Line Profile values at (a) 5 iterations, (b) 15 iterations, (c) 35 iterations, (d) 50 iterations, (e) 75 iterations and (f) 100 iterations 38 (c) 35 iterations (d) 50 iterations (e) 75 iterations (f) 100 iterations Figure 4.3.3: Line Profile values at (a) 5 iterations, (b) 15 iterations, (c) 35 iterations, (d) 50 iterations, (e) 75 iterations and (f) 100 iterations continued 39 4.4 Effect of the number of bins skipped In this section, we keep on skipping the detectors, which results in an incomplete data set. By skipping the data sets we are also decreasing the number of detectors in the system. Table 1 shows the results with following parameters: 1) image size: 32x32 2) number of angles: 60 3) number of bins: 128 4) number of iterations: 50 The reconstructed images and their respective sinograms are shown in figure 4.4.2. The results show that as we increase the number of bins skipped, the error goes on increasing. This error can be reduced by increasing the number of iterations. Table 1: Detector skipped and resulting Chi-Square error Data points Chi-Square Number skipped Error(*10^-3) 1 None 3.8 2 ½ 3.8 3 1/3 3.9 4 1/5 5.2 5 1/10 6.3 40 Figure 4.4.1: Plot of number of detectors skipped V/S the Chi-Square error (a) no detectors skipped Figure 4.4.2: Reconstructed images and their sinograms with (a) no detectors skipped, (b) ½ detectors, (c) 1/3 detectors (d) 1/5 detectors (e) 1/10 detectors 41 (b) ½ detectors (c) 1/3 detectors Figure 4.4.2: Reconstructed images and their sinograms with (a) no detectors skipped, (b) ½ detectors, (c) 1/3 detectors, (d) 1/5 detectors and (e) 1/10 detectors continued 42 (d) 1/5 detectors (e) 1/10 detectors Figure 4.4.2: Reconstructed images and their sinograms with (a) no detectors skipped, (b) ½ detectors, (c) 1/3 detectors, (d) 1/5 detectors and (e) 1/10 detectors continued 43 4.5 Reconstruction with a real SPECT image In this section, we reconstruct a single axial SPECT bone scan image through the pelvis using real sinogram data from a gamma camera. This sinogram was collected from a Trionix gamma camera. From Figure 4.5.1, we can see that as we skip the number of bins, the image looks more and more noisy. The original image (a) below is the filtered back projection reconstruction and the images b-f are reconstructed by Modified ML-EM Algorithm. As seen in section 4.3, we could have improved this image quality if we increased the number of iterations. (a) Original image (b) none skipped (c) ½ detectors (d) 1/3 detectors Figure 4.5.1: Reconstructed images (a) original image (b) all detectors(c) ½ detectors (d) 1/3 detectors (e) 1/5 detectors (f) 1/10 detectors 44 (e) 1/5 detectors (f) 1/10 detectors Figure 4.5.1: Reconstructed images (a) original image (b) all detectors (c) ½ detectors (d) 1/3 detectors (e) 1/5 detectors (f) 1/10 detectors continued 4.6 Reconstruction with a faulty detector Faulty detectors are a common scenario in real life which led to rings in the final image making it un-diagnostic. Currently vendors detect these faulty detectors and interpolate the data losing the resolution. In our method, we can modify the system matrix to give a image without losing any resolution. Figure 4.6.1 shows an image reconstructed with a faulty detector. Figure 4.6.2 shows the sinogram of this image. The line at detector number 16 shows that the detector is faulty. We modified our system matrix and the reconstructed image is shown in figure 4.6.3. 45 Figure 4.6.1: Ring artifact in the image due to a faulty detector. Figure 4.6.2: Sinogram which shows that detector 16 is bad. 46 Figure 4.6.3: Image reconstructed using ML-EM Recon Algorithm 47 CHAPTER V CONCLUSION In summary, Medical Imaging provides a non-invasive technique to look at the structural and functional information of internal organs and structures. Measurement of the radioactive distribution throughout the patient gives the physiological and pathophysiological information about the patient. The most widely used mathematical technique to reconstruct this image, using the data acquired, is known as Filtered Back Projection (FBP). The main purpose of this study is to verify whether or not we can reconstruct images with a limited dataset. This method will provide us a better estimate of the exact location of the radioactivity. Traditional reconstruction algorithms like FBP can not reconstruct an image with a limited dataset. We work with the iterative method, ML-EM, by modifying the probability matrix (system matrix). Chi-Square Goodness of Fit test is used to test whether we can reconstruct the image using a limited dataset without any statistical difference. Based on the statistical data shown in section 4.4 we fail to reject the null hypothesis. The modified ML-EM algorithm is a good alternative to the filtered back projection algorithm and can be used successfully to reconstruct images with limited dataset. The real SPECT and PET images are generally of size 512x512. 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