Introduction Diffusion Tensor Imaging Diffusion Tensor and Diffusion Kurtosis Tensor in Biomedical Engineering by Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 1 of 24 L IQUN Q I Go Back Full Screen Department of Applied Mathematics The Hong Kong Polytechnic University Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Outline Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Introduction Diffusion Tensor Imaging Home Page Title Page Diffusion Kurtosis Imaging JJ II J I Page 2 of 24 D-Eigenvalues and Other Invariants Go Back Full Screen Further Discussion Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 1. Introduction Introduction This talk was first given for Gene on November 1, 2007, when he visited me, accompanied by Michael Ng. He enjoyed this talk very much and brought a copy of this talk. He even asked several references, and I promised to send him later. It was totally unexpected that he departed only after 15 days. I was totally shocked by the sad news. I updated this talk, and present it now to memorize Gene. Diffusion Kurtosis Imaging Diffusion Tensor Imaging One year ago, in February of 2007, at the Chinese New Year time, I received an e-mail from a Hong Kong University second year biomedical engineering student. He asked questions about my paper: [1]. L. Qi, “Eigenvalues of a real supersymmetric tensor”, Journal of Symbolic Computation 40 (2005) 1302-1324. This surprised me. Why a second year biomedical engineering student would be interested in my mathematical paper on eigenvalues of higher order tensors? Eventually, started from the responses to that e-mail, I established research collaboration with that student’s supervisor, Professor Ed Xuekui Wu, Associate Professor, Director of Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong. D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 3 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 1.1. Introduction Collaboration with Ed X. Wu Diffusion Tensor Imaging Since then, we have written four papers together. The first paper in this collaboration has already been accepted for publication: Diffusion Kurtosis Imaging [2]. L. Qi, Y. Wang and E.X. Wu, “D-eigenvalues of diffusion kurtosis tensors”, to appear in: Journal of Computational and Applied Mathematics. Further Discussion [3]. L. Qi, D. Han and E.X. Wu, “Principal invariants and inherent parameters of diffusion kurtosis tensors”, Manuscript, Department of Applied Mathematics, The Hong Kong Polytechnic University, May 2007. [4]. D. Han, L. Qi and E.X. Wu, “Extreme diffusion values for non-Gaussian diffusions”, Manuscript, Department of Applied Mathematics, The Hong Kong Polytechnic University, August 2007. [5]. E.X. Wu, E.S. Hui, M.M. Cheung and L. Qi, “Towards better MR characterization of Neural tissues using directional diffusion kurtosis analysis”, Manuscript, Laboratory of Biomedical Imaging and Signal Processing, The Hong Kong University, January, 2008. Here, Matthew M. Cheung is the second year biomedical engineering student, who sent me e-mails one year ago. D-Eigenvalues and . . . Home Page Title Page JJ II J I Page 4 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . 2. Diffusion Tensor Imaging Further Discussion Diffusion magnetic resonance imaging (D-MRI) has been developed in biomedical engineering for decades. It measures the apparent diffusivity of water molecules in human or animal tissues, such as brain and blood, to acquire biological and clinical information. In tissues, such as brain gray matter, where the measured apparent diffusivity is largely independent of the orientation of the tissue (i.e., isotropic), it is usually sufficient to characterize the diffusion characteristics with a single (scalar) apparent diffusion coefficient (ADC). However, in anisotropic media, such as skeletal and cardiac muscle and in white matter, where the measured diffusivity is known to depend upon the orientation of the tissue, no single ADC can characterize the orientation-dependent water mobility in these tissues. Because of this, a diffusion tensor model was proposed years ago to replace the diffusion scalar model. This resulted in diffusion tensor imaging (DTI). Home Page Title Page JJ II J I Page 5 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 2.1. Diffusion Tensor Introduction Diffusion Tensor Imaging A diffusion tensor D is a second order three dimensional fully symmetric tensor. Under a Cartesian laboratory co-ordinate system, it is represented by a real three dimensional symmetric matrix, which has six independent elements D = (dij ) with dij = dji for i, j = 1, 2, 3. There is a relationship ln[S(b)] = ln[S(0)] − 3 X bdij xi xj . (1) Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page i,j=1 Title Page Here S(b) is the signal intensity P3 at2 the echo time, x = (x1 , x2 , x3 ) is the unit direction vector, satisfying i=1 xi = 1, the parameter b is given by δ b = (γδg)2 (∆ − ), 3 JJ II J I Page 6 of 24 γ is the proton gyromagnetic ratio, ∆ is the separation time of the two diffusion gradients, δ is the duration of each gradient lobe. See Figure 1 on the next page. There are six unknown variables dij in the formula (1). By applying the magnetic gradients in six or more non-collinear, non-coplaner directions, one can solve (1) and get the six independent elements dij . Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 7 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 2.2. Eigenvalues of Diffusion Tensor However, such elements dij cannot be directly used for biological or clinical analysis, as they vary under different laboratory coordinate systems. Thus, after obtaining the values of these six independent elements by MRI techniques, the biomedical engineering researchers will further calculate some characteristic quantities of this diffusion tensor D. These characteristic quantities are rotationally invariant, independent from the choice of the laboratory coordinate system. They include the three eigenvalues λ1 ≥ λ2 ≥ λ3 of D, the mean diffusivity (MD ), the fractional anisotropy (F A), etc. The largest eigenvalue λ1 describes the diffusion coefficient in the direction parallel to the fibres in the human tissue. The other two eigenvalues describe the diffusion coefficient in the direction perpendicular to the fibres in the human tissue. The mean diffusivity is λ1 + λ 2 + λ 3 MD = , 3 Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 8 of 24 while the fractional anisotropy is r s 3 (λ1 − MD )2 + (λ2 − MD )2 + (λ3 − MD )2 FA = , 2 λ21 + λ22 + λ23 Go Back Full Screen Close Quit where 0 ≤ F A ≤ 1. If F A = 0, the diffusion is isotropic. If F A = 1, the diffusion is anisotropic. •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 2.3. Diffusion Tensor Imaging Introduction The diffusion tensor imaging model (DTI) is now used widely in biological and clinical research. There are many papers on DTI in biomedical engineering journals, in particular, MRI journals. Even in the Mainland China, there are a number of papers on DTI in Chinese. Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion A review paper on the technique of DTI is: [6]. P.J. Basser and D.K. Jones, “Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review”, NMR in Biomedicine 15 (2002) 456-467. Home Page Title Page A paper on the DTI technique in Chinese is: JJ II [7]. D. Li, S. Bao, C. Zhu and L. Ma, “Computing the measures of DTI based on PC and Matlab”, Chinese Journal of Medical Imaging Technology 20 (2004) 90-94. (in Chinese) J I Page 9 of 24 Go Back A figure from their paper is on the next page. Paper Full Screen [8]. W. Chong and J. Zhao, “Role of diffuse tensor imaging”, Chinese Journal of CT and MRI 13 (2005) 49-51, (in Chinese) Close Quit reported eight brain and spinal diseases detectable by the DTI methods. •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 10 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction 3. Diffusion Kurtosis Imaging Diffusion Tensor Imaging Diffusion Kurtosis Imaging However, DTI is known to have a limited capability in resolving multiple fibre orientations within one voxel. This is mainly because the probability density function for random spin displacement is non-Gaussian in the confining environment of biological tissues and, thus, the modeling of self-diffusion by a second order tensor breaks down. Recently, a new MRI model is presented by [9]. J.H. Jensen, J.A. Helpern, A. Ramani, H. Lu and K. Kaczynski, “Diffusional kurtosis imaging: The quantification of non-Gaussian water diffusion by means of magnetic resonance imaging”, Magnetic Resonance in Medicine 53 (2005) 1432-1440; [10]. H. Lu, J.H. Jensen, A. Ramani and J.A. Helpern, “Three-dimensional characterization of non-Gaussian water diffusion in humans using diffusion kurtosis imaging”, NMR in Biomedicine 19 (2006) 236-247. They propose to use a fourth order three dimensional fully symmetric tensor, called the diffusion kurtosis (DK) tensor, to describe the non-Gaussian behavior. The values of the fifteen independent elements of the DK tensor W can be obtained by the MRI technique. The diffusion kurtosis imaging (DKI) has important biological and clinical significance. D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 11 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging 3.1. Diffusion Kurtosis Tensor D-Eigenvalues and . . . A diffusion kurtosis tensor W is a fourth order three dimensional fully symmetric tensor. Under a Cartesian laboratory co-ordinate system, it is represented by a real fourth order three dimensional fully symmetric array, which has fifteen independent elements W = (wijkl ) with wijkl being invariant for any permutation of its indices i, j, k, l = 1, 2, 3. The relationship (1) can be further expanded (adding a second Taylor expansion term on b) to: ln[S(b)] = ln[S(0)] − 3 X 1 bdij xi xj + b2 MD2 6 i,j=1 3 X wijkl xi xj xk xl . (2) i,j,k,l=1 There are fifteen unknown variables wijkl in the formula (2). By applying the magnetic gradients in fifteen or more non-collinear, non-coplaner directions, one can solve (2) and get the fifteen independent elements wijkl . Further Discussion Home Page Title Page JJ II J I Page 12 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion 3.2. Diffusion Kurtosis Imaging The diffusion kurtosis imaging (DKI) has important biological and clinical significance. The authors of [9] found sharp differences between the diffusion kurtosis in white and gray matters. They believe that DKI is potentially of value for the assessment of neurologic diseases, such as multiple sclerosis and epilepsy, with associated white matter abnormalities. Additional, DKI may be useful for investigating abnormalities in tissues with isotropic structures, such as gray matter, where techniques like diffusion tensor imaging (DTI) are less applicable. Home Page Title Page JJ II J I Page 13 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion 4. D-Eigenvalues and Other Invariants Again, the fifteen elements wijkl vary when the laboratory co-ordinate system is rotated. What are the coordinate system independent characteristic quantities of the DK tensor W ? Are there some type of eigenvalues of W , which can play a role here? E.X. Wu is a friend of J.H. Jensen, the main author of [9] and [10]. He and his group studied these questions. They searched by google possible papers on eigenvalues of higher order tensors. They found my paper [1]. This resulted in the surprising e-mail to me in February, 2007. In [2-5], we answered these questions. Home Page Title Page JJ II J I Page 14 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 4.1. The Apparent Kurtosis Coefficient In [2], we use x = (x1 , x2 , x3 )T to denote the direction vector. Then the apparent diffusion coefficient (ADC) Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging 2 Dapp = Dx ≡ 3 X D-Eigenvalues and . . . dij xi xj . Further Discussion i,j=1 A key formula for the DK tensor W is as follows: Kapp MD2 = 2 W x4 , Dapp Home Page (3) Title Page where Kapp is the apparent kurtosis coefficient at the direction x, and W x4 ≡ 3 X wijkl xi xj xk xl . JJ II J I Page 15 of 24 i,j,k,l=1 Go Back Note that D and W are fully symmetric. Furthermore, D is positive definite. It is easy to see that maximizing (minimizing) Kapp is equivalent to the following maximization (minimization) problem: Full Screen Close Quit 4 max W x s.t. Dx2 = 1. (4) •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging 4.2. D-Eigenvalues of The Diffusion Kurtosis Tensor Diffusion Kurtosis Imaging Obviously, the critical points of problem (4) satisfy the following equation for some λ ∈ <: W x3 = λDx, (5) Dx2 = 1. A real number λ satisfying (5) with a real vector x is called a D-eigenvalue of W , and the real vector x is called a D-eigenvector of W associated with the D-eigenvalue λ. Theorem 4.1 D-eigenvalues always exist. They are invariant under co-ordinate rotations. If x is a D-eigenvector associated with a D-eigenvalue λ, then λ = W x4 . D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 16 of 24 (6) Go Back MD2 λmax , The largest AKC value is equal to and the smallest AKC value is equal 2 to MD λmin , where λmax and λmin are the largest and the smallest D-eigenvalues of W respectively. Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging 4.3. Diffusion Kurtosis Imaging Computation of D-Eigenvalues D-Eigenvalues and . . . In [2], we presented a direct method to find all the D-eigenvalues and their corresponding D-eigenvectors. The key idea there is to reduce the four variable polynomial system (5) to a polynomial system of two variables u and v. Then regard it as a system of two polynomial equations of one variable u, whose coefficients are polynomials of v. It has complex solutions for u if and only if its resultant vanishes. By the Sylvester theorem, for this problem, its resultant is equal to the determinant of a 7 × 7 matrix, which is a one-dimensional polynomial of v. To find the approximate solutions of all the real roots of a one-dimensional polynomial to any given error tolerance, we can use the Sturm Theorem. We then substitute them back to find the corresponding approximate real solutions of u. Correspondingly, approximate values of all the D-eigenvalue and their Deigenvectors can be obtained. Further Discussion Home Page Title Page JJ II J I Page 17 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 4.4. Introduction A Numerical Example Diffusion Tensor Imaging This example is derived from data of MRI experiments on rat spinal cord specimen fixed in formalin. The MRI experiments were conducted on a 7 Tesla MRI scanner at Laboratory of Biomedical Imaging and Signal Processing at The University of Hong Kong. This example is taken from the white matter. The six elements of the diffusion tensor D are d11 = 0.1755, d12 = 0.0035, d13 = 0.0132, d22 = 0.1390, d23 = 0.0017, d33 = 0.4006 in unit of 10−3 square mm per second, and the fifteen independent elements of the diffusion kurtosis tensor W are w1111 = 0.4982, w2222 = 0, w3333 = 2.6311, w1112 = −0.0582, w1113 = −1.1719, w1222 = 0.4880, w2223 = −0.6162, w1333 = 0.7639, w2333 = 0.7631, w1122 = 0.2236, w1133 = 0.4597, w2233 = 0.1519, w1123 = −0.0171, w1223 = 0.1852 and w1233 = −0.4087, respectively. It is easy to find that 2 d + d + d 11 22 33 MD2 = = 5.6813 × 10−8 . 3 Diffusion Kurtosis Imaging Using the method provided in [2], we compute all the D-eigenvalues of W , and the associated D-eigenvectors, which are listed on the next page. Close D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 18 of 24 Go Back Full Screen Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit 4.5. D-eigenvalues and eigenvectors of W Introduction (1) λ1 = 3.8340 × 10−7 , x(1) = (−26.6953, −76.0271, 13.2301)T , Kapp = 2.1782. −7 λ2 = 2.4323 × 10 , x (2) = (8.3561, −69.1354, 28.6108) (2) , Kapp T Diffusion Tensor Imaging Diffusion Kurtosis Imaging = 1.3819. D-Eigenvalues and . . . (3) λ3 = 0.6773 × 10−7 , x(3) = (58.9844, −42.6590, 17.9274)T , Kapp = 0.3848. Further Discussion (4) λ4 = 3.8173 × 10−7 , x(4) = (−62.4736, −35.3967, 20.0392)T , Kapp = 2.1687. (5) λ5 = 2.4900 × 10−7 , x(5) = (29.1437, −52.2572, 33.9600)T , Kapp = 1.4146. −7 λ6 = 1.0247 × 10 , x (6) = (34.8925, 49.2278, 31.7172) −7 λ7 = −0.0738 × 10 , x −0.0419. (7) T (6) , Kapp Home Page = 0.5822. = (−21.9794, −31.4925, 44.7823) T (7) , Kapp Title Page = (8) λ8 = 2.0092 × 10−7 , x(8) = (24.4491, −12.3897, 46.0146)T , Kapp = 1.1415. −7 λ9 = 2.0563 × 10 , x (9) = (−12.2897, 23.6850, 47.6412) −7 (10) −7 (11) λ10 = 5.3545 × 10 , x (9) , Kapp T = (−66.1780, 11.3946, 25.5877) T JJ II J I Page 19 of 24 = 1.1682. (10) , Kapp Go Back = 3.0420. Full Screen λ11 = 2.2194 × 10 , x −7 λ12 = −1.2420 × 10 , x = (11.5201, 18.0765, 47.7258) (12) T = (65.6942, 7.1795, 21.9765) −7 (11) , Kapp = 1.2609. (12) , Kapp = −0.7056. T Close Quit −7 We see that λmin = −1.2420 × 10 , λmax = 5.3545 × 10 . •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging 4.6. Principal Invariants of the Diffusion Kurtosis Tensor In [3], we presented several principal invariants of the diffusion kurtosis tensors, and their computational formulas. These principal invariants include the largest, the smallest and the average apparent kurtosis coefficients (AKC) values, which are invariant from the co-ordinate system choices, and some parameters measured in the inherent co-ordinate system, which is formed by the eigenvector system of the second order diffusion tensor. We studied their computation formulas and relationships. We made numerical experiments, based upon the magnetic resonance diffusion data acquired out of rat spinal cord samples fixed in formalin. See the figure on the next page. The MRI experiments were conducted on a 7 Tesla MRI scanner at Laboratory of Biomedical Imaging and Signal Processing at The University of Hong Kong, led by E.X. Wu. In [4], we studied properties and formulas of extreme diffusion values of diffusion kurtosis imaging (DKI). D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 20 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion Home Page Title Page JJ II J I Page 21 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging 5. Further Discussion D-Eigenvalues and . . . Further Discussion We see that the diffusion tensor and the diffusion kurtosis tensor are important physical quantities in biomedical engineering. While eigenvalues and invariants of a second order tensor are well studied, the study on eigenvalues and invariants of a fourth order tensor has just started. There are still many things unexplored there. Here, we have the following comments: 1. We plan to put our code for calculating D-eigenvalues, written by Dr. Deren Han, on my website, such that the biomedical engineering researchers can use it. 2. There are some other non-Gaussian models, such as q-space and higher order tensor models in MRI. It will be interesting if we can apply the techniques of [2-4] to them. 3. We may find more than 15 meaningful invariants of W . Apparently, only 15 of them can be independent. Can we identify some independence or dependence relationships among them? Home Page Title Page JJ II J I Page 22 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction 5.1. Diffusion Tensor Imaging Discussion on Invariants Diffusion Kurtosis Imaging D-Eigenvalues and . . . We now know more about invariants: Further Discussion 1. In the literature invariants normally refer to the polynomials in the elements of a tensor invariant under a specific group. Here we discuss about orthogonal group. 2. For a symmetric mth order tensor, there is only one independent linear invariant, when m is even, and no linear invariant, when m is odd. For a fourth order symmetric tensor A, this linear invariant is X X aiiii + 2 aiijj . i=1,··· ,n i,j=1,··· ,n,i6=j Home Page Title Page JJ II J I Page 23 of 24 For n = 3, in [3], we show that this invariant is related with the average value of AKC. 3. A fourth order three dimensional symmetric tensor has 12 independent “basic” invariants. The other invariants can be represented by them. Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit Introduction Diffusion Tensor Imaging Diffusion Kurtosis Imaging D-Eigenvalues and . . . Further Discussion 5.2. Number of D-Eigenvalues Recently, Professor K.C. Chang at Peking University studied eigenvalues of real symmetric tensors with his co-authors: Home Page [11]. K.C. Chang, K. Pearson and T. Zhang, “On eigenvalues of real symmetric tensors”, Preprint, School of Mathematical Science, Peking University, Beijing, China, February 2008. In that paper, Professor Chang and his co-authors unified the definitions of H-eigenvalues, Z-eigenvalues and D-eigenvalues, and show that for a real n-dimensional mth order symmetric tensor, there are at least n H-/Z-/Deigenvalues. Title Page JJ II J I Page 24 of 24 Go Back Full Screen Close Quit •First •Prev •Next •Last •Go Back •Full Screen •Close •Quit
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