MEDICAL IMAGE COMPUTING (CAP 5937) LECTURE 4: Pre-Processing Medical Images (II)

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SPRING 2016 1 MEDICAL IMAGE COMPUTING (CAP 5937) LECTURE 4: Pre-Processing Medical Images (II) Dr. Ulas Bagci HEC 221, Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, FL 32814. bagci@ucf.edu or bagci@crcv.ucf.edu

2 Outline Diffusion based Smoothing in Medical Scans Intensity inhomogeneity Correction in MRI

3 Recap: How to measure for evaluating noise removal algorithms? Simultaneously suppressing noise and retaining high contrast is difficult trade-off game. Filter Operating Characteristic (FOC) curve captures this trade-off. Residual Noise RN: Relative Standard deviation of intensity within pbject region Contrast RC: - object & background mean; - object & background std. FOC is a curve of 1-RC vs 1-RN.

4 Linear and Non-Linear Filtering (Smoothing) Linear approach: Treat every pixel with the exact same convolution. Non-Linear approach: Treat a pixel with varying intensity, depending on its neighborhood qualities.

Possible? 5

6 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges

7 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion

8 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges!

9 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! How can we understand homogenous and edge regions then?

10 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! How can we understand homogenous and edge regions then? Edge likelihood (i.e, gradient for instance) can be measured by

11 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! How can we understand homogenous and edge regions then? Edge likelihood (i.e, gradient for instance) can be measured by Perona-Malik filter is based on

12 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! How can we understand homogenous and edge regions then? Edge likelihood (i.e, gradient for instance) can be measured by Perona-Malik filter is based on where it uses diffusivities such as

13 Perona-Malik (Anisotropic Diffusion) Filtering Perona and Malik propose a nonlinear diffusion method for avoiding the blurring and localization problems of linear diffusion filtering [PAMI 1990]. Smooth the images without removing significant parts of the edges The smoothing process is considered as diffusion APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! How can we understand homogenous and edge regions then? Edge likelihood (i.e, gradient for instance) can be measured by Perona-Malik filter is based on where it uses diffusivities such as approximation

14 General Idea on Anisotropic Diffusivity if (x,y) is a part of an edge è apply little smoothing Else è apply full smoothing

15 General Idea on Anisotropic Diffusivity if (x,y) is a part of an edge è apply little smoothing Else è apply full smoothing Assume, E is edge likelihood (telling you if you are in homogeneous or edge regions) CONTROLLING THE BLURRING (SMOOTHING) or

16 General Idea on Anisotropic Diffusivity if (x,y) is a part of an edge è apply little smoothing Else è apply full smoothing Define general coefficient (c) for diffusivity:

17 General Idea on Anisotropic Diffusivity if (x,y) is a part of an edge è apply little smoothing Else è apply full smoothing Define general coefficient (c) for diffusivity: d=1, direction

18 General Idea on Anisotropic Diffusivity if (x,y) is a part of an edge è apply little smoothing Else è apply full smoothing Define general coefficient (c) for diffusivity: Isotropic: Anisotropic:

Toy Example 19 Original Linear isotropic diffusion (simple Gaussian)

Toy Example 20 Original Non-linear isotropic diffusion (edge skipping)

Toy Example 21 Original Non-linear anisotropic diffusion

22

Non-linear Diffusion 23

24 Background: BrainWeb GM WM CSF MR Brain simulator

25 Magnetic Field Inhomogeneity (bias) Credit: K.Friston

26 Magnetic Field Inhomogeneity Field inhomogeneity is measured in parts per million (ppm) with respect to the external field Different tissues have different magnetic susceptibilities ð distortions in magnetic field distortions are most noticeable near air-tissue interfaces Credit: K.Friston

27 Often hardly noticeable, but registration, segmentation, and thus quantification processes are significantly affected from inhomogeneity field MR Intensity Inhomogeneity (credit: R.Gupta)

28 MR Intensity Inhomogeneity Large susceptibility variation in the human brain leads to greater field inhomogeneity and therefore image distortion. (credit: R.Gupta)

29 Intensity Inhomogeneity Correction Problem: Imperfections in the RF field cause background variations in MR images. Poses challenges in image segmentation and analysis. Goal: To develop a general method for correcting the variations that fulfills: (R1) no need for user help per scene (R2) no need for accurate prior segmentation (R3) no need for prior knowledge of tissue intensity distribution

30 Intensity Inhomogeneity Correction Methods Original Image Inhomogeneity Field Corrected Image

31 Bias Correction Approaches Numerous methods have been published in the last two decades I. Prospective Approaches i. Phantom ii. Multicoil iii. Special sequence II. Retrospective Approaches i. Filtering ii. Surface Fitting (intensity or gradient) iii. Segmentation (ML, MAP, FCM, nonparametric, ) iv. Histogram a. High frequency maximization b. Information amximization c. Histogram matching

32 Prospective Approaches-Phantom Treat intensity corruption as a systematic error of the MRI acquisition process that can either be minimized by acquiring additional images of a uniform phantom, by acquiring additional images with different coils, or by devising special imaging sequences.

33 Prospective Approaches-Phantom Treat intensity corruption as a systematic error of the MRI acquisition process that can either be minimized by acquiring additional images of a uniform phantom, by acquiring additional images with different coils, or by devising special imaging sequences. Oil or water is usually used for phantoms and median filtering is applied for image smoothing.

34 Prospective Approaches-Phantom Treat intensity corruption as a systematic error of the MRI acquisition process that can either be minimized by acquiring additional images of a uniform phantom, by acquiring additional images with different coils, or by devising special imaging sequences. Oil or water is usually used for phantoms and median filtering is applied for image smoothing. Warning: The phantom based approach cannot correct for patient-induced inhomogeneity, which is a major drawback of this approach. The remaining intensity inhomogeneity can be as high as 30%

35 Prospective Approaches-MultiCoil and Special Sequences Volume and Surface coils Volume coil: induce less inhomogeneity, poor SNR Surface coil: induce severe inhomogeneity, good SNR Method: dividing the filtered surface coil image with the body coil image and smoothing the resulting image Disadvantage: prolonged acquisition time

36 Prospective Approaches-MultiCoil and Special Sequences Volume and Surface coils Volume coil: induce less inhomogeneity, poor SNR Surface coil: induce severe inhomogeneity, good SNR Method: dividing the filtered surface coil image with the body coil image and smoothing the resulting image Disadvantage: prolonged acquisition time Sequence design (pulse design) Method: the spatial distribution of the flip angle can be estimated and used to calculate the intensity inhomogeneity. Disadvantage: Hardware design

37 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general.

38 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities.

39 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities. FILTERING: Filtering methods assume that intensity inhomogeneity is a low-frequency artifact that can be separated from the high-frequency signal of the imaged anatomical structures by low-pass filtering

40 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities. FILTERING: Filtering methods assume that intensity inhomogeneity is a low-frequency artifact that can be separated from the high-frequency signal of the imaged anatomical structures by low-pass filtering log v(x) is input image, C N is normalization constant, u(x) corrected image. However, this is true only when imaged anatomical structures are relatively small!!!

41 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities. FILTERING: Homomorphic unsharp masking probably the simplest and one of the most commonly used methods b(x) (bias field) is obtained by low-pass filtering of the input image v(x), divided by the constant C N to preserve mean or median intensity

42 Prospective Approaches-Filtering/Surface Fitting A representative example of a slice from a rat brain. a: Original image. b: after inhomogeneity correction with the phantom based correction algorithm. Credit: Hui et al, JMRI 2010.

43 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities. Segmentation-based approaches: ML (maximum likelihood) or MAP (maximum a posteriori probability) criterion may be used to estimate intensity distribution in MRI FCM (fuzzy c-means) for clustering tissue classes Connectivity criteria is used to enforce smooth labeling

44 Retrospective Approaches Only a few assumptions are needed, therefore these approaches are general. Unlike prospective approaches, these approaches can also correct patient dependent inhomogeneities apart from scanner induced inhomogeneities. Histogram-based approaches: directly on image intensity histograms the inhomogeneity field is slowly varying -> it is natural to assume smooth histogram then! N3 method is widely used, the method is iterative and seeks the smooth multiplicative field that maximizes the high frequency content of the distribution of tissue intensity.

45 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown.

46 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown. For a noise-free case, to estimate f requires some math. tricks such as

47 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown. For a noise-free case, to estimate f requires some math. tricks such as

48 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown. For a noise-free case, to estimate f requires some math. tricks such as Let U,V, and F be the probability densities of

49 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown. For a noise-free case, to estimate f requires some math. tricks such as Let U,V, and F be the probability densities of (approx.) if u and f are uncorrelated random variables, then

50 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) Consider the following model of image formation in MR: if u and f are uncorrelated random variables, where at location x, v is measured signal, u is true signal, n is noise. f (bias field) is unknown. the distribution of their sum is found by For a noise-free case, convolution! to estimate f requires some math. tricks such as Let U,V, and F be the probability densities of (approx.) if u and f are uncorrelated random variables, then

51 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f.

52 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since )

53 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since ) 3. Iterate this process until convergence

54 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since ) 3. Iterate this process until convergence The method is based on to maximize the frequency content of the image intensity distribution.

55 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since ) 3. Iterate this process until convergence How do we guess f? (F?)

56 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since ) 3. Iterate this process until convergence How do we guess f? (F?) F is set to be Gaussian field with small variance!

57 Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 2. Guess a kernel f, and estimate u! (since ) The approach is simply to propose a distribution for U by sharpening the distribution V, and then to estimate a corresponding smooth field F which produces a distribution close to the one proposed. 3. Iterate this process until convergence How do we guess f? (F?) F is set to be Gaussian field with small variance!

58 ITK Implementation of N3 itkn3mribiasfieldcorrectionimagefiltertest imagedimension inputimage outputimage [shrinkfactor] [maskimage] [numberofiterations] [numberoffittinglevels] [outputbiasfield] Input parameters opt. parameters

59 ITK Implementation of N3 itkn3mribiasfieldcorrectionimagefiltertest imagedimension inputimage outputimage [shrinkfactor] [maskimage] [numberofiterations] [numberoffittinglevels] [outputbiasfield] Input parameters opt. parameters itkn3mribiasfieldcorrectionimagefiltertest 2 t81slice.nii.gz t81corrected.nii.gz 2 t81mask.nii.gz 50 4 t81biasfield.nii.gz

(N3 based method) 60

61 Local Histogram Based and Standardization Based Correction Methods Dividing the image into small subvolumes (via fixed thresholding for instance) in which intensity inhomogeneity was supposed to be relatively constant.

62 Local Histogram Based and Standardization Based Correction Methods Dividing the image into small subvolumes (via fixed thresholding for instance) in which intensity inhomogeneity was supposed to be relatively constant. Standard intensity scale is assumed (NEXT LECTURE) Similar intensity values are assigned to similar tissues across different images

63 Local Histogram Based and Standardization Based Correction Methods Dividing the image into small subvolumes (via fixed thresholding for instance) in which intensity inhomogeneity was supposed to be relatively constant. Standard intensity scale is assumed (NEXT LECTURE) Similar intensity values are assigned to similar tissues across different images Local intensity inhomogeneity was estimated by least square fitting of the intensity histogram model to the actual histogram of a subvolume

64 Local Histogram Based and Standardization Based Correction Methods Dividing the image into small subvolumes (via fixed thresholding for instance) in which intensity inhomogeneity was supposed to be relatively constant. Standard intensity scale is assumed (NEXT LECTURE) Similar intensity values are assigned to similar tissues across different images Local intensity inhomogeneity was estimated by least square fitting of the intensity histogram model to the actual histogram of a subvolume The applied histogram model was a finite Gaussian mixture with seven parameters, initialized from the global histogram of the image. (B-splines are used to fit parameters)

65 Better (Simpler) Method Standardization Based Correction (SBC) Step 0: Set S c = S, the given scene. Step 1: Standardize S c to the standard intensity gray scale for the particular imaging protocol and body region under consideration and output scene S s ; Step 2: determine m tissue regions S B1, S B2,..., S Bm by using fixed threshold intervals on S s ; Step 3: if S Bi determined in the previous iteration are not much (<0.1%) different from the current S Bi, stop; Step 4: else, estimate background variation in S s as a scene S be, compute corrected scene S c, and go to Step 1;

66 SBC-Intuition β ( ) j x β i ( x) O i O j x The existence of discontinuity between inhomogeneity maps (continuous lines) estimated independently from different tissue regions O i and O j. We need a single combined inhomogeneity map for correcting the background intensity variation in the whole image.

67 SBC-Intuition 1. Find a weight factor λ to minimize ( c) λβ ( c) 2 β 1 2. 2. Combine the two inhomogeneity maps β 1 and β 2 to obtain a new discrete inhomogeneity map β d (c): C [0, ) such that, for any c C, δ ( co) ( ) ( ) 3. Determine a 2 nd degree polynomial β that constitutes a LSE fit to β d. The above steps merge O 1 and O 2 and are then repeated until we have only one region and a single unified inhomogeneity map. c C δ ( co) ( ) ( ),, βd ( c) = β ( c) + λβ c δ co, δ co, δ co, δ co, 2 1 1 2 1 + 2 1 + 2 ( )

68 Original Corrected

69 Standardization Based Correction (SBC) Method GM WM Iteration 1 3 5 10 20

70 SBC Method Iteration 1 3 5 10 20 The improvement in correction with increasing number of iterations. Examine the two modes corresponding to WM (large mode) and GM.

71 SBC Method-Comparison Original N3 (Sled et al.) SBC A slice of T1-weighted brain MR image. SBC shows some improvement over N3 particularly as seen in the histogram.

72 SBC Method-Comparison Original N3 (Sled et al.) SBC A slice of an abdominal MR image. SBC shows some improvement over N3 particularly as seen in the histogram.

73 SBC Method-Comparison Original N3 (Sled et al.) SBC Brainweb T2-weighted MR image. SBC shows some improvement over N3 particularly as seen in the histogram.

74 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation)?

75 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation):

76 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation): For a given tissue class C, CV shows how much intensity inhomogeneity is introduced (existed)

77 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation): For a given tissue class C, CV shows how much intensity inhomogeneity is introduced (existed) There are some drawbacks in using CV!

78 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation): For a given tissue class C, CV shows how much intensity inhomogeneity is introduced (existed) There are some drawbacks in using CV! Single tissue class is used C, (alternatively Coef. Of Joint Variation can be used)

79 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation): For a given tissue class C, CV shows how much intensity inhomogeneity is introduced (existed) There are some drawbacks in using CV! Single tissue class is used C, (alternatively Coef. Of Joint Variation can be used) Sensitive to brightness of the image (change the mean, not the std)

80 Coefficient of Variation as a quantitative evaluation metric CV (coefficient of variation): For a given tissue class C, CV shows how much intensity inhomogeneity is introduced (existed) There are some drawbacks in using CV! Single tissue class is used C, (alternatively Coef. Of Joint Variation can be used) Sensitive to brightness of the image (change the mean, not the std)

81 SBC Method Quantitative Comparison %cv (GM) %cv (WM) Set Modality Inhomo. Original N3 SBC Original N3 SBC Normal Ms Lesions T1 20% 40% T2 20% 40% PD 20% 40% T1 20% 40% T2 20% 40% PD 20% 40% 11.0 13.5 18.4 20.3 6.3 9.7 11.2 13.7 10.9 13.7 5.8 9.4 9.9 10.0 18.0 20.0 4.6 4.6 10.1 10.2 10.0 10.1 3.9 4.9 9.9 9.9 17.9 17.9 4.5 4.5 10.1 10.1 9.8 9.8 3.8 3.9 6.7 9.2 12.0 13.3 5.5 7.5 6.9 9.3 8.7 10.6 5.3 7.4 5.1 5.2 11.8 13.0 % cv of tissue intensities in segmented GM and WM regions for twelve simulated MRI scenes from Brainweb before and after correction by N3 SBC. 4.7 4.6 5.3 5.3 8.3 8.2 4.4 4.3 5.1 5.2 11.7 11.8 4.7 4.6 5.3 5.4 8.1 8.2 4.3 4.3

82 SBC Method Quantitative Comparison Modality % cv (GM) % cv (WM) Original N3 SBC Original N3 SBC T2 16.7(1.61) 14.9(1.18) 14.7(1.23) 12.9(1.12) 11.5(1.07) 11.2(0.98) PD 7.1(0.32 5.9(0.20) 5.6(0.19) 7.8(0.72) 6.6(0.62) 6.2(0.51) The mean and standard deviation of % cv of tissue intensities in segmented GM and WM regions for ten clinical T2- and PD-weighted MRI scenes of MS patients before and after correction by the N3 and SBC methods. SBC > N3; p < 0.001.

83 References and Slide Credits Jayaram K. Udupa, MIPG of University of Pennsylvania, PA. P. Suetens, Fundamentals of Medical Imaging, Cambridge Univ. Press. N. Bryan, Intro. to the science of medical imaging, Cambridge Univ. Press. N. Agam (toy examples) Next Lecture (Preprocessing of Medical Images III) Intensity Standardization in MR Images PET/SPECT Image Denoising (multiplicative noise)