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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
1SPRING 2017
Outline
• Diffusion based Smoothing in Medical Scans
• Intensity inhomogeneity Correction in MRI
2
Linear and Non-Linear Filtering (Smoothing)
3
Linear	approach:
Treat	every	pixel	with	the	exact	same	convolution.
Non-Linear	approach:
Treat	a	pixel	with	varying	intensity,	depending	on	its	
neighborhood	qualities.
4
Possible?
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
5
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
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
– The smoothing process is considered as diffusion
– APPROACH: Increase the diffusivity of filter for large (homogeneous)
regions, and decrease it nearby 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
– APPROACH: Increase the diffusivity of filter for large (homogeneous)
regions, and decrease it nearby edges!
– How can we understand homogenous and edge regions then?
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!
– How can we understand homogenous and edge regions then?
– Edge likelihood (i.e, gradient for instance) can be measured by
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?
– Edge likelihood (i.e, gradient for instance) can be measured by
– Perona-Malik filter is based on
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
– Perona-Malik filter is based on
where it uses diffusivities such as
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
where it uses diffusivities such as
– approximation
12
General Idea on Anisotropic Diffusivity
• if (x,y)	is	a	part	of	an	edge	è apply	little	smoothing
• Else	è apply	full	smoothing
13
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
14
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:
15
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:
16
d=1,… direction
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
Isotropic: Anisotropic:
Toy Example18
Original
Linear	isotropic	diffusion	
(simple	Gaussian)
Toy Example19
Original
Non-linear	anisotropic	
diffusion
20
21
Non-linear Diffusion
Background: BrainWeb
22
WM
GM
CSF
MR Brain simulator
Magnetic Field Inhomogeneity
23
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
MR Intensity Inhomogeneity
• Often hardly
noticeable, but
registration,
segmentation,
and thus
quantification
processes are
significantly
affected from
inhomogeneity
field
24
(credit: R.Gupta)
MR Intensity Inhomogeneity
25
(credit: R.Gupta)
Large
susceptibility
variation in
the human
brain leads to
greater field
inhomogeneity
and therefore
image
distortion.
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
26
Intensity Inhomogeneity Correction Methods
27
Original Image Inhomogeneity Field Corrected Image
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
28
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.
29
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.
30
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%
31
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
32
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
33
Retrospective Approaches
– Only a few assumptions are needed, therefore these approaches are
general.
34
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.
35
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 signalof the imaged
anatomicalstructures by low-pass filtering
36
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 signalof the imaged
anatomicalstructures by low-pass filtering
• log v(x) is input image, CN is normalization constant,u(x) corrected image.
• However,this is true only when imaged anatomicalstructures are
relatively small !!!
37
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 constantCN to preserve mean or median intensity
38
Prospective Approaches-Filtering/Surface Fitting
39
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.
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
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.
– 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 contentof the
distribution of tissue intensity.
41
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.
42
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
43
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
44
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
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.
• 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
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
• Let U,V, and F be the probability densities of
• (approx.) if u and f are uncorrelated random variables, then
47
if u and f are uncorrelated random variables,
the distribution of their sum is found by
convolution!
Nonparametric Non-uniform Intensity
Normalization (N3-Sled, TMI 1998)
1. Use log domain, and prob. densities of u,v, and f.
48
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 )
49
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
50
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
51
The method is based on to maximize the frequency contentof the
image intensity distribution.
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?)
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 )
3. Iterate this process until convergence
How do we guess f ? (F?)
• F is set to be Gaussian field with small variance!
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
How do we guess f ? (F?)
• F is set to be Gaussian field with small variance!
54
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.
ITK Implementation of N3
• itkN3MRIBiasFieldCorrectionImageFilterTest
imageDimension
inputImage
outputImage
[shrinkFactor] [maskImage] [numberOfIterations]
[numberOfFittingLevels] [outputBiasField]
55
Input parameters
opt. parameters
ITK Implementation of N3
• itkN3MRIBiasFieldCorrectionImageFilterTest
imageDimension
inputImage
outputImage
[shrinkFactor] [maskImage] [numberOfIterations]
[numberOfFittingLevels] [outputBiasField]
56
Input parameters
opt. parameters
itkN3MRIBiasFieldCorrectionImageFilterTest
2 t81slice.nii.gz t81corrected.nii.gz
2 t81mask.nii.gz 50 4 t81biasfield.nii.gz
57
(N3 based
method)
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.
58
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
59
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
60
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)
61
Better (Simpler) Method – Standardization
Based Correction (SBC)
Step 0: Set Sc = S, the given scene.
Step 1: Standardize Sc to the standard intensity gray scale
for the particular imaging protocol and body region
under consideration and output scene Ss;
Step 2: determine m tissue regions SB1, SB2, ..., SBm by using
fixed threshold intervals on Ss;
Step 3: if SBi determined in the previous iteration are not
much (<0.1%) different from the current SBi, stop;
Step 4: else, estimate background variation in Ss as a scene
Sbe, compute corrected scene Sc, and go to Step 1;
62
SBC-Intuition
63
Oi Oj x
( )j xβ
( )i xβ
The existence of discontinuity between inhomogeneity maps
(continuous lines) estimated independently from different
tissue regions Oi and Oj.
We need a single combined inhomogeneity map for correcting
the background intensity variation in the whole image.
SBC-Intuition
64
1. Find a weight factor λ to minimize
2. Combine the two inhomogeneity maps β1 and β2 to obtain a
new discrete inhomogeneity map βd(c): C → [0, ∞) such that, for
any c∈C,
3. Determine a 2nd degree polynomial β that constitutes a LSE fit
to βd .
The above steps merge O1 and O2 and are then repeated until we
have only one region and a single unified inhomogeneity map.
( ) ( )
2
1 2 .
c C
c cβ λβ
∈
⎡ ⎤−⎣ ⎦∑
( )
( )
( ) ( )
( )
( )
( ) ( )
( )2 1
1 2
1 2 1 2
, ,
, , , ,
d
c O c O
c c c
c O c O c O c O
δ δ
β β λβ
δ δ δ δ
= +
+ +
65
Original Corrected
Standardization Based Correction (SBC)
Method
66
Iteration 1 3 5 10 20
GM
WM
SBC Method
67
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.
SBC Method-Comparison
68
Original N3 (Sled et al.) SBC
A slice of T1-weightedbrain MR image. SBC shows some
improvement over N3 particularly as seen in the histogram.
SBC Method-Comparison
69
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.
SBC Method-Comparison
70
Original N3 (Sled et al.) SBC
Brainweb T2-weightedMR image. SBC shows some
improvement over N3 particularly as seen in the histogram.
Coefficient of Variation as a quantitative
evaluation metric
• CV (coefficient of variation)?
71
Coefficient of Variation as a quantitative
evaluation metric
• CV (coefficient of variation):
72
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)
73
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!
74
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)
75
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)
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)
• 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)
– …
77
SBC Method Quantitative Comparison
78
%cv (GM) %cv (WM)
Set Modality Inhomo. Original N3 SBC Original N3 SBC
Normal
T1 20%
40%
11.0
13.5
9.9
10.0
9.9
9.9
6.7
9.2
5.1
5.2
5.1
5.2
T2 20%
40%
18.4
20.3
18.0
20.0
17.9
17.9
12.0
13.3
11.8
13.0
11.7
11.8
PD 20%
40%
6.3
9.7
4.6
4.6
4.5
4.5
5.5
7.5
4.7
4.6
4.7
4.6
Ms
Lesions
T1 20%
40%
11.2
13.7
10.1
10.2
10.1
10.1
6.9
9.3
5.3
5.3
5.3
5.4
T2 20%
40%
10.9
13.7
10.0
10.1
9.8
9.8
8.7
10.6
8.3
8.2
8.1
8.2
PD 20%
40%
5.8
9.4
3.9
4.9
3.8
3.9
5.3
7.4
4.4
4.3
4.3
4.3
% cv of tissue intensitiesin segmented GM and WM
regions for twelve simulated MRI scenes from
Brainwebbefore and after correction by N3 SBC.
SBC Method Quantitative Comparison
79
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.
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)
80

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Lec4: Pre-Processing Medical Images (II)

  • 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 1SPRING 2017
  • 2. Outline • Diffusion based Smoothing in Medical Scans • Intensity inhomogeneity Correction in MRI 2
  • 3. Linear and Non-Linear Filtering (Smoothing) 3 Linear approach: Treat every pixel with the exact same convolution. Non-Linear approach: Treat a pixel with varying intensity, depending on its neighborhood qualities.
  • 5. 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 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 – The smoothing process is considered as diffusion 6
  • 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 – APPROACH: Increase the diffusivity of filter for large (homogeneous) regions, and decrease it nearby edges! 7
  • 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! – How can we understand homogenous and edge regions then? 8
  • 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? – Edge likelihood (i.e, gradient for instance) can be measured by 9
  • 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 – Perona-Malik filter is based on 10
  • 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 where it uses diffusivities such as 11
  • 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 – approximation 12
  • 13. General Idea on Anisotropic Diffusivity • if (x,y) is a part of an edge è apply little smoothing • Else è apply full smoothing 13
  • 14. 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 14
  • 15. 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: 15
  • 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: 16 d=1,… direction
  • 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: 17 Isotropic: Anisotropic:
  • 20. 20
  • 23. Magnetic Field Inhomogeneity 23 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
  • 24. MR Intensity Inhomogeneity • Often hardly noticeable, but registration, segmentation, and thus quantification processes are significantly affected from inhomogeneity field 24 (credit: R.Gupta)
  • 25. MR Intensity Inhomogeneity 25 (credit: R.Gupta) Large susceptibility variation in the human brain leads to greater field inhomogeneity and therefore image distortion.
  • 26. 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 26
  • 27. Intensity Inhomogeneity Correction Methods 27 Original Image Inhomogeneity Field Corrected Image
  • 28. 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 28
  • 29. 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. 29
  • 30. 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. 30
  • 31. 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% 31
  • 32. 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 32
  • 33. 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 33
  • 34. Retrospective Approaches – Only a few assumptions are needed, therefore these approaches are general. 34
  • 35. 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. 35
  • 36. 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 signalof the imaged anatomicalstructures by low-pass filtering 36
  • 37. 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 signalof the imaged anatomicalstructures by low-pass filtering • log v(x) is input image, CN is normalization constant,u(x) corrected image. • However,this is true only when imaged anatomicalstructures are relatively small !!! 37
  • 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. – 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 constantCN to preserve mean or median intensity 38
  • 39. Prospective Approaches-Filtering/Surface Fitting 39 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.
  • 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. – 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 40
  • 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. – 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 contentof the distribution of tissue intensity. 41
  • 42. 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. 42
  • 43. 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 43
  • 44. 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 44
  • 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. • For a noise-free case, to estimate f requires some math. tricks such as • Let U,V, and F be the probability densities of 45
  • 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 • Let U,V, and F be the probability densities of • (approx.) if u and f are uncorrelated random variables, then 46
  • 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 • Let U,V, and F be the probability densities of • (approx.) if u and f are uncorrelated random variables, then 47 if u and f are uncorrelated random variables, the distribution of their sum is found by convolution!
  • 48. Nonparametric Non-uniform Intensity Normalization (N3-Sled, TMI 1998) 1. Use log domain, and prob. densities of u,v, and f. 48
  • 49. 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 ) 49
  • 50. 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 50
  • 51. 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 51 The method is based on to maximize the frequency contentof the image intensity distribution.
  • 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 ) 3. Iterate this process until convergence How do we guess f ? (F?) 52
  • 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 How do we guess f ? (F?) • F is set to be Gaussian field with small variance! 53
  • 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 How do we guess f ? (F?) • F is set to be Gaussian field with small variance! 54 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.
  • 55. ITK Implementation of N3 • itkN3MRIBiasFieldCorrectionImageFilterTest imageDimension inputImage outputImage [shrinkFactor] [maskImage] [numberOfIterations] [numberOfFittingLevels] [outputBiasField] 55 Input parameters opt. parameters
  • 56. ITK Implementation of N3 • itkN3MRIBiasFieldCorrectionImageFilterTest imageDimension inputImage outputImage [shrinkFactor] [maskImage] [numberOfIterations] [numberOfFittingLevels] [outputBiasField] 56 Input parameters opt. parameters itkN3MRIBiasFieldCorrectionImageFilterTest 2 t81slice.nii.gz t81corrected.nii.gz 2 t81mask.nii.gz 50 4 t81biasfield.nii.gz
  • 58. 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. 58
  • 59. 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 59
  • 60. 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 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. • 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) 61
  • 62. Better (Simpler) Method – Standardization Based Correction (SBC) Step 0: Set Sc = S, the given scene. Step 1: Standardize Sc to the standard intensity gray scale for the particular imaging protocol and body region under consideration and output scene Ss; Step 2: determine m tissue regions SB1, SB2, ..., SBm by using fixed threshold intervals on Ss; Step 3: if SBi determined in the previous iteration are not much (<0.1%) different from the current SBi, stop; Step 4: else, estimate background variation in Ss as a scene Sbe, compute corrected scene Sc, and go to Step 1; 62
  • 63. SBC-Intuition 63 Oi Oj x ( )j xβ ( )i xβ The existence of discontinuity between inhomogeneity maps (continuous lines) estimated independently from different tissue regions Oi and Oj. We need a single combined inhomogeneity map for correcting the background intensity variation in the whole image.
  • 64. SBC-Intuition 64 1. Find a weight factor λ to minimize 2. Combine the two inhomogeneity maps β1 and β2 to obtain a new discrete inhomogeneity map βd(c): C → [0, ∞) such that, for any c∈C, 3. Determine a 2nd degree polynomial β that constitutes a LSE fit to βd . The above steps merge O1 and O2 and are then repeated until we have only one region and a single unified inhomogeneity map. ( ) ( ) 2 1 2 . c C c cβ λβ ∈ ⎡ ⎤−⎣ ⎦∑ ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( )2 1 1 2 1 2 1 2 , , , , , , d c O c O c c c c O c O c O c O δ δ β β λβ δ δ δ δ = + + +
  • 66. Standardization Based Correction (SBC) Method 66 Iteration 1 3 5 10 20 GM WM
  • 67. SBC Method 67 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.
  • 68. SBC Method-Comparison 68 Original N3 (Sled et al.) SBC A slice of T1-weightedbrain MR image. SBC shows some improvement over N3 particularly as seen in the histogram.
  • 69. SBC Method-Comparison 69 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.
  • 70. SBC Method-Comparison 70 Original N3 (Sled et al.) SBC Brainweb T2-weightedMR image. SBC shows some improvement over N3 particularly as seen in the histogram.
  • 71. Coefficient of Variation as a quantitative evaluation metric • CV (coefficient of variation)? 71
  • 72. Coefficient of Variation as a quantitative evaluation metric • CV (coefficient of variation): 72
  • 73. 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) 73
  • 74. 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! 74
  • 75. 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) 75
  • 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) • 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) 76
  • 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! – 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) – … 77
  • 78. SBC Method Quantitative Comparison 78 %cv (GM) %cv (WM) Set Modality Inhomo. Original N3 SBC Original N3 SBC Normal T1 20% 40% 11.0 13.5 9.9 10.0 9.9 9.9 6.7 9.2 5.1 5.2 5.1 5.2 T2 20% 40% 18.4 20.3 18.0 20.0 17.9 17.9 12.0 13.3 11.8 13.0 11.7 11.8 PD 20% 40% 6.3 9.7 4.6 4.6 4.5 4.5 5.5 7.5 4.7 4.6 4.7 4.6 Ms Lesions T1 20% 40% 11.2 13.7 10.1 10.2 10.1 10.1 6.9 9.3 5.3 5.3 5.3 5.4 T2 20% 40% 10.9 13.7 10.0 10.1 9.8 9.8 8.7 10.6 8.3 8.2 8.1 8.2 PD 20% 40% 5.8 9.4 3.9 4.9 3.8 3.9 5.3 7.4 4.4 4.3 4.3 4.3 % cv of tissue intensitiesin segmented GM and WM regions for twelve simulated MRI scenes from Brainwebbefore and after correction by N3 SBC.
  • 79. SBC Method Quantitative Comparison 79 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.
  • 80. 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) 80