MARS Imaging: Biomedical 3D spectroscopic X-ray imaging Anthony Butler.
Biomedical Imaging II
description
Transcript of Biomedical Imaging II
BMI II SS06 – Class 5 “DOT Theory” Slide 1
Biomedical Imaging IIBiomedical Imaging II
Class 5 – Diffuse Optical Tomography (DOT). Part 1: Theory
03/06/06
BMI II SS06 – Class 5 “DOT Theory” Slide 2
AcknowledgmentAcknowledgment
Dr. Ronald XuDr. Ronald XuAssistant ProfessorAssistant Professor
Biomedical Engineering CenterBiomedical Engineering CenterOhio State UniversityOhio State University
Columbus, OhioColumbus, Ohio
Slides 11, 14-18, 21 and 22 in this presentation were created by Prof. Xu, and can be found in their original context at the following URL:
http://medimage.bmi.ohio-state.edu/resources/medimage_ws2005_Xu-image_workshop_2.16.05.ppt
BMI II SS06 – Class 5 “DOT Theory” Slide 3
What Are We Measuring?What Are We Measuring?
Input (source): s(rs,Ωs)
Output (measurement): d(rs,Ωs;rd,Ωd)
Constitutive property/ies (contrast): x(ri[,Ωi])
Transfer function: T(ri,Ωi)= T(x(ri[,Ωi]))
BMI II SS06 – Class 5 “DOT Theory” Slide 4
What Are We Measuring?What Are We Measuring?
Input (source): s(rs,Ωs)
Output (measurement): d(rs,Ωs;rd,Ωd)
Constitutive property/ies (contrast): x(ri[,Ωi])
Transfer function: T(ri,Ωi)= T(x(ri[,Ωi])) 0
rdV = (dr)3
BMI II SS06 – Class 5 “DOT Theory” Slide 5
More on Transfer FunctionMore on Transfer Function
• Strictly speaking, is a mathematical operator, not a function
– Maps one function into another function• Familiar examples: d/dx; multiply by x and add 2; ∫dx (i.e., indefinite integral)
– Different from a function (maps a number into another number) or a functional (maps a function into a number)
• Strictly speaking, a –function is actually a functional.
• T{s} d
– If medium is linear, then:
• i.e., overall effect of entire volume of material on the input is the summation of each volume element’s individual effects
– Nonlinearity makes problem of determining x(r) far more difficult
– We’re not home free even if medium is linear, given the dependence of T on x.
3, ; , , ,i i
s s d d i i s sd T r s d d rr Ω
r Ω r Ω r Ω
BMI II SS06 – Class 5 “DOT Theory” Slide 6
When Can We Solve for x(r)?When Can We Solve for x(r)?
• Most tractable case: W is separable
– i.e., T(x) = T0·x, or T(x) = T0·f(x).
• Also sometimes doable: W is not separable, but can be treated as if it were, for the purpose of computing a successive approximation sequence:
– T0 x1 T1 x2 T2 x3 ...
• In retrospect, it is easy to see why some types of medical imaging were successfully developed long before others, and why some produce higher–resolution images than others.
BMI II SS06 – Class 5 “DOT Theory” Slide 7
x–ray CT — Tractable or Not?x–ray CT — Tractable or Not?
Because we exclude the scattered photon component from the detectors, we have T0 = –functions, and f(x) = f(μ) = e -μ
BMI II SS06 – Class 5 “DOT Theory” Slide 8
Nuclear Imaging — Tractable or Not?Nuclear Imaging — Tractable or Not?
Besides collimation, we also have to deal with the attenuation phenomenon, which makes the problem non–separable
Successive approximation strategies have been employed with some success.
BMI II SS06 – Class 5 “DOT Theory” Slide 9
Ultrasound CT — Tractable or Not?Ultrasound CT — Tractable or Not?
Successive approximation strategy can be successfully employed when spatial variation of the acoustic impedance is weak.For highly heterogeneous (scattering) media, ultrasound CT may be possible if we can apply either the Born (i.e., negligible variation in ultrasound wave amplitude within scattering objects) or Rytov (i.e., negligible variation in ultrasound wave phase within scattering objects) approximation.
BMI II SS06 – Class 5 “DOT Theory” Slide 10
An Intractable Case An Intractable Case
The light spreads out in all directions from the point of illumination, similar to a droplet of ink in water diffusing away from its initial location.1) Is T strongly (and nonlinearly) dependent on x in this case? 2) What constitutes x?
Object (tissue) is illuminated with near infrared (NIR) light (i.e., wavelengths between 750 nm and 1.2 μm). (What is photon energy?)
BMI II SS06 – Class 5 “DOT Theory” Slide 11
How Photons Interact with Biological Tissue
s s ’
Scattered and reflected
Scattered and absorbed
Scattered and transmitted
a, s
, g
BMI II SS06 – Class 5 “DOT Theory” Slide 12
[From: J. W. Pickering, S. A. Prahl, et al., “Double-integrating-sphere system for measuring the optical properties of tissue,” Applied Optics 32(4), 399-410 (1993).]
Detector
1. Inner surfaces are coated with a bright, white, highly reflective material (very high µs, very low µa)
2. Eventually, all non-absorbed photons are captured by one or another of the detectors
3. An upper limit on the sample material’s µa can
be computed from the difference between incident and detected light levels
Quantitative Assessment of Absorption and Scattering
BMI II SS06 – Class 5 “DOT Theory” Slide 13
Detector
1. Inner surfaces are coated with a dark, matte, highly absorptive material (very high µa, very low µs)
2. Detector receives photons that are not removed from the incident beam, by either absorption or scattering
3. So, measuring the decrease of detected light as the slice thickness increases gives an estimate of the sum µa + µs
Quantitative Assessment of Absorption and Scattering
BMI II SS06 – Class 5 “DOT Theory” Slide 14
Scattering is Caused by Tissue Ultrastructure
(http://omlc.ogi.edu)
BMI II SS06 – Class 5 “DOT Theory” Slide 15
Absorption is Caused by Multiple Chromophores
BMI II SS06 – Class 5 “DOT Theory” Slide 16
In NIR Region, Hb and HbO are Major Sensitive Absorber
extin
ct c
oeff
(cm
-1/m
ol/l
iter)
wavelength (nm)
650 700 750 800 850 900
500
1000
1500
2000
2500
3000
3500
4000- Deoxy-hemoglobin
- Oxy-hemoglobin
1 = 690nm
2 = 830nm
2 1 1 2
1 2 2 1
1 2 2 1
1 2 2 1
Hb
HbO
HbO a HbO a
Hb HbO Hb HbO
Hb a Hb a
Hb HbO Hb HbO
2
[ ] [ ] [ ]
[ ]
[ ]
HbT Hb HbO
HbOSO
HbT
BMI II SS06 – Class 5 “DOT Theory” Slide 17
What Near Infrared Light Can Measure?
• Absorption measurement– Tissue hemoglobin concentration– Tissue oxygen saturation– Cytochrome-c-oxidase concentration– Melanin concentration– Bilirubin, water, glucose, …
• Scattering measurement– Lipid concentration– Cell nucleus size– Cell membrane refractive index change– …
BMI II SS06 – Class 5 “DOT Theory” Slide 18
Why Tissue Oximetry?
• Tissue oxygenation and hemoglobin concentration are sensitive indicators of viability and tissue health.
• Many diseases have specific effects on tissue oxygen and blood supply: stroke, vascular diseases, cancers, …
• Non-invasive, real time, local measurement of tissue O2 and HbT is not commercially available
BMI II SS06 – Class 5 “DOT Theory” Slide 19
Why do we want to know μa?
μa = μa(Hb-oxy) + μa(Hb-deoxy) + μa(H2O) + μa(lipid)
+ μa(cyt-oxidase) + μa(myoglobin) + …
μa(X, λ) = ε(X,λ)∙[X]
Concentration of X (M, mol-L-1)
Molar extinction coefficient(cm-1M-1)
Absorption coefficient of X(cm-1)
BMI II SS06 – Class 5 “DOT Theory” Slide 20
Rule: To get quantitatively accurate chromophore concentrations, the number of distinct wavelengths used for optical imaging must be at least as large as the number of compounds that contribute to the overall μa
μa = μa(Hb-oxy) + μa(Hb-deoxy) + μa(H2O) + μa(lipid)
+ μa(cyt-oxidase) + μa(myoglobin) + …
Why do we want to know μa?
BMI II SS06 – Class 5 “DOT Theory” Slide 21
Why Near Infrared? Pros and Cons Compared with Other Imaging Modalities
• Advantages:– Deep penetration into biological tissue– Non-invasive – Non-radioactive– Real time functional imaging– Portable– Low cost– Tissue physiological parameters – Potential of molecular sensitivity
• Disadvantages:– Low spatial and depth resolution– Hard to quantify
BMI II SS06 – Class 5 “DOT Theory” Slide 22
StO2B, HbtB
StO2T
HbtT
StO2B, HbtB
StO2T
HbtT
Near Infrared Diffuse Optical Imaging: Problem Definition
• Find embedded tissue heterogeneity• By solving:
i
source
o
detector
2 2ln ( , , , )B B T Tot b t b
i
OD f S O H t S O H t
BMI II SS06 – Class 5 “DOT Theory” Slide 23
Theoretical Descriptions of NIR Propagation Through TissueTheoretical Descriptions of NIR Propagation Through Tissue
• Quantum Electrodynamics
• Classical Electrodynamics (Maxwell’s equations)
• Radiation Transport Equation
• Diffusion Equation
– Assumes (among other things) that μs(r) >> μa(r).
4
, ,1, , , , , ,
source streaming absorption and
scattering out
, ,
scattering in
a s
s
tS t t t
c t
f t d
rr r r r r
r r
¶
¶
,1, , ,a
tD t t S t
c t
rr r r r r
¶
¶
BMI II SS06 – Class 5 “DOT Theory” Slide 24
Making the Problem Tractable — Perturbation StrategyMaking the Problem Tractable — Perturbation Strategy
• For a medium of known properties x 0(r) = {μa0(r), D 0(r)}, we can find the
transfer function to any desired degree of accuracy: T(x 0){s} = d 0.– We will refer to the above as our reference medium.
• What if an (unknown) target medium is different from the reference medium by at most a small amount at each spatial location?
– i.e., μa(r) = μa0(r) + Δμa(r), |Δμa(r)| << μa
0(r);
D (r) = D 0(r) + ΔD (r), |ΔD(r)| << D 0(r).
– Δμa(r) = absorption coefficient perturbation, ΔD(r) = diffusion coefficient perturbation
• Then the resulting change in d is approximately a linear function of the coefficient perturbations
– i.e.,
0 0 0 0
0 0 0 0
0 3
, ,
0 3
, ,
,
,
a a
a a
a aD DV
a a DV
a a DD D
d d d d D D d r
d d d W W D d r
W d W d D
¶ ¶ ¶ ¶
¶ ¶ ¶ ¶
BMI II SS06 – Class 5 “DOT Theory” Slide 25
Making the Problem Tractable — Perturbation Strategy IIMaking the Problem Tractable — Perturbation Strategy II
• In practice, medium is divided into a finite number N of pixels (“picture element” – 2D imaging) or voxels (“volume element” – 3D imaging)
• We further assume that each element is sufficiently small that there is negligible spatial variation of μa or D within it.
• Integral in preceding slide becomes a sum:
• Perturbation equations for all source/detector combinations are combined into a system of linear equations, or matrix equation.
0 0 0 0
1
, ,,
a a
Nn n n n
a a Dn
na a n D nD D
d W W D
W d V W d D V¶ ¶ ¶ ¶
BMI II SS06 – Class 5 “DOT Theory” Slide 26
Making the Problem Tractable — Perturbation Strategy IIIMaking the Problem Tractable — Perturbation Strategy III
• Perturbation equations for all source/detector combinations are combined into a system of linear equations, or matrix equation:
aa D
μd W W
D
1
2
11 12 1 11 12 11
21 22 2 21 22 22
1
1 2 1 2 2
a
aN N
a a a D D DNN Naa a a D D D
M M MN M M MNM a a a D D D
N
d W W W W W Wd W W W W W W
Dd W W W W W W D
D
BMI II SS06 – Class 5 “DOT Theory” Slide 27
Many different combinations of μa and μs are consistent with any given non-invasive light intensity measurement
2 4 6 8 10
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1 -7
-6
-5
-4
-3
-2
-1
μs
μa
log10(Intensity)
Dilemma:Dilemma:
BMI II SS06 – Class 5 “DOT Theory” Slide 28
Few spatial distributions of μa and μs are consistent with many nearly simultaneous non-invasive light intensity measurement
(Cavernous hemangioma)
Solution, Part 1:Solution, Part 1:
BMI II SS06 – Class 5 “DOT Theory” Slide 29
Simplify mathematical problem by introducing an additional light-scattering medium into the mix
The problem of deducing the spatial distributions of μa and μs in this medium, from light intensity measure-ments around its border, is very difficult
Figuring out the difference between the spatial distribu-tions of μa and μs in these two media is much easier
-
=
Solution, Part 2:Solution, Part 2:
BMI II SS06 – Class 5 “DOT Theory” Slide 30
As a practical matter, most useful method is to use a spatially homogeneous second medium (i.e., reference medium)
µs = 9 cm-1
µa = 0.05 cm-1
µs = 9 cm-1
µa = 0.07 cm-1
µs = 11 cm-1
µa = 0.05 cm-1
µs = 11 cm-1
µa = 0.07 cm-1
µs = 10 cm-1
µa = 0.06 cm-1
Δµs = -1 cm-1
Δµa = -0.01 cm-1
Δµs = -1 cm-1
Δµa = 0.01 cm-1
Δµs = 1 cm-1
Δµa = -0.01 cm-1
Δµs = 1 cm-1
Δµa = 0.01 cm-1
Solution, Part 2:Solution, Part 2:
BMI II SS06 – Class 5 “DOT Theory” Slide 31
Linear perturbation strategy for image reconstruction
µs = 10 cm-1
µa = 0.06 cm-1
Use a computer simulation (or a homogeneous laboratory phantom) to derive the pattern of light intensity measurements around the reference medium boundary
Additional computer simulations determine the amount by which the detected light intensity will change, in response to a small increase (perturbation) in μa or μs in any volume element (“voxel”)
Solution, Part 3:Solution, Part 3:
BMI II SS06 – Class 5 “DOT Theory” Slide 32
Linear perturbation strategy for image reconstruction
Each of these shades of gray represents a different number. Let’s write them all as a row vector.
Because increasing μa decreases the amount of light that leaves the medium
One number (weight) for each voxel
Solution, Part 3:Solution, Part 3:
BMI II SS06 – Class 5 “DOT Theory” Slide 33
Linear perturbation strategy for image reconstruction
Repeat process just described, for all source-detector combinations.
WEIGHT matrix
Solution, Part 3:Solution, Part 3:
BMI II SS06 – Class 5 “DOT Theory” Slide 34
Measurement perturbation (difference) is directly proportional to interior optical coefficient perturbation. Weight matrix gives us the proportionality.
µs = 9 cm-1
µa = 0.05 cm-1
µs = 9 cm-1
µa = 0.07 cm-1
µs = 11 cm-1
µa = 0.05 cm-1
µs = 11 cm-1
µa = 0.07 cm-1
µs = 10 cm-1
µa = 0.06 cm-1
Δµs = -1 cm-1
Δµa = -0.01 cm-1
Δµs = -1 cm-1
Δµa = 0.01 cm-1
Δµs = 1 cm-1
Δµa = -0.01 cm-1
Δµs = 1 cm-1
Δµa = 0.01 cm-1
R W X
Linear perturbation strategy for image reconstruction
Solution, Part 3:Solution, Part 3:
BMI II SS06 – Class 5 “DOT Theory” Slide 35
Reconstructing image of μa and μs boils down to solving a large system of linear equations.
∆R and W are known, and we solve for the unknown ∆X
Formal mathematical term for this is inverting the weight matrix W.
1 R W X X W R
Solution, Part 3:Solution, Part 3:
Linear perturbation strategy for image reconstruction
BMI II SS06 – Class 5 “DOT Theory” Slide 36
Coping with noise (random error) in clinical measurement data
Linear system solutions are additive:
1 1 11 2 1 2
1 2
W R R W R W R
X X
1 1 1
E
W R W R W
XNoise in data
Noise image
Real-world Issue 1:Real-world Issue 1:
BMI II SS06 – Class 5 “DOT Theory” Slide 37
In practice it can easily happen that E is larger than ∆X.
To suppress the impact of noise, mathematical techniques known as regularization are employed.
Real-world Issue 1:Real-world Issue 1:
Coping with noise (random error) in clinical measurement data
BMI II SS06 – Class 5 “DOT Theory” Slide 38
,
,
, ; , m ns da m n
ax y
Rw s d x y
¶
¶
-1 -110 cm , 0.06 cm
1/ 3 0.0331 cm
s a
s aD
BMI II SS06 – Class 5 “DOT Theory” Slide 39
BMI II SS06 – Class 5 “DOT Theory” Slide 40
BMI II SS06 – Class 5 “DOT Theory” Slide 41
BMI II SS06 – Class 5 “DOT Theory” Slide 42
BMI II SS06 – Class 5 “DOT Theory” Slide 43
BMI II SS06 – Class 5 “DOT Theory” Slide 44
BMI II SS06 – Class 5 “DOT Theory” Slide 45
BMI II SS06 – Class 5 “DOT Theory” Slide 46
BMI II SS06 – Class 5 “DOT Theory” Slide 47
BMI II SS06 – Class 5 “DOT Theory” Slide 48
BMI II SS06 – Class 5 “DOT Theory” Slide 49
BMI II SS06 – Class 5 “DOT Theory” Slide 50
BMI II SS06 – Class 5 “DOT Theory” Slide 51
BMI II SS06 – Class 5 “DOT Theory” Slide 52
BMI II SS06 – Class 5 “DOT Theory” Slide 53
BMI II SS06 – Class 5 “DOT Theory” Slide 54
BMI II SS06 – Class 5 “DOT Theory” Slide 55
BMI II SS06 – Class 5 “DOT Theory” Slide 56
BMI II SS06 – Class 5 “DOT Theory” Slide 57
BMI II SS06 – Class 5 “DOT Theory” Slide 58
BMI II SS06 – Class 5 “DOT Theory” Slide 59
BMI II SS06 – Class 5 “DOT Theory” Slide 60
BMI II SS06 – Class 5 “DOT Theory” Slide 61
BMI II SS06 – Class 5 “DOT Theory” Slide 62
BMI II SS06 – Class 5 “DOT Theory” Slide 63
BMI II SS06 – Class 5 “DOT Theory” Slide 64
BMI II SS06 – Class 5 “DOT Theory” Slide 65
,
,
, ; , m ns dD m n
x y
Rw s d x y
D
¶
¶
, , ,
, , ,
, ; , m n m ns d s d x ys m n
s x y x y s x y
R R Dw s d x y
D
¶ ¶ ¶
¶ ¶ ¶
BMI II SS06 – Class 5 “DOT Theory” Slide 66
BMI II SS06 – Class 5 “DOT Theory” Slide 67
BMI II SS06 – Class 5 “DOT Theory” Slide 68
BMI II SS06 – Class 5 “DOT Theory” Slide 69
BMI II SS06 – Class 5 “DOT Theory” Slide 70
BMI II SS06 – Class 5 “DOT Theory” Slide 71
BMI II SS06 – Class 5 “DOT Theory” Slide 72
BMI II SS06 – Class 5 “DOT Theory” Slide 73
BMI II SS06 – Class 5 “DOT Theory” Slide 74
BMI II SS06 – Class 5 “DOT Theory” Slide 75
BMI II SS06 – Class 5 “DOT Theory” Slide 76
BMI II SS06 – Class 5 “DOT Theory” Slide 77
BMI II SS06 – Class 5 “DOT Theory” Slide 78
BMI II SS06 – Class 5 “DOT Theory” Slide 79
BMI II SS06 – Class 5 “DOT Theory” Slide 80
BMI II SS06 – Class 5 “DOT Theory” Slide 81
BMI II SS06 – Class 5 “DOT Theory” Slide 82
(8 cm)(10.06 cm-1) = 80.48
Physical diameter / thickness
Total attenuation coefficient
Optical diameter / thickness