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Geometric Reconstruction in Bioluminescence Tomography (BLT) Andreas Rieder jointly with Tim Kreutzmann KIT – University of the State of Baden-W¨ urttemberg and National Research Center of the Helmholtz Association FAKULT ¨ AT F ¨ UR MATHEMATIK – INSTITUTF ¨ UR ANGEWANDTE UND NUMERISCHE MATHEMATIK www.kit.edu (Wang et al. ’06)
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  • Geometric Reconstruction inBioluminescence Tomography (BLT)

    Andreas Rieder jointly with Tim Kreutzmann

    KIT – University of the State of Baden-Württemberg andNational Research Center of the Helmholtz Association

    FAKULTÄT FÜR MATHEMATIK – INSTITUT FÜR ANGEWANDTE UND NUMERISCHE MATHEMATIK

    www.kit.edu

    (Wang et al. ’06)

  • Overview

    2 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Mathematical model

    Inverse problem: formulation & uniqueness

    Inverse problem: reformulation & stabilization

    Gradient of the minimization functional

    Numerical experiments in 2D

    Summary

  • Mathematical model

    ⊲Mathematicalmodel

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    Gradient of the mini-mization functional

    Numerical experi-ments in 2D

    Summary

    3 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • The (stationary) radiative transfer equation (RTE)(Boltzmann transport equation)

    4 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Let u(x, θ) be the photon flux (radiance) in direction θ ∈ S2 about x ∈ Ω ⊂R

    3. Then,

    θ · ∇u(x, θ) + µ(x)u(x, θ) = µs(x)

    S2

    η(θ · θ′)u(x, θ′)dθ′ + q(x, θ)

    u(x, θ) = g−(x, θ), x ∈ ∂Ω, n(x) · θ ≤ 0

    g(x) =1

    S2

    n(x) · θu(x, θ)dθ, x ∈ ∂Ω

    where µ = µs + µa and

    µs / µa scattering/absorption coefficients

    η scattering kernel (∫S2

    η(θ · θ′)dθ′ = 1)

    q source term

    µs = 0: RTE yields integral eqs. of transmission and emission tomography(F. Natterer & F. Wübbeling, Math. Methods in Image Reconstr., SIAM, ’01)

  • Diffusion approximation: setting

    5 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Assume thatu(x, θ) = u0(x) + 3θ · u1(x)

    where

    u0(x) =1

    S2

    u(x, θ)dθ ∈ R and u1(x) =1

    S2

    θu(x, θ)dθ ∈ R3.

    By the Funk-Hecke theorem,∫

    S2

    θη(θ · θ′)dθ = η θ′

    where η =∫

    S2

    θ′ · θ η(θ · θ′)dθ is the scattering anisotropy.

  • Diffusion approximation: derivation

    6 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Integrate RTE over S2,multiply RTE by θ, integrate again, andassume g−(x, θ) = g−(x).

    Then,

    −∇ · (D∇u0) + µau0 = q0 :=1

    S2

    q(·, θ)dθ,

    u0 + 2D∂nu0 = g− on ∂Ω,

    D∂nu0 = −g on ∂Ω,

    whereD =

    1

    3(µ − ηµs)

    is the diffusion coefficient (reduced scattering coefficient).

  • Diffusion approximation: final equation

    7 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Change of notation: u = u0, q = q0, µ = µa, and g = −g.

    The photon density u obeys the BVP

    −∇ · (D∇u) + µu = q in Ω,

    u + 2D∂nu = g− on ∂Ω.

    The measurements are given by

    D∂nu = g on ∂Ω.

    Assume g− = 0 (no photons penetrate the object from outside).

  • Inverse problem: formulation & uniqueness

    Mathematical model

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    Gradient of the mini-mization functional

    Numerical experi-ments in 2D

    Summary

    8 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • Inverse problem of BLT (in the diffusive regime)

    9 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Define the (linear) forward operator

    A : L2(Ω) → H−12 (∂Ω),

    q 7→ D∂nu ,

    where u solves the BVP with g− = 0:

    −∇ · (D∇u) + µu = q in Ω,

    u + 2D∂nu = 0 on ∂Ω.

    BLT Problem : Given g ∈ R(A), find a source q ∈ L2(Ω) satisfying

    Aq = g.

  • Null Space of A

    10 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Lemma (Wang, Li & Jiang ’04, Kreutzmann ’13):There is an isomorphism Φ: H1(Ω) → H1(Ω)′ such that

    N(A) = Φ(H10 (Ω)

    )∩ L2(Ω).

    If D ∈ W 1,∞ then

    N(A) = Φ(H10 (Ω) ∩ H

    2(Ω)).

    Proof: Define

    Φ: H1(Ω) → H1(Ω)′, u 7→ (Φu)(v) = a(u, v)

    where

    a(u, v) =

    (D∇u · ∇v + µuv

    )dx +

    1

    2

    ∂Ωuv ds.

  • Singular Functions of A : L2(Ω0) → L2(∂Ω)

    11 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    H LL

    M

    B

    −8 −6 −4

    −5

    0

    5

    σ1 = 0.34221

    −0.4

    −0.3

    −0.2

    −0.1

    −8 −6 −4

    −5

    0

    5

    σ2 = 0.2932

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ3 = 0.23248

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ4 = 0.17673

    −0.4

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ5 = 0.1296

    −0.2

    0

    0.2

    0.4

    −8 −6 −4

    −5

    0

    5

    σ6 = 0.096659

    −0.4

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ7 = 0.070445

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ8 = 0.04619

    −0.2

    0

    0.2

    −8 −6 −4

    −5

    0

    5

    σ9 = 0.035356

    −0.2

    0

    0.2

    0.4

    −8 −6 −4

    −5

    0

    5

    σ10

    = 0.021841

    −0.2

    0

    0.2

    0.4

    −8 −6 −4

    −5

    0

    5

    σ11

    = 0.013265

    −0.4

    −0.2

    0

    0.2

    0.4

    −8 −6 −4

    −5

    0

    5

    σ12

    = 0.0089158

    −0.4

    −0.2

    0

    0.2

  • Can we restore uniqueness by a priori information?

    12 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Consider, for instance,

    q = λχS where λ ≥ 0 is a constant and S ⊂ Ω.

  • Can we restore uniqueness by a priori information?

    12 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Consider, for instance,

    q = λχS where λ ≥ 0 is a constant and S ⊂ Ω.

    Lemma (Wang, Li & Jiang ’04):

    There exist z ∈ Ω, λ1 6= λ2 and r1 6= r2 such that

    A(λ1χB1) = A(λ2χB2)

    with Bk = Brk(z).

  • Inverse problem:reformulation & stabilization

    Mathematical model

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    ReformulationTikhonov-likeregularizationExistence of aminimizer & stabilityRegularizationproperty

    Gradient of the mini-mization functional

    Numerical experi-ments in 2D

    Summary

    13 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • Reformulation

    14 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Ansatz: q =I∑

    i=1

    λiχSi where Si ⊂ Ω, λi ∈ [λi, λi] = Λi, and I ∈ N.

    For the ease of presentation: I = 1.

    Define the nonlinear operator

    F : Λ × L → L2(∂Ω),

    (λ, S) 7→ D∂nu|∂Ω

    where L is the set of all measurable subsets of Ω.

    Note: F (λ, S) = λAχS

    BLT Problem : Given measurements g, find an intensity λ ∈ Λ anda domain S ∈ L such that

    F (λ, S) = g.

  • Tikhonov-like regularization

    15 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Minimize Jα(λ, S) =1

    2‖F (λ, S) − g‖2L2 + αPer(S) over Λ × L

    where α > 0 is the regularization parameter and Per(S) is the perimeterof S:

    Per(S) = |D(χS)|,

    with |D(·)| denoting the BV-semi-norm (Ramlau & Ring ’07, ’10).

    AG Sahin, Univ. Mainz

  • Existence of a minimizer & stability

    16 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Theorem: For all α > 0 and g ∈ L2(∂Ω) there exists a minimizer(λ∗, S∗) ∈ Λ × L, that is,

    Jα(λ∗, S∗) ≤ Jα(λ, S) for all (λ, S) ∈ Λ × L.

    Theorem: Let gn → g in L2 as n → ∞ and let (λn, Sn) minimize

    Jnα(λ, S) =12‖F (λ, S) − gn‖

    2L2

    + αPer(S) over Λ × L.

    Then there exists a subsequence {(λnk , Snk)}k converging to aminimizer (λ∗, S∗) ∈ Λ × L of Jα in the sense that

    ‖λnkχSnk − λ∗χS∗‖L2 → 0 as k → ∞.

    Furthermore, every convergent subsequence of {(λn, Sn)}nconverges to a minimizer of Jα.

  • Regularization property

    17 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Theorem: Let g be in range(F ) and let δ 7→ α(δ) where

    α(δ) → 0 andδ2

    α(δ)→ 0 as δ → 0.

    In addition, let {δn}n be a positive null sequence and {gn}n such that

    ‖gn − g‖L2 ≤ δn.

    Then, the sequence {(λn, Sn)} of minimizers of Jnα(δn)

    possesses a sub-sequence converging to a solution (λ+, S+) where

    S+ = arg min{Per(S) : S ∈ L s.t. ∃λ ∈ Λ with F (λ, S) = g}.

    Furthermore, every convergent subsequence of {(λn, Sn)}n converges toa pair (λ†, S†) with above property.

  • Gradient of the minimization functional

    Mathematical model

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    Gradient of theminimizationfunctional

    Domain derivative:general definitionDomain derivativeof F (λ, ·) : S →L2(∂Ω)

    Domain derivative ofPer : S → RDerivative ofJα : Λ × S → R

    Approximate vari-ational principle(Ekeland 1974)

    Numerical experi-ments in 2D

    Summary

    18 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • Domain derivative: general definition

    19 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Let Γ ∈ S = {Γ̃ ⊂ Ω : ∂Γ̃ ∈ C2} and let h ∈ C20 (Ω, Rd). Define

    Γh = {x + h(x) : x ∈ Γ}.

    If h is small enough, say if ‖h‖C2 < 1/2, then Γh ∈ S.

    By the domain derivative of Φ: S → Y about Γ we understand Φ′(Γ) ∈L(C2, Y ) satisfying

    ‖Φ(Γh) − Φ(Γ) − Φ′(Γ)h‖Y = o(‖h‖C2)

    where Y is a normed space.

  • Domain derivative of F (λ, ·) : S → L2(∂Ω)

    20 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Reminder: F (λ, S) = λAχS

    Lemma: We have that∂SF (λ, S)h = u

    ′|∂Ω

    where u′ ∈ H1(Ω\∂S) solves the transmission bvp

    −∇ · (D∇u′) + µu′ = 0 in Ω\∂S,

    2D∂nu′ + u′ = 0 on ∂Ω,

    [u′]± = 0 on ∂S,[D∂nu

    ′]±

    = −λh · n on ∂S.

    Proof: similar to Hettlich’s habilitation thesis 1999.

  • Domain derivative of Per: S → R

    21 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Lemma (Simon 1980):

    We have that

    ∂SPer(S)h =

    ∂S

    H∂S(h · n) ds

    where H∂S denotes the mean curvature of ∂S.

  • Derivative of Jα : Λ × S → R

    22 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Jα(λ, S) =1

    2‖F (λ, S) − g‖2L2 + αPer(S)

    ∂λF (λ, S)k = kAχS = F (k, S)

    Theorem: We have that

    J ′α(λ, S)(k, h) =〈F (λ, S) − g, F (k, S) + u′

    〉L2(∂Ω)

    + α

    ∂S

    H∂S(h · n) ds

    for k ∈ R, h ∈ C20(Ω, R3).

    Proof:J ′α(λ, S)(k, h) = ∂λJα(λ, S)k + ∂SJα(λ, S)h

  • Approximate variational principle (Ekeland 1974)

    23 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    There exist smooth almost critical points of Jα near to any of itsminimizers.

  • Approximate variational principle (Ekeland 1974)

    23 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    There exist smooth almost critical points of Jα near to any of itsminimizers.

    Theorem: Let (λ∗, S∗) be a minimizer of Jα where λ∗ is an inner point ofΛ. Then, for any ε > 0 sufficiently small there is a (λε, Sε) ∈ Λ × S with

    Jα(λε, Sε) − Jα(λ

    ∗, S∗) ≤ ε,

    ‖λεχSε − λ∗χS∗‖L1 ≤ ε,

    ‖J ′α(λε, Sε)‖R×C2→R ≤ ε.

  • Approximate variational principle (Ekeland 1974)

    23 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    There exist smooth almost critical points of Jα near to any of itsminimizers.

    Theorem: Let (λ∗, S∗) be a minimizer of Jα where λ∗ is an inner point ofΛ. Then, for any ε > 0 sufficiently small there is a (λε, Sε) ∈ Λ × S with

    Jα(λε, Sε) − Jα(λ

    ∗, S∗) ≤ ε,

    ‖λεχSε − λ∗χS∗‖L1 ≤ ε,

    ‖J ′α(λε, Sε)‖R×C2→R ≤ ε.

    Proof: Key ingredient isTo any bounded measurable Γ ⊂ Rd with finite perimeter exists a se-quence {Γn}n of C∞-domains such that

    Rd

    |χΓn − χΓ|dx → 0 and Per(Γn) → Per(Γ) as n → ∞.

  • Numerical experiments in 2D

    Mathematical model

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    Gradient of the mini-mization functional

    Numericalexperiments in2D

    Star-shaped do-mainsAlgorithm: ProjectedGradient Method

    The model

    H3-Reconstructions

    L2-Reconstructions

    Summary

    24 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • Star-shaped domains

    25 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    For the numerical experiments we consider a star-shaped domain only:

    S = {x ∈ R2 : x = m + t θ(ϑ)r(ϑ), 0 ≤ t ≤ 1, 0 ≤ ϑ ≤ 2π}

    where m is the center (assumed to be known) and r : [0, 2π] → [0,∞[parameterizes the boundary of S.

    All previous results hold in this setting as well if we work in a space ofsmooth parameterizations, say, r ∈ H3p(0, 2π) ⊂ C

    2p(0, 2π).

    (λ, S) (λ, r) ∈ Λ × Rad where Rad ={r ∈ H3p(0, 2π) : r ≥ 0

    }.

    Gradient equation:〈gradJα(λ, r), (k, h)

    〉R×H3

    = J ′α(λ, r)(k, h).

    We have implemented star-shaped domains using trigonometric poly-nomials.

  • Algorithm: Projected Gradient Method

    26 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    (S0) Choose (λ0, r0) ∈ C := Λ × Rad, k := 0

    (S1) Iterate (S2)-(S4) until(S2) Set ∇k := −gradJα(λk, rk).(S3) Choose σk by a projected step size rule such that

    (PC

    ((λk, rk) + σk∇k

    ))< Jα(λ

    k, rk).

    (S4) Set (λk+1, rk+1) := PC((λk, rk) + σk∇k

    ).

  • The model

    27 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    lung lungheart

    bone

    muscle

    source

  • H3-Reconstructions

    28 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    0.5

    1

    1.5

    2

    2.5

    3

    30

    210

    60

    240

    90

    270

    120

    300

    150

    330

    180 0

    λ = 0.97843 for α = 0.00763

    0.5

    1

    1.5

    2

    2.5

    3

    30

    210

    60

    240

    90

    270

    120

    300

    150

    330

    180 0

    λ = 0.702 for α = 0.00762

    Reconstructions (blue) and source (red).Left: 69 iterations, right: k = 17 iterations

  • L2-Reconstructions

    29 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    0.5

    1

    1.5

    2

    2.5

    3

    30

    210

    60

    240

    90

    270

    120

    300

    150

    330

    180 0

    λ = 0.84033 for α = 0.0079

    0.5

    1

    1.5

    2

    2.5

    3

    30

    210

    60

    240

    90

    270

    120

    300

    150

    330

    180 0

    λ = 0.77183 for α = 0.008

    Reconstructions (blue) and source (red).Left: 37 iterations, right: noisy data (rel. 3%), 24 iterations

  • L2-Reconstruction with variable center

    30 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    GeoRecBioLum.aviMedia File (video/avi)

  • Summary

    Mathematical model

    Inverse problem:formulation &uniqueness

    Inverse problem:reformulation &

    stabilization

    Gradient of the mini-mization functional

    Numerical experi-ments in 2D

    ⊲ SummaryWhat to rememberfrom this talk

    31 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

  • What to remember from this talk

    32 / 32 c©Andreas Rieder – Geometric Reconstruction in Bioluminescence Tomography CBM 2013, Rio de Janeiro

    Bioluminescence tomography images cells in vivo. From a mathemati-cal point of view it is an inverse source problem which suffers from non-uniqueness (diffusion approximation) and ill-posedness.

    To overcome these difficulties the sources are modeled as ”hot spots”leading to a nonlinear problem which is stabilized by a Tikhonov-likeregularization penalizing the perimeter of the hot spots.

    The approximate variational principle justifies the restriction to hot spotswith smooth boundaries.

    For star-shaped domains in 2D a projected steepest decent solver hasbeen implemented and tested.

    Mathematical model12cm [-0.7cm]The (stationary) radiative transfer equation (RTE) (Boltzmann transport equation)Diffusion approximation: settingDiffusion approximation: derivationDiffusion approximation: final equation

    Inverse problem: formulation & uniquenessInverse problem of BLT (in the diffusive regime)Null Space of ASingular Functions of A2mu-:6muplus1muL2(0)L2()Can we restore uniqueness by a priori information?

    Inverse problem: reformulation & stabilizationReformulationTikhonov-like regularizationExistence of a minimizer & stabilityRegularization property

    Gradient of the minimization functionalDomain derivative: general definitionDomain derivative of F(,)2mu-:6muplus1muSL2()Domain derivative of Per2mu-:6muplus1muSRDerivative of J2mu-:6muplus1muSRApproximate variational principle (Ekeland 1974)

    Numerical experiments in 2DStar-shaped domainsAlgorithm: Projected Gradient MethodThe modelH3-ReconstructionsL2-ReconstructionsL2-Reconstruction with variable center

    SummaryWhat to remember from this talk


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