Source: http://www.google.com/patents/US7616985?dq=7222078
Timestamp: 2017-10-23 01:19:41
Document Index: 422598501

Matched Legal Cases: ['§119', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'art 1', 'art 1', 'art 2', 'art 1']

Patent US7616985 - Method and apparatus for 3-D imaging of internal light sources - Google Patents
The present invention provides systems and methods for obtaining a three-dimensional (3D) representation of one or more light sources inside a sample, such as a mammal. Mammalian tissue is a turbid medium, meaning that photons are both absorbed and scattered as they propagate through tissue. In the case...http://www.google.com/patents/US7616985?utm_source=gb-gplus-sharePatent US7616985 - Method and apparatus for 3-D imaging of internal light sources
Publication number US7616985 B2
Application number US 10/606,976
Also published as CA2492483A1, CN1678900A, DE60334098D1, EP1521959A1, EP1521959B1, US7603167, US7797034, US7860549, US8909326, US20040021771, US20050201614, US20080018899, US20100022872, US20110090316, WO2004008123A1
Publication number 10606976, 606976, US 7616985 B2, US 7616985B2, US-B2-7616985, US7616985 B2, US7616985B2
Inventors Daniel G. Stearns, Bradley W. Rice, Michael D. Cable
Patent Citations (105), Non-Patent Citations (63), Referenced by (11), Classifications (24), Legal Events (4)
Method and apparatus for 3-D imaging of internal light sources
US 7616985 B2
This application claims priority under 35 U.S.C. §119(e) from co-pending (1) U.S. Provisional Application No. 60/395,357, entitled “Method and Apparatus for 3-D Imaging of Internal Light Sources”, by Daniel G. Stearns, et al., (2) U.S. Provisional Application No. 60/396,458, entitled “In Vivo 3D Imaging of Light Emitting Reporters”, by Bradley W. Rice, et al. and (3) U.S. Provisional Application No. 60/396,313, entitled “3D in Vivo Imaging of Light Emitting Reporters”, by Bradley W. Rice, et al. These applications were all filed on Jul. 16, 2002 and are incorporated by reference for all purposes.
Bioluminescent imaging is a non-invasive technique for performing in vivo diagnostic studies on animal subjects in the areas of medical research, pathology and drug discovery and development. Bioluminescence is typically produced by cells that have been transfected with a luminescent reporter such as luciferase and can be used as a marker to differentiate a specific tissue type (e.g. a tumor), monitor physiological function, track the distribution of a therapeutic compound administered to the subject, or the progression of a disease. A wide range of applications have been demonstrated including areas of oncology, infectious disease, and transgenic animals. In vivo imaging of cells tagged with fluorescent reporters is a related technology that has also been general, absorption in mammalian tissues is high in the blue-green part of the spectrum (<600 nm) and low in the red and NIR part of the spectrum (600-900 nm). Firefly luciferase has a rather broad emission spectrum ranging from 500-700 nm, so at least part of the emission is in the low absorption region. Since the mean-free-path for scattering in tissue is short, on the order of ˜0.5 mm, photons from deep sources are scattered many times before reaching the surface. Bioluminescent imaging systems effectively record the spatial distribution of these photons emitted from the surface of the subject.
In a specific embodiment, a simple Kohler projection scheme is used as the structured light source. In this case, the ruling may be illuminated by a diffuse LED source and the ruling is then projected onto the animal stage with a magnification of approximately 10×. An example of this system as incorporated in system 10 is shown in FIG. 2D. The projector module 170 rides on the back of the rotating mirror assembly 120, so that lines are always projected on the sample 106 at all viewing angles. The illumination pattern is projected horizontally and reflects off of a small mirror 173 at the base of the larger turning mirror to illuminate sample 106.
I ( θ 2 ) = c 4 π n 2 T ( θ ) cos θ 2 d Ω ⌊ 1 + 3 2 1 - R eff 1 + R eff cos θ ⌋ ρ ( 1 )
Here, c is the speed of light, n is the index of refraction of the sample medium, T is the transmission coefficient for light exiting the sample through the surface element, and θ is the internal emission angle, which is related to the external emission angle θ2,through Snell's law:
R eff = R ϕ + R j 2 - R ϕ + R j R ϕ = ∫ 0 π 2 2 sin θ cos θ R ( θ ) ⅆ θ R j = ∫ 0 π 2 3 sin θ cos 2 θ R ( θ ) ⅆ θ R ( θ ) = { 1 2 ( n cos θ 2 - cos θ n cos θ 2 + cos θ ) 2 + 1 2 ( n cos θ - cos θ 2 n cos θ + cos θ 2 ) 2 for θ < arcsin ( 1 / n ) 1 for θ > arcsin ( 1 / n ) ( 3 )
ρ j ≅ ∑ i G ij S i ( 4 )
where the index i enumerates the volume elements and Si is the value of the strength of the point source (photons/sec) inside the ith volume element.
D = c 3 ( μ A + μ S ′ ) ( 6 )
G ij = 1 2 π D { exp ( - μ eff r ij ) r ij - 1 z b exp ( r ij / z b ) E 1 [ ( μ eff + 1 z b ) r ij ] } ( 7 )
Here rij=|xj−xi|, E1 is the first order exponential integral and
z b = 2 D c 1 + R eff 1 - R eff ( 9 )
Cost = ∑ j S j ( 10 )
∑ j G ij S j ≤ ρ i ( 12 )
χ 2 = ∑ j [ ρ j - ∑ i G ij S i ρ j ] 2 ( 13 )
The value of χ2 measures the difference between the observed photon density ρi and the calculated photon density
∑ i G ij S i
over the surface of the sample.
Cost = ∑ i S i / W i γ , W i = ∑ j G ij ( 14 )
The weighting factor Wi is the contribution of the ith volume element to the photon density over the entire surface. The exponent γ adjusts the relative contribution to the cost function of the interior volume elements and those volume elements close to the surface. When γ=0, then the interior volume elements have relatively greater weight. When γ=1 the volume elements near the surface have greater weight. Process flow 540 may be iterated while varying γ to search for solutions where the source is both near and far from the surface. For example, the step size may be varied by about 0.01 to about 0.2 for a range of γ from 0 to 1. In a specific embodiment, the step size was varied by about 0.05 for a range of γ from 0 to 1. Once again, quality assessment (552) may be used to identify the best solution.
G ij = G i E G ij F ( 15 )
∑ j ∈ Q G ij < κ ∑ j ∈ P G ij ( 16 )
The constant κ may have a value in the range of 1-10. The criteria (16) is applied to each volume element during the formation of the initial volume grid (542) and at each iteration, if used.
χ 2 = ∑ j 1 ρ j [ ρ j - ∑ i G ij S i ] 2 ( 17 )
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U.S. Classification 600/473, 600/407, 600/425, 600/476, 600/431, 250/363.01, 600/438
International Classification A61K49/00, A61B6/12, A61B6/03
Cooperative Classification G01B9/02041, G01B11/24, G01B9/02004, G01N21/6456, G01B9/0203, H04N13/025, H04N13/0203, A61K49/0013, H04N13/0271, G01N21/763, G01B11/2518
European Classification A61K49/00P4, G01N21/76B, G01N21/64P4
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:STEARNS, DANIEL G.;RICE, BRADLEY W.;CABLE, MICHAEL D.;REEL/FRAME:014253/0678;SIGNING DATES FROM 20030603 TO 20030606