CN108090936A

CN108090936A - The scanning mating plate tomograph imaging method of Qie Lunkefu fluorescence excitations

Info

Publication number: CN108090936A
Application number: CN201711358717.3A
Authority: CN
Inventors: 冯金超; 张娜; 贾克斌; 李哲; 孙中华
Original assignee: Beijing University of Technology
Current assignee: Beijing University of Technology
Priority date: 2017-12-17
Filing date: 2017-12-17
Publication date: 2018-05-29
Anticipated expiration: 2037-12-17
Also published as: CN108090936B

Abstract

The invention discloses the scanning mating plate tomograph imaging methods of Qie Lunkefu fluorescence excitations, belong to field of medical image processing.This method rebuilds the distribution of fluorescence quantum yield using the fluoroscopic image obtained in organism surface highly-sensitive detector.This method includes two processes, first, generating X-ray mating plate scanning organism generation Cerenkov radiation by linear accelerator and being used as internal excitation light source activation fluorogen, i.e. excitation process；Fluorescent yield can be rebuild exactly using external highly-sensitive detector acquisition fluorescence signal, i.e. emission process, this method second is that the fluorescence inspired is penetrated after biological tissue reaches organism surface.

Description

Scanning light sheet tomography method excited by Cherenkov fluorescence

Technical Field

The invention belongs to the field of medical image processing, and relates to a scanning light sheet tomography method excited by Cherenkov fluorescence.

Background

Radiotherapy is a method for treating tumors by utilizing radiation, and the role and the position in tumor treatment are highlighted increasingly. About 430 million new cases of cancer in 2015, 91.9 thousands of people use radiotherapy, which has become one of the main means for treating malignant tumors. If the physiological activities of malignant tumor cells can be revealed in vivo during radiotherapy, the method can be of great help for the treatment of malignant tumors.

Cherenkov fluorescence-excited scanning imaging (hereinafter referred to as CELSI) is an emerging medical imaging technology, and is a technology for exciting fluorophores in a living body based on radiation-generated Cherenkov light serving as a laser light source and receiving emitted fluorescence outside the living body by a high-sensitivity detector for imaging. CELSI uses cerenkov radiation as an intrinsic excitation light source to achieve lower background noise and higher imaging sensitivity. In addition, the CELSI technology utilizes an internal excitation light source to excite the fluorescent probe, effectively overcomes the problem of limited penetration capability of an external laser light source, and increases the imaging depth. In addition, the use of optical sheet scanning technology effectively improves the spatial resolution and depth sensitivity of the CELSI technology, and can image lesions with a diameter of about 1 mm and a depth of 2 cm. Due to these unique characteristics of CELSI technology, the development of this technology will facilitate its application in biomedical fields. However, CELSI is a two-dimensional planar imaging technique, and cannot provide depth information of a fluorescent probe in a living body and also cannot perform quantitative analysis, thereby limiting the application of CELSI in a living body.

Disclosure of Invention

In order to overcome the problems described in the background art, the invention provides a Cerenkov-excited fluorescence scanning tomography method for the first time.

The invention adopts the technical scheme that the scanning optical sheet tomography method excited by Cherenkov fluorescence reconstructs the distribution of fluorescence quantum yield by using a fluorescence image acquired by a high-sensitivity detector on the surface of a living body. The method comprises two processes, namely, an X-ray film generated by a linear accelerator is used for scanning an organism to generate Cerenkov radiation and is used as an internal excitation light source to excite a fluorophore, namely, an excitation process; secondly, after the excited fluorescence penetrates through biological tissues and reaches the body surface of the organism, an external high-sensitivity detector is used for acquiring a fluorescence signal, namely an emission process.

To accurately describe the excitation and emission processes, the method employs a coupled diffusion approximation equation of the form:

wherein, subscripts x and m represent excitation and emission bands respectively,. v is gradient operator,. phi_x(r) Cerenkov intensity at the excitation band at r, phi_m(r) is the intensity of the fluorescence light at the emission band r, μ_ai(r) (i ═ x, m) represents an optical absorption coefficient, D_i(r) (i ═ x, m) represents an optical diffusion coefficient, μ_af(r) is the absorption coefficient of the fluorophore for the excitation light, η is the quantum efficiency of the fluorophore, η μ_af(r) is the fluorescence quantum yield that needs to be reconstructed. For the light source term q (r) in equation (1), which is an intrinsic excitation light source rather than extrinsic, it is cerenkov radiation generated by a linear accelerator in radiotherapy. Considering that the attenuation of X-rays larger than 6 MeV in biological tissues is small and the thickness of a light beam is less than 5mm, the Cerenkov radiation is simplified into a uniformly distributed light sheet light source.

The robin type boundary conditions are adopted:

in formula (2), the subscripts x and m represent excitation and emission bands, respectively,is a boundaryA is a certain constant that depends on the deviation of the boundary optical reflection coefficient.

The cerenkov-excited fluorescence scanning tomography method is to reconstruct fluorescence quantum yield by using fluorescence images acquired in the emission process, which is a typical ill-conditioned inverse problem. For reconstruction of fluorescence quantum yield, based on regularization theory, iteration kAmount of fluorescence yield change ofUpdated by the iterative equation in equation (3) to obtain:

where k denotes the number of iterations, λ is a regularization parameter, Φ^measIs a measured image of the fluorescence light,is a calculated fluorescence image of the divergent process, i.e. obtained by solving equation (1); t denotes the matrix transposition, J_kIs a Jacobian matrix of the form:

wherein,representing the partial derivatives in mathematics, I_i(i 1.., NM) represents a measured fluorescence image Φ^measFor the ith measurement, the size of the Jacobian matrix J is (M × N) × NN. M represents the number of light sheet scans, N represents the number of boundary measurement points, and NN represents the number of nodes after finite element discretization of the organism. Jacobi matrix J_kIs obtained by dispersing the formula (1) by a finite element method.

If the current iteration number k is larger than the maximum iteration number k_maxOrAnd (3) stopping iteration by the formula (2), otherwise, continuing iteration until a stopping condition is met.

Drawings

FIG. 1 is a phantom shape with black dots indicating detector positions;

fig. 2 is a schematic view of a scanning mode, wherein arrows indicate scanning angles of light sheets, and straight lines indicate positions of the light sheets.

FIG. 3 is a schematic diagram of fluorophore distribution. The black areas in the figure indicate the position of the fluorophore.

FIG. 4 is a reconstructed fluorescence yield distribution.

Detailed Description

The invention is explained below with reference to specific embodiments and the accompanying drawings.

First, a rectangular phantom having a length and a width of 10cm and 6cm, respectively, was constructed as shown in FIG. 1. In the simulation experiments, the phantom was assumed to be homogeneous. Mu of excitation band_axIs 0.009mm-1, D_x0.25mm-1, mu of emission band_amIs 0.006mm-1, D_mIs 0.26 mm-1. A total of 67 fluorescence detectors were set up in the optical diffusion coefficient test, and these detectors were placed equidistantly at the upper boundary of the phantom, as shown in FIG. 1. In the test, the optical sheet is used for scanning once every 0.5cm interval from top to bottom of the imitation body, and the scanning mode is schematically shown in figure 2, wherein the scanning times are 21 times. In this experiment, a circular fluorophore having a diameter of 10mm and a fluorescence yield concentration of 0.008mm-1 was placed at a position (0,0) mm at the center, as shown in FIG. 3. To reconstruct the fluorescence yield, the phantom was discretized into 2747 points and 5280 triangles. Maximum number of iterations k_maxThe stop threshold epsilon is set to 10 and 0.01. Through the calculation of the method, the fluorescence yield reconstruction result shown in figure 4 can be obtained. Experimental results show that the method can accurately reconstruct the fluorescence yield.

Claims

1. The tomography method of the scanning light sheet excited by Cherenkov fluorescence is characterized in that: the method utilizes a fluorescence image acquired by a high-sensitivity detector on the biological surface to reconstruct the distribution of fluorescence quantum yield; the method comprises two processes, namely, an X-ray film generated by a linear accelerator is used for scanning an organism to generate Cerenkov radiation and is used as an internal excitation light source to excite a fluorophore, namely, an excitation process; secondly, after the excited fluorescence penetrates through biological tissues and reaches the body surface of a living body, an external high-sensitivity detector is used for acquiring a fluorescence signal, namely an emission process;

wherein, subscripts x and m represent excitation and emission bands respectively,. v is gradient operator,. phi_x(r) Cerenkov intensity at the excitation band at r, phi_m(r) is the intensity of the fluorescence light at the emission band r, μ_ai(r) (i ═ x, m) represents an optical absorption coefficient, D_i(r) (i ═ x, m) represents an optical diffusion coefficient, μ_af(r) is the absorption coefficient of the fluorophore for the excitation light, η is the quantum efficiency of the fluorophore, η μ_af(r) is the fluorescence quantum yield to be reconstructed; for the light source term q (r) in equation (1), which is an intrinsic excitation light source rather than extrinsic, it is cerenkov radiation generated by a linear accelerator in radiotherapy; considering that the attenuation of X-rays larger than 6 MeV in biological tissues is small, and the thickness of a light beam is less than 5mm, the Cerenkov radiation is simplified into a uniformly distributed light sheet light source;

the robin type boundary conditions are adopted:

<mrow> <mtable> <mtr> <mtd> <mrow> <msub> <mi>&Phi;</mi> <mrow> <mi>x</mi> <mo>,</mo> <mi>m</mi> </mrow> </msub> <mrow> <mo>(</mo> <mi>r</mi> <mo>)</mo> </mrow> <mo>+</mo> <mn>2</mn> <msub> <mi>AD</mi> <mrow> <mi>x</mi> <mo>,</mo> <mi>m</mi> </mrow> </msub> <mrow> <mo>(</mo> <mi>r</mi> <mo>)</mo> </mrow> <mo>&lsqb;</mo> <mover> <mi>v</mi> <mo>&RightArrow;</mo> </mover> <mrow> <mo>(</mo> <mi>r</mi> <mo>)</mo> </mrow> <mo>&CenterDot;</mo> <msub> <mi>&Phi;</mi> <mrow> <mi>x</mi> <mo>,</mo> <mi>m</mi> </mrow> </msub> <mrow> <mo>(</mo> <mi>r</mi> <mo>)</mo> </mrow> <mo>&rsqb;</mo> <mo>=</mo> <mn>0</mn> </mrow> </mtd> <mtd> <mrow> <mi>r</mi> <mo>&Element;</mo> <mo>&part;</mo> <mi>&Omega;</mi> </mrow> </mtd> </mtr> </mtable> <mo>-</mo> <mo>-</mo> <mo>-</mo> <mrow> <mo>(</mo> <mn>2</mn> <mo>)</mo> </mrow> </mrow>

in formula (2), the subscripts x and m represent excitation and emission bands, respectively,is a boundaryA is a specific constant depending on the deviation of the boundary optical reflection coefficient;

the fluorescence scanning tomography method excited by Cerenkov is to reconstruct fluorescence quantum yield by using a fluorescence image acquired in the emission process, which is a typical ill-conditioned inverse problem; for reconstructing fluorescence quantum yield, based on regularization theory, the amount of fluorescence yield change of the kth iterationUpdated by the iterative equation in equation (3) to obtain:

<mrow> <msubsup> <mi>&delta;&eta;&mu;</mi> <mrow> <mi>a</mi> <mi>f</mi> </mrow> <mi>k</mi> </msubsup> <mo>=</mo> <msup> <mrow> <mo>(</mo> <msubsup> <mi>J</mi> <mi>k</mi> <mi>T</mi> </msubsup> <msub> <mi>J</mi> <mi>k</mi> </msub> <mo>+</mo> <mi>&lambda;</mi> <mi>I</mi> <mo>)</mo> </mrow> <mrow> <mo>-</mo> <mn>1</mn> </mrow> </msup> <msubsup> <mi>J</mi> <mi>k</mi> <mi>T</mi> </msubsup> <mrow> <mo>(</mo> <msup> <mi>&Phi;</mi> <mrow> <mi>m</mi> <mi>e</mi> <mi>a</mi> <mi>s</mi> </mrow> </msup> <mo>-</mo> <msubsup> <mi>&Phi;</mi> <mi>k</mi> <mrow> <mi>c</mi> <mi>a</mi> <mi>l</mi> <mi>c</mi> </mrow> </msubsup> <mo>)</mo> </mrow> <mo>-</mo> <mo>-</mo> <mo>-</mo> <mrow> <mo>(</mo> <mn>3</mn> <mo>)</mo> </mrow> </mrow>

wherein,in the mathematics of representationPartial derivative operator of, I_i(i 1.., NM) represents a measured fluorescence image Φ^measFor the ith measurement value, the size of the Jacobian matrix J is (M multiplied by N) multiplied by NN; m represents the number of optical sheet scans, N represents the number of boundary measurement points, and NN represents the number of nodes after a finite element of an organism is dispersed; jacobi matrix J_kIs obtained by dispersing the formula (1) by a finite element method.

2. The cherenkov fluorescence-excited scanning light sheet tomography method of claim 1, wherein: if the current iteration number k is larger than the maximum iteration number k_maxOrAnd (3) stopping iteration by the formula (2), otherwise, continuing iteration until a stopping condition is met.