A cascaded imaging diagnostic and therapeutic system and its usage method

Abstract

This invention provides a cascaded imaging diagnostic and therapeutic integrated system, relating to the field of imaging. The system includes: a gantry, a slit collimator, a detector ring, and a base. The gantry is a hollow, regular prism. The slit collimator is mounted on the inner side wall of the gantry; the detector ring is mounted on the outer side wall of the gantry; the side wall of the gantry is mounted on the base. When a living organism to be detected is transferred into the cavity of the gantry, the detector ring images the target position within the organism through the slit collimator. The living organism carries a drug containing a nuclide that supports the emission of cascaded photons. The detector ring is connected to a host computer. This invention can collimate and detect "cascaded gamma photon pairs," thereby directly locating the nuclide decay position, achieving real-time imaging, short imaging time, and avoiding the defects of traditional nuclear medicine image reconstruction.

Description

Technical Field

[0001] This invention relates to the field of imaging, and in particular to a cascaded imaging diagnostic and therapeutic integrated system and its method of use. Background Technology

[0002] The clinical application of integrated nuclear medicine diagnosis and treatment is currently experiencing rapid development both domestically and internationally. Therapeutic nuclear medicine is a novel biomedical technology that organically combines disease diagnosis / monitoring with treatment, possessing immense potential in patient stratification, personalized medicine, real-time monitoring of cancer treatment processes, and evaluation of treatment outcomes. The development advantages of integrated nuclear medicine diagnosis and treatment are significant. Utilizing radionuclides with imaging and therapeutic properties, and employing diagnostic and therapeutic radiopharmaceuticals with shared specific targets, along with nuclear medicine imaging techniques, it is possible to diagnose and treat diseases such as tumors, making it one of the most popular research directions in the field. However, commonly used integrated clinical protocols employ different radionuclides for treatment and imaging, resulting in the separation of imaging and treatment. Due to the different biological characteristics of various radiopharmaceuticals, using different diagnostic and therapeutic radiopharmaceuticals may affect the accuracy of dose assessment, and there is also the issue of inconsistent diagnosis and treatment, increasing the cost of integrated diagnosis and treatment. With the development of radiotherapy drugs and molecular probes, nuclides such as 177Lu and 90Y, due to their short half-lives, produce beta rays that can be used for tumor treatment, while simultaneously generating gamma photons with moderate energy suitable for nuclear medicine imaging. This reduces the need for molecular probes and holds promise for achieving simultaneous treatment and imaging, making them highly promising for integrated diagnosis and treatment. Furthermore, some nuclides, such as 177Lu, exhibit cascade decay, producing two temporally and spatially correlated gamma photons. Compared to traditional single-photon imaging, this provides more imaging information, thereby improving image quality.

[0003] Emission Computed Tomography (ECT) is an imaging technique that displays specific molecules at the tissue, cellular, and subcellular levels, reflecting molecular changes in living organisms and showcasing the processes by which substances participate in various biological activities. It allows for qualitative and quantitative research on biological behavior through imaging, possessing characteristics such as high sensitivity, high specificity, and quantification. It provides crucial evidence for the early diagnosis and precision treatment of major diseases like cancer, giving it unique advantages in the field of medical imaging. Cascaded gamma-photon coincidence imaging systems use gamma photons derived from radiopharmaceuticals and are also a type of ECT system. Like positron emission tomography (PET), it requires time coincidence detection and can also employ collimation techniques from single-photon emission computed tomography (SPECT).

[0004] Cascade radiation refers to the process by which a nuclide, during a single decay, emits two or more gamma photons of specific energies in a very short time through energy level transitions from high to low. The pairs of gamma photons emitted in the same cascade radiation exhibit strong correlations in time, position, and emission angle, thus directly containing information about the nuclide's location. When the half-life of the cascade intermediate state corresponding to the gamma photon is sufficiently short, such as less than 10 ns, it is extremely short compared to the movement speed of the radioactive nuclide molecule. It can be assumed that the nuclide molecule does not shift during this time, meaning that each pair of cascade radiation gamma photons is emitted from the same location.

[0005] However, traditional nuclear medicine imaging equipment such as PET cannot image 177Lu because: PET imaging works by detecting 511 keV coincident photon pairs generated by positron annihilation, with an angle of 180 degrees, allowing the direction of motion to be determined by connecting them. However, the two photons in a cascaded coincident photon pair do not possess this characteristic, making it impossible to determine their direction of motion using PET. Although Time-of-Flight (TOF) can determine the surface where the cascaded photon emission location is located and obtain the photon emission location through image reconstruction, the spatial resolution is poor. Furthermore, PET has poor energy resolution, making it difficult to distinguish between two photons of different energies in a cascaded photon pair. SPECT, on the other hand, is a non-coincidence imaging method, relying solely on a physical collimator, and cannot directly locate the nuclide decay position. Moreover, SPECT uses multi-angle projection to obtain the photon emission position through image reconstruction, resulting in poor spatial resolution. SPECT also suffers from long imaging times, low detection efficiency, poor imaging quality, and the inability to obtain real-time imaging. Therefore, SPECT cannot utilize the cascade decay characteristics of 177Lu, making it difficult to fully exploit its imaging potential. Summary of the Invention

[0006] To address the technical problems existing in the prior art, embodiments of the present invention provide a cascaded imaging and therapeutic integrated system, which improves image quality, significantly enhances the image signal-to-noise ratio, and achieves integrated diagnosis and treatment. The technical solution is as follows:

[0007] A cascaded imaging diagnostic and therapeutic system includes:

[0008] The frame is a hollow regular prism;

[0009] A slot collimator is installed on the inner side wall of the frame;

[0010] A detector ring, mounted on the outer wall of the rack, is used for cascaded coincident gamma photon and single-photon data acquisition, and for determining cascaded coincident gamma photon pairs according to a time window;

[0011] A base, on which the sidewalls of the frame are mounted;

[0012] When the live object to be detected is transferred into the cavity of the frame, the detector ring images the target position in the live object through the aperture collimator.

[0013] The living organism to be detected carries a drug containing a nuclide that supports the emission of cascaded photons, and the detector ring is connected to the host computer.

[0014] The detector ring carries functions such as coincidence, depth of action information, and time of flight.

[0015] The host computer has a built-in image reconstruction module, which is connected to the detector ring. The image reconstruction module reconstructs the image spatial resolution based on the maximum likelihood-expectation maximization algorithm, the direct back projection algorithm for aperture coincidence γ events, and the data collected by the detector ring.

[0016] Optionally, the frame is a regular decagonal prism, the detector ring includes ten detector plates, and one detector plate is installed on the outer circumferential wall of the frame.

[0017] Optionally, the hole / slit collimator includes: a hole collimator and a slit collimator;

[0018] On any two adjacent inner sidewalls of the frame, a hole collimator is installed on one sidewall and a slot collimator is installed on the other sidewall;

[0019] or,

[0020] The hole alignment device includes: a hole alignment device, which is installed on each inner sidewall of the frame;

[0021] or,

[0022] The slot alignment device includes a slot alignment device, which is installed on each inner sidewall of the frame.

[0023] Optionally, the detector board includes: a lanthanum bromide crystal substrate, a photomultiplier tube, and an ASIC;

[0024] A lanthanum bromide crystal substrate is mounted on the rack, and the ASIC is mounted on the side of the lanthanum bromide crystal substrate facing away from the rack;

[0025] The photomultiplier tube is installed between the ASIC and the lanthanum bromide crystal substrate, and the photomultiplier tube is connected to the ASIC.

[0026] Optionally, the nuclides supporting the emission of cascaded photons include: lutetium-177, indium-111, iodine-131, copper-6, gallium-67, and selenium-75.

[0027] A method for using a cascaded imaging diagnostic and therapeutic system includes:

[0028] After injecting a drug containing a nuclide that supports the emission of cascaded photons into the living organism to be tested, the living organism to be tested is pushed into the cavity of the gantry.

[0029] In the cascaded photon pair in the living organism to be detected, one photon is projected onto the corresponding lanthanum bromide crystal substrate through the aperture collimator, and the other photon is projected onto the corresponding lanthanum bromide crystal substrate through the slit collimator.

[0030] The lanthanum bromide crystal substrate converts the received photons into optical signals, and the photomultiplier tube converts the optical signals into electrical signals, which are then transmitted to the corresponding ASIC.

[0031] The ASIC processes the received electrical signals, finds the information of the same pair of cascaded gamma photons based on the time window, and locates the nuclide decay position in real time based on the information of the same pair of cascaded gamma photons to obtain the image of the target position in the living body to be detected.

[0032] Optionally, the image reconstruction module, based on the maximum likelihood-expectation-maximization algorithm and the data acquired by the detector loop, employs a multi-data joint image algorithm to reconstruct the image grayscale values, including:

[0033] The grayscale value M of the image is obtained based on the lanthanum bromide crystal substrate of the detector ring;

[0034] Let A1 be the system transfer matrix for cascaded gamma photon pair aperture coincidence imaging;

[0035] Let the system transfer matrix of cascaded gamma photon pair aperture coincidence imaging be A2;

[0036] Let the system transfer matrix of cascaded gamma photon pair slit coincidence imaging be A3;

[0037] Let the system transfer matrix for single-photon imaging be A4;

[0038] Using the Monte Carlo method, we obtained the contribution ratios of cascaded gamma photons to aperture-slit coincidence imaging (Q1), cascaded gamma photons to aperture-aperture coincidence imaging (Q2), cascaded gamma photons to slit-slit coincidence imaging (Q3), and the contribution ratio of the single-photon imaging algorithm to the reconstructed image (Q4).

[0039] Based on single-photon information and coincident photon information, the grayscale value of the reconstructed image is obtained according to the multi-information joint image algorithm of MLEM algorithm. The grayscale value of the reconstructed image is obtained by formula (1):

[0040] I 联合 = (Q1 A1) -1 + Q2 A2 -1 + Q3 A3 -1 + Q4 A4 -1 )×M; (1)

[0041] Among them, I 联合 The image grayscale values ​​are obtained based on the maximum likelihood-expectation-maximization algorithm.

[0042] Optionally, the image reconstruction module reconstructs the image grayscale value based on the direct back-projection algorithm of the aperture coincidence γ event and the data collected by the detector ring, using formula (2):

[0043] I 反 =A DOI孔缝 ×A TOF孔缝 ×I 初孔缝 +A DOI孔孔 ×A TOF孔孔 ×I 初孔孔 (2)

[0044] Among them, I 反 The image grayscale value is obtained by the direct backprojection algorithm based on the aperture coincidence γ event;

[0045] A DOI孔缝 When the hole and slit collimator includes both the hole collimator and the slit collimator, the image correction matrix obtained using DOI is used.

[0046] A TOF孔缝 When the hole and slit collimator includes both the hole collimator and the slit collimator, the image correction matrix obtained using TOF is used.

[0047] I 初孔缝When the aperture collimator includes both the aperture collimator and the slit collimator, the uncorrected grayscale value of the reverse headshot image of the object being detected.

[0048] A DOI孔孔 When the aperture collimator is only an aperture collimator, the image correction matrix obtained using DOI is used.

[0049] A TOF孔孔 When the aperture collimator is only an aperture collimator, the image correction matrix obtained using TOF is used.

[0050] I 初孔孔 When the aperture collimator is only an aperture collimator, the grayscale value of the uncorrected reverse headshot image of the object being detected.

[0051] The beneficial effects of the technical solutions provided in the embodiments of the present invention include at least the following:

[0052] This method proposes a spatiotemporal coincidence imaging approach based on aperture collimation and coincidence detection. It can collimate and coincide with cascaded gamma photon pairs, directly locating the decay position of nuclides for real-time imaging. This approach offers short imaging time and avoids the shortcomings of traditional nuclear medicine image reconstruction. Compared to traditional single-photon imaging, cascaded photons provide more imaging information, thus improving image quality and significantly increasing the signal-to-noise ratio. This patented cascaded gamma photon coincidence imaging system can be combined with a high-performance lanthanum bromide (LaBr3) detector or quantitative image reconstruction algorithms, resulting in significantly improved imaging performance compared to SPECT. This patent has promising industrialization prospects and can be further integrated with therapeutic applications for further research and optimization, showing great application potential. Cascaded gamma photon coincidence imaging can achieve high-quality real-time imaging, contributing to the development of therapeutic integration. Attached Figure Description

[0053] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0054] Figure 1 This is a schematic diagram of the usage process provided in the embodiment of the present invention;

[0055] Figure 2 This is a cross-sectional view of the lanthanum bromide crystal provided in an embodiment of the present invention;

[0056] Figure 3 This is a cross-shaped sew alignment device provided in an embodiment of the present invention;

[0057] Figure 4It is a linear slit collimator provided by an embodiment of the present invention;

[0058] Figure 5 It is a cross-shaped slit collimator provided by an embodiment of the present invention;

[0059] Figure 6 It is a schematic diagram of a photomultiplier tube arranged on a lanthanum bromide crystal substrate provided by an embodiment of the present invention;

[0060] Figure 7 It is a schematic structural diagram of the integration of the present system and the prior art provided by an embodiment of the present invention;

[0061] Figure 8 It is an exploded view of a partial structure of the present system provided by an embodiment of the present invention;

[0062] Figure 9 It is a schematic structural diagram of a detector board provided by an embodiment of the present invention;

[0063] Figure 10 It is a schematic diagram showing that photons hitting the wedge-shaped wall of the detector board have a certain probability of passing through the collimator and the energy will decay provided by an embodiment of the present invention.

[0064] Reference numerals:

[0065] 1 - frame, 2 - hole slit collimator, 21 - hole collimator; 22 - slit collimator; 3 - detector ring, 4 - base. Detailed implementation manners

[0066] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present invention. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the described embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0067] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The terms “first,” “second,” and similar terms used in this invention do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Similarly, the terms “an,” “a,” or “the,” and similar terms do not indicate a quantity limitation, but rather indicate the presence of at least one. The terms “comprising,” “including,” or “including,” and similar terms mean that the element or object preceding the word encompasses the element or object listed following the word and its equivalents, without excluding other elements or objects. The terms “connected,” “linked,” or “connected,” and similar terms are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect.

[0068] It should be noted that the terms "up", "down", "left", "right", "front", and "back" used in this invention are only used to indicate relative positional relationships. When the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0069] like Figures 1 to 10 As shown, a cascaded imaging diagnostic and therapeutic integrated system includes: a gantry, a slit collimator, a detector ring, and a base. The gantry is a hollow regular prism. The slit collimator is mounted on the inner side wall of the gantry. The detector ring is mounted on the outer side wall of the gantry and is used for cascaded coincidence and photon and single-photon data acquisition, and for determining cascaded coincidence gamma photon pairs according to a time window. The side wall of the gantry is mounted on the base. When the living organism to be detected is transferred into the cavity of the gantry, the detector ring images the target position within the living organism through the slit collimator. When the live sample to be detected is transferred into the cavity of the rack, the detector ring images the target position within the live sample through the aperture collimator. The live sample to be detected carries a drug containing a nuclide that supports the emission of cascaded photons. The detector ring is connected to a host computer. The detector ring carries coincidence function, depth of action information, and time-of-flight function. The host computer has a built-in image reconstruction module, which is data-connected to the detector ring. The image reconstruction module reconstructs the image spatial resolution based on the maximum likelihood-expectation-maximization algorithm, the direct back-projection algorithm for aperture coincidence γ events, and the data acquired by the detector ring.

[0070] The detector ring is a gamma-ray position-sensitive detector. The detector module has time coincidence, depth of action (DOI) information, and time-of-flight (TOF) capabilities. It incorporates annular aperture-slit collimators, with aperture and slit collimators arranged alternately. The slit collimators come in three shapes: slit-shaped, cross-shaped, and fence-shaped. The field of view can be adjusted as needed. The detector ring is used to acquire data for single-photon and cascaded gamma-photon coincidence imaging.

[0071] Because detector rings possess time-matching capabilities, depth of interaction (DOI) information, and time-of-flight capabilities, using a detector ring with DOI information can obtain precise 3D positional information, leading to more accurate image reconstruction, effectively improving system spatial resolution, and reducing parallax effects, especially for locations far from the center of the field of view. DOI acquisition methods can be mainly divided into three categories: signal waveform discrimination, spectroscopic methods, and dual-ended readout methods. DOI detectors come in various shapes, including ring-shaped, flat-panel, and polygonal DOI detectors. DOI detector implementation methods include multilayer crystal, dual-ended readout, and continuous crystal multi-channel readout.

[0072] The working principle of Time-of-Flight (TOF) is that the path length of a photon from the annihilation point to the detector is different, so the arrival time of a single gamma ray is different. TOF-PET, based on the time difference of annihilation photon pairs arriving at the detector, restricts the position of positron emission to a small segment of the LOR connecting two scintillation crystals. The iterative reconstruction algorithm that generates tomographic PET images from sinusoidal images can incorporate this depth resolution information, thereby enhancing the image signal-to-noise ratio and improving the system resolution.

[0073] The ASIC within the detector ring determines cascaded coincident gamma photon pairs through time windows, including aperture-slit collimated coincidence, aperture-aperture collimated coincidence, and slit-slit collimated coincidence.

[0074] An image reconstruction algorithm is incorporated into the computer to form an image reconstruction module, which is electrically connected to the detector ring. This module performs corresponding image reconstruction and multi-data joint image reconstruction based on data collected by the detector ring. Employing a spatiotemporal coincidence imaging method based on aperture collimation, this patent develops a direct back-projection algorithm for aperture coincidence gamma events to perform real-time 3D imaging. Iterative image reconstruction is performed using the maximum likelihood-expectation-maximization (MLEM) algorithm to optimize the spatial resolution of the reconstructed image. Building upon the image reconstruction of aperture coincidence gamma events, this patent proposes a joint image reconstruction algorithm utilizing other information such as aperture coincidence, hole-aperture coincidence, and single-photon gamma events to improve the image signal-to-noise ratio. Radiopharmaceutical therapy is then directly administered based on the reconstructed images.

[0075] Compared to traditional detectors (such as SPECT, PET, etc.) that do not utilize cascaded gamma photon coincidence information for imaging, this invention uses a single-photon plus cascaded gamma photon coincidence imaging method, which greatly improves the utilization rate of radiopharmaceuticals, obtains more photon information, and makes the image more accurate.

[0076] This system is applied to MRI machines in hospitals. It can be composed of existing mechanical motion components, motion control circuits, power supply systems, manipulators, gantry motion status displays, scanning beds, and physiological signal detection devices. The base is existing technology. Generally, the live subject to be examined first lies on the scanning bed. The scanning bed carries the live subject sequentially through a CMOS detector and an X-ray tube, essentially coupling a CT scanner to this system, facilitating image detection. Then, the scanning bed carries the live subject into the gantry. The gantry is a regular decagonal prism, and the detector ring includes ten detector plates. One detector plate is installed on each of the outer circumferences of the gantry ring. The number and type of detector plates can be set according to requirements; this embodiment does not limit this. If the gantry is a regular hexagonal prism, then the detector ring can have six detector plates. Additionally, multiple probes are installed within the detector ring. The collimator position can be adjusted to adjust the imaging field of view, obtaining either a large field-of-view detector module or a small field-of-view detector module as needed.

[0077] The hole and slit collimator includes: a hole collimator and a slit collimator;

[0078] On any two adjacent inner sidewalls of the frame, a hole collimator is installed on one sidewall and a slot collimator is installed on the other sidewall;

[0079] Alternatively, the hole collimator may include: a hole collimator, wherein a hole collimator is mounted on each inner sidewall of the frame;

[0080] or,

[0081] The slot alignment device includes a slot alignment device, which is installed on each inner sidewall of the frame.

[0082] The detector board includes: a lanthanum bromide crystal substrate, a photomultiplier tube, and an ASIC;

[0083] A lanthanum bromide crystal substrate is mounted on the rack, and the ASIC is mounted on the side of the lanthanum bromide crystal substrate facing away from the rack;

[0084] The photomultiplier tube is installed between the circuit board and the lanthanum bromide crystal substrate, and the photomultiplier tube (not shown in the figure) is connected to the ASIC.

[0085] The nuclides that support the emission of cascaded photons include: lutetium-177, indium-111, iodine-131, copper-6, gallium-67, and selenium-75.

[0086] In existing technologies, imaging requirements typically involve injecting radionuclide drugs into the living organism solely for imaging purposes. These drugs do not have a therapeutic effect. However, due to the structural design and related principles applied in this application, the drug selected here is not only capable of imaging but also of treatment, achieving integrated diagnosis and therapy. For example, the drug can contain one or more radionuclides selected from lutetium-177, indium-111, iodine-131, copper-6, gallium-67, and selenium-75. For instance, for neuroendocrine tumors, this drug can be selected... 177 LU-DOTATATE, a treatment option for prostate cancer, can be used. 177 LU-PSMA-617, for tumors expressing gastrin-releasing protein receptor (GRPR+), can be selected. 177 For patients, Lu-NeoBOMB1 and other similar products are not only used for taking and viewing images, but can also achieve therapeutic effects.

[0087] The specific principles of this system include:

[0088] The detector plate is mounted circumferentially on a frame, on which aperture and slit collimators are arranged alternately. The slit collimators come in three shapes: slit-shaped, cross-shaped, and fence-shaped. The detector plate is a gamma-ray position-sensitive detector with time coincidence, depth-of-field information, and time-of-flight capabilities. The imaging field of view can be adjusted by changing the position of the detector plate.

[0089] The detector ring is used to acquire data for Single-Photon Emission Computed Tomography (SPECT) and Cascade Gamma Photon Coincidence Imaging.

[0090] The coincidence photon information detected by the detector ring also includes aperture coincidence and slot coincidence.

[0091] The image reconstruction module is electrically connected to the detector module. The image reconstruction module is used to reconstruct corresponding cascaded coincident photon and single photon images, as well as multi-data joint image reconstruction, based on the data collected by the detector module.

[0092] In this embodiment, image reconstruction is performed using a slit collimator and back projection and image iteration algorithms. Furthermore, the system improves spatial resolution using the slit collimator and enhances system sensitivity using the slit collimator.

[0093] The computer can be configured with: an acquisition unit and a reconstruction unit. The acquisition unit is used to acquire target single-photon events through single-photon event information, wherein the single-photon event information includes: the energy, position, depth of effect, and time of flight of the single-photon event; and to acquire cascaded coincident photon events through cascaded coincident photon event information, wherein the cascaded coincident photon event information includes: the energy, position, depth of effect, time of flight, and angle of the cascaded coincident photon event.

[0094] The reconstruction unit is used to reconstruct the image based on the target single-photon event and the cascaded coincident photon time. An innovative multi-data joint reconstruction technique is employed.

[0095] In this embodiment, the reconstruction unit uses analytical calculation or Monte Carlo simulation of the system transfer matrix, combined with an iterative reconstruction algorithm, to reconstruct the image. Employing a spatiotemporal coincidence imaging method based on aperture collimation, this patent develops a direct back-projection algorithm for aperture coincidence gamma events for real-time 3D imaging; it uses the maximum likelihood-expectation-maximization (MLEM) algorithm for iterative image reconstruction to optimize the spatial resolution of the reconstructed image; based on the image reconstruction of aperture coincidence gamma events, this patent proposes a joint image reconstruction algorithm utilizing other information such as aperture coincidence, hole coincidence, and single-photon gamma events to improve the image signal-to-noise ratio.

[0096] The treatment module is connected to the detector and uses radiopharmaceuticals such as 177Lu (which are both therapeutic and imaging drugs) with cascading properties for treatment.

[0097] The imaging system in this embodiment consists of a detector module comprised of a ring detector and an aperture collimator. This detector module features time-compatibility functionality, enabling the acquisition of single-photon and cascaded coincident photon data. Photon event information is obtained through the acquisition circuit, and the image is reconstructed based on the target photon events. The aperture collimator improves spatial resolution, while the slit collimator enhances system sensitivity. Cascaded coincident photon imaging technology can obtain richer data information, achieve higher image quality, and is applicable to treatment, demonstrating strong practical value in integrated diagnostic and therapeutic research.

[0098] The following examples, using application scenarios, will further illustrate the above system:

[0099] The object to be tested is injected with a radiotherapy drug, which can be a radiolabeled drug (such as indium-111, lutetium-177, etc.) that can produce cascade radiation.

[0100] The object to be detected is placed on the scanning bed, moved into the imaging field of view, and then the corresponding data is acquired. At the same time, single-photon events and cascaded gamma photon coincidence events are acquired, collimated by a slit collimator, and then discriminated by the energy window of the gamma photon coincidence module for image reconstruction. The acquired events include the location, energy and time of the gamma event.

[0101] Single-photon event information and cascaded coincident photon event information are acquired through the acquisition circuit.

[0102] The acquired data is processed by the acquisition and processing unit to reconstruct the corresponding image. The reconstructed head image can be obtained directly through backprojection using aperture collimation. A system transfer matrix is ​​generated after modeling the system using Monte Carlo simulation; image reconstruction is performed using the system transfer matrix calculated analytically or simulated by Monte Carlo, combined with backprojection and iterative reconstruction algorithms.

[0103] Treatment is performed in the treatment module using radiopharmaceuticals used for imaging.

[0104] Unlike existing technologies that utilize only single-photon event imaging, this system simultaneously acquires single-photon event information and cascaded coincident photon event information through its acquisition and processing unit, enabling multi-data joint image reconstruction. This results in more photon information being obtained, leading to higher-quality images. Furthermore, unlike existing technologies that use different radionuclides for treatment and imaging, this system can use the same drug for both diagnosis and treatment, resulting in more accurate diagnosis and better outcomes. The imaging system in this embodiment has significant practical value in integrated diagnosis and treatment, better supporting disease treatment and life science research.

[0105] A method for using a cascaded imaging diagnostic and therapeutic system includes:

[0106] After injecting a drug containing a nuclide that supports the emission of cascaded photons into the living organism to be tested, the living organism to be tested is pushed into the cavity of the gantry.

[0107] In the cascaded photon pair in the living organism to be detected, one photon is projected onto the corresponding lanthanum bromide crystal substrate through the aperture collimator, and the other photon is projected onto the corresponding lanthanum bromide crystal substrate through the slit collimator.

[0108] The lanthanum bromide crystal substrate converts the optical signal of the received photons into an electrical signal, and the lanthanum bromide crystal substrate transmits the electrical signal to the corresponding ASIC through a photomultiplier tube.

[0109] The ASIC processes the received electrical signals, finds the information of the same pair of cascaded gamma photons based on the time window, and locates the nuclide decay position in real time based on the information of the same pair of cascaded gamma photons, thereby obtaining an image of the target position in the living body to be detected.

[0110] In one specific implementation, the image reconstruction module, based on the maximum likelihood-expectation-maximization algorithm and the data acquired by the detector loop, employs a multi-data joint image algorithm to reconstruct the image grayscale values, including:

[0111] The grayscale value M of the image is obtained based on the lanthanum bromide crystal substrate of the detector ring. Let the system transfer matrix of the cascaded gamma photon pair aperture coincidence imaging be A1, and the image I1=A1 after iteration of the cascaded gamma photon pair aperture coincidence using the MLEM algorithm. -1 ×M;

[0112] Let the system transfer matrix of cascaded gamma photon pair aperture coincidence imaging be A2, and the image after cascaded gamma photon pair aperture coincidence iterated by the MLEM algorithm be I2 = A2. 1 ×M;

[0113] Let A3 be the system transfer matrix of cascaded gamma photon pairs for seam coincidence imaging.

[0114] Let the system transfer matrix of single-photon imaging be A4, and the image obtained by iterating the single-photon information using the MLEM algorithm be I4=A4. -1 ×M;

[0115] Using the Monte Carlo method, we obtained the contribution ratios of cascaded gamma photons to aperture-slit coincidence imaging (Q1), cascaded gamma photons to aperture-aperture coincidence imaging (Q2), cascaded gamma photons to slit-slit coincidence imaging (Q3), and the contribution ratio of the single-photon imaging algorithm to the reconstructed image (Q4).

[0116] Based on single-photon information and coincident photon information, the grayscale value of the reconstructed image is obtained according to the multi-information joint image algorithm of MLEM algorithm. The grayscale value of the reconstructed image is obtained by formula (1):

[0117] I 联合 = (Q1 A1) -1 + Q2 A2 -1 + Q3 A3 -1 + Q4 A4 -1 )×M; (1)

[0118] Formula (1) is based on I 联合 = Q1I1 + Q2I2 + Q3I3 + Q4I4 obtained;

[0119] Among them, I 联合 The image grayscale values ​​are obtained based on the maximum likelihood-expectation-maximization algorithm.

[0120] In one specific implementation, the image reconstruction module reconstructs the image grayscale value using the direct back-projection algorithm based on the aperture coincidence γ event and the data collected by the detector ring, as formula (2):

[0121] I 反 =A DOI孔缝 ×A TOF孔缝 ×I 初孔缝 +A DOI孔孔 ×A TOF孔孔 ×I 初孔孔 (2)

[0122] Among them, I 反 The image grayscale value is obtained by the direct backprojection algorithm based on the aperture coincidence γ event;

[0123] A DOI孔缝 When the hole and slit collimator includes both the hole collimator and the slit collimator, the image correction matrix obtained using DOI is used.

[0124] A TOF孔缝 When the hole and slit collimator includes both the hole collimator and the slit collimator, the image correction matrix obtained using TOF is used.

[0125] I 初孔缝 When the aperture collimator includes both the aperture collimator and the slit collimator, the uncorrected grayscale value of the reverse headshot image of the object being detected.

[0126] A DOI孔孔 When the aperture collimator is only a aperture collimator, the image correction matrix obtained using DOI is used.

[0127] A TOF孔孔 When the aperture collimator is only an aperture collimator, the image correction matrix obtained using TOF is used.

[0128] I 初孔孔 When the aperture collimator is only an aperture collimator, the grayscale value of the uncorrected reverse headshot image of the object being detected.

[0129] The specific principles are as follows:

[0130] 1) A real-time image reverse projection algorithm combining DOI and TOF aperture slits:

[0131] Taking a point O in a real image as an example, let the coordinates of point O in space be (x, y, z);

[0132] Crystal 1 on the detector ring corresponds to aperture collimator 1, where aperture 1 is a point in space, denoted as p.

[0133] For the slit collimator 2 on the detector ring, where the slit 1 is a line in space, it can be represented by the equation l of a straight line.

[0134] At point O, the radioactive nuclide decays, releasing a cascade of gamma photon pairs a1 and a2;

[0135] Point p, which passes through the collimator 1, hits the crystal 1 on the detector ring. Its position in space is point o1 ((x1,y1,z1)), which is a point on the detector image P1.

[0136] a2 passes through the slit l of the collimator 2 and hits the crystal 2 on the detector ring. Its position in space is point o2 ((x2,y2,z2), which is a point on the detector image P2.

[0137] Points o1 and p can form a line L;

[0138] Point o2 and line l can form a surface S;

[0139] Clearly, line L and plane S are not parallel, and their intersection point is O;

[0140] The coordinates O(x, y, z) of point O in space can be obtained using geometric mathematics.

[0141] At this point, an uncorrected reverse headshot image I of the detected object can be initially obtained. 初孔缝 .

[0142] 2) Obtain the image correction matrix A using DOI. DOI孔缝 :

[0143] In the cascaded gamma photon pairs a1 and a2, a1 hits detector crystal 1 at a depth of d1, and a2 hits detector crystal 1 at a depth of d2. This allows for a more accurate determination of the detected photon's position and the remaining energy of the photon upon impact with the detector. This is then combined with the image correction matrix A. TOF孔缝 The image can be re-collimated using a collimator, and it can be determined whether the photon struck the wedge-shaped wall of the collimator (as shown in the figure). The specific position of the photon when passing through the collimator can be determined based on its energy. Therefore, the position of the new cascaded gamma photon pair can be calculated using the back-projection method. Combining this with the Monte Carlo method, calculations can be performed at each point within the field of view to obtain the image correction matrix A, which includes DOI information. DOI孔缝

[0144] like Figure 10 Because photons hitting the wedge wall have a certain probability of passing through the collimator, but their energy will be attenuated (if the energy is too small after attenuation, it may not be able to reach the detector). At this time, the position of the photon passing through the collimator is not point p.

[0145] Finally, the grayscale value of the reverse image of the detected object is I. 反孔缝 =A DOI孔缝 ×ATOF孔缝 ×I 初孔缝

[0146] A real-time image grayscale value algorithm combining DOI and TOF aperture matching is used for reverse projection.

[0147] 3) Similarly, I 反孔孔 =A DOI孔孔 ×A TOF孔孔 ×I 初孔孔

[0148] Real-time back-projection algorithm based on DOI and TOF

[0149] 4) Using the Monte Carlo method, The final grayscale value of the real-time back-projected image is obtained:

[0150] I 反 =I 反孔缝 +I 反孔孔 =A DOI孔缝 ×A TOF孔缝 ×I 初孔缝 +A DOI孔孔 ×A TOF孔孔 ×I 初孔孔 .

[0151] The specific principle of this integrated imaging and diagnostic system is as follows:

[0152] Detector ring: A scintillation crystal (lanthanum bromide crystal substrate) is used to detect photons emitted by radiopharmaceuticals in the human body, converting the detected high-energy gamma rays into a large number of low-energy light signals. A photomultiplier tube converts the light signals into electrical signals and transmits them to the electronics module (ASIC). In the electronics module (ASIC), the coincidence module processes the electrical signals, identifies cascaded coincidence gamma photon pairs, and emits the detected coincidence photons as a pair of signals. The signals are then classified and processed by the processor and functional circuits. Finally, the processed signals are sent to the computer (image reconstruction module) for image reconstruction according to the algorithm. After the image reconstruction is performed on the electrical signals, the distribution of the labeled bioactive substances is finally obtained.

[0153] For the ASIC: A SiPM (photomultiplier tube) is placed between the ASIC and the lanthanum bromide crystal substrate. The photomultiplier tube is a Hamamatsu S14161-3050AS-08 SiPM array, which converts the optical signal into an electrical signal. The SiPM connects to the PETsys ASIC module, and the readout signal is transmitted to the FEM / D board via an HQCD flexible flat cable. The FEB / D board is equipped with a Kintex 7 FPGA, which receives data from the TOFPET2 ASIC through the FEM and sends it to the DAQ, and conversely, receives signals from the DAQ and distributes them to the ASIC. The ASIC chip (model: PETsys Electronics TOFPET2 ASIC chip) performs readout processing on the SiPM signal. The SiPM readout device used in this example is a PETsys system. The ASIC reads the signal from the fast SiPM and digitizes it. The readout system includes the following: FEM board, FEB / D board, GbE module board, and DAQ module (in the computer). These are assembled together to form a complete and scalable data acquisition system, creating a readout system with tens of thousands of SiPM channels. PETsys has a complete software system that can run on computers with a 64-bit Linux operating system, used to configure the system and process data generated by ASICs.

[0154] This method proposes a spatiotemporal coincidence imaging approach based on aperture collimation and coincidence detection. It can collimate and coincide with cascaded gamma photon pairs, directly locating the decay position of nuclides for real-time imaging. This approach offers short imaging time and avoids the shortcomings of traditional nuclear medicine image reconstruction. Compared to traditional single-photon imaging, cascaded photons provide more imaging information, thus improving image quality and significantly increasing the signal-to-noise ratio. This patented cascaded gamma photon coincidence imaging system can be combined with a high-performance lanthanum bromide (LaBr3) detector or quantitative image reconstruction algorithms, resulting in significantly improved imaging performance compared to SPECT. This patent has promising industrialization prospects and can be further integrated with therapeutic applications for further research and optimization, showing great application potential. Cascaded gamma photon coincidence imaging can achieve high-quality real-time imaging, contributing to the development of therapeutic integration.

[0155] The following points need to be explained:

[0156] (1) The accompanying drawings of the embodiments of the present invention only involve the structures involved in the embodiments of the present invention. Other structures can refer to the general design.

[0157] (2) For clarity, the thickness of layers or regions is enlarged or reduced in the drawings used to describe embodiments of the invention, i.e., these drawings are not drawn to scale. It is understood that when an element such as a layer, film, region or substrate is referred to as being “above” or “below” another element, the element may be “directly” located “above” or “below” the other element or there may be intermediate elements.

[0158] (3) Where there is no conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other to obtain new embodiments.

[0159] The above are merely specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. The scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A cascaded imaging diagnostic and therapeutic integrated system, characterized in that, include: The frame is a hollow regular prism; A slot collimator is installed on the inner side wall of the frame; A detector ring, mounted on the outer wall of the rack, is used for cascaded coincident gamma photon and single-photon data acquisition, and for determining cascaded coincident gamma photon pairs according to a time window; A base, on which the sidewalls of the frame are mounted; When the live object to be detected is transferred into the cavity of the frame, the detector ring images the target position in the live object through the aperture collimator. The living organism to be detected carries a drug containing a nuclide that supports the emission of cascaded photons, and the detector ring is connected to the host computer. The detector ring carries functions such as coincidence, depth of action information, and time of flight. The host computer has a built-in image reconstruction module, which is connected to the detector ring. The image reconstruction module is based on the maximum likelihood-expectation maximization algorithm, the direct back projection algorithm of the aperture coincidence γ event, and the data collected by the detector ring. It uses a multi-data joint image algorithm to reconstruct the image grayscale value. The image reconstruction module, based on the maximum likelihood-expectation-maximization algorithm and the data acquired by the detector loop, employs a multi-data joint image algorithm to reconstruct the image grayscale values, including: The grayscale value M of the image is obtained based on the lanthanum bromide crystal substrate of the detector ring; Let A1 be the system transfer matrix for cascaded gamma photon pair aperture coincidence imaging; Let the system transfer matrix of cascaded gamma photon pair aperture coincidence imaging be A2; Let the system transfer matrix of cascaded gamma photon pair slit coincidence imaging be A3; Let the system transfer matrix for single-photon imaging be A4; Using the Monte Carlo method, we obtained the contribution ratios of cascaded gamma photons to aperture-slit coincidence imaging (Q1), cascaded gamma photons to aperture-aperture coincidence imaging (Q2), cascaded gamma photons to slit-slit coincidence imaging (Q3), and the contribution ratio of the single-photon imaging algorithm to the reconstructed image (Q4). Based on single-photon information and coincident photon information, the grayscale value of the reconstructed image is obtained according to the multi-information joint image algorithm of MLEM algorithm. The grayscale value of the reconstructed image is obtained by formula (1): I 联合 = (Q1 A1) -1 + Q2 A2 -1 + Q3 A3 -1 + Q4 A4 -1 (×M; (1)) Among them, I 联合 The image grayscale values ​​are obtained based on the maximum likelihood-expectation-maximization algorithm.

2. The cascaded imaging diagnostic and therapeutic integrated system according to claim 1, characterized in that, The frame is a regular decagonal prism, and the detector ring includes ten detector plates. One detector plate is installed on the outer circumference of the frame.

3. The cascaded imaging diagnostic and therapeutic integrated system according to claim 2, characterized in that, The hole and slit collimator includes: a hole collimator and a slit collimator; On any two adjacent inner sidewalls of the frame, a hole collimator is installed on one sidewall and a slot collimator is installed on the other sidewall; or, The hole alignment device includes: a hole alignment device, which is installed on each inner sidewall of the frame; or, The slot alignment device includes a slot alignment device, which is installed on each inner sidewall of the frame.

4. The cascaded imaging diagnostic and therapeutic integrated system according to claim 3, characterized in that, The detector board includes: a lanthanum bromide crystal substrate, a photomultiplier tube, and an ASIC; A lanthanum bromide crystal substrate is mounted on the rack, and the ASIC is mounted on the side of the lanthanum bromide crystal substrate facing away from the rack; The photomultiplier tube is installed between the ASIC and the lanthanum bromide crystal substrate, and the photomultiplier tube is connected to the ASIC.

5. The cascaded imaging diagnostic and therapeutic integrated system according to claim 4, characterized in that, The nuclides that support the emission of cascaded photons include: lutetium-177, indium-111, iodine-131, copper-6, gallium-67, and selenium-75.

6. A method of using a cascaded imaging diagnostic and therapeutic integrated system, characterized in that, The cascaded imaging diagnostic and therapeutic system described in claim 5 includes: After injecting a drug containing a nuclide that supports the emission of cascaded photons into the living organism to be tested, the living organism to be tested is pushed into the cavity of the gantry; In the cascaded photon pair in the living organism to be detected, one photon is projected onto the corresponding lanthanum bromide crystal substrate through the aperture collimator, and the other photon is projected onto the corresponding lanthanum bromide crystal substrate through the slit collimator. The lanthanum bromide crystal substrate converts the received photons into optical signals, and the photomultiplier tube converts the optical signals into electrical signals, which are then transmitted to the corresponding ASIC. The ASIC processes the received electrical signals, finds the information of the same pair of cascaded gamma photons based on the time window, and locates the nuclide decay position in real time based on the information of the same pair of cascaded gamma photons to obtain the image of the target position in the living body to be detected. The host computer has a built-in image reconstruction module, which is data-connected to the detector ring. The image reconstruction module reconstructs the image grayscale values ​​based on the maximum likelihood-expectation-maximization algorithm and the data collected by the detector ring, using a multi-data joint image algorithm. or, The image reconstruction module reconstructs the image grayscale values ​​based on the direct back-projection algorithm of the aperture coincident γ event and the data collected by the detector ring.

Images