NL2035216B1 - alpha spectrometry detector - Google Patents
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- NL2035216B1 NL2035216B1 NL2035216A NL2035216A NL2035216B1 NL 2035216 B1 NL2035216 B1 NL 2035216B1 NL 2035216 A NL2035216 A NL 2035216A NL 2035216 A NL2035216 A NL 2035216A NL 2035216 B1 NL2035216 B1 NL 2035216B1
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- 238000004611 spectroscopical analysis Methods 0.000 title claims abstract description 39
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/16—Measuring radiation intensity
- G01T1/24—Measuring radiation intensity with semiconductor detectors
- G01T1/247—Detector read-out circuitry
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/29—Measurement performed on radiation beams, e.g. position or section of the beam; Measurement of spatial distribution of radiation
- G01T1/2914—Measurement of spatial distribution of radiation
- G01T1/2964—Scanners
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/36—Measuring spectral distribution of X-rays or of nuclear radiation spectrometry
- G01T1/366—Measuring spectral distribution of X-rays or of nuclear radiation spectrometry with semi-conductor detectors
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- Health & Medical Sciences (AREA)
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Abstract
The present invention relates to an alpha spectrometry detector for measuring one or more characteristics of radiation particles received from a radioactive sample undermtest, which sample is comprised in a radiopharmaceutical, said detector comprising: detector means comprising a pixelated detector comprising a two dimensional array of detector pixels sensitive to said radiation particles received from said sample; a readout circuit in electric communication with said detector means, arranged to readout each pixel of said array, and wherein said readout circuit is arranged to generate, based on said readout of each of said detector pixels, a charge pattern for each hit of a radiation particle on said detector means, said charge pattern comprising spatial data, temporal data and energy deposited for each detector pixel of said array; spectroscopic analyser means in electric communication with said readout circuit to receive each charge pattern generated by said readout circuit, wherein said spectroscopic analyser means are arranged for match said charge pattern with a database of charge patterns to identify a corresponding alpha particle of said sample.
Description
Title: alpha spectrometry detector
The present invention relates to an alpha spectrometry detector.
Alpha spectrometry detectors are used in alpha radionuclide therapy.
Alpha radionuclide therapy, also known as alpha particle therapy, is a type of targeted radiation therapy that utilizes alpha particles to treat certain types of cancer. It involves the administration of radionuclides that emit alpha particles to selectively destroy cancer cells while aiming to minimizing damage to surrounding healthy tissues.
Alpha particles are high-energy particles consisting of two protons and two neutrons, essentially the nucleus of a helium atom. They have a large mass and a positive charge, which gives them high linear energy transfer (LET) characteristics.
Due to their size and charge, alpha particles have a short range in tissue and deposit a large amount of energy along their path, making them highly effective in damaging cancer cells.
Radionuclides used in alpha radionuclide therapy are chosen based on their ability to emit alpha particles. These radionuclides can be produced artificially or obtained from natural sources. Commonly used alpha-emitting radionuclides include
Actinium-225 (Ac-225), Radium-223 (Ra-223), and Bismuth-213 (Bi-213). These radionuclides are typically attached or bound to targeting molecules, such as antibodies or peptides, to specifically deliver them to cancer cells.
The radionuclides are combined with specific targeting molecules that have an affinity for cancer cells. These targeting molecules can recognize and bind to specific receptors or antigens present on the surface of cancer cells, allowing the alpha-emitting radionuclides to be delivered directly to the tumour sites. This targeted approach minimizes damage to healthy tissues and maximizes the radiation dose to cancer cells.
When the alpha-emitting radionuclides decay, they emit alpha particles that deposit their energy within a short distance in the surrounding tissue. This localized energy deposition causes significant DNA damage in the targeted cancer cells, leading to cell death. Additionally, the high LET characteristics of alpha particles can induce bystander effects, where neighbouring cancer cells are also affected by radiation-induced damage.
Alpha radionuclide therapy can be administered through various routes, depending on the specific radionuclide and cancer type. It can be given intravenously, as an injection or infusion, or directly targeted to specific tumour sites using techniques such as radioimmunotherapy. The treatment is usually performed in specialized centers by trained medical professionals.
Alpha radionuclide therapy has shown promise in the treatment of certain cancers, such as metastasised tumours, particularly those with limited treatment options or resistant to conventional therapies. The highly localized and potent radiation delivered by alpha particles offers the potential for effective tumor control while minimizing damage to healthy tissues. Ongoing research and clinical trials aim to further refine this therapy and expand its applications in cancer treatment.
A promising radioisotope for this therapy is 225Ac which is a part of a decay chain having daughter radionuclides that also emit alpha radiation making it very potent with a total of four alpha particles. This decay unfortunately also has a downside, the emission of the alpha particles also results in breaking of the chemical bond holding the alpha emitter to the molecule targeting the cancer cells, which can result in many adverse side effects. This breaking of bonds due to the alpha emission as well as the destructive power of the alpha particles themselves can also destroy the radiopharmaceutical, therefore it is of great importance to perform quality control tests (e.g., accurate measurement of the activity) as fast as possible and just before administering in the patient.
It is an object of the present invention to provide a device that is able to reduce the time to perform the quality control activity measurements from hour(s) to minutes making the treatment four times more efficient and with that saving costs and be able to treat more patients. The device should be able to enables fast and very accurate measurement of the activity of 225Ac.
In a first aspect, there is provided, an alpha spectrometry detector for measuring one or more characteristics of radiation particles received from a radioactive sample under test, which sample is comprised in a radiopharmaceutical, said detector comprising: - detector means comprising a pixelated detector comprising a two dimensional array of detector pixels sensitive to said radiation particles received from said sample; - a readout circuit in electric communication with said detector means, arranged to readout each pixel of said array, and wherein said readout circuit is arranged to generate, based on said readout of each of said detector pixels, a charge pattern for each hit of a radiation particle on said detector means, said charge pattern comprising spatial data, temporal data and energy deposited for each detector pixel of said array; - spectroscopic analyser means in electric communication with said readout circuit to receive each charge pattern generated by said readout circuit, wherein said spectroscopic analyser means are arranged for match said charge pattern with a database of charge patterns to identify a corresponding alpha particle of said sample.
Alpha spectrometry detectors may be comprised of several components, at least comprising a detector, a circuitry arranged for readout of the detector and means to perform spectroscopic analysing.
The detector means is the component of the system responsible for detecting and capturing radiation particles from the sample under test. The detector means consists of a pixelated detector, which is a type of detector that is subdivided into small discrete units called detector pixels. Each detector pixel represents a tiny area or element within the detector.
The pixelated detector is arranged in a two-dimensional array, meaning that the detector pixels are organized in rows and columns, forming a grid-like structure. The two-dimensional nature of the array enables the detector to capture information about the position and distribution of the radiation particles across a two- dimensional space.
Each of these detector pixels is sensitive to said radiation particles received from the sample. This means that the detector pixels are designed or configured to respond to the radiation particles emitted or transmitted by the sample under examination. They are capable of detecting and converting the energy or interaction of the radiation particles into measurable signals or electrical signals that can be further processed and analyzed.
By utilizing a two-dimensional array of detector pixels, the detector means can provide detailed spatial information about the radiation particles detected from the sample.
The readout circuit is an electronic circuit that is connected to the detector means, allowing it to communicate with and retrieve information from each pixel of the detector array. It is thus arranged for of reading out the signals generated by individual detector pixels.
The readout circuit generates a charge pattern for each instance when a radiation particle interacts with the detector means, when a signal is being produced in one or more detector pixels. This charge pattern represents the spatial information, temporal information, and energy deposition associated with the interaction of the radiation particle.
The spatial data is the position or location of the hit within the detector array. It provides information about which specific detector pixel(s) were affected by the radiation particle. 5 The temporal data defines the timing or sequence of the interaction. It records when the radiation particle hit occurred, allowing for the tracking of the chronological order of events. Hence, the temporal data can also be considered a time stamp.
The energy deposited is the amount of energy transferred from the radiation particle to the detector pixel(s) during the interaction. It quantifies the energy loss or absorption resulting from the particle's impact, providing valuable information about the characteristics of the radiation.
By combining the spatial data, temporal data, and energy deposition for each detector pixel, the readout circuit enables the generation of a comprehensive charge pattern for each hit of a radiation particle. This charge pattern captures essential information about the location, timing, and energy deposition associated with the particle's interaction, facilitating subsequent analysis, interpretation, and processing of the collected data.
The spectroscopic analyzer means is connected to the readout circuit, allowing it to receive the charge patterns generated for each hit of a radiation particle.
Its primary function is to analyze these charge patterns and extract relevant information.
The spectroscopic analyzer means is arranged to compare or "match" the received charge patterns, e.g. with a pre-existing database of known charge patterns.
The database may also be implemented otherwise, for example in the form of a list having charge patterns or a derivative thereof. To this end, the analyzer means may comprise a storage to store the database or the list. This database (or list) preferably contains a collection of charge patterns that correspond to alpha particles present in the sample, such that the analysis can be performed.
The purpose of this matching process is to identify the corresponding alpha particle based on the similarity or correlation between the received charge pattern and the patterns in the database. By comparing the characteristics and features of the charge pattern with those stored in the database, the spectroscopic analyzer means can determine the specific alpha particle that caused the observed charge pattern.
This matching process may involve implementation of one or various algorithms or techniques that assess the similarity between the received charge pattern and the patterns in the database. It may include statistical analysis, pattern recognition algorithms, or machine learning methods to find the best match.
Once a match is found, the spectroscopic analyzer means can provide information about the identified alpha particle, such as its energy, intensity, or other relevant properties. This identification process enables the characterization and analysis of the alpha particles present in the sample under investigation, facilitating the understanding and interpretation of the spectroscopic data obtained from the detector system.
Known spectrometers may have a high sensitivity but have a low throughput, which is a major drawback. This is not the only drawback as known spectrometers also typically require an expert to interpret the results. Typically, the sample is liquified and dried on a metal plate before being placed into a vacuum chamber in which a single-channel detector can perform the analysis on the sample.
Changing samples and potential contamination of the vacuum chamber are time- consuming, making these devices unsuitable for use in many application amongst which hospitals.
The presented alpha spectrometer is arranged for high-throughput use in for example hospitals, which allow a rapid quality check of radiopharmaceuticals right after the production and just before treatment of patients. The presented spectrometer does not require a vacuum chamber since the detector means is a semiconductor based pixelated detector. Due to the absence of the vacuum chamber, rapid sample changes are possible and contamination of the chamber and sample is less likely.
The presented spectrometer is a radiation detector which is preferably implemented as a semiconductor integrated circuit chip, and more preferably as an
Application Specific Integrated Circuit, ASIC. The chip preferably has a matrix of at least 32x32 radiation-sensitive pixels, and more preferably at least a 64x64 array, even more preferably at least a 128x128 array and most preferably an array of 256x256 pixels or higher.
The detector is arranged to record the incoming particle and its energy deposition, temporal data or arrival time, and the spatial data or the index number of the respective pixels, and retrieve this data simultaneously on an event basis, to generate a charge pattern.
The detector may preferably be calibrated prior to use, for example by correcting for pixel-to-pixel variations and/or temporal data or timing of the recording.
The detector may preferably be comprised of a silicon sensor, a top layer to block or enhance light sensitivity, a layer of pixel contacts below the silicon and a matrix of solder bumps in accordance with the matrix of pixel contacts to the semiconductor chip in which the readout circuit is comprised to readout all pixels and for further analysis.
In an example, the detector comprises a timepix3 sensor or the like.
The proposed detector has a matrix or array of pixels, which do not require a vacuum chamber and thus do not have the corresponding disadvantages of known spectrometry detectors which have vacuum chambers. Moreover, the detector is multi- channel due to the pixelized array, which, in comparison with the single-channel detector, enables high-throughput. The detector is also able to generate the data (charge profile) on an event basis instead of a frame basis, which is also beneficial.
In an example, said spectroscopic analyser means is further arranged to match said charge pattern with a database of charge patterns to identify a corresponding beta particle of said sample.
In an example, said spectroscopic analyser means is further arranged to match said charge pattern with a database of charge patterns to identify corresponding alpha and preferably beta particles for generating an alpha and preferably beta spectrum of said sample.
The analyzer means may be configured to have patterns or derivatives corresponding to not only alpha particles, but may also be configured for beta or gamma particles, depending on the application and intended use of the detector.
In an example, said readout circuit is arranged for continuous readout of each pixel.
The detector may be read-out on frame-based manner, on an event-based manner and/or may be arranged to be readout continuously.
In an example, said charge pattern generated by said readout circuit is arranged for comprising pixel coordinates, time of arrival and time over threshold data for detector pixel of said array.
In an example, said readout circuit is arranged for filtering said energy deposited in said charge pattern, wherein said filtering comprises pixel grouping to generate charge peaks in said pattern with high contrast.
To further enhance the acquired data, the detector and more particularly, the readout circuit or the detector means itself, may further comprise a filter or filters.
The filter or filters may be arranged to remove background noise, for example from high beta and gamma radiation. The filter may also be arranged to enhance the contrast for example by grouping certain pixels to generate a charge peak with high contrast to neighbouring pixels.
In an example, said spectroscopic analyser means comprises a programmable logic device.
In an example, a programmable logic device is a Field Programmable
Gate Array, FPGA, arranged for matching said charge pattern with a database of charge patterns to identify a corresponding alpha particle of said sample.
To improve processing of the spectroscopic analyser means, they may comprise a programmable logic device such as an FPGA. An FPGA may improve performance significantly such that real-time or near-real-time analysis can be performed. Moreover, embodying the analyser means into an FPGA is very power efficient, allows reconfiguration and has many more advantages.
In an example, said FPGA is configured for one or more functions of noise filtering, signal amplification, baseline correction, and data formatting, and wherein one or more of these functions are implemented into said FPGA as one or more logic circuits.
In an example, said FPGA is configured for one or more functions of data transformation, event identification, particle tracking, and wherein one or more of these functions are implemented into said FPGA as one or more logic circuits.
In an example, said FPGA is configured for performing pattern recognition to determine one or more characteristics of each charge pattern as a particle event, by identing each particle's spatial data, temporal data and energy deposited and wherein the pattern recognition function is implemented into said FPGA as one or more logic circuits.
In an example, wherein said detector further comprises: - a collimator for directing said radiation particles from said radioactive sample under test, towards said detector means.
In an example, said collimator is positioned in front of said detector means, and is comprised of an alpha particle vacuum collimator arranged to restrict the passage of said radiation particles and direct particles towards the pixels of the array of the pixelated detector.
In an example, said collimator is a 3D printed collimator.
In an example, said collimator comprises a plurality wave guides, preferably having plural guides per pixel or more preferably having of the array of the pixelated detector.
In an example, said collimator is a collimator system, further comprising one or more of lenses, filters and gratings to enhance resolution by path definition said radiation particles onto said pixels of the array of the pixelated detector.
With a collimator each pixel may be comprised of a plurality of parallel channels to guide the alpha particles onto each pixel. The collimator may provide one or more of improved spatial resolution, enhanced contrast, reduced noise and background interference, increased dynamic range, precise imaging geometry, and selective radiation detection. By effectively controlling the radiation incident on the sensor pixels, a collimator optimizes the sensor's performance, resulting in high- quality imaging, accurate measurements, and improved overall sensitivity in various imaging and detection applications.
In an example, the collimator further comprises vacuum means comprising a vacuum port in communication with each of said vacuum channels and arranged for connecting a vacuum pump to generate a vacuum in said particle channels of said collimator during use of said particle sensor device.
In an example, the collimator is configured as a two-dimensional array comprising a plurality of particle channels arranged to guide particles from an input face to an output face of said collimator, said output face of said collimator being arranged to be disposed onto an active area of said particle sensor device, and wherein said collimator further comprises vacuum means comprising a vacuum port in communication with each of said vacuum channels and arranged for connecting a vacuum pump to generate a vacuum in said particle channels of said collimator during use of said particle sensor device.
In an example, a surface area of said collimator input face is larger than a surface area of said collimator output face.
In an example, the channels have a tapered configuration, narrowing from said input face towards said output face of said collimator.
In an example, the collimator has a number of channels corresponding to a number of pixels of a particle sensor on which said collimator is used, and wherein each of said plurality of channels is aligned with a single pixel of said particle sensor.
In an example, the vacuum port comprises an appendage for controlling air in and out of said collimator.
In an example, the vacuum means comprise a valve.
In an example, the valve is a one-way valve configured to maintain said vacuum in said channels.
In an example, the vacuum means comprise a plurality of vacuum channels connecting the vacuum port with each of the particle channels of the collimator.
In an example, the vacuum channels are disposed transversely onto said channels of said collimator.
In an example, the collimator is comprised of a material having low outgassing properties to minimize contamination and maintain the vacuum within the particle channels.
In an example, the collimator is comprised of thermoplastic material.
In an example, the thermoplastic material is selected in accordance with particles to be detected by said particle sensor device, and in particular, wherein said selection is based on an enhanced particle reflection.
In an example, the collimator is manufactured by three-dimensional additive printing.
These and other aspects of the present disclosure will be elucidated further with reference to the attached figures. In these figures:
Figure 1 schematically shows an embodiment of an alpha spectrometry detector according to an aspect of the present disclosure;
Figure 2 shows an example of a 3D plot of a charge pattern generated by an alpha spectrometry detector according to an aspect of the present disclosure;
Figure 3 shows an example of a 2D plot of a charge pattern comprising visualized alpha particles generated by an alpha spectrometry detector according to an aspect of the present disclosure.
Figure 1 schematically shows an embodiment of an alpha spectrometry detector 1 according to an aspect of the present disclosure. The alpha spectrometry detector 1 is arranged for measuring one or more characteristics of radiation particles 3 received from a radioactive sample 5 under test. The radioactive sample 5 is comprised in a radiopharmaceutical, for example used in alpha radionuclide therapy for treating cancer that has metastasised in the body.
The alpha spectrometry detector 1 comprises detector means 7, a readout circuit 11, a spectroscopic analyser means 13 and a collimator 17.
The detector means 7 comprise a pixelated detector 9 comprising a two dimensional array of detector pixels 9x y sensitive to the radiation particles 3 received from the radioactive sample 5, wherein the radiation particles 3 can comprise alpha particles, beta particles and/or gamma particles. The detector means 7 are arranged to record the incoming radiation particles 3 and its energy deposition, temporal data or arrival time, and the spatial data or the index number of the respective pixels 9x,v, and retrieve this data simultaneously on an event basis, to generate a charge pattern 21x.y.
The detector means 7 are implemented as an Application Specific
Integrated Circuit, ASIC, comprising a 256x256 pixilated event mode detector chip with a pixel size of 55 um, for example a timepix3 sensor, and are calibrated prior to use, for example by correcting for pixel-to-pixel variations and/or temporal data or timing of the recording.
The readout circuit 11 is in electric communication with the detector means 7, integrated into the detector chip which turns every individual 55 um pixel in single event readout detector with few ns timeline. The readout circuit 11 is arranged to continuous readout each pixel 9x vy of the array. The readout circuit 11 is arranged to generate, based on the readout of each of the detector pixels 9x v, a charge pattern 21x vy for each hit of a radiation particle 3 on the detector means 7. The charge pattern 21x y comprises spatial data, temporal data, energy deposited, pixel coordinates, time of arrival and/or time over threshold data for each detector pixel 9x vy of the array.
Continuous readout of each pixel 9xy enables real time analysis of the radiation particles 3. The readout circuit 11 is furthermore arranged for filtering the energy deposited in the charge pattern 21x v, wherein the filtering comprises pixel grouping to generate charge peaks in the pattern 21x y with high contrast.
The spectroscopic analyser means 13 are in electric communication with the readout circuit 11 and are arranged to receive each charge pattern 21x vy generated by the readout circuit 11. The spectroscopic analyser means 13 are further arranged for matching the charge pattern with a database of charge patterns to identify corresponding alpha particles, beta particles and/or gamma particles of the sample 5, for generating an alpha, beta and/or gamma spectrum of the sample 5.
The spectroscopic analyser means 13 comprises a programmable logic device 15, wherein the programmable logic device 15 is a Field Programmable Gate
Array, FPGA. The FPGA is arranged for matching the charge pattern 21x vy with a database of charge patterns to identify corresponding alpha particles, beta particles and/or gamma particles of the radioactive sample 5 under test. The matching process involves implementation of one or various algorithms or techniques that assess the similarity between the received charge pattern 21x y and the patterns in the database, for example by statistical analysis, pattern recognition algorithms, or machine learning methods to find the best match.
The FPGA is configured for one or more functions of noise filtering, signal amplification, baseline correction, data formatting, data transformation, event identification, particle tracking, and wherein one or more of these functions are implemented into the FPGA as one or more logic circuits. Furthermore, the FPGA is configured for performing pattern recognition to determine one or more characteristics of each charge pattern 21xy as a particle event, by identing each particle's spatial data, temporal data and energy deposited and wherein the pattern recognition function is implemented into the FPGA as one or more logic circuits.
The collimator 17, for example a 3D printed collimator, is arranged for directing the radiation particles 3 from the radioactive sample 5 under test, towards the detector means 7. The collimator 17 is positioned in front of the detector means 7, and is comprised of an alpha particle vacuum collimator arranged to restrict the passage of the radiation particles 3 and direct the radiation particles 3 towards the pixels 9x y of the array of the pixelated detector 9.
The collimator comprises a plurality wave guides, and can furthermore comprise one or more of lenses, filters and gratings to enhance guiding the radiation particles 3 onto the pixels 9x v of the array of the pixelated detector 9. The collimator may have guides as small as 1/10 of the pixel size for subpixel spatial resolution or 40 times larger for coarse spatial resolution but with high intensity and good energy resolution.
Figure 2 shows an example of a 3D plot of a charge pattern 21xv generated by an alpha spectrometry detector 1 according to an aspect of the present disclosure. The z-axis shows a measure of energy deposited in the individual pixel 9x y in relation to the respective pixel 9x vy in the detector plane defined by the x-axis and y-axis. Different types of particles give very distinct patterns, such as the spread, shape and ns timing, as can be seen by the patterns of alpha particles 23, gamma particles 25, beta particles 27 and muon particles 29. One or various algorithms or techniques are arranged to assess the similarity between the received charge pattern 21x y and the patterns in the database to identify the alpha particles.
Figure 3 shows an example of a 2D plot of a charge pattern 21xy comprising visualized alpha particles generated by an alpha spectrometry detector 1 according to an aspect of the present disclosure. The data 31 is obtained from a timepix3 sensor wherein the individual spots represent the individual alpha hits determined by the algorithm, wherein the sample 5 under test are two kidneys of a mouse that was treated with a radiopharmaceutical.
Claims (17)
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PCT/NL2024/050347 WO2025005801A1 (en) | 2023-06-29 | 2024-06-28 | Alpha spectrometry scanner |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US5812191A (en) * | 1994-06-01 | 1998-09-22 | Simage Oy | Semiconductor high-energy radiation imaging device |
US20200049607A1 (en) * | 2014-11-12 | 2020-02-13 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Particle Emission Tomography |
EP3659513B1 (en) * | 2017-06-05 | 2021-08-11 | General Electric Company | Methods for improving imaging by sub-pixel calibration |
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US11955250B2 (en) * | 2021-08-30 | 2024-04-09 | Vladimir Kochergin | Porous silicon charged particle, X-ray, gamma-ray and/or thermal neutron collimators and methods of manufacturing the same |
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US5812191A (en) * | 1994-06-01 | 1998-09-22 | Simage Oy | Semiconductor high-energy radiation imaging device |
US20200049607A1 (en) * | 2014-11-12 | 2020-02-13 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Particle Emission Tomography |
EP3659513B1 (en) * | 2017-06-05 | 2021-08-11 | General Electric Company | Methods for improving imaging by sub-pixel calibration |
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