Methods and technologies for gamma-ray imaging

Abstract

A coded sensor gamma imager module includes a scintillation crystal layer for detecting photons and a spatial-encoding sensor element positioned above the scintillation crystal layer. The spatial-encoding sensor element includes scintillator material arranged to form a nonuniform structure in at least one dimension above the scintillation crystal layer providing coded-aperture functionality and having at least one outer edge.

Description

METHODS AND TECHNOLOGIES FOR GAMMA-RAY IMAGINGCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S.Provisional Patent Application No. 63 / 673,518, filed July 19, 2024, which is hereby incorporated by reference in its entirety .BACKGROUND

[0002] The field relates generally to imaging devices, systems, and methods. Some aspects of this disclosure relate generally to devices, systems and methods of gamma-ray imaging. Some aspects of the is disclosure relate to devices, systems, and methods of Single-Photon Emission Computed Tomography (SPECT) and more specifically of Coded Sensing Single-Photon Emission Computed Tomography (CS-SPECT) , which, in at least some embodiments, may be designed to guide and optimize application of alpha particle-emitting radiopharmaceutical therapy (aRPT) . Some aspects are directed to gamma cameras for gamma ray imaging

[0003] Over 50% of cancer patients receive radiation treatment in some form in the course of disease management. This is a staggering number given the 1.7 million new cases a year in the U.S. Therapies in the form of X-ray orproton therapy, or implanted as brachytherapy, can eradicate or provide long-term control for primary disease in many common cancers . In the metastatic setting however, highly ef fective conventional radiotherapy is mostly limited to palliative applications . An emerging class of internal radiotherapies using radiolabeled molecules that are systemically administered and locali ze to sites of disease have generated intense academic, industrial and clinical excitement .

[0004] aRPT is an emerging internal radiotherapy that sparks signi ficant interest due to the advantages of densely ioni zing track and a short path length of only several cells . Alpha particles are highly potent and shows more ef ficacy than conventional external beam therapy . Other benefits of aRPT such as imperviousness to resistance and independence of oxygenation make it superior to standard therapy in terms of systemically administered radiotherapies . Of particular interest are aRPT that deposit highly cytotoxic MeV doses along a length scale o f only several cells . This provides ablating doses to cancer cells , while sparing adj acent normal tissues . Thus , aRPT overcomes several limitations of conventional radiotherapies . Many investigational aRPTs are in late-stage development and clinical trials . RaC12 is one example approved aRPT , providing a survival benefit for men with bone metastatic castration-resistant prostate . Beyond RaC12 , there is even greater interest in molecularly targetedagents ( antibody and small molecule based) , with strong pre- and clinical data with alpha-emitting radioisotopes that include : Pb, Ac, Th, At and Tb .

[0005] Systemically administered RPT present opportunities but also great challenges . aRPT is typically hindered by limited information of quantitative radionuclides distribution, which is needed for dose assessment , treatment monitoring and drug development . Compared to conventional conformal external beam therapy, aRPT distributes throughout the patient , accumulates to unknown levels at sites of disease and in radiosensitive vital organs . This whole-body distribution means that measures of drug distribution to assess absorbed doses in the patient extend far beyond a pre-defined treatment field . The use of biopsy to measure uptake values with RPTs has been limited and beyond blood sampling, is nearly nonexistent for background organs . This lack of information of aRPT distribution is a critical problem that 1 ) confounds treatment monitoring, 2 ) complicates dose and schedule personali zation and 3 ) impedes drug development . Quantitative determination of in vivo distribution of these radionuclides is analogous to treatment planning for conventional radiation oncology and may benefit the aRPT landscape .

[0006] Photons generated upon decay of aRPTs can be captured by gamma cameras through planar scintigraphy . Thisnon-quantitative assessment is currently sometimes used for evaluation of aRPT distribution . However, this method suffers from inaccuracy caused by organ overlap and background activity, complexity of the decay spectra, and the energy values detected . SPECT uses a gamma camera to provide tomographic images of radioactivity distribution in 3D . It has been widely used to diagnose and monitor cardiac, neurological and oncologic patients . However, known gamma camera typically use lead or tungsten collimators to select gamma rays that meet speci fic spatial and directional information for image formation . The maj ority of gamma rays ( in at least some cases , more than 99% ) are rej ected by the collimator through absorption . This rej ection of a maj ority of gamma rays is practically a rej ection of a large amount of information contents . For diagnostic procedures , the administered radioactivity levels are high enough that the rej ection of a large amount of the gamma rays by the coll imator does not generally pose a problem . Levels in aRPT administered activities , however, are two to three orders of magnitude lower than those used with diagnostic procedures . This presents a di f ficulty for the quantitative accuracy of SPECT when imaging aRPT because the much more limited amount of information available is being rej ected by the collimator at a very high rate ( e . g . , >99% ) .

[0007] In recent years , numerous approaches have been proposed for the next-generation SPECT systems with improved sensitivity, such as multi-pinhole SPECT scanner, micro-slit and micro-ring collimators , coded-aperture-based SPECT imaging, and Compton imaging . Apart from collimator optimi zation, there is also growing interest in solid-state detectors such as CZT and CdTe . CZT detectors of fer excellent energy resolution thus can identi fy gamma-rays from alpha emitters that often have complex decay schemes . However, CZT based detectors are often thinner than scintillator based detectors due to cost and signal integrity . As a result , they have typically not improved the sensitivity of SPECT signi ficantly .

[0008] Despite all the ef forts above , SPECT systems that rely on heavy metal collimation to encode directional information in the detected gamma-rays have not improved the sensitivity of SPECT by orders of magnitude to address the specific challenges for imaging aRPT . Therefore , quantitative imaging of alpha radionuclides remains challenging, and SPECT technologies with sensitivity suf ficient for reliable , accurate , and precise reporting of activity distribution under these ultra-low count rate imaging conditions (which level of sensitivity may be referred to herein as "ultrasensitive" as compared to " sensitive" or "highly sensitive" known systems ) are needed . The ability toresolve heterogeneous distribution of aRPT uptake in vivo may allow accurate quanti fication of radiation dosimetry in radiosensitive critical organs as wel l as uptake of aRPTs to the target lesions . The therapeutic index of such treatments may thus be optimi zed for each patient , facilitating the goal of precision medicine for image-guided dose selection for maximum ef ficacy .

[0009] This background section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure , which are described and / or claimed below . This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure . Accordingly, it should be understood that these statements are to be read in this light , and not as admissions of prior art .BRIEF SUMMARY

[0010] One aspect of the disclosure is a coded sensor gamma imager module including a scintillation crystal layer for detecting photons and a spatial-encoding sensor element positioned above the scintillation crystal layer . The spatial-encoding sensor element includes scintillator material arranged to form a nonuni form structure in at least one dimension above the scintillation crystal layer providingcoded-aperture functionality and having at least one outer edge .

[0011] According to another aspect of the disclosure , a system for coded sensor gamma imager singlephoton emission computed tomography ( CSGI-SPECT ) includes one or more coded sensor gamma imager ( CSGI ) modules configured for detecting one or more emitted photons without using a heavy metal collimator and a computer device in communication with the one or more CSGI modules . Each CSGI module including a spatial-encoding sensor element providing gamma-ray collimation and coded-aperture functionalities . The computer device includes at least one processor in communication with at least one memory device . The at least one processor is programmed to : receive output data from the one or more CSGI modules , and reconstruct an image based on the received output data .

[0012] Another aspect of this disclosure is a method for coded sensor gamma imager single-photon emission computed tomography ( CSGI-SPECT ) . The method includes positioning a coded sensor gamma imager ( CSGI ) module to receive gamma photons , collimating the received gamma photons using a spatial-encoding sensor element comprising scintillator material arranged to have at least one outer edge and an interior pinhole aperture , detecting the gamma photonsthat pass through the pinhole aperture with a scintillation crystal layer positioned below the spatial-encoding sensor element, outputting, to a computing device, data on the gamma photons that pass through the pinhole aperture and are detected by the scintillation crystal layer, and reconstructing, by the computing device, an image based at least in part on the data output to the computing device.

[0013] Various refinements exist of the features noted in relation to the above-mentioned aspects. Further features may also be incorporated in the above-mentioned aspects. These refinements and additional features may exist individually or in any combination. For instance, various features discussed below in relation to any of the illustrated embodiments may be incorporated into any of the above-described aspects, alone or in any combination.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The following figures illustrate various aspects of the disclosure.

[0015] Fig. 1 is a system for performing coded sensor gamma imager (CSGI)-SPECT imaging.

[0016] Fig. 2 is a simplified block diagram of a computing device that may be used in the system of Fig. 1.

[0017] Fig. 3A is a top view of an example CSGI module for use in the system of Fig. 1.

[0018] Fig. 3B is a cross-section view along the line A-A of the CSGI module shown in Fig. 3A.

[0019] Fig. 4A is an isometric view of another example CSGI module.

[0020] Fig. 4B is a simplified cross-sectional view of the CSGI module shown in Fig. 4A taken along the X axis as viewed from the Y direction in Fig. 4A.

[0021] Fig. 4C is the simplified cross-sectional view of Fig. 4B with the paths of example photons shown as dashed arrows and indicating detection events.

[0022] Fig. 5 is a simplified view of six scintillation crystals of a portion of a coded sensor (CS) element for the gamma camera module of Figs. 4A-4C.

[0023] Fig. 6 is a gamma ray distribution on a sidewall of the CSGI module of Figs. 4A-4C.

[0024] Fig. 7 shows gamma-rays undergoing Compton scattering followed by photoelectric interaction in the CSGI module of Figs. 4A-4C.

[0025] Fig. 8A is the five types of crystal columns used to construct an example CSGI module.

[0026] Fig. 8B is a top view of an example CSGI module constructed using the five types of crystal columns shown in Fig. 5A.

[0027] Fig. 9A is a prototype CSGI module and readout circuitry.

[0028] Fig. 9B is the prototype CSGI module of Fig. 9A mounted in a housing.

[0029] Fig. 10 is an analytical model of the system response function of a prototype CSGI module, where a representative scintillation crystal at rd is irradiated by a point source located at rO.

[0030] Fig. 11 is a map of histograms of energy ratio measured by the 64 crystal columns when an example CSGI module of Fig. 9B was irradiated by a Na-22 source.

[0031] Fig. 12 is energy ratio histograms from different radioactive sources: Na-22, Tc-99m, Lu-177, and Pb- 212 as detected by the five different types of crystal columns shown in Fig. 8A.

[0032] Fig. 13 graphically presents the energy spectra of top and bottom cuboids in an example crystal column of type B in an example CSGI module.

[0033] Fig. 14 is the sensitivity images of the three subsets of detectors in a CSGI module in Fig. 4A: (a) a bottom camera, (b) spatial-encoding sensors, and (c) side wall detectors. The surface plots are calculated using the system model in Fig. 10 while the Monte Carlo simulation results are presented as symbols overlaid on the surface plots.

[0034] Fig. 15 is a phantom used for testing imaging using an example CSGI module of the present disclosure.

[0035] Fig. 16 is a transverse view of a 3D reconstructed image of the phantom of Fig. 15 acquired using an example CSGI module.

[0036] Fig. 17 is another phantom used for additional testing of imaging using an example CSGI module of the present disclosure.

[0037] Fig. 18 are reconstructed images of the phantom of Fig. 17 acquired using an example CSGI module and a traditional clinical SPECT system.

[0038] Corresponding reference characters indicate corresponding parts throughout the drawings.DETAILED DESCRIPTION

[0039] This disclosure relates generally to imaging devices, systems, and methods. Some aspects of thisdisclosure relate generally to devices, systems and methods of gamma-ray imaging. Some aspects of the is disclosure relate to devices, systems, and methods of Single-Photon Emission Computed Tomography (SPECT) and more specifically of Coded Sensor gamma imager Single-Photon Emission Computed Tomography (CSGI-SPECT) , which, in at least some embodiments, may be designed to guide and optimize application of alpha particleemitting radiopharmaceutical therapy (aRPT) . Some aspects are directed to gamma cameras for gamma ray imaging

[0040] Fig. 1 is a system 100 for performing CSGI-SPECT imaging in a radiopharmaceutical therapy environment 105 in accordance with at least one embodiment.

[0041] In the exemplary embodiment, a patient 110 has a plurality of organs 115, where one or more of the organs 115 are radio sensitive. The patient 110 also has one or more tumors 120. The one or more tumors 120 are being treated with an alpha particle-emitting radiopharmaceutical therapy (a- RPT) , which is shown in Fig. 1 dispersed through the patient 110 after administration as a-RPT 125. The a-RPT 125 emits alpha (a) particles, which are absorbed by the surrounding tissue, and gamma (y) -ray photons 130, which exit the patient's body. A CSGI module 135 (also referred to sometimes herein as a sensing collimator imager or SCI) detects the Y-raY photons 130. The CSGI module 135 is coupled to a computer system 145for receiving data from the CSGI module 135 and performing the calculations described herein to detect the location of the a- RPT 125 based on the detected y-ray photons 130 and to reconstruct an image based on the data received from the CSGI module. Although a single CSGI module 135 is shown, the CSGI- SPECT system 100 may include more than one CSGI module 135. In some embodiments, the gamma CSGI 135 is be coupled to the computer system 145 via one or more readout circuit 140. In other embodiments, suitable readout circuitry is incorporated in the CSGI module 135 and separate readout circuitry 140 may not be needed.

[0042] In some embodiments, the CSGI-SPECT system 100 includes, or is in communication with a computed tomography (CT) device 150. The CT device 150 may be a CT machine or CT scanning machine. The CT device 150 provides scans of the patient, or item being imaged, to allow the system 100 to determine where on the patient's body the photons originated. In some embodiments, the computer system 145 controls the CT device 150 to produce the scans of the patient.

[0043] Turning to Fig. 2, an example configuration of a computing device 200 that may be used as the computing device 145 and / or any other computers, computing device, controllers, or the like described herein is shown. The computing device 200 includes a processor 202, a memory204, a media output component 206, an input device 210, and communications interfaces 212. Other embodiments include different components, additional components, and / or do not include all components shown in Fig. 2.

[0044] The processor 202 is configured for executing instructions. In some embodiments, executable instructions are stored in the memory 204. The processor 202 may include one or more processing units (e.g., in a multicore configuration) . As used herein, the term "processor" refers not only to integrated circuits, but also to a controller, a microcontroller, a microcomputer, a programmable logic controller (PLC) , an application-specific integrated circuit, a graphic processing unit, and other programmable circuits. The memory 204 may generally be or include memory element (s) including, but not limited to, computer readable medium (e.g., random access memory (RAM) ) , computer readable non-volatile medium (e.g., a flash memory) , a floppy disk, a compact disc-read only memory (CD-ROM) , a magneto-optical disk (MOD) , a digital versatile disc (DVD) and / or other suitable non-transitory memory elements and is generally any device allowing information such as executable instructions and / or other data to be stored and retrieved. Such memory 204 may generally be configured to store suitable computer-readable instructions that, when implemented by the processor 202,configure, cause, or program the computing device 200 to perform various functions described herein.

[0045] The media output component 206 is configured for presenting information to user 208. The media output component 206 is any component capable of conveying information to the user 208. In some embodiments, the media output component 206 includes an output adapter such as a video adapter and / or an audio adapter. The output adapter is operatively connected to the processor 202 and operatively connectable to an output device such as a display device (e.g., a liquid crystal display (LCD) , organic light emitting diode (OLED) display, cathode ray tube (CRT) , "electronic ink" display, one or more light emitting diodes (LEDs) ) or an audio output device (e.g., a speaker or headphones) .

[0046] The computing device 200 includes, or is connected to, the input device 210 for receiving input from the user 208. The input device is any device that permits the computing device 200 to receive analog and / or digital commands, instructions, or other inputs from the user 208, including visual, audio, touch, button presses, stylus taps, etc. The input device 210 may include, for example, a variable resistor, an input dial, a keyboard / keypad, a pointing device, a mouse, a stylus, a touch sensitive panel (e.g., a touch pad or a touch screen) , a gyroscope, an accelerometer, a position detector,or an audio input device . A single component such as a touch screen may function as both an output device of the media output component 206 and the input device 210 .

[0047] The communication interfaces 212 enable the computing device 200 to communicate with remote devices and systems , such as allowing communication between the computing device 145 and the CSGI module 135 , the CT device 150 , remote computing devices or servers (not shown) , and the like . The communication interfaces 212 may be wired or wireless communications interfaces that permit the computing device to communicate with the remote devices and systems directly or via a network . Wireless communication interfaces 212 may include a radio frequency (RF) transceiver, a Bluetooth® adapter, a Wi-Fi transceiver, a ZigBee® transceiver, a near field communication (NFC ) transceiver, an infrared ( IR) transceiver, and / or any other device and communication protocol for wireless communication . (Bluetooth is a registered trademark of Bluetooth Special Interest Group of Kirkland, Washington; ZigBee is a registered trademark of the ZigBee Alliance of San Ramon, Cali fornia . ) Wired communication interfaces 212 may use any suitable wired communication protocol for direct communication including, without limitation, USB, RS232 , I2C, SRI , analog, and proprietary I / O protocols . In some embodiments , the wired communication interfaces 212 include a wired network adapter allowing thecomputing device to be coupled to a network, such as the Internet , a local area network ( LAN) , a wide area network (WAN) , a mesh network, and / or any other network to communicate with remote devices and systems via the network . Although two communication devices 212 are shown, the computing device 200 may include more or fewer computing devices .

[0048] It should be understood that in some embodiments the computing device 200 does not include or use an input 210 or a media output 206 and a user 208 may not directly interact with the computing device . Rather, the user 208 ( or another computing device ) may only interact remotely with computing device 200 through the communication interface 212 .

[0049] Moreover, in some embodiments the computing device 200 , or parts thereof , may not be a physical computing device local to the user 208 , but instead is cloud based . Thus , for example , the computing device 145 may be a cloud-based computing device or may be a physical computing device 200 using cloud-based storage for all or part of its memory, using cloud-based processing instead of local processing for some or all of its processing, or the like . Cloud computing is a model of service delivery for enabling convenient , on-demand network access to a shared pool of configurable computing resources ( e . g . , networks , networkbandwidth, servers, processing, memory, storage, applications, virtual machines, and services) that can be rapidly provisioned and released with minimal management effort or interaction with a provider of the service. As used herein, the term "cloud computing" and related terms, e.g., "cloud computing devices" refers generally to a computer architecture allowing for the use of multiple heterogeneous computing devices for data storage, retrieval, and processing. The heterogeneous computing devices may use a common network or a plurality of networks so that some computing devices are in networked communication with one another over a common network but not all computing devices. In other words, a plurality of networks may be used to facilitate the communication between and coordination of all computing devices.

[0050] Figs. 3A and 3B are a simplified diagrams of an example CSGI module 300 that may be used as the CSGI module 135. Fig. 3A is a top view of the CSGI module and Fig. 3B is a cross-section view of the CSGI module along the line A-A in Fig. 3A. The example CSGI module is not drawn to scale and may not include all elements / components (i.e., it is "simplified") . The example CSGI module is cuboid in shape, but other embodiments may have any other suitable shape. The CSGI module 300 is specially designed for higher sensitivity than known gamma cameras used in traditional SPECT imaging generally, and for use in CSGI-SPECT imaging specifically. TheCSGI module 300 does not use a heavy metal collimator as known gamma cameras do . As will be described in more detail below, rather than rej ecting photons with a heavy metal collimator, the CSGI module 300 uses coded sensor element that accepts substantially all photons that interact with it and provides spatial and directional selectivity .

[0051] The CSGI module 300 includes a scintillation crystal layer 302 for detecting photons , a coded sensor element 304 , and sidewalls 310 . In the example embodiment , the scintillation crystal layer is composed of gadolinium aluminum gallium garnet ( GAGG) scintillation crystals . Some embodiments use solid-state detectors such as CZT instead of GAGG scintillation crystals . Other embodiments may use any other suitable scinti llation crystals or detector material such as gadolinium oxyorthosilicate ( GSO) , bismuth germanate (BGO) , cadimium telluride ( CdTe ) , or any materials that can interact with gamma rays and produce detectable signals .

[0052] The coded sensor element 304 is a spatial- encoding element positioned above ( as viewed in Fig . 3B ) the scintillation crystal layer . The coded sensor element also includes scintillator material arranged to form a pinhole lens having an interior pinhole aperture 306 above the scintillation crystal layer and outer edges 308 . Other embodiments may useany other collimation configuration, such as parallel hole or complex coded apertures . Because the example CSGI module is cuboid in shape , it includes four outer edges . In other embodiments , the gamma camera module may have any other suitable shape with any other number of outer edges , including only one outer edge ( in embodiments having a cyl indrical , spherical , or hemispherical shape , for example ) . In additional to the scintillator material , the coded sensor element also includes a non- scintillator material . The non-scintillator material is a non-heavy metal material . In the example embodiment , the non-scintillator, non-heavy metal material is an acrylic material . Other embodiments may use other suitable material such as polycarbonate or other transparent materials that allow light photons generated in the scintillation crystals to be transmitted to the outer surfaces of the CSGI module and be detected by light sensors .

[0053] In the example embodiment , the scintillator material and the acrylic in the coded sensor element 304 are cuboid crystals and are arranged in an alternating pattern in both the X , Y, and Z directions . Thus , when viewed from above as in Fig . 3A and as viewed in cross section as in Fig . 3B, the alternating scintillator material and the acrylic in the coded sensor element would form a checkerboard pattern . In the example embodiment , the assembled scintillator material and acrylic in the coded sensor elementgenerally have similar dimensions when viewed from the directions shown in Figs. 3A and 3B. The spaces 312 and 314 are illustrated unfilled (or filled with the atmosphere that surrounds the CSGI module 300) in the example embodiment. In other embodiments, the spaces 312 and 314 are filled with a non-scintillator , non-heavy metal material. In such embodiments, the pinhole aperture 306 is typically also filled with the non-scintillator, non-heavy metal material. The non- scintillator, non-heavy metal material embodiments that include it in spaces 312 and 314 is any non-scintillator, non- heavy metal material that gamma photons may readily pass through with low probability of interaction. In some embodiments, the spaces 312 and 314 are filled with the same non-scintillator, non-heavy metal material that is used in the coded sensor element 304 (e.g., an acrylic) . Other embodiments use a material that is different than the non-scintillator, non-heavy metal material that is used in the coded sensor element 304. In some embodiments in which signals are readout from the top and bottom, it is preferable to fill both of the spaces 312 and 314 with the same non-scintillator, non-heavy metal material (e.g., the same as is used in the coded sensor element 304) . Embodiments that readout signals from only the bottom may leave the space 314 empty (i.e., filled with air or ambient atmosphere) and fill the space 312 with a non-scintillator, non-heavy metal material (e.g., the same as is used in the coded sensor element 304) .

[0054] Sidewalls 310 are disposed above the scintillation crystal layer 302 and adjacent the outer edges 308 of the coded sensor element 304. Thus, the example CSGI module 300 includes four sidewalls. Other embodiments may include more or fewer sidewalls depending on the shape of the CSGI module and the number of outer edges that the coded sensor element has. Typically, it is desired that each outer edge of the coded sensor element has a sidewall disposed ad acent to it. However, some embodiments may include fewer sidewalls than coded sensor element outer edges. The sidewalls are made of scintillator material. Each sidewall works in conjunction with the coded sensor element (and specifically with the alternately arranged scintillator material and acrylic in the coded sensor element) to function as a coded aperture camera.

[0055] Thus, the CSGI module 300 functions as a pinhole camera and multiple (depending on how many sidewalls 310 are present) coded aperture cameras to detect gamma photons that reach the CSGI module. The CSGI module does this without rejecting (as a standard heavy metal collimator would) most gamma photons that reach it and provides significantly increased sensitivity and additional information as compared to at least some known gamma cameras.

[0056] A more detailed embodiment of a CSGI module according to the present disclosure will now be discussed beginning with reference to Figs. 4A and 4B and CSGI module 400. Similar components will be identified with the same reference numbers as the CSGI module 300 in Fig. 3 and they generally function similarly unless described otherwise.

[0057] Fig. 4A is an isometric view of CSGI module 400 and Fig. 4B is a simplified cross-sectional view of the CSGI module 400 taken along the X axis as viewed from the Y direction in Fig. 4A. Fig. 4C is the CSGI module 400 from Fig. 4B with the paths of example photons shown as dashed arrows and indicating detection events by the scintillation crystals that are used to construct the module 400.

[0058] The CSGI module 400 replaces heavy metal (e.g., lead) with dense, inorganic scintillator material, thereby integrating the collimator as a part of the sensor, contributing more detected photons and hence higher sensitivity to an imaging system. In consideration of the complexity of manufacturing and signal readout, a simplified collimation geometry employing 3x3x3 mm crystal cubes is used. To achieve a preferred tradeoff between sensitivity and resolution, the example CSGI module employs a pinhole structure with checkerboard pattern, denoted as Coded Sensor. The main feature of this structure is that the lower layer of crystalsis collimated by the crystal elements above it, hence each detected photon contains more directional information to decode the location of the source. In general, the design principles behind Coded Sensor Gamma Imager (CSGI) SPECT are: (a) to arrange the crystal cubes in alternating pattern that play the roles of pinhole aperture, coded aperture, and small active sensors 402 (non-scintillator cubes are identified nonshaded in Fig. 4B and identified by reference number 404) ; (b) to incorporate a bottom layer 302 of scintillator crystal that resembles the same geometry and functionality of a pinhole camera; (c) to include four side walls 310 of scintillator to provide information of coded aperture imaging based on the pattern of count distribution on side-wall detector surfaces.

[0059] As can be seen in Fig. 4C, a high percentage of photons whose trajectory intersects the CSGI module 400 will be detected. There are three general grouping for detection: 1) photons detected by the scintillation crystal layer 302, 2) photons detected by the coded sensor element 304, and 3) photons detected by the sidewalls 310. The photons whose trajectory passes through the aperture 306 of the coded sensor element 304 without interacting with the coded sensor element will reach the scintillation crystal layer 302 and be detected by the scintillation material in that layer, similar to the functioning of traditional gamma camera with a heavy metal pinhole collimator. Unlike, known traditional gammacameras, photons whose trajectory intersects the coded sensor element will be either detected by the scintillation material in the coded sensor element itself, or will pass through (because of the alternation between photon transparent, nonscintillator material with the scintillation material) and strike and be detected by the scintillation material in the sidewall 310.

[0060] In addition to functioning as a pinhole camera style collimator for the scintillation crystal layer 302, the coded sensor element 304 itself functions as a detector / sensor . The alternating crystal structure encodes directional information in events detected by the scintillation crystals in the coded sensor element 304. Fig. 5 is a simplified view of six scintillation crystals (numbered 1-6) of a portion of the coded sensor element 304. In the example shown in Fig. 5, detection of a gamma ray by a scintillation crystal #5 is collimated by the detector elements above it (e.g., crystals 2 and 3) . Therefore, photons detected by crystals at the lower layers of the coded sensor (e.g., #4- 6) contain more directional information than those detected at the top layer (e.g., crystals 1-3) .

[0061] The four side walls 310 providing coded aperture imaging in conjunction with the alternating structure of the coded sensor element 304 will be described with respectto Fig. 6. The alternating crystal structure in the coded sensor element and the detectors (e.g., the cuboid scintillation crystal material) in each of the 4 side walls function as a coded aperture camera. Fig. 6 shows the gammaray distribution on the detector surface of the upper sidewalls 310 (as viewed in Fig. 4A) when a Tc-99m point source is placed at (0, -25, 50) mm (assuming the origin is at the center of the coded sensor where the pinhole aperture is in Fig. 4A) . This count distribution exhibits a coded aperture pattern defined by the alternating crystal structure in the coded sensor element 304.

[0062] A further aspect of some embodiments is the functioning of the CSGI module as a Compton camera. Fig. 7 shows gamma-rays undergoing Compton scattering followed by photoelectric interaction in CSGI module 400, which can be utilized for Compton camera imaging.

[0063] Thus, a single CSGI module according to the present disclosure may provide the spatial and directional information from a conventional pinhole collimated gamma camera, a self-collimation camera, four coded-aperture cameras, and a Compton camera; resulting in substantially more counts and information content.

[0064] An example CSGI module 500 was constructed as will be described with reference to Figs. 8A and 8B. Exceptas otherwise described, the CSGI module 500 is similar to the CSGI modules described above. The module 500 consists of five types of crystal columns denoted as A through E in Fig. 8A. These columns exhibit an alternating crystal pattern, comprised of seven types of segments with different dimensions listed in Table 1 below. Cuboids 402 represent GAGG scintillator material, and cuboids 404 are acrylic. The low density acrylic parts serve as both supporting structure and light guides that transport scintillation photons towards top and bottom ends. All crystals and acrylic surfaces are polished. In some embodiments, reflective films (ESR from 3M, 70 pm thick) are applied to the 4 long side surfaces of each detector column to provide optical isolation and to improve light extraction efficiency. Each crystal column is measured 3 mm x 3 mm x 24 mm, forming an 8x8 crystal array shown in top view in Fig. 8B. The letters in Fig. 8B correspond to the column types in Fig. 5A. All these columns are arranged in a specific sequence to be shaped into a pinhole structure, with column D forming the pinhole aperture. Due to readout limitations, this example module was constructed with only two sidewalls, which are composed of columns of the type E.Table 1Material: M=GAGG; N=Acrylic

[0065] Each crystal column is coupled in a 1:1 ratio to a silicon photomultiplier (SiPM) array 600 (S14161- 3050HS-08, Hamamatsu Photonics, Japan) at the top and bottom (i.e., double-ended readout) , as shown in Figs. 9A and 9B . A data acquisition system (DAQ) 602 using a TOFPET2 ASIC (PETSys Electronics, Portugal) enables independent readout of 64 SiPM channels. Scintillation light photons produced in each detector column are read out by two SiPM channels - one on top and one at the bottom. The sum of the 2 signals is proportional to the total energy deposited by the gamma-ray interaction. The location of a gamma-ray interaction within the detector column is determined by the ratio of the two SiPM signals according to (T-B) / (T+B) , where T and B are the intensity of the top and bottom SiPM signal, respectively. The SiPM array 600 and the DAQ 602 collectively form the readout circuitry for the CSGI module. If all four sidewalls were included in the example CSGI module, the module would be a 9x9 crystalcolumn array . However, due to constraints with the available 64 SiPM readout channels , two of the side walls were removed in this example embodiment . This adj ustment does not compromise the functionality of the module which still provides the spatial and directional information from a conventional pinhole collimated gamma camera, a sel f-collimation camera, two coded-aperture cameras , and a Compton camera . Alternatively, any resulting asymmetry can be readily compensated by f lipping the example CSGI module 180 degrees relative to the central axis of the pinhole aperture to acquire additional data from the missing side wal ls . In Fig . 9B, the module 500 and the readout circuitry are mounted in a prototype housing .

[0066] Unlike traditional pinhole collimationSPECT , the point spread function of the CSGI modules of this disclosure ( including module 500 ) are not a simply blurred point-like distribution on a camera surface , but rather, shows more complicated pattern in a three dimensional detector volume . Therefore , a new method for analytical derivation of the system response function is developed . Fig . 10 is an analytical model of system response function, where a representative scintillation crystal ( the mthcrystal ) is irradiated by a point source located at r0within the nthvoxel . To simpli fy the calculation of solid angle , the scintillation crystal is divided into 10 by 10 by 10 sub-crystals . Based onthe assumption that the detector response in one sub-crystal is uniform if sub-crystals are small enough, the (m, n)thelement of system matrix can be derived as:where rmt is the center of ithsub-crystal at mthcrystal, AV is the volume of a sub-crystal,denotes photoelectric coefficient of scintillator, / z is the attenuation coefficient. The exponential term represents for the survival probability of traveling through different materials along the direction

[0067] Monte Carlo simulations were conducted using GATE v9.4 to validate the analytical framework described by equation (1) above. This study used the same geometry configuration and coordinate system as the CSGI module 400 discussed above, which consists of 450 cubic GAGG scintillator components and 198 cubic plastic components. The energy resolution of GAGG scintillator is set as 10% full-width-at- half-maximum (FWHM) for 140 keV gamma rays. Each cubic component measures 3 mm x 3 mm x 3 mm, and the overall dimensions of the detector module are 27 mm x 27 mm x 24 mm.

[0068] The center of the pinhole aperture serves as the origin of the coordinate system. A Tc-99m point sourcewas moved across the XY plane at Z=150 mm, with increments of 3 mm, within a 60 mm x 60 mm imaging field of view (FOV) . The activity of the point source was set as 1 kBq, with an acquisition time of 25 minutes for each location. By summing up photo-electric events detected from all GAGG components corresponding to each source location, a sensitivity image of plane Z=150 mm was generated for one CSGI module. This sensitivity image was then compared with the analytically derived sensitivity image from the system model Eq. (1) above.

[0069] The preliminary tests of the CSGI module 500 using dual-ended readout scheme and ASIC boards in Fig. 9B show the location of gamma ray interaction in the CSGI module 500 and the amount of energy deposition can be resolved successfully for a broad range of gamma ray energies from 70 to more than 511 keV. Fig. 11 is a map of histograms of energy ratio (defined by the difference between the top (T) and bottom (B) SiPM signal intensity divided by the total light collected: (T-B) / (T+B) ) when the example CSGI module 500 in Fig. 9B was irradiated by a Na-22 source. Each GAGG segment contributes a peak to this histogram. For instance, column B comprises two scintillator segments, the energy ratio histogram will display two distinct peaks. The histograms are the distribution of event energy ratio measured by 2 SiPM for each of the 64 detector columns. Gamma rays detected by scintillation crystals 402 in a CSGI module form discreate peaks in theenergy ratio histograms because the scintillation light photons are originated from a discrete scintillator volume that is sandwiched by adjacent acrylic elements to create unique optical transport patterns for each coded sensor element 402. As a result, gamma ray interaction point in a CSGI module can be clearly identified. The side-wall detectors are made of 24mm long GAGG crystals, showing a continuous and broad event distribution in the ratio plots. These ratio plots are used to calibrate the depth-of-interaction (DOI) of a gamma ray as a function of the SiPM signal ratio to create a lookup table for subsequent imaging experiment. Fig. 12 shows energy ratio histograms from different radioactive sources: Na-22, Tc-99m, Lu-177, and Pb-212. In Figs. 11 and 12, the different types of columns discussed above are identified by the same corresponding letters "A"-"E". After re-sorting events based on DOI classifier, the energy spectra of each cuboids show better energy resolution of ~10% for 511 keV photopeak (shown in Fig . 13 ) .

[0070] The sensitivity images of bottom camera 302, coded sensor element 304 (also known as sensing collimator) , and side walls 310 are visualized as surface plots shown in Fig. 14. The object space has 31 x 31 voxels, and each voxel is 2 mm x2 mm in size. The Monte Carlo simulation results, indicated by are overlaid onto surface plots calculated using the system model of Eq. (1) with a grid sizeof 3 mm. Note that the total counts detected by three types of detectors from Monte Carlo simulation were normalized based on the number of decays to calculate the sensitivity. The surface plots match well with Monte Carlo simulation data points, providing validation of the system model.

[0071] A light-tight enclosure was created to house the prototype gamma camera module 500 (Fig.9B) and the module was mounted to a robotic arm to position the CSGI module's center at 15 cm away from a phantom (Fig. 15) containing a total of 101 pCi Tc-99m solution in the three outer chambers. The phantom was rotated through 12 angles spanning 0° to 330° in 30° increments. The total acquisition time was 1 hour. Fig. 16 is a transaxial view of the 3D reconstructed image, demonstrating that all rods are resolved and the spatial resolution reaching or potentially exceeding 6 mm FWHM .

[0072] A phantom (shown in Fig. 17) containing four chambers of rods (3 mm 0, 10 mm H, 20 mm apart) was each filled with 0.12 mCi of Cu-64 solution. Cu-64 is a positron emitting radionuclide and was selected to assess the performance of the prototype CSGI module 500 against a clinical SPECT scanner due to its high y-ray energy at 511 keV, comparable to the 440 keV of Bi-213. First, the phantom was imaged using a clinical dual-head SPECT system (Siemens SymbiaIntevo) equipped with a high-energy general-purpose (HEGP) collimator and a standard-of-care (SOC) body imaging protocol, capturing 64 views at 30 seconds per view. Image reconstruction was performed using an ordered-subset expectation maximization (OSEM) algorithm with 4 subsets, 20 iterations, and a voxel size of 2.4 x 2.4 x 2.4 mm.

[0073] The same phantom was then imaged using the CSGI module 500. Data acquisition was conducted from 7 angles (0° to 180°) at 30° increments, with a total acquisition time equivalent to 32 minutes after accounting for Cu-64 decay. Fig.18 presents the CSGI SPECT images reconstructed in 3D using the maximum likelihood expectation maximization (MLEM) algorithm with a voxel size of 2 x 2 x 4 mm. The images from the CSGI module 500 (identified as "SCI SPECT" in Fig. 18) clearly delineate all rod sources and capture the heterogeneous activity distribution within the phantom, which is not visible in the clinical SPECT images.

[0074] The same phantom was also imaged by the clinical dual-head SPECT camera and the CSGI module 500 for a short acquisition time of 30 seconds each. The results are also shown in Fig. 18. Notably, despite the significant difference in detector size, a single CSGI module 500 detected more photopeak events than the entire clinical dual-head SPECT system under a low dose scenario as shown in Table 2 below.Table 2

[0075] The CSGI module of the present disclosure measure information-rich data. To extract information encoded in measurements from all detector elements, a reconstruction algorithm developed from the system matrix of Equation (1) above. One example such algorithm is a maximum-likelihood expectation-maximization (MLEM) based algorithm that uses measurements from the scintillation material in the coded sensor element 304, the scintillation crystal layer 302, and the side walls 310 to jointly reconstruct isotope distribution. The algorithm models the system geometry, detector physics, and compensates for Poisson noise in the projection data.

[0076] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples areintended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.

[0077] As used herein, the terms "about," "substantially," "essentially" and "approximately" when used in conjunction with ranges of dimensions, concentrations, temperatures or other physical or chemical properties or characteristics is meant to cover variations that may exist in the upper and / or lower limits of the ranges of the properties or characteristics, including, for example, variations resulting from rounding, measurement methodology or other statistical variation.

[0078] When introducing elements of the present disclosure or the embodiment ( s ) thereof, the articles "a", "an", "the" and "said" are intended to mean that there are one or more of the elements. The terms "comprising," "including," "containing" and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements. The use of terms indicating a particular orientation (e.g., "top", "bottom", "side", etc.) is for convenience of description and does not require any particular orientation of the item described.

[0079] As various changes could be made in the above constructions and methods without departing from the scope of the disclosure , it is intended that all matter contained in the above description and shown in the accompanying drawing [ s ] shall be interpreted as illustrative and not in a limiting sense .

Claims

WHAT IS CLAIMED IS :1 . A coded sensor gamma imager module comprising : a scintillation crystal layer for detecting photons ; and a spatial-encoding sensor element positioned above the scintillation crystal layer, the spatial-encoding sensor element comprising scintillator material arranged to form a nonuni form structure in at least one dimension above the scintillation crystal layer providing coded-aperture functionality and having at least one outer edge .2 . The coded sensor gamma imager module of claim 1 , wherein the scintillator material arranged to form a pinhole geometry having an interior pinhole aperture above the scintillation crystal layer and at least one outer edge .3 . The coded sensor gamma imager module of claim 2 , wherein the scintillator material compri ses cuboid scintillator crystals .4 . The coded sensor gamma imager module of claim 3 , wherein the spatial-encoding sensor element further comprises a cuboid, non-scintillator , non-heavy metal material .

5. The coded sensor gamma imager module of claim 4, wherein the cuboid, non-scintillator , non-heavy metal material comprises an acrylic material.

6. The coded sensor gamma imager module of claim 4, wherein the spatial-encoding sensor element comprises a plurality of columns extending upward from the scintillation crystal layer, and the plurality of columns includes at least two different types of columns, each type of column including a different arrangement of cuboid scintillator crystals and cuboid, non-scintillator, non-heavy metal material.

7. The coded sensor gamma imager module of claim 1, further comprising at least one sidewall disposed above the scintillation crystal layer and adjacent the outer edge of the spatial-encoding sensor element.

8. The coded sensor gamma imager module of claim 7, wherein the at least one outer edge of the spatial-encoding sensor element comprises four outer edges, the at least one sidewall comprises four sidewalls, and each sidewall of the four sidewalls is positioned adjacent a different outer edge of the four outer edges.

9. The coded sensor gamma imager module of claim 7, wherein the at least one sidewall comprises scintillator material .10 . The coded sensor gamma imager module of claim 1 , wherein the scintillation material and the scintillation crystal layer comprise gadolinium aluminum gallium garnet ( GAGG) scintillation crystals .11 . The coded sensor gamma imager module of claim 7 , further comprising one or more optical sensors and a readout circuit , the one or more optical sensors and the readout circuit coupled to one or more surfaces of the coded sensor gamma imager module .12 . The coded sensor gamma imager module of claim 11 , wherein signals from the scintillation material and the scintillation crystal layer are read out by the one or more optical sensors and the readout circuit from a single side of the coded sensor gamma imager module .13 . The coded sensor gamma imager module of claim 11 , wherein signals from the scintillation material and the scintillation crystal layer are read out by the one or more optical sensors and the readout circuit from multiple sides of the coded sensor gamma imager module .14 . A system for coded sensor gamma imager singlephoton emission computed tomography ( CSGI-SPECT ) comprising : one or more coded sensor gamma imager ( CSGI ) modules configured for detecting one or more emitted photons withoutusing a heavy metal collimator, each CSGI module including a spatial-encoding sensor element providing gamma-ray collimation and coded-aperture functionalities ; and a computer device in communication with the one or more CSGI modules , wherein the computer device comprises at least one processor in communication with at least one memory device , wherein the at least one processor is programmed to : receive output data from the one or more CSGI modules ; and reconstruct an image based on the received output data .15 . The system of claim 14 further comprising one or more readout circuit , each readout circuit coupled to a di f ferent one of the one or more CSGI modules and the computer device , wherein the output data from each CSGI module is communicated from said CSGI module to the computing device by the readout circuit .16 . The system of claim 14 , wherein each CSGI module comprises : a scintillation crystal layer for detecting photons ;the spatial-encoding sensor element positioned above the scintillation crystal layer, the spatial-encoding sensor element comprising scintillator material arranged to form a nonuni form structure in at least one dimension above the scintillation crystal layer and having at least one outer edge .17 . The system of claim 16 , wherein each spatial encoding sensor element ' s scintillator material comprises cuboid scintillator crystal s and each spatial encoding sensor element further comprises a cuboid, non-scintillator , nonheavy metal material .18 . The system of claim 17 , wherein each spatial encoding sensor element further comprises at least one sidewall comprising scintillator material disposed above the scintillation crystal layer and adj acent the outer edge of the spatial-encoding sensor element .19 . The system of claim 18 , wherein each spatial encoding sensor element includes alternations of the cuboid scintillator crystals and the cuboid, non-scintillator, nonheavy metal material , and each CSGI module ' s at least one sidewall is configured to function as a coded-aperture camera in conj unction with its spatial encoding sensor element .20 . A method for coded sensor gamma imager singlephoton emission computed tomography ( CSGI-SPECT ) comprising :positioning a coded sensor gamma imager ( CSGI ) module to receive gamma photons ; collimating the received gamma photons using a spatial-encoding sensor element comprising scintillator material arranged to have at least one outer edge and an interior pinhole aperture ; detecting the gamma photons that pass through the pinhole aperture with a scintillation crystal layer positioned below the spatial-encoding sensor element ; outputting, to a computing device , data on the gamma photons that pass through the pinhole aperture and are detected by the scintillation crystal layer ; and reconstructing, by the computing device , an image based at least in part on the data output to the computing device .21 . The method of claim 20 , wherein the spatial- encoding sensor element comprises a sidewall comprising scintillator material disposed above the scintillation crystal layer and adj acent the at least one outer edge of the spatial- encoding sensor element , the scintillator material of the spatial-encoding sensor element comprises cuboid scintillator crystals , at least some of the cuboid scintillator crystals are alternated with a cuboid, non-scintillator , non-heavymetal material in the spatial-encoding sensor element , the sidewall and the alternated cuboid scintillator crystals and cuboid, non-scintillator , non-heavy metal material in the spatial-encoding sensor element cooperatively operate as a coded-aperture camera, and the method comprises : detecting gamma photons that reach the sidewall through the alternated cuboid scintillator crystals and cuboid, non-scintillator, non-heavy metal material in the spatial-encoding sensor element ; and outputting, to the computing device , additional data based on the gamma photons that reached the sidewall , wherein reconstructing the image by the computing device comprises reconstructing the image based on the data output to the computing device and the additional data output to the computing device .22 . The method of claim 21 , wherein positioning the CSGI module comprises positioning the CSGI module to receive gamma photons produced by application of alpha particleemitting radiopharmaceutical therapy (aRPT ) .23 . The method of claim 22 , further comprising guiding the aRPT based at least in part on the reconstructed image .

Images