WO2025165895A1 - Robotically-assisted high-throughput scanning of live animals - Google Patents

Abstract

An instrument for high-throughput scanning of live anesthetized animals, incorporating a robotic scanning device, a multi-slot animal loading dock, and an automatically controlled gas anesthesia delivery unit such that: when a subject test animal is present in a slot of said animal loading dock, gas anesthesia is delivered uninterruptedly to said test animal in the loading dock; when said test animal is being manipulated and/or scanned with said robotic scanning device, gas anesthesia is delivered uninterruptedly to said test animal.

Description

ROBOTICALLY-ASSISTED HIGH-THROUGHPUT SCANNING OF LIVE ANIMALS

[0001] This application is a non-provisional of and claims priority to U.S. Provisional Patent Application No. 63/626,325 filed January 29, 2024, the entire disclosure of which is incorporated herein by reference.

[0002] This application includes material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent disclosure, as it appears in the Patent and Trademark Office files or records, but otherwise reserves all copyright rights whatsoever.

[0003] FIELD

[0004] The invention relates to the field of imaging of live anesthetized animals.

[0005] BACKGROUND

[0006] Non-invasive imaging of live animals is extensively used in veterinary, development and characterization of small animal models of human disease, and in discovery and evaluation of new therapeutics during pre-clinical studies. Magnetic resonance imaging (MRT), nuclear imaging (PET, SPECT), computed tomography (CT), ultrasound (US), optical imaging (fluorescence, FLI and bioluminescence, BLI), and thermoacoustic imaging (TAI) are examples of those imaging technologies providing anatomical, physiological, and molecular information on the studied animal. However, with the exception of optical imaging, those said technologies employ sequential scanning of individual subjects (scanning imagers) and currently cannot be used in high-throughput (HT) setting, which requires less than 12 minutes of total imaging time per animal, and more typically about 3-4 minutes per animal, including set up, load/unload, and scanning. An example of a HT setting is a longitudinal preclinical study of a therapeutic effect of a new drug, which is performed on an animal cohort of 15-20 individual subjects, the entire cohort needs to be interrogated within 1 hour time frame. Non-high-throughput (non-HT) imaging technologies are mostly used when time of a procedure is not a critical resource, for example in testing research hypotheses and conducting small-sample studies.

[0007] For example, well-established, cheap, and convenient rodent models of human disease currently represent the golden standard and the first step of in vivo preclinical studies. Development, characterization, and use of such models requires high-throughput whole body functional and molecular imaging techniques with high-resolution anatomical referencing. There are no commercial or research scanning imagers that can provide the required high-throughput whole body assessment of animal models.

[0008] Gas anesthesia is commonly used in the animal imaging. A non-HT scanning imaging instrument requires an anesthetized and restrained animal to be manually set in the scanner, adjusted for best imaging, and then, after the scan is complete, removed and replaced with another animal. Those overhead imaging processes now typically take extra 10-20 minutes per each scanned animal. A high-throughput imaging device should minimize that overhead imaging time to no longer than 2-3 minutes.

[0009] Thermoacoustics is a physical phenomenon that is manifested by conversion of electromagnetic energy absorbed by matter into broadband ultrasound waves (TA waves). Those TA waves can be measured at a single point or at multiple spatial locations by transducers, and then converted into parameters, signals or images (TAI) informing on the spatial and temporal distribution of electromagnetic energy absorbed inside the matter. Some particular types of thermoacoustics, which are used in biology and medicine include photoacoustics or optoacoustics (visible and infrared light is used for excitation), microwave acoustics (millimeterrange wavelengths of electromagnetic energy), and X-ray acoustics.

[0010] SUMMARY

[0011] In an embodiment, we disclose a critical component of a device enabling a scanning imaging instrument for high-throughput interrogation of live animals. Such critical component integrates an automatically controlled gas anesthesia delivery system, an anesthesia-enabled and scanning-enabled robot (a high-throughput animal scanner), and an animal loading dock (with a plurality or at least one animal loading position) in such a way that: (1) prior to the scan each animal in the loading dock is resting under gas anesthesia delivered through its specific slot in the loading dock, (2) the robot picks an animal from the loading dock, and at that time the gas anesthesia switches on for delivery to the animal through the robot and switches off at the loading dock slot, where the subject is picked from, (3) the robot is then performs the required scanning imaging procedure of the anesthetized animal, (4) the robot returns the subject animal to its slot in the loading dock, and the anesthesia delivery switches back from the robot to the loading dock slot, allowing the subject animal to remain under the uninterrupted gas anesthesia for the entire time of the robotically-assisted operation of the scanning imaging system, (5) finally, if more than one animal subject has to be scanned and is present in the loading dock, the steps (1 )-(4) are then repeated. The high-throughput animal scanner can be optionally upgraded with controlled heating of the animal loading dock, monitoring of the animal’s vital parameters, and an intravenous delivery unit. Such device can have a transformative impact on the entire field of animal imaging, enabling high-throughput routines for a variety of existing and future scanning imaging instruments.

[0012] In an embodiment of the high-throughput animal scanner, we disclose a particular implementation utilizing a robotic arm designed to pick the anesthetized animal and move it in 3D space without constraints (allowing for up to three-degrees of rotation and up to three- degrees of translation of the animal subject). The robotic arm also performs presenting, precise positioning, and controlled movement (a combination of translation and rotation) of the subject animal within a scanning imaging modality according to an imaging protocol of that said imaging modality with accuracy and precision sufficient to use the data collected from the sensors of the robotic arm (such as positioning, angles, speed, acceleration, time of the events, etc), synchronized with the data collected from the sensors of the said imaging modality, for reconstruction of the anatomical, physiological, or molecular images of the interrogated animal. [0013] In an embodiment, we disclose various configurations of robotically-assisted high- throughput scanning imaging of anesthetized live animals, using the disclosed high-throughput animal scanner in combination with a single scanning imaging modality, a multimodality imager, or a plurality of animal scanning imagers. The said scanning imaging modalities could be represented by magnetic resonance imaging (MRI), nuclear imaging (PET, SPECT), computed tomography (CT), ultrasound (US), scanning optical imaging, thermoacoustic imaging (TAI), any other scanning imaging modality or any multimodality combination of said scanning imaging modalities.

[0014] In an embodiment we disclose a high-throughput scanning imager combining a robotic arm based high-throughput animal scanner with a thermoacoustic imaging modality.

[0015] BRIEF DESCRIPTIONS OF THE DRAWINGS

[0016] The foregoing and other objects, features, and advantages of the invention will be apparent from the following more particular description of preferred embodiments as illustrated in the accompanying drawings, in which reference characters refer to the same parts throughout the various views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating principles of the invention. The disclosed embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings in which like references indicate similar elements.

[0017] FIG. 1 shows an example of a workflow in a high-throughput photoacoustic imaging system.

[0018] FIG. 2 demonstrates a concept of a high-throughput multimodality imaging system using photoacoustic and fluorescence imaging technologies.

[0019] FIG. 3 is a top-view diagram showing one of the ways to arrange some of the components of a high-throughput multimodality imaging system using photoacoustic and fluorescence imaging technologies with respect to positions of the system operator.

[0020] FIG. 4 illustrates one of the possible implementations of an automatically controlled gas anesthesia delivery system within a high-throughput animal scanner.

[0021] FIG. 5 illustrates one of the possible implementations of an anesthesia-enabled and scanning-enabled robot with an externally routed anesthesia line.

[0022] DETAILED DESCRIPTION

[0023] The following description and drawings are illustrative and are not to be construed as limiting. Numerous specific details are described to provide a thorough understanding. However, in certain instances, well-known or conventional details are not described in order to avoid obscuring the description. References to one or an embodiment in the present disclosure are not necessarily references to the same embodiment, and such references mean at least one.

[0024] Reference in this specification to “an embodiment” or “the embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least an embodiment of the disclosure. The appearances of the phrase “in an embodiment” in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Moreover, various features are described which may be exhibited by some embodiments and not by others. Similarly, various requirements are described which may be requirements for some embodiments but not other embodiments.

[0025] The present invention is described below with reference to block diagrams and operational illustrations of methods and devices that enable high-throughput scanning of live animals. It is understood that each block of the block diagrams or operational illustrations, and combinations of blocks in the block diagrams or operational illustrations, may be implemented by means of analog or digital hardware and computer program instructions. These computer program instructions may be stored on computer-readable media and provided to a hard-core or soft-core processor of a general purpose computer, special purpose computer, field- programmable gate array (FPGA), ASIC, or other programmable data processing apparatus, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, implements the functions/acts specified in the block diagrams or operational block or blocks. In some alternate implementations, the functions/acts noted in the blocks may occur out of the order noted in the operational illustrations. For example, two blocks shown in succession may in fact be executed substantially concurrently or the blocks may sometimes be executed in the reverse order, depending upon the fiinctionality/acts involved. [0026] As used herein, the following terms and phrases shall have the meanings set forth below. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art.

[0027] As used herein, the term, "a" or "an" may mean one or more. As used herein "another" or “other” may mean at least a second or more of the same or different elements or components thereof. The terms "comprise" and "comprising" are used in the inclusive, open sense, meaning that additional elements may be included. As used herein, the term “or” refers to “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive.

[0028] As used herein, the term “about” refers to a numeric value, including, for example, whole numbers, fractions, and percentages, whether or not explicitly indicated. The term “about” generally refers to a range of numerical values (e.g., ± 25% of the recited value unless explicitly stated otherwise) that one of ordinary skill in the art would consider approximately equal to the recited value (e.g., having the same function or result). In some instances, the term “about” may include numerical values that are rounded to the nearest significant digit.

[0029] The term “animal models” refers to animals and other live organisms, which are typically used in biomedical research to learn various aspects of animal biology, study diseases and pathological conditions, and develop novel therapeutic agents, methodologies, and interventional medical procedures.

[0030] The term “biomedical imaging” refers to various techniques and processes of creating visual representations of the interior of an animal’s or human’s body for biological or medical research, diagnostics, therapy or intervention. Examples include: thermoacoustic imaging, fluorescence imaging, bioluminescence imaging, ultrasound, magnetic resonance imaging, computed tomography, X-ray imaging, nuclear imaging.

[0031] The term “image” refers to a 2D or 3D representation of an object, part of an object or collection of objects; static or recorded and played as a function of time (movie or video).

[0032] The term “internal structure” refers to certain features of animal’s anatomy visualized by a particular biomedical imaging technique. Examples: bones, internal organs, blood vessels, tissue layers, cavities, lumens.

[0033] The term “photoacoustic imaging”, or “photoacoustic tomography” or “PAT” refers to a method of biomedical imaging of an interrogated optically absorbing region by means of illuminating the region with nanosecond-range optical pulses, detecting the resulting ultrasound (photoacoustic) stress waves at a variety of known locations around the region, and using the temporal or spectral profiles of the detected PA waves in mathematical tomographic image reconstruction procedure allowing to solve the inverse problem of PA wave propagation and restore original location and magnitude of the induced PA sources.

[0034] The term “vital parameters” refers to parameters and characteristics pertinent to and identifying a live body, which can be measured or visualized. Examples: body temperature, breathing, heart rhythm.

[0035] Specifically, the embodiment shows a way to enable high-throughput high-resolution whole body 3D molecular imaging by integrating robotic scanning and photoacoustic tomography (PAT). In that embodiment, the high-throughput, which is adequate for a single time point (1 hr) assessment of a large animal cohort (at least 20 animals), is enabled via fully automated robotic process of loading/unloading and scanning studied animals. The total scanning imaging time per animal is reduced down to 3 minutes or less, including 2 minutes loading/positioning/unloading and 1 minute for photoacoustic tomographic scanning with multiwavelength laser excitation. The embodiment (Figure 2) utilizes accurate, reliable, and easily programmable robotic arm (1) (e.g. from Olympus Controls) speeding up and automating the scans and animal load/unload processes. Prior to imaging, each animal from the study group is anesthetized with gas anesthesia and restrained in the holder (cassette) (3). The cassette is inserted into the computer-controlled loading dock (4) accommodating up to 5 animals at a time. Once inserted to the dock, the cassette activates the anesthesia valve directing a controlled mixture of anesthesia gas (e.g. isoflurane) and oxygen to the animal’s breathing cap. Excess anesthesia gas is removed by forced downdraft through a screen located below the animal (e.g. a mouse) in the dock. Once the animal is selected for the scan, the cassette is pushed up by a solenoid plunger (5) and its head terminal is presented to be picked by the robotic arm with a magnetic gripper and internally or externally routed gas anesthesia delivery channel. A rubber bellow (2) at the tip of the robotic arm maintains a seal for the anesthesia gas delivered from the arm to the cassette. The robot then transports the animal into the imaging chamber, performs the required multiwavelength imaging scan, and returns it back to the loading dock. The robot is programmed to repeat this procedure or perform a different individual procedure for each animal in the loading dock. The operator can replace each scanned animal with a new one from the studied cohort, without interrupting this automatic imaging process, achieving the imaging throughput of >20 animals per hour. The robot performs accurate scans (in this case logs angular and linear coordinates and corresponding time stamps) with speeds up to 60 rpm moving in one direction or with a reverse, enabling future real-time 3D functional and molecular imaging (up to 1 volume per second). The UR type robot proposed in this design has force feedback sensors and will pause its operation upon mechanical interference providing extra safety and reliability. The system will use isoflurane for gas anesthesia with a standard vaporizer connected to a valve block, regulating the flow and relaying the gas to the induction chamber, the five ports of the loading dock, and the robotic arm. Sensors at each port will determine if a cassette is present and automatically direct flow towards that location.

[0036] A high-throughput PAT system can be equipped with a microcontroller unit to interface with peripheral hardware devices to integrate communication and control of these devices with a high-throughput data acquisition software.

[0037] In a high-throughput PAT device shown in Figure 2 the animal slots of the loading dock are set to one of two vertical positions by utilizing linear actuators. When a linear actuator is retracted, its sample is in close proximity to the heated surface of the loading dock and the airway of the sample, if applicable, is coupled to the anesthesia line corresponding to the appropriate loading dock position. When the linear actuator is extended, the sample is momentarily decoupled from anesthesia and the heated surface, but the back of the sample holder is exposed and available for pickup by the robot arm, where anesthesia flow is resumed. [0038] A 6 degree-of-freedom robot arm (Universal Robots UR3e) is used in the example shown in Figure 2. The robot arm features anesthesia routing to deliver anesthesia to animals while they are coupled to the robot arm. This is a critical function as it keeps the animals continuously anesthetized during the imaging scan and transfer from/to the loading dock. An emergency stop function could be also implemented in the control software for halting any active robotics operations.

[0039] Control of anesthesia delivery can be managed by electronically controlled valves on a manifold block and adjusting the flow rates through manual flow meters for the flow paths to the loading dock and through a Festo VEMD proportional flow control valve for the flow path to the robot arm. The proportional flow valve ensures that the target flow rate applied by the microcontroller is maintained for all conditions and positions of the scanned animal. The relative anesthesia concentration can be manually adjusted at the vaporizer. The vaporizer output is connected to the manifold which contains separate output lines for each loading dock position, the robot arm, and an induction chamber.

[0040] A high-throughput scanning imaging instrument may be optionally equipped with additional sensors. Examples of important external sensors include sensors of vital parameters and environmental temperature sensors. A sensor of vital parameters is used for evaluation of vital signs and physiological conditions of the interrogated animal. Some examples include: (a) camera, which allows visual observation of the animal, its motion, and breathing during an imaging scan; (b) breathing monitor, which may be a pressure or flow sensor incorporated into an anesthesia/breathing line and measuring variations associated with breathing of the interrogated animal; (c) electrocardiography unit, allowing to monitor heart activity; (d) body temperature monitor; (e) pulse oximeter, measuring oxygenation levels of arterial blood. Environmental temperature sensors, like thermocouples, provide continuous temperature readings from outside of the interrogated animal.

[0041] A high-throughput scanning imager or any of its components can be further configured for communication with a processing unit (Processor), which processes acquired data and uses the processed data to reconstruct images of the interrogated object. In such configuration the Processor can be physically integrated with the entire instrument and communicate using a local protocol (e.g. USB 2.0, USB 3.0, USB Type-C, PCI Express, FireWire or Ethernet). Alternatively, the instrument can communicate with a Processor remotely using, for example, TCP/IP or other remote communication protocol. The Processor can be further configured to communicate with a display unit (Display) providing visualization of the reconstructed images. Examples of the Display include a 2D or a 3D monitor, a mobile device or a virtual reality system. The Display may be also a remote terminal communicating with the Processor over a TCP/IP or other remote communication protocol.

[0042] In an embodiment, the invention provides an instrument for scanning of live anesthetized animals that incorporates a robotic scanning device, a multi-slot animal loading dock, and an automatically controlled gas anesthesia delivery unit. The instrument is constructed and programmed such that when a subject test animal is present in a slot of the said animal loading dock, the gas anesthesia is being delivered uninterruptedly to that animal in the loading dock. When a subject test animal is being manipulated and/or scanned with the said robotic scanning device, the gas anesthesia is being delivered uninterruptedly to that animal. When the robotic scanning device picks up an animal from its slot in the loading dock, the gas anesthesia delivery switches from its loading dock channel to the channel integrated within the robotic scanning device with the switching time not exceeding 5 (five) seconds. When the said robotic scanning device returns an animal to its slot in the loading dock, the gas anesthesia delivery switches from the channel integrated within the robotic scanning device to the gas anesthesia channel of the said loading dock channel with the switching time not exceeding 5 (five) seconds. The robotic scanning device can be programmed such that it can sequentially manipulate and scan 5 (five) or more animals per hour, enabling a high-throughput animal scanning procedure.

[0043] The instrument can integrate one or more animal imaging devices such that their imaging acquisition procedures are synchronized with the operation of the high-throughput scanner, enabling a high-throughput animal imaging procedure. Integrated means arranged spatially within the same facility (room). The operation of the high-throughput scanner is coordinated and synchronized with the operation of the imaging device, such that the imaging device is using positional, timing and other data and metadata from the high-throughput scanner, which is required for reconstruction of subject images using the data from the sensors and the detectors provided by the imaging device. The imaging device can use thermoacoustic, optoacoustic, photoacoustic, X-ray acoustic, or any essentially similar imaging technology to produce images of each scanned animal.

[0044] The imaging device can use magnetic resonance imaging (MRI), or any essentially similar imaging technology to produce images of each scanned animal. The imaging device can use nuclear imaging technology such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), or any essentially similar imaging technology to produce images of each scanned animal. The imaging device can use X-ray imaging, computed tomography (CT), or any essentially similar imaging technology to produce images of each scanned animal. The imaging device can use ultrasound imaging, or any essentially similar imaging technology to produce images of each scanned animal. The imaging device can use optical imaging, fluorescence imaging, bioluminescence imaging, or any essentially similar imaging technology to produce images of each scanned animal. The imaging device can be configured for multimodality imaging using any combination of the above imaging technologies to produce images of each scanned animal.

[0045] The robotic scanning device disclosed herein can utilize a robotic arm designed to pick the anesthetized animal and move it in 3D space without constraints, allowing for up to 3 (three) degrees of freedom in rotation and up to 3 (three) degrees of freedom in translation of the animal subject. This can be further configured by integrating one or more animal imaging devices such that their imaging acquisition procedures are synchronized with the robotic arm movement and positioning, enabling a high-throughput animal imaging procedure, wherein the robotic arm also performs presenting, precise positioning, and controlled movement (a combination of translation and rotation) of the subject test animal within the imaging device according to an imaging protocol of that said imaging device with accuracy and precision sufficient to use the data collected from the sensors of the robotic arm (such as positioning, angles, speed, acceleration, time of the events, etc.), synchronized with the data collected from the sensors and the detectors of the said imaging device, for reconstruction of the anatomical, physiological, or molecular images of the interrogated animal.

[0046] At least some aspects disclosed can be embodied, at least in part, in software. That is, the techniques may be carried out in a special purpose or general purpose computer system or other data processing system in response to its processor, such as a microprocessor, executing sequences of instructions contained in a memory, such as ROM, volatile RAM, non-volatile memory, cache or a remote storage device. Functions expressed in the claims may be performed by a processor in combination with memory storing code and should not be interpreted as meansplus-function limitations.

[0047] Routines executed to implement the embodiments may be implemented as part of an application, operating system, firmware, ROM, middleware, service delivery platform, SDK (Software Development Kit) component, web services, or other specific application, component, program, object, module or sequence of instructions referred to as “computer programs.” Invocation interfaces to these routines can be exposed to a software development community as an API (Application Programming Interface). The computer programs typically comprise one or more instructions set at various times in various memory and storage devices in a computer, and that, when read and executed by one or more processors in a computer, cause the computer to perform operations necessary to execute elements involving the various aspects.

[0048] A machine-readable medium can be used to store software and data which when executed by a data processing system causes the system to perform various methods. The executable software and data may be stored in various places including for example ROM, volatile RAM, non-volatile memory and/or cache. Portions of this software and/or data may be stored in any one of these storage devices. Further, the data and instructions can be obtained from centralized servers or peer-to-peer networks. Different portions of the data and instructions can be obtained from different centralized servers and/or peer-to-peer networks at different times and in different communication sessions or in a same communication session. The data and instructions can be obtained in entirety prior to the execution of the applications. Alternatively, portions of the data and instructions can be obtained dynamically, just in time, when needed for execution. Thus, it is not required that the data and instructions be on a machine-readable medium in entirety at a particular instance of time.

[0049] Examples of computer-readable media include but are not limited to recordable and non- recordable type media such as volatile and non-volatile memory devices, read only memory (ROM), random access memory (RAM), flash memory devices, floppy and other removable disks, magnetic disk storage media, optical storage media (e.g., Compact Disk Read-Only Memory (CD ROMS), Digital Versatile Disks (DVDs), etc.), among others.

[0050] In general, a machine readable medium includes any mechanism that provides (e.g., stores) information in a form accessible by a machine (e.g., a computer, network device, personal digital assistant, manufacturing tool, any device with a set of one or more processors, etc.). [0051] In various embodiments, hardwired circuitry may be used in combination with software instructions to implement the techniques. Thus, the techniques are neither limited to any specific combination of hardware circuitry and software nor to any particular source for the instructions executed by the data processing system. [0052] As used herein, and especially within the claims, ordinal terms such as first and second are not intended, in and of themselves, to imply sequence, time or uniqueness, but rather are used to distinguish one claimed construct from another. In some uses where the context dictates, these terms may imply that the first and second are unique. For example, where an event occurs at a first time, and another event occurs at a second time, there is no intended implication that the first time occurs before the second time. However, where the further limitation that the second time is after the first time is presented in the claim, the context would require reading the first time and the second time to be unique times. Similarly, where the context so dictates or permits, ordinal terms are intended to be broadly construed so that the two identified claim constructs can be of the same characteristic or of different characteristic.

Claims

WHAT IS CLAIMED IS:

1. An instrument for high-throughput scanning of live anesthetized animals, incorporating a robotic scanning device, a multi-slot animal loading dock, and an automatically controlled gas anesthesia delivery unit such that: when a subject test animal is present in a slot of said animal loading dock, gas anesthesia is delivered uninterruptedly to said test animal in the loading dock; when said test animal is being manipulated and/or scanned with said robotic scanning device, gas anesthesia is delivered uninterruptedly to said test animal; when said robotic scanning device picks up an animal from a slot in the loading dock, gas anesthesia delivery switches from a loading dock channel to a channel integrated within the robotic scanning device with the switching time not exceeding five seconds; when the said robotic scanning device returns an animal to said slot in the loading dock, said gas anesthesia delivery switches from the channel integrated within the robotic scanning device to the gas anesthesia channel of said loading dock slot with the switching time not exceeding five seconds; the robotic scanning device is programmed such that it can sequentially manipulate and scan five or more animals per hour, enabling a high-throughput animal scanning procedure.

2. The instrument of Claim 1 comprising one or more animal imaging devices configured such that their operation and imaging acquisition procedures are coordinated and synchronized with the operation of the high-throughput scanner, such that the imaging devices use positional, timing and other data and metadata from the high-throughput scanner, which is required for reconstruction of subject images using the data from the sensors and the detectors provided by the imaging device, that way enabling a high-throughput animal imaging procedure.

3. The instrument of Claim 2 wherein the high-throughput scanner and the imaging devices are integrated into a single instrument or arranged spatially within the same room.

4. The instrument of Claim 2 wherein the imaging device uses thermoacoustic, optoacoustic, photoacoustic, X-ray acoustic, or any essentially similar imaging technology to produce images of each scanned animal.

5. The instrument of Claim 2 wherein the imaging device uses magnetic resonance imaging (MRI), or any essentially similar imaging technology to produce images of each scanned animal.

6. The instrument of Claim 2 wherein the imaging device uses nuclear imaging technology such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), or any essentially similar imaging technology to produce images of each scanned animal.

7. The instrument of Claim 2 wherein the imaging device uses X-ray imaging, computed tomography (CT), or any essentially similar imaging technology to produce images of each scanned animal.

8. The instrument of Claim 2 wherein the imaging device uses ultrasound imaging, or any essentially similar imaging technology to produce images of each scanned animal.

9. The instrument of Claim 2 wherein the imaging device uses optical imaging, fluorescence imaging, bioluminescence imaging, or any essentially similar imaging technology to produce images of each scanned animal.

10. The instrument of Claim 2 wherein the imaging device is configured for multimodality imaging using any combination of the imaging technologies from Claims 4-9 to produce images of each scanned animal.

11. The instrument of Claim 1 wherein the robotic scanning device utilizes a robotic arm designed to pick the anesthetized animal and move it in three-dimensional space without constraints, allowing for up to three degrees of freedom in rotation and up to three degrees of freedom in translation of the animal subject.

12. The instrument of Claim 11 further configured by integrating one or more animal imaging devices such that their imaging acquisition procedures are synchronized with the robotic arm movement and positioning, enabling a high-throughput animal imaging procedure, wherein the robotic arm also performs presenting, precise positioning, and controlled movement, the movement including a combination of translation and rotation, of the subject test animal within the imaging device according to an imaging protocol of said imaging device with accuracy and precision sufficient to use data collected from sensors of the robotic arm synchronized with the data collected from the sensors and the detectors of the said imaging device, for reconstruction of anatomical, physiological, or molecular images of the interrogated animal.

13. The instrument of Claim 12, wherein said sensors of the robotic arm comprise at least one positioning sensor, at least one angle sensor, at least one speed sensor, at least one acceleration sensor, or at least one sensor for sensing time of events.