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Title:
IMAGING METHOD AND APPARATUS
Document Type and Number:
WIPO Patent Application WO/2019/075514
Kind Code:
A1
Abstract:
A method for use in imaging a subject, the method including: using an array of Compton cameras to detect photons as a result of positron emission within the subject; analyzing detected photons to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection; and, using the scattered pairs to construct a density map at least partially indicative of an anatomical structure of the subject.

Inventors:
CARADONNA, Pietro (Centre for Advanced Imaging, University of QueenslandSt Lucia, Queensland 4072, 4072, AU)
Application Number:
AU2018/051121
Publication Date:
April 25, 2019
Filing Date:
October 16, 2018
Export Citation:
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Assignee:
THE UNIVERSITY OF QUEENSLAND (St Lucia, Queensland 4072, 4072, AU)
International Classes:
G01N23/22; A61B6/03; G01N23/00; G01T1/161; G01T1/167; G03B42/02
Foreign References:
US20100059682A12010-03-11
Attorney, Agent or Firm:
DAVIES COLLISON CAVE (Level 10, 301 Coronation DriveMilton, Queensland 4064, 4064, AU)
Download PDF:
Claims:
THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1) A method for use in imaging a subject, the method including:

a) using an array of Compton cameras to detect photons as a result of positron emission within the subject;

b) analyzing detected photons to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection; and,

c) using the scattered pairs to construct a density map at least partially indicative of an anatomical structure of the subject.

2) An imaging method according to claim 1, wherein the method includes using signals from the Compton cameras to determine, for detected photons, at least one of:

a) a photon energy;

b) a photon trajectory;

c) a Compton cone indicative of a photon trajectory;

d) a detection time; and,

e) a scattered electron trajectory.

3) An imaging method according to claim 2, wherein the method includes using the photon energy to determine if a detected photon is a scattered photon or an unscattered photon that has not undergone scattering prior to detection.

4) An imaging method according to claim 3, wherein the method includes:

a) identifying scattered photons and unscattered photons from a plurality of detected photons; and,

b) analyzing the scattered and unscattered photons to identify scattered pairs.

5) An imaging method according to claim 4, wherein the method includes:

a) identifying unscattered pairs, each unscattered pair being a pair of entangled unscattered photons; and,

b) analyzing the detected photons not forming part of unscattered pairs to identify scattered pairs.

6) An imaging method according to claim 5, wherein the method includes identifying the unscattered pairs based on at least one of the photon trajectory and detection time of unscattered photons. 7) An imaging method according to any one of the claims 1 to 6, wherein the method includes identifying scattered pairs by:

a) identifying candidate scattered pairs, each candidate scattered pair including a scattered photon and an unscattered photon;

b) performing an assessment of each candidate pair based at least in part on respective detection times and the photon trajectory; and

c) identifying the candidate pair as a scattered pair depending on results of the assessment.

8) An imaging method according to any one of the claims 1 to 7, wherein the method includes identifying an scattered pair by determining if at least one of:

a) a scattered and unscattered photon have orthogonal polarizations;

b) an unscattered photon is polarized in a direction orthogonal to a scatter plane of a scattered photon; and,

c) a Compton cone of a scattered photon has an axis of symmetry that is tangential to a surface of a Compton cone of an unscattered photon.

9) An imaging method according to any one of the claims 1 to 8, wherein the method includes:

a) calculating scattering locations for multiple scattered pairs; and,

b) constructing a density map using the scattering locations.

10) An imaging method according to claim 9, wherein the method includes calculating a scattering location for a scattered pair based on at least one of:

a) an intersection location of Compton cones of the scattered and unscattered photons; b) a scatter angle calculated based on the photon energy of the scattered photon; and, c) the photon trajectory of the scattered and unscattered photons.

11) An imaging method according to any one of claims 1 to 10, wherein the method includes: a) calculating an emission location for at least one of unscattered pairs and scattered pairs; and,

b) using the emission location to construct a concentration map indicative of molecular activity within the subject. 12) An imaging method according to claim 11, wherein the method includes calculating the emission location for a unscattered pair using the photon trajectory and a relative detection time.

13) An imaging method according to claim 11 or claim 12, wherein the method includes calculating the emission location for a scattered pair using the photon trajectories, a scatter angle and a relative detection time.

14) An imaging method according to any one of the claims 1 to 13, wherein the method includes generating a composite representation indicative of a concentration map and the density map.

15) An imaging method according to any one or more of the claims 1 to 14, wherein the method is performed at least in part using one or more electronic processing devices.

16) An imaging method according to any one of the claims 1 to 15, wherein the method is performed as part of positron emission tomography process.

17) An imaging method according to any one of the claims 1 to 16, wherein the subject is a biological subject.

18) An imaging method according to any one of the claims 1 to 17, wherein positron emission is caused by a radioactive tracer ingested by the subject.

19) Apparatus for use in imaging a subject, the apparatus including:

a) an array of Compton cameras to detect photons as a result of positron emission within the subject;

b) one or more electronic processing devices that:

i) analyze detected photons to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection; and,

ii) use the scattered pairs to construct a density map at least partially indicative of an anatomical structure of the subject.

20) Apparatus according to claim 19, wherein the array of Compton cameras are circumferentially spaced around a field-of-view.

21) Apparatus according to claim 19 or claim 20, wherein each Compton camera includes a scatterer plate spaced from an absorber plate, and connections allowing electrical signals to be generated based on Compton interactions within the scatterer and absorber plates. 22) Apparatus according to any one of the claims 19 to 21, wherein the subject is a biological subject and the apparatus includes a bore configured to accommodate the subject so that the subject is at least partially positioned within the field-of-view.

23) Apparatus according to any one of the claims 19 to 22, wherein the apparatus performs the method of any one of the claims 1 to 18.

Description:
IMAGING METHOD AND APPARATUS Background of the Invention

[0001] The present invention relates to a method and apparatus for imaging a subject, and in one particular example to a method and apparatus for constructing a density map indicative of an anatomical structure of the subject using positron emission imaging.

Description of the Prior Art

[0002] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[0003] Positron-emission tomography (PET) is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule, such as fluorodeoxyglucose (FDG). Concentrations of tracer within the body are determined based on the amount and position of gamma ray emission, with this being used to construct three-dimensional images of tracer concentration within the body by computer analysis.

[0004] The tracer concentration is typically indicative of tissue metabolic activity, for example as it corresponds to regional glucose uptake in the case of FDG. Accordingly, this can be used to map metabolic activity within the subject, for example using FDG to identify cancer metastasis, which is one of the most common type of PET scan in standard medical care. It will be appreciated that other radioactive tracers are used in PET to image the tissue concentration of other types of molecules of interest.

[0005] However, PET suffers from a number of drawbacks. For example, PET is only able to image the concentration of the tracers within the body, and hence does not directly provide any information regarding the anatomical structure of the subject, although some information can be derived based on the tracer concentration. Furthermore, PET imaging only performs construction of images based on emitted photons that have not undergone scattering. However, as 50% to 90% of the emitted radiation field undergoes scattering within the subject, this leads to a reduction in signal quality necessitating a longer acquisition time. Additionally, it is necessary to compensate for this attenuation by using an attenuation map, generated by scanning the patient with X-rays, allowing for correction and alignment between molecular activity and anatomical features. To achieve this, modern PET scanners typically also incorporate computer X-ray tomography (CT) apparatus, which adds to the cost of the equipment, adds to the complexity of image reconstruction and subjects a patient to increased levels of ionising radiation.

[0006] Compton cameras are compact gamma ray photon detectors that are able to provide three dimensional imaging for radioisotope tracing capability. Compton cameras replace mechanical coUimation with electronic coUimation using a position sensitive semiconductor material, and are capable of measuring photon energies between 60 keV to several MeV (between 1% and 3% energy resolution) and imaging multiple molecular agents.

[0007] "First demonstration of multi-color 3-D in vivo imaging using ultracompact Compton camera" by Aya Kishimoto, Jun Kataoka, Takanori Taya, Leo Tagawa, Saku Mochizuki, Shinji Ohsuka, Yuto Nagao, Keisuke Kurita, Mitsutaka Yamaguchi, Naoki Kawachi, Keiko Matsunaga, Hayato Ikeda, Eku Shimosegawa & Jun Hatazawa published in Scientific Reports | 7: 2110 | DOI: 10.1038/s41598-017-02377-w, describes the use of a Compton camera in single photon emission tomography and positron emission tomography. Specifically the document describes the use of an ultra-compact Compton camera to perform 3-D color imaging of a live mouse using tri-color gamma-ray fusion images using 1311, 85Sr, and 65Zn tracers that concentrate in each target organ. However, whilst this approach allows the detection of multiple tracers, this does not obviate the need for an additional CT scan to be performed in order to determine the anatomical structures of the subject. Summary of the Present Invention

[0008] In one broad form, an aspect of the present invention seeks to provide a method for use in imaging a subject, the method including: using an array of Compton cameras to detect photons as a result of positron emission within the subject; analyzing detected photons to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection; and, using the scattered pairs to construct a density map at least partially indicative of an anatomical structure of the subject.

[0009] In one embodiment the method includes using signals from the Compton cameras to determine, for detected photons, at least one of: a photon energy; a photon trajectory; a Compton cone indicative of a photon trajectory; a detection time; and, a scattered electron trajectory.

[0010] In one embodiment the method includes using the photon energy to determine if a detected photon is a scattered photon or an unscattered photon that has not undergone scattering prior to detection.

[0011] In one embodiment the method includes: identifying scattered photons and unscattered photons from a plurality of detected photons; and, analyzing the scattered and unscattered photons to identify scattered pairs.

[0012] In one embodiment the method includes: identifying unscattered pairs, each unscattered pair being a pair of entangled unscattered photons; and, analyzing the detected photons not forming part of unscattered pairs to identify scattered pairs.

[0013] In one embodiment the method includes identifying the unscattered pairs based on at least one of the photon trajectory and detection time of unscattered photons.

[0014] In one embodiment the method includes identifying scattered pairs by: identifying candidate scattered pairs, each candidate scattered pair including a scattered photon and an unscattered photon; performing an assessment of each candidate pair based at least in part on respective detection times and the photon trajectory; and identifying the candidate pair as a scattered pair depending on results of the assessment.

[0015] In one embodiment the method includes identifying an scattered pair by determining if at least one of: a scattered and unscattered photon have orthogonal polarizations; if an unscattered photon is polarized in a direction orthogonal to a scatter plane of a scattered photon; and, a Compton cone of a scattered photon has an axis of symmetry that is tangential to a surface of a Compton cone of an unscattered photon.

[0016] In one embodiment the method includes: calculating scattering locations for multiple scattered pairs; and, constructing a density map using the scattering locations.

[0017] In one embodiment the method includes calculating a scattering location for a scattered pair based on at least one of: an intersection location of Compton cones of the scattered and unscattered photons; a scatter angle calculated based on the photon energy of the scattered photon; and, the photon trajectory of the scattered and unscattered photons.

[0018] In one embodiment the method includes: calculating an emission location for at least one of unscattered pairs and scattered pairs; and, using the emission location to construct a concentration map indicative of molecular activity within the subject.

[0019] In one embodiment the method includes calculating the emission location for a unscattered pair using the photon trajectory and a relative detection time.

[0020] In one embodiment the method includes calculating the emission location for a scattered pair using the photon trajectories, a scatter angle and a relative detection time.

[0021] In one embodiment the method includes generating a composite representation indicative of a concentration map and the density map.

[0022] In one embodiment the method is performed at least in part using one or more electronic processing devices. [0023] In one embodiment the method is performed as part of positron emission tomography process.

[0024] In one embodiment the subject is a biological subject.

[0025] In one embodiment positron emission is caused by a radioactive tracer ingested by the subject.

[0026] In one broad form, an aspect of the present invention seeks to provide apparatus for use in imaging a subject, the apparatus including: an array of Compton cameras to detect photons as a result of positron emission within the subject; one or more electronic processing devices that: analyze detected photons to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection; and, use the scattered pairs to construct a density map at least partially indicative of an anatomical structure of the subject.

[0027] In one embodiment the array of Compton cameras are circumferentially spaced around a field-of-view.

[0028] In one embodiment each Compton camera includes a scatterer plate spaced from an absorber plate, and connections allowing electrical signals to be generated based on Compton interactions within the scatterer and absorber plates.

[0029] In one embodiment the subject is a biological subject and the apparatus includes a bore configured to accommodate the subject so that the subject is at least partially positioned within the field-of-view.

[0030] It will be appreciated that the broad forms of the invention and their respective features can be used in conjunction, interchangeably and/or independently, and reference to separate broad forms is not intended to be limiting. Brief Description of the Drawings

[0031] Various examples and embodiments of the present invention will now be described with reference to the accompanying drawings, in which: -

[0032] Figure 1A is schematic end view of an example of apparatus for use in imaging a subject;

[0033] Figure IB is a schematic side view of the apparatus of Figure 1A;

[0034] Figure 2 is a schematic diagram of an example of a Compton camera;

[0035] Figure 3 is a schematic diagram of an example of a processing system;

[0036] Figure 4A is a flow chart of an example of a method of imaging a subject;

[0037] Figure 4B is a schematic diagram illustrating a scattering event;

[0038] Figures 5A and 5B are a flow chart of a specific example of a method of imaging a subject;

[0039] Figure 6 is a schematic diagram illustrating a scattering geometry;

[0040] Figure 7 is a schematic diagram illustrating a scattering pattern for detection of an entangled pair of photons in which one of the photons has undergone scattering prior to detection;

[0041] Figure 8 is a schematic diagram illustrating a scattering pattern nomenclature;

[0042] Figure 9 is a schematic diagram illustrating a scattering geometry for entangled photons; and,

[0043] Figure 10 is a schematic diagram illustrating a double scattering geometric configuration.

Detailed Description of the Preferred Embodiments

[0044] An example of an apparatus for use in imaging a subject will now be described with reference to Figures 1A and IB.

[0045] In this example, the apparatus 100 includes an array of Compton cameras 111. The Compton cameras are typically mounted to a body 1 10, which in this example has an annular shape defining a bore 120 surrounding a field-of-view. In use, a subject S can be positioned on a support such as a bed 121 and provided within the bore 120, allowing imaging of the subject to be performed. [0046] The Compton cameras 111 are gamma ray photon detectors that utilise Compton scattering in order to determine information regarding the energy and incident direction of a gamma ray photon, and an example of a Compton camera is illustrated schematically in Figure 2.

[0047] In this example, the Compton camera includes two spaced apart position sensitive detector plates, referred to as a scatterer 211 and an absorber 212. In use, at least some photons incident on a scatterer plate 211 undergo Compton scattering, with the resulting scattered photons being subsequently absorbed by the absorber plate 212. The plates can be made from any suitable material including, but not limited to germanium, bismuth germanate (BGO), sodium iodide (Nal), xenon, silicon and lanthanum bromide (LaBr 3 ), are Ce-doped Gd 3 Al 2 Ga 3 0i 2 plates, or the like, with the plate dimensions and relative positioning being selected to achieve a suitable interaction cross section.

[0048] Position sensitivity is achieved through pixelated detectors in the form of metal squares or orthogonal metal strips, provided on the front and/or back surfaces of each plate 211, 212. The overlap between two orthogonal strips can be considered to be equivalent to a pixel and these pixels function as a collection site for the free moving electron-hole pairs that have been generated by the collision of the incoming photon with an electron in the detector plates, thereby resulting in a signal detectors, which can be used to derive information regarding the energy and trajectory of the incident photon. The configuration and operation of Compton cameras to allow photon detection are known in the art, and this will not therefore be described in any further detail.

[0049] The position and energy of an incoming photon is measured to reduce the uncertainty in the trajectory of an incident photon 214 to the surface of a cone 213 (the so-called 'Compton cone'). Specifically the axis of symmetry of the Compton cone 213 is the projected line that passes through the pixel of the scatterer plate 211 and the (m' th ,

pixel of the absorber plate, with the apex of the Compton cone being coincident with the pixel of the scatterer plate 211. The scattering angle Θ is defined as the half angle

subtended by the axis of symmetry of the cone and its surface and is determined based on the measured energies at the scatterer plate 211 and absorber plate 212, given by the Compton scattering equation:

[0050] The apparatus typically also includes one or more electronic processing devices, typically forming part of one or more processing systems used to control the imaging apparatus and/or process collected data to generate resulting images. The processing systems could be in the form of servers, personal computers or the like, and may optionally be connected to one or more other processing systems, via a network architecture, or the like.

[0051] An example of a suitable processing system is shown in Figure 3. In this example, the processing system 300 includes at least one microprocessor 301, a memory 302, an optional input/output device 303, such as a keyboard and/or display, and an external interface 304, interconnected via a bus 305 as shown. In this example the external interface 304 can be utilised for connecting the processing system 300 to the Compton cameras 111 and any other control equipment, and optionally any one other peripheral devices, such as one or more communications networks, databases, other storage devices, or the like. Although a single external interface 304 is shown, this is for the purpose of example only, and in practice multiple interfaces using various methods (eg. Ethernet, serial, USB, wireless or the like) may be provided.

[0052] In use, the microprocessor 301 executes instructions in the form of applications software stored in the memory 302 to allow the required processes to be performed. The applications software may include one or more software modules, and may be executed in a suitable execution environment, such as an operating system environment, or the like. [0053] Accordingly, it will be appreciated that the processing system 300 may be formed from any suitable processing system, such as a suitably programmed PC, web server, network server, or the like. In one particular example, the processing system 300 is a standard processing system such as an Intel Architecture based processing system, which executes software applications stored on non-volatile (e.g., hard disk) storage, although this is not essential. However, it will also be understood that the processing system could be any electronic processing device such as a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement.

[0054] Examples of the processes for imaging a subject will now be described in further detail. For the purpose of these examples it is assumed that actions performed by the one or more respective processing systems 300 are performed by the processor 301 in accordance with instructions stored as applications software in the memory 302 and/or input commands received from a user via the I/O device 303, or a remote computing device. However, it will be appreciated that the above described configuration assumed for the purpose of the following examples is not essential, and numerous other configurations may be used. It will also be appreciated that the partitioning of functionality between the different processing systems may vary, depending on the particular implementation.

[0055] An example of operation of the apparatus to perform the imaging will now be described with reference to Figures 4A and 4B .

[0056] In this example, at step 400, the array of Compton cameras 111 are used to detect photons as a result of positron emission within the subject. In this regard, as part of a PET imaging process, the subject is administered with a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. The nature of the tracer will vary depending on the preferred implementation, and specifically on the biological activity being targeted. For example in oncology a fluorine- 18 (F-18) fluorodeoxyglucose (FDG) tracer is widely used as this is a glucose analog that is taken up by glucose using cells, such as tumours, allowing the presence and location of tumours to be identified. Other example tracers include HC-labelled metomidate (HC-metomidate) for detecting adrenocortical tumours of origin, radioligands for specific neuroreceptor subtypes such as [11C] raclopride, [18F] fallypride and [18F] desmethoxyfallypride for dopamine D2/D3 receptors, [11C] McN 5652 and [11C] DASB for serotonin transporters, [18F] Mefway for serotonin 5HT1A receptors, [18F] Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). Such tracers are known in the art, and are application dependent, so will not be described in further detail.

[0057] Following administration of the tracer, positrons are emitted from the tracer, with these combining with an electron within the subject to form para-positronium, which undergoes annihilation to generate a pair of entangled gamma ray photons that are emitted from the subject and detected by the Compton cameras. An example of this is illustrated in Figure 4B, which shows an annihilation event 451, resulting in photons being emitted along respective trajectories 452.1, 452.2. As the para-positronium typically has a low net velocity at the point of decay, the photons are initially emitted in substantially opposite directions. It will be appreciated that this process is independent of positron range.

[0058] In many cases emitted photons undergo Compton scattering by interacting within an electron causing the photon to be deflected as shown at 453. It will also be understood that such scattering will typically occur within the subject due to the higher electron density within the subject versus the surrounding air, although this is not necessarily essential and scattering could occur outside of the subject, for example in the air within the bore 120, or within the scanner body 110.

[0059] In general, photons from a number of annihilation events will be collected, with multiple detected photons being analysed concurrently. In this regard, at step 410 detected photons are analysed in order to identify scattered pairs, with each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection, as shown at 453. It will be noted that in this context, reference to scattering prior to detection refers to a scattering event occurring prior to the photon reaching a scatterer plate 211, and does not include scattering events forming part of the operation of the Compton camera. [0060] At step 420, scattered pairs are used to construct a density map at least partially indicative of an anatomical structure of the subject. In this regard, Compton scattering arises when an emitted photon interacts with an electron and accordingly, the likelihood of a scattering event will depend on the electron density of the medium through which photons are travelling. Thus, by analysing multiple scattering events occurring at different locations within the subject, this allows the density of the different locations to be determined, which can be used to generate a density map indicative of anatomical features, such as a skeletal structure, presence and/or types of tissues, fluids or the like.

[0061] It will be appreciated that the above described process can be performed as part of positron emissions tomography (PET) imaging, allowing anatomical information to be obtained as part of the PET imaging process, without necessarily requiring additional equipment such as scanning with X-ray computed tomography (CT). This results in a decrease in the complexity of the scanning apparatus, allowing the resulting scanning apparatus to be cheaper, more reliable and smaller, allowing it to be deployed more widely. This also can be performed using the same tracer used to perform PET imaging, and without requiring exposure to further radiation, thereby reducing overall exposure to ionising radiation. Additionally, as information is captured from scattered as well as unscattered photons, this can allow PET images to be captured using a lower dose of tracer, as will be discussed in more detail below. Finally, the above described arrangement allows a concentration map, indicative of molecular activity within the subject, as well as the density map to be captured simultaneously, thereby avoiding issues associated with registration of separate PET and CT images.

[0062] A number of further features will now be described.

[0063] In one example, the method includes using signals from the Compton cameras to determine one or more of a photon energy, a photon trajectory, a Compton cone indicative of a photon trajectory and/or a detection time, for each detected photon. This information can then be analysed in order to identify pairs of entangled photons and in particular scattered pairs. It will also be appreciated that some Compton cameras also include the ability to at least partially determine a scattered electron trajectory, which in turn can be used to further resolve the trajectory of the incident photon, for example reducing this to an arc portion of the Compton cone.

[0064] In one example, the process of identifying scattered pairs involves segmenting a plurality of detected photons into groups of scattered and unscattered photons, based on the respective photon energy, with the scattered and unscattered photons being analysed to identify scattered pairs. In this regard, photons are created based on the decay of para- positronium, meaning each emitted photon will have a substantially similar energy in a defined energy range, typically about 0.5 MeV. Consequently, if a photon is detected by a Compton camera with a significantly lower energy, this indicates that the photon has undergone scattering. Accordingly, it is possible to use the photon energy to determine if a detected photon is a scattered photon or an unscattered photon that has not undergone scattering prior to detection.

[0065] Having identified scattered and unscattered photons, these are then analysed to identify pairs of entangled photons. This process is typically performed by initially identifying unscattered pairs, corresponding to pairs of entangled unscattered photons, as these are generally easier to identify. Once this has been completed, any unpaired unscattered photons and the scattered photons can be analysed to identify scattered pairs. By effectively eliminating the unscattered pairs from this latter stage of the analysis, this reduces the computational complexity in identifying the scattered pairs.

[0066] To identify unscattered pairs, unscattered photons are paired based at least in part on the relative detection times, and optionally also taking into account the photon trajectory of each unscattered photon. In this regard, the time of flight between decay of the para- positronium and detection of the emitted photons is limited by the speed of light and distanced travelled by the photons, meaning the relative time of detection between two photons can be used to place constraints on whether two detected photons form part of an entangled pair. In particular, there are maximum and minimal temporal separations between two photons being received by detectors in order for these to correspond to a pair of entangled photons, governed by the speed of light and the distance between the Compton cameras. [0067] Assuming that unscattered photons are detected within the relevant time window the trajectory of the unscattered photons can be compared to ensure that these are travelling in substantially opposite directions, based on the detected Compton cone of each unscattered photon. In particular, this requires that the Compton cones have surfaces that interest substantially along a line between the Compton cameras.

[0068] Having eliminated unscattered photons which correspond to unscattered pairs, the remaining photons, including the remaining unscattered photons and the scattered photons are used to determine candidate pairs, with each candidate pair including a scattered photon and unscattered photon. An assessment of each candidate pair can then be performed based on respective detection times and the photon trajectory in order to identify scattered pairs.

[0069] Identification of scattered pairs can be assisted by making certain assumption regarding scattering, in particular to take into account the polarisation of photons. In this regard, and as will be discussed in more detail below, pairs of entangled photons generated by the disintegration of para-positronium in the ground state have orthogonal polarisations. Furthermore, when a photon undergoes Compton scattering, the photon will preferentially scatter with its plane of polarisation perpendicular to the scattering plane, defined by the plane containing the incident and scattered photon trajectories. These two factors mean that for a scattered pair, in which one photon is unscattered, the unscattered photon will tend to have a polarisation in the scatter plane of the scattered photon. As a result of this, and the fact that the photons will undergo further scattering during detection, the Compton cone of the scattered photon has an axis of symmetry that is tangential to a surface of the Compton cone of the unscattered photon, allowing scattered pairs to be identified, as will be described in more detail below.

[0070] Accordingly, this allows scattered pairs to be identified based on the relative detection time of the photons, and the photon trajectories, particularly based on the Compton cones of a scattered and unscattered photon. From this, it will be appreciated that whilst the above described approach eliminates unscattered pairs first, in order to reduce processing requirements, this is not essential and alternatively direct identification of scattered pairs could be performed based on the relative detection times and Compton cones/trajectories of scattered and unscattered photons.

[0071] Once scattered pairs have been identified, scatter locations for each of multiple scattered pairs are calculated, for example based on a location of intersection for the surfaces of the Compton cones, a scatter angle calculated based on the photon energy of the scattered photon, and/or the photon trajectory of the scattered and unscattered photons. Determining the scatter locations for a sufficiently large number of scattered pairs can then be used to construct a density map.

[0072] In addition to examining scattering, it is also possible to examine emission of photon pairs in order to generate a concentration map indicative of concentrations of molecular activity within the subject, which in one example is performed in accordance with normal PET imaging techniques.

[0073] In one particular example, an emission location is determined for at least unscattered pairs of entangled photons, with the emission location being used to construct the concentration map. The emission location for an unscattered pair can be calculated using the photon trajectory and optionally the relative photon detection time. Specifically the photon trajectory can be used to identify a line along which the emission occurred, based on the assumption that the photons are emitted in substantially opposite directions, with a difference in the detection time of each photon being used to determine a relative position off the emission along the line.

[0074] It will also be appreciated that a scatter location can be determined for a scattered pair based on the photon trajectories, a scatter angle and a relative detection time. In this regard, the trajectories, scatter angle and relative detection time can be used to resolve the distance travelled by the scattered and unscaterred photons along their respective trajectories, in turn allowing the emission location to be determined. It will be appreciated that in traditional techniques, no attempt is made to identify the emission location of scattered photons, meaning this information is normally lost. However by retaining this, this allows improved imaging contrast to be achieved, which in turn allows equivalent images to be collected using a reduced amount of tracer compared to traditional techniques, thereby reducing patient exposure to ionising radiation.

[0075] In one example of the method includes generating a representation based on a composite of the concentration map and the density map, thereby showing both concentrations of molecular activity and anatomical structures in a single combined map. This is particularly useful in identifying the location of features, such as tumours, within the subject.

[0076] Typically the array of Compton cameras includes multiple cameras. Any number of cameras could be provided in the array, although typically the array includes at least two cameras to allow entangled photons to be detected. Typically many more, cameras are used to maximize the spatial coverage over which photons can be detected. In one example, the Compton cameras are circumferentially spaced around a field-of-view. This allows the system to include a bore that can accommodate the subject so that the subject is at least partially positioned within the field-of-view. However, it will be appreciated that other arrangements could additionally and/or alternatively be used, for example including Compton cameras spaced along the bore, or to provide multiple annular arrays of cameras spaced along the bore to maximize spatial coverage.

[0077] A more detailed example process will now be described with reference to the flow chart of Figures 5 A and 5B.

[0078] In this example, signals from the Compton cameras 111 are used to detect photons emitted from the subject at step 500, with a photon energy of each detected photon is calculated at step 505 to allow scattered and unscattered photons to be identified at step 510.

[0079] Following identification of scattered and unscattered photons, a next pair of unscattered photons is selected at step 515, with a relative detection time being calculated at step 520. The relative detection time is compared to a time window, which is set based on the physical separation of the Compton cameras, to determine if the unscattered photons are a possible match and potentially form part of an entangled unscattered pair at step 525. If there is a possible match, Compton cones for the unscattered photons can be compared step 530, to ascertain whether the photons have trajectories aligned. Assuming this to be the case, it is determined that the unscattered photons form an unscattered pair at step 540, with the photons being removed from further consideration.

[0080] Once the pair of photons has been assessed, at step 545 it is determined if all possible pairs of unscattered photons have been assessed and if not the process returns to step 515. Thus, the above described process initially analyses all unscattered photons, to identify unscattered pairs, allowing these paired photons to be removed from the subsequent parts of the analysis.

[0081] Once all unscattered pairs have been identified, the process moves onto step 550 to select a next candidate pair including a scattered and an unscattered photon. Again, a relative detection time is determined at step 555, with this being compared to a time window to identify a possible match at step 560, in a manner similar to that described above. If there is a potential match, it is determined if the Compton cones have a necessary tangential arrangement, with the Compton cone of the scattered photon having an axis of symmetry that is tangential to a surface of the Compton cone of the unscattered photon at step 565. In this regard, the axis of symmetry of the Compton cone of the scattered photon can be easily calculated based on the the (m th , n th ) pixel of the scatterer plate 211 and the (m' th , n ' th ) pixel of the absorber plate 212 with which the photon interacts, whilst the Compton cone of the unscattered photon can be based on the interaction pixels and the energy loss in the scatterer plate 211, as previously described.

[0082] Assuming the tangential requirement is met, this is used to identify a match at step 570, meaning the photons form part of a scattered pair at step 575. Assuming this to be the case, the photons are removed from the scattered and unscattered group, otherwise at step 580 it is assessed if all pairs are finished and if not the process returns to step 550.

[0083] Once all unscattered photons have been matched or all candidate pairs considered, scattering locations are determined at step 585 based on the intersection of the surface of the Compton cones of each photon in the scattered pair. This process can additionally/alternatively take into account the energy of the scattered photon, which can in turn be used to calculate a scattering angle, with this being used to determine the scattering location.

[0084] The scattering locations of multiple scattered pairs are then used to generate a density map at step 590, which can optionally be displayed as part of a composite map together with concentration information generated in accordance with standard PET protocols. In this regard, it will be appreciated that this process can involve determining the emission location of scattered photons, resulting in improved images compared to traditional PET approaches in which only unscattered photons are used for image reconstruction.

[0085] It will also be appreciated that the process of performing image reconstruction could involve incorporating information from other image modalities, with this optionally being used to fuse the results of multiple modalities, making it possible to incorporate the best features of each modality. In this example, this could be used to fuse the density maps generated by entangled gamma rays with the X-ray CT images, using techniques similar to those described in "Image fusion of mass spectrometry and microscopy: a multimodality paradigm for molecular tissue mapping" by Raf Van de Plas, Junhai Yang, Jeffrey Spraggins & Richard M Caprioli published in Nature Methods, 23 February 2015; doi: 10.1038/nmeth.3296.

[0086] A specific example of a process for performing structural imaging using entangled gamma ray photons will now be described in further detail.

[0087] As previously mentioned, traditional positron emission tomography (PET) is only interested in measuring pairs of gamma ray photons that have passed straight through the body. It is estimated that anywhere between 50 to 90% of the emitted radiation field is composed of attenuated radiation, which is almost entirely caused by Compton interactions. To compensate for attenuation in PET, an attenuation map is generated by scanning the patient with X-rays which is then applied to the gamma ray generated PET image. However, the disadvantages of this method are that it adds to the cost of the PET scanners and adds complication to image reconstruction and it involves subjecting a patient with increased levels of ionising radiation. [0088] In Compton interactions, a highly energetic photon (energies greater than 100 to 150 keV) will ionise an atom by freeing a valence electron. Since the probability for a Compton interaction is directly proportional to electron density, Compton interaction measurements can provide information on both the bulk density of a sample and on its chemical composition.

[0089] The above described approach operates by pinpointing locations of Compton interactions providing a means to reduce costs and complications while also decreasing the level of radiation exposure, while at the same time providing physicians and researchers valuable information on the density and chemical composition about the specimen.

[0090] To achieve this, the approach uses information that can be derived from Compton interactions due to the fact that emitted photons are made up of sets of entangled gamma ray photons generated as a result of para-positronium disintegration.

[0091] For the purpose of explanation it is useful to understand how entanglement can assist in identifying photon pairs where one or more of the photons have undergone Compton scattering prior to detection.

[0092] In particular, quantum entanglement is a physical phenomenon which is found to exist between pairs of gamma ray photons when generated by the rapid disintegration of a para- positronium atom. The property of entanglement dictates that the quantum state for each of these photons cannot be described independently of the other, even when the photons are separated by any distance imaginable, and therefore can be considered as one whole. Thus, entanglement binds particles together into an integral whole, with collective properties that individual particles lack, which can facilitate detection of photon pairs.

[0093] For entangled photons, the planes of polarisation should be cross-polarised. This correlation is equivalent of angular momentum conservation in the process of annihilation of a positron-electron pair with zero relative velocity and in the singlet state. Since the initial state of para-positronium has zero angular momentum, it has no natural axis in a magnetic field-free region and so it is symmetric under all rotations. The final state in which two back- to-back photons are created must then also be symmetric under all rotations too, meaning it is equally probable for the photon pair to be emitted in any direction about the disintegration point, with the photons being emitted in opposing directions. In the language of quantum information science, these cross-polarised photons represent a pure state which is formed in one of the four possible Bell states, labelled by the ket vector |Φ ~ ).

[0094] Conservation of angular momentum permits the generation of photon pairs in one of two possible configuration states with each configuration being equally probable. The pair can both be in the right circularly polarised state (\R)) or are both in the left circularly polarised state Since para-positronium decays electromagnetically, the parity of para- positronium prior to disintegration and the parity of the resulting entangled photon pair state must be the same, such that:

[0095] The cross-polarisation mathematically reveals itself by expressing the right and left circular polarisation states through a change of basis in terms of orthogonal polarisation planes that point along the x and y axes with respect to a scattering plane, with these states being 90° out of phase relative to each other such that:

[0096] The right and left circularly polarised photons are the same for any such rotation; the definition is independent of any choice of the x-direction (except that the photon direction is given), such that:

[0097] Accordingly, if a first photon is measured in the state of linear polarisation perpendicular to its plane of scattering then the state of polarisation of the second photon of an entangled pair will be found with a polarisation in the plane of scattering \y 2 ), and a similar argument holds of the state

[0098] Additionally, in Compton interactions, high energy photons are preferentially scattered in the state of polarisation which is perpendicular to the scattering plane. It is possible to utilize this preferential scattering reaction and the cross -polarised correlations to determine the impact site field equations for the case of three Compton interactions which preserve the cross-scattering-plane configuration and calculate the triple Compton probability distribution for this scattering reaction, as will be described in more detail below.

[0099] It is advantageous to use Compton cameras, as described above, to perform position measurements using cross-polarised photons, especially for gamma ray photons which have an energy of about The collisions at this scale are so energetic and therefore happen so quickly that an Impulse Approximation model can be applied to the interaction of a photon with an electron bounded to an atom or molecule. The Impulse Approximation is generally valid provided that the energy transfer to the electron involved in the scattering is more than about four times its binding energy to the atom or molecule to which it belongs to. This particularly case holds for gamma ray interactions with organic and inorganic matter. That is to say, the spectator electrons cannot relax to take account of the hole left behind by the recoiling electron until such time it has completely escaped from the system. As a result, the potential energy term therefore cancels in the conservation of energy equation which gives the Compton scattering relation described in equation (1) above. Doppler broadening which is caused by the electron motion has a negligible effect on the position resolution compared to the position resolution of the technological itself.

[0100] The dynamics of Compton interactions show that photons preferentially scatter with the incident polarisation state pointing perpendicular to the plane of scatter, as opposed to the case when its incident polarisation state is pointing in the plane of scatter. These effects are readily described by the Klein-Nishina formula which has previously been used as confirmation of the Dirac electron.

[0101] The Klein-Nishina defines the differential collision cross section in the case of plane polarised incident radiation, with reference to the geometry shown in Figure 6, such that: where:

[0102] In Figure 6, the incoming photon has incident polarisation 601 in plane ODAC, and is incoming along trajectory 602, aligned with the z-axis, with the scattered photon being scattered in scattering plane OAB, at an angle ξ relative to the x-axis, travelling along trajectory 603 with scattered polarisation 604. Basis vectors 605, 606 for the polarisation state of the scattered photon in and perpendicular to the ODAC plane are shown.

[0103] Since the photons are initially cross-polarised, and the photons preferentially scatter in a plane perpendicular to the plane of polarisation, scattering will preferentially occur according to the pattern shown in Figure 7.

[0104] In this example, a para-positronium decay 700 results in respective first and second entangled photons 701, 702 being emitted in substantially opposing directions, with the photons having respective polarisations 703, 704, which are respectively perpendicular to the plane 705, which is a scatter plane of the first photon 701, when it undergoes Compton scattering with an electron 706, resulting in scattered first photon 701.1. The first and second photons 701, 702 are detected by respective first and second Compton cameras 111.1, 111.2, with the first and second photons being scattered by the Compton camera scatterer plates in respective first and second detection planes 707, 708, which are respectively parallel and perpendicular to the scatter plane 705.

[0105] The saddle shaped surface 709 marks an intersection between the Compton cones of the scattered and unscattered photons 701, 702. The boundary of this surface corresponds to a curve on which the electron collision site could have occurred, with this being further narrowed to interaction at sites 706, 709.1 based on the assumption of scattering in a plane perpendicular to the plane of photon polarisation.

[0106] From a geometrical analysis, it is apparent that an axis of symmetry 710 of the Compton cone for the scattered photon 701 is tangential to the Compton cone for the unscattered photon 702. This 'tangential' constraint severely restricts the possibility of confusing a random detection event for the scattered entangled photon and hence can be used to provide a severe constraint on the possibility of incorrectly pairing up photons that are not entangled. This results in just three possible trajectories for the entangled photons. The first trajectory is for the unscattered photon, which is defined as the trajectory which lies on its Compton cone and which intersects with the axis of symmetry of the scattered photon. On either side of the axis of symmetry lies two possible trajectories 701.1, 701.2 for the scattered photon. The second trajectory 701.2 is referred to as a 'phantom' trajectory and out of the two possible trajectories, the actual trajectory 701.1 of the scattered photon can be found using a Compton scattering relation similar to that described above in equation (1), based on the degree of scattering of the photon, as derived from the energy loss during scattering.

[0107] The 'tangential criteria' acts like a fingerprint that can be used to pair-up entangled photons but the severity of this constraint mainly depends on the limitation set by the technology. In particular, the size of the field of view at a distance the front (scattered plate) pixel is from the impact site. To first order, the size of the field of view is proportional to dimensions of the pixels themselves and the distance between the two pixels. Since the activation of the back (absorber plate) pixel is not necessarily directly behind the front pixel, the field of view formed between any two activated pixels forms a skewed rectangular prism with its focal point lying somewhere in between the front and back pixels.

[0108] Considering the case when we have a Compton camera that has 1 mm diameter circular pixels and has the scattering plate and absorber plate separated by 45 mm. For a scattering angular range of 30 - 150°, the volume of uncertainty about the scattering site is estimated to be between 25 to 50 mm when the scattering site is situated approximately 500 mm away from a pair of detectors. This equates to an uncertainty in the length scale of between 3 to 4 mm. These length scales can in principle be reduced using Compton cameras that use sub-millimetre pixel dimensions and by increasing the distances between the front (scattered) and back (absorber) plates.

[0109] As discussed above, pairs of cross-polarised photons preferentially scatter in a manner which causes the intersection of two Compton cones to reduce to the problem of finding two photon trajectories out of a possibility of three. However, it will also be appreciated that scattering is not necessarily constrained to being within a plane perpendicular to the plane of polarisation of the incident photon, and that instead this could be in a plane at another angle relative to the plane of polarisation. In this instance, it will be appreciated that other geometrical considerations will apply, and the scattering location and hence photon trajectory will instead need to be calculated based on different curves besides the saddle shaped intersection other than 709 between the two Compton cones.

[0110] It will also be noted that the above discussion has focused on a modality in which the Compton cameras are only used to detect a scatter angle and trajectory after scattering, resolving the photon trajectory to being coincident with a Compton cone. However, as previously discussed Compton cameras have been developed which incorporate sensing to determine a trajectory of an electron emitted as a result of scattering within the front (scatterer) plate. This information can be used to further resolve the photon trajectory to be coincident with an arc segment of the Compton cone. This can assist in detection of photons pairs, and in one particular example can be used to assist detection of scattering in a plane that is not perpendicular to the polarisation of the incident photon.

[0111] Next the triple Compton probability distribution is calculated and used to give an estimate of resulting signal strength. To do this it is necessary to show there is sufficient information to find these trajectories and provide the impact field equations for the scattering pattern outlined above.

[0112] Nomenclature for the following calculation is shown in Figure 8, in which two Cartesian coordinate systems are constructed, including a reference frame coordinate system shown by axes 801, which is used to define four position vectors (denoted with the letter D which stands for the detector). These position vectors point to the location of the activated pixels on a pair of Compton cameras, for the camera (s), the direction vectors are:

[0113] The impact site is defined by the position (field) vector r a and is the quantity to be identified. The geometric scattering pattern uses a natural orthogonal coordinate system shown by axes 802, with unit vectors (¾, ¾, ¾). These unit vectors can be defined using the information provided b the cameras such that:

[0114] This can be used to define:

[0115] The trigonometric expressions can be determined using the Compton scattering relation given in equation (1).

where: Θ is the Compton scattering angle

[0116] From this vectors can be defined:

[0117] For positive identification of a scatter pair, this leads to the condition that:

[0118] Next a probability distribution formula is derived and used to derive the number of impact sites that can be detected based on standard PET protocols and technological constraints.

[0119] To calculate the triple Compton interaction probability distribution the coordinates defined in Figures 9 and 10 are used. [0120] Specifically the geometry of Figure 9 shows an annihilation event 900 resulting in first and second photons 901, 902, travelling along initial respective trajectories with polarisations 903, 904. The photons are scattered in respective planes 905, 906, with the scattered photons have resulting polarisations 907, 908.

[0121] A further scattering event is shown in Figure 10, based on the first photon undergoing a scattering event to create a third photon, prior to detection. In this example, the first photon 1001 having an initial polarisation state 1002 undergoes scattering 1000 within the subject, in scattering plane 1005, creating a third photon 1003 having an initial polarisation state 1004, which is rotated relative to the first photon initial polarisation state 1002. The third photon interacts 1006 with the front (scatterer) plate of the Compton camera, resulting in a final polarisation 1007 upon impact 1008 with the rear (absorber) plate.

[0122] The coordinate system is defined for each photon, so that the first photon 901 is moving in the positive zi direction while the second photon 902 moves away in the -zi direction. The cross-polarisation, which signifies the entanglement, between these pair of photons is accounted for so that the incident polarisation state of the first photon 901 is aligned with the xi axis, and that the incident polarisation state of the second photon 902 is aligned along the )¾ axis. In this geometry and that the relationship

between their azimuthal angles is given by

[0123] Using the scattering geometry in Figures 9 and 10, and equation (4) we find the following probability collision cross sections:

such that:

where: are the differential absolute probability that photon (i)

will scatter at an angle (0,·) through a differential solid angle dQi

[0124] Using vector analysis, the phase shift (δ) given in equation (13d) can be defined as the result of a rotation into new frame of reference (rotated clockwise by an angle (δ) about the ¾ axis) such that this rotated frame has one of its cross-hairs lying in the scattering plane while the other cross-hair is perpendicular to the scattering plane. These cross-hairs define a coordinate system whose basis lies parallel and perpendicular to the scattering plane which can then be used to expand the initial polarisation state of the third photon with relation to the scattering plane. It will be understood that βι is summed over the values βι = -δ (for the consequence that the first photon 901 has its plane of polarisation perpendicular to the scattering plane).

[0125] Applying the three absolute probability equations (12a), (12b) & (12c) to the calculation of scattering of the third photon 1003 by an electron, the normalised relative differential form of the probability distribution can be determined for two entangled photons, assuming that a total of three Compton interactions have occurred is given by:

where:

[0126] In this form, the probability distribution function can be used to calculate probability distributions for linearly and circularly initial states of polarisation and for specific types of detection systems. The current scenario relates to single particle collisions that involve either pairs of right circularly polarised or pairs of left handed circularly polarised photons.

[0127] A preliminary calculation, assuming detection only of events meeting the perpendicular scattering plane arrangement of Figure 7 gives an estimate for the triple Compton probability distribution for entangled photons. The preliminary calculation is based on a patient dose of 370 MBq and 70% scattering, and the case when the patient is scanned for 30 minutes an hour after the dose has been administered using a i m diameter Compton ring. Taking into account a detection efficiency of 0.0012, measurements will be received for approximately < 60 million impact sites, which relatively speaking is approximately 60% the intensity of the image produced by the detection of true events in current positron emission tomography scanners. It will be appreciated that further improvements in signal strength could be achieved by analysing off-perpendicular scattering events.

[0128] Accordingly, although two entangled particles cannot transmit a signal on their own, they can be combined with Compton cameras to extract more information from the environment through which they propagate. In particular, using a scattering pattern in which two cross-polarised photons preferentially scatter with their incident polarisation perpendicular to the scattering plane can be used to locate scattering within the subject. Under these conditions, the axis of symmetry of the Compton cone for the scattered photon is tangential to a surface of the Compton cone of the entangled unscattered photon. This 'tangential criteria' places a constraint on the possibility of incorrectly pairing up photons that are not entangled. This provides sufficient information to determine scattering locations using the derived impact site field equations. Since the probability of Compton scattering is proportional to the electron density of the atom or molecule, these field equations will generate density maps using the pre-existing attenuated fields, and preliminary calculations indicate that these density maps will be about 60% the intensity of a typical PET images using the unscattered component to within a volume of uncertainty about the impact site of at 500 mm distance or less.

[0129] The knowledge of these scattering locations can also be used to directly correct for attenuation. In medical imaging, measuring scattering locations has the potential to broaden the functionality of PET to improve analysis of regions of anatomy and potentially physiology.

[0130] Whilst the above described applications have focused on imaging of subjects, and particularly biological subjects as part of a PET imaging process, it will be appreciated that applicants of the above described techniques are not necessarily so limited, and potentially can be applied to any scenario in which positronium formation results in the generation of entangled gamma ray photons. In this instance, the invention can provide a method for use in imaging using any target object or region, using an array of Compton cameras to detect photons as a result of positron emission. Detected photons are analysed to identify scattered pairs, each scattered pair being a pair of entangled photons for which at least one photon is a scattered photon that has undergone scattering prior to detection, with the scattered pairs being used to construct a density map at least partially indicative of an anatomical structure of the target.

[0131] The term "Compton camera" refers to any detector arrangement that utilises Compton scattering in order to detect a particle such as a photon, typically using spaced apart scatterer and absorber plates, and optionally including multiple stacked plates, and use of the term is not intended to be limiting.

[0132] The terms "biological subject", "subject," "individual" and "patient" are used interchangeably herein to refer to an animal subject, particularly a vertebrate subject, and even more particularly a mammalian subject. Suitable vertebrate animals that fall within the scope of the invention include, but are not restricted to, any member of the subphylum Chordata including primates, rodents (e.g., mice rats, guinea pigs), lagomorphs (e.g., rabbits, hares), bovines (e.g., cattle), ovines (e.g., sheep), caprines (e.g., goats), porcines (e.g., pigs), equines (e.g., horses), canines (e.g., dogs), felines (e.g., cats), avians (e.g., chickens, turkeys, ducks, geese, companion birds such as canaries, budgerigars etc.), marine mammals (e.g., dolphins, whales), reptiles (snakes, frogs, lizards, etc.), and fish. A preferred subject is a primate (e.g., a human, ape, monkey, chimpanzee).

[0133] However, it will also be appreciated from the above, that the invention is not so limited and could cover other biological and non-biological applications, such as imaging minerals, slurries, plants, or the like, and the term "subject" will therefore be understood to apply to any target that could be imaged. Furthermore, the invention whilst described in conjunction with PET-CT, could be used as part of a standalone PET system, could be used as part of a PET-MR system or the like.

[0134] Throughout this specification and claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers or steps but not the exclusion of any other integer or group of integers. As used herein and unless otherwise stated, the term "approximately" means ±20%.

[0135] It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a support" includes a plurality of supports. In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings unless a contrary intention is apparent.

[0136] Persons skilled in the art will appreciate that numerous variations and modifications will become apparent. All such variations and modifications which become apparent to persons skilled in the art, should be considered to fall within the spirit and scope that the invention broadly appearing before described.