NL2013261B1

NL2013261B1 - A high energy radiation imaging focused pinhole collimator and device, and method for imaging.

Info

Publication number: NL2013261B1
Application number: NL2013261A
Authority: NL
Inventors: Johannes Beekman Frederik
Original assignee: Milabs Bv
Priority date: 2014-07-25
Filing date: 2014-07-25
Publication date: 2016-09-09

Abstract

A high energy radiation imaging focused pinhole collimator for small animal imaging, for example a mouse. The collimator has a tubular body with a small animal receiving bore that extends along a central longitudinal axis and is bounded by an inner face of the tubular body. The collimator has an axial imaging section provided with a plurality of focussed pinholes in the tubular body, each of said focussed pinholes embodied with a fixed dimension pinhole aperture and having an individual field-of-view. The focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume. In the axial imaging section of the collimator the inner face of the bore has a smallest radius relative to said central longitudinal axis in the range between 18 and 25 millimetres. The plurality of focussed pinholes comprises a first focussed pinholes group that are each arranged with the pinhole aperture thereof at a radial distance relative to said central longitudinal axis that is at least 15 millimeters greater than said smallest radius, and a second focussed pinholes group at a radial distance between 1 and 10 millimeters greater than said smallest radius.

Description

A HIGH ENERGY RADIATION IMAGING FOCUSED PINHOLE COLLIMATOR AND DEVICE, AND METHOD FOR IMAGING

According to an aspect thereof the present invention relates to the field of high energy radiation imaging of a small animal, in particular of a mouse, e.g. for biological or pharmaceutical research.

It is known in the field of small animal imaging to make use of high energy radiation imaging device wherein the animal, e.g. a mouse, is placed on a bed or in a carrier tube of the device and then introduced into the animal receiving bore of a pinhole collimator having multiple pinholes. The device has a detector device that is sensitive to high energy radiation and is arranged to receive high energy radiation emitted from the small animal to be imaged through the pinholes of the collimator onto the detector device. A known high energy radiation imaging device is marketed under the name U-SPECT. This known device comprises a collimator having a tubular body of high energy radiation opaque material with a small animal receiving bore that extends along a central longitudinal axis of the tubular body and is bounded by an inner face of the tubular body. The collimator has an axial imaging section wherein the tubular body is provided with a plurality of focussed pinholes. Each of these focussed pinholes is embodied with a fixed dimension pinhole aperture as well as an entrance cone and exit cone, leading to and from said pinhole aperture. Each pinhole has an individual field-of-view and the focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view. This common overlap defines a focus volume of the collimator.

It is known, as an optional feature, to arrange a shielding tube concentrically about the collimator, the shielding tube having openings for the high energy radiation emerging from the collimator and these openings being dimensioned so as to avoid overlapping projections on the detector.

The U-SPECT device is nowadays offered with collimator embodiments that are most preferred for application in imaging of a mouse, wherein the inner face of the animal receiving bore, at least in the axial imaging section of the collimator, has a smallest radius relative to the central longitudinal axis of 22 millimeters, and therefore a diameter of 44 millimeters. This internal diameter allows for placement of the tubular carrier and the mouse supported therein within the collimator bore, e.g. as the carrier tube has a diameter of 26 millimeters. The radial play between the carrier tube and the inner face of the bore allows for variation of the position of the mouse within the collimator in directions in a plane transverse to the central longitudinal axis. For example the carrier tube may be moved in the U-SPECT device in a helical path relative to the central longitudinal axis of the collimator. At the same time the limit diameter of the bore allows for a limited distance between the apertures of the pinholes and the mouse. In a known embodiment the pinhole apertures are arranged very close to the inner face, e.g. at a radius of 24 millimeters relative to the central longitudinal axis with the bore having a radius of 22 millimeters. The provision of the focussed pinholes in the U-SPECT and the resulting focus volume allows for a high resolution and sensitivity. For example practical resolutions of 0.25 millimeters when imaging a structure of interest in the mouse have been achieved.

The U-SPECT device is also offered with collimator embodiments that are most preferred in the imaging of a rat. Herein the inner face of the animal receiving bore, in the axial imaging section of the collimator, has a smallest radius relative to the central longitudinal axis of 49 millimeters, and therefore a diameter of 98 millimeters, with the pinhole apertures being arranged on a diameter of 106 millimeters.

It is an object of the first aspect of the present invention to provide a more versatile collimator, in particular suited for the high energy radiation imaging of a mouse, the collimator e.g. allowing for a reduction of the time that is needed to create a useful image of the small animal, e.g. of the structure of interest in the mouse.

Another, more general object of the invention, is to provide an alternative collimator, in particular a collimator for use in the imaging of a mouse emitting high energy radiation, e.g. gamma radiation.

The first aspect of the invention proposes a high energy radiation imaging focused pinhole collimator for small animal imaging, for example a mouse, the collimator having a tubular body of high energy radiation opaque material with a small animal receiving bore that extends along a central longitudinal axis of the tubular body and is bounded by an inner face of the tubular body, wherein the collimator has an axial imaging section that is provided with a plurality of focussed pinholes in the tubular body, each of said focussed pinholes embodied with a fixed dimension pinhole aperture and having an individual field-of-view, wherein said focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume, wherein, in said axial imaging section of the collimator, the inner face of the animal receiving bore has a smallest radius relative to said central longitudinal axis in the range between 18 and 25 millimetres, wherein said plurality of focussed pinholes comprises a first focussed pinholes group that are each arranged with the pinhole aperture thereof at a first radial distance relative to said central longitudinal axis, and said plurality of focussed pinholes comprises a second focussed pinholes group that are each arranged with the pinhole aperture thereof at a second radial distance relative to said central longitudinal axis, wherein the first radial distance is at least 2 millimeters greater than the second radial distance.

The high energy radiation emitted by the small animal to be imaged will commonly stem from introduced radioactive tracer material, e.g. allowing for in-vivo study of the distribution of a pharmaceutical agent in the mouse. In particular gamma radiation may be used. Such high energy radiation offers a useful range of radiation, having high penetration power.

In this application, and as generally understood in the art, a field of view of a pinhole corresponds to a solid angle that is imageable by the pinhole, in other words the part of three-dimensional space that can be seen by the detector through the pinhole.

The focus volume or central field of view (CFOV), which terms are used interchangeably here, can be defined as the volume that can be seen by all focussed pinholes of the collimator, i.e. the overlap of all their fields of view.

The present invention allows, at least for the lower regions of the mentioned 2 millimeters difference to obtain a noticeable increase of the diameter to the field of view of the first focussed pinholes group compared to the second focussed pinholes group. This e.g. enhances the view on the animal, e.g. reduces the change of missing relevant details within the animal that would otherwise be outside the effective view of the plurality of pinholes. If the difference is significantly increased, so that the second focussed pinholes group remains close to the animal and the first focussed pinholes group is moved drastically further away, the invention allows e.g. to perform a quick scan of the animal without having to resort to a complex motion path of the animal through the bore. For example the quick scan can be limited to a simple rectilinear path along the longitudinal axis. This e.g. allows to rapidly locate a region of interest in the animal.

The second focussed pinholes group allows to perform the imaging with a far greater sensitivity than the first focussed pinholes group, as sensitivity roughly has an inverse square dependence on distance. Since the second focussed pinholes group are much closer to the small animal, it is relatively easy to obtain a large image magnification factor and also a good image resolution.

In an embodiment the first radial distance is at least 3 millimeters greater than the second radial distance, e.g. at least 4 millimeters.

In an embodiment the first radial distance is at least 10 millimeters greater than said smallest radius, preferably at least 20 millimeters greater than said smallest radius.

In an embodiment the second radial distance is between 0 and 8 millimeters, preferably between 0 and 4 millimeters, greater than said smallest radius.

In an embodiment the animal receiving bore has a cylindrical inner face, preferably, in the axial imaging section of the collimator, the animal receiving bore having a uniform radius over the length thereof corresponding to said smallest radius.

In another embodiment the bore has a polygonal cross-section, however for small animal imaging a cylindrical inner face is preferred as it allows for a smaller distance to the animal of the second focussed pinholes group.

In an embodiment the first focussed pinhole group is arranged in one or more, preferably a single one, circular arrays of pinholes in a plane perpendicular to the central longitudinal axis. Possibly the second focussed pinhole group is arranged in one or more, preferably two or more, circular arrays of pinholes in a plane perpendicular to the central longitudinal axis. For example the first focussed pinholes group are arranged in one or more circular arrays that are sandwiched between arrays of the second focussed pinholes group.

The pinholes of the second focussed pinholes group are, preferably , arranged within a range of the radius that is now commonly used in a collimator for a mouse, e.g. as in the mentioned U-SPECT collimator for imaging a mouse.

The apertures of the pinholes in the first focussed pinholes group may be arranged at a significantly greater radius, e.g. more resembling the radius as nowadays employed in a collimator for a rat although the radius need not be that great to achieve benefits of this invention as explained above.

The first focussed pinholes group allows, in a structurally attractive manner, to obtain a greater effective field of view of the small animal without having to resort to a very large opening angle of the corresponding pinholes. A very large opening angle would result in a loss of directional information and thus information would be obtained that is less effective for image construction. In fact, in embodiments, the opening angle of the pinholes of the first pinholes group may be the same or even less than the opening angle of the pinholes in the second group, e.g. in view of the desire to arrange the pinholes in the collimator rather close together.

The image information obtained by means of the first focussed pinholes group may, in embodiments, be used to perform a fast scan of the small animal, e.g. to determine the actual location of the structure of interest within the animal, followed by a high-resolution imaging of said structure of interest. It is noted that the image information obtained by means of the first focussed pinholes group, as these pinholes also see the focus volume, is preferably used in the image reconstruction in combination with the image information obtained by means of the second focussed pinholes group, e.g. allowing for efficient reconstruction of a high-resolution image.

For example the provision of the first focussed pinholes group as provided according to the first aspect of the invention may allow for the detection of a tumour or the like close to the skin of the small animal, which location may be missed or be hard to retrieve if only pinholes at the radius of the second focussed pinholes group were present in the collimator.

In an embodiment of the focused pinhole collimator, in the axial imaging section of the collimator, the animal receiving bore has a uniform cross-section, e.g. a circular section, over the length thereof corresponding to said smallest radius. This allows for a simple structure of the collimator.

In an embodiment the axial imaging section of the collimator is composed of a series of exchangeable ring members that are axially stacked, wherein the first focussed pinhole group is arranged in one or more, preferably a single one, first focussed pinhole group ring members, and wherein the second focussed pinhole group is arranged in or more, preferably at least two, second focussed pinhole group ring members distinct from the first focussed pinhole group ring members. This assembly of the collimator allows for significant cost reduction as the ring members can be made individually and due to their limited axial length machining of the ring member, e.g. including making the pinholes or reception bores for pinhole inserts, is greatly facilitated. Further, by exchanging one or more ring members, the collimator can be changed as to the effective field of view of the pinholes, e.g. in view of different imaging actions to be performed. One can also envisage that, in case the first focussed pinhole group is not desired, the one or more ring members containing these pinholes are removed from the stack, possibly to be replaced by one or more further second ring members provided with additional pinholes having a field of view that overlaps the common field of view of other second ring members. So in general the structuring with the first focussed pinholes group in one or more ring members that are distinct from the second ring members allows for great cost reduction and versatility of the collimator. The one or more ring members may be cylindrical as is preferred, but one or more ring members could also have a polygonal shape, e.g. a hexagonal shape or octagonal shape.

In an embodiment the inner face of said at least one first focussed pinhole group ring member has a greater radius than said smallest radius, with said smallest radius being defined by the inner face of one or more, preferably all, second focussed pinhole group ring members. This e.g. allows for a significant opening angle of the first pinholes in a structurally simple manner.

In an embodiment one or more, e.g. each, of the pinholes of the first focussed pinhole group is arranged with a central line of the pinhole in a plane normal to the central longitudinal axis of the collimator. One can e.g. envisage these pinholes to be arranged in a single first ring member, wherein provision is made for one or more second ring members at each side of the single first ring member.

In an embodiment one or more of the pinholes of the first focussed pinhole group are arranged with a central line of the pinhole having an axial component directed to one end of the imaging section and one or more other pinholes of the first focussed pinhole group are arranged with a central line of the pinhole having an axial component direction to the other end of the imaging section. For example one first ring member is provided with first group pinholes directed towards one end of the imaging section and a further first ring member is provided with first group pinholes directed towards the other end. For example the pinholes in one ring member are circumferentially offset from the pinholes in the other ring member. It will be appreciated that the same arrangement and orientation of these pinholes is possible of the collimator does not have ring members as discussed herein.

In an embodiment the one or more of the pinholes of the first focussed pinhole group, preferably all, have a pinhole aperture with an area that is greater than the area of each of the pinholes of the second focussed pinhole group, e.g. an area that is at least 1.2 times greater, e.g. at least 1.4 times greater, e.g. between 1.8 and 2.2 times greater. The increased aperture area compensates, at least partially for the increased radius relative to the pinholes of the second focussed pinholes group. In a practical embodiment the first pinholes have a circular aperture of between 1.0 and 1.5 millimeter, e.g. 1.2 millimeter, whereas the second pinholes may each have a circular aperture of 0.6 millimeter.

In an embodiment, e.g. as in the known U-SPECT collimators, the tubular body of the collimator has an axial mounting section, devoid of pinholes, as an axial extension of the axial imaging section, the axial mounting section being adapted to mount the collimator to an imaging device.

At least in the axial imaging section of the collimator the inner face preferably is cylindrical but in another embodiment the inner face is a regular polygon, e.g. a hexagon or an octagon.

In embodiments the tubular body of the collimator has an outer face that is rotation symmetrical.

The focus volume may be centered with respect to the central longitudinal axis, yet in another embodiment the focus volume is located eccentrically with respect to said axis.

In embodiments the opening angle of the pinholes which are closer to the focus volume can be taken larger than the opening angle of pinholes further away, at least in the case of a circular focus volume. In the present invention, this can be a characteristic of some collimators. However, this is only desirable if one wants no overlap of projections, or a similar amount of overlap, and it is certainly possible to provide a collimator with equal pinholes, providing e.g. a non-spherical focus volume, or varying overlap of projections.

The collimator has its usual function of selecting certain directions of the radiation emitted by the small animal to be imaged onto the detector. True and practical lenses do not yet exist for high energy radiation, like gamma radiation, but in order to select, collimators use pinholes that transmit only radiation coming from certain directions, i.e. from their individual field-of-view, often a true cone or a pyramid-like cone. These fields-of-view are imaged onto the detector surface(s), providing as many images as there are pinholes. Suitable image reconstruction techniques, using a computer and specific image processing software can then be employed to reconstruct the isotope distribution in the small animal.

In advantageous embodiments, the collimator has at least ten pinholes, preferably more than twenty pinholes. This ensures not only sufficient angle information and sensitivity of the device, but also a limited complexity.

The possible number of pinholes is of course not limited. The pinholes are preferably arranged in a three-dimensional structure, such as in parallel circular series or on one or more helical lines. Still, the pinholes are focused onto the object space. This configuration allows even more angular information to be obtained. The number and arrangement of the pinholes could for example be 75, cfr. the prior art devices U-SPECT-I and -II with 75 individual pinholes, arranged as five rings with 15 pinholes each.

Note that further details, such as of a movability of the object carrier, graphical user interfaces, additional so-called shielding tube or framing plates between the collimator and the detector, and so on, are generally known in the art and may be included where desired. Details may be found in e.g. prior devices and applications by applicant, such as the already mentioned U-SPECT.

In an embodiment of the invention, the pinholes in the collimator are arranged such that their individual fields-of-view provide two distinct focus volumes, e.g. axially offset from one another and/or one or more located eccentrically with respect to the central longitudinal axis. That is to say, a first collection of pinholes focuses on a first focus volume, while a second collection of pinholes focuses a second focus volume. Advantageously, though not necessarily, each collection comprises neighbouring pinholes. If the focus volumes are located eccentrically, there will be enough space on the collimator for pinholes to be positioned such that for each focus volume full 180° angular information can be obtained. An advantage of having two eccentric focus volumes is that the average distance of the collimator to the corresponding focus volume is much smaller, relatively speaking. This ensures an increased sensitivity and resolution.

Furthermore, two positions in an object can be imaged at the same time. In particular with two substantially symmetrically positioned eccentric parts in an object, this is already very useful. An example is the kidneys in an animal or a human. Note that it is possible, in some cases, to provide even more than two focus volumes, in particular three focus volumes. This holds in particular for imaging in which it is not necessary to obtain complete data, such as for sparse objects.

The tubular body of the collimator blocks unwanted radiation, e.g. the body being made of heavy, dense metal, such as lead, tungsten, gold, iridium or (depleted) uranium.

In a preferred embodiment the animal receiving bore has a uniform diameter cylindrical inner face over the length of the imaging section, or at least over each ring member of which said imaging section is composed. Preferably the outer surface of the collimator imaging section is of similar cross-sectional shape, e.g. cylindrical. Because of the regular shape of the wall, reconstruction algorithms are less complex.

The first aspect of the present invention also relates to a high energy radiation imaging focused pinhole collimator for small animal imaging, for example a mouse, said collimator having a tubular body of high energy radiation opaque material with a small animal receiving bore that extends along a central longitudinal axis of the tubular body and is bounded by an inner face of the tubular body, wherein the collimator has an axial imaging section that is provided with a plurality of focussed pinholes in the tubular body, each of said focussed pinholes embodied with a fixed dimension pinhole aperture and having an individual field-of-view, wherein said focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume, wherein, in said axial imaging section of the collimator, the inner face of the animal receiving bore has a smallest radius relative to said central longitudinal axis, for example in the range between 18 and 25 millimetres, and wherein said plurality of focussed pinholes comprises a first focussed pinholes group that are each arranged with the pinhole aperture thereof at a first radial distance relative to said central longitudinal axis and wherein said plurality of focussed pinholes comprises a second focussed pinholes group that are each arranged with the pinhole aperture thereof at a second radial distance relative to said central longitudinal axis and wherein said first radial distance is at least 1.2 times the second radial distance.

The first aspect of the invention also relates to a high energy radiation imaging device for small animal imaging, said device comprising: - a high energy radiation imaging focused pinhole collimator according to the first aspect of the invention, - a detector device sensitive to said high energy radiation and arrange to receive high energy radiation emitted from the small animal to be image through the pinholes of the collimator onto the detector device.

The detector device may comprise several detector units, e.g. three detector units having generally planar detector plates that are arranged in a triangular arrangement around the collimator as in the mentioned U-SPECT device. A particularly advantageous device according to the invention is a single photon emission computed tomography scanner, or so-called SPECT scanner.

In an embodiment, e.g. as known from the mentioned prior art, the imaging device further comprises a cantilevered animal carrier, e.g. a bed or carrier tube, adapted to support the small animal thereon, e.g. a mouse, and a motion device that supports said animal carrier and is adapted to move said carrier at least in the direction of the central longitudinal axis of the collimator to allow introduction and removal of the animal supported on the bed into and out of the animal receiving bore of the collimator, preferably said motion device further being adapted to move said bed at least in one or more other directions, e.g. also in two orthogonal directions in a plane normal to said central longitudinal axis, e.g. in a helical path relative to said central longitudinal axis. As is known in the art, the carrier is preferably of a radiation transparent material, e.g. plastic or carbon fibre.

In favourable embodiments, the imaging device the animal carrier is moveable in at least the longitudinal axis direction and preferably two directions perpendicular to said longitudinal axis, more preferably by means of a motion device, e.g. a computer controlled electric motion device. This allows shifting of the animal along the longitudinal axis, e.g. to perform a quick scan of the animal on the basis of information obtained by the first focussed pinholes group. The provision of motion in one or more other directions may be of great benefit when performing a high resolution scan of a region or structure of interest, e.g. using the entire plurality of focussed pinholes as the region of structure is positioned within the focus volume or moved to pass (e.g. stepwise) through said focus volume, e.g. when the region is larger than the focus volume.

In embodiments, the imaging device is adapted to allow for controlled rotation of the collimator around an axis of rotation that extends parallel to the central longitudinal axis of the collimator, which axis of rotation intersects the bore. Preferably the axis of rotation coincides with the central longitudinal axis of the collimator. This is in particular advantageous in combination with an eccentric focus volume relative to said axis of rotation. This rotation of the collimator allows scanning of the focus volume through the small animal, and in some cases also collecting even more angular information of a region or structure of interest in the animal. In the case of an axis of rotation not coinciding with the longitudinal axis, the collimator will wobble around said longitudinal axis. Nevertheless, image reconstruction is still possible, and the specific orbit may be useful. However, when the axis of rotation coincides with the longitudinal axis, a simple rotation results, and image reconstruction is less complex.

In particular embodiments, the device is adapted to rotate the collimator over at least 20° around the central longitudinal axis. A relatively small rotational angle may suffice when imaging a region of interest that is not substantially larger than the focus volume, for only little additional angular information will do in such case. An example is a heart, which is a relatively small organ positioned relatively eccentrically. In another embodiment, the device is adapted for rotation of the collimator over at least 180°, or preferably 180° plus the (average) opening angle of the pinholes. This suffices to scan through a maximum part of the object to be imaged, especially if it is possible to image the object after rotating the object 180°, since rescanning the object then comes down to a full 360° rotation. In an embodiment, the collimator is rotatable over 360°. This of course allows a full scan without having to turn the animal, which turning is not always possible or advisable. However, in an embodiment one can envisage that the collimator is held stationary and the animal carrier is made to rotate as described here relative to the stationary collimator.

In embodiments, the imaging device further comprises a collimator rotator drive adapted to cause controlled rotation of the collimator. Although it may in embodiments be possible to rotate the collimator by hand, through a suitable mechanical coupling, it is advantageous (more precise, less error prone etc.) if such rotation may be performed automatically by a dedicated collimator rotator drive. In such case it is important to store the angle of rotation as a function of (scanning) time, in order to be able to correlate detector counts and time.

The detector device, having a detector surface and being sensitive to said high energy radiation, and extending at least partially around the collimator, may also be rotatable. Thereto, the detector may be coupled to the collimator, allowing simultaneous rotation. The detector could be concentric to the collimator(s). Preferably, the detectors comprise detector surfaces arranged on a, preferably regular, polygon, such as a triangle (cfr. the U-SPECT designs), a square box or e.g. an octagon. Having multiple but flat detector surface allows simpler detector production and image reconstruction, although rounded detector surfaces are not excluded.

As in the prior art a shielding tube may be arranged concentrically around the collimator, e.g. to avoid or reduce undesired overlapping of images on the detector.

The first aspect of the invention also relates to a method for imaging a small animal by means of high energy radiation emitted from the small animal using a high energy radiation imaging focused pinhole collimator or high energy radiation imaging device according to the first aspect of the invention.

According to a second aspect thereof the present invention envisages the use of the disclosed technology for larger objects to be imaged, e.g. for use on a human object, e.g. in a head imaging device for imaging a human head, a breast imaging device for imaging a female breast or an imaging device for another part or portion of the human body, e.g. an arm.

The second aspect of the invention provides a high energy radiation imaging focused pinhole collimator for imaging an object, said collimator having a tubular body of high energy radiation opaque material with an object receiving bore that extends along a central longitudinal axis of the tubular body and is bounded by an inner face of the tubular body, wherein the collimator has an axial imaging section that is provided with a plurality of focussed pinholes in the tubular body, each of said focussed pinholes embodied with a fixed dimension pinhole aperture and having an individual field-of-view, wherein said focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume, wherein, in said axial imaging section of the collimator, the inner face of the animal receiving bore has a smallest radius relative to said central longitudinal axis, and wherein said plurality of focussed pinholes comprises a first focussed pinholes group that are each arranged with the pinhole aperture thereof at a first radial distance relative to said central longitudinal axis, and wherein said plurality of focussed pinholes comprises a second focussed pinholes group that are each arranged with the pinhole aperture thereof at a second radial distance relative to said central longitudinal axis, and wherein said first radial distance is at least 1.2 times the second radial distance.

For example, in the second aspect of the invention, the bore of the collimator can be 0.15 meters or more, e.g. between 0.15 and 0.25 meter, or even greater, e.g. more than 0.30 meter, e.g. between 0.40 meter and 1.00 meter. For example the bore is sized to accept a human head therein in order to image the human head. In another embodiment the bore is sized to allow for a human to be passed into the bore when supported on a bed.

It will be appreciated that the collimator of the second aspect of the invention may, in embodiments, have one or more of the optional features discussed herein with reference to the first aspect of the invention, possibly without the limitation of the first radial distance being at least 1.2.times the second radial distance. For example the design with stacked ring members may be incorporated in such a collimator.

In a specific embodiment the object is a human head.

In another embodiment a female breast to be imaged, with the bore being adapted to receive a female breast therein, e.g. the bore being vertical and the female person being supported on a table of the imaging device so that the breast hangs in the bore of the collimator.

For example the collimator is movable relative to a human person support table, e.g. up and down and possibly also in one or more horizontal directions, for example relative to the head or breast in order to scan the focus volume through the head or breast or one or more regions of interest thereof.

In an embodiment, e.g. as known from the mentioned prior art, the imaging device further comprises a cantilevered object carrier, e.g. a bed or carrier tube, adapted to support the object thereon, and a motion device that supports said carrier and is adapted to move said object carrier at least in the direction of the central longitudinal axis of the collimator to allow introduction and removal of the object supported on the carrier into and out of the bore of the collimator. The carrier may, in an embodiment, be a bed that is adapted to support a human person thereon, e.g. the bore being dimensioned to pass the bed into the bore. Preferably said motion device further being adapted to move said bed at least in one or more other directions, e.g. also in two orthogonal directions in a plane normal to said central longitudinal axis, e.g. in a helical path relative to said central longitudinal axis.

The second aspect of the invention also relates to a high energy radiation imaging device for imaging an object, said device comprising: - a high energy radiation imaging focused pinhole collimator according to the second aspect of the invention, - a detector device sensitive to said high energy radiation and arrange to receive high energy radiation emitted from the object to be image through the pinholes of the collimator onto the detector device.

The second aspect of the invention also relates to a method for imaging an object by means of high energy radiation emitted from the object using a high energy radiation imaging focused pinhole collimator or high energy radiation imaging device according to the second aspect of the invention.

The invention will now be explained by means of non-limiting embodiments, with reference to the drawings in which:

Figure 1 diagrammatically shows an imaging device 1 according to the invention; Figure 2 diagrammatically shows a mouse with internal organs, as well as a prior art high energy radiation imaging focused pinhole collimator for small animal imaging;

Figure 3 diagrammatically shows the mouse carried by an animal carrier within the bore of the prior art collimator of figure 2;

Figure 4 diagrammatically shows an embodiment of the imaging section of a high energy radiation imaging focused pinhole collimator according to the invention, with the mouse in the bore thereof supported on an animal carrier;

Figure 5 diagrammatically shows the collimator of figure 4 in an imaging device according to the invention, and

Figure 6 diagrammatically shows the collimator of figure 4 assembled from ring members.

Figure 1 diagrammatically shows an example of a high energy radiation, e.g. gamma radiation, imaging device 1 according to the invention. The device 1 comprises a frame 2, a detector 10, a high energy radiation imaging focused pinhole collimator 20, and a small animal carrier assembly 40.

The detector 10 is sensitive to high energy radiation and arrange to receive high energy radiation emitted from the small animal to be imaged through the pinholes of the collimator 20 onto the detector device. Here the detector 10 is shown in the form of a triangular constellation of three detector plates 11,12 (one left out for clarity), each e.g. comprising a scintillation device for detecting high energy photons, such as gamma photons. Other detector shapes are possible, such as the ones described below.

The collimator 20 is shown only very diagrammatically in figure 1 is attached to the device 1, e.g. to a rotation drive for the collimator.

The device 1 is provided with an animal carrier assembly 40 including a cantilevered animal carrier 41, e.g. a bed or carrier tube, that is adapted to support the small animal thereon. A motion device 42 supports the animal carrier 41 and is adapted to move the carrier 41 at least in the direction of the central longitudinal axis, here horizontal as is preferred, of the collimator 20 to allow introduction and removal of the animal supported on the carrier 41 into and out of the animal receiving bore of the collimator 20. As is preferred the motion device 42 is further adapted to move the carrier 41 at least in one or more other directions, e.g. also in two orthogonal directions in a plane normal to said central longitudinal axis, e.g. in a helical path relative to said central longitudinal axis.

In order to facilitate the understanding of the present invention first, with reference to figures 2 and 3, a prior art high energy radiation imaging focused pinhole collimator 60 for small animal imaging, here for a mouse 70, will be discussed.

Figure 2 shows the prior art mouse collimator 60 having a tubular body 61 of high energy radiation opaque material with a small animal receiving bore 62 that extends along a central longitudinal axis 63 of the tubular body and is bounded by an inner face 64 of the tubular body.

The figures 2 and 3 only show an axial imaging section 65 of the collimator 60, which is in the prior art extended as discussed above.

The axial imaging section 65 is provided with a plurality of focussed pinholes 66-1,66-2,66-3, 66-4,. .. , 66 -10, e.g. in the tubular body. Here pinholes are depicted as in a common longitudinal sectional plane intersecting the axis 63 which is done for clarity here. In reality the pinholes may be arranged in a helix at different circumferential locations.

Each of these focussed pinholes 66-1, etc. is embodied with a fixed dimension pinhole aperture and has an individual field-of-view depicted by lines emerging from the pinhole. These pinholes 66-1, etc. are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume reference with FV.

As mentioned in the introduction, in the axial imaging section 65 of the collimator, the inner face 64 of the animal receiving bore 62 has a smallest radius relative to the central longitudinal axis 63 of 20 millimetres, so the bore has a 40 millimeters diameter.

In figure 3 it is depicted that mouse 70 is arranged on carrier 41 which has been introduced into the prior art collimator 60. The focus volume is positioned on a region of interest of the mouse.

With reference to figures 4 and 5 now an example of a high energy radiation imaging focused pinhole collimator 20 for small animal imaging, for example mouse 70, will be discussed.

The collimator 20 has a tubular body 21 of high energy radiation opaque material with a small animal receiving bore 22 that extends along a central longitudinal axis 23, here horizontal, of the tubular body and is bounded by an inner face 24 of the tubular body.

The collimator 20 has an axial imaging section 25 that is provided with a plurality of focussed pinholes in the tubular body, each of said focussed pinholes embodied with a fixed dimension pinhole aperture and having an individual field-of-view. The focussed pinholes are constructed and arranged so as to establish a common overlap of their individual fields of view, said common overlap defining a focus volume FV.

In the axial imaging section 25 of the collimator 20, the inner face 24 of the animal receiving bore has a smallest radius SR relative to the central longitudinal axis in the range between 18 and 25 millimetres, so encompassing and rather similar to the 20 millimeters of the prior art design.

In contrast to the prior art design depicted in figures 2, 3 the plurality of focussed pinholes comprises a first focussed pinholes group 26-1,26-2 that are each arranged with the pinhole aperture thereof at a first radial distance relative to said central longitudinal axis and a second focussed pinholes group 27-1, 27-2, 27-3, 27-4...... 27-8, that are each arranged with the pinhole aperture thereof at a second radial distance relative to said central longitudinal axis 23, wherein the first radial distance is at least 2 millimeters greater than the second radial distance. As can be seen here the difference is much greater, with the first pinholes at a distance that is now common for a rat collimator. As explained advantages are also achieved when the difference is much smaller, as the field of view increase significantly even for small differences.

Other preferred arrangements of the pinholes and possible structural features of the collimator have been discussed above and are mentioned in the subclaims.

As explained above the presence of the first focussed pinholes group at a great first radial distance within the plurality of focussed pinholes having the focus volume FV e.g. allows for an enhanced scanning of the mouse, e.g. by merely passing the animal in a single rectilinear path through the bore. Other advantages are discussed in detail above.

In the embodiment shown here, in the axial imaging section of the collimator, the animal receiving bore is circular in cross-section and has a uniform radius over the length thereof corresponding to said smallest radius SR.

By dividing the unitary structure of the collimator body in ring members, one can obtain a structure wherein the axial imaging section of the collimator is composed of a series of exchangeable ring members 80, 82, 84, 86, 88, that are axially stacked. This is shown in figure 6. This may also be done for polygonal ring members.

In embodiment schematically shown in figure 6, the first focussed pinhole group 26-1, 26-2 is arranged in one or more, preferably a single one 80, first focussed pinhole group ring members.

The second focussed pinhole group is arranged in or more, preferably at least two, here four 82, 84, 86, 88, second focussed pinhole group ring members distinct from the one or more first focussed pinhole group ring members 80.

In this example one or more, here all, of the pinholes 26-1, 26-2, of the first focussed pinhole group is arranged with a central line of the pinhole in a plane normal to the central longitudinal axis 23 of the collimator 20.

As can be seen in figure 6 the tubular body of the collimator 20 has an axial mounting section 29, devoid of pinholes, as an axial extension of the axial imaging section 25, the axial mounting section being adapted to mount the collimator to the imaging device 1.

Claims

A focussed pinhole collimator (20) for high energy radiation imaging for imaging small animals, for example a mouse (70), which collimator has a tubular body (21) made of high energy radiation impermeable material with a recording bore ( 22) for a small animal extending along a central longitudinal axis (23) of the tubular body and bounded by an inner surface (24) of the tubular body, the collimator having an axial imaging section (25) provided with a plurality of focused pinholes in the tubular body, each of those focused pinholes being formed with a pinhole opening of fixed dimensions and having an individual field of view, the focused pinholes being arranged and arranged to form a common overlap of their individual fields of view, which common overlap forms a focus volume (FV), wherein, in the axial imaging section (25) of the collimator, the inner surface of the the recording bore for the small animal has a smallest radius (SR) with respect to the central longitudinal axis (23) in the range between 18 and 25 millimeters, and wherein said plurality of focused pinholes has a first focused pinholes group (26-1, 26-) 2) each of which is arranged with its pinhole opening at a first radial distance with respect to the central longitudinal axis (23), and said plurality of focused pinholes a second focused pinholes group (27-1, ..., 27-8) ) each arranged with its pinhole opening at a second radial distance from the central longitudinal axis (23), the first radial distance being at least 2 millimeters greater than the second radial distance.

A focused pinhole collimator according to claim 1, wherein the first radial distance is at least 3 millimeters greater than the second radial distance, for example at least 4 millimeters.

A focused pinhole collimator according to claim 1 or 2, wherein the first radial distance is at least 10 millimeters greater than the smallest radius (SR), preferably at least 20 millimeters greater than that smallest radius.

A focused pinhole collimator according to any one of the preceding claims, wherein the second radial distance between 0 and 8 millimeters, preferably between 0 and 4 millimeters, is greater than said smallest radius (SR).

A focused pinhole collimator according to any of the preceding claims, wherein the recording bore for the animal has a cylindrical inner surface, wherein, preferably, in the axial imaging portion (25) of the collimator, the animal recording bore has a uniform radius corresponding to its length with the smallest radius mentioned.

The focused pinhole collimator according to any of the preceding claims, wherein the first focused pinhole group is arranged in one or more, preferably a single (80), circular array of pinholes in a plane perpendicular to the central longitudinal axis, and wherein, possibly the second focused pinhole group is arranged in one or more, preferably two or more, circular arrays of pinholes in a plane perpendicular to the central longitudinal axis.

The focused pinhole collimator according to any of the preceding claims, wherein the axial imaging section of the collimator (20) is composed of a series of interchangeable ring members (80, 82, 84, 86, 88) stacked axially, the first focused pinhole group is arranged in one or more, preferably in a single (80), first focused pinhole group of ring members, and wherein the second focused pinhole group is arranged in one or more, preferably at least two, second focused pinhole group of ring members ( 82, 84, 86, 88) that differ from the first focused pinhole group of ring members.

The focused pinhole collimator according to claim 7, wherein the inner surface of the at least one first focused pinhole group ring member has a greater radius than said smallest radius, the smallest radius being defined by the inner surface of one or more, preferably all, second focused pinhole group of ring organs.

The focused pinhole collimator according to any of claims 1-8, wherein one or more, for example, each of the pinholes of the first focused pinhole group (26-1, 26-2) is arranged with a central line of the pinhole in a plane perpendicular to the central longitudinal axis of the collimator.

The focused pinhole collimator according to any of claims 1-9, wherein one or more of the pinholes of the first focused pinhole group are arranged with the central line of the pinhole with an axial component directed toward one end of the imaging portion and one or more other pinholes of the first focused pinhole group are arranged with a central line of the pinhole with an axial component facing the other end of the display portion.

A focused pinhole collimator according to any one of claims 1-10, wherein one or more of the pinholes of the first focused pinhole group (26-1, 26-2), preferably all, have a pinhole opening with a surface that is larger is then the surface of each of the pinholes of the second focused pinhole group (27-1, .... 27-8), for example a surface that is at least 1.2 times larger, for example at least 1.4 times larger, for example between 1.8 and 2.2 times larger.

The focused pinhole collimator according to any of claims 1-11, wherein the tubular body of the collimator has an axial attachment section (29) that is free from pinholes, as an axial extension of the axial imaging section, the axial attachment portion is adapted to attach the collimator to a display device.

A high energy radiation imaging device for imaging a small animal, which device comprises: - a focused pinhole collimator (20) for high energy radiation imaging according to one or more of the preceding claims, - a detector device (10) which is sensitive to the said high energy radiation and is arranged to receive high energy radiation emitted by the small animal to be imaged through the pinholes of the collimator on the detector device.

The high energy radiation display device of claim 13, further comprising an animal carrier (41) supported at one end, for example a bed or carrier tube, which is adapted to support the small animal (70) thereon, and a moving device (42), for example with one or more electric motors, which supports the animal carrier and is adapted to move the carrier at least in the direction of the central longitudinal axis of the collimator in order to introduce or remove the animal supported on the carrier into the animal receiving bore (23) of the collimator wherein the moving device is preferably further adapted to move the carrier (41) at least in one or more directions, for example also in two orthogonal directions in a plane perpendicular to the central longitudinal axis (23), for example in a helical path relative to the central longitudinal axis.

A method for imaging a small animal by high energy radiation emitted by the small animal using a focused pinhole collimator (20) for high energy radiation imaging or a high energy radiation imaging device (1) according to one of the preceding claims.