EP0710363A1

EP0710363A1 - Nmr sample holder

Info

Publication number: EP0710363A1
Application number: EP94916081A
Authority: EP
Inventors: James Field; Ross Thomas Mckenna; Stephen Edward Rose; Ian Malcolm Brereton; Wolfgang Roffmann; Stephen James Wilson; Stuart Crozier; David Michael Doddrell
Original assignee: University of Queensland UQ
Current assignee: University of Queensland UQ
Priority date: 1993-05-21
Filing date: 1994-05-20
Publication date: 1996-05-08
Also published as: EP0710363A4; WO1994028431A1

Abstract

A sample holder (10) for use with an NMR probe comprises a contoured element (11) in which a small animal or other sample is placed. The sample is fixed longitudinally and rotationally relative to the contoured element (11) by fixing means comprising a transverse bar (20) and callipers (24, 25), both of which can be adjusted from outside the sample holder. Anaesthetic gases are delivered by tube (17) while waste vapours are extracted by suction. The axial position of the sample holder relative to its associated probe resonator is adjustable via a knob (44) on the exterior of the resonator.

Description

NMRSAMPLEHOLDER THIS INVENTION relates to an NMR (Nuclear Magnetic Resonance) probe and associated components which enable Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Imaging (MRI) to be performed on subjects such as living tissues and organs, as well as inanimate materials. In particular, the invention is directed to a removable sample holder for use with the probe, means for precise positioning of the sample holder relative to the probe, and means for secure and accurate fixing of the sample relative to the holder.

BACKGROUND ART The techniques derived from the study of nuclear magnetic resonance allow those skilled in the art to acquire both spectra representative of chemical species present in a sample, and images representative of cross-sections of the sample. A key device in the production of such data is the radio frequency (RF) probe. This probe provides the means by which sample material of any suitable nature is positioned in a magnetic field, and excited by electromagnetic radiation in the radio frequency region of the spectrum. The radiation emitted from the sample is then detected. Single or multiple electrically resonant devices or resonators provide the means by which the sample is excited and emitted radiation is detected.

Examples of such devices can be found in U.S. patents nos. 4,680,548 and 4,694,255, and described in NMR and Living Systems: Gadian, D.G., Oxford University Press, page 156 et. seg.

Commercially available NMR probes are currently constructed so that all of the RF electronics and sensing hardware are enclosed in the body of the probe. These probes have been designed primarily for microscopy on inanimate objects. Attempts have been made to employ such hardware to study living animals, namely laboratory mice. To date, when conducting magnetic resonance imaging of live laboratory rodents, the animal has been attached to a minimally contoured member and positioned appropriately in the resonator prior to the imaging procedure. The animal has been attached in an improvised manner, either by fixing of its incisor teeth by a rigid member or ligature, or the fixation of external auditory meatus by adjustable conical members, or both. There has been no provision on the probe for the application of anaesthetic compounds nor removal of waste products from the animal. Importantly, the probes do not have any animal control processes (such as temperature, respiration, ECG monitoring) built into them.

The physical wellbeing of the animal is typically monitored electrocardiographically by separate means. To immobilise the animal, anaesthetic gases and vapours are administered to the animal by an added tube, this being an additional procedure for the technician, and requiring entities. In any case, this facility is normally provided only on state of the art probes.

Once the probe has been fixed in place however, it is not possible to change the position of the rodent or other sample. Typically, the probe is placed in a superconducting magnetic bore which precludes any physical alteration to the sample during the experimental procedure. It is an object of the present invention to provide a sample holder for an RF probe, which overcomes or ameliorates the abovedescribed disadvantages, or which at least provides the user with a useful choice.

It is another object of the invention to provide a sample holder adapted for functional integration with a radio frequency resonator and its associated NMR hardware.

SUMMARY OF THE INVENTION In one broad form, the present invention provides a sample holder suitable for use with a RF probe having a tubular resonator, the sample holder comprising an elongate member removably insertible axially within the bore of the resonator and having means for fixing a sample relative thereto.

The axial position of the elongate member relative to the resonator can be varied by adjustment means on the resonator. In this manner, different regions of interest in the sample may be optimally placed relative to the resonator by the adjustment means.

As the sample holder is removable from within the resonator, the sample under examination can be changed without the necessity of removing the RF probe from its superconducting magnet. That is, a plurality of sample holders may be provided, each containing a respective sample. The sample under examination may be interchanged with another sample simply by interchanging the associated sample holders. Thus, the efficiency of multiple examinations is improved substantially.

In the preferred embodiment, the adjustment means comprises a knob on the exterior of the resonator base which has a pinion on its inner end. This pinion engages a rack fixed relative to the sample holder. Rotation of the knob causes the sample holder to move axially within the resonator.

The means for fixing the sample relative to the sample holder preferably comprises a pair of callipers adapted to grasp the inanimate sample therebetween. For a live sample, such as a rodent, the callipers each have a conical element at their free end which locates in a respective ear opening in the rodent's hea . The opening and closing of the callipers is suitably controlled by a manually operable knob on the exterior of the sample holder.

In addition, the sample holder preferably comprises a member for fixing the anterior of the cranium. This may suitably comprise a transverse bar which locates behind the upper incisor teeth of the rodent. The axial position of the bar is adjustable to accommodate different sized animals. Again, the position of the bar is adjustable via a knob on the exterior of the sample holder. The sample holder suitably includes means for delivering anaesthetic gas to the region of the animal's head. In the preferred embodiment, such means comprises a delivery tube extending longitudinally along the holder. One end of the tube terminates adjacent the rodent's head, while the other end extends beyond the opposite end of the holder for connection to a gas supply.

In order that the invention may be more fully understood and put into practice, a preferred embodiment thereof will now be described by way of example only, with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic exploded view of a sample holder for an NMR probe, principally adapted for laboratory animal studies;

Fig. 2 is a perspective view of the contoured element of the holder of Fig. 1, with rodent sample fixed thereon; Fig. 3a is a perspective view (from one end) of the animal fixing means of the holder of Fig. 1.;

Fig. 3b is a perspective view (from the other end) of the animal fixing means;

Fig. 4 is a perspective view of a modified form of the fixing means for inanimate objects;

Fig. 5 is a perspective view illustrating the sample holder of Fig. 1 relative to its associated resonator; and

Fig. 6 is a schematic perspective view of the position adjustment means of the sample holder.

DESCRIPTION OF PREFERRED EMBODIMENT As shown in Fig. 1, a sample holder 10 for an NMR probe comprises a contoured element 11 in which the animal or other sample is accommodated in use. The animal/sample is precisely located and fixed in position relative to the contoured element 11 by a shroud member 12 (described in more detail later). The contoured element 11 is connected to a spacer member 13 via an intermediate member 14. A rack member 15 is connected to the other end of spacer member 13.

The rack member 15 forms part of a position adjustment mechanism, also described in more detail later. The end of the sample holder 10 is capped by base member 16. The various elements of the sample holder are keyed to prevent relative axial rotation between them.

As depicted in Fig. 2, the laboratory animal (a mouse) is placed on its back on the contoured element 11, and the cranium of the animal is fixed relative to the sample holder 10 by fixing means on shroud member 12.

As shown more clearly in Figs. 3a and 3b, the fixing means comprises a transverse bar 20 which is located behind the upper incisor teeth of the mouse, thereby fixing the cranium in the axial direction. The bar 20 is mounted on a sliding element 21 which is threadedly connected to a threaded rod 22 which functions as a lead screw. The threaded rod 22 is connected to a manually operable knob 23 on the exterior of the shroud 12. Thus, the axial position of the bar 20 can be adjusted by rotating knob 23 to thereby place the mouse in the desired position, or to accommodate different sized mice.

The base of the mouse cranium is located transversely by a pair of callipers 24, 25 each of which has a respective conical element 26, 27 adjacent its end. The callipers 24, 25 are pivotally connected to a crank 28 which, in turn, is able to be rotated by knob 29 on the exterior of the shroud 12. In this manner, the callipers 24, 25 can be open and closed by manual rotation of the knob 29. In use, the conical elements 26, 27 locate in the external auditory meatus of the mouse.

Anaesthetic gases are delivered to the head of the mouse by a tube 17 which extends from base 16, through spacer member 13 and along the reverse side of the contoured element 11 to be delivered to the mouth and nose of the animal held by shroud 12. The mouse end of the tube 17 is suitably located in a channel 29 in the end face of the shroud 12, as shown in Figs. 3a and 3b. The exhausting of waste vapours and gases is performed by a negative pressure applied via base 16 to the lumen of tubular spacer 13. Waste vapours and gases flow through the interstices of element 14 from all regions adjacent to the subject animal.

Fig. 4 illustrates a modified version of the shroud 12a suitable for locating an inanimate sample 30. In this embodiment, callipers 31, 32 have contoured lengthened arms to grasp the sample 30 in a secure grip. Of course, the modified shroud 12a of Fig. 4 can also be used for fixing live samples.

Once the sample has been located and fixed in position on the contoured element 11, the sample holder 10 is inserted into the probe resonator 40, as shown in Fig. 5. (The sample is omitted from Fig. 5 for clarity). Controls 42, 43 on the resonator 40 alter the resonant frequency and electrical impedance of the resonator. A further control knob 44 is used to provide axial adjustment of the sample holder 10 relative to resonator 40.

As shown in more detail in Fig. 6, control knob 44 is mounted on a shaft which has a pinion 45 at its inner end. The pinion 45 engages a toothed rack 46 on the rack member 15 when the sample is placed in the resonator 40. Thus, by rotation of knob 44, the axial position of the sample relative to the resonator 40 can be adjusted, and locked. The sample holder of this invention overcomes, or at least ameliorates, the difficulties of performing Magnetic Resonance Imaging and Spectroscopy on samples in a vertical bore magnet system. The living sample is securely, but safely, held. During the imaging procedure, the position of the sample can be adjusted accurately without interfering with the imaging procedure.

Furthermore, the mechanism is non-invasive to the magnet and the image and spectra quality are not compromised. The sample holder 10 forms an integrated system with the resonator 40, which is readily useable by the untrained operator. Moreover, the sample holder described above enables samples to be interchanged quickly and simply.

The foregoing describes only one embodiment of this invention, specifically the examination of small rodents by MRS and/or MRI. Modifications which are obvious to those skilled in the art may be made thereto without departing from the scope of the invention. For example, the contouring of element 10 and the shape of callipers 24, 25 can be changed to suit particular samples.

Claims

CLAIMS :

1. A sample holder suitable for use with a RF probe having a tubular resonator, the sample holder comprising an elongate member removably insertible axially within the bore of the resonator, and fixing means for fixing a sample in position relative to the elongate member.

2. A sample holder as claimed in claim 1, further comprising adjustment means for varying the axial position of the elongate member relative to the resonator.

3. A sample holder as claimed in claim 2, wherein the adjustment means comprises a manually rotatable member on the exterior of the resonator having a pinion at its inner end within the resonator, the pinion operatively engaging a rack member fixed longitudinally to the elongate member, whereby rotation of the manually rotatably member causes axial movement of the elongate member relative to the resonator.

4. A sample holder as claimed in claim 2, wherein the fixing means comprises a pair of callipers adapted to grasp the sample therebetween, the callipers being controllable by a manually operable fitting on the exterior of the sample holder.

5. A sample holder as claimed in claim 4, wherein the callipers are eccentrically mounted on a crank rotatable by the manually operable fitting.

6. A sample holder as claimed in claim 4, wherein each calliper has a conical element at its free end for engagement with the sample.

7. A sample holder as claimed in claim 2, further comprising a transverse bar mounted to the elongate member, the axial position of the transverse bar being adjustable by a manually operable fitting on the exterior of the sample holder.

8. A sample holder as claimed in claim 1, wherein the elongate member has a contoured surface on which the sample is mounted in use.

9. A sample holder as claimed in claim 1, further comprising a conduit for delivering gas from outside the resonator to a position adjacent the sample in use.

10. A sample holder as claimed in claim 1, further comprising a tubular spacer member connected to one end of the elongate member, said tubular spacing member providing fluid communication between the sample and the exterior of the resonator.