Animal holder for performing neuroimaging

An animal holder for use with an imaging device includes a body tube for receiving a first body portion of the animal. The animal holder also includes a head immobilization mechanism disposed adjacent one end of the body tube for receiving a head of the animal. The head immobilization mechanism includes opposing first and second flexible fingers that have free ends configured to contact and immobilize the head of the animal when the fingers are moved to a compressed position.

TECHNICAL FIELD

The present invention is generally directed to magnetic resonance imaging and more particularly, to a holder for a small animal (e.g., a rodent, such as a mouse) for holding a head of an animal in a stationary position as imaging (e.g., magnetic resonance imaging (e.g., fMRI)) is performed when the animal is either in a conscious state or an unconscious (i.e., anesthetized) state.

BACKGROUND

Human studies utilizing MRI have advanced our understanding of the regional and functional interplay between populations of neurons serving sensory, integrative and motor functions. Changes in neuronal activity are accompanied by specific changes in hemodynamics such as cerebral blood flow, cerebral blood volume, and blood oxygenation. Functional MRI has been used to detect these changes in response to visual stimulation, somatosensory activation, motor tasks, and emotional and cognitive activity.

Braining imaging in animals using SPECT, PET and MR are common practices in academia and the biotechnology and pharmaceutical industries. Key to any brain imaging study is: 1) securing the head to prevent motion artifact caused by movement and 2) minimizing the discomfort to the animals. At present, head immobilization is achieved through surgically implanted head posts that can be anchored to the hardware in the imaging equipment or by ear bars and skull pins compressed against the head originating from various head support structures anchored to the imaging equipment. Head posts are invasive, while ear bars and skull pins are painful and require the application of local anesthetics to the area of contact to minimize discomfort. These problems are motion and pain reduction are exacerbated in awake animal imaging, which represents a practice that is supplanting the use of anesthetics when imaging the brain.

Thus, there is a need for an animal holder that provides an alternative means for head immobilization which overcomes the disadvantages of the conventional techniques mentioned above.

SUMMARY

In accordance with the present invention, an animal holder for use with an imaging device includes a body tube for receiving a first body portion of the animal. The animal holder also includes a head immobilization mechanism disposed adjacent one end of the body tube for receiving a head of the animal. The head immobilization mechanism includes opposing first and second flexible fingers that have free ends configured to contact the head of the animal. The first and second flexible fingers move between first and second positions, wherein in the first position, at which the first and second fingers are at rest, the first and second fingers extend beyond an outer side wall of the body tube and define a maximum width of the holder, whereas in the second position, the first and second fingers are in a inwardly flexed position in which the width of the holder at a location of the free ends of the first and second fingers is substantially the same as the width of the body tube. In the inwardly flexed position, the first and second fingers are configured to contact and immobilize the head of the animal.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

FIGS. 6 and 7show one application of an animal holder100(FIG. 1) in accordance with the present invention and more specifically,FIGS. 6 and 7show the animal holder100in an operative position and fully inserted into and mated with an imaging device10. The imaging device10can be any number of different conventional imaging devices including but not limited to SPECT, PET and MR devices.

In the illustrated embodiment, the imaging device10is in the form of an MR imaging device that includes conventional components including a chassis15that has a first end12and an opposing second end14. The device10also includes tuning rods20that are positioned above the chassis15as shown. At the first end12of the device10, a coil assembly30is provided and can be any number of different types of coil assemblies depending upon the particular imaging device10and the intended application and operating modes. In the illustrated embodiment, the coil assembly30is in the form of a quadrature transmit/receive coil. As is well known, the coil assembly30has a hollow interior that is accessed through an opening40formed at the first end12of the device10. The opening40is configured (shaped) to receive the animal holder100. As described herein, the opening40can include a stop or locator and locking feature which ensures that the animal holder100is inserted into the opening40in a correct orientation and can serve to releasably lock the animal holder20in a select target location to ensure that the animal is in the correct, desired location to perform the imaging.

It will be understood that the imaging device10includes additional components, including electronics and control systems, that are not described in detail herein since the present invention is directed to animal holder100and the imaging device10is merely included to show one exemplary application for the animal holder100.

FIGS. 1-5depict the various components of the animal holder100. The animal holder100has a first end102and an opposing second end104and includes a body tube110having a first end112and an opposing second end114. The body tube110is configured and intended to receive a majority (e.g., a substantial portion) of the animal's body. In the case of a rodent, such as a mouse, the body tube110receives most of the rodent's body with the exception being the head which, as described below, is contained in a different section of the holder100. The body tube110can be formed of several parts including a base portion120and a cover portion130. In the illustrated embodiment, the base portion120has a concave shape and has semi-circular shape with curved side walls. The base portion120is intended to act as a floor and support the animal's body. The cover portion130is complementary to the base portion120and is designed to mate with and enclose the base portion120(as a result, the cover portion130can have a semi-circular shape). The cover portion130acts as a roof (ceiling) for the base portion120and when combined with the base portion120, the assembled parts120,130defined a tubular structure that is open at least at the first end112and also likely at the second end114.

In the illustrated embodiment, the cover portion130is a separate part relative to the base portion120; however, it will be appreciated that the two portions120,130can be coupled to one another as by a living hinge or the like to permit the cover portion130to pivot open.

At the second end114, the body tube110includes a member115for guiding the holder100into the opening40of the imaging device10and for positioning the holder100at a target location within the opening40. The member115can thus represent a handle by which the holder100can be grasped and moved into position. The body tube110can also include a locking mechanism (which can be incorporated into and be a part of the coupling member115) for releasably locking the body tube110within the opening40. In one embodiment, the locating and locking mechanism can be in the form of a pin that extends downwardly from the bottom of the base portion120and contacts a stop/locking feature formed in the imaging device10within the opening40. In other words, the opening40can be defined along its bottom by a guide track or the like on which the holder100rides until reaching the target position (where imaging occurs on the target body part (i.e., head)).

At the first end112, the body tube110and in particular, the base portion120thereof includes a shoulder yoke assembly140for restraining a shoulder/neck portion of the animal that is contained within the body tube110. The shoulder yoke assembly140includes a pair of slots142,144formed in the side walls of the base portion120. The slot142is thus formed one side of the base portion120and the slot144is formed in the other side of the base portion120such that the two are opposite one another, with an opening145being formed between the two walls structures that defines the slots142,144. The opening145receives the neck of the animal such that the head of the animal is located forward of the two slots142,144, while the lower body of the animal is located rearward of the two slots142,144.

The assembly140also includes a shoulder yoke148that is configured to fit around the shoulder/neck portion of the animal and be received and locked in place within the two slots142,144, to thereby secure and lock the animal's body in the desired position. The shoulder yoke148has a U-shape with two free ends that are inserted into the slots142,144. The dimensions (including thickness, etc.) of the shoulder yoke148are selected to produce a secure mechanical fit (friction fit) between the shoulder yoke148and the body tube110. The shoulder yoke148thus locks into place within the body tube110. The neck of the animal is located below the shoulder yoke148. It will be understood that different sized yokes148can be used to accommodate different sized animals since the yoke148needs to securely fit around the neck of the animal sufficiently to prevent undesirable body movement.

The animal holder100also includes a head immobilization mechanism150that is intended, as described herein, to immobilize the head for awake brain imaging without the need for surgery, head posts, ear bars, skull pins or the use of local anesthetics. The head immobilization mechanism150is located at the first end102of the holder100and thus is located forward of the body tube110. More specifically, the area immediately forward of the shoulder yoke148is a head receiving space151in which the head of the animal is received and immobilized and maintained in the desired position using mechanism150.

The first end102of the holder100at which the head immobilization mechanism150is located includes a bottom wall300. The bottom wall300is preferably integrally connected to the base portion120of the body tube110. The head immobilization mechanism150is defined by a pair of flexible (compressible) fingers310,320that are connected to the bottom wall300but spaced therefrom and extend longitudinally along the device100. More specifically, each of the fingers310,320includes a first end312that is connected to the bottom wall300and a free second314that is proximate and spaced from the shoulder yoke148. The fingers310,320are flexible and can move between a first position (FIGS. 2 and 3) and a second position (FIGS. 4 and 5). The first position is a normal rest position of the fingers310,320(free of an applied force), while the second position is a position in which an inwardly directed force is applied to the fingers310,320to cause inward flexing thereof.

As shown inFIG. 4, the first end312of each respective finger310,320is connected to the bottom wall300by a side wall350. The two side walls350are thus opposite one another. The width of the device100at the location of the side walls350is at least substantially equal to the width of the device100at the location of the body tube110.

The free second ends314can include an inwardly directed portion315that extends inward toward the other opposing finger.

It will be appreciated that a distance between the fingers310,320is greatest when the fingers310,320are in the first (rest) position and the distance between the fingers310,320is less when the fingers310,320are in the second (flexed) position. In particular, the fingers310,320are formed such that in the first position, at least an outer portion of each finger extends beyond the side walls of the body tube110. In other words, when the fingers310,320are in the first (rest) position, the width of the device100is at its greatest at the location of the fingers310,320.

The fingers310,320can carry pads, such as foam head pads, at or near the free second ends314. The fingers310,320are formed such that in the normal rest (first) position, the animal's head can easily fit between the free second ends314of the fingers310,320. The first position of the fingers310,320is thus a loading position for the head of the animal. The fingers310,320are constructed such that when the holder100is inserted into the opening40of the imaging device10, the side walls of the imaging device that define the opening40apply a compressive (inwardly directed) force against the fingers310,320, thereby causing the fingers310,320to flex inwardly and assume the second position (FIGS. 4 and 5) in which the width of the device100is the same in both the location of the fingers310,320and the body tube110. This movement is smooth since the first ends312of the fingers310,320do not exhibit appreciable flexing and instead the distance between the ends312(that defines the width of the device100at this location) is at least substantially the same as at the body tube110. The fingers310,320are thus angled outwardly and thus, when the first end102of the device100is inserted into the opening40and the device100is continually advanced into the opening (slot)40of the imaging device10, the side walls of the imaging device10contact and press the fingers310,320inward until the fingers310,320assume the second position.

The natural movement of the fingers310,320from the first position to the second position, causes the inner sections315of the fingers310,320to be drawn into contact with the head of the animal (e.g., mouse). This movement causes immobilization of the animal's head.

The animal holder100can also include a nose support member200for receiving the nose of the animal. The nose support member200can be in the form of a nose cone structure210that is located in front of the head receiving space151. The nose support member200is located between the flexible fingers310,320and extends longitudinally along the bottom wall. A bite plate is also preferably included and can be part of the nose support member200. The bite plate faces the head receiving space151and is positioned such that it can be inserted into the mouth of the immobilized animal.

An incisor tube210is also provided and extends outwardly from the nose support member200. The tube210serves as a connector to an odor source, such as isoflurane or stimulus odors.

As shown inFIG. 4, the nose support member200is locked in place using a fastener360. The fastener360mates with an opening in one side wall350and the nose support member200includes an elongated extension365that connects a main portion of the nose support member200. The elongated extension365has an elongated slot370formed therein. The fastener360includes a stem portion that is received through the slot370and into the opening in the side wall350. The slot370permits adjustment of the nose support member200in the longitudinal direction by loosening the fastener360and adjusting the nose support member200in the longitudinal direction and then retightening the fastener360.

When setting up and animal, the animal's neck is stretched by adjusting the position of nose cone (animal's mouth) relative to the shoulder yoke. This slight tension prevents the animal from using his shoulder muscles to lift his head. This feature also has the following advantage: the fastener360also allows the nose cone (nose support member200) to be “flipped” out of the holder (like a folding knife). This feature allows for the user to conveniently hook the animal's mouth into the bite bar, situate the nose cone200and then roll the animal into the holder100. This is much faster than the traditional method of using the bite bar/nose cone on conventional products which is rigidly fixed or only slides along the body tube.

One of the main advantages of the present holder100is the ease of use and the greatly reduced amount of time that is needed to load and immobilize the head of the animal prior to performing the imaging. In the present invention, the animal is simply loaded into the body tube110and position such that the head is in space151and the lower body is in the body tube110and then the animal is secured in place with the shoulder yoke148. The nose cone and bite bar assembly200are then placed in the desired position and the holder is now in a final pre-load position. It will be noted that the head of the animal is not yet immobilized. When it is time to image the animal, the user holds the holder100by the handle115and then inserts the first end102of the device100into the opening40. As the holder100is further inserted into the opening40, the side walls of the imaging device10that define the opening40contact the fingers310,320which are protruding outwardly beyond the rest of the holder100since they are in the first (rest) position. Continued advancement into the opening40results in a compressive force being applied to the fingers310,320and the fingers310,320flex inward until they assume the second position. As the fingers310,320flex inward, the inner portions315of the opposing fingers310,320contact the head of the animal and serve to not only position it in the desired position but also serve to immobilize the head since the head is effectively sandwiched between the two compressed fingers310,320. This immobilization process requires no additional steps by the user but instead is automatic and results merely by insertion of the holder100into the opening40. This allows significantly more animals to be imaged per a set period of time compared to conventional holders which are manually intensive.

Once the imaging is completed, the holder100is grasped by the handle115and is pulled out of the opening40of the imaging device10. Once the fingers310,320clear the side walls that define the opening40, the fingers310,320naturally flex outwardly until the fingers310,320assume the first (rest) position. As the fingers310,320flex outwardly, the fingers310,320separate from the head of the animal and thus, the animal is free to move its head. The animal can then be easily removed from the holder100by then removing the shoulder yoke148and the cover portion of the body tube110.

It will also be understood that while the illustrated embodiment includes two fingers310,320, the holder100can be constructed so as to include a different number of fingers. For example, the holder100can include a single finger (e.g., finger310) that compresses in the same manner described herein (e.g., when the holder is inserted into the opening of the imaging device, the single finger compresses. Instead of an opposing compressible finger, the holder can include a padded side wall or a fixed head rest for placement against one side of the animal's head, with the single compressible finger being in contact with the other side of the animal's head.

FIG. 8shows results of motion detection software that shows that motion in six degrees is reduced to less than 20 microns. This data shows the advantages obtained by the present holder.

The holder100accommodates small rodents from 10-60 gm and thus is ideal for transgenic mice, voles and post-natal rats. In addition, with the coil stationary in the magnet, the holder100can be withdrawn and replaced with one another. There is no need to retune or rematch. The ease of efficiency of the holder100allows a significant number of more animals to be imaged per hour due to the increased speed at which the animals can be loaded and unloaded from the imaging device using the holders100of the present invention. In addition, the holder100can be used with both aware or anesthetized animals and can accommodate a heating element to allow for temperature regulation. As mentioned above, no head post, ear bars or skull pins are used and instead, head cushions are provided (as part of the flexible fingers) to minimize stress and discomfort.

While the invention has been described in connection with certain embodiments thereof, the invention is capable of being practiced in other forms and using other materials and structures. Accordingly, the invention is defined by the recitations in the claims appended hereto and equivalents thereof.