Abstract .edu



Vanderbilt University School of Engineering

Department of Biomedical Engineering

Senior Design Final Report

3T NeuroImaging Primate Chair

Jennifer R. Pryweller

April 25, 2006

Advisor:

Professor Malcolm J. Avison

Vanderbilt University Institute of Imaging Science

Abstract

The synergistic activity of large neural populations remains largely unexplored in the visual cortex. Studies explore the brains of rhesus macaques by presenting the monkey with a visual stimulus while simultaneously collecting imaging and electrophysiological data from the occipital lobe. A primate chair will be constructed to restrain awake rhesus macaques during BOLD fMRI brain scans. Based on MR compatibility and other specific factors, the chair will be constructed using polycarbonate, ABS, brass and nylon. The primate chair, while conforming to the highest of ethical standards, provides the macaque with physical comfort and minimal emotional distress. It also promotes a high level of safety for both the monkey and the researcher. Most importantly, the chair is easily modifiable, allowing for the future addition of functional components.

Introduction

The synergistic activity of large neural populations remains largely unexplored in the visual cortex. Hemodynamic metabolic approaches to exploring this activity are based on the fact that energy metabolism (measured as a function of cerebral blood flow and volume change) is coupled to neuronal activity. Studies explore the brains of rhesus macaques by presenting the monkey with a visual stimulus while simultaneously collecting imaging and electrophysiological data from the occipital lobe. Specifically, the correlation of BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) brain data and neuron action potential signal localization is used to map the visual cortex. Since these investigations require the use of awake monkeys, it is necessary to develop a device to restrain animal movement in an ethical manner while performing simultaneous data acquisition.

A primate chair will be constructed to accommodate fMRI brain scans in awake rhesus macaques. The chair will include adjustable features to provide for variable monkey size. The neck plate diameter and angle will also be adjustable to account for different monkey sizes. Key features of the chair include a removable waste tray, a reward and reinforcement system, stereotaxic devices and electrophysiological monitoring systems. A juice reward system will be automated so that upon correct response to visual task stimuli an air pump will allow the monkey to drink a set amount of juice. In addition, a tone will sound that the monkey is trained to recognize as positive reinforcement. Negative audio tone reinforcement will be used for incorrect visual response. Stereotaxic devices that serve to assist the monkey in holding still (eliminating artifacts in the scan and the need for post-processing motion correction) include and a head post and head bar. Electrophysiological measures of interest during an awake monkey scan include heart rate, blood pressure, body temperature and facial activity. Electrodes will be placed above each eyebrow and on the side of each jaw to monitor muscle twitches in the face. A video camera will be put in place to monitor the monkey's facial and visual responses. A custom circuit will be designed to accommodate electrodes placed in the visual cortex of the brain during scans to identify and monitor individual neurons that are activated in response to specific visual tasks. The diagram in Figure 1 was created to outline and organize the functional components of the entire system. The entire chair will be designed with the monkey's comfort as forethought while conforming to high ethical standards. Holes will be drilled in the walls of the chair to allow for air flow. Since the monkey is trained to sit in the sphinx position for the duration of the scan, the chair will be ergonomically designed to accommodate comfort.

Due to the large size of the project a more specific goal was set to be accomplished in conjunction with the senior design project. Based on design constraints and specifications the design and construction of the physical chair, while accounting for the addition of functional components, was the established as the short term goal.

Previous Primate Chair Designs

Previous designs of primate chairs to meet similar study objectives include those of Wim Vanduffel and Mark Pinsk. The design of Vanduffel’s chair (Figure 2) for use in his 1991 BOLD fMRI studies was not the primary focus of his experiments, and therefore published data describing the monkey chair is very limited. His chair was constructed to fit a 3-4kg rhesus macaque, sitting in the sphinx position. A head post, permanently fixed on the monkey’s head, was use to immobilize the monkey’s head by attaching it to a head bar built into the chair. The head bar was supported by a cross bar and head frame (Figure 3). This technique of head stabilization was adequate, but BOLD fMRI is so sensitive to movement that better signal could be obtained by further stabilizing the monkey’s head and body. Even with the head held completely still, subtle body movements during scanning can still have a large enough effect on the brain’s magnetic field to cause artifacts in the scan image, resulting in inaccurate measurements and conclusions. The materials used for the construction of Vanduffel’s chair are not published. Though contact was made with Vanduffel in which he agreed to share the blueprints of the chair, subsequent efforts to obtain the plans proved fruitless.

Mark Pinsk, of Princeton University published a paper in 2005 relating methods of fMRI imaging in awake monkeys. His construction of a primate chair was much more detailed in his published work than that of Vanduffel. Pinsk constructed the chair out of all magnetic resonance (MR) compatible materials, from the siding of the chair, to the implanted head post and all the bolts and screws along the way. His chair was constructed from a cast acrylic tube, 62cm in length and 28cm in diameter. The rear plate was constructed of polycarbonate and left a hole to allow for extension of the monkey’s tail. The front end of the tube was cut at an angle of 30 degrees with respect to the direction of the chair’s length. Several plates were constructed to fit at the front of the tube, each with a large hole in the middle, suitable to encompass the circumference of a monkey’s neck. A flat piece of delrin, with holes, was placed across the bottom of the tube to allow for drainage and separate the monkey from its waste. The head immobilization system was made out of delrin and included a head bar, cross bar and head frame. Two support posts were added to further immobilize the head, and were placed perpendicular to the cross bar on either side. Pinsk’s design, while it is a progression from Vanduffel’s, leaves room for improvements to be specified in this design project.

Crist Instrument is a major manufacturer for primate research equipment. Their design of an MRI compatible primate chair is seen in Figure 5a. They also manufacture a commonly implanted head post known as a footed head post. The VUIIS cohort will be implanted with head posts similar to those in Figure 5b, but made of MR compatible material. It is not sufficient to purchase a primate chair from Crist for use in these experiments because the Crist chair is not large enough in diameter, nor would it snuggly fit the bore of the 3T Achieva MRI scanner.

Ethical Considerations

Rhesus macaques were chosen for use in these studies because they are the most anatomically and physiologically similar to humans. They are also easy to maintain and breed in captivity. The Institutional Animal Care and Use Committee (IACUC) at every research institution is charged with reviewing animal welfare issues and approving all research involving the use of animal subjects. IACUC also provides training for all researchers to promote awareness of ethical considerations and make them more accountable for their actions. The Vanderbilt University IACUC approved all portions of the proposed visual studies, including the construction and use of a primate chair to restrain awake monkeys. The student involved in designing and constructing the primate chair voluntarily took an IACUC research training course on the ethical care and use of animals. A certificate was obtained at the end of the course after passing an examination.

A group of physicians, statisticians, researchers, community advocates and others come together to form the Institutional Review Board (IRB) at all research institutions. The IRB reviews studies proposed by investigators and ensures the ethical treatment and rights of all subjects. Just as it was approved by IACUC, all portions of these proposed studies have been approved by the IRB at Vanderbilt University.

Methods

Designs by Pinsk and Vanduffel, while both adequate for some applications, were not suitable for the needs of the Vanderbilt University Institute of Imaging Science in their desire to restrain awake rhesus macaques for visual studies. Unique constraints were imposed upon the design of a primate chair for the VUIIS by the physical dimensions of the bore of the scanner, the specification of the available rhesus cohort, and the inherent constraints of magnetic compatibility in an MRI scanner.

Several constraints were imposed by the bore of the magnet since every MRI scanner is slightly different in shape and size. A Philips Achieva 3T MRI scanner is seen in Figure 6, with the bore (inner radius) shown in red. The patient bed, which runs through the MRI scanner, restricts the available bore radius. The radius of the bore is of utmost importance since the monkey’s brain must fall exactly at the point known as isocenter. Isocenter is the point in the exact center of the magnet’s bore at which maximal signal is obtained. The loading of the chair into the magnet also needs to be taken into consideration since the entrance to the bore is roughly three feet off the ground. A consideration of weight must be kept in mind when selecting materials. The end weight of the chair must be considered to be the weight of the physical chair, plus the weight of any subsequent functional components as well as the weight of the monkey.

The cohort available for these studies is a group of rhesus macaques. Though only two monkeys will be chosen from the cohort for further training and use in visual experiments, the chair must be accommodative of variable monkey size. The cohort, currently residing in quarantine, ranges in size from 6.5-8.5kg in weight and 28-32” in length (in the prone position). The chair design and construction must be started while the monkeys are still in quarantine so that when they are released, the two monkeys chosen for training can make use of the primate chair during training.

The properties of materials were only considered for performance within the range of 10-35 degrees Celsius, as this is the complete temperature range to which the chair would ever potentially be exposed. All materials must be MR compatible and provide for optimal signal in imaging. Some materials provide better signal than others, but multiple factors must be taken into account during selection. It is very important that the materials are strong enough to contain the monkey and resist any force resulting from a non-behaving monkey. The material used for siding must provide isolation of the monkey from its environment. Waste from the monkey, which will likely collect at the base of the chair, must be prevented from leaking out into the environment of the bore. Finally, the chair must be translucent to allow for the monitoring of the monkey during the scan. A comparison of various known MR compatible materials was performed to evaluate the best material choice for the siding, boot piece and binding of the chair (Table 1). Though no budget restrictions were specified for this project, the cost of materials still needed to be considered, regardless of the material’s property qualifications.

Different materials, when placed near each other in an MR environment, have the potential to cause image artifacts due to their differing susceptibilities. Acquisitions of echo-planar MRI images reveal subtle differences in MR compatible materials. Chair siding necessitates the use of MR compatible materials, but head post apparatus and binding materials and screws closer to isocenter require a higher level of MR compatibility. The closer a material is to isocenter the more sensitive the image is to differing susceptibilities. A discussion of materials selection for head post apparatus and binding screws near isocenter is found in the Results and Discussion section of the paper.

Results & Discussion

Bore Constraints

Normally during an MRI scan the subject is loaded onto the patient bed and the bed is then electronically moved into the bore. As the bed begins to move into the scanner it briefly stops and marks what is known as the “landmark”. The bed continues to scroll into the bore and stops when the landmark reaches the center of the bore. In other words, the landmark is moved to the position y=0 along what would be the x-axis on planar coordinates relating isocenter. Before beginning chair design, the parameters of the bore were measured and recorded (Figure 7). The height between the base of the bore and isocenter, when measured with the patient bed inside the bore, proved to be suboptimal. It was determined that a monkey would not be comfortable, even in a sphinx position, with an available height of only 15cm.

By removing the patient bed, it was found that an extra 8cm of height was made available. Though this provides for the comfort of the monkey, the issue of setting a landmark arose. Without the patient bed in use, a landmark can not be set, and the isocenter not determined. A second patient bed was modified to include an acrylic plate near the end, flush with the bed’s surface, which had several holes drilled in it. Normally this patient bed is used for other experiments at the VUIIS, but its use in conjunction with the primate chair during rhesus scanning had the potential to be beneficial. The primate chair will be manually loaded into the bore. As a feature of the chair a lip will be constructed, that attaches to the end of the chair. The lip will be attached to the chair end with two bolts placed through vertical slots allowing the height of the lip to be adjusted. When set to the proper height, the lip will come off of the chair and extend onto the acrylic slab of the modified patient bed where it will be bolted to the bed using ¼”-20 brass screws. Once the chair is attached, a “fake” landmark point will be set a known distance from the monkey’s brain. Once the landmark is set, the scanner will automatically roll the patient bed into the bore a proper distance. The rolling of the patient bed provides sufficient force to push the chair into the proper position for the monkey’s head to be at isocenter, while avoiding cumbersome and awkward manual pushing. It also allows for a more accurate positioning of the monkey’s head at isocenter, as the scanner automatically pushes the bed (and chair) the required distance. The patient bed, now just outside of the bore, is adjacent to the monkey chair which resides inside the bore. The attachment of the chair to the bed also provides additional stabilization of the chair to avoid image artifacts resulting from primate movement.

Cohort Specifications

Accommodation of variable monkey size is accounted for in the design of multiple chair features. To further provide monkey comfort, an angled wedge will be placed under the chest to support the macaque sitting in a “sphinx” position, similar to the monkey positioning and wedge seen in Figure 4. The chest support will be physically independent from the chair to allow for unique placement under the chest of monkeys of varying size.

The neck plate, placed to enclose the font end of the tube, will be constructed of two pieces of polycarbonate. The neck plate will have a fixed front plate and a removable rear plate that screw together to allow for variable neck diameter. An example of a neck plate currently manufactured by Crist Instrument is seen in Figure 8. The neck plate helps to restrain the monkey without chafing. The rear plate will have two holes suitable for the monkey to put its hands through. The holes should allow for comfortable movement, while still restraining the monkey enough to disallow action such as touching of the head. By permitting the animal to use its hands, task response can be interactive beyond the tracking of eye movement. Further investigation is needed to determine the exact dimensions and parameters for integrating the neck apparatus.

The head apparatus must be very stable. The post that attaches the chair to the post in the monkey’s head must account for variable size of the monkey and position of the head in three dimensions. To accomplish this task a head apparatus was proposed with six degrees of freedom. Initial design ideas include a cylindrical rod running perpendicular to the monkey’s head post allowing for a site of attachment. The cylinder will be able to move toward and away from the monkey’s head as well as up and down through 3 rods attached to the chair. The cylinder will be attached to the rods in a manner that allows for angular rotation. No drawings are yet available to elucidate the concepts involved, though this should be the next step taken in the design process. After sketches are made and presented to the investigator, rigorous strength testing must be done to ensure that the six degrees of freedom don’t compromise the stability of the head apparatus. To further stabilize the head apparatus and address problems seen in the past, two vertical support rods connected to the horizontal head bar (cylinder) should be put in place. In the Pinsk model the support rods, though improved from Vanduffel’s design, did not produce optimal stability. To improve on the model the vertical supports should be set at an angle (to be determined), connected to the head bar and base of the chair at either end. This angular formation should provide more overall stability than the previous design using 90 degree angles. Figure 9, though it does not include the concept of head apparatus with six degrees of freedom, does show the relationship of the angled support rods to the head bar and base of the chair.

Materials

In evaluating materials to be used for chair siding, the opacity, strength (as measured by Young’s modulus) and ease of machining the material were the most important properties to consider. Comparing acrylic, delrin, peek, and polycarbonate, all of which are MR compatible materials, delrin and peek were immediately ruled out because they are opaque. Between polycarbonate and acrylic the deciding factor was the cited Young’s modulus. Polycarbonate is much stronger and would be better to resist the force of a misbehaving monkey. Both materials are easily machined. Polycarbonate was therefore chosen as the material of choice for constructing the sides of the primate chair.

A selection of materials to be used near isocenter differed in the weighting of material properties. The most important property of any material near isocenter is its potential to cause image artifacts. Measured at a magnetic field of 10 kA/m, the relative magnetic permeability of brass Naval brass type CZ114 was approximately 1.060 and that of Stainless steel AISI type 316 was approximately 1.0030. Nylon is non-magnetic and is therefore the screw of choice for use near isocenter. Brass screws however, in combination with polycarbonate, provide for a much stronger binding. Therefore brass screws were chosen for use in the binding of chair vertices near the base of the chair. Selection of head post apparatus material was possibly the most crucial. Since the head post material is the closest to the brain, it is very important that the material used to construct it be of the highest quality. The most MR compatible material is peek. Though it’s properties of strength qualify its use to stabilize the primate’s head, the cost is very high. While one piece of polycarbonate or acrylic (size 12”x12”x1/2”) costs approximately $10, the same size piece of peek costs $280. The investigator, desiring the best signal acquisition possible, consented to paying for the use of peek in the construction of the head apparatus. The construction of the head bar, head frame and cross bar will require just over two square feet of material, for a total peek cost of approximately $500. Since the construction of the head apparatus was not a specified part of the project, but rather it qualified as a component to be kept in mind, the materials cost was discussed with the investigator, but was not factored into the cost analysis of the chair.

The selection for the boot piece material, used to stabilize the chair in the bore, was clear. The only available material for constructions using the rapid prototype machine is ABS. The properties of ABS were evaluated against those of the chair siding materials to account for adequate MR compatibility, cost and machinability. The evaluation of these properties proved adequate for use in the chair, mostly based on the non-magnetic property of the material.

Design Iterations

The original design was based on an extruded tube, similar to that of Mark Pinsk. A design was constructed based on the chair being a tube. A design for a cradle to set the tube in was also created. This cradle was designed to fit snuggly in the bore so that the effect of all monkey movement would be minimized. Several months were spent studying the specific needs of a primate chair and designing a tube-based chair, neck plate, end plate and head post apparatus to fit. When it was time to place the materials order for the tube, it was found that no manufacturer produces a polycarbonate tube with a diameter large enough to accommodate the needs for this chair. The necessary diameter of the chair, based on monkey size, bore diameter and apparatus size was approximately 15”. The longest manufactured diameter in extruded polycarbonate tubes was 8”. Though custom made tubes are available, they were not available at a price that was acceptable to the primary investigator funding the primate chair construction.

Since acrylic had been used in previous designs, namely the Pinsk design, and the Young’s modulus of the material was adequate for the task of imaging awake monkeys, the option of purchasing a cast acrylic tube was explored. A cast acrylic tube, 15” in diameter is only manufactured with a wall thickness of .125”. It was specified by the rhesus caretakers and the primary investigator, that the walls be at least 3/8” thick. A 16” diameter acrylic tube was available, but the cost was over $800. Though expensive, the investigator was willing to pay. Upon investigation of machinability, it was found that a 16” tube would be nearly impossible to cut, as it is too large to fit on any available machines. Mark Pinsk and the Princeton University machine shop, where their chair was machined, was contacted to ask for details regarding the machining of their tube. Though Pinsk’s tube was 11” in diameter, and slightly too large for machines similar to those at Vanderbilt, the Princeton machine shop was able to manipulate and maneuver the machines as well as the chair to make a “rough cut” for the angled front end of the tube. A tube with a diameter of 15” or more would not be able to be machined in the same creative way. Also, the specified tolerances of the to-be-manufactured tube were deemed to be unacceptable with a possible 16% error in wall thickness. Accepting a tube with substantial error in wall thickness would throw off all subsequent parameters, especially for the addition of a neck plate, end plate and any future functional components.

At this point it was clear that a tube-based design large enough to accommodate the specified rhesus sizes was not possible. Several more iterations of the design were explored including a chair the shape of a box, with a small square recession through the base of the box to utilize the extended available height from the removal of the patient bed. When the bore parameters were drawn in a CAD program with the proposed box-like chair, the dimensions were sub-optimal. The recession, in which the monkey would stand, was a maximum of 6” wide. This is not enough space to fit the width of a rhesus body. The idea of using multiples sides, bound together, however, proved to be worthy.

The final iteration of the chair was a hexagonal design similar to, but more complex than, the original tube design. Instead of using a round tube, a tube shaped like a hexagon was designed using six sheets of polycarbonate. A CAD program was used to find the exact dimension of the pieces when fit to the bore of the magnet. Figure 10a shows the dimensions obtained for the cross-section of the chair based on the parameters of the bore. In the drawing, the bore is shown in green and drawn to scale. The hexagonal chair was fit inside the bore, maximizing the width of the base and use of the available bore radius. Isocenter is marked by the crossing of the two pink lines and a black “X”. Ample room was left above isocenter to allow for variation in monkey height as well as an adjustable, and potentially bulky, head apparatus. Maximizing the available bore radius allows for modifications to be made to the chair in the future, including the addition of functional components which will also be isolated from the bore environment. Maximization of area occurred by designing the two lower vertices of the hexagon to be cut at an angle of 30 degrees relative to the base of the bore. Cutting the top vertices at an angle of 45 degrees provided for the inclusion of additional area in the bore above isocenter. A side-view of the chair showing the 30 degree angle at which the “tube” will be cut, and the relative dimensions associated with the specified length of the chair (28” extended from isocenter) is seen in Figure 10b.

Though the base of the hexagon is still only 6” in length, the conservative slope of 30 degree angles allows space for variable monkey width while still providing comfort. A slab of polycarbonate, running the length of the tube will be placed two inches above the base of the chair. This piece of polycarbonate will be cut in a fashion similar to a grate. This will allow for the retention of waste, separate from the monkey. A disposable liner should be placed along the bottom of the chair to collect the waste and be removed after each use. This provides an easy was to dispose of waste and avoids excessive cleaning of the chair after use. The liner should be made of a non-magnetic, plastic material similar to a trash-bag or tarp. Specific materials must be investigated and be strong enough to hold waste after removal from the chair. The material should also be completely non-permeable to isolate the waste from the surface of the chair.

Boot pieces were fit to the lower vertices of the chair so that they would align with the shelf found in the bore of the magnet (see yellow binding in Figure 9). They will be attached using brass screws. A CAD drawing relating the dimensions of the boot piece, for rapid prototyping, is seen in Figure 10c. The weight of the chair will rest on the boot pieces, since the base of the chair does not touch the bore. This symmetry and stability will help stabilize the whole chair. The two vertices at the base of the chair will be bound using glue. This will provide complete isolation of any liquid or fluids from the exterior environment. The four vertices at the top of the chair (seen when looking at a cross-section) will be bound using a 28” long, 1/16” thick piece of polycarbonate, bent down the middle, long ways (see blue binding in Figure 9). The concept of this binding is very similar to that of a piano hinge. The binding will run the length of the tube and be secured every inch using ¼”-20 nylon screws.

The materials for a 28” long hexagonal chair (inclusive of siding and binding) weigh close to 50kg when combined. This weight can be reduced by drilling any number of lightning holes in the siding of the chair. Not only is this a practical modification, but it promotes air flow through the chair, providing more comfort for the monkey. Using a CAD program, it was calculated that the maximum number of lighting holes that can be drilled, without compromising the structural integrity or stability of the chair, could reduce the weight of the chair up to twenty percent.

Economic Analysis

The primate chair is being designed and constructed for experiments that will study the visual cortex in two rhesus macaques. While it seems that a much larger number of subjects is necessary, due to the challenge associated with obtaining, training and maintaining rhesus monkeys two is a common and acceptable number of subject for awake monkey brain research. It is the goal of the investigator to use the chair at least 2-3 days a week (1-2 hours at a time) to run experiments with the macaques, though he hopes to be able to do so every day. The limiting factor in the situation is the availability of professionally trained research associates whose presence is required during the experiments.

Though the focus of these visual cortex studies seems small, their implication is large. The ability to map the visual cortex, by neuron, opens the door to endless possibilities for biomedical technologies as well as potential therapies in the field of human vision research. While this specific primate chair may not reach beyond the VUIIS, the publishing of new techniques in monkey restraint, applied to the world of MRI, has the potential to promote the progress of medical imaging sciences as a whole.

The materials for the construction of the physical primate chair, only inclusive of the hexagonal tube and its bindings specific to this project, are very cost effective. The cost of labor to machine the chair materials is the majority of the expense. A cost analysis is seen in Table 2. The addition of the head apparatus will significantly increase the price of the chair, as it is estimated to require roughly $500. The construction of the grate in the bottom of the tube, the rear plate and the customized, adjustable neck plate, all made of polycarbonate, will also contribute to an increase in cost. Any future modifications to allow for the addition of functional components, as well as the addition of functional components themselves and any associated hardware or software, have the potential to add incalculable cost.

Safety Analysis

A forethought throughout the entire design process has been to secure the safety of

not only the monkey, but the researchers involved in the study. The process of ensuring a well-trained monkey’s safety is threefold: the monkey must be properly restrained, comfortable, and well monitored. To ensure the researchers safety it is necessary that they be trained in the proper use of the primate chair as well as proper techniques for monitoring the monkey’s wellbeing. Only professionals trained in the area should handle the monkeys or interact with them in any physical manner. This not only ensures the researcher’s safety, but the monkey’s at the same time. Procedures should be laid out ahead of time to address necessary action in response to multiple modes of failure including, but not limited to, animal escape or non-cooperation as animal emotional or physiological distress.

Future Direction

Much work remains to be done before the primate chair reaches its optimal level of functioning. First, the head apparatus needs to be incorporated in conjunction with the neck and end plates. A custom head coil must then be constructed for use in conjunction with the imaging studies. Normal head coils will not fit around the monkey’s head due to the chair’s head apparatus and other possible functional equipment. At this point the chair will be functional enough to use for restraint during brain imaging alone. The chair can subsequently be fit for electrophysiological monitoring. Visual task binoculars, worn by the monkey during scanning, have already been ordered. The binoculars will be used instead of projecting images onto a task screen. The binoculars also provide integrated eye tracking in place of a cumbersome and less accurate infrared camera and monitor. Before visual tasks can be put in place, a reward system must be set up.

The reward system will consist of a hydraulic or air pump used to dose juice to the monkey as a reward for good behavior or accurate response. The investigator may chose to use a pump that delivers automated, timed rewards, manual rewards or both. All manufactured juice pumps are made with metal that is not MRI compatible. For this reason the pump will have to be outside of the enclosed MRI room, and a length of tube run through a small hole in the wall to reach the reward straw. Pumping juice for a long distance presents the challenge of reward receipt timing as well as the difficulty involved in making sure the pump is strong enough to get the sip of juice all the way through the tube. The use of gravity should be explored in a manner such that the pump could be set outside the room, perched on a shelf, and gravity would help the juice travel the majority of the distance through the tubing. Finally it must be ensured that the tubing used to pump the juice, as well as the reward straw, are both MR compatible. The investigator has also showed interest in the use of an audio tone for reinforcement. When the monkey responds improperly to a task, not only will the animal receive no juice reward, but it will hear an audio tone, which conditioned in training, will be associated with negative a response. The desire is to expedite behavior reform by providing a more rigid reinforcement system. Since there is a magnetic metal at the base of the speaker’s cone, a significant challenge is presented in the addition of audio reinforcement. Superheating the base of the cone causes the magnetic portion of the speaker to become unattached without losing any necessary functioning of the speaker. The resource of the VUIIS shop has been identified to perform this task.

It is also desirable that a heart rate monitor be added to the chair. The addition of more equipment in physical contact with the monkey has the potential to further distress a monkey. An EMG circuit and device should be constructed to monitor for facial twitches through the placement of four electrodes on the monkey’s face – one above each eyebrow, and one on either side of the jaw. Monitoring for facial twitches and the consideration of facial movement as a negative response from the monkey, promotes the monkey holding its head absolutely still. This is necessary because any movement, especially near isocenter, can drastically alter the data by causing artifacts in the images. Even movement of one millimeter can cause an image to have blurred voxels. It must be kept in mind when deciding how to attach the heart rate monitor and EMG to the primate that the addition of more equipment coming into physical contact with the monkey has the potential for further distress.

Conclusion

The primate chair, while conforming to the highest of ethical standards, provides the macaque with physical comfort and minimal emotional distress. It also promotes a high level of safety for both the monkey and the researcher. The developed chair will be used to restrain rhesus macaques to obtain BOLD fMRI images with minimal artifacts resulting from motion and material magnetic susceptibility. The chair allows for modifications to conduct simultaneous acquisition of electrophysiological data (readings of individual neuron action potentials). Most importantly, the chair is easily modifiable, allowing for the future addition of functional components. The addition of functional components to the primate chair allows for increased monitoring of the monkey’s well-being, provides for the acquisition of additional data, implements a positive-reinforcement system through reward and increases control for subject movement.

Acknowledgements

Professor Malcolm J. Avison, Vanderbilt University Institute of Imaging Science

LiMin Chen, Vanderbilt University Department of Psychology

Ken Wilkens, Vanderbilt University Institute of Imaging Science

Bruce Williams, Kennedy Center Institute

Heather Scott, Vanderbilt University Institute of Imaging Science

References

Andersen AH, Zhang Z, Barber T, Rayens W S, Zhang J, Grondin R, Hardy P,

Gerhardt GA, Gash D M. Functional MRI studies in awake rhesus monkeys: Methodological and analytical strategies. Journal of Neuroscience

Methods 2002;118:141-152.

Pfeuffer J, Merkle H, Beyerlein M, Steudel T, Logothetis N. Anatomical and functional

MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup. Magnetic Resonance Imaging 2004;22:1343-1359.

Pinsk MA, Moore T, Richter MC, Gross CG, Kastner S. Methods for functional

magnetic resonance imaging in normal and lesioned behaving monkey. Journal of Neuroscience Methods 2005;143(2):179-195.

Vanduffel W, Fize D, Mandeville JB, Nelissen K, Van Hecke P, Rosen BR,

Tootell RBH, Orban GA. Visual moption processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys. Neurotechnique 2001;32(4):565-577.

Subsequent references identified for outlined future work:

Baker JT, Patel GH, Corbetta M, Snyder LH. Distribution of activcity across the

monkey cerebral cortical surface, thalamus and midbrain during rapid, visually guided saccades. Cerebral Cortex 2005;16(4):447-59. Epub Jun 15, 2005.

Foeller P, Tychsen L. Eye movement training and recording in alert macaque

monkeys: 1. Operant visual conditioning; 2. Magnetic search coil and head restraint surgical implantation; 3. Calibration and recording. Strabismus. 2000;10(1):5-22.

-----------------------

[pic]

Figure 2. Primate chair constructed by Vanduffel et al. to seat rhesus macaques in sphinx position.

[pic]

Figure 3. Head restraint using skull implanted head post and chair component – the head bar, which is supported by a cross bar and head frame.

[pic]

Figure 1. Diagram showing relationship between functional components in the primate chair.

[pic]

Figure 4. Mark Pinsk’s tube based primate chair.

[pic]

Table 1. Evaluation of potential chair materials based on desirable material properties.

[pic]

Figure 6. Philips Achieva 3T MRI scanner. Bore of the scanner is shown in red.

[pic]

Figure 7. Bore parameters of interest to the design of a primate chair. Absolute center of bore, isocenter, marked by red star. Measurements in centimeters.

[pic]

Figure 5. Crist Instrument manufactured MRI compatible primate chair (a) and footed head post (b).

[pic]

Figure 9. CAD drawings showing the cross-section of the primate chair (a), the side-view (b) and dimensions of the boot piece to be bound to lower chair vertices (c).

[pic]

Figure 8. Two piece, adjustable neck plate manufactured by Crist Instrument.

[pic]

Figure 9. Cross-section of primate chair showing connectivity of angled support rods from head bar to the base of the chair.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download