U.S. patent application number 09/928052 was filed with the patent office on 2001-12-20 for method and apparatus for performing neuroimaging.
Invention is credited to Allard, Arthur C., Ferris, Craig F., King, Jean A..
Application Number | 20010053878 09/928052 |
Document ID | / |
Family ID | 22616382 |
Filed Date | 2001-12-20 |
United States Patent
Application |
20010053878 |
Kind Code |
A1 |
Ferris, Craig F. ; et
al. |
December 20, 2001 |
Method and apparatus for performing neuroimaging
Abstract
The present invention relates to a restraining assembly used in
neuroimaging of animals in magnetic resonance imaging (MRI)
systems. The body of the animal under study is secured within a
tube with a head holder to reduce motion artifacts, particularly
when the animal is awake. The tube is placed in the bore of the MRI
system to conduct imaging procedures with a radio frequency coil
adjacent to the animal's head.
Inventors: |
Ferris, Craig F.; (Holden,
MA) ; King, Jean A.; (Worc, MA) ; Allard,
Arthur C.; (Templeton, MA) |
Correspondence
Address: |
THOMAS O. HOOVER, ESQ.
BOWDITCH & DEWEY, LLP
161 Worcester Road
P.O. Box 9320
Framingham
MA
01701-9320
US
|
Family ID: |
22616382 |
Appl. No.: |
09/928052 |
Filed: |
August 10, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09928052 |
Aug 10, 2001 |
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09169602 |
Oct 9, 1998 |
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6275723 |
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Current U.S.
Class: |
600/415 |
Current CPC
Class: |
A61B 5/0042 20130101;
A61B 2503/40 20130101; A61B 5/055 20130101 |
Class at
Publication: |
600/415 |
International
Class: |
A61B 005/055 |
Claims
1. A restraining assembly to immobilize an awake animal for
magnetic resonance imaging (MRI) device, comprising: a chassis; a
first mounting plate at one end of the chassis; a second mounting
plate at a second end of said chassis opposite said first mounting
plate; an elongated body tube extending along said chassis; and a
head holder that restrains the head of an animal, the head holder
having an rf coil.
2. The restraining assembly of claim 1 wherein said head holder
further comprises a pair of lateral ear clamping screws extending
horizontally through the sides of said head holder into the bore of
said aperture and generally perpendicular to an elongated axis
thereof and above a horizontal bite bar, and a protective ear
piece.
3. The restraining assembly of claim 1 wherein said head holder
further comprises a nose clamping screw extending inward through
the top of said head holder into a bore of said aperture.
4. The restraining assembly claim 1 wherein said head holder
further comprises a pair of jaw anchor screws extending inward
through said head holder into bore of said aperture.
5. The restraining assembly claim 1 wherein said head holder
further comprises a head clamping screw located at the top of said
head holder and extending inward through said head holder into a
bore of said aperture.
6. The restraining assembly of claim 1 further comprising a
restraining jacket for immobilizing the animal.
7. The restraining assembly claim 2 further comprising ear pads
wherein said ear pads are placed under said protective ear
piece.
8. A method of imaging a brain of a conscious awake animal,
comprising: restraining an un-anesthetized animal in an assembly
slidably mounted in an MRI device, the assembly including a
chassis; a front mounting plate located at a first end of the
chassis; a rear mounting plate located at a second end of the
chassis opposite the front mounting plate; an elongated body tube
extending along the chassis the tube enclosing the animal; and
conducting an imaging procedure on the brain conscious animal.
9. The method of claim 8 further comprising the step of amplifying
the sensitivity of low field strength magnets by implementing
exogenous contrast agents, blood oxygenation-level-dependant
contrast and radio frequency sequences.
10. The method of claim 8 further comprising the steps of:
obtaining a computerized histological representation of an fMRI
signal; and forming a three dimensional digital map of the imaged
brain from a computerized histological representation of the fMRI
signal
11. The method of claim 9 further comprising the steps of:
obtaining a computerized histological representation of a fMRI
signal; and forming a three dimensional digital map of the imaged
brain from a computerized histological representation of the fMRI
signal.
12. The method of claim 8 further comprising performing an fMRI
sequence using a real-time three dimensional functioning unit.
13. The method of claim 9 further comprising performing an fMRI
sequence using a real-time three dimensional functioning unit.
14. Apparatus for restraining a conscious animal during a magnetic
resonance imaging procedure comprising; a head holder with which an
animal's head is restrained; a chassis mounted within an MRI device
on which the head holder is attached, the chassis having a first
end plate and a second end plate mounted thereon such that the
animal's body is positioned between the first end plate and the
second end plate; and a body tube in which the animal's body is
enclosed.
15. The apparatus of claim 14 further comprising an rf coil that is
mounted on the head holder.
16. The apparatus of claim 14 further comprising a hole in the
second end plate, the body tube having a size such that the body
tube can be inserted through the hole.
17. The apparatus of claim 14 further comprising a clamp on the
head holder that is be secured to the animal's head and a bite
bar.
18. The apparatus of claim 14 further comprising a restraining
jacket that restrains an un-anesthetized animal during an imaging
procedure.
Description
RELATED APPLICATION
[0001] This is a continuation of U.S. patent application Ser. No.
09/169,602, filed Oct. 9, 1998 which is claims priority from U.S.
patent application Ser. No. 09/073,546, filed May 6, 1998, the
above applications being incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to magnetic resonance imaging,
and more particularly to a method and apparatus for performing
functional magnetic resonance imaging (fMRI) in animals.
BACKGROUND OF THE INVENTION
[0003] Human studies utilizing functional magnetic resonance
imaging (fMRI) have advanced our understanding of the regional and
functional interplay between populations of neurons serving
sensory, integrative and motor functions.
[0004] Changes in neuronal activity are accompanied by specific
changes in hemodynamic functions such as cerebral blood flow,
cerebral blood volume, and blood oxygenation. fMRI has been used to
detect these physiologically induced changes in response to visual
stimulation, somatosensory activation, motor tasks, and cognitive
activity. During cognitive activity, the blood flow into the active
region of the brain increases considerably compared with the tissue
oxygen uptake which results in an increase in blood oxy-hemoglobin
(HbO.sub.2) content. The susceptibility difference between
diamagnetic oxy-hemoglobin and paramagnetic deoxy-hemoglobin (Hb)
creates local magnetic field distortions that cause a dispersion in
the processional frequency of the water protons and a concomitant
change in the magnetic resonance (MR) signal intensity which is
proportional to the ration of HbO.sub.2 to Hb. These
signal-intensity alterations related to blood oxygenation are
termed the BOLD (blood oxygenation-level-dependent) effect. The
voxels in which paramagnetic Hb content is decreased are
illuminated in the image.
[0005] Unfortunately, extending these studies to animals has been
difficult because technological limitations prevent restraining a
conscious animal for prolonged periods of time in a magnetic
resonance imaging (MRI) instrument. As a result most studies to
date have been limited to animals which are typically anesthetized
in order to minimize motion artifacts. In the last 5 years over
7,000 fall length publications on MRI in animals have been written
without a single reference to an awake animal. The low level of
arousal during anesthesia either partially or completely suppresses
the fMRI response and has impeded fMRI application to the more
physiologically relevant functions that have been noted in
humans.
[0006] Significant challenges remain in utilizing MRI techniques in
both humans and anesthetized animals. One problem encountered in
human studies has been artifacts from head movements. Studies in
humans using invasive head fixation has shown improved image
quality over non-invasive fixation and absence of fixation.
However, this fixation method limits the amount of research time
available for human subjects. On the other hand, animal studies
must be performed under anesthetized conditions due to
indiscriminate movement of conscious animals. Since image
resolution is a salient feature of fMRI, precautions to ensure
improved image quality with minimized head movements are essential.
In addition to head movement, it has been observed that any motion
outside the field of view can obscure or mimic the signal from
neuronal activation.
SUMMARY OF THE INVENTION
[0007] Applicant's method and apparatus overcomes the difficulties
of performing fMRI on awake animals by utilizing a novel
restraining assembly to eliminate movement artifacts and to map
neuronal activation after exposure to sensorimotor stimulation in
conscious animals. The significance of applicant's method of
neuroimaging in awake animals will change current imagery of the
brain from either a static (as seen with most neurochemical
measurements) or a low activation dynamic system in an anesthetized
state (as seen with current fMRI or positron emission tomography
(PET) measurements) to a real-time three dimensional functioning
unit.
[0008] A novel stereotaxic assembly has been developed that can
immobilize the head and body of awake animals for several hours,
without restricting respiratory physiological functioning. The
apparatus allows for collection of a consistent pixel by pixel
representation of the brain over several data acquisitions under
various experimental conditions. Applicants have demonstrated fMRI
signal changes associated with neuronal activation in response to
footshock and during odor stimulation. Changes are measured in
conscious animals with and without the use of contrast agents and
are correlated with significant alterations in cerebral blood flow.
Importantly, the information is obtained without animal
sacrifice.
[0009] It has been found that the foregoing objects may be readily
obtained in the novel stereotaxic non-magnetic restraining assembly
to immobilize the head and body of awake animals for insertion into
the tunnel bore of a magnetic resonance imaging assembly.
[0010] In a first embodiment of the invention, the assembly has a
generally planar horizontal chassis with a front mounting plate and
rear mounting plate extending perpendicular to the chassis and
located adjacent to each end of the chassis. A body tube bracket
also extends perpendicular to the chassis and is located between
the front and rear mounting plates. The body tube bracket can be
fastened (via aligning screws) at different locations along the
chassis to accept different sized animals. The animal is placed in
a body tube with its head in the circular aperture of a head
holder. The body tube slides into a central access hole located in
the approximate center of the rear mounting plate and the body tube
bracket is thereby attached to the chassis. The head holder fastens
to the chassis between the body tube bracket and the front mounting
plate.
[0011] The head holder restrains the head of the animal to prohibit
vertical and horizontal movement of the animal during imaging. The
head holder has a bite bar extending horizontally creating a chord
along the bottom of its circular aperture. A vertical nose clamp
extends through the top of the head holder and abuts the animal's
nose to clamp the animal's mouth thereon.
[0012] The animal's head is further restrained by a pair of lateral
ear clamping screws that extend horizontally through the sides of
the head holder and a nose clamping screw that extends vertically
through the head holder. A protective earpiece is placed over the
animal's ears and receives the tips of the lateral ear clamping
screws.
[0013] The head holder may be fitted with a radio frequency (rf)
coil used to transmit rf radiation and receive the resulting MR
signal.
[0014] A second embodiment of the invention has a general structure
similar to the first embodiment with the following adaptations. The
rear mounting plate has a removable crown to allow for simplified
placement of the body tube into the rear mounting plate. In
addition to the nose clamping screw as in the first embodiment, the
means for restraining the head includes two additional bottom jaw
anchor screws located below the bite bar and extending radially
inward toward the circular access hole to secure the animal's lower
jaw against the horizontal bite bar. A head clamping screw
extending located to the rear of the nose clamp and extending
radially inward is included to further secure the animal's
head.
[0015] A further adaptation of the first embodiment includes a
means of restraining an animal and prohibit limb movement. An
animal is placed into a restraining jacket that is wrapped at the
back to restrain the animal. Holders for the arms and legs further
restrict the animal's movement. Soft rubber ear pads may be fitted
into the ear canals to minimize any irritation to the area and
mollify background noise.
[0016] Accordingly, it is an object of this invention to provide a
new and useful method and apparatus for performing neuroimaging on
awake animals.
[0017] It is a further object of this invention to provide a method
and apparatus for stereotaxically restraining an awake animal to
prevent movement while undergoing fMRI.
[0018] Yet another object of this invention is to provide a
stereotaxic restraining assembly which is adaptable to different
sized animals.
[0019] Another object of this invention is to amplify the
sensitivity of low field strength magnets with the use of exogenous
contrast agents, blood oxygenation-level-dependent contrast and
radio frequency sequences.
[0020] A further object of this invention is to register into a
three-dimensional digital map of the brain created from a
computerized histological representation of fMRI data obtained from
fMRI scans.
[0021] Further objects and advantages of the present invention will
become apparent from a consideration of the drawings and ensuing
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] With respect to the first embodiment:
[0023] FIG. 1 is a side perspective of fMRI restraint assembly
components;
[0024] FIG. 2 is a side perspective view of the mounting unit;
[0025] FIG. 3 is a front view of the front mounting plate;
[0026] FIG. 4 is a front view of the rear mounting plate;
[0027] FIG. 5 is a front view of the body tube bracket;
[0028] FIG. 6 is a side perspective view of the body tube;
[0029] FIG. 7 is a front perspective view of the cylindrical head
holder;
[0030] FIG. 8 is a side view of a rat in the cylindrical head
holder;
[0031] FIG. 9 is a front view of a rat in the cylindrical head
holder;
[0032] FIG. 10 is a front perspective view of a rat with the
semi-circular earpiece;
[0033] FIG. 11 is a side view of a rat with the semi-circular ear
piece; and
[0034] FIG. 12 is a side view of a rat in the assembled fMRI
restraint.
[0035] With respect to the second embodiment:
[0036] FIG. 13 is a side perspective view of the fMRI restraint
assembly components;
[0037] FIG. 14 is a view of the restraining jacket.
DETAILED DESCRIPTION OF THE INVENTION
EXAMPLE 1
[0038] To test the first embodiment of the invention, gold plated
surface electrodes were attached to the skin of the right or left
hindpaw of five male Sprague-Dawley rats (300-350 g) and connected
to an electrical stimulator that provided 25 V pulses of 0.3 ms
duration of 3 Hz (current of approximately 2.6 mA depending on skin
resistance). Animals were lightly anesthetized with intraperitoneal
administration of chloral hydrate (300 mg/kg; Sigma, St. Louis,
Mo.). The head was mounted and secured in a head holder custom
fitted with a "birdcage" rf coil. The body of the animal was placed
tightly into an animal holder, designed to allow for unrestricted
respiration with lateral movement. Animals routinely recovered from
the anesthesia within 30 mins., as evidenced by tail withdrawal,
hindlimb movement and occasional vocalizations. Blood pressure and
heart rate were continuously monitored for signs of distress. The
apparatus was inserted into the tunnel bore of a MRI device.
[0039] Magnetic resonance images were acquired using CSI-II 2.OT/45
cm imaging spectrometer (GE NMR Instruments, Fremont, Calif.)
equipped with self-shielded gradient coils capable of producing a
maximum field strength of .+-.20 G/cm. The image processing was
performed off-line on a computer workstation (100 MHz Iris Indigo
R4000 Silicon Graphics, Inc., Mountain View, Calif.) and analyzed
on a Power MAC 610/66 using NIH image software (version 1.54).
Prior to acquisition of the fMR images, a series of scout images
were acquired with an eight-slice, echo-planar imaging (EPI)
sequence (field-of-view), FOV=25.6.times.25.6 mm; 64.times.64 data
matrix; 65 ms image acquisition window, to determine the exact
position of the animal. Approximately 120 minutes after positioning
the animal in the magnet, axial T.sub.2*-weighted, BOLD images of
the rat brain (under resting and stimulated conditions) were
acquired using a 2D gradient-echo imaging sequence (repetition
time, TR=200 ms; echo time, TE=20 ms; 2-mm slice thickness;
128.times.128 data matrix). After a baseline study, the stimulus
was applied for two minutes at 25 V and 1 minute at 10 V before
data collection. The resulting stimulated and baseline images were
subtracted to reveal regions of activation. The region of greatest
activation were on the contralateral (to stimulated hind-paw)
somatosensory frontal and parietal cortices was integrated from the
subtraction image by pixels.+-.2SD above the signal-to-noise
threshold with computer-assisted tomography. The corresponding
region of the baseline and stimulated datasets were demarcated and
the relative signal intensity was calculated on a pixel-by-pixel
basis.
[0040] BOLD-based signal intensity was correlated to hemodynamic
changes through measurement of relative cerebral blood flow (rCBF)
in the region of interest. A T.sub.2*-weighted, gradient-echo EPI
sequence (TR=900 ms; TE=38 ms: 65 ms image acquisition window,
number of signal averages, NEX=1) was used to acquire 25 images
from the same slice which gave the maximum BOLD signal intensity
changes. A bolus of contrast agent gadopentetate dimeglumine (0.15
ml) was administered after the seventh image. The change in the
T.sub.2* rate, .LAMBDA.R.sub.2*(t)=was obtained from the change in
signal intensity based on the following relationship:
.LAMBDA.R.sub.2*(t)=1n[S(t)S.sub.0]/TE (where S(t) is the signal
intensity at the time t). The relative cerebral blood volume (rCBV)
and mean transit time (MTT) were determined for each pixel by the
integration of .LAMBDA.R.sub.2*(t) and an estimate of the first
moment of t, respectively. The rCBF was determined, on a
pixel-by-pixel basis, from the ratio of rCBV to MTT and rCBF maps
were calculated from the 25 images. Since the cerebral hemodynamic
state in a non-activated brain is quite stable over time, the
resting-state rCBF maps were subtracted from the stimulated-state
rCBF maps to create a new functional map depicting local changes
caused by the hind-paw stimulation. Then the baseline and
stimulated rCBF maps were anatomically correlated to BOLD-based
images allowing for delineation of boundaries between the activated
and the non-activated regions. The relative signal intensity was
calculated, on a pixel-by-pixel basis, from the selected
region.
[0041] Functional MRI can be performed in conscious animals
provided that there is adequate restraint. The acquired images had
minimal motion artifacts, even with maximum stimulus strength. The
signal enhancement was related to stimulation intensity and was
independent of which hind-paw was stimulated. For example, the
increase in signal intensity with the 25 V stimulation was
approximately 18% and with 100 V it increased to 30%. The activated
regions can be clearly discerned in the subtraction images. The
region of activation in individual animals varied with exact
location and size since non-invasive skin electrodes (with large
surface area) were used to minimize distress in the conscious
animals.
[0042] Concurrent perfusion studies in the region identified by the
BOLD technique showed corresponding increases in cerebral blood
flow. An average local increase in rCBV of 67.+-.15% and in rCBF of
64.+-.8%, corresponding to the initial BOLD changes of 18.+-.1%
(mean.+-.SE, n-5), was observed. The subtraction images revealed
good regional association between the activated cortical region
measured for rCBF and BOLD signal changes, respectively. The
average 1/T.sub.2*, change of XXXX correspondence to BOLD change of
XXXX (mean.+-.SE, n-X) was measured in the region of interest.
[0043] Since this study was done on conscious animals, comparisons
with similar studies are somewhat limited. However, the results of
this study are consistent with a number of previous investigations.
First, studies examining signal intensities in anesthetized animals
post-stimulation range from 5% obtained at 2.0 Tesla (T) to 5-17%
(peak voxels 30%) obtained at 7.0T magnet. The relatively large
BOLD signal intensity changes observed in this study may be due to
the increased neuronal activation status of conscious animals,
compared to the anesthetized counterparts. In this case, however,
comparisons of signal intensity changes between different studies
can be misleading due to differences in image acquisition
parameters and/or magnetic field strengths. To circumvent this
problem, applicant has attempted to estimate the signal-intensity
changes for our experimental conditions. In an in vivo study,
Prielmeier et al. Have determined 1/T.sub.2* rates of rat brain
during hypoxia and interleaved normoxic phases (x). They found that
1/T.sub.2* increases in a linear manner with arterial
deoxygenation. In the study, a mild and moderate deoxygenation
(less than 40%) corresponds to an approximate change of 5.5 1/s in
1/T.sub.2*. A severe deoxygenation (over 40%) has lead to a
plateau, which authors expect to result from enhanced cerebral
blood flow (X). In applicant's study, a change of XXX in 1/T.sub.2*
was measured. Also, in an in-vitro study by Thulburn et al. (K. R.
Thulbum, J. C. Waterton, P. M. Metthews, G. K. Radda, Biochemica et
Biophysica Acta, 714, p. 265-270, 1982), a 1/T2 change of 8.3
S.sup.-1 correlated with a 75% change in oxygenation at 1.9T (close
to our 2.0T field strength). Third, in a static mathematical model,
an approximate 60% change in blood oxygenation corresponded to a
64% increase in CBF at 1.50 level of CBV. Taken together, the above
studies support the current quantitative data generated in
conscious animals lining changes in BOLD and rCBF. Although one
must be aware that extrapolation across differences in neuronal
activation state (awake vs. anesthetized) and experimental
parameters, as well as interspecies variations, may complicate more
direct comparisons. Furthermore, other reported stimulus duration
and intensity dependent phenomena like signal saturation and
undershoot after stimulation period were observed in these
studies.
EXAMPLE II
[0044] To test a second embodiment of the invention, an adult male
marmoset was lightly anesthetized and fit into a custom-made cloth
jacket to keep the arms and legs from being pulled forward. A
plastic semicircular headpiece with blunted ear supports and soft
rubber ear pads were fit into the ear canals to minimize any
irritation to the area and mollify the sound of the radio frequency
pulses. The marmoset's head was placed into the cylindrical head
restrainer with the animals canines secured over a bite bar and
ears positioned stereotaxically inside the head restrainer with
adjustable screws fit into lateral slits. The head holder was
secured to the mounting unit with plastic screws. The body of the
animal was placed into the body restrainer. The body restrainer was
secured onto the mounting unit and the assembly was placed into the
tunnel bore of a MRI device. (The marmoset generally awoke from
anesthesia after approximately 45 to 60 minutes).
[0045] Magnetic resonance images were acquired on a General
Electric CSI-II 2.0-T/45-cm bore imaging spectrometer equipped with
self-shielded gradient coils capable of producing a maximum field
strength of .+-.20 G/cm (General Electric Co., Fremont, Calif.).
Prior to the experiment, the head restrainer is custom-fit with a
birdcage radio frequency coil. These coils are used to transmit the
rf radiation and receive the resulting MR signal. Radio frequency
coils are usually custom-fitted to the desired anatomy to give
maximum filling factor which results in optimal sensitivity. A
prototype birdcage coil of 5.8 cm diameter by 4.4 cm in length was
custom-fitted around the head holder. The circuitry was tuned to
85.557 MHz frequency.
[0046] There is a paucity of MRI data in non-human primates, hence
it was necessary to collect a set of serial images focusing on the
brain anatomy of the adult male marmoset. T.sub.1-weighted
anatomical images were acquired from three orthogonal planes using
multi-slice spin-echo imaging sequence. Two sets of eight slices
were acquired in an interleaved fashion, resulting in 16 continuous
slices, each 2 mm thick. The repetition time (TR) of acquisitions
(NA) was 2 and the digital resolution was 256.times.128.
[0047] Prior to acquisition of the fMR images, scout images from
the three planes were acquired with a single slice, spin-echo
sequence (FOV=50.times.50 cm, digital resolution of 256.times.128,
NA=2), to determine the exact position of the animal's head. BOLD
based fMRI data sets were acquired from rest, control and
stimulated conditions using multi-slice gradient-echo sequence
(TR=240 ms, TE=20 ms, NA=2, and digital resolution of
128.times.128). First, a series of baseline images were acquired to
record background noise level and detect possible motion
artifacts.
[0048] After baseline acquisitions were taken, data from the rest
period for room air, stimulus scent (odor of a receptive female)
and control scent were collected. At the onset of olfactory
stimulation, a stimulus cup was opened and placed 1.2 cm from the
nose of the marmoset. A fan was positioned at the back of the
magnet pointing outward, pulling a gentle draft of air through the
bore. After three minutes, the stimulus cup was removed, exposing
the animal to room air for two minutes followed by a three minute
period with the control cup. This sequence was repeated four times
with a five minute rest period in between. Data was collected
during stimulus and control exposures. When the stimulus cup was
not in use, it was sealed. Two sets of images were acquired during
each presentation of the scent.
[0049] The image processing was performed off-line on a 100 MHz HP
Apollo 735 workstation using IDL imaging software, Version 4.0 and
analyzed on a Power Mac 60/66 using NIH imaging software, Version
1.56 (Apple Computer, Inc., Cupertino, Calif.). The stimulated and
baseline images were subtracted to reveal regions of activation.
The region of greatest activation was determined from the
subtraction image. The corresponding region of the baseline and
stimulated data sets were demarcated and the relative signal
intensity was calculated on a pixel-by-pixel basis. Brain activity
increased with time of exposure to the scent of the receptive
female.
DETAILED DESCRIPTION OF THE DRAWINGS
[0050] Turning first to FIG. 1, therein illustrated is a
disassembled fMRI restraining assembly having a Plexiglas.TM.
chassis generally designated by the numeral 1, a Plexiglas.TM.
cylindrical head holder generally designated by the numeral 2, a
Plexiglas.TM. body tube generally designated by the numeral 3, a
rear mounting plate generally designated by numeral 7, a front
mounting plate generally designated by numeral 8, and a body tube
bracket generally designated by numeral 9. One end of the chassis 1
is fitted into chassis mounting slot 10 (not shown) of rear
mounting plate 7 and the opposite end of chassis 1 is fitted into
chassis mounting slot 10 of the front mounting plate 8.
[0051] Turning in detail to the assembly as seen in FIG. 2, therein
is illustrated an elongated rectangular Plexiglas.TM. chassis 1
with a series of parallel opposing adjusting holes 6 drilled
approximately midway therein. At one end of the chassis 1 is a
circular Plexiglas.TM. rear mounting plate 7 and at the opposite
end of the chassis is a circular Plexiglas.TM. front mounting plate
8. Also, shown in FIG. 2 is a square Plexiglas.TM. body tube
bracket 9 adjustably mounted to the chassis 1 by a pair of screws
35 (shown in FIG. 13) extending through the chassis in the
correlating mounting screw holes 6 and into body bracket tube
9.
[0052] FIG. 3 is a detailed view of the front mounting plate 8
having a centrally located circular access hole 11 extending
through the approximate mid-section of the front mounting plate and
a chassis mounting slot 10 extending horizontally below the
circular access hole 11 which receives the chassis 1. Screw
alignment slots 12 are located radially from the central circular
access hole 11 to allow access through the front mounting plate 8
for adjustment of head holder 2. An assembly mounting block 13 and
assembly mounting screw 14 penetrating the assembly mounting block
13 are located an outer surface of the front mounting plate 8 above
the circular access hole 11 to secure the assembly in the
cylindrical bore of a MRI tunnel (not shown). At radially
equidistant points located on the perimeter of the front mounting
plate 8 are three assembly centralizers 15 which provide further
stability to the assembly when placed into the cylindrical bore of
a MRI tunnel.
[0053] FIG. 4 shows a detailed view of the rear mounting plate 7
having a central circular access hole 11 and a horizontal chassis
mounting slot 10 extending horizontally below the circular access
hole 11 which receives the chassis 1. Arcuate cable access slot 16
is located above the access hole 11 to allow access through the
rear mounting plate 7. At radially equidistant points located on
the perimeter of the rear mounting plate are three assembly
centralizers 15 provide further stability to the assembly when
placed into the cylindrical bore of a MRI tunnel. Assembly
centralizers 15 also act as feet to stabilize the assembly when it
is free standing outside the cylindrical bore of a MRI tunnel.
[0054] FIG. 5 shows a detail of the body tube bracket 9 which has
an access hole 11 therein for receiving the body tube 3 and a
clamping screw hole 17 located through the top surface to receive a
clamping screw 18 for temporarily fastening the body tube 3 to the
body tube bracket 9. The bottom surface of the body tube bracket 9
has a pair of threaded mounting screw holes 19 for receiving
aligning screws 35 (shown in FIG. 13) which detachably attach the
body tube bracket 9 to the chassis 1.
[0055] FIG. 6 shows the body tube 3 which is an elongated
Plexiglas.TM. tube having two elongated animal access slots 20. By
turning to FIG. 12 it will be appreciated that body tube 3 may be
slideably inserted through access hole 11 of the rear mounting
plate 7 and into access hole 11 of body tube bracket 9. Once
inserted, clamping screw 18 may be tightened to releasably secure
the body tube 3 in body tube bracket 9.
[0056] FIGS. 7, 8 and 9 illustrate the head holder 2 having lateral
ear clamping screws 4 inserted into lateral screw slots 21. The
head holder 2 is a cylindrical tube having a central aperture 22
therethrough for receiving the head of an animal 23 and a bite bar
24 extending horizontally along a chord of the circular aperture 22
to provide a rest for the upper jaw of a restrained animal 23.
Mounted through the top of the cylindrical head holder is a nose
clamping screw 25 to secure the nose of a restrained animal 23 to
the bite bar 24 as shown in FIG. 9. A pair of opposed lateral screw
slots 21 are located in the sides of the cylindrical head holder to
receive lateral ear clamping screws 4. Encompassing the head holder
2 is a birdcage coil 26. The head holder 2 is connected to the
chassis 1 by a pair of mounting screws 29 (not shown) extending
through the chassis 1 and into the head holder mount 28.
[0057] As shown in FIGS. 10 and 11, the semi-circular earpierce 5
is fitted over the head of the animal 23 whereupon the animal's
head is placed into head holder 2. Lateral ear clamping screws 4
are inserted through a pair of lateral screw slots 21 and tightened
against divots in a semi-circular earpiece 5 to prevent the animal
from moving horizontally. The upper jaw of the animal 23 is fitted
over the bite bar 24 and nose clamping screw 25 is tightened
against the snout of the animal to secure it to the bite bar 24 and
thereby eliminate vertical movement maintaining a stereotaxic
position of the animal's head.
[0058] As shown in FIG. 12, the cylindrical head holder is fixedly
mounted to the chassis 1 by a pair of head holder mounting screws
29 threadably fastened into the head holder mount 28 allow
adjustment of the cylindrical head holder 2 to properly fit
different size animals. Once assembled the various components of
the fMRI restraining assembly cooperate to minimize movement in an
awake animal and thereby allows for a method of performing
neuroimaging on an awake animal 23.
[0059] Turning now to FIG. 13 depicting a side perspective view of
a second embodiment of the restraining assembly having an elongated
rectangular chassis designated by the numeral 1, a Plexiglas.TM.
head holder usually designated by the numeral 2, a Plexiglas.TM.
body tube generally designated by the numeral 3, a rear mounting
plate generally designated by the numeral 7, a front mounting plate
generally designated by the numeral 8, and a body tube generally
designated by the numeral 8, and a body tube generally designated
bracket by the numeral 9. The front mounting plate 8 has an access
hole extending horizontally therethrough. Attached to the top front
of the front mounting plate 8 is an assembly mounting block 13 and
screw 14 and attached to the bottom front of the front mounting
pate 8 is an anchor screw 30. The assembly mounting block 13 and
the front anchor screw 30 are adapted to hold the assembly in place
when inserted into the magnetic bore of a MRI tunnel. The front
mounting plate 8 and rear mounting plate 7 each contain a chassis
mounting slot 10 along the interior bottom to accept and interlock
with the chassis 1.
[0060] A series of parallel opposing adjusting holes 6 are located
approximately in the middle section of chassis 1. The head holder 2
connects to the chassis 1 through head holder mounting screw 29 and
corresponding adjusting holes 6. The head holder 2 has a central
generally circular aperture running horizontally therethrough and
along the central axis of the chassis. The head holder 2 has a head
clamping screw 31 located at the top front of the head holder 2
extending radially downward to the front of the head holder 2 and
extends into the central aperture. The head holder 2 also has a
nose clamping screw 25 at the top front of the head holder 2
extending radially downward to the rear of the head holder 2 and
extends into the central aperture. The head holder 2 further has a
pair of jaw screws 32 located at the bottom front of the head
holder 2 and extending radially inward into the head holder's
central aperture.
[0061] Ear clamping screws 4 are located on opposite sides of the
head holder 2 within the lateral screw slots 21 and extend
horizontally into the central axis of the chassis. The lateral
screw slots 21 are located on opposite sides of the head holder 2
and extend from the rear edge of the head holder 2 toward the front
of the head holder 2. The restrained animal wears a semi-circular
earpiece 6 and soft rubber pads 36 to protect the animal's ear
canals. The animal's head is fitted into the head holder 2 and the
ear clamping screws 4, which slide into the lateral screw slots 21,
fasten onto divots on the disk end portions of the semi-circular
earpiece 6.
[0062] The body tube 3 is an elongated Plexisglas.TM. cylinder
attached to the chassis 1 through a rear mounting plate 7 at the
end of the chassis opposite the front mounting plate 8. An anchor
screw 30 is located at the bottom rear of the rear mounting plate 7
that is adapted to hold the assembly in place when inserted into
the magnetic bore of a MRI tunnel. The rear mounting plate 7 has an
access hole running generally horizontally through the center to
receive and align the body tube 3. The rear mounting plate 7 also
contains a body tube clamp 33 located at the top of the rear
mounting plate 7. The rear mounting plate 7 has a chassis mounting
slot 10 along the bottom front to accept and interlock with the
chassis 1. The rear mounting plate 7 further has a removable crown
34 to allow easier placement of the body tube 3 into rear mounting
plate 7. The rear body tube clamp 33 acts to hold the crown in
place.
[0063] The body tube bracket 9 is located along the chassis 1
between the head holder 2 and the rear mounting plate 7 and is
adjustably attached to the chassis 1 by a pair of aligning screws
35 (not shown) in a corresponding adjusting holes 6. The body tube
bracket 9 has an access hole running horizontally therethrough to
receive and align the body tube 3. A clamping screw 18 and
corresponding hole are located at the top of the body tube bracket
9 pointing downwards to holds the body tube in place.
[0064] FIG. 14 describes a novel restraining jacket 37 used to
restrain an animal. The jacket is made of a Velcro.TM. lined,
non-flexible fabric with a Velcro.TM. closure 38. Arm and leg
holders 39 and 40, respectively, further restrict the animal's
movement. The jacket has holes for the animal's head 41 and 42,
respectively.
[0065] The present invention demonstrates novel images of neuronal
activation in conscious animals. Current methods utilizing
anesthetized animals, which are known to exhibit dampened neuronal
activity, may mask low signals levels. Furthermore, since the level
of arousal (conscious vs. anesthetized) is inextricably linked to
behavior, the future use of this assembly will be a significant
step in providing a better understanding of the neural circuitry
that facilitates behaviors such as responses to visual stimulation,
temperature regulation, and motor stimulation, in addition to a
range of different environmental stressors and
interneurodevelopmental and intraneurodevelopmental studies.
Therefore, researchers interested in the brain and/or behavior
(utilizing laboratory animals) will be further assisted in their
discoveries, with the utilization of this new assembly.
[0066] It will be appreciated that the above description contains
many specificities, these should not be construed as limitations on
the scope of the invention, but rather as an exemplification of a
preferred embodiment thereof. Many other variations are
possible.
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