Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1998-10-09
2001-08-14
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S422000, C324S318000
Reexamination Certificate
active
06275723
ABSTRACT:
FIELD OF THE INVENTION
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
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.
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
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 ratio of HbO
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.
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 full 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 fMRl application to the more physiologically relevant functions that have been noted in humans.
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
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.
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.
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.
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 and is thereby attached to the chassis. The head holder fastens to the chassis between the body tube bracket and the front mounting plate.
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.
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 ear piece is placed over the animal's ears and receives the tips of the lateral ear clamping screws.
The head holder may be fitted with a radio frequency (rf) coil used to transmit rf radiation and receive the resulting MR signal.
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.
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.
Accordingly, it is an object of this invention to provide a new and useful method and apparatus for performing neuroimaging on awake animals.
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.
Yet another object of this invention is to provide a stereotaxic restraining assembly which is adaptable to different sized animals.
Another object of this invention is to amplify the sensitivity of low field strength magnets with the use of exog
Allard Arthur C.
Ferris Craig F.
King Jean A.
Hamilton Brook Smith & Reynolds P.C.
Insight Neuroimaging Systems, Inc.
Lateef Marvin M.
Shaw Shawna J.
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