Patent Application
20050177200
The present invention generally relates to vagus nerve stimulation. More particularly, the present invention relates to a method, apparatus, and system for determining effects and optimizing parameters of vagus nerve stimulation by interleaving vagus nerve stimulation with functional magnetic resonance imaging.
Vagus nerve stimulation (VNS) has shown beneficial clinical effects in treating epilepsy and has shown promise in treating patients with major depressions. VNS involves applying mild, intermittent electrical impulses to the vagus nerve of the human neck. Little is known about the mechanism responsible for VNS effects. Researchers have typically applied the maximum tolerable intensity while other parameters of the stimulation, such as frequency, pulse width, and stimulation duration, are held constant. Multi-parameter optimizations of the technique have been largely unexplored. Clinical trials in epilepsy have shown a pattern of progressive efficacy over time.
Positron emission tomography (PET) has been used to investigate the effects of VNS. Unfortunately, the low temporal resolution of PET limits its observations to integrated effects over time periods longer than typical VNS stimulation. Further, the dependence of PET methods on the use of radioactive tracers is unsuitable for repeated use on a single patient.
Therefore, there is a need to develop a technique and apparatus for determining effects of VNS and optimizing parameters of VNS so as to improve the performance and applications of VNS.
According to exemplary embodiments, a method, system and apparatus are provided for performing VNS-synchronized functional magnetic resonance imaging (fMRI to determine effects and optimize parameters of VNS application on a patent.
According to one embodiment, a computer is used to detect the electrical impulses generated by a VNS stimulator and synchronize fMRI image acquisition with the VNS impulses.
VNS-fMRI may be used to determine the effects of the many VNS parameters on regional brain activity to help set optimal dosage and protocols in clinical use of VNS.
VNS-synchronized fMRI may also be used study the blood oxygenation level-dependent (BOLD) response of several brain regions to VNS stimulation. The VNS responses of the orbitofrontal cortex, parieto-occipital cortex, left temporal cortex, hypothalamus, and left amygdala regions of the human brain can be determined.
Further, VNS-fMRI may be used to determine useful VNS applications in the treatments of neuropsychiatric diseases. The mappings of VNS effects on brain regions are considered in relation to the regional effects of such diseases.
Also, because of its safe, noninvasive nature, VNS-fMRI provides for long-term and repeated studies of VNS treatment to assess whether regional brain effects change with continued use.
These and other aspects will become apparent from the following description of various embodiments taken in conjunction with the Appendices, although variations and modifications may be effected without departing from the spirit and scope of the novel concepts of the disclosure.
Several embodiments of the invention are now described in detail in connection with the disclosures made in the Appendices. As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein and throughout the appendices that follow, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
An exemplary system for synchronizing VNS application with fMRI is schematically shown in
Referring to
In one embodiment, a VNS generator is implanted within the neck of a human subject in an MRI-compatible fashion with the lead pins oriented along the long axis of the body. Adhesive-backed, MRI-compatible electrodes and electrocardiogram leads are placed on the subject's neck. At least one electrode is placed over the route of the implanted VNS leads just above and/or below the incision scar. An additional electrode is placed about 3 to 4 cm posterior to the scar to serve as an electrical ground. The subject is given earphones and instructed to lie quietly with eyes closed and to listen for an auditory tone. The head of the subject is stabilized within the scanner head coil with foam-padded adjustable restraints. The VNS pulses are detected by the electrodes and analyzed to achieve synchronization with fMRI scanning.
A patient's VNS device may be programmed to a predetermined time cycle such as a 7-seconds-on/108-seconds-off stimulation cycle. This cycle is the shortest stimulation duration setting of some available devices and best delineates the time course of the VNS response. During the fMRI scan procedure, a 440-Hz tone is fed through the headphones in 7-second trains of 100-ms pulses.
In some embodiments, structural fMRI images are transferred to a computing platform and stored in a memory device for anatomic reference. A check can be performed to ensure that the subject movement during scanning is within acceptable limits. The images can be motion corrected when necessary. Images can be spatially normalized to match standard brain template configurations with an affine transformation. A high-pass filter can be utilized to remove signal drift, cardiac and respiratory effects, and other low-frequency artifacts.
According to one embodiment, a determination of neuropsychiatric diseases that VNS might treat, may be made by outlining the neurobiologic effects of VNS, listing the functional neuroanatomic maps and pathophysiological cascades of neuropsychiatric diseases, identifying overlaps between the mappings of VNS effects and neuropsychiatric diseases, and carrying out preclinical and clinical trials in those diseases which show high probabilities of VNS therapeutic effects.
In one embodiment, an automated shimming apparatus, system and method allow real-time analysis in determining the best VNS device settings based on pre-determined regional brain activation. A VNS generator is provided which can be variably programmed to enable the use of single event fMRI to efficiently explore VNS parameters. Remote programming of the VNS generator allows shimming of the generator settings so that maximum brain effect settings can be determined.
Computer software may be used to determine the exact time of each VNS pulse. This provides images that are sensitive to the small changes that occur in areas of the brain activated by VNS. This involves averaging a series of images that follow VNS pulses in lock-step fashion and associating the time course of brain activity with a single event, such as a sensory stimulation, a movement, or a thought.
More details of the present invention are further disclosed in the Appendices including all texts and drawings therein, which form an integral part of the present application.
While various embodiments of the invention are described above and in the Appendices, it is to be understood that certain changes can be made in the form and arrangement of the elements of each system and steps of each method according to the present invention as would be known to one skilled in the art without departing from the underlying scope of the invention as is particularly described above including the Appendices. Furthermore, the embodiments described above are only intended to illustrate the principles of the present invention and are not intended to limit the invention to the disclosed elements.
This application claims priority to U.S. Provisional Application No. 60/377,692, herein incorporated by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US03/14245 | 5/5/2003 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 60377692 | May 2002 | US |
