The overall goal of this procedure is to investigate using a novel 3D neuronavigation. Approach the endogenous mu opioid transmission in the brain during a spontaneous migraine headache attack in vivo. This is accomplished by first scanning a migraine patient in a typical headache and non headache phase, using positron emission tomography with a selective radio tracer, carbon 11 carfentanil, which allows us to measure mu opioid receptor availability in the brain.
The second step is to verify co-registration and normalization accuracy by comparing the transformed MR and PET images to the MNI Atlas template. In order to apply region of interest ROI analysis, the final step is to organize and store subject activation data in the nifty data format to display the volume in a fully immersive multi-screen clustered configuration. Ultimately, the 3D neuro navigation system allows for real-time exploration of the dataset and enables dynamic control and dissection of the neuro imaging data of the patient during a migraine attack in a virtual reality environment.
The main advantage of this technique over existing methods is that it permits the full interaction and navigation in real time through the brain of a patient during a migraine attack. This method can help answer key questions in the migraine field, such as which areas in the brain are more or less active during a migraine attack At molecular level with in vivo using carbon 11 corfe, a specific MU opioid visual tracer tapping into one of the main analog mechanisms in the brain. Generally, individuals new to this method will struggle because of the complexity to adapt the neuroimaging data and the challenge of making a fully interactive virtual reality environment.
Virtual, virtual reality, The software was developed to create a complete immersive experience. The computer uses advanced motion tracking equipment to track the user's point of view and gestures in the virtual reality space. Special shutter glasses deliver separate left and right perspectives to the brain, which merged to form the perception of A 3D experience for the user, and they're really cool.
Prior to preparing the subject for this scans in this protocol, first obtain written and informed consent. Then on the day of the MRI scan, have the research subject fill out an MRI safety screening form During an interictal phase for the patient, acquire a high resolution T one weighted anatomical MRI image on a three Tesla MRI scanner. A one millimeter slice thickness is recommended for this scan.
Then prior to confirming the date for the subject's PET scan, contact the subject to verify in which phase of the menstrual cycle she will be on the day of the scan. It is recommended to perform the PET scan during mid to late follicular phase. Once the scan date is confirmed, submit a request to produce carbon 11 carfentanil a short life radio tracer with a selective affinity for mu opioid receptors using a cyclotron in the vicinity of the scanner site.
Note that this tracer must be produced two hours before the scan. Then on the day of the potential ictal PET scan, contact the subject two hours before the appointment to confirm the presence of a spontaneous migraine attack. If a migraine attack is present, validate the migraine diagnosis following the international classification of headache disorders.
After diagnosis, confirm that the participant is able to safely go to the hospital to undergo the scan. Provide transportation if the subject is not comfortable driving or if no designated driver is available. When the participant arrives at the hospital, escort her to the pet suite for revalidation of diagnosis using the same international criteria.
Then before the scan perform a urine drug test to confirm that the subject did not take any substance that could interact with the tracer as well as a pregnancy test. Confirm that the participant understands the PET procedure risks and benefits, and verify informed consent following the guidance of the nuclear medicine technologist. Help the subject to settle in the scanner for each dose of tracer.
Administer 50%as a bolus with the remainder continuously infused over the course of the scan to achieve steady state tracer levels. Approximately 35 minutes after tracer administration perform one 90 minute PET scan here a Siemens HR plus scanner in 3D mode is used. The reconstructed images should have a full width at half maximum resolution of about 5.5 millimeters in plain and 5.0 millimeters.
Axially also run an INTERICTAL PET scan by repeating these steps during a non headache phase during the following menstrual cycle. Then reconstruct the PET data and perform data analysis including normalization and region of interest analysis. See the text accompanying this protocol for more detail.
To prepare for the 3D interactive neuronavigation experience, first, organize the data provided in nifty volumetric data format as a stack of images with density and activation levels defined as 16 bit. Wear active LCD shutter glasses to enable the time sequential stereoscopic 3D effect. The shutter glasses operate by blocking the image for one eye while the image for the other eye is displayed.
The process alternates between eyes to generate a 3D effect and occurs at 110 hertz. Use a joystick for interactions with the simulation and instructions on its use outfit, both the shutter glasses and joystick with reflective markers to enable precise six DOF tracking of the objects in space via a vicon motion capture system. Next, display the subject activation data use XML configuration files to define color mappings of density and activation levels, which are loaded when the application begins and are shared with each computer in the cluster.
Acquire three dimensional volumetric cells from the provided nifty dataset by way of jugulars internal loading functions and the nifty lab open source software library. Typical loading time is less than one minute, but sharing resulting volumetric cells with each computer and the cluster will improve speed. Interpret volumetric cells by an open GL shader that conducts ray marching and displays voxels with varying colors and transparencies defined by the previously shared color mapping XML configuration files.
Obtain the location through the Vicon motion capture system and use this to update the drawn perspectives of the volumetric data on each screen. Record interactions and use them to dynamically adjust and cut planes through the data and to navigate in the virtual space for three dimensional interactive neuro navigation. First store the subject activation data in the nifty data format, a volumetric data type that is interpreted using the nifty live library.
Then to display the volume in a fully immersive multi-screen clustered configuration, apply the volumetric data to the back faces of a scaled cube and render using a single pass GL SL shader. The shader array marches through the volume displaying voxels with varying colors and transparencies based on density and activation levels. Obtain interactions and the location through the tracking system, joystick device and gestural input.
Use this information to ensure the displayed image represents the correct vantage point, allowing for real time exploration of the dataset. Also enable dynamic control for up to three arbitrary cutting planes using familiar movements and control schemes. Here we can see an mu opioid brain profile of a migraine headache in vivo.
The ictal or headache phase shows a decrease in mu opioid receptor availability in the pain matrix regions. This possibly represents an increase in endogenous mu opioid release during the migraine attack as a regulatory response to the ongoing severe headache. Here we can see an example of midbrain, pons and medulla mu opioid receptor availability during a migraine attack in vivo.
The ictal headache phase shows a decrease in mu opioid receptor availability along the peri aqueduct gray matter as compared to the interictal non headache phase. The implications of this technique extend to therapy of migraine because it can define with more accuracy, potential targets in the brain for future treatments, including neuromodulation. Though this method can provide insight into migraine, it can also be applied to other neurological disorders such as neurologists, depression and addiction.
The combination of 3D neuro navigation and neuroimaging allows for researchers, clinicians, and educators in the field of pain, neuroscience to explore the brain in a much more interactive and immersive virtual environment. The results presented demonstrate important mechanistic information on the impact of migraine headache on the MO opioid system.
