The overall goal of this procedure is to provide a training resource for convection enhanced delivery into agros gel models of the brain. This is accomplished by first properly preparing an accurate AGROS gel model of the brain. The second step is to prepare the line and catheter for infusion, ensuring no air is present in the line to impair the infusion.
The next step is to start the infusion, taking careful steps to prevent reflux and continuously monitoring the rate and infuse a cloud via MRI. After completing the infusion, the final step is to analyze the data provided by the MRI of the infusion. Ultimately, MR data analysis is used to show the volume of distribution and the VD to VI ratio accomplished by the infusion.
The main advantage of this technique over existing methods of pharmacological therapy is that it allows direct bulk infusion of therapeutics that have had limited utility due to their pharmacokinetic properties and the blood-brain barrier. The implications of this technique extend towards the treatment of brain tumor metabolic disorders. Neurodegenerative disorders such as Parkinson's disease, stroke, and trauma historical treatments have relied on pharmacotherapy or direct surgery.
This procedure may allow the delivery of substances that had limited utility in diseases up until now To begin dissolve two grams of 0.1%aros powder in 1000 milliliters of deionized water. To prepare a 0.2%AROS gel, stir the solution for one minute to ensure proper mixing and immediately microwave the solution in three minute intervals for nine minutes or until clear and stir between intervals. Next, pour the solution into five cubic centimeter containers leaving space at the top of the container to add water, allow the AGROS gel to cool and settle for one to two hours.
Once the agros gel has solidified, add one centimeter of water to the top of the gel and refrigerated overnight. Use the gel within 24 to 48 hours of mixing. Then combine 8.5 milligrams of bromo phenol blue, or BPB dye with 50 milliliters of deionized water to create a 0.017%BPB solution.
Next, add 0.2 milliliters of 0.5 molar gato erol stock to 50 milliliters of the 0.017%BPB solution to create a two millimolar gato Toradol radio contrast dye solution, then place 50 milliliters of the radio contrast die in a 60 milliliter syringe. Connect the syringe containing the radio contrast dye to the infusion pump. Next, attach the pressure sensor to the pump outlet with the transducer attached to the IV monitor.
Then attach a 16 gauge infusion catheter to the open end of the pressure sensor. Purge the system for approximately 15 minutes at 16.667 microliters per minute. To remove any air bubbles, do not exceed the 16.667 microliters per minute flow rate, or the machine will cease infusion due to high line pressure.
Next, attach the infusion catheter mount and trajectory frame to the gel phantom container and place it in the MRI zero the pressure value recorded by the IV monitor before beginning the infusion. Next, insert the infusion catheter into the aros gel with the infusion pump running at the lowest flow rate possible, 1.667 microliters per minute. Begin the MR scan using the parameters listed here and continue infusing at a rate of 1.667 microliters per minute until the total volume infused reaches 60 microliters.
Scan the gel continuously in consecutive intervals. Record the pressure readings every 60 seconds. Once the infused volume reaches 60 microliters, turn off the infusion pump and complete MR.Scanning.
While continuing to record pressure readings, use the eRx DICOM viewer with region of interest or ROI segmentation functionality to analyze MR.Images. Then select the correct frame in each scan marked by the cross section of the catheter. Next, using the ROI rectangle tool, select the largest portion of the gel.
That does not include any portion of the infusion site. The software will output a mean pixel density with standard deviation. Then identify the value that is three standard deviations from the mean.
This value is used as the threshold for determining when contrast is present with a confidence of 99.7%Next, use the ROI circle tool to circle the infusion site. Then give it a unique name, select the circle. Using the ROI set pixel values tool and input the threshold value into the if current value is larger than box and check mark this line only.
Then enter a large value in the new value box. Reset the pixel density to select the area encompassed by the threshold. Next, using the ROI Grow region tool, select the 2D growing region, the confidence algorithm with initial radius, parameter two, and the brush ROI click inside of the infusion site for the software to compute the total area of this region.
Air is detrimental to the procedure and can be identified by monitoring the infusion pressure. A key parameter for identifying air in the infusion line as demonstrated by this graph. Air was noted in the infusion line at 15 minutes.
At 17 minutes, there was a spike in pressure. Magnetic resonance images show the growth of the infusion cloud and the enclosed air bubble. These images show the gel prior to insertion of the catheter and after beginning the infusion and insertion of the catheter.
The subsequent time lapse is in four minute intervals. While attempting this procedure, it is important to be meticulous about line preparation, specifically avoiding line air. It's also important to maintain a slow and steady infusion rate during catheter insertion and the onset of the infusion to avoid air entry in the line and catheter reflux.
After watching this video, you should now have a good understanding of how to use convection enhanced delivery as a new method of drug delivery to the brain.
