Evaluating retrodialysis as a focal delivery method in human brain

Mr. Matthew G. Stovell, Prof. Peter J. Hutchinson, Dr. T. Adrian Carpenter, Prof. Mark Wilson and Dr. Keri L.H. Carpenter

CMA Microdialysis AB
CMA Microdialysis AB

Microdialysis is a technique that is increasingly used in neuro-intensive care to monitor patients’ brain chemistry, particularly monitoring the disturbances of brain energy metabolism that occur following traumatic brain injury. Microdialysis involves inserting fine semi-permeable tubes (microdialysis catheters) into the brain to collect small samples of brain fluid for analysis at the bedside. Because the tube is semi-permeable, molecules can diffuse in both directions (see schematic illustration), so as well as being used to collect molecules from the brain for monitoring, microdialysis can also be used to deliver molecules into the brain if desired. The latter process is referred to as retrodialysis.

As well as its clinical monitoring role, microdialysis has versatile research applications. Study molecules can be administered into patients’ brains to help better understand the different damaging processes that occur after traumatic brain injury and in the same way potential medications that may help the recovery of the brain can be discovered.

We believe that delivering treatments to the brain via retro-microdialysis has excellent potential for treating diseases that affect specific regions of the brain, such as areas of brain bruising following head injury, chemotherapy drugs into brain tumours, and treatments to known affected sites deep inside the brain in certain neurodegenerative conditions such as Parkinson’s disease.

C. Zimphango / Camb. Neurochem
C. Zimphango / Camb. Neurochem

Up to now, the distance and pattern that small molecules diffuse within the human brain when delivered via microdialysis (retrodialysis) are not known. Also, it is not known what size volume of brain the microdialysis catheters sample from in standard clinical microdialysis monitoring. The image (in an artificial model) illustrates how we can visualise this.

To answer these questions, we will infuse MRI-visible gadolinium contrast agent in standard microdialysis catheters that have been inserted for neocritical care monitoring into the brains of patients suffering from severe traumatic brain injury. After a period of infusion, the patients will have an MRI scan and the distance that the gadolinium contrast agent has diffused will be characterised. We will then perform MRI scans of “brain phantoms” (dummy objects) made with known concentrations of gadolinium contrast agent to provide reference data to convert the patients’ brain images into calibrated concentration maps.

This study will advance our understanding of the clinical use of microdialysis in brain pathology and provide a platform for future development of new catheters optimally designed to deliver agents by retromicrodialysis to specific targets of focal brain pathologies.