Author:
Riviere-Cazaux Cecile,Rajani Karishma,Rahman Masum,Oh Juhee,Brown Desmond A.,White Jaclyn F.,Himes Benjamin T.,Jusue-Torres Ignacio,Rodriguez Moses,Warrington Arthur E.,Kizilbash Sani H.,Elmquist William F.,Burns Terry C.
Abstract
Abstract
Background
Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations.
Methods
Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry.
Results
Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed.
Conclusions
Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis.
Trial registration NCT04047264
Funder
National Institutes of Health
National Cancer Institute
National Institute of Neurological Disorders and Stroke
Center for Clinical and Translational Science, Mayo Clinic
American Brain Tumor Association
Brains Together for a Cure
Humor to Fight the Tumor
Lucius and Terrie McKelvey
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,General Medicine