Intra-operative, real-time, three-dimensional ultrasound assisted positioning of catheters in the microdialysis of glial tumours

Homapour, Bob; Bowen, Jon; Want, Elizabeth J.; O’Neill, Kevin; Apostolopoulos, Vasileios; Nandi, Dipankar; Dellen, James R. van; Roncaroli, Federico

doi:10.1016/j.jocn.2009.06.022

Cited by 14 publications

(9 citation statements)

References 8 publications

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“…However, low molecular weight catheters preclude collection of most extracellular analytes; slow flowrates combined with short intra-operative sampling times prevent acquisition of enough microdialysate volumes to enable multi-omic analyses. We hypothesized that we could safely and feasibly deploy intra-operative high molecular weight (HMW, 100kDA) microdialysis using an elevated perfusion rate of 2 µL/min 15 to recover a usable volume of microdialysate containing diverse analytes, including metabolites, during a standard-of-care surgery. To that end, we initiated our intra-operative microdialysis trial in an initial cohort of five patients.…”

Section: Resultsmentioning

confidence: 99%

“…The pre-flushed catheter was then advanced to the intended trajectory. Microdialysis was performed at 2 µL/min based on a prior intra-operative study demonstrating that this flowrate could enable sufficient collection of analytes for mass spectrometry 15 , with collection vials exchanged every 20 minutes. See supplemental methods for details of microdialysis procedure, pathology, and molecular tumor analyses.…”

Section: Methodsmentioning

confidence: 99%

“…Microdialysis is also a well-established method to quantify central nervous system (CNS) drug delivery in early phase clinical trials [8][9][10] and has been used longitudinally to study metabolites present in human gliomas when compared to adjacent brain 11,12 . However, while some studies have utilized intraoperative microdialysis to enable quantification of select extracellular metabolites [13][14][15] , no study thus far has deployed intra-operative microdialysis to characterize the global extracellular glioma metabolome. To that end, we initiated a pilot feasibility study leveraging high molecular weight (HMW) microdialysis 5 catheters in 5 surgeries, followed by validation in 10 additional surgeries to characterize the global extracellular metabolome of glioma across multiple regions of diverse gliomas.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Does Blood-Brain Barrier Disruption Define the Glioma Extracellular Metabolome?

Riviere-Cazaux

Carlstrom

Rajani

et al. 2021

Preprint

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Gliomas present a formidable challenge for translational progress. Heterogeneity within and between tumors may demand empirically individualized insights, though relatively little is known about the biochemical milieu within which malignant cells thrive in the in vivo human glioma. We performed a pilot study of intraoperative high molecular weight microdialysis to sample the extracellular tumor environment within three locations in each of five molecularly diverse human gliomas spanning WHO grade 2 oligodendroglioma to WHO grade 4 glioblastoma (GBM). Microdialysates were subjected to targeted (D/L-2-hydroxyglutarate (2-HG)) and untargeted metabolomic analyses, enabling correlation, clustering, fold change, and enrichment analyses. IDH-mutant tumor microdialysate contained markedly higher levels of D2-HG than IDH-wild type tumors. However, IDH status was not predictive of the global metabolomic signature. Rather, two distinct metabolic phenotypes (α and β) emerged, with IDH-WT and IDH-mutant patient samples in each group. Individualized metabolic signatures of enhancing tumor versus adjacent brain were conserved across patients with glioblastoma regardless of metabolic phenotype. Untargeted metabolomic analysis additionally enabled correlative quantification of multiple peri-operatively administered drugs, illustrating regional heterogeneity of blood-brain barrier permeability. As such, acute intraoperative microdialysis affords a previously unharnessed window into individualized heterogeneous microenvironments within and between live human gliomas. Such access to the interstitial milieu of live human gliomas may provide a complementary tool for the development of individualized glioma therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Does Blood-Brain Barrier Disruption Define the Glioma Extracellular Metabolome?

Riviere-Cazaux

Carlstrom

Rajani

et al. 2021

Preprint

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“…During DBS surgery, the site of catheter placement may be confirmed with fluoroscopy. Probes have also been implanted in gliomas under CT, MRI or three-dimensional ultrasonography guidance (49,50). On the other hand, during standard clinical microdialysis, a suture is used to hold the catheter in order to make measurements in the same location throughout the procedure.…”

Section: Insertionmentioning

confidence: 99%

Optimizing microdialysis for deep brain stimulation

Martinez¹

2016

Front Biosci

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Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring probe. The interstitial space of biological tissues and fluids is sampled through a thin fenestrated dialysis catheter inserted into the brain. The technique has been reported in patients with Parkinson's disease. However, the procedure is not widely used by neurosurgeons, possibly owing to unclear indications and poor effective benefits, mostly secondary to significant pitfalls. In spite of the feasibility of microdialysis in humans, many factors can affect the quality of the process. Possible pitfalls include improperly designed probe, probe insertion effects, ineffective perfusion rate, issues to optimize stabilization period, and insufficient volume sample. This article reviews those key technical features necessary for performing microdialysis in humans during deep brain stimulation for Parkinson's Disease.

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“…US navigation is a real-time method for delineating solid, cystic, and necrotic tissues based on their different acoustic impedances and reflection coefficients. Three-dimensional ultrasonography has been widely adapted for placement of catheters, needles, or other instruments into sites of abnormal tissue ( 19 ). US is optimal for accurate placement of needles for glioma biopsy.…”

Section: Intraoperative Delineation Of Gliomasmentioning

confidence: 99%

The Art of Intraoperative Glioma Identification

et al. 2015

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A major dilemma in brain-tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture, which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of (1) image-based navigation, (2) intraoperative sampling, (3) electrophysiological monitoring, and (4) enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease.

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Intra-operative, real-time, three-dimensional ultrasound assisted positioning of catheters in the microdialysis of glial tumours

Cited by 14 publications

References 8 publications

Does Blood-Brain Barrier Disruption Define the Glioma Extracellular Metabolome?

Does Blood-Brain Barrier Disruption Define the Glioma Extracellular Metabolome?

Optimizing microdialysis for deep brain stimulation

The Art of Intraoperative Glioma Identification

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