Magnetic resonance imaging-guided microdialysis cannula implantation in a spontaneous high-grade glioma murine model
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Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Mohamed A Elmeliegy1, Angel M Carcaboso, Lionel M L Chow
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163.
Abstract:
Cerebral microdialysis is used to study anticancer drug penetration in the central nervous system (CNS) and brain tumors in animal models. Genetically engineered murine models (GEMMs) have been recently used to study many aspects of CNS tumors since they represent a more relevant model than orthotopic brain tumor xenograft models. However, it is challenging to implant microdialysis cannula in these animals because T2-weighted magnetic resonance imaging (MRI) does not show the reference point (bregma) traditionally used to obtain stereotactic coordinates. Thus, an alternative reference point that can be visualized on MRI images is needed. In this study, a novel reference point, identified as the intersection between the olfactory bulb/frontal lobe border and the midline between cerebral hemispheres on T2-weighted MRI images, was used to calculate anterior-posterior and medial-lateral coordinates of brain tumors in a GEMM. This point overlies a visible crossover between the rostral rhinal vein and the midline suture on the mouse skull, allowing for the conversion of the MRI coordinates into surgical stereotactic coordinates. Postmortem MRI and histological examination confirmed accurate probe placement. This procedure will facilitate the accurate and precise implantation of microdialysis probes for the study of anticancer drug penetration in brain tumors of GEMMs.
Insights
Researchers developed a new MRI reference point for precise brain tumor targeting in genetically engineered mouse models. This method improves microdialysis probe implantation for studying anticancer drug delivery to the central nervous system.
Area of Science:
- Neuroscience
- Oncology
- Medical Imaging
Background:
- Cerebral microdialysis is crucial for studying anticancer drug penetration in the central nervous system (CNS).
- Genetically engineered murine models (GEMMs) offer a more relevant platform for CNS tumor research compared to traditional xenograft models.
- Accurate stereotactic coordinates are essential for microdialysis probe implantation, but traditional reference points like the bregma are not visible on T2-weighted MRI in GEMMs.
Purpose of the Study:
- To establish a novel, MRI-visible reference point for precise stereotactic targeting of brain tumors in GEMMs.
- To enable accurate implantation of microdialysis probes for studying drug delivery in CNS tumors within GEMMs.
Main Methods:
- A new reference point was identified on T2-weighted MRI at the olfactory bulb/frontal lobe border and midline between cerebral hemispheres.
- This MRI reference point was correlated with a visible anatomical landmark on the mouse skull (rostral rhinal vein and midline suture).
- Stereotactic coordinates derived from the novel MRI reference point were used for microdialysis cannula implantation, with accuracy confirmed by postmortem MRI and histology.
Main Results:
- A novel, reliable MRI reference point was successfully identified and utilized for calculating stereotactic coordinates in GEMMs.
- Accurate implantation of microdialysis probes into brain tumors within GEMMs was achieved using the new coordinate system.
- The method demonstrated the feasibility of precise probe placement, crucial for drug penetration studies.
Conclusions:
- The novel MRI reference point provides a practical solution for accurate stereotactic targeting in GEMMs, overcoming limitations of traditional methods.
- This technique facilitates advanced research into anticancer drug efficacy within the CNS by enabling precise microdialysis studies in relevant GEMMs.
- The described procedure is expected to enhance the study of drug delivery and efficacy in brain tumors using GEMMs.
