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Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM).

ABSTRACT: Rationale: Glioblastoma is the most frequent, primary brain tumor that is characterized by a highly immunosuppressive tumor microenvironment (TME). The TME plays a key role for tumor biology and the effectiveness of immunotherapies. Composition of the TME correlates with overall survival and governs therapy response. Non invasive assessment of the TME has been notoriously difficult. Methods: We have designed an in vivo imaging approach to non invasively visualize innate immune cell dynamics in the TME in a mouse glioma model by correlated MRI and multiphoton microscopy (MR-MPM) using a bimodal, fluorescently labeled iron oxide nanoparticle (NP). The introduction of Teflon cranial windows instead of conventional Titanium rings dramatically reduced susceptibility artifacts on MRI and allowed longitudinal MR-MPM imaging for innate immune cell tracking in the same animal. Results: We visualized tumor associated macrophage and microglia (TAM) dynamics in the TME and dissect the single steps of NP uptake by blood-born monocytes that give rise to tumor-associated macrophages. Next to peripheral NP-loading, we identified a second route of direct nanoparticle uptake via the disrupted blood-brain barrier to directly label tissue resident TAMs. Conclusion: Our approach allows innate immune cell tracking by MRI and multiphoton microscopy in the same animal to longitudinally investigate innate immune cell dynamics in the TME.

SUBMITTER: Karimian-Jazi K

PROVIDER: S-EPMC6993231 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We present the development of a microfluidically cryo-cooled planar coil for magnetic resonance (MR) microscopy. Cryogenically cooling radiofrequency (RF) coils for magnetic resonance imaging (MRI) can improve the signal to noise ratio (SNR) of the experiment. Conventional cryostats typically use a vacuum gap to keep samples to be imaged, especially biological samples, at or near room temperature during cryo-cooling. This limits how close a cryo-cooled coil can be placed to the sample. At the same time, a small coil-to-sample distance significantly improves the MR imaging capability due to the limited imaging depth of planar MR microcoils. These two conflicting requirements pose challenges to the use of cryo-cooling in MR microcoils. The use of a microfluidic based cryostat for localized cryo-cooling of MR microcoils is a step towards eliminating these constraints. The system presented here consists of planar receive-only coils with integrated cryo-cooling microfluidic channels underneath, and an imaging surface on top of the planar coils separated by a thin nitrogen gas gap. Polymer microfluidic channel structures fabricated through soft lithography processes were used to flow liquid nitrogen under the coils in order to cryo-cool the planar coils to liquid nitrogen temperature (-196 °C). Two unique features of the cryo-cooling system minimize the distance between the coil and the sample: (1) the small dimension of the polymer microfluidic channel enables localized cooling of the planar coils, while minimizing thermal effects on the nearby imaging surface. (2) The imaging surface is separated from the cryo-cooled planar coil by a thin gap through which nitrogen gas flows to thermally insulate the imaging surface, keeping it above 0 °C and preventing potential damage to biological samples. The localized cooling effect was validated by simulations, bench testing, and MR imaging experiments. Using this cryo-cooled planar coil system inside a 4.7 Tesla MR system resulted in an average image SNR enhancement of 1.47 ± 0.11 times relative to similar room-temperature coils.

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Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM).

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