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The Inscopix Multimodal Image Registration and Analysis (MIRA) platform: Registration Across in vivo Neuronal Imaging Modalities

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Posted by Alice Stamatakis, PhD - 07.08.2020

Another product launch is upon us! We are excited to officially launch our new Multimodal Image Registration and Analysis (MIRA) platform, a fully integrated solution to facilitate the incorporation of data sets collected with Inscopix miniscopes to data sets collected from benchtop high-resolution laser scanning microscopes. Our goal for this project was to capture the best of both worlds- the capabilities of Inscopix miniscope imaging and the benefits of high-resolution benchtop microscopy. 

Before I get into the details, let me introduce myself. My name is Alice Stamatakis and I’m a Senior Lead Scientist at Inscopix, where I lead our application development team. My career here began over 5 years ago when I was a postdoc at Inscopix, working on applying the nVokeTM technology to study the causal relationship between neural circuits and behavior. I’ve since worked on various exciting projects to expand our products and applications to include imaging in multiple species, integrating multiple modalities and integrating our workflow. The latest of these projects is the MIRA platform, and to lead it from conceptualization to product release has been an incredibly rewarding experience. 

With the introduction of our nVistaTM system back in 2012, Inscopix has enabled the ability to record the activity patterns of genetically-defined neuronal populations in deep brain regions of naturally behaving animals, transforming neural circuit research and advancing our understanding of the brain in action. Nevertheless, we realized there was a need to integrate multiple imaging modalities to achieve a more thorough understanding of the brain in health and disease. To enable this, we sought to combine our miniature microscope platform for free-behaving imaging with 2-photon and confocal microscopy platforms in order to better understand the nature of the cells being recorded from with respect to their genetic identity, connectivity patterns and their relationship to non-neuronal cell types and brain pathologies. 

As proof-of-principle of this technology, we applied the MIRA platform to investigate medial prefrontal cortical (mPFC) circuitry during free behavior. Our goal was to record from the mPFC circuit during free behavior, and classify the cells based on whether or not they were contralateral mPFC-projecting neurons (Figure 1A). To determine whether an individual mPFC was a contralateral projector, we tagged these neurons with a static red indicator, and imaged the cells under a Zeiss Airyscan 880 Confocal microscope. We used the MIRA confocal adapter to align the two fields of view to ensure that we were imaging from the exact same focal plane (Figure 1B). We then co-registered the cells imaged with the confocal to cells imaged with our Inscopix miniscope using our analysis solution. We were then able to identify projection-specific mPFC neurons (Figure 1C), as well as non-projecting mFPC neurons (Figure 1C).

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Figure 1: MIRA platform to enable multimodal imaging between an nVista miniscope and ZEISS Airyscan Confocal. A) Schematic of projection-identification application. B) MIRA confocal adapter. C) Cell map of GCaMP neurons (imaged with Inscopix nVista) overlaid with projection specific tdTomato neurons (imaged with ZEISS Airyscan) and corresponding traces of non-contralaterally projecting (green traces) and contralaterally-projecting cells (yellow traces).


 

Working on the MIRA project has been a true collaborative effort. This project required coordination and cross-functional teamwork from almost every area of Inscopix, from Application Science, Engineering, Manufacturing, Marketing and Customer Support. It was such a fun experience seeing the whole company coming together to conceptualize, develop, test, and prepare for the upcoming launch of the MIRA platform at FENS 2020. Be sure to virtually visit our official MIRA launch at our FENS virtual exhibit, and check out our team's poster presentations for more details. Our MIRA platform will provide a next-generation, multimodal brain mapping solution that we hope will greatly benefit neuroscience researchers performing in vivo neuronal imaging, and we are excited to see the scientific discoveries that will be made with it!

Topics: nVista, MIRA, The MIRA Platform


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