Columbia University

Technology Ventures

Holographic system for simultaneously imaging multiple neural regions

Technology #cu15310

Detecting the activity of individual neurons and the spatiotemporal pattern in which they fire is important for understanding brain function. While conventional two-photon microscopy has been shown to be a valuable tool for deep-brain imaging, its temporal resolution and size of imaged regions are limited by its use of only a single incident laser beam. This technology is a holographic microscopy method that uses a combination of several smaller “beamlets” for simultaneous imaging of multiple cortical layers. In doing so, it allows for increased resolution while capturing images across larger three-dimensional volumes of the brain.

Enhanced two-photon microscopy for increased resolution in large volume brain scans

This technology achieves the difficult task of simultaneously imaging multiple layers of the brain using high resolution two-photon microscopy. Conventional two-photon microscopy is limited by the fact that it rasters a single laser beam across the area of interest, and for a single beam, increasing the size of the imaged region leads to a decrease in resolution. In this technology, a spatial light modulator (SLM), which is a holographic device capable of modifying the phase profile of a laser wavefront, is placed in the beam path of a two-photon microscope to generate multiple beamlets that can be independently and dynamically controlled. These multiple beams are then scanned across the sample. Unlike with a single beam, in this approach, multiple different sample regions are simultaneously recorded, and subsequently processed and reconstructed into a single, coherent image.

This technology has been demonstrated on in vivo imaging of L2/3 in the primary visual cortex of a mouse and on simultaneous imaging of L2/3 and L5. This method is a further development of previous holographic microscopy methods licensed by the inventors.

Lead Inventor:

Rafael Yuste, M.D., Ph.D.


  • Functional imaging of multiple cortical layers
  • Potential evaluation of effectiveness and mechanisms of therapeutics
  • High spatiotemporal neuronal imaging
  • Functional brain imaging research
  • Visualizing brain function during psychiatric illness, intoxication, and other altered mental states


  • Increases resolution of large volume, three-dimensional deep brain scans
  • Non-invasive imaging technique
  • Infrared scans do not expose patients to harmful radiation
  • Faster imaging speeds than conventional two-photon microscopy methods

Patent Information:

Patent Pending

Tech Ventures Reference: IR CU15310

Related Technologies: IR M08-107, IR CU13147

Related Publications: