Yicong Wu, a staff scientist in Shroff’s lab, developed the new system capable of obtaining a resolution of up to 235 x 235 x 340 nanometers, which is double the volumetric resolution of conventional fluorescence microscopy techniques.
The new microscope consists of three objective lenses, which acquires views of the samples simultaneously, allowing it to obtain more of the available light and providing additional details about the specimen. These views are then arranged and merged by a computational process called deconvolution.
The computations were all worked out by developing an alliance with co-author Patrick La Rivière of the University of Chicago’s Radiology Department, who generally develops algorithms for enhancing “dose efficiency” in human-scale medical imaging, such as CAT scans.
In medical imaging, we are always worried about dose, about capturing every X-ray [used on the patient to improve scan resolution]. We are concerned with ‘How can we do more with less?' If you use very intense illuminations to image something microscopic like a worm embryo, you might change its biology or even kill it. You need to be dose efficient with your light.
Patrick La Rivière, Radiology Department, University of Chicago
La Rivière and Shroff initially met at an MBL workshop on microscopy research in 2014. “On the plane [from Chicago], I read Hari’s paper about an earlier version of this microscope, and I saw he was using a very familiar, bread-and-butter deconvolution algorithm from the medical imaging world,” LaRivière says. “To me, that was the perfect entry point [into light imaging research]; it was something I knew. I chased Hari down after the workshop to see if he was open to collaboration, which he was.”
Financially aided by a University of Chicago-MBL Exploratory Research Fund award, the two started collaborating to enhance Shroff’s microscope, the diSPIM, which comprises two objective lenses, and eventually the newly developed three-lensed microscope called triSPIM.
This year La Rivière was named an MBL Fellow. Shroff is a Whitman Center Scientist and co-director of the MBL’s Optical Microscopy and Imaging in the Biomedical Sciences course.