Wadduwage Lab for Differentiable Microscopy (๐œ•๐œ‡)

In Wadduwage Lab, we work on novel computational microscopy solutions that can measure biological systems at their most information rich form, with minimum redundancy.

twitter | @nawodyaw
email | wadduwage@fas.harvard.edu

๐œ•๐œ‡ – Differentiable Microscopy | With applications ranging from, rare cellular event detection to drug screening, high content imaging provides biomedically important morphological features of cells or tissues via high speed acquisition hardware and fast image processing algorithms. Despite significant advances in faster and more multiplexed imaging sensors, the imaging throughput is currently limited by the speed of electronics hardware. In Wadduwage Lab we use an orthogonal approach, termed differential microscopy (๐œ•๐œ‡), to improve the imaging throughput beyond existing electronic hardware bottleneck. The rationale for ๐œ•๐œ‡ is that low-dimensional compressed representations of image signals exists and can be found through learning-based techniques; instruments can thus be designed to perform measurements on the lower dimensional compressed representation, improving the throughput by the factor of compression. To achieve this, ๐œ•๐œ‡ models the front-end optics, the back-end image -reconstruction and -processing algorithms together as a differentiable model of learnable parameters.

DEEP: De-scattering with Excitation Patterning | Nonlinear optical microscopy has enabled in vivo deep tissue imaging on the millimeter scale. A key unmet challenge is its limited throughput especially compared to rapid wide-field modalities that are used ubiquitously in thin specimens. Any wide-field approach would suffer from emission photons scattering inside the specimen, resulting degraded image contrast and image resolution. To address this challenge, we introduce a novel technique called De-scattering with Excitation Patterning, or โ€˜DEEPโ€™, which uses patterned nonlinear excitation followed by computational imaging assisted wide-field detection. Multiphoton temporal focusing allows high resolution excitation patterns to be projected deep inside specimen at multiple scattering lengths due to the use of long wavelength light. Computational reconstruction allows high resolution structural features to be reconstructed from tens to hundreds of DEEP images, instead of millions of point-scanning measurements.

Team

  • Mithunjha Anandakumar – Remote Undergraduate Researcher
  • Naeem Ahmad – Post Graduate Research Fellow
  • Kithmini Herath – Remote Undergraduate Researcher
  • Ramith Hettiarachchi – Remote Undergraduate Researcher
  • Udith Haputhanthri – Remote Undergraduate Researcher
  • Yasith Jayawardana โ€“ Visiting Doctoral Student
  • Vinith Kugathasan – Remote Undergraduate Researcher
  • Shehan Munasinghe – Remote Undergraduate Researcher
  • Hasindu Piyumantha – Remote Undergraduate Researcher
  • Jathurshan Pradeepkumar – Remote Undergraduate Researcher
  • Dushan Wadduwage – PI

Alumni

  • David Andre Coucheron, Associate Professor, University of Tromso (Former Collaborative PhD student)
  • Ishan Baliyan – Undergraduate Student, University of Waterloo(Former High School Research Intern)
  • Liana Owen – Undergraduate Student, HU โ€˜22 (Former Undergraduate Researcher)
  • Navodini Wijethilake – Doctoral Student, Kingโ€™s College London (Former Post Graduate Researcher)
  • Zhun Wei – Assistant Professor, Zhejiang University (Former Postdoctoral Fellow)

Publications

  • Pradeepkumar J., Anandakumar M., Kugathasan V., Seeber A., & Wadduwage, D.N.*, 2021. Physics Augmented U-Net: A High-Frequency Aware Generative Prior for Microscopy. bioRxiv 2021.12.01.470743.
  • Zheng, C., Park, J.K., Yildirim, M., Boivin, J.R., Xue, Y., Sur, M., So, P.T. & Wadduwage, D.N.*, 2021. De-scattering with Excitation Patterning enables rapid wide-field imaging through scattering media. Science Advances, 7(28), p.eaay5496.
  • Kay, J.E., Corrigan, J.J., Armijo, A.L., Nazari, I.S., Kohale, I.N., Torous, D.K., Avlasevich, S.L., Croy, R.G., Wadduwage, D.N., Carrasco, S.E. and Dertinger, S.D., 2021. Excision of mutagenic replication- blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice. Cell Reports, 34(11), p.108864.
  • Kay, J.E., Mirabal, S., Briley, W.E., Kimoto, T., Poutahidis, T., Ragan, T., So, P.T., Wadduwage, D.N., Erdman, S.E. and Engelward, B.P., 2021. Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection. Environmental and Molecular Mutagenesis, 62(2), pp.108-123.
  • Agbleke, A.A., Amitai, A., Buenrostro, J.D., Chakrabarti, A., Chu, L., Hansen, A.S., Koenig, K.M., Labade, A.S., Liu, S., Nozaki, T. and Ovchinnikov, S., Seeber, A., Shaban, H. A., Spille, J., Stephens, A. D., Su, J., Wadduwage, D.N., 2020. Advances in chromatin and chromosome research: perspectives from multiple fields. Molecular Cell.
  • Wei, Z., Boivin, J.R., Xue, Y., Chen, X., So, P.T., Nedivi, E. & Wadduwage, D.N.*, 2019. 3D Deep Learning Enables Fast Imaging of Spines through Scattering Media by Temporal Focusing Microscopy. arXiv preprint arXiv:2001.00520.
  • Coucheron, D.A., Wadduwage, D.N., Murugan, G.S., So, P.T. & Ahluwalia, B.S.*, 2019. Chip-based resonance Raman spectroscopy using tantalum pentoxide waveguides. IEEE Photonics Technology Letters, 31(14), pp.1127-1130.
  • Xue, Y., Berry, K.P., Boivin, J.R., Wadduwage, D. N., Nedivi, E. & So, P.T.*, 2018. Scattering reduction by structured light illumination in line-scanning temporal focusing microscopy. Biomedical optics express, 9(11), p.5654.
  • Wadduwage, D.N.*, Kay, J., Singh, V.R., Kiraly, O., Sukup-Jackson, M.R., Rajapakse, J., Engelward, B.P. & So, P.T., 2018. Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Scientific reports, 8(1), p.12108.
  • Wadduwage, D.N., Singh, V.R., Choi, H., Yaqoob, Z., Heemskerk, H., Matsudaira, P. and So, P.T.*, 2017. Near-common-path interferometer for imaging Fourier-transform spectroscopy in wide-field microscopy. Optica, 4(5), pp.546-556.
  • Wadduwage, D.N., Parrish, M., Choi, H., Engelward, B.P., Matsudaira, P. and So, P.T.*, 2015, June. Subnuclear foci quantification using high-throughput 3D image cytometry. In European Conference on Biomedical Optics (p. 953607). Optical Society of America.
  • Choi, H., Wadduwage, D.N., Tu, T.Y., Matsudaira, P. and So, P.T.*, 2015. Threeรขdimensional image cy- tometer based on widefield structured light microscopy and highรขspeed remote depth scanning. Cytometry Part A, 87(1), pp.49-60.
  • Choi, H., Wadduwage, D.N., Matsudaira, P.T. and So, P.T.*, 2014. Depth resolved hyperspectral imag- ing spectrometer based on structured light illumination and Fourier transform interferometry. Biomedical optics express, 5(10), pp.3494-3507.
  • Sukup-Jackson, M.R., Kiraly, O., Kay, J.E., Na, L., Rowland, E.A., Winther, K.E., Chow, D.N., Kimoto, T., Matsuguchi, T., Jonnalagadda, V.S., Maklakova, V.I., Singh V.R., Wadduwage D.N., Rajapakse J., So P.T., Collier L.S., & Engelward* B.P., 2014. Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS genetics, 10(6), p.e1004299.