Longitudinal imaging of single cells in opaque tissue with cell chirp ultrasound
- 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Abstract
Small numbers of cells can determine the fate of an entire organism. For example, metastatic cancer cells seed distant organs, therapy-resistant clones repopulate tumors, and T cells infiltrate and expand in tissues with matching antigens. Visualizing the activity of such cells in living organisms requires highly sensitive, specific and repeatable imaging in optically opaque tissues. Here we introduce cell chirp, an ultrasound imaging method for real-time imaging of single cells in living organs inaccessible to light. Cell chirp exploits the harmonic response of genetically encoded gas vesicles to frequency-coded ultrasound to sensitively and specifically visualize single cells in scattering background. We first develop this method in tissue-mimicking phantoms, demonstrating the ability to quantitatively detect single cells as validated by optical cell counts. We then establish the ability of cell chirp to image thousands of genetically labeled cells within a million-cell background tissue, track reporter gene expression over days, and suppress background signals by more than two orders of magnitude. Finally, we use cell chirp to track the fate of antigen-positive or antigen-negative tumor-cell minorities during weeks-long T-cell engager treatments. Cell chirp reveals the dynamics of sparsely distributed, genetically defined cells in opaque tissues.
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BibTeX
@misc{nayak2026longitudinal,
title = {{Longitudinal imaging of single cells in opaque tissue with cell chirp ultrasound}},
author = {R. Nayak and H. An and T. Fochtman and Z. Jin and M. Duan and K. Luo and M. G. Shapiro},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.756957},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.756957v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Longitudinal imaging of single cells in opaque tissue with cell chirp ultrasound
AU - R. Nayak
AU - H. An
AU - T. Fochtman
AU - Z. Jin
AU - M. Duan
AU - K. Luo
AU - M. G. Shapiro
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.756957
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.756957v1
AB - Small numbers of cells can determine the fate of an entire organism. For example, metastatic cancer cells seed distant organs, therapy-resistant clones repopulate tumors, and T cells infiltrate and expand in tissues with matching antigens. Visualizing the activity of such cells in living organisms requires highly sensitive, specific and repeatable imaging in optically opaque tissues. Here we introduce cell chirp, an ultrasound imaging method for real-time imaging of single cells in living organs inaccessible to light. Cell chirp exploits the harmonic response of genetically encoded gas vesicles to frequency-coded ultrasound to sensitively and specifically visualize single cells in scattering background. We first develop this method in tissue-mimicking phantoms, demonstrating the ability to quantitatively detect single cells as validated by optical cell counts. We then establish the ability of cell chirp to image thousands of genetically labeled cells within a million-cell background tissue, track reporter gene expression over days, and suppress background signals by more than two orders of magnitude. Finally, we use cell chirp to track the fate of antigen-positive or antigen-negative tumor-cell minorities during weeks-long T-cell engager treatments. Cell chirp reveals the dynamics of sparsely distributed, genetically defined cells in opaque tissues.
ER -