Deep living brain tissue imaging at single-cell resolution

• Combining several cutting-edge imaging technologies yields a microscope system for unprecedentedly deep and precise visualization of metabolic and neuronal activity in living brain tissue.¹
• The approach achieves single-cell resolution and could potentially be applied in humans for neural activity assessment.^{1 1}

Gardner updates

• A new microscope system combining several imaging technologies promises unprecedentedly deep visualization of metabolic and neuronal activity at single-cell resolution, potentially in humans. ¹

Weekly enrichment (2026-07-20)

• The system, named label-free multiphoton photoacoustic microscopy (LF-MP-PAM), detects endogenous NAD(P)H via three-photon excitation with a near-infrared femtosecond laser; the peer-reviewed study appeared in Light: Science & Applications in August 2025.²³
• Imaging reached 700 μm depth in mouse brain slices and 1,100 μm in human stem-cell-derived cerebral organoids, versus the ~100 μm ceiling of conventional all-optical NAD(P)H imaging — more than a five-fold improvement in depth.²⁴
• Excitation uses intense ~quadrillionth-of-a-second light pulses at roughly three times NAD(P)H’s normal absorption wavelength, so the longer-wavelength light scatters less in dense brain tissue (“like fog lamps”).⁴
• Most of the absorbed energy produces a localized (~10 μm) thermal expansion that generates ultrasound waves; a sensitive ultrasound microphone detects them, an approach the team calls “Multiphoton-In and Acoustic-Out.”⁴
• The method was validated by detecting NAD(P)H uptake in HEK293T and HepG2 cells, and it demonstrated simultaneous third-harmonic-generation structural imaging alongside photoacoustic NAD(P)H detection.²
• Because it is label-free (no added dyes or genetic modification), it could be applied in humans, for example during brain surgery; NAD(P)H levels are known to shift in Alzheimer’s disease, Rett syndrome, and seizures, making it a candidate biomarker.⁴
• The team reports that imaging at ~2 mm depth in live brains is feasible; the next step is demonstration in living animals, which requires repositioning the microphone to the same side as the light source.⁴
• Corresponding authors are neuroscientist Mriganka Sur with engineers Peter So and Brian Anthony; the photoacoustic method could also detect the genetically encoded calcium indicator GCaMP used to signal neural electrical activity.⁴

Footnotes

1. https://news.mit.edu/2025/imaging-tech-promises-deepest-looks-yet-brain-tissue-single-cell-resolution-0822 ↩ ↩² ↩³ ↩⁴

2. https://doi.org/10.1038/s41377-025-01895-x ↩ ↩² ↩³

3. https://www.eurekalert.org/news-releases/1095451 ↩

4. https://meche.mit.edu/news-media/imaging-tech-promises-deepest-looks-yet-living-brain-tissue-single-cell-resolution ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶