Users are excited about Aleph's ultrasound localization microscopy result because a vial of microbubbles plus a coin-sized chip can map living human brain vessels at high resolution.
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A big enabling factor for all the advances you’re seeing in ultrasound is the hardware. Aleph built on the ultrasound-on-chip from @ButterflyNetInc - the same chip we used for sub-mm functional brain imaging at @ForestNeurotech.
One coin-sized chip, capable of whole heart ULM, whole brain functional imaging, and even whole body imaging @midjourney.
So the real climb ahead: measuring brain function in humans that’s transcranial (i.e. non-invasvie), 3D + single-trial + real-time.
Each one alone is hard. E.g. single-trial functional imaging alone was the backbone of our Neuron 2021 paper & real-time was a major contribution in our Nature Neuroscience 2023 paper.
Together they're the frontier - the gap between a beautiful vascular map and someday decoding a thought non-invasively.
ULM is a structural image. It's a map of the pipes - anatomy and angiography. It's not (yet) mapping what the brain is *doing*.
That's the classic super-res tradeoff. To pin down each bubble you need them sparse, so you stack localizations over a long acquisition (e.g. ~4 min). You buy ~10µm resolution by spending temporal resolution. Great anatomy - but you can't watch the fast dynamics that comprise brain function.
Getting through the human skull is hard - bone scatters and soaks up sound. But it's possible with contrast agents.
The first transcranial human ULM came from @CharlieDemene and the Paris group in 2021 (Nature BME).
Still in 2D, but absolutely landmark work.
Tl;dr -- Aleph's result is mega-cool. A vial of microbubbles + a chip the size of a coin mapping a living human brain. It’s built on a decade-long revolution in ultrasound science and technology. And we’re just getting started 🔊🔊🔊
Sources 👇
Aleph writeup: https://alephneuro.com/blog/ultrasound-brain
ULM origin - Errico et al., Nature 2015 (10.1038/nature16066)
Human transcranial ULM - Demené et al., Nature BME 2021 (5:219)
3D transcranial in NHP - Xing & Provost, arXiv 2404.03547
fULM - Renaudin et al., Nature Methods 2022 (http://nature.com/articles/s41592-022-01549-5)
Heart clip - Demeulenaere et al., JACC: CV Imaging 2022 (http://doi.org/10.1016/j.jcmg.2022.02.008). Credit: A. Dizeux / @PhysMedParis
First ultrasound BCI, single-trial decoding: Norman et al., Neuron 2021 (10.1016/j.neuron.2021.03.003)
First real-time/closed loop ultrasound BCI: Griggs and Norman et al., Nature Neuroscience 2023 (https://www.nature.com/articles/s41593-023-01500-7)
First human ultrasound BCI: Rabut and Norman et al., Science Translational Medicine 2024 (10.1126/scitranslmed.adj3143)
3D-through-the-skull then showed up in animals - @JeanProvost's macaques through an intact skull, and sheep at Institut Langevin in 2024. Insane detail.
Brain function is a different, harder problem - tracking blood-flow changes tied to neural activity.
Functional ULM *does* exist (Renaudin et al., Nature Methods 2022). It's currently working in anesthetized rats, skull open, averaging many blocks of trials to gain signal back. ~6.5µm, ~1s.