They just used the MRI to map a high-resolution image obtained via light sheet microscopy. I doubt you can do that with living animals. Without slicing the brain that is.
The number in the title is misleading but what you write here is also misleading.
> The diffusion tensor images (DTI) @ 15 μm spatial resolution are 1,000 times the resolution of most preclinical rodent DTI/MRI. Superresolution track density images are 27,000 times that of typical preclinical DTI/MRI.
The resolution of the raw MRI images is significantly higher, without that increased resolution it would be impossible to align the light sheet images. The light sheet images are not use to "improve" MRI resolution.
Yeah, they kind of blow past light sheet microscopy, but I'm optimistic that this can still be quite useful. There are brain banks with already donated brains that we could use to learn about diseases, and I imagine many organ donors would be happy to have their brains sliced up for science.
Light sheet microscopy is actually pretty neat. You can use it on a whole brain without slicing it but not on a living animal. The tissue needs to go through a special fixing procedure first
A key problem with high-res MRI in a living organism is the scan time. Even fast acquisition techniques like EPI require around 50 milliseconds per slice. But if you want good resolution and contrast you're doing a spin echo which takes quite a bit longer. At some point you run into motion blur caused by the mere involuntary contraction of blood vessels, and that's before you consider the difficulty with patient compliance to the directive: "hold still".
Indeed. To say nothing of gating acquisitions to breathing, head motion, eye cicadas, glymphatic flow, etc.
The highest resolution MR images I have (yet) obtained were ~20 µm^3 voxels on ex vivo (human) tissue samples fixed in agar with Gd3+ as a dopant, scanned at 12 T on a preclinical scanner. The coupled vibration of the gradient set causing blurring in the image domain at the extremities of the FOV was the limiting factor. I recall I did a partial Fourier acquisition – as ultimately we were limited by both T2* and vibration – and ended up trying to do POCS on a 4096^3 dataset and just needing tons and tons of ram to do it over something useful, like a weekend. Happy memories.
If you want to scan the entire organism, sure. But higher resolution MRI can also mean "scan a smaller part, with good detail, in the same amount of time". I could imagine this being useful for e.g. getting a high resolution image of a tumour after conventional imaging was used to locate it.
One more leap like this and we'll be able to resolve individual dendrites and obtain a complete connectome. Combined with microscopic slices (with suitable immunohistological staining), we'd be getting close to obtaining the data necessary for brain uploading - at least in mice.
Yes, I'm aware of what the connectome is. Someone in my lab is working on a piece of it. My question was regarding the term upload, most people don't mean a replica when they use that term
One thing that the MRI studies don't address are the types of synaptic connections. Neurons aren't all just excitatory of inhibitory. There's a massive amount of modulation happen with numerous types of neurotransmitters and other signaling molecules.
There is also a significant amount of non-synaptic interaction through neuropeptides, extracellular vesicles, diffusible molecules and active pumping of the CFS, glial networks, electric field effects, plus all of the unknowns.
We've had the complete C. elegans connectome for 30+ years, and know very little about how it actually generates behaviour... because synapses are only a small part of the picture.
I'm not sure why you got downvoted, you're absolutely correct. There are so many pieces to how biological neurons work, we barely understand it. Even electrophysiological studies are missing out on a ton of info
I case somebody else wonders, here [1] are some electron microscope pictures of neurons [and other stuff] to better understand what 5 µm voxels means. Seems about one order of magnitude away from being able to image all the connections.
Would be nice to have a better resolution for a sample video on YouTube (https://www.youtube.com/watch?v=FtOQddvp_U4), 64 million times sharper, but video quality is only 240p :)
You're probably being snarky, but that completely disregards compression. The artifacts on the video are atrocious. An uncompressed 480p stream is worlds different from a compressed 480p stream.
> How can 14 million pixels be 64 million times more pixels?
It’s Voxels not pixels. Voxels are 3D objects so to be clear this particular advancement isn’t 64 million (roughly 400 in each linear dimension^3) times better than the best that came before. Think 400x400 = 160,000 more pixels and 400 times as many slices.
Also the comparison is to a “typical clinical MRI for humans” which not only have 10 billion neurons but also tend to have relatively few slices. There’s little point in having people spend hours in a machine if a faster scan with fewer slices is good enough.
To be clear I used the term "pixels" in describing the characteristics of the final images produced, which are a series of stacked 2D images comprised of pixels.
But, I don't think it matters what we label the units we're counting, as long as we count them accurately.
The paper you've referenced states:
> field-of-view = 12 × 12 × 24 mm and matrix size = 200 × 200 × 400 giving an image with (60μm)[cubed] isotropic voxels
The "64 million times better" article states a resolution of 5μm voxels (for one aspect of the imaging). The paper the article references, by contrast, states 15μm when specifically comparing to MRI, and claims 1,000x improvement.
Diambiguating what is meant by "resolution" is a common problem, as it can refer to either the length of the axes or the overall area when multiplying them.
Conservatively, I'm going with 12x better resolution with the new technique when comparing apples to apples, or, to hype it reasonably: 5 cubed vs 60 cubed = a difference of 1,728 times more voxels in the same given area.
I’ve always wanted to have an MRI. I want to know how it feels to have all of my protons reoriented by a giant magnet. Would I be the same person after?
The MRI didn’t feel like anything. It wasn’t until the neurologist showed me images of my brain with my eyeballs right there in the front that I felt like I was going to have a panic attack. I have no idea how regular people just laugh off stuff like that. Awful existential crisis level dread seeing my mental meat.
For anyone wanting to relive that experience, you should know that (in the US at least) you can go to the imaging department at the hospital and get all of that data on a CD, and there's some good free software to render it. I've got a 3D print of my head somewhere that I made from a CT scan.
I think it can handle a few other formats as well. Once they are .nii(.gz) files, then mricrogl (https://www.nitrc.org/projects/mricrogl) should be able to render it - of course, for a brain scan - this would be your whole head. Brain extraction is performed by more specialized software, but that would get you started.
When I did it, I got the guy in the office next to me to put his DVD drive on a file share so I could copy to modern media. That was probably at least four years ago, so not sure if I could do the same now.
I had a similar feeling when the doctor showed the MRI images going progressively deeper into my brain. It was truly bizarre and made me squirm in discomfort. I hadn't expected to feel that way.
Former epileptic, I've had dozens of MRs and CTs. It's rote for me to see and I never had a visceral reaction and in fact I find it pretty fascinating. The one that I do have that's a standout and quite shocking is my first post-lobeectomy MRI. There's a very noticeable void where my right temporal lobe (+amygdala, cerebellum and hippocampus) were resected. Great conversation starter.
Having to hold perfectly still (possibly in an uncomfortable pose) in a giant machine that's making loud, uncanny noises for 20+ minutes is indeed a very bizarre, meditative experience. It is interesting, but, in my opinion, you're probably going to be happier not having the health concerns that lead to getting an MRI in the first place!
I had a MRI in college as part of a psychology experiment.
If you can get into one of those studies, it's a free way to get a picture of your brain!
I think I may have skewed their results, though. MRI is a very meditative experience and I'm pretty sure I fell asleep for brief moments when I was (supposed to be) memorizing and recalling pictures and words they were showing me on a monitor as part of the university experiment.
Your protons are also oriented by the Earth's magnetic field, and the magnets in your phone speakers. Larmor precession (the effect) occurs in low fields just as in high fields. The energy state differences from Earth's field are generally too small to be useful for MRI with enough quality in a reasonable time, but low-field MRI is a research area.
I actually felt a strong sensation when I had a high resolution brain MRI for research, and I rather enjoyed it. It switched on and off a few times during the scan, and it felt a bit like having a back massage, or significant mechanical vibrations in my back, or that feeling like gentle electric currents during some therapies, except for switching on and off abruptly.
I asked about this after the scan because I had been told you don't feel anything. Surely it wasn't just my imagination, from the noises? Was it from machine vibrations? I didn't have any metal in my body except amalgam fillings, and they said those wouldn't affect it. And, if I could feel something, perhaps it wasn't as harmless as they made out.
They explained after, some people feel a stimulation of their peripheral nervous system when the RF is on, from the tens of kW of microwave energy beamed through the body. For a few people this sensation is too much, even painful, and they have to stop which is one reason for the patient having the mechanical alert button. But most people don't feel anything at all from the MRI, just psychological feelings associated with the strange noises and confinemnt.
They said it's a peripheral nerve stimulation sensation, a kind of phantom feeling, rather than a physical effect on the body being sensed by the nerves. Don't ask me why I felt it in my back given it was a head and neck scan.
I enjoyed how it felt when I didn't know what it was, as it felt like it might loosen up my back a bit. I was a bit disappointed to not feel anything the next time I had a head MRI, for a medical reason (thankfully nothing found). The research scan had twice the field strength of the medical scan, and presumably different RF settings. Perhaps that made the difference.
Not just a research area! Recently on the DXMP mailing list someone was asking about QA procedures for their 0.064 tesla scanner. You can buy permanent magnets that strong without much trouble. I was very surprised since I wasn't aware they were in production — even searching Web results for "low-field MRI" in due diligence for this comment, I still only find papers and projections. Nonetheless, the Hyperfine Swoop exists, and you can buy it today:
I've had a couple. Proton alignment is an imperceptible state. You're experiencing more significant neurological changes reading this message than having your protons reoriented.
My wife works on MRI sequencing and has pretty long (> 1 hour) MRI scans quite often (2/3 times a week) as they all test each others research on themselves. She mentioned there are some scans where you actually do feel them and it's quite uncomfortable.
If you had nanoparticle contrast (ferumoxytol) it very well could have stuck around for weeks. Gadolinium chelate contrast is supposed to wash out in a few days, though.
This is incorrect - all of the protons align along the static (the strong 1.5, 3 , 9.4 etc Tesla) field, some point one way, and some the other - but they have all shifted so that they line up. The excite portion is a separate step, distinct from the static (B0) field. edit: distinct in some ways - the strength of the static field determines the RF used to flip the protons out of alignment.
You are mixing up a few things here, but they are all missing the point. At normal body temperatures, their thermal energy distribution prevents most protons in a human from aligning parallel or antiparallel with the static field, even at MRI field level strengths of several Tesla. The excitation by the varying field, which only affects another one-in-a-million of those aligend protons, is indeed another step, meaning that even fewer protons actually get to experience the precession effect. So about one in a million protons gets aligned with the static field and less than one in a trillion gets to produce a measurable signal. But since there are so many of them, (~10^20 per mm^3 for water), you still get enough (about 1000 protons or so per voxel) to measure a signal at 2 Tesla. With higher field strengths you can get a bit more and thus more resolution but even at 10 Tesla you won't align all of your protons - not even close.
I've felt a bit of heat from the radio waves, especially during the fMRI sequence. Personally, I get a bit claustrophobic during brain MRIs because of the restricting face coils, and you have to go pretty deep into the tube. No idea why people get weirded out by seeing pictures of their brain. I've never felt that. I think its cool.
In the hospital where I went a few times, they show a relaxing video while the MRI is taken. You look at a projection via a tilted mirror close to your eyes. Once it was featuring pandas, it is really nice to experience the panda effect inside the machine. I've never been anxious about the scan.
I've had a few. There is definitely a weird feeling I get inside of them at specific certain points in the process, but I don't know if it is from the magnetic field, or if it is from some really high pitch vibrations/sounds that come off the machine.
This is the most stupidest comment I ever seen. No, it's not fun to be at a hospital. No, you shouldn't want to be at a hospital. And yes, it's a bit masochist.
It's pretty impressive to say that the linear resolution increased 400x, but I guess at 400x it's barely even clickbait. It's far more impressive to cube it and claim 64000000x improvement.
Well, do you think a 4 Megapixel camera sensor has 2x resolution compared to a 2 MP?
If no, I agree with you, but if it indeed does... Why should we not compare resolution in the higest dimension here too? We already have a term for linear resolution, voxel size.
(But yes. I agree with your clickbait argument here. Could have been better to use voxel size in the heading)
9.4 T is quite a strong magnetic field, as it is half the strength of the magnetic field used for plasma confinement in Tokamak Energy’s Demo4 facility. Scaling this technology for human-sized animals will likely be incredibly expensive, but the 5 micron accuracy is surely worth the investment.
7T is already regularly used for human research, and approval for human usage has been granted for 10.5T and I believe for 11.7T (though I'm not sure how many images they've gotten out of that yet).
Yes it is incredibly expensive, but it is in fact already done.
They are human size research (and now clinical, albeit limited so far) magnets, so big enough, think about 60cm. It's an elbow rubbing environment, but sufficient for even somewhat large adults. The animals magnets are super tiny, of course.
> For decades, that [Abbe diffraction] limit has operated as a sort of roadblock to engineering materials, drugs, or other objects at scales smaller than the wavelength of light manipulating them. But now, the researchers from Southampton, together with scientists from the universities of Dortmund and Regensburg in Germany, have successfully demonstrated that a beam of light can not only be confined to a spot that is 50 times smaller than its own wavelength but also “in a first of its kind” the spot can be moved by minuscule amounts at the point where the light is confined.
> According to that research, the key to confining light below the previous impermeable Abbe diffraction limit was accomplished by “storing a part of the electromagnetic energy in the kinetic energy of electric charges.” This clever adaptation, the researchers wrote, “opened the door to a number of groundbreaking real-world applications, which has contributed to the great success of the field of nanophotonics.”
> “Looking to the future, in principle, it could lead to the manipulation of micro and nanometre-sized objects, including biological particles,” De Liberato says, “or perhaps the sizeable enhancement of the sensitivity resolution of microscopic sensors.”
> Several detrimental effects limit the use of ultrafast lasers in multi-photon processing and the direct manufacture of integrated photonics devices, not least, dispersion, aberrations, depth dependence, undesirable ablation at a surface, limited depth of writing, nonlinear optical effects such as supercontinuum generation and filamentation due to Kerr self-focusing. We show that all these effects can be significantly reduced if not eliminated using two coherent, ultrafast laser-beams through a single lens - which we call the Dual-Beam technique. Simulations and experimental measurements at the focus are used to understand how the Dual-Beam technique can mitigate these problems. The high peak laser intensity is only formed at the aberration-free tightly localised focal spot, simultaneously, suppressing unwanted nonlinear side effects for any intensity or processing depth. Therefore, we believe this simple and innovative technique makes the fs laser capable of much more at even higher intensities than previously possible, allowing applications in multi-photon processing, bio-medical imaging, laser surgery of cells, tissue and in ophthalmology, along with laser writing of waveguides.
TL Transfer Learning might be useful for training a model to predict e.g. [portable] low-field MRI with NIRS Infrared and/or Ultrasound? FWIU,
"Mind2Mind" is one way to ~train a GAN from another already-trained GAN?
This is interesting for basic research but this strategy is unlikely to ever make it to human research. We need to find ways of extracting more information at reasonable Tesla. 9T just isn't gonna make its way to clinic
64e6^(1/3) = 400, in case you were wondering. So I would take it that clinical MRI voxels measure 2 mm (400 * 5 um) usually? The article does a really bad job at explaining the number from their headline.
In the research setting, if a structural MRI is being acquired for anatomical research, they'll go below than by more than half. We acquire 2mm voxel structural MRIs since we only use it to help us find a warp from subject space to template space in fMRI analysis.
Clinical scanners often use 2mm isotropic voxels, or even 3. Clinical usage is almost a bad reference point!. Research MRI at ultra high field (7T) goes to 0.8mm isotropic and below (0.5 or 0.6 is possible).
I wonder if this resolution is possible only when the fov is about the size of a mouse brain. Also, I bet the bore is tiny. However, I didnt think 9.4T was enough.
I didn't know who Chuck Close was to appreciate the article's metaphor, so for those wondering:
"Close was an American painter, visual artist, and photographer who made massive-scale photorealist and abstract portraits of himself and others. Close also created photo portraits using a very large format camera."
Can a technology like this at some point be used for brain uploads? Or like a cheaper and better version of cryonics - to "backup" the brain until it can be resurrected in some way?
If quantum information is never destroyed – and classical information is quantum information without the complex term i – perhaps our brain states are already preserved in the universe; like reflections in water droplets in the quantum foam.
Lagrangian points, non-intersecting paths through accretion discs, and microscopic black holes all preserve data - modulated energy; information - for some time before reversible or unreversible transformation.
Perhaps Superfluid quantum gravity can afford insight into the interior topology of black holes and other quantum foam phenomena?
That's useful. 5 microns is very good. Probably more than is needed for medical purposes. Some intermediate level between current technology and this scale is a useful product.
Mice brains are a lot easier to image than human brains afaik, solely because they can fit into such a tiny MRI tube, with far simpler magnets. So if any mouse MRI tech is scaled to a human device, it will almost certainly have far less resolution.
