Computing the best high-resolution 3-D tissue images

Real-time, 3-D microscopic tissue imaging could be a revolution for medical fields such as cancer diagnosis, minimally invasive surgery and ophthalmology.

University of Illinois researchers have developed a technique to computationally correct for aberrations in optical tomography, bringing the future of medical imaging into focus.

The computational technique could provide faster, less expensive and higher resolution tissue imaging to a broader population of users. The group describes its technique this week in the online early edition of the Proceedings of the National Academy of Sciences.

“Computational techniques allow you to go beyond what the optical system can do alone, to ultimately get the best quality images and three-dimensional datasets,” said Steven Adie, a postdoctoral researcher at the Beckman Institute for Advanced Science and Technology at Illinois. “This would be very useful for real-time imaging applications such as image-guided surgery.” 

Aberrations, such as astigmatism or distortion, plague high-resolution imaging. They make objects that should look like fine points appear to be blobs or streaks. The higher the resolution, the worse the problem becomes. It’s especially tricky in tissue imaging, when precision is vital to a correct diagnosis.

Adaptive optics can correct aberrations in imaging. It’s widely used in astronomy to correct for distortion as starlight filters through the atmosphere. A complex system of mirrors smooth out the scattered light before it enters the lens. Medical scientists have begun applying adaptive optics hardware to microscopes, hoping to improve cell and tissue imaging.

“It’s the same challenge, but instead of imaging through the atmosphere, we’re imaging through tissue, and instead of imaging a star, we’re imaging a cell,” said Stephen Boppart, a professor of electrical and computer engineering, of bioengineering and of internal medicine at the U. of I. “But a lot of the optical problems are the same.”

Unfortunately, hardware-based adaptive optics are complicated, tedious to align and extremely expensive. They can only focus on one focal plane at a time, so for tomography – 3-D models constructed from sectional images as in a CT scan, for example – the mirrors have to be adjusted and a new image scanned for each focal plane. In addition, complex corrective systems are impractical for handheld or portable devices, such as surgical probes or retinal scanners.

Therefore, instead of using hardware to correct a light profile before it enters the lens, the Illinois team uses computer software to find and correct aberrations after the image is taken.

Boppart's group teamed up with with Scott Carney, a professor of electrical and computer engineering and the head of the Optical Science Group at the Beckman Institute, to develop the technique, called computational adaptive optics.

They demonstrated the technique in gel-based phantoms laced with microparticles as well as in rat lung tissue. They scan a tissue sample with an interferometric microscope, which is an optical imaging device using two beams of light.

The computer collects all of the data and then corrects the images at all depths within the volume. Blurry streaks become sharp points, features emerge from noise, and users can change parameters with the click of a mouse.

“Being able to correct aberrations of the entire volume helps us to get a high-resolution image anywhere in that volume,” said Adie. “Now you can see tissue structures that previously were not very clear at all.”

Computed adaptive optics can be applied to any type of interferometric imaging, such as optical coherence tomography, and the computations can be performed on an ordinary desktop computer, making it accessible for many hospitals and clinics.

Next, the researchers are working to refine the algorithms and explore applications. They are combining their computational adaptive optics with graphics processors, looking forward to real-time in-vivo applications for surgery, minimally invasive biopsy and more.  

RatCAP: mini wearable brain scanner links neurochemisty with behaviour

A new portable brain scanner for rats can, for the first time, show how brain activity influences behaviour.

Positron emission tomography (PET) imaging help researchers look into brain activity – by measuring flashes of light to reveal blood flow.

Now, scientists have created a PET scanner that’s small enough for rats to wear.

Because it fits on rats while they’re awake and moving around, the new tech assesses brain function and behavior at the same time – allowing a glimpse of all the info lost when looking at behavior and neurochemistry separately and as they say, this can eventually help researchers better understand functions in the human brain.

“It means we can watch how the animals behave and observe their brain chemistry at the same time,” says study author David Schlyer of Brookhaven National Laboratory (BNL).

PET scans use injections of very small amounts of radiopharmaceuticals to show the metabolism of chemicals in real time. In addition to brain activity and blood flow, it helps in examining organ function, uncovering drug addiction or depression, diagnosing cancer early, and researching neurological conditions from Alzheimer’s disease to epilepsy.

In humans, it’s pretty straightforward to use. Just lie down and relax. But rats can’t really stay still inside an imaging scanner without being restrained, paralyzed, or anesthetized – ruling out many types of studies.
The team engineered a mini PET scan – known as RatCAP for Rat Conscious Animal PET (pictured). It’s about 38mm in diameter and weighs 250g.

Most importantly, it allows neuroscientists to study molecular processes that occur in the brain during consciousness.

“It’s a methodological issue,” says study author Paul Vaska of BNL. “If you start to make assumptions that what you’re seeing under anesthesia is what you’ll see awake, you may make a mistake in your interpretation.”

Other techniques to simultaneously track brain function and behavior, such as the more invasive in vivo microdialysis, which involves inserting a probe into brain tissue, are limited to small regions of the brain.

The RatCAP, by contrast, allows researchers to look globally across the brain.

For the inaugural test, the team decided to look at the neurotransmitter dopamine, comparing levels in anesthetized rats using conventional PET with those in awake rats using the RatCAP:

• Unexpectedly, dopamine levels in the awake rats were lower. (More behavioural activity would traditionally be associated with higher levels of dopamine.)
• There was a strong correlation between dopamine levels and behavioral activity – like head turns and body motion.
• Changes can be monitored on a minute-to-minute basis. (Currently, PET studies tend to average 30 to 60 minutes.)

“We can study changes in dopamine connected to drug abuse,” says first author Daniela Schulz of BNL, “but also the effect of change in other psychiatric disorders where proteins in the brain are important, like schizophrenia, attention deficit hyperactivity disorder and depression.”

The team hopes to develop wearable scanners for people and monkeys, so they too can move around and engage in activities while their brains are being scanned.

“We’re considering this at the moment,” says Schlyer. “It would be something like a football helmet.”

The study was published in Nature Methods this week.

ESA Planck scanning - Galactic, mollweide

The ring of sky which the Planck satellite scans at any one time is shown as a white ring. As it orbits the Sun, it maps out the sky, shown here as the sky as measured by the WMAP satellite (credit NASA/WMAP Science Team).

The map is shown in Galactic coordinates, aligned with the plane of our Galaxy, and projected in a "Mollweide" projection, meaning that entire sky is shown in one oval, just like in some maps of the world in an Atlas.

The solar system is tilted relative to the plane of the Galaxy, so the ring which Planck scans moves oddly around the sky in this view.

http://planck.cf.ac.uk/scanning