Brain Surgery Without a Scalpel

The School of Medicine from the University of Virginia (UVA) researchers have developed a noninvasive way to remove faulty brain circuits that could allow doctors to treat debilitating neurological diseases without the need for conventional brain surgery. The UVA team, together with colleagues at Stanford University, indicate that the approach, if successfully translated to the operating room, could revolutionize the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more. The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defenses and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

A new alternative to brain surgery developed at UVA can wipe out out problematic neurons, a type of brain cell, without causing collateral damage.

This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that don’t respond to medication,” said researcher Kevin S. Lee, PhD, of UVA’s Departments of Neuroscience and Neurosurgery and the Center for Brain Immunology and Glia (BIG). “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

The new approach is called PING, and it has already demonstrated exciting potential in laboratory studies. For instance, one of the promising applications for PING could be for the surgical treatment of epilepsies that do not respond to medication. Approximately a third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team, along with their collaborators at Stanford, have shown that PING can reduce or eliminate seizures in two research models of epilepsy. The findings raise the possibility of treating epilepsy in a carefully-targeted and noninvasive manner without the need for traditional brain surgery.

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery. In a scientific paper newly published in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a brain region, while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region.

A key advantage of the approach is its incredible precision. PING harnesses the power of magnetic-resonance imaging (MRI) to let scientists peer inside the skull so that they can precisely guide sound waves to open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it also prevents the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons, a type of brain cell, without causing collateral damage.


How To Detect Very Small Tumors

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis, (UC Davis) offers a significant advance in using magnetic resonance imaging (MRI) to pick out even very small tumors from normal tissue.

Chemical probes that produce a signal on magnetic resonance imaging, or MRI, can be used to target and image tumors. The new research is based on a phenomenon called magnetic resonance tuning that occurs between two nanoscale magnetic elements. One acts to enhance the signal, and the other quenches it. Previous studies have shown that quenching depends on the distance between the magnetic elements. This opens new possibilities for noninvasive and sensitive investigation of a variety of biological processes by MRI.

The UC Davis team created a probe that generates two magnetic resonance signals that suppress each other until they reach the target, at which point they both increase contrast between the tumor and surrounding tissue. They call this two-way magnetic resonance tuning, or TMRET. Combined with specially developed imaging analysis software, the double signal enabled researchers to pick out brain tumors in a mouse model with greatly increased sensitivity.

It’s a significant advance,” said senior author Yuanpei Li, associate professor of biochemistry and molecular medicine at the UC Davis School of Medicine and Comprehensive Cancer Center. “This could help detect very small early-stage tumors.”

The probe developed by the UC Davis team contains two components: nanoparticles of superparamagnetic iron oxide, or SPIO, and pheophorbide a–paramagnetic manganese, or P-Mn, packaged together in a lipid envelope. SPIO and P-Mn both give strong, separate signals on MRI, but as long as they are physically close together those signals tend to cancel each other out, or quench. When the particles enter tumor tissue, the fatty envelope breaks down, SPIO and P-Mn separate, and both signals appear.

Li’s laboratory focuses on the chemistry of MRI probes and developed a method to process the data and reconstruct images, which they call double-contrast enhanced subtraction imaging, or DESI. But for expertise in the physical mechanisms, they reached out to professors Kai Liu and Nicholas Curro at the UC Davis Department of Physics (Liu is now at Georgetown University). The physicists helped elucidate the mechanism of the TMRET method and refine the technique.

The researchers tested the method in cultures of brain and prostate cancer cells and in mice. For most MRI probes, the signal from the tumor is up to twice as strong as from normal tissue – a “tumor to normal ratio” of 2 or less. Using the new dual-contrast nanoprobe, Li and colleagues could get a tumor-to-normal ratio as high as 10.

The findings are published in the journal Nature Nanotechnology.


The Science Of BioPrinting a Human Heart

A company called Biolife4D has developed the technology to print human cardiac tissue by collecting blood cells from a patient and converting these cells to a type of stem cell called Induced Pluripotent Stem (iPS) cells. The technology could eventually be used to create thousands of much-needed hearts for transplantation.

What we’re working on is literally bioprinting a human heart viable for transplantation out of a patient’s own cells, so that we’re not only addressing the problem with the lack of [organ] supply, but by bioengineering the heart out of their own cells, we’re eliminating the rejection,Biolife4D CEO Steven Morris said during an appearance on Digital Trends Live, referring to the body’s impulse to reject a transplanted organ.

It starts with a patient’s own cells and ends with a 3D bioprinted heart that’s a precise fit and genetic match. The BIOLIFE4D bioprinted organ replacement process begins with a magnetic resonance imaging (MRI) procedure used to create a detailed three-dimensional image of a patient’s heart. Using this image, a computer software program will construct a digital model of a new heart for the patient, matching the shape and size of the original.

A “bio-ink” is created using the specialized heart cells combined with nutrients and other materials that will help the cells survive the bioprinting processHearts created through the BIOLIFE4D bioprinting process start with a patient’s own cells. Doctors safely take cells from the patient via a blood sample, and leveraging recent stem cell research breakthroughs, BIOLIFE4D plans to reprogram those blood cells and convert them to create specialized heart cells.

Bioprinting is done with a 3D bioprinter that is fed the dimensions obtained from the MRI. After printing, the heart is then matured in a bioreactor, conditioned to make it stronger and readied for patient transplant.


How To Recreate Memories Of Faces From Brain Data

A new technique developed by neuroscientists at the University of Toronto can reconstruct images of what people perceive based on their brain activity. The technique developed by Dan Nemrodov, a postdoctoral fellow in Assistant Professor Adrian Nestor’s lab at U of T Scarborough, is able to digitally reconstruct images seen by test subjects based on electroencephalography (EEG) data.


When we see something, our brain creates a mental percept, which is essentially a mental impression of that thing. We were able to capture this percept using EEG to get a direct illustration of what’s happening in the brain during this process,” says Nemrodov.

For the study, test subjects hooked up to EEG equipment were shown images of faces. Their brain activity was recorded and then used to digitally recreate the image in the subject’s mind using a technique based on machine learning algorithms. It’s not the first time researchers have been able to reconstruct images based on visual stimuli using neuroimaging techniques. The current method was pioneered by Nestor, who successfully reconstructed facial images from functional magnetic resonance imaging (fMRI) data in the past, but this is the first time EEG has been used.