Engineers and neurologists collaborate to create a device that could help brain injury and stroke patients  

Cerebral blood flow (CBF) is essential to human brain functioning, and yet current imaging techniques are costly and usually do not provide continuous measurements for physicians. Recognizing this problem, Vivek Srinivasan, an adjunct associate professor of biochemical engineering at UC Davis, and his team have developed a method to measure cerebral blood flow non-invasively—functional interferometric diffusing wave spectroscopy (fidWS).

    “fiDWS can assess optical BFI signals, driven either by neural activity or cerebrovascular reactivity, with an unmatched combination of speed and brain specificity,” said Wenjun Zhou, an assistant project scientist in the Department of Biomedical Engineering at UC Davis and the first author of the study, via email. “The methodology and its variants are projected to achieve increasingly competitive cost.”

    Ryan Martin, an assistant professor in the Department of Neurology at the UC Davis Medical Center explained that there are a number of current methods to measure CBF, such as through transcranial dopplers which measure the velocity of blood flow in the brain, or CT perfusion scans. There are also indirect methods to measure CBF, such as by subtracting the intracranial pressure measurement from the mean arterial pressure in the body. However, Martin elaborated that the main problem with current methods being used is that they are not very practical—some can only be used once or twice a day or require intensive labor to perform.

    In order to develop this new method, Zhou explained that their team used the knowledge that near-infrared light can propagate diffusively in the adult human brain through the scalp where it can be collected and measured. Through the use of near-infrared light-based Diffusing Wave Spectroscopy (DWS) and Diffuse Correlation Spectroscopy (DCS), experimenters are able to derive a blood flow index (BFI) which serves as a surrogate for CBF. Zhou stated that DWS/DCS can perform continuous optical BFI monitoring of the adult human brain with relatively low instrument cost.

    However, this technique also comes with a drawback—there is a limit to the signal-to-noise ratio that can be achieved, contaminating desired brain signals. According to their published paper, “Extracerebral contamination can confound results in neurosurgery if weakly regulated scalp blood flow is mistaken for dysregulated CBF, or in a brain-computer interface, where an incorrect decision is made in response to a systemic, corrupting physiological change.” Thus, in order to optimize their fiDWS system, Zhou explained he and his team spent multiple years engineering and developing it to ensure the final quality.

    “In fiDWS, we use a strong coherent reference light to boost (interfere) weak sample light from the brain, so that the interference signal, containing sample dynamics information (i.e. BFI), can be directly measured by a non-scientific CMOS sensor,” Zhou said via email.

    Martin explained that there are multiple clinical advantages to the fiDWS method, such as the increased opportunity to manipulate blood pressure and to make sure the cerebral blood flow stays within the desired range. He emphasized that such functions are necessary to make sure the brain continues to be metabolically active by having a constant blood flow.

“How we’re going to use this [device] clinically is it’s still very rudimentary, but it allows us to titrate blood pressure parameters on patients,” Martin said. “We can use it to assess reperfusion after someone’s had a stroke and they’ve gotten to remove the blood clot that’s causing the stroke. So there’s lots of practical things that the NIRS [near-infrared spectroscopy] device that we use now, or have used, doesn’t really provide.”

Martin explained that the engineers are currently looking for ways to make the device smaller and more practical to be taken into a patient’s room to use. He believes that with time, they will be able to start testing the device on patients to collect data on how well it functions. Martin added that he thinks there is certainly opportunity for the fiDWS device to be used as a treatment and diagnostic tool in neurocritical care. 

      “Beyond monitoring in cardiac surgery, neurotrauma, ischemic stroke and neonatal intensive care, fiDWS promises to facilitate assessing CBF at the point of care, in athletes or soldiers after head injury, and possibly even in portable devices that monitor brain activity,” Zhou said via email. 

Written by: Michelle Wong — science@theaggie.org

Chaparral shrublands, found all throughout the state, are facing increasingly frequent wildfires that may threaten the native lichen communities

A collaborative study that looked at the impact of wildfires on chaparral ecosystems and long-term lichen recolonization in California was published in the journal Diversity and Distributions on May 10. The paper was co-authored by Alexandra Weill, a fire ecologist and past UC Davis graduate student researcher, Jesse Miller, an ecology lecturer at Stanford University, and John Villella, a lichenologist. 

According to a recent press release from UC Davis, “the study indicates that lichen communities may not receive the window of opportunity they need to return to chaparral shrublands after wildfire.”

Found all across California, chaparral ecosystems are dominated by shrubs rather than trees. Lichens are composite organisms made up of both fungi and algae that are able to grow on the side of these shrubs as well as on rocks and branches, according to Villella. The dense population of California, among other factors, has contributed to increased fire danger in these areas. 

Weill elaborated on the study’s argument about the challenge posed by wildfires. 

“Historically, the forests in the mountains have had sort of these low-intensity fires,” Weill said. “But the chaparral ecosystems, they’re dense, you’ve got these tall shrubs sort of edge-to-edge, and while there historically has been fire there, it was different, not these larger, high-intensity fires. Fires in the chaparral ecosystem occurred about every 45 years.” 

The abstract of the study notes that the majority of chaparral lichen taxa may be lost if fire intervals shorten to 20 years or less, which has already taken place in some parts of California. 

Weill went on to explain how the study began. 

“I was studying fire and I was pretty far into my dissertation research,” Weill said. “I met Jesse when he was a postdoc at UC Davis, and he was like, you know, I’m teaching this class about lichens, you should take it. I knew almost nothing about lichens. I think the extent was that in my college biodiversity class there was like one day where we gathered lichens. It was like, I really should be focusing on my research, but this class seemed cool, so I decided to take it.” 

According to Weill, during the class she worked on a project that was a very small-scale version of the recent study. After the class, Miller asked her if she wanted to apply with him to a grant from the California Lichen Society (CLS) and revamp her project. 

“We’re very grateful to the California Lichen Society for the grant they gave us,” Miller said. “I’m not sure that we would’ve been able to do this study without it.”

As for how Villella got involved, he explained that he has known Miller for quite some time. 

“I met him when he was an undergrad,” Villella said. “We worked together for several years, and we’ve just maintained a friendship since then. We’ve worked on many projects together, many of which involved lichen.”

Miller shared why he believes collaboration to have been of particular importance in this project. 

“I think with fire, it’s this huge challenge we face both as scientists and as a society,” Miller said. “Problems like this are sometimes referred to as ‘wicked problems.’ They have no clear, easy answer. So with wicked problems, I think it’s really important to take sort of a holistic approach, looking at it from all these different viewpoints. So we got input from several experienced experts.”

Villella added his thoughts on how the three co-authors’ unique perspectives made the project work. 

“I’m sort of the lichen expert, and then Jesse did sort of the statistical part, and Allie brought in the fire ecology perspective,” Villella said. “She also came up with the idea.” 

Miller talked about the approach that the team took in their research. 

“We’ve known for a while that lichens aren’t very tolerant of fires, but what we don’t know so much about is how much time it takes for them to grow back after disturbances like fire,” Miller said. “It’s just difficult to do such long-term studies. So we took this approach called a chronosequence approach; instead of waiting a hundred years to see what happens, we just went around and looked at areas of lichens that had burned at different times.” 

According to the study, their team compared lichen communities at sites that burned 3, 13, 22, 30 and 65 years previously, among other old-growth chaparral sites that don’t have a recorded fire in the last century. 

“We were lucky, there were a lot of sites with very different fire history, which is pretty rare in such a small geographic area so it was a really unique opportunity,” Miller said. 

Villella explained why he found this study important, and why there is value in protecting lichen biodiversity. 

“I think that people don’t realize that they’re really important to the ecosystem for a number of reasons,” Villella said. “First, they’re moisture sponges. They act as a filter and a gathering mechanism for moisture, which is really important in these dry areas. They’re also a home for many different vertebrates, and those in turn become food for birds.”

As far as the impact of increased fire frequency and intensity on ecosystems, Miller offered one solution. 

“It might seem like the answer is to try to just stop fires from burning, but it turns out that trying to suppress fires just ends up with more severe fires when they do burn,” Miller said. “Frequent fire keeps fuel down, and makes fires easier to control when they do burn. So funnily enough, the answer might be more prescribed fires.” 

Villella said something similar. 

“Prescribed fire is a really useful tool for managing landscapes, especially in California where there’s been a historic suppression of fire, although that’s starting to change,” Villella said. “Our point was to also be careful to protect some landscape from burning to protect the lichen diversity as a source population for the lichen to recolonize.” 

However, Weills explained that the logistics of using prescribed fires in chaparral ecosystems is slightly more complex than it may first appear. 

“In Southern California in particular, controlled burns are much more complicated than in other places,” Weills said. “In the forests there’s not much debate, but in chaparral there is sort of more debate.”

She went on to explain the reasoning behind this debate.

“The thing is that there’s no lack of fire, fires haven’t really stopped there,” Weill said. “So what do prescribed burns do? Well, maybe if we have a fire when we decide rather than when someone sets one, maybe it’s safer for people, maybe there’s less fuel, maybe we can do it so we’re protecting some of the older, more diverse native chaparral. But to do it frequently enough to reduce the risk, you might be pretty much getting rid of chaparral.”

She elaborated that this doesn’t mean they shouldn’t use prescribed burns, only that doing so will require caution.

“The goal is to strike this balance very carefully,” Weill said. “It’s not just going in and burning it, It’s thinking about, ‘Do we burn some of these areas to protect others?’”

Apart from exploring fire management possibilities, Miller said that the study aimed to bring awareness to ecologically important remnant chaparral patches. 

“If people even know what lichens are, that’s still above average. Most people don’t know what they are at all,” Miller said. “This whole project originated because I was teaching this class at Davis; I think that just having basic natural history education is hugely important.”

Weill cited similar thoughts, mentioning how chaparral ecosystems exist all across California, making them especially relevant to California residents who both walk through them frequently and have a disproportionate effect on the potential for wildfire. 

“These systems are close to so many of us,” Weill said. “It’s really cool. I think me and Jesse both think lichens are awesome. They’re things you can sort of pass by and not appreciate them; they’re such a cool part of nature, but they’re easy to miss. 

In reference to the lichenology class she took, she praised how it’s impacted her.

“I’m not exaggerating when I say it was life-changing,” Weill said. “Once you start learning about lichens, you really start seeing them everywhere.” 

Written by: Sonora Slater — science@theaggie.org

Correction: The original version of this article misspelled Jesse Miller’s name. The article has been updated to correct this error.

A discovery regarding T cells can help the creators of a future vaccine know how to produce the best immune response

    Research at the Center for Immunology and Infectious Disease at UC Davis found that tissue-resident immune cells are not necessary for secondary protection in the female reproductive tract, suggesting that a vaccine can potentially be made against the female reproductive disease chlamydia. The protection is provided through circulating immune memory, which contributes to the potential for a vaccine. 

    A total of 1,808,703 cases of C. trachomatis infections were reported in 2019, making it the most common notifiable condition in the United States that year, according to the Centers for Disease Control and Protection (CDC). The highest rates of chlamydia were reported among adolescents and young adults, with two-thirds of all reported cases being among individuals between the ages of 15-24 in 2019, according to the CDC. 

    The Center for Immunology and Infectious Diseases has a mission to “advance the understanding of immunology and infectious diseases through excellence in research and mentorship of scientists and educators.” Stephen McSorley is the director of the Center for Immunology and Infectious Diseases, a professor of anatomy, physiology, and cell biology and a contributor to this study.

    McSorley has been working on chlamydia for a long time and directed the study as a principal investigator. His role was to talk to the students in his lab about their ideas and give them advice and mentorship along the way while they perform the experimental work. They also discuss the impacts of their findings and publish them together, according to McSorley.

    McSorley’s lab has been working with T cells for the past few years, which controls all the other parts of the immune system such as antibodies and defenses against pathogens. CD4 T cells, a population of T cells, are crucial to preventing chlamydia infections. It is known through the study that mice without CD4 T cells are able to resolve chlamydia infections, but humans need the presence of CD4 T cells that recognize chlamydia to resolve the bacterial infection, according to McSorley.

    “The idea for a vaccine would be to make an army of CD4 T cells that would be able to combat infection, and then you would not get chlamydia,” McSorely said. 

    The specific issue the lab has been dealing with is related to memory. Memory is important for the immune system so that if an individual gets sick again, their immune system is prepared to fight it off. A vaccination is like an artificial way to try to develop memory in the immune system, according to McSorley.

    “Unfortunately, memory is complicated in immunology and it’s broken into different populations of memory cells. It is not clear which populations of memory cells are important for each different infection,” McSorely said.

    A new population of memory cells called tissue resident memory cells was discovered a few years ago. These are cells that scientists think go into your tissues and stay there to protect you against the second infection after you resolve one infection or you have a vaccination. An example of these tissues can exist in the female reproductive tract, according to McSorley.

    Researchers initially thought that the immune system circulates around the body all the time instead of taking residence in the tissues. However, McSorley’s lab determined that it was necessary for the T cells to be resident in the female reproductive tract for the vaccine to work, but getting them to stay is difficult  since it is not well understood how the T cells become resident.

    The study shed some new light on the previous thought process of the lab. Jasmine Labuda is a graduate student in the Department of Anatomy, Physiology, and Cell biology at UC Davis and is a part of the McSorley Lab. Her role in the study consisted of leading the study, designing and performing the experiments, analyzing the data, writing the manuscript and creating the figures of the paper. 

    “The main question of the study was to understand whether lymphocytes that are resident in the issue or that circulate through blood or lymph [systems] are required for protection against chlamydia infection,” Labuda said. “The main way we answered this question was using a technique called parabiosis.”

    The experiment consisted of immunizing one mouse against the infection that would generate both the tissue resident lymphocytes and the circulating lymphocytes and surgically joining that mouse to another mouse that had not been infected. This allowed the circulatory cells to transfer from one mouse to the other. The mouse that had not been infected with chlamydia was challenged with the infection to see if the circulating cells were protective. 

It was found that the circulating cells were indeed protective and that resident T cells were not needed to be immune to the bacterial infection. 

“My overall takeaway from this work is not just related to chlamydia but overall vaccines that protect against sexually transmitted diseases in the female reproductive tract,” Labuda said. “Not all infections that affect a certain tissue are going to have the same vaccine, so it really varies pathogen to pathogen.”

Written by: Francheska Torres — science@theaggie.org