A research team from the School of Engineering at The Hong Kong University of Science and Technology (HKUST) has achieved a breakthrough in brain imaging by developing the world’s first technology to capture high-resolution images of the brains of awake experimental mice in a nearly noninvasive manner.

By eliminating the need for anesthesia, this innovation enables scientists to study brain tissue in its fully functional state. The advancement promises deeper insights into human brain function in both healthy and diseased conditions, opening new frontiers in neuroscience research.

The study was recently published in Nature Communications in a paper titled “Rapid adaptive optics enabling near-noninvasive high-resolution brain imaging in awake behaving mice.”

The human brain is extraordinarily complex, and scientists have long sought to uncover its functions through brain imaging technologies. However, existing methods, such as magnetic resonance imaging (MRI), electroencephalography (EEG), computed tomography (CT), and positron emission tomography (PET), are limited in their ability to reveal the fine structural and functional details of brain activity.

Mice are widely used as model organisms to study treatments for neurological disorders such as Alzheimer’s, Huntington’s disease, and epilepsy, as well as therapies for various cancers and vaccine efficacy, due to their close genetic and biological similarity to humans. However, anesthesia profoundly alters blood circulation, glial cell morphology, and neuronal activity, leading to less reliable experimental results than those obtained from awake animals. Moreover, natural movements in awake mice often blur scanned images, hindering observation of the brain’s fine structures.

The new technology, dubbed Multiplexing Digital Focus Sensing and Shaping (MD-FSS), was developed by a team led by Prof. QU Jianan, Professor of the Department of Electronic and Computer Engineering (ECE) of the School of Engineering. This innovation builds upon Prof. Qu’s earlier work, “Analog lock-in phase detection focus sensing and shaping (ALPHA-FSS),” published in Nature Biotechnology in 2022.

ALPHA-FSS achieved subcellular resolution in brain imaging using three-photon microscopy. Despite its high accuracy and high correction order, its scanning speed was too slow to capture high-quality images of brain issues of awake animals, where natural movements caused blurring.

Furthermore, the skull’s thickness and density strongly absorb and scatter incoming light, severely limiting the ability of two-photon microscopy to penetrate it. Even in superficial brain regions, image quality is degraded, resulting in poor imaging performance.

Sharper images, speeds increased tenfold

To address these challenges, the team developed MD-FSS, which drastically accelerates the measurement of point spread function (PSF)—the three-dimensional image of a point-like object under the microscope. This groundbreaking method directs multiple spatially separated weak laser beams alongside a strong primary beam to generate nonlinear interference within the brain. Each beam is encoded at a unique frequency and carries distinct spatial information.

Through parallel decoding via digital phase demodulation—a powerful technique for extracting faint signals from noisy backgrounds—the system achieves PSF measurements in less than 0.1 seconds, more than tenfold faster than prior methods, while tracking dynamic brain activity and producing sharp, precise images.

The resolution of multiphoton microscopy is hundreds to thousands of times higher than that of conventional methods such as EEG and CT, allowing for the observation of individual neurons, immune cells, and even the finest capillary structures and their functions.

By integrating MD-FSS with multiphoton microscopy to develop the “Adaptive Optics Three-photon Microscopy,” the research team demonstrated the technology’s capability to track functional changes in brain immune cells, measure blood flow in the smallest cerebral vessels, monitor neuronal activity during cognitive and sensory processing, and capture interactions between brain cells and vasculature.

Prof. Qu said, “Such detailed, near-noninvasive, and real-time observations in awake animals were previously impossible. With the rapid aberration-correction capability of this novel adaptive optics technology, high-quality imaging is now achievable without injuring the subject’s brain.

“We can now capture the neuronal, glial, and vascular dynamics at subcellular resolution in their natural physiological state—free from the confounding effects of anesthesia. This breakthrough opens entirely new avenues for understanding brain function in both health and disease.”

A scalable platform for future neuroscience

MD-FSS is engineered for future scalability. The current system, using eight beams for PSF measurement, can be expanded to dozens or even hundreds, enabling faster and broader imaging as advances in light-control technologies continue to emerge.

Prof. Qu added, “Our latest work represents far more than an incremental improvement. We now have a versatile platform that can be scaled for faster imaging, expanded into larger brain regions, and integrated with functional assays.

“This will empower neuroscientists to investigate rapid brain events, complex network interactions, and disease progression in ways that were previously technically unattainable—opening the door to transformative discoveries in learning, memory, mental health, and neurological disorders.”

Foreigners seeking visas to live in the U.S. might be rejected if they have certain medical conditions, including diabetes or obesity, under a directive from the Trump administration.

The guidance, issued in a cable the State Department sent to embassy and consular officials and examined by KFF Health News, directs visa officers to deem applicants ineligible to enter the U.S. for several new reasons, including age or the likelihood they might rely on public benefits. The guidance says that such people could become a “public charge”—a potential drain on U.S. resources—because of their health issues or age.

While assessing the health of potential immigrants has been part of the visa application process for years, including screening for communicable diseases like tuberculosis and obtaining vaccine history, experts said the new guidelines greatly expand the list of medical conditions to be considered and give visa officers more power to make decisions about immigration based on an applicant’s health status.

The directive is part of the Trump administration’s divisive and aggressive campaign to deport immigrants living without authorization in the U.S. and dissuade others from immigrating into the country. The White House’s crusade to push out immigrants has included daily mass arrests, bans on refugees from certain countries, and plans to severely restrict the total number permitted into the U.S.

The new guidelines mandate that immigrants’ health be a focus in the application process. The guidance applies to nearly all visa applicants but is likely to be used only in cases in which people seek to permanently reside in the U.S., said Charles Wheeler, a senior attorney for the Catholic Legal Immigration Network, a nonprofit legal aid group.

“You must consider an applicant’s health,” the cable reads. “Certain medical conditions—including, but not limited to, cardiovascular diseases, respiratory diseases, cancers, diabetes, metabolic diseases, neurological diseases, and mental health conditions—can require hundreds of thousands of dollars’ worth of care.”

About 10% of the world’s population has diabetes. Cardiovascular diseases are also common; they are the globe’s leading killer.

The cable also encourages visa officers to consider other conditions, like obesity, which it notes can cause asthma, sleep apnea, and high blood pressure, in their assessment of whether an immigrant could become a public charge and therefore should be denied entry into the U.S.

“All of these can require expensive, long-term care,” the cable reads. Spokespeople for the State Department did not immediately respond to a request for comment on the cable.

Visa officers were also directed to determine if applicants have the means to pay for medical treatment without help from the U.S. government.

“Does the applicant have adequate financial resources to cover the costs of such care over his entire expected lifespan without seeking public cash assistance or long-term institutionalization at government expense?” the cable reads.

The cable’s language appears at odds with the Foreign Affairs Manual, the State Department’s own handbook, which says that visa officers cannot reject an application based on “what if” scenarios, Wheeler said.

The guidance directs visa officers to develop “their own thoughts about what could lead to some sort of medical emergency or sort of medical costs in the future,” he said. “That’s troubling because they’re not medically trained, they have no experience in this area, and they shouldn’t be making projections based on their own personal knowledge or bias.”

The guidance also directs visa officers to consider the health of family members, including children or older parents.

“Do any of the dependents have disabilities, chronic medical conditions, or other special needs and require care such that the applicant cannot maintain employment?” the cable asks.

Immigrants already undergo a medical exam by a physician who’s been approved by a U.S. embassy.

They are screened for communicable diseases, like tuberculosis, and asked to fill out a form that asks them to disclose any history of drug or alcohol use, mental health conditions, or violence. They’re also required to have a number of vaccinations to guard against infectious diseases like measles, polio, and hepatitis B.

But the new guidance goes further, emphasizing that chronic diseases should be considered, said Sophia Genovese, an immigration lawyer at Georgetown University. She also noted that the language of the directive encourages visa officers and the doctors who examine people seeking to immigrate to speculate on the cost of applicants’ medical care and their ability to get employment in the U.S., considering their medical history.

“Taking into consideration one’s diabetic history or heart health history—that’s quite expansive,” Genovese said. “There is a degree of this assessment already, just not quite as expansive as opining over, ‘What if someone goes into diabetic shock?’ If this change is going to happen immediately, that’s obviously going to cause a myriad of issues when people are going into their consular interviews.”

2025 KFF Health News. Distributed by Tribune Content Agency, LLC.

Traumatic brain injury, or TBI, affects millions of Americans each year, often resulting in long-term health challenges. New national recommendations are now paving the way for more effective short- and long-term care for patients with TBI.

Monica Verduzco-Gutierrez, MD, a physiatrist with UT Health San Antonio, the academic health center of The University of Texas at San Antonio, and professor and chair of the Department of Physical Medicine and Rehabilitation at UT San Antonio’s Long School of Medicine, served on the National Academies of Sciences, Engineering and Medicine working group that wrote the updated guidelines for diagnosing, monitoring and rehabilitation of individuals with traumatic brain injury.

This is the most comprehensive update in more than a decade and provides new strategies for patient follow-up care beyond the acute phase, especially for individuals who did not require hospitalization.

“We know that even TBIs not requiring hospitalization can lead to long-term symptoms and disability, and traditional classifications like ‘mild’ often fail to capture the complexity of these injuries,” Verduzco-Gutierrez said.

The updated guidelines were published in September in both the Annals of Family Medicine and the Journal of Neurotrauma.

“Updating the clinical practice guidelines for outpatient traumatic brain injury care was essential to address the wide variability and gaps in follow-up care that patients often experience. Less than half of patients receive any form of follow-up,” Verduzco-Gutierrez said.

The Clinical Practice Guideline Working Group reviewed the latest evidence on brain injury care to establish standards that hospitals, rehabilitation centers and outpatient clinics can apply across the country.

The new guidelines call for structured follow-up, early referral to rehabilitation and attention to cognitive, mood and functional changes that may develop after TBI. The recommendations include approaches that primary care providers can use to recognize when patients may need additional support or referral to a specialist.

Verduzco-Gutierrez said one of the most important updates is the call for health professionals to screen all TBI patients for health-related social needs such as food, housing, transportation and financial insecurity. These factors can directly impact whether patients are able to attend follow-up visits, access medications or continue rehabilitation.

“If we don’t identify and address these barriers, even the best medical plan can fall short,” she said.

The guidelines are intended to improve TBI outpatient care for individuals with any level of severity and from any cause, whether or not hospitalization was required. They also include specific considerations for older adults, athletes, military service members and survivors of intimate partner violence.

“These new guidelines offer practical, evidence-informed strategies that empower primary care providers to deliver more consistent, equitable and effective care. This will ultimately improve outcomes for millions of individuals living with TBI,” Verduzco-Gutierrez said.

Routine screening is limited to only a few cancer types. New research indicates that routine liquid biopsy testing (multi-cancer early detection testing) could substantially reduce late-stage cancer diagnoses, allowing patients to receive treatment at earlier cancer stages, which are more likely to respond to interventions.

The findings are published in Cancer.

Currently, routine screening is only recommended for four types of cancer, leaving approximately 70% of new cancer cases to be detected only after symptoms appear, often at an advanced stage when survival rates are lower. Multi-cancer early detection tests offer a revolutionary approach by screening for multiple cancer types simultaneously from a single blood draw.

To evaluate the impact of one such test, Cancerguard, investigators used epidemiological data from the Surveillance, Epidemiology, and End Results database and developed a simulation model of 14 cancer types, which account for nearly 80% of cancer incidence and mortality.

The researchers simulated 10-year disease progression for 5 million US adults aged 50–84 years and assessed the effects of incorporating an annual blood-based multi-cancer early detection test into standard care.

The model estimated that over 10 years, supplemental multi-cancer early detection testing would lead to a 10% increase in stage I diagnoses, a 20% increase in stage II diagnoses, a 30% increase in stage III diagnoses, and a 45% decrease in stage IV diagnoses, relative to standard care. The largest absolute reductions in stage IV diagnoses were in lung, colorectal, and pancreatic cancers. The largest relative reductions were in cervical, liver, and colorectal cancers.

“Our analysis shows that multi-cancer blood tests could be a game changer for cancer control,” said Jagpreet Chhatwal, Ph.D., the study’s lead author and Director of the Institute for Technology Assessment at Massachusetts General Hospital and Harvard Medical School.

“By detecting cancers earlier—before they spread—these tests could potentially improve survival and reduce the personal and economic burden of cancer.”