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  • Ultrasound alone improves cognitive function in neurodegenerative disorders, UQ study finds

    Ultrasound alone improves cognitive function in neurodegenerative disorders, UQ study finds

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    University of Queensland researchers have found targeting amyloid plaque in the brain is not essential for ultrasound to deliver cognitive improvement in neurodegenerative disorders.

    Dr Gerhard Leinenga and Professor Jürgen Götz from UQ’s Queensland Brain Institute (QBI) said the finding challenges the conventional notion in Alzheimer’s disease research that targeting and clearing amyloid plaque is essential to improve cognition.

    Amyloid plaques are clumps of protein that can build up in the brain and block communication between brain cells, leading to memory loss and other symptoms of Alzheimer’s disease.


    Previous studies have focused on opening the blood-brain barrier with microbubbles, which activate the cell type in the brain called microglia which clears the amyloid plaque.


    But we used scanning ultrasound alone on mouse models and observed significant memory enhancement.”


    Dr. Gerhard Leinenga, from UQ’s Queensland Brain Institute 

    Dr Leinenga said the finding shows ultrasound without microbubbles can induce long-lasting cognitive changes in the brain, correlating with memory improvement.

    “Ultrasound on its own has direct effects on the neurons, with increased plasticity and improved brain networks,” he said.

    “We think the ultrasound is increasing the plasticity or the resilience of the brain to the plaques, even though it’s not specifically clearing them.”

    Professor Götz said the study also revealed the effectiveness of ultrasound therapy varied depending on the frequency used.

    “We tested two types of ultrasound waves, emitted at two different frequencies,” he said.

    “We found the higher frequency showed superior results, compared to frequencies currently being explored in clinical trials for Alzheimer’s disease patients.”

    The researchers hope to incorporate the findings into Professor Götz’s pioneering safety trial using non-invasive ultrasound to treat Alzheimer’s disease.

    “By understanding the mechanisms underlying ultrasound therapy, we can tailor treatment strategies to maximize cognitive improvement in patients,” Dr Leinenga said.

    “This approach represents a significant step towards personalized, effective therapies for neurodegenerative disorders.”

    The research paper has been published in Molecular Psychiatry.

    Source:

    The University of Queensland

    Journal reference:

    Leinenga, G., et al. (2024). Scanning ultrasound-mediated memory and functional improvements do not require amyloid-β reduction. Molecular Psychiatry. doi.org/10.1038/s41380-024-02509-5.

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  • Study reveals breakthrough in non-invasive detection of endometrial cancer

    Study reveals breakthrough in non-invasive detection of endometrial cancer

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    In a recent study published in eBioMedicine, researchers evaluated proteomic signatures in blood plasma and cervicovaginal fluid to detect endometrial cancer.

    Study: Detection of endometrial cancer in cervicovaginal fluid and blood plasma: leveraging proteomics and machine learning for biomarker discovery. Image Credit: crystal light / Shutterstock.comStudy: Detection of endometrial cancer in cervicovaginal fluid and blood plasma: leveraging proteomics and machine learning for biomarker discovery. Image Credit: crystal light / Shutterstock.com

    Diagnosing endometrial cancer

    The prevalence of endometrial cancer, which is the most common gynecological malignancy in high-income countries, continues to rise throughout the world. Endometrial cancer is amenable to curative hysterectomy when diagnosed early, with a five-year survival rate of over 90% following treatment. Comparatively, individuals with metastatic or advanced disease often have poor outcomes, with the five-year survival rate estimated at 15%.

    Over 90% of females with endometrial cancer present with postmenopausal bleeding, thus triggering urgent investigations through sequential transvaginal ultrasound, hysteroscopy, and endometrial biopsy, all of which could be anxiety-provoking and painful procedures. Therefore, developing simple, cost-effective, and non-invasive tests for early cancer diagnosis is crucial for both patients and clinicians.

    Cervicovaginal fluid, which is a mix of vaginal, uterine, and cervical secretions, has been investigated as a source of biomarkers for inflammatory conditions of the lower reproductive tract, pregnancy-related pathologies, and cervical neoplasia. In fact, one recent study found that cervicovaginal fluid can be used to detect endometrial cancer.

    About the study

    In the present study, researchers evaluate the performance of proteomic signatures from cervicovaginal fluid and plasma for endometrial cancer detection. Cases comprised females with histopathological evidence of endometrial cancer based on hysterectomy, whereas controls included symptomatic females without endometrial cancer or atypical hyperplasia. Individuals with a history of gynecological malignancy or hysterectomy were excluded.

    Cervicovaginal fluid and blood were collected, and mass spectrometry was performed. Digitized proteomic maps were derived using sequential window acquisition of all theoretical mass spectra.

    Spectral data were converted and searched against a human plasma library and a previously published library of 19,394 peptides and 2,425 proteins in the cervicovaginal fluid. Random forest (RF) modeling was used for feature selection. The most discriminatory proteins were ranked based on the mean decrease in accuracy.

    Nested logistic regression models were built by sequentially adding proteins based on their rank. The parsimonious model was identified, and its performance was evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC). Likelihood ratio tests and Akaike information criteria (AIC) were used to compare the performance of nested models.

    Study findings

    Overall, 118 postmenopausal females with symptoms were included in the study, 53 of whom had confirmed endometrial cancer and 65 with no evidence of cancer. About 86% of the study cohort were White. Individuals with endometrial cancer were likely to be older and have a higher body mass index (BMI) than controls.

    Taken together, 597, 310, and 533 proteins were quantified in the cervicovaginal fluid supernatant, cell pellets, and plasma samples, respectively. Overall, 941 unique proteins were identified across sample types. There was evidence of separation between cancers and controls based on cervicovaginal fluid supernatant proteins.

    Classifiers were selected based on the mean decrease accuracy metric of the RF model. Principal component analyses (PCA) using the top discriminatory proteins revealed more substantial discrimination between cancers and controls.

    The model with the top five discriminatory proteins had the lowest AIC value and was selected as a parsimonious model. This model predicted endometrial cancer with AUC, sensitivity, and specificity of 0.95, 91%, and 86%, respectively.

    Feature selection analysis indicated that 38 proteins were important for discrimination between cancers and controls. Proteins in cervicovaginal fluid cell pellets were less promising as cancer biomarkers than supernatant-derived proteins.

    Fewer differentially expressed proteins were observed in plasma samples between cases and controls as compared to the cervicovaginal fluid, with little evidence of discrimination based on plasma proteins. PCA indicated a modest separation between cancers and controls. A three-plasma biomarker panel predicted endometrial cancer with AUC, sensitivity, and specificity of 0.87, 75%, and 84%, respectively.

    Feature selection analysis revealed six plasma proteins as important classifiers. Furthermore, three- and four-marker panels of cervicovaginal fluid and plasma proteins predicted early-stage endometrial cancer with AUCs of 0.92 and 0.88, respectively. Five- and six-marker panels of cervicovaginal fluid and plasma proteins predicted advanced-stage endometrial cancer with AUCs of 0.96 and 0.93, respectively.

    Conclusions

    Cervicovaginal fluid proteins were more accurate in detecting endometrial cancer than plasma proteins. The five-marker panel of cervicovaginal fluid proteins comprised the immunoglobulin heavy constant mu (IGHM), haptoglobin (HPT), fibrinogen alpha chain (FGA), lymphocyte antigen 6D (LY6D), and galectin-3-binding protein (LG3BP), whereas the three-marker panel of plasma proteins included HPT, proteasome 20S subunit alpha 7 (PSMA7), and apolipoprotein D (APOD).

    Further confirmatory studies using larger cohorts are needed to validate these findings.

    Journal reference:

    • Njoku, K., Pierce, A., Chiasserini, D., et al. (2024). Detection of endometrial cancer in cervicovaginal fluid and blood plasma: leveraging proteomics and machine learning for biomarker discovery. eBioMedicine. doi:10.1016/j.ebiom.2024.105064

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  • AI analyzes lung ultrasound images to spot COVID-19

    AI analyzes lung ultrasound images to spot COVID-19

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    Artificial intelligence can spot COVID-19 in lung ultrasound images much like facial recognition software can spot a face in a crowd, new research shows.

    The findings boost AI-driven medical diagnostics and bring health care professionals closer to being able to quickly diagnose patients with COVID-19 and other pulmonary diseases with algorithms that comb through ultrasound images to identify signs of disease.

    The findings, newly published in Communications Medicine, culminate an effort that started early in the pandemic when clinicians needed tools to rapidly assess legions of patients in overwhelmed emergency rooms.

    We developed this automated detection tool to help doctors in emergency settings with high caseloads of patients who need to be diagnosed quickly and accurately, such as in the earlier stages of the pandemic. Potentially, we want to have wireless devices that patients can use at home to monitor progression of COVID-19, too.”


    Muyinatu Bell, senior author, the John C. Malone Associate Professor of Electrical and Computer Engineering, Biomedical Engineering, and Computer Science at Johns Hopkins University

    The tool also holds potential for developing wearables that track such illnesses as congestive heart failure, which can lead to fluid overload in patients’ lungs, not unlike COVID-19, said co-author Tiffany Fong, an assistant professor of emergency medicine at Johns Hopkins Medicine.

    “What we are doing here with AI tools is the next big frontier for point of care,” Fong said. “An ideal use case would be wearable ultrasound patches that monitor fluid buildup and let patients know when they need a medication adjustment or when they need to see a doctor.”

    The AI analyzes ultrasound lung images to spot features known as B-lines, which appear as bright, vertical abnormalities and indicate inflammation in patients with pulmonary complications. It combines computer-generated images with real ultrasounds of patients -; including some who sought care at Johns Hopkins.

    “We had to model the physics of ultrasound and acoustic wave propagation well enough in order to get believable simulated images,” Bell said. “Then we had to take it a step further to train our computer models to use these simulated data to reliably interpret real scans from patients with affected lungs.”

    Early in the pandemic, scientists struggled to use artificial intelligence to assess COVID-19 indicators in lung ultrasound images because of a lack of patient data and because they were only beginning to understand how the disease manifests in the body, Bell said.

    Her team developed software that can learn from a mix of real and simulated data and then discern abnormalities in ultrasound scans that indicate a person has contracted COVID-19. The tool is a deep neural network, a type of AI designed to behave like the interconnected neurons that enable the brain to recognize patterns, understand speech, and achieve other complex tasks.

    “Early in the pandemic, we didn’t have enough ultrasound images of COVID-19 patients to develop and test our algorithms, and as a result our deep neural networks never reached peak performance,” said first author Lingyi Zhao, who developed the software while a postdoctoral fellow in Bell’s lab and is now working at Novateur Research Solutions. “Now, we are proving that with computer-generated datasets we still can achieve a high degree of accuracy in evaluating and detecting these COVID-19 features.”

    Source:

    Journal reference:

    Zhao, L., et al. (2024). Detection of COVID-19 features in lung ultrasound images using deep neural networks. Communications Medicine. doi.org/10.1038/s43856-024-00463-5

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  • Ultrasound technology shows promise in detecting thoracic surface vibrations

    Ultrasound technology shows promise in detecting thoracic surface vibrations

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    The thorax, the part of the body between the neck and abdomen, provides medical professionals with a valuable window into a patient’s respiratory health. By evaluating sound vibrations produced by the airflow induced within the lungs and bronchial tree during normal breathing as well as those produced by the larynx during vocalizations, doctors can identify potential disease-related abnormalities within the respiratory system.

    But, among other shortcomings, common respiratory assessments can be subjective and are only as good as the quality of the exam. While the advent of multipoint electronic stethoscopes has helped in terms of identifying abnormalities during normal breathing, there remains a dearth of technological devices that can help characterize surface vibrations produced by vocalizations.

    In AIP Advances, by AIP Publishing, a team of French researchers demonstrated the efficacy of ultrasound technology to detect low-amplitude movements produced by vocalizations at the surface of the chest. They also demonstrated the possibility of using the “airborne ultrasound surface motion camera” (AUSMC) to map these vibrations during short durations so as to illustrate their evolution.

    AUSMC is a new imaging technology that allows the observation of the human thorax surface vibrations due to respiratory and cardiac activities at high frame rates of typically 1,000 images per second. The technology shares the physical principle of conventional ultrasound Doppler imaging, but it does not require a probe to be applied on the skin.”


    Mathieu Couade, Author

    The researchers tested the AUSMC on 77 healthy volunteers to image the surface vibrations caused by natural vocalizations with the aim of reproducing the “vocal fremitus” – vocalization-induced vibrations on the surface of the body – as typically analyzed during physical examination of the thorax. Surface vibrations induced were detectable on all subjects, they reported.

    “The spatial distribution of vibrational energy was found to be asymmetric to the benefit of the right size of the chest, and frequency dependent in the anteroposterior axis,” said Couade. “As expected, the frequency distribution of vocalization does not overlap between men and women, with the latter being higher.”

    Ongoing clinical trials will use the AUSMC to focus on the identification of lung pathologies. But the researchers are hopeful that the technology, coupled with artificial intelligence algorithms, could usher in a new era of thorax examination in which vibration patterns can be isolated. This would offer a much better window on respiratory health and enable better diagnoses of respiratory diseases.

    Source:

    American Institute of Physics

    Journal reference:

    Wintzenrieth, F., et al. (2024) Airborne ultrasound for the contactless mapping of surface thoracic vibrations during human vocalizations: A pilot study. AIP Advances. doi.org/10.1063/5.0187945.

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  • Spleen stiffness measurement could revolutionize the diagnosis and management of portal hypertension

    Spleen stiffness measurement could revolutionize the diagnosis and management of portal hypertension

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    Portal hypertension (PHT) is a severe complication of chronic liver disease, like cirrhosis, where increased pressure builds up in the portal vein. This major blood vessel drains blood from the intestines, spleen, and stomach to the liver. This can lead to life-threatening complications such as internal bleeding and liver failure.

    Currently, the most accurate way to diagnose PHT is an invasive procedure that measures pressure directly in the liver. However, this procedure is uncomfortable for patients and carries a small risk of complications.

    Researchers are excited about a new, noninvasive technique called spleen stiffness measurement (SSM), which uses sound waves to assess the stiffness of the spleen. The spleen is an organ located near the stomach that filters blood and fights infection. When PHT is present, the spleen becomes enlarged and stiffer. SSM uses a painless technique similar to an ultrasound to measure these changes in stiffness.

    Several studies have shown that SSM is highly accurate in detecting PHT. SSM may be more accurate in some cases than existing methods, such as measuring liver stiffness with ultrasound. This could be because the spleen is more directly affected by changes in portal pressure than the liver.

    The benefits of a non-invasive test like SSM are numerous. First, it would eliminate the need for invasive procedures in many patients, making diagnosis safer and more comfortable. Second, SSM could be used to screen patients with chronic liver disease for PHT at an earlier stage, allowing for earlier intervention and potentially preventing complications. Third, SSM could be a valuable tool for monitoring how well treatments for PHT are working. By tracking changes in spleen stiffness over time, doctors could determine if a patient’s PHT improves or worsens in response to medication or procedures like a transjugular intrahepatic portosystemic shunt (TIPS).

    While SSM is promising, further research is needed to confirm its effectiveness in different patient populations and optimize its use in clinical practice. For example, researchers are still determining the best cut-off values for spleen stiffness to diagnose PHT definitively.

    Overall, SSM is a promising new tool that could revolutionize the diagnosis and management of portal hypertension. This non-invasive technique can potentially improve patient care, reduce healthcare costs, and ultimately save lives.

    Source:

    First Hospital of Jilin University

    Journal reference:

    Xu, X., et al. (2024). Spleen stiffness measurement as a non-invasive assessment in patients with portal hypertension. eGastroenterology. doi.org/10.1136/egastro-2023-100031.

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  • 99mTc-maraciclatide holds potential as a non-invasive test for early-stage endometriosis

    99mTc-maraciclatide holds potential as a non-invasive test for early-stage endometriosis

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    The presentation summarized the preliminary findings from patients with known or suspected endometriosis who were imaged with a SPECT-CT camera and subsequently underwent planned laparoscopic surgery, a key-hole surgical procedure to establish the presence, absence and location of endometriotic lesions. The imaging findings were compared to the surgical and histology reports and indicate that 99mTc-maraciclatide holds potential as a non-invasive test for early-stage endometriosis.

    Specifically these preliminary findings demonstrate that 99mTc-maraciclatide has the potential to:

    • Visualize superficial peritoneal endometriosis which is found in the thin peritoneum lining which covers the abdomen and pelvis, and currently can only be identified accurately by surgery. This subtype accounts for c. 80% of all endometriosis diagnoses. In the patients in this study 99mTc-maraciclatide correctly identified superficial peritoneal endometriosis in those who went on to have this early-stage endometriosis confirmed by laparoscopy.

    • Highlight areas of activity in patients with deep endometriosis (often found on the organs e.g., bladder, bowel, rectum, ovaries) and endometrioma (cysts which are commonly found in the ovaries)

    The presentation also outlined a case study on one patient with superficial peritoneal endometriosis which had not been identified by ultrasound, but which had been visualized with 99mTc-maraciclatide, and later confirmed by laparoscopic surgery.

    The ongoing study which will recruit 20-25 patients in total is being led by Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford, together with Professor Krina Zondervan, Head of Department at the Nuffield Department of Women’s and Reproductive Health, University of Oxford. It is anticipated that the study will complete later this year.

    99mTc-maraciclatide is a radio-labeled tracer which binds with high affinity to the cell adhesion protein αvβ3 integrin and images angiogenesis (new blood vessel formation) which is known to be critical to the establishment and growth of endometriotic lesions.

    David Hail, Chief Executive Officer of Serac Healthcare, said:

    “These promising initial findings indicate that there is real potential for maraciclatide as a novel non-invasive method of diagnosing early-stage endometriosis. The ability to visualize the early-stage of this disease is particularly significant as it cannot be seen by other imaging modalities, which contributes to the almost nine year average delay to secure a diagnosis. We are hugely encouraged by these results and look forward to continuing this work with the world-leading specialists from Oxford University.”

    Endometriosis is a common disease affecting many millions of women worldwide with pain and infertility. The current delay in diagnosis results in prolonged suffering and uncertainty. Therefore, a novel imaging tool to assist healthcare professionals in identifying or ruling out the disease is urgently needed.”


    Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford

    Professor Krina Zondervan, Head of Department at the Nuffield Department of Women’s and Reproductive Health, University of Oxford added:

    “Superficial peritoneal endometriosis is the most prevalent form of the disease. It often affects younger women for whom earlier diagnosis could enable intervention at an earlier stage, with the potential to significantly change outcomes and improve prospects. At the Endometriosis CaRe Centre at the University of Oxford our studies focus on identifying novel genetic, diagnostic and therapeutic targets for endometriosis. We are delighted about the early results of the DETECT study and are looking forward to recruiting more patients to consolidate the data.”

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  • Biocompatible, bioresorbable sticker detects anastomotic leaks

    Biocompatible, bioresorbable sticker detects anastomotic leaks

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    Researchers led by Northwestern University and Washington University School of Medicine in St. Louis have developed a new, first-of-its-kind sticker that enables clinicians to monitor the health of patients’ organs and deep tissues with a simple ultrasound device.

    When attached to an organ, the soft, tiny sticker changes in shape in response to the body’s changing pH levels, which can serve as an early warning sign for post-surgery complications such as anastomotic leaks. Clinicians then can view these shape changes in real time through ultrasound imaging.

    Currently, no existing methods can reliably and non-invasively detect anastomotic leaks -; a life-threatening condition that occurs when gastrointestinal fluids escape the digestive system. By revealing the leakage of these fluids with high sensitivity and high specificity, the non-invasive sticker can enable earlier interventions than previously possible. Then, when the patient has fully recovered, the biocompatible, bioresorbable sticker simply dissolves away -; bypassing the need for surgical extraction.

    The study will be published on Friday (March 8) in the journal Science. The paper outlines evaluations across small and large animal models to validate three different types of stickers made of hydrogel materials tailored for the ability to detect anastomotic leaks from the stomach, the small intestine and the pancreas.

    “These leaks can arise from subtle perforations in the tissue, often as imperceptible gaps between two sides of a surgical incision,” said Northwestern’s John A. Rogers, who led device development with postdoctoral fellow Jiaqi Liu. “These types of defects cannot be seen directly with ultrasound imaging tools. They also escape detection by even the most sophisticated CT and MRI scans. We developed an engineering approach and a set of advanced materials to address this unmet need in patient monitoring. The technology has the potential to eliminate risks, reduce costs and expand accessibility to rapid, non-invasive assessments for improved patient outcomes.”

    “Right now, there is no good way whatsoever to detect these kinds of leaks,” said gastrointestinal surgeon Dr. Chet Hammill, who led the clinical evaluation and animal model studies at Washington University with collaborator Dr. Matthew MacEwan, an assistant professor of neurosurgery. “The majority of operations in the abdomen -; when you have to remove something and sew it back together -; carry a risk of leaking. We can’t fully prevent those complications, but maybe we can catch them earlier to minimize harm. Even if we could detect a leak 24- or 48-hours earlier, we could catch complications before the patient becomes really sick. This new technology has potential to completely change the way we monitor patients after surgery.”

    A bioelectronics pioneer, Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, with appointments at the McCormick School of Engineering and Northwestern University Feinberg School of Medicine. He also directs the Querrey Simpson Institute for Bioelectronics. At the time of the research, Hammill was an associate professor of surgery at Washington University. Rogers, Hammill and MacEwan co-led the research with Heling Wang, an associate professor at Tsinghua University in Beijing.

    The importance of being early

    All gastrointestinal surgeries carry the risk of anastomotic leaks. If the leak is not detected early enough, the patient has a 30% chance of spending up to six months in the hospital and a 20% chance of dying, according to Hammill. For patients recovering from pancreatic surgery, the risks are even higher. Hammill says a staggering 40-60% of patients suffer complications after pancreas-related surgeries.

    The biggest problem is there’s no way to predict who will develop such complications. And, by the time the patient is experiencing symptoms, they already are incredibly ill.

    “Patients might have some vague symptoms associated with the leak,” Hammill said. “But they have just gone through big surgery, so it’s hard to know if the symptoms are abnormal. If we can catch it early, then we can drain the fluid. If we catch it later, the patient can get sepsis and end up in the ICU. For patients with pancreatic cancer, they might only have six months to live as it is. Now, they are spending half that time in the hospital.”

    In search of improved outcomes for his patients, Hammill contacted Rogers, whose laboratory specializes in developing engineering solutions to address health challenges. Rogers’ team had already developed a suite of bioresorbable electronic devices to serve as temporary implants, including dissolving pacemakers, nerve stimulators and implantable painkillers.

    The bioresorbable systems piqued Hammill’s interest. The greatest odds of developing an anastomotic leak occur either three days or two weeks after surgery.

    “We like to monitor patients for complications for about 30 days,” Hammill said. “Having a device that lasts a month and then disappears sounded ideal.”

    Enhancing ultrasound

    Instead of developing new imaging systems, Rogers speculated that his team might be able to enhance current imaging methods -; allowing them to “see” features that otherwise would be invisible. Ultrasound technology already has many advantages: it’s inexpensive, readily available, does not require cumbersome equipment and does not expose patients to radiation or other risks.

    But, of course, there is a major drawback. Ultrasound technology -; which uses sound waves to determine the position, shape and structure of organs -; cannot reliably differentiate between various bodily fluids. Blood and gastric fluid, for example, appear the same.

    “The acoustic properties of the leaking fluids are very similar to those of naturally occurring biofluids and surrounding tissues,” Rogers said. “The clinical need, however, demands chemical specificity, beyond the scope of fundamental mechanisms that create contrast in ultrasound images.”

    Ultimately, Rogers’ team devised an approach to overcome this limitation by using tiny sensor devices designed to be readable by ultrasound imaging. Specifically, they created a small, tissue-adhesive sticker out of a flexible, chemically responsive, soft hydrogel material. Then, they embedded tiny, paper-thin metal disks into the thin layers of this hydrogel. When the sticker encounters acidic fluids, such as stomach acid, it swells. When the sticker encounters caustic fluids, such as pancreatic fluids, it contracts.

    Making the invisible visible

    As the hydrogel swells or shrinks in response to changing pH, the metal disks either move apart or closer together, respectively. Then, the ultrasound can view these subtle changes in placement.

    “Because the acoustic properties of the metal disks are much different than those of the surrounding tissue, they provide very strong contrast in ultrasound images,” Rogers said. “In this way, we can essentially ‘tag’ an organ for monitoring.” Because the need for monitoring extends only during a postsurgical recovery, Rogers team designed these stickers with bioresorbable materials. They simply disappear naturally and harmlessly in the body after they are no longer needed.

    Computational collaborator Yonggang Huang, the Jan and Marcia Achenbach Professorship in Mechanical Engineering and professor of civil and environmental engineering at McCormick, used acoustic and mechanical simulation techniques to help guide optimized choices in materials and device layouts to ensure high visibility in ultrasound images, even for stickers located at deep positions within the body.

    “CT and MRI scans just take a picture,” Hammill added. “The fluid might show up in a CT image, but there’s always fluid collections after surgery. We don’t know if it’s actually a leak or normal abdominal fluid. The information that we get from the new patch is much, much more valuable. If we can see that the pH is altered, then we know that something isn’t right.”

    Rogers team constructed stickers of varying sizes. The largest measures 12 millimeters in diameter, while the smallest is just 4 millimeters in diameter. Considering that the metal disks are each 1 millimeter or smaller, Rogers realized that it might be difficult for radiologists to assess the images manually. To overcome this challenge, his team also developed software that can automatically analyze the images to detect with high accuracy any relative movement of the disks.

    Improving quality of life

    To evaluate the efficacy of the new sticker, Hammill’s team tested it in both small and large animal models. In the studies, ultrasound imaging consistently detected changes in the shape-shifting sticker -; even when it was 10 centimeters deep inside of tissues. When exposed to fluids with abnormally high or low pH levels, the sticker altered its shape within minutes.

    Rogers and Hammill imagine that the device could be implanted at the end of a surgical procedure. Or, because it’s small and flexible, the device also fits (rolled up) inside a syringe, which clinicians can use to inject the tag into the body.

    “These tags are so small and thin and soft that surgeons can easily place collections of them at different locations,” Rogers said. “For example, if an incision extends by a few centimeters in length, an array of these tags can be placed along the length of the site to develop a map of pH for precisely locating the position of the leak.”

    “It’s obviously an early prototype, but I can envision the final product where, at the end of surgery, you just place these little patches for monitoring,” Hammill said. “It does its job and then completely disappears. This could have a huge impact on patients, their recovery time and, ultimately, their quality of life.”

    Next, Rogers and his team are exploring similar tags that could detect internal bleeding or temperature changes. “Detecting changes in pH is a good starting point,” Rogers said. “But this platform can extend to other types of applications by use of hydrogels that respond to other changes in local chemistry, or to temperature or other properties of clinical relevance.”

    Source:

     Northwestern University

    Journal reference:

    Liu, J., et al. (2024) Bioresorbable shape-adaptive structures for ultrasonic monitoring of deep-tissue homeostasis. Science. doi.org/10.1126/science.adk9880.

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  • Comparing CEUS imaging features in patients with hepatic lymphoepithelioma-like carcinoma and HCC

    Comparing CEUS imaging features in patients with hepatic lymphoepithelioma-like carcinoma and HCC

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    Announcing a new article publication for BIO Integration journal. Primary hepatic lymphoepithelioma-like carcinoma (LELC) is a malignant tumor with a low incidence, but the number of case reports has increased in recent years. The prognosis of hepatic LELC is better than hepatocellular carcinoma (HCC). The differentiation between hepatic LELC and HCC has clinical value during follow-up treatment. The purpose of our study was to compare contrast-enhanced ultrasound (CEUS) imaging features in patients with hepatic LELC and HCC.

    Twelve patients with an average age of 60.1±9.5 years and histopathologically confirmed hepatic LELC were included in the study. Forty-three patients with an average age of 57.4±9.0 years and a histopathological diagnosis of HCC were designated as the control group by means of propensity score matching (1:4). The clinical data, B-mode ultrasound (BMUS), and CEUS features were retrospectively analyzed between patients with hepatic LELC and HCC.

    The serum a-fetoprotein (58.1% [25/43] vs.16.7% [2/12]; p=0.017) and des-gamma-carboxy prothrombin levels (74.4% [32/43] vs.16.7% [2/12]; p=0.001) were not significantly elevated in patients with hepatic LELCs compared to HCCs. LELCs were mainly hypoechoic based on BMUS, while the echogenicity of HCCs varied (p=0.016). A halo sign was less common in patients with hepatic LELCs than HCCs (16.7% [2/12] vs. 58.1% [25/43]; p=0.011). Of hepatic LELCs, 75% (9/12) had homogeneous hyperenhancement based on CEUS, whereas 58.1% (25/43) of HCCs had heterogeneous hyperenhancement (p=0.004). Early washout was noted in 91.7% (11/12) of hepatic LELCs compared to 46.5% (20/43) of HCCs (p=0.005). Furthermore, hepatic LELCs were more likely to exhibit peripheral rim-like hyperenhancement (83.3% [10/12] vs. 11.6% [5/43]; p < 0.001).

    BMUS and CEUS are helpful in discriminating between hepatic LELC and HCC. A hypoechoic mass, the rare halo sign, homogeneous hyperenhancement in the arterial phase, higher frequencies of early washout, and peripheral rim-like hyperenhancement are useful ultrasound features that can help differentiate hepatic LELCs from HCCs.

     

    Source:

    Journal reference:

    Qin, H., et al. (2024) Contrast-Enhanced Ultrasound Features of Primary Hepatic Lymphoepithelioma-Like Carcinoma: Comparison with Hepatocellular Carcinoma. BIO Integration. doi.org/10.15212/bioi-2023-0019.

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  • Novel technique could transform the treatment landscape for brain disorders

    Novel technique could transform the treatment landscape for brain disorders

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    The human brain’s adaptability to internal and external changes, known as neural plasticity, forms the foundation for understanding cognitive functions like memory and learning, as well as various neurological disorders. New research conducted by a team led by Dr. PARK Joo Min of the Center for Cognition and Sociality within the Institute for Basic Science (IBS) unveils a novel technique that could transform the treatment landscape for brain disorders. The team developed a non-invasive brain stimulation method called Patterned Low-Intensity Low-Frequency Ultrasound (LILFUS), which holds tremendous potential for inducing long-lasting changes in brain function.

    Traditionally, magnetic and electrical brain stimulation methods have been used to modulate brain function. However, these methods come with inherent limitations that restrict their spatial resolution and penetration depth, making it challenging to precisely stimulate specific brain regions with optimal efficacy. More invasive methods, such as those that require surgical procedures, exhibit superior control and therapeutic effects for specific deep brain stimulation, but they come with risks such as tissue damage, inflammation, and infection. These limitations have fueled the search for alternative approaches that can overcome these constraints and provide more efficient and precise modulation of brain function.

    In the latest study unveiled by the IBS, researchers used ultrasound to enable precise stimulation of specific brain areas. Unlike electromagnetic waves, ultrasound has the advantage of being able to penetrate deep into the brain tissues. The researchers discovered that ultrasound stimulation can modulate neural plasticity – the brain’s ability to rewire itself – through the activation of key molecular pathways. Specifically, the study pinpointed the ultrasound’s effect on mechanosensitive calcium channels in astrocytes, which controls the cells’ ability to uptake calcium and release neurotransmitters.

    LILFUS was designed based on specific ultrasound parameters that mimic the brainwave patterns of theta (5 Hz) and gamma (30 Hz) oscillations observed during learning and memory processes. The new tool allowed the researchers to either activate or deactivate specific brain regions at will – intermittent delivery of the ultrasound was found to induce long-term potentiation effects, while continuous patterns resulted in long-term depression effects.

    One of the most promising aspects of this new technology is its ability to facilitate the acquisition of new motor skills. When the researchers delivered ultrasound stimulation to the cerebral motor cortex in mice, they observed significant improvements in motor skill learning and the ability to retrieve food. Interestingly, researchers were even able to change the forelimb preference of the mice. This suggests potential applications in rehabilitation therapies for stroke survivors and individuals with motor impairments.

    The implications of this research extend far beyond motor function. It may be used to treat conditions such as depression, where altered brain excitability and plasticity are prominent features. With further exploration, LILFUS could be adapted for various brain stimulation protocols, offering hope for various conditions ranging from sensory impairments to cognitive disorders.

    This study has not only developed a new and safe neural regulation technology with long-lasting effects but has also uncovered the molecular mechanism changes involved in brainwave-patterned ultrasound neural regulation. We plan to continue follow-up studies to apply this technology for the treatment of brain disorders related to abnormal brain excitation and inhibition and for the enhancement of cognitive functions.”


    Dr. Park Joo Min of the Center for Cognition and Sociality, Institute for Basic Science

    Source:

    Institute for Basic Science

    Journal reference:

    Kim, H-J., et al. (2024) Long-lasting forms of plasticity through patterned ultrasound-induced brainwave entrainment. Science Advances. doi.org/10.1126/sciadv.adk3198.

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  • Next-gen implants could be powered by dual-energy harvesting technology

    Next-gen implants could be powered by dual-energy harvesting technology

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    Implantable biomedical devices -; like pacemakers, insulin pumps and neurostimulators -; are becoming smaller and utilizing wireless technology, but hurdles remain for powering the next-generation implants. A new wireless charging device developed by Penn State scientists could dramatically improve powering capability for implants while still being safe for our bodies, the researchers said.

    The new device can harvest energy from magnetic field and ultrasound sources simultaneously, converting this energy to electricity to power implants, the scientists reported in the journal Energy & Environmental Science. It is the first device to harvest these dual-energy sources simultaneously with high efficiency and operate within the safety limits for human tissue, the team said.

    Our device may unlock next-generation biomedical applications because it can generate 300% higher power than the current state-of-the-art devices. By combining two energy sources in a single generator, power generated from a given volume of the device can be significantly improved which can unlock many applications that were not possible before.”


     Bed Poudel, research professor in the Department of Materials Science and Engineering at Penn State and co-author of the study

    Using this technology, battery-free bioelectronic devices could be miniaturized to millimeter-sized dimensions, making them easily implantable and allowing distributed networks of sensors and actuators to measure and manipulate physiological activity throughout the body. This would enable precise and adaptive bioelectronic therapies with minimal risks or interference with daily activities, according to the scientists.

    More traditional implants like pacemakers are typically powered by batteries and charged using cables. But the lifespan of batteries is limited and surgery may be necessary to replace them, posing a risk of infection or other medical complications.

    Charging or directly powering implants wirelessly could extend their lifespan, the scientists said. But conventional wireless charging technology used for cell phones and electric vehicles may not be ideal as implants continue to shrink.

    “The problem is that as you make these implants less invasive by making them smaller and smaller, the efficiency of wireless charging becomes much lower,” said Mehdi Kiani, associate professor of electrical engineering at Penn State and co-author of the study. “To address this, you need to increase the power. But the problem is that high frequency electromagnetic waves could be harmful to the body.”

    Magnetic field and ultrasound energy operating at lower frequencies are attractive options for wirelessly powering or charging implants, according to the researchers. Previous work by other scientists has focused on creating devices that can harvest one of these sources of energy, but not at the same time, the scientists said. However, this single source approach may not provide enough power to charge smaller future medical implants.

    “Now we can combine two modalities in a single receiver,” said Sumanta Kumar Karan, a postdoctoral scholar in the Department of Materials Science and Engineering at Penn State and the lead author of the paper. “This can exceed any of the individual modalities because we now have two sources of energy. We can increase the power by a factor of four, which is really significant.”

    The devices use a two-step process for converting magnetic field energy to electricity. One layer is magnetostrictive, which converts a magnetic field into stress, and the other is piezoelectric, which converts stress, or vibrations, into an electric field. The combination allows the device to turn a magnetic field into an electric current.

    And the piezoelectric layer also can simultaneously convert ultrasound energy into an electric current, the researchers said.

    “We have combined these sources of energy in the same footprint, and we can generate sufficient power that can be used to do the things that next generation implants will be asked to do,” Poudel said. “And we can do this without damaging tissue.”

    Technology also has implications for powering things like wireless sensor networks in smart buildings. These networks do things like monitor energy and operational patterns and use that information for remotely adjusting control systems, the scientists said.

    Other Penn State researchers contributing were Andrew Patterson, professor in the Department of Veterinary and Biomedical Sciences; Anitha Vijay, research technologist; and Sujay Hosur, doctoral candidate. Kai Wang and Rammohan Sriramdas, former assistant research professors at Penn State and Shashank Priya, vice president for research at the University of Minnesota and former professor at Penn State also contributed.

    The National Science Foundation supported this work. Some of the researchers on this study received support from the DARPA MATRIX program and the Army RIF program.

    Source:

    Journal reference:

    Karan, S. K., et al. (2024). Magnetic field and ultrasound induced simultaneous wireless energy harvesting. Energy and Environmental Science. doi.org/10.1039/d3ee03889k

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