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World’s first fiber-optic ultrasonic imaging probe for future nanoscale disease diagnostics

Credit: Dr Salvatore La Cavera Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalitie

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Credit: Dr Salvatore La Cavera

Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalities in 3D.

The new technology produces microscopic and nanoscopic resolution images that will one day help clinicians to examine cells inhabiting hard-to-reach parts of the body, such as the gastrointestinal tract, and offer more effective diagnoses for diseases ranging from gastric cancer to bacterial meningitis.

The high level of performance the technology delivers is currently only possible in state-of-the-art research labs with large, scientific instruments – whereas this compact system has the potential to bring it into clinical settings to improve patient care.

The Engineering and Physical Sciences Research Council (EPSRC)-funded innovation also reduces the need for conventional fluorescent labels – chemicals used to examine cell biology under a microscope – which can be harmful to human cells in large doses.

The findings are being reported in a new paper, entitled ‘Phonon imaging in 3D with a fibre probe’ published in the Nature journal, Light: Science & Applications.

Paper author, Salvatore La Cavera, an EPSRC Doctoral Prize Fellow from the University of Nottingham Optics and Photonics Research Group, said of the ultrasonic imaging system: “We believe its ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics.”

Currently at prototype stage, the non-invasive imaging tool, described by the researchers as a “phonon probe”, is capable of being inserted into a standard optical endoscope, which is a thin tube with a powerful light and camera at the end that is navigated into the body to find, analyse, and operate on cancerous lesions, among many other diseases. Combining optical and phonon technologies could be advantageous; speeding up the clinical workflow process and reducing the number of invasive test procedures for patients.

3D mapping capabilities

Just as a physician might conduct a physical examination to feel for abnormal ‘stiffness’ in tissue under the skin that could indicate tumours, the phonon probe will take this ‘3D mapping’ concept to a cellular level.

By scanning the ultrasonic probe in space, it can reproduce a three-dimensional map of stiffness and spatial features of microscopic structures at, and below, the surface of a specimen (e.g. tissue); it does this with the power to image small objects like a large-scale microscope, and the contrast to differentiate objects like an ultrasonic probe.

“Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap,” adds Salvatore La Cavera.

How it works

The new ultrasonic imaging system uses two lasers that emit short pulses of energy to stimulate and detect vibrations in a specimen. One of the laser pulses is absorbed by a layer of metal – a nano-transducer (which works by converting energy from one form to another) – fabricated on the tip of the fibre; a process which results in high-frequency phonons (sound particles) getting pumped into the specimen. Then a second laser pulse collides with the sound waves, a process known as Brillouin scattering. By detecting these “collided” laser pulses, the shape of the travelling sound wave can be recreated and displayed visually.

The detected sound wave encodes information about the stiffness of a material, and even its geometry. The Nottingham team was the first to demonstrate this dual-capability using pulsed lasers and optical fibres.

The power of an imaging device is typically measured by the smallest object that can be seen by the system, i.e. the resolution. In two dimensions the phonon probe can “resolve” objects on the order of 1 micrometre, similar to a microscope; but in the third dimension (height) it provides measurements on the scale of nanometres, which is unprecedented for a fibre-optic imaging system.

Future applications

In the paper, the researchers demonstrate that the technology is compatible with both a single optical fibre and the 10-20,000 fibres of an imaging bundle (1mm in diameter), as used in conventional endoscopes.

Consequently, superior spatial resolution and wide fields of view could routinely be achieved by collecting stiffness and spatial information from multiple different points on a sample, without needing to move the device – bringing a new class of phonon endoscopes within reach.

Beyond clinical healthcare, fields such as precision manufacturing and metrology could use this high-resolution tool for surface inspections and material characterisation; a complementary or replacement measurement for existing scientific instruments. Burgeoning technologies such as 3D bio-printing and tissue engineering could also use the phonon probe as an inline inspection tool by integrating it directly to the outer diameter of the print-needle.

Next, the team will be developing a series of biological cell and tissue imaging applications in collaboration with the Nottingham Digestive Diseases Centre and the Institute of Biophysics, Imaging and Optical Science at the University of Nottingham; with the aim to create a viable clinical tool in the coming years.

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More information is available from Salvatore La Cavera III on salvatore.lacaveraiii@nottingham.ac.uk or Emma Lowry, Media Relations Manager (Engineering) on 0115 84 67156 or Emma.Lowry@nottingham.ac.uk.

Notes to editors

The University of Nottingham

The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world’s top 100. Studying at the University of Nottingham is a life-changing experience and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia – part of a globally connected network of education, research and industrial engagement. The University’s state-of-the-art facilities and inclusive and disability sport provision is reflected in its status as The Times and Sunday Times Good University Guide 2021 Sports University of the Year. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer and industry partner – locally and globally. Alongside Nottingham Trent University, we lead the Universities for Nottingham initiative, a pioneering collaboration which brings together the combined strength and civic missions of Nottingham’s two world-class universities and is working with local communities and partners to aid recovery and renewal following the COVID-19 pandemic.

Media Contact
Emma Lowry
Emma.Lowry@nottingham.ac.uk

Original Source

https://www.nottingham.ac.uk/news/worlds-first-fibre-optic-ultrasonic-imaging-probe-for-future-nanoscale-disease-diagnostics

Related Journal Article

http://dx.doi.org/10.1038/s41377-021-00532-7

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The next pandemic? It’s already here for Earth’s wildlife

Bird flu is decimating species already threatened by climate change and habitat loss.

I am a conservation biologist who studies emerging infectious diseases. When people ask me what I think the next pandemic will be I often say that we are in the midst of one – it’s just afflicting a great many species more than ours.

I am referring to the highly pathogenic strain of avian influenza H5N1 (HPAI H5N1), otherwise known as bird flu, which has killed millions of birds and unknown numbers of mammals, particularly during the past three years.

This is the strain that emerged in domestic geese in China in 1997 and quickly jumped to humans in south-east Asia with a mortality rate of around 40-50%. My research group encountered the virus when it killed a mammal, an endangered Owston’s palm civet, in a captive breeding programme in Cuc Phuong National Park Vietnam in 2005.

How these animals caught bird flu was never confirmed. Their diet is mainly earthworms, so they had not been infected by eating diseased poultry like many captive tigers in the region.

This discovery prompted us to collate all confirmed reports of fatal infection with bird flu to assess just how broad a threat to wildlife this virus might pose.

This is how a newly discovered virus in Chinese poultry came to threaten so much of the world’s biodiversity.

H5N1 originated on a Chinese poultry farm in 1997. ChameleonsEye/Shutterstock

The first signs

Until December 2005, most confirmed infections had been found in a few zoos and rescue centres in Thailand and Cambodia. Our analysis in 2006 showed that nearly half (48%) of all the different groups of birds (known to taxonomists as “orders”) contained a species in which a fatal infection of bird flu had been reported. These 13 orders comprised 84% of all bird species.

We reasoned 20 years ago that the strains of H5N1 circulating were probably highly pathogenic to all bird orders. We also showed that the list of confirmed infected species included those that were globally threatened and that important habitats, such as Vietnam’s Mekong delta, lay close to reported poultry outbreaks.

Mammals known to be susceptible to bird flu during the early 2000s included primates, rodents, pigs and rabbits. Large carnivores such as Bengal tigers and clouded leopards were reported to have been killed, as well as domestic cats.

Our 2006 paper showed the ease with which this virus crossed species barriers and suggested it might one day produce a pandemic-scale threat to global biodiversity.

Unfortunately, our warnings were correct.

A roving sickness

Two decades on, bird flu is killing species from the high Arctic to mainland Antarctica.

In the past couple of years, bird flu has spread rapidly across Europe and infiltrated North and South America, killing millions of poultry and a variety of bird and mammal species. A recent paper found that 26 countries have reported at least 48 mammal species that have died from the virus since 2020, when the latest increase in reported infections started.

Not even the ocean is safe. Since 2020, 13 species of aquatic mammal have succumbed, including American sea lions, porpoises and dolphins, often dying in their thousands in South America. A wide range of scavenging and predatory mammals that live on land are now also confirmed to be susceptible, including mountain lions, lynx, brown, black and polar bears.

The UK alone has lost over 75% of its great skuas and seen a 25% decline in northern gannets. Recent declines in sandwich terns (35%) and common terns (42%) were also largely driven by the virus.

Scientists haven’t managed to completely sequence the virus in all affected species. Research and continuous surveillance could tell us how adaptable it ultimately becomes, and whether it can jump to even more species. We know it can already infect humans – one or more genetic mutations may make it more infectious.

At the crossroads

Between January 1 2003 and December 21 2023, 882 cases of human infection with the H5N1 virus were reported from 23 countries, of which 461 (52%) were fatal.

Of these fatal cases, more than half were in Vietnam, China, Cambodia and Laos. Poultry-to-human infections were first recorded in Cambodia in December 2003. Intermittent cases were reported until 2014, followed by a gap until 2023, yielding 41 deaths from 64 cases. The subtype of H5N1 virus responsible has been detected in poultry in Cambodia since 2014. In the early 2000s, the H5N1 virus circulating had a high human mortality rate, so it is worrying that we are now starting to see people dying after contact with poultry again.

It’s not just H5 subtypes of bird flu that concern humans. The H10N1 virus was originally isolated from wild birds in South Korea, but has also been reported in samples from China and Mongolia.

Recent research found that these particular virus subtypes may be able to jump to humans after they were found to be pathogenic in laboratory mice and ferrets. The first person who was confirmed to be infected with H10N5 died in China on January 27 2024, but this patient was also suffering from seasonal flu (H3N2). They had been exposed to live poultry which also tested positive for H10N5.

Species already threatened with extinction are among those which have died due to bird flu in the past three years. The first deaths from the virus in mainland Antarctica have just been confirmed in skuas, highlighting a looming threat to penguin colonies whose eggs and chicks skuas prey on. Humboldt penguins have already been killed by the virus in Chile.

A colony of king penguins.
Remote penguin colonies are already threatened by climate change. AndreAnita/Shutterstock

How can we stem this tsunami of H5N1 and other avian influenzas? Completely overhaul poultry production on a global scale. Make farms self-sufficient in rearing eggs and chicks instead of exporting them internationally. The trend towards megafarms containing over a million birds must be stopped in its tracks.

To prevent the worst outcomes for this virus, we must revisit its primary source: the incubator of intensive poultry farms.

Diana Bell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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This is the biggest money mistake you’re making during travel

A retail expert talks of some common money mistakes travelers make on their trips.

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Travel is expensive. Despite the explosion of travel demand in the two years since the world opened up from the pandemic, survey after survey shows that financial reasons are the biggest factor keeping some from taking their desired trips.

Airfare, accommodation as well as food and entertainment during the trip have all outpaced inflation over the last four years.

Related: This is why we're still spending an insane amount of money on travel

But while there are multiple tricks and “travel hacks” for finding cheaper plane tickets and accommodation, the biggest financial mistake that leads to blown travel budgets is much smaller and more insidious.

A traveler watches a plane takeoff at an airport gate.

Jeshoots on Unsplash

This is what you should (and shouldn’t) spend your money on while abroad

“When it comes to traveling, it's hard to resist buying items so you can have a piece of that memory at home,” Kristen Gall, a retail expert who heads the financial planning section at points-back platform Rakuten, told Travel + Leisure in an interview. “However, it's important to remember that you don't need every souvenir that catches your eye.”

More Travel:

According to Gall, souvenirs not only have a tendency to add up in price but also weight which can in turn require one to pay for extra weight or even another suitcase at the airport — over the last two months, airlines like Delta  (DAL) , American Airlines  (AAL)  and JetBlue Airways  (JBLU)  have all followed each other in increasing baggage prices to in some cases as much as $60 for a first bag and $100 for a second one.

While such extras may not seem like a lot compared to the thousands one might have spent on the hotel and ticket, they all have what is sometimes known as a “coffee” or “takeout effect” in which small expenses can lead one to overspend by a large amount.

‘Save up for one special thing rather than a bunch of trinkets…’

“When traveling abroad, I recommend only purchasing items that you can't get back at home, or that are small enough to not impact your luggage weight,” Gall said. “If you’re set on bringing home a souvenir, save up for one special thing, rather than wasting your money on a bunch of trinkets you may not think twice about once you return home.”

Along with the immediate costs, there is also the risk of purchasing things that go to waste when returning home from an international vacation. Alcohol is subject to airlines’ liquid rules while certain types of foods, particularly meat and other animal products, can be confiscated by customs. 

While one incident of losing an expensive bottle of liquor or cheese brought back from a country like France will often make travelers forever careful, those who travel internationally less frequently will often be unaware of specific rules and be forced to part with something they spent money on at the airport.

“It's important to keep in mind that you're going to have to travel back with everything you purchased,” Gall continued. “[…] Be careful when buying food or wine, as it may not make it through customs. Foods like chocolate are typically fine, but items like meat and produce are likely prohibited to come back into the country.

Related: Veteran fund manager picks favorite stocks for 2024

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As the pandemic turns four, here’s what we need to do for a healthier future

On the fourth anniversary of the pandemic, a public health researcher offers four principles for a healthier future.

John Gomez/Shutterstock

Anniversaries are usually festive occasions, marked by celebration and joy. But there’ll be no popping of corks for this one.

March 11 2024 marks four years since the World Health Organization (WHO) declared COVID-19 a pandemic.

Although no longer officially a public health emergency of international concern, the pandemic is still with us, and the virus is still causing serious harm.

Here are three priorities – three Cs – for a healthier future.

Clear guidance

Over the past four years, one of the biggest challenges people faced when trying to follow COVID rules was understanding them.

From a behavioural science perspective, one of the major themes of the last four years has been whether guidance was clear enough or whether people were receiving too many different and confusing messages – something colleagues and I called “alert fatigue”.

With colleagues, I conducted an evidence review of communication during COVID and found that the lack of clarity, as well as a lack of trust in those setting rules, were key barriers to adherence to measures like social distancing.

In future, whether it’s another COVID wave, or another virus or public health emergency, clear communication by trustworthy messengers is going to be key.

Combat complacency

As Maria van Kerkove, COVID technical lead for WHO, puts it there is no acceptable level of death from COVID. COVID complacency is setting in as we have moved out of the emergency phase of the pandemic. But is still much work to be done.

First, we still need to understand this virus better. Four years is not a long time to understand the longer-term effects of COVID. For example, evidence on how the virus affects the brain and cognitive functioning is in its infancy.

The extent, severity and possible treatment of long COVID is another priority that must not be forgotten – not least because it is still causing a lot of long-term sickness and absence.

Culture change

During the pandemic’s first few years, there was a question over how many of our new habits, from elbow bumping (remember that?) to remote working, were here to stay.

Turns out old habits die hard – and in most cases that’s not a bad thing – after all handshaking and hugging can be good for our health.

But there is some pandemic behaviour we could have kept, under certain conditions. I’m pretty sure most people don’t wear masks when they have respiratory symptoms, even though some health authorities, such as the NHS, recommend it.

Masks could still be thought of like umbrellas: we keep one handy for when we need it, for example, when visiting vulnerable people, especially during times when there’s a spike in COVID.

If masks hadn’t been so politicised as a symbol of conformity and oppression so early in the pandemic, then we might arguably have seen people in more countries adopting the behaviour in parts of east Asia, where people continue to wear masks or face coverings when they are sick to avoid spreading it to others.

Although the pandemic led to the growth of remote or hybrid working, presenteeism – going to work when sick – is still a major issue.

Encouraging parents to send children to school when they are unwell is unlikely to help public health, or attendance for that matter. For instance, although one child might recover quickly from a given virus, other children who might catch it from them might be ill for days.

Similarly, a culture of presenteeism that pressures workers to come in when ill is likely to backfire later on, helping infectious disease spread in workplaces.

At the most fundamental level, we need to do more to create a culture of equality. Some groups, especially the most economically deprived, fared much worse than others during the pandemic. Health inequalities have widened as a result. With ongoing pandemic impacts, for example, long COVID rates, also disproportionately affecting those from disadvantaged groups, health inequalities are likely to persist without significant action to address them.

Vaccine inequity is still a problem globally. At a national level, in some wealthier countries like the UK, those from more deprived backgrounds are going to be less able to afford private vaccines.

We may be out of the emergency phase of COVID, but the pandemic is not yet over. As we reflect on the past four years, working to provide clearer public health communication, avoiding COVID complacency and reducing health inequalities are all things that can help prepare for any future waves or, indeed, pandemics.

Simon Nicholas Williams has received funding from Senedd Cymru, Public Health Wales and the Wales Covid Evidence Centre for research on COVID-19, and has consulted for the World Health Organization. However, this article reflects the views of the author only, in his academic capacity at Swansea University, and no funding or organizational bodies were involved in the writing or content of this article.

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