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Study suggests non-invasive spectroscopy could be used to monitor blood glucose levels.

Patients with diabetes have to test their blood sugar levels several times a day to make sure they are not getting too high or too low.

Studies have shown that more than half of patients don’t test often enough, in part because of the pain and inconvenience of the needle prick.

One possible alternative is Raman spectroscopy, a non-invasive technique that reveals the chemical composition of tissue, such as skin, by shining near-infrared light on it.

MIT scientists have now taken an important step towards making this technique practical for patient use: they have shown that they can use it to directly measure glucose concentrations through the skin.

Until now, glucose levels had to be calculated indirectly, based on a comparison between Raman signals and a reference measurement of blood glucose levels.

While more work is needed to develop the technology into a user-friendly device, this advance shows that a Raman-based sensor for continuous glucose monitoring could be feasible, says Peter So, a professor of biological and mechanical engineering at MIT.

“Today, diabetes is a global epidemic,” says So, who is one of the senior authors of the study and the director of MIT’s Laser Biomedical Research Center.

“If there were a good method for continuous glucose monitoring, one could potentially think about developing better management of the disease.”

Sung Hyun Nam of the Samsung Advanced Institute of Technology in Seoul is also a senior author of the study, which appears today in Science Advances. Jeon Woong Kang, a research scientist at MIT, and Yun Sang Park, a research staff member at Samsung Advanced Institute of Technology, are the lead authors of the paper.

Seeing through the skin

Raman spectroscopy can be used to identify the chemical composition of tissue by analysing how near-infrared light is scattered, or deflected, as it encounters different kinds of molecules.

MIT’s Laser Biomedical Research Center has been working on Raman-spectroscopy-based glucose sensors for more than 20 years.

The near-infrared laser beam used for Raman spectroscopy can only penetrate a few millimetres into tissue, so one key advance was to devise a way to correlate glucose measurements from the fluid that bathes skin cells, known as interstitial fluid, to blood glucose levels.

However, another key obstacle remained: the signal produced by glucose tends to get drowned out by the many other tissue components found in skin.

“When you are measuring the signal from the tissue, most of the strong signals are coming from solid components such as proteins, lipids, and collagen.

"Glucose is a tiny, tiny amount out of the total signal. Because of that, so far we could not actually see the glucose signal from the measured signal,” says Kang.

To work around that, the MIT team has developed ways to calculate glucose levels indirectly by comparing Raman data from skin samples with glucose concentrations in blood samples taken at the same time.

However, this approach requires frequent calibration, and the predictions can be thrown off by movement of the subject or changes in environmental conditions.

For the new study, the researchers developed a new approach that lets them see the glucose signal directly. The novel aspect of their technique is that they shine near-infrared light onto the skin at about a 60-degree angle, but collect the resulting Raman signal from a fiber perpendicular to the skin.

This results in a stronger overall signal because the glucose Raman signal can be collected while unwanted reflected signal from the skin surface is filtered out.

The researchers tested the system in pigs and found that after 10 to 15 minutes of calibration, they could get accurate glucose readings for up to an hour. They verified the readings by comparing them to glucose measurements taken from blood samples.

“This is the first time that we directly observed the glucose signal from the tissue in a transdermal way, without going through a lot of advanced computation and signal extraction,” says So.

Continuous monitoring

Further development of the technology is needed before the Raman-based system could be used to monitor people with diabetes, say the researchers.

They now plan to work on shrinking the device, which is about the size of a desktop printer, so that it could be portable, in hopes of testing such a device on diabetic patients.

“You might have a device at home or a device in your office that you could put your finger on once in a while, or you might have a probe that you hold to your skin,” says So. “That’s what we’re thinking about in the shorter term.”

In the long term, they hope to create a wearable monitor that could offer continuous glucose measurements.

Other MIT authors of the paper include former postdoc Surya Pratap Singh, who is now an assistant professor at the Indian Institute of Technology; Wonjun Choi, a former visiting scientist from the Institute for Basic Science in South Korea; research technical staff member Luis Galindo; and principal research scientist Ramachandra Dasari. Hojun Chang, Woochang Lee, and Jongae Park of the Samsung Advanced Institute of Technology are also authors of the study.

Researchers hope to make needle pricks for diabetics a thing of the past

Virtual reality and scenario-testing models are being built to help urban planners and architects get real-time feedback about the impact of their designs on mental health, particularly for older people.

Europe’s cities are getting greyer. The EU’s 2018 ageing report claims that by 2070, more than half of Europeans will be over the age of 65. Poor health and a limited income mean older people can be more susceptible to isolation, depression and mental decline.

But what if city design could instead be used to boost wellbeing? A combination of neurologists, architects, artists, and epidemiologists are now seeing how to do just that, by testing people’s emotional response to spaces such as redeveloped buildings and plazas before a single brick is laid.

As part of the MINDSPACES project, artists and architects first come up with a blueprint for a city square, for example, which can then be turned into a digital simulation. Locals can then ‘see’ what the simulated blueprint looks like by donning a pair of virtual reality (VR) goggles.

"During the VR experience, the (physical) space in which the person will react will interact with the (digital) space," says Dr Stefanos Vrochidis, senior researcher at the Centre for Research and Technology Hellas, Greece.

‘You might walk in the square and you see a bench that you don’t like. And then when you revisit it in the next two seconds the bench is not there, and there is something else.’
Dr Stefanos Vrochidis

Users also wear lightweight devices that measure their brain activity, skin response, and heart rate while they explore the virtual space. Using these devices, neurologists then use machine-learning programs to figure out the most pleasant, inspiring or emotionally appealing aspects about the proposed design.

"Based on the emotions, the space will be adapted in real time," says Dr Vrochidis. "This means you might walk in the square and you see a bench that you don’t like. And then when you revisit it in the next two seconds the bench is not there, and there is something else."

Emotionally friendly

One of the project’s test cases involves redesigning and refurbishing seniors’ homes in Paris, France, to make them more ‘emotionally friendly’ for the residents.

Working with the healthcare initiative eSeniors, architects and artists will redesign this space so that it offers different artworks and furniture to address emotions such as isolation and loss.

Artists will be first given the 3D plan of someone’s living space and information from interviews about their habits at home.

The resident will then use VR goggles to explore the virtual space, interact with the artwork and furniture and have their emotional reactions to their proposed living space recorded.

Dr Vrochidis is convinced this real-time feedback can also democratise urban planning for both older people and the wider community.

"This gives you the ability to implicitly have an important say in how the space is designed, and you see it in real time. That, I think, is a very important interaction capability which is very different to simply having an image," says Dr Vrochidis.

But it’s not just the physical design of cities that can impact mental health, according to Frank van Lenthe, professor of social epidemiology at Erasmus Medical Centre Rotterdam, the Netherlands.

"A city has a physical shape and a social shape that may be beneficial for the elderly," he says.

He leads a project called MINDMAP which is looking at what policies and designs in cities across Europe and North America could boost mental health among older city dwellers.

Bus passes

The project has already suggested a link between a UK initiative of giving the elderly free bus passes and an increase in mental wellbeing. This, says Prof van Lenthe, may be due to bus journeys helping people to go and meet others, and thus reducing loneliness.

The researchers have also found more nuanced features of urban design. Building high-density apartments helps to encourage walking and cycling, boosting mental health. But building apartments too densely has the opposite effect.

"If you make them even denser, the stress related to that would be worse than the benefits of more walking and cycling," says Prof van Lenthe.

The team is also comparing the policies and design of European and US cities to see how different factors affect wellbeing.

"American cities are built on completely different policies and different starting points," says Prof van Lenthe. "The huge car dependency for example is completely incomparable [to Europe], but also the very market driven economies."

The differences extend to low-income areas and nutrition. "In the small and dense cities that we have in Europe, for example, the availability of shops for healthy food is relatively easily accessible for everyone - whereas in the US, this differs much more by level of deprivation," says Prof van Lenthe.

Link between depression and alcoholism

In March, the project published a paper on the link between depression and alcoholism, and possible policy solutions, among the older adults in Los Angeles. Using data from a previous LA healthcare study, they used computer models to see what affected the alcoholism rate among the elderly.

These models include personal factors (for example, a history of depression) alongside city life (for example, living close to shops selling alcohol and alcohol taxes).

Their results suggest that although depression and alcohol abuse are linked, it is not as strong as some may believe. A combination of social-based therapy to fight depression and alcohol taxes could help lower the rate of alcoholism among the elderly.

The project, which ends later this year, aims to pull all their results together in a digital model so that policymakers can test different scenarios for their cities.

"Currently we’re in a bit of a situation where, given the challenges we face with urbanisation, policies need to be made - and I understand fully that policymakers can’t wait," says Prof van Lenthe.

"But I do hope that our project will provide lots of evidence to further underlie policies in different cities."

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