New light-based technologies that facilitate a ‘look inside’ the human body using light – and without cutting into the tissue – promise to enable both compact, wearable devices for point-of-care diagnostics as well as powerful new systems that provide even more information and from even deeper under the skin.
Recent work and visionary future directions are detailed in a new open-access article by Antonio Pifferi and colleagues at the Politecnico di Milano and Istituto di Fotonica e Nanotechnologie CNR .
The article is part of a special section on Clinical Near-Infrared Spectroscopy and Imaging under Guest Editors Marco Ferrari (Universita degli Studi dell Aquila), Joseph Culver (Washington University School of Medicine in St. Louis), Yoko Hoshi (Hamamatsu University School of Medicine), and Heidrun Wabnitz (Physikalisch-Technische Bundesanstalt).
The desirability of noninvasively probing human tissues and their functions has sparked new physical concepts, theoretical models, instruments, measurement approaches, and applications, note the authors in ‘New frontiers in time-domain diffuse optics.’
We are at the dawn of the next generation of time-domain systems, with a breakthrough in performance, size, cost, and flexibility that has the potential for great impact on new and widespread applications, the authors assert. This breakthrough is enabled by impressive advancements in single-photon detection boosted by high-energy physics and positron-emission tomography systems.
In diffuse optical imaging, light is injected into the surface of a medium, such as the body. The light signal is re-emitted elsewhere on the surface and analysed as to how it has changed. The analysis yields information about the chemical composition of the tissues, their densities, and other aspects.
The simplest methods compare continuous-wave properties of the original signal and the re-emitted light.
Systems that also analyse frequency or time changes in the light signal provide additional data. Current state-of-the-art methods use technologies that enable time-to-digital conversion of the signal, providing even more detail.
Wearable time-domain devices already have been developed for continuous-wave systems, enabling studies in breast cancer detection, brain mapping, muscle monitoring, and non-invasive assessment of lipids, bone, and collagen. Time-domain techniques have also been used in non-destructive characterization of food, wood, pharmaceuticals, and semiconductor powers.
Over the next 20 years researchers envision that such systems will become smaller, making feasible their integration into wearable devices, and smarter, increasing their overall accuracy in detecting and identifying tissue components.
Future devices could be used in brain monitors or muscle oximeters, even for in vivo detection of the brain function during motor or cognitive tasks.
‘What makes the future technology unique is its potential to probe noninvasively and in greater depth into human functions and chemical composition, yet with simple personal appliances usable at home and compatible with normal life,’ Pifferi said. Currently unreachable organs and functions would be accessible, including the heart.
Quite surprisingly, Pifferi noted, after the thermometer and the blood pressure meter, not many other diagnostic devices for personal healthcare have been brought into the home.
‘The new smart sensors, interacting in the ambient environment and transmitting hidden internal information over the cloud, will populate the Internet of Things to the benefit of clinical, industrial, and consumer-level applications,’ he said.

SPIE http://tinyurl.com/j3v43kn

A portable power-free test for the rapid detection of bacterial resistance to antibiotics has been developed by academics at Loughborough University and the University of Reading.
The new test termed Lab-on-a-Stick is an inexpensive microfluidic strip – comprising of tiny test tubes about the size of a human hair – capable of identifying bacteria found in urine samples and checking if they are resistant to common antibiotics.
Simple to use and cheap to manufacture, the Lab-on-a-Stick is a dip and read’ method using a transparent micro-capillary film suitable for naked eye detection or measurement with portable, inexpensive equipment such as a smartphone camera.
The test, which is at least 12 times faster than current microbiological tests, is the result of research by Dr Nuno Reis, Lecturer in Chemical Engineering at Loughborough University, and Dr Al Edwards, Associate Professor in Biomedical Technology at the University of Reading.
The study showed that dipstick tests routinely used for testing in a variety of scenarios from soil pH strips for the garden to pregnancy tests, could be updated using the latest approach in miniaturized testing technology to help form the basis of a new generation of advanced, yet affordable, point-of-care tests for global diagnostics.
As part of the study, different cellular tests were carried out to demonstrate the full potential of Lab-on-a-Stick devices for a range of clinical situations:
Anti-microbial resistance – this was measured with E. coli samples typical of common urinary tract infection (UTIs). UTIs can be hard to treat with antibiotics because antibiotic resistance is so common and lab testing takes at least two days. The assay detects antibiotic resistance – in other words, can the cells grow in the presence of the antibiotic, and how much antibiotic is needed to stop cell growth? This demonstrated the advantage of using the microcapillary film which enables 10 different concentrations of antibiotic per sample to be tested with a single test strip. The research team are currently optimizing this so that the test, which currently requires overnight incubation in a multi-well plate, could in the future be completed in less than two hours in a single test strip.
Bacteria identification – classical analytical microbiology tests used for the identification of bacteria were miniaturized and performed in parallel microcapillaries, resulting in simple and rapid identification of bacteria. To identify bacteria, many different tests must be performed on every sample, illustrating again the benefits of microcapillary film which performs 10 tests per test strip. This study demonstrated a four-hour test to distinguish two very closely related bacteria – a harmless laboratory strain of E. coli from a type of Salmonella that causes food poisoning.
ABO blood typing – a simple blood test that takes only two minutes was miniaturized and the results were recorded using an everyday digital camera.
Dr Reis said: ‘This is a major step towards miniaturizing complex, routine microbiological and clinical tests that cannot at the moment be performed outside of the laboratory setting.
‘Our secret is simplicity. We have shown how micro-engineered film material made from a very transparent plastic with special optical properties, makes it easy to perform laboratory tests without lab equipment. Previously, we showed how a portable Lab-in-a-briefcase made it possible to record blood test results with the assistance of a simple smartphone.’

Loughborough University http://tinyurl.com/hb4mrph

Researchers at the University of Adelaide are urging doctors and patients to refrain from using a specific steroid treatment to treat infertility in women unless clinically indicated, because of its links to miscarriage, preterm birth and birth defects.

Researchers from the University’s Robinson Research Institute, led by Professor Sarah Robertson, say widespread use of the drug is not warranted, given there is a high degree of suspicion that corticosteroid drugs – such as prednisolone – can interfere with embryo implantation, and may have harmful effects on pregnancy and the child.

Corticosteroids are increasingly used to treat infertility in women with repeated IVF failure and recurrent miscarriage. Many women receive the drug in the belief that reducing immune cells called ‘natural killer’ cells will facilitate a pregnancy. However, this belief is mistaken, as despite their alarming name these cells are actually required for healthy pregnancy.

Professor Robertson says there is a great deal of medical and consumer misunderstanding about the role of the immune system in fertility and healthy pregnancy.

‘Steroid drugs such as prednisolone act as immune suppressants, preventing the body’s immune system from responding to pregnancy. But by suppressing the natural immune response, these drugs may lead to further complications,’ Professor Robertson says.

‘The immune system plays a critical role in reproduction and fertility. Natural killer cells and other immune cells help to build a robust placenta to support healthy fetal growth. But if we suppress or bypass the body’s natural biology, there can be dire consequences that don’t appear until later,’ she says.

‘For example, suppression of the immune system through inappropriate use of these drugs is linked to impaired placental development, which in turn elevates the risk of miscarriage, preterm birth and birth defects.’

Research shows that women taking corticosteroids over the first trimester of pregnancy have a 64percent increase in miscarriage; the risk of preterm birth is more than doubled; and their children have an elevated risk of birth defects, including a 3-4 times greater risk of cleft palate.

‘Our main message to clinicians and to women hoping to achieve pregnancy is that they should be focused on achieving good-quality pregnancy and the life-time health of the child, not just getting pregnant,’ Professor Robertson says.

‘Corticosteroids such as prednisolone may impair healthy pregnancy, which may lead to poorer long-term outcomes for the baby.

‘We believe IVF doctors should not be offering this treatment to most patients, and should discuss concerns with women who request it.

‘The exception would be in specific cases where the patient has a diagnosed autoimmune condition, but those cases are rare,’ she says.

University of Adelaide www.adelaide.edu.au/news/news87602.html

Michigan Medicine researchers employ novel technology to monitor vulnerabilities for cardiovascular events, aid in diagnosis and treatment
Strokes and heart attacks often strike without warning. But, a unique application of a medical camera could one day help physicians know who is at risk for a cardiovascular event by providing a better view of potential problem areas.

‘The camera actually goes inside the vessels,’ says first author Luis Savastano, M.D., a Michigan Medicine resident neurosurgeon. ‘We can see with very high resolution the surface of the vessels and any lesions, such as a ruptured plaque, that could cause a stroke. This technology could possibly find the smoking gun’ lesion in patients with strokes of unknown cause, and may even be able to show which silent, but at-risk, plaques may cause a cardiovascular event in the future.’

The scanning fibre endoscope, or SFE, used in the study was invented and developed by co-author and University of Washington mechanical engineering research professor Eric Seibel, Ph.D.. He originally designed it for early cancer detection by clearly imaging cancer cells that are currently invisible with clinical endoscopes.

The Michigan Medicine team used the instrument for a new application: acquiring high-quality images of possible stroke-causing regions of the carotid artery that may not be detected with conventional radiological techniques.

Researchers generated images of human arteries using the SFE, which illuminates tissues with multiple laser beams, and digitally reconstructs high-definition images to determine the severity of atherosclerosis and other qualities of the vessel wall.

A unique application of a medical camera could one day help physicians know who is at risk for a cardiovascular event by providing a better view of potential problem areas.

‘In addition to discovering the cause of the stroke, the endoscope can also assist neurosurgeons with therapeutic interventions by guiding stent placement, releasing drugs and biomaterials and helping with surgeries,’ Seibel says.

In addition, the SFE uses fluorescence indicators to show key biological features associated with increased risk of stroke and heart attacks in the future.

‘The ability to identify and monitor the biological markers that render a plaque unstable and at risk for rupture could enable the detection of individuals within high-risk populations who are most likely to suffer from cardiovascular events, and therefore benefit the most from preventive treatment during the asymptomatic stage,’ says B. Gregory Thompson, M.D., professor of neurosurgery at the University of Michigan Medical School and a senior author on the new paper.

University of Michigan www.uofmhealth.org/news/archive/201702/laser-based-camera-improves-view-carotid-artery

Patients with spinal cord injuries might one day regain use of paralyzed arms and legs thanks to research that demonstrates how limbs can be controlled via a tiny array of implanted electrodes.

The work focused on controlling electrical stimulation pulses delivered to peripheral nerve fibres. When a patient is paralyzed, one of the possible causes is damage to the spinal cord, which along with the brain makes up the central nervous system. The brain is working, and so are motor and sensory nerves in the peripheral nervous system, but electrical signals can’t flow between those nerves and the brain because of the spinal cord injury.

That communication problem is what researchers sought to address, through experiments that involved transmitting precisely controlled electrical pulses into nerves activating plantar-flexor muscles in an ankle of an anesthetized cat.

V John Mathews, professor of electrical engineering and computer science in the Oregon State University College of Engineering, lead researcher Mitch Frankel, then a Ph.D. student at the University of Utah, and three other researchers, all faculty members at Utah, conducted the study.

Researchers sent the pulses using an optimized PIV controller – proportional-integral-velocity – and the cat’s nerves received them via a 100-electrode array whose base measured just 16 square millimeters; it’s known as the Utah Slanted Electrode Array, named for where it was developed and the angled look produced by the electrode rows’ differing heights.

Thanks to specific electrodes being able to activate the right nerve fibres at the right times, the controller made the cat’s ankle muscles work in a smooth, fatigue-resistant way.

The results suggest that someday a paralyzed person might be equipped with a wearable, smartphone-sized control box that would deliver impulses to implanted electrodes in his or her peripheral nervous system, thus enabling at least some level of movement.

‘Say someone is paralyzed and lies in bed all day and gets bed sores,’ Mathews said. ‘Early versions of this technology could be used to help the person get up, use a walker and make a few steps. Even those kinds of things would have an enormous impact on someone’s life, and of course we’d like people to do more. My hope is in five or 10 years there will be at least elemental versions of this for paralyzed persons.’

While this particular study focused on helping the paralyzed, a related research area involves amputees: neuroprostheses that can be controlled by thought based on decoding what goes on electrically inside a person’s brain when he or she wants to, for example, move his or her arm or leg.

‘We can learn from the brain what the intent is and then produce the signals to make the movement happen,’ Mathews said. ‘Another way to get the control information is from the peripheral nerves,’ via electromyography, a diagnostic procedure for evaluating muscle and nerve health.

Generally, Mathews said, an electromyogram can produce the necessary control information.

Putting sensors in a person’s brain, either by deep brain implant or just inside the cranium, is another way to crack the intent code. Electroencephalography – electrode plates attached to the scalp that upload the brain’s electrical activity to a computer – can be used as well.

‘There are a lot of things going on right now in the prosthetic arena,’ Mathews said.

OSU College of Engineering oregonstate.edu/ua/ncs/archives/2016/nov/precise-nerve-stimulation-electrode-implants-offers-new-hope-paralysis-patients