Heart stopping science: Raman sensor

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  • Published: Nov 1, 2017
  • Author: David Bradley
  • Channels: Raman
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Warning signs

A new device that uses resonance Raman spectroscopy can determine whether the body's tissues are adequately oxygenated and if placed on the heart, predict cardiac arrest in critically ill patients.

A new device that uses resonance Raman spectroscopy can determine whether the body's tissues are adequately oxygenated and if placed on the heart, predict cardiac arrest in critically ill patients. Researchers at Boston Children's Hospital and scientists from Cambridge device maker Pendar Technologies describe details of their animal study of the device in the journal Science Translational Medicine.

"With current technologies, we cannot predict when a patient's heart will stop," explains co-leader of the study, John Kheir of Boston Children's Heart Center. "We can examine heart function on the echocardiogram and measure blood pressure, but until the last second, the heart can compensate quite well for low oxygen conditions. Once cardiac arrest occurs, its consequences can be life-long, even when patients recover."

The new device has emerged from a collaboration between the Translational Research Lab in Boston Children's Heart Center, co-led by Kheir and Brian Polizzotti and Pendar Technologies of Cambridge, Massachusetts. Kheir adds that, "At the bedside, we saw patients who had a limitation to coronary blood flow, and wanted a device that could provide an early warning sign."

Detecting dysfunction

Conventional methods of determining tissue oxygenation, such as mixed venous saturation (SvO2), requires repeated blood draws, adding extra risk in critically ill patients. Moreover, SvO2 cannot show whether or not oxygen supply is adequate for the ever-changing demands of the heart muscle."We wanted to create an organ-specific, continuous, reliable readout of how adequately mitochondria are being fed oxygen," explains Kheir. "This is the first demonstration of a device that can monitor mitochondria in living tissues to predict impending organ failure." The device in question uses resonance Raman spectroscopy to measure whether enough oxygen is reaching the mitochondria within heart cells. The device will give clinicians a metric Kheir and his colleagues refer to as "3RMR", which uses light readings generated by the spectroscopic technique to quantify oxygenation and mitochondrial function in real time.

More specifically, when the oxygen level in a cell is too low, mitochondrial activity and the cell's energy balance changes. Electrons begin to accumulate in certain cellular proteins, including haemoglobin, myoglobin, and mitochondrial cytochromes. This shift in energy levels leads to a fall or even the complete shutdown of mitochondrial energy production. Ultimately, that triggers cell death. This set of circumstances results in organ injury or dysfunction and, in the case of the heart, cardiac arrest. Resonance Raman spectroscopy can determine the proportion of mitochondrial proteins with raised levels of electrons based on how the spectrometer's laser light is scattered. "This system tells us how satisfied the mitochondria are with their oxygen supply," Kheir explains. An algorithm interprets the spectra in real time to give the clinician a usable read out and essentially an early warning of imminent cardiac arrest.

Surgical applications

The team has tested the device in simulated congenital heart surgery in a pig model. They were able to measure how satisfied the heart muscle was with its oxygen supply, something that cannot currently be done. "Our likely first application of this device will be to monitor oxygen delivery during and after heart surgery," adds Kheir. The probe is about the size of a pen at this stage of development but the team would like to progress to a much smaller device that could be left in the chest for ongoing monitoring in the intensive care unit.

The same technology might be adapted for monitoring other organs and perhaps even for evaluating and sustaining organs destined for transplant. Kheir also thinks the device might have applications in cancer research where mitochondrial function is central to cancer biology.

Related Links

Sci Transl Med 2017, 9(408) eaan0117: "Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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