A fairly new biomedical imaging modality, optoacoustic imaging is based on the use of laser-generated ultrasound. According to the National Center for Biotechnology Information, it is a hybrid method that has emerged over the past two decades, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging.

Full view of Noninvasix optoacoustic monitor for measuring the amount of oxygen in preterm infants’ brains.

As documented by the American Journal of Science, research into the underlying physics of optoacoustic (OA) techniques has a relatively long, if sporadic, history dating back to 1880 when Alexander Graham Bell first discovered the OA effect following his observation of the generation of sound owing to the absorption of modulated sunlight. Thereafter, relatively little active scientific research or technological development took place until the development of the laser in the 1960s, which provided the high peak power, spectral purity, and directionality that many optoacoustic sensing applications require. Given the well-known sensitivity of piezo-electric transducers, it was first suggested to use optoacoustics as a sensitive method for detection of lesions in biological tissues based on analysis of the temporally resolved signals (International Journal of Medical Research).

An optoacoustic image is provided by optical contrast in tissue while mapping tissue structures with ultrasonic resolution. Because blood has different absorption properties depending on its oxygenation status, the main advantage of the optical contrast is its spectroscopic selectivity, which allows users to not only map the distribution of blood concentration, but also its oxygen saturation in the given tissue. This is important for diagnosing of cancer, ischemia, hemorrhage, tissue hypoxia, etc.

As optoacoustic technology progresses, so do the medical innovations. An example of one innovation that has developed from the enhancing OA technology is being developed as the next generation of neonatal monitoring.

The superior sagittal sinus (SSS) is the largest dural venous sinus that runs down the middle of the brain. Noninvasix’s probe emits NIR light into the SSS, where it is absorbed by hemoglobin, which thermally expands as it is oxygenated. The pulse of NIR light generates a measurable acoustic signal from the oxygenated hemoglobin.

Each year 340,000 preterm and low birth-weight babies are born into a life of brain impairment due to a lack of blood flow to the brain after birth. Called hypoxia-ischemia, this dangerous condition is a precursor to cerebral palsy and is responsible for 23 percent of all neonatal deaths and costs an average of $28,000 per patient. Shortly after delivery, infants begin to breathe on their own. If they are deprived of oxygen, there is only a small window of time that physicians have in order to treat the problem. Until now, doctors have not been able to reliably and easily monitor brain oxygenation.

Researchers in Houston, Texas have developed a novel monitoring system using optoacoustic technology to provide accurate, real-time measurement of cerebral venous blood oxygen saturation in preterm neonates in real time. This preclinical patient monitoring system from Noninvasix, Inc., enables neonatologists to promptly recognize if an infant is in distress and take immediate, corrective action. With its enhanced technology, the company aims to decrease the rate of neurodevelopment issues associated with brain hypoxia while also reducing costs associated with treating its complications.

The infant wears a head strap fitted with laser diode arrays. Pulsing frequencies at 1,000 times per second of near-infrared light are sent into the brain’s Superior Sagittal Sinus vein. Hemoglobin in the blood absorbs the light at different frequencies depending on whether or not it is carrying oxygen. Absorption causes rapid thermal expansion of the hemoglobin, resulting in a measurable acoustic wave. The software analyzes the signal and returns an absolute measurement of oxygen saturation.

Noninvasix’s monitoring system involves a head strap with an optoacoustic probe consisting of a compact nanosecond Nd:YAG laser that sits above the superior sagittal sinus (SSS).

From a design and development standpoint, an array of integrated technologies within the system provided significant engineering challenges. Developing a laser system for safely pulsing light at several thousand watts of peak power for a remarkably short few nanosecond pulse duration, while controlling the light wavelength to within a few nanometers and switching between two lasers with different wavelengths, was a daunting challenge. The earliest prototype utilized a large optical parametric oscillator (OPO) laser that required a water-cooling system mounted in a custom cart about the size of a washing machine. The third-generation prototype has an electronic console with a 13'' by 13'' footprint and is fitted with laser diode arrays that have thermoelectric cooling elements. The current iteration is lightweight and compact for portability, and moreover, provides improved signal measurement performance.

The development of the signal processing hardware and software to measure the low-level acoustic signal and to average it over hundreds of repetitive cycles to extract the waveform out of the background noise and then to analyze this waveform to compute the oxygen concentration required significant innovation. Refinement of the measurement software system has progressed. The system is able to make the measurement while ignoring movement artifacts, and moreover, alerts the user when the sensor is improperly mounted.

To ensure ease and accuracy of use in the NICU, engineers collaborated with neonatologists at the University of Texas Medical Branch in Galveston to design a comfortable and snug fit for the probe, which is held to the infant’s head by a head strap.

Noninvasix has worked closely with Houston-based Cooper Consulting Service to integrate the laser module with the acoustic signal processing system to measure cerebral oxygen saturation. A LabView software program running under Microsoft Windows on a single board computer with a touchscreen display was used to bring these technologies together.

The module has two separate laser diode arrays with sophisticated optical components to combine the array outputs and focus them down to a small-diameter optical fiber. Each laser is mounted on a thermoelectric cooler, which is connected to a controller that maintains the laser at an optimal operating temperature to keep the light frequency and light energy output constant. A high-speed driver pulses current through the laser diodes in the array to generate the light pulse output.

Safe operation is ensured by separate supervisory circuitry that performs watchdog verification of software operation and that monitors the light pulse energy and laser temperatures. Other safety measures include lockouts for proper sensor connections and system hardware operation. The single board computer software controls and monitors the laser module operation by sending commands through a USB interface. Engineers developed the software to control the laser module and the circuitry to power the laser module and implement safety features.

The acoustic signal processing involves the sensor, signal processing circuitry, and a high-speed digitizer module that captures the waveform data and transfers it to the single board computer for analysis. In the sensor, the low-level ultrasound signal is picked up through an acoustic sensor, which is interfaced to a miniature low noise preamplifier. The signal is connected by a sensor cable to a second amplifier-filter stage in the system enclosure to boost the signal level for the digitizer. The high-speed digitizer module captures each acoustic signal wave invoked by the optical pulses. The signal data is transferred from the digitizer through a USB port to the single board computer where it is averaged point by point to extract the waveform from the background noise. The extracted waveform is analyzed by the single board computer software to detect key waveform features that indicate the oxygen saturation levels.

The optoacoustic technology, conceived by bioengineering professor Rinat O. Esenaliev, Ph.D. and Donald S. Prough, M.D., chairman of the University of Texas Medical Branch department of anesthesiology and an expert in traumatic brain injury management, is also currently being tested in traumatic brain injury and in fetuses during active labor in the labor and delivery room. In this application, a tiny probe, about the size of a stethoscope ear tip, is inserted transvaginally and cerebral venous oxygenation measurements are taken through the baby’s anterior fontanel.

This article was written by Graham Randall, Ph.D., CEO, Noninvasix, Inc. (Galveston, TX). For more information, contact Mr. Randall at This email address is being protected from spambots. You need JavaScript enabled to view it. or visit http://info.hotims.com/65847-200 .


Photonics & Imaging Technology Magazine

This article first appeared in the January, 2017 issue of Photonics & Imaging Technology Magazine.

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