MSOT is a non-invasive imaging modality that provides real-time, quantifiable in vivo visualization that is dependent on the intrinsic difference in optical absorption properties of tissues. By operating in the near-infrared (NIR) spectral region, where low attenuation enables interrogation deep into tissues, MSOT can penetrate up to several centimetres without image blurring and can quantify pathophysiological parameters without the use of contrast agents. Nevertheless, MSOT can also utilize targeted contrast agents to enable high sensitivity and specificity detection of molecular parameters of disease.

Senior author Vasilis Ntziachristos, director of the IBMI and chair for biological imaging at the Technical University of Munich, and colleagues are developing a handheld MSOT system capable of providing diagnostic image quality and the flexibility needed in a clinical setting. Their most recent design has the ability to visualize a new set of human tissue features by resolving absorbing structures with a resolution similar to that of clinical ultrasound imaging.

Initial images

The research team first optimized the MSOT system for image quality, speed and portability. They employed a new class of laser that can provide video-rate optoacoustic images at multiple wavelengths, minimizing the motion effects. They further developed a compact, lightweight detector head, adapted to the dimensions and geometry of the human neck, which employs a curved ultrasound array to optimize image performance.

They used MSOT to image both thyroid lobes and the connecting isthmus on the necks of two healthy female volunteers. In a subsequent session, volunteers were imaged using ultrasound and Doppler ultrasound. After comparative analysis, the researchers could detect the outline of the thyroid and identify vascular features up to 20 mm below the skin. The optoacoustic images provided better visualization of thyroid vascularization and revealed vascular networks undetected by Doppler ultrasound.

Next, the researchers will conduct a larger clinical study. They plan to employ a new generation of spectral processing algorithms developed at IBMI in order to optimally process information collected by MSOT at multiple wavelengths. They expect this improvement to further suppress imaging artefacts and increase the quantification accuracy of different pathophysiology parameters, including vascularization or the oxygenation state of thyroid lesions.

Additional areas of research

Ntziachristos told medicalphysicsweb that the handheld MSOT device is currently being used for several other clinical studies, including breast cancer and cardiovascular imaging. "Through use of the handheld MSOT, we are able to distinguish and quantify for the first time tissue oxygenation and hypoxia without using contrast agents," he explained. "In addition, we use the technique for visualizing vascularization, inflammation and several other disease biomarkers. The use of different wavelengths also allows us to evaluate metabolic activity is tissues. Imaging disease biomarkers with a label-free technique of pathophysiological biomarkers can offer a breakthrough in allowing clinicians to reach earlier detection and better methods to evaluate treatment in a personalized manner."

The results of a clinical study comparing the performance of clinical ultrasound imaging and MSOT were published last month (Radiology doi: 10.1148/radiol.2016152160). The objective of this study (Netherlands National Trial Registry NTR 4125) was to examine the image quality achieved by label-free MSOT and standard ultrasound imaging in resolving blood vessels as a function of their size. The study, performed on 10 healthy volunteers, demonstrated a marked superiority of MSOT over ultrasound to resolve microvasculature.

The study confirmed that the handheld MSOT was capable of clinical vascular imaging. It provided visualization of major blood vessels as small as 100 µm in diameter and within 1 cm depth, as well as larger blood vessels. MSOT also produced images reflecting haemoglobin oxygen saturation in blood vessels. Arteries and veins were identified and pulsation in arteries during imaging could be seen.

With respect to the current research, Ntziachristos said: "We have recently developed and published a new algorithm that solves the problem of photon propagation in tissue and allows for accurate quantification of tissue oxygenation [Nature Communications 7 12121]. We are now adapting this algorithm to our handheld MSOT system to provide unprecedented ability to quantify tissue oxygenation and hypoxia in clinical measurements. This ability can open a new window in the observation of pathophysiological processes in oncology, surgery and other clinical segments."

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