Originally developed for diagnostic ultrasound imaging, piezoelectric transducers are the most widespread technology employed in optoacoustic (photoacoustic) signal detection. However, the detection requirements of optoacoustic sensing and imaging differ from those of conventional ultrasonography and lead to specifications not sufficiently addressed by piezoelectric detectors. Consequently, interest has shifted to utilizing entirely optical methods for measuring optoacoustic waves. All-optical sound detectors yield a higher signal-to-noise ratio per unit area than piezoelectric detectors and feature wide detection bandwidths that may be more appropriate for optoacoustic applications, enabling several biomedical or industrial applications. Additionally, optical sensing of sound is less sensitive to electromagnetic noise, making it appropriate for a greater spectrum of environments. In this review, we categorize different methods of optical ultrasound detection and discuss key technology trends geared towards the development of all-optical optoacoustic systems. We also review application areas that are enabled by all-optical sound detectors, including interventional imaging, non-contact measurements, magnetoacoustics, and non-destructive testing.

A photoacoustic microscope system provides label-free multilayered histology-like imaging of unprocessed human breast specimens.

The noninvasive determination of glucose in the interstitial layer of the human skin by mid-infrared spectroscopy is reported. The sensitivity for this measurement was obtained by combining the high pulse energy from an external cavity quantum cascade laser (EC-QCL) tunable in the infrared glucose fingerprint region (1000-1220 cm(-1)) focused on the skin, with a detection of the absorbance process by photoacoustic spectroscopy in the ultrasound region performed by a gas cell coupled to the skin. This combination facilitates a quantitative measurement for concentrations of skin glucose in the range from <50 mg/dL to >300 mg/dL, which is the relevant range for the glucose monitoring in diabetes patients. Since the interstitial fluid glucose level is representative of the blood glucose level and follows it without significant delay (<10 min), this method could be applied to establish a noninvasive, painless glucose measurement procedure that is urgently awaited by diabetes patients. We report here the design of the photoacoustic experiments, the spectroscopy of glucose in vivo, and the calibration method for the quantitative determination of glucose in skin. Finally, a preliminary test with healthy volunteers and volunteers suffering from diabetes mellitus demonstrates the viability of a noninvasive glucose monitoring for patients based on the combination of infrared QCL and photoacoustic detection.

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Due to the implication of altered metabolism in a large spectrum of tissue function and disease, assessment of metabolic processes becomes essential in managing health. In this regard, imaging can play a critical role in allowing observation of biochemical and physiological processes. Nuclear imaging methods, in particular positron emission tomography, have been widely employed for imaging metabolism but are mainly limited by the use of ionizing radiation and the sensing of only one parameter at each scanning session. Observations in healthy individuals or longitudinal studies of disease could markedly benefit from non-ionizing, multi-parameter imaging methods. We therefore focus this review on progress with the non-ionizing radiation methods of MRI, hyperpolarized magnetic resonance and magnetic resonance spectroscopy, chemical exchange saturation transfer, and emerging optoacoustic (photoacoustic) imaging. We also briefly discuss the role of nuclear and optical imaging methods for research and clinical protocols.

The application of a novel open, windowless cell for the photoacoustic infrared spectroscopy of human skin is described. This windowless cavity is tuned for optimum performance in the ultrasound range between 50 and 60 kHz. In combination with an external cavity tunable quantum cascade laser emitting in the range from ~1000 cm(-1) to 1245 cm(-1), this approach leads to high signal-to-noise-ratio (SNR) for mid-infrared spectra of human skin. This opens the possibility to measure in situ the absorption spectrum of human epidermis in the mid-infrared region at high SNR in a few (~5) seconds. Rapid measurement of skin spectra greatly reduces artifacts arising from movements. As compared to closed resonance cells, the windowless cell exhibits the advantage that the influence of air pressure variations, temperature changes, and air humidity buildup that are caused by the contact of the cell to the skin surface can be minimized. We demonstrate here that this approach can be used for continuous and non-invasive monitoring of the glucose level in human epidermis, and thus may form the basis for a non-invasive monitoring of the glucose level for diabetes patients.

Keywords: non-invasive glucose measurement, photoacoustic spectroscopy, photothermal spectroscopy, interstitial fluid glucoseWe have reported two methods to analyze glucose in the interstitial fluid of skin based on mid-infrared excitation with a tunable quantum cascade laser and photoacoustic or photothermal detection. These methods were evaluated for optimum skin locations to obtain reproducible glucose information. The lower part of the arm, the hypothenar, the tips of the index finger and the thumb were tested. The thumb appears to be the optimal skin location, followed by the index finger. Basic requirements for an optimum site are good capillary blood perfusion, low Stratum corneum thickness and the absence of fat layers. To obtain a correlation on such a site, spectra were recorded on volunteers continuously after blood glucose manipulation. However, continuous measurements on an in vivo sample such as the skin have to cope with physiological alterations such as the formation of sweat. We have used both detection schemes to investigate the acid mantle reformation after washing during time scales similar to continuous measurements for calibration spectra. We found that reconstitution of the acid mantle of skin may be seen in less than one hour. Precleaning of the measurement site may thus be useful for intermittent, but not for long term continuous measurements.