Photoacoustic imaging (PAI) takes advantage of both optical and ultrasound imaging properties to visualize optical absorption with high resolution and contrast. Photoacoustic microscopy (PAM) is usually categorized with all-optical microscopy techniques such as optical coherence tomography or confocal microscopes. Despite offering high sensitivity, novel imaging contrast, and high resolution, PAM is not generally an all-optical imaging method unlike the other microscopy techniques. One of the significant limitations of photoacoustic microscopes arises from their need to be in physical contact with the sample through a coupling media. This physical contact, coupling, or immersion of the sample is undesirable or impractical for many clinical and pre-clinical applications. This also limits the flexibility of photoacoustic techniques to be integrated with other all-optical imaging microscopes for providing complementary imaging contrast. To overcome these limitations, several non-contact photoacoustic signal detection approaches have been proposed. This paper presents a brief overview of current non-contact photoacoustic detection techniques with an emphasis on all-optical detection methods and their associated physical mechanisms.

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Surgical oncologists depend heavily on visual field acuity during cancer resection surgeries for in-situ margin assessment. Clinicians must wait up to two weeks for results from a pathology lab to confirm a post-operative diagnosis, potentially resulting in subsequent treatments. Currently, there are no clinical tools that can visualize diagnostically pertinent tissue information in-situ. Here, we present the first microscopy capable of non-contact label-free visualization of human cellular morphology in a reflection-mode apparatus. This is possible with the recently reported imaging modality called photoacoustic remote sensing microscopy which enables non-contact detection of optical absorption contrast. By taking advantage of the 266-nanometer optical absorption peak of DNA, photoacoustic remote sensing is efficacious in recovering qualitatively similar nuclear information in comparison to that provided by the hematoxylin stain in the gold-standard hematoxylin and eosin (H&E) prepared samples. A photoacoustic remote sensing system was employed utilizing a 266-nanometer pulsed excitation beam to induce photoacoustic pressures within the sample resulting in refractive index modulation of the optical absorber. A 1310-nanometer continuous-wave interrogation beam detects these perturbed regions as back reflected intensity variations due to the changes in the local optical properties. Using this technique, clinically useful histologic images of human tissue samples including breast cancer (invasive ductal carcinoma), tonsil, gastrointestinal, and pancreatic tissue images were formed. These were qualitatively comparable to standard H&E prepared samples.

Photoacoustic imaging (PAI) is an emerging imaging technique that bridges the gap between pure optical and acoustic techniques to provide images with optical contrast at the acoustic penetration depth. The two key components that have allowed PAI to attain high-resolution images at deeper penetration depths are the photoacoustic signal generator, which is typically implemented as a pulsed laser and the detector to receive the generated acoustic signals. Many types of acoustic sensors have been explored as a detector for the PAI including Fabry–Perot interferometers (FPIs), micro ring resonators (MRRs), piezoelectric transducers, and capacitive micromachined ultrasound transducers (CMUTs). The fabrication technique of CMUTs has given it an edge over the other detectors. First, CMUTs can be easily fabricated into given shapes and sizes to fit the design specifications. Moreover, they can be made into an array to increase the imaging speed and reduce motion artifacts. With a fabrication technique that is similar to complementary metal-oxide-semiconductor (CMOS), CMUTs can be integrated with electronics to reduce the parasitic capacitance and improve the signal to noise ratio. The numerous benefits of CMUTs have enticed researchers to develop it for various PAI purposes such as photoacoustic computed tomography (PACT) and photoacoustic endoscopy applications. For PACT applications, the main areas of research are in designing two-dimensional array, transparent, and multi-frequency CMUTs. Moving from the table top approach to endoscopes, some of the different configurations that are being investigated are phased and ring arrays. In this paper, an overview of the development of CMUTs for PAI is presented.

Current methods to visualize cancer margins can be time consuming or unreliable. Employing PARS microscopy, the first non-contact reflection-mode label-free histology-like images of cellular morphology in unstained thin and thick human tissue samples are presented.