From bench to bedside

Review on practical photoacoustic microscopy.

The Delaunay triangulation, in both classic and more generalized sense, is studied in this paper for minimizing the linear interpolation error (measure in L^P-norm) for a given function. The classic Delaunay triangulation can then be characterized as an optimal triangulation that minimizes the interpolation error for the isotropic function ‖x‖^2 among all the triangulations with a given set of vertices. For a more general function, a functiondependent Delaunay triangulation is then defined to be an optimal triangulation that minimizes the interpolation error for this function and its construction can be obtained by a simple lifting and projection procedure. The optimal Delaunay triangulation is the one that minimizes the interpolation error among all triangulations with the same number of vertices, i.e. the distribution of vertices are optimized in order to minimize the interpolation error. Such a function-depend entoptimal Delaunay triangulation is proved to exist for any given convex continuous function.On an optimal Delaunay triangulation associated with f, it is proved that △↓f at the interior vertices can be exactly recovered by the function values on its neighboring vertices.Since the optimal Delaunay triangulation is difficult to obtain in practice, the concept of nearly optimal triangulation is introduced and two sufficient conditions are presented for a triangulation to be nearly optimal.

Optimal delaunay triangulations

Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50 s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0 s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO3)2] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.

High-speed intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque enabled by a 2-kHz barium nitrite raman laser

Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas

Photoacoustic imaging techniques have been extensively developed for biomedical applications, including functional and molecular imaging, due in part to their high optical contrast, high spatial resolution, and non-ionizing imaging properties. However, there are currently depth limitations in cellular-resolution, optically focused photoacoustic microscopy systems. In addition, most common photoacoustic systems need to be in contact with the sample through an ultrasound medium. In this work, by taking advantage of large photoacoustic initial pressures, all-optical non-contact optical resolution photoacoustic imaging is reported at depths beyond the optical transport mean-free path of the excitation wavelength. The proposed technique is called deep photoacoustic remote sensing (dPARS) microscopy. Visible pulsed excitation wavelengths are used to produce large initial-pressure-induced refractive index modulations in absorbing targets. These localized pressure rises create transient variations to the local scattering properties, which are detected as back-reflected intensity modulations from a deep-penetrating interrogation beam and do not require an interferometric detection pathway. Experiments demonstrate that dPARS is capable of providing optical resolution images to depths of 2.5 mm in tissue-mimicking scattering media. Signal-to-noise ratio ∼50  dB is reported for in vivo imaging of microvascular networks. Also, imaging of single red blood cells, oxygen saturation mapping, and deep-vascular imaging applications are demonstrated. dPARS’s capabilities such as remote sensing, deep optical resolution imaging, and high signal-to-noise ratio, may yield new opportunities for several pre-clinical and clinical applications.

Deep non-contact photoacoustic initial pressure imaging

A photoacoustic remote sensing system (PARS) for imaging a subsurface structure in a sample has an excitation beam configured to generate ultrasonic signals in the sample at an excitation location; an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals; an optical system that focuses at least one of the excitation beam and the interrogation beam with a focal point that is below the surface of the sample; and a detector that detects the returning portion of the interrogation beam.

Photoacoustic remote sensing (pars)

Towards non-contact photoacoustic imaging [review].

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.

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All-optical Reflection-mode Microscopic Histology of Unstained Human Tissues.

Identifying positive surgical margins after resection of cancer often triggers re-excision and adjuvant treatments. Incomplete initial resections result in poorer patient outcomes, psychological and financial stress to the patient and increased healthcare costs. Surgical margins are typically assessed post-operatively using time consuming and expensive slide-based histopathology tissue analysis. Currently, a real-time non-contact virtual histology-like intraoperative margin assessment tool is not available. To address this need, we have developed a non-contact multi-wavelength reflection-mode, photoacoustic remote sensing (PARS) microscope demonstrating chromophore selective contrast in human tissues. We show the capabilities of multi-wavelength PARS microscopy utilizing both 266 nm and 532 nm excitation wavelengths and a 1310 nm detection wavelength. Cell nuclei and hemoglobin were visualized at the cellular scale without the addition of exogenous contrast agents. These works provide a critical step towards a virtual histology tool to provide intraoperative histology-like information in living tissue.

Parsin Haji Reza

Papers

Deep non-contact photoacoustic initial pressure imaging

Photoacoustic remote sensing (pars)

Towards non-contact photoacoustic imaging [review].

All-optical Reflection-mode Microscopic Histology of Unstained Human Tissues.

Chromophore selective multi-wavelength photoacoustic remote sensing of unstained human tissues.