Microscale characterization of prostate biopsies tissues using optical coherence elastography and second harmonic generation imaging.

Photonics, especially optical coherence elastography (OCE) and second harmonic generation (SHG) imaging are novel high-resolution imaging modalities for characterization of biological tissues. Following our preliminary experience, we hypothesized that OCE and SHG imaging would delineate the microstructure of prostate tissue and aid in distinguishing cancer from the normal benign prostatic tissue. Furthermore, these approaches may assist in characterization of the grade of cancer, as well. In this study, we confirmed a high diagnostic accuracy of OCE and SHG imaging in the detection and characterization of prostate cancer for a large set of biopsy tissues obtained from men suspected to have prostate cancer using transrectal ultrasound (TRUS). The two techniques and methods described here are complementary, one depicts the stiffness of tissues and the other illustrates the orientation of collagen structure around the cancerous lesions. The results showed that stiffness of cancer tissue was ~57.63% higher than that of benign tissue (Young's modulus of 698.43±125.29 kPa for cancerous tissue vs 443.07±88.95 kPa for benign tissue with OCE. Using histology as a reference standard and 600 kPa as a cut-off threshold, the data analysis showed sensitivity and specificity of 89.6 and 99.8%, respectively. Corresponding positive and negative predictive values were 99.5 and 94.6%, respectively. There was a significant difference noticed in terms of Young's modulus for different Gleason scores estimated by OCE (P-value<0.05). For SHG, distinct patterns of collagen distribution were seen for different Gleason grade disease with computed quantification employing a ratio of anisotropic to isotropic (A:I ratio) and this correlated with disease aggressiveness.

Quantitative elastography provided by surface acoustic waves measured by phase-sensitive optical coherence tomography.

We report on a quantitative elastography technique achieved by combining phase-sensitive optical coherence tomography (PhS-OCT) with the surface acoustic wave (SAW) method. Different from traditional optical coherence elastography, the elastography is achieved by impulse-stimulated SAW, rather than by shear waves. PhS-OCT serves not only as a detector to measure SAW signals but also as a means to provide a cross-sectional image of the sample. The experimental results indicate that the combination of PhS-OCT with SAW is feasible to provide quantitative elastography of heterogeneous tissue samples.

Loose powder detection and surface characterization in selective laser sintering via optical coherence tomography.

Defects produced during selective laser sintering (SLS) are difficult to non-destructively detect after build completion without the use of X-ray-based methods. Overcoming this issue by assessing integrity on a layer-by-layer basis has become an area of significant interest for users of SLS apparatus. Optical coherence tomography (OCT) is used in this study to detect surface texture and sub-surface powder, which is un-melted/insufficiently sintered, is known to be a common cause of poor part integrity and would prevent the use of SLS where applications dictate assurance of defect-free parts. To demonstrate the capability of the instrument and associated data-processing algorithms, samples were built with graduated porosities which were embedded in fully dense regions in order to simulate defective regions. Simulated in situ measurements were then correlated with the process parameters used to generate variable density regions. Using this method, it is possible to detect loose powder and differentiate between densities of ±5% at a sub-surface depth of approximately 300 µm. In order to demonstrate the value of OCT as a surface-profiling technique, surface texture datasets are compared with focus variation microscopy. Comparable results are achieved after a spatial bandwidth- matching procedure.

Detection and characterisation of biopsy tissue using quantitative optical coherence elastography (OCE) in men with suspected prostate cancer.

We present first quantitative three-dimensional (3D) data sets recorded using optical coherence elastography (OCE) for the diagnosis and detection of prostate cancer (PCa). 120 transrectal ultrasound guided prostate biopsy specimens from 10 men suspected with prostate cancer were imaged using OCE. 3D quantitative mechanical assessment of biopsy specimens obtained in kilopascals (kPa) at an interval of 40 µm was compared with histopathology. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE in comparison to histopathology. The results show OCE imaging could reliably differentiate between benign prostate tissue, acinar atypical hyperplasia, prostatic intraepithelial neoplasia and malignant PCa. The sensitivity and specificity of OCE for the detection of prostate cancer was 0.98 and 0.91 with AUC > 0.99. Quantitative 3D OCE based on the assessment of mechanical properties of tissues can reliably differentiate prostate tissue specimen in an ex-vivo setting. This is a promising imaging modality for characterising different grades of cancers.

Laser induced surface acoustic wave combined with phase sensitive optical coherence tomography for superficial tissue characterization: a solution for practical application.

Mechanical properties are important parameters that can be used to assess the physiologic conditions of biologic tissue. Measurements and mapping of tissue mechanical properties can aid in the diagnosis, characterisation and treatment of diseases. As a non-invasive, non-destructive and non-contact method, laser induced surface acoustic waves (SAWs) have potential to accurately characterise tissue elastic properties. However, challenge still exists when the laser is directly applied to the tissue because of potential heat generation due to laser energy deposition. This paper focuses on the thermal effect of the laser induced SAW on the tissue target and provides an alternate solution to facilitate its application in clinic environment. The solution proposed is to apply a thin agar membrane as surface shield to protect the tissue. Transient thermal analysis is developed and verified by experiments to study the effects of the high energy Nd:YAG laser pulse on the surface shield. The approach is then verified by measuring the mechanical property of skin in a Thiel mouse model. The results demonstrate a useful step toward the practical application of laser induced SAW method for measuring real elasticity of normal and diseased tissues in dermatology and other surface epithelia.

Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves.

The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.

Frequency dependence of laser ultrasonic SAW phase velocities measurements.

Advances in the field of laser ultrasonics have opened up new possibilities in applications in many areas. This paper verifies the relationship between phase velocities of different materials, including hard solid and soft solid, and the frequency range of SAW signal. We propose a novel approach that utilizes a low coherence interferometer to detect the laser-induced surface acoustic waves (SAWs). A Nd:YAG focused laser line-source is applied to steel, iron, plastic plates and a 3.5% agar-agar phantom. The generated SAW signals are detected by a time domain low coherence interferometry system. SAW phase velocity dispersion curves were calculated, from which the elasticity of the specimens was evaluated. The relationship between frequency content and phase velocities was analyzed. We show that the experimental results agreed well with those of the theoretical expectations.

Quantitative evaluation of degenerated tendon model using combined optical coherence elastography and acoustic radiation force method.

Damage of collagen fibers in tendons is often directly related to changes in a tendon's mechanical properties. Direct quantitative elasticity measurement of tendons will provide important information in tendon dysfunction diagnosis and treatment assessment. A feasibility study of quantifying the mechanical properties of a degenerated tendon model by a nondestructive imaging modality, which combines optical coherence elastography and acoustic radiation force (ARF) method, is presented. The degenerated tendon model was produced by the partial degradation of chicken tendons through incubation with collagenase at different concentrations and incubation times. A 30-kHz longitudinal ultrasound transducer was used to provide an ARF signal, which was detected by an ultra-high sensitive phase sensitive optical coherence tomography (PhS-OCT) system. The experimental results demonstrate that the combination of ARF method and PhS-OCT can measure the elasticity of tendon quantitatively. The corresponding changes in tendon elasticity due to the application of collagenase have been revealed by this new imaging modality. This method can potentially be used in the assessment of tissue engineering products and in the diagnosis and treatment progression of tendon diseases.

Determining elastic properties of skin by measuring surface waves from an impulse mechanical stimulus using phase-sensitive optical coherence tomography.

The mechanical properties of skin are important tissue parameters that are useful for understanding skin patho-physiology, which can aid disease diagnosis and treatment. This paper presents an innovative method that employs phase-sensitive spectral-domain optical coherence tomography (PhS-OCT) to characterize the biomechanical properties of skin by measuring surface waves induced by short impulses from a home-made shaker. Experiments are carried out on single and double-layer agar-agar phantoms, of different concentrations and thickness, and on in vivo human skin, at the forearm and the palm. For each experiment, the surface wave phase-velocity dispersion curves were calculated, from which the elasticity of each layer of the sample was determined. It is demonstrated that the experimental results agree well with previous work. This study provides a novel combination of PhS-OCT technology with a simple and an inexpensive mechanical impulse surface wave stimulation that can be used to non-invasively evaluate the mechanical properties of skin in vivo, and may offer potential use in clinical situations.

Evaluating elastic properties of heterogeneous soft tissue by surface acoustic waves detected by phase-sensitive optical coherence tomography.

The combined use of surface acoustic wave (SAW) and phase-sensitive optical coherence tomography (PhS-OCT) is useful to evaluate the elasticity of layered biological tissues, such as normal skin. However, the pathological tissue is often originated locally, leading to the alternation of mechanical properties along both axial and lateral directions. We present a feasibility study on whether the SAW technique is sensitive to detect the alternation of mechanical property along the lateral direction within tissue, which is important for clinical utility of this technique to localize diseased tissue. Experiments are carried out on purposely designed tissue phantoms and ex vivo chicken breast samples, simulating the localized change of elasticity. A PhS-OCT system is employed not only to provide the ultra-high sensitive measurement of the generated surface waves on the tissue surface, but also to provide the real time imaging of the tissue to assist the elasticity evaluation of the heterogeneous tissue. The experimental results demonstrate that with PhS-OCT used as a pressure sensor, the SAW is highly sensitive to the elasticity change of the specimen in both vertical and lateral directions with a sensing depth of ∼5 mm with our current system setup, thus promising its useful clinical applications where the quantitative elasticity of localized skin diseases is needed to aid in diagnosis and treatment.

Multifunctional nanoprobe to enhance the utility of optical based imaging techniques.

Several imaging modalities such as optical coherence tomography, photothermal, photoacoustic and magnetic resonance imaging, are sensitive to different physical properties (i.e. scattering, absorption and magnetic) that can provide contrast within biological tissues. Usually exogenous agents are designed with specific properties to provide contrast for these imaging methods. In nano-biotechnology there is a need to combine several of these properties into a single contrast agent. This multifunctional contrast agent can then be used by various imaging techniques simultaneously or can be used to develop new imaging modalities. We reported and characterized a multifunctional nanoparticle, made from gold nanoshells, which exhibits scattering, photothermal, photoacoustic, and magnetic properties.

Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography.

A model that describes the concentration of photothermal (light-to-heat converters) compounds as a function of depth in a turbid medium is developed. The system consists of a pump laser (808 nm modulated at 400 Hz), which heats a photothermal compound, and a phase sensitive spectral domain optical coherence tomography system, which detects the changes in the optical path length of the sample induced by the temperature increase. The model is theoretically derived and the coefficients are empirically determined using solid homogeneous gel phantoms. The model is validated by reconstructing the concentration of a photothermal compound in thick single and double layer solid phantoms.

High-speed 1310 nm-band spectral domain optical coherence tomography at 184,000 lines per second.

We propose a useful method to boost the imaging speed for spectral domain optical coherence tomography (SDOCT) by multiplying a number of high-speed spectrometers used in the system with selective precise control of data-recording and data-reading phases for spectral cameras employed in each spectrometer. To demonstrate the proposed method, we use two spectrometers built in a 1310 nm-band SDOCT system, each equipped with a high-speed InGaAs line-scan camera capable of 92-kHz line-scan rate, to achieve an unprecedented imaging speed at 184,000 lines/s. We validate the multiplied imaging speed by measuring Doppler-induced phase shift in the spectrograms using a flow phantom.