This tutorial-review introduces the fundamentals of polarized light interaction with biological tissues and presents some of the recent key polarization optical methods that have made possible the ...quantitative studies essential for biomedical diagnostics. Tissue structures and the corresponding models showing linear and circular birefringence, dichroism, and chirality are analyzed. As the basis for a quantitative description of the interaction of polarized light with tissues, the theory of polarization transfer in a random medium is used. This theory employs the modified transfer equation for Stokes parameters to predict the polarization properties of single- and multiple-scattered optical fields. The near-order of scatterers in tissues is accounted for to provide an adequate description of tissue polarization properties. Biomedical diagnostic techniques based on polarized light detection, including polarization imaging and spectroscopy, amplitude and intensity light scattering matrix measurements, and polarization-sensitive optical coherence tomography are described. Examples of biomedical applications of these techniques for early diagnostics of cataracts, detection of precancer, and prediction of skin disease are presented. The substantial reduction of light scattering multiplicity at tissue optical clearing that leads to a lesser influence of scattering on the measured intrinsic polarization properties of the tissue and allows for more precise quantification of these properties is demonstrated.
The recent developments in time-domain diffuse optics that rely on physical concepts (e.g., time-gating and null distance) and advanced photonic components (e.g., vertical cavity source-emitting ...laser as light sources, single photon avalanche diode, and silicon photomultipliers as detectors, fast-gating circuits, and time-to-digital converters for acquisition) are focused. This study shows how these tools could lead on one hand to compact and wearable time-domain devices for point-of-care diagnostics down to the consumer level and on the other hand to powerful systems with exceptional depth penetration and sensitivity.
A pioneer in optics based on his development of novel optical imaging techniques and acknowledged by a long list of honors, Lihong V. Wang is a model for the aspiring young student or investigator ...pursuing a career in the rapidly expanding field of biomedical optics and biophotonics.
Biomedical photoacoustic tomography, which can provide high-resolution 3D soft tissue images based on optical absorption, has advanced to the stage at which translation from the laboratory to ...clinical settings is becoming possible. The need for rapid image formation and the practical restrictions on data acquisition that arise from the constraints of a clinical workflow are presenting new image reconstruction challenges. There are many classical approaches to image reconstruction, but ameliorating the effects of incomplete or imperfect data through the incorporation of accurate priors is challenging and leads to slow algorithms. Recently, the application of deep learning (DL), or deep neural networks, to this problem has received a great deal of attention. We review the literature on learned image reconstruction, summarizing the current trends and explain how these approaches fit within, and to some extent have arisen from, a framework that encompasses classical reconstruction methods. In particular, it shows how these techniques can be understood from a Bayesian perspective, providing useful insights. We also provide a concise tutorial demonstration of three prototypical approaches to learned image reconstruction. The code and data sets for these demonstrations are available to researchers. It is anticipated that it is in in vivo applications—where data may be sparse, fast imaging critical, and priors difficult to construct by hand—that DL will have the most impact. With this in mind, we conclude with some indications of possible future research directions.
SignificancePhotoacoustic microscopy (PAM) is a promising imaging technique to provide structural, functional, and molecular information for preclinical and clinical studies. However, expensive and ...bulky lasers and motorized stages have limited the broad applications of conventional PAM systems. A recent trend is to use low-cost light sources and miniaturized designs to develop a compact PAM system and expand its applications from benchtop to bedside.AimWe provide (1) an overview of PAM systems and their limitations, (2) a comprehensive review of PAM systems with low-cost light sources and their applications, (3) a comprehensive review of PAM systems with miniaturized and handheld scanning designs, and (4) perspective applications and a summary of the cost-effective and miniaturized PAM systems.ApproachPapers published before July 2023 in the area of using low-cost light sources and miniaturized designs in PAM were reviewed. They were categorized into two main parts: (1) low-cost light sources and (2) miniaturized or handheld designs. The first part was classified into two subtypes: pulsed laser diode and continuous-wave laser diode. The second part was also classified into two subtypes: galvanometer scanner and micro-electro-mechanical system scanner.ResultsSignificant progress has been made in the development of PAM systems based on low-cost and compact light sources as well as miniaturized and handheld designs.ConclusionsThe review highlights the potential of these advancements to revolutionize PAM technology, making it more accessible and practical for various applications in preclinical studies, clinical practice, and long-term monitoring.
Advancements in label-free microscopy could provide real-time, non-invasive imaging with unique sources of contrast and automated standardized analysis to characterize heterogeneous and dynamic ...biological processes. These tools would overcome challenges with widely used methods that are destructive (e.g., histology, flow cytometry) or lack cellular resolution (e.g., plate-based assays, whole animal bioluminescence imaging).
This perspective aims to (1) justify the need for label-free microscopy to track heterogeneous cellular functions over time and space within unperturbed systems and (2) recommend improvements regarding instrumentation, image analysis, and image interpretation to address these needs.
Three key research areas (cancer research, autoimmune disease, and tissue and cell engineering) are considered to support the need for label-free microscopy to characterize heterogeneity and dynamics within biological systems. Based on the strengths (e.g., multiple sources of molecular contrast, non-invasive monitoring) and weaknesses (e.g., imaging depth, image interpretation) of several label-free microscopy modalities, improvements for future imaging systems are recommended.
Improvements in instrumentation including strategies that increase resolution and imaging speed, standardization and centralization of image analysis tools, and robust data validation and interpretation will expand the applications of label-free microscopy to study heterogeneous and dynamic biological systems.
SignificanceThe classification of melasma is critical for correct clinical diagnosis, treatment selection, and postoperative measures. However, preoperative quantitative determination of melasma type ...remains challenging using conventional Wood's lamp and optical dermoscopy techniques.AimUsing photoacoustic microscopy (PAM) to simultaneously obtain the two diagnostic indicators of melanin and blood vessels for melasma classification and perform quantitative analysis to finally achieve accurate classification, rather than relying solely on physicians' experience.ApproachFirst, the patients were classified by experienced dermatologists with Wood's lamp and optical dermoscopy. Next, the patients were examined in vivo using the PAM imaging system. Further, the horizontal section images (X-Y plane) of epidermal melanin and dermal vascular involvement were extracted from the 3D photoacoustic imaging results, which are important basis for PAM to quantitatively classify melasma.ResultsPAM can quantitatively reveal epidermal thickness and dermal vascular morphology in each case and obtain the quantitative diagnostic indicators of melanin and blood vessels. The mean vascular diameter in lesional skin (223.2 μm) of epidermal M+V-type was much larger than that in non-lesional skin (131.6 μm), and the mean vascular density in lesional skin was more than three times that in non-lesional skin. Importantly, vascular diameter and density are important parameters for distinguishing M type from M+V type.ConclusionsPAM can obtain the data of epidermal thickness, pigment depth, subcutaneous vascular diameter, and vascular density, and realize the dual standard quantitative melasma classification by combining the parameters of melanin and blood vessels. In addition, PAM can provide new diagnostic information for uncertain melasma types and further refine the typing.
Quantitative optical polarimetry has received considerable recent attention owing to its potential for being an efficient diagnosis and characterizing tool with potential applications in biomedical ...research and various other disciplines. In this regard, it is crucial to validate various Mueller matrix (MM) decomposition methods, which are utilized to extract and quantify the intrinsic individual polarization anisotropy properties of various complex optical media.
To quantitatively compare the performance of both polar and differential MM decomposition methods for probing the structural and morphological changes in complex optical media through analyzing their intrinsic individual polarization parameters, which are extracted using the respective decomposition algorithms. We also intend to utilize the decomposition-derived anisotropy parameters to distinguish among the cervical tissues with different grades of cervical intraepithelial neoplasia (CIN) and to characterize the healing efficiency of an organic crystal.
Polarization MM of the cervical tissues with different grades of CIN and the different stages of the self-healing crystal are recorded with a home-built MM imaging setup in the transmission detection geometry with a spatial resolution of
. The measured MMs are then processed with both the polar and differential MM decomposition methods to extract the individual polarization parameters of the respective samples. The derived polarization parameters are further analyzed to validate and compare the performance of both the MM decomposition methods for probing and characterizing the structural changes in the respective investigated optical media through their decomposition-derived intrinsic individual polarization properties.
Pronounced differences in the decomposed-derived polarization anisotropy parameters are observed for cervical tissue sections with different grades of CIN. While a significant increase in the depolarization parameter
is obtained with the increment of CIN stages for both the polar
for CIN grade one (CIN-I) and
for CIN grade two (CIN-II)) and differential (
for CIN-I and
for CIN-II) decomposition methods, a trend reversal is seen for the linear diattenuation parameter
, indicating the structural distortion in the cervical morphology due to the CIN disease. More importantly, with the differential decomposition algorithm, the magnitude of the derived
parameter decreases from 0.26 to 0.19 with the progression of CIN, which was not being probed by the polar decomposition method.
Our results demonstrate that the differential decomposition of MM holds certain advantages over the polar decomposition method to characterize and probe the structural changes in the cervical tissues with different grades of CIN. Although the quantified individual polarization parameters obtained through both the MM decomposition methods can be used as useful metrics to characterize various optical media, in case of complex turbid media such as biological tissues, incorporation of the differential decomposition technique may yield more efficient information. Also, the study highlights the utilization of MM polarimetry with an appropriate decomposition technique as an efficient diagnostic and characterizing tool in the realm of biomedical clinical research, and various other disciplines.
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