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.
Most biological fibrous tissues have anisotropic optical characteristics, which originate from scattering by their fibrous microstructures and birefringence of biological macromolecules. The ...orientation-related anisotropic interpretation is of great value in biological tissue characterization and pathological diagnosis.
We focus on intrinsic birefringence and form birefringence in biological tissue samples. By observing and comparing the forward Mueller matrix of typical samples, we can understand the interpretation ability of orientation-related polarization parameters and further distinguish the sources and trends of anisotropy in tissues.
For glass fiber, silk fiber, skeletal muscle, and tendon, we construct a forward measuring device to obtain the Mueller matrix image and calculate the anisotropic parameters related to orientation. The statistical analysis method based on polar coordinates can effectively analyze the difference in anisotropic parameters.
For those birefringent fibers, the statistical distribution of fast-axis values derived from Mueller matrix polar decomposition was found to exhibit bimodal characteristics, which is a key point in distinguishing the single-layer birefringent fiber sample from a layered, multioriented fibrous sample. The application conditions and interference factors of anisotropic orientation parameters are analyzed. Based on the parameters extracted from the orientation bimodal distribution, we can evaluate the relative change trend of intrinsic birefringence and form birefringence in anisotropic samples.
The cross-vertical bimodal distribution of the fast axis of anisotropic fibers is beneficial to accurately analyze the anisotropic changes in biological tissues. The results imply the potential of anisotropic orientation analysis for applications in pathological diagnosis.
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.
Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled ...improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)-induced PpIX fluorescence in a series of patients with LGG.
Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 mg/kg of ALA approximately 3 hours prior to surgery under an institutional review board-approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology.
Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX CPpIX > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively.
The authors' initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors' initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs.
Deep Learning in Biomedical Optics Tian, Lei; Hunt, Brady; Bell, Muyinatu A. Lediju ...
Lasers in surgery and medicine,
August 2021, Letnik:
53, Številka:
6
Journal Article
In nonballistic regime, optical scattering impedes high-resolution imaging through/inside complex media, such as milky liquid, fog, multimode fiber, and biological tissues, where confocal and ...multiphoton modalities fail. The significant tissue inhomogeneity-induced distortions need to be overcome and a technique referred as optical wavefront shaping (WFS), first proposed in 2007, has been becoming a promising solution, allowing for flexible and powerful light control. Understanding the principle and development of WFS may inspire exciting innovations for effective optical manipulation, imaging, stimulation, and therapy at depths in tissue or tissue-like complex media.
We aim to provide insights about what limits the WFS towards biomedical applications, and how recent efforts advance the performance of WFS among different trade-offs.
By differentiating the two implementation directions in the field, i.e., precompensation WFS and optical phase conjugation (OPC), improvement strategies are summarized and discussed.
For biomedical applications, improving the speed of WFS is most essential in both directions, and a system-compatible wavefront modulator driven by fast apparatus is desired. In addition to that, algorithm efficiency and adaptability to perturbations/noise is of concern in precompensation WFS, while for OPC significant improvements rely heavily on integrating physical mechanisms and delicate system design for faster response and higher energy gain.
Substantial improvements in WFS implementations, from the aspects of physics, engineering, and computing, have inspired many novel and exciting optical applications that used to be optically inaccessible. It is envisioned that continuous efforts in the field can further advance WFS towards biomedical applications and guide our vision into deep biological tissues.
SignificanceWavefront shaping (WFS) can compensate for distortions by optimizing the wavefront of the input light or reversing the transmission matrix of the media. It is a promising field of ...research. A thorough understanding of principles and developments of WFS is important for optical research.AimTo provide insight into WFS for researchers who deal with scattering in biomedicine, imaging, and optical communication, our study summarizes the basic principles and methods of WFS and reviews recent progress.ApproachThe basic principles, methods of WFS, and the latest applications of WFS in focusing, imaging, and multimode fiber (MMF) endoscopy are described. The practical challenges and prospects of future development are also discussed.ResultsData-driven learning-based methods are opening up new possibilities for WFS. High-resolution imaging through MMFs can support small-diameter endoscopy in the future.ConclusionThe rapid development of WFS over the past decade has shown that the best solution is not to avoid scattering but to find ways to correct it or even use it. WFS with faster speed, more optical modes, and more modulation degrees of freedom will continue to drive exciting developments in various fields.
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