Author Affiliations
Abstract
1 Britton Chance Laboratory of Redox Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2 Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA
3 Center for Biostatistics and Epidemiology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Adenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles. Mutations or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular diseases. We aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-deficient mice. Hearts and quadriceps resected from age-matched wild type (WT) and ANT1-deficient mice were snap-frozen in liquid nitrogen. The Chance redox scanner was utilized to perform 3D optical redox imaging. Each sample underwent scanning across 3–5 sections. Global averaging analysis showed no significant differences in the redox indices (NADH, flavin adenine dinucleotide containing-flavoproteins Fp, and the redox ratio Fp/(NADH+Fp) between WT and ANT1-deficient groups. However, quadriceps had higher Fp than hearts in both groups (p=0.0004 and 0.01, respectively). Furthermore, the quadriceps were also more oxidized (a higher redox ratio) than hearts in WT group (p=0.004). NADH levels were similar in all cases. Our data suggest that under non-stressful physical condition, the ANT1-deficient muscle cells were in the same mitochondrial state as WT ones and that the significant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-deficient ones. Redox imaging of muscles under physical stress can be conducted in future.
ANT1 redox ratio flavoproteins 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350032
Author Affiliations
Abstract
Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA
Nicotinamide adenine dinucleotide (NADH) is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS). NADH is autofluorescent, and its fluorescence lifetime can be used to infer metabolic dynamics in living cells. Fiber-coupled time-correlated single photon counting (TCSPC) equipped with an implantable needle probe can be used to measure NADH lifetime in vivo, enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration. This study illustrates a proof of concept for point-based, minimally-invasive NADH fluorescence lifetime measurement in vivo. Volumetric muscle loss (VML) injuries were created in the left tibialis anterior (TA) muscle of male Sprague Dawley rats. NADH lifetime measurements were collected before, during, and after a 30s tetanic contraction in the injured and uninjured TA muscles, which was subsequently fit to a biexponential decay model to yield a metric of NADH utilization (cytoplasmic vs protein-bound NADH, the A1τ1/A2τ2 ratio). On average, this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest, suggesting higher levels of free NADH in contracting and recovering muscle, indicating increased rates of glycolysis. In injured muscle, this ratio was higher than uninjured muscle overall but decreased over time, which is consistent with current knowledge of inflammatory response to injury, suggesting tissue regeneration has occurred. These data suggest that fiber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.
Glycolysis oxidative phosphorylation energy metabolism volumetric muscle loss 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350030
Author Affiliations
Abstract
1 State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical, Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou 310058, P. R. China
2 Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, P. R. China
3 College of Biomedical Engineering and Instrument Science, Interdisciplinary Institute of Neuroscience and Technology (ZIINT), Zhejiang University, Hangzhou 310027, P. R. China
Fluorescence imaging in the second near-infrared window (NIR-II, 900–1880nm) with less scattering background in biological tissues has been combined with the confocal microscopic system for achieving deep in vivo imaging with high spatial resolution. However, the traditional NIR-II fluorescence confocal microscope with separate excitation focus and detection pinhole makes it possess low confocal efficiency, as well as difficultly to adjust. Two types of upgraded NIR-II fluorescence confocal microscopes, sharing the same pinhole by excitation and emission focus, leading to higher confocal efficiency, are built in this work. One type is fiber-pinhole-based confocal microscope applicable to CW laser excitation. It is constructed for fluorescence intensity imaging with large depth, high stabilization and low cost, which could replace multiphoton fluorescence microscopy in some applications (e.g., cerebrovascular and hepatocellular imaging). The other type is air-pinhole-based confocal microscope applicable to femtosecond (fs) laser excitation. It can be employed not only for NIR-II fluorescence intensity imaging, but also for multi-channel fluorescence lifetime imaging to recognize different structures with similar fluorescence spectrum. Moreover, it can be facilely combined with multiphoton fluorescence microscopy. A single fs pulsed laser is utilized to achieve up-conversion (visible multiphoton fluorescence) and down-conversion (NIR-II one-photon fluorescence) excitation simultaneously, extending imaging spectral channels, and thus facilitates multi-structure and multi-functional observation.
Self-confocal fiber-pinhole air-pinhole multi-channel fluorescence lifetime imaging multi-color imaging 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350025
Shan Long 1,2Yibing Zhao 3Yuanyuan Xu 2Bo Wang 4[ ... ]Ying Gu 1,2,**
Author Affiliations
Abstract
1 School of Medicine, Nankai University, Tianjin, 300072, P. R. China
2 Department of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. China
3 Department of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing 100039, P. R. China
4 School of Basic Medicine, Guizhou Medical University, Guiyang 550025, Guizhou, P. R. China
5 College of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
6 Medical School of Chinese PLA, Beijing 100853, P. R. China
Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4+T, CD8+T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100mW/cm2 and 40, 60 and 80J/cm2, primary tumors were suppressed and CD4+T, CD8+T and CRT were elevated; however, distant tumors couldn’t be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4+T, CD8+T, IFN-γ+CD4+T and TNF-α+CD4+T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.
Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor immune effects metastatic breast cancer 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350020
Author Affiliations
Abstract
1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, P. R. China
2 College of Biophotonics, South China Normal University, Guangzhou 510631, P. R. China
3 School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350004, P. R. China
In this work, we present an intravascular dual-mode endoscopic system capable of both intravascular photoacoustic imaging (IVPAI) and intravascular optical coherence tomography (IVOCT) for recognizing spontaneous coronary artery dissection (SCAD) phantoms. IVPAI provides high-resolution and high-penetration images of intramural hematoma (IMH) at different depths, so it is especially useful for imaging deep blood clots associated with imaging phantoms. IVOCT can readily visualize the double-lumen morphology of blood vessel walls to identify intimal tears. We also demonstrate the capability of this dual-mode endoscopic system using mimicking phantoms and biological samples of blood clots in ex vivo porcine arteries. The results of the experiments indicate that the combined IVPAI and IVOCT technique has the potential to provide a more accurate SCAD assessment method for clinical applications.
Spontaneous coronary artery dissection (SCAD) intravascular optical coherence tomography (IVOCT) intravascular photoacoustic imaging (IVPAI) 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350016
Author Affiliations
Abstract
1 Department of Pain Management, The First Affiliated Hospital, Jinan University, Guang Zhou, Guangdong 510630, P. R. China
2 Department of Pain Management, The First People’s Hospital of Foshan, Foshan City, Guangdong 528000, P. R. China
Temporary spinal cord stimulation (tSCS) can effectively reduce the pain and severity of postherpetic neuralgia (PHN). However, there are no effective and objective methods for predicting the effects of tSCS on PHN. Laser speckle contrast imaging (LSCI) is frequently used in neurology to evaluate the effectiveness of treatment. To assess the accuracy of LSCI in predicting the impact of tSCS on PHN, 14 adult patients receiving tSCS treatments for spinal nerve-innervated (C6-T2) PHN participated in this observational study. Visual analog scale (VAS) assessments and LSCI blood flow images of the fingers were recorded after the tSCS procedure. The results showed that the VAS scores of all patients decreased significantly. Moreover, the blood flow index (BFI) values were significantly higher than they were before the procedure. Increased blood flow and pain alleviation were positively correlated. The findings indicated that spinal nerve PHN (C6-T2) was significantly reduced by tSCS. Pain alleviation by tSCS was positively correlated with increased blood flow in the hand. The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.
Laser speckle contrast imaging temporary spinal cord stimulation postherpetic neuralgia 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350014
Author Affiliations
Abstract
Key Laboratory of Optoelectronic Devices, and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060 P. R. China
Measurement of blood flow velocity is key to understanding physiology and pathology in vivo. While most measurements are performed at the middle of the blood vessel, little research has been done on characterizing the instantaneous blood flow velocity distribution. This is mainly due to the lack of measurement technology with high spatial and temporal resolution. Here, we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation (THG) imaging technology. Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of blood flow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo. Our results clearly show that the instantaneous blood flow velocity is not symmetric under general conditions.
1700nm-Window third-harmonic generation imaging blood flow velocity 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350011
Author Affiliations
Abstract
1 The Key Laboratory of Weak-Light Nonlinear, Photonics of Education Ministry, School of Physics and TEDA Institute of Applied Physics, Nankai University, Tianjin 300071, P. R. China
2 State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, P. R. China
3 Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006, P. R. China
4 Shenzhen Research Institute of Nankai University, Shenzhen, Guangdong 518083, P. R. China
Cells are highly sensitive to their geometrical and mechanical microenvironment that directly regulate cell shape, cytoskeleton and organelle, as well as the nucleus morphology and genetic expression. The emerging two-dimensional micropatterning techniques offer powerful tools to construct controllable and well-organized microenvironment for single-cell level investigations with qualitative analysis, cellular standardization, and in vivo environment mimicking. Here, we provide an overview of the basic principle and characteristics of the two most widely-used micropatterning techniques, including photolithographic micropatterning and soft lithography micropatterning. Moreover, we summarize the application of micropatterning technique in controlling cytoskeleton, cell migration, nucleus and gene expression, as well as intercellular communication.
Two-dimensional micropatterning cytoskeleton cell migration extracellular matrix intercellular communication gene expression 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2330011
Author Affiliations
Abstract
1 Department of General Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, P. R. China
2 Department of Hepatobiliary Surgery and Centre for Leading, Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
3 Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, P. R. China
4 Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, P. R. China
In liver tumor surgery, the recognition of tumor margin and radical resection of microcancer focis have always been the crucial points to reduce postoperative recurrence of tumor. However, naked-eye inspection and palpation have limited effectiveness in identifying tumor boundaries, and traditional imaging techniques cannot consistently locate tumors in real time. As an intraoperative real-time navigation imaging method, NIR fluorescence imaging has been extensively studied for its simplicity, reliable safety, and superior sensitivity, and is expected to improve the accuracy of liver tumor surgery. In recent years, the research focus of NIR fluorescence has gradually shifted from the first near-infrared window (NIR-I, 700–900 nm) to the second near-infrared window (NIR-II, 1000–1700nm). Fluorescence imaging in NIR-II reduces the scattering effect of deep tissue, providing a preferable detection depth and spatial resolution while significantly eliminating liver autofluorescence background to clarify tumor margin. Developing fluorophores combined with tumor antibodies will further improve the precision of fluorescence-guided surgical navigation. With the development of a bunch of fluorophores with phototherapy ability, NIR-II can integrate tumor detection and treatment to explore a new therapeutic strategy for liver cancer. Here, we review the recent progress of NIR-II fluorescence technology in liver tumor surgery and discuss its challenges and potential development direction.
Fluorescence guided-surgery liver cancer near infrared-II optical imaging 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2330010
Author Affiliations
Abstract
1 Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University Chengdu 610064, Sichuan, P. R. China
2 Research Center of Analytical Instrumentation, School of Mechanical Engineering, Sichuan University, Chengdu 610064, Sichuan, P. R. China
3 Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University Chengdu 610064, Sichuan, P. R. China
4 State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, P. R. China
Laser spectroscopic imaging techniques have received tremendous attention in the field of cancer diagnosis due to their high sensitivity, high temporal resolution, and short acquisition time. However, the limited tissue penetration of the laser is still a challenge for the in vivo diagnosis of deep-seated lesions. Nanomaterials have been universally integrated with spectroscopic imaging techniques for deeper cancer diagnosis in vivo. The components, morphology, and sizes of nanomaterials are delicately designed, which could realize cancer diagnosis in vivo or in situ. Considering the enhanced signal emitting from the nanomaterials, we emphasized their combination with spectroscopic imaging techniques for cancer diagnosis, like the surface-enhanced Raman scattering (SERS), photoacoustic, fluorescence, and laser-induced breakdown spectroscopy (LIBS). Applications of the above spectroscopic techniques offer new prospects for cancer diagnosis.
Laser spectroscopy tumor imaging tumor diagnosis nanomaterials 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2330008

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