Real-time in vivo visualization of tissue oxygenation and autofluorescence with a snapshot hyperspectral camera for detection of precancerous lesions

Author(s):  
Noah Bedard ◽  
Tomasz Tkaczyk
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chenchen Ren ◽  
Xianxu Zeng ◽  
Zhongna Shi ◽  
Chunyan Wang ◽  
Huifen Wang ◽  
...  

AbstractIn this prospective study of an in-vivo cervical examination using optical coherence tomography (OCT), we evaluated the diagnostic value of non-invasive and real-time OCT in cervical precancerous lesions and cancer diagnosis, and determined the characteristics of OCT images. 733 patients from 5 Chinese hospitals were inspected with OCT and colposcopy-directed biopsy. The OCT images were compared with the histological sections to find out the characteristics of various categories of lesions. The OCT images were also interpreted by 3 investigators to make a 2-class classification, and the results were compared against the pathological results. Various structures of the cervical tissue were clearly observed in OCT images, which matched well with the corresponding histological sections. The OCT diagnosis results delivered a sensitivity of 87.0% (95% confidence interval, CI 82.2–90.7%), a specificity of 84.1% (95% CI 80.3–87.2%), and an overall accuracy of 85.1%. Both good consistency of OCT images and histological images and satisfactory diagnosis results were provided by OCT. Due to its features of non-invasion, real-time, and accuracy, OCT is valuable for the in-vivo evaluation of cervical lesions and has the potential to be one of the routine cervical diagnosis methods.


2020 ◽  
Author(s):  
Chenchen Ren ◽  
Xianxu Zeng ◽  
Zhongna Shi ◽  
Chunyan Wang ◽  
Huifen Wang ◽  
...  

Objective: In this prospective study of an in-vivo cervical examination using optical coherence tomography (OCT), we evaluated the diagnostic value of non-invasive and real-time OCT in cervical precancerous lesions and cancer diagnosis, and determined the characteristics of OCT images. Methods: 733 patients from 5 Chinese hospitals were inspected with OCT and colposcopy-directed biopsy. The OCT images were compared with the histological sections to find out the characteristics of various categories of lesions. The OCT images were also interpreted by 3 investigators to make a 2-class classification, and the results were compared against the pathological results. Results: Various structures of the cervical tissue were clearly observed in OCT images, which matched well with the corresponding histological sections. The OCT diagnosis results delivered a sensitivity of 87.0% (95% confidence interval, CI, 82.2%-90.7%), a specificity of 84.1% (95% CI, 80.3%-87.2%), and an overall accuracy of 85.1%. Conclusion: Both good consistency of OCT images and histological images and satisfactory diagnosis results were provided by OCT. Due to its features of non-invasion, real-time, and accuracy, OCT is valuable for the in-vivo evaluation of cervical lesions and has the potential to be one of the routine cervical diagnosis methods.


2007 ◽  
Vol 61 (8) ◽  
pp. 797-803 ◽  
Author(s):  
Nicole J. Crane ◽  
Zachary D. Schultz ◽  
Ira W. Levin

Results are presented illustrating a straightforward algorithm to be used for real-time monitoring of oxygenation levels in blood cells and tissue based on the visible spectrum of hemoglobin. Absorbance images obtained from the visible reflection of white light through separate red and blue bandpass filters recorded by monochrome charge-coupled devices (CCDs) are combined to create enhanced images that suggest a quantitative correlation between the degree of oxygenated and deoxygenated hemoglobin in red blood cells. The filter bandpass regions are chosen specifically to mimic the color response of commercial 3-CCD cameras, representative of detectors with which the operating room laparoscopic tower systems are equipped. Adaptation of this filter approach is demonstrated for laparoscopic donor nephrectomies in which images are analyzed in terms of real-time in vivo monitoring of tissue oxygenation.


2019 ◽  
Vol 15 (5) ◽  
pp. 567-574
Author(s):  
Huck Jun Hong ◽  
Suw Young Ly

Background: Tetrodotoxin (TTX) is a biosynthesized neurotoxin that exhibits powerful anticancer and analgesic abilities by inhibiting voltage-gated sodium channels that are crucial for cancer metastasis and pain delivery. However, for the toxin’s future medical applications to come true, accurate, inexpensive, and real-time in vivo detection of TTX remains as a fundamental step. Methods: In this study, highly purified TTX extracted from organs of Takifugu rubripes was injected and detected in vivo of mouse organs (liver, heart, and intestines) using Cyclic Voltammetry (CV) and Square Wave Anodic Stripping Voltammetry (SWASV) for the first time. In vivo detection of TTX was performed with auxiliary, reference, and working herring sperm DNA-immobilized carbon nanotube sensor systems. Results: DNA-immobilization and optimization of amplitude (V), stripping time (sec), increment (mV), and frequency (Hz) parameters for utilized sensors amplified detected peak currents, while highly sensitive in vivo detection limits, 3.43 µg L-1 for CV and 1.21 µg L-1 for SWASV, were attained. Developed sensors herein were confirmed to be more sensitive and selective than conventional graphite rodelectrodes modified likewise. A linear relationship was observed between injected TTX concentration and anodic spike peak height. Microscopic examination displayed coagulation and abnormalities in mouse organs, confirming the powerful neurotoxicity of extracted TTX. Conclusion: These results established the diagnostic measures for TTX detection regarding in vivo application of neurotoxin-deviated anticancer agents and analgesics, as well as TTX from food poisoning and environmental contamination.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yusaku Hontani ◽  
Mikhail Baloban ◽  
Francisco Velazquez Escobar ◽  
Swetta A. Jansen ◽  
Daria M. Shcherbakova ◽  
...  

AbstractNear-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes are widely used for structural and functional deep-tissue imaging in vivo. To fluoresce, NIR FPs covalently bind a chromophore, such as biliverdin IXa tetrapyrrole. The efficiency of biliverdin binding directly affects the fluorescence properties, rendering understanding of its molecular mechanism of major importance. miRFP proteins constitute a family of bright monomeric NIR FPs that comprise a Per-ARNT-Sim (PAS) and cGMP-specific phosphodiesterases - Adenylyl cyclases - FhlA (GAF) domain. Here, we structurally analyze biliverdin binding to miRFPs in real time using time-resolved stimulated Raman spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations. Biliverdin undergoes isomerization, localization to its binding pocket, and pyrrolenine nitrogen protonation in <1 min, followed by hydrogen bond rearrangement in ~2 min. The covalent attachment to a cysteine in the GAF domain was detected in 4.3 min and 19 min in miRFP670 and its C20A mutant, respectively. In miRFP670, a second C–S covalent bond formation to a cysteine in the PAS domain occurred in 14 min, providing a rigid tetrapyrrole structure with high brightness. Our findings provide insights for the rational design of NIR FPs and a novel method to assess cofactor binding to light-sensitive proteins.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


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