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Single-photon-level imaging has been utilized for decades in closed dark environments; however, the utility for macroscopic imaging is more limited because it involves time-gating, filtering, and processing to view signals of interest. In radiation therapy delivery, a low-level signal called Cherenkov emission occurs from patients’ bodies, which is imaged with single-photon level sensitivity, mapping radiation dose deposition in tissue. Several key technological advances have been leveraged to make this extremely low-light signal overcome high background and noise in clinical settings.
Aim
Our review summarizes specific technological advances that have led to a single-photon imaging in high radiation noise and high optical background environments possible. Our work discusses applications and future opportunities.
Approach
Physical fundamentals of Cherenkov light, ambient room light, optical filtering, time-gating, and image processing are reviewed with key technological camera choices. This is followed by discussion of image quality, noise, and postprocessing, with current and future applications.
Results
Invention and optimization of time-gating techniques and cameras with a single-photon capability were required to achieve real-time Cherenkov imaging. Requirements of video frame rate (≈10 to 30 fps), fast triggering (≈μs), clinically relevant spatial resolution (≈mm), single-photon/pixel sensitivity, and large field of view all led to intensified complementary metal-oxide-semiconductor cameras. Additional innovations in wavelength filtering, lens choices, and spatial and temporal postprocessing have allowed imaging that is not overwhelmed by ambient radiation noise or room lights. The current use provides real-time visualization of external beam radiotherapy on patient’s skin. Several emerging research areas may improve image quality and provide additional capabilities in biochemical sensing and quantification of delivery.
Conclusion
The technical inventions and discoveries on how this light signal is sampled have led to real-time beam observation for dose delivery verification in settings where single-photon sensitive imaging is seemingly implausible while also opening the door to additional research applications.
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Diagnosis of cancerous and pre-cancerous oral lesions at early stages is critical for the improvement of patient care, to increase survival rates and minimize the invasiveness of tumor resection surgery. Unfortunately, oral precancerous and early-stage cancerous lesions are often difficult to distinguish from oral benign lesions with the existing diagnostic tools used during standard clinical oral examination. In consequence, early diagnosis of oral cancer can be achieved in only about 30% of patients. Therefore, clinical diagnostic technologies for fast, minimally invasive, and accurate oral cancer screening are urgently needed.
Aim
This study investigated the use of multispectral autofluorescence imaging endoscopy for the automated and noninvasive discrimination of cancerous and precancerous from benign oral epithelial lesions.
Approach
In vivo multispectral autofluorescence endoscopic images of clinically suspicious oral lesions were acquired from 67 patients undergoing tissue biopsy examination. The imaged lesions were classified as precancerous (n=4), cancerous (n=29), and benign (n=34) lesions based on histopathology diagnosis. Multispectral autofluorescence intensity feature maps were generated for each oral lesion and used to train and optimize support vector machine (SVM) models for automated discrimination of cancerous and precancerous from benign oral lesions.
Results
After a leave-one-patient-out cross-validation strategy, an optimized SVM model developed with four multispectral autofluorescence features yielded levels of sensitivity and specificity of 85% and 71%, respectively and overall accuracy of 78% in the discrimination of cancerous/precancerous versus benign oral lesions.
Conclusion
This study demonstrates the potentials of a computer-assisted detection system based on multispectral autofluorescence imaging endoscopy for the early detection of cancerous and precancerous oral lesions.
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Emerging evidence that aggressive breast tumors rely on various substrates including lipids and glucose to proliferate and recur necessitates the development of tools to track multiple metabolic and vascular endpoints concurrently in vivo.
Aim
Our quantitative spectroscopy technique provides time-matched measurements of the three major axes of breast cancer metabolism as well as tissue vascular properties in vivo.
Approach
We leverage exogenous fluorophores to quantify oxidative phosphorylation, glucose uptake, and fatty acid oxidation, and endogenous contrast for measurements of hemoglobin and oxygen saturation. An inverse Monte Carlo algorithm corrects for aberrations resulting from tissue optical properties, allowing the unmixing of spectrally overlapping fluorophores.
Results
Implementation of our inverse Monte Carlo resulted in a linear relationship of fluorophore intensity with concentration (R2<0.99) in tissue-mimicking phantom validation studies. We next sequenced fluorophore delivery to faithfully recapitulate independent measurement of each fluorophore. The ratio of Bodipy FL C16/2-NBDG administered to a single animal is not different from that in paired animals receiving individual fluorophores (p=n.s.). Clustering of five variables was effective in distinguishing tumor from mammary tissue (sensitivity = 0.75, specificity = 0.83, and accuracy = 0.79).
Conclusions
Our system can measure major axes of metabolism and associated vascular endpoints, allowing for future study of tumor metabolic flexibility.
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