Significance: Expanded use of fluorescence-guided surgery with devices approved for use with indocyanine green (ICG) has led to a range of commercial systems available. There is a compelling need to ...be able to independently characterize system performance and allow for cross-system comparisons.
Aim: The goal of this work is to expand on previous proposed fluorescence imaging standard designs to develop a long-term stable phantom that spectrally matches ICG characteristics and utilizes 3D printing technology for incorporating tissue-equivalent materials.
Approach: A batch of test targets was created to assess ICG concentration sensitivity in the 0.3- to 1000-nM range, tissue-equivalent depth sensitivity down to 6 mm, and spatial resolution with a USAF test chart. Comparisons were completed with a range of systems that have significantly different imaging capabilities and applications, including the Li-Cor® Odyssey, Li-Cor® Pearl, PerkinElmer® Solaris, and Stryker® Spy Elite.
Results: Imaging of the ICG-matching phantoms with all four commercially available systems showed the ability to benchmark system performance and allow for cross-system comparisons. The fluorescence tests were able to assess differences in the detectable concentrations of ICG with sensitivity differences >10× for preclinical and clinical systems. Furthermore, the tests successfully assessed system differences in the depth-signal decay rate, as well as resolution performance and image artifacts. The manufacturing variations, photostability, and mechanical design of the tests showed promise in providing long-term stable standards for fluorescence imaging.
Conclusions: The presented ICG-matching phantom provides a major step toward standardizing performance characterization and cross-system comparisons for devices approved for use with ICG. The developed hybrid manufacturing platform can incorporate long-term stable fluorescing agents with 3D printed tissue-equivalent material. Further, long-term testing of the phantom and refinements to the manufacturing process are necessary for future implementation as a widely adopted fluorescence imaging standard.
The 3D printing of fluorescent materials could help develop, validate, and translate imaging technologies, including systems for fluorescence-guided surgery. Despite advances in 3D printing ...techniques for optical targets, no comprehensive method has been demonstrated for the simultaneous incorporation of fluorophores and fine-tuning of absorption and scattering properties. Here, we introduce a photopolymer-based 3D printing method for manufacturing fluorescent material with tunable optical properties. The results demonstrate the ability to 3D print various individual fluorophores at reasonably high fluorescence yields, including IR-125, quantum dots, methylene blue, and rhodamine 590. Furthermore, tuning of the absorption and reduced scattering coefficients is demonstrated within the relevant mamalian soft tissue coefficient ranges of 0.005-0.05 mm
and 0.2-1.5 mm
, respectively. Fabrication of fluorophore-doped biomimicking and complex geometric structures validated the ability to print feature sizes less than 200 μm. The presented methods and optical characterization techniques provide the foundation for the manufacturing of solid 3D printed fluorescent structures, with direct relevance to biomedical optics and the broad adoption of fast manufacturing methods in fluorescence imaging.
Purpose
Interventional fluorescence imaging is increasingly being utilized to quantify cancer biomarkers in both clinical and preclinical models, yet absolute quantification is complicated by many ...factors. The use of optical phantoms has been suggested by multiple professional organizations for quantitative performance assessment of fluorescence guidance imaging systems. This concept can be further extended to provide standardized tools to compare and assess image analysis metrics.
Procedures
3D-printed fluorescence phantoms based on solid tumor models were developed with representative bio-mimicking optical properties. Phantoms were produced with discrete tumors embedded with an NIR fluorophore of fixed concentration and either zero or 3% non-specific fluorophore in the surrounding material. These phantoms were first imaged by two fluorescence imaging systems using two methods of image segmentation, and four assessment metrics were calculated to demonstrate variability in the quantitative assessment of system performance. The same analysis techniques were then applied to one tumor model with decreasing tumor fluorophore concentrations.
Results
These anatomical phantom models demonstrate the ability to use 3D printing to manufacture anthropomorphic shapes with a wide range of reduced scattering (
μ
s
′: 0.24–1.06 mm
−1
) and absorption (
μ
a
: 0.005–0.14 mm
−1
) properties. The phantom imaging and analysis highlight variability in the measured sensitivity metrics associated with tumor visualization.
Conclusions
3D printing techniques provide a platform for demonstrating complex biological models that introduce real-world complexities for quantifying fluorescence image data. Controlled iterative development of these phantom designs can be used as a tool to advance the field and provide context for consensus-building beyond performance assessment of fluorescence imaging platforms, and extend support for standardizing how quantitative metrics are extracted from imaging data and reported in literature.
Purpose: Unlike fluorescence imaging utilizing an external excitation source, Cherenkov emissions and Cherenkov-excited luminescence occur within a medium when irradiated with high-energy x-rays. ...Methods to improve the understanding of the lateral spread and axial depth distribution of these emissions are needed as an initial step to improve the overall system resolution.
Methods: Monte Carlo simulations were developed to investigate the lateral spread of thin sheets of high-energy sources and compared to experimental measurements of similar sources in water. Additional simulations of a multilayer skin model were used to investigate the limits of detection using both 6- and 18-MV x-ray sources with fluorescence excitation for inclusion depths up to 1 cm.
Results: Simulations comparing the lateral spread of high-energy sources show approximately 100 × higher optical yield from electrons than photons, although electrons showed a larger penumbra in both the simulations and experimental measurements. Cherenkov excitation has a roughly inverse wavelength squared dependence in intensity but is largely redshifted in excitation through any distance of tissue. The calculated emission spectra in tissue were convolved with a database of luminescent compounds to produce a computational ranking of potential Cherenkov-excited luminescence molecular contrast agents.
Conclusions: Models of thin x-ray and electron sources were compared with experimental measurements, showing similar trends in energy and source type. Surface detection of Cherenkov-excited luminescence appears to be limited by the mean free path of the luminescence emission, where for the given simulation only 2% of the inclusion emissions reached the surface from a depth of 7 mm in a multilayer tissue model.
Abstract
Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO
2
) between the ...capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO
2
responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO
2
distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.
The use of a 3D-printing additive manufacturing process is reported for the first time for the extrusion of chalcogenide glasses by using a filament feed. Several challenges were overcome: ...preparation of chalcogenide glass filaments by the crucible technique, optimization of extrusion temperature or even filament feeding. The As40S60 chalcogenide glass was selected for its low glass transition temperature (Tg = 188°C) and ease of synthesis and processing. It was extruded using a commercial 3D-printer at a temperature around 140°C above the glass transition temperature. 3D-printed glass specimens were then characterized and no significant difference was observed in comparison with the bulk precursor glass in terms of chemical and thermal properties. This first report of additive manufacturing of chalcogenide glass complex shapes paves the way for the development of novel specialty optical components that could not be produced by conventional methods, including the fabrication of multimaterial optical fiber preforms.
Cyanobacteria produce a variety of secondary metabolites, including toxins that may contribute to the development of disease. Previous work was able to detect the presence of a cyanobacterial marker ...in human nasal and broncoalveolar lavage samples; however, it was not able to determine the quantification of the marker. To further research the relationship between cyanobacteria and human health, we validated a droplet digital polymerase chain reaction (ddPCR) assay to simultaneously detect the cyanobacterial 16S marker and a human housekeeping gene in human lung tissue samples. The ability to detect cyanobacteria in human samples will allow further research into the role cyanobacteria plays in human health and disease.
Background
Photodynamic therapy (PDT) is widely used as a treatment for actinic keratoses (AK), with new sunlight‐based regimens proposed as alternatives to lamp‐based treatments. Prescribing indoor ...daylight activation could help address the seasonal temperature, clinical supervision, and access variability associated with outdoor treatments.
Objective
To compare the AK lesion clearance efficacy of indoor daylight PDT treatment (30 min of 5‐aminolevulinic acid (ALA) pre‐incubation, followed by 2 h of indoor sunlight) versus a lamp‐based PDT treatment (30 min of ALA preincubation, followed by 10 min of red light).
Methods
A prospective clinical trial was conducted with 41 patients. Topical 10% ALA was applied to the entire treatment site (face, forehead, scalp). Patients were assigned to either the lamp‐based or indoor daylight treatment. Actinic keratosis lesion counts were determined by clinical examination and recorded for pre‐treatment, 1‐month, and 6‐month follow‐up visits.
Results
There was no statistical difference in the efficacy of AK lesion clearance between the red‐lamp (1‐month clearance = 57 ± 17%, 6‐month clearance = 57 ± 20%) and indoor daylight treatment (1‐month clearance = 61 ± 19%, 6‐month clearance = 67 ± 20%). A 95% confidence interval of the difference of the means was measured between −4.4% and 13.4% for 1‐month, and −2.2% and +23.6% for 6‐month timepoints when comparing the indoor daylight to the red‐lamp treatment, with a priori interval of equivalence of ±20%.
Limitations
Ensuring an equivalent dose between the indoor and lamp treatment cohorts limited randomisation since it required performing indoor daylight treatments only during sunny days.
Conclusion
Indoor‐daylight PDT provided equivalent AK treatment efficacy to a lamp‐based regimen while overcoming temperature limitations and UV‐block sunscreen issues associated with outdoor sunlight treatments in the winter.
Clinical trial registration
Clinicaltrials.gov listing: NCT03805737.
Indoor daylight photodynamic therapy (PDT) for actinic keratoses (AKs) could overcome the treatment limitations associated with lamp‐based PDT and outdoor daylight treatments. This study shows AK clearance equivalency between indoor daylight and red‐lamp PDT treatments, such that its adoption could enable accessible, well‐tolerated, treatments throughout all seasons.
Slow antihydrogen (H) is produced within a Penning trap that is located within a quadrupole Ioffe trap, the latter intended to ultimately confine extremely cold, ground-state Hover atoms. Observed ...Hover atoms in this configuration resolve a debate about whether positrons and antiprotons can be brought together to form atoms within the divergent magnetic fields of a quadrupole Ioffe trap. The number of detected H atoms actually increases when a 400 mK Ioffe trap is turned on.
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