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Blood vessels transport blood and deliver essential molecules to cells. In cancer, the tumour vasculature evolves very differently from healthy tissue, not only in morphology but also in functionality. Comprehensive 3D in vivo imaging of the tumour microcirculatory system thus might lead to a clearer understanding of the vascular role in tumour growth and response to cancer therapy. Here, we employed two optical coherence tomography (OCT) extensions, speckle-variance and Doppler, to study the microvascular architecture and blood flow in normal murine and xenograft tumour tissue. We explored the biophysics of blood flow in microcirculation and extracted relevant quantification features such as vessel diameters and velocity histograms, and combined diameter–velocity plots. It was demonstrated that tumour microcirculation evolves in time and differs from healthy tissue, impacting tumour growth kinetics. This proof-of-principle study demonstrates the potential of OCT to provide an understanding of the temporal evolution of the tumour vasculature and its relationship with tumour development. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer worldwide and a leading cause of cancer-related deaths in women. Mammographic breast density, the relative amount of fibroglandular tissue as seen on a mammogram, is one of the strongest predictors of breast cancer risk, with higher breast density associated with greater risk. Breasts undergo extensive fibroglandular tissue proliferation in early life, making this a potential window of vulnerability for carcinogen exposures. Early-life growth (e.g., height and weight) is also associated with breast cancer risk. Research into the 'developmental origins of health and disease' paradigms investigate the pathways of risk for disease in later life from early-life exposures across developmental phases. However, little is known about the association between early-life growth and breast density. Further investigation into these risk pathways could increase knowledge of disease etiology and help identify women at increased risk at an earlier age and inform potential mediation of breast cancer risk. Breast density is a strong intermediate endpoint to investigate the association between early-life exposures and breast cancer risk. This study investigates the association between early-life growth and breast density in young adult women measured using Optical Breast Spectroscopy (OBS) and Dual X-ray Absorptiometry (DXA). OBS measurements were obtained for 536 female Raine Cohort Study participants at ages 27–28, with 268 completing DXA measurements. Participants with three or more height and weight measurements from ages 8 to 22 were used to generate linear growth curves for height, weight and body mass index (BMI) using SITAR modelling. Three growth parameters (size, velocity and timing) were examined for association with breast density measures, adjusting for potential confounders. Women who reached their peak height rapidly (velocity) and later in adolescence (timing) had lower OBS-breast density. Overall, women who were taller (size) had higher OBS-breast density. For weight, women who grew quickly (velocity) and later in adolescence (timing) had higher absolute DXA-breast density. Overall, weight (size) was also inversely associated with absolute DXA-breast density, as was BMI. These findings provide new evidence that adolescent growth is associated with breast density measures in young adult women, suggesting potential mediation pathways for breast cancer risk in later life. [ABSTRACT FROM AUTHOR]

BackgroundAlthough the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls' development include girls at increased breast cancer risk due to their family history.MethodsThe Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6-13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy.ResultsDuring this initial 5-year phase of the study, follow-up visits are conducted every 6 months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were premenarcheal and 49% were at breast Tanner stage T1.ConclusionsThis study design allows thorough examination of events affecting girls' growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease.

Background: Socioeconomic status (SES) at birth is associated with breast cancer risk. Whether this association is driven by changes in breast tissue composition (BTC) prior to adulthood remains unclear. Methods: We used multivariable linear regression models to examine whether SES at birth is associated with BTC in adolescence and adulthood using data from a New York City cohort of daughters (n = 165, 11-20 years) and mothers (n = 160, 29-55 years). We used maternal-reported data on daughters' household income and maternal education at birth, analyzed individually and in combination (SES index). Women also reported their own mothers' education at birth. We used optical spectroscopy to evaluate BTC measures that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized breast cancer risk factor. Results: Being in the highest versus lowest category of the SES index was associated with lower lipid content [βadjusted (βadj) = -0.80; 95% confidence interval (CI), -1.30 to -0.31] and higher collagen content (βadj = 0.54; 95% CI, 0.09-0.99) in adolescence. In women with a body mass index (BMI) <30 kg/m², higher maternal education at birth (= vs. < high school degree) was associated with lower lipid content (βadj = -0.57; 95% CI, -0.97 to -0.17), higher water content (βadj = 0.70; 95% CI, 0.26-1.14), and higher optical index (βadj = 0.53; 95% CI, 0.10-0.95). Conclusions: This study supports that SES at birth is associated with BTC in adolescence and adulthood, although the latter association may depend on adult BMI. Impact: Further research is needed to identify the socially patterned early life factors influencing BTC. [ABSTRACT FROM AUTHOR]

Cylindrical fiber diffusers have become common tools for various medical therapies. However, their large outer diameters and short lengths restrict their clinical application in some newly developed light therapies. Here, a 250-[micro]m outer-diameter diffuser with an active length that exceeds 5 cm is presented. Diffusers are created in photosensitive optical fibers with outer cladding diameters of 140 [micro]m by use of a structured beam from an excimer laser. Predetermined emission profiles can be achieved. Photometric characteristics, including longitudinal, polar, and azimuthal emission diagrams, were determined by use of a goniometer to assess the light-emission performance of the diffuser. Longitudinal isotropy of better than [+ or -] 10% was achieved. Polar and azimuthal emissions were within [+ or -] 15% of those of an ideal linear Lambertian emitter. Polar uniformity could be improved by an insignificant increase in the outer diameter by use of a diffusing recoating compound. The residual leakage of light at the distal end of the diffuser can be as little as 1%. Other physical parameters tested include minimal bending radius after recoating (1.0 W [cm.sup.-1]). All materials employed were biocompatible. OCIS codes: 170.5180, 170.3890.

Performing single-cell electrophoresis separations using multiple parallel microchannels offers the possibility of both increasing throughput and eliminating cross-contamination between different separations. The instrumentation for such a system requires spatial and temporal control of both single-cell selection and lysis. To address these problems, a compact platform is presented for single-cell capillary electrophoresis in parallel microchannels that combines optical tweezers for cell selection and electromechanical lysis. Calcein-labeled acute myloid leukemia (AML) cells were selected from an on-chip reservoir and transported by optical tweezers to one of four parallel microfluidic channels. Each channel entrance was manufactured by [F.sub.2]-1aser ablation to form a 20-to 10-[micro]m tapered lysis reservoir, creating an injector geometry effective in confining the cellular contents during mechanical shearing of the cell at the 10-/[micro]m capillary entrance. The contents of individual cells were simultaneously injected into parallel channels resulting in electrophoretic separation as recorded by laser-induced fluorescence of the labeled cellular contents.

Mammographic breast density is a strong breast cancer risk factor, and its routine clinical measurement could potentially be used to identify women at higher risk of breast cancer and/or monitor primary prevention strategies. Previous reports of optical breast spectroscopy (OBS), a novel approach to measuring breast density, demonstrated that it is safe (no ionizing radiation), portable, low-cost, and does not require image interpretation but have been limited to small, single-center studies. Reference measurements taken on a phantom breast prior to and after each woman's OBS assessment are required for the calibration of the system transfer function as a part of processing participant data. To inform the validity of participant data, a detailed description of the reference measurements and a repeatability analysis of these measurements taken before and after participant assessment is presented. Reference measurements for OBS from 539 women aged 18–40 years were obtained as a part of a high-throughput epidemiological pilot study. Of these, measurements from 20 women with no useable data due to device failure (3.7%) were excluded and from another 12 women due to user error. The intra-class correlation (ICC) within complete pairs of reference data (taken before and after assessment) was high (all ICC > 0.84). The analysis presented here confirms the OBS participant data as valid for use in ongoing epidemiological research, providing further supporting evidence of OBS as a measure of breast density. A novel method of measuring breast density is needed to bridge large gaps in the knowledge of breast density in younger women and its relation to later-life breast cancer risk. [ABSTRACT FROM AUTHOR]

A dosimetric system has been developed to measure the spatially resolved light dose absorbed by a photosensitizer in a tissue-simulating medium. These gelatin-based dosimeters had macroscopic optical scattering and absorption properties that are typical for homogeneous tissue and contained the photosensitizer benzoporphyrin derivative monoacid (BPD-MA). A reporter molecule, 2[prime]7[prime]-dichlorofluorescin diacetate (DCF-DA), served as an actinometer, which could be photosensitized by BPD-MA to generate a highly fluorescent photoproduct. The relative photosensitizing efficiencies of high-intensity pulsed and cw laser light were compared in these tissue-simulating dosimeters. These measurements demonstrate an increase in penetration for pulsed light as compared with cw light in the dosimeters. A numerical simulation of the light propagation based on optical diffusion theory was used along with the energy levels of the photosensitizer molecule to examine the mechanisms involved in the absorbed dose. The increased penetration of high-intensity pulsed light was due to a transient decrease in the absorption of the photosensitizer, resulting from saturation of the photosensitizer optical transitions. This study provides the first direct comparison of the photodynamic dose absorbed by a photosensitizer using both high-intensity pulsed and cw laser light in a tissue-simulating medium. These measurements demonstrate that a small increase in depth of treatment is possible with pulsed laser light as compared with cw laser light simply on the basis of the unique photochemistry of the photosensitizer. However, this effect still needs to be examined carefully in tumor tissue, where other biological or chemical effects may become significant. Key words: Photodynamic therapy, photosensitizer, benzoporphyrin derivative, tissue optical property, tissue phantom.

The absorption and transport scattering coefficients of biological tissues determine the radial dependence of the diffuse reflectance that is due to a point source. A system is described for making remote measurements of spatially resolved absolute diffuse reflectance and hence noninvasive, noncontact estimates of the tissue optical properties. The system incorporated a laser source and a CCD camera. Deflection of the incident beam into the camera allowed characterization of the source for absolute reflectance measurements. It is shown that an often used solution of the diffusion equation cannot be applied for these measurements. Instead, a neural network, trained on the results of Monte Carlo simulations, was used to estimate the absorption and scattering coefficients from the reflectance data. Tests on tissue-simulating phantoms with transport scattering coefficients between 0.5 and 2.0 [mm.sup.-1] and absorption coefficients between 0.002 and 0.1 [mm.sup.-1] showed the rms errors of this technique to be 2.6% for the transport scattering coefficient and 14% for the absorption coefficients. The optical properties of bovine muscle, adipose, and liver tissue, as well as chicken muscle (breast), were also measured ex vivo at 633 and 751 nm. For muscle tissue it was found that the Monte Carlo simulation did not agree with experimental measurements of reflectance at distances less than 2 mm from the incident beam. Key words: Tissue optics, reflectance, Monte Carlo, neural network.

We investigate why vessels that contain blood, which has a red or a dark red color, may look bluish in human tissue. A CCD camera was used to make images of diffusely reflected light at different wavelengths. Measurements of reflectance that are due to model blood vessels in scattering media and of human skin containing a prominent vein are presented. Monte Carlo simulations were used to calculate the spatially resolved diffuse reflectance for both situations. We show that the color of blood vessels is determined by the following factors: (i) the scattering and absorption characteristics of skin at different wavelengths, (ii) the oxygenation state of blood, which affects its absorption properties, (iii) the diameter and the depth of the vessels, and (iv) the visual perception process.

It was shown that PSN was renal clearable and could rapidly accumulate and retain at tumor sites, achieving a tumor-inhibiting effect better than phthalocyanine micelle without pH response. To evaluate the SP 1 sp O SB 2 sb luminescence-based PDT dosimetry, a set of highly sensitive optical fiber detection system was developed to detect the SP 1 sp O SB 2 sb luminescence at 1270 nm during photosensitization.[9] The SP 1 sp O SB 2 sb luminescence could be quantified in pig skin ex vivo. We welcome the readers to Part II of the special issue on Enhanced Photodynamic Therapy (PDT), an issue dedicated to highlighting the latest developments in both fundamental mechanisms and clinical applications for enhanced PDT. [Extracted from the article]

The study presented a Monte Carlo simulation of light transport in eight commonly used filtered facepiece respirators (FFRs) to assess the efficacy of UV at 254 nm for the inactivation of SARS‐CoV‐2. The results showed different fluence rates across the thickness of the eight different FFRs, implying that some FFR models may be more treatable than others, with the following order being (from most to least treatable): models 1512, 9105s, 1805, 9210, 1870+, 8210, 8110s and 1860, for single side illumination. The model predictions did not coincide well with some previously reported experimental data on virus inactivation when applied to FFR surfaces. The simulations predicted that FFRs should experience higher log reductions (>>6‐log) than those observed experimentally (often limited to ~5‐log). Possible explanations are virus shielding by aggregation or soiling, and a lack of the Monte Carlo simulations considering near‐field scattering effects that can create small, localized regions of low UV photon probability on the surface of the fiber material. If the latter is the main cause in limiting practical UV viral decontamination, improvement might be achieved by exposing the FFR to UV isotropically from all directions, such as by varying the UV source to the FFR surface angle during treatment. [ABSTRACT FROM AUTHOR]

In Photodynamic Therapy (PDT), light is used to activate photosensitizers (PS) to generate reactive oxygen species (ROS) as a cell-killing mechanism. However, PDT's application is limited to the surface and small size tumors because of the inefficiency of light in penetrating larger and deep-seated tumors. We have developed novel nanoparticles (NPs) that can be activated by radiation, a process known as the radiation-activated PDT (radioPDT). In our studies we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSC) and ruthenium-based photosensitizer (Ru/rPDT) that exhibits minimal cell toxicity while having significant cell killing effect upon radiation activation. Our data suggest that radioPDT with Ru/rPDT can be a more effective strategy than previous protoporphyrin-based iterations in treating many deep-seated tumors. Introduction and Background : Toxicity and normal tissue damage are limiting factors for the application of radiotherapy (RT) where higher doses of radiation is required to cure deep-seated tumor such as prostate cancer. In Photodynamic Therapy (PDT), photosensitizers (PS) are activated by light to generate reactive oxygen species (ROS) to kill tumor cells. However, the main limitation of the current PDT is the limited tissue penetration of PS-activating light. Thus, PDT cannot be effectively used to treat deep-seated and larger size tumors. RT has higher tissue penetration depth, making the radiation-activated PDT (radioPDT) advantageous in treating deep seated tumors. We aim to develop novel radioPDT nanoparticles (NP) with more efficient anti-cancer therapeutic effect in vitro and in vivo to enhance targeted radiotherapy. Methods: LaF3:Ce3+ nanoscintillators (NSCs) were synthesized in a single step wet chemistry technique. The NSCs along with Ruthenium-based PS (Ru) with matching excitation/emission spectra were successfully encapsulated in PEG-PLGA. UV-Vis spectrometry and inductively coupled plasma mass spectrometry (ICP-MS) were used to confirm the presence of NSCs and Ru, and dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size of NP. Singlet oxygen generation was measured by Singlet Oxygen Sensor Green (SOSG) and direct singlet oxygen fluorescence. RadioPDT therapeutic potential was evaluated in PC3 prostate cancer cell under radiation by Alamar Blue cell viability assay. Results: UV-Vis spectrometry and ICP-MS determined the successful PEG-PLGA encapsulation of NSC and Ru. The TEM imaging confirmed the encapsulation NSC inside the nanocarrier PEG-PLGA. TEM and DLS measurements showed the size of radioNP ranged from 90nm to 150nm with polydispersity index of <0.3. Singlet oxygen generation by Ru/rPDT NPs was greater than PPIX based radioPDT (PPIX/rPDT) NPs. Furthermore, the direct measurement of singlet oxygen generation with fluorescence spectroscopy of Ru/rPDT showed preserved singlet oxygen yield and no evidence of quenching. The Ru/rPDT and PPIX/rPDT showed minimal PC3 cell cytotoxicity in dark conditions. The PC3 cell killing efficiency was comparable between Ru/rPDT and PPIX/rPDT either under light or radiation activation. Conclusion: Our in vitro studies show Ru/rPDT significantly increases anti-cancer therapeutic effect of RT, with minimal toxicity. Future studies will refine in vivo NP biodistribution, dosing, and RT dose/fractionation schemes. [ABSTRACT FROM AUTHOR]

Interstitial photodynamic therapy (iPDT) has shown promising results recently as a minimally invasive stand-alone or intra-operative cancer treatment. The development of non-toxic photosensitizing drugs with improved target selectivity has increased its efficacy. However, personalized treatment planning that determines the number of photon emitters, their positions and their input powers while taking into account tissue anatomy and treatment response is still lacking to further improve outcomes. Objective: To develop new algorithms that generate high-quality plans by optimizing over the light source positions, along with their powers, to minimize the damage to organs-at-risk while eradicating the tumor. The optimization algorithms should also accurately model the physics of light propagation through the use of Monte-Carlo simulators. Methods: We use simulated-annealing as a baseline algorithm to place the sources. We propose different source perturbations that are likely to provide better outcomes and study their impact. To minimize the number of moves attempted (and effectively runtime) without degrading result quality, we use a reinforcement learning-based method to decide which perturbation strategy to perform in each iteration. We simulate our algorithm on virtual brain tumors modeling real glioblastoma multiforme cases, assuming a 5-ALA PpIX induced photosensitizer that is activated at  $\text{635 nm}$ wavelength. Results: The algorithm generates plans that achieve an average of 46% less damage to organs-as-risk compared to the manual placement used in current clinical studies. Significance: Having a general and high-quality planning system makes iPDT more effective and applicable to a wider variety of oncological indications. This paves the way for more clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: photobiomodulation was showed positive effects on bone healing, however, several studies search safe protocols and dosimetry, beyond good experimental models. Thus, the present study aimed to conduct a systematic review of photobiomodulation (PBM) effects on bone healing increase, focusing on animal experimental models. Revision: the studies search on the PBM use in bone repair was carried out in the PubMed / MEDLINE and Lilacs databases, excluding studies that included systemic conditions and biomaterials or medications use. Sixteen studies were selected, within the inclusion and exclusion criteria stipulated. Animal models included rats (n = 14) and rabbits (n = 2). The laser parameters applied ranging between 650 nm and 830 nm and the power density ranging from 0.03 W to 6 W. Animal models were mainly concentrated in rodents, and the most utilized defect type was the tibial bone defect with 2.5 mm of diameter. Conclusion: through this review we concluded that the location and size of the defects, as well as the laser irradiation parameters are diverse and have shown the lack of consensus on the topic, however the results for using PBM therapy are encouraging. [ABSTRACT FROM AUTHOR]

This study presents numerical simulations of UVC light propagation through seven different filtered face respirators (FFR) to determine their suitability for Ultraviolet germicidal inactivation (UVGI). UV propagation was modeled using the FullMonte program for two external light illuminations. The optical properties of the dominant three layers were determined using the inverse adding doubling method. The resulting fluence rate volume histograms and the lowest fluence rate recorded in the modeled volume, sometimes in the nW cm−2, provide feedback on a respirator's suitability for UVGI and the required exposure time for a given light source. While UVGI can present an economical approach to extend an FFR's useable lifetime, it requires careful optimization of the illumination setup and selection of appropriate respirators. [ABSTRACT FROM AUTHOR]

TLD1433, a Ru(II) polypyridyl complex, was recently introduced. It can be activated in the 520 to 540 nm range. Here we report on the use of TLD1433 for the treatment of bladder carcinomas in vitro and in an in vivo orthotopic model. The electrostatic properties of the normal urothelium vs a tumor compromised urothelium provide for a high selective uptake ratio. In vitro, a 1000 difference in the LD50 between dark and 22.5 J cm−2 irradiation at 530 nm was achieved for two bladder cell lines (T24 and AY‐27). In dogs and rats the plasma concentration for TLD1433 was below 100 ng kg−1 at 72 hours following intravenous injection at a dose of up to 3.5 mg kg−1 and below 10 ng kg−1 following intrabladder instillation for 1 hour at a concentration of 6 mg mL−1. Successful tumor necrosis close to 1.5 mm in depth was achieved. [ABSTRACT FROM AUTHOR]