Socioeconomic Status at Birth and Breast Tissue Composition in Adolescence and Adulthood.

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 [ßadjusted (ßadj) = -0.80; 95% confidence interval (CI), -1.30 to -0.31] and higher collagen content (ßadj = 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 (ßadj = -0.57; 95% CI, -0.97 to -0.17), higher water content (ßadj = 0.70; 95% CI, 0.26-1.14), and higher optical index (ßadj = 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.

Special Section Guest Editorial: Introduction to the Special Section Celebrating 30 years of Open Source Monte Carlo Codes in Biomedical Optics.

The editorial introduces the JBO Special Section Celebrating 30 Years of Open Source Monte Carlo Codes in Biomedical Optics for Volume 27, Issue 8.

Scalable and accessible personalized photodynamic therapy optimization with FullMonte and PDT-SPACE.

SIGNIFICANCE: Open-source software packages have been extensively used in the past three decades in medical imaging and diagnostics, aiming to study the feasibility of the application ex vivo. Unfortunately, most of the existing open-source tools require some software engineering background to install the prerequisite libraries, choose a suitable computational platform, and combine several software tools to address different applications. AIM: To facilitate the use of open-source software in medical applications, enabling computational studies of treatment outcomes prior to the complex in-vivo setting. APPROACH: FullMonteWeb, an open-source, user-friendly web-based software with a graphical user interface for interstitial photodynamic therapy (iPDT) modeling, visualization, and optimization, is introduced. The software can perform Monte Carlo simulations of light propagation in biological tissues, along with iPDT plan optimization. FullMonteWeb installs and runs the required software and libraries on Amazon Web Services (AWS), allowing scalable computing without complex set up. RESULTS: FullMonteWeb allows simulation of large and small problems on the most appropriate compute hardware, enabling cost improvements of 10 × versus always running on a single platform. Case studies in optical property estimation and diffuser placement optimization highlight FullMonteWeb's versatility. CONCLUSION: The FullMonte open source suite enables easier and more cost-effective in-silico studies for iPDT.

Assessment of repeated reference measurements to inform the validity of optical breast spectroscopy.

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.

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer.

SIGNIFICANCE: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient. AIM: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall. APPROACH: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer's specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram. RESULTS: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties. CONCLUSIONS: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer's specific uptake ratio.

FullMonteCUDA: a fast, flexible, and accurate GPU-accelerated Monte Carlo simulator for light propagation in turbid media.

Optimizing light delivery for photodynamic therapy, quantifying tissue optical properties or reconstructing 3D distributions of sources in bioluminescence imaging and absorbers in diffuse optical imaging all involve solving an inverse problem. This can require thousands of forward light propagation simulations to determine the parameters to optimize treatment, image tissue or quantify tissue optical properties, which is time-consuming and computationally expensive. Addressing this problem requires a light propagation simulator that produces results quickly given modelling parameters. In previous work, we developed FullMonteSW: currently the fastest, tetrahedral-mesh, Monte Carlo light propagation simulator written in software. Additional software optimizations showed diminishing performance improvements, so we investigated hardware acceleration methods. This work focuses on FullMonteCUDA: a GPU-accelerated version of FullMonteSW which targets NVIDIA GPUs. FullMonteCUDA has been validated across several benchmark models and, through various GPU-specific optimizations, achieves a 288-936x speedup over the single-threaded, non-vectorized version of FullMonteSW and a 4-13x speedup over the highly optimized, hand-vectorized and multi-threaded version. The increase in performance allows inverse problems to be solved more efficiently and effectively.

High-performance, robustly verified Monte Carlo simulation with FullMonte.

We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for simulation, visualization, and analysis of light propagation in heterogeneous turbid media including tissue. It provides the highest computational performance and richest set of input, output, and analysis facilities of any open-source tetrahedral-mesh MC light simulator. It also provides a robust framework for statistical verification. A scripting interface makes set-up of simulation runs simple, including parameter sweeps, while simultaneously providing customization options. Data formats shared with class-leading visualization tools, VTK and Paraview, facilitate interactive generation of publication-quality fluence and irradiance maps. The simulator can read and write file formats supported by other similar simulators, such as TIM-OS, MMC, COMSOL (finite-element simulations), and MCML to support comparison. Where simulator features permit, FullMonte can take a single test case, run it in multiple software packages, and load the results together for comparison. Example meshes, optical properties, set-up scripts, and output files are provided for user convenience. We demonstrate its use in several test cases, including photodynamic therapy of the brain, bioluminescence imaging (BLI) in a mouse phantom, and a comparison against MCML for layered geometries. Application domains that can benefit from use of FullMonte include photodynamic, photothermal, and photobiomodulation therapies, BLI, diffuse optical tomography, MC software development, and biophotonics education. Since MC results may be used for preclinical or even clinical experiments, a robust and rigorous verification process is essential. Being a stochastic numerical method, MC simulation has unique challenges associated with verification of output results since observed differences may be due simply to output variance or actual differences in expected output. We describe and have implemented a rigorous and statistically justified framework for comparing between simulators of the same class and for performing regression testing.

Optical assessment of mammographic breast density by a 12-wavelength vs a continuous-spectrum optical spectroscopy device.

A 12-laser-wavelength, fixed source-detector position, cup-based optical breast spectroscopy (OBS) device was developed for use in large-scale, multicenter trials as a mammographic breast density (MBD) quantification and breast cancer (BC) risk prescreening tool. In this study, the device was evaluated in comparison with a spectrometer-based device used in previous studies. The devices were compared on their ability to predict mammographic percent density (MPD) and to identify women with high MBD from optical spectra. OBS measurements were made on 60 women, (age 29-73), using both devices. Recent mammograms were collected for all women and MPD quantified from the mammograms. Principal components (PCs) analysis was performed on both sets of OBS spectra, and multivariate logistic regression analysis of the resulting PC scores was used to identify women with high MBD. Both devices are able to identify high MBD with very high sensitivity and specificity. Partial least-squares regression of the spectra was used to predict MPD. Both devices show a strong correlation between OBS-predicted MPD and MPD read from mammograms, however, the correlation is stronger for the continuous-spectrum device (r = 0.74, P = .001) than for the 12-wavelength device (r = 0.62, P = .004). Improvements to the cup-based device to reduce detector saturation should improve the prediction of MPD from the spectra.

A multi-wavelength, laser-based optical spectroscopy device for breast density and breast cancer risk pre-screening.

Optical Breast Spectroscopy (OBS) has been shown to predict mammographic breast density, a strong breast cancer risk factor. OBS is a low-cost technique applicable at any age. OBS information may be useful for personalizing breast cancer screening programs based on risk to improve consensus on and adherence to screening guidelines. To facilitate the use of OBS in population-wide studies, a research prototype OBS device was modified to make it portable and cheaper and to require less operator interaction. Two major changes were made: (1) the broadband light source was replaced with a laser module with 13 individual wavelengths turned on sequentially, enabling the use of photodiode detectors instead of a spectrometer, and (2) the light sources and detectors were placed in fixed positions within 4 sizes of cup, eliminating the need for placement by the operator. Wavelengths were selected using data from two previous studies. The reduction in spectral content did not significantly reduce the ability to distinguish between different risk groups. Positions for the light sources and detectors were chosen based on Monte Carlo simulations to match the optically interrogated volumes of the original device. Two light sources and six detectors per cup were used in the final design.

Hardware acceleration of a Monte Carlo simulation for photodynamic therapy [corrected] treatment planning.

Monte Carlo (MC) simulations are being used extensively in the field of medical biophysics, particularly for modeling light propagation in tissues. The high computation time for MC limits its use to solving only the forward solutions for a given source geometry, emission profile, and optical interaction coefficients of the tissue. However, applications such as photodynamic therapy treatment planning or image reconstruction in diffuse optical tomography require solving the inverse problem given a desired dose distribution or absorber distribution, respectively. A faster means for performing MC simulations would enable the use of MC-based models for accomplishing such tasks. To explore this possibility, a digital hardware implementation of a MC simulation based on the Monte Carlo for Multi-Layered media (MCML) software was implemented on a development platform with multiple field-programmable gate arrays (FPGAs). The hardware performed the MC simulation on average 80 times faster and was 45 times more energy efficient than the MCML software executed on a 3-GHz Intel Xeon processor. The resulting isofluence lines closely matched those produced by MCML in software, diverging by only less than 0.1 mm for fluence levels as low as 0.00001 cm(-2) in a skin model.

Towards conformal light delivery using tailored cylindrical diffusers: attainable light dose distributions.

Interstitial light delivery for therapeutic applications requires the use of fibre-based light diffusers. Such diffusers are presently manufactured to emit with a flat longitudinal power profile. Recently, diffusers with tailored longitudinal emission profiles have become available opening an avenue to improve conformal light delivery. This paper explores the ability of tailored diffusers to improve light dose confinement to the target volume. A formalism to calculate the light dose from an arbitrary source distribution is presented based on the convolution with an appropriate point source function. By choosing a source distribution corresponding to a cylindrical diffuser emitting with a sinusoidal profile, the set of attainable light dose distributions is characterized via a relationship between the diffuser's spatial frequency, the radial distance and the amplitude of the isodose contour.

Non-ionizing near-infrared radiation transillumination spectroscopy for breast tissue density and assessment of breast cancer risk.

There is increasing attention to prevention as a means to reduce cancer incidence. Prevention interventions or therapies in turn rely on risk assessment programs to identify those women most likely to benefit from education and lifestyle changes. These programs are usually based either on interviews to identify ethnic, genetic, and lifestyle factors contributing to risk or on physical examination of the breast. For the latter it has been shown that the parenchymal density pattern observed in X-ray mammography can be used to assess an individual's risk. Extensive areas of dense, glandular tissue that are relatively radio-opaque are associated with higher breast cancer risk, with an odds ratio of 4 to 6 compared with women in whom the breast density is low owing to an abundance of adipose tissue. Near-infrared optical transillumination spectroscopy has been used previously to investigate the physiological properties of breast tissue. In this study, women were recruited who underwent recently X-ray mammography. The tissue density was assessed by a radiologist. The women then underwent optical transillumination spectroscopy, for which an instrument was developed that delivered visible and near-infrared light to the breast. After being transmitted through the breast craniocaudally in one of four quadrants, the spectrum from 625 to 1050 nm was measured. The spectra were used as input to a Principal Component Analysis (PCA) that used the corresponding mammographic density as the reference standard. The study group consisted of 92 women aged 39 to 72 years. Without further stratification for age, menopausal status, or measurement position, the PCA numerical model predicted the radiological assessment of tissue density in the mid 80% to low 90%.