The transcranial photobiomodulation (t-PBM) technique is a promising approach for the treatment of a wide range of neuropsychiatric disorders, including disorders characterized by poor regulation of emotion such as major depressive disorder (MDD). We examine various approaches to deliver red and near-infrared light to the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) in the human brain, both of which have shown strong relevance to the treatment of MDD. We apply our hardware-accelerated Monte Carlo simulations to systematically investigate the light penetration profiles using a standard adult brain atlas. To better deliver light to these regions-of-interest, we study, in particular, intranasal and transcranial illumination approaches. We find that transcranial illumination at the F3-F4 location (based on 10-20 system) provides excellent light delivery to the dlPFC, while a light source located in close proximity to the cribriform plate is well-suited for reaching the vmPFC, despite the fact that accessing the latter location may require a minimally invasive approach. Alternative noninvasive illumination strategies for reaching vmPFC are also studied and both transcranial illumination at the Fp1-FpZ-Fp2 location and intranasal illumination in the mid-nose region are shown to be valid. Different illumination wavelengths, ranging from 670 to 1064 nm, are studied and the amounts of light energy deposited to a wide range of brain regions are quantitatively compared. We find that 810 nm provided the overall highest energy delivery to the targeted regions. Although our simulations carried out on locations and wavelengths are not designed to be exhaustive, the proposed illumination strategies inform the design of t-PBM systems likely to improve brain emotion regulation, both in clinical research and practice.
The Monte Carlo (MC) method is widely recognized as the gold standard for modeling light propagation inside turbid media. Due to the stochastic nature of this method, MC simulations suffer from inherent stochastic noise. Launching large numbers of photons can reduce noise but results in significantly greater computation times, even with graphics processing units (GPU)-based acceleration. We develop a GPU-accelerated adaptive nonlocal means (ANLM) filter to denoise MC simulation outputs. This filter can effectively suppress the spatially varying stochastic noise present in low-photon MC simulations and improve the image signal-to-noise ratio (SNR) by over 5 dB. This is equivalent to the SNR improvement of running nearly 3.5× more photons. We validate this denoising approach using both homogeneous and heterogeneous domains at various photon counts. The ability to preserve rapid optical fluence changes is also demonstrated using domains with inclusions. We demonstrate that this GPU-ANLM filter can shorten simulation runtimes in most photon counts and domain settings even combined with our highly accelerated GPU MC simulations. We also compare this GPU-ANLM filter with the CPU version and report a threefold to fourfold speedup. The developed GPU-ANLM filter not only can enhance three-dimensional MC photon simulation results but also be a valuable tool for noise reduction in other volumetric images such as MRI and CT scans.
Significance: Major depressive disorder (MDD) affects over 40 million U.S. adults in their lifetime. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for head and brain anatomical changes due to aging. Aim: We study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Carlo simulations and age-dependent brain atlases ranging between 5 and 85 years of age. Approach: Age-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions-dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC)-are quantified. Results: An overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extracerebral tissues (ECT) and energy deposition was observed, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position. Conclusions: Quantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the need for personalized and age-adaptive t-PBM treatment planning.
The mesh-based Monte Carlo (MMC) technique has grown tremendously since its initial publication nearly a decade ago. It is now recognized as one of the most accurate Monte Carlo (MC) methods, providing accurate reference solutions for the development of novel biophotonics techniques. In this work, we aim to further advance MMC to address a major challenge in biophotonics modeling, i.e. light transport within highly complex tissues, such as dense microvascular networks, porous media and multi-scale tissue structures. Although the current MMC framework is capable of simulating light propagation in such media given its generality, the run-time and memory usage grow rapidly with increasing media complexity and size. This greatly limits our capability to explore complex and multi-scale tissue structures. Here, we propose a highly efficient implicit mesh-based Monte Carlo (iMMC) method that incorporates both mesh- and shape-based tissue representations to create highly complex yet memory-efficient light transport simulations. We demonstrate that iMMC is capable of providing accurate solutions for dense vessel networks and porous tissues while reducing memory usage by greater than a hundred- or even thousand-fold. In a sample network of microvasculature, the reduced shape complexity results in nearly 3x speed acceleration. The proposed algorithm is now available in our open-source MMC software at http://mcx.space/#mmc.
There is growing interest in developing X-ray computed tomography (CT) imaging systems with improved ability to discriminate material types, going beyond the attenuation imaging provided by most current systems. Dualenergy CT (DECT) systems can partially address this problem by estimating Compton and photoelectric (PE) coefficients of the materials being imaged, but DECT is greatly degraded by the presence of metal or other materials with high attenuation. Here we explore the advantages of multi-energy CT (MECT) systems based on photon-counting detectors. The utility of MECT has been demonstrated in medical applications where photoncounting detectors allow for the resolution of absorption K-edges. Our primary concern is aviation security applications where K-edges are rare. We simulate phantoms with differing amounts of metal (high, medium and low attenuation), both for switched-source DECT and for MECT systems, and include a realistic model of detector energy 0resolution. We extend the DECT sinogram decomposition method of Ying et al. to MECT, allowing estimation of separate Compton and photoelectric sinograms. We furthermore introduce a weighting based on a quadratic approximation to the Poisson likelihood function that deemphasizes energy bins with low signal. Simulation results show that the proposed approach succeeds in estimating material properties even in high-attenuation scenarios where the DECT method fails, improving the signal to noise ratio of reconstructions by over 20 dB for the high-attenuation phantom. Our work demonstrates the potential of using photon counting detectors for stably recovering material properties even when high attenuation is present, thus enabling the development of improved scanning systems.
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