Simulation study of protoacoustics as a real-time in-line dosimetry tool for FLASH proton therapy.

BACKGROUND: Applying ultra-high dose rates to radiation therapy, otherwise known as FLASH, has been shown to be just as effective while sparing more normal tissue compared to conventional radiation therapy. However, there is a need for a dosimeter that is able to detect such high instantaneous dose, particularly in vivo. To fulfill this need, protoacoustics is introduced, which is an in vivo range verification method with submillimeter accuracy. PURPOSE: The purpose of this work is to demonstrate the feasibility of using protoacoustics as a method of in vivo real-time monitoring during FLASH proton therapy and investigating the resulting protoacoustic signal when dose per pulse and pulsewidth are varied through multiple simulation studies. METHODS: The dose distribution of a proton pencil beam was calculated through a Monte Carlo toolbox, TOPAS. Next, the k-Wave toolbox in MATLAB was used for performing protoacoustic simulations, where the initial proton dose deposition was inputted to model acoustic propagations, which were also used for reconstructions. Simulations involving the manipulation of the dose per pulse and pulsewidth were performed, and the temporal and spatial resolution for protoacoustic reconstructions were investigated as well. A 3D reconstruction was performed with a multiple beam spot profile to investigate the spatial resolution as well as determine the feasibility of 3D imaging with protoacoustics. RESULTS: Our results showed consistent linearity in the increasing dose-per-pulse, even up to rates considered for FLASH. The simulations and reconstructions were performed for a range of pulsewidths from 0.1 to 10 µs. The results show the characteristics of the proton beam after convolving the protoacoustic signal with the varying pulsewidths. 3D reconstruction was successfully performed with each beam being distinguishable using an 8 cm × 8 cm planar array. These simulation results show that measurements using protoacoustics has the potential for in vivo dosimetry in FLASH therapy during patient treatments in real time. CONCLUSION: Through this simulation study, the use of protoacoustics in FLASH therapy was verified and explored through observations of varying parameters, such as the dose per pulse and pulsewidth. 2D and 3D reconstructions were also completed. This study shows the significance of using protoacoustics and provides necessary information, which can further be explored in clinical settings.

Towards quantitative in vivo dosimetry using x-ray acoustic computed tomography.

BACKGROUND: Radiation dosimetry is essential for radiation therapy (RT) to ensure that radiation dose is accurately delivered to the tumor. Despite its wide use in clinical intervention, the delivered radiation dose can only be planned and verified via simulation. This makes precision radiotherapy challenging while in-line verification of the delivered dose is still absent in the clinic. X-ray-induced acoustic computed tomography (XACT) has recently been proposed as an imaging tool for in vivo dosimetry. PURPOSE: Most of the XACT studies focus on localizing the radiation beam. However, it has not been studied for its potential for quantitative dosimetry. The aim of this study was to investigate the feasibility of using XACT for quantitative in vivo dose reconstruction during radiotherapy. METHODS: Varian Eclipse system was used to generate simulated uniform and wedged 3D radiation field with a size of 4 cm × $ \times \ $ 4 cm. In order to use XACT for quantitative dosimetry measurements, we have deconvoluted the effects of both the x-ray pulse shape and the finite frequency response of the ultrasound detector. We developed a model-based image reconstruction algorithm to quantify radiation dose in vivo using XACT imaging, and universal back-projection (UBP) reconstruction is used as comparison. The reconstructed dose was calibrated before comparing it to the percent depth dose (PDD) profile. Structural similarity index matrix (SSIM) and root mean squared error (RMSE) are used for numeric evaluation. Experimental signals were acquired from 4 cm × $ \times \ $ 4 cm radiation field created by Linear Accelerator (LINAC) at depths of 6, 8, and 10 cm beneath the water surface. The acquired signals were processed before reconstruction to achieve accurate results. RESULTS: Applying model-based reconstruction algorithm with non-negative constraints successfully reconstructed accurate radiation dose in 3D simulation study. The reconstructed dose matches well with the PDD profile after calibration in experiments. The SSIMs between the model-based reconstructions and initial doses are over 85%, and the RMSEs of model-based reconstructions are eight times lower than the UBP reconstructions. We have also shown that XACT images can be displayed as pseudo-color maps of acoustic intensity, which correspond to different radiation doses in the clinic. CONCLUSION: Our results show that the XACT imaging by model-based reconstruction algorithm is considerably more accurate than the dose reconstructed by UBP algorithm. With proper calibration, XACT is potentially applicable to the clinic for quantitative in vivo dosimetry across a wide range of radiation modalities. In addition, XACT's capability of real-time, volumetric dose imaging seems well-suited for the emerging field of ultrahigh dose rate "FLASH" radiotherapy.

Clenching-Related Motion Artifacts in Functional Near-Infrared Spectroscopy in the Auditory Cortex.

Functional near-infrared spectroscopy (fNIRS), a non-invasive optical neuroimaging technique, has demonstrated its great potential in monitoring cerebral activity as an alternative to functional magnetic resonance imaging (fMRI) in research and clinical usage. fNIRS has seen increasing applications in studying the auditory cortex in healthy subjects and cochlear implant users. However, fNIRS is susceptible to motion artifacts, especially those related to jaw movement, which can affect fNIRS signals in speech and auditory tasks. This study aimed to investigate the motion artifacts related to jaw movements including clenching, speaking, swallowing, and sniffing in a group of human subjects, and test whether our previously established denoising algorithm namely PCA-GLM can reduce the motion artifacts. Our results have shown that the jaw movements introduced artifacts that resemble task-evoked activations and that the PCA-GLM method effectively reduced the motion artifacts due to the clenching movements. The preliminary results of the present study underline the importance of the removal of the jaw-movement-related artifacts in fNIRS signals and suggest the efficacy of our PCA-GLM method in reducing the motion artifacts. Clinical Relevance- This work studies the motion artifacts due to jaw movements that frequently occur in speech perception and production tasks and validates the efficacy of an established denoising algorithm which benefits fNIRS studies on auditory and language functions.

Ring artifacts removal in X-ray-induced acoustic computed tomography.

X-ray-induced acoustic computed tomography (XACT) is a hybrid imaging modality for detecting X-ray absorption distribution via ultrasound emission. It facilitates imaging from a single projection X-ray illumination, thus reducing the radiation exposure and improving imaging speed. Nonuniform detector response caused by the interference between multichannel data acquisition for ring array transducers and amplifier systems yields ring artifacts in the reconstructed XACT images, which compromises the image quality. We propose model-based algorithms for ring artifacts corrected XACT imaging and demonstrate their efficacy on numerical and experimental measurements. The corrected reconstructions indicate significantly reduced ring artifacts as compared to their conventional counterparts.

Task-Related Systemic Artifacts in Functional Near-Infrared Spectroscopy.

Functional near-infrared spectroscopy (fNIRS) has the potential to become the next common noninvasive neuroimaging technique for routine clinical use. Compared to the current standard for neuroimaging, functional magnetic resonance imaging (fMRI), fNIRS boasts several advantages which increase its likelihood for clinical adoption. However, fNIRS suffers from an intrinsic interference from the superficial tissues, which the near-infrared light must penetrate before reaching the deeper cerebral cortex. Therefore, the removal of signals captured by SS channels has been proposed to attenuate the systematic interference. This study aimed to investigate the task-related systemic artefacts, in a high-density montage covering the sensorimotor cortex. We compared the association between LS and SS channels over the contralateral motor cortex which was activated by a hand clenching task, with that over the ipsilateral cortex where no task-related activation was expected. Our findings provide important guidelines regarding how to removal SS signals in a high-density whole-head montage.

Regional sequence expansion or collapse in heterozygous genome assemblies.

High levels of heterozygosity present a unique genome assembly challenge and can adversely impact downstream analyses, yet is common in sequencing datasets obtained from non-model organisms. Here we show that by re-assembling a heterozygous dataset with variant parameters and different assembly algorithms, we are able to generate assemblies whose protein annotations are statistically enriched for specific gene ontology categories. While total assembly length was not significantly affected by assembly methodologies tested, the assemblies generated varied widely in fragmentation level and we show local assembly collapse or expansion underlying the enrichment or depletion of specific protein functional groups. We show that these statistically significant deviations in gene ontology groups can occur in seemingly high-quality assemblies, and result from difficult-to-detect local sequence expansion or contractions. Given the unpredictable interplay between assembly algorithm, parameter, and biological sequence data heterozygosity, we highlight the need for better measures of assembly quality than N50 value, including methods for assessing local expansion and collapse.

Caveolin-1 regulation of disrupted-in-schizophrenia-1 as a potential therapeutic target for schizophrenia.

Schizophrenia is a debilitating psychiatric disorder manifested in early adulthood. Disrupted-in-schizophrenia-1 (DISC1) is a susceptible gene for schizophrenia (Hodgkinson et al. 2004; Millar et al. 2000; St Clair et al. 1990) implicated in neuronal development, brain maturation, and neuroplasticity (Brandon and Sawa 2011; Chubb et al. 2008). Therefore, DISC1 is a promising candidate gene for schizophrenia, but the molecular mechanisms underlying its role in the pathogenesis of the disease are still poorly understood. Interestingly, caveolin-1 (Cav-1), a cholesterol binding and scaffolding protein, regulates neuronal signal transduction and promotes neuroplasticity. In this study we examined the role of Cav-1 in mediating DISC1 expression in neurons in vitro and the hippocampus in vivo. Overexpressing Cav-1 specifically in neurons using a neuron-specific synapsin promoter (SynCav1) increased expression of DISC1 and proteins involved in synaptic plasticity (PSD95, synaptobrevin, synaptophysin, neurexin, and syntaxin 1). Similarly, SynCav1-transfected differentiated human neurons derived from induced pluripotent stem cells (hiPSCs) exhibited increased expression of DISC1 and markers of synaptic plasticity. Conversely, hippocampi from Cav-1 knockout (KO) exhibited decreased expression of DISC1 and proteins involved in synaptic plasticity. Finally, SynCav1 delivery to the hippocampus of Cav-1 KO mice and Cav-1 KO neurons in culture restored expression of DISC1 and markers of synaptic plasticity. Furthermore, we found that Cav-1 coimmunoprecipitated with DISC1 in brain tissue. These findings suggest an important role by which neuron-targeted Cav-1 regulates DISC1 neurobiology with implications for synaptic plasticity. Therefore, SynCav1 might be a potential therapeutic target for restoring neuronal function in schizophrenia. NEW & NOTEWORTHY: The present study is the first to demonstrate that caveolin-1 can regulate DISC1 expression in neuronal models. Furthermore, the findings are consistent across three separate neuronal models that include rodent neurons (in vitro and in vivo) and human differentiated neurons derived from induced pluripotent stem cells. These findings justify further investigation regarding the modulatory role by caveolin on synaptic function and as a potential therapeutic target for the treatment of schizophrenia.