Multiple-Input-Multiple-Output Filtered Multitone Time Reversal Acoustic Communications Using Direct Adaptation-Based Turbo Equalization.

This paper proposes using direct adaptation (DA)-based turbo equalization in multiple-input-multiple-output (MIMO) filtered multitone (FMT) time reversal (TR) acoustic communications to jointly suppress noise, residual co-channel interference (CCI) and intersymbol interference (ISI) after the TR process. Soft information-based adaptive decision feedback equalization (ADFE) adjusted according to the recursive expected least squares (RELS) algorithm, including interference cancellation and decoding, is used to construct the DA-based turbo equalization. In the proposed method, soft information is exchanged between soft symbols with soft decisions of decoding iteratively, and interference suppression is proceeded successively and iteratively until the performance is stable. The principle of the proposed method is analyzed, and based on the acoustic channel responses measured in a real experiment, the performance is assessed in relation to that of anther two methods. Compared with the MIMO-FMT TR underwater acoustic communication using interference suppression without error control coding (ECC), the proposed method performs better, benefitting from the ECC included in turbo equalization. Additionally, compared with the MIMO-FMT TR underwater acoustic communication using interference suppression based on hard decision equalization and decoding, the proposed method exhibits superior performance by exploiting soft information.

Marine Application Evaluation of Monocular SLAM for Underwater Robots.

With the development of artificial intelligence technology, visual simultaneous localization and mapping (SLAM) has become a cheap and efficient localization method for underwater robots. However, there are many problems in underwater visual SLAM, such as more serious underwater imaging distortion, more underwater noise, and unclear details. In this paper, we study these two problems and chooses the ORB-SLAM2 algorithm as the method to obtain the motion trajectory of the underwater robot. The causes of radial distortion and tangential distortion of underwater cameras are analyzed, a distortion correction model is constructed, and five distortion correction coefficients are obtained through pool experiments. Comparing the performances of contrast-limited adaptive histogram equalization (CLAHE), median filtering (MF), and dark channel prior (DCP) image enhancement methods in underwater SLAM, it is found that the DCP method has the best image effect evaluation, the largest number of oriented fast and rotated brief (ORB) feature matching, and the highest localization trajectory accuracy. The results show that the ORB-SLAM2 algorithm can effectively locate the underwater robot, and the correct distortion correction coefficient and DCP improve the stability and accuracy of the ORB-SLAM2 algorithm.

Time-delayed interactions on acoustically driven bubbly screens.

The influence of the compressibility effects is discussed, including the time delays on the dynamics of acoustically excited bubbly screens. In the linear regime, it is shown that the proposed model for the infinite bubbly screen recovers the results predicted by the effective medium theory (EMT) up to the second order without introducing any fitting parameter when the wavelength is large compared to the inter-bubble distance. However, the effect of boundaries on the finite bubbly screens is shown to lead to the appearance of multiple local resonances and characteristic periodic structures, which limit the applicability of the EMT. In addition, a local resonance phenomenon in the liquid spacings between the bubbles is observed for both the infinite and finite bubbly screens with crystal structures, and these effects vanish as the crystal structure is perturbed. In the nonlinear regime, the current model is treated with time-delay effects as a delay differential equation, which is directly solved numerically. The appearance of an optimal distance for the subharmonic emission for the crystal structures is shown, and the accuracy of the EMT in the strong nonlinear regime is discussed.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

PURPOSE: We performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp-Davis-Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms. METHODS: Both FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set. After daily dose distributions were computed, they were mapped to planning CT to obtain deformed doses. Dosimetric and image registration results based CBCT images reconstructed by two algorithms were compared at three levels: (A) voxel doses over entire dose calculation volume, (B) clinical constraint results on targets and sensitive structures, and (C) contours propagated to CBCT images using DIR results based on three algorithms (SmartAdapt, Velocity, and Elastix) were compared with manually delineated contours as ground truth. RESULTS: (A) Average daily dose differences and average normalized DDA differences between FDK_CBCT and iterative_CBCT were ≤1 cGy. Maximum daily point dose differences increased from 0.22 ± 0.06 Gy (before the deformable dose mapping operation) to 1.33 ± 0.38 Gy after the deformable dose mapping. Maximum differences of normalized DDA per fraction were up to 0.80 Gy (0.42 ± 0.19 Gy). (B) Differences in target minimum doses were up to 8.31 Gy (-0.62 ± 4.60 Gy) and differences in critical structure doses were 0.70 ± 1.49 Gy. (C) For mapped prostate contours based on iterative_CBCT (relative to standard FDK_CBCT), dice similarity coefficient increased by 0.10 ± 0.09 (p < 0.0001), mass center distances decreased by 2.5 ± 3.0 mm (p < 0.00005), and Hausdorff distances decreased by 3.3 ± 4.4 mm (p < 0.00015). CONCLUSIONS: The new iterative CBCT reconstruction algorithm leads to different mapped volumes of interest, deformed and cumulative doses than results based on conventional FDK_CBCT.

Design and Experiments of a Portable Seabed Integrated Detection Sonar.

The integrated observation of seabed topography, sediment geomorphology and sub-bottom profile information is very important for seabed remote sensing and mapping. To improve the efficiency of seabed detection and meet the needs of portable development of detection equipment, we developed a portable seabed feature integrated detection sonar (PSIDS) with whcih a single sonar device can simultaneously detect the above three types of seabed information. The underwater transducer is mainly composed of the following three components: a parametric emission array as the sound source, a high frequency receiving linear array for multibeam echo signal collection, and a two-dimensional vector hydrophone for receiving the low-frequency sediment echo signal. Field experiments were conducted to validate the performance of the PSIDS on 11-17 January 2018 in Jiaozhou Bay, China. (1) PSIDS could perform the functions of both multibeam sonar and sub-bottom profiler; (2) The synchronously and integrated measurement of various seabed information was achieved by alternately emitting multibeam echo-sounding and sub-bottom profiling signal using parametric source. The detection results proved the feasibility and practicability of PSIDS to achieve multiple seafloor characteristics. PSIDS provides a new idea for developing integrated seabed detection sonar. In terms of convenience and data fusion, it is a good option to use this equipment for integrated seabed detection.

Joint Time-Reversal Space-Time Block Coding and Adaptive Equalization for Filtered Multitone Underwater Acoustic Communications.

Underwater acoustic (UWA) sensor networks demand high-rate communications with high reliability between sensor nodes for massive data transmission. Filtered multitone (FMT) is an attractive multicarrier technique used in high-rate UWA communications, and can obviously shorten the span of intersymbol interference (ISI) with high spectral efficiency and low frequency offset sensitivity by dividing the communication band into several separated wide sub-bands without guard bands. The joint receive diversity and adaptive equalization scheme is often used as a general ISI suppression technique in FMT-UWA communications, but large receive array for high diversity gain has an adverse effect on the miniaturization of UWA sensor nodes. A time-reversal space-time block coding (TR-STBC) technique specially designed for frequency-selective fading channels can replace receive diversity with transmit diversity for high diversity gain, and therefore is helpful for ISI suppression with simple receive configuration. Moreover, the spatio-temporal matched filtering (MF) in TR-STBC decoding can mitigate ISI obviously, and therefore is of benefit to lessen the complexion of adaptive equalization for post-processing. In this paper, joint TR-STBC and adaptive equalization FMT-UWA communication method is proposed based on the merit of TR-STBC. The proposed method is analyzed in theory, and its performance is assessed using simulation analysis and real experimental data collected from an indoor pool communication trial. The validity of the proposed method is proved through comparing the proposed method with the joint single-input-single-output (SISO) and adaptive equalization method and the joint single-input-multiple-output (SIMO) and adaptive equalization method. The results show that the proposed method can achieve better communication performance than the joint SISO and adaptive equalization method, and can achieve similar performance with more simpler receive configuration as the joint SIMO and adaptive equalization method.

Influence of bubble distributions on the propagation of linear waves in polydisperse bubbly liquids.

The influence of the spatial distributions of bubbles on the propagation of linear acoustic waves in polydisperse bubbly liquids is studied. Using the diagrammatic approach, the effective wavenumber, which includes both spatial information and higher orders of multiple scattering, is presented. The phase speed and attenuation coefficient of acoustic waves in bubbly liquids are calculated from the effective wavenumber. A three-dimensional random model, the Generalized Matérn's hard-core point process, is used to close the model. Numerical simulations reveal that as the bubble volume fraction becomes larger so does the effect of the bubble distributions on the attenuation and phase speed. The irregular discrepancy between previously reported experimental results and the classical theory is attributed to the influence of bubble clustering on the propagation of linear waves. The comparison between the present model and the experimental measurements [Leroy, Strybulevych, Page, and Scanlon. (2011). Phys. Rev. E 83, 046605] reveals that the proposed correction term significantly improves the theoretical predictions.

Theoretical and experimental study on multibeam synthetic aperture sonar.

High-resolution imaging method is one of the researching focuses of underwater acoustic detection. Underwater small-target detection also requires detailed imaging technology. Multibeam echo sounders (MBESs) and synthetic aperture sonar (SAS) are the effective instruments widely researched to obtain underwater acoustic images. Constrained by the theory, the along-track resolution of MBES decreases with distance and the gaps problem of SAS always exists and both inevitably limit the quality of acoustic imaging. In this paper, a two dimensional multibeam synthetic aperture sonar (MBSAS) model is designed to overcome the shortcomings of conventional underwater imaging instruments. MBSAS can provide a three dimensional (3D) high-resolution acoustic image without a gap problem. An echo model and transducer array manifold are designed to meet the requirements of engineering applications. Imaging theory and target simulations prove the feasibility of the MBSAS model. The performance of the proposed model is demonstrated with a tank experiment. A detailed image is obtained through an experiment that can indicate the shapes of targets and has the ability to separate adjacent targets. The simulations and experimental results indicate that MBSAS can obtain a more detailed 3D full-scan image than conventional MBES and SAS system with a better energy focusing ability.

Filtered Multitone Modulation Underwater Acoustic Communications Using Low-Complexity Channel-Estimation-Based MMSE Turbo Equalization.

Filtered multitone (FMT) modulation divides the communication band into several subbands to shorten the span of symbols affected by multipath in underwater acoustic (UWA) communications. However, there is still intersymbol interference (ISI) in each subband of FMT modulation degrading communication performance. Therefore, ISI suppression techniques must be applied to FMT modulation UWA communications. The suppression performance of traditional adaptive equalization methods often exploited in FMT modulation UWA communications is limited when the effect of ISI spans tens of symbols or large constellation sizes are used. Turbo equalization consisting of adaptive equalization and channel decoding can improve equalization performance through information exchanging and iterative processes. To overcome the shortcoming of traditional minimum mean square error (MMSE) equalization and effectively suppress the ISI with relatively low computation complexity, an FMT modulation UWA communication using low-complexity channel-estimation-based (CE-based) MMSE turbo equalization is proposed in this paper. In the proposed method, turbo equalization is first exploited to suppress the ISI in FMT modulation UWA communications, and the equalizer coefficients of turbo equalization are adjusted using the low-complexity CE-based MMSE algorithm. The proposed method is analyzed in theory and verified by simulation analysis and real data collected in the experiment carried out in a pool with multipath propagation. The results demonstrate that the proposed method can achieve better communication performance with a higher bit rate than the FMT modulation UWA communication using traditional MMSE adaptive equalization.

Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis.

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation.

On the improvement of CBCT image quality for soft tissue-based SRS localization.

PURPOSE: We explore the optimal cone-beam CT (CBCT) acquisition parameters to improve CBCT image quality to enhance intracranial stereotactic radiosurgery (SRS) localization and also assess the imaging dose levels associated with each imaging protocol. METHODS: Twenty-six CBCT acquisition protocols were generated on an Edge® linear accelerator (Varian Medical Systems, Palo Alto, CA) with different x-ray tube current and potential settings, gantry rotation trajectories, and gantry rotation speeds. To assess image quality, images of the Catphan 504 phantom were analyzed to evaluate the following image quality metrics: uniformity, HU constancy, spatial resolution, low contrast detection, noise level, and contrast-to-noise ratio (CNR). To evaluate the imaging dose for each protocol, the cone-beam dose index (CBDI) was measured. To validate the phantom results, further analysis was performed with an anthropomorphic head phantom as well as image data acquired for a clinical SRS patient. RESULTS: The Catphan data indicates that adjusting acquisition parameters had direct effects on the image noise level, low contrast detection, and CNR, but had minimal effects on uniformity, HU constancy, and spatial resolution. The noise level was reduced from 34.5 ± 0.3 to 18.5 ± 0.2 HU with a four-fold reduction in gantry speed, and to 18.7 ± 0.2 HU with a four-fold increase in tube current. Overall, the noise level was found to be proportional to inverse square root of imaging dose, and imaging dose was proportional to the product of total tube current-time product and the cube of the x-ray potential. Analysis of the anthropomorphic head phantom data and clinical SRS imaging data also indicates that noise is reduced with imaging dose increase. CONCLUSIONS: Our results indicate that optimization of the imaging protocol, and thereby an increase in the imaging dose, is warranted for improved soft-tissue visualization for intracranial SRS.

Characterization and evaluation of 2.5 MV electronic portal imaging for accurate localization of intra- and extracranial stereotactic radiosurgery.

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging. Scatter effect in large patient body was simulated by adding solid water slabs along the beam path. The 2.5 MV imaging mode was also evaluated using clinically acquired images from 24 patients for the sites of brain, head and neck, lung, and abdomen. With respect to 6 MV, the 2.5 MV achieved higher contrast and preserved sharpness on bony structures with only half of the imaging dose. The quality of 2.5 MV imaging was comparable to that of kV imaging when the lateral separation of patient was greater than 38 cm, while the kV image quality degraded rapidly as patient separation increased. Based on the results of patient images, 2.5 MV imaging was better for cranial and extracranial SRS than the 6 MV imaging.

Generation and verification of QFix kVue Calypso-compatible couch top model for a dedicated stereotactic linear accelerator with FFF beams.

This study details the generation, verification, and implementation of a treatment planning system (TPS) couch top model for patient support system used in conjunction with a dedicated stereotactic linear accelerator. Couch top model was created within the TPS using CT simulation images of the kVue Calpyso-compatible couchtop (with rails). Verification measurements were compared to TPS dose prediction for different energies (6 MV FFF and 10 MV FFF) and rail configurations (rails in and rails out) using: 1) central axis point-dose measurements with pinpoint chamber in water-equivalent phantom at 42 gantry angles for various field sizes (2 × 2 cm², 4 × 4 cm², 10 × 10 cm²); and 2) Gafchromic EBT3 film parallel to beam in acrylic slab to assess changes in surface and percent depth doses in PA geometry. To assess sensitivity of delivered dose to variations in patient lateral position, measurements at central axis using the pinpoint chamber geometry were taken at lateral couch displacements of 2, 5, and 10 mm for 6 MV FFF. The maximum percent difference for point-dose measurements was 3.24% (6 MV FFF) and 2.30% (10 MV FFF). The average percent difference for point-dose measurements was less than 1.10% for all beam energies and rail geometries. The maximum percent difference between calculated and measured dose can be as large as 13.0% if no couch model is used for dose calculation. The presence of the couch structures also impacts surface dose and PDD, which was evaluated with Gafchromic film measurements. The upstream shift in the depth of dose maximum (dmax) was found to be 10.5 mm for 6 MV FFF and 5.5 mm for 10 MV FFF for 'Rails In' configuration. Transmission of the treatment beam through the couch results in an increase in surface dose (absolute percentage) of approximately 50% for both photon energies (6 MV FFF and 10MV FFF). The largest sensitivity to lateral shifts occurred at the lateral boundary of the rail structures. The mean magnitude (standard deviation) of the deviation between shifted and centered measurements over all field sizes tested was 0.61% (0.61%) for 2 mm shifts, 0.46% (0.67%) for 5 mm shifts, and 0.86% (1.46%) for 10 mm shifts.

Characteristics of a novel treatment system for linear accelerator-based stereotactic radiosurgery.

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the system was performed by CT imaging a phantom and registering hidden targets on the treatment couch to determine the localization accuracy of the optical surface monitoring system (OSMS), cone-beam CT (CBCT), and MV imaging systems, as well as the radiation isocenter targeting accuracy. The deviations between the percent depth-dose curves acquired on the new linac-based system (Edge), and the previously published machine with FFF beams (TrueBeam) beyond D(max) were within 1.0% for both energies. The maximum deviation of output factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap values, which were fitted using Eclipse dose calculations and measurements based on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm, respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2-1.8 mm (80%-20%) and 1.9-3.8 mm (90%-10%) relative to 10X FFF, which has 1.2-2.2mm and 2.3-5.1mm, respectively. The relative attenuation measurements of the couch for PA, PA (rails-in), oblique, oblique (rails-out), oblique (rails-in) were: -2.0%, -2.5%, -15.6%, -2.5%, -5.0% for 6X FFF and -1.4%, -1.5%, -12.2%, -2.5%, -5.0% for 10X FFF, respectively, with a slight decrease in attenuation versus field size. The systematic deviation between the OSMS and CBCT was -0.4 ± 0.2 mm, 0.1± 0.3mm, and 0.0 ± 0.1 mm in the vertical, longitudinal, and lateral directions. The mean values and standard deviations of the average deviation and maximum deviation of the daily Winston-Lutz tests over three months are 0.20 ± 0.03 mm and 0.66 ± 0.18 mm, respectively. Initial testing of this novel system demonstrates the technology to be highly accurate and suitable for frameless, linac-based SRS and SBRT treatment.

Time Reversal Acoustic Communication Using Filtered Multitone Modulation.

The multipath spread in underwater acoustic channels is severe and, therefore, when the symbol rate of the time reversal (TR) acoustic communication using single-carrier (SC) modulation is high, the large intersymbol interference (ISI) span caused by multipath reduces the performance of the TR process and needs to be removed using the long adaptive equalizer as the post-processor. In this paper, a TR acoustic communication method using filtered multitone (FMT) modulation is proposed in order to reduce the residual ISI in the processed signal using TR. In the proposed method, FMT modulation is exploited to modulate information symbols onto separate subcarriers with high spectral containment and TR technique, as well as adaptive equalization is adopted at the receiver to suppress ISI and noise. The performance of the proposed method is assessed through simulation and real data from a trial in an experimental pool. The proposed method was compared with the TR acoustic communication using SC modulation with the same spectral efficiency. Results demonstrate that the proposed method can improve the performance of the TR process and reduce the computational complexity of adaptive equalization for post-process.

The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.

Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

Protein quality control and aggregation in the endoplasmic reticulum: From basic to bedside.

Endoplasmic reticulum (ER) is the largest membrane-bound compartment in all cells and functions as a key regulator in protein biosynthesis, lipid metabolism, and calcium balance. Mammalian endoplasmic reticulum has evolved with an orchestrated protein quality control system to handle defective proteins and ensure endoplasmic reticulum homeostasis. Nevertheless, the accumulation and aggregation of misfolded proteins in the endoplasmic reticulum may occur during pathological conditions. The inability of endoplasmic reticulum quality control system to clear faulty proteins and aggregates from the endoplasmic reticulum results in the development of many human disorders. The efforts to comprehensively understand endoplasmic reticulum quality control network and protein aggregation will benefit the diagnostics and therapeutics of endoplasmic reticulum storage diseases. Herein, we overview recent advances in mammalian endoplasmic reticulum protein quality control system, describe protein phase transition model, and summarize the approaches to monitor protein aggregation. Moreover, we discuss the therapeutic applications of enhancing endoplasmic reticulum protein quality control pathways in endoplasmic reticulum storage diseases.

Clinical commissioning and use of the Novalis Tx linear accelerator for SRS and SBRT.

The purpose of this study was to perform comprehensive measurements and testing of a Novalis Tx linear accelerator, and to develop technical guidelines for com-missioning from the time of acceptance testing to the first clinical treatment. The Novalis Tx (NTX) linear accelerator is equipped with, among other features, a high-definition MLC (HD120 MLC) with 2.5 mm central leaves, a 6D robotic couch, an optical guidance positioning system, as well as X-ray-based image guidance tools to provide high accuracy radiation delivery for stereotactic radiosurgery and stereotactic body radiation therapy procedures. We have performed extensive tests for each of the components, and analyzed the clinical data collected in our clinic. We present technical guidelines in this report focusing on methods for: (1) efficient and accurate beam data collection for commissioning treatment planning systems, including small field output measurements conducted using a wide range of detectors; (2) commissioning tests for the HD120 MLC; (3) data collection for the baseline characteristics of the on-board imager (OBI) and ExacTrac X-ray (ETX) image guidance systems in conjunction with the 6D robotic couch; and (4) end-to-end testing of the entire clinical process. Established from our clinical experience thus far, recommendations are provided for accurate and efficient use of the OBI and ETX localization systems for intra- and extracranial treatment sites. Four results are presented. (1) Basic beam data measurements: Our measurements confirmed the necessity of using small detectors for small fields. Total scatter factors varied significantly (30% to approximately 62%) for small field measurements among detectors. Unshielded stereotactic field diode (SFD) overestimated dose by ~ 2% for large field sizes. Ion chambers with active diameters of 6 mm suffered from significant volume averaging. The sharpest profile penumbra was observed for the SFD because of its small active diameter (0.6 mm). (2) MLC commissioning: Winston Lutz test, light/radiation field congruence, and Picket Fence tests were performed and were within criteria established by the relevant task group reports. The measured mean MLC transmission and dynamic leaf gap of 6 MV SRS beam were 1.17% and 0.36 mm, respectively. (3) Baseline characteristics of OBI and ETX: The isocenter localization errors in the left/right, posterior/anterior, and superior/inferior directions were, respectively, -0.2 ± 0.2 mm, -0.8 ± 0.2 mm, and -0.8 ± 0.4 mm for ETX, and 0.5 ± 0.7 mm, 0.6 ± 0.5 mm, and 0.0 ± 0.5 mm for OBI cone-beam computed tomography. The registration angular discrepancy was 0.1 ± 0.2°, and the maximum robotic couch error was 0.2°. (4) End-to-end tests: The measured isocenter dose differences from the planned values were 0.8% and 0.4%, measured respectively by an ion chamber and film. The gamma pass rate, measured by EBT2 film, was 95% (3% DD and 1 mm DTA). Through a systematic series of quantitative commissioning experiments and end-to-end tests and our initial clinical experience, described in this report, we demonstrate that the NTX is a robust system, with the image guidance and MLC requirements to treat a wide variety of sites - in particular for highly accurate delivery of SRS and SBRT-based treatments.

CRISPR-Based Therapeutic Gene Editing for Duchenne Muscular Dystrophy: Advances, Challenges and Perspectives.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease arising from loss-of-function mutations in the dystrophin gene and characterized by progressive muscle degeneration, respiratory insufficiency, cardiac failure, and premature death by the age of thirty. Albeit DMD is one of the most common types of fatal genetic diseases, there is no curative treatment for this devastating disorder. In recent years, gene editing via the clustered regularly interspaced short palindromic repeats (CRISPR) system has paved a new path toward correcting pathological mutations at the genetic source, thus enabling the permanent restoration of dystrophin expression and function throughout the musculature. To date, the therapeutic benefits of CRISPR genome-editing systems have been successfully demonstrated in human cells, rodents, canines, and piglets with diverse DMD mutations. Nevertheless, there remain some nonignorable challenges to be solved before the clinical application of CRISPR-based gene therapy. Herein, we provide an overview of therapeutic CRISPR genome-editing systems, summarize recent advancements in their applications in DMD contexts, and discuss several potential obstacles lying ahead of clinical translation.