Large-conductance calcium-activated potassium channels mediate lipopolysaccharide-induced activation of murine microglia.

Large-conductance calcium-activated potassium (BK) channels are ubiquitously expressed in most cell types where they regulate many cellular, organ, and organismal functions. Although BK currents have been recorded specifically in activated murine and human microglia, it is not yet clear whether and how the function of this channel is related to microglia activation. Here, using patch-clamping, Griess reaction, ELISA, immunocytochemistry, and immunoblotting approaches, we show that specific inhibition of the BK channel with paxilline (10 µm) or siRNA-mediated knockdown of its expression significantly suppresses lipopolysaccharide (LPS)-induced (100 ng/ml) BV-2 and primary mouse microglial cell activation. We found that membrane BK current is activated by LPS at a very early stage through Toll-like receptor 4 (TLR4), leading to nuclear translocation of NF-κB and to production of inflammatory cytokines. Furthermore, we noted that BK channels are also expressed intracellularly, and their nuclear expression significantly increases in late stages of LPS-mediated microglia activation, possibly contributing to production of nitric oxide, tumor necrosis factor-α, and interleukin-6. Of note, a specific TLR4 inhibitor suppressed BK channel expression, whereas an NF-κB inhibitor did not. Taken together, our findings indicate that BK channels participate in both the early and the late stages of LPS-stimulated murine microglia activation involving both membrane-associated and nuclear BK channels.

Bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia: a rare case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST), a rare cause of cerebral infarction, is often unrecognized at initial presentation. We report the case of a patient with bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia. CASE PRESENTATION: A 30-year-old female patient presented with headache, vomiting, and motor aphasia. She was 20 days post-partum and had a lower than normal food intake following a normal vaginal delivery. Brain magnetic resonance images revealed a bilateral corpus callosum and corona radiata infarction. MR venography (MRV) and digital subtraction angiography (DSA) images showed a signal void in the anterior aspect of the superior sagittal sinus and inferior sagittal sinus, ophthalmic vein expansion, and the reversed direction of venous flow. In addition, images showed non-visualization of the left transverse sinus. The left slender sigmoid sinus and small internal jugular vein were also noted. The diagnosis of cerebral venous thrombosis was considered based on the above findings. The patient was managed with anticoagulation therapy, and recovered substantially after treatment. CONCLUSIONS: Bilateral corpus callosum and corona radiata infarction is very rare. However, for patients who clinically show cranial hypertension and neurological deficits during the puerperium period, the possibility of CVST should be considered. Furthermore, DSA plays an important role in the diagnosis of CVST, and should be routinely checked. Early diagnosis is crucial for the patient suffering from CVST.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Effect of atovastatin treatment on porcine circovirus 2 infection in BALB/c mice.

The HMG-CoA reductase (HMGCR) pathway is an important metabolic route, which is not only present in almost every organism, but also involves virus infection. It has recently been shown that expression levels of IFN-responsive genes were significantly increased in HMGCR-downregulated cells and HMGCR inhibitor-treated cells. The aim of this study was to determine whether inhibition of HMGCR by atovastatin would significantly affect Porcine circovirus type 2 (PCV2) infection and immunological reaction in BALB/c mice. The results showed atovastatin significantly stimulated PCV2 replication in vivo. Immunological reaction in atovastatin-treated mice was also significantly enhanced during PCV2 infection. Atovastatin also enhanced PCV2-induced illness in mice. The results of this study will provide new insight into the role of atovastatin in PCV2 infection.

[Effect of Naoshuantong capsule on change of SSQOL index in patients with ischemic stroke in six mouths follow-up].

To evaluate the effect of Naoshuantong capsule on the life quality of patients with ischemic stroke in six months of follow-up studies, and observe the adverse events. The results would provide reference for the secondary prevention on the recovery stage of ischemic stroke. 696 patients from 12 Class III Grade I hospitals nationwide were divided into 2 groups by central randomization system. The study group, 344 cases, were treated with Naoshuantong capsule plus Aspirin, and the control group, 352 cases, were treated with Aspirin. The patients were treated for 6 months. At the end of treatment, SS-QOL used for evaluating the quality of life was observed. The safety index was defined by adverse observation event. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. The results indicated that compared to the control group, the treatment group had significant statistical difference in the impact of effort, self-care ability and the the work or labor ability of patients (P < 0.05). No serious adverse events were observed. Naoshuantong capsule showed some superiority to Asprin on improving the quality of life on patients with ischemic stroke, and it could be used in secondary prevention on the recovery stage of ischemic stroke. Naoshuantong capsule is safe and effective in the treatment of convalescence ischemic stroke.

Validation of the TOPAS Monte Carlo toolkit for LDR brachytherapy simulations.

PURPOSE: This work has the purpose of validating the Monte Carlo toolkit TOol for PArticle Simulation (TOPAS) for low-dose-rate (LDR) brachytherapy uses. METHODS AND MATERIALS: Simulations of 12 LDR sources and 2 COMS eye plaques (10 mm and 20 mm in diameter) and comparisons with published reference data from the Carleton Laboratory for Radiotherapy Physics (CLRP), the TG-43 consensus data and the TG-129 consensus data were performed. Sources from the IROC Houston Source Registry were modeled. The OncoSeed 6711 and the SelectSeed 130.002 were also modeled for historical reasons. For each source, the dose rate constant, the radial dose function and the anisotropy functions at 0.5, 1 and 5 cm were extracted. For the eye plaques (loaded with 125I sources), dose distribution maps, dose profiles along the central axis and transverse axis were calculated. RESULTS: Dose rate constants for 11 of the 12 sources are within 4% of the consensus data and within 2% of the CLRP data. The radial dose functions and anisotropy functions are mostly within 2% of the CLRP data. In average, 92% of all voxels are within 1% of the CLRP data for the eye plaques dose distributions. The dose profiles are within 0.5% (central axis) and 1% (transverse axis) of the reference data. CONCLUSION: The TOPAS MC toolkit was validated for LDR brachytherapy applications. Single-seed and multi-seed results agree with the published reference data. TOPAS has several benefits such as a simplified approach to MC simulations and an accessible brachytherapy package including comprehensive learning resources.

Smart enzyme-free amplification dual-mode self-powered platform designed on two-dimensional networked graphdiyne and DNA nanorods for ultra-sensitive detection of breast cancer biomarkers.

Research has shown that microRNAs exhibit regular dysregulation in cancers, making them potential biomarkers for cancer diagnosis. However, achieving specific and sensitive detection of microRNAs has been a challenging task. To address this issue, two-dimensional networked graphdiyne is used to fabricate a self-powered biosensor and establish a new approach for ultra-responsive dual-mode detection of miRNA-141, a breast cancer biomarker. This method detects miRNA-141 using both electrochemical and colorimetric modes by measuring the output electrical signal of an enzyme-based biofuel cell and the RGB blue value of the electrolyte solution. Tetrahedral DNA and DNA nanorods also are immobilized on the electrode as a biocathode and methylene blue is used as the electron acceptor, which is fixed in the DNA phosphate backbone through electrostatic adsorption. The bioanode catalyzes the oxidation of glucose to produce electrons, which reduces methylene blue to its reduced form, resulting in a high open-circuit voltage (EOCV) and a highger RGB Blue value, enabling dual-mode detection. A reliable linear correlation is observed between EOCV values and miRNA-141 concentrations ranging from 0.0001 to 100 pM, with a detection limit of 21.9 aM (S/N = 3). Additionally, the colorimetric mode also demonstrates a reliable linear correlation with a concentration range of 0.0001-10000 pM, and this method can detect a concentration of 22.2 aM (S/N = 3). This innovative research realizes sensitive and accurate determination of miRNA-141 and provides an important new method for cancer diagnosis.

AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy.

The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for 192 Ir-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.

Comparison of novel shielded nasopharynx applicator designs for intracavitary brachytherapy.

PURPOSE: Nasopharyngeal brachytherapy is limited in part by the radiotolerance of nearby organs like the soft palate. This study explores several novel shielding designs for an intracavitary applicator to significantly reduce soft palate dose while adhering to the constraints of standard treatment procedure. METHODS: The Monte Carlo code TOPAS is used to characterize each prototype under typical high-dose-rate treatment conditions. Mucosal surface dose maps are collected to evaluate the shields on their dose reduction to the central and soft palate planning points and uniformity in their shielding profile. Practicality with respect to patient comfort and pretreatment imaging is discussed. History-by-history standard deviations are calculated for each simulation. RESULTS: A design with elliptical tubing containing bundles of tantalum wires provides the most significant attenuation with 39% and 27% dose reduction to the center and soft palate locations, respectively. Another design utilizing miniature lead spheres loaded into a constructed cavity shows 27% and 24% dose reduction to the same locations while providing more uniform shielding and several practical benefits. Both shields are designed to be completely removable for applicator insertion and pretreatment imaging. The mean and maximum standard error of relative dose measurements was 0.36 and 1.14 percentage points, respectively. CONCLUSION: Each shielding design presented in this study provides a novel approach to safely and effectively shield healthy tissue during intracavitary nasopharyngeal brachytherapy. Analysis performed using Monte Carlo suggests that the design using metal spheres most practically shields the soft palate and should be advanced to the next stages of clinical optimization.

[Post-marketed re-evaluation of fleabane injection and Dengzhan Shengmai capsule study on treatment in patients with ischemic stroke].

OBJECTIVE: To verify the efficacy and safety of post-marketed fleabane injection combined with Dengzhan Shengmai capsules in the treatment of ischemic stroke (IS). METHOD: A multicentre, prospective, practical, randomized controlled study was carried out to compare the efficacy and safety of Dengzhan group (n = 343) and western medicine group (n = 335), appling "clinical study central stochastic system". The treatment of Dengzhan group is using fleabane injection in acute stage and Dengzhan Shengmai capsules in convalescence. The primary indexes of effect evaluation are the important outcome events in 360 days' follow-up, including mortality, recurrence, disability and quality of life to reflect the effect of clinical study. The indexes of safety evaluation involve laboratory examination results and incidence of adverse events. RESULT: After 360 days' follow-up, 4 people died of IS in Dengzhan group, and the mortality rate of which is 1.17%, while 16 died in Western medicine group (WM group), and the mortality rate is 4.78%, suggesting that the mortality rate of Dengzhan group is significantly lower than WM group (P<0.05). Eleven cases recurred in Dengzhan group, and the recurrence rate of which is 3.21%, while 12 recurred in WM group, and the recurrence rate is 3.59%, indicating that the recurrence rate of Dengzhan group is slightly lower than WM group. The disability rate of Dengzhan group is 39.53%, among which the rate of severely disabled cases are 1.49%, while the disability rate of WM group is 40.13%, among which the rate of severely disabled cases are 3.13%, suggesting that the disability rate of Dengzhan group is lower and the severity of disability is also lighter than WM group. In the field of quality of life, the activity ability and the upper limb function store of stroke patients in Dengzhan group improved far much better than WM group (P<0.05). Analysis of safety suggested that, adverse events occurred in 11 cases in Dengzhan group, among which 4 cases is related with the drug treatment, the incidence of adverse events of which is 1.17%, and the main manifestations involve fever and chilling, rash, nausea, dizziness, palpitation, etc. which were all appeared after the treatment of fleabane injection, and disappeared 1 to 2 days after drug withdrawal. 13 cases occurred abnormal liver function and 2 cases abnormal kidney function in Dengzhan group. According to the judgment of clinical physicians, 3 case of ALT abnormality is possibly related to the treatment, the others are all unrelated with the treatment. CONCLUSION: Fleabane injection and Dengzhan Shengmai capsules are all safe and effective TCM in the treatment of ischemic stroke.

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

OBJECTIVE: To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. METHOD: Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. RESULT: Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. CONCLUSION: Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

Validation of the TOPAS Monte Carlo toolkit for HDR brachytherapy simulations.

PURPOSE: The goal of this work is to validate the user-friendly Geant4-based Monte Carlo toolkit TOol for PArticle Simulation (TOPAS) for brachytherapy applications. METHODS AND MATERIALS: Brachytherapy simulations performed with TOPAS were systematically compared with published TG-186 reference data. The photon emission energy spectrum, the air-kerma strength, and the dose-rate constant of the model-based dose calculation algorithm (MBDCA)-WG generic Ir-192 source were extracted. For dose calculations, a track-length estimator was implemented. The four Joint AAPM/ESTRO/ABG MBDCA-WG test cases were evaluated through histograms of the local and global dose difference volumes. A prostate, a palliative lung, and a breast case were simulated. For each case, the dose ratio map, the histogram of the global dose difference volume, and cumulative dose-volume histograms were calculated. RESULTS: The air-kerma strength was (9.772 ± 0.001) × 10-8 U Bq-1 (within 0.3% of the reference value). The dose-rate constant was 1.1107 ± 0.0005 cGy h-1 U-1 (within 0.01% of the reference value). For all cases, at least 96.9% of voxels had a local dose difference within [-1%, 1%] and at least 99.9% of voxels had a global dose difference within [-0.1%, 0.1%]. The implemented track-length estimator scorer was more efficient than the default analog dose scorer by a factor of 237. For all clinical cases, at least 97.5% of voxels had a global dose difference within [-1%, 1%]. Dose-volume histograms were consistent with the reference data. CONCLUSIONS: TOPAS was validated for high-dose-rate brachytherapy simulations following the TG-186 recommended approach for MBDCAs. Built on top of Geant4, TOPAS provides broad access to a state-of-the-art Monte Carlo code for brachytherapy simulations.

Inverse planning for four-dimensional (4D) volumetric modulated arc therapy.

PURPOSE: To develop a 4D volumetric modulated arc therapy (VMAT) inverse planning framework. METHODS: 4D VMAT inverse planning aims to derive an aperture and weight modulated arc therapy treatment plan that optimizes the accumulated dose distribution from all gantry angles and breathing phases. Under an assumption that the gantry rotation and patient breathing are synchronized (i.e., there is a functional relationship between the phase of the patient breathing cycle and the beam angle), the authors compute the contribution from different respiration phases through the registration of the phased CT images. The accumulative dose distribution is optimized by iteratively adjusting the aperture shape and weight of each beam through the minimization of the planning objective function. For comparison, traditional 3D VMAT plans are also performed for the two cases and the performance of the proposed technique is demonstrated. RESULTS: A framework for 4D VMAT inverse planning has been proposed. With the consideration of the extra dimension of time in VMAT, a tighter target margin can be achieved with a full duty cycle, which is otherwise not achievable simultaneously by either 3D VMAT optimization or gated VMAT. CONCLUSIONS: The 4D VMAT planning formulism proposed here provides useful insight on how the "time" dimension can be exploited in rotational arc therapy to maximally compensate for the intrafraction organ motion.

Four-dimensional inverse treatment planning with inclusion of implanted fiducials in IMRT segmented fields.

The purpose of this study is to develop a 4D inverse planning strategy capable of controlling the appearance of the implanted fiducial(s) in segmented IMRT fields for cine MV or combined MV/kV image-guided IMRT. This work is focused on enhancing the visibility of the implanted fiducial(s) in 4D IMRT inverse planning, whose goal is to derive a set of time-resolved (or phase-tagged) MLC segments to cater for the motion of the patient anatomy extracted from the emerging 4D images. The task is to optimize the shapes and weights of all the segments for each incident beam, with the fiducial(s) being forced/encouraged to be inside the segmented fields. The system is modeled by a quadratic objective function with inclusion of a hard/soft constraint characterizing the authors' level of preference for the fiducial(s) to be included in the segmented fields. A simulated annealing algorithm is employed to optimize the system. The proposed technique is demonstrated using two clinical cases. A segment-based inverse planning framework for 4D radiation therapy, capable of providing tempospatially optimized IMRT plans, has been established. Furthermore, using the described 4D optimization approach, it is demonstrated that the MLC blockage of the implanted fiducial(s) during the segmented delivery is avoided without severely compromising the final dose distribution. The visibility of implanted fiducials in 4D IMRT can be improved without significantly deteriorating final dose distribution. This is a foundation for the authors to use cine MV or combined MV/KV to effectively guide the 4D IMRT delivery.

Conceptual formulation on four-dimensional inverse planning for intensity modulated radiation therapy.

Four-dimensional computed tomography (4DCT) offers an extra dimension of 'time' on the three-dimensional patient model with which we can incorporate target motion in radiation treatment (RT) planning and delivery in various ways such as in the concept of internal target volume, in gated treatment or in target tracking. However, for all these methodologies, different phases are essentially considered as non-interconnected independent phases for the purpose of optimization, in other words, the 'time' dimension has yet to be incorporated explicitly in the optimization algorithm and fully exploited. In this note, we have formulated a new 4D inverse planning technique that treats all the phases in the 4DCT as one single entity in the optimization. The optimization is formulated as a quadratic problem for disciplined convex programming that enables the problem to be analyzed and solved efficiently. In the proof-of-principle examples illustrated, we show that the temporal information of the spatial relation of the target and organs at risk could be 'exchanged' amongst different phases so that an appropriate weighting of dose deposition could be allocated to each phase, thus enabling a treatment with a tight target margin and a full duty cycle otherwise not achievable by either of the aforementioned methodologies. Yet there are practical issues to be solved in the 4D RT planning and delivery. The 4D concept in the optimization we have formulated here does provide insight on how the 'time' dimension can be exploited in the 4D optimization process.

[Therapeutic effect of early applying hydrotherapy with Chinese drugs on children hypoxic ischemic encephalopathy].

OBJECTIVE: To observe the therapeutic effect of hydrotherapy with Chinese drugs (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE). METHODS: HIE children were assigned to the treatment group and the control group, 50 in each, at random depending on the willingness of patients' parents. Both groups received the conventional functional training, according to the "0 -3-year-old early intervention outline", but for the treatment group, HT-C was applied additionally. Indexes for quality of sleep, gross motor function, severity of spasm and intellectual development were observed and compared before and after treatment to assess the therapeutic effects. RESULTS: Therapeutic effect in the treatment group was better than that in the control group in all the indexes observed, showing statistical significance (all P <0.05). CONCLUSION: Early intervention of HT-C could improve clinical symptom, promote the functional recovery and intellectual development in children HIE, and also could reduce or prevent the sequelae occurrence of the nervous system in them.

Rehmannioside A attenuates cognitive deficits in rats with vascular dementia (VD) through suppressing oxidative stress, inflammation and apoptosis.

Vascular dementia (VD) is a degenerative cerebrovascular disorder, leading to progressive decline of cognitive abilities and memory. Rehmannioside A (ReA) is isolated from Rehmanniae Radix, which exhibits protective role against various diseases. The present study was performed to calculate the possible neuroprotective effects of ReA on VD. Here, the morris water maze (MWM) test and electrophysiological recordings indicated that ReA reduced cognitive deficits. Additionally, through hematoxylin and eosin (H&E) and Nissl staining, ReA attenuated the histological alterations of hippocampus in rats with VD. ReA group significantly reduced oxidative stress, inflammatory response and apoptosis in the hippocampus of rats with VD, which was linked to the activation of nuclear erythroid related factor-2 (Nrf2), while the inactivation of nuclear factor-κB (NF-κB) and Caspase-3. Further, the anti-oxidative, anti-inflammatory and anti-apoptosis abilities of ReA were confirmed in cells stimulated by hydrogen peroxide. Overall, the results above demonstrated the protective effects of ReA against cognitive deficits and indicated the potential value of ReA in the therapy of VD in future.

A GPU-based multi-criteria optimization algorithm for HDR brachytherapy.

Currently in HDR brachytherapy planning, a manual fine-tuning of an objective function is necessary to obtain case-specific valid plans. This study intends to facilitate this process by proposing a patient-specific inverse planning algorithm for HDR prostate brachytherapy: GPU-based multi-criteria optimization (gMCO). Two GPU-based optimization engines including simulated annealing (gSA) and a quasi-Newton optimizer (gL-BFGS) were implemented to compute multiple plans in parallel. After evaluating the equivalence and the computation performance of these two optimization engines, one preferred optimization engine was selected for the gMCO algorithm. Five hundred sixty-two previously treated prostate HDR cases were divided into validation set (100) and test set (462). In the validation set, the number of Pareto optimal plans to achieve the best plan quality was determined for the gMCO algorithm. In the test set, gMCO plans were compared with the physician-approved clinical plans. Our results indicated that the optimization process is equivalent between gL-BFGS and gSA, and that the computational performance of gL-BFGS is up to 67 times faster than gSA. Over 462 cases, the number of clinically valid plans was 428 (92.6%) for clinical plans and 461 (99.8%) for gMCO plans. The number of valid plans with target [Formula: see text] coverage greater than 95% was 288 (62.3%) for clinical plans and 414 (89.6%) for gMCO plans. The mean planning time was 9.4 s for the gMCO algorithm to generate 1000 Pareto optimal plans. In conclusion, gL-BFGS is able to compute thousands of SA equivalent treatment plans within a short time frame. Powered by gL-BFGS, an ultra-fast and robust multi-criteria optimization algorithm was implemented for HDR prostate brachytherapy. Plan pools with various trade-offs can be created with this algorithm. A large-scale comparison against physician approved clinical plans showed that treatment plan quality could be improved and planning time could be significantly reduced with the proposed gMCO algorithm.

Using total-variation regularization for intensity modulated radiation therapy inverse planning with field-specific numbers of segments.

Currently, there are two types of treatment planning algorithms for intensity modulated radiation therapy (IMRT). The beamlet-based algorithm generates beamlet intensity maps with high complexity, resulting in large numbers of segments in the delivery after a leaf-sequencing algorithm is applied. The segment-based direct aperture optimization (DAO) algorithm includes the physical constraints of the deliverable apertures in the calculation, and achieves a conformal dose distribution using a small number of segments. However, the number of segments is pre-fixed in most of the DAO approaches, and the typical random search scheme in the optimization is computationally intensive. A regularization-based algorithm is proposed to overcome the drawbacks of the DAO method. Instead of smoothing the beamlet intensity maps as in many existing methods, we include a total-variation term in the optimization objective function to reduce the number of signal levels of the beam intensity maps. An aperture rectification algorithm is then applied to generate a significantly reduced number of deliverable apertures. As compared to the DAO algorithm, our method has an efficient form of quadratic optimization, with an additional advantage of optimizing field-specific numbers of segments based on the modulation complexity. The proposed approach is evaluated using two clinical cases. Under the condition that the clinical acceptance criteria of the treatment plan are satisfied, for the prostate patient, the total number of segments for five fields is reduced from 61 using the Eclipse planning system to 35 using the proposed algorithm; for the head and neck patient, the total number of segments for seven fields is reduced from 107 to 28. The head and neck result is also compared to that using an equal number of four segments for each field. The comparison shows that using field-specific numbers of segments achieves a much improved dose distribution.

Intratumoral Injection of Low-Energy Photon-Emitting Gold Nanoparticles: A Microdosimetric Monte Carlo-Based Model.

Gold nanoparticles (Au NPs) distributed in the vicinity of low-dose rate (LDR) brachytherapy seeds could multiply their efficacy thanks to the secondary emissions induced by the photoelectric effect. Injections of radioactive LDR gold nanoparticles (LDR Au NPs), instead of conventional millimeter-size radioactive seeds surrounded by Au NPs, could further enhance the dose by distributing the radioactivity more precisely and homogeneously in tumors. However, the potential of LDR Au NPs as an emerging strategy to treat cancer is strongly dependent on the macroscopic diffusion of the NPs in tumors, as well as on their microscopic internalization within the cells. Understanding the relationship between interstitial and intracellular distribution of NPs, and the outcomes of dose deposition in the cancer tissue is essential for considering future applications of radioactive Au NPs in oncology. Here, LDR Au NPs (103Pd:Pd@Au-PEG NPs) were injected in prostate cancer tumors. The particles were visualized at time-points by computed tomography imaging ( in vivo), transmission electron microscopy ( ex vivo), and optical microscopy ( ex vivo). These data were used in a Monte Carlo-based dosimetric model to reveal the dose deposition produced by LDR Au NPs both at tumoral and cellular scales. 103Pd:Pd@Au-PEG NPs injected in tumors produce a strong dose enhancement at the intracellular level. However, energy deposition is mainly confined around vesicles filled with NPs, and not necessarily close to the nuclei. This suggests that indirect damage caused by the production of reactive oxygen species might be the leading therapeutic mechanism of tumor growth control, over direct damage to the DNA.