Robust treatment planning for small animal radio-neuromodulation using focused kV x-ray beams.

BACKGROUND: In preclinical radio-neuromodulation research, small animal experiments are pivotal for unraveling radiobiological mechanism, investigating prescription and planning techniques, and assessing treatment effects and toxicities. However, the target size inside a rat brain is typically in the order of sub-millimeters. The small target inside the visual cortex neural region in rat brain with a diameter of around 1 mm was focused in this work to observe the physiological change of this region. Delivering uniform doses to the small target while sparing health tissues is challenging. Focused kV x-ray technique based on modern x-ray polycapillary focusing lens is a promising modality for small animal radio-neuromodulation. PURPOSE: The current manual planning method could lead to sub-optimal plans, and the positioning uncertainties due to mechanical accuracy limitations, animal immobilization, and robotic arm motion are not considered. This work aims to design a robust inverse planning method to optimize the intensities of focused kV x-ray beams located in beam trajectories to irradiate small mm-sized targets in rat brains for radio-neuromodulation. METHODS: Focused kV x-ray beams were generated through polycapillary x-ray focusing lenses on achieving small (≤0.3 mm) focus perpendicular to the beam. The beam trajectories were manually designed in 3D space in scanning-while-rotating mode. Geant4 Monte Carlo (MC) simulation generated a dose calculation matrix for each focused kV x-ray beam located in beam trajectories. In the proposed robust inverse planning method, an objective function combining a voxel-wise stochastic programming approach and L1 norm regularization was established to overcome the positioning uncertainties and obtain a high-quality plan. The fast iterative shrinkage thresholding algorithm (FISTA) was utilized to solve the objective function and obtain the optimal intensities. Four cases were employed to validate the feasibility and effectiveness of the proposed method. The manual and non-robust inverse planning methods were also implemented for comparison. RESULTS: The proposed robust inverse planning method achieved superior dose homogeneity and higher robustness against positioning uncertainties. On average, the clinical target volume (CTV) homogeneity index (HI) of robust inverse plan improved to 13.3 from 22.9 in non-robust inverse plan and 53.8 in manual plan if positioning uncertainties were also present. The average bandwidth at D90 was reduced by 6.5 Gy in the robust inverse plan, compared to 9.6 Gy in non-robust inverse plan and 12.5 Gy in manual plan. The average bandwidth at D80 was reduced by 3.4 Gy in robust inverse plan, compared to 5.5 Gy in non-robust inverse plan and 8.5 Gy in manual plan. Moreover, the dose delivery time of manual plan was reduced by an average reduction of 54.7% with robust inverse plan and 29.0% with non-robust inverse plan. CONCLUSION: Compared to manual and non-robust inverse planning methods, the robust inverse planning method improved the dose homogeneity and delivery efficiency and was resistant to the uncertainties, which are crucial for radio-neuromodulation utilizing focused kV x-rays.

Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method.

Cancer patients should be concerned about depression, which can negatively impact their mental health. To develop efficient therapies, it is essential to comprehend the connection between cancer and depression. This study used neuroimaging to investigate the use of mediator-deuterium acupuncture (MDA) for people with cancer-induced depression and its effects on brain regions associated with depression. Resting-state functional magnetic resonance imaging and neurocognitive testing were conducted on the participants, and statistical package for the social sciences was utilized to analyze the behavioral data. Clinical and theoretical data were analyzed to evaluate acupuncture's effectiveness against gynecological cancer. In the research, there were 40 participants, 20 in each group. Except for psychomotor speed, there was no discernible difference in pre-chemotherapy cognitive test results between patients and healthy controls (HCs). However, there were substantial differences in post-treatment cognition test results, showing that the patient group had progressed. According to longitudinal graph analysis, the patient group's local and global brain efficiency significantly declined, and lower local efficiency was associated with lower raw Trail Making Test-A results. Furthermore, poorer verbal memory scores were associated with lower overall performance in the sick group but not in the HC group. According to the research, MDA has potential as a supplemental therapy since it may improve brain function and address depression-related neurological abnormalities in cancer patients. More research is required to fully comprehend the variations between cancer and depression-related brain areas during patient therapy, maybe incorporating MDA.

Parallel interrogation of the chalcogenide-based micro-ring sensor array for photoacoustic tomography.

Photoacoustic tomography (PAT), also known as optoacoustic tomography, is an attractive imaging modality that provides optical contrast with acoustic resolutions. Recent progress in the applications of PAT largely relies on the development and employment of ultrasound sensor arrays with many elements. Although on-chip optical ultrasound sensors have been demonstrated with high sensitivity, large bandwidth, and small size, PAT with on-chip optical ultrasound sensor arrays is rarely reported. In this work, we demonstrate PAT with a chalcogenide-based micro-ring sensor array containing 15 elements, while each element supports a bandwidth of 175 MHz (-6 dB) and a noise-equivalent pressure of 2.2 mPaHz-1/2. Moreover, by synthesizing a digital optical frequency comb (DOFC), we further develop an effective means of parallel interrogation to this sensor array. As a proof of concept, parallel interrogation with only one light source and one photoreceiver is demonstrated for PAT with this sensor array, providing images of fast-moving objects, leaf veins, and live zebrafish. The superior performance of the chalcogenide-based micro-ring sensor array and the effectiveness of the DOFC-enabled parallel interrogation offer great prospects for advancing applications in PAT.

Grating-free quantitative phase retrieval for x-ray phase-contrast imaging with conventional sources.

X-ray phase-contrast imaging can display subtle differences in low-density materials (e.g. soft tissues) more readily than conventional x-ray imaging. However, producing x-ray phase images requires significant spatial coherence of the beam which in turn requires highly specialized sources such as synchrotrons, small and low power microfocus sources, or complex procedures, such as multiple exposures with several carefully stepped precision gratings. To find appropriate approaches for producing x-ray phase-contrast imaging in a clinically meaningful way, we employed a grating-free method that utilized a low-cost, coarse wire mesh and simple processing. This method relaxes the spatial coherence constraint and allows quantitative phase retrieval for not only monochromatic but also polychromatic beams. We also combined the mesh-based system with polycapillary optics to significantly improve the accuracy of quantitative phase retrieval.

Phase and dark-field imaging with mesh-based structured illumination and polycapillary optics.

PURPOSE: X-ray phase and dark-field (DF) imaging have been shown to improve the diagnostic capabilities of X-ray systems. However, these methods have found limited clinical use due to the need for multiple precision gratings with limited field of view or requirements on X-ray coherence that may not be easily translated to clinical practice. This work aims to develop a practicable X-ray phase and DF imaging system that could be translated and practiced in the clinic. METHODS: This work employs a conventional source to create structured illumination with a simple wire mesh. A mesh-shifting algorithm is used to allow wider Fourier windowing to enhance resolution. Deconvolution of the source spot width and camera resolution improves accuracy. Polycapillary optics are employed to enhance coherence. The effects of incorporating optics with two different focal lengths are compared. Information apparent in enhanced absorption images, phase images, and DF images of fat embedded phantoms were compared and subjected to a limited receiver operator characteristic (ROC) study. The DF images of the moist and dry porous object (sponges) were compared. RESULTS: The mesh-based phase and DF imaging system constructs images with three different information types: scatter-free absorption images, differential phase images, and scatter magnitude/DF images, simultaneously from the same original image. The polycapillary optic enhances the coherence of the beam. The deblurring technique corrects the phase signal error due to geometrical blur and the limitation of the camera modulation transfer function (MTF) and removes image artifacts to improve the resolution in a single shot. The mesh-shifting method allows the use of a wider Fourier processing window, which gives even higher resolution, at the expense of an increased dose. The limited ROC study confirms the efficacy of the system over the conventional system. DF images of moist and dry porous object show the significance of the system in the imaging of lung infections. CONCLUSION: The mesh-based X-ray phase and DF imaging system is an inexpensive and easy setup in terms of alignment and data acquisition and can produce phase and DF images in a single shot with wide field of view. The system shows significant potential for use in diagnostic imaging in a clinical setting.

Dosimetry modeling of focused kV x-ray radiotherapy for wet age-related macular degeneration.

PURPOSE: Wet (neovascular) age-related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti-VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet-AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation-based radiotherapy device uses fixed 4 mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting-edge polycapillary x-ray optics. METHODS: Simulation of the polycapillary optics was achieved via Monte Carlo (MC)-based three-dimensional (3D) geometric ray tracing. Phase-space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall ~0.2 mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4-based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including ±0.75 mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball. RESULTS: The simulated CNV treatments by 60-kVp focused x-ray beams show highly conformal delivery of dose to the lesion plus margin (0.75 mm) with sharp dose fall-offs and controllable spatial modulation patterns. The 90%-10% isodose penumbra is <0.5 mm. With a prescription dose of 16 Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75-mm linear displacements and 5-degree gaze angle rotation of the eyeball. CONCLUSION: Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques.

Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

PURPOSE: Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling. METHODS: A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor. RESULTS: The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively. CONCLUSION: Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

Absolute measurement of optical flat surface shape based on the conjugate differential method.

In this paper the conjugate differential method is proposed to measure the absolute surface shape of the flat mirror using a phase-shifting interferometer. The conjugate differential method is derived from the differential method, which extracts absolute phase differences by introducing the slight transverse shifts of the optic. It employs the measurement schemes making transverse shifts on the orthogonally bilateral symmetry positions. So the measurement procedures have been changed into four-step tests to get the phase difference map instead of three-step tests for the differential method. The precision of the slope approximation is enhanced by reducing couplings between multi-step tests, and the reliability of the measurements can be improved. Several differential wavefront reconstruction methods, such as Fourier transform, Zernike polynomial fitting and Hudgin model method, can be applied to reconstruct the absolute surface shape from the differencing phase maps in four different simulation environment. They were also used to reconstruct the absolute surface shape with the conjugate differential method in the experiment. Our method accords with the classical three-flat test better than the traditional differential method, where the deviation of RMS value between the conjugate differential method and the three-flat test is less than 0.3 nm.

[The immunological characteristics of tonsil mesenchymal stem cells].

OBJECTIVE: To investigate the immunological characteristics of human tonsil mesenchymal stem cells (TMSCs). METHODS: Human tonsil tissues were obtained from the children patients with chronic tonsillitis. TMSCs were separated, cultured, and were detected the expression profiles of HLA-I, HLA-II, CD80, CD86 by flow cytometry. The measurement of immunogenicity, the effect on phytohemagglutinin (PHA) induced peripheral blood mononuclear cell (PBMCs) proliferation and mixed lymphocytes reaction (MLR) were performed to identify the immunological characteristics of TMSCs. The co-cultures of TMSCs + PBMCs + PHA and TMSCs + MLR were established, respectively, and the concentration of kynurenine, which is the metabolin of indoleamine 2, 3-dioxygenase, in the culture supernatant were examined. Then we added 1-methyl-L-tryptophan into the co-culture of TMSCs + PBMCs + PHA and TMSCs + MLR, respectively, and tested the proliferation of PBMCs. Each experiment was repeated three times, and there were six samples in each group. Statistical significance was assessed by analysis of variance (ANOVA), and a P value less than 0.05 was considered statistically significant. RESULTS: TMSCs expressed HLA-I, were negative for HLA-II and co-stimulatory molecules CD80 and CD86. The stimulation index in the group of TMSCs + allogeneic PBMCs was 1.38 ± 0.26, whereas the stimulation index in the group of allogeneic PBMCs was 1.22 ± 0.28, and there was no significant difference between the two groups (P > 0.05), indicating that TMSCs could not initiate the proliferation of allogeneic PBMCs. The stimulation indexes in the group of TMSCs + allogeneic PBMCs + PHA were 1.49 ± 0.29 and 1.23 ± 0.22, respectively, whereas the stimulation index in the group of allogeneic PBMCs + PHA was 4.60 ± 0.81, and the difference between the two groups had a statistical significance (P < 0.05) suggesting that TMSCs could inhibit PHA-induced PBMCs proliferation. The stimulation indexes in the group of TMSCs + MLR were 1.29 ± 0.23 and 1.26 ± 0.27, respectively, however, the stimulation index in the group of MLR was 3.04 ± 0.66, and the difference between the two groups had a statistical significance (P < 0.05), demonstrating that TMSCs could suppress MLR-induced PBMCs proliferation. The levels of kynurenine were (26.0 ± 2.3) µmol/L and (23.5 ± 4.5) µmol/L in the culture of TMSCs + PBMCs + PHA and TMSCs + MLR, respectively, thus elevating significantly. After adding of 1-methyl-L-tryptophan, TMSCs-mediated-proliferation suppression of PBMCs restored to normal levels. CONCLUSION: TMSCs possess low immunogenecity and immunosuppressive function, may be used in allogeneic transplantation.

Application of confocal X-ray fluorescence micro-spectroscopy to the investigation of paint layers.

A confocal micro X-ray fluorescence (MXRF) spectrometer based on polycapillary X-ray optics was used for the identification of paint layers. The performance of the confocal MXRF was studied. Multilayered paint fragments of a car were analyzed nondestructively to demonstrate that this confocal MXRF instrument could be used in the discrimination of the various layers in multilayer paint systems.

[Application of confocal micro-beam X-ray fluorescence in nondestructive scanning analysis of the distribution of elements in a single hair].

The confocal micro X-ray fluorescence (XRF) based on polycapillary X-ray lens and conventional X-ray source was used to carry out the scanning analysis of the distribution of the elements in a single hair. The elemental distribution in the single hair was obtained. In the confocal micro XRF technology, the output focal spot of the polycapillary focusing X-ray lens and the input focal spot of the polycapillary parallel X-ray lens were adjusted confocally. The detector could only detect the X-rays from the overlapping foci. This confocal structure decreased the effects of the background on the X-ray spectra, and was accordingly helpful for improving the accuracy of this XRF technology. A polycapillary focusing X-ray lens with a high gain in power density was used to decrease the requirement of power of the X-ray source used in this confocal technology, and made it possible to perform such confocal micro XRF analysis by using the conventional X-ray source with low cost. Experimental results indicated that the confocal micro X-ray fluorescence based on polycapillary X-ray lens had potential applications in analyzing the elemental distribution of individual hairs.

[Endoscopic surgery and endoscopy-assisted surgery for the malignant transformation of sinonasal inverted papilloma].

OBJECTIVE: To investigate malignant transformation of sinonasal inverted papilloma (SIP) treated by nasal endoscopic and endoscopy-assisted surgery. METHODS: Seven cases with malignant transformation of SIP treated by nasal endoscopic and endoscopy-assisted surgery from February 2001 to December 2010 were reviewed. Followed-up time after surgery for each case was over 3 years. All cases were unilateral disease and at grade IV according to the SIP grading standards of Krouse. One case was T2, five T3, and one T4. The surgery were performed under general anaesthesia or local and strengthen anaesthesia. Postoperative radiotherapy was applied, with the doses of 60 - 70 GY. RESULTS: All cases were squamous cell carcinoma confirmed pathologically after surgery. The patients were followed up with endoscopic examination for 3 - 5 years. Of 7 cases, recurrent disease occurred in 3 years after operation, but no recurrence in other 4 cases. CONCLUSIONS: Nasal endoscopic and endoscopy-assisted surgery can be used in the treatment for the malignant transformation of SIP, with the advantages of minimally invasion, fewer complications and the well-preserved nasal functions. Application of radiotherapy after surgery could improve long-term survival efficacy of the patients.