On the use of bolus for pacemaker dose measurement and reduction in radiation therapy.

Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is large among CIEDs. Clinically significant defects have been reported at dose as low as 0.15 Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2-Gy limit. We investigated the use of bolus in in vivo dosimetry for CIEDs. Solid water phantom measurements of out-of-field dose for a 6-MV beam were performed using parallel plate chamber with and without 1- to 2-cm bolus covering the chamber. In vivo dosimetry at skin surface above the CIED was performed with and without bolus covering the CIED for three patients with the CIED <5 cm from the field edge. Chamber measured dose at depth ~0.5-1.5 cm below the skin surface, where the CIED is normally located, was reduced by ~7-48% with bolus. The dose reduction became smaller at deeper depths and with smaller field size. In vivo dosimetry at skin surface also indicated ~20%-60% lower dose when using bolus for the three patients. The dose measured with bolus more accurately reflects the dose to CIED and is less affected by contaminant electrons and linac head scatter. In general, the treatment planning system (TPS) calculation underestimated the dose to CIED, but it predicts the CIED dose more accurately when bolus is used. We recommend the use of 1- to 2-cm bolus to cover the CIED during in vivo CIED dose measurements for more accurate CIED dose estimation. If the CIED is placed <2 cm in depth and its dose is mainly from anterior beams, we recommend using the bolus during the entire course of radiation delivery to reduce the dose to CIED.

A scaling aneurysm model-based approach to assessing the role of flow pattern and energy loss in aneurysm rupture prediction.

BACKGROUND AND PURPOSE: Energy loss (EL) was regarded to be one of the key parameters in predicting the rupture risk of IA. In this paper, we took varied aspect ratio (AR) as a scaling law to create a series of longitudinal models to investigate the longitudinal changes of flow pattern and EL as the AR varies, in order to explore the relationship between the longitudinal characteristic EL parameters with aneurysm rupture risk. METHODS: Seven original intracranial aneurysms (IA) models with similar locations were reconstructed from patient 3D rotational angiography (3DRA) images. Based on these models, a series of scaling aneurysm models with different ARs were created with our proposed scaling algorithms. Fluid-solid interaction (FSI) simulations were performed on every model to obtain hemodynamics flow pattern and EL. RESULTS: With AR increasing, flow pattern became more complex, with vortices appearing gradually in the aneurysms (AR > 1.5). Furthermore, the velocity significantly decreased in aneurysms with high ARs (>1.5). Meanwhile, the aneurysm EL increased with increasing AR. Once AR exceeded 1.5, EL changed drastically. CONCLUSION: EL was a potential parameter predicting future rupture of unruptured aneurysms. If the EL during the growth of the unruptured aneurysms increased sharply, we strongly recommend an intervention.

[Effects of posterior lumbar spinal fusion on the stability of unstable lumbar segment and biomechanical properties of adjacent segments: a finite element study].

OBJECTIVE: To explore the effects of posterolateral lumbar fusion (PLF) and posterior lumbar interbody fusion (PLIF) on the stability of postoperative unstable single lumbar segment and the biomechanical alterations of the adjacent segments. METHODS: A finite element model of L3-S1 segments with a single segmental degeneration at the L4-5 level was established, and the model of L4-5 segmental instability after posterior laminectomy and facetectomy was also established, in which laminar and interior 2/3 area of bilateral facet joints were resected. Physical loads were applied to the models and the changes of the range of motion (ROM) at L4-5 level in different models were recorded at the condition of flexion, extension, lateral bending and rotation. PLF and PLIF were performed on postoperative unstable model respectively, the changes of the ROM at L4-5 level, the ROM and the stress on the adjacent discs in different models were recorded. RESULTS: Compared to the unstable model, the L4-5 segmental stability was restored after PLF or PLIF. The ROMs of L3-4 and L5-S1 levels were similar to the preoperative unstable model. The stress on adjacent discs (L3-4 and L5-S1) was increased significantly, and maximum stress distribution changed and concentrated in the anterior annulus fiber in the two fusion models. There was no significant difference of the maximum stress on adjacent discs between PLF and PLIF models [(1.056 ± 0.061) mPa vs (1.070 ± 0.075) mPa; (1.147 ± 0.055) mPa vs (1.162 ± 0.075)mPa, P>0.05]. CONCLUSIONS: Lumbar segmental stability after posterior laminectomy and facetectomy can be recovered by both PLF and PLIF. Both PLF and PLIF may increase the possibility of adjacent segment degeneration because of the augmentation of maximum stress on adjacent discs.

A stationary wavelet transform based approach to registration of planning CT and setup cone beam-CT images in radiotherapy.

Image registration between planning CT images and cone beam-CT (CBCT) images is one of the key technologies of image guided radiotherapy (IGRT). Current image registration methods fall roughly into two categories: geometric features-based and image grayscale-based. Mutual information (MI) based registration, which belongs to the latter category, has been widely applied to multi-modal and mono-modal image registration. However, the standard mutual information method only focuses on the image intensity information and overlooks spatial information, leading to the instability of intensity interpolation. Due to its use of positional information, wavelet transform has been applied to image registration recently. In this study, we proposed an approach to setup CT and cone beam-CT (CBCT) image registration in radiotherapy based on the combination of mutual information (MI) and stationary wavelet transform (SWT). Firstly, SWT was applied to generate gradient images and low frequency components produced in various levels of image decomposition were eliminated. Then inverse SWT was performed on the remaining frequency components. Lastly, the rigid registration of gradient images and original images was implemented using a weighting function with the normalized mutual information (NMI) being the similarity measure, which compensates for the lack of spatial information in mutual information based image registration. Our experiment results showed that the proposed method was highly accurate and robust, and indicated a significant clinical potential in improving the accuracy of target localization in image guided radiotherapy (IGRT).

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.

Radio-luminescent imaging for rapid, high-resolution eye plaque loading verification.

BACKGROUND: Eye plaque brachytherapy is currently an optimal therapy for intraocular cancers. Due to the lack of an effective and practical technique to measure the seed radioactivity distribution, current quality assurance (QA) practice according to the American Association of Physicists in Medicine TG129 only stipulates that the plaque assembly be visually inspected. Consequently, uniform seed activity is routinely adopted to avoid possible loading mistakes of differential seed loading. However, modulated dose delivery, which represents a general trend in radiotherapy to provide more personalized treatment for a given tumor and patient, requires differential activities in the loaded seeds. PURPOSE: In this study, a fast and low-cost radio-luminescent imaging and dose calculating system to verify the seed activity distribution for differential loading was developed. METHODS: A proof-of-concept system consisting of a thin scintillator sheet coupled to a camera/lens system was constructed. A seed-loaded plaque can be placed directly on the scintillator surface with the radioactive seeds facing the scintillator. The camera system collects the radioluminescent signal generated by the scintillator on its opposite side. The predicted dose distribution in the scintillator's sensitive layer was calculated using a Monte Carlo simulation with the planned plaque loading pattern of I-125 seeds. Quantitative comparisons of the distribution of relative measured signal intensity and that of the relative predicted dose in the sensitive layer were performed by gamma analysis, similar to intensity-modulated radiation therapy QA. RESULTS: Data analyses showed high gamma (3%/0.3 mm, global, 20% threshold) passing rates for correct seed loadings and low passing rates with distinguished high gamma value area for incorrect loadings, indicating that possible errors may be detected. The measurement and analysis only required a few extra minutes, significantly shorter than the time to assay the extra verification seeds the physicist already must perform as recommended by TG129. CONCLUSIONS: Radio-luminescent QA can be used to facilitate and assure the implementation of intensity-modulated, customized plaque loading.

Microdosimetric Investigation and a Novel Model of Radiosensitization in the Presence of Metallic Nanoparticles.

Auger cascades generated in high atomic number nanoparticles (NPs) following ionization were considered a potential mechanism for NP radiosensitization. In this work, we investigated the microdosimetric consequences of the Auger cascades using the theory of dual radiation action (TDRA), and we propose the novel Bomb model as a general framework for describing NP-related radiosensitization. When triggered by an ionization event, the Bomb model considers the NPs that are close to a radiation sensitive cellular target, generates dense secondary electrons and kills the cells according to a probability distribution, acting like a "bomb." TDRA plus a distance model were used as the theoretical basis for calculating the change in α of the linear-quadratic survival model and the relative biological effectiveness (RBE). We calculated these quantities for SQ20B and Hela human cancer cells under 250 kVp X-ray irradiation with the presence of gadolinium-based NPs (AGuIXTM), and 220 kVp X-ray irradiation with the presence of 50 nm gold NPs (AuNPs), respectively, and compared with existing experimental data. Geant4-based Monte Carlo (MC) simulations were used to (1) generate the electron spectrum and the phase space data of photons entering the NPs and (2) calculate the proximity functions and other related parameters for the TDRA and the Bomb model. The Auger cascade electrons had a greater proximity function than photoelectric and Compton electrons in water by up to 30%, but the resulting increases in α were smaller than those derived from experimental data. The calculated RBEs cannot explain the experimental findings. The relative increase in α predicted by TDRA was lower than the experimental result by a factor of at least 45 for SQ20B cells with AGuIX under 250 kVp X-ray irradiation, and at least four for Hela cells with AuNPs under 220 kVp X-ray irradiation. The application of the Bomb model to Hela cells with AuNPs under 220 kVp X-ray irradiation indicated that a single ionization event for NPs caused by higher energy photons has a higher probability of killing a cell. NPs that are closer to the cell nucleus are more effective for radiosensitization. Microdosimetric calculations of the RBE for cell death of the Auger electron cascade cannot explain the experimentally observed radiosensitization by AGuIX or AuNP, while the proposed Bomb model is a potential candidate for describing NP-related radiosensitization at low NP concentrations.

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.

Identifying Mild Cognitive Impairment with Random Forest by Integrating Multiple MRI Morphological Metrics.

Mild cognitive impairment (MCI) exhibits a high risk of progression to Alzheimer's disease (AD), and it is commonly deemed as the precursor of AD. It is important to find effective and robust ways for the early diagnosis of MCI. In this paper, a random forest-based method combining multiple morphological metrics was proposed to identify MCI from normal controls (NC). Voxel-based morphometry, deformation-based morphometry, and surface-based morphometry were utilized to extract morphological metrics such as gray matter volume, Jacobian determinant value, cortical thickness, gyrification index, sulcus depth, and fractal dimension. An initial discovery dataset (56 MCI/55 NC) from the ADNI were used to construct classification models and the performances were testified with 10-fold cross validation. To test the generalization of the proposed method, two extra validation datasets including longitudinal ADNI data (30 MCI/16 NC) and collected data from Xuanwu Hospital (27 MCI/32 NC) were employed respectively to evaluate the performance. No matter whether testing was done on the discovery dataset or the extra validation datasets, the accuracies were about 80% with the combined morphological metrics, which were significantly superior to single metric (accuracy: 45% ∼76%) and also displayed good generalization across datasets. Additionally, gyrification index and cortical thickness derived from surface-based morphometry outperformed other features in MCI identification, suggesting they were some key morphological biomarkers for early MCI diagnosis. Combining the multiple morphological metrics together resulted in a significantly better and reliable identification model, which may be helpful to assist in the clinical diagnosis of MCI.

Tumor-targeted pH-low insertion peptide delivery of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy.

Tumor targeting studies using metallic nanoparticles (NPs) have shown that the enhanced permeability and retention effect may not be sufficient to deliver the amount of intratumoral and intracellular NPs needed for effective in vivo radiosensitization. This work describes a pH-Low Insertion Peptide (pHLIP) targeted theranostic agent to enable image-guided NP-enhanced radiotherapy using a clinically feasible amount of injected NPs. Conventional gadolinium (Gd) NPs were conjugated to pHLIPs and evaluated in vitro for radiosensitivity and in vivo for mouse MRI. Cultured A549 human lung cancer cells were incubated with 0.5 mM of pHLIP-GdNP or conventional GdNP. Mass spectrometry showed 78-fold more cellular Gd uptake with pHLIP-GdNPs, and clonogenic survival assays showed 44% more enhanced radiosensitivity by 5 Gy irradiation with pHLIP-GdNPs at pH 6.2. In contrast to conventional GdNPs, MR imaging of tumor-bearing mice showed pHLIP-GdNPs had a long retention time in the tumor (>9 h), suitable for radiotherapy, and penetrated into the poorly-vascularized tumor core. The Gd-enhanced tumor corresponded with low-pH areas also independently measured by an in vivo molecular MRI technique. pHLIPs actively target cell surface acidity from tumor cell metabolism and deliver GdNPs into cells in solid tumors. Intracellular delivery enhances the effect of short-range radiosensitizing photoelectrons and Auger electrons. Because acidity is a general hallmark of tumor cells, the delivery is more general than antibody targeting. Imaging the in vivo NP biodistribution and more acidic (often more aggressive) tumors has the potential for quantitative radiotherapy treatment planning and pre-selecting patients who will likely benefit more from NP radiation enhancement.

Adaptive Imaging Versus Periodic Surveillance for Intrafraction Motion Management During Prostate Cancer Radiotherapy.

OBJECTIVE: To evaluate the benefits of adaptive imaging with automatic correction compared to periodic surveillance strategies with either manual or automatic correction. METHODS: Using Calypso trajectories from 54 patients with prostate cancer at 2 institutions, we simulated 5-field intensity-modulated radiation therapy and dual-arc volumetric-modulated arc therapy with periodic imaging at various frequencies and with continuous adaptive imaging, respectively. With manual/automatic correction, we assumed there was a 30/1 second delay after imaging to determine and apply couch shift. For adaptive imaging, real-time "dose-free" cine-MV images during beam delivery are used in conjunction with online-updated motion pattern information to estimate 3D displacement. Simultaneous MV-kV imaging is only used to confirm the estimated overthreshold motion and calculate couch shift, hence very low additional patient dose from kV imaging. RESULTS: Without intrafraction intervention, the prostates could on average have moved out of a 3-mm margin for ∼20% of the beam-on time after setup imaging in current clinical situation. If the time interval from the setup imaging to beam-on can be reduced to only 30 seconds, the mean over-3 mm percentage can be reduced to ∼7%. For intensity-modulated radiation therapy simulation, with manual correction, 110 and 70 seconds imaging periods both reduced the mean over-3 mm time to ∼4%. Automatic correction could give another 1% to 2% improvement. However, with either manual or automatic correction, the maximum patient-specific over-3 mm time was still relatively high (from 6.4% to 12.6%) and those patients are actually clinically most important. In contrast, adaptive imaging with automatic intervention significantly reduced the mean percentage to 0.6% and the maximum to 2.7% and averagely only ∼1 kV image and ∼1 couch shift were needed per fraction. The results of volumetric-modulated arc therapy simulation show a similar trend to that of intensity-modulated radiation therapy. CONCLUSIONS: Adaptive continuous monitoring with automatic motion compensation is more beneficial than periodic imaging surveillance at similar or even less imaging dose.

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.

Comparison of 2D and 3D modeled tumor motion estimation/prediction for dynamic tumor tracking during arc radiotherapy.

Many real-time imaging techniques have been developed to localize a target in 3D space or in a 2D beam's eye view (BEV) plane for intrafraction motion tracking in radiation therapy. With tracking system latency, the 3D-modeled method is expected to be more accurate even in terms of 2D BEV tracking error. No quantitative analysis, however, has been reported. In this study, we simulated co-planar arc deliveries using respiratory motion data acquired from 42 patients to quantitatively compare the accuracy between 2D BEV and 3D-modeled tracking in arc therapy and to determine whether 3D information is needed for motion tracking. We used our previously developed low kV dose adaptive MV-kV imaging and motion compensation framework as a representative of 3D-modeled methods. It optimizes the balance between additional kV imaging dose and 3D tracking accuracy and solves the MLC blockage issue. With simulated Gaussian marker detection errors (zero mean and 0.39 mm standard deviation) and ~155/310/460 ms tracking system latencies, the mean percentage of time that the target moved >2 mm from the predicted 2D BEV position are 1.1%/4.0%/7.8% and 1.3%/5.8%/11.6% for the 3D-modeled and 2D-only tracking, respectively. The corresponding average BEV RMS errors are 0.67/0.90/1.13 mm and 0.79/1.10/1.37 mm. Compared to the 2D method, the 3D method reduced the average RMS unresolved motion along the beam direction from ~3 mm to ~1 mm, resulting in on average only <1% dosimetric advantage in the depth direction. Only for a small fraction of the patients, when tracking latency is long, the 3D-modeled method showed significant improvement of BEV tracking accuracy, indicating potential dosimetric advantage. However, if the tracking latency is short (~150 ms or less), those improvements are limited. Therefore, 2D BEV tracking has sufficient targeting accuracy for most clinical cases. The 3D technique is, however, still important in solving the MLC blockage problem during 2D BEV tracking.

Identifying current and remitted major depressive disorder with the Hurst exponent: a comparative study on two automated anatomical labeling atlases.

Major depressive disorder (MDD) is a leading world-wide psychiatric disorder with high recurrence rate, therefore, it is desirable to identify current MDD (cMDD) and remitted MDD (rMDD) for their appropriate therapeutic interventions. In the study, 19 cMDD, 19 rMDD and 19 well-matched healthy controls (HC) were enrolled and scanned with the resting-state functional magnetic resonance imaging (rs-fMRI). The Hurst exponent (HE) of rs-fMRI in AAL-90 and AAL-1024 atlases were calculated and compared between groups. Then, a radial basis function (RBF) based support vector machine was proposed to identify every pair of the cMDD, rMDD and HC groups using the abnormal HE features, and a leave-one-out cross-validation was used to evaluate the classification performance. Applying the proposed method with AAL-1024 and AAL-90 atlas respectively, 87% and 84% subjects were correctly identified between cMDD and HC, 84% and 71% between rMDD and HC, and 89% and 74% between cMDD and rMDD. Our results indicated that the HE was an effective feature to distinguish cMDD and rMDD from HC, and the recognition performances with AAL-1024 parcellation were better than that with the conventional AAL-90 parcellation.

Fast Virtual Stenting with Active Contour Models in Intracranical Aneurysm.

Intracranial stents are becoming increasingly a useful option in the treatment of intracranial aneurysms (IAs). Image simulation of the releasing stent configuration together with computational fluid dynamics (CFD) simulation prior to intervention will help surgeons optimize intervention scheme. This paper proposed a fast virtual stenting of IAs based on active contour model (ACM) which was able to virtually release stents within any patient-specific shaped vessel and aneurysm models built on real medical image data. In this method, an initial stent mesh was generated along the centerline of the parent artery without the need for registration between the stent contour and the vessel. Additionally, the diameter of the initial stent volumetric mesh was set to the maximum inscribed sphere diameter of the parent artery to improve the stenting accuracy and save computational cost. At last, a novel criterion for terminating virtual stent expanding that was based on the collision detection of the axis aligned bounding boxes was applied, making the stent expansion free of edge effect. The experiment results of the virtual stenting and the corresponding CFD simulations exhibited the efficacy and accuracy of the ACM based method, which are valuable to intervention scheme selection and therapy plan confirmation.

A support vector machine-based method to identify mild cognitive impairment with multi-level characteristics of magnetic resonance imaging.

Mild cognitive impairment (MCI) represents a transitional state between normal aging and Alzheimer's disease (AD). Non-invasive diagnostic methods are desirable to identify MCI for early therapeutic interventions. In this study, we proposed a support vector machine (SVM)-based method to discriminate between MCI patients and normal controls (NCs) using multi-level characteristics of magnetic resonance imaging (MRI). This method adopted a radial basis function (RBF) as the kernel function, and a grid search method to optimize the two parameters of SVM. The calculated characteristics, i.e., the Hurst exponent (HE), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and gray matter density (GMD), were adopted as the classification features. A leave-one-out cross-validation (LOOCV) was used to evaluate the classification performance of the method. Applying the proposed method to the experimental data from 29 MCI patients and 33 healthy subjects, we achieved a classification accuracy of up to 96.77%, with a sensitivity of 93.10% and a specificity of 100%, and the area under the curve (AUC) yielded up to 0.97. Furthermore, the most discriminative features for classification were found to predominantly involve default-mode regions, such as hippocampus (HIP), parahippocampal gyrus (PHG), posterior cingulate gyrus (PCG) and middle frontal gyrus (MFG), and subcortical regions such as lentiform nucleus (LN) and amygdala (AMYG). Therefore, our method is promising in distinguishing MCI patients from NCs and may be useful for the diagnosis of MCI.

Numerical analysis of the influence of nucleus pulposus removal on the biomechanical behavior of a lumbar motion segment.

Nucleus replacement was deemed to have therapeutic potential for patients with intervertebral disc herniation. However, whether a patient would benefit from nucleus replacement is technically unclear. This study aimed to investigate the influence of nucleus pulposus (NP) removal on the biomechanical behavior of a lumbar motion segment and to further explore a computational method of biomechanical characteristics of NP removal, which can evaluate the mechanical stability of pulposus replacement. We, respectively, reconstructed three types of models for a mildly herniated disc and three types of models for a severely herniated disc based on a L4-L5 segment finite element model with computed tomography image data from a healthy adult. First, the NP was removed from the herniated disc models, and the biomechanical behavior of NP removal was simulated. Second, the NP cavities were filled with an experimental material (Poisson's ratio = 0.3; elastic modulus = 3 MPa), and the biomechanical behavior of pulposus replacement was simulated. The simulations were carried out under the five loadings of axial compression, flexion, lateral bending, extension, and axial rotation. The changes of the four biomechanical characteristics, i.e. the rotation degree, the maximum stress in the annulus fibrosus (AF), joint facet contact forces, and the maximum disc deformation, were computed for all models. Experimental results showed that the rotation range, the maximum AF stress, and joint facet contact forces increased, and the maximum disc deformation decreased after NP removal, while they changed in the opposite way after the nucleus cavities were filled with the experimental material.

Difference in amplitude of low-frequency fluctuation between currently depressed and remitted females with major depressive disorder.

Medical intervention for major depressive disorder (MDD) can be more appropriately focused through the identification and characterization of neurobiological markers that are specific to the disorder, and this study aims to examine the abnormality in the fractional amplitude of low-frequency fluctuation (fALFF) and the amplitude of low-frequency fluctuation (ALFF) in currently depressed and remitted female MDD patients and to correlate these fluctuations with clinical markers of MDD. Nineteen currently depressed female patients, 19 remitted female patients, as well as 19 age- and education-matched healthy females participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the fALFF/ALFF maps among the three groups and investigated the correlation between clinical measurements and statistically significant differences in the fALFF/ALFF of various brain regions. Compared with healthy controls, both currently depressed and remitted patients showed increased fALFF/ALFF in the right putamen. Currently depressed MDD patients showed increased fALFF/ALFF in the right ventral median frontal gyrus relative to both the remitted MDD group and the healthy control group. The ALFF of the right precuneus was found to be positively correlated with the number of depressive episodes and the fALFF of the right precuneus to be positively correlated with the disease duration in currently depressed MDD patients. An abnormal fALFF/ALFF in the right ventral median frontal gyrus was found only in currently depressed patients, suggesting that such an anomaly may play a critical role in depressive symptomatology and may be a therapeutic target for MDD. An abnormal fALFF/ALFF in the right putamen is a potential candidate as a trait-related marker of vulnerability to major depression.

Hybrid MV-kV 3D respiratory motion tracking during radiation therapy with low imaging dose.

A novel real-time adaptive MV-kV imaging framework for image-guided radiation therapy is developed to reduce the thoracic and abdominal tumor targeting uncertainty caused by respiration-induced intrafraction motion with ultra-low patient imaging dose. In our method, continuous stereoscopic MV-kV imaging is used at the beginning of a radiation therapy delivery for several seconds to measure the implanted marker positions. After this stereoscopic imaging period, the kV imager is switched off except for the times when no fiducial marker is detected in the cine-MV images. The 3D time-varying marker positions are estimated by combining the MV 2D projection data and the motion correlations between directional components of marker motion established from the stereoscopic imaging period and updated afterwards; in particular, the most likely position is assumed to be the position on the projection line that has the shortest distance to the first principal component line segment constructed from previous trajectory points. An adaptive windowed auto-regressive prediction is utilized to predict the marker position a short time later (310 ms and 460 ms in this study) to allow for tracking system latency. To demonstrate the feasibility and evaluate the accuracy of the proposed method, computer simulations were performed for both arc and fixed-gantry deliveries using 66 h of retrospective tumor motion data from 42 patients treated for thoracic or abdominal cancers. The simulations reveal that using our hybrid approach, a smaller than 1.2 mm or 1.5 mm root-mean-square tracking error can be achieved at a system latency of 310 ms or 460 ms, respectively. Because the kV imaging is only used for a short period of time in our method, extra patient imaging dose can be reduced by an order of magnitude compared to continuous MV-kV imaging, while the clinical tumor targeting accuracy for thoracic or abdominal cancers is maintained. Furthermore, no additional hardware is required with the proposed method.