High-sensitivity liquid chromatography-tandem mass spectrometry quantitative for alkyl imidazolium ionic liquids in human serum: Advancing biomonitoring of human exposure concerns.

Alkyl imidazolium ionic liquids (Cn[MIM]), initially heralded as eco-friendly green solvents for diverse industrial applications, have increasingly been recognized fortheir biodegradability challenges and multiple biotoxicity. Despite potential health risks, research into the effects of Cn[MIM] on human health remains scarce, particularly regarding their detection in biological serum samples. This study validated a matrix-matched calibration quantitative method that utilizes solid-phase extraction (SPE) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was used to analyze the presence of 10 ionic liquids (ILs) with varying alkyl carbon chain lengths (C2-C12) across 300 human serum samples. Efficient separation was achieved using optimized SPE conditions and a BEH C18 column with an appropriate mobile phase. Results demonstrated a strong linear relationship (0.05-100 ng/mL; R2 = 0.995-0.999), with detection and quantification limits with detection and quantification limits ranging from 0.001 to 0.107 ng/mL and 0.003-0.355 ng/mL, respectively. Intraday and inter-day precisions were 0.85-6.99 % and 1.50-7.46 %, with recoveries between 82 and 113 %. The validated method detected C6MIM in 19 % of samples and C8MIM in 8.3 % of samples, with concentrations ranging from 0.02 to 111.70 µg/L and 0.09-16.99 µg/L, respectively, suggesting a potential risk of human exposure. This underscores the importance of robust detection methods in monitoring environmental and human health impacts of alkyl imidazolium compounds.

Practical approaches to four-dimensional heavy-charged-particle lung therapy.

We have developed new design algorithms for compensating boli to facilitate the implementation of four-dimensional charged-particle lung therapy in clinical applications. Four-dimensional CT (4DCT) data for eight lung cancer patients were acquired with a 16-slice CT under free breathing. Six compensating boli were developed that may be categorized into three classes: (1) boli-based on contoured gross tumor volumes (GTV) from a 4DCT data set during each respiratory phase, subsequently combined into one (GTV-4DCT bolus); (2) boli-based on contoured internal target volume (ITV) from image-processed 3DCT data only [temporal-maximum-intensity-projection (TMIP)/temporal-average-intensity-projection (TAIP)] with calculated boli (ITV-TMIP and ITV-TAIP boli); and (3) boli-based on contoured ITV utilizing image-processed 3DCT data, applied to 4DCT for design of boli for each phase, which were then combined. The carbon beam dose distribution within each bolus was calculated as a function of time and compared to plans in which respiratory-ungated/gated strategies were used. The GTV-4DCT treatment plan required a prohibitively long time for contouring the GTV manually for each respiratory phase, but it delivered more than 95% of the prescribed dose to the target volume. The TMIP and TAIP treatments, although more time-efficient, resulted in an unacceptable excess dose to normal tissues and underdosing of the target volume. The dose distribution for the ITV-4DCT bolus was similar to that for the GTV-4DCT bolus and required significantly less practitioner time. The ITV-4DCT bolus treatment plan is time-efficient and provides a high-quality dose distribution, making it a practical alternative to the GTV-4DCT bolus treatment plan.

Boundary Recovery For Delaunay Tetrahedral Meshes Using Local Topological Transformations.

Numerous high-quality, volume mesh-generation systems exist. However, no strategy can address all geometry situations without some element qualities being compromised. Many 3D mesh generation algorithms are based on Delaunay tetrahedralization which frequently fails to preserve the input boundary surface topology. For biomedical applications, this surface preservation can be critical as they usually contain multiple material regions of interest coherently connected. In this paper we present an algorithm as a post-processing method that optimizes local regions of compromised element quality and recovers the original boundary surface facets (triangles) regardless of the original mesh generation strategy. The algorithm carves out a small sub-volume in the vicinity of the missing boundary facet or compromised element, creating a cavity. If the task is to recover a surface boundary facet, a natural exit hole in the cavity will be present. This hole is patched with the missing boundary surface face first followed by other patches to seal the cavity. If the task was to improve a compromised region, then the cavity is already sealed. Every triangular facet of the cavity shell is classified as an active face and can be connected to another shell node creating a tetrahedron. In the process the base of the tetrahedron is removed from the active face list and potentially 3 new active faces are created. This methodology is the underpinnings of our last resort method. Each active face can be viewed as the trunk of a tree. An exhaustive breath and depth search will identify all possible tetrahedral combinations to uniquely fill the cavity. We have streamlined this recursive process reducing the time complexity by orders of magnitude. The original surfaces boundaries (internal and external) are fully restored and the quality of compromised regions improved.

Mutual-information-based image to patient re-registration using intraoperative ultrasound in image-guided neurosurgery.

An image-based re-registration scheme has been developed and evaluated that uses fiducial registration as a starting point to maximize the normalized mutual information (nMI) between intraoperative ultrasound (iUS) and preoperative magnetic resonance images (pMR). We show that this scheme significantly (p<0.001) reduces tumor boundary misalignment between iUS pre-durotomy and pMR from an average of 2.5 mm to 1.0 mm in six resection surgeries. The corrected tumor alignment before dural opening provides a more accurate reference for assessing subsequent intraoperative tumor displacement, which is important for brain shift compensation as surgery progresses. In addition, we report the translational and rotational capture ranges necessary for successful convergence of the nMI registration technique (5.9 mm and 5.2 deg, respectively). The proposed scheme is automatic, sufficiently robust, and computationally efficient (<2 min), and holds promise for routine clinical use in the operating room during image-guided neurosurgical procedures.

Evaluation of deformable registration of patient lung 4DCT with subanatomical region segmentations.

Deformable registration is needed for a variety of tasks in establishing the voxel correspondence between respiratory phases. Most registration algorithms assume or imply that the deformation field is smooth and continuous everywhere. However, the lungs are contained within closed invaginated sacs called pleurae and are allowed to slide almost independently along the chest wall. This sliding motion is characterized by a discontinuous vector field, which cannot be generated using standard deformable registration methods. The authors have developed a registration method that can create discontinuous vector fields at the boundaries of anatomical subregions. Registration is performed independently on each subregion, with a boundary-matching penalty used to prevent gaps. This method was implemented and tested using both the B-spline and Demons registration algorithms in the Insight Segmentation and Registration Toolkit. The authors have validated this method on four patient 4DCT data sets for registration of the end-inhalation and end-exhalation volumes. Multiple experts identified homologous points in the lungs and along the ribs in the two respiratory phases. Statistical analyses of the mismatch of the homologous points before and after registration demonstrated improved overall accuracy for both algorithms.

Dosimetric impact of motion in free-breathing and gated lung radiotherapy: a 4D Monte Carlo study of intrafraction and interfraction effects.

The purpose of this study was to investigate if interfraction and intrafraction motion in free-breathing and gated lung IMRT can lead to systematic dose differences between 3DCT and 4DCT. Dosimetric effects were studied considering the breathing pattern of three patients monitored during the course of their treatment and an in-house developed 4D Monte Carlo framework. Imaging data were taken in free-breathing and in cine mode for both 3D and 4D acquisition. Treatment planning for IMRT delivery was done based on the free-breathing data with the CORVUS (North American Scientific, Chatsworth, CA) planning system. The dose distributions as a function of phase in the breathing cycle were combined using deformable image registration. The study focused on (a) assessing the accuracy of the CORVUS pencil beam algorithm with Monte Carlo dose calculation in the lung, (b) evaluating the dosimetric effect of motion on the individual breathing phases of the respiratory cycle, and (c) assessing intrafraction and interfraction motion effects during free-breathing or gated radiotherapy. The comparison between (a) the planning system and the Monte Carlo system shows that the pencil beam algorithm underestimates the dose in low-density regions, such as lung tissue, and overestimates the dose in high-density regions, such as bone, by 5% or more of the prescribed dose (corresponding to approximately 3-5 Gy for the cases considered). For the patients studied this could have a significant impact on the dose volume histograms for the target structures depending on the margin added to the clinical target volume (CTV) to produce either the planning target (PTV) or internal target volume (ITV). The dose differences between (b) phases in the breathing cycle and the free-breathing case were shown to be negligible for all phases except for the inhale phase, where an underdosage of the tumor by as much as 9.3 Gy relative to the free-breathing was observed. The large difference was due to breathing-induced motion/deformation affecting the soft/lung tissue density and motion of the bone structures (such as the rib cage) in and out of the beam. Intrafraction and interfraction dosimetric differences between (c) free-breathing and gated delivery were found to be small. However, more significant dosimetric differences, of the order of 3%-5%, were observed between the dose calculations based on static CT (3DCT) and the ones based on time-resolved CT (4DCT). These differences are a consequence of the larger contribution of the inhale phase in the 3DCT data than in the 4DCT.

Stereopsis-guided brain shift compensation.

Brain deformation models have proven to be a powerful tool in compensating for soft tissue deformation during image-guided neurosurgery. The accuracy of these models can be improved by incorporating intraoperative measurements of brain motion. We have designed and implemented a passive intraoperative stereo vision system capable of estimating the three-dimensional shape of the surgical scene in near real-time. This intraoperative shape is compared with the cortical surface in the co-registered preoperative magnetic resonance (MR) volume for the estimation of the cortical motion resulting from the open cranial surgery. The estimated cortical motion is then used to guide a full brain model, which updates a preoperative MR volume. We have found that the stereo vision system is accurate to within approximately 1 mm. Based on data from two representative clinical cases, we show that stereopsis guidance improves the accuracy of brain shift compensation both at and below the cortical surface.

Adaptive model initialization and deformation for automatic segmentation of T1-weighted brain MRI data.

A fully automatic, two-step, T1-weighted brain magnetic resonance imaging (MRI) segmentation method is presented. A preliminary mask of parenchyma is first estimated through adaptive image intensity analysis and mathematical morphological operations. It serves as the initial model and probability reference for a level-set algorithm in the second step, which finalizes the segmentation based on both image intensity and geometric information. The Dice coefficient and Euclidean distance between boundaries of automatic results and the corresponding references are reported for both phantom and clinical MR data. For the 28 patient scans acquired at our institution, the average Dice coefficient was 98.2% and the mean Euclidean surface distance measure was 0.074 mm. The entire segmentation for either a simulated or a clinical image volume finishes within 2 min on a modern PC system. The accuracy and speed of this technique allow us to automatically create patient-specific finite element models within the operating room on a timely basis for application in image-guided updating of preoperative scans.

Comparative evaluation of strain-based and model-based modulus elastography.

Elastography based on strain imaging currently endures mechanical artefacts and limited contrast transfer efficiency. Solving the inverse elasticity problem (IEP) should obviate these difficulties; however, this approach to elastography is often fraught with problems because of the ill-posed nature of the IEP. The aim of the present study was to determine how the quality of modulus elastograms computed by solving the IEP compared with those produced using standard strain imaging methodology. Strain-based modulus elastograms (i.e., modulus elastograms computed by simply inverting strain elastograms based on the assumption of stress uniformity) and model-based modulus elastograms (i.e., modulus elastograms computed by solving the IEP) were computed from a common cohort of simulated and gelatin-based phantoms that contained inclusions of varying size and modulus contrast. The ensuing elastograms were evaluated by employing the contrast-to-noise ratio (CNR(e)) and the contrast transfer efficiency (CTE(e)) performance metrics. The results demonstrated that, at a fixed spatial resolution, the CNR(e) of strain-based modulus elastograms was statistically equivalent to those computed by solving the IEP. At low modulus contrast, the CTE(e) of both elastographic imaging approaches was comparable; however, at high modulus, the CTE(e) of model-based modulus elastograms was superior.

Cortical surface tracking using a stereoscopic operating microscope.

OBJECTIVE: To measure and compensate for soft tissue deformation during image-guided neurosurgery, we have developed a novel approach to estimate the three-dimensional (3-D) topology of the cortical surface and track its motion over time. METHODS: We use stereopsis to estimate the 3-D cortical topology during neurosurgical procedures. To facilitate this process, two charge-coupled device cameras have been attached to the binocular optics of a stereoscopic operating microscope. Before surgery, this stereo imaging system is calibrated to obtain the extrinsic and intrinsic camera parameters. During surgery, the 3-D shape of the cortical surface is automatically estimated from a stereo pair of images and registered to the preoperative image volume to provide navigational guidance. This estimation requires robust matching of features between the images, which, when combined with the camera calibration, yields the desired 3-D coordinates. After the 3-D cortical surface has been estimated from stereo pairs, its motion is tracked by comparing the current surface with its previous locations. RESULTS: We are able to estimate the 3-D topology of the cortical surface with an average error of less than 1.2 mm. Executing on a 1.1-GHz Pentium machine, the 3-D estimation from a stereo pair of 1024 x 768 resolution images requires approximately 60 seconds of computation. By applying stereopsis over time, we are able to track the motion of the cortical surface, including the pulsatile movement of the cortical surface, gravitational sag, tissue bulge as a result of increased intracranial pressure, and the parenchymal shape changes associated with tissue resection. The results from 10 surgical patients are reported. CONCLUSION: We have demonstrated that a stereo vision system coupled to the operating microscope can be used to efficiently estimate the dynamic topology of the cortical surface during surgery. The 3-D surface can be coregistered to the preoperative image volume. This unique intraoperative imaging technique expands the capability of the current navigational system in the operating room and increases the accuracy of anatomic correspondence with preoperative images through compensation for brain deformation.

Activation of neural pathways associated with sexual arousal in non-human primates.

PURPOSE: To evaluate brain activity associated with sexual arousal, fully conscious male marmoset monkeys were imaged during presentation of odors that naturally elicit high levels of sexual activity and sexual motivation. MATERIAL AND METHODS: Male monkeys were lightly anesthetized, secured in a head and body restrainer with a built-in birdcage resonator and positioned in a 9.4-Tesla spectrometer. When fully conscious, monkeys were presented with the odors of a novel receptive female or an ovariectomized monkey. Both odors were presented during an imaging trial and the presentation of odors was counterbalanced. Significant changes in both positive and negative BOLD signal were mapped and averaged. RESULTS: Periovulatory odors significantly increased positive BOLD signal in several cortical areas: the striatum, hippocampus, septum, periaqueductal gray, and cerebellum, in comparison with odors from ovariectomized monkeys. Conversely, negative BOLD signal was significantly increased in the temporal cortex, cingulate cortex, putamen, hippocampus, substantia nigra, medial preoptic area, and cerebellum with presentation of odors from ovariectomized marmosets as compared to periovulatory odors. A common neural circuit comprising the temporal and cingulate cortices, putamen, hippocampus, medial preoptic area, and cerebellum shared both the positive BOLD response to periovulatory odors and the negative BOLD response to odors of ovariectomized females. CONCLUSION: These data suggest the odor-driven enhancement and suppression of sexual arousal affect neuronal activity in many of the same general brain areas. These areas included not only those associated with sexual activity, but also areas involved in emotional processing and reward.