Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.

Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA)

OBJECTIVE Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). METHODS We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle grading of MS-lesions.

Differential dynamic properties of scleroderma fibroblasts in response to perturbation of environmental stimuli.

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.

Sequential updating via dynamic hierarchical models: A Bayesian approach to longitudinal data analysis

Most statistical analysis, theory and practice, is concerned with static models; models with a proposed set of parameters whose values are fixed across observational units. Static models implicitly assume that the quantified relationships remain the same across the design space of the data. While this is reasonable under many circumstances this can be a dangerous assumption when dealing with sequentially ordered data. The mere passage of time always brings fresh considerations and the interrelationships among parameters, or subsets of parameters, may need to be continually revised. ^ When data are gathered sequentially dynamic interim monitoring may be useful as new subject-specific parameters are introduced with each new observational unit. Sequential imputation via dynamic hierarchical models is an efficient strategy for handling missing data and analyzing longitudinal studies. Dynamic conditional independence models offers a flexible framework that exploits the Bayesian updating scheme for capturing the evolution of both the population and individual effects over time. While static models often describe aggregate information well they often do not reflect conflicts in the information at the individual level. Dynamic models prove advantageous over static models in capturing both individual and aggregate trends. Computations for such models can be carried out via the Gibbs sampler. An application using a small sample repeated measures normally distributed growth curve data is presented. ^

Running the Gauntlet: Inhibitory Effects of Algal Turfs on the Processes of Coral Recruitment

Mortality of corals is increasing due to bleaching, disease and algal overgrowth. In the Caribbean, low rates of coral recruitment contribute to the slow or undetectable rates of recovery in reef ecosystems. Although algae have long been suspected to interfere with coral recruitment, the mechanisms of that interaction remain unclear. We experimentally tested the effects of turf algal abundance on 3 sequential factors important to recruitment of corals: the biophysical delivery of planktonic coral larvae, their propensity to settle, and the availability of microhabitats where they survive. We deployed coral settlement plates inside and outside damselfish Stegastes spp. gardens and cages. Damselfish aggression reduced herbivory from fishes, and cages became fouled with turf algae, both locally increasing algal biomass surrounding the plates. This reduced flushing rates in nursery microhabitats on the plate underside, limiting larvae available for settlement. Coral spat settled preferentially on an early successional crustose coralline alga Titanoderma prototypum but also on or near other coralline algae, biofilms, and calcareous polychaete worm tubes. Post-settlement survival was highest in the fully grazed, lowest algal biomass treatment, and after 27 mo 'spat' densities were 73 % higher in this treatment. The 'gauntlet' refers to the sequence of ecological processes through which corals must survive to recruit. The highest proportion of coral spat successfully running the gauntlet did so under conditions of low algal biomass resulting from increased herbivory. If coral recruitment is heavily controlled at very local scales by this gauntlet, then coral reef managers could improve a reef's recruitment potential by managing for reduced algal biomass.

Impact of epinephrine and norepinephrine on two dynamic indices in a porcine hemorrhagic shock model

Abstract BACKGROUND: Pulse pressure variations (PPVs) and stroke volume variations (SVVs) are dynamic indices for predicting fluid responsiveness in intensive care unit patients. These hemodynamic markers underscore Frank-Starling law by which volume expansion increases cardiac output (CO). The aim of the present study was to evaluate the impact of the administration of catecholamines on PPV, SVV, and inferior vena cava flow (IVCF). METHODS: In this prospective, physiologic, animal study, hemodynamic parameters were measured in deeply sedated and mechanically ventilated pigs. Systemic hemodynamic and pressure-volume loops obtained by inferior vena cava occlusion were recorded. Measurements were collected during two conditions, that is, normovolemia and hypovolemia, generated by blood removal to obtain a mean arterial pressure value lower than 60 mm Hg. At each condition, CO, IVCF, SVV, and PPV were assessed by catheters and flow meters. Data were compared between the conditions normovolemia and hypovolemia before and after intravenous administrations of norepinephrine and epinephrine using a nonparametric Wilcoxon test. RESULTS: Eight pigs were anesthetized, mechanically ventilated, and equipped. Both norepinephrine and epinephrine significantly increased IVCF and decreased PPV and SVV, regardless of volemic conditions (p < 0.05). However, epinephrine was also able to significantly increase CO regardless of volemic conditions. CONCLUSION: The present study demonstrates that intravenous administrations of norepinephrine and epinephrine increase IVCF, whatever the volemic conditions are. The concomitant decreases in PPV and SVV corroborate the fact that catecholamine administration recruits unstressed blood volume. In this regard, understanding a decrease in PPV and SVV values, after catecholamine administration, as an obvious indication of a restored volemia could be an outright misinterpretation.

Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method

OBJECT The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4-2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated. METHODS The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r(2) = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11-20 mA, 13 patients; 6-10 mA, 8 patients; 4-5 mA, 17 patients; and 1-3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST. CONCLUSIONS Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Combination of MRI and dynamic FET PET for initial glioma grading

AIM MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. PATIENTS, METHODS 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. RESULTS Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). CONCLUSION Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin

One-dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP-β-CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP-β-CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.

Comparison of gadoteric acid and gadobutrol for detection as well as morphologic and dynamic characterization of lesions on breast dynamic contrast-enhanced magnetic resonance imaging

OBJECTIVE In contrast to conventional breast imaging techniques, one major diagnostic benefit of breast magnetic resonance imaging (MRI) is the simultaneous acquisition of morphologic and dynamic enhancement characteristics, which are based on angiogenesis and therefore provide insights into tumor pathophysiology. The aim of this investigation was to intraindividually compare 2 macrocyclic MRI contrast agents, with low risk for nephrogenic systemic fibrosis, in the morphologic and dynamic characterization of histologically verified mass breast lesions, analyzed by blinded human evaluation and a fully automatic computer-assisted diagnosis (CAD) technique. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. In this prospective, single-center study, 45 women with 51 histopathologically verified (41 malignant, 10 benign) mass lesions underwent 2 identical examinations at 1.5 T (mean time interval, 2.1 days) with 0.1-mmol kg doses of gadoteric acid and gadobutrol. All magnetic resonance images were visually evaluated by 2 experienced, blinded breast radiologists in consensus and by an automatic CAD system, whereas the morphologic and dynamic characterization as well as the final human classification of lesions were performed based on the categories of the Breast imaging reporting and data system MRI atlas. Lesions were also classified by defining their probability of malignancy (morpho-dynamic index; 0%-100%) by the CAD system. Imaging results were correlated with histopathology as gold standard. RESULTS The CAD system coded 49 of 51 lesions with gadoteric acid and gadobutrol (detection rate, 96.1%); initial signal increase was significantly higher for gadobutrol than for gadoteric acid for all and the malignant coded lesions (P < 0.05). Gadoteric acid resulted in more postinitial washout curves and fewer continuous increases of all and the malignant lesions compared with gadobutrol (CAD hot spot regions, P < 0.05). Morphologically, the margins of the malignancies were different between the 2 agents, whereas gadobutrol demonstrated more spiculated and fewer smooth margins (P < 0.05). Lesion classifications by the human observers and by the morpho-dynamic index compared with the histopathologic results did not significantly differ between gadoteric acid and gadobutrol. CONCLUSIONS Macrocyclic contrast media can be reliably used for breast dynamic contrast-enhanced MRI. However, gadoteric acid and gadobutrol differed in some dynamic and morphologic characterization of histologically verified breast lesions in an intraindividual, comparison. Besides the standardization of technical parameters and imaging evaluation of breast MRI, the standardization of the applied contrast medium seems to be important to receive best comparable MRI interpretation.

Automatic estimation of noise parameters in Fourier-domain optical coherence tomography cross sectional images using statistical information

We present an application and sample independent method for the automatic discrimination of noise and signal in optical coherence tomography Bscans. The proposed algorithm models the observed noise probabilistically and allows for a dynamic determination of image noise parameters and the choice of appropriate image rendering parameters. This overcomes the observer variability and the need for a priori information about the content of sample images, both of which are challenging to estimate systematically with current systems. As such, our approach has the advantage of automatically determining crucial parameters for evaluating rendered image quality in a systematic and task independent way. We tested our algorithm on data from four different biological and nonbiological samples (index finger, lemon slices, sticky tape, and detector cards) acquired with three different experimental spectral domain optical coherence tomography (OCT) measurement systems including a swept source OCT. The results are compared to parameters determined manually by four experienced OCT users. Overall, our algorithm works reliably regardless of which system and sample are used and estimates noise parameters in all cases within the confidence interval of those found by observers.

Which Radiographic Hip Parameters Do Not Have to Be Corrected for Pelvic Rotation and Tilt?

Background Acetabular anatomy on AP pelvic radiographsdepends on pelvic orientation during radiograph acquisition. However, not all parameters may change to a clinically relevant degree with differences in pelvic orientation. This issue may influence the diagnosis of acetabular pathologies and planning of corrective acetabular surgery (reorientation or rim trimming). However, to this point, it has not been well characterized. Questions/purposes We asked (1) which radiographic parameters change in a clinical setting when normalized to neutral pelvic orientation; (2) which parameters do not change in an experimental setting when the pelvis is experimentally rotated/tilted; and (3) which of these changes are ‘‘ultimately’’ relevant based on a prespecified definition of relevance. Methods In a clinical setup, 11 hip parameters were evaluated in 101 patients (126 hips) by two observers and the interobserver difference was calculated. All parameters were normalized to an anatomically defined neutral pelvic orientation with the help of a lateral pelvic radiograph and specific software. Differences between nonnormalized and normalized values were calculated (effect of normalization). In an experimental setup involving 20 cadaver pelves (40 hips), the maximum range for each parameter was computed with the pelvis rotated (range, −12° to 12°) and tilted (range, −24° to 24°). ‘‘Ultimately’’ relevant changes existed if the effect of normalization exceeded the interobserver difference (eg, 37% versus 6% for prevalence of a positive crossover sign) and/or the maximum experimental range exceeded 1 SD of interobserver difference (eg, 27% versus 6% for anterior acetabular coverage). Results In the clinical setup, all parameters except the ACM angle and craniocaudal acetabular coverage changed when being normalized, eg, effect of normalization for lateral center-edge angle, acetabular index, and sharp angle ranged from −5° to 4° (p values < 0.029). In the experimental setup, five parameters showed no major changes, whereas six parameters did change (all p values < 0.001). Ultimately relevant changes were found for anteroposterior acetabular coverage, retroversion index, and prevalence of a positive crossover or posterior wall sign. Conclusions Lateral center-edge angle, ACM angle, Sharp angle, acetabular and extrusion index, and craniocaudal acetabular coverage showed no relevant changes with varying pelvic orientation and can therefore be acquired independent from individual pelvic tilt and rotation in clinical practice. In contrast, anteroposterior acetabular coverage, crossover and posterior wall sign, and retroversion index call for specific efforts that address individual pelvic orientation such as computer-assisted evaluation of radiographs. Level of Evidence Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging

Purpose. The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). Methods. We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions () were prestratified into enhancing lesions with increased permeability (EL+; ) and enhancing lesions with subtle permeability (EL−; ). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. Results. Significant differences () were found between EL+ and EL− and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL− and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL− and EL+ versus NEL), while EL− and NEL differed only in their SD during outflow. Conclusion. DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL− were similar to NEL, while EL+ differed significantly from EL− and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

A Dynamic Stochastic Frontier Production Model with Time-Varying Efficiency

In this paper we introduce technical efficiency via the intercept that evolve over time as a AR(1) process in a stochastic frontier (SF) framework in a panel data framework. Following are the distinguishing features of the model. First, the model is dynamic in nature. Second, it can separate technical inefficiency from fixed firm-specific effects which are not part of inefficiency. Third, the model allows one to estimate technical change separate from change in technical efficiency. We propose the ML method to estimate the parameters of the model. Finally, we derive expressions to calculate/predict technical inefficiency (efficiency).

Dynamic contrast agent -enhanced magnetic resonance imaging assessment of tumor microvasculature

Dynamic contrast agent-enhanced magnetic resonance imaging (DCE MRI) data, when analyzed with the appropriate pharmacokinetic models, have been shown to provide quantitative estimates of microvascular parameters important in characterizing the angiogenic activity of malignant tissue. These parameters consist of the whole blood volume per unit volume of tissue, v b, transport constant from the plasma to the extravascular, extracellular space (EES), k1 and the transport constant from the EES to the plasma, k2. Parameters vb and k1 are expected to correlate with microvascular density (MVD) and vascular permeability, respectively, which have been suggested to serve as surrogate markers for angiogenesis. In addition to being a marker for angiogenesis, vascular permeability is also useful in estimating tumor penetration potential of chemotherapeutic agents. ^ Histological measurements of the intratumoral microvascular environment are limited by their invasiveness and susceptibility to sampling errors. Also, MVD and vascular permeability, while useful for characterizing tumors at a single time point, have shown less utility in longitudinal studies, particularly when used to monitor the efficacy of antiangiogenic and traditional chemotherapeutic agents. These limitations led to a search for a non-invasive means of characterizing the microvascular environment of an entire tumor. ^ The overall goal of this project was to determine the utility of DCE MRI for monitoring the effect of antiangiogenic agents. Further applications of a validated DCE MRI technique include in vivo measurements of tumor microvascular characteristics to aid in determining prognosis at presentation and in estimating drug penetration. DCE MRI data were generated using single- and dual-tracer pharmacokinetic models with different molecular-weight contrast agents. The resulting pharmacokinetic parameters were compared to immunohistochemical measurements. The model and contrast agent combination yielding the best correlation between the pharmacokinetic parameters and histological measures was further evaluated in a longitudinal study to evaluate the efficacy of DCE MRI in monitoring the intratumoral microvascular environment following antiangiogenic treatment. ^