Detection of areas with viable remnant tumor in postchemotherapy patients with Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokinetic modeling

An approach is presented for monitoring the effects of neoadjuvant chemotherapy in patients with Ewing's sarcoma using dynamic contrast-enhanced perfusion magnetic resonance (MR) images. For that purpose, we modify the three-compartment pharmacokinetic permeability model introduced by Tofts et al. (Magn Reson Med 1991;17:357-67) to a two-compartment model. Perfusion MR images acquired using an intravenous injection with Gadolinium (Gd-DTPA) are analyzed with this two-compartment pharmacokinetic model as well as the with an extended pharmacokinetic model that includes the (local) arrival time t(0) of the tracer as an endogenous (estimated) parameter. For each MR section, a wash-in parameter associated with each voxel is estimated twice by fitting each of the two pharmacokinetic models to the dynamic MR signal. A comparison of the two wash-in parametric images (global versus local arrival time) with matched histologic macroslices demonstrates a good correspondence between areas with viable remnant tumor and a high wash-in rate. This can be explained by the high number and permeability of the (leaking) capillaries in viable tumor tissue. The novel pharmacokinetic model based on a local arrival time of tracer results in the best fit of the wash-in rate, the most important factor discerning viable from nonviable tumor components. However, parameter estimates obtained with this model are also more sensitive to noise in the MR signal. The novel pharmacokinetic model resulted in a sensitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The model based on a global arrival time gave sensitivities between 0.33 and 0.77 and specificities between 0.58 and 0.99. Both statistics are computed as the fraction of correctly labeled voxels (viable or nonviable tumor) within a specified ROI, which delineates the tumor. We conclude that the added value of estimating the local arrival time of tracer first manifests itself for moderate noise levels in the MR signal. The novel pharmacokinetic model should moreover be preferred when pharmacokinetic modeling is applied on the average signal intensity within a ROI, where noise has less effect on the fitted parameters.     

Renal perfusion in acute kidney injury with DCE-MRI: Deconvolution analysis versus two-compartment filtration model

Purpose

To investigate the results of different pharmacokinetic models of a quantitative analysis of renal blood flow (RBF) in acute kidney injury using deconvolution analysis and a two-compartment renal filtration model.

Materials and methods

MRI data of ten male Lewis rats were analyzed retrospectively. Six animals were subjected to unilateral acute kidney injury and underwent perfusion imaging by dynamic contrast-enhanced MRI (DCE-MRI). Renal blood flow was estimated from regions-of-interest depicting the cortex in the DCE-MRI perfusion maps. The perfusion models were compared by a paired t-test and Bland–Altman plots.

Results

No significant difference was found between the two compartment model and the deconvolution analysis (P = 0.2807). Differences between healthy and diseased kidney in the AKI model were significant for both methods (P < 0.05). A Bland–Altman plot showed no systematic errors, and values were equally distributed around the mean difference between the methods lying within the range of 1.96 standard deviations.

Conclusion

Both quantification strategies could detect the kidneys that were impaired by AKI. When just aiming at RBF as a marker, a deconvolution analysis can provide similar values as the 2CFM. If functional parameters beyond RBF like glomerular filtration rate are needed, the 2CFM should be employed.     

A variational approach to image registration in dynamic contrast-enhanced MRI of the human kidney

Kidney function can be accessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measurements which yield spatially resolved maps of physiological parameters like perfusion or filtration. The motion of the kidneys during the scan is a dominant limitation of the measurement quality, and image registration is necessary for accurate quantification. We analyzed the feasibility of applying an algorithm, originally developed for multimodal registration, to kidney perfusion time series. The algorithm uses a variational calculation scheme to align the images. In four out of five data sets, kidney motion could be reduced to below the spatial resolution of the images of 1.6 mm while preserving the enhancement pattern of kidney perfusion. Fitting a pharmacokinetic model to the data showed an average reduction of the Akaike fit error of 10% for the registered data, suggesting more stable parameters. We conclude that this image registration algorithm is feasible for correcting kidney motion in renal DCE-MRI.     

High resolution rotational spectrum of FCO2 radical (extension to lower frequencies)

We have subsequently extended the measurement of the FC¹⁶O₂ radical to the lower frequency region, between 210 and 245 GHz with the recently developed Prague microwave spectrometer. About 60 new a-type R-branch transitions have been observed. Our present analysis enabled us to improve significantly the determination of the ground state constants: most of the parameters are now determined with higher precision up to an order of magnitude better than the previous study. In addition eight new constants could be determined or nearly determinable for the first time.     

扩散噪声下协方差矩阵重构的语音分离与降噪

针对传统多通道语音分离算法在扩散噪声下性能下降的问题,提出了一种用于语音分离及降噪的空间协方差模型及参数估计方法。该方法将扩散噪声视为独立声源,利用由导向矢量重构的空间协方差矩阵建模目标声源的空间特性,并通过空间协方差分析方法估计用于语音分离的多通道维纳滤波器。同时,还提出了一种联合该方法的后置滤波器参数框架,为输出信号降噪和失真的折中提供了更多选择。在扩散噪声下的单目标和多目标实验中,所提方法的语音提取和分离性能都优于对比算法,联合参数的后置滤波器可提供更为符合人们要求的降噪语音,验证了所提模型与参数估计方法的有效性。      

Enhancement in sensitivity of a blood perfusion parameter for frame-rate analysis of bio-speckle image

We have previously presented a blood perfusion parameter by means of the spatial contrast of speckle patterns observed for blood perfusion in skin tissue and a blood vessel. This parameter permits us to visualize a relative blood perfusion distribution from a single speckle pattern. Therefore, it can estimate the blood perfusion with a frame rate of an imaging device employed. This parameter is, however, dependent on the speckle size and the condition of image processing of speckle patterns. In the present study, we estimated this condition with relation to the speckle size for obtaining high sensitivity and good linearity of the parameter to the blood perfusion. Experiments were conducted for ground-glass model, flow model and human wrist to investigate perfusion sensing characteristics of the present parameter.

     

Modeling of CW laser diode irradiation of amorphous silicon films

The purpose of this work is to determine the optimal parameters required to crystallize thin amorphous silicon films on glass substrate with a continuous wave (CW) laser diode (λ = 808 nm), using a numerical model developed in COMSOL Multiphysics. The numerical simulation of the laser crystallization process takes into account the solid-liquid phase change and the difference between the melting temperature of amorphous (Tm_a-Si = 1420 K) and that of crystalline silicon (Tm_c-Si = 1690 K). We have varied the main parameters controlling the crystallization process, namely the power and the scan speed of the laser beam. Furthermore the initial temperature as well as the thickness of the a-Si:H layer were also taken as a parameter to optimize the process. We have determined the melting, crystallization and ablation energy threshold versus the different operational parameters.     

Blood oxygenation level dependent magnetic resonance imaging and diffusion weighted MRI imaging for benign and malignant breast cancer discrimination

PurposeThe purpose of this study is to assess Blood oxygenation level dependent Magnetic Resonance Imaging (BOLD-MRI) and Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) in the differentiation of benign and malignant breast lesions.MethodsFifty-nine breast lesions (26 benign and 33 malignant lesions) pathologically proven in 59 patients were included in this retrospective study. As BOLD parameters were estimated basal signal S₀ and the relaxation rate R2*, diffusion and perfusion parameters were derived by DWI (pseudo-diffusion coefficient (Dp), perfusion fraction (fp) and tissue diffusivity (Dt)). Wilcoxon-Mann-Whitney U test and Receiver operating characteristic (ROC) analyses were calculated and area under ROC curve (AUC) was obtained. Moreover, pattern recognition approaches (linear discrimination analysis (LDA), support vector machine, k-nearest neighbours, decision tree) with least absolute shrinkage and selection operator (LASSO) method and leave one out cross validation approach were considered.ResultsA significant discrimination was obtained by the standard deviation value of S0, as BOLD parameter, that reached an AUC of 0.76 with a sensitivity of 65%, a specificity of 85% and an accuracy of 76%. No significant discrimination was obtained considering diffusion and perfusion parameters. Considering LASSO results, the features to use as predictors were all extracted parameters except that the mean value of R2* and the best result was obtained by a LDA that obtained an AUC = 0.83, with a sensitivity of 88%, a specificity of 77% and an accuracy of 83%.ConclusionsGood performance to discriminate benign and malignant lesions could be obtained using BOLD and DWI derived parameters with a LDA classification approach. However, these findings should be proven on larger and several dataset with different MR scanners.     

An analysis of the pharmacokinetic parameter ratios in DCE-MRI using the reference region model

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed by obtaining sequential MRI images, before, during and after the injection of a contrast agent. It is usually used to observe the exchange of contrast agent between the vascular space and extravascular extracellular space (EES), and provide information about blood volume and microvascular permeability. To estimate the kinetic parameters derived from the pharmacokinetic model, accurate knowledge of the arterial input function (AIF) is very important. However, the AIF is usually unknown, and it remains very difficult to obtain such information noninvasively. In this article, without knowledge of the AIF, we applied a reference region (RR) model to analyze the kinetic parameters. The RR model usually depends on kinetic parameters found in previous studies of a reference region. However, both the assignment of reference region parameters (intersubject variation) and the selection of the reference region itself (intrasubject variation) may confound the results obtained by RR methods. Instead of using literature values for those pharmacokinetic parameters of the reference region, we proposed to use two pharmacokinetic parameter ratios between the tissue of interest (TOI) and the reference region. Specifically, one parameter K_R is calculated as the ratio between the volume transfer constant K^trans of the TOI and RR. Similarly, another parameter V_R is calculated as the ratio between the extravascular extracellular volume fraction v_e of the TOI and RR. To investigate the consistency of the two ratios, the K^trans of the RR was varied ranging from 0.1 to 1.0 min⁻¹, covering the cited literature values. A simulated dataset with different levels of Gaussian noises and an in vivo dataset acquired from five canine brains with spontaneous occurring brain tumors were used to study the proposed ratios. It is shown from both datasets that these ratios are independent of K^trans of the RR, implying that there is potentially no need to obtain information about literature values from the reference region for future pharmacokinetic modeling and analysis.     

Effectiveness of in situ NH3 annealing treatments for the removal of oxygen from GaN surfaces

An in situ NH₃ annealing procedure for the cleaning of GaN(0 0 0 1) is studied in detail using density functional theory (DFT), microkinetic modeling and X-ray photoelectron spectroscopy (XPS). The microkinetic model was calibrated and tested against published H₂ and NH₃ temperature programmed desorption (TPD) experiments on GaN(0 0 0 1). We find that an NH₃ treatment is efficient for the removal of carbon contaminants, but a complete removal of oxygen contaminants cannot be achieved. The remaining oxygen coverage after the treatment was estimated from XPS measurements to be 0.92 ML. In contrast, our microkinetic model based on DFT derived parameters predicts complete removal of OH species and a final oxygen coverage of 0.19 ML. We assign the difference between model and experiments to the formation of a surface oxide phase, which is not included in the model. DFT results also indicate strong adsorbate-adsorbate interactions for H, N, NH, NH₂, O, and OH on the GaN(0 0 0 1) surface which were incorporated into the microkinetic model to a first approximation. XPS experiments and microkinetic modeling demonstrate that the final surface composition shows little dependence on process parameters such as temperature or the time the sample is kept at an elevated temperature. Furthermore, the microkinetic model suggests that complete removal of OH from the surface can also be achieved using a NH₃/H₂ mixture, or even pure H₂ as a hydrogen source. The amount of H₂ present in the feed changes the coverage of NH_x species, but a certain amount of adsorbed oxygen is always left on the surface.     

The Okinawa study: an estimation of noise-induced hearing loss on the basis of the records of aircraft noise exposure around Kadena Air Base

Aircraft noise measurements were recorded at the residential areas in the vicinity of Kadena Air Base, Okinawa in 1968 and 1972 at the time of the Vietnam war. The estimated equivalent continuous A-weighted sound pressure level L_Aeq for 24 h was 85 dB.The time history of sound level during 24 h was estimated from the measurement conducted in 1968, and the sound level was converted into the spectrum level at the centre frequency of the critical band of temporary threshold shift (TTS) using the results of spectrum analysis of aircraft noise operated at the airfield. With the information of spectrum level and its time history, TTS was calculated as a function of time and level change. The permanent threshold shift was also calculated by means of Robinson's method and ISO's method. The results indicate the noise exposure around Kadena Air Base was hazardous to hearing and is likely to have caused hearing loss to people living in its vicinity.     

3-D Model of sound pressure field in a meridinal section plane of fruit

A theoretical model was suggested for qualitative evaluation of a sound pressure field in fruit tissue, as affected by ultrasonic probe dimensions and fruit properties. The classic directivity pattern of an ideal fluid model, expressed by Bessel function of the first kind, was extended to include energy dissipation of a real material. The directional characteristics of wave propagation, as influenced by transmitter frequency and diameter, and by fruit properties, were discussed. The model indicates how to select the parameters of the ultrasonic transducer (transducer diameter, frequency and excitation power) to control the magnitude and directivity of the ultrasonic waves in the fruit tissue. The suggested theoretical model represented fairly well the experimental sound wave distribution over the half-cut surface of potato and avocado (R² > 0.862 and 0.977, respectively); the same theoretical model could not represent the sound wave distribution over a half-cut melon. Results of the study were applied in a new probe design for ultrasonic testing of whole fruit.     

The effect of perfusion on the temperature distribution during thermotherapy: Study on perfused porcine kidneys

The effect of perfusion on the temperature distribution during radio-frequency hyperthermia and laser-induced thermotherapy was investigated with the perfused porcine kidney model. The phase shift-based proton resonance frequency shift method was used to map the temperature distribution. In experiments with modulated perfusion rates it was demonstrated that perfusion dissipates a significant amount of the absorbed energy and, therefore, the resulting heat distribution is strongly dependent on the perfusion rate. The measured time course of the temperature distribution was used to estimate the thermal conductivity, local perfusivity and heat absorption rate of the tissue. These parameters were in a good agreement with literature data. This approach can also be extended to measure heat absorption and heat transfer parameters in vivo, which can significantly improve the accuracy of thermotherapy session planning.     

Evolution of structure, microstructure and hyperfine properties of nanocrystalline Fe50Co50 powders prepared by mechanical alloying

Nanostructured Fe₅₀Co₅₀ powders were prepared by mechanical alloying of Fe and Co elements in a vario-planetary high-energy ball mill. The structural properties, morphology changes and local iron environment variations were investigated as a function of milling time (in the 0-200 h range) by means of X-ray diffraction, scanning electron microscopy (SEM), energy dispersive X-ray analysis and ⁵⁷Fe Mössbauer spectroscopy. The complete formation of bcc Fe₅₀Co₅₀ solid solution is observed after 100 h milling. As the milling time increases from 0 to 200 h, the lattice parameter decreases from 0.28655 nm for pure Fe to 0.28523 nm, the grain size decreases from 150 to 14 nm, while the meal level of strain increases from 0.0069% to 1.36%. The powder particle morphology at different stages of formation was observed by SEM. The parameters derived from the Mössbauer spectra confirm the beginning of the formation of Fe₅₀Co₅₀ phase at 43 h of milling. After 200 h of milling the average hyperfine magnetic field of 35 T suggests that a disordered bcc Fe-Co solid solution is formed.     

Effect of temperature on the intrinsic viscosity of poly(ethylene glycol) in water/dimethyl sulfoxide solutions

In this work, the intrinsic viscosities of poly(ethylene glycol) with molar mass of 20 kg mol^− 1 were measured in water/dimethyl sulfoxide solutions from (298.15 to 318.15) K. The expansion factors of the polymer chains were calculated from the intrinsic viscosity data. The expansion factor were decreased by increasing temperature; therefore the chain of PEG shrinks and the end-to-end distance become smaller by increasing temperature. Perhaps the interactions of segment-segment are favored toward segment-solvent by increasing temperature; therefore the hydrodynamic volumes of the polymer coils become smaller by increasing temperature. The thermodynamic parameters (entropy of dilution parameter, the heat of dilution parameter, theta temperature and polymer-solvent interaction parameter) were derived by the temperature dependence of the polymer chain expansion factor. The thermodynamic parameters indicate that the interactions of segment-segment were increased by increasing temperature.     

Intravoxel incoherent motion diffusion-weighted imaging in head and neck squamous cell carcinoma: Assessment of perfusion-related parameters compared to dynamic contrast-enhanced MRI

Purpose

To investigate the correlation between perfusion-related parameters obtained with intravoxel incoherent motion (IVIM) and classical perfusion parameters obtained with dynamic contrast-enhanced (DCE) magnetic resonance imaging in patients with head and neck squamous cell carcinoma (HNSCC), and to compare direct and asymptotic fitting, the pixel-by-pixel approach, and a region of interest (ROI)-based approach respectively for IVIM parameter calculation.

Materials and methods

Seventeen patients with HNSCC were included in this retrospective study. All magnetic resonance (MR) scanning was performed using a 3 T MR unit. Acquisition of IVIM was performed using single-shot spin-echo echo-planar imaging with three orthogonal gradients with 12 b-values (0, 10, 20, 30, 50, 80, 100, 200, 400, 800, 1000, and 2000). Perfusion-related parameters of perfusion fraction ‘f’ and the pseudo-diffusion coefficient ‘D*’ were calculated from IVIM data by using least square fitting with the two fitting methods of direct and asymptotic fitting, respectively. DCE perfusion was performed in a total of 64 dynamic phases with a 3.2-s phase interval. The two-compartment exchange model was used for the quantification of tumor blood volume (TBV) and tumor blood flow (TBF). Each tumor was delineated with a polygonal ROI for the calculation of f, f ? D* performed using both the pixel-by-pixel approach and the ROI-based approach. In the pixel-by-pixel approach, after fitting each pixel to obtain f, f ? D* maps, the mean value in the delineated ROI on these maps was calculated. In the ROI-based approach, the mean value of signal intensity was calculated within the ROI for each b-value in IVIM images, and then fitting was performed using these values. Correlations between f in a total of four combinations (direct or asymptotic fitting and pixel-by-pixel or ROI-based approach) and TBV were respectively analyzed using Pearson's correlation coefficients. Correlations between f ? D* and TBF were also similarly analyzed.

Results

In all combinations of f and TBV, f ? D* and TBF, there was a significant correlation. In the comparison of f and TBV, a moderate correlation was observed only between f obtained by direct fitting with the pixel-by-pixel approach, whereas a good correlation was observed in the comparisons using the other three combinations. In the comparison of f ? D* and TBF, a good correlation was observed only with f ? D* obtained by asymptotic fitting with the ROI-based approach. In contrast, moderate correlations were observed in the comparisons using the other three combinations.

Conclusion

IVIM was found to be feasible for the analysis of perfusion-related parameters in patients with HNSCC. Especially, the combination of asymptotic fitting with the ROI-based approach was better correlated with DCE perfusion.     

Single voxel vascular transport functions of arteries,capillaries and veins; and the associated arterial input function in dynamic susceptibility contrast magnetic resonance brain perfusion imaging

PurposeThe composite vascular transport function of a brain voxel consists of one convolutional component for the arteries, one for the capillaries and one for the veins in the voxel of interest. Here, the goal is to find each of these three convolutional components and the associated arterial input function.Pharmacokinetic modellingThe single voxel vascular transport functions for arteries, capillaries and veins were all modelled as causal exponential functions. Each observed multipass tissue contrast function was as a first approximation modelled as the resulting parametric composite vascular transport function convolved with a nonparametric and voxel specific multipass arterial input function. Subsequently, the residue function was used in the true perfusion equation to optimize the three parameters of the exponential functions.Deconvolution methodsFor each voxel, the parameters of the three exponential functions were estimated by successive iterative blind deconvolutions using versions of the Lucy-Richardson algorithm. The final multipass arterial input function was then computed by nonblind deconvolution using the Lucy-Richardson algorithm and the estimated composite vascular transport function.ResultsSimulations showed that the algorithm worked. The estimated mean transit time of arteries, capillaries and veins of the simulated data agreed with the known input values. For real data, the estimated capillary mean transit times agreed with known values for this parameter. The nonparametric multipass arterial input functions were used to derive the associated map of the arrival time. The arrival time map of a healthy volunteer agreed with known arterial anatomy and physiology.ConclusionClinically important new voxelwise hemodynamic information for arteries, capillaries and veins separately can be estimated using multipass tissue contrast functions and the iterative blind Lucy-Richardson deconvolution algorithm.     

Magnetic Properties of Nanoparticles Useful for SQUID Relaxometry in Biomedical Applications

We use dynamic susceptometry measurements to extract semiempirical temperature-dependent, 255-400 K, magnetic parameters that determine the behavior of single-core nanoparticles useful for SQUID relaxometry in biomedical applications. Volume susceptibility measurements were made in 5 K degree steps at nine frequencies in the 0.1-1000 Hz range, with a 0.2 mT amplitude probe field. The saturation magnetization (M_s) and anisotropy energy density (K) derived from the fitting of theoretical susceptibility to the measurements both increase with decreasing temperature; good agreement between the parameter values derived separately from the real and imaginary components is obtained. Characterization of the Néel relaxation time indicates that the conventional prefactor, 0.1 ns, is an upper limit, strongly correlated with the anisotropy energy density. This prefactor decreases substantially for lower temperatures as K increases. We find, using the values of the parameters determined from the real part of the susceptibility measurements at 300 K, that SQUID relaxometry measurements of relaxation and excitation curves on the same sample are well described.     

Semiquantitative perfusion combined with diffusion-weighted MR imaging in pre-operative evaluation of endometrial carcinoma: Results in a group of 57 patients

Purpose

To evaluate the semiquantitative DCE and quantitative DWI parameters in endometrial cancer, in order to assess the presence of neoplastic tissue and normal myometrium and to ascertain a potential relationship with tumor grade.

Methods and materials

A total of 57 patients with biopsy-proven endometrial adenocarcinoma who underwent MR imaging examination for staging purposes were retrospectively evaluated. Imaging protocol included multiplanar T₁- and T₂-weighted TSE, DCE T₁-weighted (THRIVE; 0, 30, 90 and 120 seconds after intravenous injection of gadolinium) and DWIBS sequences (b values = 0 and 1000 mm²/s). Color perfusion and ADC maps were automatically generated on dedicated software. Relative enhancement (RE, %), maximum enhancement (ME, %), maximum relative enhancement (MRE, %), time to peak (TTP, s) and mean apparent diffusion coefficient (ADC) were calculated by manually drawing a region of interest (ROI) both on the neoplastic tissue and the normal myometrium. Histopathology was used as reference standard.

Results

Histopathological analysis confirmed the presence of endometrial carcinoma in all patients. Neoplastic tissue demonstrated significantly lower (P < 0.001) values of RE (%) 63.92 ± 35.68; ME (%) 864.91 ± 429.54 and MRE (%) 75.97 ± 38.26 as compared to normal myometrium (RE (%) 151.43 ± 55.99; ME (%) 1800.73 ± 721.32; MRE (%) 158.28 ± 54.05). TTP was significantly higher (P < 0.05) in tumor lesion (385.51 ± 1630.27 vs 195.44 ± 78.69). Mean ADC value of neoplastic tissue (775.09 ± ?220.73 × 10^− 3 mm²/s) was significantly lower (P < 0.05) than in myometrium (1602.37 ± 378.54 × 10^− 3 mm²/s). The analysis of perfusion and diffusion parameters classified according to tumor grades, showed a statistically significant difference only for RE (P = 0.043) and ME (P = 0.007).

Conclusions

Perfusion parameters and mean ADC differ significantly between endometrial cancer and normal myometrium, potentially reflecting the different microscopical features of cellularity and vascularity; however a significant relationship with tumor grade was not found in our series.     

Preparation of activated carbon from Enteromorpha prolifera and its use on cationic red X-GRL removal

Enteromorpha prolifera was pyrolyzed to prepare activated carbon using chemical activation by zinc chloride. The effect of activation parameters such as activation temperature, weight ratio (Enteromorpha prolifera to ZnCl₂), and activation time was investigated. The BET results showed that the surface area and pore volume of activated carbons were achieved as high as 1722 m²/g and 1.11 cm³/g, respectively, in the optimal activation conditions. Batch adsorption studies were carried out to study the adsorption properties of cationic red X-GRL onto activated carbon by varying the parameters like initial solution pH, contact time, and temperature. The kinetic studies showed that the adsorption data followed a pseudo second-order model. The isotherm analysis indicated that the adsorption data could be represented by the Langmuir isotherm model. The Langmuir monolayer adsorption capacity of cationic red X-GRL was estimated as 263.16 mg/g at pH 6.0.