Dynamic contrast-enhanced MRI of gastric cancer: Correlations of the pharmacokinetic parameters with histological type,Lauren classification,and angiogenesis

PurposeTo compare the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in gastric cancers of different histological type and Lauren classification, and to investigate whether DCE-MRI parameters correlate with vascular endothelial growth factor (VEGF) expression levels in gastric cancer.MethodsIncluded were 32 patients with gastric cancer who underwent DCE-MRI of the upper abdomen before tumor resection. DCE-MRI parameters including the volume transfer coefficient (K^trans), reverse reflux rate constant (K_ep), and extracellular extravascular volume fraction (V_e) were calculated from the tumor region. Post-operative specimens were used for determination of histological differentiation (i.e., non-mucinous, mucinous, or signet-ring-cell adenocarcinoma) as well as Lauren classification (intestinal type or diffuse type). VEGF expression was examined for assessing angiogenesis. DCE-MRI parameters with different histological type and Lauren classification were compared using independent samples t-test and analysis of variance, respectively. Correlations between DCE-MRI parameters and VEGF expression grades were tested using Spearman correlation analysis.ResultsAmong gastric adenocarcinomas of three different histological types, mucinous adenocarcinomas showed a higher V_e and lower K^trans than the others (P < 0.01). Between the two Lauren classifications, the diffuse type showed a higher V_e than the intestinal type (P < 0.001). The mean K^trans showed a significantly positive correlation with VEGF (r = 0.762, P < 0.001).ConclusionDCE-MRI permits noninvasive prediction of tumor histological type and Lauren classification and estimation of tumor angiogenesis in gastric cancer. DCE-MRI parameters can be used as imaging biomarkers to predict the biologic aggressiveness of a tumor as well as patient prognosis.     

Dynamic contrast-enhanced magnetic resonance imaging parameters independent of baseline T10 values

A baseline T₁₀ value is typically needed for dynamic contrast-enhanced (DCE-) MRI studies. However, an assumed baseline T₁₀ has to be used when T₁₀ measurements for patients are not available. In this work, we systematically investigate the dependence on T₁₀ of the commonly used DCE-MRI parameters (K^trans, k_ep, v_e and IAUC) as well as several newly defined parameters [the normalized ratios (NRs) of k_ep, K^trans and v_e, which are measures of relative changes in these parameters between two time points] for a spoiled gradient-echo pulse sequence using simulations and in vivo studies. Effects of various factors on the T₁₀ dependence, such as the true T₁₀ value, flip angle and the potential changes in T₁₀ due to treatment, were also assessed using simulations. We found that DCE-MRI parameters k_ep and the NR of k_ep are largely independent of T₁₀, especially when larger flip angles are used (e.g., 30–40°). Their estimations therefore do not require any knowledge of T₁₀. The NRs of K^trans, v_e and IAUC also exhibit independence to T₁₀, but only when T₁₀ remains constant between pre- and posttreatment. The estimation of parameters themselves (K^trans, v_e and IAUC) is highly dependent on the T₁₀ value.     

Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

Background

Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date.

Results

In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na⁺, K⁺-ATPase and increased cerebral blood flow (CBF). In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A₁ adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A₁ adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na⁺, K⁺-ATPase, in A₁ agonist-treated rats.

Conclusion

The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na⁺, K⁺-ATPase and CBF.     

Critical surface of the ising model with first-neighbor,second-neighbor,and four-spin interactions

Exact values are obtained for the slopesK ₁ ^c (0, 0)/K ₂,K ₁ ^c (0, 0)/K ₄ of the critical surface of paramagnetic-ferromagnetic transitionsK ₁ ^c (K ₂,K ₄) for the two-dimensional Ising model on a square lattice with first-neighbor, second-neighbor, and four-spin couplingsK ₁,K ₂, andK ₄, respectively. The results are obtained using universality arguments to relate the slopes to known spin-spin correlation functions forK ₂=K ₄=0. The equivalence of different expressions for the slopes in terms of correlation functions yields sum rules for the divergent part of certain sums over the second-neighbor and four-spin energy-energy correlation functions.     

Free-breathing radial volumetric interpolated breath-hold examination sequence and dynamic contrast-enhanced MRI combined with diffusion-weighted imaging for assessment of solitary pulmonary nodules

ObjectiveTo test the performance of free-breathing Dynamic Contrast-Enhanced MRI (DCE-MRI) using a radial volumetric interpolated breath-hold examination (VIBE) sequence combined with diffusion-weighted imaging (DWI) for quantitative solitary pulmonary nodule (SPN) assessment.MethodsA total of 67 SPN cases receiving routine MRI routine scans, DWI, and dynamic-enhanced MRI in our hospital from May 2017 to November 2018 were collected. These cases were divided into a malignant group and a benign group according to the characteristics of the SPNs. The quantitative DCE-MRI parameters (K^trans, K_ep, V_e) and apparent diffusion coefficient (ADC) values of the nodules were measured.ResultsThe K^trans and K_ep values in the malignant group were higher than those in the benign group, while the ADC values in the malignant group were lower than those in the benign group. Furthermore, the K^trans value of adenocarcinoma was higher than that of squamous cell carcinoma and small cell carcinoma (P < 0.05). The V_e value was significantly different between non-small cell carcinoma and small cell carcinoma (P < 0.05). With an ADC value of 0.98 × 10⁻³ mm²/s as the threshold, the specificity and sensitivity to diagnose benign and malignant nodules was 90.6% and 80%, respectively.ConclusionHigh-temporal-resolution DCE-MRI using the r-VIBE technique in combination with DWI could contribute to pulmonary nodule analysis and possibly serve as a potential alternative to distinguish malignant from benign nodules as well as differentiate different types of malignancies.     

Assessment of early response to concurrent chemoradiotherapy in cervical cancer: value of diffusion-weighted and dynamic contrast-enhanced MR imaging

Purpose

To investigate diffusion-weighted (DWI) and dynamic contrast-enhanced MR imaging (DCE-MRI) as early response predictors in cervical cancer patients who received concurrent chemoradiotherapy (CCRT).

Materials and methods

Sixteen patients with cervical cancer underwent DWI and DCE-MRI before CCRT (preTx), at 1 week (postT1) and 4 weeks (postT2) after initiating treatment, and 1 month after the end of treatment (postT3). At each point, apparent diffusion coefficient (ADC) and DCE-MRI parameters were measured in tumors and gluteus muscles (GM). Tumor response was correlated with imaging parameters or changes in imaging parameters at each point.

Results

At each point, ADC, K^trans and V_e in tumors showed significant changes (P < 0.05), as compared with those of GM (P > 0.05). PostT1 tumor ADCs showed a significant correlation with tumor size response at postT2 (P = 0.041), and changes in tumor ADCs at postT1 had a significant correlation with tumor size (P = 0.04) and volume response (P = 0.003) at postT2. In tumors, preTx K^trans and V_e showed significant correlations with tumor size at postT3 (P = 0.011) and tumor size response at postT2 (P = 0.019), respectively.

Conclusion

DWI and DCE-MRI, as early biomarkers, have the potential to evaluate therapeutic responses to CCRT in cervical cancers.     

Dynamic contrast-enhanced MRI with Gd-EOB-DTPA for the quantitative assessment of early-stage liver fibrosis induced by carbon tetrachloride in rabbits

PurposeTo explore quantitative parameters obtained by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gd-EOB-DTPA in discriminating early-stage liver fibrosis (LF) in a rabbit model.Materials and methodsLF was established in 60 rabbits by the injection of 50% CCl₄ oil solution, whereas 30 rabbits served as the control group. All rabbits underwent pathological examination to determine the LF stage using the METAVIR classification system. DCE MRI was performed, and quantitative parameters, including K^trans, K_ep, V_e, V_p and Re were measured and evaluated among the different LF stages using spearman correlation coefficients and receiver operating characteristic curve.ResultsIn all, 24, 25, and 22 rabbits had stage F0, stage F1, and stage F2 LF, respectively. K^trans (r = 0.803) increased, and K_ep (r = −0.495) and Re (r = −0.701) decreased with LF stage progression (P < 0.001), while no significant correlation was found for V_e or V_p. K^trans and Re were significantly different between all LF stage pairs compared (F0 vs. F1, F0 vs. F2, F1 vs. F2, F0 vs. F1-F2, P < 0.05). With the exception of F0 vs. F1, K_ep differed significantly between stages (P < 0.05). The AUC of K^trans was higher than that of other quantitative parameters, with an AUC of 0.92, 0.99, 0.94 and 0.92 for staging F0 vs. F1, F0 vs. F2, F1 vs. F2, and F0 vs. F1-F2, respectively.ConclusionAmong quantitative parameters of Gd-EOB-DTPA DCE MRI, K^trans was the best predictor for quantitatively differentiating early-stage LF.     

Differentiation of bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone with multiparametric MRI

PurposeTo investigate the diagnostic utilities of imaging parameters derived from T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone.Materials and methodsThirty-six lesions from 36 patients with prostate cancer were analyzed with T1WI, DWI, and DCE-MRI. The lesions were classified in the bone metastases (n = 22) and benign red marrow depositions (n = 14). Lesion-muscle ratio (LMR), apparent diffusion coefficient (ADC), volume transfer constant (K^trans), reflux rate (Kep), and volume fraction of the extravascular extracellular matrix (Ve) values were obtained from the lesions. The imaging parameters of the both groups were compared using the Mann-Whitney U test, receiver operating characteristics (ROC) curves were analyzed. For the ROC curves, area under the curves (AUCs) were compared.ResultsThe ADC, K^trans, K_ep, and V_e values of bone metastases were significantly higher than those of benign red marrow depositions (Mann-Whitney U test, p < 0.05). However, there was no significant difference in LMR between the two groups (Mann-Whitney U test, p = 0.360). The AUCs of K^trans_, K_ep, ADC, V_e, and LMR were 0.896, 0.844, 0.812, 0.724, and 0.448, respectively. In the pairwise comparison of ROC curves, the AUCs of K^trans and K_ep was significantly higher than LMR.ConclusionsK^trans, K_ep, V_e, and ADC values can be used as imaging tools to differentiate bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone.     

A general dual-bolus approach for quantitative DCE-MRI

Purpose

To present a dual-bolus technique for quantitative dynamic contrast-enhanced MRI (DCE-MRI) and show that it can give an arterial input function (AIF) measurement equivalent to that from a single-bolus protocol.

Methods

Five rabbits were imaged using a dual-bolus technique applicable for high-resolution DCE-MRI, incorporating a time resolved imaging of contrast kinetics (TRICKS) sequence for rapid temporal sampling. AIFs were measured from both the low-dose prebolus and the high-dose main bolus in the abdominal aorta. In one animal, TRICKS and fast spoiled gradient echo (FSPGR) acquisitions were compared.

Results

The scaled prebolus AIF was shown to match the main bolus AIF, with 95% confidence intervals overlapping for fits of gamma-variate functions to the first pass and linear fits to the washout phase, with the exception of one case. The AIFs measured using TRICKS and FSPGR were shown to be equivalent in one animal.

Conclusion

The proposed technique can capture even the rapid circulation kinetics in the rabbit aorta, and the scaled prebolus AIF is equivalent to the AIF from a high-dose injection. This allows separate measurements of the AIF and tissue uptake curves, meaning that each curve can then be acquired using a protocol tailored to its specific requirements.     

Luminescence Studies of the trans-[Cr–Cyclam(CN)2]ClO4(Cyclam = 1,4,7,11-Tetraazacyclotetradecane) Complex: Its Luminescence Spectra in Several Solvents and the Concentration Dependence of Its Luminescence Lifetime

The luminescence lifetime (_lum) and the luminescence spectra of the title complex (I) were determined in eight solvents. We found that in spite of former assumptions, the _lum of I depends on the concentration of the complex. We determined the self-quenching (k _Q) and Stern–Volmer (K _SV) constants, and the relative values of luminescence quantum yields in eight solvents. There was no measurable self-quenching in 1,2-ethanediol and N,N-dimethylformamide; dynamic self-quenching was found (the concentration dependence of _lum and _lum was the same) in N,N-dimethylacetamide, dimethylsulfoxide, water, propylene–carbonate, and pyridine. In acetonitrile we found both dynamic and static self-quenching based on the different concentration dependence of _lum and _lum of I; K _SV and the association constant of I in acetonitrile were computed     

One criterion of semigroup product convergence

Let exp(-tA) and exp(-tB) be C ₀ contraction semigroups on both K and , where K is a Hilbert space and is a reflexive Banach space such that the linear space K is dense both in K and . Let ^* be a dual pair of Banach spaces. In this paper we study some properties of infinitesimal operators of these semigroups. We show that under suitable assumptions there is some connection between the form-sum A+B and a closure of A ₁+B₁, where -A ₁ is an infinitesimal operator of C ₀ contraction semigroup exp(-tA ₁) which is the extension by continuity on of C ₀ contraction semigroup exp(-tA) Kin . In particular we give some criterion of an m-accretive closability A ₁+B ₁ which may be applied for example to the Schrödinger operators acting in suitable L ^p-spaces. Also this criterion together with properties of semigroups under consideration results in the establishment of the Lie-Trotter formulae.     

Evaluation of time-intensity curves in ductal carcinoma in situ (DCIS) and mastopathy obtained using dynamic contrast-enhanced magnetic resonance imaging

Purpose

The aim of this study was to retrospectively evaluate the ability of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their signal intensities (SIs).

Methods

After the pre-contrast MRI was performed using a 1.5-T MRI system, DCE-MRI was performed four times following intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland and obtained the SIs in these VOIs. We calculated the entropy (EPY) in the pre-contrast (EPY0) and four post-contrast scans (EPY1, EPY2, EPY3, and EPY4 for the first, second, third and fourth scans, respectively) using the volume histogram method, and the wash-in (WR_in) and washout rates (WR_out) according to the Breast-Imaging Reporting and Data System developed by the American College of Radiology. We also calculated the early slope (Slope_early) from the pre- and post-contrast SIs in the tumor and normal gland. We evaluated the usefulness of the above parameters for differentiating between DCIS and mastopathy using the area under the receiver operating characteristic curve (Az).

Results

There were significant differences in EPY2 (P=.009), EPY3 (P=.017), EPY4 (P=.034), WR_in (P=.036), WR_out (P=.019), and Slope_early (P=.002) between DCIS and mastopathy. The average Az values were 0.67, 0.52, 0.64, 0.63, 0.67 and 0.70 for EPY2, EPY3, EPY4, WR_in, WR_out and Slope_early, respectively.

Conclusion

We evaluated the usefulness of various parameters calculated from SIs obtained by DCE-MRI for differentiating between DCIS and mastopathy. Our results suggested that Slope_early is more useful than EPYs, WR_in and WR_out.     

Prediction of early response to radiotherapy of uterine carcinoma with dynamic contrast-enhanced MR imaging using pixel analysis of MR perfusion imaging

Purpose

To assess the predictability of the response to radiotherapy of uterine carcinoma, this study retrospectively analyzed dynamic contrast-enhanced magnetic resonance images (DCE-MRI) taken before radiotherapy.

Materials and Methods

Forty-two patients with uterine carcinoma were studied, of whom 22 had adenocarcinoma and 20 had squamous cell carcinoma (SCC). In DCE-MRI analysis, two parameters, SIe and R_down, were measured. SIe is a median value for the degree of signal intensity change in all selected pixels in the tumor at 1–2 min after contrast agent injection. R_down is the ratio of the number of down-sloped pixels to that of all selected pixels 3–7 min after injection. The tumor volume reduction rate (TVRR) was measured by MRI-based volumetry in pre- and post-radiotherapy transverse T2-weighted images.

Results

Overall, TVRR was significantly correlated to both SIe (r=0.37, P=.015) and R_down (r=0.73, P<.0001). In the separate patient groups, SIe but not R_down was significantly different between the adenocarcinoma and SCC patients (t=3.64, P<.001). TVRR was not correlated to SIe in any group. TVRR was significantly correlated to R_down in adenocarcinoma patients (r=0.78, P<.001) but not in SCC patients.

Conclusion

SIe may reflect differences in histological characteristics. R_down may be useful for predicting the response to radiotherapy of uterine carcinoma.     

The theory of neutron scattering from mixed harmonic solids

In the intermediate valent cerium alloys Ce_1–xY_xPd₃, Ce(Pd_1–xRh_x)₃ and Ce(Pd_1–xAg_x)₃ the Gd³⁺-ESR shows a non-linear increase of the linewidth H(T) in the temperature range 4.2KT300K. The deviation from the linear Korringa law can be described by a reduced conduction electron density of states at the Gd site (which is a Ce lattice site) in the energy range E _4f (=width of the Ce 4f states). This supposition allows a determination of E _4f from the H(T)-data. For CePd₃:Gd³⁺ we find E _4f=(650±100) K. E _4f increases with Y- and Rh-concentration and decreases with Ag-concentration.     

Re-entrant ferromagnetism in a two-dimensional mixed spin Ising model with random nearest-neighbour interactions

Using the finite cluster approximation we study a mixed spin model with random interactions on a ferrimagnetic square lattice (with spins =1/2 andS=1). The interactions are assumed to be independent random variables with distribution,P(K _ij )=p(K _ij –K)+(1–p) (K _ij –K), whereK>0 and ||1. In a certain range of negative values of the phase diagrams exhibit re-entrant behaviour. This indicates that re-entrance seems to be a characteristic feature of systems in which both frustration and disorder are present.On leave from Faculté des Sciences I, Université Hassan II, Casablanca, Morocco; and Laboratoire de Magnétisme Université de Rabat, MoroccoSupported by the agreement of cooperation between the DFG and the CNR-Maroc.     

Possibility of a Lifshitz phase transition in Cd observed by a singularity in the muon Knight shift

During the past much effort has been devoted to a systematic study of the muon Knight shiftK in metallic environments and its implications on the local electronic structure of hydrogen in metals [1]. These measurements in simple metals were essentially all carried out in polycrystalline samples at room temperature. The present measurements in Cd in polycrystalline and single crystal samples cover a temperature range between 20 K and the melting point of this strongly anisotropic metal (hcp crystal structure,c/a ratio 1.89 — idealc/a ratio 1.63). These measurements add qualitatively new and interesting aspects and insights on the screening of a light hydrogen isotope in a metal as well as on certain properties of the host material itself. The outstanding features of the muon Knight shift in Cd are: (i) a strong intrinsic temperature dependence with an increase ofK of more than 100% between 20 K and the melting point (T=593 K), (ii) an anomaly at 110 K in the form of a singularity in the isotropic part ofK which is interpreted as a band structure effect, (iii) an anisotropic Knight shift contribution fitting the expressionK(T,)=K _iso(T)+K _ax(T) * (3 · cos² –1)/2, where both, the isotropic and the axial contribution ofK , are strongly temperature dependent.     

Far-Infrared Laser Stark Spectroscopy of CH3OD

The high resolution Stark spectra of the singly deuterated methanol isotope, CH₃OD, have been studied using the HCN laser with Stark fields up to approximately 60 000 V/cm. Numerous families of absorption lines have been observed in both parallel and perpendicular polarizations, resulting in the following assignments: with the 311 m line – J _K = 18₁ 18₀ E ₂, _t = 1; and with the 337 m line – J _k = 6₄ 5₃ E ₂, _t = 0 and J _K = 14₆ 13₅ A, _t = 1. Zero-field frequencies for the assigned transitions are in agreement with Fourier transform measurements and those calculated from the available molecular constants.     

Experimental study of hard photon radiation processes at HERA

We present an experimental study of theepe+p andepe+X processes using data recorded by the H1 detector in 1993 at the electron-proton collider HERA. These processes are employed to measure the luminosity with an accuracy of 4.5 %. A subsample of theepe+X events in which the hard photon is detected at angles 0.45 mrad with respect to the incident electron direction is used to verify experimentally the size of radiative corrections to theepeX inclusive cross section and to investigate the structure of the proton in theQ ² domain down to 2 GeV², lower than previously attained at HERA.Supported by the Bundesministerium für Forschung und Technologie, FRG under contract numbers 6AC17P, 6AC47P, 6DO57I, 6HH17P, 6HH27I, 6HD17I, 6HD27I, 6KI17P, 6MP17I, and 6WT87P     

Driven dynamics of the Frenkel Kontorova Aubry model

The dynamics of the Frenkel-Kontorova model in the presence of an accelerating fieldE is studied analytically and numerically in the damping-free limit and for small periodic potential strengthK. ForE>K ^4/3, the velocityV(t) increases linearly with time while the internal vibration amplitude remains small. ForK ²<E<K ^4/3,V(t) stops increasing after a timet ₁=1/E, after which the whole power is absorbed by internal vibrations. These vibrations become (unphysically) huge, and stop increasing after a time which cannot exceedt ₂8.33/E. Then the velocity goes on increasing linearly with time. The effect of a weak damping is also considered.