bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic efficacy of 5‐fluorouracil‐loaded microspheres on rat glioma: a magnetic resonance imaging study
Authors: Lemaire L. , Roullin V.‐G. , Franconi F. , Venier‐Julienne M.‐C. , Menei P. , Jallet P. , Le Jeune J.‐J. , Benoit J.‐P. 
Published: January 2005

AbstractThe aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5‐fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast‐growing C6‐glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13 ± 2 µl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow‐up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p < 0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection. Copyright © 2001 John Wiley & Sons, Ltd.
Differential sensitivity of two adenocarcinoma xenografts to the anti‐vascular drugs combretastatin A4 phosphate and 5,6‐dimethylxanthenone‐4‐acetic acid, assessed using MRI and MRS
Authors: Beauregard Daniel A. , Pedley R. Barbara , Hill Sally A. , Brindle Kevin M. 
Published: January 2005

AbstractThe effects of two anti‐vascular agents, combretastatin A4 phosphate (CA4P), and 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA), on the perfusion of two human colon adenocarcinomas implanted in SCID mice, were assessed for up to 3 h using non‐invasive magnetic resonance imaging (MRI) and spectroscopy techniques (MRS). MRI measurements of GdDTPA inflow showed that treatment with CA4P had little effect on the perfusion of HT29 tumours. Localized 31P MRS measurements also showed that the drug had no significant effect on tumour cell energy status, as assessed from the ratio of the integrals of the signals from inorganic phosphate (Pi) and nucleoside triphosphates. However, after treatment with DMXAA, perfusion was reduced and the Pi/NTP ratio increased, indicating that the HT29 tumour is susceptible to the action of this drug. The LS174T tumour model was susceptible to both CA4P and DMXAA, using the criteria of changes in GdDTPA inflow and Pi/NTP ratio. Copyright © 2002 John Wiley & Sons, Ltd.
MRI and fluorescence microscopy of the acute vascular response to VEGF165: vasodilation, hyper‐permeability and lymphatic uptake, followed by rapid inactivation of the growth factor
Authors: Dafni Hagit , Landsman Limor , Schechter Bilha , Kohen Fortune , Neeman Michal 
Published: January 2005

AbstractVascular endothelial growth factor (VEGF) is one of the key growth factors regulating tumor angiogenesis and thus it is one of the primary targets for antiangiogenic therapy. The long‐term effects of VEGF include induction of proliferation and migration of endothelial cells, tube formation and maintenance of the immature capillaries. The early effects of VEGF include vasodilation and increased permeability. We hypothesize that the early responses to VEGF can serve to develop a quantitative measure of the activity of VEGF, and therefore may be applicable for monitoring the efficacy of systemic suppression of VEGF signaling during antiangiogenic therapy. For that end we tested the ability of MRI and fluorescence microscopy to detect the early response to intradermal VEGF165 in nude mice. VEGF‐induced local vasodilation and increased permeability was detected by intravenous administration of macromolecular biotin‐BSA‐GdDTPA23 30 min after intradermal administration of VEGF. Contrast leak showed saturation kinetics. Delayed contrast administration (90 min after intradermal administration of VEGF) resulted in low contrast leak and demonstrated that the saturation kinetics is not due to contrast equilibration between plasma and the interstitial space, but rather is due to suppression of vascular permeability. Permeability was restored by a second bolus of VEGF, showing that the saturation kinetics is primarily due to inactivation of the growth factor. Confocal microscopy of fluorescent BSA‐FITC confirmed the permeability changes monitored by MRI. Moreover, confocal microscopy showed efficient lymphatic uptake of the extravasated contrast material specifically in regions of VEGF induced hyper‐permeability. Copyright © 2002 John Wiley & Sons, Ltd.
Breath‐hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first‐pass leakage profile model
Authors: Jackson A. , Haroon H. , Zhu X. P. , Li K. L. , Thacker N. A. , Jayson G. 
Published: January 2005

AbstractWe have applied a novel pharmacokinetic model of the distribution of contrast media to dynamic contrast‐enhanced MRI data from patients with hepatic neoplasms. The model uses data collected during the passage of a bolus of contrast medium and allows breath‐hold image acquisition. The aims of the study were to investigate the feasibility of permeability mapping using the first pass technique and breath‐hold acquisitions, and to examine the reproducibility of the technique and the effect of the liver's dual vascular supply on the assumptions of the model. Imaging was performed in 14 patients with hepatic neoplasms. Dynamic data clearly demonstrated differences in the timing and shape of the contrast medium concentration–time course curve in the systemic arterial and portal venous systems. Mapping of the arrival time (T0) of contrast medium allowed identification of tissue supplied by the hepatic arteries and portal vein. Hepatic tumours all showed typical hepatic arterial enhancement. Repeated measurements of endothelial permeability surface area product (kfp) and relative blood volume (rBV), performed in five patients, showed excellent reproducibility with variance ratios (Vr) of 0.134 and 0.113, respectively. Measurement of enhancing tumour volume was also highly reproducible (Vr = 0.096) and this was further improved by the use ofT0maps to identify pixels supplied by the hepatic artery (Vr = 0.026). Estimates ofkfpand rBV in normal hepatic tissue supplied by the portal vein were highly inaccurate and these pixels were identified by use of theT0parameter and excluded from the analysis. In conclusion, dynamic MRI contrast enhancement combined with a pharmacokinetic model of the distribution of contrast media in the first pass allows us to produce highly reproducible parametric maps ofkfpand rBV from hepatic tumours that are supplied by the hepatic arterial system using breath‐hold acquisitions. Copyright © 2002 John Wiley & Sons, Ltd.
Assessment of protamine‐induced thrombosis of tumor vessels for cancer therapy using dynamic contrast‐enhanced MRI
Authors: Su Min‐Ying , Samoszuk Michael K. , Wang Jun , Nalcioglu Orhan 
Published: January 2005

AbstractSince the role of angiogenesis in cancer development has been recognized, the study of anti‐angiogenic or anti‐vascular therapeutic agents has become increasingly important for cancer treatment. Selective thrombosis is one approach towards this goal. Since many types of carcinoma accumulate large numbers of degranulating mast cells which will release heparin, intravenously injected protamine may bind to heparin, neutralize its anti‐coagulant effect and induce thrombosis. In this work we studied the formation of thrombosis by using dynamic contrast enhanced MRI. The enhancement kinetics of the contrast medium measured before and after protamine treatment were compared to assess the thrombotic effect. The underlying concept was that if the vessels became clotted, the subsequently injected contrast medium could not be delivered into the tissue to cause enhancement. In addition to the tissue‐specific changes, protamine may also induce systemic effect in the host. The therapy‐induced changes measured in tumors were compared to changes in normal tissues: liver, kidney, and especially the muscle adjacent to tumor. The results showed that protamine induced pronounced changes in the tumor. However, the degree of change measured by MRI was not associated with the results of semiquantitative assessment of thrombosis assessed by histology, perhaps due to the heterogeneous nature of the tumor and the difficulty in sampling sufficient regions histologically. The protamine‐induced temporal effects were also studied. We demonstrated that protamine could induce selective thrombosis in tumors, and that the effect could last for several hours. Dynamic contrast‐enhanced MRI can serve as a suitable means to investigate the mechanism of this novel approach to induce selective thrombosis for anti‐vascular cancer therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Reproducibility of dynamic contrast‐enhanced MRI in human muscle and tumours: comparison of quantitative and semi‐quantitative analysis
Authors: Galbraith Susan M. , Lodge Martin A. , Taylor N. Jane , Rustin Gordon J. S. , Bentzen Søren , Stirling J. James , Padhani Anwar R. 
Published: January 2005

AbstractThe purpose of this study was to determine the reproducibility of dynamic contrast‐enhanced (DCE)‐MRI and compare quantitative kinetic parameters with semi‐quantitative methods, and whole region‐of‐interest (ROI) with pixel analysis. Twenty‐one patients with a range of tumour types underwent paired MRI examinations within a week, of which 16 pairs were evaluable. A proton density‐weighted image was obtained prior to a dynamic series of 30 T1‐weighted spoiled gradient echo images every 11.9 s with an intravenous bolus of gadopentetate dimeglumine given after the third baseline data point. Identical ROIs around the whole tumour and in skeletal muscle were drawn by the same observer on each pair of examinations and used for the reproducibility analysis. Semi‐quantitative parameters, gradient, enhancement and AUC (area under the curve) were derived from tissue enhancement curves. Quantitative parameters (Ktrans, kep, ve) were obtained by the application of the Tofts' model. Analysis was performed on data averaged across the whole ROI and on the median value from individual pixels within the ROI. No parameter showed a significant change between examinations. For all parameters except Ktrans, the variability was not dependent on the parameter value, so the absolute values for the size of changes needed for significance should be used for future reference rather than percentages. The size of change needed for significance in a group of 16 in tumours for Ktrans, kep and ve was −14 to +16%, ±0.20 ml/ml/min (15%) and ±1.9 ml/ml (6%), respectively (pixel analysis), and −16 to +19%, ±0.23 ml/ml/min (16%) and ±1.9 ml/ml (6%) (whole ROI analysis). For a single tumour, changes greater than −45 to +83%, ± 0.78 ml/ml/min (60%) and ± 7.6 ml/ml (24%), respectively, would be significant (pixel analysis). For gradient, enhancement and AUC the size of change needed for significance in tumours was ±0.24 (17%), ±0.05 (6%) and ±0.06 (8%), respectively for a group of 16 (pixel analysis), and ±0.96 (68%), ±0.20 (25%) and ±0.22 (32%) for individuals. In muscle, the size of change needed for significance in a group of 16 for Ktrans, kep and ve was −30 to +44%, ±0.81 ml/ml/min (61%) and ±1.7 ml/ml (13%). For gradient, enhancement and AUC it was ±0.09 (20%), ±0.02 (8%) and ±0.03 (12%). ve, enhancement and AUC are highly reproducible DCE‐MRI parameters. Ktrans, kep and gradient have greater variability, with larger changes in individuals required to be statistically significant, but are nevertheless sufficiently reproducible to detect changes greater than 14–17% in a cohort of 16 patients. Pixel analyses slightly improve reproducibility estimates and retain information about spatial heterogeneity. Reproducibility studies are recommended when treatment effects are being monitored. Copyright © 2002 John Wiley & Sons, Ltd.
Reproducibility of quantitative dynamic MRI of normal human tissues
Authors: Padhani Anwar R. , Hayes Carmel , Landau Sabine , Leach Martin O. 
Published: January 2005

AbstractThe aim of the study was to establish the normal range and to evaluate the reproducibility of dynamic contrast enhanced MRI (DCE‐MRI) parameter estimates in normal human pelvic tissues. Nineteen patients with prostate cancer, undergoing androgen deprivation treatment, had paired DCE‐MRI examinations of the pelvis using spoiled gradient‐echo sequences. Quantitative enhancement parameters were calculated for each examination: transfer constant (Ktrans), leakage space (ve) and maximum contrast medium accumulation (MCMA) of pelvic muscles, bone marrow and fat. Descriptive and reproducibility statistics were calculated: within‐patient standard deviation (wSD), repeatability and within‐patient coefficient of variation (wCV). The femoral head and ischiorectal fat showed large numbers of non‐enhancing pixels (81 and 88%, respectively). The ischial bone marrow had the highest values of kinetic parameter estimates (Ktrans 0.554 min−1, ve 18.5% and MCMA 0.164 mmol/kg). Muscle parameters values were lower (Ktrans 0.126–0.137 min−1, ve 10.6–11.5% and MCMA 0.077–0.086 mmol/kg). The mean difference between paired examinations was not significantly different from zero for any parameter. ve and MCMA had the lowest wCV (between 19 and 29%). For individuals, a log10 Ktrans change of approximately 0.90 in muscles and 0.52 in the ischium would be statistically significant. The corresponding absolute changes for ve are 6.7% in muscle and 13.6% in the ischium. For a group of 19 patients, small changes are statistically significant (muscle log10 Ktrans 0.208 and ve 1.5% and ischium log10 Ktrans 0.123 and ve 3.1%). Fat and the femoral head are unreliable tissues from which to obtain kinetic parameter estimates due to poor enhancement. ve and MCMA have smaller coefficient of variation than Ktrans in muscles and ischium. Reproducibility studies of normal and pathological tissues should be incorporated into clinical research protocols that measure treatment effects by DCE‐MRI techniques. Copyright © 2002 John Wiley & Sons, Ltd.
Combined vascular and extracellular pH imaging of solid tumors
Authors: Bhujwalla Z. M. , Artemov D. , Ballesteros P. , Cerdan S. , Gillies R. J. , Solaiyappan M. 
Published: January 2005

AbstractThe unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi‐parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest ‘metastatic threat’. Here, we present measurements of pHe, vascular volume and permeability from co‐localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA‐MB‐231) and non‐metastatic (MCF‐7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co‐registered regions in a solid tumor. Copyright © 2002 John Wiley & Sons, Ltd.
Evaluation of the anti‐vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI
Authors: Maxwell Ross J. , Wilson John , Prise Vivien E. , Vojnovic Borivoj , Rustin Gordon J. , Lodge Martin A. , Tozer Gillian M. 
Published: January 2005

AbstractThe anti‐vascular effects of the tubulin binding agent, disodium combretastatin A‐4 3‐O‐phosphate (CA‐4‐P), have been investigated in the rat P22 carcinosarcoma by measurements of radiolabelled iodoantipyrine uptake and dynamic contrast‐enhanced MRI. The iodoantipyrine estimates of absolute tumour blood flow showed a reduction from 0.35 to 0.04 ml g−1 min−1 6 h after 10 mg kg−1 CA‐4‐P and to <0.01 ml g−1 min−1 after 100 mg kg−1. Tumour blood flow recovered to control values 24 h after 10 mg kg−1 CA‐4‐P, but there was no recovery by 24 h after the higher dose. Dynamic contrast‐enhanced MR images were obtained at 4.7 T, following injection of 0.1 mmol kg−1 Gd‐DTPA and analysed assuming a model arterial input function. A parameter, Ktrans, which is related to blood flow rate and permeability of the tumour vasculature to Gd‐DTPA, was calculated from the uptake data. Ktrans showed a reduction from 0.34 to 0.11 min−1 6 h after 10 mg kg−1 CA‐4‐P and to 0.07 min−1 after 100 mg kg−1. Although the magnitude of changes in Ktrans was smaller than that in tumour blood flow, the time course and dose‐dependency patterns were very similar. The apparent extravascular extracellular volume fraction, νe, showed a four‐fold reduction 6 h after 100 mg kg−1 CA‐4‐P, possibly associated with vascular shutdown within large regions of the tumour. These results suggest that Ktrans values for Gd‐DTPA uptake into tumours could be a useful non‐invasive indicator of blood flow changes induced by anti‐vascular agents such as combretastatin. Copyright © 2002 John Wiley & Sons, Ltd.
Applications of sliding window reconstruction with cartesian sampling for dynamic contrast enhanced MRI
Authors: d'Arcy J. A. , Collins D. J. , Rowland I. J. , Padhani A. R. , Leach M. O. 
Published: January 2005

AbstractApplications of dynamic contrast enhanced MR imaging are increasing and require both high spatial resolution and high temporal resolution. Perfusion studies using susceptibility contrast in particular require very high temporal resolution. The sliding window reconstruction is a technique for increasing temporal resolution. It has previously been applied to radial and spiral sampling, but these schemes require extensive correction and interpolation during image reconstruction. Fourier raw data can be reconstructed simply and quickly using the fast fourier transform (FFT). This paper presents a new Fourier‐based sampling scheme and sliding window reconstruction that facilitates fast scanning without needing correction or interpolation. This technique can be used on virtually any MR scanner since it requires no specialized hardware. It is implemented here as a dual gradient echo sequence providing simultaneous T1‐ and T2*‐weighted images with a time resolution of 1.1 s. Copyright © 2002 John Wiley & Sons, Ltd.
Assessing changes in tumour vascular function using dynamic contrast‐enhanced magnetic resonance imaging
Authors: Hayes Carmel , Padhani Anwar R. , Leach Martin O. 
Published: January 2005

AbstractDynamic contrast‐enhanced MRI (DCE‐MRI) is widely used in the diagnosis and staging of cancer and is emerging as a promising method for monitoring tumour response to treatment. However, DCE‐MR imaging techniques are still evolving and methods of image analysis remain variable and non‐standard, and range from relative changes in the pattern of enhancement to pharmacokinetic modelling of contrast agent uptake. The combination of results from different institutions is therefore difficult and the sensitivities of different methods have not been compared. The purpose of this study is to investigate correlations between qualitatative and quantitative methods of analysis for DCE‐MR images from breast cancer patients undergoing neo‐adjuvant chemotherapy. Fifteen patients underwent DCE‐MRI examinations before and after one course of chemotherapy. Changes in the temporal pattern of signal enhancement, the rate and amplitude of enhancement and the volume transfer constant of contrast agent between the blood plasma and the extravascular extracellular space (EES), Ktrans, and the EES fractional volume, νe, were determined. In addition, whole tumour region‐of‐interest analysis was compared with histogram analysis to investigate the extent of tumour heterogeneity. It was found that changes in the rate of enhancement correlated strongly with changes in Ktrans values (Kendall's τ = 0.68, P < 0.001). Furthermore, it was found that the shape of the signal enhancement curve only changed when the Ktrans values changed by 50% or more. Median Ktrans values determined following histogram analysis of pixel maps of Ktrans were approximately equal to those determined by whole tumour region‐of‐interest analysis. The absolute change in the Ktrans values correlated negatively with the pre‐treatment values, particularly for responding patients. Thus, for higher pre‐treatment Ktrans values, a greater decrease was observed. Greater changes were observed in the upper extremes of the Ktrans histogram than in the median values after one course of treatment. Copyright © 2002 John Wiley & Sons, Ltd.
Enterprise traffic with a differentiated service mechanism
Authors: Yang Chyan , Fu Chen‐Hua , Tu Yueh‐Heng 
Published: January 2005

AbstractAs an enterprise grows, its network bandwidth requirement also increases dramatically. Network performance of an enterprise will impact its operational performance. How do we efficiently manage an enterprise network's resources in an E‐business era? This research proposes a differentiated service mechanism to manage traffic flows in an enterprise. This mechanism would enhance the performance of an enterprise network and help an enterprise efficiently transmits important information. With a high‐performance enterprise network, the enterprise can then operate more efficiently and improves its competitive capability. Copyright © 2001 John Wiley & Sons, Ltd.
Solution of large‐scale weighted least‐squares problems
Authors: Baryamureeba Venansius 
Published: January 2005

AbstractA sequence of least‐squares problems of the form miny∥G1/2(AT y−h)∥2, where G is an n×n positive‐definite diagonal weight matrix, and A an m×n (m⩽n) sparse matrix with some dense columns; has many applications in linear programming, electrical networks, elliptic boundary value problems, and structural analysis. We suggest low‐rank correction preconditioners for such problems, and a mixed solver (a combination of a direct solver and an iterative solver). The numerical results show that our technique for selecting the low‐rank correction matrix is very effective. Copyright © 2002 John Wiley & Sons, Ltd.
On the growth factor in Gaussian elimination for generalized Higham matrices
Authors: George Alan , Ikramov Khakim D. , Kucherov Andrey B. 
Published: January 2005

AbstractA Higham matrix is a complex symmetric matrix A=B+iC, where both B and C are real, symmetric and positive definite. We prove that, for such A, the growth factor in Gaussian elimination is less than 3. Moreover, a slightly larger bound $${3\sqrt{2}}$$ holds true for a broader class of complex matrices A=B+iC, where B and C are Hermitian and positive definite. Copyright © 2002 John Wiley & Sons, Ltd.
A parallel block overlap preconditioning with inexact submatrix inversion for linear elasticity problems
Authors: Kaporin Igor E. , Konshin Igor N. 
Published: January 2005

AbstractWe present a parallel preconditioned iterative solver for large sparse symmetric positive definite linear systems. The preconditioner is constructed as a proper combination of advanced preconditioning strategies. It can be formally seen as being of domain decomposition type with algebraically constructed overlap. Similar to the classical domain decomposition technique, inexact subdomain solvers are used, based on incomplete Cholesky factorization. The proper preconditioner is shown to be near optimal in minimizing the so‐called K‐condition number of the preconditioned matrix. The efficiency of both serial and parallel versions of the solution method is illustrated on a set of benchmark problems in linear elasticity. Copyright © 2002 John Wiley & Sons, Ltd.