Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

In vivo positive contrast IRON sequence and quantitative T2* measurement confirms inflammatory burden in a patient with asymptomatic carotid atheroma after USPIO-enhanced MR Imaging

The authors report an in vivo human examination of carotid atheroma by using the inversion-recovery ON resonance (IRON) sequence, which is able to produce positive contrast after the infusion of an ultrasmall super paramagnetic iron oxide (USPIO) contrast medium. This technique provides a method of potentially identifying inflammatory burden within carotid atheroma. This may be particularly useful in patients who currently do not meet criteria for intervention (ie, moderate symptomatic stenosis or <70% asymptomatic stenosis) to further risk-stratify this important patient cohort. A 63-year-old man was imaged at 1.5 T before and 36 hours after USPIO infusion by using the IRON sequence. Regions of interest showing profound signal loss at T2*-weighted imaging corresponded well with regions of positive contrast at IRON imaging after the administration of USPIO. These regions also showed a profound decrease in T2* measurements after USPIO infusion, whereas surrounding tissue did not. It has been shown that such strong signal loss on T2*-weighted images after USPIO infusion is indicative of USPIO uptake.

Scattering and Refraction as Contrast Mechanisms in X-Ray Imaging

Differentiation of various types of soft tissues is of high importance in medical imaging, because changes in soft tissue structure are often associated with pathologies, such as cancer. However, the densities of different soft tissues may be very similar, making it difficult to distinguish them in absorption images. This is especially true when the consideration of patient dose limits the available signal-to-noise ratio. Refraction is more sensitive than absorption to changes in the density, and small angle x-ray scattering on the other hand contains information about the macromolecular structure of the tissues. Both of these can be used as potential sources of contrast when soft tissues are imaged, but little is known about the visibility of the signals in realistic imaging situations. In this work the visibility of small-angle scattering and refraction in the context of medical imaging has been studied using computational methods. The work focuses on the study of analyzer based imaging, where the information about the sample is recorded in the rocking curve of the analyzer crystal. Computational phantoms based on simple geometrical shapes with differing material properties are used. The objects have realistic dimensions and attenuation properties that could be encountered in real imaging situations. The scattering properties mimic various features of measured small-angle scattering curves. Ray-tracing methods are used to calculate the refraction and attenuation of the beam, and a scattering halo is accumulated, including the effect of multiple scattering. The changes in the shape of the rocking curve are analyzed with different methods, including diffraction enhanced imaging (DEI), extended DEI (E-DEI) and multiple image radiography (MIR). A wide angle DEI, called W-DEI, is introduced and its performance is compared with that of the established methods. The results indicate that the differences in scattered intensities from healthy and malignant breast tissues are distinguishable to some extent with reasonable dose. Especially the fraction of total scattering has large enough differences that it can serve as a useful source of contrast. The peaks related to the macromolecular structure come to angles that are rather large, and have intensities that are only a small fraction of the total scattered intensity. It is found that such peaks seem to have only limited usefulness in medical imaging. It is also found that W-DEI performs rather well when most of the intensity remains in the direct beam, indicating that dark field imaging methods may produce the best results when scattering is weak. Altogether, it is found that the analysis of scattered intensity is a viable option even in medical imaging where the patient dose is the limiting factor.

High contrast imaging and thickness determination of graphene with in-column secondary electron microscopy

We report a new method for quantitative estimation of graphene layer thicknesses using high contrast imaging of graphene films on insulating substrates with a scanning electron microscope. By detecting the attenuation of secondary electrons emitted from the substrate with an in-column low-energy electron detector, we have achieved very high thickness-dependent contrast that allows quantitative estimation of thickness up to several graphene layers. The nanometer scale spatial resolution of the electron micrographs also allows a simple structural characterization scheme for graphene, which has been applied to identify faults, wrinkles, voids, and patches of multilayer growth in large-area chemical vapor deposited graphene. We have discussed the factors, such as differential surface charging and electron beam induced current, that affect the contrast of graphene images in detail. (C) 2011 American Institute of Physics. doi:10.1063/1.3608062]

High Value of Proton Relaxivity Achieved by Graphene Oxide-Cobalt Ferrite Nanoparticle Composite: A Potential Contrast Agent in Magnetic Resonance Imaging

This work investigates the potential of graphene oxide-cobalt ferrite nanoparticle (GO-CoFe2O4) composite as image contrast enhancing material in Magnetic Resonance Imaging (MRI). In the preset work, GO-CoFe2O4 composites were produced by a two-step synthesis process. In the first step, graphene oxide (GO) was synthesized, and in the second step CoFe2O4 nanoparticles were synthesized in a reaction mixture containing GO to yield graphene GO-CoFe2O4 composite. Proton relaxivity value obtained from the composite was 361 mM(-1)s(-1). This value of proton relaxivity is higher than a majority of reported relaxivity values obtained using several ferrite based contrast agents.

MnFe2O4-Fe3O4 core-shell nanoparticles as a potential contrast agent for magnetic resonance imaging

In recent years, magnetic core-shell nanoparticles have received widespread attention due to their unique properties that can be used for various applications. We introduce here a magnetic core-shell nanoparticle system for potential application as a contrast agent in magnetic resonance imaging (MRI). MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized by the wet-chemical synthesis method. Detailed structural and compositional charaterization confirmed the formation of a core-shell microstructure for the nanoparticles. Magnetic charaterization revealed the superparamagnetic nature of the as-synthesized core-shell nanoparticles. Average size and saturation magnetization values obtained for the as-synthesized core-shell nanoparticle were 12.5 nm and 69.34 emu g(-1) respectively. The transverse relaxivity value of the water protons obtained in the presence of the core-shell nanoparticles was 184.1 mM(-1) s(-1). To investigate the effect of the core-shell geometry towards enhancing the relaxivity value, transverse relaxivity values were also obtained in the presence of separately synthesized single phase Fe3O4 and MnFe2O4 nanoparticles. Average size and saturation magnetization values for the as-synthesized Fe3O4 nanoparticles were 12 nm and 65.8 emu g(-1) respectively. Average size and saturation magnetization values for the MnFe2O4 nanoparticles were 9 nm and 61.5 emu g(-1) respectively. The transverse relaxivity value obtained in the presence of single phase Fe3O4 and MnFe2O4 nanoparticles was 96.6 and 83.2 mM(-1) s(-1) respectively. All the nanoparticles (core-shell and single phase) were coated with chitosan by a surfactant exchange reaction before determining the relaxivity values. For similar nanoparticle sizes and saturation magnetization values, the highest value of the transverse relaxivity in the case of core-shell nanoparticles clearly illustrated that the difference in the magnetic nature of the core and shell phases in the core-shell nanoparticles creates greater magnetic inhomogeneity in the surrounding medium yielding a high value for proton relaxivity. The MnFe2O4-Fe3O4 core-shell nanoparticles exhibited extremely low toxicity towards the MCF-7 cell line. Taken together, this opens up new avenues for the use of core-shell nanoparticles in MRI.

Ultrafine graphene oxide-CoFe2O4 nanoparticle composite as T-1 and T-2 contrast agent for magnetic resonance imaging

Graphene oxide-CoFe2O4 nanoparticle composites were synthesized using a two step synthesis method in which graphene oxide was initially synthesized followed by precipitation of CoFe2O4 nanoparticles in a reaction mixture containing graphene oxide. Samples were extracted from the reaction mixture at different times at 80 degrees C. All the extracted samples contained CoFe2O4 nanoparticles formed over the graphene oxide. It was observed that the increase in the reflux time significantly increased the saturation magnetization value for the superparamagnetic nanoparticles in the composite. It was also noticed that the size of the nanoparticles increased with increase in the reflux time. Transverse relaxivity of the water protons increased monotonically with increase in the reflux time. Whereas, the longitudinal relaxivity value initially increased and then decreased with the reflux time. Graphene oxide-CoFe2O4 nanoparticle composites also exhibit biocompatibility towards the MCF-7 cell line.

Near-field x-ray phase contrast imaging and phase retrieval algorithm

Theoretical analyses of x-ray diffraction phase contrast imaging and near field phase retrieval method are presented. A new variant of the near field intensity distribution is derived with the optimal phase imaging distance and spatial frequency of object taken into account. Numerical examples of phase retrieval using simulated data are also given. On the above basis, the influence of detecting distance and polychroism of radiation on the phase contrast image and the retrieved phase distribution are discussed. The present results should be useful in the practical application of in-line phase contrast imaging.

Instability of solution of phase retrieval in direct diffraction phase-contrast imaging with partially coherent X-ray source

The theoretical model of direct diffraction phase-contrast imaging with partially coherent x-ray source is expressed by an operator of multiple integral. It is presented that the integral operator is linear. The problem of its phase retrieval is described by solving an operator equation of multiple integral. It is demonstrated that the solution of the phase retrieval is unstable. The numerical simulation is performed and the result validates that the solution of the phase retrieval is unstable.