Correction of B0 susceptibility induced distortion in diffusion-weighted images using large-deformation diffeomorphic metric mapping

Geometric distortion caused by B0 inhomogeneity is one of the most important problems for diffusion-weighted images (DWI) using single-shot, echo planar imaging (SS-EPI). In this study, large-deformation, diffeomorphic metric mapping (LDDMM) algorithm has been tested for the correction of geometric distortion in diffusion tensor images (DTI). Based on data from nine normal subjects, the amount of distortion caused by B0 susceptibility in the 3-T magnet was characterized. The distortion quality was validated by manually placing landmarks in the target and DTI images before and after distortion correction. The distortion was found to be up to 15 mm in the population-averaged map and could be more than 20 mm in individual images. Both qualitative demonstration and quantitative statistical results suggest that the highly elastic geometric distortion caused by spatial inhomogeneity of the B0 field in DTI using SS-EPI can be effectively corrected by LDDMM. This postprocessing method is especially useful for correcting existent DTI data without phase maps.     

Optimization of the irradiation power in chemical exchange dependent saturation transfer experiments

In chemical exchange dependent saturation transfer imaging experiments, exchangeable solute protons are saturated and the transfer of saturation to water is subsequently detected. When the applied irradiation power is comparable to the resonance frequency difference between the water protons and saturated solute protons, the proton transfer (PT) efficiency is reduced due to concomitant direct saturation effects. In this study, the PT process is modeled using a two-pool system. An empirical general proton transfer ratio (PTR) equation for arbitrary RF irradiation power is derived, and its optimal power to maximize the PTR is analyzed. The results are confirmed experimentally on 4.7 T using a poly-L-lysine solution. The theory provides a useful tool for optimizing the irradiation power of the PT sequences in the presence of direct saturation effects.     

MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T

Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS₄, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS₃, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.     

Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent

Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance imaging (MRI) contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after deamination by recombinant CDase, the CEST contrast disappears. In addition, expression of the enzyme in three different cell lines exhibiting different expression levels of CDase shows good agreement with the CDase activity measured with CEST MRI. Consequently, CDase activity was imaged with high-resolution CEST MRI. These data demonstrate the ability to detect enzyme activity based on proton exchange. Consequently, CEST MRI has the potential to follow the kinetics of multiple enzymes in real time in living tissue.     

Carbon Dots as a New Class of Diamagnetic Chemical Exchange Saturation Transfer (diaCEST) MRI Contrast Agents

While carbon dots (C‐dots) have been extensively investigated pertaining to their fluorescent, phosphorescent, electrochemiluminescent, optoelectronic, and catalytic features, their inherent chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) properties are unknown. By virtue of their hydrophilicity and abundant exchangeable protons of hydroxyl, amine, and amide anchored on the surface, we report here that C‐dots can be adapted as effective diamagnetic CEST (diaCEST) MRI contrast agents. As a proof‐of‐concept demonstration, human glioma cells were labeled with liposomes with or without encapsulated C‐dots and implanted in mouse brain. In vivo CEST MRI was able to clearly differentiate labeled cells from non‐labeled cells. The present findings may encourage new applications of C‐dots for in vivo imaging in deep tissues, which is currently not possible using conventional fluorescent (near‐infrared) C‐dots.     

Catalytic enantioselective synthesis of vicinal dialkyl arrays

With a consecutive "asymmetric allylic alkylation (AAA)/cross-metathesis (CM)/conjugate addition (CA)" protocol it is possible to synthesize either stereoisomer of compounds containing a vicinal dialkyl array with excellent stereoselectivity. The versatility of this protocol in natural product synthesis is demonstrated in the preparation of the ant pheromones faranal and lasiol.     

Highly enantioselective Cu-catalysed allylic substitutions with Grignard reagents

A catalyst system able to perform highly enantioselective Cu-catalysed allylic alkylations with Grignard reagents is described.     

Comparison of Two Mathematical Models for 3D Groundwater Flow: Block-Centered Heads and Edge-Based Stream Functions

Traditionally, groundwater flow models, as well as oil reservoir models, are based on the block-centered finite difference method. Well-known models based on this approach are MODFLOW (groundwater) and ECLIPSE (oil and gas). Such models are well proven and robust; their underlying principles are well understood by hydrologists and petroleum reservoir engineers. Nevertheless, the desire to improve the block-centered finite difference paradigm has always been alive, for instance, to be able to apply deformed grid blocks, or to model anisotropy that is not aligned along the coordinate axes. This article introduces the edge-based stream function as a potential alternative to the paradigmatic model, not only to mitigate the above mentioned limitations, but especially for its promise to inverse modeling. Computer programs have been developed for the discrete analog equations of the stream function method and the conventional method. The two methods are tested by using synthetic forward modeling problems of uniform and radial flow. The theoretical formulation and the numerical results show that the two methods are algebraically equivalent and yield the same flux output. However, for rectangular grid blocks and anisotropy aligned along the coordinate axes, the block-centered method is shown to be computationally more efficient than the edge-based stream function method. The major advantage of the stream function method is that it is linear in the resistivities, proving it an ideal candidate for direct inverse modeling. Moreover, any arbitrary specification of stream functions yields a solution that satisfies the mass balance.     

NMR studies of brain C-glucose uptake and metabolism: Present status

One of the common features of epilepsy is a change in glucose metabolism at the site of seizure activity during and between seizures. The noninvasive in situ study of glucose transport and metabolism by NMR can potentially provide detailed information about this phenomena. In this short review, we will discuss the principles of ¹³C-glucose NMR studies of the brain and compare the advantages and disadvantages of this method to those of ¹⁸F-deoxyglucose studies using positron emission tomography (PET).     

Generalized potential flow theory and direct calculation of velocities applied to the numerical solution of the Navier-Stokes and the Boussinesq equations

A formulation based on three scalar functions or potentials is applied to analyse the Navier-Stokes and Boussinesq equations in three dimensions. In this formulation an explicit expression for the pressure exists, the so-called generalized Bernoulli equation. Therefore the scalar functions formulation may be considered as a generalization of the well-known potential flow and Bernoulli theory for irrotational fluid motion. The many advantages of this formulation applied to three-dimensional Navier-Stokes and Boussinesq flow will be discussed, and a numerical example is given as an illustration.