Biomedical subjects

Manuel Cortijo

Publications and source records attributed to Manuel Cortijo.

8 recordsLinked to original sources

PubMed2005

Diffusion-weighted 19F-MRI of lung periphery: Influence of pressure and air-SF6 composition on apparent diffusion coefficients.

Lung functional magnetic resonance imaging (MRI) has become a reality using different inert hyperpolarized gases, such as 3He and 129Xe, which have provided an extraordinary boost in lung imaging and has also attracted interest to other chemically inert gaseous contrast agents. In this context, we have recently demonstrated the first diffusion-weighted images using thermally polarized inhaled sulfur hexafluoride (SF6) in small animals. The aim of this study was to evaluate whether or not the diffusion coefficient of this fluorinated gas is sensitive to pulmonary structure, gas concentration and air pressure in the airways. Diffusion coefficients of SF6 (both pure and in air mixtures) measured in vitro at different pressures and 20 degrees C showed an excellent agreement with theoretical values. Measurements of diffusion coefficients were also performed in vivo and post-mortem on healthy rats, achieving satisfactory signal-to-noise ratios (SNRs), and SF6 gas was found to be in an almost completely restricted diffusion regime in the lung, i.e., the transport by molecular diffusion is delayed by collisions with barriers such as the alveolar septa. This observed low diffusivity means that this gas will be less sensitive to structural changes in the lungs than other magnetic resonance sensitive gas such as 3He, particularly at human scale. However, it is still possible that SF6 plays a role since it opens a new structural window. Thus, the interest of researchers in delimiting the important limiting technical factors that makes this process very challenging is obvious. Among them, T2 relaxation is very fast, so gradient systems with very fast switching rate and probably large radiofrequency (RF) power and high field systems will be needed for hexafluoride to be used in human studies.

Animals↗

PubMed2005

In vivo diffusion weighted 19F MRI using SF6.

Diffusion weighted 19F images of rat lung in vivo using SF6 are presented. Projection-reconstruction images were acquired by filling the rat lung with a mixture of SF6 and air, during 64 successive apneas. Each apnea lasted for 6 s, the time required to perform 100 accumulations of each k-space radial phase step for the five values of the diffusion gradient (TR = 10 ms). After diffusion images were acquired, an apparent diffusion coefficient (ADC) map was generated, yielding an average value for the ADC of 2.22 x 10(-6) m2/s and SD for ADC values of 1.27 x 10(-6) m2/s. To the best of our knowledge, this is the first in vivo diffusion weighting imaging application and the first ADC map obtained using 19F MRI.

Administration, Inhalation↗

PubMed2004

The long and short flavodoxins: II. The role of the differentiating loop in apoflavodoxin stability and folding mechanism.

Flavodoxins are classified in two groups according to the presence or absence of a approximately 20-residue loop of unknown function. In the accompanying paper (36), we have shown that the differentiating loop from the long-chain Anabaena PCC 7119 flavodoxin is a peripheral structural element that can be removed without preventing the proper folding of the apoprotein. Here we investigate the role played by the loop in the stability and folding mechanism of flavodoxin by comparing the equilibrium and kinetic behavior of the full-length protein with that of loop-lacking, shortened variants. We show that, when the loop is removed, the three-state equilibrium thermal unfolding of apoflavodoxin becomes two-state. Thus, the loop is responsible for the complexity shown by long-chain apoflavodoxins toward thermal denaturation. As for the folding reaction, both shortened and wild type apoflavodoxins display three-state behavior but their folding mechanisms clearly differ. Whereas the full-length protein populates an essentially off-pathway transient intermediate, the additional state observed in the folding of the shortened variant analyzed seems to be simply an alternative native conformation. This finding suggests that the long loop may also be responsible for the accumulation of the kinetic intermediate observed in the full-length protein. Most revealing, however, is that the influence of the loop on the overall conformational stability of apoflavodoxin is quite low and the natively folded shortened variant Delta(120-139) is almost as stable as the wild type protein. The fact that the loop, which is not required for a proper folding of the polypeptide, does not even play a significant role in increasing the conformational stability of the protein supports our proposal (36) that the differentiating loop of long-chain flavodoxins may be related to a recognition function, rather than serving a structural purpose.

Anabaena↗

PubMed2004

Automatic tuning and matching of a small multifrequency saddle coil at 4.7 T.

A new circuit design for automatically tuning and matching a saddle coil for small animal imaging is presented. This design allows working at (1)H, (19)F, and (3)He resonance frequencies in a 4.7 T spectrometer. It is based on a balanced circuit with commercial variable capacity diodes controlled by a computer using digital potentiometers. The change between two different frequencies can be accurately performed in a few seconds. System Q is compared, between 140-210 MHz, to the same coil tuned and matched with high Q variable capacitors. Differences lower than 5% were found with a loaded coil. The proposed design has initially been evaluated in (19)F and (1)H NMR images acquired with a five-tube phantom. An application is also shown for the acquisition of (3)He, (19)F, and (1)H lung images in a control rat.

Analog-Digital Conversion↗

PubMed2004

Resonance energy transfer between tryptophan-214 in human serum albumin and acrylodan, prodan, and promen.

It has been proposed that acrylodan (6-acryloyl-2-dimethylaminonaphthalene) and prodan (6-propionyl-2-dimethylaminonaphthalene) bind to site I of human serum albumin, whereas promen (6-propionyl-2-methoxynaphthalene) binds to site II of this carrier protein. Because human albumin contains only one single tryptophan, at position 214, it has been possible to measure the distances from this amino-acid residue to each of the three probes by nonradiative energy transfer. The distances calculated, 2.97 +/- 0.10 nm, 3.14 +/- 0.11 nm, and 2.62 +/- 0.17 nm, respectively, confirm the locations previously proposed for all three probes.

2-Naphthylamine↗

PubMed2003

Computer-assisted enhanced volumetric segmentation magnetic resonance imaging data using a mixture of artificial neural networks.

An accurate computer-assisted method able to perform regional segmentation on 3D single modality images and measure its volume is designed using a mixture of unsupervised and supervised artificial neural networks. Firstly, an unsupervised artificial neural network is used to estimate representative textures that appear in the images. The region of interest of the resultant images is selected by means of a multi-layer perceptron after a training using a single sample slice, which contains a central portion of the 3D region of interest. The method was applied to magnetic resonance imaging data collected from an experimental acute inflammatory model (T(2) weighted) and from a clinical study of human Alzheimer's disease (T(1) weighted) to evaluate the proposed method. In the first case, a high correlation and parallelism was registered between the volumetric measurements, of the injured and healthy tissue, by the proposed method with respect to the manual measurements (r = 0.82 and p < 0.05) and to the histopathological studies (r = 0.87 and p < 0.05). The method was also applied to the clinical studies, and similar results were derived of the manual and semi-automatic volumetric measurement of both hippocampus and the corpus callosum (0.95 and 0.88).

Abscess↗

PubMed2002

Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results.

We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2-weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity. The MRS results show a statistically significant increase in inorganic phosphate and a significant decrease in phosphocreatine levels in the inflamed region. Image segmentation made with a self-organizing, neural-network map yielded a set of ordered representatives that remained constant for all animals during the inflammatory process, allowing a non-invasive, three-dimensional identification and quantification of the inflamed infected regions by MRI.

Acute Disease↗

PubMed2002

Urea-induced denaturation of human serum albumin labeled with acrylodan.

We induced the denaturation of unlabeled human serum albumin (HSA) and of similar albumin labeled with acrylodan (6-acryloyl-2-dimethylamino naphthalene) with urea and studied the transition profiles using circular dichroism and fluorescence spectroscopy. The circular dichroism spectra for both albumin preparations resulted in the same curves, thus indicating that labeling with acrylodan does not perturb the conformation of HSA. Our results indicate that the denaturation of both albumin preparations takes place at a single, two-state transition with midpoint at about 6 M urea, due to the unfolding of its domain II. It is important to point out that even at 8 M urea, some residual structure remains in the HSA. Great changes in the fluorescence of the dye bound to the protein were observed by addition of solid guanidine hydrochloride to the protein labeled with acrylodan dissolved in 8 M urea, indicating that domain I of this protein was not denatured by urea.

2-Naphthylamine↗