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Manuel Desco

Publications and source records attributed to Manuel Desco.

At least 19 recordsLinked to original sources
PubMed2006

Minimum-norm reconstruction for sensitivity-encoded magnetic resonance spectroscopic imaging.

In this work we propose minimum-norm reconstruction as a means to enhance the spatial response behavior in parallel spectroscopic MRI. By directly optimizing the shape of the spatial response function (SRF), the new method accounts for coil sensitivity variation across individual voxels and their side lobes. In this fashion, it mitigates the signal contamination and side-lobe aliasing, to which previous techniques are susceptible at low resolution. Although the computational burden is higher, minimum-norm reconstruction is shown to be feasible using an iterative algorithm. Benefits in terms of SRF shape and artifact suppression are demonstrated.

Algorithms↗
PubMed2005

The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma.

Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs. Zebularine (1-[beta-D-ribofuranosil]-1,2-dihydropyrimidin-2-1) has been recently described as a new DNA methylation inhibitor. Here we have studied its effects in a mouse model of radiation-induced lymphomagenesis using nuclear magnetic resonance (NMR) and positron emission tomography (PET). All control animals presented large thymic T lymphomas and died between 4 and 5.5 months. In contrast, 40% (12 of 30) of zebularine-treated animals were still alive after 1 year (Kaplan-Meier P < .001). NMR and PET imaging showed that surviving animals presented a thymus structure/volume similar to normal mice of the same age. Most important, zebularine demonstrated a complete lack of toxicity in nonirradiated control mice. DNA hypomethylation induced by zebularine occurred in association with depletion in extractable DNA methyltransferase 1 protein. Thus, our data support the role of zebularine as a DNA demethylating agent with antitumor activity and little toxicity.

Animals↗
PubMed2005

Ventricular enlargement in schizophrenia is associated with a genetic polymorphism at the interleukin-1 receptor antagonist gene.

Magnetic resonance imaging (MRI) studies have shown some morphological and volumetric peculiarities in brains of schizophrenic patients. The authors explored the influence of genetic polymorphisms at interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genes on these abnormalities. Hippocampus, lateral ventricles, and dorsolateral prefrontal cortex gray matter volumes were measured in a sample of 23 DSM-IV diagnosed schizophrenic patients of Spanish origin using MRI scans; MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n = 45). IL-1B and IL-1RN genes, involved in neurodevelopment and neurodegenerative processes, were analyzed in the patient sample. Patients carrying VNTR-allele*2 of IL-1RN gene showed a significant enlargement of both left (P = 0.002) and right (P = 0.01) ventricles. Sex and illness duration were controlled for in the analyses. Our results, though preliminary, suggest that IL-1RN gene might contribute to the ventricular volumetric changes observed in schizophrenic patients.

Adult↗
PubMed2005

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.

Adult↗
PubMed2005

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Adult↗
PubMed2005

ROC evaluation of statistical wavelet-based analysis of brain activation in [15O]-H2O PET scans.

This paper presents and evaluates a wavelet-based statistical analysis of PET images for the detection of brain activation areas. Brain regions showing significant activations were obtained by performing Student's t tests in the wavelet domain, reconstructing the final image from only those wavelet coefficients that passed the statistical test at a given significance level, and discarding artifacts introduced during the reconstruction process. Using Receiver Operating Characteristic (ROC) curves, we have compared this statistical analysis in the wavelet domain to the conventional image-domain Statistical Parametric Mapping (SPM) method. For obtaining an accurate assessment of sensitivity and specificity, we have simulated realistic single subject [15O]-H2O PET studies with different hyperactivation levels of the thalamic region. The results obtained from an ROC analysis show that the wavelet approach outperforms conventional SPM in identifying brain activation patterns. Using the wavelet method, activation areas detected were closer in size and shape to the region actually activated in the reference image.

Algorithms↗
PubMed2005

Age-related intramyocardial patterns in healthy subjects evaluated with Doppler tissue imaging.

BACKGROUND: The aim of this study is to analyse spatial distribution of myocardial velocities (MV) and myocardial velocity gradient (MVG) with color M-mode Doppler tissue imaging (DTI) and to analyse the influence of age in such parameters. METHODS AND RESULTS: A prospective study including 66 healthy volunteers was carried out with color M-mode DTI. Postprocessing of images was performed using proprietary software allowing the division of the myocardial wall into subendocardium, mesocardium and subepicardium. MV corresponding to the three layers and MVG time curves were obtained and systolic, early diastolic and late diastolic peak values were identified. MV were highest in subendocardium in systole, protodiastole and telediastole compared to external layers. Protodiastolic peak MV decreased in all layers with age, but with a higher impact in the subendocardium (r = 0.72, b = 0.136 (IC 95% 0.107-0.164), p = 0.0005). Older age resulted in larger telediastolic peak MV, without significant differences among layers. Linear correlation between protodiastolic peak mitral flow and peak protodiastolic velocity was higher in endocardium than in other layers (r = 0.79, p = 0.0005). CONCLUSIONS: Color M-mode DTI multilayer analysis showed that endocardium is more susceptible to age-related changes involving diastolic function. This dependency on age should be considered when assessing MV in other clinical settings.

Adolescent↗
PubMed2005

Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

Adult↗
PubMed2005

Structural neuroimaging in adolescents with a first psychotic episode.

OBJECTIVE: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. METHOD: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent inpatient unit and on 37 normal controls (13-18 years, 23 males, 14 females) matched for age, sex, and years of education. Diagnosis was made at baseline on the basis of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and confirmed after 12 months of follow-up. Total brain volume and gray matter, white matter, and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured bilaterally using a segmentation method based on the Talairach grid system. RESULTS: Male patients showed significantly larger volumes than did male controls in overall CSF and left frontal and right parietal sulci CSF. Male patients also showed significantly lower volumes of gray matter in the right and left frontal lobes. No significant volumetric differences were found in females. There were no differences between individuals with a diagnosis of schizophrenia at follow-up and the rest of the patients. CONCLUSIONS: This study suggests that larger CSF and lower gray matter volumes in the frontal lobes may be a nonspecific vulnerability marker for psychosis in male adolescents.

Adolescent↗
PubMed2005

Spatio-temporal nonrigid registration for ultrasound cardiac motion estimation.

We propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method.

Artificial Intelligence↗
PubMed2005

The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem.

In the present work, several experimental approaches were used to determine the presence of the glucagon-like peptide-1 receptor (GLP-1R) and the biological actions of its ligand in the human brain. In situ hybridization histochemistry revealed specific labelling for GLP-1 receptor mRNA in several brain areas. In addition, GLP-1R, glucose transporter isoform (GLUT-2) and glucokinase (GK) mRNAs were identified in the same cells, especially in areas of the hypothalamus involved in feeding behaviour. GLP-1R gene expression in the human brain gave rise to a protein of 56 kDa as determined by affinity cross-linking assays. Specific binding of 125I-GLP-1(7-36) amide to the GLP-1R was detected in several brain areas and was inhibited by unlabelled GLP-1(7-36) amide, exendin-4 and exendin (9-39). A further aim of this work was to evaluate cerebral-glucose metabolism in control subjects by positron emission tomography (PET), using 2-[F-18] deoxy-D-glucose (FDG). Statistical analysis of the PET studies revealed that the administration of GLP-1(7-36) amide significantly reduced (p < 0.001) cerebral glucose metabolism in hypothalamus and brainstem. Because FDG-6-phosphate is not a substrate for subsequent metabolic reactions, the lower activity observed in these areas after peptide administration may be due to reduction of the glucose transport and/or glucose phosphorylation, which should modulate the glucose sensing process in the GLUT-2- and GK-containing cells.

Adult↗
PubMed2004

Cerebral metabolic changes induced by clozapine in schizophrenia and related to clinical improvement.

RATIONALE: The study of the different effects on brain metabolism between typical and atypical antipsychotics would aid in understanding their mechanisms of action. Clozapine is of special interest, since it is one of the most effective antipsychotic drugs and demonstrates a distinctive mechanism of action in pre-clinical studies with respect to typical neuroleptics. OBJECTIVE: To study the differences in cerebral activity induced by clozapine as compared to those produced by haloperidol. METHODS: [18F]Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) scans were obtained in the resting condition before and after 6 months of treatment with clozapine in 22 treatment-resistant patients with schizophrenia. Before inclusion, patients had been chronically treated with classical drugs, and all of them received haloperidol during the last month. Data were analyzed with statistical parametric mapping (SPM'99) methods, comparing pre-treatment and post-treatment conditions. The association between the changes in symptom scores and metabolism was also assessed to corroborate the functional relevance of possible metabolic changes. RESULTS: Clozapine decreased prefrontal and basal ganglia activity, and increased occipital metabolism, including primary and association visual areas. The change in negative symptoms was related with the decrease of basal ganglia activity; the improvement in disorganization related to the metabolic decrease in the motor area, and the change in positive symptoms was associated to the increase of activity in the visual area. CONCLUSIONS: These results show that haloperidol and clozapine produce different patterns of metabolic changes in schizophrenia. Compared to the haloperidol baseline, clozapine inhibited the metabolic activity of the prefrontal and motor cortical regions and basal ganglia and induced a higher activation of the visual cortex. The improvement in disorganization, negative and positive syndromes with clozapine may be respectively associated with metabolic changes in the motor area, basal ganglia, and visual cortex.

Adult↗
PubMed2004

18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation.

PURPOSE: To assess the information supplied by FDG-PET in patients with locally advanced rectal cancer both in the initial staging and in the evaluation of tumor changes induced by preoperative chemoradiation (restaging). METHODS AND MATERIALS: Twenty-five consecutive patients with rectal cancer were included, with tumor stages (c)T(2-4)N(x)M(0), during the period 1997-1999. We prospectively performed two FDG-PET scans in all patients to assess disease stage (1) at initial diagnosis and (2) presurgically, 4 to 5 weeks after protracted chemoradiation. Protracted chemoradiation was carried out during 5-6 weeks with 45-50 Gy, plus concurrent oral tegafur 1200 mg/day or 5-fluorouracil 500-1000 mg/m(2) administered as a 24-h continuous i.v. infusion on Days 1-4 and 21-25 of the radiotherapy treatment. Tumors were staged with CT in 95% of patients, whereas endorectal ultrasound was used in 90% of patients. Maximum standardized uptake value (SUVmax) was used as the quantitative parameter to estimate the tumor:tissue metabolic ratio. RESULTS: Preoperative chemoradiation significantly decreased the SUVMAX: 5.9 (mean SUVmax at initial staging) vs. 2.4 (mean SUVmax after chemoradiation) with p < 0.001. Unknown liver metastases were detected by FDG-PET in 2 patients, in 1 of them with the initial staging FDG-PET scan, and with the restaging FDG-PET scan in the other. After an average follow-up of 39 months, the value of SUVmax > or =6 allowed us to discriminate for survival at 3 years: 92% vs. 60% (p = 0.04). T downstaging (total 62%) was significantly correlated with SUVmax changes: 1.9 vs. 3.3 (p = 0.03). The degree of rectal cancer response to chemoradiation, established as mic vs. mac categories, was not associated with SUVmax differences (mean values of 2.0 vs. 2.7). CONCLUSION: Preliminary results observed suggest the potential utility of FDG-PET as a complementary diagnostic procedure in the initial clinical evaluation (8% of unsuspected liver metastases) as well as in the assessment of chemoradiation response (any T downstaged event) of locally advanced rectal cancer. Initial SUVmax might be of prognostic value related to long-term patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Method for bias field correction of brain T1-weighted magnetic resonance images minimizing segmentation error.

This work presents a new algorithm (nonuniform intensity correction; NIC) for correction of intensity inhomogeneities in T1-weighted magnetic resonance (MR) images. The bias field and a bias-free image are obtained through an iterative process that uses brain tissue segmentation. The algorithm was validated by means of realistic phantom images and a set of 24 real images. The first evaluation phase was based on a public domain phantom dataset, used previously to assess bias field correction algorithms. NIC performed similar to previously described methods in removing the bias field from phantom images, without introduction of degradation in the absence of intensity inhomogeneity. The real image dataset was used to compare the performance of this new algorithm to that of other widely used methods (N3, SPM'99, and SPM2). This dataset included both low and high bias field images from two different MR scanners of low (0.5 T) and medium (1.5 T) static fields. Using standard quality criteria for determining the goodness of the different methods, NIC achieved the best results, correcting the images of the real MR dataset, enabling its systematic use in images from both low and medium static field MR scanners. A limitation of our method is that it might fail if the bias field is so high that the initial histogram does not show bimodal distribution for white and gray matter.

Algorithms↗
PubMed2004

Resolution recovery in Turbo Spin Echo using segmented Half Fourier acquisition.

Turbo Spin Echo (TSE) is a sequence of choice for obtaining T(2)-weighted images. TSE reduces acquisition time by acquiring several echoes within each TR, at the cost of introducing an exponential weighting in the k-space that leads to a certain image blurring. This is particularly important for short-T(2) structures, which can even disappear if their size in the phase encoding direction is comparable to the degree of blurring. This article suggests the use of a combination of Half Fourier (HF) and segmented (multishot) TSE (sHF-TSE) to recover the original resolution of the SE images. The improved symmetry of the dataset achieved by HF reconstruction is used to increase the resolution of the TSE images. The proposed combination, available in most clinical scanners, reduces the blurring artifact inherent to the TSE sequence without increasing the scan time or the number of acquisitions, but at the cost of a slight reduction of the signal-to-noise ratios (SNR). Qualitative and quantitative results are presented using both numerical simulation and imaging. Significant edge enhancement has been achieved for structures with short T(2), (narrowing of the full width at half maximum [FWHM] up to 45%). The proposed sequence is more sensitive to movement artifacts but has proven to be superior to the conventional TSE for imaging static structures.

Abdomen↗
PubMed2004

Tracking of regions-of-interest in myocardial contrast echocardiography.

Analysis of intramyocardial perfusion by contrast echocardiography provides quantitative parameters for the assessment of ischemic disease. This analysis can be achieved by applying an ultrasound (US) burst of high mechanical index to destroy contrast bubbles, measuring various myocardial refilling parameters from the time curves obtained from regions-of-interest (ROIs) within the myocardial wall. To obtain reliable intensity curves, the position of the ROIs must be tracked to compensate for the heart motion along the sequence. In this work, we studied the use of optical flow techniques for ROI repositioning. Two block-matching and one differential technique were evaluated for this purpose. Performance was measured by comparing the result of automatic tracking with results of ROI repositioning by a human expert. This evaluation was carried out on experimental data from animals as well as on sequences from clinical studies. Results are considered to be accurate enough for clinical purposes, and computation times may allow for a real-time processing if incorporated into a US scanner.

Algorithms↗
PubMed2004

Risk factors of invasive aspergillosis after heart transplantation: protective role of oral itraconazole prophylaxis.

The study was designed to identify a subset of heart transplant (HT) recipients who could benefit from the administration of targeted antifungal prophylaxis and to evaluate the efficacy of oral itraconazole as the preventive drug. We have analyzed the risk factors for invasive aspergillosis (IA) in our entire population of HT recipients (1988-2002) and also the role of oral itraconazole prophylaxis that was provided to all patients since 1995 [400 mg q.d. of itraconazole oral (PO) for 3-6 months]. There were 24 cases of IA. Our main results indicate that the independent risk factors for IA after heart transplantation are: re-operation (RR 5.8; 95% CI 1.8-18, p=0.002), cytomegalovirus (CMV) disease (RR 5.2; 95% CI 2-13.9, p=0.001), post-transplant hemodialysis (RR 4.9; 95% CI 1.2-18, p=0.02), and the existence of an episode of IA in the HT program 2 months before or after the transplantation date (RR 4.6; 95% CI 1.5-14.4, p=0.007). Itraconazole prophylaxis showed an independent protective value against developing IA (RR 0.2; 95% CI 0.07-0.9, p=0.03) and also determined a significantly prolonged 1-year survival (RR 0.5; 95% CI 0.3-0.8, p=0.01). We believe that antifungal prophylaxis in heart transplant patients should be offered at least to patients with one or more of these predisposing conditions.

Administration, Oral↗