Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study

Objective To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer''s disease (AD). Methods Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD. Results After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate + glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%. Conclusion Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings

First-Episode Psychotic Patients Showed Longitudinal Brain Changes Using fMRI With an Emotional Auditory Paradigm

Most previous longitudinal studies of functional magnetic resonance imaging (fMRI) in first-episode psychosis (FEP) using cognitive paradigm task found an increased activation after antipsychotic medications. We designed an emotional auditory paradigm to explore brain activation during emotional and nonemotional word processing. This study aimed to analyze if longitudinal changes in brain fMRI BOLD activation is present in patients vs. healthy controls. A group of FEP patients (n = 34) received clinical assessment and had a fMRI scan at baseline and follow-up (average, 25-month interval). During the fMRI scan, both emotional and nonemotional words were presented as a block design. Results were compared with a pair of healthy control group (n = 13). Patients showed a decreased activation at follow-up fMRI in amygdala (F = 4.69; p = 0.04) and hippocampus (F = 5.03; p = 0.03) compared with controls. Middle frontal gyrus was the only area that showed a substantial increased activation in patients (F = 4.53; p = 0.04). A great heterogeneity in individual activation patterns was also found. These results support the relevance of the type of paradigm in neuroimaging for psychosis. This is, as far as we know, the first longitudinal study with an emotional auditory paradigm in FEP. Our results suggested that the amygdala and hippocampus play a key role in psychotic disease. More studies are needed to understand the heterogeneity of response at individual level

The Role of Imaging Biomarkers in the Assessment of Sarcopenia

The diagnosis of sarcopenia through clinical assessment has some limitations. The literature advises studies that include objective markers along with clinical assessment in order to improve the sensitivity and specificity of current diagnostic criteria. The decrease of muscle quality precedes the loss of quantity, so we studied the role magnetic resonance imaging biomarkers as indicators of the quantity and quality of muscle in sarcopenia patients.This work was supported by a grant from Universidad Católica de Valencia San Vicente Mártir (grant number 2018-158-002) to APM. JBI is in receipt of a Generalitat Valenciana doctoral fellowship (grant number ACIF 2017/126. The APC was funded by Universidad Católica de Valencia San Vicente Mártir.Medicin

FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls.This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Methodological developments and clinical applications of pharmacokinetic models in contrast-enhanced magnetic resonance perfusion studies

La angiogénesis y la neovascularización son procesos biológicos que tienen lugar en los tejidos y que están asociados al aumento de las demandas de oxígeno y nutrientes. En adultos normales estos procesos no suelen ocurrir. Sin embargo, en condiciones de enfermedad, como en inflamaciones o en el desarrollo de tumores, el VEGF (factor de crecimiento vascular endotelial, del inglés vascular endothelial growth factor), ls proteína señalizadora causante de la angiogénesis,está fuertemente expresada. En estas circunstancias se formas rápidamente nuevos vasos y capilares. Esta nueva red vascular es caótica y no presenta una estructura normal, especialmente en el caso de tumores. La cuantificación de la angiogénesis es esencial para evaluar el grado de agresividad de un tumor y la eficacia de los tratamientos. Es necesario desarrollar herramientas fiables y reproducibles que sean sensibles a cambios tempranos, lo cual puede permitir utilizar tratamientos más individualizados. En este sentido, el modelado farmacocinético de imágenes de perfusión por resonancia magnética (RM) es una valiosa herramienta para la evaluación de parámetros como la permeabilidad capilar, el coeficiente de extracción, el volumen intersiticial y el volumen vascular.Sanz Requena, R. (2010). Methodological developments and clinical applications of pharmacokinetic models in contrast-enhanced magnetic resonance perfusion studies [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8422Palanci

Semi-automated Knee Joint Segmentation from Magnetic Resonance Images based on a Subchondral Bone Approach

Abstract: The aim of this paper is to present the development of a semi-automatic segmentation method for human knee cartilage and bones from magnetic resonance images (MRI). This segmentation process belongs to a higher aim that consists of a 3D simulation of knee joint to find how stresses are distributed in contact regions between cartilages and to quantify them as well as the contact region size. Imaging acquisition was performed in a 3T scanner with high spatial resolution (voxel size 0.293 x 0.293 x 1 mm). This method consists of a 2D segmentation of each sagittal plane and a reconstruction of the volumetric image with the segmented masks

Radiographic assessment of pectoral flipper bone maturation in bottlenose dolphins (Tursiops truncatus), as a novel technique to accurately estimate chronological age.

Accurate age estimation in wildlife conservation is an important diagnostic tool in the interpretation of biological data, necropsy examination, reproductive status and population demographics. The most frequently utilized methods to age bottlenose dolphins (Tursiops truncatus) include tooth extraction; counting dental growth layer groups and dental radiography. These methods are inaccurate in dolphins > 13 years old, due to overlapping of the growth layer groups in dolphins and worn teeth. Establishing a non-invasive method of accurately aging bottlenose dolphins across the entire age range is important to long term conservation efforts to understand health status, lifespan, reproduction and survivability. A database of 126 radiographs from 94 dolphins of known chronological age was utilized to establish the stages of skeletal ossification over time. A numerical score from -1 to 8 was assigned to 16 anatomic locations on the pectoral radiograph, to create a formula to estimate age. The most informative areas to evaluate morphologically were the metaphyseal regions of the radius and ulna, and the proximal and distal epiphysis of metacarpals II and III. Third order polynomial regression calculated separate age predictor formulas for male and female dolphins, with females reaching sexual maturity earlier than males. Completion of epiphyseal closure of the long bones correlated with average sexual maturity. Managed care dolphin ages could be properly estimated with decreasing precision from within 3 months in animals 30 years old. This diagnostic tool could also be applied to diagnose atypical ossification patterns consistent with nutritional, developmental or growth abnormalities, and identifying subclinical health issues. In conclusion, knowledge of the lifespan and the onset of sexual maturity for each species will allow this model to be applied to other cetaceans, facilitating age estimation via pectoral radiography in future research

The Role of Imaging Biomarkers in the Assessment of Sarcopenia

Background: The diagnosis of sarcopenia through clinical assessment has some limitations. The literature advises studies that include objective markers along with clinical assessment in order to improve the sensitivity and specificity of current diagnostic criteria. The decrease of muscle quality precedes the loss of quantity, so we studied the role magnetic resonance imaging biomarkers as indicators of the quantity and quality of muscle in sarcopenia patients. Methods: a cross-sectional analysis was performed to analyze what MR-derived imaging parameters correlate better with sarcopenia diagnostic criteria in women of 70 years of age and over (independent walking and community-dwelling women who were sarcopenic in accordance with EWGSOP criteria with muscle mass adjusted to Spanish population were chosen). Results: The study included 26 women; 81 ± 8 years old. A strong correlation was obtained between cineanthropometric variables (BMI; thigh perimeter and fat mass) and imaging biomarkers (muscle/fat ratio, fatty infiltration, muscle T2*, water diffusion coefficient, and proton density fat fraction) with coefficients around 0.7 (absolute value). Conclusions: Knowing the correlation of clinical parameters and imaging-derived muscle quality indicators can help to identify older women at risk of developing sarcopenia at an early stage. This may allow taking preventive actions to decrease disability, morbidity, and mortality in sarcopenia patients