Efecto de la segmentación por tejidos en los mapas de atenuación sobre la cuantificación PET con especial hincapié en grandes arterias / The effect of tissue-segmented attenuation maps on PET quantification with a special focus on large arteries

Objetivos. La precisión cuantitativa en PET requiere una adecuada aplicación de la corrección de atenuación, lo cual representa uno de los mayores retos que aún están por resolver en la técnica PET/RM. El propósito de este estudio es evaluar el efecto de utilizar mapas de atenuación basados en RM y el uso de antenas flexibles sobre la precisión cuantitativa en PET con especial hincapié en grandes arterias. Materiales y métodos. Se utilizaron datos PET/TC de 8 pacientes oncológicos. Los datos PET fueron reconstruidos utilizando mapas de atenuación con diferente nivel de detalle emulando las distintas aproximaciones utilizadas actualmente por lo equipos PET/RM. Las imágenes PET obtenidas con mapas de atenuación basados en TC y RM fueron comparadas para evaluar las desviaciones cuantitativas obtenidas. El efecto producido por las antenas flexibles fue también estudiado. Resultados. El uso de mapas de atenuación más simplificados da lugar a un incremento en las desviaciones cuantitativas en grasa, tejido blando y hueso. Las desviaciones en pulmón son altas debido a su heterogeneidad y a la variabilidad entre pacientes. La cuantificación en grandes arterias muestra pequeñas desviaciones excepto en el caso de utilizar antenas flexibles. La cuantificación mediante TBR proporciona menores desviaciones al cancelarse las desviaciones medidas en arterias y las venas utilizadas como referencia. Conclusiones. Los mapas de atenuación simplificados que se utilizan en PET/RM producen un incremento significativo de variabilidad cuantitativa especialmente en pulmones y huesos. La cuantificación aplicada al estudio de la aterosclerosis produce pequeñas desviaciones, especialmente cuando se utiliza el TBR (AU)

Objectives. Accuracy on quantitative PET image analysis relies on the correct application of attenuation correction which is one of the major challenges for PET/MRI that remains to be solved. The purpose of this study is to evaluate the effect of MRI-based attenuation maps and the use of flexible coils on the quantitative accuracy of PET images with a special focus on large arteries. Materials and methods. PET/CT data from eight oncologic patients was used. PET data was reconstructed using attenuation maps with different level of detail emulating several approaches available on current PET/MRI scanners. PET images obtained with CT-based and MRI-based attenuation maps were compared to evaluate the quantitative biases obtained. The quantitative effect produced by flexible MRI receiver coils on the attenuation maps was also studied. Results. The use of simpler attenuation maps produced increased biases between PET data reconstructed with CT-based and MRI-based attenuation maps for fat, non-fat soft-tissues and bone. Biases in lung were very high due to the large heterogeneity and inter-patient variability of the lung. The quantification on large arteries had small deviations except for the case when flexible coils were used. The TBR provided smaller biases in all cases as it cancelled out the similar deviations obtained for arteries and reference veins. Conclusions. Simplified attenuation maps used on PET/MRI significantly increase the quantitative variability of PET images especially on lungs and bones. The quantification of PET images acquired with PET/MRI scanners applied to studies of atherosclerosis has small deviations, especially when the TBR is considered (AU)

The effect of tissue-segmented attenuation maps on PET quantification with a special focus on large arteries. / Efecto de la segmentación por tejidos en los mapas de atenuación sobre la cuantificación PET con especial hincapié en grandes arterias.

OBJECTIVES: Accuracy on quantitative PET image analysis relies on the correct application of attenuation correction which is one of the major challenges for PET/MRI that remains to be solved. The purpose of this study is to evaluate the effect of MRI-based attenuation maps and the use of flexible coils on the quantitative accuracy of PET images with a special focus on large arteries. MATERIALS AND METHODS: PET/CT data from eight oncologic patients was used. PET data was reconstructed using attenuation maps with different level of detail emulating several approaches available on current PET/MRI scanners. PET images obtained with CT-based and MRI-based attenuation maps were compared to evaluate the quantitative biases obtained. The quantitative effect produced by flexible MRI receiver coils on the attenuation maps was also studied. RESULTS: The use of simpler attenuation maps produced increased biases between PET data reconstructed with CT-based and MRI-based attenuation maps for fat, non-fat soft-tissues and bone. Biases in lung were very high due to the large heterogeneity and inter-patient variability of the lung. The quantification on large arteries had small deviations except for the case when flexible coils were used. The TBR provided smaller biases in all cases as it cancelled out the similar deviations obtained for arteries and reference veins. CONCLUSIONS: Simplified attenuation maps used on PET/MRI significantly increase the quantitative variability of PET images especially on lungs and bones. The quantification of PET images acquired with PET/MRI scanners applied to studies of atherosclerosis has small deviations, especially when the TBR is considered.

Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.

Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.

Superparamagnetic Nanoparticles for Atherosclerosis Imaging.

The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound.

Apparent diffusion coefficient of hyperpolarized (3)He with minimal influence of the residual gas in small animals.

The apparent diffusion coefficient (ADC) of hyperpolarized (HP) gases is a parameter that reflects changes in lung microstructure. However, ADC is dependent on many physiological and experimental variables that need to be controlled or specified in order to ensure the reliability and reproducibility of this parameter. A single breath-hold experiment is desirable in order to reduce the amount of consumed HP gas. The application of a positive end-expiratory pressure (PEEP) causes an increase in the residual gas volume. Depending on the applied PEEP, the ratio between the incoming and residual gas volumes will change and the ADC will vary, as long as both gases do not have the same diffusion coefficient. The most standard method for human applications uses air for breathing and a bolus of pure HP (3)He for MRI data acquisition. By applying this method in rats, we have demonstrated that ADC values are strongly dependent on the applied PEEP, and therefore on the residual gas volume in the lung. This outcome will play an important role in studies concerning certain diseases, such as emphysema, which is characterized by an increase in the residual volume. Ventilation with an oxygen-helium mixture (VOHeM) is a proposed single breath-hold method that uses two different gas mixtures (O(2)-(4)He for ventilation and HP (3)He-N(2) for imaging). The concentration of each gas in its respective mixture was calculated in order to obtain the same diffusion coefficient in both mixtures. ADCs obtained from VOHeM are independent of PEEP, thus minimizing the effect of the different residual volumes.

Dynamic ventilation 3He MRI for the quantification of disease in the rat lung.

Pulmonary diseases are known to be largely inhomogeneous. To evaluate such inhomogeneities, we are testing an image-based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized (3)He MR images performed during slow inhalation of this gas were analyzed to quantify regional inflation rate. This parameter was measured in regions of interest (ROIs) that were defined by a rectangular grid that covered the entire rat lung and grew dynamically with it during its inflation. We used regional inflation rate to quantify elastase-induced emphysema and to differentiate healthy (n = 8) from elastase-treated (n = 9) rat lungs as well as healthy from elastase-treated areas of one rat unilaterally treated with elastase in the left lung. Emphysema was also assessed by gold standard morphological and well-established hyperpolarized (3)He MRI diffusion measurements. Mean values of regional inflation rates were significantly different for healthy and elastase-treated animals and correlated well with the apparent diffusion coefficient of (3)He and morphological measurements. The image-based biomarker inflation rate may be useful for the assessment of regional lung ventilation.

Magnetic resonance methods and applications in pharmaceutical research.

This review presents an overview of some recent magnetic resonance (MR) techniques for pharmaceutical research. MR is noninvasive, and does not expose subjects to ionizing radiation. Some methods that have been used in pharmaceutical research MR include magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) methods, among them, diffusion-weighted MRI, perfusion-weighted MRI, functional MRI, molecular imaging and contrast-enhance MRI. Some applications of MR in pharmaceutical research include MR in metabonomics, in vivo MRS, studies in cerebral ischemia and infarction, degenerative joint diseases, oncology, cardiovascular disorders, respiratory diseases and skin diseases. Some of these techniques, such as cardiac and joint imaging, or brain fMRI are standard, and are providing relevant data routinely. Skin MR and hyperpolarized gas lung MRI are still experimental. In conclusion, considering the importance of finding and characterizing biomarkers for improved drug evaluation, it can be expected that the use of MR techniques in pharmaceutical research is going to increase in the near future.

Magnetic resonance microscopy versus light microscopy in human embryology teaching.

A study was carried out on the application of magnetic resonance microscopy (MRM) in teaching prenatal human development. Human embryos measuring 8 mm, 15 mm, 18.5 mm, and 22 mm were fixed in a 4% paraformaldehyde solution and sections obtained with magnetic resonance imaging (MRI) were compared to those prepared for light microscopy (LM), using the same embryos. The MRM and LM slices were of a similar quality. In the MRM sections, embryonic organs and systems were clearly visible, particularly the peripheral and central nervous systems, and the cardiovascular and digestive systems. The digitalization and clarity of the MRM images make them an ideal teaching aid that is suitable for students during the first years of a health-science degree, particularly medicine. As well as providing students with their first experience of MRM, these images allow students to access, at any time, all embryos used, to assess changes in the positions of different organs throughout their stages of development, and to acquire spatial vision, an absolute requirement in the study of human anatomy. We recommend that this technique be incorporated into the wealth of standard embryonic teaching methods already in use.

Interventional magnetic resonance imaging for guiding gene and cell transfer in the heart.

BACKGROUND: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time. OBJECTIVES: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model. METHODS: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography. RESULTS: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, beta-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area (r = 0.70; p < 0.0001) and change in left ventricular area with time (r = 0.75; p < 0.0001). CONCLUSIONS: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema.

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung (i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium-3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134 +/- 25 microm) versus control (85 +/- 14 microm). The apparent diffusion coefficients were significantly different between the two groups (0.18 +/- 0.02 and 0.15 +/- 0.01 cm2 x s(-1) for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.

The human embryo development through MMR.

This study evaluates the use of the Microscopic Magnetic Resonance (MMR) in the human prenatal development. Human embryos (8mm, 15mm, 18mm and 22mm in length) fixed in 4% paraformaldehyde were used. Results were compared with light microscopy (LM) images. The internal configuration of the embryos can be clearly observed as well as many organs such as liver, lungs, heart, including their spatial relationships. In general MMR sections are less clear and show minor details than those by LM. Neverthless, many advantages are provided by using this technique. For example it is possible: a) to make three-dimensional (3-D) surface and internal full or partial reconstructions; b) to evaluate the presence of developmental anomalies; c) to evaluate the tissular preservation degree of the specimens; and d) to apply morphometric techniques to unfixed specimens. In our opinion the advantages derived by using MMR are many and overcome the disadvantages. This study demonstrates that MMR can be incorporated into ordinary laboratory techniques in human development studies, being also an initial election technique opposite to others more aggressive.

Neumonía por Mycoplasma pneumoniae en una zona básica de salud / Pneumonia due to mycoplasma pneumoniae in a primary health care district

Objetivo: Se pretende conocer las características epidemiológicas, clínicas, radiológicas y evolutivas de la neumonía atípica por Mycoplasma pneumoniae en pacientes extrahospitalarios, ya que la mayoría de los estudios realizados son revisiones de pacientes que han requerido hospitalización. Métodos: Se realizó un estudio observacional prospectivo de 31 casos de neumonía atípica por M. pneumoniae en la población infantil de una zona básica de salud desde mayo a julio de 1996. Todos los casos tuvieron confirmación serológica de infección por M. pneumoniae mediante la reacción de fijación de complemento. Resultados: La edad de los niños afectados osciló entre los 4 y 13 años. Las manifestaciones clínicas más frecuentes fueron tos (93%), fiebre elevada (84%) y faringitis (48%). El hallazgo auscultatorio más frecuente fueron los crepitantes (93%), siendo bilaterales en 14 pacientes. Hubo disociación clinicorradiológica en el 16%; 27 pacientes (87%) tuvieron alteración radiológica, sin que se observara un patrón radiológico característico, ya que se presentaron con igual frecuencia el alveolar que el intersticial, con un predomino de afectación de bases pulmonares (67,7%).En todos los pacientes la respuesta a los macrólidos fue excelente y la fiebre cedió en 48-72 h con mejoría progresiva del resto de los síntomas. Conclusiones: La neumonía atípica por M. pneumoniae suele presentarse en la edad escolar y adolescencia sin que haya ningún síntoma, signo o patrón radiológico que oriente claramente hacia esta etiología. Por su frecuencia debe ser el primer diagnóstico de sospecha del síndrome neumónico en la edad escolar y adolescencia, siendo los macrólidos el fármaco de elección (AU)

High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis.

OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes. RESULTS: MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies.

[Pneumonia due to mycoplasma pneumoniae in a primary health care district]. / Neumonía por Mycoplasma pneumoniae en una zona básica de salud.

OBJECTIVE: Most studies of atypical pneumonia due to Mycoplasma pneumoniae have been performed in hospitalized patients. The aim of this study was to determine the epidemiological, clinical and radiological characteristics as well as the evolution of patients with atypical pneumonia due to Mycoplasma pneumoniae in an out-of-hospital setting. METHODS: A prospective observational study was conducted in 31 patients with atypical pneumonia due to Mycoplasma pneumoniae in the pediatric population of a primary health care district from May to July 1996. In all patients serological confirmation of infection by Mycoplasma pneumoniae was obtained using a complement-fixation test. RESULTS: The age of the children in the study ranged from 4-13 years. The most common clinical manifestations were cough (93 %), high fever (84 %) and pharyngitis (48 %). The most frequent auscultatory finding was crackles (93 %), which were bilateral in 14 patients. Clinical-radiological dissociation was found in 16 % of the children; 27 (87 %) showed radiological alterations. No characteristic radiological pattern was detected because alveolar and interstitial alterations were equally frequent, with a predominance of lung base involvement (67.7 %). In all patients response to macrolides was excellent, fever abated within 48-72 h and the remaining symptoms progressively improved. CONCLUSIONS: Atypical pneumonia due to Mycoplasma pneumoniae normally presents in children aged more than 5 years old or in adolescents. No signs, symptoms, or radiological patterns clearly indicate the etiology. However, because of its frequency, this disease should be suspected when school-aged children or adolescents present a pneumonia syndrome. Macrolides administration

Mealiness assessment in apples and peaches using MRI techniques.

Mealiness (woolliness in peaches) is a negative attribute of sensory texture that combines the sensation of a desegregated tissue with the sensation of lack of juiciness. In this study, 24 apples cv. Top Red and 8 peaches cv. Maycrest, submitted to 3 and 2 different storage conditions respectively have been tested by mechanical and MRI techniques to assess mealiness. With this study, the results obtained on apples in a previous work have been validated using mathematical features from the histograms of the T2 maps: more skewed and the presence of a tail in mealy apples, similar to internal breakdown. In peaches, MRI techniques can also be used to identify woolly fruits. Not all the changes found in the histograms of woolly peaches are similar from those observed in mealy apples pointing to a different underlying physiological change in both disorders.

Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy.

We have used diffusion-weighted proton magnetic resonance spectroscopy (DWMRS) to noninvasively selectively observe only the intracellular metabolites of breast cancer and melanoma cell lines in vitro in real time. Breast cancer cell lines representing different stages in breast cancer progression were chosen for study. Intracellular biochemical profiles of six cell lines perfused in alginate beads were obtained. Spectral differences between groups of cell lines, including choline, lactate, and threonine peaks, were investigated. We also monitored response to the antineoplastic agent, lonidamine (LND), as a function of time and drug concentration in perfused cancer cells. Previous studies reported that this drug induced intracellular acidification and lactate accumulation. Diffusion weighted proton spectra demonstrated a 2- to 9-fold increase in the intracellular lactate signal as a response to LND treatment in several cancer cell lines. These results are consistent with the hypothesis that the principal mechanism of LND in some cancer cells is marked inhibition of lactate transport. Moreover, we have shown that there is a factor of two to three between the response of melanoma cells and that of some types of breast cancer cells. The higher sensitivity of the melanoma cells, as predicted by proton DWMRS, was correlated with changes in water-suppressed magnetic resonance spectra and confirmed by a biological assay. This study demonstrates the feasibility of using DWMRS for monitoring intracellular metabolism and for studying the effects and mechanisms of action of anticancer drugs. We believe that this method can be used for noninvasive clinical applications, such as the differentiation between benign and malignant tissue, real-time monitoring of response to therapy, dose response, and toxicity effects.