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1.
Magn Reson Imaging ; 27(4): 549-56, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-18930366

RESUMEN

Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.


Asunto(s)
Pruebas Respiratorias/métodos , Aumento de la Imagen/métodos , Pulmón/fisiología , Imagen por Resonancia Magnética/métodos , Intercambio Gaseoso Pulmonar/fisiología , Hexafluoruro de Azufre/farmacocinética , Administración por Inhalación , Animales , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espirometría/métodos , Porcinos
2.
J Magn Reson Imaging ; 28(1): 51-9, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18581352

RESUMEN

PURPOSE: To compare three different autocalibrated parallel acquisition techniques (PAT) for quantitative and semiquantitative myocardial perfusion imaging. MATERIALS AND METHODS: Seven healthy volunteers underwent myocardial first-pass perfusion imaging at rest using an SR-TrueFISP pulse sequence without PAT and while using GRAPPA, mSENSE, and TSENSE. signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), normalized upslopes (NUS), and myocardial blood flow (MBF) were calculated. Artifacts, image noise, and overall image quality were qualitatively assessed. Furthermore, the relation between signal intensity (SI) and contrast medium (CM) concentration was determined in phantoms. RESULTS: Using PAT the linear range of the SR-TrueFISP sequence was increased about 40%. All three PAT methods introduced significant loss in SNR and CNR. GRAPPA yielded slightly better values then mSENSE and TSENSE. Both SENSE techniques introduced significantly residual aliasing artifacts. Image noise was increased with all three PAT methods. However, overall image quality was reduced only with mSENSE. Even though GRAPPA yielded smaller NUS values than non-PAT, mSENSE, and TSENSE, no differences were found in MBF between all applied techniques. CONCLUSION: Quantitative and semiquantitative myocardial perfusion imaging can benefit from PAT due to shorter acquisition times and increased linearity of the pulse sequence. GRAPPA and TSENSE turned out to be well suited for quantitative myocardial perfusion imaging.


Asunto(s)
Circulación Coronaria , Imagen por Resonancia Magnética/métodos , Adulto , Femenino , Humanos , Masculino , Fantasmas de Imagen
3.
J Magn Reson Imaging ; 26(3): 569-79, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17685447

RESUMEN

PURPOSE: To investigate the parallel acquisition technique sensitivity encoding incorporating temporal filtering (TSENSE) with three saturation-recovery (SR) prepared pulse sequences (SR turbo fast low-angle shot [SR-TurboFLASH], SR true fast imaging with steady precession [SR-TrueFISP], and SR-prepared segmented echo-planar-imaging [SR-segEPI]) for semiquantitative first-pass myocardial perfusion imaging. MATERIALS AND METHODS: In blood- and tissue-equivalent phantoms the relationship between signal intensity (SI) and contrast-medium concentration was evaluated for the three pulse sequences. In volunteers, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and normalized upslopes (NUS) were calculated from signal-time curves (STC). Moreover, artifacts, image noise, and overall image quality were qualitatively evaluated. RESULTS: Phantom data showed a 40% increased linear range of the relation between SI and contrast-medium concentration with TSENSE. In volunteers, TSENSE introduced significantly residual artifacts and loss in SNR and CNR. No differences were found for NUS values with TSENSE. SR-TrueFISP yielded highest SNR, CNR, and quality scores. However, in SR-True-FISP images, dark-banding artifacts were most pronounced. NUS values obtained with SR-TrueFISP were significantly higher and with SR-segEPI significantly lower than with SR-TurboFLASH. CONCLUSION: Semiquantitative myocardial perfusion imaging can significantly benefit from TSENSE due to shorter acquisition times and increased linearity of the pulse sequences. Among the three pulse sequences tested, SR-TrueFISP yielded best image quality. SR-segEPI proved to be an interesting alternative due to shorter acquisition times, higher linearity and fewer dark-banding artifacts.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Miocardio/patología , Adulto , Medios de Contraste/farmacología , Imagen Eco-Planar , Femenino , Frecuencia Cardíaca , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Perfusión , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
J Magn Reson Imaging ; 24(6): 1291-7, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17078046

RESUMEN

PURPOSE: To study the influence of admixing inert buffer gases to laser-polarized (3)He in terms of resulting diffusion coefficients and the consequences for image contrast and resolution. MATERIALS AND METHODS: The diffusion coefficient of (3)He was altered by admixing buffer gases of various molecular weights ((4)He, N(2), and SF(6)). The influence of the pulse sequence and the diffusion coefficient on the appearance of MRI of (laser-polarized) gases was analyzed by comparison of basic theoretical concepts with demonstrative experiments. RESULTS: Excellent agreement between theoretical description and observed signal in simple gradient echoes was observed. A maximum signal gain can be predicted and was experimentally validated. Images acquired under such conditions revealed improved resolution. The nature and concentration of the admixed gas defines a structural threshold for the observed apparent diffusion coefficient (ADC) as demonstrated with diffusion-weighted MRI on a pig's lung flooded with suitable gas mixtures. CONCLUSION: A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. Their molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this enables images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion.


Asunto(s)
Medios de Contraste/química , Imagen de Difusión por Resonancia Magnética/métodos , Helio/química , Aumento de la Imagen/métodos , Pulmón/anatomía & histología , Pulmón/química , Imagen de Difusión por Resonancia Magnética/instrumentación , Gases/química , Humanos , Isótopos/química , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
5.
Z Med Phys ; 16(2): 114-22, 2006.
Artículo en Alemán | MEDLINE | ID: mdl-16875024

RESUMEN

Imaging methods to study the lung are traditionally based on x-ray or on radioactive contrast agents. Conventional magnetic resonance imaging (MRI) has only limited applications for lung imaging because of the low tissue density of protons concentration of hydrogen atoms, which are usually the basis for the imaging. The introduction of hyperpolarized noble gases as a contrast agent in MRI has opened new possibilities for lung diagnosis. The present paper describes this new technique. Diffusion-weighted MRI for assessment of the lung microstructure is presented here as an example of the new possibilities of functional imaging. Studies to determine the sensitivity of the diffusion measurement and regarding the correlation with traditionally established methods are also presented, along with results of the measurement of the reproducibility determined in a clinical pilot study on healthy volunteers and patients. Furthermore, a pilot measurement of the 3He diffusion tensor in the lung is presented.


Asunto(s)
Pulmón/ultraestructura , Tritio , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética , Radiografía , Cintigrafía
6.
Med Klin (Munich) ; 100(7): 413-24, 2005 Jul 15.
Artículo en Alemán | MEDLINE | ID: mdl-16010478

RESUMEN

Lung imaging is traditionally done using X-ray-based methods, since MRI is limited by low proton density as well as inherent magnetic field inhomogeneities of the lung tissue. After introduction of MRI using hyperpolarized noble gases, a totally new field of MRI of the chest has rapidly evolved. These techniques reveal new functional information of the lungs, which could not be obtained before. The first part of this review describes the underlying MR technology explaining distribution of static ventilation, dynamic distribution of ventilation, lung microstructure (apparent diffusion coefficient [ADC]), measurement of oxygen partial pressure (pO(2)), and safety. The clinical potential is afterwards demonstrated in the second part. Therefore, the effort in normal lungs and the mainly focused diseases chronic obstructive pulmonary disease (COPD), smoker's lung, cystic fibrosis, asthma, lung transplantation, and pulmonary embolism are reported.


Asunto(s)
Medios de Contraste/administración & dosificación , Helio , Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Enfermedades Pulmonares/diagnóstico , Imagen por Resonancia Magnética/métodos , Administración por Inhalación , Humanos , Isótopos , Enfermedades Pulmonares/fisiopatología , Oxígeno/sangre , Capacidad de Difusión Pulmonar/fisiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Intercambio Gaseoso Pulmonar/fisiología , Valores de Referencia , Sensibilidad y Especificidad , Fumar/fisiopatología , Relación Ventilacion-Perfusión/fisiología
7.
Respir Physiol Neurobiol ; 148(1-2): 23-42, 2005 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-15967737

RESUMEN

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Paro Cardíaco/diagnóstico , Helio/metabolismo , Pulmón/fisiopatología , Animales , Anisotropía , Pruebas Respiratorias/métodos , Estudios de Casos y Controles , Paro Cardíaco/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Isótopos/metabolismo , Pulmón/patología , Persona de Mediana Edad , Porcinos , Factores de Tiempo , Distribución Tisular
8.
J Magn Reson Imaging ; 21(6): 765-74, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15906344

RESUMEN

PURPOSE: To determine the reproducibility of several parameters of the ADC measurement by calculating the scan-to-scan intrasubject variability. MATERIALS AND METHODS: Measurements were performed using a gradient-echo sequence with a bipolar gradient for diffusion weighting (b=3.89 sec/cm2). Five patients with pulmonary emphysema, and six healthy-lung volunteers were included in the study. Images were acquired after inspiration of 3He during a single inspiratory breath-hold. To assess the reproducibility, the measurement was performed twice (time between measurements=20 minutes) without repositioning the subjects. Analysis was performed on the basis of region-of-interest (ROI) analysis and global lung ADC histograms. RESULTS: The mean ADC of a ROI varied by 5.1% between two measurements for volunteers and by 6.1% for patients. In the global evaluation, the 75th percentile demonstrated the best reproducibility (2%), while other parameters showed variations up to 12%. Only the variation of the standard deviation (SD) and the measure of homogeneity of the ADC map showed a significant difference between patients and volunteers. CONCLUSION: Diffusion-weighted imaging (DWI) is a well-reproducible method for assessing the lung microstructure.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Helio , Enfisema Pulmonar/patología , Administración por Inhalación , Adulto , Anciano , Femenino , Helio/administración & dosificación , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estadísticas no Paramétricas
9.
Phys Med Biol ; 50(8): 1659-73, 2005 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-15815088

RESUMEN

In this study, an algorithm was developed to measure the distribution of pulmonary time constants (TCs) from dynamic computed tomography (CT) data sets during a sudden airway pressure step up. Simulations with synthetic data were performed to test the methodology as well as the influence of experimental noise. Furthermore the algorithm was applied to in vivo data. In five pigs sudden changes in airway pressure were imposed during dynamic CT acquisition in healthy lungs and in a saline lavage ARDS model. The fractional gas content in the imaged slice (FGC) was calculated by density measurements for each CT image. Temporal variations of the FGC were analysed assuming a model with a continuous distribution of exponentially decaying time constants. The simulations proved the feasibility of the method. The influence of experimental noise could be well evaluated. Analysis of the in vivo data showed that in healthy lungs ventilation processes can be more likely characterized by discrete TCs whereas in ARDS lungs continuous distributions of TCs are observed. The temporal behaviour of lung inflation and deflation can be characterized objectively using the described new methodology. This study indicates that continuous distributions of TCs reflect lung ventilation mechanics more accurately compared to discrete TCs.


Asunto(s)
Algoritmos , Interpretación de Imagen Asistida por Computador/métodos , Pulmón/diagnóstico por imagen , Pulmón/fisiología , Modelos Biológicos , Ventilación Pulmonar/fisiología , Tomografía Computarizada por Rayos X/métodos , Animales , Simulación por Computador , Aumento de la Imagen/métodos , Imagenología Tridimensional/métodos , Almacenamiento y Recuperación de la Información/métodos , Cinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Porcinos
10.
Magn Reson Med ; 53(5): 1223-7, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15844154

RESUMEN

Qualitative and semiquantitative contrast-enhanced (CE) dynamic perfusion MRI techniques are established as noninvasive diagnostic means of assessing coronary artery disease. However, to date quantification of myocardial blood flow (MBF) has not reached the same acceptance as MBF quantification with nuclear techniques. To validate quantification of MBF at rest using the extracellular contrast agent (CA) Gd-DTPA, we performed an animal study in a pig model of acute myocardial ischemia. We quantified MBF from MRI data with a mathematical model (MMID4) of the underlying vasculature. These MBF results were subsequently compared with the results from fluorescent microspheres. The study showed a correlation of r = 0.66 between MBF estimates obtained with MRI and those obtained with fluorescent microspheres. The correlation for ischemic and nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion, quantification of resting MBF using MMID4 is a valid method under conditions of acute myocardial ischemia.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Isquemia Miocárdica/diagnóstico , Enfermedad Aguda , Animales , Medios de Contraste , Circulación Coronaria , Modelos Animales de Enfermedad , Gadolinio DTPA , Estadísticas no Paramétricas , Porcinos
11.
Eur Radiol ; 15(9): 1915-22, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15856240

RESUMEN

The aim of this study was to validate oxygen-sensitive 3He-MRI in noninvasive determination of the regional, two- and three-dimensional distribution of oxygen partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung phantom, oxygen sensitive two- and three-dimensional 3He-MRI measurements were performed at different oxygen concentrations which had been equilibrated in a range of normal and pathologic values. The oxygen partial pressure distribution was determined from 3He-MRI using newly developed software allowing for mapping of oxygen partial pressure. The reference bulk oxygen partial pressure inside the phantom was measured by conventional respiratory gas analysis. In two-dimensional measurements, image-based and gas-analysis results correlated with r=0.98; in three-dimensional measurements the between-methods correlation coefficient was r=0.89. The signal-to-noise ratio of three-dimensional measurements was about half of that of two-dimensional measurements and became critical (below 3) in some data sets. Oxygen-sensitive 3He-MRI allows for noninvasive determination of the two- and three-dimensional distribution of oxygen partial pressure in gas-filled airspaces.


Asunto(s)
Helio , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Pulmón/metabolismo , Imagen por Resonancia Magnética/métodos , Consumo de Oxígeno/fisiología , Fantasmas de Imagen , Humanos , Inhalación/fisiología , Isótopos , Oxígeno/administración & dosificación , Presión Parcial
12.
Eur Radiol ; 14(12): 2188-97, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15517280

RESUMEN

The purpose of this study was to use cine-MRI during continuous respiration to measure the respiratory lumenal diameter change in the pharynx and at an upper tracheal level. Fifteen non-smokers and 23 chronic obstructive pulmonary disease (COPD) patients with smoking history (median 50 pack-years) were included. Cine-MRI with seven frames/s was performed during continuous respiration. Minimal and maximal cross-sectional lumenal diameters within the pharynx and the upper tracheal lumen area were measured. The median diameter change in the pharynx (tracheal area) was 70% (1.4 cm(2)) in volunteers and 76% (1.7 cm(2)) in smokers (P=0.98, P=0.04). Tracheal lumenal collapse was a median of 43% in volunteers and 64% in smokers (P=0.011). No clear disease-related difference of the pharynx-lumen was found. The maximal cross-sectional area of the upper trachea lumen as well as the respiratory collapse was larger in COPD patients than in normal subjects. This information is important for the modelling of ventilation and prediction of drug deposition, which are influenced by the airway diameter.


Asunto(s)
Imagen por Resonancia Cinemagnética , Faringe/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Tráquea/fisiología , Anciano , Humanos , Persona de Mediana Edad , Faringe/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Respiración , Fumar/fisiopatología , Tráquea/fisiopatología
13.
Invest Radiol ; 39(7): 427-34, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15194914

RESUMEN

PURPOSE: To assess the emphysematous enlargement of distal airspaces and concomitant large and small airway disease using diffusion-weighted Helium-magnetic resonance imaging (MRI), high-resolution computed tomography (HRCT), and lung function tests (LFT). METHODS: Seven patients were examined after single lung transplantation (LTx) and 1 before double LTx for various forms of emphysema. Five patients after double LTx served as controls. Patients were assessed by Helium-MRI (apparent diffusion coefficient [ADC]), HRCT (mean lung density [MLD], emphysema index [EI]), and LFT. RESULTS: Transplanted lungs: mean ADC = 0.17 cm/s, MLD = -848 H, EI = 22%. Emphysematous lungs: mean ADC = 0.33 cm/s, MLD = -922 H; EI = 54%. Good correlations were found between ADC and MLD (r = 0.6), EI (r = 0.8), intrathoracic gas volume (r = 0.7), forced expiratory volume in 1 second (r = 0.7), and forced expiratory flows (r = 0.7). In contrast, HRCT only provided moderate correlations with LFT (EI: r = 0.5; MLD: r [le] 0.4). CONCLUSION: In this initial study, He-MRI yield good correlations with HRCT and agrees better than HRCT with the functional characterization of emphysema regarding hyperinflation, large and small airway disease as provided by LFT.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Enfisema Pulmonar/fisiopatología , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X/métodos , Femenino , Helio , Humanos , Isótopos , Trasplante de Pulmón , Masculino , Persona de Mediana Edad
14.
Int J Cardiovasc Imaging ; 19(5): 409-16, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14609190

RESUMEN

AIMS: Contrast enhanced magnetic resonance imaging (ceMRI) has been shown to reliably identify irreversible myocardial injury. The aim of this study was to compare the findings on ceMRI with routine clinical markers of myocardial injury in patients with acute myocardial infarction (MI). METHODS AND RESULTS: Twenty-four patients with acute MI were investigated at 1.5 T. The global myocardial function was analysed with a standard cine MR protocol and a stack of short axis slices encompassing the entire left ventricle. Corresponding short axis slices were acquired for delayed ceMRI 15-20 min after the administration of 0.2 mmol gadolinium-DTPA/kg body weight. Mass of hyperenhancement and peak creatine kinase release (peak CK) was determined for each patient. The presenting 12-lead ECG was analysed for ST-elevation on admission and later development of Q-waves. Mass of hyperenhancement correlated moderately well to peak CK (r = 0.65, p < 0.01) and endsystolic volume index (r = 0.55, p < 0.01). Mass of hyperenhancement was inversely correlated to ejection fraction (r = -0.50, p = 0.02). Neither the presence of ST elevation on the admission ECG nor the later development of Q-waves did relate to the transmural extent of hyperenhancement and to the mass of hyperenhancement. CONCLUSION: Mass of hyperenhancement significantly correlates to global myocardial function and to peak CK. However, there is no relationship between the findings in ceMRI and 12-lead ECG abnormalities on admission suggesting an advantage of ceMRI in defining transmural extent and depicting small areas of necrosis.


Asunto(s)
Pruebas Diagnósticas de Rutina , Infarto del Miocardio/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Medios de Contraste , Angiografía Coronaria , Creatina Quinasa/sangre , Electrocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Intensificación de Imagen Radiográfica , Estadística como Asunto , Volumen Sistólico/fisiología , Factores de Tiempo
15.
Cancer Res ; 63(21): 7221-31, 2003 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-14612517

RESUMEN

Overexpression of the receptor tyrosine kinase HER-2/neu is associated with poor prognosis in patients with breast and ovarian cancer. Recent excitement has surrounded the therapeutic effects of HER-2-blocking therapy strategies and has rekindled interest on the molecular mechanisms of HER-2/neu in tumor biology. To study the role of HER-2/neu overexpression in vivo, we used a murine fibroblast cell line (NIH3T3-her2) conditionally expressing human HER-2/neu under control of a tetracycline-responsive promoter. Expression of HER-2 could be down-regulated below detection limit (>625-fold dilution) by exposure of NIH3T3-her2 cells to anhydrotetracycline (ATc). Subcutaneous injection of NIH3T3-her2 cells into nude mice resulted in rapid tumor growth. Mice with mean tumor volumes of 0.2, 0.8, 1.9, and 14.9 cm(3) were treated daily with 10 mg/kg ATc to switch off HER-2/neu expression, producing reductions in tumor size of 100, 98.1, 81.4, and 74.2%, respectively, by 7 days after onset of ATc administration (P = 0.005, Kruskal-Wallis test). Different long-term effects of HER-2 down-regulation were observed when mice with small (0.2 cm(3); n = 7), intermediate (0.8-1.2 cm(3); n = 10) and large (> or =1.9 cm(3); n = 11) tumors received ATc for up to 40 days. Complete remission was observed for 100, 40, and 18% of the small-, intermediate-, and large-sized tumors, respectively (P = 0.003). However, after 20-45 days of ATc administration, recurrent tumor growth was observed for all mice, even in those with previous complete remissions. The time periods for which mean tumor volume could be suppressed to volumes <0.1 cm(3) under ATc administration were 34, 22, 8, and 0 days for tumors with initial volumes of 0.2, 0.8, 1.9 and 14.9 cm(3), respectively (P = 0.005, Kruskal-Wallis test). Interestingly, HER-2 remained below the detection limit in recurrent tumor tissue, suggesting that initially HER-2-dependent tumors switched to HER-2 independence. The "second hits" leading to HER-2-independent tumor growth have not yet been identified. The rapid regression of tumors after down-regulation of HER-2 was explained by two independent mechanisms: (a) a block in cell cycle progression, as evidenced by a decrease in Ki-67 antigen expression from 40% before ATc treatment to 8.3% after 7 days of ATc treatment; and (b) induction of apoptosis as demonstrated by caspase-3 activation and by the terminal deoxynucleotidyltransferase (Tdt)-mediated nick end labeling assay (TUNEL). In conclusion, we have shown that switching off HER-2 may disturb the sensitive balance between cell proliferation and cell death, leading to apoptosis and tumor remission. Tumor remission was dependent on the volume of the tumors before down-regulation of HER-2/neu.


Asunto(s)
Apoptosis/fisiología , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/biosíntesis , Animales , Ciclo Celular/fisiología , División Celular/fisiología , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Desnudos , Células 3T3 NIH , Neoplasias Experimentales/genética , Regiones Promotoras Genéticas , Receptor ErbB-2/genética , Tetraciclina/farmacología , Tetraciclinas/farmacología
16.
Invest Radiol ; 38(10): 635-41, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14501491

RESUMEN

RATIONALE AND OBJECTIVES: Partial liquid ventilation using Perfluorcarbon (PFC) is an innovative treatment of acute respiratory distress syndrome. However, the underlying mechanisms are not totally clear. The aim was to investigate the distribution of oxygen partial pressure within the PFC-filled lung (ppO2). METHODS: Nine pigs underwent partial liquid ventilation, receiving 20 mL PFC/kg bodyweight (bw). Measurements were obtained by a chemical shift selective TurboFLASH sequence at different axial lung levels. ppO2 was calculated from 19F-MRI by nonlinear curve T1-fitting technique after noise correction. RESULTS: Quantification and distribution of ppO2 was performed successfully. A narrow relationship of the inspiratory O2 fraction and ppO2, as well as a significant ventral-to-dorsal gradient of ppO2 (ventral:dependent lung = 1.9:1) were detected in all subjects and slice positions. CONCLUSIONS: In vivo measurement of local ppO2 gains new and clinical important insights into the physiology of PLV. The previously unknown ppO2 gradient within PFC fits to distribution of perfusion. Dependent lung regions appear to have limited access to O2 from central airways.


Asunto(s)
Ventilación Liquida/métodos , Imagen por Resonancia Magnética/métodos , Oxígeno/análisis , Alveolos Pulmonares/fisiología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Animales , Polímeros de Fluorocarbono , Presión Parcial , Ventilación Pulmonar/fisiología , Síndrome de Dificultad Respiratoria/sangre
17.
Invest Radiol ; 38(6): 341-8, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12908701

RESUMEN

RATIONALE AND OBJECTIVES: The ability of motion corrected dynamic 3He-magnetic resonance imaging (MRI) to discriminate distributional patterns of inhaled hyperpolarized 3He between different groups of lung transplant recipients was evaluated. METHODS: An ultrafast low-angle shot 2D sequence (temporal resolution 128 ms) was used for ventilation 3He-MRI of 11 single and 6 double lung transplant recipients. After digital motion correction, signal kinetics were evaluated in a tracheal and 7 pulmonary regions of interest. Results from grafts and native lungs as well as from normal and rejected grafts were compared with each other and to reference values from healthy subjects. RESULTS: In emphysema patients, median alveolar rise time, a parameter for increase of alveolar signal, was 0.28 seconds for the graft and 0.48 seconds for the native lung, in fibrosis patients its median was 0.46 seconds for the graft and 0.21 seconds for the native lung. In double lung recipients, alveolar rise time was 0.29 seconds in normal and clinically rejected grafts. CONCLUSIONS: Dynamic ventilation 3He-MRI discriminated normal lung grafts from diseased native lungs in single lung recipients. Graft rejection in double lung recipients could not be discriminated.


Asunto(s)
Helio , Trasplante de Pulmón , Pulmón/anatomía & histología , Imagen por Resonancia Magnética , Relación Ventilacion-Perfusión , Femenino , Humanos , Isótopos , Masculino , Persona de Mediana Edad , Movimiento (Física) , Enfisema Pulmonar/patología , Fibrosis Pulmonar/patología
18.
Bioelectromagnetics ; 24(4): 241-50, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12696084

RESUMEN

The purpose of this study was to examine whether exposure to magnetic fields (MFs) relevant for magnetic resonance imaging (MRI) in clinical routine influences cell cycle progression in two tumor cell lines in vitro. HL60 and EA2 cells were exposed to four types of MFs: (i) static MF of 1.5 and 7.05 T, (ii) extremely low frequency magnetic gradient fields (ELFMGFs) with +/- 10 mT/m and 100 Hz, as well as +/- 100 mT/m and 100 Hz, (iii) pulsed high frequency MF in the radiofrequency (RF) range (63.6 MHz, 5.8 microT), and (iv) a combination of (i-iii). Exposure periods ranged from 1 to 24 h. Cell cycle distribution (G(0)/G(1), S, and G(2)/M phases) was analyzed by flow cytometry. Cell cycle analysis did not reveal differences between the exposed and the control cells. As expected, positive controls with irradiated (8 Gy) HL60 and EA2 cells showed a strong G(2)/M arrest. Using conditions that are relevant for patients during MRI, no influence of MFs on cell cycle progression was observed in these cell lines. Care was taken to control secondary parameters of influence, such as vibration by the MR scanner or temperature to avoid false positive results.


Asunto(s)
Ciclo Celular/efectos de la radiación , Campos Electromagnéticos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Radiometría/métodos , Relación Dosis-Respuesta en la Radiación , Exposición a Riesgos Ambientales/análisis , Células HL-60 , Humanos , Dosis de Radiación
19.
J Magn Reson Imaging ; 16(2): 137-46, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12203760

RESUMEN

PURPOSE: To compare dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) and the flow-sensitive alternating inversion recovery (FAIR) technique for measuring brain perfusion. MATERIALS AND METHODS: We investigated 12 patients with acute stroke, and 10 healthy volunteers with FAIR and DSC maps of regional cerebral blood volume (rCBV), mean transit time (MTT), and regional cerebral blood flow (rCBF). RESULTS: In volunteers good gray/white-matter contrast was observed in FAIR, rCBF, and rCBV maps. Regions with high signal intensities in FAIR matched well with high values of rCBV and rCBF. In ischemic stroke patients a high correlation (r = 0.78) of the ipsi- to contralateral signal intensity ratios in FAIR and rCBF was observed in areas with perfusion abnormalities. In contrast, FAIR and rCBV (r = 0.50), and FAIR and MTT (r = -0.22) correlated only modestly. Furthermore, FAIR and rCBF demonstrated similar sizes of perfusion abnormality. CONCLUSION: This study demonstrates for the first time that FAIR and rCBF depict similar relations of perfusion in ischemic stroke patients and healthy subjects.


Asunto(s)
Circulación Cerebrovascular , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/fisiopatología , Enfermedad Aguda , Adulto , Anciano , Estudios de Casos y Controles , Medios de Contraste , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional
20.
Magn Reson Med ; 47(4): 687-95, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11948729

RESUMEN

In this work some of the factors that can influence the signal-to-noise ratio (SNR) and spatial resolution in MR images of inhaled hyperpolarized gases are systematically addressed. In particular, the effects of RF depletion of longitudinal polarization and image gradient diffusion dephasing were assessed in terms of their contribution to a k-space filter. By means of theoretical simulations and a novel method of experimental validation using a variable transverse magnetization of the 1H signal, systematic quantitative and qualitative investigations of the effects of k-space filtering intrinsic to imaging of hyperpolarized gas were made. A 2D gradient-echo image is considered for a range of flip angles with centric, sequential, and half-Fourier Cartesian phase-encoding strategies, and the results are assessed in terms of SNR and spatial resolution in the reconstructed images. Centric phase encoding was found to give the best SNR at higher flip angles, with a trade-off in spatial resolution compared to sequential phase encoding. A half-Fourier approach potentially offers increased SNR through the use of higher flip angles without compromising the spatial resolution, which is comparable to that achieved with sequential encoding.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Análisis de Fourier , Helio , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Isótopos
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