Knorpelqualität an den Fingergelenken: delayed Gd(DTPA)²-enhanced MRI of the cartilage (dGEMRIC) bei 3T [Cartilage quality in finger joints: delayed Gd(DTPA)²-enhanced MRI of the cartilage (dGEMRIC) at 3T]

To evaluate the feasibility of molecular cartilage MRI in finger joints.

DWI: factores que influenciam a medição do coeficiente de difusão aparente (ADC) no estudo da mama

Mestrado em Radiações Aplicadas às Tecnologias da Saúde. Área de especialização: Ressonância Magnética

Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

Selective coronary artery plaque visualization and differentiation by contrast-enhanced inversion prepared MRI.

AIMS: We sought to evaluate the utility of contrast-enhanced coronary magnetic resonance imaging (CE-MRI) for selective visualization and non-invasive differentiation of atherosclerotic coronary plaque in humans. METHODS AND RESULTS: Nine patients with coronary artery disease (CAD) as confirmed by X-ray angiography and multidetector computed tomography (MDCT) were studied by T1-weighted black blood inversion recovery coronary MRI before (N-IR) and after administration of Gd-DTPA (CE-IR). Plaques were categorized as calcified, non-calcified, and mixed based on their Hounsfield number derived from MDCT. With MDCT, a total of 29 plaques were identified, including calcified (n=6), non-calcified (n=6), and mixed calcified/non-calcified (n=17). On N-IR MRI, 26 plaques (90%) were dark, whereas three plaques (two non-calcified and one mixed) appeared bright. On CE-MRI, 13/29 (45%) plaques, 11 of which were mixed, one non-calcified, and one calcified showed contrast uptake. All others remained dark. CONCLUSION: In this preliminary study, we demonstrate the potential utility of CE-IR MRI for selective plaque visualization and differentiation of plaque types. The observed contrast uptake may be associated with endothelial dysfunction, neovascularization, inflammation, and/or fibrosis.

Development of a hepatocyte hollow fiber bioreactor for the study of contrast agents by magnetic resonance imaging

Thanks to the continuous progress made in recent years, medical imaging has become an important tool in the diagnosis of various pathologies. In particular, magnetic resonance imaging (MRI) permits to obtain images with a remarkably high resolution without the use of ionizing radiation and is consequently widely applied for a broad range of conditions in all parts of the body. Contrast agents are used in MRI to improve tissue discrimination. Different categories of contrast agents are clinically available, the most widely used being gadolinium chelates. One can distinguish between extracellular gadolinium chelates such as Gd-DTPA, and hepatobiliary gadolinium chelates such as Gd-BOPTA. The latter are able to enter hepatocytes from where they are partially excreted into the bile to an extent dependent on the contrast agent and animal species. Due to this property, hepatobiliary contrast agents are particularly interesting for the MRI of the liver. Actually, a change in signal intensity can result from a change in transport functions signaling the presence of impaired hepatocytes, e.g. in the case of focal (like cancer) or diffuse (like cirrhosis) liver diseases. Although the excretion mechanism into the bile is well known, the uptake mechanisms of hepatobiliary contrast agents into hepatocytes are still not completely understood and several hypotheses have been proposed. As a good knowledge of these transport mechanisms is required to allow an efficient diagnosis by MRI of the functional state of the liver, more fundamental research is needed and an efficient MRI compatible in vitro model would be an asset. So far, most data concerning these transport mechanisms have been obtained by MRI with in vivo models or by a method of detection other than MRI with cellular or sub-cellular models. Actually, no in vitro model is currently available for the study and quantification of contrast agents by MRI notably because high cellular densities are needed to allow detection, and no metallic devices can be used inside the magnet room, which is incompatible with most tissue or cell cultures that require controlled temperature and oxygenation. The aim of this thesis is thus to develop an MRI compatible in vitro cellular model to study the transport of hepatobiliary contrast agents, in particular Gd-BOPTA, into hepatocytes directly by MRI. A better understanding of this transport and especially of its modification in case of hepatic disorder could permit in a second step to extrapolate this knowledge to humans and to use the kinetics of hepatobiliary contrast agents as a tool for the diagnosis of hepatic diseases.

Angio-RM das artérias carótidas e vertebrais: análise de diferentes técnicas de volume e diluição de contraste em aparelho de 1,0 t e gradiente de 15 mt/m

OBJETIVO: Avaliar as artérias cervicais (carótidas e vertebrais) por meio da angio-RM, utilizando-se diferentes dosagens e diluições de contraste paramagnético. MATERIAIS E MÉTODOS: Estudo prospectivo em 15 pacientes, com análise de 30 artérias carótidas comuns, 30 artérias carótidas internas, 30 artérias carótidas externas e 30 artérias vertebrais, utilizando-se diferentes volumes e dosagens de contraste paramagnético: grupo I - dose única (14 ml de Gd-DTPA); grupo II -dose dupla (28 ml de Gd-DTPA); grupo III - dose única e diluída a 50%. A injeção de contraste foi realizada com a utilização de bomba injetora e com velocidades de injeção de 2 ml/s (grupo I) e 3 ml/s (grupos II e III). Os segmentos arteriais foram analisados por três examinadores em consenso de forma subjetiva, avaliando-se o grau de visibilidade, intensidade de contrastação e definição de seus contornos. RESULTADOS: Em todos os itens analisados os pacientes do grupo II apresentaram melhor resultado (visibilização total, boa contrastação dos vasos e contornos bem definidos). No grupo I houve boa visibilização das artérias carótidas e vertebrais, porém a intensidade de contraste e a definição dos contornos apresentaram variabilidade qualitativa. O grupo III apresentou os piores resultados, com dificuldade de visibilização, intensidade de contrastação baixa e contornos mal definidos. CONCLUSÃO: Entre os grupos analisados, a técnica utilizando dose dupla de gadolínio é a que permite melhor avaliação das artérias cervicais. A utilização de contraste diluído prejudica a avaliação dos vasos do pescoço.

Estudo da circulação hepatomesentérica pela angiografia por ressonância magnética com gadolínio: comparação entre doses simples e dupla no estudo de pacientes esquistossomóticos

OBJETIVO: Determinar a freqüência de visualização dos segmentos da circulação hepatomesentérica pela angiografia por ressonância magnética (angio-RM) com contraste e comparar o valor do método, utilizando-se duas diferentes dosagens de gadolínio (doses simples e dupla). MATERIAIS E MÉTODOS: Estudo prospectivo de 36 pacientes esquistossomóticos submetidos a angio-RM. Os exames foram realizados em equipamento de RM de 1,5 T, usando-se bobina de corpo e bomba injetora para a administração endovenosa do contraste. Foram utilizadas, de maneira randomizada, dose dupla do contraste paramagnético (0,2 mmol/kg de Gd-DTPA) em 21 pacientes e dose simples (0,1 mmol/kg) em outros 15 pacientes. Os exames foram interpretados por dois observadores em consenso, que classificaram o grau de visualização de 25 segmentos vasculares estabelecidos para análise, sem conhecimento da dose de gadolínio utilizada. RESULTADOS: Os segmentos vasculares proximais e de maior calibre foram as estruturas com melhor grau de visualização na maioria da amostra em estudo. O tronco celíaco, a artéria hepática comum, a artéria esplênica, a croça e terço médio da artéria mesentérica superior, a veia porta, a veia esplênica e a veia mesentérica superior apresentaram grau 2 de visualização em mais de 70% da amostra. Quanto à comparação das diferentes dosagens, não houve diferença significante (p < 0,05) no grau de visualização das diversas estruturas analisadas entre os grupos dose simples e dose dupla, com uma exceção isolada: na avaliação da artéria hepática direita (p = 0,008), o grupo dose simples apresentou maior freqüência de visualização grau 2, com valor significante. CONCLUSÃO: O grau de visualização dos segmentos vasculares hepatomesentéricos pela angio-RM com contraste é elevado, sendo maior nos segmentos proximais e de maior calibre. A comparação entre os grupos que utilizaram dose simples e dupla de contraste demonstrou resultados semelhantes.

Realce por contraste de lesões hepáticas em pacientes com cirrose: estudo cruzado comparativo de dois agentes de contraste para RM realizado em uma única instituição. Resultados preliminares

OBJETIVO: Comparar, prospectivamente, gadopentato de dimeglumina (Gd-DTPA) e gadobenato de dimeglumina (Gd-BOPTA), ambos em dose plena, na detecção de lesões hepáticas focais, por meio de RM em pacientes com doença hepática crônica. MATERIAIS E MÉTODOS: Oito pacientes com cirrose hepática e forte suspeita de um pequeno carcinoma hepatocelular, baseada em RM anterior, foram submetidos a exames de RM contrastada, um com dose plena de Gd-DTPA e outro com dose plena de Gd-BOPTA. Os exames foram realizados com um intervalo de 72 a 108 horas. Dois radiologistas independentes realizaram avaliação às cegas das imagens, considerando número, caracterização e realce das lesões, além de preferências subjetivas. RESULTADOS: Não houve diferença estatisticamente significante entre os dois exames quanto à detecção e caracterização das lesões. Observou-se um incremento de 18% no realce da lesão dominante pelo Gd-BOPTA, em comparação com o Gd-DTPA. Na maioria dos casos, ambos os observadores cegos subjetivamente preferiram as imagens utilizando Gd-BOPTA àquelas com Gd-DTPA, com base no maior realce e melhor definição das margens das lesões. CONCLUSÃO: Em doses plenas equivalentes, Gd-BOPTA e Gd-DTPA são similares na detecção e caracterização de lesões hepáticas focais em pacientes com doença hepática crônica. Entretanto, o Gd-BOPTA foi superior em relação ao realce da lesão, assim como na preferência subjetiva dos observadores.

Development and in vitro testing of liposomal gadolinium-formulations for neutron capture therapy of glioblastoma multiforme

For the improvement of current neutron capture therapy, several liposomal formulations of neutron capture agent gadolinium were developed and tested in a glioma cell model. Formulations were analyzed regarding physicochemical and biological parameters, such as size, zeta potential, uptake into cancer cells and performance under neutron irradiation. The neutron and photon dose derived from intracellular as well as extracellular Gd was calculated via Monte Carlo simulations and set in correlation with the reduction of cell survival after irradiation. To investigate the suitability of Gd as a radiosensitizer for photon radiation, cells were also irradiated with synchrotron radiation in addition to clinically used photons generated by linear accelerator.rnIrradiation with neutrons led to significantly lower survival for Gd-liposome-treated F98 and LN229 cells, compared to irradiated control cells and cells treated with non-liposomal Gd-DTPA. Correlation between Gd-content and -dose and respective cell survival displayed proportional relationship for most of the applied formulations. Photon irradiation experiments showed the proof-of-principle for the radiosensitizer approach, although the photon spectra currently used have to be optimized for higher efficiency of the radiosensitizer. In conclusion, the newly developed Gd-liposomes show great potential for the improvement of radiation treatment options for highly malignant glioblastoma.rn

Gadolinium diethylenetriaminepentaacetate enhancement kinetics in the menisci of asymptomatic subjects: a first step towards a dedicated dGEMRIC (delayed gadolinium-enhanced MRI of cartilage)-like protocol for biochemical imaging of the menisci

It was our aim to investigate the gadolinium diethylenetriaminepentaacetate (Gd-DTPA(2-) ) enhancement kinetics in the menisci of the knee joint over a prolonged period of time. Six asymptomatic volunteers (four men and two women; mean age, 25 ± 2.4 years) were enrolled. Sagittal, T(1) -weighted, spin-echo MR sequences of the right knee joint were obtained at 3 T. Imaging was performed before (baseline), 1 h after and in half-hour intervals up to 9 h after the intravenous administration of 0.2 mmol/kg of Gd-DTPA(2-) . To measure the rates of contrast enhancement relative to the baseline, regions of interest that covered the anterior and posterior horns of the medial and lateral meniscus were defined on each of two adjacent sections, and enhancement curves were constructed. An enhancement peak between 2.5 and 4.5 h after Gd-DTPA(2-) administration was observed, and analysis of variance also revealed no significant difference (p=0.94), in terms of enhancement, within this time interval. Pair-wise, post hoc testing also revealed no significant differences between 2.5 and 3, 3 and 3.5, 3.5 and 4, and 4 and 4.5 h post Gd-DTPA(2-) application. Our preliminary data therefore suggest that the time window suitable for a dGEMRIC (delayed gadolinium-enhanced MRI of cartilage)-like T(1) mapping of the menisci is relatively short, and lies between 2.5 and 4.5 h after Gd-DTPA(2-) injection.

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

PURPOSE: The aim of this study was to investigate the effect of magnetization transfer on multislice T(1) and T(2) measurements of articular cartilage. MATERIALS AND METHODS: A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA(2-)) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T(1) and T(2) measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T(1) and T(2) values between that measured by single-slice acquisition and that measured by multislice acquisition. RESULTS: Regarding T(1) measurement, a large drop of T(1) in all slices and also a large interslice variation in T(1) were observed when multislice acquisition was used. Regarding T(2) measurement, a substantial drop of T(2) in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. CONCLUSION: This study demonstrated that the adaptation of multislice acquisition technique for T(1) measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T(2) measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account. J. Magn. Reson. Imaging 2007;26:109-117. (c) 2007 Wiley-Liss, Inc.

In vivo biochemical 7.0 Tesla magnetic resonance: preliminary results of dGEMRIC, zonal T2, and T2* mapping of articular cartilage

INTRODUCTION: Ultra-high-field whole-body systems (7.0 T) have a high potential for future human in vivo magnetic resonance imaging (MRI). In musculoskeletal MRI, biochemical imaging of articular cartilage may benefit, in particular. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping have shown potential at 3.0 T. Although dGEMRIC, allows the determination of the glycosaminoglycan content of articular cartilage, T2 mapping is a promising tool for the evaluation of water and collagen content. In addition, the evaluation of zonal variation, based on tissue anisotropy, provides an indicator of the nature of cartilage ie, hyaline or hyaline-like articular cartilage.Thus, the aim of our study was to show the feasibility of in vivo dGEMRIC, and T2 and T2* relaxation measurements, at 7.0 T MRI; and to evaluate the potential of T2 and T2* measurements in an initial patient study after matrix-associated autologous chondrocyte transplantation (MACT) in the knee. MATERIALS AND METHODS: MRI was performed on a whole-body 7.0 T MR scanner using a dedicated circular polarization knee coil. The protocol consisted of an inversion recovery sequence for dGEMRIC, a multiecho spin-echo sequence for standard T2 mapping, a gradient-echo sequence for T2* mapping and a morphologic PD SPACE sequence. Twelve healthy volunteers (mean age, 26.7 +/- 3.4 years) and 4 patients (mean age, 38.0 +/- 14.0 years) were enrolled 29.5 +/- 15.1 months after MACT. For dGEMRIC, 5 healthy volunteers (mean age, 32.4 +/- 11.2 years) were included. T1 maps were calculated using a nonlinear, 2-parameter, least squares fit analysis. Using a region-of-interest analysis, mean cartilage relaxation rate was determined as T1 (0) for precontrast measurements and T1 (Gd) for postcontrast gadopentate dimeglumine [Gd-DTPA(2-)] measurements. T2 and T2* maps were obtained using a pixelwise, monoexponential, non-negative least squares fit analysis; region-of-interest analysis was carried out for deep and superficial cartilage aspects. Statistical evaluation was performed by analyses of variance. RESULTS: Mean T1 (dGEMRIC) values for healthy volunteers showed slightly different results for femoral [T1 (0): 1259 +/- 277 ms; T1 (Gd): 683 +/- 141 ms] compared with tibial cartilage [T1 (0): 1093 +/- 281 ms; T1 (Gd): 769 +/- 150 ms]. Global mean T2 relaxation for healthy volunteers showed comparable results for femoral (T2: 56.3 +/- 15.2 ms; T2*: 19.7 +/- 6.4 ms) and patellar (T2: 54.6 +/- 13.0 ms; T2*: 19.6 +/- 5.2 ms) cartilage, but lower values for tibial cartilage (T2: 43.6 +/- 8.5 ms; T2*: 16.6 +/- 5.6 ms). All healthy cartilage sites showed a significant increase from deep to superficial cartilage (P < 0.001). Within healthy cartilage sites in MACT patients, adequate values could be found for T2 (56.6 +/- 13.2 ms) and T2* (18.6 +/- 5.3 ms), which also showed a significant stratification. Within cartilage repair tissue, global mean values showed no difference, with 55.9 +/- 4.9 ms for T2 and 16.2 +/- 6.3 ms for T2*. However, zonal assessment showed only a slight and not significant increase from deep to superficial cartilage (T2: P = 0.174; T2*: P = 0.150). CONCLUSION: In vivo T1 dGEMRIC assessment in healthy cartilage, and T2 and T2* mapping in healthy and reparative articular cartilage, seems to be possible at 7.0 T MRI. For T2 and T2*, zonal variation of articular cartilage could also be evaluated at 7.0 T. This zonal assessment of deep and superficial cartilage aspects shows promising results for the differentiation of healthy and affected articular cartilage. In future studies, optimized protocol selection, and sophisticated coil technology, together with increased signal at ultra-high-field MRI, may lead to advanced biochemical cartilage imaging.

High resolution fast T1 mapping technique for dGEMRIC

PURPOSE: To determine the feasibility of using a high resolution isotropic three-dimensional (3D) fast T1 mapping sequence for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to assess osteoarthritis in the hip. MATERIALS AND METHODS: T1 maps of the hip were acquired using both low and high resolution techniques following the administration of 0.2 mmol/kg Gd-DTPA(2-) in 35 patients. Both T1 maps were generated from two separate spoiled GRE images. The high resolution T1 map was reconstructed in the anatomically equivalent plane as the low resolution map. T1 values from the equivalent anatomic regions containing femoral and acetabular cartilages were measured on the low and high resolution maps and compared using regression analysis. RESULTS: In vivo T1 measurements showed a statistically significant correlation between the low and high resolution acquisitions at 1.5 Tesla (R(2) = 0.958, P < 0.001). These results demonstrate the feasibility of using a fast two-angle T1 mapping (F2T1) sequence with isotropic spatial resolution (0.8 x 0.8 x 0.8 mm) for quantitative assessment of biochemical status in articular cartilage of the hip. CONCLUSION: The high resolution 3D F2T1 sequence provides accurate T1 measurements in femoral and acetabular cartilages of the hip, which enables the biochemical assessment of articular cartilage in any plane through the joint. It is a powerful tool for researchers and clinicians to acquire high resolution data in a reasonable scan time (< 30 min).

High Resolution Vascular Imaging of the Rat Spine using Liposomal Blood Pool MR Agent

High resolution, vascular magnetic resonance imaging of the spine region in small animals poses several challenges. The small anatomical features, extravascular diffusion, and the low signal-to-noise ratio limit the use of conventional contrast agents. We hypothesize that a long circulating, intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would facilitate visualization of small anatomical features of the perispinal vasculature not visible with conventional contrast agent (Gd-DTPA).