<p>In contrast-enhanced magnetic resonance angiography (CE-MRA),vascular signal is produced by the acquisition of a T1-weighted magnetic resonance imaging scan while the presence of a contrast agent induces a low T1 in blood. In this thesis,CE-MRA of the aortoiliac arteries was evaluated.Different contrast agents and techniques for synchronisation of the scan with the contrast bolus passage were assessed.</p><p>In 30 patients with clinically suspected iliac artery stenoses,contrast-enhanced magnetic resonance angiography was compared with duplex ultrasound scanning and digital subtraction x-ray angiography (DSA),with intraarterial pressure measurements as reference method. No statistically significant differences in sensitivity or specificity were observed between the techniques regarding the detection of hemodynamically significant iliac stenoses. The use of multiplanar reformats and source images in the MRA examinations was of value for the differentiation between high-grade stenoses and occlusions. With DSA as reference method, MRA had significantly higher sensitivity and specificity than duplex for the detection of ≥50% stenoses.</p><p>In fourteen patients examined with iliac artery MRA, differences in contrast arrival time of up to 7 s was observed between the aorta and the common femoral artery.A dual-station timing technique adjusting for this difference was found feasible. Compared with a fluoroscopically triggered technique (n=13),which is used in clinical rotine, the dual-station technique was more reliable for the visualisation of distal vessels.</p><p>In a clinical phase II study comparing different doses of t he contrast agent gadobenate dimeglumine for the enhancement of iliac artery MRA, a significant improvement in subjective diagnostic quality compared with time-of-flight MRA was found at all doses from 0.025 mmol/kg.An increasing trend with dose was observed up to a dose level of 0.05-0.1 mmol/kg.</p><p>In a phase I clinical study on the intravascular, iron oxide contrast agent NC100150 Injection, a positive dose response was observed for abdominal vascular enhancement, with the highest contrast-to-noise ratio observed at 4.0 mg Fe/kg bw at 1.5 T and at 2.5-4 mg Fe/kg bw at 0.5 T.At 1.5 T higher R2*values were calculated for the aorta than for the IVC.</p>

In contrast-enhanced magnetic resonance angiography (CE-MRA),vascular signal is produced by the acquisition of a T1-weighted magnetic resonance imaging scan while the presence of a contrast agent induces a low T1 in blood. In this thesis,CE-MRA of the aortoiliac arteries was evaluated.Different contrast agents and techniques for synchronisation of the scan with the contrast bolus passage were assessed. In 30 patients with clinically suspected iliac artery stenoses,contrast-enhanced magnetic resonance angiography was compared with duplex ultrasound scanning and digital subtraction x-ray angiography (DSA),with intraarterial pressure measurements as reference method. No statistically significant differences in sensitivity or specificity were observed between the techniques regarding the detection of hemodynamically significant iliac stenoses. The use of multiplanar reformats and source images in the MRA examinations was of value for the differentiation between high-grade stenoses and occlusions. With DSA as reference method, MRA had significantly higher sensitivity and specificity than duplex for the detection of ≥50% stenoses. In fourteen patients examined with iliac artery MRA, differences in contrast arrival time of up to 7 s was observed between the aorta and the common femoral artery.A dual-station timing technique adjusting for this difference was found feasible. Compared with a fluoroscopically triggered technique (n=13),which is used in clinical rotine, the dual-station technique was more reliable for the visualisation of distal vessels. In a clinical phase II study comparing different doses of t he contrast agent gadobenate dimeglumine for the enhancement of iliac artery MRA, a significant improvement in subjective diagnostic quality compared with time-of-flight MRA was found at all doses from 0.025 mmol/kg.An increasing trend with dose was observed up to a dose level of 0.05-0.1 mmol/kg. In a phase I clinical study on the intravascular, iron oxide contrast agent NC100150 Injection, a positive dose response was observed for abdominal vascular enhancement, with the highest contrast-to-noise ratio observed at 4.0 mg Fe/kg bw at 1.5 T and at 2.5-4 mg Fe/kg bw at 0.5 T.At 1.5 T higher R2*values were calculated for the aorta than for the IVC.

Renal artery stenosis (RAS) is a potentially curable cause of hypertension and azotemia. Besides intra-arterial renal angiography there are several non-invasive techniques utilized to diagnose patients with suspicion of renal artery stenosis. Removing the stenosis by revascularization to restore unobstructed blood flow to the kidney is known to improve and even cure hypertension/azotemia, but is associated with a significant complication rate. To visualize renal arteries with x-ray techniques a contrast medium must be used. In a randomized, prospective study the complications of two types of contrast media (CO2 and ioxaglate) were compared. CO2 was not associated with acute nephropathy, but induced nausea and had lower attenuation differences compared to Ioxaglate. Acute nephropathy was related to the ioxaglate dose and the risk was evident even at very low doses if the patients were azotemic with creatinine clearance &lt;40 ml/min. Evaluating patients for clinically relevant renal artery stenosis can be done utilizing several non-invasive techniques. MRA was retrospectively evaluated and shown to be accurate in detecting hemodynamically significant RAS. In a prospective study of 58 patients, evaluated with four methods for renal artery stenosis, it was shown that MRA and CTA were significantly better than ultrasonography and captopril renography in detecting hemodynamically significant RAS. The standard of reference was trans-stenotic pressure gradient measurement, defining a stenosis as significant at a gradient of ≥15 mmHg. The discrepancies were mainly found in the presence of borderline stenosis. The outcome of percutaneous revascularization procedures showed a technical success rate of 95%, clinical benefit in 63% of treated patients, 30-day mortality 1.5% and major complication rate of 13%. The major complication rate for patients with baseline serum creatinine &gt;300µmol/l was 32%. Our results compare favorably with published studies and guidelines.

Vergleich der Ultraschallkontrastmittel Levovist und SonoVue verabreicht als Bolus und Infusionsapplikation bei Hunden. Klinik für Kleintiere, Veterinärmedizinische Fakultät, Universität Leipzig Eingereicht im Juni 2005 99 Seiten, 20 Abbildungen, 14 Tabellen, 217 Literaturstellen, 2 Anhänge. In der Veterinärmedizin existieren bisher kaum Veröffentlichungen über den klinischen Einsatz von Ultraschallkontrastmitteln, obwohl eine ähnliche Verbesserung von Spezifität und Sensitivität der sonographischen Diagnostik wie in der Humanmedizin denkbar ist. So war es Ziel dieser Arbeit, die Ultraschallkontrastmittel Levovist und SonoVue nach periphervenöser Bolus- und Infusionsapplikation bei Hunden zu vergleichen. Der Effekt dieser Substanzen wurde anhand der zeitabhängigen Intensitätsveränderungen des PW-Doppler-Audiosignals in der Aorta abdominalis untersucht. Die hierfür verwandten 48 Hunde stammten aus dem Patientengut der Klinik für Kleintiere der Veterinärmedizinischen Fakultät, Universität Leipzig und zeigten keine anamnestischen, klinischen oder sonographischen Hinweise auf eine Erkrankung. Sie wurden nach dem Zufallsprinzip vier Untersuchungsgruppen zu je zwölf Tieren zugeordnet Gruppe LB : Levovist Bolusapplikation - Gruppe SB : SonoVue Bolusapplikation Gruppe LI : Levovist Infusionsapplikation - Gruppe SI : SonoVue Infusionsapplikation Die Bolusgruppen erhielten 0,2 ml/kg Körpermasse Levovist in der Konzentration 300 mg/ml und 0,1 ml/kg Körpermasse SonoVue. Diese Mengen sind in den Infusionsgruppen in einer Rate von 0,1 ml/min/kg bei Levovist und 0,05 ml/min/kg bei SonoVue appliziert worden. Das Audiosignal des PW-Dopplers wurde anschließend mit einer für diesen Zweck konzipierten Analyseeinheit ausgewertet. Für jede Messreihe konnte so die Kontrastdauer über der Nulllinie, über 6, 12, 18 und 24 Dezibel, die maximale Signalverstärkung und die für die effektive Anzahl der streuenden Partikel stehende Fläche unter der Kurve über einem Niveau von 6, 12, 18 und 24 Dezibel ermittelt und eine gewisse Vergleichbarkeit der Untersuchungen ermöglicht werden. Die Mittelwerte der Parameter innerhalb der einzelnen Untersuchungsgruppen sind in Tabelle 14 angeführt. Die Dokumentation von einem Wert der Audiosignallautstärke pro Herzzyklus erlaubte die Erstellung und Beurteilung der Zeit-Verstärkungskurven für die jeweiligen Messreihen. Tab.14: Mittelwerte der bestimmten Parameter der einzelnen Untersuchungsgruppen. Levovist Bolus (Gruppe LB) Levovist Infusion (Gruppe LI) SonoVue Bolus (Gruppe SB) SonoVue Infusion (Gruppe SI) Parameter Kontrastdauer > Nulllinie [sek] 276,25 335,57 292,05 325,91 Kontrastdauer > 6 dB [sek] 166,42 239,92 223,17 260,25 Kontrastdauer > 12dB [sek] 95,67 133,17 164,17 196,92 Kontrastdauer > 18dB [sek] 20,50 -- 22,80 71,43 Maximale Signalverstärkung [dB] 19,84 16,28 19,68 18,53 AUC > 6 dB [dB*sek] 2154,17 2803,92 3160,83 3639 AUC > 12 dB [dB*sek] 1531 1819,67 2645,92 3073,42 AUC > 18 dB [dB*sek] 391,20 -- 460 1347 Bei Vergleich der Parameter zwischen den einzelnen Untersuchungsgruppen (Signifikanzniveau 1,25 %) konnte eine statistisch signifikant längere Kontrastdauer über der Nulllinie und über sechs Dezibel nach Infusionsapplikation gegenüber der Bolusapplikation von Levovist ermittelt werden. Die Bolusgabe von Levovist hingegen resultierte in signifikant höheren Maximalverstärkungen als bei kontinuierlicher Verabreichung der gleichen Substanz. Die Infusionsapplikation von SonoVue führte zu einer höheren Maximalverstärkung und größeren Fläche unter der Kurve über 12 Dezibel als bei Levovist. Bei Vergleich der beiden Bolusgruppen und bei Vergleich der beiden SonoVue Applikationsformen ergaben sich keine statistisch signifikanten Unterschiede. Um eine bessere Einschätzung der Eigenschaften des Signalverstärkers beziehungsweise der Applikationsform in wechselseitiger Unabhängigkeit zu ermöglichen, sind entsprechende Einzelgruppen zusammengefasst worden. Der statistische Vergleich der nach Signalverstärker zusammengefassten Gruppen (Signifikanzniveau 5 %) zeigte signifikant bessere Werte für SonoVue bei Verstärkungen über 12 Dezibel, der maximalen Signalverstärkung und der Fläche unter der Kurve über 6 und 12 Dezibel. Bei den nach Applikationsform zusammengefassten Gruppen führte die Infusion zu signifikant längerer Kontrastdauer über der Nulllinie und über 6 Dezibel, während bei Bolusapplikationen höhere Maximalverstärkungen resultierten. Unter den Bedingungen dieser Studie ist SonoVue dem Levovist in den genannten Verstärkungsparametern überlegen und zeigt auch in der Handhabung und Stabilitätsdauer der injektionsfertigen Suspension Vorteile. Bei zeitaufwendigen Untersuchungen kann durch eine kontinuierliche Verabreichung des Signalverstärkers der Kontrasteffekt zum Teil verlängert werden, birgt aber neben dem größeren apparativen Aufwand eine höhere Gefahr die akustischen Eigenschaften der Mikrobläschen negativ zu beeinflussen. Daher scheint sie insbesondere dann angezeigt, wenn die Bolusapplikation nicht zum Ziel führt. Mit den gewählten Dosierungen und Infusionsraten konnte bei allen Hunden eine deutliche Signalverstärkung erzielt werden. Somit erscheint ihr klinischer Einsatz in der Tiermedizin beispielsweise bei unzureichender nativer Signalintensität oder zur weiteren Charakterisierung sonomorphologisch pathologischer Strukturen möglich.

Introdução: Nefropatia induzida por contraste (NIC) está associada a piores desfechos intra-hospitalar e a longo prazo. Estudos recentes sugerem que hidratação com bicarbonato de sódio possa ser útil na sua prevenção; no entanto, essa medida de prevenção de NIC não foi, ainda, avaliada em pacientes diabéticos. Método: Subanálise de um estudo multicêntrico envolvendo 301 pacientes com creatinina sérica ≥ 1,2 mg/dl ou depuração de creatinina endógena (DCE) < 50 ml/min submetidos a cineangiocoronariografia ou angioplastia coronária, randomizados para receber hidratação com bicarbonato de sódio ou solução salina (soro fisiológico – SF) a 0,9%. Todos os procedimentos foram realizados com contraste iônico de baixa osmolaridade. Os desfechos avaliados foram incidência de NIC (definida como aumento de 0,5 mg/dl) e variação da creatinina e da DCE em 48 horas após o procedimento. Da totalidade de pacientes, 87 tinham diabetes melito e foram incluídos nesse subestudo. Resultados: Não houve diferença entre os grupos em relação a características demográficas, volume de contraste e níveis basais de creatinina e DCE. Entre os pacientes avaliados, 8 desenvolveram NIC: 4 (9,8%) pacientes no grupo bicarbonato e 4 (8,9%) no grupo SF 0,9% (p = 0,9). A variação da creatinina sérica e da DCE foi similar entre os grupos. Conclusão: Hidratação com bicarbonato de sódio não demonstrou benefício em reduzir a incidência de NIC em pacientes diabéticos submetidos a cateterismo cardíaco ou angioplastia coronária em comparação à hidratação com SF 0,9%. / Background: Contrast-induced nephropathy (CIN) is associated with worse clinical outcomes both at short and long-term follow-up. Recent evidence indicates that intravenous hydration with sodium-bicarbonate may reduce the incidence of CIN. However, this strategy has not been reported in diabetic patients. Methods: Sub-analysis of a multicenter study involving 301 patients with serum creatinine ≥ 1,2 mg/dL or creatinine clearance < 50 mL/min submitted to coronary angiography or percutaneous coronary intervention and randomized to intravenous hydration with sodium-bicarbonate or normal saline. All patients received low-osmolar contrast media. We assessed the incidence of CIN (defined as creatinine increase ≥ 0,5 mg/dL), and the average change in creatinine and creatinine clearance 48 hours after the procedure. A total of 87 diabetic patients were analyzed. Results: There was no difference between groups regarding baseline characteristics, contrast volume used, baseline creatinine levels and creatinine clearance. Eight patients presented CIN: 4 (9.8%) in the bicarbonate group and 4 (8.9%) in the saline group (p = 0.9). The average change in serum creatinine and creatinine clearance were similar between groups. Conclusion: Intravenous hydration with sodium-bicarbonate did not reduce the incidence of CIN in diabetic patients undergoing coronary angiography or percutaneous coronary intervention as compared to hydration with normal saline.

Introdução: Nefropatia induzida por contraste (NIC) está associada a piores desfechos intra-hospitalar e a longo prazo. Estudos recentes sugerem que hidratação com bicarbonato de sódio possa ser útil na sua prevenção; no entanto, essa medida de prevenção de NIC não foi, ainda, avaliada em pacientes diabéticos. Método: Subanálise de um estudo multicêntrico envolvendo 301 pacientes com creatinina sérica ≥ 1,2 mg/dl ou depuração de creatinina endógena (DCE) < 50 ml/min submetidos a cineangiocoronariografia ou angioplastia coronária, randomizados para receber hidratação com bicarbonato de sódio ou solução salina (soro fisiológico – SF) a 0,9%. Todos os procedimentos foram realizados com contraste iônico de baixa osmolaridade. Os desfechos avaliados foram incidência de NIC (definida como aumento de 0,5 mg/dl) e variação da creatinina e da DCE em 48 horas após o procedimento. Da totalidade de pacientes, 87 tinham diabetes melito e foram incluídos nesse subestudo. Resultados: Não houve diferença entre os grupos em relação a características demográficas, volume de contraste e níveis basais de creatinina e DCE. Entre os pacientes avaliados, 8 desenvolveram NIC: 4 (9,8%) pacientes no grupo bicarbonato e 4 (8,9%) no grupo SF 0,9% (p = 0,9). A variação da creatinina sérica e da DCE foi similar entre os grupos. Conclusão: Hidratação com bicarbonato de sódio não demonstrou benefício em reduzir a incidência de NIC em pacientes diabéticos submetidos a cateterismo cardíaco ou angioplastia coronária em comparação à hidratação com SF 0,9%. / Background: Contrast-induced nephropathy (CIN) is associated with worse clinical outcomes both at short and long-term follow-up. Recent evidence indicates that intravenous hydration with sodium-bicarbonate may reduce the incidence of CIN. However, this strategy has not been reported in diabetic patients. Methods: Sub-analysis of a multicenter study involving 301 patients with serum creatinine ≥ 1,2 mg/dL or creatinine clearance < 50 mL/min submitted to coronary angiography or percutaneous coronary intervention and randomized to intravenous hydration with sodium-bicarbonate or normal saline. All patients received low-osmolar contrast media. We assessed the incidence of CIN (defined as creatinine increase ≥ 0,5 mg/dL), and the average change in creatinine and creatinine clearance 48 hours after the procedure. A total of 87 diabetic patients were analyzed. Results: There was no difference between groups regarding baseline characteristics, contrast volume used, baseline creatinine levels and creatinine clearance. Eight patients presented CIN: 4 (9.8%) in the bicarbonate group and 4 (8.9%) in the saline group (p = 0.9). The average change in serum creatinine and creatinine clearance were similar between groups. Conclusion: Intravenous hydration with sodium-bicarbonate did not reduce the incidence of CIN in diabetic patients undergoing coronary angiography or percutaneous coronary intervention as compared to hydration with normal saline.

Introdução: Nefropatia induzida por contraste (NIC) está associada a piores desfechos intra-hospitalar e a longo prazo. Estudos recentes sugerem que hidratação com bicarbonato de sódio possa ser útil na sua prevenção; no entanto, essa medida de prevenção de NIC não foi, ainda, avaliada em pacientes diabéticos. Método: Subanálise de um estudo multicêntrico envolvendo 301 pacientes com creatinina sérica ≥ 1,2 mg/dl ou depuração de creatinina endógena (DCE) < 50 ml/min submetidos a cineangiocoronariografia ou angioplastia coronária, randomizados para receber hidratação com bicarbonato de sódio ou solução salina (soro fisiológico – SF) a 0,9%. Todos os procedimentos foram realizados com contraste iônico de baixa osmolaridade. Os desfechos avaliados foram incidência de NIC (definida como aumento de 0,5 mg/dl) e variação da creatinina e da DCE em 48 horas após o procedimento. Da totalidade de pacientes, 87 tinham diabetes melito e foram incluídos nesse subestudo. Resultados: Não houve diferença entre os grupos em relação a características demográficas, volume de contraste e níveis basais de creatinina e DCE. Entre os pacientes avaliados, 8 desenvolveram NIC: 4 (9,8%) pacientes no grupo bicarbonato e 4 (8,9%) no grupo SF 0,9% (p = 0,9). A variação da creatinina sérica e da DCE foi similar entre os grupos. Conclusão: Hidratação com bicarbonato de sódio não demonstrou benefício em reduzir a incidência de NIC em pacientes diabéticos submetidos a cateterismo cardíaco ou angioplastia coronária em comparação à hidratação com SF 0,9%. / Background: Contrast-induced nephropathy (CIN) is associated with worse clinical outcomes both at short and long-term follow-up. Recent evidence indicates that intravenous hydration with sodium-bicarbonate may reduce the incidence of CIN. However, this strategy has not been reported in diabetic patients. Methods: Sub-analysis of a multicenter study involving 301 patients with serum creatinine ≥ 1,2 mg/dL or creatinine clearance < 50 mL/min submitted to coronary angiography or percutaneous coronary intervention and randomized to intravenous hydration with sodium-bicarbonate or normal saline. All patients received low-osmolar contrast media. We assessed the incidence of CIN (defined as creatinine increase ≥ 0,5 mg/dL), and the average change in creatinine and creatinine clearance 48 hours after the procedure. A total of 87 diabetic patients were analyzed. Results: There was no difference between groups regarding baseline characteristics, contrast volume used, baseline creatinine levels and creatinine clearance. Eight patients presented CIN: 4 (9.8%) in the bicarbonate group and 4 (8.9%) in the saline group (p = 0.9). The average change in serum creatinine and creatinine clearance were similar between groups. Conclusion: Intravenous hydration with sodium-bicarbonate did not reduce the incidence of CIN in diabetic patients undergoing coronary angiography or percutaneous coronary intervention as compared to hydration with normal saline.

No description available.

INTRODUÇÃO: O Gadolínio (Gd) é um raro metal da classe dos lantanídios usado como meio de contraste devido as suas propriedades paramagnéticas. Após sua descoberta, foi considerado um contraste pouco nefrotóxico em pacientes com doença renal crônica (DRC). Atualmente, existem evidências de que o Gd pode apresentar nefrotoxicidade semelhante aos contrastes iodados. A administração de Gadolínio em ratos com DRC pode levar a piora da função renal aferida por clearance de inulina e mobilização do ferro corporal gerando stress oxidativo. OBJETIVOS: O objetivo do estudo foi avaliar o efeito do Gd na função renal, nos parâmetros de cinética do ferro em ratos com DRC e o possível efeito protetor do anti-oxidante N-Acetilcisteína (NAC). MATERIAIS E MÉTODOS: Ratos Wistar machos foram submetidos à nefrectomia 5/6 (Nx) para induzir DRC. Gadoterate Meglumine, um contraste à base de Gadolínio iônico e macrocíclico foi administrado via intravenosa na dose de 1,5mmol/kg de peso de rato 21 dias após a nefrectomia. Para avaliar o efeito do Gd sobre a função renal, estudos de clearance de inulina foram realizados em 4 grupos de ratos 48 hs após a aplicação do Gd: grupo controle 1- Nx (n=7); 2- Nx+NAC (n=6); 3- Nx+Gd (n=8); 4- Nx+Gd+NAC (n=5). O NAC foi administrado no grupo 4 diluído em água 48 hs antes e 48 hs depois da administração do Gd na dose de 4800mg/l. O grupo 2 recebeu NAC durante o mesmo período de tempo do grupo 4. O Gd também foi administrado em ratos com função renal normal, grupo Normal (n=8) na mesma dose dos grupos nefrectomizados com avaliação da função renal e proteinúria. Além da taxa de filtração glomerular (TFG), foram avaliados: proteinúria de 24hs (ptn), parâmetros de gaiola metabólica, pressão arterial (PA), paramêtros de cinética do ferro representados pelo ferro sérico (Fe), capacidade total de ligação do ferro (CTLF), saturação de transferrina, ferritina sérica e stress oxidativo por meio da dosagem de espécies reativas ao ácido tiobarbitúrico (TBARS). Os dados foram submetidos à análise de variância ANOVA utilizando o programa Graph Prism com nível de significância p<0,05 e erro padrão. RESULTADOS: A aplicação de Gd em ratos nefrectomizados resultou em queda na TFG no grupo 3 em relação ao grupo controle 1 (p<0,01). Houve uma tendência de aumento da ptn no grupo 3 em relação aos demais grupos. O grupo 4 que recebeu tratamento com NAC apresentou TFG e ptn semelhante ao grupo 1 e TFG estatisticamente maior que o grupo 3 (p<0,05). Com relação ao grupo de ratos normais não houve alteração da TFG nem aumento de ptn após a aplicação do Gd em relação à ratos não nefrectomizados que não receberam contraste. Com relação aos parâmetros da cinética do ferro, o grupo 3 apresentou elevação da ferritina e da saturação da transferrina comparados ao grupo 1 (p<0,05) e (p<0,01) respectivamente. Houve diminuição da capacidade total de ligação do ferro (CTLF) no grupo 3 comparado ao grupo 1(p<0,01). O uso profilático do NAC no grupo 4 reverteu todas as alterações descritas anteriormente no grupo 3 com significância estatística (p<0,05), (p<0,01) e (p<0,01) respectivamente. Com relação ao stress oxidativo, o grupo 3 apresentou níveis de TBARS significativamente maiores que o grupo 1 (p<0,05). O grupo 4 apresentou níveis de TBARS semelhantes ao grupo 1 e menores que o grupo 3 (p<0,05). O grupo 2 que recebeu apenas NAC por curto período de tempo apresentou TFG, Ptn e parâmetros de cinética de ferro semelhantes aos grupos 1 e 4. Com relação aos dados de gaiola metabólica e pressão arterial não houve diferença estatística entre os grupos 1,2,3 e 4. CONCLUSÕES: Os resultados mostram que a administração de Gd em ratos nefrectomizados resulta em dimuição da TFG, aumento da proteinúria associado a aumento da ferritina sérica, saturação de transferrina e diminuição da CTLF. Em ratos normais o Gd não mostrou ser nefrotóxico e o uso do NAC isoladamente no grupo 2 por curto período de tempo não demonstrou nenhum efeito, pois todos os parâmetros avaliados foram semelhantes ao grupo controle. Indução de stress oxidativo foi representado pelo aumento do TBARS nos ratos que receberam o Gd. O uso de NAC reverteu todas as alterações provocadas pelo Gd. Concluímos que o NAC pode ser usado como profilaxia da toxicidade associada ao Gd. / INTRODUCTION: Gadolinium (Gd) is a rare class of lanthanide metal used as a contrast agent due to its paramagnetic properties. After its discovery, was considered a bit of contrast nephrotoxicity in patients with chronic kidney disease (CKD). Currently, there is evidence that Gd may present similar to iodine contrast media nephrotoxicity. The administration of Gadolinium in rats with CKD can lead to worsening renal function measured by inulin clearance and mobilization of iron body causing oxidative stress. OBJECTIVES: The aim of this study was to evaluate the effect of Gd on renal function, iron parameters and oxidative stress in rats with CKD and a possible effect of antioxidant N-Acetylcisteine (NAC). MATERIALS AND METHODS: Male Wistar rats underwent nephrectomy 5/6 (Nx) to induce CKD. Gadoterate meglumine, a Gadolinium based contrast ionic and macrocyclic was administrated intravenously at a dose of 1.5 mmol / kg BW of rats 21 days after nephrectomy. To evaluate the effect of Gd on renal function, inulin clearance studies were performed in 3 groups of animals 48 hours (hs) after application of Gd: a control group 1 - Nx (n =7), 2- Nx+NAC (n = 6); 3- Nx+Gd (n=8) e 4- Nx+Gd+NAC (n=5). The NAC was administrated in group 4, diluted with water 48 hs before and 48 hs after administration of gadolinium at a dose of 4800mg / l. Group 2 received NAC four days before clearance study. Gd was also administrated in rats with normal renal function, group normal (n = 8) at the same dose of nephrectomized rats with assessment of renal function and proteinuria. In addition to the glomerular filtration rate (GFR) were evaluated: 24 hours proteinuria (ptn), cage metabolic parameters, blood pressure (BP), serum iron (Fe), total capacity of iron binding (TIBC), transferrin saturation, serum ferritin and oxidative stress through measurement of thiobarbituric acid reactive species (TBARS). Data were submitted to ANOVA using the program Prism Graph with a significance level p <0.05 and standard error. RESULTS: Gd administration to group 3 results in a decrease of GFR compared with group 1 (p<0,01). There was a trend of increase ptn in group 3 compared to other groups. Normal rats treated with the same dose of Gd presented similar GFR and proteinuria when compared with normal controls. In group 3, there was a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS elevation compared with group 1 (p<0,01), (p<0,05), (p<0,01) and (p<0,05) repectively. The treatment with NAC in group 4 reversed the decreased in GFR and proteinuria compared with group 3 (p<0,05) for both variables. Treatment with NAC in group 4 also reversed all alterations in iron parameters and oxidative stress described earlier with statistical significance (p<0,01), (p<0,05), (p<0,01) and (p<0,05) respectively. Group 2 received NAC for a short period of time had GFR, Ptn and kinetic parameters of iron similar to groups 1 and 4. With respect to metabolic cage data and blood pressure showed no statistical difference between groups 1,2,3 and 4.CONCLUSIONS: These results show that Gd administration to nephrectomized rats results in a decrease of GFR and increased proteinuria associated with increased serum ferritin and transferrin saturation with decreased TIBC. In normal rats, Gd was not nephrotoxic. These effects were not due to a possible effect of NAC on Nx, since all parameters measured in group 2 were not different from the group 1. There was induction of oxidative stress represented by the increase in TBARS in rats receiving gadolinium. The use of NAC reversed all these changes caused by Gd. We conclude that the NAC can be used as prophylaxis of toxicity associated with Gd.

Magnetic resonance imaging (MRI) has increasingly become the preferred imaging modality in modern day research to study disease. MRI presents an imaging technique that is practically non-invasive and without any ionizing radiation. This dissertation presents the use of contrast agents in MRI studies to differentiate compartments, to study dose dependence of relaxation times, and to characterize tumors using signal amplifying enzymes in the brain. Differentiating compartments in the brain can be useful in diffusion studies to detect stroke at an early stage. Diffusion-weighted NMR techniques have established that the apparent diffusion coefficient (ADC) of cerebral tissue water decreases during ischemia. However, it is unclear whether the ADC change occurs due to changes in the intracellular (IC) space, extracellular (EC) space, or both. To better understand the mechanism of water ADC changes in response to ischemic injury, making IC and EC compartment specific measurements of water diffusion is essential. The first study was done where manganese (Mn2+) was used as an IC contrast agent. Mn2+ uptake by cells causes shortening of the T1 relaxation time of IC water. The relative difference in T1 relaxation times between the IC and EC compartments can be used to discriminate between the MR signals arising from water in the respective compartments. Mn2+ is also widely used in manganese-enhanced MRI (MEMRI) studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, the goal is to use a dose of Mn2+ that will maximize the contrast while minimizing its toxic effects. The goal of dose study was to investigate the MRI dose response of Mn2+ in rat brain following SC administration of Mn2+. The dose dependence and temporal dynamics of Mn2+ after SC injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. Contrast agents, in addition to their use in compartmental differentiation and dose studies, can be used for imaging tumors. The last study in this dissertation focuses on imaging EGF receptors in brain tumors. We tested a novel pretargeting imaging approach that includes the administration of humanized monoclonal antibody (anti-EGFR mAb, EMD72000) linked to enzymes with complementing activities that use a low-molecular weight paramagnetic molecule (diTyr-GdDTPA) as a reducing substrate administered following the mAb conjugates. We analyzed the differential MR tumor signal decay in vivo using orthotopic models of human glioma. The patterns of MR signal change following substrate administration revealed differences in elimination patterns that allowed distinguishing between non-specific and specific modes of MR signal decay.