RESUMEN
AIM: The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [(99m)Tc]-conjugated AP39 ([(99m)Tc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice. METHODS: Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [(99m)Tc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry. RESULTS: In vivo [(99m)Tc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236 ± 40.646 cpm/cm³) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468 ± 4.976 cpm/cm³) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P<0.01). CONCLUSION: [(99m)Tc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.
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Anticuerpos Monoclonales/farmacocinética , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/metabolismo , Fibronectinas/metabolismo , Aumento de la Imagen/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Animales , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/metabolismo , Apolipoproteínas E/genética , Biomarcadores/sangre , Ratones , Ratones Noqueados , Imagen Molecular/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tecnecio/farmacocinéticaRESUMEN
PURPOSE: To prospectively evaluate the feasibility and diagnostic accuracy of high spatial resolution myocardial perfusion imaging during high dose dobutamine/atropine stress magnetic resonance (DSMR) for the detection of coronary artery disease (CAD). METHODS AND RESULTS: DSMR-wall motion was combined with perfusion imaging (DSMR-perfusion) in 78 patients prior to clinically indicated invasive coronary angiography. For DSMR-perfusion an in-plane spatial resolution of 1.5 × 1.5mm(2) was attained by using 8 × k-space and time sensitivity encoding (k-t SENSE). Image quality and extent of artifacts during perfusion imaging were evaluated. Wall motion and perfusion data were interpreted sequentially. Significant CAD (stenosis ≥ 70%) was present in 52 patients and involved 86 coronary territories. One patient did not reach target heart rate despite maximum infusion of dobutamine/atropine. Two studies (3%) were non-diagnostic due k-t SENSE related artifacts resulting from insufficient breathhold capability. Overall image quality was good. Dark-rim artifacts were limited to the endocardial border at a mean width of 1.8mm. The addition of DSMR-perfusion to DSMR-wall motion data improved sensitivity for the detection of CAD (92% vs. 81%, P=0.03) and accurate determination of disease extent (85% vs. 66% of territories, P<0.001). There were no significant differences between DSMR-perfusion and DSRM-wall motion regarding overall specificity (83% vs. 87%, P=1) and accuracy (89% vs. 83%, P=0.13). CONCLUSION: High spatial resolution DSMR-perfusion imaging at maximum stress level was feasible, improved sensitivity over DSMR-wall motion for the detection of CAD and allowed an accurate determination of disease extent. Specificity of DSMR-perfusion with k-t SENSE improved compared to prior studies using lower spatial resolution.
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Técnicas de Imagen Cardíaca/métodos , Enfermedad de la Arteria Coronaria/patología , Prueba de Esfuerzo/métodos , Imagen por Resonancia Magnética/métodos , Isquemia Miocárdica/patología , Anciano , Artefactos , Atropina/administración & dosificación , Cardiotónicos/administración & dosificación , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Dobutamina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Isquemia Miocárdica/diagnóstico por imagen , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Dobutamine stress magnetic resonance (DSMR) imaging represents an excellent imaging approach for the detection of coronary artery disease (CAD). However, most studies have predominantly reported the utility of DSMR in men. OBJECTIVE: To evaluate the diagnostic value of DSMR in men and women. METHODS AND RESULTS: High-dose dobutamine/atropine stress magnetic resonance imaging was performed and new or worsening wall motion abnormalities evaluated in 745 consecutive patients (204 women, 541 men). Invasive coronary angiography was performed within 30 days and served as the reference standard (> or =70% stenosis). DSMR was technically successful and had diagnostic image quality in all patients except one woman and three men (p=NS). In the absence of ischaemia, target heart rate was not reached in 9.3% of women and 8.5% of men (P=NS) despite maximum pharmacological infusion (1% and 2.2%, respectively, p=NS) or owing to limiting side effects (8.3% and 6.3%, respectively, p=NS). Diagnostic values (sensitivity/specificity/accuracy) for the detection of significant coronary stenoses were similar for men (86%/83%/85%) and women (85%/86%/85%). There was no gender-based difference in regional diagnostic accuracy of DSMR for all three coronary vascular territories in patients with single-vessel CAD (81% vs 81%, p=NS, respectively). CONCLUSION: The diagnostic capability of DSMR for the detection of haemodynamically relevant, obstructive CAD is independent of gender.