Etude de la cyclostationnarité du signal Doppler sanguin pour la détection de micro-emboles : étude préliminaire

Ce papier traite de la détection ultrasonore de micro-emboles par un système Doppler transcrânien. L'originalité de ce travail réside dans le fait que nous utilisons les propriétés cyclostationnaires du signal Doppler ultrasonore sanguin pour détecter des micro-emboles, depuis lors, masqués dans les phases de systoles-diastoles du cycle cardiaque. Dans cette étude nous évaluons théoriquement, à partir d'un modèle réaliste du signal Doppler sanguin, le spectre de corrélation. Nous proposons un paramètre informatif permettant la détection de micro-emboles et nous quantifions les performances du détecteur associé pour le comparer à un détecteur standard

Ultrasound-Mediated Gene Delivery with Cationic Versus Neutral Microbubbles: Effect of DNA and Microbubble Dose on In Vivo Transfection Efficiency

<p><b>Objective</b>: To assess the effect of varying microbubble (MB) and DNA doses on the overall and comparative efficiencies of ultrasound (US)-mediated gene delivery (UMGD) to murine hindlimb skeletal muscle using cationic versus neutral MBs.</p><p><b>Materials and Methods:</b> Cationic and control neutral MBs were characterized for size, charge, plasmid DNA binding, and ability to protect DNA against endonuclease degradation. UMGD of a codon optimized firefly luciferase (Fluc) reporter plasmid to endothelial cells (1 MHz, 1 W/cm&#178;, 20% duty cycle, 1 min) was performed in cell culture using cationic, neutral, or no MBs. <i>In vivo</i> UMGD to mouse hindlimb muscle was performed by insonation (1 MHz, 2 W/cm&#178;, 50% duty cycle, 5 min) after intravenous administration of Fluc combined with cationic, neutral, or no MBs. Gene delivery efficiency was assessed by serial <i>in vivo</i> bioluminescence imaging. Efficiency of <i>in vivo </i>UMGD with cationic versus neutral MBs was systematically evaluated by varying plasmid DNA dose (10, 17.5, 25, 37.5, and 50 &#181;g) while maintaining a constant MB dose of 1x10⁸ MBs and by changing MB dose (1x10⁷, 5x10⁷, 1x10⁸, or 5x10⁸ MBs) while keeping a constant DNA dose of 50 &#181;g.</p><p><b>Results: </b>Cationic and size-matched control neutral MBs differed significantly in zeta potential with cationic MBs being able to bind plasmid DNA (binding capacity of 0.03 pg/MB) and partially protect DNA from nuclease degradation while neutral MBs could not. Cationic MBs enhanced UMGD compared to neutral MBs as well as no MB and no US controls both in cell culture (<i>P</i> &#60; 0.001) and <i>in vivo</i> (<i>P &#60; </i>0.05). Regardless of MB type, <i>in vivo</i> UMGD efficiency increased dose-dependently with DNA dose and showed overall maximum transfection with 50 &#181;g DNA. However, there was an inverse correlation (&#961; = -0.90; <i>P</i> = 0.02) between DNA dose and the degree of enhanced UMGD efficiency observed with using cationic MBs instead of neutral MBs. The delivery efficiency advantage associated with cationic MBs was most prominent at the lowest investigated DNA dose (7.5-fold increase with cationic versus neutral MBs at a DNA dose of 10 &#181;g; <i>P</i> = 0.02) compared to only a 1.4-fold increase at a DNA dose of 50 &#181;g (<i>P</i> &#60; 0.01). With increasing MB dose, overall <i>in vivo </i>UMGD efficiency increased dose-dependently with a maximum reached at a dose of 1x10⁸ MBs with no further significant increase with 5x10⁸ MBs (<i>P</i> = 0.97). However, compared to neutral MBs, cationic MBs enhanced UMGD efficiency the most at low MB doses. Relative enhancement of UMGD efficiency using cationic over neutral MBs decreased from a factor of 27 for 1x10⁷ MBs (<i>P</i> = 0.02) to a factor of 1.4 for 1x10⁸ MBs (<i>P</i> &#60; 0.01) and no significant difference for 5x10⁸ MBs.</p><p><b>Conclusions:</b> Cationic MBs enhance UMGD to mouse skeletal muscle relative to neutral MBs but this is dependent on MB and DNA dose. The enhancement effect of cationic MBs on UMGD efficiency is more evident when lower doses of MBs or DNA are used, whereas the advantage of cationic MBs over neutral MBs is substantially reduced in the presence of excess MBs or DNA.</p

Dynamic contrast-enhanced ultrasound parametric imaging for the detection of prostate cancer

\u3cp\u3eOBJECTIVE: To investigate the value of dynamic contrast-enhanced (DCE)-ultrasonography (US) and software-generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores.\u3c/p\u3e\u3cp\u3eMATERIALS AND METHODS: For 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE-US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE-US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false-negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value (NPV) and positive predictive value (PPV) on a per-prostate level.\u3c/p\u3e\u3cp\u3eRESULTS: Based on DCE-US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false-negatives (5.6%). In the per-prostate clinical analysis, DCE-US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE-US alone and 91, 56, 57 and 90%, respectively, with parametric maps.\u3c/p\u3e\u3cp\u3eCONCLUSION: The interpretation of DCE-US with parametric maps allows good prediction of biopsy outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis.\u3c/p\u3