First-Trimester Evaluation of Cleft Lip and Palate by A Novel Two-Dimensional Sonographic Technique: A Prospective Study.

OBJECTIVES: The study aims to evaluate the value of the mandible transection head-side shifting method (MTHSM) by 2-dimensional sonography in the screening of fetal cleft lip and palate (CLP) during the nuchal translucency scans. METHODS: A total of 7,336 fetuses enrolled for first-trimester aneuploidy screening were included in this prospective study. A sequential scanning approach from the mandible transection toward the head was used for the assessment of the palate in the midsagittal, axial, and coronal sections. Observe the continuity of the palatal line, upper alveolar ridge, and primary palate. All fetuses were followed by second-trimester scans and postnatal evaluation. RESULTS: A total of 18 cases of CLP were identified in the first trimester based on this method. Out of 18, 9 (50.0%) were unilateral CLP, 4 (22.2%) were bilateral CLP, and 5 (27.8%) were median CLP. There were no false-positive results found. Three were missed but confirmed in the second-trimester anomaly scan, including 2 cases of isolated cleft palate (CP) and one of isolated cleft lip (CL). Firsttrimester diagnosis of CLP using MTHSM had a sensitivity of 85.7%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 99.9%. CONCLUSION: The mandible transection head-side shifting method is feasible in assessing CLP at the time of routine first-trimester sonographic screening.

Label-free CEST MRI Detection of Citicoline-Liposome Drug Delivery in Ischemic Stroke.

Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively. To facilitate the targeted drug delivery of citicoline to ischemic regions, we prepared liposomes encapsulating citicoline (CDPC-lipo) and characterized the particle properties and CEST MRI properties. The in vivo CEST MRI detection of liposomal citicoline was then examined in a rat brain model of unilateral transient ischemia induced by a two-hour middle cerebral artery occlusion. The results showed that the delivery of CPDC-lipo to the brain ischemic areas could be monitored and quantified by CEST MRI. When administered intra-arterially, CDPC-lipo clearly demonstrated a detectable CEST MRI contrast at 2 ppm. CEST MRI revealed that liposomes preferentially accumulated in the areas of ischemia with a disrupted blood-brain-barrier. We furthermore used CEST MRI to detect the improvement in drug delivery using CDPC-lipo targeted against vascular cell adhesion molecule (VCAM)-1 in the same animal model. The MRI findings were validated using fluorescence microscopy. Hence, liposomal citicoline represents a prototype theranostic system, where the therapeutic agent can be detected directly by CEST MRI in a label-free fashion.