Ultrasound methods in conjunction with microbubbles have been used for brain drug delivery, treatment of stroke, and imaging of cerebral blood flow. Despite advances in these areas, questions remain regarding the range of ultrasound parameters that disrupt the blood-brain barrier (BBB). In this study, several conditions were investigated to either enhance or reduce the likelihood of BBB disruption. Pulsed focused ultrasound (frequency: 1.5 MHz, pressure: 0.46 MPa, pulse repetition frequency (PRF): 0.1 to 25 Hz, pulse length (PL): 0.03 to 30 milliseconds) was noninvasively and locally administered to a predetermined region in the left hemisphere in the presence of circulating preformed microbubbles (Definity, Lantheus Medical Imaging, N. Billerica, MA, USA; 0.01, 0.05, 0.25 μL/g). Trans-BBB delivery of 3-kDa dextran was observed at PRFs as low as 1 Hz, whereas consistent delivery was observed at 5 Hz and above. Delivery was demonstrated at a PL as low as 33 microseconds. Although the delivered dextran concentration increased with the PL, this also increased the heterogeneity of the resulting distribution. In conclusion, key parameters that disrupt the BBB were identified out of a wide range of conditions. Reducing the total number of emitted acoustic cycles by shortening the PL, or decreasing the PRF, was also found to facilitate a more spatially uniform distribution of delivered dextran.

Non‐immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty‐one studies reporting 445 NIHF cases had a 37% (95% CI: 32%–41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non‐consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X‐linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity.

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nonobese women (Table) and occurred in 50% of patients with CL <20mm in both groups. CL performed equally well as a predictor for sPTB <34 weeks in obese and nonobese women (Figure). The sensitivity and specificity of CL <20mm for sPTB <34 weeks did not differ between groups. CONCLUSION: Obese women are at higher risk for sPTB prior to 34, 28, and 24 weeks. This risk appears to be independent of midtrimester CL, suggesting that the etiology of PTB in obese patients may not be cervical insufficiency.