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Introduction: The optimal protocol for diagnostic workup of craniosynostosis and the role of specific imaging modalities remain controversial. Skull X-rays and 3-dimensional head CTs are options when physical exam is equivocal but involve ionizing radiation. Ultrasound has emerged as an alternative modality for visualization of cranial sutures, but its use is not widespread. Methods: The authors performed a systematic review of the literature on the use of ultrasound for the diagnosis of craniosynostosis. Results: A total of 12 studies involving 1062 patients were included. Overall, 300 patients (28.2%) were diagnosed with craniosynostosis. A total of 369 (34.7%) patients had their diagnosis (craniosynostosis vs. patent sutures) confirmed with another imaging modality in addition to ultrasound. Among studies, the specificity of ultrasound ranged from 86 to 100%, and the sensitivity from 71 to 100%. Conclusions: Ultrasonography of cranial sutures is a feasible and accurate tool for the diagnosis of single-suture craniosynostosis when physical exam findings are insufficient. Although technical aspects of ultrasonography and its interpretation have an associated learning curve, ultrasound can achieve high sensitivity and specificity among patients with suspected craniosynostosis. [ABSTRACT FROM AUTHOR]

Generating spatially controlled, non-destructive changes in the interstitial spaces of the brain has a host of potential clinical applications, including enhancing the delivery of therapeutics, modulating biological features within the tissue microenvironment, altering fluid and pressure dynamics, and increasing the clearance of toxins, such as plaques found in Alzheimer’s disease. Recently we demonstrated that ultrasound can non-destructively enlarge the interstitial spaces of the brain ex vivo. The goal of the current study was to determine whether these effects could be reproduced in the living brain using non-invasive, transcranial MRI-guided focused ultrasound (MRgFUS). The left striatum of healthy rats was treated using MRgFUS. Computer simulations facilitated treatment planning, and targeting was validated using MRI acoustic radiation force impulse imaging. Following MRgFUS treatments, Evans blue dye or nanoparticle probes were infused to assess changes in the interstitial space. In MRgFUS-treated animals, enhanced dispersion was observed compared to controls for 70 nm (12.8 ± 0.9 mm3 vs. 10.6 ± 1.0 mm3, p = 0.01), 200 nm (10.9 ± 1.4 mm3 vs. 7.4 ± 0.7 mm3, p = 0.01) and 700 nm (7.5 ± 0.4 mm3 vs. 5.4 ± 1.2 mm3, p = 0.02) nanoparticles, indicating enlargement of the interstitial spaces. No evidence of significant histological or electrophysiological injury was identified. These findings suggest that transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses. This has the potential to expand the therapeutic uses of MRgFUS. [ABSTRACT FROM AUTHOR]

Background: The clinical applications of transcranial focused ultrasound continue to expand and include ablation as well as drug delivery applications in the brain, where treatments are typically guided by MRI. Although MRI-guided focused ultrasound systems are also preferred for many preclinical investigations, they are expensive to purchase and operate, and require the presence of a nearby imaging center. For many basic mechanistic studies, however, MRI is not required. The purpose of this study was to design, construct, characterize and evaluate a portable, custom, laser-guided focused ultrasound system for noninvasive, transcranial treatments in small rodents.Methods: The system comprised an off-the-shelf focused ultrasound transducer and amplifier, with a custom cone fabricated for direct coupling of the transducer to the head region. A laser-guidance apparatus was constructed with a 3D stage for accurate positioning to 1 mm. Pressure field simulations were performed to demonstrate the effects of the coupling cone and the sealing membrane, as well as for determining the location of the focus and acoustic transmission across rat skulls over a range of sizes. Hydrophone measurements and exposures in hydrogels were used to assess the accuracy of the simulations. In vivo treatments were performed in rodents for opening the blood-brain barrier and to assess the performance and accuracy of the system. The effects of varying the acoustic pressure, microbubble dose and animal size were evaluated in terms of efficacy and safety of the treatments.Results: The simulation results were validated by the hydrophone measurements and exposures in the hydrogels. The in vivo treatments demonstrated the ability of the system to open the blood-brain barrier. A higher acoustic pressure was required in larger-sized animals, as predicted by the simulations and transmission measurements. In a particular sized animal, the degree of blood-brain barrier opening, and the safety of the treatments were directly associated with the microbubble dose.Conclusion: The focused ultrasound system that was developed was found to be a cost-effective alternative to MRI-guided systems as an investigational device that is capable of accurately providing noninvasive, transcranial treatments in rodents. [ABSTRACT FROM AUTHOR]