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Late infantile neuronal ceroid lipofuscinosis (LINCL) is a lysosomal storage disorder caused by mutations in the CLN2 gene and a deficiency of tripeptidyl peptidase I (TPP-I). Prior studies with adeno-associated virus (AAV) serotype 2 or 5 mediated transfer of the CLN2 complementary DNA to the central nervous system (CNS) of CLN2(-/-) mice cleared CNS storage granules, but provided no improvement in the phenotype or survival of this model of LINCL. In this study, AAV serotypes (AAV2, AAV5, AAV8, and AAVrh.10) were compared for the delivery of the same CLN2 expression cassette. AAVrh.10, derived from rhesus macaque, provided the highest TPP-I level and maximum spread beyond the site of injection. The AAVrh.10-based vector functioned equally well in naive rats and in rats previously immunized against human serotypes of AAV. When administered to the CNS of CLN2(-/-) mice, the AAVrh.10CLN2 vector provided widespread TPP-I activity comparable to that in the wild-type mice. Importantly, the AAVrh.10CLN2-treated CLN2(-/-) mice had significant reduction in CNS storage granules and demonstrated improvement in gait, nest-making abilities, seizures, balance beam function, and grip strength, as well as having a survival advantage.

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Artifacts are frequently encountered at clinical US, and while some are unwanted, others may reveal valuable information related to the structure and composition of the underlying tissue. They are essential in making ultrasonography (US) a clinically useful imaging modality but also can lead to errors in image interpretation and can obscure diagnoses. Many of these artifacts can be understood as deviations from the assumptions made in generating the image. Therefore, understanding the physical basis of US image formation is critical to understanding US artifacts and thus proper image interpretation. This review is limited to gray-scale artifacts and is organized into discussions of beam- and resolution-related, location-related (ie, path and speed), and attenuation-related artifacts. Specifically, artifacts discussed include those related to physical mechanisms of spatial resolution, speckle, secondary lobes, reflection and reverberation, refraction, speed of sound, and attenuation. The underlying physical mechanisms and appearances are discussed, followed by real-world strategies to mitigate or accentuate these artifacts, depending on the clinical application. Relatively new US modes, such as spatial compounding, tissue harmonic imaging, and speckle reduction imaging, are now often standard in many imaging protocols; the effects of these modes on US artifacts are discussed. The ability of a radiologist to understand the fundamental physics of ultrasound, recognize common US artifacts, and provide recommendations for altering the imaging technique is essential for proper image interpretation, troubleshooting, and utilization of the full potential of this modality. RSNA, 2017.

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