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GSD1a, the most prevalent type among the glycogen storage disease families, is caused by an inherited glycogen-6-phosphatase gene defectresulting in an impaired glycogen to glucose conversion pathway. Strict dietary management continues to be the only treatment for GSD1apatients. Recently, the advent of targeted ultrasound mediated delivery (USMD) of pDNA to the liver of GSD1a patients in conjunction with microbubbles may provide an alternative treatment option. As thesuccess of USMD of agents is largely dependent on the accessibilityof the targeted tissue by the ultrasound beam, there is a need to quantitatively determine this parameter. For this reason, this study focused on determining the acoustically accessible liver volume in GSD1a patients using transducer models of various apertures and focallengths using suitable CT and MRI datasets, following a geometry-driven approach. Results show that GSD1a patients generally have a larger acoustic accessible liver volume compared to a normal patient group for a given transducer geometry, and that transducers with a smaller aperture and longer focal length would be better suited for these applications. This data is a necessary initial design criterion for ultrasound mediated delivery systems for liver applications in general, and USMD pDNA delivery systems to the liver for GSD1a patientsin particular.

Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatmentsis largely dependent on the accessibility of the targeted tissue bythe focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIapatients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and 2D rotations with the intent of targetingand exposing the entire liver to ultrasound. Results indicate thatacoustically accessible liver volumes can be as large as 60% of theentire liver volume for GSDIa patients and on average 3 times largercompared to a normal group due to GSDIa patients’ increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models will be presented, together with implications forUSMD treatments of GSDIa patients and transducer designs for USMD applications.