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OBJECTIVES For improved thrombolysis therapy based on ultrasound irradiation, researchers and practitioners would strongly benefit from an easy and efficient in vitro assay system of thrombolysis activity involving irradiated ultrasound. For the present study, we designed a new in vitro sonothrombolysis assay system using a sheet-type clot. METHODS We designed a cell for clot assay, and we confirmed that this clot cell did not significantly intervene in the acoustic field. Using human plasma, we made a sheet-type clot in the cell. Clot thicknesses at 100 points along 4 directions were measured photometrically at a rate of approximately 4 points/s. RESULTS The sonothrombolysis effects at 13 levels of ultrasonic intensity were obtained with only one sheet-type clot. With this method, we used a clinically oriented probe at 0.7 and 0.3 W/cm2 to confirm that sonothrombolysis took place. CONCLUSIONS We successfully established a new, easy, and efficient method for conducting in vitro sonothrombolysis assays. This method involves little intervention of either ultrasound reflection or standing waves in the clot cell. We believe that this new assay method is very useful for fundamental analyses of ultrasound's thrombolysis effects.

Case A 40-year-old man presented to the emergency room with visual impairment, dysesthesia of lower legs, and urinary retention. Two days before admission, he was consulted to the neurology department due to bilateral optic neuritis and scheduled the magnetic resonance imaging of spine. However, the urinary retention deteriorated acutely and he came to the emergency room. On arrival, the plain magnetic resonance image of his spine showed diffuse hyperintensity signals of the spinal cord in T2-weighted images. He was diagnosed with neuromyelitis optica and steroid pulse therapy was initiated. Outcome We began treatment immediately in the emergency room, cooperating with the neurology team. After admission, plasmapheresis was added for his fluctuating symptoms. On hospital day 7, he was discharged without complication. Conclusion It is important to understand the various clinical manifestations of neuromyelitis optica. In emergency settings, immediate steroid therapy is necessary for better outcomes.

Sonothrombolysis is one of the most feasible methods for enhancing clot lysis with a recombinant tissue plasminogen activator (rt-PA) in cases of acute ischemic strokes. For safe and efficient clinical practices of sonothrombolysis, accurate estimation of ultrasound transmittance through the human skull is critical. Previously, we reported substantial and periodic fluctuation of ultrasound transmittance through a bone-phantom plate following changes to ultrasound frequency, the thickness of the bone-phantom plate, and the distance between a transducer and the bone-phantom plate. In the present study, we clarify the transmittance behavior of medium-frequency ultrasound (from 400kHz to 600kHz) through the human skull, and examine reduction of the transmittance fluctuation. For the study, we measured transmittance of sinusoidal ultrasound waves at 400kHz, 500kHz, and 600kHz at 13 temple spots on 3 human skulls by changing the distance between a transducer and the skull bone, and found substantial and periodic fluctuation in the transmittance behaviors for these sinusoidal voltage excitations. Degrees of the fluctuation varied depending on the measurement spots. A fluctuation ratio between the maximum transmittance and the minimum transmittance reached 3 in some spots. This large transmittance fluctuation is considered to be a risk factor for sonothrombolysis therapies. We examined a modulated ultrasound wave to reduce the fluctuation, and succeeded in obtaining considerable reduction. The average fluctuation ratios for 400-kHz, 500-kHz, and 600-kHz waves were 2.38, 2.38, and 2.07, respectively. We successfully reduced the ratio to 1.72 by using a periodic selection of random frequency (PSRF)-type of modulation wave. The thus obtained results indicate that attention to the fluctuation in ultrasound transmittance through the skull is necessary for safe and effective sonothrombolysis therapies, and that modulated ultrasound waves constitute a powerful method for reducing the risk of fluctuation.

For improved thrombolysis therapy based on ultrasound irradiation, researchers and practitioners would strongly benefit from an easy and efficient in vitro assay system of thrombolysis activity involving irradiated ultrasound. For the present study, we designed a new in vitro sonothrombolysis assay system using a sheet-type clot.We designed a cell for clot assay, and we confirmed that this clot cell did not significantly intervene in the acoustic field. Using human plasma, we made a sheet-type clot in the cell. Clot thicknesses at 100 points along 4 directions were measured photometrically at a rate of approximately 4 points/s.The sonothrombolysis effects at 13 levels of ultrasonic intensity were obtained with only one sheet-type clot. With this method, we used a clinically oriented probe at 0.7 and 0.3 W/cmWe successfully established a new, easy, and efficient method for conducting in vitro sonothrombolysis assays. This method involves little intervention of either ultrasound reflection or standing waves in the clot cell. We believe that this new assay method is very useful for fundamental analyses of ultrasound's thrombolysis effects.