Evaluation of keratoprosthesis biointegration in situ with quantitative ultrasound backscatter microscopy

OBJECT Urgent ventriculostomy placement can be a lifesaving procedure in the setting of hydrocephalus or elevated intracranial pressure. While external ventricular drain (EVD) insertion is common, there remains a high rate of suboptimal drain placement. Here, the authors seek to demonstrate the feasibility of an ultrasound-based guidance system that can be inserted into an existing EVD catheter to provide a linear ultrasound trace that guides the user toward the ventricle. METHODS The ultrasound stylet was constructed as a thin metal tube, with dimensions equivalent to standard catheter stylets, bearing a single-element, ceramic ultrasound transducer at the tip. Ultrasound backscatter signals from the porcine ventricle were processed by custom electronics to offer real-time information about ventricular location relative to the catheter. Data collected from the prototype device were compared with reference measurements obtained using standard clinical ultrasound imaging. RESULTS A study of porcine ventricular catheterization using the experimental device yielded a high rate of successful catheter placement after a single pass (10 of 12 trials), despite the small size of pig ventricles and the lack of prior instruction on porcine ventricular architecture. A characteristic double-peak signal was identified, which originated from ultrasound reflections off of the near and far ventricular walls. Ventricular dimensions, as obtained from the width between peaks, were in agreement with standard ultrasound reference measurements (p < 0.05). Furthermore, linear ultrasound backscatter data permitted in situ measurement of the stylet distance to the ventricular wall (p < 0.05), which assisted in catheter guidance. CONCLUSIONS The authors have demonstrated the ability of the prototype ultrasound stylet to guide ventricular access in the porcine brain. The alternative design of the device makes it potentially easy to integrate into the standard workflow for bedside EVD placement. The availability of a fast, easy-to-use, inexpensive guidance system can play a role in reducing the complication rate for EVD placement.

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Quantitative Ultrasound Characterization of Tumor Cell Death: Ultrasound-Stimulated Microbubbles for Radiation Enhancement

10.32920/14668827.v1 ◽

2021 ◽

Author(s):

Raffi Karshafian ◽

Hyunjung Christina Kim ◽

Azza Al-Mahrouki ◽

Alborz Gorjizadeh ◽

Ali Sadeghi-Naini ◽

...

Keyword(s):

Cell Death ◽

Quantitative Ultrasound ◽

Radiation Effects ◽

Severe Combined Immunodeficiency ◽

Cyclophilin A ◽

Tumor Cell Death ◽

Backscatter Intensity ◽

Non Invasive ◽

Cancer Cell Death ◽

Ultrasound Backscatter

The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID) mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy) to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

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