Pulsed-high intensity focused ultrasound (HIFU) exposures without ultrasound contrast agents have been used for non-invasively enhancing the delivery of various agents to improve their therapeutic efficacy in a variety of tissue models in a non-destructive manner. Despite the versatility of these exposures, little is known about the mechanisms by which their effects are produced. In this study pulsed-HIFU exposures were given in the flank muscle of mice, followed by the administration a variety of fluorophores, both soluble and particulate, by local or systemic injection. In vivo imaging (whole animal and microscopic) was used to quantify observations of increased extravasation and interstitial transport of the fluorophores as a result of the exposures. Histological analysis indicated that the exposures caused some structural alterations such as enlarged gaps between muscle fibers. These effects were consistent with increasing the permeability of the tissues; however they were found to be transient and reversed themselves gradually within 72 hrs. Simulations of radiation force induced displacements and the resulting local shear strain they produced were carried out to potentially explain the manner by which these effects occurred. A better understanding of the mechanisms involved with pulsed-HIFU exposures for non-invasively enhancing delivery will facilitate the process for optimizing their use.
PURPOSE-To assess the feasibility of the use of preprocedural imaging for guide wire, catheter, and needle navigation with electromagnetic tracking in phantom and animal models. MATERIALS AND METHODS-An image-guided intervention software system was developedbased on open-source software components. Catheters, needles, and guide wires were constructed with small position and orientation sensors in the tips. A tetrahedral-shaped weak electromagnetic field generator was placed in proximity to an abdominal vascular phantom or three pigs on the angiography table. Preprocedural computed tomographic (CT) images of the phantom or pig were loaded into custom-developed tracking, registration, navigation, and rendering software. Devices were manipulated within the phantom or pig with guidance from the previously acquired CT scan and simultaneous real-time angiography. Navigation within positron emission tomography (PET) and magnetic resonance (MR) volumetric datasets was also performed. External and endovascular fiducials were used for registration in the phantom, and registration error and tracking error were estimated. RESULTS-The CT scan position of the devices within phantoms and pigs was accurately determined during angiography and biopsy procedures, with manageable error for some applications. Preprocedural CT depicted the anatomy in the region of the devices with real-time position updating and minimal registration error and tracking error (<5 mm). PET can also be used with this system to guide percutaneous biopsies to the most metabolically active region of a tumor.CONCLUSIONS-Previously acquired CT, MR, or PET data can be accurately codisplayed during procedures with reconstructed imaging based on the position and orientation of catheters, guide wires, or needles. Multimodality interventions are feasible by allowing the real-time updated display of previously acquired functional or morphologic imaging during angiography, biopsy, and ablation.Address correspondence to B.J.W.; E-mail: bwood@nih.gov. B.J.W. and K.C. are coinventors on related US Patent Application #10/377,528, "Interstitial Magnetic Position Sensor System and Needle for Surgical and Image-guided Therapy Navigation." B.J.W. and N.G. are coinventors on US Patent Application: "Design for Guiding and Electromagnetic Tracking of Radiofrequency Ablation Needle" (US Provisional Patent Application # 60/625,186). Philips owns intellectual property and has market interest in this area. J.K., J.B., and S.K. are salaried employees of Philips Electronics. The mention of commercial devices or products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the National Institutes of Health, the Department of Health and Human Services, or the Public Health Service. N.G. is President and a major shareholder of Traxtal, Inc. DEVICE navigation in angiography and interventional radiology has traditionally relied on real-time imaging to monitor anatomic position...
Several percutaneous local ablative therapies have been used to treat unresectable malignancies including percutaneous ethanol injection therapy (PEIT), acetic acid, hyperthermic saline and distilled water, gene therapy, liposomal or micelle vectors, and chemotherapeutic agents such as cisplatin. However, mechanical methods for injection of therapeutics remain primitive. Treatments must be able to distribute a small volume of therapeutic agent evenly and widely throughout the tumor, including the tumor margin, without tracking along fascial planes and killing healthy tissue.
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