Browsing by Subject "Cryoablation"
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Item The Comparative assessment of clinical ablative therapies: effects on physiological and biomechanical properties of contractile tissues in response to therapeutic doses(2014-09) Singal, AshishTissue ablation is a common medical procedure that involves manipulation of the target tissue with an aim to restore normal structure and function. Ablations are performed throughout the human body for treating various carcinomas and disease conditions. Although a routine clinical procedure, in a small percentage of patients it may cause collateral damage to surrounding structures which can have severe clinical implications. The collateral damage results in altered tissue properties those are dependent on the level of ablative energy and extent of tissue injury. Therefore, assessment of tissue properties is fundamental to advancing the understanding of underlying basic and clinical science of ablations, especially to maximize therapy efficacy and minimize procedural complications. Thus, a thorough understanding of tissue properties is essential to the successful outcome of all ablation procedures.Unique laboratory methodologies were developed that were used to assess the physiological and biomechanical properties of respiratory diaphragm, esophagus, cardiac trabeculae, and vastus lateralis tissues following exposure to five different therapeutic ablative modalities: radiofrequency ablation, cryoablation, high-intensity focused ultrasound, microwave ablation, and chemical ablation (with acetic acid, ethanol, hypertonic sodium chloride, and urea). The changes in physiological properties were quantified by measuring changes in peak force (strength of contractions) and baseline force (resting muscle tension) in response to ablations. The changes in biomechanical properties were quantified by measuring the stress-strain characteristics, avulsion forces, and elastic moduli in response to ablations. Dose effect responses of each ablative modality were quantified. To our knowledge these are the first reports of such methodological comparative assessment of tissue properties following treatment with therapeutic ablative modalities at clinically relevant doses. The understanding of tissue properties has wide applications ranging from applied research to the development of novel tools, ablation techniques, and innovative clinical treatment options. These findings may provide novel insights into the effects of ablations which may allow further improvements in ablative techniques to increase the overall safety and efficacy of ablative procedures. It is clear that the understanding of collateral damage at the cellular level, isolated tissue level, and whole organ level will be important to the future of this evolving era of ablations.Item The Role of Protein Change (Cellular Protein Loss and Denaturation) in Determining Outcomes of Heating, Cryotherapy and Irreversible Electroporation(2018-04) Liu, FengAtrial fibrillation currently affects millions of people in the US alone. Focal therapy is an increasingly attractive treatment for atrial fibrillation that avoids the debilitating effects of drugs for disease control. Perhaps the most widely used focal therapy for atrial fibrillation (AF) is heat-based radiofrequency (heating), although cryotherapy (cryo) is rapidly replacing it due to a reduction in side effects and positive clinical outcomes. A third focal therapy, irreversible electroporation (IRE), is also being considered in some settings. This study was designed to help guide treatment thresholds and compare mechanism of action across heating, cryo, and IRE. Testing was undertaken on HL-1 cells, a well-established cardiomyocyte cell line, to assess injury thresholds for each treatment method. Cell viability, as assessed by Hoechst and PI staining, was found to be minimal after exposure to temperatures ≤-40 °C (cryo), ≥60 °C (heating), and when field strengths ≥1500 V/cm (IRE) were used. Viability was then correlated to protein denaturation fraction (PDF) as assessed by Fourier Transform Infrared (FTIR) spectroscopy, and protein loss fraction (PLF) as assessed by Bicinchoninic Acid (BCA) assay after the three treatments. These protein changes were assessed both in the supernatant and the pellet of cell suspensions post treatment. We found that dramatic viability loss (≥50%) correlated strongly with ≥12% protein change (PLF, PDF or a combination of the two) in every focal treatment. These studies help in defining both cellular thresholds and protein-based mechanisms of action that can be used to improve focal therapy application for atrial fibrillation.Item Studies of cryothermal ablation for the treatment of atrial fibrillation(2014-04) Goff, Ryan PatrickAtrial fibrillation (AF) remains as the most prevalent tachyarrhythmia, with a prevalence in the U.S., of 1% in the general population. The current therapeutic/treatment paradigm for the patient with atrial fibrillation, is to first attempt to restore normal rhythm via anti-arrhythmic pharmaceuticals. If this does not ameliorate the problem, or the patient does not well tolerate the drug side-effects, a transcatheter ablation is usually performed. The relatively recent introduction of cryoballoon based ablation has provided the electrophysiologist with an easier method of treating AF via pulmonary vein isolation. However, despite current clinical use research questions regarding anatomy, dosing, and device-tissue interactions have remained unanswered.Anatomical studies of the phrenic nerve, coronary sinus, left atria, and pulmonary vein anatomy were performed using high-resolution MRI and direct measurements on heart specimens. These novel anatomical studies may guide future device iterations and the computer based models used for numerical simulation. The amount of cooling required to injure and/or kill cardiac tissue, lung tissue, and the phrenic nerve was quantified using novel in-vitro models. These data may be used for procedural modeling and dosing optimization. Device-tissue interactions were studied using a functional, isolated heart-lung bloc model and a patent has been filed for this methodology. Using this model infrared imaging was performed to quantify the level of cooling being achieved by cryoballoon catheters. A separate study was performed using MRI to quantify ice dynamics and to our knowledge is the first cardiac cryoablation performed in an MR environment. This collection of work will aid the clinical, scientific, and engineering communities in further optimization of cardiac cryoablation.