Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions

Percutaneous thermal ablation has proved to be an effective modality for treating both benign and malignant tumors in various tissues. Among these modalities, radiofrequency ablation (RFA) is the most promising and widely adopted approach that has been extensively studied in the past decades. Microwave ablation (MWA) is a newly emerging modality that is gaining rapid momentum due to its capability of inducing rapid heating and attaining larger ablation volumes, and its lesser susceptibility to the heat sink effects as compared to RFA. Although the goal of both these therapies is to attain cell death in the target tissue by virtue of heating above 50 oC, their underlying mechanism of action and principles greatly differs. Computational modelling is a powerful tool for studying the effect of electromagnetic interactions within the biological tissues and predicting the treatment outcomes during thermal ablative therapies. Such a priori estimation can assist the clinical practitioners during treatment planning with the goal of attaining successful tumor destruction and preservation of the surrounding healthy tissue and critical structures. This review provides current state-of- the-art developments and associated challenges in the computational modelling of thermal ablative techniques, viz., RFA and MWA, as well as touch upon several promising avenues in the modelling of laser ablation, nanoparticles assisted magnetic hyperthermia and non- invasive RFA. The application of RFA in pain relief has been extensively reviewed from modelling point of view. Additionally, future directions have also been provided to improve these models for their successful translation and integration into the hospital work flow

Brain Tumour Classification Using Deep Features from Structural MRI

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Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/0967-3334/31/4/009[EN] The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min¿1). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 °C; (3) substantial errors (larger than 15 °C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 °C).This work was supported by the 'Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica del Ministerio de Educacion y Ciencia' of Spain (TEC200801369/ TEC) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd and the Spanish National Research Council (CSIC). The English revision and correction of this paper was funded by the Universidad Politecnica de Valencia, Spain. We thank L Melecio for his invaluable technical support in conducting the experiments.Blasco-Giménez, R.; Lequerica, JL.; Herrero, M.; Hornero, F.; Berjano, E. (2010). Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model. Physiological Measurement. 31(4):581-594. https://doi.org/10.1088/0967-3334/31/4/009S581594314Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459Hong Cao, Vorperian, V. R., Jang-Zem Tsai, Tungjitkusolmun, S., Eung Je Woo, & Webster, J. G. (2000). Temperature measurement within myocardium during in vitro RF catheter ablation. IEEE Transactions on Biomedical Engineering, 47(11), 1518-1524. doi:10.1109/10.880104Hamner, C. E., Potter, D. D., Cho, K. R., Lutterman, A., Francischelli, D., Sundt, T. M., & Schaff, H. V. (2005). Irrigated Radiofrequency Ablation With Transmurality Feedback Reliably Produces Cox Maze Lesions In Vivo. The Annals of Thoracic Surgery, 80(6), 2263-2270. doi:10.1016/j.athoracsur.2005.06.017HARTUNG, W. M., BURTON, M. E., DEAM, A. G., WALTER, P. F., McTEAGUE, K., & LANGBERG, J. J. (1995). Estimation of Temperature During Radiofrequency Catheter Ablation Using Impedance Measurements. Pacing and Clinical Electrophysiology, 18(11), 2017-2021. doi:10.1111/j.1540-8159.1995.tb03862.xDing Sheng He, Bosnos, M., Mays, M. Z., & Marcus, F. (2003). Assessment of myocardial lesion size during in vitro radio frequency catheter ablation. IEEE Transactions on Biomedical Engineering, 50(6), 768-776. doi:10.1109/tbme.2003.812161KO, W.-C., HUANG, S. K. S., LIN, J.-L., SHAU, W.-Y., LAI, L.-P., & CHEN, P. H. (2001). New Method for Predicting Efficiency of Heating by Measuring Bioimpedance During Radiofrequency Catheter Ablation in Humans. Journal of Cardiovascular Electrophysiology, 12(7), 819-823. doi:10.1046/j.1540-8167.2001.00819.xLabonte, S. (1994). Numerical model for radio-frequency ablation of the endocardium and its experimental validation. IEEE Transactions on Biomedical Engineering, 41(2), 108-115. doi:10.1109/10.284921Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Lequerica, J. L., Berjano, E. J., Herrero, M., Melecio, L., & Hornero, F. (2008). A cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: experimental study based on an agar phantom. Physics in Medicine and Biology, 53(4), N25-N34. doi:10.1088/0031-9155/53/4/n01Mattingly, M., Bailey, E. A., Dutton, A. W., Roemer, R. B., & Devasia, S. (1998). Reduced-order modeling for hyperthermia: an extended balanced-realization-based approach. IEEE Transactions on Biomedical Engineering, 45(9), 1154-1162. doi:10.1109/10.709559PILCHER, T. A., SANFORD, A. L., SAUL, J. P., & HAEMMERICH, D. (2006). Convective Cooling Effect on Cooled-Tip Catheter Compared to Large-Tip Catheter Radiofrequency Ablation. Pacing and Clinical Electrophysiology, 29(12), 1368-1374. doi:10.1111/j.1540-8159.2006.00549.xRodríguez, I., Lequerica, J. L., Berjano, E. J., Herrero, M., & Hornero, F. (2007). Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model. Physiological Measurement, 28(5), 453-463. doi:10.1088/0967-3334/28/5/001SCHUMACHER, B., EICK, O., WITTKAMPF, F., PEZOLD, C., TEBBENJOHANNS, J., JUNG, W., & LUDERITZ, B. (1999). Temperature Response Following Nontraumatic Low Power Radiofrequency Application. Pacing and Clinical Electrophysiology, 22(2), 339-343. doi:10.1111/j.1540-8159.1999.tb00448.xTeixeira, C. A., Ruano, A. E., Ruano, M. G., Pereira, W. C. A., & Negreira, C. (2006). Non-invasive temperature prediction of in vitro therapeutic ultrasound signals using neural networks. Medical & Biological Engineering & Computing, 44(1-2), 111-116. doi:10.1007/s11517-005-0004-2Teixeira, C. A., Ruano, M. G., Ruano, A. E., & Pereira, W. C. A. (2008). A Soft-Computing Methodology for Noninvasive Time-Spatial Temperature Estimation. IEEE Transactions on Biomedical Engineering, 55(2), 572-580. doi:10.1109/tbme.2007.90102

Translational considerations for the design of untethered nanomaterials in human neural stimulation

Neural stimulation is a powerful tool to study brain physiology and an effective treatment for many neurological disorders. Conventional interfaces use electrodes implanted in the brain. As these are often invasive and have limited spatial targeting, they carry a potential risk of side-effects. Smaller neural devices may overcome these obstacles, and as such, the field of nanoscale and remotely powered neural stimulation devices is growing. This review will report on current untethered, injectable nanomaterial technologies intended for neural stimulation, with a focus on material-tissue interface engineering. We will review nanomaterials capable of wireless neural stimulation, and discuss their stimulation mechanisms. Taking cues from more established nanomaterial fields (e.g., cancer theranostics, drug delivery), we will then discuss methods to modify material interfaces with passive and bioactive coatings. We will discuss methods of delivery to a desired brain region, particularly in the context of how delivery and localization are affected by surface modification. We will also consider each of these aspects of nanoscale neurostimulators with a focus on their prospects for translation to clinical use

Ultrasound and microbubbles for the treatment of ocular diseases : From preclinical research towards clinical application

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood–retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed.Peer reviewe

DEVELOPMENT OF NANOPARTICLE RATE-MODULATING AND SYNCHROTRON PHASE CONTRAST-BASED ASSESSMENT TECHNIQUES FOR CARDIAC TISSUE ENGINEERING

Myocardial infarction (MI) is the most common cause of heart failure. Despite advancements in cardiovascular treatments and interventions, current therapies can only slow down the progression of heart failure, but not tackle the progressive loss of cardiomyocytes after MI. One aim of cardiac tissue engineering is to develop implantable constructs (e.g. cardiac patches) that provide physical and biochemical cues for myocardium regeneration. To this end, vascularization in these constructs is of great importance and one key issue involved is the spatiotemporal control of growth-factor (GF)-release profiles. The other key issue is to non-invasively quantitatively monitor the success of these constructs in-situ, which will be essential for longitudinal assessments as studies are advanced from ex-vivo to animal models and human patients. To address these issues, the present research aims to develop nanoparticles to modulate the temporal control of GF release in cardiac patches, and to develop synchrotron X-ray phase contrast tomography for visualization and quantitative assessment of 3D-printed cardiac patch implanted in a rat MI model, with four specific objectives presented below. The first research objective is to optimize nanoparticle-fabrication process in terms of particle size, polydispersity, loading capacity, zeta potential and morphology. To achieve this objective, a comprehensive experimental study was performed to examine various process parameters used in the fabrication of poly(lactide-co-glycolide) (PLGA) nanoparticles, along with the development of a novel computational approach for the nanoparticle-fabrication optimization. Results show that among various process parameters examined, the polymer and the external aqueous phase concentrations are the most significant ones to affect the nanoparticle physical and release characteristics. Also, the limitations of PLGA nanoparticles such as initial burst effect and the lack of time-delayed release patterns are identified. The second research objective is to develop bi-layer nanoparticles to achieve the controllable release of GFs, meanwhile overcoming the above identified limitations of PLGA nanoparticles. The bi-layer nanoparticle is composed of protein-encapsulating PLGA core and poly(L-lactide) (PLLA)-rate regulating shell, thus allowing for low burst effect, protein structural integrity and time-delayed release patterns. The bi-layer nanoparticles, along with PLGA ones, were successfully fabricated and then used to regulate simultaneous and/or sequential release of multiple angiogenic factors with the results demonstrating that they are effective to promote angiogenesis in fibrin matrix. The third objective is to develop novel mathematical models to represent the controlled-release of bioactive agents from nanoparticles. For this, two models, namely the mechanistic model and geno-mechanistic model, were developed based on the local and global volume averaging approaches, respectively, and then validated with experiments on both single- and bi-layer nanoparticles, by which the ovalbumin was used as a protein model for the release examination. The results illustrates the developed models are able to provide insight on the release mechanism and to predict nanoparticle transport and degradation properties of nanoparticles, thus providing a means to regulate and control the release of bioactive agents from the nanoparticles for tissue engineering applications. The fourth objective of this research is to develop a synchrotron-based phase contrast non-invasive imaging technique for visualization and quantitative assessment of cardiac patch implanted in a rat MI model. To this end, the patches were created from alginate strands using the three-dimensional (3D) printing technique and then surgically implanted on rat hearts for the assessment based on phase contrast tomography. The imaging of samples was performed at various sample-to-detector distances, CT-scan time, and areas of the region of interest (ROI) to examine their effects on imaging quality. Phase-retrieved images depict visible and quantifiable structural details of the patch at low radiation dose, which, however, are not seen from the images by means of dual absorption-phase and a 3T clinical magnetic resonance imaging. Taken together, this research represents a significant advance in cardiac tissue engineering by developing novel nano-guided approaches for vascularization in myocardium regeneration as well as non-invasive and quantitative monitoring techniques for longitudinal studies on the cardiac patch implanted in animal model and eventually in human patients

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Multimodal Ultrasound Imaging for Improved Metastatic Lymph Node Detection

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is complex in nature due to the variety of organs located in the head and neck region. Knowing the metastatic state of the lymph nodes is paramount in accurately staging and treating HNSCC patients. Currently, metastatic lymph node detection involves the use of magnetic resonance imaging and/or x-ray computed tomography, followed by biopsies for histological confirmation. The main diagnostic criteria is the size of the nodes; however, current imaging methods are not 100% accurate due natural lymph node variability. Ultrasound imaging is able to provide additional biological information in addition to lymph node size such as the hilus state, presence of necrosis and vascular information, but it is hindered by poor resolution and limited contrast. Augmenting ultrasound for metastatic lymph node detection has clinical potential due to the availability of ultrasound in the clinic, reduced radiation exposure and minimized patient morbidity. This thesis focuses on augmenting ultrasound with photoacoustic imaging or with nanoparticle contrast agents for improved detection of lymph node metastasis. First, the development of an ultrasound-photoacoustic (USPA) imaging system is described. The USPA system is capable of imaging blood oxygen saturation (sO2), a promising criteria to differentiate between metastatic and healthy lymph nodes. To correct for tissue-dependent attenuation of light in tissue, a deep neural network was developed and trained using Monte-Carlo simulated and experimentally acquired photoacoustic data for better sO2 predictions. Secondly, to improve ultrasound sensitivity to metastatic cells, molecularly targeted phase change perfluorohexane nanodroplets conjugated to epidermal growth factor receptor (EGFR) antibodies (PFHnD-Abs) were developed. It is shown that the PFHnD-Abs are able to specifically bind to HNSCC cells and improve the ultrasound contrast of the cells, opening the door to targeted metastatic lymph node detection. Lastly, to validate the use of the PFHnD-Abs in-vivo, a paired agent imaging approach was adopted by using using a perfluoropentane core nanodroplet (PFPnD) as a non-targeted imaging agent to enable multiplex ultrasound imaging in vivo. Overall, this work expands the potential of ultrasound for metastatic lymph node detection