{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:35Z","timestamp":1760144195694,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EPSRC Case Studentship and Zilico","award":["X\/162619-11-2"],"award-info":[{"award-number":["X\/162619-11-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Electrical impedance spectroscopy (EIS) has been proposed as a promising noninvasive method to differentiate healthy thyroid from parathyroid tissues during thyroidectomy. However, previously reported similarities in the in vivo measured spectra of these tissues during a pilot study suggest that this separation may not be straightforward. We utilise computational modelling as a method to elucidate the distinguishing characteristics in the EIS signal and explore the features of the tissue that contribute to the observed electrical behaviour. Firstly, multiscale finite element models (or \u2018virtual tissue constructs\u2019) of thyroid and parathyroid tissues were developed and verified against in vivo tissue measurements. A global sensitivity analysis was performed to investigate the impact of physiological micro-, meso- and macroscale tissue morphological features of both tissue types on the computed macroscale EIS spectra and explore the separability of the two tissue types. Our results suggest that the presence of a surface fascia layer could obstruct tissue differentiation, but an analysis of the separability of simulated spectra without the surface fascia layer suggests that differentiation of the two tissue types should be possible if this layer is completely removed by the surgeon. Comprehensive in vivo measurements are required to fully determine the potential for EIS as a method in distinguishing between thyroid and parathyroid tissues.<\/jats:p>","DOI":"10.3390\/s24072198","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T06:33:16Z","timestamp":1711693996000},"page":"2198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Use of Virtual Tissue Constructs That Include Morphological Variability to Assess the Potential of Electrical Impedance Spectroscopy to Differentiate between Thyroid and Parathyroid Tissues during Surgery"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-335X","authenticated-orcid":false,"given":"Malwina","family":"Matella","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of Sheffield, Sheffield S1 4DP, UK"},{"name":"Insigneo Institute for In Silico Medicine, Sheffield S1 3JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Hunter","sequence":"additional","affiliation":[{"name":"Liverpool Head and Neck Centre, Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 7TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, Royal Hallamshire Hospital School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield S10 2RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-8093","authenticated-orcid":false,"given":"Dawn","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Sheffield, Sheffield S1 4DP, UK"},{"name":"Insigneo Institute for In Silico Medicine, Sheffield S1 3JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","unstructured":"British Association of Endocrine and Thyroid Surgeons (2021). BAETS Sixth National Audit Report, BAETS."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.21037\/gs.2017.05.08","article-title":"Intraoperative Real-time Localization of Parathyroid Gland with Near Infrared Fluorescence Imaging","volume":"6","author":"Kim","year":"2017","journal-title":"Gland. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1007\/s00268-017-3903-0","article-title":"Intraoperative Identification of the Parathyroid Gland with a Fluorescence Detection System","volume":"41","author":"Shinden","year":"2017","journal-title":"World J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.surg.2004.06.024","article-title":"Prospective Evaluation of Sestamibi Scan, Ultrasonography, and Rapid PTH to Predict the Success of Limited Exploration for Sporadic Primary Hyperparathyroidism","volume":"136","author":"Siperstein","year":"2004","journal-title":"Surgery"},{"key":"ref_5","unstructured":"Schwan, H.P. (1994, January 3\u20136). Electrical Properties of Tissues and Cell Suspensions: Mechanisms and Models. Proceedings of the 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Baltimore, MD, USA."},{"key":"ref_6","unstructured":"Zilico Limited (2013). ZedScan\u2122 a New Standard in Colposcopy\u2014Technical Brochure, Zilico Ltd."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.elstat.2007.11.005","article-title":"Electrical Impedance Spectroscopy Study of Biological Tissues","volume":"66","author":"Dean","year":"2008","journal-title":"J. Electrost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1109\/TBME.2011.2166116","article-title":"Novel Estimation of the Electrical Bioimpedance Using the Local Polynomial Method. Application to In Vivo Real-Time Myocardium Tissue Impedance Characterization During the Cardiac Cycle","volume":"58","author":"Sanchez","year":"2011","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.medengphy.2012.09.004","article-title":"In Vivo Electrical Bioimpedance Characterization of Human Lung Tissue During the Bronchoscopy Procedure. A Feasibility Study","volume":"35","author":"Sanchez","year":"2013","journal-title":"Med Eng. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/srt.12008","article-title":"Electrical Impedance Spectroscopy as a Potential Adjunct Diagnostic Tool for Cutaneous Melanoma","volume":"19","author":"Mohr","year":"2013","journal-title":"Ski. Res. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"636075","DOI":"10.1155\/2015\/636075","article-title":"Electrical Bioimpedance Analysis: A New Method in Cervical Cancer Screening","volume":"2015","author":"Das","year":"2015","journal-title":"J. Med Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.2147\/IJN.S64087","article-title":"Use of Electrical Impedance Spectroscopy to Detect Malignant and Potentially Malignant Oral Lesions","volume":"9","author":"Murdoch","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1200\/JCO.2005.06.155","article-title":"Electrical Impedance Scanning for the Early Detection of Breast Cancer in Young Women: Preliminary Results of a Multicenter Prospective Clinical Trial","volume":"23","author":"Stojadinovic","year":"2005","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mishra, V., Bouayad, H., Schned, A., Heaney, J., and Halter, R.J. (September, January 28). Electrical Impedance Spectroscopy for Prostate Cancer Diagnosis. Proceedings of the 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, San Diego, CA, USA.","DOI":"10.1109\/EMBC.2012.6346660"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4006407","DOI":"10.1109\/TIM.2021.3105241","article-title":"Bioimpedance Spectroscopy Measurement and Classification of Lung Tissue to Identify Pulmonary Nodules","volume":"70","author":"Baghbani","year":"2021","journal-title":"IEEE Trans. Instrum. Meas."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.snb.2018.01.155","article-title":"Ex Vivo Identification of Thyroid Cancer Tissue Using Electrical Impedance Spectroscopy on a Needle","volume":"261","author":"Yun","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1245\/ASO.2005.03.062","article-title":"Electrical Impedance Scanning of Thyroid Nodules Before Thyroid Surgery: A Prospective Study","volume":"12","author":"Stojadinovic","year":"2005","journal-title":"Ann. Surg. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1089\/thy.2012.0413","article-title":"Classification of Thyroid Nodules Using a Resonance-frequency-based Electrical Impedance Spectroscopy: A Preliminary Assessment","volume":"23","author":"Zheng","year":"2013","journal-title":"Thyroid. Off. J. Am. Thyroid. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00268-019-05169-7","article-title":"Use of Electrical Impedance Spectroscopy for Intraoperative Tissue Differentiation During Thyroid and Parathyroid Surgery","volume":"44","author":"Hillary","year":"2019","journal-title":"World J. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"963520","DOI":"10.3389\/fendo.2022.963520","article-title":"Bioelectrical Impedance Spectroscopy Can Assist to Identify the Parathyroid Gland During Thyroid Surgery","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Matella, M., Hunter, K., Balasubramanian, S., and Walker, D.C. (2023). Multiscale Model Development for Electrical Properties of Thyroid and Parathyroid Tissues, IEEE Open Journal of Engineering in Medicine and Biology.","DOI":"10.1109\/OJEMB.2023.3275536"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.envsoft.2019.01.012","article-title":"Why So Many Published Sensitivity Analyses are False: A Systematic Review of Sensitivity Analysis Practices","volume":"114","author":"Saltelli","year":"2019","journal-title":"Environ. Model. Softw."},{"key":"ref_23","unstructured":"Matella, M. (2023). Computational Modelling of Electrical Properties of Thyroid and Parathyroid Tissue. [Ph.D. Thesis, University of Sheffield]."},{"key":"ref_24","unstructured":"Walker, D.C. (2001). Modeling the Electrical Properties of Cervical Epithelium. [Ph.D. Thesis, University of Sheffield]."},{"key":"ref_25","first-page":"59","article-title":"Macro- and Micro-Morphological Studies on the Parathyroid Glands of Dromedary Camel","volume":"37","year":"2017","journal-title":"Pak. Vet. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5455\/medarh.2019.73.249-252","article-title":"Correlation Between the Parathyroid Glands Size and Parathormones Value in Patients with Hyperparathyroidism","volume":"73","author":"Ramas","year":"2019","journal-title":"Med. Arch."},{"key":"ref_27","first-page":"239","article-title":"A Comparison of Three Methods for Selecting Values of Input Variables in the Analysis of Output from a Computer Code","volume":"21","author":"McKay","year":"1979","journal-title":"Technometrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jtbi.2008.04.011","article-title":"A Methodology for Performing Global Uncertainty and Sensitivity Analysis in Systems Biology","volume":"254","author":"Marino","year":"2008","journal-title":"J. Theor. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0378-4754(00)00270-6","article-title":"Global Sensitivity Indices for Nonlinear Mathematical Models and Their Monte Carlo Estimates","volume":"55","year":"2001","journal-title":"Math. Comput. Simul."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.acra.2005.04.005","article-title":"Receiver Operating Characteristic Analysis: A Primer","volume":"12","author":"Eng","year":"2005","journal-title":"Acad. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1002\/mus.27664","article-title":"Using machine learning algorithms to enhance the diagnostic performance of electrical impedance myography","volume":"66","author":"Pandeya","year":"2022","journal-title":"Muscle Nerve"},{"key":"ref_32","first-page":"2825","article-title":"Scikit-learn: Machine Learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chang, E.T., Strong, M., and Clayton, R.H. (2015). Bayesian Sensitivity Analysis of a cCrdiac Cell Model using a Gaussian Process Emulator. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137004"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1109\/TBME.2022.3163428","article-title":"Global Sensitivity Analysis of Four Chamber Heart Hemodynamics Using Surrogate Models","volume":"69","author":"Karabelas","year":"2022","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0302-4598(91)87003-Y","article-title":"To What Extent is the Magnitude of the Cole-Cole \u03b1 of the \u03b2-dielectric Dispersion of Cell Suspensions Explicable in Terms of the Cell Size Distribution?","volume":"25","author":"Markx","year":"1991","journal-title":"Bioelectrochem. Bioenerg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.procs.2017.11.256","article-title":"Machine Learning Techniques for Classification of Breast Tissue","volume":"120","author":"Helwan","year":"2017","journal-title":"Procedia Comput. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tian, D., Lang, Z.Q., Zhang, D., and Anumba, D.O. (2023). A filter-predictor polynomial feature based machine learning approach to predicting preterm birth from cervical electrical impedance spectroscopy. Biomed. Signal Process. Control, 80.","DOI":"10.1016\/j.bspc.2022.104345"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2478\/joeb-2021-0018","article-title":"Cervical cancer prognosis and diagnosis using electrical impedance spectroscopy","volume":"12","author":"Li","year":"2021","journal-title":"J. Electr. Bioimpedance"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1615\/CritRevBiomedEng.2015012486","article-title":"Review of Temperature Dependence of Thermal Properties, Dielectric Properties, and Perfusion of Biological Tissues at Hyperthermic and Ablation Temperatures","volume":"42","author":"Rossmann","year":"2015","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_40","first-page":"390","article-title":"Der Einfluss von Thyrotropem Hormon auf das Elektrogramm der Schilddruese","volume":"34","author":"Reichertz","year":"1960","journal-title":"Acta Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17218","DOI":"10.1038\/s41598-020-73684-y","article-title":"Skin Hydration Dynamics Investigated by Electrical Impedance Techniques In Vivo and In Vitro","volume":"10","author":"Morin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Matella, M., Walker, D.C., and Hunter, K. (2023, January 14\u201316). Computational Modelling of Probe Configurations for Electrical Impedance Spectroscopy-based Differentiation of Thyroid and Parathyroid Tissues. Proceedings of the 2023 IEEE International Symposium on Medical Measurements and Applications (MeMeA), Jeju, Republic of Korea.","DOI":"10.1109\/MeMeA57477.2023.10171880"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/7\/2198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:20:50Z","timestamp":1760106050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/7\/2198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["s24072198"],"URL":"https:\/\/doi.org\/10.3390\/s24072198","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}