{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:13:11Z","timestamp":1762956791154,"version":"3.37.3"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008363","name":"Kr\u00e6ftens Bek\u00e6mpelse","doi-asserted-by":"publisher","award":["R234-A13871"],"award-info":[{"award-number":["R234-A13871"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006088","name":"Direkt\u00f8r Emil C. Hertz og Hustru Inger Hertz\u2019 Fond","doi-asserted-by":"crossref","award":["KJR-13016"],"award-info":[{"award-number":["KJR-13016"]}],"id":[{"id":"10.13039\/501100006088","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Research Foundation of Odense University Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40\u00a0months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.<\/jats:p>","DOI":"10.1038\/s41598-022-05889-2","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T11:15:53Z","timestamp":1644232553000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preclinical cerebral cryoablation in non-tumor bearing pigs"],"prefix":"10.1038","volume":"12","author":[{"given":"Irena","family":"Jankovic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frantz Rom","family":"Poulsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian Bonde","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarne Winther","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tine","family":"Schytte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Lund","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Langhorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Graumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willy","family":"Krone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poul Flemming","family":"H\u00f8ilund-Carlsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Halle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"issue":"32","key":"5889_CR1","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1200\/JCO.20.01255","volume":"38","author":"PW Sperduto","year":"2020","unstructured":"Sperduto, P. W. et al. Survival in patients with brain metastases: Summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient. J. Clin. Oncol. 38(32), 3773\u20133784 (2020).","journal-title":"J. Clin. Oncol."},{"issue":"7","key":"5889_CR2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.jvir.2019.01.029","volume":"30","author":"J Wu","year":"2019","unstructured":"Wu, J. et al. A comparison of cryoablation with heat-based thermal ablation for treatment of clinical T1a renal cell carcinoma: A national cancer database study. J. Vasc. Interv. Radiol. 30(7), 1027-1033.e3 (2019).","journal-title":"J. Vasc. Interv. Radiol."},{"issue":"7","key":"5889_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207107","volume":"14","author":"B Surtees","year":"2019","unstructured":"Surtees, B. et al. Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation. PLoS\u00a0One 14(7), e0207107 (2019).","journal-title":"PLoS\u00a0One"},{"issue":"2","key":"5889_CR4","first-page":"69","volume":"23","author":"AA Gage","year":"2002","unstructured":"Gage, A. A. & Baust, J. G. Cryosurgery\u2014A review of recent advances and current issues. Cryo Lett. 23(2), 69\u201378 (2002).","journal-title":"Cryo Lett."},{"key":"5889_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1159\/000469677","volume":"32","author":"BV Martynov","year":"2018","unstructured":"Martynov, B. V. et al. Stereotactic cryodestruction of gliomas. Prog. Neurol. Surg. 32, 27\u201338 (2018).","journal-title":"Prog. Neurol. Surg."},{"issue":"3","key":"5889_CR6","first-page":"431","volume":"22","author":"J Tacke","year":"2001","unstructured":"Tacke, J. et al. Experimental MR imaging-guided interstitial cryotherapy of the brain. AJNR Am. J. Neuroradiol. 22(3), 431\u2013440 (2001).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"5889_CR7","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/978-1-4471-6765-5_2","volume-title":"Dermatological Cryosurgery and Cryotherapy","author":"JG Baust","year":"2016","unstructured":"Baust, J. G., Gage, A. A. & Baust, J. M. Principles of cryoablation. In Dermatological Cryosurgery and Cryotherapy (eds Abramovits, W. et al.) 9\u201316 (Springer, 2016)."},{"issue":"Suppl 4","key":"5889_CR8","first-page":"S9","volume":"6","author":"D Theodorescu","year":"2004","unstructured":"Theodorescu, D. Cancer cryotherapy: Evolution and biology. Rev. Urol. 6(Suppl 4), S9\u2013S19 (2004).","journal-title":"Rev. Urol."},{"issue":"2","key":"5889_CR9","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1007\/s00330-009-1554-8","volume":"20","author":"C Li","year":"2010","unstructured":"Li, C. et al. MR imaging-guided cryoablation of metastatic brain tumours: Initial experience in six patients. Eur. Radiol. 20(2), 404\u2013409 (2010).","journal-title":"Eur. Radiol."},{"key":"5889_CR10","volume-title":"On the Treatment of Cancer, by the Regulated Application of an Anaesthetic Temperature","author":"J Arnott","year":"1851","unstructured":"Arnott, J. On the Treatment of Cancer, by the Regulated Application of an Anaesthetic Temperature (J Churchill, 1851)."},{"key":"5889_CR11","doi-asserted-by":"publisher","first-page":"921","DOI":"10.3171\/jns.1963.20.11.0921","volume":"20","author":"IS Cooper","year":"1963","unstructured":"Cooper, I. S. & Stellar, S. Cryogenic freezing of brain tumors for excision or destruction in situ. J. Neurosurg. 20, 921\u2013930 (1963).","journal-title":"J. Neurosurg."},{"key":"5889_CR12","first-page":"308","volume":"7","author":"MA Hatiboglu","year":"2013","unstructured":"Hatiboglu, M. A., Wildrick, D. M. & Sawaya, R. The role of surgical resection in patients with brain metastases. Ecancermedicalscience 7, 308 (2013).","journal-title":"Ecancermedicalscience"},{"key":"5889_CR13","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cryobiol.2018.06.002","volume":"83","author":"M Ismail","year":"2018","unstructured":"Ismail, M. et al. Renal cryoablation: Multidisciplinary, collaborative and perspective approach. Cryobiology 83, 90\u201394 (2018).","journal-title":"Cryobiology"},{"issue":"1","key":"5889_CR14","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1148\/radiol.2431052133","volume":"243","author":"TD Atwell","year":"2007","unstructured":"Atwell, T. D. et al. Percutaneous cryoablation of 40 solid renal tumors with US guidance and CT monitoring: Initial experience. Radiology 243(1), 276\u2013283 (2007).","journal-title":"Radiology"},{"issue":"4","key":"5889_CR15","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.nec.2017.05.015","volume":"28","author":"D Silva","year":"2017","unstructured":"Silva, D., Sharma, M., Juthani, R., Meola, A. & Barnett, G. H. Magnetic resonance thermometry and laser interstitial thermal therapy for brain tumors. Neurosurg. Clin. N. Am. 28(4), 525\u2013533 (2017).","journal-title":"Neurosurg. Clin. N. Am."},{"issue":"1","key":"5889_CR16","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/S0022-5347(17)61690-2","volume":"104","author":"WA Soanes","year":"1970","unstructured":"Soanes, W. A., Ablin, R. J. & Gonder, M. J. Remission of metastatic lesions following cryosurgery in prostatic cancer: Immunologic considerations. J. Urol. 104(1), 154\u2013159 (1970).","journal-title":"J. Urol."},{"issue":"1","key":"5889_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cryobiol.2008.10.126","volume":"58","author":"MS Sabel","year":"2009","unstructured":"Sabel, M. S. Cryo-immunology: A review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 58(1), 1\u201311 (2009).","journal-title":"Cryobiology"},{"issue":"4","key":"5889_CR18","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1245\/s10434-009-0846-1","volume":"17","author":"MS Sabel","year":"2010","unstructured":"Sabel, M. S., Su, G., Griffith, K. A. & Chang, A. E. Rate of freeze alters the immunologic response after cryoablation of breast cancer. Ann. Surg. Oncol. 17(4), 1187\u20131193 (2010).","journal-title":"Ann. Surg. Oncol."},{"issue":"1","key":"5889_CR19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s10549-004-3289-1","volume":"90","author":"MS Sabel","year":"2005","unstructured":"Sabel, M. S. et al. Immunologic response to cryoablation of breast cancer. Breast Cancer Res. Treat. 90(1), 97\u2013104 (2005).","journal-title":"Breast Cancer Res. Treat."},{"key":"5889_CR20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.inat.2018.07.006","volume":"14","author":"P-O Champagne","year":"2018","unstructured":"Champagne, P.-O. et al. Safety of performing craniotomy in the elderly: The utility of co-morbidity indices. Interdiscip. Neurosurg. 14, 97\u2013101 (2018).","journal-title":"Interdiscip. Neurosurg."},{"issue":"3","key":"5889_CR21","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3171\/2008.11.JNS08984","volume":"111","author":"BJ Williams","year":"2009","unstructured":"Williams, B. J. et al. Stereotactic radiosurgery for metastatic brain tumors: A comprehensive review of complications. J. Neurosurg. 111(3), 439\u2013448 (2009).","journal-title":"J. Neurosurg."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05889-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05889-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05889-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T22:01:48Z","timestamp":1669327308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05889-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["5889"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-05889-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2022,2,7]]},"assertion":[{"value":"10 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1977"}}