{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T11:15:54Z","timestamp":1793272554243,"version":"4.5.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["667933"],"award-info":[{"award-number":["667933"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["871212"],"award-info":[{"award-number":["871212"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["I4166-B"],"award-info":[{"award-number":["I4166-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["DOC33-B27"],"award-info":[{"award-number":["DOC33-B27"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph. First-level binary classification for discrimination of pituitary gland and adenomas was performed by feature extraction via radiomic analysis on OCT and MPM images and achieved an accuracy of 88%. Second-level multi-class classification was performed based on molecular analysis of the specimen via LSRM to discriminate pituitary adenomas subtypes with accuracies of up to 99%. Chemical compounds such as lipids, proteins, collagen, DNA and carotenoids and their relation could be identified as relevant biomarkers, and their spatial distribution visualized to provide deeper insight into the chemical properties of pituitary adenomas. Thereby, the aim of the current work was to assess a unique label-free and non-invasive multimodal optical imaging platform for pituitary tissue imaging and to perform a multiparametric morpho-molecular metabolic analysis and classification.<\/jats:p>","DOI":"10.3390\/cancers13133234","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T04:31:07Z","timestamp":1624941067000},"page":"3234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging"],"prefix":"10.3390","volume":"13","author":[{"given":"Gabriel","family":"Giardina","sequence":"first","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9105-3519","authenticated-orcid":false,"given":"Alexander","family":"Micko","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Bovenkamp","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Krause","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5449-745X","authenticated-orcid":false,"given":"Fabian","family":"Placzek","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9049-9989","authenticated-orcid":false,"given":"Laszlo","family":"Papp","sequence":"additional","affiliation":[{"name":"QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1786-4297","authenticated-orcid":false,"given":"Denis","family":"Krajnc","sequence":"additional","affiliation":[{"name":"QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4409-8324","authenticated-orcid":false,"given":"Clemens P.","family":"Spielvogel","sequence":"additional","affiliation":[{"name":"Christian Doppler Laboratory for Applied Metabolomics, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Winklehner","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"H\u00f6ftberger","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1918-1959","authenticated-orcid":false,"given":"Greisa","family":"Vila","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8212-0545","authenticated-orcid":false,"given":"Marco","family":"Andreana","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-4111","authenticated-orcid":false,"given":"Rainer","family":"Leitgeb","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Drexler","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wolfsberger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, 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Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/cncr.20412","article-title":"The prevalence of pituitary adenomas: A systematic review","volume":"101","author":"Ezzat","year":"2004","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.pathol.4.110807.092259","article-title":"The Pathogenesis of Pituitary Tumors","volume":"4","author":"Asa","year":"2009","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3171\/jns.1986.65.6.0733","article-title":"Pathology of invasive pituitary tumors with special reference to functional classification","volume":"65","author":"Scheithauer","year":"1986","journal-title":"J. Neurosurg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101278","DOI":"10.1016\/j.beem.2019.05.002","article-title":"Modern imaging of pituitary adenomas","volume":"33","author":"Bashari","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1530\/EJE-14-0144","article-title":"The incidence rate of pituitary adenomas in western Sweden for the period 2001\u20132011","volume":"171","author":"Gunnarsson","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11102-012-0454-0","article-title":"Prevalence and incidence of pituitary adenomas: A population based study in Malta","volume":"16","author":"Gruppetta","year":"2013","journal-title":"Pituitary"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s11060-013-1354-5","article-title":"Epidemiology and etiopathogenesis of pituitary adenomas","volume":"117","author":"Aflorei","year":"2014","journal-title":"J. Neuro Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.3171\/2019.3.JNS19367","article-title":"Challenging Knosp high-grade pituitary adenomas","volume":"132","author":"Micko","year":"2020","journal-title":"J. Neurosurg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1039\/C7AN01871A","article-title":"Clinical applications of infrared and Raman spectroscopy: State of play and future challenges","volume":"143","author":"Baker","year":"2018","journal-title":"Analyst"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1046\/j.1365-2818.2000.00738.x","article-title":"Multiphoton microscopy in life sciences","volume":"200","year":"2000","journal-title":"J. Microsc."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Drexler, W., and Fujimoto, J.G. (2015). Optical Coherence Tomography, Springer International Publishing.","DOI":"10.1007\/978-3-319-06419-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/10520290500138372","article-title":"The long history of hematoxylin","volume":"80","author":"Titford","year":"2005","journal-title":"Biotech. Histochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jphotobiol.2008.12.010","article-title":"Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level","volume":"95","author":"Yu","year":"2009","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1021\/ac1032325","article-title":"Second Harmonic Generation Imaging Microscopy: Applications to Diseases Diagnostics","volume":"83","author":"Campagnola","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"071412","DOI":"10.1117\/1.JBO.19.7.071412","article-title":"Optical coherence tomography today: Speed, contrast, and multimodality","volume":"19","author":"Drexler","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s11102-018-0882-6","article-title":"Diagnosing pituitary adenoma in unstained sections based on multiphoton microscopy","volume":"21","author":"Lin","year":"2018","journal-title":"Pituitary"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185401","DOI":"10.1088\/1361-6463\/ab06ec","article-title":"Prediction of the consistency of pituitary adenomas based on multiphoton microscopy","volume":"52","author":"Fang","year":"2019","journal-title":"J. Phys. D Appl. Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1364\/BOE.409987","article-title":"Towards ultrahigh resolution OCT based endoscopical pituitary gland and adenoma screening: A performance parameter evaluation","volume":"11","author":"Placzek","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bovenkamp, D., Micko, A., P\u00fcls, J., Placzek, F., H\u00f6ftberger, R., Vila, G., Leitgeb, R., Drexler, W., Andreana, M., and Wolfsberger, S. (2019). Line Scan Raman Microspectroscopy for Label-Free Diagnosis of Human Pituitary Biopsies. Molecules, 24.","DOI":"10.3390\/molecules24193577"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ejca.2011.11.036","article-title":"Radiomics: Extracting more information from medical images using advanced feature analysis","volume":"48","author":"Lambin","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s41747-018-0068-z","article-title":"Radiomics: The facts and the challenges of image analysis","volume":"2","author":"Rizzo","year":"2018","journal-title":"Eur. Radiol. Exp."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaba6156","DOI":"10.1126\/sciadv.aba6156","article-title":"Detection of response to tumor microenvironment\u2013targeted cellular immunotherapy using nano-radiomics","volume":"6","author":"Devkota","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_24","unstructured":"Lloyd, R.V., Osamura, R.Y., Kloppel, G., and Rosai, J. (2017). WHO Classification of Tumours of Endocrine Organs, WHO."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.3171\/2020.2.JNS2018","article-title":"Expression of additional transcription factors is of prognostic value for aggressive behavior of pituitary adenomas","volume":"134","author":"Micko","year":"2021","journal-title":"J. Neurosurg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1475-925X-2-13","article-title":"ScanImage: Flexible software for operating laser scanning microscopes","volume":"2","author":"Sabatini","year":"2003","journal-title":"BioMed. Eng. OnLine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1039\/c8pp00410b","article-title":"Depth resolved label-free multimodal optical imaging platform to study morpho-molecular composition of tissue","volume":"18","author":"Andreana","year":"2019","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1364\/OL.28.000905","article-title":"Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography","volume":"28","author":"Unterhuber","year":"2003","journal-title":"Opt. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19494","DOI":"10.1073\/pnas.0708425104","article-title":"In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia","volume":"104","author":"Skala","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1158\/0008-5472.CAN-09-2572","article-title":"Optical Redox Ratio Differentiates Breast Cancer Cell Lines Based on Estrogen Receptor Status","volume":"70","author":"Ostrander","year":"2010","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.aca.2011.06.043","article-title":"How to pre-process Raman spectra for reliable and stable models?","volume":"704","author":"Bocklitz","year":"2011","journal-title":"Anal. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1366\/000370203322554518","article-title":"Automated Method for Subtraction of Fluorescence from Biological Raman Spectra","volume":"57","author":"Lieber","year":"2003","journal-title":"Appl. Spectrosc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1021\/ac60214a047","article-title":"Smoothing and Differentiation of Data by Simplified Least Squares Procedures","volume":"36","author":"Savitzky","year":"1964","journal-title":"Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pdpdt.2019.05.029","article-title":"Diagnosis of cervical squamous cell carcinoma and cervical adenocarcinoma based on Raman spectroscopy and support vector machine","volume":"27","author":"Zheng","year":"2019","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101932","DOI":"10.1016\/j.pdpdt.2020.101932","article-title":"Rapid, non-invasive screening of keratitis based on Raman spectroscopy combined with multivariate statistical analysis","volume":"31","author":"Xie","year":"2020","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF01891203","article-title":"Approximating the Shapiro-Wilk W-test for non-normality","volume":"2","author":"Royston","year":"1992","journal-title":"Stat. Comput."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00259-020-05140-y","article-title":"Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET\/MRI","volume":"48","author":"Papp","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"864","DOI":"10.2967\/jnumed.118.217612","article-title":"Optimized Feature Extraction for Radiomics Analysis of 18F-FDG PET Imaging","volume":"60","author":"Papp","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Krajnc, D., Papp, L., Nakuz, T., Magometschnigg, H., Grahovac, M., Spielvogel, C., Ecsedi, B., Bago-Horvath, Z., Haug, A., and Karanikas, G. (2021). Breast Tumor Characterization Using [18F]FDG-PET\/CT Imaging Combined with Data Preprocessing and Radiomics. Cancers, 13.","DOI":"10.3390\/cancers13061249"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/2907070","article-title":"A Survey of Predictive Modeling on Imbalanced Domains","volume":"49","author":"Branco","year":"2016","journal-title":"ACM Comput. Surv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7940","DOI":"10.1109\/ACCESS.2016.2619719","article-title":"Comparing Oversampling Techniques to Handle the Class Imbalance Problem: A Customer Churn Prediction Case Study","volume":"4","author":"Amin","year":"2016","journal-title":"IEEE Access"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.suronc.2019.10.011","article-title":"Multiphoton microscopy in surgical oncology- a systematic review and guide for clinical translatability","volume":"31","author":"Goedeke","year":"2019","journal-title":"Surg. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1021\/ac034169h","article-title":"Raman Microspectroscopy: A Comparison of Point, Line, and Wide-Field Imaging Methodologies","volume":"75","author":"Schaeberle","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9417","DOI":"10.1038\/s41598-018-27752-z","article-title":"Raman Spectroscopy detects changes in Bone Mineral Quality and Collagen Cross-linkage in Staphylococcus Infected Human Bone","volume":"8","author":"Khalid","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1109\/21.44046","article-title":"Textural features corresponding to textural properties","volume":"19","author":"Amadasun","year":"1989","journal-title":"IEEE Trans. Syst. Man Cybern."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-60761-411-1_11","article-title":"Multiphoton Redox Ratio Imaging for Metabolic Monitoring In Vivo","volume":"Volume 594","author":"Armstrong","year":"2010","journal-title":"Advanced Protocols in Oxidative Stress II"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1364\/BOE.9.001375","article-title":"Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging","volume":"9","author":"Wu","year":"2018","journal-title":"Biomed. Opt. Express"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1366\/0003702011953018","article-title":"Near-Infrared Raman Spectroscopy for in vivo Detection of Cervical Precancers","volume":"55","author":"Utzinger","year":"2001","journal-title":"Appl. Spectrosc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jrs.4684","article-title":"Study of both fingerprint and high wavenumber Raman spectroscopy of pathological nasopharyngeal tissues: Fingerprint and high wavenumber Raman spectroscopy","volume":"46","author":"Huang","year":"2015","journal-title":"J. Raman Spectrosc."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Brozek-Pluska, B., Musial, J., Kordek, R., and Abramczyk, H. (2019). Analysis of Human Colon by Raman Spectroscopy and Imaging-Elucidation of Biochemical Changes in Carcinogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143398"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s10103-006-0432-8","article-title":"Raman spectroscopy and multivariate analysis of serum samples from breast cancer patients","volume":"22","year":"2007","journal-title":"Lasers Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.bbrc.2018.02.097","article-title":"Lipid metabolism and lipophagy in cancer","volume":"504","author":"Maan","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.jff.2014.10.017","article-title":"Carotenoids modulate the hallmarks of cancer cells","volume":"18","author":"Niranjana","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/bip.360230206","article-title":"Characterization of DNA structures by laser Raman spectroscopy","volume":"23","author":"Prescott","year":"1984","journal-title":"Biopolymers"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/05704928.2014.923902","article-title":"Raman Spectroscopy of Biological Tissues","volume":"50","author":"Talari","year":"2015","journal-title":"Appl. Spectrosc. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00401-017-1769-8","article-title":"The 2017 World Health Organization classification of tumors of the pituitary gland: A summary","volume":"134","author":"Lopes","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Snyder, P.J. (2011). Gonadotroph Adenomas. The Pituitary, Elsevier.","DOI":"10.1016\/B978-0-12-380926-1.10018-5"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3171\/JNS\/2008\/109\/8\/0306","article-title":"Proton magnetic resonance spectroscopy in pituitary macroadenomas: Preliminary results: Laboratory investigation","volume":"109","author":"Stadlbauer","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1038\/s41598-019-38542-6","article-title":"Ex Vivo 1H NMR study of pituitary adenomas to differentiate various immunohistochemical subtypes","volume":"9","author":"Ijare","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s40618-018-0939-4","article-title":"Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas","volume":"42","author":"Hu","year":"2018","journal-title":"J. Endocrinol. Investig."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:20Z","timestamp":1760163980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":61,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13133234"],"URL":"https:\/\/doi.org\/10.3390\/cancers13133234","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]}}}