MR Görüntüleme ve MR Kontrast Ajanlarına Güncel Bir Bakış
Özet
Bu derleme çalışmasında, kontrastlı görüntülemenin tarihsel gelişimi, noninvazif görüntüleme teknikleri ve özellikle manyetik rezonans görüntüleme (MRG) teknolojisindeki yeri güncel veriler ışığında ele alınmaktadır. 1920'lerde sodyum iyodürün şans eseri keşfiyle başlayan süreç, zamanla iyonik ve noniyonik kontrast ajanların geliştirilmesiyle ilerlemiştir. Dokular arasında yoğunluk farkı yaratarak anatomik yapıların netleşmesini sağlayan bu maddeler; bilgisayarlı tomografi, ultrason ve MRG gibi farklı modalitelerde pozitif, negatif veya bifazik karakterde kullanılabilmektedir. Günümüzde MRG incelemelerinin büyük bir kısmı, T1 ve T2 relaksasyon sürelerini kısaltan gadolinyum, demir oksit veya manganez bazlı kontrast ajanlar yardımıyla gerçekleştirilmektedir. Bu ajanlar kimyasal yapılarına, veriliş yollarına ve vücuttaki biyodağılımlarına göre ekstraselüler, kan havuzu ya da organa özgü olarak sınıflandırılmaktadır. Her ne kadar iyotlu bileşiklere kıyasla daha güvenli kabul edilseler de toksisite, yan etkiler ve dokularda birikme gibi bazı güvenlik riskleri barındırmaktadırlar. Son yıllarda nanoteknolojideki gelişmeler sayesinde, hem tanısal görüntülemeyi hem de tedaviyi tek bir sistemde sunan "teranostik" lipozomlar ve manyetik nanopartiküller üzerine yapılan yeni nesil taşıyıcı sistem çalışmaları hız kazanmıştır. Ekonomik açıdan da büyümesini sürdüren küresel kontrast ajan pazarının, artan talep ve teknolojik inovasyonlarla birlikte milyarlarca dolarlık hacme ulaşması öngörülmektedir.
This review study addresses the historical development of contrast imaging, noninvasive imaging techniques, and particularly its role in magnetic resonance imaging (MRI) technology in light of current data. The process, which began in the 1920s with the accidental discovery of sodium iodide, progressed over time with the development of ionic and non-ionic contrast agents. These substances, which enable the visualization of anatomical structures by creating density differences between tissues, can be used in positive, negative, or biphasic characters across different modalities such as computed tomography, ultrasound, and MRI. Today, a large portion of MRI examinations is performed using gadolinium, iron oxide, or manganese-based contrast agents that shorten T1 and T2 relaxation times. These agents are classified as extracellular, blood pool, or organ-specific based on their chemical structures, administration routes, and biodistribution in the body. Although considered safer than iodinated compounds, they carry certain safety risks such as toxicity, adverse effects, and accumulation in tissues. In recent years, due to advancements in nanotechnology, research on next-generation carrier systems such as "theranostic" liposomes and magnetic nanoparticles, which combine diagnostic imaging and therapy into a single system, has gained momentum. Physically growing, the global contrast agent market is also expected to reach a volume of billions of dollars driven by increasing demand and technological innovations.
Referanslar
Özgür BC. Kontrast Maddeler Hakkında Bilinmesi Gerekenler. Endoüroloji Bülteni. 2016; 9: 23-25.
Cintaş D, İlem Özdemir D, Aşıkoğlu M. Kontrast Maddeler. Türk Farmakope Dergisi. 2019;4(3): 129-138.
Thomsen HS, Webb JA. Contrast media. In: Thomsen, Henrik S., Webb, Judith A. W (eds.) Springer Press; 2009.
Buschur M, Aspelin P. Contrast media: History and chemical properties. Interventional Cardiology Clinics. 2014; 3: 333-339.
Swick M. Intravenous urography by means of the sodium salt of 5-iodo2-pyridon-N-acetic acid. Journal of the American Medical Association. 1930;95: 1403-1409.
Zamora CA, Castillo M. Historical perspective of ımaging contrast agents. Magnetic Resonance Imaging Clinics of North America. 2017;25(4): 685-696.
Hoppe JO, Larsen A, Coulston F. Observations on the toxicity of a new urographic contrast medium, sodium 3,5-diacetamido-2,4,6-triiodobenzoate (hypaquesodium) and related compounds. Journal of Pharmacology and Experimental Therapeutics. 1956;116: 394-403.
Almén T, Boijsen E, Lindell SE. Metrizamide in angiography I. Femoral angiography. Acta radiologica: Diagnosis (Stockh). 1977;18(1): 33-38.
Quader MA, Sawmiller CJ, Sumpio BE. Radio Contrast Agents: History and Evolution. In: Chang JB, (eds.) Textbook of Angiology. 1st ed. New York: Springer; 2000. p.775-783.
Goodwill PW, Saritas EU, Croft LR, et al. X‐space MPI: Magnetic nanoparticles for safe medical imaging. Advanced Materials. 2012;24: 3870-3877.
Costa N. Understanding contrast media. Journal of Infusion Nursing. 2004;27: 302-312.
Yang J-S, Peng Y-R, Tsai S-C, et al. The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM). Biomedicine. 2018;8: 1-11.
Frangioni JV. New technologies for human cancer imaging. Journal of Clinical Oncology. 2008;26: 4012-4021.
Günay O, Gündoğdu Ö, Demir M, Tet al. Bilgisayarlı tomografi çekimlerinde lens tiroid ve oral mukoza absorbe radyasyon doz düzeylerinin belirlenmesi: Fantom çalışması. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi. 2020;6 (1): 23-27.
Oyar O. Radyolojide Temel Fizik Kavramlar. İzmir: Nobel Tıp Kitabevleri; 1998.
Caschera L, Lazzara A, Piergallini L, et al. Contrast agents in diagnostic imaging: Present and future. Pharmacological Research. 2016;110: 65-75.
Squire LF, Novelline RA. Fundamentals of radiology. Stuttgart: Schattauer; 1993.
Thorsen AJ, Lakin GE. Basic Physics of ultrasonography. Seminars in Colon and Rectal Surgery. 2010;21: 186-190.
Calliada F, Campani R, Bottinelli et al. Ultrasound contrast agents: Basic principles. European Journal of Radiology. 1998;27: 157-160.
Rhodes CJ. Magnetic resonance spectroscopy. Science Progress. 2017;100: 241-292.
Grover VP, Tognarelli JM, Crossey MM, et al. Magnetic resonance imaging: Principles and techniques: Lessons for clinicians. Journal of Clinical and Experimental Hepatology. 2015;5: 246-255.
Giunta CJ, Mainz VV. Discovery of nuclear magnetic resonance In: Pioneers of magnetic resonance. American Chemical Society; 2020. p. 3-20.
Kauffman, G. Nobel prize for MRI imaging denied to Raymond V. Damadian a decade ago. Chemical Educator. 2014;19: 73-90.
Bottomley PA. NMR imaging techniques and applications: A review. Review of Scientific Instruments. 1982;53: 1319-1337.
Geva T. Magnetic resonance ımaging: Historical perspective. Journal of cardiovascular magnetic resonance: Official journal of the Society for Cardiovascular Magnetic Resonance. 2006; 8: 573-580.
Slavkovsky P, Uhliar R. The Nobel prize in physiology or medicine in 2003 to Paul C. Lauterbur, Peter Mansfield magnetic resonance imaging. Bratislavske lekarske listy. 2004;105: 245-249.
Herek D, Karabulut N. Manyeti̇k rezonans görüntüleme. TTD Toraks Cerrahisi Bülteni. 2010;1(3): 214-222.
Orhan O. Magnetik rezonans görüntüleme mrg’nin klinik uygulamaları ve endikasyonları. Harran Üniversitesi Tıp Fakültesi Dergisi. 2008;5: 31-40.
Ibrahim MA, Hazhirkarzar B, Dublin AB. Gadolinium Magnetic Resonance Imaging. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
De Leon-Rodriguez LM, Martins AF, Pinho MC, et al. Basic MR relaxation mechanisms and contrast agent design. Journal of Magnetic Resonance Imaging. 2015;42: 545-565.
de Haen C. Conception of the first magnetic resonance imaging contrast agents: A brief history. Topics in Magnetic Resonance Imaging. 2001;12: 221-230.
Young I, Clarke G, Bailes D, et al. Enhancement of relaxation rate with paramagnetic contrast agents in NMR imaging. The Journal of Computed Tomography. 1981;5: 543-547.
van der Molen AJ, Bellin MF. Extracellular gadolinium-based contrast media: differences in diagnostic efficacy. European Journal of Radiology. 2008; 66: 168-174.
Cai X, Zhu Q, Zeng Y, et al. Manganese oxide nanoparticles as MRI contrast agents in tumor multimodal imaging and therapy. International Journal of Nanomedicine. 2019;14: 8321-8344.
Geraldes CF, Laurent S. Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media & Molecular Imaging. 2009;4: 1-23.
Xiao YD, Paudel R, Liu J, et al. MRI contrast agents: Classification and application (Review). International Journal of Molecular Medicine. 2016;38: 1319-1326.
Talbot BS, Weinberg EP. MR imaging with metal-suppression sequences for evaluation of total joint arthroplasty. Radiographics. 2016;36: 209-225.
Thunus L, Lejeune R. Overview of transition metal and lanthanide complexes as diagnostic tools. Coordination Chemistry Reviews. 1999;184: 125-155.
Hermann P, Kotek J, Kubíček V, Lukeš I. Gadolinium (III) complexes as MRI contrast agents: Ligand design and properties of the complexes. Dalton Transactions. 2008;23: 3027-3047.
Runge VM, Clanton JA, Herzer W, et al. Intravascular contrast agents suitable for magnetic resonance imaging. Radiology. 1984;153: 171-176.
Giovagnoni A, Fabbri A, Maccioni F. Oral contrast agents in MRI of the gastrointestinal tract. Abdominal Radiology. 2002;27: 367-375.
Paley M, Ros P. MRI of the gastrointestinal tract. European Radiology. 1997;7: 1387-1397.
Cordova-Fraga T, Sosa M, Hernandez-Gonzalez MA, et al. Medlar (Achras sapota L.) as oral contrast agent for MRI of the gastrointestinal tract. Applied Magnetic Resonance. 2012;42: 161-167.
Lee, Joseph KT (ed.). Computed body tomography with MRI correlation. Philadelphia : Lippincott Williams & Wilkins; 2006.
Jacobs KE, Behera D, Rosenberg J, et al. Oral manganese as an MRI contrast agent for the detection of nociceptive activity. NMR in Biomedicine. 2012;25: 563-569.
Li KC, Tart RP, Fitzsimmons JR, et al. Barium sulfate suspension as a negative oral MRI contrast agent: In vitro and human optimization studies. Magnetic Resonance Imaging. 1991;9: 141-150.
Laghi A, Paolantonio P, Iafrate F, et al. Oral contrast agents for magnetic resonance imaging of the bowel. Topics in Magnetic Resonance Imaging. 2002;13: 389-396.
Hiraishi K, Narabayashi I, Fujita O, et al. Blueberry juice: Preliminary evaluation as an oral contrast agent in gastrointestinal MR imaging. Radiology. 1995;194: 119-123.
Balzarini L, Aime S, Barbero L, et al. Magnetic resonance imaging of the gastrointestinal tract: Investigation of baby milk as a low cost contrast medium. European Journal of Radiology. 1992;15: 171-174.
Weissleder R, Bogdanov A, Papisov M. Drug targeting in magnetic resonance imaging. Magnetic Resonance Quarterly. 1992;8: 55-63.
Xiao Y-D, Paudel R, Liu J, et al. MRI contrast agents: Classification and application. International Journal of Molecular Medicine. 2016;38: 1319-1326.
Bernardino ME, Weinreb JC, Mitchell DG, et al. Safety and optimum concentration of a manganese chloride–based oral MR contrast agent. Journal of Magnetic Resonance Imaging. 1994;4: 872-876.
Radiopaedia. MRI Contrast Agents. (17/08/2022 tarihinde https://radiopaedia.org/articles/mri-contrast-agents?lang=us adresinden ulaşılmıştır).
Kim SH, Lee JM, Lee MW, et al. Sonography transmission gel as endorectal contrast agent for tumor visualization in rectal cancer. American Journal of Roentgenology. 2008;191: 186-189.
Bellin M, Vasile M, Morel-Precetti S. Currently used non-specific extracellular MR contrast media. European Radiology. 2003;13: 2688-2698.
Bellin M-F. MR contrast agents, the old and the new. European Journal of Radiology. 2006;60: 314-323.
Reimer P, Rummeny EJ, Daldrup HE, et al. Clinical results with Resovist: A phase 2 clinical trial. Radiology. 1995;195: 489-496.
Poduslo JF, Wengenack TM, Curran GL, et al. Molecular targeting of Alzheimer's amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiology of Disease. 2002;11: 315-329.
Bogdanov Jr AA, Lewin Mt, Weissleder R. Approaches and agents for imaging the vascular system. Advanced Drug Delivery Reviews. 1999;37: 279-293.
Løkling K-E, Fossheim SL, Skurtveit R, et al. pH-sensitive paramagnetic liposomes as MRI contrast agents: In vitro feasibility studies. Magnetic Resonance Imaging. 2001;19: 731-738.
Kanal E, Shellock FG. Safety reference manual on magnetic resonance imaging contrast agents. Lippincott-Raven Healthcare. 1996.
Cacheris WP, Quay SC, Rocklage SM. The relationship between thermodynamics and the toxicity of gadolinium complexes. Magnetic Resonance Imaging. 1990;8: 467-481.
Shellock FG, Kanal E. Safety of magnetic resonance imaging contrast agents. Journal of Magnetic Resonance Imaging: An Official Journal of the International Society for Magnetic Resonance in Medicine. 1999;10: 477-484.
Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. Journal of Allergy and Clinical Immunology. 1991;87: 867-872.
Kanda T, Fukusato T, Matsuda M, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 2015;276: 228-232.
Lum M, Tsiouris AJ. MRI safety considerations during pregnancy. Clinical Imaging. 2020;62: 69-75.
Estelrich J, Sánchez-Martín MJ, Busquets MA. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents. International Journal of Nanomedicine. 2015;10: 1727-1741.
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology. 2018;16(1): 1-33.
Ekinci M, Derya İÖ. Nanoteranostikler. Journal of Faculty of Pharmacy of Ankara University. 2021;45(1): 131-155.
Chistè E, Ischia G, Gerosa M, et al. Porous Si microparticles ınfiltrated with magnetic nanospheres. Nanomaterials (Basel). 2020;10(3): 463-474.
Mueller R, Moreau M, Yasmin-Karim S, et al. Imaging and characterization of sustained gadolinium nanoparticle release from next generation radiotherapy biomaterial. Nanomaterials (Basel). 2020;10(11): 2249-2262.
Sim S, Wong NK. Nanotechnology and its use in imaging and drug delivery (Review). Biomedical Reports. 2021;14(5): 1-9.
Pellico J, Ellis CM, Davis JJ. Nanoparticle-based paramagnetic contrast agents for magnetic resonance ımaging. Contrast Media & Molecular Imaging. 2019;5: 1-13.
Kostevšek N, Cheung CCL, Serša I, et al. Magneto-liposomes as MRI contrast agents: A systematic study of different liposomal formulations. Nanomaterials (Basel). 2020;10(5): 889-907.
Man F, Lammers T, T M de Rosales R. Imaging nanomedicine-based drug delivery: A review of clinical studies. Molecular Imaging and Biology. 2018;20(5): 683-695.
DataIntelo. MRI Contrast Agents Market Size, Analysis | Industry Report 2026. (25/08/2022 tarininde https://dataintelo.com/report/mri-contrast-agents-market/ adresinden ulaşılmıştır).
Türkiye İlaç ve Tıbbi Cihaz Kurumu. Türkiye İlaç Pazarı Gözlem Raporu-2. (29/08/2022 tarihinde https://www.titck.gov.tr/PortalAdmin/Uploads/UnitPageAttachment/XswrEocV.pdf adresinden ulaşılmıştır).
Future Market Insights Global and Consulting. Magnetic Resonance Imaging (MRI) Contrast Agents Market. (29/08/2022 tarihinde https://www.globenewswire.com/news-release/2022/01/25/2372992/0/en/Magnetic-Resonance-Imaging-MRI-Contrast-Agents-Market-is-reaching-a-valuation-of-U-S-1-23-Billion-by-2029-Comprehensive-Research-Report-by-FMI.html adresinden ulaşılmıştır).
