Manyetik Rezonans Kontrast Ajanların Sıçan Beyni Üzerine Etkilerinin Histopatolojik Değerlendirilmesi
Abstract
Amaç: Gadolinyum tabanlı kontrast ajanlar (GBCA), manyetik rezonans görüntülemelerde (MRG) kontrast sağlamak amaçlı kullanılmaktadır. GBKA yapısına bağlı olarak beyin dokusu ve diğer dokularda birikim olduğu ile ilgili çalışmalar mevcuttur. Bu prospektif hayvan çalışmasında, makrosiklik iyonik (Gadoterik asit) ve lineer noniyonik (Gadodiamide) GBCA'ın çoklu enjeksiyonlarının sıçan santral sinir sistemindeki etkisini histopatolojik olarak değerlendirmek ve moleküler yapısına göre karşılaştırmak amaçlanmıştır.
Gereç ve Yöntemler: Sprague-Dawley cinsi erkek sıçanlara haftada 4 gün gün aşırı, ve her seferinde 0.1 mmol (0,2 ml/kg) /mg/kg gadodiamide ve gadoterik asid 5 hafta boyunca uygulandıktan sonra 5 hafta ilaçsız bekletildi. Onuncu haftanın sonunda sıçanlar anestezi altında uyutulup beyin dokusundan örnekler alındı. Beyin dokusu örnekleri beyin dokusu üzerine yapılmış toksisite çalışmalarına uygun bir şekilde, serebral korteksden farklı alanlarda atipik nöron ve oligodendositler körleme olarak iki histopatolog tarafından ışık mikroskobu altında skorlanarak değerlendirildi. Elde edilen veriler Kruskal-Wallis testi ile ve gruplar arası karşılaştırmalar ise Tamhane T2 ile değerlendirildi.
Bulgular: Kontrol ve serum fizyolojik grubuna ait deneklerin beyin dokusu ışık mikroskobik kesitlerinde gri ve beyaz cevher normal histolojik yapı özellikleri sergilediği izlendi. Gadodiamide uygulanmış grubun beyin dokusuna ait kesitlerinde tipik yapıda nöronlar ve oligodendrositler mevcut olup herhangi bir patoloji gözlemlenmedi. Gadoterik asit grubunda tipik yapıda oligodenraositler gözlenmekle beraber birkaç atipik nöron dışında herhangi bir patolojik yapı izlenmedi.
Sonuç: Gadolinium uzun süreli diagnostik alımlarında sıçan beyin hücrelerinde patolojik bulguya neden olmamaktadır. Bu bulgular kontrast maddenin kimyasal yapısına göre (lineer ya da makrosiklik ) farklılık göstermemektedir.
References
- Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications. Chem Rev. 1999; 99(9): 2293-352.
- Grobner T. Gadolinium - A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 2006; 21(4): 1104-8.
- Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37°C. Invest Radiol. 2008; 43(12) :817-28.
- Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: Relationship with increasing cumulative dose of a gadoliniumbased contrast material. Radiology. 2014; 270(3): 834-41.
- Huang XX, Jiang RH, Xu XQ, Zu QQ, Wu FY, Liu S, et al. Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents. J Magn Reson Imaging. 2021; 53(4): 1282-92.
- Smith APL, Marino M, Roberts J, Crowder JM, Castle J, Lowery L, et al. Clearance of gadolinium from the brain with no pathologic effect after repeated administration of gadodiamide in healthy rats: An analytical and histologic study. Radiology. 2017; 282(3): 743-51.
- Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idee JM, et al. T1-Weighted Hypersignal in the Deep Cerebellar Nuclei after Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference between Linear and Macrocyclic Agents. Invest Radiol. 2015; 50(8): 473-80.
- Tedeschi E, Caranci F, Giordano F, Angelini V, Cocozza S, Brunetti A. Gadolinium retention in the body: what we know and what we can do. Radiol Medica. 2017; 122(8): 589-600.
- Ramalho J, Ramalho M. Gadolinium deposition and chronic toxicity. Magn Reson Imaging Clin N Am. 2017;
- Al-boukai A a, Al-kassimi F a, Ibrahim GF, Shaik S a. Prediction of pulmonary hypertension in patients with or without ınterstitial lung disease. Radiology. 2011; 260(3): 875-83.
- Olchowy C, Cebulski K, Lasecki M, Chaber R, Olchowy A, Kałwak K, et al. The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity-A systematic review. PLoS One. 2017; 12(2): 1-14.
- Abnormalities I, Mcdonald RJ, Mcdonald JS, Kallmes DF, Jentoft ME, Paolini MA, et al. Gadolinium deposition in human brain tissues after contrast-enhanced mr ımaging in adult patients without. Radiology. 2017; 000(0): 1-9.
- Öner AY, Barutcu B, Aykol Ş, Tali ET. Intrathecal Contrast-enhanced magnetic resonance ımaging-related brain signal changes: residual gadolinium deposition? Invest Radiol. 2017; 52(4): 195-7.
- Lenkinski RE. Gadolinium retention and deposition revisited: how the chemical properties of gadolinium-based contrast agents and the use of animal models ınform us about the behavior of these agents in the human brain. Radiology. 2017; 285(3): 721-4.
- McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015; 275(3): 772-82.
- Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, et al. Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: Preliminary results from 9 patients with normal renal function. Invest Radiol. 2016; 51(7): 447-53.
- Jost G, Lenhard DC, Sieber MA, Lohrke J, Frenzel T, Pietsch H. Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents comparison of linear and macrocyclic agents. Invest Radiol. 2016; 51(2): 83-9.
- Mamourian AC, Hoopes PJ, Lewis LD. Visualization of intravenously administered contrast material in the CSF on fluid-attenuated inversion-recovery MR images: An in vitro and animal- model investigation. Am J Neuroradiol. 2000; 21(1): 105-11.
- Taoka T, Naganawa S. Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: Possible mechanisms for the deposition of gadolinium in the brain. Magn Reson Med Sci. 2018; 17(2): 111-9.
- Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging. 2009; 30(6): 1259-67.
- Feng XD, Xia Q, Yuan L, Huang HF, Yang X Da, Wang K. Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca 2+. Cell Biol Toxicol. 2011; 27(1): 1-12.
Abstract
Aim : Gadolinium-based contrast agents (GBCA) are used to provide contrast in magnetic resonance imaging (MRI). Previous studies have reported that repeated administrations of linear gadolinium- based contrast agents lead to their accumulation in the brain and other tissues depending on the GBKA structure. The purpose of this prospective animal study was to investigate the effect of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium-based contrast agents (GBCAs) on rat brain tissue and to compare these molecules in terms of tissue damage.
Material and Methods: Sprague-Dawley male rats were administered 0.1 mmol (0.2 ml/kg)/mg/kg gadodiamide and gadoteric acid 4 days per week for 5 weeks. He was then kept drug-free for 5 weeks. At the end of the tenth week, the rats were put to sleep under anesthesia and samples were taken from the brain tissue. Atypical neurons and oligodendocytes from brain tissue samples were scored and evaluated by two histopathologists under a light microscope. The data obtained were evaluated with the Kruskal-Wallis test and the comparisons between the groups were Tamhane T2.
Results: Gray and white matter tissue in the brain tissue of the subjects belonging to the control and saline groups were normal histological. Brain tissue sections of the gadodiamide group had typical neurons and oligodendrocytes, and no pathology was observed. However, no pathological structure was observed except for a few atypical neurons.
Conclusion: Gadolinium does not cause pathological findings in rat brain cells in long-term diagnostic intakes. These findings do not differ according to the chemical structure of the contrast agent (linear or macrocyclic).
References
- Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications. Chem Rev. 1999; 99(9): 2293-352.
- Grobner T. Gadolinium - A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 2006; 21(4): 1104-8.
- Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37°C. Invest Radiol. 2008; 43(12) :817-28.
- Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: Relationship with increasing cumulative dose of a gadoliniumbased contrast material. Radiology. 2014; 270(3): 834-41.
- Huang XX, Jiang RH, Xu XQ, Zu QQ, Wu FY, Liu S, et al. Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents. J Magn Reson Imaging. 2021; 53(4): 1282-92.
- Smith APL, Marino M, Roberts J, Crowder JM, Castle J, Lowery L, et al. Clearance of gadolinium from the brain with no pathologic effect after repeated administration of gadodiamide in healthy rats: An analytical and histologic study. Radiology. 2017; 282(3): 743-51.
- Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idee JM, et al. T1-Weighted Hypersignal in the Deep Cerebellar Nuclei after Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference between Linear and Macrocyclic Agents. Invest Radiol. 2015; 50(8): 473-80.
- Tedeschi E, Caranci F, Giordano F, Angelini V, Cocozza S, Brunetti A. Gadolinium retention in the body: what we know and what we can do. Radiol Medica. 2017; 122(8): 589-600.
- Ramalho J, Ramalho M. Gadolinium deposition and chronic toxicity. Magn Reson Imaging Clin N Am. 2017;
- Al-boukai A a, Al-kassimi F a, Ibrahim GF, Shaik S a. Prediction of pulmonary hypertension in patients with or without ınterstitial lung disease. Radiology. 2011; 260(3): 875-83.
- Olchowy C, Cebulski K, Lasecki M, Chaber R, Olchowy A, Kałwak K, et al. The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity-A systematic review. PLoS One. 2017; 12(2): 1-14.
- Abnormalities I, Mcdonald RJ, Mcdonald JS, Kallmes DF, Jentoft ME, Paolini MA, et al. Gadolinium deposition in human brain tissues after contrast-enhanced mr ımaging in adult patients without. Radiology. 2017; 000(0): 1-9.
- Öner AY, Barutcu B, Aykol Ş, Tali ET. Intrathecal Contrast-enhanced magnetic resonance ımaging-related brain signal changes: residual gadolinium deposition? Invest Radiol. 2017; 52(4): 195-7.
- Lenkinski RE. Gadolinium retention and deposition revisited: how the chemical properties of gadolinium-based contrast agents and the use of animal models ınform us about the behavior of these agents in the human brain. Radiology. 2017; 285(3): 721-4.
- McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015; 275(3): 772-82.
- Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, et al. Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: Preliminary results from 9 patients with normal renal function. Invest Radiol. 2016; 51(7): 447-53.
- Jost G, Lenhard DC, Sieber MA, Lohrke J, Frenzel T, Pietsch H. Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents comparison of linear and macrocyclic agents. Invest Radiol. 2016; 51(2): 83-9.
- Mamourian AC, Hoopes PJ, Lewis LD. Visualization of intravenously administered contrast material in the CSF on fluid-attenuated inversion-recovery MR images: An in vitro and animal- model investigation. Am J Neuroradiol. 2000; 21(1): 105-11.
- Taoka T, Naganawa S. Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: Possible mechanisms for the deposition of gadolinium in the brain. Magn Reson Med Sci. 2018; 17(2): 111-9.
- Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging. 2009; 30(6): 1259-67.
- Feng XD, Xia Q, Yuan L, Huang HF, Yang X Da, Wang K. Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca 2+. Cell Biol Toxicol. 2011; 27(1): 1-12.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | January 20, 2023 |
| Submission Date | March 14, 2022 |
| Published in Issue | Year 2023 Volume: 13 Issue: 1 |
