Research on Biomedical Engineering
Research on Biomedical Engineering
Review article

Methods for quantification of cerebral glycolytic metabolism using 2-deoxy-2-[18F]fluoroglucose in small animals - Published Ahead of Print

Silvana Prando, Carla Rachel Ono, Cecil Chow Robilotta, Marcelo Tatit Sapienza


Introduction: The use of the same imaging and quantification techniques in small animals and clinical studies presents the opportunity for direct translational research in drug discovery and development, in neuropharmacological basis of neurological and psychiatric diseases, and in optimization of drug therapy. Thus, positron emission tomography
(PET) studies in rodents can bridge the gap between pre-clinical and clinical research. The aim should be to find a method with capability to measure, without compromising accuracy, glucose distribution in the structures of the brain, which can also be used in pathological situations and with applicability for other substances than glucose analogue. Methods: This is a systematic review of several assessment techniques available, including visual and quantitative methods that enable the investigation of the transport mechanisms and enzymes involved in glucose metabolism in the brain. In addition to the ex vivo methods, PET with glucose analogues allows in vivo analyses using qualitative, semiquantitative and quantitative methods. Results: These techniques provide different results, and the applicability of a specific method is related to the purpose of the study and the multiple factors that may interfere in the process. Conclusion: This review provides a solid background of tools and quantification methods for medical physicists and other professionals interested in cerebral glycolytic metabolism quantification in experimental animals. It also addresses the main factors related to animals, equipment and techniques that are used, as well as how these factors should be understood to better interpret the results obtained from experiments.


Nuclear medicine, Quantification, Positron emission tomography, Metabolism, FDG, Brain.


Abdel el Motal SM, Sharp GW. Inhibition of glucose-induced insulin release by xylazine. Endocrinology. 1985; 116(6):2337-40. PMid:2986946.

Adams MC, Turkington TG, Wilson JM, Wong TZ. A systematic review of the factors affecting accuracy of measurements. AJR Am J Roentgenol. 2010; 195(2):310-20. PMid:20651185.

Alf MF, Duarte J, Lei H, Krämer S, Mlynarik V, Schibli R, Gruetter R. MRS glucose mapping and PET joining forces: re-evaluation of the lumped constant in the rat brain under isoflurane anaesthesia. J Neurochem. 2014; 129(4):672-82. PMid:24471521.

Alf MF, Duarte J, Schibli R, Gruetter R, Krämer S. Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study. J Nucl Med. 2013; 54(12):2153-60. PMid:24159048.

Allen-Auerbach M, Weber WA. Measuring response with FDG-PET: methodological aspects. Oncologist. 2009; 14(4):369-77. PMid:19357228.

Alstrup AK, Smith D. Anaesthesia for positron emission tomography scanning of animals brains. Lab Anim. 2013; 47(1):12-8. PMid:23349451.

Blake P, Johnson B, VanMeter J. Positron emission tomography (PET) and single photon emission computed tomography (SPECT): clinical applications. J Neuroophthalmol. 2003; 23(1):34-41. PMid:12616088.

Boellaard R, Krak N, Hoekstra O, Lammertsma A. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake value: a simulation study. J Nucl Med. 2004; 45(9):1519-27. PMid:15347719.

Boellaard R, van Lingen A, van Balen SC, Hoving BG, Lammertsma AA. Characteristics of a new fully programmable blood-sampling device for monitoring blood radioactivity during PET. Eur J Nucl Med. 2001; 28(1):81-9. PMid:11202456.

Buchert R, Wilke F, Chakrabarti B, Martin B, Brenner W, Mester J, Clausen M. Adjusted scaling of FDG positron emission tomography images for statistical evaluation in patients with suspected Alzheimer’s disease. J Neuroimaging. 2005; 15(4):348-55. PMid:16254400.

Byrnes KR, Wilson C, Brabazon F, von Leden R, Jurgens J, Oakes T, Selwyn RG. FDG-PET imaging in mild traumatic brain injury: a critical review. Front Neuroenergetics. 2014; 5:13-24. PMid:24409143.

Carson RE, Channing MA, Blasberg RG, Dunn BB, Cohen RM, Rice KC, Herscovitch P. Comparison of bolus and infusion methods for receptor quantitation: Application to [18F] cyclofoxy and positron emission tomography. J Cereb Blood Flow Metab. 1993; 13(1):24-42. PMid:8380178.

Casteels C, Martinez E, Bormans G, Camon L, Vera N, Baekelandt V, Planas AM, van Laere K. Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism. Eur J Nucl Med Mol Imaging. 2010; 37(12):2354-63. PMid:20680268.

Casteels C, Vermaelen P, Nuyts J, van der Linden A, Baekelandt V, Mortelmans L, Bormans G, van Laere K. Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med. 2006; 47(11):1858-66. PMid:17079820.

Catafau AM. Brain SPECT in clinical practice. Part I: perfusion. J Nucl Med. 2001; 42(2):259-71. PMid:11216525.

Chan E, Kovacevic N, Ho SKY, Henkelman RM, Henderson JT. Development of a high resolution three-dimensional surgical atlas of the murine head for strains 129S1/SvImJ and C57Bl/6J using magnetic resonance imaging and micro-computed tomography. Neuroscience. 2007; 144(2):604-15. PMid:17101233.

Claeys J, Mertens K, D’Asseler Y, Goethals I. Normoglycemic plasma glucose levels affects F-18 FDG uptake in the brain. Ann Nucl Med. 2010; 24(6):501-5. PMid:20237872.

Coelho C, Hjornevik T, Courivaud F, Willoch F. Anatomical standardization of small animal brain FDG-PET images using synthetic functional template: experimental comparison with anatomical template. J Neurosci Methods. 2011; 199(1):166-72. PMid:21550366.

Convert L, Morin-Brassard G, Cadorette J, Archambault M, Bentourkia M, Lecomte R. A new tool for molecular imaging: the microvolumetric {beta} blood counter. J Nucl Med. 2007; 48(7):1197-1206. PMid:17574990.

Crane PD, Pardridge WM, Braun LD, Oldendorf WH. Kinetics of transport and phosphorylation of 2-fluoro-2-deoxy-D-glucose in rat brain. J Neurochem. 1983; 40(1):160-7. PMid:6848656.

Crone C. Facilitated transfer of glucose from blood into brain tissue. J Physiol. 1965; 181(1):103-13. PMid:5866278.

Cui Y, Toyoda H, Sako T, Onoe K, Hayashinaka E, Wada Y, Yokoyama C, Onoe H, Kataoka Y, Watanabe Y. A voxel-based analysis of brain activity in high-order trigeminal pathway in the rat induced by cortical spreading depression. Neuroimage. 2015; 108:17-22. PMid:25536498.

Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-

Gateau P, Fulop T, Rapoport SI. Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition. 2011; 27(1):3-20. PMid:21035308.

Cunningham VJ, Jones T. Spectral analysis of dynamic PET studies. J Cereb Blood Flow Metab. 1993; 13(1):15-23. PMid:8417003.

Deleye S, Verhaeghe J, Wyffels L, Dedeurwaerdere S, Stroobants S, Staelens S. Towards a reproducible protocol for repetitive and semi-quantitative rat brain imaging with 18F-FDG: exemplified in a memantine pharmacological challenge. Neuroimage. 2014; 96:276-87. PMid:24736171.

Dienel GA. Fueling and imaging brain activation. ASN Neuro. 2012; 4(5):267-321. PMid:22612861.

Dukart J, Mueller K, Horstmann A, Vogt B, Frisch S, Barthel H, Becker G, Möller HE, Villringer A, Sabri O, Schroeter ML. Differential effects of global and cerebellar normalization on detection and differentiation of dementia in FDG-PET studies. Neuroimage. 2010; 49(2):1490-5. PMid:19770055.

Dukart J, Perneczky R, Förster S, Barthel H, Diehl-Schmid J, Draganski B, Obrig H, Santarnecchi E, Drzezga A, Fellgiebel A, Frackowiak R, Kurz A, Müller K, Sabri O, Schroeter ML, Yakushev I. Reference cluster normalization improves detection of frontotemporal lobar degeneration by means of FDG-PET. PLoS One. 2013; 8(2):e55415. PMid:23451025.

Durand E, Besson F. How is the standard uptake value (SUV) linked to the influx constant in Sokoloff’s model for 18F-FDG? Med Nucl (Paris). 2015; 39(1):11-7.

Fang YH, Muzic R Jr. Spillover and partial-volume correction for image-derived input functions for small-animal 18F-FDG PET studies. J Nucl Med. 2008; 49(4):606-14. PMid:18344438.

Fasihi M, Mikhael W. Overview of current biomedical image segmentation methods. In: International Conference on Computational Science and Computational Intelligence (CSCI); Dec 2016 15-16; Las Vegas. Las Vegas: IEEE; 2016, p. 803-8. doi:

Frey EC, Humm J, Ljungberg M. Accuracy and precision of radioactivity quantification in nuclear medicine images. Semin Nucl Med. 2012; 42(3):208-18. PMid:22475429.

Friston K. Statistics I: Experimental design and statistical parametric mapping. In: Toga A, Mazziotta J, editors. Brain Mapping: The Methods. 2nd ed. San Diego: Academic Press; 2002. p. 605-10.

Friston K. Introduction. In: Friston K, Ashburner J, Kiebel S, Nichols T, Penny W. Statistical parametric mapping: the analysis of functional brain imaging. San Diego: Academic Press; 2007. p. 3-9.

Friston KJ, Holmes AP, Worsley KJ, Poline J-P, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp. 1994; 2(4):189-210.

Frumberg DB, Fernando M, Lee D, Biegon A, Schiffer W. Metabolic and behavioral deficits following a routine surgical procedure in rats. Brain Res. 2007; 1144:209-18. PMid:17346680.

Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA. Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med. 2006; 47(6):999-1006. PMid:16741310.

Germino M, Gallezot JD, Yan J, Carson RE. Direct reconstruction of parametric images for brain PET with event-by-event motion correction: evaluation in two tracers across count levels. Phys Med Biol. 2017; 62(13):5344-64. PMid:28504644.

Gispert JD, Pascau J, Reig S, Garcia-Barreno P, Desco M. Mapas de estadísticos paramétricos (SPM) en medicina nuclear. Rev Esp Med Nucl. 2003; 22(1):43-53. PMid:12550034.

Golla SSV, Adriaanse SM, Yaqub M, Windhorst AD, Lammertsma AA, van Berckel BNM, Boellaard R. Model selection criteria for dynamic brain PET studies. EJNMMI Phys. 2017; 4(1):30. PMid:29209862.

Green LA, Gambhir SS, Srinivasan A, Banerjee PK, Hoh CK, Cherry SR, Sharfstein S, Barrio JR, Herschman HR, Phelps ME. Noninvasive methods for quantitating blood time-activity curves from mouse PET images obtained with fluorine-18-fluorodeoxyglucose. J Nucl Med. 1998; 39(4):729-34. PMid:9544690.

Gunn RN, Gunn S, Cunningham V. Positron emission tomography compartmental models. J Cereb Blood Flow Metab. 2001; 21(6):635-52. PMid:11488533.

Gustafson C, Tretiak O, Bertrand L, Nissanov J. Design and implementation of software for assembly and browsing of 3D brain atlases. Comput Methods Programs Biomed. 2004; 74(1):53-61. PMid:14992826.

Hargreaves RJ, Rabiner E. Translational PET imaging research. Neurobiol Dis. 2014; 61:32-8. PMid:24055214.

Huang S, Phelps M. Principles of tracer kinetic modeling in positron emission tomography and autoradiography. In: Mazziota J, Phelps M, Schelbert H editors. Positron Emission Tomography and Autoradiography. Philadelphia: Raven Press; 1985. p. 287-346.

Huang S-C, Wong K-P. Dynamic PET imaging. In: M Dahlbom, editor. Physics of PET and SPECT imaging: Imaging in medical diagnosis and therapy. Boca Raton: CRC Press, Taylor & Francis Group; 2017. p. 321-36.

Huang SC. Anatomy of SUV: Standardized Uptake Value. Nucl Med Biol. 2000; 27(7):643-6. PMid:11091106.
Ido T, Wan CN, Casella V, Fowler J, Wolf A, Reivich M, Kuhl DE. Labeled 2-deoxy-D-glucose analogs. 18F-labeled 2-deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2-fluoro-D-glucose. J Labelled Comp Radiopharm. 1978; 14(2):175-83.

Ingvar D. Mental-illness and regional brain metabolism. Trends Neurosci. 1982; 5:199-203.

Ishizu K, Nishizawa S, Yonekura Y, Sadato N, Magata Y, Tamaki N, Tsuchida T, Okazawa H, Miyatake S, Ishikawa M, et al. Effects of hyperglycemia on FDG uptake in human brain and glioma. J Nucl Med. 1994; 35(7):1104-9. PMid:8014665.

Jadvar H, Parker J. PET radiotracers. In Jadvar H, Parker J editors. Clinical PET and PET/CT. London: Springer; 2005. p. 45-67.

Jagoda EM, Vaquero J, Seidel J, Green M, Eckelman W. Experiment assessment of mass effects in the rat: implications for small animal PET imaging. Nucl Med Biol. 2004; 31(6):771-9. PMid:15246368.

Jensen TL, Kiersgaard MK, Sorensen DB, Mikkelsen LF. Fasting of mice: a review. Lab Anim. 2013; 47(4):225-40. PMid:24025567.

Karsch K, He Q, Duan Y. A fast, semiautomatic brain structure segmentation algorithm for magnetic resonance imaging. In: IEEE International Conference on Bioinformatics and Biomedicine; 2009 Nov 1-4; Washington, DC. Washington: IEEE Computer Society; 2009. p. 297-302. DOI: 10.1109/BIBM.2009.40.

Kawasaki K, Ishii K, Saito Y, Oda K, Kimura Y, Ishiwata K. Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping. Ann Nucl Med. 2008; 22(3):191-200. PMid:18498034.

Keramida G, Anagnostopoulos C, Peters M. The extent to which standardized uptake values reflect FDG phosphorylation in the liver and spleen as functions of time after injection of 18F-fluorodeoxyglucose. EJNMMI Res. 2017; 7(1):13. PMid:28176243.

Kim J, Herrero P, Sharp T, Laforest R, Rowland DJ, Tai Y-C, Lewis JS, Welch MJ. Minimally invasive method of determining blood input function from PET images in rodents. J Nucl Med. 2006; 47(2):330-6. PMid:16455640.

Knol RJ, de Bruin K, de Jong J, van Eck-Smit B, Booij J. In vitro and ex vivo storage phosphor imaging of short-living radioisotopes. J Neurosci Methods. 2008; 168(2):341-57. PMid:18164072.

Köroğlu R, Köksal İ, Şimşek FS, Gezer F, Kekilli E, Ünal B. Considering the relationship between quantitative parameters and prognostic factors in breast cancer: can mean standardized uptake value be an alternative to maximum standardized uptake value? World J Nucl Med. 2017; 16(4):275-80. PMid:29033675.

Kotasidis F, Tsoumpas C, Rahmim A. Advanced kinetic modeling strategies: towards adoption in clinical PET imaging. Clin Transl Imaging. 2014; 2(3):219-37.

Krak NC, Boellaard R, Hoekstra O, Twisk J, Hoekstra C, Lammertsma A. Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging. 2005; 32(3):294-301. PMid:15791438.

Krohn KA, Muzi MSA, Spence AM. What is in a number? The FDG lumped constant in the rat brain. J Nucl Med. 2007; 48(1):5-7. PMid:17204692.

Kung M-P, Kung H. Mass effect of injection dose in small rodent imaging by SPECT and PET. Nucl Med Biol. 2005; 32(7):673-8. PMid:16243641.

Kyme AZ, Zhou VW, Meikle SR, Baldock C, Fulton RR. Optimized motion tracking for positron emission tomography studies of brain function in awake rats. PLoS One. 2011; 6(7):e21727. PMid:21747951.

Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen T-M, Chi Chin M, Chong J, Crook BE,

Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong H-W, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C,

Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf K-R, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Feng Yuan X, Zhang B, Zwingman TA, Jones AR. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007; 445(7124):168-76. PMid:17151600.

Leybaert L, De Bock M, van Moorhem M, Decrock E, de Vuyst E. Neurobarrier coupling in the brain: adjusting glucose entry with demand. J Neurosci Res. 2007; 85(15):3213-20. PMid:17265466.

Litaudon P, Bouillot C, Zimmer L, Costes N, Ravel N. Activity in the rat olfactory cortex is correlated with behavioral response to odor: a microPET study. Brain Struct Funct. 2017; 222(1):577-86. PMid:27194619.

MacKenzie-Graham A, Lee EF, Dinov ID, Bota M, Shattuck DW, Ruffins S, Yuan H, Konstantinidis F, Pitiot A, Ding Y, Hu G, Jacobs RE, Toga AW. A multimodal, multidimensional atlas of the C57BL/6J mouse brain. J Anat. 2004; 204(2):93-102. PMid:15032916.

Matsumura A, Mizokawa S, Tanaka M, Wada Y, Nozaki S, Nakamura F, Shiomi S, Ochi H, Watanabe Y. Assessment of microPET performance in analyzing the rat brain under different types of anesthesia: comparison between quantitative data obtained with microPET and ex vivo autoradiography. Neuroimage. 2003; 20(4):2040-50. PMid:14683708.

McLaughlin KJ, Gomez JL, Baran SE, Conrad CD. The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Res. 2007; 1161(1):56-64. PMid:17603026.

Meyer M, Le-Bras L, Fernandez P, Zanotti-Fregonara P. Standardized input function for 18F-FDG PET studies in mice: a cautionary study. PLoS One. 2017; 12(1):e0168667. PMid:28125579.

Meyer PT, Circiumaru V, Cardi CA, Thomas DH, Bal H, Acton PD. Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function. Eur J Nucl Med Mol Imaging. 2006; 33(8):948-54. PMid:16699768.

Mizuma H, Shukuri M, Hayashi T, Watanabe Y, Onoe H. Establishment of in vivo brain imaging method in conscious mice. J Nucl Med. 2010; 51(7):1068-75. PMid:20554730.

Moore AH, Osteen C, Chatziioannou A, Hovda D, Cherry S. Quantitative assessment of longitudinal metabolic changes in vivo after traumatic brain injury in the adult rat using FDG-microPET. J Cereb Blood Flow Metab. 2000; 20(10):1492-501. PMid:11043912.

Munk OL, Keiding S, Bass L. A method to estimate dispersion in sampling catheters and to calculate dispersion-free blood time-activity curves. Med Phys. 2008; 35(8):3471-81. PMid:18777907.

Nehlig A. Cerebral energy metabolism, glucose transport and blood flow: changes with maturation and adaptation to hypoglycaemia. Diabetes Metab. 1997; 23(1):18-29. PMid:9059763.

Nie B, Chen K, Zhao S, Liu J, Gu X, Yao Q, Hui J, Zhang Z, Teng G, Zhao C, Shan B. A rat brain MRI template with digital stereotaxic atlas of fine anatomical delineations in paxinos space and its automated application in voxel-wise analysis. Hum Brain Mapp. 2013; 34(6):1306-18. PMid:22287270.
Nie B, Liu H, Chen K, Jiang X, Shan B. A statistical parametric mapping toolbox used for voxel-wise analysis of FDG-PET images of rat brain. PLoS One. 2014; 9(9):e108295. PMid:25259529.

Orzi F, Lucignani G, Dow-Edwards D, Namba H, Nehlig A, Patlak CS, Pettigrew K, Schuier F, Sokoloff L. Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat. J Cereb Blood Flow Metab. 1988; 8(3):346-56. PMid:3366796.

Paquet N, Albert A, Foidart J, Hustinx R. Within-patient variability of 18F-FDG: standardized uptake values in normal tissues. J Nucl Med. 2004; 45(5):784-8. PMid:15136627.

Park TY, Nishida KS, Wilson CM, Jaiswal S, Scott J, Hoy AR, Selwyn RG, Dardzinski BJ, Choi KH. Effects of isoflurane anesthesia and intravenous morphine self-administration on regional glucose metabolism ([18F]FDG-PET) of male Sprague-Dawley rats. Eur J Neurosci. 2017; 45(7):922-31. PMid:28196306.

Patlak CS, Blasberg R, Fenstermacher J. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab. 1983; 3(1):1-7. PMid:6822610.

Patlak CS, Blasberg R. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab. 1985; 5(4):584-90. PMid:4055928.

Paxinos G, Watson C. The rat brain in stereotaxic coordinates: compact. 7th ed. San Diego: Elsevier Academic Press; 2017.

Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in man with (18F) fluorodeoxyglucose: Validation of method. Ann Neurol. 1979; 6(5):371-88. PMid:117743.

Poussier S, Maskali F, Vexiau G, Verger A, Boutley H, Karcher G, Raffo E, Marie PY. Quantitative SPM analysis involving an adaptive template may be applied to [18F]FDG PET images of the rat brain. Mol Imaging Biol. 2017; 19(5):731-5. PMid:28108871.

Reimold M, Slifstein M, Heinz A, Mueller-Schauenburg W, Bares R. Effect of spatial smoothing on t-maps: arguments for going back from t-maps to masked contrast images. J Cereb Blood Flow Metab. 2006; 26(6):751-9. PMid:16208316.

Roy CS, Sherrington C. On the Regulation of the blood-supply of the brain. J Physiol. 1890; 11(1-2):85-158, 17. PMid:16991945.

Sapienza M, Buchpiguel CA. Bases da tomografia por emissão de pósitrons (PET). In Hironaka F, Sapienza M, Ono C, Lima M, Buchpiguel C, editors. Medicina nuclear: princípios e aplicações. 2nd ed. Rio de Janeiro: Atheneu; 2017. p. 372-7.

Schiffer WK, Mirrione M, Dewey S. Optimizing experimental protocols for quantitative behavioral imaging with 18F-FDG in rodents. J Nucl Med. 2007; 48(2):277-87. PMid:17268026.

Schmidt KC, Smith C. Resolution, sensitivity and precision with autoradiography and small animal positron emission tomography: implications for functional brain imaging in animal research. Nucl Med Biol. 2005; 32(7):719-25. PMid:16243647.

Schuier F, Orzi F, Suda S, Lucignani G, Kennedy C, Sokoloff L. Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: effects of hyperglycemia in the rat. J Cereb Blood Flow Metab. 1990; 10(6):765-73. PMid:2211874.

Schulz D, Southekal S, Junnarkar SS, Pratte JF, Purschke ML, Stoll SP, Ravindranath B, Maramraju SH, Krishnamoorthy S, Henn FA, O’Connor P, Woody CL, Schlyer DJ, Vaska P. Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph. Nat Methods. 2011; 8(4):347-52. PMid:21399637.

Schwarz AJ, Danckaert A, Reese T, Gozzi A, Paxinos G, Watson C, Merlo-Pich EV, Bifone A. A stereotaxic MRI template set for rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI. Neuroimage. 2006; 32(2):538-50. PMid:16784876.

Schweinhardt P, Fransson P, Olson L, Spenger C, Andersson J. A template for spatial normalisation of MR images of the rat brain. J Neurosci Methods. 2003; 129(2):105-13. PMid:14511814.

Senda M, Nishizawa S, Yonekura Y, Mukai T, Saji H, Konishi J, Torizuka K. Measurement of arterial time-activity curve by monitoring continuously drawn arterial blood with an external detector: errors and corrections. Ann Nucl Med. 1988; 2(1):7-12. PMid:3275106.

Sijbesma JW, Zhou X, Vállez García D, Houwertjes MC, Doorduin J, Kwizera C, Maas B, Meerlo P, Dierckx RA, Slart RH, Elsinga PH, van Waarde A. Novel approach to repeated arterial blood sampling in small animal PET: application in a test-retest study with the adenosine A1 receptor ligand [11C]MPDX. Mol Imaging Biol. 2016; 18(5):715-23. PMid:27091332.

Silva-Rodríguez J, Aguiar P, Domínguez-Prado I, Fierro P, Ruibal Á. Simulated FDG-PET studies for the assessment of SUV quantification methods. Rev Esp Med Nucl Imagen Mol. 2015; 34(1):13-8. PMid:25107595.

Silverman DH. Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging. J Nucl Med. 2004; 45(4):594-607. PMid:15073255.

Sokoloff L, Reivich M, Kennedy C, Rosiers MHD, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977; 28(5):897-16. PMid:864466.

Sokoloff L. Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab. 1981b; 1(1):7-36. PMid:7035471.

Sokoloff L. The deoxyglucose method: theory and practice. Eur Neurol. 1981a; 20(3):137-45. PMid:7262108.

Solon EG. Autoradiography techniques and quantification of drug distribution. Cell Tissue Res. 2015; 360(1):87-107. PMid:25604842.

Sossi V, Ruth T. MicroPET imaging: in vivo biochemistry in small animals. J Neural Transm. 2005; 112(3):319-30. PMid:15723157.

Spangler-Bickell MG, de Laat B, Fulton R, Bormans G, Nuyts J. The effect of isoflurane on 18F-FDG uptake in the rat brain: a fully conscious dynamic PET study using motion compensation. EJNMMI Res. 2016; 6(1):86. PMid:27888500.

Spence A, Muzi M, Graham M, O’Sullivan F, Krohn K, Link J, Lewellen TK, Lewellen B, Freeman SD, Berger MS, Ojemann GA. Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant. J Nucl Med. 1998; 39(3):440-8. PMid:9529289.

Stout D, Pastuskovas C. In vitro methods for in vivo quantitation of PET and SPECT imaging probes: autoradiography and gamma counting. In: Kiessling F, Pichler BJ, editors. Small animal imaging: basics and practical guide. 2nd ed. Heidelberg: Springer; 2011. p. 511-25.

Strauss LG, Pan L, Cheng C, Haberkorn U, Dimitrakopoulou-Strauss A. Shortened acquisition protocols for the quantitative assessment of the 2-tissue-compartment model using dynamic PET/CT 18F-FDG studies. J Nucl Med. 2011; 52(3):379-85. PMid:21321263.

Suda S, Shinohara M, Miyaoka M, Lucignani G, Kennedy C, Sokoloff L. The lumped constant of the deoxyglucose method in hypoglycemia: effects of moderate hypoglycemia on local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab. 1990; 10(4):499-509. PMid:2347881.

Sugawara Y, Zasadny K, Grossman H, Francis I, Clarke M, Wahl R. Germ cell tumor: differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling. Radiology. 1999; 211(1):249-56. PMid:10189480.

Sung KK, Jang DP, Lee S, Kim M, Lee SY, Kim YB, Park CW, Cho ZH. Neural responses in rat brain during acute immobilization stress: a [18F]FDG micro PET imaging study. Neuroimage. 2009; 44(3):1074-80. PMid:18952183. doi: 10.1016/j.neuroimage.2008.09.032.

Swanson LW. Brain maps: structure of the rat brain. San Diego: Elsevier Academic Press; 2004.

Takikawa S, Dhawan V, Spetsieris P, Robeson W, Chaly T, Dahl R, Margouleff D, Eidelberg D. Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve. Radiology. 1993; 188(1):131-6. PMid:8511286.

Thie JA. Clarification of a fractional uptake concept. J Nucl Med. 1995; 36(4):711-2. PMid:7699475.

Toyama H, Ichise M, Liow JS, Vines D, Seneca N, Modell K, Seidel J, Green MV, Innis RB. Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol. 2004; 31(2):251-6. PMid:15013491.

Tsukada H. Animal PET research with non-human primates for drug development in pre-clinical stage - The Hamamatsu experience. In: Elsinga PH, Waarde A van, Paans AMJ, Dierckx RAJO, editors. Trends on the role of PET in drug development. Singapore: Word Scientific; 2012. p. 241-60.

Tylski P, Stute S, Grotus N, Doyeux K, Hapdey S, Gardin I, Vanderlinden B, Buvat I. Comparative assessment of methods for estimating tumor volume and standardized uptake value in (18)F-FDG PET. J Nucl Med. 2010; 51(2):268-76. PMid:20080896.

Vállez Garcia D, Casteels C, Schwarz A, Dierckx R, Koole M, Doorduin J. A standardized method for the construction of tracer specific PET and SPECT rat brain templates: validation and implementation of a toolbox. PLoS One. 2015; 10(3):e0122363. PMid:25823005.
van den Hoff J. Kinetic modeling. In Kiessling F, Pichler BJ, editors. Small animal imaging: basics and practical guide. 2nd ed. Heidelberg: Springer; 2011. p. 559-80.

Vanhove C, Bankstahl J, Krämer S, Visser E, Belcari N, Vandenberghe S. Accurate molecular imaging of small animals taking into account animal models, handling, anaesthesia, quality control and imaging system performance. EJNMMI Phys. 2015; 2(1):31. PMid:26560138.

Vaska P, Woody CL, Schlyer DJ, Shokouhi S, Stoll SP, Pratte JF et al. RatCAP: miniaturized head-mounted PET for conscious rodent brain imaging. IEEE Trans Nucl Sci. 2004; 51(5 II):2718-22. doi:10.1109/NSSMIC.2003.1352223.

Veronese M, Rizzo G, Bertoldo A, Turkheimer FE. Spectral analysis of dynamic PET studies: a review of 20 years of method developments and applications. Comput Math Methods Med. 2016; 2016:1-15. PMid:28050197.

Viglianti BL, Wong K, Wimer S, Parameswaran A, Nan B, Ky C, Townsend DM, Rubello D, Frey KA, Gross MD. Effect of hyperglycemia on brain and liver 18F-FDG standardized uptake value (FDG SUV) measured by quantitative positron emission tomography (PET) imaging. Biomed Pharmacother. 2017; 88:1038-45. PMid:28192877.

Wang G, Qi J. Direct estimation of kinetic parametric images for dynamic PET. Theranostics. 2013; 3(10):802-15. PMid:24396500.

Weber B, Burger C, Biro P, Buck A. A femoral arteriovenous shunt facilitates arterial whole blood sampling in animals. Eur J Nucl Med Mol Imaging. 2002; 29(3):319-23. PMid:12002705.

Weber WA, Ziegler S, Thodtmann R, Hanauske AR, Schwaiger M. Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med. 1999; 40(11):1771-7. PMid:10565769.

Weisenberger AG, Gleason SS, Goddard J, Kross B, Majewski S, Meikle SR. A restraint-free small animal SPECT imaging system with motion tracking. IEEE Trans Nucl Sci. 2005; 52(3I):638-44. doi:10.1109/TNS.2005.851399.

Welch A, Mingarelli M, Riedel G, Platt B. Mapping changes in mouse brain metabolism with PET/CT. J Nucl Med. 2013; 54(11):1946-53. PMid:24009277.

White DRR, Houston A, Sampson W, Wilkins G. Intra-and interoperator variations in region-of-interest drawing and their effect on the measurement of glomerular filtration rates. Clin Nucl Med. 1999; 24(3):177-81. PMid:10069728.

Yakushev I, Hammers A, Fellgiebel A, Schmidtmann I, Scheurich A, Buchholz H-G, Peters J, Bartenstein P, Lieb K, Schreckenberger M. SPM-based count normalization provides excellent discrimination of mild Alzheimer’s disease and amnestic mild cognitive impairment from healthy aging. Neuroimage. 2009; 44(1):43-50. PMid:18691659.

Zanotti-Fregonara P, Chen K, Liow JS, Fujita M, Innis RB. Image derived input function for brain PET studies: many challenges and few opportunities. J Cereb Blood Flow Metab. 2011; 31(10):1986-98. PMid:21811289.

Zanotti-Fregonara P, Fadaili IM, Maroy R, Comtat C, Souloumiac A, Jan S, Ribeiro MJ, Gaura V, Bar-Hen A, Trébossen R. Comparison of eight methods for the estimation of the image-derived input function in dynamic [(18)F]-FDG PET human brain studies. J Cereb Blood Flow Metab. 2009; 29(11):1825-35. PMid:19584890.

Zanotti-Fregonara P, Hirvonen J, Lyoo CH, Zoghbi SS, Rallis-Frutos D, Huestis MA, Morse C, Pike VW, Innis RB. Population-based input function modeling for [18F]FMPEP-d2, an inverse agonist radioligand for cannabinoid CB1 receptors: validation in clinical studies. PLoS One. 2013; 8(4):e60231. PMid:23577094.

Zanotti-Fregonara P, Liow JS, Comtat C, Zoghbi SS, Zhang Y, Pike VW, Fujita M, Innis RB. Image-derived input function in PET brain studies: blood-based methods are resistant to motion artifacts. Nucl Med Commun. 2012; 33(9):982-9. PMid:22760300.

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