Abstract
Neuroimaging greatly expanded the fundamental understanding of brain functions, and it has revealed novel treatment options in disciplines such as neurology, neurosurgery, and neuropsychiatry. The last 30 years have witnessed a flourish of approaches that include novel opportunities to image not only structure in ever-increasing resolution but also, and perhaps more importantly, the basic mechanisms of brain work that include the roles of regional cerebral blood flow and energy metabolism, neuronal network and neurotransmitter system activity, and most recently the abnormal deposition of amyloid-beta in brain tissue and the abnormalities of second messenger cascades that likely underlie important neuropathology.
The quantification of brain images is vital to the appropriate understanding and interpretation of these experimental and clinical findings. While many brain imaging agents, such as markers of amyloid-beta in dementia, are used with the ultimate goal of application to clinical prognostication and differential diagnosis, others will be fundamental research tools for understanding new drugs, such as antipsychotics, antidepressants, and anxiolytics, as well as drugs for relief of devastating neurological disorders such as multiple sclerosis, stroke, and dementia.
This chapter provides a brief introduction to some of the quantitative methods of understanding brain work and brain functions that neuroscientists developed in the last 30 years, and it highlights their importance to future tests of treatment. Here, an overall description of the basic elements of quantification, and, in particular, mathematical modeling of dynamic brain images, is presented both to justify the role of such modeling in initial study development, and to validate specifications for use in clinical settings. Quantification and kinetic modeling are just as important as image reconstruction and structural identification of regions of interest, and they are fundamental components of all new brain imaging tools. The quantitative methods presented in this brief introduction continue to underpin the routine approaches and hence matter to most clinicians and clinician scientists involved in brain imaging.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gjedde A, Bauer WR, Wong DF (2011) Neurokinetics: The dynamics of neurobiology in vivo. Springer, New York
Kuikka JT et al (1991) Mathematical modelling in nuclear medicine. Eur J Nucl Med 18(5):351–362
Sheppard CW (1948) The theory of the study of transfers within a multi-compartment system. J Appl Phys 19(70)
Rescigno A, Beck J (1972) Compartments. In: Rosen R (ed) Foundations of mathematical biology, 1st edn. Academic, New York, pp 255–322
Rescigno A, Beck JS (1987) The use and abuse of models. J Pharmacokinet Biopharm 15(3):327–344
Gjedde A (1980) Rapid steady-state analysis of blood-brain glucose transfer in rat. Acta Physiol Scand 108(4):331–339
Gjedde A (2008) Functional brain imaging celebrates 30th anniversary. Acta Neurol Scand 117(4):219–223
Kety SS, Schmidt CF (1948) The nitrous oxide method for the quantitative determination of cerebral blood flow in man; theory, procedure and normal values. J Clin Invest 27(4):476–483
Raichle ME et al (1983) Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J Nucl Med 24(9):790–798
Ohta S et al (1996) Cerebral [15O]water clearance in humans determined by PET: I. Theory and normal values. J Cereb Blood Flow Metab 16(5):765–780
Gjedde A (1981) High- and low-affinity transport of d-glucose from blood to brain. J Neurochem 36(4):1463–1471
Ter-Pogossian MM et al (1970) The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen-15. J Clin Invest 49(2):381–391
Ohta S et al (1992) Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen. J Cereb Blood Flow Metab 12(2):179–192
Sokoloff L et al (1977) 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 28(5):897–916
Gjedde A (1982) Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Brain Res 257(2):237–274
Gjedde A et al (1985) Comparative regional analysis of 2-fluorodeoxyglucose and methylglucose uptake in brain of four stroke patients. With special reference to the regional estimation of the lumped constant. J Cereb Blood Flow Metab 5(2):163–178
Reivich M et al (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44(1):127–137
Bass L et al (2011) Analogue tracers and lumped constant in capillary beds. J Theor Biol 285(1):177–181
Hasselbalch SG et al (2001) The [18F]fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of [18F]F-fluorodeoxyglucose and glucose. J Cereb Blood Flow Metab 21(8):995–1002
Kuwabara H, Evans AC, Gjedde A (1990) Michaelis-Menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F]fluorodeoxyglucose. J Cereb Blood Flow Metab 10(2):180–189
Garnett ES, Firnau G, Nahmias C (1983) Dopamine visualized in the basal ganglia of living man. Nature 305(5930):137–138
Gjedde A et al (1991) Dopa decarboxylase activity of the living human brain. Proc Natl Acad Sci U S A 88(7):2721–2725
Kumakura Y et al (2005) PET studies of net blood-brain clearance of FDOPA to human brain: age-dependent decline of [18F]fluorodopamine storage capacity. J Cereb Blood Flow Metab 25(7):807–819
Wagner HN Jr et al (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221(4617):1264–1266
Wong DF et al (1984) Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226(4681):1393–1396
Wong DF et al (1997) Quantification of neuroreceptors in the living human brain: III. D2-like dopamine receptors: theory, validation, and changes during normal aging. J Cereb Blood Flow Metab 17(3):316–330
Wong DF, Gjedde A, Wagner HN Jr (1986) Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metab 6(2):137–146
Wong DF et al (1986) Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity. J Cereb Blood Flow Metab 6(2):147–153
Gjedde A, Wong DF (2001) Quantification of neuroreceptors in living human brain. v. endogenous neurotransmitter inhibition of haloperidol binding in psychosis. J Cereb Blood Flow Metab 21(8):982–994
Mintun MA et al (1984) A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15(3):217–227
Farde L et al (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231(4735):258–261
Gjedde A et al (2005) Mapping neuroreceptors at work: on the definition and interpretation of binding potentials after 20 years of progress. Int Rev Neurobiol 63(1):1–20
Kuhar MJ et al (1978) Dopamine receptor binding in vivo: the feasibility of autoradiographic studies. Life Sci 22(2):203–210
Innis RB et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27(9):1533–1539
Wong DF et al (1997) Quantification of neuroreceptors in the living human brain: IV Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness. J Cereb Blood Flow Metab 17(3):331–342
Wong DF et al (1998) Quantification of extracellular dopamine release in schizophrenia and cocaine use by means of TREMBLE. In: Carson RE, Herscovitch P, Daube-Witherspoon ME (eds) Quantitative functional brain imaging with positron emission tomography, 1st edn. Academic, San Diego, pp 463–468
Gjedde A et al (2010) Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking. Proc Natl Acad Sci U S A 107(8):3870–3875
Koepp MJ et al (1998) Evidence for striatal dopamine release during a video game. Nature 393(6682):266–268
Wong DF et al (2006) Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology 31(12):2716–2727
Wong DF et al (2008) Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology 33(6):1239–1251
Laruelle M, Abi-Dargham A (1999) Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol 13(4):358–371
McConathy J, Kilts CD, Goodman MM (2001) Radioligands for PET and SPECT imaging of the central noradrenergic system. CNS Spectr 6(8):704–709
Scott DJ et al (2007) Time-course of change in [11C]carfentanil and [11C]raclopride binding potential after a nonpharmacological challenge. Synapse 61(9):707–714
Maarrawi J et al (2007) Motor cortex stimulation for pain control induces changes in the endogenous opioid system. Neurology 69(9):827–834
Laruelle M et al (1997) Imaging D2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology 17(3):162–174
Yokoi F et al (2002) Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride. Neuropsychopharmacology 27(2):248–259
Acknowledgements
Global Excellence Award 2010, Capital Region, Denmark (Gjedde). NIH-NIDA midcareer award K24 DA000412 (Wong). Special thanks for technical assistance to Ayon Nandi, MS; and Rebecca Mellinger-Pilgram, BS, Johns Hopkins University.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media New York
About this protocol
Cite this protocol
Gjedde, A., Wong, D.F. (2012). Mathematical Modeling and the Quantification of Brain Dynamics. In: Gründer, G. (eds) Molecular Imaging in the Clinical Neurosciences. Neuromethods, vol 71. Humana Press, Totowa, NJ. https://doi.org/10.1007/7657_2012_55
Download citation
DOI: https://doi.org/10.1007/7657_2012_55
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-988-4
Online ISBN: 978-1-61779-989-1
eBook Packages: Springer Protocols