Abstract
Positron emission tomography (PET) in combination with receptor-selective high-affinity radioligands allows the characterization of neuroreceptor distributions in the living human brain. Thus far, the visualization and quantification of receptors with PET have been limited to series of two-dimensional (2D) image planes of the anatomic receptor distribution. The development of high-resolution PET has increased the number of planes to approximately 50, supplying an excessive amount of image information from a single experiment. The inherent limitations of 2D techniques make them insufficient to apprehend and efficiently analyze this cumbersome amount of data. In the present communication we describe procedures to visualize and quantify in three dimensions (3D) the total image information from the compound set of 47 2D planes of a PET experiment using commercially available software. Three-dimensional computer graphic and volume rendering techniques were used to analyze and display the results. For the experimental application the benzodiazepine (BZ) antagonist [t1C]flumazenil was used as radioligand to visualize the BZ receptor (BZR) population in the brain of a healthy human subject. Three-dimensional images of the radioligand binding receptor population were displayed with regard to volume and form in relation to the corresponding anatomic structures in the brain reconstructed from MR images. The volume-rendering technique allowed the inspection of PET signals representing BZR populations in the interior of the hemisphere as viewed from the medial projection. Thresholding and seeding techniques were used to define volumes and quantities. Using the PET data and volume rendering, the total amount of cerebral BZRs (NCerebrum) and the apparent volume they take into account (Vapp BZR, Cerebrum) could be calculated for the first time using an automated procedure. The cerebrum of the healthy subject contained 17.6 nmol of BZRs in a voulume of approximately 1.25 L. The principles and application of the technical development described offer new dimensions to clinical neuroscience and should be practically useful for automated quantitative determination of neuroreceptor number in brain regions of patients with neuropsychiatric disorders and in relation to drug treatment.
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References
Andreasen NC, Oleary DS, Arndt S, Cizadlo T, Hurtig R, Rezai K, Watkins GL, Ponto LLB, Hichwa RD (1995a) Short-term and long-term verbal memory: a positron emission tomography study. Proc Natl Acad Sci USA 92:5111–5115
Andreasen NC, Swayze V, Oleary DS, Nopoulos P, Cizadlo T, Harris G, Arndt S, Flaum M (1995b) Abnormalities in midline attentional circuitry in schizophrenia: evidence from magnetic resonance and positron emission tomography. Eur Neuropsychopharmacol 5: 37–41
Argiro VJ (1990) Seeing in volume. Pixel 1:35–39
Bergström M, Boetius J, Eriksson L, Greitz T, Ribbe T, Widén L (1981) Head fixation device for reproducible position alignment in transmission CT and positron emission tomography. J Comput Assist Tomogr 5:136–141
Blomqvist G, Pauli S, Farde L, Eriksson L, Persson A, Halldin C (1990) Maps of receptor binding parameters in the human brain: a kinetic analysis of PET measurements. Eur J Nucl Med 16:257–265
Catmull EA (1974) Subdivision algorithm for computer display of curved surfaces. PhD thesis report UTEC-CSc-74-133, Computer Science Department, University of Utah, Salt Lake City, Utah
Drebin RA, Carpenter L, Hanrahan P (1988) Volume rendering. Comput Graph 22:65–74
Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231:258–261
Fiez JA, Raichle ME, Balota DA, Tallal P, Petersen SE (1996) PET activation of posterior temporal regions during auditory word presentation and verb generation. Cereb Cortex 6: 1–10
Foley JD, Dam A van, Feiner SK, Hughes JF (1990) The Phong lighting model. In: Computer graphics: principles and practice, 2nd edn. Addison-Wesley, London, pp 729–731
Friston KJ, Frith CD, Liddle PF, Frackoviack RSJ (1991) Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11: 690–699
Frost J, Meltzer C, Zubieta J, Links J, Brakeman P, Stumpf M, Kruger M (1996) MR-based correction of partial volume effects in brain PET imaging. In: Myers R, Cunningham V, Bailey D, Jones T (eds) Quantification of brain function using PET. Academic Press, New York, pp 152–157
Hall H, Litton J-E, Halldin C, Kopp J, Sedvall G (1992) Studies on the binding of [3H]flumazenil and [3H]sarmazenil in post mortem human brain. Hum Psychopharmacol 7: 367–377
Hall H, Sedvall G, Magnusson O, Kopp J, Halldin C, Farde L (1994) Distribution of D1- and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology 11(4): 245–256
Halldin C, Stone-Elander S, Thorell J-O, Persson A, Sedvall G (1988) 11C-labeling of Ro 15-1788 in two different positions, and also I IC-labeling of its main metabolite Ro 15-3890, for PET studies of benzodiazepine receptors. Appl Radiat Isot 39: 993–997
Harris LD, Robb RA, Yuen TS, Ritman EL (1978) Non-invasive numerical dissection and display of anatomic structure using computerized X-ray tomography. Proc SPIE 152:10–18
Herman GT, Liu HK (1979) Three-dimensional display of organs from computed tomograms. Comput Graph Image Process 9(1): 1–21
Kuhar MJ, Lloyd DG, Appel N, Loats HL (1991) Imaging receptors by computer-assisted approaches. J Chem Neuroanat 4: 319–327
Lammertsma A, Lassen N, Prevett M et al. (1993) Quantification of benzodiazepin receptors in vivo using IIC-flumazenil: application of the steady-state principle. In: Uemura K, Lassen NA, Jones T, Kanno I (eds) Quantification of brain function. Excerpta Medica, Amsterdam, pp 303–311
Lassen NA (1992) Neuroreceptor quantitation in vivo by the steady-state principle using constant infusion or bolus injection of radioactive tracers. J Cereb Blood Flow Metab 12:709–716
Lassen NA, Bartenstein PA, Lammertsma AA, Prevett MC, Turton DR, Luthra SK, Osman S, Bloomfield PM, Jones T, Patsalos PN et al. (1995) Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle. J Cereb Blood Flow Metab 15 (1): 152–165
Latchaw RE, Ugurbil K, Hu X (1995) Functional MR imaging of perceptual and cognitive functions. Neuroimaging Clin North Am 5:193–205
Levoy M (1988) Display of surfaces from volume data. IEEE Comput Graph Applications 8:29–37
Lorenson WE, Harvey CC (1987) Marching cubes: a high-resolution 3-D surface construction algorithm. Comput Graph ACM SIGGRAPH ’87 Conference Proceedings
Mazière M, Hantraye P, Prenant C, Sastre J, Comar D (1984) Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4Himidazo[1,5-a][1, 4]benzodiazepine-3-carboxylate (RO15.1788 11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiat Isot 35:973–978
Persson A, Ehrin E, Farde L, Litton J-E, Mindus P, Sedvall G (1985) Imaging of 11-C-labeled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography. J Psychiatr Res 19:609–622
Persson A, Pauli S, Halldin C, Stone-Elander S, Farde L, Sjögren I, Sedvall G (1989) Saturation analysis of specific I IC Ro 151788 binding in the human neocortex using positron emission tomography. Hum Psychopharmacol 4:21–31
Price JC, Mayberg HS, Dannals RF, Wilson AA, Ravert HT, Sadzot B, Rattner Z, Kimball A, Feldman MA, Frost JJ (1993) Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil. J Cereb Blood Flow Metab 13(4):656–667
Raichle ME (1994) Images of the mind: studies with modern imaging techniques. Annu Rev Psychol 45:333–356
Roland PE, Zilles K (1994) Brain atlases: a new research tool. Trends Neurosci 17:458–467
Russ JC (1995) The image processing handbook, 2nd edn. CRC Press, Boca Raton, Florida
Sedvall G, Farde L, Persson A, Wiesel F-A (1986) Imaging of neurotransmitter receptors in the living human brain. Arch Gen Psychiatry 43:995–1005
Sedvall G, Karlsson P, Lundin A, Anvret M, Suhara T, Halldin C, Farde L (1994) Dopamine D 1 receptor number: a sensitive PET marker for early brain degeneration in Huntington’s disease. Eur Arch Psychiatry Clin Neurosci 243:249–255
Sedvall G, Farde L (1995) Dopamine receptors in schizophrenia. Lancet 346:743–749
Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (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 28:897–916
Toga AW (1990) Three-dimensional neuroimaging. Raven Press, New York
Van Zandt WL, Argiro VJ (1989) A new inlook on life. UNIX Rev 7:52–57
Wagner HNJ, Burns HD, Dannals RF, Wong DF, Långström B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221:1264–1266
Watt A (1991) Volume rendering. In: 3D Computer graphics. Addison-Wesley, London, pp 313–319
Weinhard K, Dahlbom M, Eriksson L, Michel C, Bruckbauer T (1994) The ECAT EXACT HR: performance of a new highresolution positron scanner. J Comput Assist Tomogr 18: 110–118
Wilhems J, Van Gelder A (1991) A coherent projection approach for direct volume rendering. Comput Graph 25:275–284
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Pauli, S., Sedvall, G. Three-dimensional visualization and quantification of the benzodiazepine receptor population within a living human brain using PET and MRI. Eur Arch Psychiatry Clin Nuerosci 247, 61–70 (1997). https://doi.org/10.1007/BF02900195
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DOI: https://doi.org/10.1007/BF02900195