We review statistical methods being applied in four key areas connected with PET and SPECT neuroimaging: (i) image reconstruction (briefly); (ii) tracer-kinetic, or compartmental, modelling; (iii) inference from region-of-interest data; (iv) inference at the pixel or voxel level. Under the last heading, we pay particular attention to the analysis of data from serial scans. We conclude by identifying some topics for future statistical research.
Get full access to this article
View all access options for this article.
References
1.
Herman GTImage reconstruction from projections. New York : Academic Press, 1980.
2.
Vardi Y., Shepp LA, Kaufman L.A statistical model for positron emission tomography. Journal of the American Statistical Association1985; 80:8-20.
3.
Green PJBayesian reconstructions from emission tomography data using a modified EM algorithm. IEEE Transactions on Medical Imaging1990; 9: 84-93.
4.
Snyder, DL, Politte DGImage reconstruction from list-mode data in an emission tomography system having time-of-flight measurements. IEEE Transactions on Nuclear Science1983; NS-20: 1843-49.
5.
Defrise M., Townsend DW, Clark R.Three-dimensional image reconstruction from complete projections. Physics in Medicine andBiology1989; 34: 573-87.
6.
Defrise M., Townsend DW, Geissbuhler A.Implementation of three-dimensional image reconstruction for multi-ring tomographs. Physics in Medicine andBiology1990; 35: 1361-72.
7.
Townsend DW, Geissbuhler A., Defrise M., et al. Fully three-dimensional reconstruction for a PET camera with retractable septa. IEEE Transactions on Medical Imaging1991;10: 505-12.
8.
Defrise M., Townsend DE, Deconinck F.Statistical noise in three-dimensional positron tomography. Physics in Medicine and Biology1990; 35: 131-38.
9.
Jones T., Bailey DL, Watson Jdg, Schnorr L., Frackowiak Rsj.Activation studies in 3D PET: evaluation of true signal gain. Annals of Nuclear Medicine1993; 7: S64-S65.
10.
Cherry SR, Woods RP, Hoffman EJ, Mazziotta JCImproved detection of focal cerebral blood flow changes using three-dimensional positron emission tomography. Journal of Cerebral Blood Flow andMetabolism1993; 13: 630-38.
11.
Ghambir SS, Huang S-C., Hawkins RA, Phelps MEA study of the single compartment tracer kinetic model for the measurement of local cerebral blood flow using 15O-water and positron emission tomography . Journal of Cerebral Blood Flow and Metabolism1987; 7: 13-20.
12.
Iida H.Methodological and theoretical considerations in the H215O-CBF method. Annals of Nuclear Medicine1993; 7: S9-S10.
13.
Sokoloff L. , Reivich M., Kennedy C. et al. The [14C] deoxyglucose method for the measurement of local cerebral glucose utilisation: theory, procedure, and normal values in the conscious and anesthetized albino rat . Journal of Neurochemistry1977; 28: 897-916.
14.
Reivich M., Alavi A., Greenberg J. et al. Metabolic mapping of functional cerebral activity in man using the 18F-2-Fluoro-2-Deoxyglucose technique. Journal of Computer Assisted Tomography1978; 2: 656-60.
15.
Reivich M., Kuhl DE, Wolf A. et al. The [18F] fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circulation Research1979; 44: 127-37.
16.
Reivich M., Alavi A., Greenberg JH et al. Use of 2-Deoxy-D-[1-11C]glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects . Journal of Cerebral Blood Flow and Metabolism1982; 2: 307-19.
17.
Phelps ME, Huang SC, Hoffman EJ, Sehn C., Sokoloff L., Kuhl DETomographic measurement of cerebral glucose metabolic rate in humans with (F-18)2-Fluoro-2-Deoxy-D-glucose: validation of method. Annals of Neurology1979; 6: 371-88.
18.
Huang SC, Phelps ME, Hoffman EJ, Sidens K., Selin CL, Kuhl DENoninvasive determination of local cerebral metabolic rate of glucose in man . American Journal of Physiology1980; 238: B69-B82.
19.
Gjedde A., Wienhard K., Heiss W-D. et al. 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. Journal of Cerebral Blood Flow and Metabolism1985; 5: 163-78.
20.
Reivich M., Alavi A., Wolf A. et al. Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. Journal of Cerebral Blood Flow and Metabolism1985; 5: 179-92.
21.
Wong DF, Gjedde A., Wagner HN Jr.Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. Journal of Cerebral Blood Flow andMetabolism1986; 6:137-46.
22.
Wong DF, Gjedde A., Wagner HN Jr et al. Quantification of neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity. Journal of Cerebral Blood Flow andMetabolism1986; 6: 147-53.
23.
Perlmutter JS, Larson KB, Raichle ME et al. Strategies for in vivo measurement of receptor binding using positron emission tomography. Journal of Cerebral Blood Flow andMetabolism1986; 6: 154-69.
24.
Huang S-C., Barrio JR, Phelps MENeuroreceptor assay with positron emission tomography: equilibrium versus dynamic approaches. Journal of Cerebral Blood Flow andMetabolism1986; 6: 515-21.
25.
Leenders KL, Gibbs JM, Frackowiak Rsj, Lammertsma AA, Jones T.Positron emission tomography of the brain: new possibilities for the investigation of human cerebral pathophysiology. Progress in Neurobiology1984; 23: 1-38.
26.
Ginsberg MD , Lockwood, AH, Busto R. et al. A simplified in vivo autoradiographic strategy for the determination of regional cerebral blood flow by positron emission tomography: theoretical considerations and validation studies in the rat. Journal of Cerebral Blood Flow andMetabolism1982; 2: 89-98.
27.
Carson RE, Huang S-C., Green MVWeighted integration method for local cerebral blood flow measurements with positron emission tomography. Journal of Cerebral Blood Flow andMetabolism1986; 6: 245-58.
28.
Carson REParameter estimation in positron emission tomography. In: Phelps M, Mazziotta J, Schelbert H eds. Positron emission tomography and autoradiography: principles and applications for the brain and heart. New York: Raven Press, 1986: 347-90.
29.
Snyder DLParameter estimation for dynamic studies in emission tomography systems having list mode data. IEEE Transactions on NuclearScience1984; NS-31: 925-31.
30.
Patlak CS, Blasberg RG, Fernstermacher JDGraphical evaluation of blood-to-brain transfer constants from mutliple time uptake data. Journal of Cerebral Blood Flow andMetabolism1983; 3:1-7.
31.
Patlak CS, Blasberg RGGraphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. Journal of Cerebral Blood Flow andMetabolism1985 ; 5: 584-90.
32.
Logan J., Fowler JS, Volkow ND et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-Cocaine PET studies in human subjects . Journal of Cerebral Blood Flow and Metabolism1998; 10: 740-47.
33.
Farde L., Hakan H., Ehrin E., Sedvall G.Quantitative analysis of D2 Dopamine receptor binding in the living human brain by PET. Science1982; 231: 258-61.
34.
Cunningham VJ, Jones T.Spectral analysis of dynamic PET studies. Journal of Cerebral Blood Flow andMetabolism1993; 13: 15-23.
35.
Carmago EE, Szabo Z., Links JM, Sostre S., Dannals RF, Wagner HN Jr. The influence of biological and technical factors on the variability of global and regional brain metabolism of 2-[18F]Fluoro-2-deoxy-D-glucose . Journal of Cerebral Blood Flow and Metabolism1992; 12: 281-90.
36.
Yoshii F., Barker WW, Chang JY et al. Sensitivity of cerebral glucose metabolism of age, gender, brain volume, brain atrophy, and cerebrovascular risk factors. Journal of Cerebral Blood Flow and Metabolism1988; 8: 654-61.
37.
Videen TO, Perlmutter JS, Mintun MA, Raichle MERegional correction of positron emission tomography data for the effects of cerebral atrophy. Journal of Cerebral Blood Flow andMetabolism1988; 8: 662-70.
38.
Martin AJ, Friston KJ, Colebatch JG, Frackowiak Rsj.Decreases in regional cerebral blood flow with normal aging. Journal of Cerebral Blood Flow and Metabolism1991 ; 11: 684-89.
39.
McCrory SJ, Ford I.Multivariate analysis of SPECT images with illustrations in Alzheimer's disease . Statistics in Medicine1991; 10: 1711-18.
40.
Greenhouse SW, Geisser S.On methods in the analysis of profile data . Psychometrika1959; 49: 257-67.
41.
Huynh H., Feldt LSEstimation of the Box correction for degrees of freedom for sample data in randomised block and split-plot designs. Journal of Educational Statistics1976; 1:69-82.
42.
Clark CM, Ammann W., Martin Wrw, Ty P., Hayden MRThe FDG/PET methodology for early detection of disease onset: a statistical model. Journal of Cerebral Blood Flow and Metabolism1991;11A96-A102.
43.
Azari NP, Pettigrew KD, Schapiro MB et al. Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data. Journal of Cerebral Blood Flow andMetabolism1993; 13: 438-47.
44.
Worsley KJ, Evans AC, Strother SC, Tyler JLA linear spatial correlation model, with applications to positron emission tomography. Journal of the American Statistical Association1991; 86: 55-67.
45.
Tyler JL, Strother SC, Zatorre RJ, Alivisatos B., Worsley KJ, Diksic M.Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography. Journal of Nuclear Medicine1988; 29: 631-42.
46.
Horwitz B., Duara R., Rapoport SIIntercorrelations of glucose metabolic rates between brain regions: application to healthy males in a state of reduced sensory input. Journal of Cerebral Blood Flow andMetabolism1984 ; 4: 484-99.
47.
Metter EJ, Riege WH, Kuhl DE, Phelps MECerebral metabolic relationships for selected brain regions in healthy adults . Journal of Cerebral Blood Flow and Metabolism1984; 4: 1-7.
48.
Metter EJ, Riege WH, Kameyama M., Kuhl DE, Phelps MECerebral metabolic relationships for selected brain regions in Alzheimer's, Huntington's and Parkinson's diseases. Journal of Cerebral Blood Flow and Metabolism1984; 4: 500-506.
49.
Ford I.Confounded correlations: statistical limitations in the analysis of interregional relationships of cerebral metabolic activity. Journal of Cerebral Blood Flow andMetabolism1986;6:385-88.
50.
Horwitz B., Duara R., Rapoport SIAge differences in intercorrelations between regional cerebral metabolic rates for glucose. Annals of Neurology1986 ; 19: 60-67.
51.
Clark C., Carson R., Kessler R. et al. Alternative statistical models for the examination of clinical positron emission tomography/ fluorodeoxyglucose data. Journal of Cerebral Blood Flow andMetabolism1985; 5: 142-50.
52.
Moeller JR, Strother SC, Sidtis JJ, Rottenberg DAScaled subprofile model: a statistical approach to the analysis of functional patterns in positron emission tomographic data. Journal of Cerebral Blood Flow andMetabolism1987; 7: 649-58.
53.
Moeller JR, Strother SCA regional covariance approach to the analysis of functional patterns in positron emission tomographic data. Journal of Cerebral Blood Flow andMetabolism1991; 11: A121-A135.
54.
McLaughlin T., Steinberg B., Christensen B., Law I., Parving A., Friberg L.Potential language and attentional networks revealed through factor analysis of rCBF data measured with SPECT. Journal of Cerebral Blood Flow and Metabolism1992; 12: 535-45.
55.
Friston KJ, Passingham RE, Nutt JG, Heather JD, Sawle GV, Frackowiak Rsj.Localisation in PET images: direct fitting of the intercommissural (AC-PC) line. Journal of Cerebral Blood Flow andMetabolism1989; 9: 690-95.
56.
Friston KJ, Frith CD, Liddle PF, Frackowiak Rsj.Plastic transformation of PET images. Journal of Computer Assisted Tomography1991; 15: 634-39.
57.
Woods RP, Cherry SR, Mazziotta JCRapid automated algorithm for aligning and reslicing PET images. Journal of Computer Assisted Tomography1992;16: 620-33.
Eberl S., Kanno I., Fulton RR et al. Automatic 3D spatial alignment for correcting inter-study patient motion in serial PET studies. Annals of Nuclear Medicine1993; 7: S76-77.
60.
Seitz RJ, Bohm C., Greitz T. et al. Specification and selection of regions of interest in a computerised brain atlas. Journal of Cerebral Blood Flow andMetabolism1991; 11: A64-A68.
61.
Fox PT, Perlmutter JS, Raichle MEA stereotactic method of anatomical localization for positron emission tomography . Journal of Computer Assisted Tomography1985; 9: 141-53.
62.
Watson Jdg, Myers R., Frackowiak Rsj et al. Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. Cerebral Cortex1993; 3: 79-94.
63.
Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak Rsj.The relationship between global and local changes in PET scans. Journal of Cerebral Blood Flow and Metabolism1990 ; 10: 458-66.
64.
Worsley KJ, Evans AC, Marrett S., Neelin P.A three-dimensional statistical analysis for CBF activation studies in human brain. Journal of Cerebral Blood Flow andMetabolism1992; 12: 900-18.
65.
Fox PT, Mintun MA, Reiman EM, Raichle MEEnhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images. Journal of Cerebral Blood Flow andMetabolism1988; 8: 642-53.
66.
Hochberg Y., Tamhane ACMultiple comparison procedures. New York: John Wiley and Sons, 1987: 1-5.
67.
Friston KJ, Frith CD, Liddle, PF, Frackowiak Rsj.Comparing functional (PET) images: the assessment of significant change . Journal of Cerebral Blood Flow and Metabolism1991;11: 690-99.
68.
Adler RJThe geometry of random fields. New York: John Wiley and Sons, 1981.
69.
Roland PE, Levin B., Kawashima R., Åkerman S.Cluster analysis of quantitative 150-Butanol activation subtraction images. Journal of Cerebral Blood Flow andMetabolism1993 ; 13: S731.
70.
Poline J-B. , Mazoyer BMAnalysis of individual positron emission tomography activation maps by detection of high signal-tonoise clusters. Journal of Cerebral Blood Flow andMetabolism1993; 13: 425-37.
71.
Blair RC, Karniski W.Distribution-free statistical analyses of surface and volumetric maps . In: Thatcher RW, John ER, Huerta M eds. Functional neuroimaging: technical foundations. San Diego : Academic Press, 1994 (in press).
72.
Holmes AP, Blair RC, Watson Jdg, Ford I.Nonparametric analysis of statistic images from functional mapping experiments. Journal of Cerebral Blood Flow andMetabolism1994 (in press).
73.
Edgington ESRandomization Tests. New York: Marcel Dekker, 1980.
74.
Ardekani BA , Braun M., Hutton BFImproved quantification with the use of anatomical information in PET image reconstruction. Annals of Nuclear Medicine1993; 7: S66-S67.
75.
Silbersweig DA, Stern E., Frith CD et al. Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H215O regional cerebral blood flow three-dimensional imaging technique . Journal of Cerebral Blood Flow and Metabolism1993; 13: 617-29.
76.
Holmes AP, Ford I.A Bayesian approach to significance testing for statistic images from PET . Annals of Nuclear Medicine1993; 7: S106-S107.
77.
Friston KJ, Frith CD, Liddle PF, Frackowiak Rsj.Functional connectivity: the principal-component analysis of large (PET) data sets. Journal of Cerebral Blood Flow andMetabolism1993;13:5-14.
78.
Belliveau JWExploring human brain function using MRI. Annals of Nuclear Medicine1993; 7: S7-S8.
