Comparison of manual and automated quantification methods of ¹²³I-ADAM

Summary:

¹²³I-ADAM is a novel radioligand for imaging of the brain serotonin transporters (SERTs). Traditionally, the analysis of brain receptor studies has been based on observer-dependent manual region of interest definitions and visual interpretation. Our aim was to create a template for automated image registrations and volume of interest (VOI) quantifications and to show that an automated quantification method of ¹²³I-ADAM is more repeatable than the manual method. Patients, methods: A template and a predefined VOI map was created from ¹²³I-ADAM scans done for healthy volunteers (n = 15). Scans of another group of healthy persons (HS, n = 12) and patients with bulimia nervosa (BN, n = 10) were automatically fitted to the template and specific binding ratios (SBRs) were calculated by using the VOI map. Manual VOI definitions were done for the HS and BN groups by both one and two observers. The repeatability of the automated method was evaluated by using the BN group. Results: For the manual method, the interobserver coefficient of repeatability was 0.61 for the HS group and 1.00 for the BN group. The intraobserver coefficient of repeatability for the BN group was 0.70. For the automated method, the coefficient of repeatability was 0.13 for SBRs in midbrain. Conclusion: An automated quantification gives valuable information in addition to visual interpretation decreasing also the total image handling time and giving clear advantages for research work. An automated method for analysing ¹²³I-ADAM binding to the brain SERT gives repeatable results for fitting the studies to the template and for calculating SBRs, and could therefore replace manual methods.

Zusammenfassung:

¹²³I-ADAM ist ein neuer Radioligand für die bildgebende Diagnostik der zerebralen Serotonintransporter (SERTs). Bisher beruhte die Analyse zerebraler Rezeptorstudien auf der Beobachter-abhängigen Definition der Bereiche besonderen Interesses und der visuellen Interpretation. Unser Ziel war, eine Schablone für automatische Bilddeckungen und für Quantifizierungen des interessierenden Volumens (VOI) zu erstellen und zu zeigen, dass eine automatische Methode zur Quantifizierung von ¹²³I-ADAM reproduzierbarer ist als die manuelle Methode. Patienten, Methoden: Aus ¹²³I-ADAM-Scans, die bei Gesunden durchgeführt wurden (n = 15), wurden eine Schablone und eine vordefinierte VOI-Karte erstellt. Scans einer anderen Gruppe Gesunder (GP, n = 12) und von Patienten mit Bulimia nervosa (BN, n = 10) wurden automatisch in die Schablone eingepasst, und es wurden spezielle Bindungsquotienten (specific binding ratios – SBRs) unter Verwendung der VOIKarte berechnet. Die manuellen VOI-Definitionen wurden für die GP- und BN-Gruppe sowohl von einem als auch von zwei Beobachtern vorgenommen. Die Reproduzierbarkeit der automatischen Methode wurde anhand der BN-Gruppe ausgewertet. Ergebnisse: Bei der manuellen Methode betrug der Interbeobachter-Koeffizient der Reproduzierbarkeit bei der GP-Gruppe 0,61 und bei der BN-Gruppe 1,00. Der Intrabeobachter-Koeffizient der Reproduzierbarkeit für die BN-Gruppe betrug 0,70. Bei der automatischen Methode betrug der Koeffizient der Reproduzierbarkeit für die SBRs im Mittelhirn 0,13. Schlussfolgerung: Eine automatische Quantifizierung liefert zusätzlich zur visuellen Interpretation wertvolle Informationen und verkürzt gleichzeitig die Gesamt-Bildbearbeitungszeit und bietet eindeutige Vorteile für wissenschaftliche Arbeiten. Eine automatische Methode für die Analyse der ¹²³I-ADAM-Bindung an den zerebralen SERT liefert reproduzierbare Ergebnisse für die Einpassung der Studien in die Schablone und für die Berechnung der SBRs; sie könnte manuelle Methoden ersetzen.

Key words:

Brain quantification - single photon emission tomography - serotonin receptor - SERT

Schlüsselwörter:

Gehirnquantifizierung - Single-Photonenemissions-Computertomographie - Serotoninrezeptor - SERT

• References

• 1 Acton PD, Choi SR, Hou C. et al. Quantification of serotonin transporters in nonhuman primates using ¹²³I-ADAM and SPECT. J Nucl Med 2001; 42: 1556-62.
• 2 Acton PD, Kung MP, Mu M. et al. Single-photon emission tomography imaging of serotonin transporters in the non-human primate brain with the selective radioligand ¹²³I-IDAM. Eur J Nucl Med 1999; 26: 854-61.
• 3 Acton PD, Mu M, Plossl K. et al. Single-photon emission tomography imaging of serotonin transporters in the nonhuman primate brain with ¹²³I-ODAM. Eur J Nucl Med 1999; 26: 1359-62.
• 4 Acton PD, Pilowsky LS, Kung HF. et al. Automatic segmentation of dynamic neuroreceptor singlephoton emission tomography images using fuzzy clustering. Eur J Nucl Med 1999; 26: 581-90.
• 5 Ahonen A, Koskela A, Kauppinen T. et al. Serotonin transporter availability in patients with symptomatic bulimia using a novel SPET ligand ¹²³I-ADAM. Eur J Nucl Med 2003; 30 suppl S214.
• 6 Ahonen AK, Kauppinen TA, Heikman P. et al. I-123 labeled ADAM – a selective novel radioligand for imaging of serotonin transporters in the human brain. J Nucl Med 2002; 43 suppl 232P.
• 7 Anderluh MB, Tchanturia K, Rabe-Hesketh S. et al. Childhood obsessive-compulsive personality traits in adult women with eating disorders: defining a broader eating disorder phenotype. Am J Psychiatry 2003; 160: 242-7.
• 8 Asembaum S, Füger B, Diemling M. et al. ¹²³IADAM SPECT – a new method for investigating serotonin transporter in humans. Eur J Nucl Med 2003; 30 suppl S309.
• 9 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307-10.
• 10 British Standards Institution. Precision of the methods. 1: Guide for the determination and reproducibility of a standard test method (BS5497, part 1). London, UK: BSI; 1979
• 11 Catafau AM. Brain SPECT in Clinical Practice. Part I: Perfusion. J Nucl Med 2001; 42: 259-71.
• 12 Cortes R, Soriano E, Pazos A. et al. Autoradiography of antidepressant binding sites in the human brain: localization using 3H-imipramine and 3H-paroxetine. Neuroscience 1988; 27: 473-96.
• 13 First MB, Spitzer RL, Gibbon M. et al. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Nonpatient Edition. New York, USA: Biometrics Res., New York State Psychiatr. Inst.; 2002
• 14 Garner DM, Olmsted MP, Polivy J. et al. Comparison between weight-preoccupied women and anorexia nervosa. Psychosom Med 1984; 46: 255-66.
• 15 Habraken JBA, Booij J, Slomka P. et al. Quantification and visualization of defects of the functional dopaminergic system using an automatic algorithm. J Nucl Med 1999; 40: 1091-7.
• 16 Huang WS, Ma KH, Chou YH. et al. ¹²³I-ADAM SPECT in healthy nonhuman primates: a preliminary report. Ann Nucl Med Sci 2002; 15: 27-32.
• 17 Hudson HM, Larkin RS. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 1994; 13: 601-9.
• 18 Kang X, Bertrand O, Alho K. et al. Local landmark- based mapping of human auditory cortex. Neuroimage 2004; 22: 1657-70.
• 19 Kaprio J, Pulkkinen L, Rose RJ. Genetic and environmental factors in health-related behaviors: studies on Finnish twins and twin families. Twin Res 2002; 5: 366-71.
• 20 Kauppinen TA, Bergstrom KA, Heikman P. et al. Biodistribution and radiation dosimetry of ¹²³I-ADAM in healthy human subjects: preliminary results. Eur J Nucl Med Mol Imaging 2003; 30: 132-6.
• 21 Kuikka JT. Quantitative accuracy of serotonergic neurotransmission imaging with high-resolution ¹²³I SPECT. Nuklearmedizin 2004; 43: 185-9.
• 22 Kung MP, Hou C, Oya S. et al. Characterization of ¹²³I-IDAM as a novel single-photon emission tomography tracer for serotonin transporters. Eur J Nucl Med 1999; 26: 844-53.
• 23 Lin KJ, Ye XX, Yen TC. et al. Biodistribution study of ¹²³I-ADAM in mice: correlation with whole body autoradiography. Nucl Med Biol 2002; 29: 643-50.
• 24 Maes F, Collignon A, Vandermeulen D. et al. Multimodality image registration by maximization of mutual information. IEEE Trans Med Imaging 1997; 16: 187-98.
• 25 Oya S, Choi SR, Hou C. et al. 2-(2-dimethylaminomethyl- phenyl-thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand. Nuc Med Biol 2000; 27: 249-54.
• 26 Radau PE, Linke R, Slomka PJ. et al. Optimization of automated quantification of ¹²³I-IBZM uptake in the striatum applied to Parkinsonism. J Nucl Med 2000; 41: 220-7.
• 27 Slomka P, Stephenson J, Reid R. et al. Automated template-based quantification of brain SPECT. In: De Deyn PP, Dierckx RA, Alavi A. et al. (eds). SPECT in neurology and psychiatry. London: John Libbey Company Ltd.; 1997: 507-12.
• 28 Van Laere K, de Sadeleer C, Dobbelair A. Quantification of ^99mTc-HMPAO brain SPET in two series of healthy volunteers using different tripleheaded SPET configurations: normal databases and methodological considerations. Nuc Med Commun 1999; 20: 1031-40.
• 29 Van Laere K, Koole M, D’Asseler Y. et al. Automated stereotactic standardization of brain SPECT receptor data using single-photon transmission images. J Nucl Med 2001; 42: 361-75.
• 30 Van Laere KJ, Warwick J, Versijpt J. et al. Analysis of clinical brain SPECT data based on anatomic standardization and reference to normal data: An ROC-based comparison of visual, semiquantitative, and voxel-based methods. J Nucl Med 2002; 43: 458-69.
• 31 Wade T, Heath AC, Abraham S. et al. Assessing the prevalence of eating disorders in an Australian twin population. Aust N Z J Psychiatry 1996; 30: 845-51.