Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT.
OBJECTIVE
The serotonin system is involved in many physiological functions and clinical conditions. Serotonergic neurons originate from the raphe nuclei in the brainstem, and reliable estimates of receptor/transporter availability in the raphe in vivo are thus of interest. Though positron emission tomography (PET) can be used to quantify receptor distribution in the brain, high noise levels prevent reliable estimation of radioligand binding in small regions such as the raphe. For this purpose, parametric imaging in combination with high-resolution PET systems may provide images with reduced noise levels and sufficient contrast for reliable quantification. This study examined the potential to evaluate radioligand binding in brainstem nuclei, and assessed the effect of improved resolution on the outcome measures.


METHODS
For comparative purposes, radioligand binding was measured with an ECAT EXACT HR PET system (resolution about 4.5 mm FWHM) and a high-resolution research tomograph (HRRT) system (resolution about 1.5 mm FWHM). Six subjects were examined with both systems on the same day using the serotonin transporter radioligand [(11)C]MADAM. Parametric images of binding potential (BP (ND)) were obtained using a wavelet-aided approach. Regions of interest (ROIs) were delineated using a threshold-based semiautomatic delineation procedure for five brainstem structures. Regional BP (ND) values were estimated by applying the ROIs to the parametric images, and the percentage difference in BP (ND) between the systems was calculated.


RESULTS
Signals for [(11)C]MADAM binding were obtained for all five brainstem structures. Overall, the HRRT provided 30-40 % higher BP (ND) values than the HR (p = 0.0017), independent of thresholds used in the ROI delineation procedure.


CONCLUSIONS
The methodology used enabled the estimation of [(11)C]MADAM binding in the small nuclei of the brainstem. Differences in the BP (ND) values calculated using data from the two systems were mainly attributable to their differing resolutions. The estimated BP (ND) values provided lower across-subject variability than those previously obtained using compartment analysis. This procedure may therefore facilitate quantitative studies of receptor/transporter availability in the brainstem.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Karolinska Hospital, R5:02, SE-171 76, Stockholm, Sweden. martin.schain@ki.se
Martin
M
Schain
Miklós
M
Tóth
Zsolt
Z
Cselényi
Ryosuke
R
Arakawa
Christer
C
Halldin
Lars
L
Farde
Andrea
A
Varrone
D000328:Adult; D001331:Automation; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging; D001931:Brain Mapping / Q000379:methods*; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D001330:Electronic Data Processing; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D019636:Neurodegenerative Diseases / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D015203:Reproducibility of Results; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000493:pharmacokinetics*; D015398:Signal Transduction; D014057:Tomography, X-Ray Computed / Q000379:methods
D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin