Quantitative evaluation of the tracer distribution in dopamine transporter SPECT for objective interpretation

Purpose

Quantification of the tracer distribution would add objectivity to the visual assessments of dopamine transporter (DAT) single photon emission computed tomography (SPECT) data. Our study aimed to evaluate the diagnostic utility of fractal dimension (FD) as a quantitative indicator of tracer distribution and compared with the conventional quantitative value: specific binding ratio (SBR). We also evaluated the utility of the combined index SBR/FD (SBR divided by FD).

Materials and methods

We conducted both clinical and phantom studies. In the clinical study, 150 patients including 110 patients with Parkinsonian syndrome (PS) and 40 without PS were enrolled. In the phantom study, we used a striatal phantom with the striatum chamber divided into two spaces, representing the caudate nucleus and putamen. The SBR, FD, and SBR/FD were calculated and compared between datasets for evaluating the diagnostic utility. Mann–Whitney test and receiver-operating characteristics (ROC) analysis were used for analysis.

Results

ROC analysis revealed that the FD value had high diagnostic performance [the areas under the curve (AUC)?=?0.943] and the combined use of SBR and FD (SBR/FD) delivered better results than the SBR alone (AUC, 0.964 vs 0.899; p?<?0.001). The sensitivity, specificity, and accuracy, respectively, were 79.1, 85.0, and 80.7% with SBR, 84.5, 97.5, and 88.0% with FD, and 92.7, 87.5, and 91.3% with SBR/FD.

Conclusion

Our results confirmed that the FD value is a useful diagnostic index, which reflects the tracer distribution in DAT SPECT images. The combined use of SBR and FD was more useful than either used alone.

     

Is iterative reconstruction an alternative to filtered backprojection in routine processing of dopamine transporter SPECT studies?

In general, striatal dopamine transporter (DAT) binding is assessed by use of data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate whether the use of an iterative reconstruction algorithm (ordered-subset expectation maximization [OSEM]) may provide results comparable to or even better than those obtained by standard FBP. METHODS: In 50 patients with parkinsonian syndromes, SPECT scans were acquired 4 h after injection of 185 MBq of (123)I-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) by use of a triple-head gamma-camera fitted with low-energy, high-resolution fanbeam collimators. After reconstruction by FBP and OSEM, data were filtered with a Butterworth filter and corrected for attenuation. Patient studies were automatically fitted to a mean template with a corresponding 3-dimensional (3D) volume-of-interest map covering the striatum, caudate, and putamen as well as an occipital reference region to calculate specific DAT binding. In addition, studies with an anthropomorphic 3D striatal phantom were performed to mimic different pathologies. RESULTS: Visual assessment of phantom and patient data suggested a better separation between the caudate and the putamen in studies reconstructed by OSEM than in those reconstructed by FBP. There was an excellent correlation between specific DAT binding assessed by OSEM and that assessed by FBP (R(2) values: striatum, 0.999; caudate, 0.998; putamen, 0.998). Mean specific striatal binding obtained by OSEM was approximately 6% lower than that obtained by FBP. In no case was diagnostic information from OSEM inferior to that from FBP. CONCLUSION: Iterative reconstruction of (123)I-FP-CIT SPECT studies for the assessment of DAT is feasible in routine clinical practice. A close correlation between FBP and OSEM data suggested that the latter also allow reliable quantification of DAT binding. Because of a better separation between the caudate and the putamen in the visual evaluation, as suggested by phantom and patient studies, OSEM may even be considered the preferable approach.     

Computed-tomography-guided anatomic standardization for quantitative assessment of dopamine transporter SPECT

Purpose

For the quantitative assessment of dopamine transporter (DAT) using [¹²³I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson’s disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization.

Methods

We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.

Results

The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.

Conclusion

CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.

     

IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT studies

Purpose Visual reading of [¹²³I]IBZM SPECT scans depends on the experience of the interpreter. Therefore, semi-quantification of striatal IBZM uptake is commonly considered mandatory. However, semi-quantification is time consuming and prone to error, particularly if the volumes of interest (VOIs) are positioned manually. Therefore, the present paper proposes a new software tool (“IBZM tool”) for fully automated and standardised processing, evaluation and documentation of [¹²³I]IBZM SPECT scans. Methods The IBZM tool is an easy-to-use SPM toolbox. It includes automated procedures for realignment and summation of multiple frames (motion correction), stereotactic normalisation, scaling, VOI analysis of striatum-to-reference ratio R, classification of R and standardised display. In order to evaluate the tool, which was developed at the University of Hamburg, the tool was transferred to the University of Hannover. There it was applied to 27 well-documented subjects: eight patients with multi-system atrophy (MSA), 12 patients with Parkinson’s disease (PD) and seven controls. The IBZM tool was compared with manual VOI analysis. Results The sensitivity and specificity of the IBZM tool for the differentiation of the MSA subjects from the controls were 100% and 86%, respectively. The IBZM tool provided improved statistical power compared with manual VOI analysis. Conclusion The IBZM tool is an expert system for the detection of reduced striatal D₂ availability on [¹²³I]IBZM SPECT scans. The standardised documentation supports visual and semi-quantitative evaluation, and it is useful for presenting the findings to the referring physician. The IBZM tool has the potential for widespread use, since it appears to be fairly independent of the performance characteristics of the particular SPECT system used. The tool is available free of charge.     

18F-FDG PET studies in patients with extratemporal and temporal epilepsy: evaluation of an observer-independent analysis.

The aim of this study was to evaluate an observer-independent analysis of 18F-fluorodeoxyglucose (FDG) PET studies in patients with temporal or extratemporal epilepsy. METHODS: Twenty-seven patients with temporal epilepsy and 22 patients with extratemporal epilepsy were included in the study. All patients with temporal epilepsy and 7 patients with extratemporal epilepsy underwent surgical treatment. In patients who showed significant postoperative improvement (temporal, n = 23; extratemporal, n = 6), the epileptogenic focus was assumed to be located in the area of surgical resection. In extratemporal epilepsy patients who did not undergo surgery, the focus localization was determined using a combination of semiology, ictal and interictal electroencephalography, [99mTc]ethyl cysteinate dimer SPECT, MRI and [11C]flumazenil PET. Visual analysis was performed by two experienced and two less experienced blinded observers using sagittal, axial and coronal images. In the automated analysis after anatomic standardization and generation of three-dimensional stereotactic surface projections (SSPs), a pixelwise comparison of 18F-FDG uptake with an age-matched reference database (n = 20) was performed, resulting in z score images. Pixels with the maximum deviation were detected, summarized and attached to one of 20 predefined surface regions of interest. For comparison with 18F-FDG PET and MR images, three-dimensional overlay images were generated. RESULTS: In patients with temporal epilepsy, the sensitivity was comparable for visual and observer-independent analysis (three-dimensional SSP 86%, experienced observers 86%-90%, less experienced observers 77%-86%). In patients with extratemporal epilepsy, three-dimensional SSP showed a significantly higher sensitivity in detecting the epileptogenic focus (67%) than did visual analysis (experienced 33%-38%, each less experienced 19%). In temporal lobe epilepsy, there was moderate to good agreement between the localization found with three-dimensional SSP and the different observers. In patients with extratemporal epilepsy, there was a high interobserver variability and only a weak agreement between the localization found with three-dimensional SSP and the different observers. Although three-dimensional SSP detected multiple lesions more often than visual analysis, the determination of the highest deviation from the reference database allowed the identification of the epileptogenic focus with a higher accuracy than subjective criteria, especially in extratemporal epilepsy. CONCLUSION: Three-dimensional SSP increases sensitivity and reduces observer variability of the analysis of 18F-FDG PET images in patients with extratemporal epilepsy and is, therefore, a useful tool in the evaluation of this patient group. The benefit of this analytical approach in patients with temporal epilepsy is less apparent.     

(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy

Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [(11)C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [(11)C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [(11)C]cocaine.     

EANM procedure guidelines for brain neurotransmission SPECT using 123I-labelled dopamine transporter ligands, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using ¹²³I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the “Kompetenznetz-Parkinson” sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.     

Integrated software for the analysis of brain PET/SPECT studies with partial-volume-effect correction.

We present software for integrated analysis of brain PET studies and coregistered segmented MRI that couples a module for automated placement of regions of interest (ROI) with 4 alternative methods for partial-volume-effect correction (PVEc). The accuracy and precision of these methods have been measured using 4 simulated (18)F-FDG PET studies with increasing degrees of atrophy. METHODS: The software allows the application of a set of labels, defined a priori in the Talairach space, to segmented and coregistered MRI. Resulting ROIs are then transferred onto the PET study, and corresponding values are corrected according to the 4 PVEc techniques under investigation, providing corresponding corrected values. To evaluate the PVEc techniques, the software was applied to 4 simulated (18)F-FDG PET studies, introducing increasingly larger experimental errors, including errors in coregistration (0- to 6-pixel misregistration), segmentation (-13.7% to 14.1% gray matter [GM] volume change) and resolution estimate errors (-16.9% to 26.8% full-width-at-half-maximum mismatch). RESULTS: Even in the absence of segmentation and coregistration errors, uncorrected PET values showed -37.6% GM underestimation and 91.7% WM overestimation. Voxel-based correction only for the loss of GM activity as a result of spill-out onto extraparenchymal tissues left a residual underestimation of GM values (-21.2%). Application of the method that took into account both spill-in and spill-out effects between any possible pair of ROIs (R-PVEc) and of the voxel-based method that corrects also for the WM activity derived from R-PVEC (mMG-PVEc) provided an accuracy above 96%. The coefficient of variation of the GM ROIs, a measure of the imprecision of the GM concentration estimates, was 8.5% for uncorrected PET data and decreased with PVEc, reaching 6.0% for mMG-PVEc. Coregistration errors appeared to be the major determinant of the imprecision. CONCLUSION: Coupling of automated ROI placement and PVEc provides a tool for integrated analysis of brain PET/MRI data, which allows a recovery of true GM ROI values, with a high degree of accuracy when R-PVEc or mMG-PVEc is used. Among the 4 tested PVEc methods, R-PVEc showed the greatest accuracy and is suitable when corrected images are not specifically needed. Otherwise, if corrected images are desired, the mMG-PVEc method appears the most adequate, showing a similar accuracy.     

Clinical correlative evaluation of an iterative method for reconstruction of brain SPECT images

BACKGROUND: Brain SPECT and PET investigations have showed discrepancies in Alzheimer's disease (AD) when considering data deriving from deeply located structures, such as the mesial temporal lobe. These discrepancies could be due to a variety of factors, including substantial differences in gamma-cameras and underlying technology. Mesial temporal structures are deeply located within the brain and the commonly used Filtered Back-Projection (FBP) technique does not fully take into account either the physical parameters of gamma-cameras or geometry of collimators. In order to overcome these limitations, alternative reconstruction methods have been proposed, such as the iterative method of the Conjugate Gradients with modified matrix (CG). However, the clinical applications of these methods have so far been only anecdotal. The present study was planned to compare perfusional SPECT data as derived from the conventional FBP method and from the iterative CG method, which takes into account the geometrical and physical characteristics of the gamma-camera, by a correlative approach with neuropsychology. METHODS: Correlations were compared between perfusion of the hippocampal region, as achieved by both the FBP and the CG reconstruction methods, and a short-memory test (Selective Reminding Test, SRT), specifically addressing one of its function. A brain-dedicated camera (CERASPECT) was used for SPECT studies with 99mTc-hexamethylpropylene-amine-oxime in 23 consecutive patients (mean age: 74.2 +/- 6.5) with mild (Mini-Mental Status Examination score > or =15, mean 20.3 +/- 3), probable AD. Counts from a hippocampal region in each hemisphere were referred to the average thalamic counts. RESULTS: Hippocampal perfusion significantly correlated with the MMSE score with similar statistical significance (p < 0.01) between the two reconstruction methods. Correlation between hippocampal perfusion and the SRT score was better with the CG method (r = 0.50 for both hemispheres, p < 0.01) than with the FBP method (r = 0.37 and 0.43, respectively for the right and left hemisphere, p < 0.05 and p < 0.02). The bootstrap procedure showed that such correlation indexes were statistically different both in the right (p < 0.01) and in the left (p < 0.05) hemisphere. CONCLUSION: These results are interpreted as a better performance of the CG reconstruction method in correctly detecting counts from hippocampal ROI. By using the same gamma-camera or collimator, alternative methods for brain SPECT reconstruction may improve quality of data and then help SPECT diagnostic accuracy.     

Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis.

Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET). METHODS: One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique. RESULTS: Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV). CONCLUSION: Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.     

Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons.

The central nervous system dopamine transporters (DATs) and dopamine D2/D3 receptors are implicated in a variety of neurological disorders. Both sites are also targets for drug treatment. With the successful development of [99mTc]TRODAT-1, single-isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of 123I-labeled D2/D3 receptor ligand co-injected to assess both pre- and postsynaptic sites of the dopaminergic system simultaneously. METHODS: Twelve SPECT scans of the brain were obtained in two baboons after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl ](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [123I]iodobenzamide or [123I]iodobenzofuran. SPECT data were acquired by a triple-head gamma camera equipped with ultra-high-resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10% asymmetric with a lower bound at 159 keV for 123I. After coregistration with MRI, region-of-interest analysis was performed using predefined templates from coregistered MRI. In blocking studies, baboons were pretreated with N-methyl-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D2/D3 binding site, respectively. RESULTS: Image quality of dual-isotope studies was similar to that obtained from single-isotope studies. When one site was blocked with CFT or raclopride, the binding of the respective ligand to the other site was not affected. CONCLUSION: This is the first example that clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic sites of the dopaminergic system in baboons with dual-isotope SPECT studies. With or without corrections for cross-contamination of 123I into the 99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual-isotope experiments did not differ significantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopaminergic system in one SPECT imaging session.     

Assessment of intima-media thickness of carotid arteries: evaluation of an automated computer software

Introduction  The aim of this study was to evaluate the feasibility and accuracy of commercially available software directly implemented on the ultrasound scanner for automated measurement of the intima-media thickness (IMT) of the common carotid artery on source images. Materials and methods  Measurements were performed on a GE Vivid 3 ultrasound scanner. First, inter- and intraobserver correlations were assessed for the automated and the manual measurements. Second, the correlation between automated and manual measurements was assessed in 199 asymptomatic patients with a mean age of 30 years (range 20–41 years). Results  The measurement was feasible in all patients and a standard configuration with optimum quality was determined. The inter- and intraobserver correlations obtained using the automated software were excellent and slightly inferior to the manual measurements. The correlation of the automated and manual measurements was significant (r = 0.86; P < 0.01) and the mean difference between both measurements was low (0.023 ± 0.034 mm). Conclusions  The software allowed an efficient and quick measurement by providing at the same time comparable results to the manual measurement and a better inter- and intraobserver variability.     

Diagnostic performance of a 3-D automated quantification method of dopamine D2 receptor SPECT studies in the differential diagnosis of parkinsonism

BACKGROUND: Assessment of post-synaptic D2 receptors with 123I-IBZM SPECT is helpful in distinguishing idiopathic (IPS) from other parkinsonian syndromes (non-IPS). AIM: To evaluate the diagnostic performance of a recently introduced three-dimensional automated quantification method in a large group of parkinsonian patients. METHODS: IBZM SPECT was performed in 101 consecutive patients with IPS (n = 49) and non-IPS (n = 52). Striatal/frontal cortex binding ratios were assessed by a standard manual quantification method and by the automated method. For the latter patient studies were registered to a mean template of healthy controls (n = 13). IBZM binding was calculated from a 3-D volume-of-interest map established on the normal template. The diagnostic performance of the automated and manual approaches were assessed by receiver operating characteristic (ROC) analyses. RESULTS: Specific striatal binding ratios of both quantification methods showed a close linear relationship (y = 0.81x + 0.1188; R2 = 0.8062). At optimal decision thresholds sensitivity and specificity were 87% and 90% for the automated, and 85% and 90% for the manual method, respectively. The area under the ROC curve was 0.92 for the automated and 0.93 for the manual method, showing no statistical difference. The area under the ROC curve corresponding to a false positive fraction from 0% to 20% was 0.163 for the automated and 0.166 for the manual evaluation. CONCLUSIONS: The diagnostic performance of an automated 3-D quantification method for IBZM SPECT studies has been shown to be equal to, or even better than, a standard manual technique. Advantages of automated quantifications are observer independence and fast processing times. This method may be also used as a platform for processing large data sets/multicentre studies in order to objectively evaluate basal ganglia disorders.     

多巴胺D2受体乃131I-epidepride显像对帕金森病的临床研究

目的 评价多巴胺D2受体显像剂131I-(s)-(-)-N-[(1-乙基-2-吡咯烷基)甲基]-5-碘-2,3-二甲氧基苯甲酰胺(epidepride)对帕金森病(PD)的临床应用价值.方法 PD患者38例(H/YⅠ～Ⅳ级,病程4个月～6年),健康对照组12例,静脉注射131I-epidepride 18.5 MBq 3 h后行SPECT显像,并应用感兴趣区(ROI)技术计算纹状体/枕叶放射性(ST/OC)比值,分析ST/OC比值与PD患者临床严重程度的相关性.采用SPSS 10.0软件对数据进行校正t检验,配对t检验及Spearman相关分析.结果 对照组131I-epidepride显像示双侧纹状体内有高度放射性浓聚,纹状体显示清晰,双侧基本对称,额叶、颞叶、顶叶、枕叶及小脑放射性较低.与健康对照组比较,PD患者ST内131I-epide-pride浓聚增加,但差异无统计学意义.早期PD患者(H/Y Ⅰ级)病侧肢体的对侧ST放射性显著增加、体积增大(壳核尤为显著),与同侧ST相比差异有统计学意义(t=7.89,P＜0.05).ST/OC比值与PD临床严重程度(H/Y分级)无明显相关性(r=0.12,P＞0.05).结论 多巴胺D2受体131I-Epi-depride SPECT显像有助于了解PD患者ST内突触后膜的多巴胺D2受体变化,PD患者D2上调,在偏侧PD中以病变对侧壳核尤为显著.ST/OC比值与PD临床严重程度无相关性.     

Quantification of 123I-PE2I binding to dopamine transporter with SPECT after bolus and bolus/infusion.

The aim of the present study was to describe a method combining easy implementation in a clinical setting with accuracy and precision in quantification of 123I-labeled N-(3-iodoprop-(2E)-enyl)-2beta-carboxymethoxy-3beta-(4'-methylphenyl)nortropane (PE2I) binding to brain dopamine transporter. METHODS: Five healthy subjects (mean age, 50 y; range, 40-68 y) were studied twice. In the first experiment, dynamic SPECT data and arterial plasma input curves obtained after 123I-PE2I bolus injection were assessed using Logan, kinetic, transient equilibrium, and peak equilibrium analyses. Accurate and precise determination of BP1 (binding potential times the free fraction in the metabolite-corrected plasma compartment) and BP2 (binding potential times the free fraction in the intracerebral nonspecifically bound compartment) was achieved using Logan analysis and kinetic analysis, with a total study time of 90 min. In the second experiment, (123)I-PE2I was administrated as a combined bolus and constant infusion. The bolus was equivalent to 2.7 h of constant infusion. RESULTS: The bolus-to-infusion ratio of 2.7 h was based on the average terminal clearance rate from plasma in the bolus experiments. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 2 h. Even when an average bolus-to-infusion ratio was used, the striatal BP1 and BP2 values calculated with kinetic analysis (BP1 = 21.1 +/- 1.1; BP2 = 4.1 +/- 0.4) did not significantly differ from those calculated with bolus/infusion analysis (BP1 = 21.0 +/- 1.2; BP2 = 4.3 +/- 0.3). Computer simulations confirmed that a 2-fold difference in terminal clearance rate from plasma translates into only a 10% difference in BP1 and BP2 calculated from 120 to 180 min after tracer administration. CONCLUSION: The bolus/infusion approach allows accurate and precise quantification of 123I-PE2I binding to dopamine transporter and is easily implemented in a clinical setting.     

Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease.

(E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with (123)I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed (123)I-PE2I SPECT on healthy volunteers and patients with Parkinson's disease (PD) to validate the Logan graphical method for quantification of (123)I-PE2I binding and to analyze the relationship between (123)I-PE2I SPECT and clinical features of this frequent degenerative disease. METHODS: Eight PD patients (3 women, 5 men; mean age, 64 +/- 7.9 y; disease duration range, 1-8 y, Hoehn and Yahr stage range, 1-2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 +/- 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 +/- 30 MBq of (123)I-PE2I. RESULTS: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. (123)I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, (123)I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, (123)I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that (123)I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. CONCLUSION: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that (123)I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that (123)I-PE2I SPECT can be used for preclinical and early diagnosis of PD.     

Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects

Purpose

Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [¹²³I]FP-CIT SPECT in healthy subjects.

Methods

We performed a whole-brain [¹²³I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p?<?0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79?years.

Results

We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices.

Conclusion

This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders.