Quantitative accuracy of dopaminergic neurotransmission imaging with (123)I SPECT.

123I-Labeled radiotracers are suitable for in vivo imaging of the dopaminergic system by SPECT. However, precise measurement of striatal uptake is limited by scatter, attenuation, and the finite spatial resolution of the camera. We studied the quantitative accuracy that can be achieved with (123)I SPECT of the dopaminergic neurotransmission system. METHODS: Using a Monte Carlo simulation and brain phantom experiments, we studied the biases in brain and striatal absolute uptake estimates and in binding potential (BP) values for different processing schemes with corrections for attenuation, scatter, and the partial-volume effect. RESULTS: Without any correction, brain activity was underestimated by at least 65%, and absolute striatal activity measured in regions corresponding to the anatomic contours of the striata was underestimated by about 90%. With scatter and attenuation corrections only, estimated brain activity was accurate within 10%; however, striatal activity remained underestimated by about 50%, and BP values were underestimated by more than 50%. When combined with attenuation and scatter corrections, anatomically guided partial-volume effect correction (PVC) reduced the biases in striatal activity estimates and in BP values to about 10%. PVC reliability was affected by errors in registering SPECT with anatomic images, in segmenting anatomic images, and in estimating the spatial resolution. With registration errors of 1 voxel (2.1 x 2.1 x 3.6 mm(3)) in all directions and of 15 degrees around the axial direction, PVC still improved the accuracy of striatal activity and BP estimates compared with scatter and attenuation corrections alone, the errors being within 25%. A 50% overestimation of the striatal volume yielded an approximate 30% change in striatal activity estimates with respect to no overestimation but still provided striatal activity estimates that were more accurate than those obtained without PVC (average errors +/- 1 SD were -22.5% +/- 1.0% with PVC and -49.0% +/- 5.5% without PVC). A 2-mm error in the spatial resolution estimate changed the striatal activity and BP estimates by no more than 10%. CONCLUSION: Accurate estimates of striatal uptake and BP in (123)I brain SPECT are feasible with PVC, even with small errors in registering SPECT with anatomic data or in segmenting the striata.     

123I-FP-CIT semi-quantitative SPECT detects preclinical bilateral dopaminergic deficit in early Parkinson's disease with unilateral symptoms

BACKGROUND AND AIM: 123I-FP-CIT SPECT has been successfully used to detect the loss of dopaminergic nigrostriatal neurons in Parkinson's disease at an early stage. In this study we evaluated the capacity of 123I-FP-CIT SPECT to assess bilateral dopamine transporter (DAT) loss in de-novo hemi-Parkinson's disease (PD) patients with one-sided clinical symptoms. PATIENTS AND METHODS: Twenty-nine de-novo hemi-PD patients at an early stage (Hoehn & Yahr stage 1) and 18 gender and age matched healthy subjects were studied. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (P(put)/O), and the putamen to caudate nucleus index (P(put)/C) were calculated in both the basal ganglia. RESULTS: In PD patients S/O, C/O and P(put)/O ratio values contralateral to the clinically affected side were significantly lower (P<0.001) than in the control group (-38%, -34% and -42%, respectively). A significant reduction (P<0.001) of the striatal binding ratios was also found ipsilaterally (S/O, -31%; C/O, -28%; P(put)/O, -33%). The P(put)/C index was also bilaterally significantly reduced (P<0.01). DAT loss was significantly greater (P<0.001) in the contralateral than in the ipsilateral S; and putamen bilaterally presented a higher dopaminergic deficit than did caudate. CONCLUSION: Our results indicate that semi-quantitative 123I-FP-CIT SPECT detects a bilateral dopaminergic deficit in early PD with unilateral symptoms and preclinical DAT loss in the ipsilateral striatal binding, corresponding to the side not yet affected by motor signs. Semi-quantitative analysis may thus be used to diagnose PD at an early stage as well as to identify individuals developing bilateral dopaminergic damage.     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.     

Calibration of gamma camera systems for a multicentre European 123I-FP-CIT SPECT normal database

Purpose

A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [¹²³I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved.

Methods

¹²³I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the ??Southampton?? methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV).

Results

The relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69?C89%, ACSC range 87?C116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p?Conclusion A satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.     

Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation

PURPOSE: (123)I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation. METHODS: The SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed. RESULTS: For both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV. CONCLUSION: Our findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies.     

Validation of a resolution-independent method for the quantification of 123I-FP-CIT SPECT scans

OBJECTIVE: To verify the applicability of a recently described resolution-independent method for the semi-quantification of 123I-FP-CIT scans. METHODS: Visual interpretation, 'conventional' and resolution-independent semi-quantification was performed on 60 123I-FP-CIT scans. Using ROC analysis, the results were compared to the final clinical diagnosis after a follow-up of at least 18 months. Sensitivity and specificity values were calculated and a cut-off value of the specific binding, which differentiated between normal and abnormal scans with high sensitivity and specificity, was given. RESULTS: Application of the resolution-independent method to a new set of 123I-FP-CIT SPECT data yielded a cut-off value of the specific striatal binding of 55 ml. Corresponding values of sensitivity and specificity were 95% and 72%, respectively. Further, based on the values of the area under the ROC curve and the 95% confidence interval of different semi-quantitative methods, the resolution-independent semi-quantification agreed best with the final clinical diagnosis. CONCLUSION: We found a similar value of the specific 123I-FP-CIT binding as the one previously described in the literature, which proved the validity of the resolution-independent method. Further, this method, among other 'conventional' semi-quantitative methods, agreed best with the final clinical diagnosis. For this reason we recommend its use to aid in the diagnostic process.     

123I-FP-CIT in progressive supranuclear palsy and in Parkinson's disease: a SPECT semiquantitative study

BACKGROUND AND AIM: It is still debated whether or not I-FP-CIT single photon emission computerized tomography (SPECT) is able to differentiate between Parkinson's disease and progressive supranuclear palsy (PSP). Our aim was to use SPECT semiquantitative analysis to assess the capacity of I-FP-CIT to characterize Parkinson's disease versus PSP. PATIENTS AND METHODS: Twenty-one Parkinson's disease patients, 15 disease duration- and age-matched PSP patients and 20 age-matched healthy controls were included in this study. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (P/O) were calculated in both the basal ganglia. The asymmetric index (AI) for the whole striatum was also calculated for Parkinson's disease and PSP. RESULTS: Compared to healthy controls, S/O, C/O and P/O were significantly reduced (P<0.001) both in Parkinson's disease (-46%, -43%, -49%, contralaterally to the most affected side; -41%, -37%, -41%, ipsilaterally) and in PSP (-58%, -57%, -59%, contralaterally; -58%, -57%, -59%, ipsilaterally). S/O, C/O and P/O ratio values were significantly (P<0.001) lower in PSP patients when compared to Parkinson's disease group. The asymmetric index (AI) was significantly higher (P<0.001) in Parkinson's disease than in PSP (AI: 23.6%+/-15.07% vs. 9.66%+/-5.83), but with an overlap between the two groups. CONCLUSION: Our results confirm that I-FP-CIT SPECT is clinically useful for detecting nigrostriatal degeneration both in Parkinson's disease and PSP. Moreover, in our series, semiquantitative analysis using I-FP-CIT SPECT allowed Parkinson's disease and PSP to be discriminated because PSP patients presented a more severe and symmetric dopamine transporter loss, and the results for S/O were more accurate.     

Applications of SPECT imaging of dopaminergic neurotransmission in neuropsychiatric disorders

Single photon emission computed tomography (SPECT) tracers selective for pre- and post-synaptic targets have allowed measurements of several aspects of dopaminergic (DA) neurotransmission. In this article, we will first review our DA transporter imaging in Parkinson's disease. We have developed the in vivo dopamine transporter (DAT) imaging with [123I]beta-CIT ((1R)-2beta-Carbomethoxy-3beta-(4-iodophenyl)tropane). This method showed that patients with Parkinson's disease have markedly reduced DAT levels in striatum, which correlated with disease severity and disease progression. Second, we applied DA imaging techniques in patients with schizophrenia. Using amphetamine as a releaser of DA, we observed the enhanced DA release, which was measured by imaging D2 receptors with [123I]IBZM (iodobenzamide), in schizophrenics. Further we developed the measurement of basal synaptic DA levels by AMPT (alpha-methyl-paratyrosine)-induced unmasking of D2 receptors. Finally, we expanded our techniques to the measurement of extrastriatal DA receptors using [123I]epidepride. The findings suggest that SPECT is a useful technique to measure DA transmission in human brain and may further our understanding of the pathophysiology of neuropsychiatric disorders.     

123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism.

The purpose of our study was to prospectively evaluate the striatal uptake of 123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP). METHODS: Twenty consecutive patients who developed VP in the course of CVD were prospectively enrolled in the study. All patients had CT evidence of CVD (17 patients had lacunar infarcts, 3 patients had territorial strokes). The clinical stage of the patients was assessed using the Hoehn and Yahr scale, and the severity of the symptoms was measured using the Unified Parkinson's Disease Rating Scale score. Ten age-matched subjects were used as controls. SPECT was performed 180 min after injection of 185 MBq 123I-FP-CIT using a dual-head gamma-camera. The ratio of the mean specific-to-nonspecific striatal binding for the entire striatum, caudate, and putamen was calculated in all patients and compared with that of controls. Putamen-to-caudate binding ratios were compared as well. The response to therapy was compared between patients with normal and abnormal 123I-FP-CIT binding. RESULTS: No correlation was found between any of the clinical variables and response to therapy in patients with VP. Nine patients had normal striatal 123I-FP-CIT binding with no significant differences in striatal or subregional binding ratios compared with those of the controls. In contrast, 11 patients had significantly diminished striatal binding compared with that of controls (P < 0.001). Subanalyses showed significantly decreased binding in the caudate (P < 0.04 and P < 0.01 for the right and left caudate, respectively), diminished binding in the putamen (P < 0.04 and P < 0.01 for the right and left putamen, respectively), and a decreased putamen-to-caudate ratio on the right side (P < 0.001). The latter ratio was not significant on the left. Two of the 3 patients with territorial strokes had significantly diminished striatal 123I-FP-CIT binding in the hemisphere contralateral to the CT lesion. All 9 patients with normal scan findings had a poor response to L-dopa. Six of 11 patients with abnormal studies had no response to L-dopa, whereas 5 patients had a good response (P < 0.03). CONCLUSION: The diagnosis of VP cannot be accurately confirmed on the basis of clinical features alone because CVD may alter the typical presentation of PD. Functional imaging with 123I-FP-CIT is highly recommended in patients with CVD who develop symptoms of VP to confirm or exclude the existence of nigrostriatal dopaminergic degeneration. Identifying a subset of patients with reduced 123I-FP-CIT binding in the striatum is important for better treatment selection.     

Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson’s disease

Purpose  

To determine clinical predictors and accuracy of ¹²³I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson’s disease (PD).     

Metabolism of 123I-FP-CIT in humans]

The metabolism of N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-FP-CIT) in healthy humans was studied. Plasma and urine samples, obtained after i.v. administration of 123I-FP-CIT, were analyzed using the two-dimensional thin-layer chromatography technique. Eleven radiochemical components were detected in both plasma and urine, and four of them were the parent 123I-FP-CIT and its metabolites, N-(3-fluoropropyl)-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-acid), 2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-acid) and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-CIT). These four identified radiochemical components occupied about 80% or more in ratio of the radiochemical components in the plasma and urine. In the metabolites of 123I-FP-CIT, the high polar metabolites--123I-acid and 123I-nor-acid--were found to be the major components, while lipophilic 123I-nor-CIT was a minor component. Free iodide (123I-) was not found in the plasma or urine. Thus, the main metabolic reactions which 123I-FP-CIT undergoes in humans seem to be hydrolysis of the ester bond and N-dealkylation. In vivo deiodination of 123I-FP-CIT was found to be minimum. Current results suggest that the metabolites of 123I-FP-CIT hardly influence evaluation of the dopamine transporter in the human brain.