Correlations between dopamine transporter density measured by <Superscript>123</Superscript>I-FP-CIT SPECT and regional gray matter volume in Parkinson’s disease

Purpose

Parkinson’s disease (PD) is caused by a selective degeneration of dopamine neurons. The relationship between dopamine transporter (DAT) density and gray matter volume has been unclear. Here we investigated the voxelwise correlation between gray matter volume and DAT binding measured by ¹²³I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (¹²³I-FP-CIT) single-photon emission computed tomography (SPECT; DaTscan? imaging) in PD.

Materials and methods

Thirty-one male patients with PD were examined with MRI and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships between the regional gray matter volume and the SBR in the striatum.

Results

There were significant positive correlations between the SBR and the gray matter volume in the right pulvinar and posterior middle temporal gyrus and a trend level in the left pulvinar, all of which are associated with the second visual pathway.

Conclusion

The nigrostriatal dopaminergic degeneration might affect the secondary visual pathway, leading to visual dysfunctions in PD.

     

The effect of levodopa therapy on dopamine transporter SPECT imaging with 123I-FP-CIT in patients with Parkinson’s disease

Purpose The aim of this study was to evaluate, by means of ¹²³I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinsons disease.Methods Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest–occipital)/occipital.Results During levodopa wash-out, despite a worsening in patients clinical disability (H&Y mean stage 2.53±0.58 versus 1.73±0.45 on therapy, p<0.001), striatal ¹²³I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined.Conclusion The results of this study suggest that levodopa does not affect ¹²³I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT.     

Clinical correlation of the binding potential with <Superscript>123</Superscript>I-FP-CIT in de novo idiopathic Parkinson’s disease patients

Purpose  The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[¹²³I]iodophenyl-nortropane (¹²³I-FP-CIT) binding in de novo Parkinson’s disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Methods  Thirty-six de novo PD patients underwent ¹²³I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal ¹²³I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP_FBP, BP_OSEM, BP_LS). Results  The range of values of striatal BP_LS was significantly greater than BP_FBP and BP_OSEM. For all striatal regions, estimates of BP_FBP correlated well with BP_OSEM (r = 0.84) and with BP_LS (r = 0.64); BP_OSEM correlated significantly with BP_LS (r = 0.76). A good correlation was found between putaminal BP_LS and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = −0.46, r = −0.42, r = −0.39, respectively). Neither putaminal BP_FBP nor putaminal BP_OSEM correlated with any of these motor scores. Conclusions  In de novo PD patients, ¹²³I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of ¹²³I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.     

Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson’s disease

Purpose

Parkinson’s disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor.

Methods

[¹²³I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates.

Results

Patients with PD had 28.1 – 65.0 % lower binding in all striatal regions compared to controls (p?p?Conclusion The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.     

Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [<Superscript>123</Superscript>I]β-CIT SPECT

Purpose  

We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD).     

Diagnostic value of asymmetric striatal D<Subscript>2</Subscript> receptor upregulation in Parkinson’s disease: an [<Superscript>123</Superscript>I]IBZM and [<Superscript>123</Superscript>I]FP-CIT SPECT study

Introduction Striatal postsynaptic D₂ receptors in Parkinson’s disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D₂ binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool. Methods Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of ≤5 years and 26 age-matched controls. Striatal D₂ binding was assessed with [¹²³I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [¹²³I]FP-CIT SPECT. Results The mean striato-occipital ratio of [¹²³I]IBZM binding was significantly higher in PD patients (1.56 ±0.09) than in controls (1.53 ±0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 ±0.09 vs 1.55 ±0.10 ipsilaterally), suggesting D₂ receptor upregulation, and the reverse was seen using [¹²³I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation. Conclusion Our study confirms asymmetric D₂ receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [¹²³I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D₂ receptors, assessed with [¹²³I]IBZM SPECT.     

The clinical utility of 99<Superscript>m</Superscript>Tc-HMPAO SPECT in Fahr’s disease

Fahr's disease is a rare neurodegenerative syndrome, characterized by massive symmetrical intracerebral calcifications of the basal ganglia, dentate nuclei of the cerebellum, and the adjacent parenchyma. Computerized tomography (CT) is considerably more sensitive to detect these intracranial calcifications than other imaging modalities. The clinical, CT scan, and 99(m)Tc-D,L-hexamethylpropylene amine oxime (99(m)Tc-HMPAO) brain perfusion single-photon emission computerized tomography (SPECT) findings in a 42-year-old woman with Fahr's disease are reported, and the clinical utility of 99(m)Tc-HMPAO SPECT findings in Fahr's disease is discussed in this article. In conclusion, 99(m)Tc-HMPAO brain perfusion SPECT seems to be useful in the clinical approach to Fahr's disease, and may provide more specific and clinically relevant information when compared with anatomical imaging.     

Automated striatal uptake analysis of <Superscript>18</Superscript>F-FDOPA PET images applied to Parkinson’s disease patients

Objective  

6-[¹⁸F]Fluoro-l-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson’s disease (PD) patients.     

Imaging of dopamine transporters and D<Subscript>2</Subscript> receptors in patients with Parkinson’s disease and multiple system atrophy

Purpose The aim of this study was to ascertain whether combined presynaptic and postsynaptic dopaminergic single-photon emission computed tomography (SPECT) scanning is useful for differentiation between patients with idiopathic Parkinsons disease (IPD), patients with multiple system atrophy of the striatonigral type (MSA) and healthy subjects.Methods SPECT measurements of the dopamine transporter (DAT) were done with ¹²³I--CIT, while for determination of the dopamine D₂-like receptors (D₂), ¹²³I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight patients with MSA and 11 healthy age-matched control subjects.Results Putaminal DAT binding was reduced to 32% of control values in IPD and to 19% of control values in MSA . Significantly higher striatal asymmetry in DAT binding was found in MSA than in controls, but IPD patients had significantly higher asymmetry than MSA patients. Striatal D₂ binding did not differ significantly between patients and healthy controls but the ratio between caudate DAT and D₂ binding was significantly higher in patients with IPD than in those with MSA, even when disease severity was taken into account.Conclusion Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference greater than 15% are likely to suffer from IPD. Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference of between 5% and 15% are more likely to have MSA. ¹²³I-epidepride SPECT measurements may add further diagnostic information, since the ratio between DAT and D₂ receptor binding is significantly higher in IPD than in MSA.     

Five-year follow-up of <Superscript>11</Superscript>C-PIB uptake in Alzheimer’s disease and MCI

Purpose

The aim of this study was to evaluate the longitudinal changes in [¹¹C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) over a long-term follow-up.

Methods

Six AD patients, ten MCI patients and eight healthy subjects underwent a [¹¹C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months.

Results

The MCI group showed a significant increase in [¹¹C]PIB uptake over time (p?<?0.001), with a similar increase from baseline to 2 years (4.7 % per year) and from 2 to 5 years (5.0 % per year). Eight MCI patients (80 %) converted to AD, and two of these patients showed a normal [¹¹C]PIB scan at baseline but increased uptake later. There was an increase in [¹¹C]PIB uptake with time in the AD group (p?=?0.02), but this did not significantly differ from the change in the control group.

Conclusion

Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [¹¹C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD.

     

Evaluation of <Superscript>99m</Superscript>Tc-TRODAT-1 SPECT in the diagnosis of Parkinson’s disease versus other progressive movement disorders

Objective

Parkinson disease (PD), parkinsonian syndromes (PS) and essential tremor (ET) are different types of movement disorders which share some symptoms resulting in a difficulty of certain diagnosis. This study was conducted to determine the value of ^99mTc-TRODAT-1 scan to differentiate PD from ET and other PS cases.

Methods

Totally, 75 patients were studied including 29 PD, 6 possible PD, 22 ET and 18 PS cases. A dual-head SPECT-CT was used to perform basal ganglia (BG) imaging following administration of ^99mTc-TRODAT-1. The BG uptake values were normalized to whole brain and occipital activity. All patients were followed for 2–22 months to reach a certain diagnosis.

Results

Patients with ET and drug-induced parkinsonism show significantly higher normalized BG uptake as compared to the other subgroups; however, no significant difference was noted between PD and PS patients. The sensitivity and specificity of the findings for the differentiation between patients with the disease associated versus not associated with BG dysfunction were 80 and 83.3 %, respectively. A predictive positive value of 82.6 % was obtained using an additive scaling index defined as asymmetry and unevenness of uptake in putamen and/or caudate contralateral to the dominant side of current symptoms.

Conclusions

^99mTc-TRODAT-1 scan is an appropriate method to differentiate PD or PS versus ET. A combination of scan pattern including asymmetry of BG uptake and unevenness of activity in caudate and putamen along with the side of dominant symptoms may be valuable for the differentiation of Parkinson’s disease from the other parkinsonian syndromes.

     

Extraction,selection and comparison of features for an effective automated computer-aided diagnosis of Parkinson’s disease based on [<Superscript>123</Superscript>I]FP-CIT SPECT images

Purpose

This work aimed to assess the potential of a set of features extracted from [¹²³I]FP-CIT SPECT brain images to be used in the computer-aided “in vivo” confirmation of dopaminergic degeneration and therefore to assist clinical decision to diagnose Parkinson’s disease.

Methods

Seven features were computed from each brain hemisphere: five standard features related to uptake ratios on the striatum and two features related to the estimated volume and length of the striatal region with normal uptake. The features were tested on a dataset of 652 [¹²³I]FP-CIT SPECT brain images from the Parkinson’s Progression Markers Initiative. The discrimination capacities of each feature individually and groups of features were assessed using three different machine learning techniques: support vector machines (SVM), k-nearest neighbors and logistic regression.

Results

Cross-validation results based on SVM have shown that, individually, the features that generated the highest accuracies were the length of the striatal region (96.5%), the putaminal binding potential (95.4%) and the striatal binding potential (93.9%) with no statistically significant differences among them. The highest classification accuracy was obtained using all features simultaneously (accuracy 97.9%, sensitivity 98% and specificity 97.6%). Generally, slightly better results were obtained using the SVM with no statistically significant difference to the other classifiers for most of the features.

Conclusions

The length of the striatal region uptake is clinically useful and highly valuable to confirm dopaminergic degeneration “in vivo” as an aid to the diagnosis of Parkinson’s disease. It compares fairly well to the standard uptake ratio-based features, reaching, at least, similar accuracies and is easier to obtain automatically. Thus, we propose its day to day clinical use, jointly with the uptake ratio-based features, in the computer-aided diagnosis of dopaminergic degeneration in Parkinson’s disease.

     

A new model for separation between brain dopamine and serotonin transporters in <Superscript>123</Superscript>I-β-CIT SPECT measurements: normal values and sex and age dependence

¹²³I--CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since ¹²³I--CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble ¹²³I--CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for ¹²³I--CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1–2 h and DAT imaging at 20–24 h; (2) blocking the 5HTT re-uptake with citalopram renders ¹²³I--CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved ¹²³I--CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT.     

<Superscript>18</Superscript>p-FDG PET is superior to<Superscript>67</Superscript>Ga SPECT in the staging of non-Hodgkin’s lymphoma

OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and 67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT for the pretreatment staging of malignant lymphoma between August 1999 and March 2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga SPECT were performed within one month. Both imagings were performed on the area from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET. The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga-negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F-FDG PET. Five lesions were not identified by either technique. No 18F-FDG-negative but 67Ga-positive nodal or extranodal lesions were observed. The difference in findings between the two studies is related to the difference in the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET detected significantly more lesions particularly small lesions than 67Ga SPECT. Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of non-Hodgkin' s lymphoma.     

Dopamine transporter SPECT using fast kinetic ligands: <Superscript>123</Superscript>I-FP-β-CIT versus <Superscript>99m</Superscript>Tc-TRODAT-1

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, ¹²³I-FP--CIT (FP) and ^99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1–2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinsons disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (–8.8%/year, =–0.41, P=0.025) and the putamen/caudate ratio (–7.4%/year, =–0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.     

Usefulness of brain <Superscript>99m</Superscript>Tc-TRODAT-1 SPET for the evaluation of Parkinson’s disease

Nigral dopaminergic projections to the striatum are targeted in Parkinsons disease (PD). The extent of the degeneration of the dopaminergic system in PD can be visualised by dopamine transporter imaging using single-photon emission tomography (SPET). In this study in 188 patients with PD, we analysed the image patterns and compared them with the clinical features in order to verify the usefulness of technetium-99m TRODAT-1 brain SPET in the evaluation of patients with PD. Two independent readers visually assessed SPET slices from three brain axes according to a fine visual scale; results were also grouped according to a rough visual scale. Results of both visual and semi-quantitative analyses were compared among patients with different stages of PD and healthy controls. There was good agreement between the readers in the interpretation of the image patterns [kappa statistic ()=0.85 for the presence of PD; =0.88 for the rough scale and 0.81 for the fine scale]. Good concordance was obtained when visual interpretation was used to evaluate the presence of PD (sensitivity =98%, specificity =86%, =0.85). Semi-quantitative analyses revealed significant negative correlations between both striatal and putaminal uptake and disease severity as assessed using the Hoehn and Yahr scale (=–0.89 and –0.93 respectively). An apparent decrease in striatal uptake in early PD, hardly discernible from the uptake level in advanced PD, was commonly found in visual analyses. The results suggest that both visual and semi-quantitative analyses of ^99mTc-TRODAT-1 SPET images reflect neurodegeneration in PD, and that ^99mTc-TRODAT-1 SPET represents an adequate means for evaluation of the status of patients with PD.     

Intra-individual comparison of p-[<Superscript>123</Superscript>I]-iodo-L-phenylalanine and L-3-[<Superscript>123</Superscript>I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

Objectives Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[¹²³I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[¹²³I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. Methods Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. Results Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. Conclusions IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. This work was supported by a grant from the “Deutsche Krebshilfe” (70-3024-He 1).     

Serotonin transporter binding with [<Superscript>123</Superscript>I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Purpose  The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods  We included 49 depressed outpatients (mean±SD 42.3 ± 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [¹²³I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP_ND) in the midbrain and diencephalon with cerebellar binding as a reference. Results  In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p = 0.002) and an additional smoking×gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Conclusion  Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.     

Development of “super rapid dynamic SPECT,” and analysis of retention process of<Superscript>99m</Superscript>Tc-ECD in ischemie lesions: Comparative study with<Superscript>133</Superscript>Xe SPECT

To analyze the retention process of technetium-99m ethyl cysteinate dimer (99mTc-ECD) in normal and ischemic lesions, we developed a super rapid dynamic SPECT system based on the CERASPECT (DSI, Inc., Waltham, MA, USA). The system made it possible to take a SPECT series every 2 seconds. Each SPECT series contains a maximum of 16 slices (6.6 mm slice interval) in a matrix size of 32 x 32. The sensitivity of this system is 175 kcps/MBq/ml/cm slice thickness, and resolution is 12 mm FWHM at the center of a 20 cm(phi) water phantom. Using the super rapid SPECT system, the kinetic behavior of the 99mTc-ECD during retention in normal and ischemic lesions was analyzed. Twenty patients with ischemic lesions that were clearly demonstrated by 133Xe-rCBF (regional cerebral blood flow) SPECT but unclear on static 99mTc-ECD SPECT were examined. For the dynamic SPECT, 700 MBq of 99mTc-ECD was injected intravenously, and dynamic SPECT data were acquired every 2 seconds during a 90-second period. The serial dynamic SPECT and time-activity curves at some lesions with reduced rCBF and at the contralateral normal brain were analyzed. These dynamic SPECT data were compared with conventional static 99mTc-ECD SPECT and quantitative 133Xe-rCBF SPECT. All of mildly or moderately reduced rCBF lesions on the 133Xe-rCBF SPECT were recognized as low activity regions only at the early phase (during about 2-20 sec or less), with the lesions then gradually vanishing. These lesions were not recognized on the conventional static SPECT taken after the dynamic study. The time-activity curve at the reduced rCBF lesion was lower than that of contralateral normal brain at the early phase, and overtook the activity in the normal region with a gradual increase. The early phase images of 99mTc-ECD SPECT within 20 seconds by the super rapid dynamic SPECT were very useful to the same extent as the 133Xe-rCBF SPECT for detecting mild or moderate ischemic lesions. This study suggests that esterase activity, participating in the ECD retention mechanism, may be tolerable to mild or moderate ischemia. This tolerance may be the main cause of the nonlinear relationship between ECD accumulation and cerebral blood flow.     

Longitudinal Decline of Striatal Subregional [<Superscript>18</Superscript>F]FP-CIT Uptake in Parkinson’s Disease

Purpose

Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson’s disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [¹⁸F]FP-CIT uptake in PD.

Methods

We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [¹⁸F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.

Results

Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.

Conclusions

The longitudinal decline of striatal [¹⁸F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.