Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson’s disease

Purpose Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [^99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders.Methods Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [^99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Students t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures.Results Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49±0.30) compared with PD patients (0.74±0.25).Conclusion Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [^99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.     

Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson’s disease with and without dementia assessed using 123I-FP-CIT SPECT

Purpose The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinsons disease (PD) and PD with dementia (PDD) using serial ¹²³I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders.Methods We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated.Results Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p0.01), anterior putamen (DLB, PDD, p0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD.Conclusion In conclusion, this is the first study to show that significant progressive dopaminergic loss occurs in DLB and PDD using serial ¹²³I-FP-CIT SPECT. Dementia severity and motor impairment were correlated with decline, suggesting that dopaminergic loss may play an important role in cognitive as well as motor features.     

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.     

Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson’s disease by 123I-FP-CIT brain SPECT

Purpose  

To contribute to the differentiation of Parkinson’s disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using ¹²³I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT).     

Differentiating between multiple system atrophy and Parkinson’s disease by positron emission tomography with18F-dopa and18F-FDG

Both the striatal¹⁸F-dopa uptake and brain glucose metabolism were studied by PET with 6-l-[¹⁸F]fluorodopa (FD) and [¹⁸F]fluorodeoxyglucose (FDG) in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson’s disease (PD). Five of the 9 MSA patients were diagnosed as having olivopontocerebellar atrophy, whereas 2 had striatonigral degeneration and 2 demonstrated Shy-Drager syndrome. The FD uptake ratios to the occipital cortex in the MSA patients at 120 min after the administration of FD were 2.07 ± 0.31 (mean ± SD) and 1.96 ± 0.29 in the caudate and the putamen, respectively, and decreased compared to those in the controls (2.72 ± 0.11, 2.71 ± 0.10). The same ratios in the PD patients were 2.07 ± 0.36 and 1.74 ± 0.24, respectively, which also decreased, but the decreased uptake in the putamen was more prominent. The caudate-putamen index (CPI) (%), which was calculated by a formula based on the difference in the uptakes in the caudate and putamen divided by the caudate uptake, indicated 5.6 ± 4.6 in the MSA patients and 14.8 ± 5.4 in the PD patients. The CPI for all PD patients was more than 7.0, which was the mean + 2SD for the controls, but the CPI for 3 MSA patients was more than 7.0 (accuracy: 88%). The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal and the temporal cortical glucose metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in the MSA patients decreased significantly in comparison to those in the controls. But, as the glucose metabolic rates in such regions of each patient overlapped in the two groups, the accuracy of the FDG study for differentiation was lower than that of the FD study. The putaminal glucose metabolic rates, for example, in 3 PD patients were less than 6.8 (mg/min/100 ml), which was the mean — 2SD for the controls, while those in 3 MSA patients were more than 6.8 (accuracy: 75%). In addition, the combination of these two methods slightly improved the accuracy. The glucose metabolism is useful for evaluating the regional metabolic activity of the brain, and the FD study, which is specific to the dopamine system, seems to be more useful for differentiating between MSA and PD.     

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson’s disease

Purpose  

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD).     

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.     

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.

     

SPECT and PET imaging in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.     

Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson’s disease patients

^99mTc-TRODAT-1 is the first clinical routine ^99mTc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). ¹⁸ F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects.MethodsEighteen subjects (8 HC and 10 PD) were recruited for ^99mTc-TRODAT-1 SPECT, ¹⁸ F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts − 1). The nonparametric Mann–Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities.ResultsThe SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p < 0.001), and showed significant different between HC and PD subjects. Of note, the ¹⁸ F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to ^99mTc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from ¹⁸ F-AV-133 image as compared to ^99mTc-TRODAT-1 especially at the substantia nigra region.Conclusion¹⁸ F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of ^99mTc-TRODAT-1 SPECT. ¹⁸ F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, ¹⁸ F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients.     

Using ‘swallow-tail’ sign and putaminal hypointensity as biomarkers to distinguish multiple system atrophy from idiopathic Parkinson’s disease: A susceptibility-weighted imaging study

Objective

To investigate the value of ‘swallow-tail’ sign and putaminal hypointensity on 3 T susceptibility-weighted imaging (SWI) for distinguishing multiple system atrophy (MSA) from idiopathic Parkinson’s disease (IPD).

Methods

Three groups – 39 MSA patients, 18 IPD patients,and 31 healthy controls (HCs) – were administered a 3 T SWI sequence to evaluate ‘swallow-tail’ sign and putaminal hypointensity using visual scales from 0 to 2 and 0 to 3 scores, respectively. The diagnostic accuracy of the two signs separately and combined was calculated using a receiver operating characteristic curve, with clinical diagnosis as the gold standard.

Results

The scores of ‘swallow-tail’ sign were lower in IPD than in MSA or in HCs, as well as for putaminal hypointensity in IPD or HCs than in MSA (p?<?0.05). The sensitivity and specificity of ‘swallow-tail’ sign and putaminal hypointensity were 87.9% and 83.3%, and 35.9% and 100%, respectively, in the respective patient groups. The area under the curve of combined signs was increased from 0.85 (‘swallow tail’) or 0.68 (putaminal hypointensity) to 0.93.

Conclusion

The combination of ‘swallow-tail’ sign and putaminal hypointensity can increase the accuracy of discriminating between MSA and IPD.

Key Points

? Differential diagnosis of MSA and IPD is still challenging in clinical practice.? Absence of ‘swallow-tail’ sign is a valuable biomarker for IPD on SWI.? Putaminal hypointensity is a valuable biomarker for MSA on SWI.? Combined ‘swallow- tail’ sign and putaminal hypointensity increase diagnostic accuracy.

     

The Utility of Segmental Analysis in Cardiac I-123 MIBG SPECT in Parkinson’s Disease

Purpose

Cardiac images using I-123 metaiodobenzylguanidine (MIBG) are widely used to evaluate cardiac sympathetic denervation in Parkinson’s disease (PD). The aim of this study was to evaluate the utility of segmental analysis on cardiac MIBG SPECT in PD patients.

Materials and Methods

In total, 36 patients with PD (n = 26) or essential tremor (ET, n = 10) who underwent MIBG cardiac SPECT were enrolled. The heart-to-mediastinum (H/M) ratios of MIBG uptake were acquired on planar images. For the segmental analysis of SPECT images, we evaluated the summed defect score (SDS) using a 17-segment model. The diagnostic abilities of H/M ratios and segmental parameters on MIBG SPECT were assessed by ROC curve analysis.

Results

The H/M ratios were significantly lower in PD than in ET patients (p < 0.05). On segmental analysis, SDS was significantly higher in PD patients than in the ET group (7.04 ± 4.09 vs. 2.90 ± 2.80; p = 0.006). The defect score of the anteroseptal region showed a significant difference between the groups (p = 0.002). The ROC analysis suggested only SDS (AUC = 0.785, p = 0.0003) and defect scores in the anteroseptal (AUC = 0.800, p < 0.0001) and inferior (AUC = 0.667, p = 0.013) regions showed significant diagnostic ability to differentiate PD from ET.

Conclusions

Segmental parameters from cardiac MIBG SPECT images can provide additional information to differentiate PD from ET patients. Beyond H/M ratios from planar images, we recommend an MIBG SPECT study to evaluate sympathetic denervation in PD.     

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson’s disease and healthy controls

Purpose  Diagnosing Parkinson’s disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Methods  Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. Results  FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. Conclusion  FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.     

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).

Methods

This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4?±?11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7?±?8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.

Results

Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ² ?=?0.1501) particularly in the head of the ipsilateral caudate nucleus (p?<?0.0001), whereas increasing disease duration was associated with a linear decrease in ¹²³I-ioflupane uptake (p?<?0.0001; R ² ?=?0.1532) particularly in the contralateral anterior putamen (p?<?0.0001).

Conclusion

We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications.

     

Underwater gait analysis in Parkinson’s disease

Although hydrotherapy is one of the physical therapies adopted to optimize gait rehabilitation in people with Parkinson disease, the quantitative measurement of gait-related outcomes has not been provided yet. This work aims to document the gait improvements in a group of parkinsonians after a hydrotherapy program through 2D and 3D underwater and on land gait analysis. Thirty-four parkinsonians and twenty-two controls were enrolled, divided into two different cohorts. In the first one, 2 groups of patients underwent underwater or land based walking training; controls underwent underwater walking training. Hence pre-treatment 2D underwater and on land gait analysis were performed, together with post-treatment on land gait analysis. Considering that current literature documented a reduced movement amplitude in parkinsonians across all lower limb joints in all movement planes, 3D underwater and on land gait analysis were performed on a second cohort of subjects (10 parkinsonians and 10 controls) who underwent underwater gait training. Baseline land 2D and 3D gait analysis in parkinsonians showed shorter stride length and slower speed than controls, in agreement with previous findings. Comparison between underwater and on land gait analysis showed reduction in stride length, cadence and speed on both parkinsonians and controls. Although patients who underwent underwater treatment exhibited significant changes on spatiotemporal parameters and sagittal plane lower limb kinematics, 3D gait analysis documented a significant (p < 0.05) improvement in all movement planes. These data deserve attention for research directions promoting the optimal recovery and maintenance of walking ability.     

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Purpose Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinsons disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis.Methods The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [¹²³I]-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained.Results In the group of patients with APS, baseline [¹²³I]-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups.Conclusion [¹²³I]-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.     

Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson’s disease

Purpose Diagnosis of Parkinsons disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system.Methods Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the off state (UPDRS-III and H&Y stage).Results Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r=0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r=0.84, both p<0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (=–0.52 for both techniques), UPDRS-III (=–0.38 for F-DOPA; =–0.45 for FP-CIT) and disease duration (=–0.59 for F-DOPA; =–0.49 for FP-CIT, all p<0.05).Conclusion FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.