Duccio Volterrani

Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study

BACKGROUND Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimers disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. METHODS We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025. FINDINGS Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimers disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohens kappa=0.87). The procedure was well tolerated with few adverse events. INTERPRETATION A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimers disease.

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.

Differences in nigro‐striatal impairment in clinical variants of early Parkinson’s disease: evidence from a FP‐CIT SPECT study

Introduction:  In idiopathic Parkinson’s disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic‐rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP‐CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor.

Feasibility and Diagnostic Accuracy of a Gated SPECT Early-Imaging Protocol: A Multicenter Study of the Myoview Imaging Optimization Group

The aim of this study was to investigate whether early (time 1, or T1) myocardial tetrofosmin imaging is feasible and as accurate in detecting coronary artery disease as is standard delayed (time 2, or T2) imaging. Methods: One hundred twenty patients (100 men and 20 women; mean age ± SD, 61 ± 10 y) with anginal symptoms underwent tetrofosmin gated SPECT. Stress/rest T1 imaging was performed at 15 min and T2 at 45 min after injection. Image quality was visually evaluated using a 4-point scale (from 0 = poor to 3 = optimal). Myocardial perfusion analysis was performed on a 20-segment model using quantitative perfusion SPECT software, and reversible ischemia was scored as a summed difference score (SDS). Coronary angiography was performed within 1 mo on all patients, and stenosis of more than 50% of the diameter was considered significant. Results: Overall, quality was scored as optimal or good for 94% of T1 images and 95% of T2 images (P = not statistically significant). Heart, lung, liver, and subdiaphragmatic counts did not differ for stress and rest T1 and T2 imaging. A good linear relationship was seen between T1 and T2 SDS (r = 0.69; P < 0.0001), and Bland–Altman analysis showed good agreement between the 2 conditions. In terms of global diagnostic accuracy, areas under the receiver-operating-characteristic curve were comparable between T1 and T2 (0.80 vs. 0.81, P = not statistically significant). Discrepancies between T1 and T2 SDS were observed in 44% of patients (T1 − T2 SDS > 2). Linear regression analysis showed a good correlation between T1 and T2 SDS (r = 0.67; P < 0.0001), whereas the Bland–Altman method showed a shift in the mean value of the difference of +2.67 ± 2.73. In patients with a T1 − T2 SDS of more than 2, areas under the receiver-operating-characteristic curves were significantly higher for T1 than for T2 images (0.79 vs. 0.70, P < 0.001). Conclusion: T1 imaging is feasible and as accurate as T2 imaging in identifying coronary artery disease. However, in a discrete subset of patients, early acquisition strengthens the clinical message of defect reversibility by permitting earlier, more accurate identification of more severe myocardial ischemia.

Presynaptic nigro-striatal function in a group of Alzheimer's disease patients with parkinsonism: evidence from a dopamine transporter imaging study

Summary.The occurrence of parkinsonism in Alzheimer’s disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson’s disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p<0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.

Gleason Score at Diagnosis Predicts the Rate of Detection of 18F-Choline PET/CT Performed When Biochemical Evidence Indicates Recurrence of Prostate Cancer: Experience with 1,000 Patients

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with 18F-choline PET/CT in a large cohort of patients. Methods: Data from 1,000 patients who had undergone 18F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ2 test. Univariable and multivariable analyses were performed by logistic regression. Results: The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1–2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of 18F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of 18F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1–2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive 18F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). Conclusion: A high GS at diagnosis is a strong predictive factor for positive 18F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Dopamine Transporter SPECT Imaging in Corticobasal Syndrome

Objective To investigate dopaminergic function in a large cohort of patients with corticobasal syndrome (CBS) and describe its relationship with clinical features in comparison to Parkinsons disease and healthy control subjects. In addition, we assessed prevalence and features of individuals with CBS and in vivo evidence of preserved nigral neuronal density. Background Substantia nigra pars compacta (SNc) neuronal degeneration is a mandatory pathological criterion for definite corticobasal degeneration, though sporadic autopsy-proven cases with ante-mortem imaging evidence of preserved nigral terminals have been recently described. Methods In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for “probable corticobasal degeneration” (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans. Results FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake. Conclusions Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD.

Renal nuclear medicine

The measurement of renal function has been a major field of interest in nuclear medicine. Many studies in the literature are still dedicated to this subject, with the aim of replacing the traditional urinary clearance methods with simpler and easier techniques. Simplified plasma clearance methods appear of sufficient accuracy to estimate global kidney function, except in very low function in which urinary clearance is still indicated. Gamma-camera methods have also been developed that, although of a lesser accuracy than the in vitro techniques, offer the important advantage of allowing renal imaging with the estimation of separate kidney function. Because of the intimate link between kidney function and structure, the diagnosis of nephrourological diseases has represented an important goal of nuclear medicine research. The functional information attainable with radionuclides is a valuable complement to the morphological information of imaging techniques such as x-ray computed tomography, ultrasonography, and magnetic resonance imaging. Recent contributions of nuclear medicine to the progress of clinical nephrology include the evaluation of renal function and the diagnostic work-up of renovascular hypertension, obstructive nephropathy, urinary tract infection, and renal transplantation.

Paroxysmal arousal in epilepsy associated with cingulate hyperperfusion.

A patient with nocturnal frontal lobe epilepsy characterized by paroxysmal motor attacks during sleep had brief paroxysmal arousals (PAs), complex episodes of nocturnal paroxysmal dystonia, and epileptic nocturnal wandering since childhood. Ictal SPECT during an episode of PA demonstrated increased blood flow in the right anterior cingulate gyrus and cerebellar cortex with hypoperfusion in the right temporal and frontal associative cortices.

Dopaminergic degeneration and perfusional impairment in Lewy body dementia and Alzheimer's disease

Abstract.The clinical differentiation of Lewy body dementia (LBD) from Alzheimer’s disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with 123I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly (p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) 123I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant (p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant (p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.