Zoulikha Malek

Is 18F‐fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in takayasu arteritis?

OBJECTIVE (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning has been proposed as a new way of assessing disease activity in Takayasu arteritis (TA), but previous studies have used the nonvalidated National Institutes of Health (NIH) global activity criteria, and thus might be biased. This study was undertaken to determine the value of PET scanning for assessment of disease activity in TA, by comparing PET scan data with clinical, biologic, and magnetic resonance imaging (MRI) data assessed separately. METHODS Twenty-eight patients with TA (according to the American College of Rheumatology criteria) underwent a total of 40 PET scans. Images were reviewed by 2 pairs of independent nuclear medicine physicians and assessed for pattern and intensity of vascular uptake. TA activity data were obtained within 15 days of the PET scans. RESULTS PET scanning revealed abnormal vascular uptake in 47% of the 40 examinations. The uptake intensity grade was 0 in 7 scans, grade 1 in 7 scans, grade 2 in 13 scans, and grade 3 in 13 scans. Morphologic analysis was conducted by grading the pattern of the vascular uptake as diffuse (73%), segmental (20%), or focal (13%). There was a trend toward an association between clinically active disease and the semiquantitative assessment of FDG uptake (P = 0.08). We found no statistical association between levels of acute-phase reactants and intensity of uptake. There was no significant association between the semiquantitative assessment of FDG uptake and the presence of vascular wall thickening (P = 0.23), gadolinium uptake (P = 0.73), or the presence of vascular wall edema (P = 0.56). CONCLUSION Our findings indicate that there is no association between FDG vascular uptake intensity and clinical, biologic, or MRI assessment of disease activity. Previous studies using the nonvalidated NIH global activity criteria are likely biased.

Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images

123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) is a SPECT dopamine transporter (DAT) tracer that probes dopaminergic cell loss in Parkinsons disease (PD). Quantification of 123I-FP-CIT images is performed at equilibrium using a ratio (BR) of specific (striatal) to nonspecific (occipital) uptake with values obtained from regions of interest drawn manually over these structures. Statistical parametric mapping (SPM) is a fully automated voxel-based statistical approach that has great potential in the context of DAT imaging. However, the accuracy of the spatial normalization provided by SPM has not been validated for 123I-FP-CIT images. Our first aim was to create an 123I-FP-CIT template that does not require the acquisition of patient-specific MRI and to validate the spatial normalization procedure. Next, we hypothesized that this customized template could be used by different SPECT centers without affecting the outcomes of imaging analyses. Methods: The spatial normalization to the customized template created with SPM (template A1) was validated using 123I-FP-CIT images obtained from 6 subjects with essential tremor (ET) with normal DAT status and 6 PD patients. Variability in BR values due to the normalization was evaluated using striatal volume of interest (VOI). To determine whether different SPECT centers could use a unique 123I-FP-CIT template, we generated 3 other 123I-FP-CIT templates using different subjects and image-processing schemes. The interchangeability of these templates was assessed using (a) putamen BR values analyzed with the intraclass correlation coefficient (ICC) and the Bland–Altman graphical analysis, and (b) SPM analysis comparing the results of group comparisons—that is, ET versus PD, obtained after normalization to each of the 4 templates. Results: There was no significant difference between pre- and postnormalization striatal BR values in our study. The mean variability calculated with putamen VOI values after normalization to each template was <10%, with the lowest ICC of 98%. Intergroup analyses performed with VOI and SPM approaches provided similar results independently of the template used. Conclusion: SPM normalization was accurate even in subjects with low striatal 123I-FP-CIT uptake, making it a promising approach for automatic analysis of 123I-FP-CIT images using a single customized template at different centers.

Quantitative simultaneous 99mTc-ECD/123I-FP-CIT SPECT in Parkinson’s disease and multiple system atrophy

PurposeThe purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA).MethodsSimultaneous 99mTc-ECD/123I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus.ResultsStriatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p<0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p<0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p<0.05).ConclusionDual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes.

Differential automatic diagnosis between Alzheimer's disease and frontotemporal dementia based on perfusion SPECT images

OBJECTIVE Alzheimers disease (AD) and frontotemporal dementia (FTD) are among the most frequent neurodegenerative cognitive disorders, but their differential diagnosis is difficult. The aim of this study was to evaluate an automatic method returning the probability that a patient suffers from AD or FTD from the analysis of brain perfusion single photon emission computed tomography images. METHODS AND MATERIALS A set of 116 descriptors corresponding to the average activity in regions of interest was calculated from the images of 82 AD and 91 FTD patients. A set of linear (logistic regression and linear discriminant analysis) and non-linear (support vector machines, k-nearest neighbours, multilayer perceptron and kernel logistic PLS) classification methods was subsequently used to ascertain diagnoses. Validation was carried out by means of the leave-one-out protocol. Diagnoses by the classifier and by four physicians (visual assessment) were compared. Since images were acquired in different hospitals, the impact of the medical centre on the diagnosis of both the classifier and the physicians was investigated. RESULTS Best results were obtained with support vector machine and partial least squares regression coupled with k-nearest neighbours methods (PLS+K-NN), with an overall accuracy of 88%. PLS+K-NN was however considered as the best method since performances obtained with leave-one-out cross-validation were closer to whole-database learning. The performances of the classifier were higher than those of experts (accuracy ranged from 65 to 72%). Physicians found it more difficult to diagnose the images from centres other than their own, and it affected their performances. CONCLUSIONS The performances obtained by the classifier for the differential diagnosis of AD and FTD were found convincing. It could help physicians in daily practice, particularly when visual assessment is inconclusive, or when dealing with multicentre data.

Dopamine transporter imaging under high-dose transdermal nicotine therapy in Parkinsonʼs disease: an observational study

ObjectivesNicotine therapy might improve the course of Parkinsons disease. This observational study evaluated the performance of dopamine transporter imaging in follow-up patients under nicotine therapy. MethodsSix Hoehn and Yahr stage III patients underwent 123I-FP-CIT imaging prior to, 3 months, and 1 year after the onset of nicotine therapy. Nicotine was administered transdermally with increasing daily doses during 3 months (up to 105 mg/day) and decreased progressively. On co-registered magnetic resonance imaging, striatal regions of interest were drawn and binding potentials of 123I-FP-CIT were calculated. Changes in Unified Parkinsons Disease Rating Scale-III over time were compared with binding potentials using regression analysis. ResultsAll patients improved motor scores at 3 months (−65±22% ‘off’, −89±12% ‘on’) and most received fewer dopaminergic drugs (−30% dosage in average). Motor improvement persisted to a lesser extent at 1 year (−39±31% ‘off’, −13±43% ‘on’), partly because one patient stopped the treatment. Interestingly, the decrease in binding potentials (−4.0±10.5%) was slower than that expected in Parkinsonian patients (usually −10% per year) and was inversely correlated with Unified Parkinsons Disease Rating Scale-III improvement, r = 0.83 ‘off’ and 0.91 ‘on’. ConclusionThis observational study emphasizes a potential effect of nicotine therapy on striatal dopamine transporter density, which may be interpreted as direct pharmacological effect or deceleration of neuronal loss.