Arnoldo Piccardo

Diagnostic and Clinical Significance of F-18-FDG-PET/CT Thyroid Incidentalomas

CONTEXT Thyroid incidentaloma diagnosed by 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (F-18-FDG-PET/CT) is defined as a thyroid uptake incidentally and newly detected in a patient studied for nonthyroid purpose. In this review, we have comprehensively analyzed the diagnostic and clinical significance of F-18-FDG-PET/CT thyroid incidentalomas revealed during studies performed for an unrelated and nonthyroid purpose. EVIDENCE ACQUISITION A comprehensive literature research of the PubMed/MEDLINE databases was conducted to find relevant published articles about the F-18-FDG-PET or F-18-FDG-PET/CT thyroid incidentalomas. EVIDENCE SYNTHESIS All studies considered in this review have investigated a very large number of patients, achieving overall about 147,505 units. The pooled incidence of thyroid incidentalomas detected by F-18-FDG-PET or PET/CT was 2.46% (95% confidence interval, 1.68-3.39%). The malignancy ratio was 34.6% (95% confidence interval, 29.3-40.2%). CONCLUSION F-18-FDG-PET/CT thyroid incidentaloma is a relevant clinical finding; diffuse uptakes and most focal uptakes are commonly caused by benign diseases, whereas about one third of focal uptakes are malignant; the most frequent malignant histological type responsible for F-18-FDG-PET/CT thyroid incidentaloma is papillary thyroid carcinoma.

Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study

Purpose18F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on 18F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of 18F-dopa PET/CT in NB and compare its diagnostic value with that of 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3–4 NB.MethodsWe prospectively evaluated 28 paired 123I-MIBG and 18F-dopa PET/CT scans in 19 patients: 4 at the time of the NB diagnosis and 15 when NB relapse was suspected. For both imaging modalities we performed a scan-based and a lesion-based analysis and calculated sensitivity, specificity and accuracy. The standard of reference was based on clinical, imaging and histological data.ResultsNB localizations were confirmed in 17 of 19 patients. 18F-Dopa PET/CT and 123I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, 18F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while 123I-MIBG scanning showed a sensitivity and accuracy of 68 and 64%, respectively (p < 0.05). No significant difference in terms of specificity was found. In 9 of 28 paired scans (32%) PET/CT results influenced the patient management. We identified 156 NB localizations, 141 of which were correctly detected by 18F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, 18F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas 123I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found.ConclusionIn our NB population 18F-dopa PET/CT displayed higher overall accuracy than 123I-MIBG scintigraphy. Consequently, we suggest 18F-dopa PET/CT as a new opportunity for NB assessment.

Resting SPECT-neuropsychology correlation in very mild Alzheimer's disease

OBJECTIVE To investigate the relationships between brain function and some of the most frequently impaired cognitive domains in the first stages of Alzheimers disease (AD), we searched for correlation between the scores on 3 neuropsychological tests and brain perfusion, assessed by single photon emission computed tomography (SPECT) in patients with very mild AD. METHODS Twenty-nine consecutive outpatients (mean age 78.2+/-5.5) affected by probable AD in the very mild phase (i.e. with a score > or =20 on the mini-mental state examination, MMSE) underwent brain SPECT with (99m)Tc-ethylcisteinate dimer. For correlative purposes, word list learning (by the selective reminding test, SRT), constructional praxis test (CPT) and visual search test (VST) were chosen a priori out of an extended battery employed to diagnose AD at first patient evaluation. Voxel-based correlation analysis was achieved by statistical parametric mapping (SPM99) with a height threshold of P=0.005. Age, years of education and the MMSE score were inserted in the correlative analysis as confounding variables. RESULTS The SRT score showed correlation with brain perfusion in 3 clusters of the left hemisphere, including the post-central gyrus, the parietal precuneus, the inferior parietal lobule and the middle temporal gyrus, and in one cluster in the right hemisphere including the middle temporal gyrus and the middle occipital gyrus. The CPT score was significantly correlated with brain perfusion in the parietal precuneus and the posterior cingulate gyrus in the left hemisphere, whereas the VST score gave a significant correlation with brain perfusion in a left cluster including the parietal precuneus and the superior temporal gyrus. CONCLUSIONS Cognitive impairment in very mild AD is reflected by brain dysfunction in posterior associative areas, with peculiar topographical differences proper of each domain. The parietal precuneus was a common site of correlation of all 3 neuropsychological tests. This region, together with the posterior cingulate and the superficial posterior temporal-parietal cortex, is thought to be affected by disconnection from the mesial temporal lobe, besides being directly affected by increased oxidative stress and by atrophy as well. The impairment of these areas is thought to contribute to cognitive decline in verbal memory, constructional praxis and visual sustained attention which are indeed among the earliest signs of cognitive impairment in AD. SIGNIFICANCE Assessing the relationships between neuropsychology and brain functional imaging is a key approach to clarify the pathophysiology of cognitive failure in AD; the specificity of these findings in AD remains to be proven through comparison with correlation achieved in matched controls.

Giant Cell Arteritis: A Systematic Review of the Qualitative and Semiquantitative Methods to Assess Vasculitis with 18F-Fluorodeoxyglucose Positron Emission Tomography

Giant cell arteritis (GCA) is the most common vasculitis affecting medium and large vessels. It shows a close clinical association with polymyalgia rheumatica (PMR), a musculoskeletal inflammatory disorder, which is clinically characterized by girdles pain and stiffness. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an effective tool for the diagnosis, grading, and follow-up of patients affected by GCA involving the aorta and its proximal branches, but the lack of a standardized method for the assessment of vascular inflammation remains a critical issue, potentially leading to misclassification. In our systematic review, including 19 original articles for a total of 442 GCA patients (with or without PMR symptoms) and 535 healthy controls, we described the different qualitative, semiquantitative and combined methods that have been proposed throughout the literature for assessing the presence and grading the severity of GCA-related vascular inflammation on 18F-FDG PET scans, focusing on the diagnostic performance and examining their respective advantages and limitations. The majority of the included studies adopted qualitative methods of PET image analysis, which are less sensitive but more specific than semiquantitative ones. Among the semiquantitative approaches, the aortic-to-blood pool uptake ratio of the aortic arch seems to be the most accurate method.

Quantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer's disease

OBJECTIVE There is an increasing interest in the effects of the acetylcholinesterase inhibitors (AChEIs) in Alzheimers disease (AD), as investigated by means of objective, neurophysiological tools. In an open-label study, we evaluated the neurophysiological effects of chronic administration of donepezil to AD patients, by means of a correlative approach between quantitative EEG (qEEG) and perfusional brain single photon emission computed tomography (SPECT). METHODS Sixteen patients (mean age: 74.8+/-7.9 years) with mild to moderate AD (MMSE score >13, mean: 20.7+/-4.6) underwent qEEG and SPECT examinations at the time of diagnosis (t0) and after approximately 1 year of donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime) was performed by means of a high-resolution SPECT camera; the qEEG was recorded from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4 brain regions (one frontal and one temporal-parietal in each hemisphere) was chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and t1, as well as the relationships between SPECT and qEEG changes, were assessed by statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster level). RESULTS Between t0 and t1, the MMSE score significantly (P<0.05) decreased (from 20.7+/-4.64 to 19.1+/-5.09; 95% confidence interval: 1.14) and qEEG was unchanged. There was no regional perfusion decrease; a small area of relative perfusion increase was observed, including the right occipital cuneus and the left lingual gyrus. A positive correlation was found between the right frontal MF and brain perfusion in the left superior parietal lobule. A post hoc SPM analysis (height threshold: P=0.01) showed a positive correlation between brain perfusion and each of the 4 qEEG MF values in the left parietal lobe, including the precuneus, the superior parietal lobule, and the post-central gyrus. CONCLUSIONS The posterior parietal region, which is involved in memory and attention, is often affected by hypoperfusion in AD, as a likely consequence of disconnection from the atrophic mesial temporal cortex. Metabolic activation induced by AChEIs may especially influence this disconnected but still not grossly impaired area, which could be one of the pathophysiological substrates of the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG, reflecting the rather diffuse changes in AD, is further confirmed.

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma.

Background. The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS). Methods. A comprehensive literature search of published studies through October 10th, 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. Results. We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS Conclusions. Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning.

Value of Fused 18F-Choline-PET/MRI to Evaluate Prostate Cancer Relapse in Patients Showing Biochemical Recurrence after EBRT: Preliminary Results

Purpose. We compared the accuracy of 18F-Choline-PET/MRI with that of multiparametric MRI (mMRI), 18F-Choline-PET/CT, 18F-Fluoride-PET/CT, and contrast-enhanced CT (CeCT) in detecting relapse in patients with suspected relapse of prostate cancer (PC) after external beam radiotherapy (EBRT). We assessed the association between standard uptake value (SUV) and apparent diffusion coefficient (ADC). Methods. We evaluated 21 patients with biochemical relapse after EBRT. Patients underwent 18F-Choline-PET/contrast-enhanced (Ce)CT, 18F-Fluoride-PET/CT, and mMRI. Imaging coregistration of PET and mMRI was performed. Results. 18F-Choline-PET/MRI was positive in 18/21 patients, with a detection rate (DR) of 86%. DRs of 18F-Choline-PET/CT, CeCT, and mMRI were 76%, 43%, and 81%, respectively. In terms of DR the only significant difference was between 18F-Choline-PET/MRI and CeCT. On lesion-based analysis, the accuracy of 18F-Choline-PET/MRI, 18F-Choline-PET/CT, CeCT, and mMRI was 99%, 95%, 70%, and 85%, respectively. Accuracy, sensitivity, and NPV of 18F-Choline-PET/MRI were significantly higher than those of both mMRI and CeCT. On whole-body assessment of bone metastases, the sensitivity of 18F-Choline-PET/CT and 18F-Fluoride-PET/CT was significantly higher than that of CeCT. Regarding local and lymph node relapse, we found a significant inverse correlation between ADC and SUV-max. Conclusion. 18F-Choline-PET/MRI is a promising technique in detecting PC relapse.

18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR.

Aim: Role of 18F-DOPA PET/CT in neuroblastoma (NB) compared with CT/MR. Materials and Methods: In all, 21 patients (M:F = 14:7; mean age, 7.4 years) affected by advanced stage NB (III-IV) were prospectively enrolled. Overall, 37 paired 18F-DOPA PET and CT/MR scans were performed, and for each, we identified site and number of lesions. Standard of reference was based on a multidisciplinary assessment, including 123I-MIBG, selective biopsy, and clinical-instrumental monitoring. Both scan-based and a lesion-based analysis was performed, and for each modality, we calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results: On the scan-based analysis, 18F-DOPA PET and CT/MR showed the following rates: sensitivity, specificity, NPV, PPV, and accuracy were 100%, 92.3%, 100%, 96%, and 97.3% versus 91.7%, 61.5%, 80%, 81.5%, and 81.1%, respectively (P = 0.014). Overall 179 findings were reported at imaging, of which 139 (77.7%) resulted true sites of disease at final outcome. On the lesion-based analysis, the 2 imaging modalities showed the following sensitivity, specificity, NPV, PPV, and accuracy rates: 90.6%, 90%, 73.5%, 96.9%, and 90.5% versus 47.5%, 27.5%, 13.1%, 69.5%, and 43% (P < 0.00001). Conclusions: In our study, 18F-DOPA PET/CT results more accurate than CT/MR in advanced stage NB therefore should be taken into consideration for the diagnostic workup of these patients.

Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival.

Introduction No parameters predicting recurrence are available for high-risk differentiated thyroid cancer (DTC) patients, and 2-year-follow-up is required to modify the initial prognostic classification. High thyroglobulin (Tg) levels before 131I-remnant-ablation, during L-thyroxine-withdrawal (ablation-Tg) have undetermined predictive/prognostic significance in low-risk DTC patients. Our study aimed to assess the positive predictive value (PPV) of ablation-Tg in high-risk DTC patients and to evaluate whether high ablation-Tg levels were associated with progression-free-survival (PFS) and overall survival (OS). Patients and Methods We selected 243 high-risk DTC patients. All patients underwent total thyroidectomy and 131I-remnant-ablation (initial therapy). Clinical data obtained during a median 5-year follow-up were used to assess the response and outcome. The association between disease persistence/recurrence after initial therapy, ablation-Tg, and other risk-factors (T, N, G, histology, and MACIS score) was evaluated through univariate and multivariate analyses, as was the association between PFS, OS ablation-Tg, and other risk factors. Results Ablation-Tg of 50 &mgr;g/L or greater displayed the highest PPV(97%) for disease persistence. In the univariate analysis, high levels of ablation-Tg were confirmed in patients with persistent disease after initial therapy: the higher the odds ratios, the higher the ablation-Tg levels. On multivariate analysis, ablation-Tg was the best predictive factor, especially on comparing patients with ablation-Tg levels of 50 &mgr;g/L or greater and those with ablation-Tg less than 2 &mgr;g/L (adjusted OR, 818). In a multivariate Cox model, ablation-Tg was the factor most closely associated with PFS (HR, 65.9). The prognostic value of ablation-Tg was confirmed by the overall-survival curves and adjusted risk estimates (adjusted HR = 26.7). Conclusions Ablation-Tg levels of 50 &mgr;g/L or greater are a valuable initial predictor of disease persistence/recurrence in high-risk DTC patients. A significant association emerged between high ablation-Tg levels of 50 &mgr;g/L or greater and both progression-free survival (PFS) and overall survival (OS).

18F-NaF Uptake by Atherosclerotic Plaque on PET/CT Imaging: Inverse Correlation Between Calcification Density and Mineral Metabolic Activity

Several studies have highlighted the role of vascular 18F-NaF uptake as a marker of ongoing calcium deposition. However, accumulation of 18F-NaF is often inconsistent with localization of arterial plaque. Calcification activity and thus 18F-NaF uptake might prevail in the earlier plaque stages. To test this hypothesis, we evaluated 18F-NaF uptake in plaque of 3 different densities, using density as a marker of calcification progression. We also tested whether attenuation-weighted image reconstruction affects 18F-NaF uptake in the different plaque stages. Methods: Sixty-four oncologic patients (14 men and 50 women; mean age, 65.3 ± 8.2 y; range, 26–81 y) underwent 18F-NaF PET/CT. A volume of interest was drawn on each plaque within the infrarenal aorta to assess mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque was then categorized as light (<210 HU), medium (211–510 HU), or heavy (>510 HU). Standardized uptake value was normalized for blood 18F-NaF activity to obtain the plaque target-to-background ratio (TBR). During this process, several focal, noncalcified areas of 18F-NaF were identified (hot spots). The TBR of the hot spots was computed after isocontour thresholding. The TBR of a noncalcified control region was also calculated. In 35 patients, the TBR of non–attenuation-corrected images was calculated. Results: The average TBR was highest in light plaque (2.21 ± 0.88), significantly lower in medium plaque (1.59 ± 0.63, P < 0.001), and lower still in heavy plaque (1.14 ± 0.37, P < 0.0001 with respect to both light and medium plaque). The TBR of the control region was not significantly different from that of heavy plaque but was significantly lower than that of light and medium plaque (P < 0.01). Hot spots had the highest absolute TBR (3.89 ± 1.87, P < 0.0001 vs. light plaque). TBRs originating from non–attenuation-corrected images did not significantly differ from those originating from attenuation-corrected images. Conclusion: Our results support the concept that 18F-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanisms are the main determinants of calcium presence, but that retention of 18F-NaF progressively decreases with increasing calcium deposition in the arterial wall. Our data suggest that non–attenuation-corrected reconstruction does not significantly affect evaluation of plaque of any thickness.