FDG PET in the differential diagnosis of degenerative parkinsonian disorders: usefulness of voxel-based analysis in clinical practice.

BACKGROUND: The early differential diagnosis among neurodegenerative parkinsonian disorders becomes essential to set up the correct clinical-therapeutic approach. The increased utilization of [18F] fluoro-deoxy-glucose positron emission tomography (FDG PET) and the pressure for cost-effectiveness request a systematic evaluation and a validation of its utility in clinical practice. This retrospective study aims to consider the contribution, in terms of increasing accuracy and increasing diagnostic confidence, of voxel-based FDG PET analyses in the differential diagnosis of these disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and cortico-basal syndrome. METHOD: Eighty-three subjects with a clinically confirmed diagnosis of degenerative parkinsonian disorders who underwent FDG brain PET/CT were selected. A voxel-based analysis was set up using statistical parametric mapping (SPM) on MATLAB to produce maps of brain hypometabolism and relative hypermetabolism. Four nuclear physicians (two expert and two not expert), blinded to the patients' symptoms, other physicians' evaluations, and final clinical diagnosis, independently evaluated all data by visual assessment and by adopting metabolic maps. RESULTS: In not-expert evaluators, the support of both hypometabolism and hypermetabolism maps results in a significant increase in diagnostic accuracy as well as clinical confidence. In expert evaluators, the increase in accuracy and in diagnostic confidence is mainly supported by hypometabolism maps alone. CONCLUSIONS: In this study, we demonstrated the additional value of combining voxel-based analyses with qualitative assessment of brain PET images. Moreover, maps of relative hypermetabolism can also make their contribution in clinical practice, particularly for less experienced evaluators.

Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements.

BACKGROUND: Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. OBJECTIVE: We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aß42 and Aß42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. METHOD: Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aß42, Aß42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. RESULTS: Groups were defined basing on the agreement among CSF Aß42 (A), CSF Aß42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aß42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aß42 results, with Aß42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. CONCLUSION: The amyloid discordant cases could be overcome by combining CSF Aß42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aß42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

[18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival.

CONTEXT: 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE: We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS: Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS: Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS: Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Baseline metabolic tumor volume calculation using different SUV thresholding methods in Hodgkin lymphoma patients: interobserver agreement and reproducibility across software platforms.

AIM: Although it is not yet used in clinical practice, metabolic tumor volume (MTV) assessed on the baseline FDG-PET has shown consistent prognostic value in various lymphoma types. The aim of our study was to compare interobserver agreement and reproducibility across platforms of MTV calculation using different SUV thresholding methods in a large series of patients with newly diagnosed Hodgkin lymphoma. MATERIALS AND METHODS: We retrospectively studied 121 patients. MTV at baseline FDG-PET was independently computed by three readers with three programs of semi-automatic segmentation, Fiji, LifeX, and Accurate. MTV measurement was performed with different thresholds: SUV >2.5, SUV >4, and SUV >41% of SUV max. RESULTS: At inter-observer agreement analysis all Intraclass Correlation Coefficients (ICCs) were excellent (ICC >0.9), except for Accurate SUV >41% of SUV max (ICC = 0.8). The highest correlations were obtained at the SUV >4 threshold. The second best was SUV >2.5 threshold. Regarding reproducibility across software, we found statistically significant differences between Fiji versus LifeX and Accurate at fixed thresholds and between LifeX and Accurate at SUV >41% of SUV max, while no significant differences emerged between LifeX and Accurate using fixed thresholds. CONCLUSION: The three SUV thresholds studied are all suitable for MTV calculation in terms of reproducibility. The best reproducibility is achieved using fixed thresholds, both SUV >4 and SUV >2.5. If more than one software has to be used in a study, we suggest the use of fixed thresholds and the platforms LifeX and Accurate.

Myocardial blood flow in patients with hypertrophic cardiomyopathy receiving perindopril (CARAPaCE): a pilot study.

AIMS: Coronary microvascular dysfunction (CMD) represents a powerful independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). No treatment for CMD exists. The angiotensin-converting enzyme (ACE)-inhibitor perindopril improves myocardial blood flow (MBF) in animal models of cardiac hypertrophy and in hypertensive patients. Whether HCM patients with CMD may benefit is unknown. METHODS: Fourteen HCM patients aged 18-60 years with CMD [MBF post 0.56 mg/kg dipyridamole (Dip) infusion <2.1 ml/min∗g] were included. Presence of left ventricular outflow obstruction, hypertension and coronary artery disease were exclusion criteria. Perindopril was administered after the initial Dip 13N-NH3 PET study at 10 mg for 6 months. After wash-out, a second PET was performed. MBF before and after treatment was compared. RESULTS: No relevant associations were found between baseline MBF values and sex, genetics, history of angina, type of HCM (apical/classic), maximum left ventricular thickness and left ventricular mass. No significant improvement in Dip-MBF was observed with treatment (1.79 ±â€Š0.30 vs.1.76 ±â€Š0.26 ml/min∗g at baseline; P = 0.59). A limited but significant improvement in Dip-MBF was seen only in the subset without evidence of fibrosis at cardiac MRI (n = 4; 28%; 2.03 ±â€Š0.13 vs.1.77 ±â€Š0.26 ml/min∗g at baseline; P = 0.014). The drug was generally well tolerated: only one patient temporarily stopped the drug, because of cough. CONCLUSION: A 6-month perindopril treatment course in HCM patients with CMD was not associated with significant improvement in Dip-MBF. A limited but significant improvement was observed only in the subset of patients without myocardial fibrosis, suggesting potential utility in early disease stages.

Assessment of swallowing function with oro-pharyngeal-esophageal scintigraphy in patients with idiopathic inflammatory myopathies.

BACKGROUND: Swallowing impairment is frequently present in patients with idiopathic inflammatory myopathies (IIMs), and it represents an important cause of morbidity, dramatically reducing the quality of life of patients. Moreover, dysphagia is associated to a worst prognosis. Unfortunately, no standardized instrumental techniques for the assessment of the upper gastrointestinal tract in IIM patients are available. In this study, we explored the characteristics of the alterations in the upper gastrointestinal tract using oro-pharyngeal-esophageal scintigraphy (OPES) in a cohort of IIM patients and we correlated the alterations with clinical parameters. METHODS: A total of 51 IIM patients were examined with OPES, both with liquids and semisolids, and the data acquired were examined to compute the transit time and the percentage of retention at oral, pharyngeal, and esophageal level. Patient-reported outcome data (PRO) on dysphagia, disease activity, and clinical parameters were collected. KEY RESULTS: Oro-pharyngeal-esophageal scintigraphy identified at least one alteration in all patients, particularly with the semisolid test and oral and pharyngeal levels presented a higher frequency of involvement compared to the esophageal tract (P < 0.05). A very good correlation between dysphagia severity assessed by PRO and many OPES results was identified. In patients with a shorter disease duration, there was a higher prevalence of alterations at the oral and pharyngeal level and they were correlated to higher swallowing difficulties and higher disease activity parameters. CONCLUSIONS & INFERENCES: Our results showed that OPES may represent a novel reproducible tool to assess dysphagia in IIM patients, thus opening new possibilities to evaluate dysphagia in these patients.

Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.

BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.

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.

UNLABELLED: 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 (18)F-choline PET/CT in a large cohort of patients. METHODS: Data from 1,000 patients who had undergone (18)F-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 χ(2) 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 (18)F-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 (18)F-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 (18)F-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 (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Caudate dopaminergic denervation and visual hallucinations: evidence from a ¹²³I-FP-CIT SPECT study.

OBJECTIVE: The pathogenesis of visual hallucinations (VHs) in Parkinson's disease (PD) has been considered multifactorial. In the pathophysiology of VHs a combination of impaired visual processing and attention has been reported. Imaging studies evidenced a role of the primary visual system and visual association areas as well as a dysfunctional activation of frontal areas in the occurrence of VHs. Due to the functional connections between basal ganglia and frontal areas, a role of basal ganglia and of the fronto-striatal circuits in the pathogenesis of VHs may be postulated. Aim of this study is to unveil whether a presynaptic dopamine deficiency at baseline may predict the development of VHs. METHODS: A group of 18 non demented PD patients with VHs was matched with 18 non demented PD patients without VHs as regards age of onset of disease, disease duration and severity and levodopa equivalent dose. We retrospectively analyzed the (123)I-FP CIT SPECT performed on the two groups at the onset of their disease. The striatal uptake values in the two groups were examined, in order to evaluate nigrostriatal differences between the groups with different behavioral phenotype. RESULTS: The group of patients with VHs had a significant reduction (p < 0.05) in right caudate uptake values at baseline when compared with patients without VHs. No significant differences were found between the groups regarding left caudate and putaminal uptake values. CONCLUSIONS: The frontal impairment reported in PD patients with VHs may be due to a right caudate dysfunction, as it is connected to the frontal brain areas via neuronal loops.