Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Derivation and Validation of a Phenoconversion-Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. OBJECTIVE: The aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analysis (Scaled Subprofile Model and Principal Component Analysis [SSM-PCA]). METHODS: Seventy-six consecutive iRBD patients (70 ± 6 years, 15 women) were enrolled in two centers and prospectively evaluated to assess phenoconversion (30 converters, 73 ± 6 years, 14 Parkinson's disease and 16 dementia with Lewy bodies, follow-up time: 21 ± 14 months; 46 nonconverters, 69 ± 6 years, follow-up time: 33 ± 19 months). All patients underwent [18 F]FDG-PET (18 F-fluorodeoxyglucose positron emitting tomography) to investigate brain glucose metabolism at baseline. SSM-PCA was applied to obtain the iRBDconvRP; nonconverter patients were considered as the reference group. Survival analysis and Cox regression were applied to explore prediction power. RESULTS: First, we derived and validated two distinct center-specific iRBDconvRP that were comparable and significantly able to predict phenoconversion. Then, SSM-PCA was applied to the whole set, identifying the iRBDconvRP. The iRBDconvRP included positive voxel weights in cerebellum; brainstem; anterior cingulate cortex; lentiform nucleus; and middle, mesial temporal, and postcentral areas. Negative voxel weights were found in posterior cingulate, precuneus, middle frontal gyrus, and parietal areas. Receiver operating characteristic analysis showed an area under the curve of 0.85 (sensitivity: 87%, specificity: 72%), discriminating converters from nonconverters. The iRBDconvRP significantly predicted phenoconversion (hazard ratio: 7.42, 95% confidence interval: 2.6-21.4). CONCLUSIONS: We derived and validated an iRBDconvRP to efficiently discriminate converter from nonconverter iRBD patients. [18 F]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Detection rate of 18F-Choline positron emission tomography/computed tomography in patients with non-metastatic hormone sensitive and castrate resistant prostate cancer.

BACKGROUND: To assess the detection rate of 18F-choline PET/CT in non-metastatic hormone-sensitive prostate cancer (hsPCa) and non-metastatic castrate resistant prostate cancer (CRPCa), based on the criteria proposed in the phase III SPARTAN trial and with high Gleason Score (GS). METHODS: Between October 2008 and September 2019, data from a retrospective multicenter study (N.=4 centers), involving patients undergoing 18F-choline PET/CT scans for a biochemical recurrence of PCa, were collected. The following inclusion criteria were used: 1) histologically proven PCa; 2) a non-metastatic disease in accordance with conventional imaging findings; 3) a PSA doubling time (PSAdt) <10 months; 4) a GS>8; and 5) no pelvic node>2 cm. The group of hsPCa and CRPCa patients, were compared by using a non-parametric statistical analysis. Moreover, a logistic regression analysis and ROC curves were used. RESULTS: One hundred forty patients were included. Of these, 82 patients were affected by hsPCa, and 58 had a CRPCa. Overall, 18F-Choline PET/CT was positive in 99/140 (70.7%). It was positive in 55/82 (67.1%) hsPCa patients and in 44/58 (75.9%) CRPCa subjects, respectively. The site of recurrence at 18F-Choline PET/CT were: 16 (27.6%) and 20 (24.4%) in prostatic bed, 25 (43.1%) and 24 (29.3%) in loco-regional lymph nodes and in 27 (46.6%) and 28 (34.1%) in distant organs, respectively for CRPCa and hsPCa patients. The optimal cut-off values for PSA at the time of PET/CT for the prediction or recurrence were 0.5 vs. 2.5 ng/mL for all site of recurrence (AUC: 0.70 vs. 0.72), 0.48 vs. 3.4 ng/mL for prostatic bed (AUC: 0.60 vs. 0.59), 0.5 vs. 1.5 for loco-regional lymph nodes (AUC: 0.62 vs. 0.57) and 2.2 vs. 2.8 ng/mL for distant metastasis (AUC: 0.74 vs. 0.71), respectively in CRPCa and hsPCa (all P=NS). Sensitivities and specificities of 18F-Choline PET/CT for the identification of recurrence disease in all patient population, in hsPCa and CRPCa were 83.7% and 87.5%, 78.9% and 88.9%, 91.4% and 85.7%, respectively. CONCLUSIONS: The rate of positive 18F-Choline PET/CT is similar in patients with a hsPCa and CRPCa, in case of low PSAdt and high GS. Therefore, non-metastatic PCa patients should be assessed by molecular imaging, in order to adapt the most appropriate therapeutic approach.

Validation of the REM behaviour disorder phenoconversion-related pattern in an independent cohort.

BACKGROUND: A brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients. METHODS: Forty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [18F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power. RESULTS: The iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18-15.39). CONCLUSIONS: The iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials.

Functional Correlates of Striatal Dopamine Transporter Cerebrospinal Fluid Levels in Alzheimer's Disease: A Preliminary 18F-FDG PET/CT Study.

The aim of our study was to investigate regional glucose metabolism with 18F-FDG positron emission tomography/computed tomography in a population of patients with Alzheimer's disease (AD) in relation to cerebrospinal (CSF) levels of striatal dopamine transporter (DAT). All patients underwent lumbar puncture and received a biomarker-based diagnosis of AD. Differences in regional brain glucose metabolism were assessed by Statistical Parametric Mapping version 12 with the use of age, gender, and MMSE as covariates in the analysis. A positive correlation between CSF DAT levels and glucose metabolism at the level of two brain areas involved in the pathophysiological process of Alzheimer's disease, the substantia nigra and the posterior cingulate gyrus, has been highlighted. Results indicate that patients with higher CSF DAT levels have a better metabolic pattern in two key zones, suggesting less advanced disease status in patients with more conserved dopaminergic systems.

Cognitive functioning, cerebrospinal fluid Alzheimer's disease biomarkers and cerebral glucose metabolism in late-onset epilepsy of unknown aetiology: A prospective study.

Epilepsy is increasing, being more common in older adults, with more than 20% of late-onset cases with unknown aetiology (LOEU). Although epilepsy was associated with cognitive impairment, few studies evaluated the trajectories of cognitive decline in patients with LOEU. The present study aimed at assessing biomarkers of Alzheimer's disease (AD) in patients with LOEU and evaluating their cognitive performance for 12 months. For this study, 55 patients diagnosed with LOEU and 21 controls were included. Participants underwent cognitive evaluation and cerebrospinal fluid (CSF) biomarker analysis (ß-amyloid42 , tau proteins) before starting anti-seizure medication and then repeated the cognitive evaluation at the 12-month follow-up. A subgroup of LOEU patients and controls also performed 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) before starting anti-seizure medication. At baseline, LOEU patients showed lower Mini-Mental State Examination (MMSE) score, worse cognitive performance in several domains, lower ß-amyloid42 and higher tau proteins CSF levels than controls. Significantly reduced glucose consumption was observed in the right posterior cingulate cortex and left praecuneus areas in LOEU patients than controls, and this finding correlated with memory impairment. In the longitudinal analysis, a significant decrease in MMSE and an increase in verbal fluency scores were found in LOEU patients. These findings evidence that LOEU patients have a significant cognitive impairment, and alteration of cerebral glucose consumption and CSF AD biomarkers than controls. Moreover, they showed a progressive global cognitive decline at follow-up, although verbal fluency was preserved. Further studies are needed to better understand the pathophysiological aspects of LOEU and its association with AD.

Tau Biomarkers in Dementia: Positron Emission Tomography Radiopharmaceuticals in Tauopathy Assessment and Future Perspective.

Abnormal accumulation of Tau protein is closely associated with neurodegeneration and cognitive impairment and it is a biomarker of neurodegeneration in the dementia field, especially in Alzheimer's disease (AD); therefore, it is crucial to be able to assess the Tau deposits in vivo. Beyond the fluid biomarkers of tauopathy described in this review in relationship with the brain glucose metabolic patterns, this review aims to focus on tauopathy assessment by using Tau PET imaging. In recent years, several first-generation Tau PET tracers have been developed and applied in the dementia field. Common limitations of first-generation tracers include off-target binding and subcortical white-matter uptake; therefore, several institutions are working on developing second-generation Tau tracers. The increasing knowledge about the distribution of first- and second-generation Tau PET tracers in the brain may support physicians with Tau PET data interpretation, both in the research and in the clinical field, but an updated description of differences in distribution patterns among different Tau tracers, and in different clinical conditions, has not been reported yet. We provide an overview of first- and second-generation tracers used in ongoing clinical trials, also describing the differences and the properties of novel tracers, with a special focus on the distribution patterns of different Tau tracers. We also describe the distribution patterns of Tau tracers in AD, in atypical AD, and further neurodegenerative diseases in the dementia field.

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients' pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called "theranostic" approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors' analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.

Radiological imaging in multiple myeloma: review of the state-of-the-art.

PURPOSE: Multiple myeloma is a type of blood cancer arising from the uncontrolled clonal proliferation of malignant plasma cells resulting in impaired hematopoiesis, hyper production of monoclonal protein, bone tissue destruction leading and renal system alterations up to kidney failure. The aim is to review the state-of-the-art of radiological imaging in multiple myeloma. METHODS: Radiological techniques as well as the advancements in imaging technology have been reviewed and summarized. The main radiological findings of different imaging techniques in patients suffering from multiple myeloma are also illustrated. RESULTS: Different radiological techniques provide structural and functional data. In the last years, conventional skeletal survey has gradually lost its utility and it has been replaced by whole body low-dose computed tomography which allows to identify also small lytic lesions, the medullary and the extramedullary involvement. Nowadays, magnetic resonance is the most sensitive imaging technique for detecting of skeletal as well as medullary involvement in patients with multiple myeloma. Thanks to the multiparametric evaluation (morphological, diffusion weighted and perfusion imaging sequences) and to the quantitative analysis, magnetic resonance imaging is proved to be useful in the early evaluation of response to therapy. Finally, positron emission tomography has greater sensibility compared to computed tomography as it provides quantitative data; however, the lower expression levels of the specific gene involved in the glycolysis pathway are associated with false-negative results with consequent underestimation of the disease. CONCLUSION: The only use of the advanced combined multimodal imaging allows a better evaluation, staging and early assessment of treatment response in patients with multiple myeloma.

MGMT Promoter Methylation and IDH1 Mutations Do Not Affect [18F]FDOPA Uptake in Primary Brain Tumors.

The aim of our study was to investigate the effects of methylation of O6-methylguanine-DNA methyltransferase promoter (MGMTp) and isocitrate dehydrogenase 1 (IDH 1) mutations on amino acid metabolism evaluated with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Seventy-two patients with primary brain tumors were enrolled in the study (33 women and 39 men; mean age 44 ± 12 years old). All of them were subjected to PET/CT examination after surgical treatment. Of them, 29 (40.3%) were affected by grade II glioma and 43 (59.7%) by grade III. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs that of the background. Statistical analysis was performed with the Mann-Whitney U test. Methylation of MGMTp was detectable in 61 out of the 72 patients examinated. Mean SUVr in patients without methylation of MGMTp was 1.44 ± 0,38 vs. 1.35 ± 0.48 of patients with methylation (p = 0.15). Data on IDH1 mutations were available for 43 subjects; of them, 31 are IDH-mutant. Mean SUVr was 1.38 ± 0.51 in patients IDH mutant and 1.46 ± 0.56 in patients IDH wild type. MGMTp methylation and IDH1 mutations do not affect [18F] FDOPA uptake in primary brain tumors and therefore cannot be assessed or predicted by radiopharmaceutical uptake parameters.

Theragnostic Aspects and Radioimmunotherapy in Pediatric Tumors.

The use of theragnostic radiopharmaceuticals in nuclear medicine has grown rapidly over the years to combine the diagnosis and therapy of tumors. In this review, we performed web-based and desktop literature research to investigate and explain the potential role of theragnostic imaging in pediatric oncology. We focused primarily on patients with aggressive malignancies such as neuroblastoma and brain tumors, to select patients with the highest chance of benefit from personalized therapy. Moreover, the most critical and groundbreaking applications of radioimmunotherapy in children's oncology were examined in this peculiar context. Preliminary results showed the potential feasibility of theragnostic imaging and radioimmunotherapy in pediatric oncology. They revealed advantages in the management of the disease, thereby allowing an intra-personal approach and adding new weapons to conventional therapies.

Positron Emission Tomography (PET) and Neuroimaging in the Personalized Approach to Neurodegenerative Causes of Dementia.

Generally, dementia should be considered an acquired syndrome, with multiple possible causes, rather than a specific disease in itself. The leading causes of dementia are neurodegenerative and non-neurodegenerative alterations. Nevertheless, the neurodegenerative group of diseases that lead to cognitive impairment and dementia includes multiple possibilities or mixed pathologies with personalized treatment management for each cause, even if Alzheimer's disease is the most common pathology. Therefore, an accurate differential diagnosis is mandatory in order to select the most appropriate therapy approach. The role of personalized assessment in the treatment of dementia is rapidly growing. Neuroimaging is an essential tool for differential diagnosis of multiple causes of dementia and allows a personalized diagnostic and therapeutic protocol based on risk factors that may improve treatment management, especially in early diagnosis during the prodromal stage. The utility of structural and functional imaging could be increased by standardization of acquisition and analysis methods and by the development of algorithms for automated assessment. The aim of this review is to focus on the most commonly used tracers for differential diagnosis in the dementia field. Particularly, we aim to explore 18F Fluorodeoxyglucose (FDG) and amyloid positron emission tomography (PET) imaging in Alzheimer's disease and in other neurodegenerative causes of dementia.

Brain metabolic patterns in patients with suspected non-Alzheimer's pathophysiology (SNAP) and Alzheimer's disease (AD): is [18F] FDG a specific biomarker in these patients?

PURPOSE: The present study was conducted to compare the pattern of brain [18F] FDG uptake in suspected non-Alzheimer's pathophysiology (SNAP), AD, and healthy controls using 2-deoxy-2-[18F]fluoroglucose ([18F] FDG) positron emission tomography imaging. Cerebrospinal fluid (CSF) biomarkers amyloid-ß1-42 peptide (Aß1-42) and tau were used in order to differentiate AD from SNAP. METHODS: The study included 43 newly diagnosed AD patients (female = 23; male = 20) according to the NINCDS-ADRDA criteria, 15 SNAP patients (female = 12; male =3), and a group of 34 healthy subjects that served as the control group (CG), who were found to be normal at neurological evaluation (male = 20; female = 14). A battery of neuropsychological tests was administrated in AD and SNAP subjects; cerebrospinal fluid assay was conducted in both AD and SNAP as well. Brain PET/CT acquisition was started 30 ± 5 min after [18F] FDG injection in all subjects. SPM12 [statistical parametric mapping] implemented in MATLAB 2018a was used for the analysis of PET scans in this study. RESULTS: As compared to SNAP, AD subjects showed significant hypometabolism in a wide cortical area involving the right frontal, parietal, and temporal lobes. As compared to CG, AD subjects showed a significant reduction in [18F] FDG uptake in the parietal, limbic, and frontal cortex, while a more limited reduction in [18F] FDG uptake in the same areas was found when comparing SNAP to CG. CONCLUSIONS: SNAP subjects show milder impairment of brain [18F] FDG uptake as compared to AD. The partial overlap of the metabolic pattern between SNAP and AD limits the use of [18F] FDG PET/CT in effectively discriminating these clinical entities.

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

PURPOSE: The aim of this study was to determine the performance of 18F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. METHODS: FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. RESULTS: SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥ 2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P < 0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P < 0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. CONCLUSION: Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Does fatigue in Parkinson's disease correlate with autonomic nervous system dysfunction?

BACKGROUND: Despite its negative impact on quality of life, fatigue in Parkinson's disease (PD) remains an under-recognized issue and the underlying pathology is undetermined. OBJECTIVE: To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients. METHODS: In a Caucasian population of PD patients (n = 27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests. RESULTS: PFS-16 score correlated with disease duration (R = 0.57, p = 0.002). Fatigue showed a clear correlation with deep breathing test (R = - 0.53, p = 0.004) but not with the MIBG H/M ratios. CONCLUSIONS: Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.

Cerebral metabolic changes related to clinical parameters in idiopathic anosmic patients during olfactory stimulation: a pilot investigation.

Idiopathic olfactory loss neural consequences have been studied especially by means of magnetic resonance imaging. Since other functional neuroimaging technique findings are lacking in the literature, present study used a validated 18F-2-fluoro-2-deoxy-D-glucose (FDG) functional positron emission tomography procedure under olfactory stimulation (OS) to assess brain changes in idiopathic anosmic patients (IAPs) in comparison with healthy subjects (HS). A voxel-based analysis between these groups was used to evaluate FDG uptake in the brain and perform a correlation analysis between metabolic responses and the Sniffin' stick test as well as intensity visuo-analogue scores and disease duration (DD). A significant relative decrease of glucose metabolism in the right and left frontal lobes, left insula, right parietal lobe, and left occipital, temporal and parietal lobes was found in IAPs during OS. The same condition resulted in a relative higher glucose metabolism in the right cerebellum in IAPs. Moreover, a negative correlation between DD and FDG uptake in the left temporo-parietal joint was found in IAPs. Such a correlation suggested a possible involvement of this area metabolic decrease in self-consciousness impairment, which is known to affect IAPs. Present preliminary functional results could be of interest to further deepen such neural impairments possibly useful for future perspective in pharmaceutical and rehabilitative protocols.

PET/CT with (18)F-choline after radical prostatectomy in patients with PSA ≤2 ng/ml. Can PSA velocity and PSA doubling time help in patient selection?

PURPOSE: To investigate the performance of (18)F-fluorocholine ((18)F-FCH) PET/CT in relation to the prostate-specific antigen (PSA) kinetic indexes, PSA doubling time (PSAdt) and PSA velocity (PSAve), in detecting recurrent prostate cancer (PC) in a selected population of patients treated with radical prostatectomy and with PSA ≤2 ng/ml. METHODS: The study group comprised 79 patients (mean age 70 ± 7 years, range 58 - 77 years) who had been treated with radical surgery 30 to 90 months previously and with biochemical failure (defined as a measurable serum PSA level) who were evaluated with (18)F-FCH PET/CT. In order to establish the optimal threshold for PSAdt and PSAve, the diagnostic performance of PSA, PSAdt and PSAve were compared by receiver operating characteristic analysis. RESULTS: In the population examined, PSA (mean ± SD) was 1.37 ± 0.44 ng/ml (range 0.21 - 2 ng/ml) before PET/CT examination, PSAdt was 10.04 ± 16.67 months and PSAve was 2.75 ± 3.11 ng/ml per year. (18)F-FCH PET/CT was positive in 44 patients (55 %). PSAve and PSAdt were significantly different between patients with a positive and a negative (18)F-FCH PET/CT scan. Thresholds of 6 months for PSAdt and 1 ng/ml per year for PSAve were selected. For PSAdt ≤6 months the detection rate (DR) was 65 %, and for PSAve >1 ng/ml per year the DR was 67 %. PSA values were not significantly different between patients with a positive and a negative PET/CT scan. CONCLUSION: The results of our study suggest that (18)F-FCH PET/CT could be considered for the evaluation of patients with biochemical recurrence of PC and with low PSA levels. Fast PSA kinetics could be useful in the selection of these patients.

Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease.

PURPOSE: It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. METHODS: AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. RESULTS: AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). CONCLUSION: We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.

Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.