Piercarlo Fania

Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset

PurposeTo identify the neurobiological traits of amyotrophic lateral sclerosis (ALS) and to elucidate functional differences between ALS of spinal and bulbar onset. We hypothesized that glucose metabolism distribution might vary between groups.MethodsThe study groups comprised 32 patients with ALS of either bulbar (n = 13) or spinal (n = 19) onset and 22 subjects as controls. They were investigated by [18F]fluorodeoxyglucose (FDG) positron emission tomography (FDG PET), comparing the patient groups with each other and with the controls by statistical parametric mapping.ResultsHighly significant relative increases in glucose metabolism distribution were found in the group comprising all 32 ALS patients as compared with the controls in the bilateral amygdalae, midbrain, pons and cerebellum. Relative hypermetabolism was also found in patients with spinal onset as compared with the controls in the right midbrain. In patients with bulbar onset compared with the controls and with patients with spinal onset, large relatively hypometabolic areas were found in the bilateral frontal cortex, right insula, anterior cingulate, precuneus and inferior parietal lobe. Patients with spinal onset had significantly higher scores in a neuropsychological test assessing verbal fluency compared with patients with bulbar onset.ConclusionThis large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions.

Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis

Objective: We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of 18F-2-fluoro-2-deoxy-d-glucose (18F-FDG) PET as a biomarker to discriminate patients from controls. Methods: A total of 195 patients with ALS and 40 controls underwent brain 18F-FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS were also investigated. Twenty-five bilateral cortical and subcortical volumes of interest and cerebellum were taken into account, and 18F-FDG uptakes were individually normalized by whole-brain values. Group analyses investigated the ALS-related metabolic changes. Discriminant analysis investigating sensitivity and specificity was performed using the 51 volumes of interest as well as age and sex. Metabolic connectivity was explored by voxel-wise interregional correlation analysis. Results: Hypometabolism was found in frontal, motor, and occipital cortex and hypermetabolism in midbrain, temporal pole, and hippocampus in patients with ALS compared to controls. A similar metabolic pattern was also found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a specificity of 83% in separating patients from controls. Connectivity analysis found a highly significant positive correlation between midbrain and white matter in corticospinal tracts in patients with ALS. Conclusions: 18F-FDG distribution changes in ALS showed a clear pattern of hypometabolism in frontal and occipital cortex and hypermetabolism in midbrain. The latter might be interpreted as the neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis resulted in high sensitivity and specificity in differentiating patients with ALS from controls. Once validated by diseased-control studies, the present methodology might represent a potentially useful biomarker for ALS diagnosis. Classificaton of evidence: This study provides Class III evidence that 18F-FDG-PET accurately distinguishes patients with ALS from normal controls (sensitivity 95.4%, specificity 82.5%).

The role of 18F-FDG PET/CT in the metabolic characterization of lung nodules in pediatric patients with bone sarcoma†‡

The principal aim of this study was to identify the lowest nodule diameter and the SUVmax capable of characterizing lung nodules in pediatric patients with bone sarcoma.

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in patients with chronic inflammatory bowel disease: a systematic review and a meta-analysis.

OBJECTIVE To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in patients with chronic inflammatory bowel disease (IBD). METHODS A comprehensive computer literature search of studies published through May 2012 regarding (18)F-FDG-PET and PET/CT in patients with IBD was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG PET and PET/CT in patients with IBD on a per segment-based analysis were calculated. The area under the ROC curve was calculated to measure the accuracy of (18)F-FDG PET and PET/CT in patients with IBD. RESULTS Nineteen studies comprising 454 patients with suspected IBD were included in the qualitative analysis (systematic review) and discussed. The quantitative analysis (meta-analysis) of seven selected studies (including 219 patients with IBD) provided the following results on a per segment-based analysis: sensitivity was 85% [95% confidence interval (95%CI) 81-88%], specificity 87% (95%CI 84-90%), LR+ 6.19 (95%CI: 2.86-13.41), LR- 0.19 (95%CI: 0.10-0.34), and DOR 44.35 (95%CI: 11.77-167.07). The area under the ROC curve was 0.933. CONCLUSIONS In patients with suspected IBD (18)F-FDG PET and PET/CT demonstrated good sensitivity and specificity, being accurate methods in this setting. Nevertheless, the literature focusing on the use of PET and PET/CT in IBD remains still limited; thus, further large multicenter studies will be necessary to substantiate the diagnostic accuracy of these methods in patients with IBD.

18F-FDG-PET correlates of cognitive impairment in ALS

Objective: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). Methods: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. Results: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. Conclusions: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing 18 F-FDG PET/CT SUV quantification

Abstract Background. The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up. Patients and methods. Forty-nine patients with stage I-II NSCLC were included in this study. Pre-surgical 2-deoxy- 2-[18F]fluoro-D-glucose positron-emission tomography (18F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated. Results. There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9. Conclusions. In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.

Metabolic spatial connectivity in amyotrophic lateral sclerosis as revealed by independent component analysis.

Positron emission tomography (PET) and volume of interest (VOI) analysis have recently shown in amyotrophic lateral sclerosis (ALS) an accuracy of 93% in differentiating patients from controls. The aim of this study was to disclose by spatial independent component analysis (ICA) the brain networks involved in ALS pathological processes and evaluate their discriminative value in separating patients from controls. Experimental design: Two hundred fifty‐nine ALS patients and 40 age‐ and sex‐matched control subjects underwent brain 18F‐2‐fluoro‐2‐deoxy‐D‐glucose PET (FDG‐PET). Spatial ICA of the preprocessed FDG‐PET images was performed. Intensity values were converted to z‐scores and binary masks were used as data‐driven VOIs. The accuracy of this classifier was tested versus a validated system processing intensity signals in 27 brain meta‐VOIs. A support vector machine was independently applied to both datasets and the ‘leave‐one‐out’ technique verified the general validity of results. Principal observations: The 8 components selected as pathophysiologically meaningful discriminated patients from controls with 99.0% accuracy, the discriminating value of bilateral cerebellum/midbrain alone representing 96.3%. Among the meta‐VOIs, right temporal lobe alone reached an accuracy of 93.7%. Conclusions: Spatial ICA identified in a very large cohort of ALS patients distinct spatial networks showing a high discriminatory value, improving substantially on the previously obtained accuracy. The cerebellar/midbrain component accounted for the highest accuracy in separating ALS patients from controls. Spatial ICA and multivariate analysis perform better than univariate semi‐quantification methods in identifying the neurodegenerative features of ALS and pave the way for inclusion of PET in clinical trials and early diagnosis. Hum Brain Mapp 37:942–953, 2016.

Neural processing of emotions in traumatized children treated with Eye Movement Desensitization and Reprocessing therapy: A hdEEG study

Eye Movement Desensitization and Reprocessing (EMDR) therapy has been proven efficacious in restoring affective regulation in post-traumatic stress disorder (PTSD) patients. However, its effectiveness on emotion processing in children with complex trauma has yet to be explored. High density electroencephalography (hdEEG) was used to investigate the effects of EMDR on brain responses to adults’ emotions on children with histories of early maltreatment. Ten school-aged children were examined before (T0) and within one month after the conclusion of EMDR (T1). hdEEGs were recorded while children passively viewed angry, afraid, happy, and neutral faces. Clinical scales were administered at the same time. Correlation analyses were performed to detect brain regions whose activity was linked to children’s traumatic symptom-related and emotional-adaptive problem scores. In all four conditions, hdEEG showed similar significantly higher activity on the right medial prefrontal and fronto-temporal limbic regions at T0, shifting toward the left medial and superior temporal regions at T1. Moreover, significant correlations were found between clinical scales and the same regions whose activity significantly differed between pre- and post-treatment. These preliminary results demonstrate that, after EMDR, children suffering from complex trauma show increased activity in areas implicated in high-order cognitive processing when passively viewing pictures of emotional expressions. These changes are associated with the decrease of depressive and traumatic symptoms, and with the improvement of emotional-adaptive functioning over time.

Uncommon 18F-FDG-PET/CT findings in patients affected by limbic encephalitis: hyper-hypometabolic pattern with double antibody positivity and migrating foci of hypermetabolism☆ , ☆☆

Autoimmune limbic encephalitis (LE) is a rare disorder; its diagnosis can be challenging. We report two uncommon cases of LE evaluated by brain 2-deoxy-2-[18F]fluoro-d-glucose ((18)F-FDG) positron emission tomography/computed tomography describing the metabolic imaging patterns, which were different from those observed in previous studies: the first one presented an unprecedented (18)F-FDG brain mixed pattern, involving also the midbrain, despite negative magnetic resonance imaging exams; the second one showed migrating foci of hypermetabolism, one of which turned into hypometabolism at a later examination.

A comparison between ¹⁸F-FDG PET/CT imaging and biological and radiological findings in restaging of hepatoblastoma patients.

Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients.