Accuracy and reproducibility of lymphoscintigraphy for sentinel node detection in patients with cutaneous melanoma.

Lymphoscintigraphy is an important part of the mapping and identification of sentinel lymph nodes (SLNs). However, few studies report its reproducibility, and some concerns prevail. The aim of the study was to determine the reproducibility of lymphoscintigraphy performed by different team members following a strict protocol to assess lymphatic drainage and the location and number of SLNs. Methods: Sixty-eight melanoma patients were included. All underwent 2 separate lymphoscintigraphy studies, which followed the same acquisition protocol. Discordance was defined as a change in localization or a failure to identify the SLN in one of the studies. Results: All patients showed lymphatic drainage, and in all cases at least 1 sentinel node was identified. In 65 of 68 patients (96%), the findings of the first lymphoscintigraphy study were similar to those of the second. This similarity was also found in the number of sentinel nodes (171 in the first study and 173 in the second). Eighty percent of patients showed 1-3 SLNs in both lymphoscintigraphy studies. The 2 studies differed in 3 patients (4%): 2 melanomas were located on the trunk and 1 on the head and neck. Drainage was visualized to more than 1 lymphatic basin in 19 patients (28%) in the first study versus 18 patients in the second study. Conclusion: Lymphoscintigraphy is highly reproducible in the detection of sentinel nodes in melanoma patients. The classic protocol of radiotracer injection is reproducible and reliable enough to guarantee SLN identification, although a slight variation in isolated cases (especially when primary lesions are located on the trunk or the head and neck regions) is inevitable

Clinical role of subtraction ictal SPECT coregistered to MR Imaging and 18F-FDG PET in pediatric epilepsy

A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach

Epileptogenic zone localization with (18)FDG PET using a new dynamic parametric analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization

Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers

Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880). We studied individual uptake patterns, group differences, and correlation with estimated years to symptoms onset, as well as adverse events. We found that asymptomatic carriers (N = 14) showed increased FBB uptake across the cerebral cortex and in the caudate. FBB accumulation appeared more than 15 years before onset in the precuneus and bankssts, among other regions, overlapping regions showing increased cortical thickness in the same subjects. FBB uptake correlated with estimated years to symptoms onset in several areas, especially the rostral anterior cingulate. Symptomatic carriers (N = 7) had an elevated FBB uptake plateau. No adverse events were reported. Overall, we found progressive FBB uptake in ADAD starting 2 decades before symptoms. The rostral anterior cingulate is a candidate area to track Aβ deposition in addition to the precuneus

Quantitative informant- and self-reports of subjective cognitive decline predict amyloid beta PET outcomes in cognitively unimpaired individuals independently of age and APOE ε4

Introduction: Amyloid beta (Aβ) pathology is an Alzheimer's disease early hallmark. Here we assess the value of longitudinal self- and informant reports of cognitive decline to predict Aβ positron emission tomography (PET) outcome in cognitively unimpaired middle-aged individuals. Methods: A total of 261 participants from the ALFA+ study underwent [18F]flutemetamol PET and Subjective Cognitive Decline Questionnaire (SCD-Q) concurrently, and 3 years before scan. We used logistic regressions to evaluate the ability of SCD-Q scores (self and informant) to predict Aβ PET visual read, and repeated analysis of variance to assess whether changes in SCD-Q scores relate to Aβ status. Results: Self-perception of decline in memory (odds ratio [OR] = 1.2), and informant perception of executive decline (OR = 1.6), increased the probability of a positive scan. Informant reports 3 years before scanning predicted Aβ PET outcome. Longitudinal increase of self-reported executive decline was predictive of Aβ in women (P = .003). Discussion: Subjective reports of cognitive decline are useful to predict Aβ and may improve recruitment strategies

Impact of simulated reduced injected dose on the assessment of amyloid PET scans

PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were  80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances

Brain alterations in the early Alzheimer's continuum with amyloid-β, tau, glial and neurodegeneration CSF markers

Higher grey matter volumes/cortical thickness and fluorodeoxyglucose uptake have been consistently found in cognitively unimpaired individuals with abnormal Alzheimer's disease biomarkers compared with those with normal biomarkers. It has been hypothesized that such transient increases may be associated with neuroinflammatory mechanisms triggered in response to early Alzheimer's pathology. Here, we evaluated, in the earliest stages of the Alzheimer's continuum, associations between grey matter volume and fluorodeoxyglucose uptake with CSF biomarkers of several pathophysiological mechanisms known to be altered in preclinical Alzheimer's disease stages. We included 319 cognitively unimpaired participants from the ALFA+ cohort with available structural MRI, fluorodeoxyglucose PET and CSF biomarkers of amyloid-β and tau pathology (phosphorylated tau and total tau), synaptic dysfunction (neurogranin), neuronal and axonal injury (neurofilament light), glial activation (soluble triggering receptor on myeloid cells 2, YKL40, GFAP, interleukin-6 and S100b) and α-synuclein using the Roche NeuroToolKit. We first used the amyloid-β/tau framework to investigate differences in the neuroimaging biomarkers between preclinical Alzheimer's disease stages. Then, we looked for associations between the neuroimaging markers and all the CSF markers. Given the non-negative nature of the concentrations of CSF biomarkers and their high collinearity, we clustered them using non-negative matrix factorization approach (components) and sought associations with the imaging markers. By groups, higher grey matter volumes were found in the amyloid-β-positive tau-negative participants with respect to the reference amyloid-β-negative tau-negative group. Both amyloid-β and tau-positive participants showed higher fluorodeoxyglucose uptake than tau-negative individuals. Using the obtained components, we observed that tau pathology accompanied by YKL-40 (astrocytic marker) was associated with higher grey matter volumes and fluorodeoxyglucose uptake in extensive brain areas. Higher grey matter volumes in key Alzheimer-related regions were also found in association with two other components characterized by a higher expression of amyloid-β in combination with different glial markers: one with higher GFAP and S100b levels (astrocytic markers) and the other one with interleukin-6 (pro-inflammatory). Notably, these components' expression had different behaviours across amyloid-β/tau stages. Taken together, our results show that CSF amyloid-β and phosphorylated tau, in combination with different aspects of glial response, have distinctive associations with higher grey matter volumes and increased glucose metabolism in key Alzheimer-related regions. These mechanisms combine to produce transient higher grey matter volumes and fluorodeoxyglucose uptake at the earliest stages of the Alzheimer's continuum, which may revert later on the course of the disease when neurodegeneration drives structural and metabolic cerebral changes

Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's continuum

PURPOSE: Glial activation is one of the earliest mechanisms to be altered in Alzheimer's disease (AD). Glial fibrillary acidic protein (GFAP) relates to reactive astrogliosis and can be measured in both cerebrospinal fluid (CSF) and blood. Plasma GFAP has been suggested to become altered earlier in AD than its CSF counterpart. Although astrocytes consume approximately half of the glucose-derived energy in the brain, the relationship between reactive astrogliosis and cerebral glucose metabolism is poorly understood. Here, we aimed to investigate the association between fluorodeoxyglucose ([18F]FDG) uptake and reactive astrogliosis, by means of GFAP quantified in both plasma and CSF for the same participants. METHODS: We included 314 cognitively unimpaired participants from the ALFA + cohort, 112 of whom were amyloid-β (Aβ) positive. Associations between GFAP markers and [18F]FDG uptake were studied. We also investigated whether these associations were modified by Aβ and tau status (AT stages). RESULTS: Plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP associations with [18F]FDG uptake were only observed in specific smaller areas like temporal pole and superior temporal lobe. These associations persisted when accounting for biomarkers of Aβ pathology but became negative in Aβ-positive and tau-positive participants (A + T +) in similar areas of AD-related hypometabolism. CONCLUSIONS: Higher astrocytic reactivity, probably in response to early AD pathological changes, is related to higher glucose consumption. With the onset of tau pathology, the observed uncoupling between astrocytic biomarkers and glucose consumption might be indicative of a failure to sustain the higher energetic demands required by reactive astrocytes

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms

Epileptogenic Zone Localization With 18FDG PET Using a New Dynamic Parametric Analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM).Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p &lt; 0.05 and cluster size k = 50 and at uncorrected p &lt; 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up.Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p &lt; 0.05) than that obtained with the SPM threshold p &lt; 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p &lt; 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242).Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization