Radiofàrmacs: leucòcits marcats amb radionúclids

L'estratègia de l'exploració consisteix a aprofitar la localització dels leucòcits en el lloc on hi ha el procés inflamatori o infecciós. Amb aquesta característica fisiopatològica, els leucòcits del pacient queden marcats amb un radionúclid emissor de radiació gamma i s'introdueixen de nou al pacient amb la finalitat que s'acumulin al lloc patològic i detectar-los des de l'exterior

Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer’s disease: additional results from the AMBAR study

Albumin; Intravenous immunoglobulin; PlasmapheresisAlbúmina; Inmunoglobulina intravenosa; PlasmaféresisAlbúmina; Immunoglobulina intravenosa; PlasmafèresiPurpose This study was designed to detect structural and functional brain changes in Alzheimer’s disease (AD) patients treated with therapeutic plasma exchange (PE) with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial. Methods Mild-to-moderate AD patients were randomized into four arms: three arms receiving PE with albumin (one with low-dose albumin, and two with low/high doses of albumin alternated with IVIG), and a placebo (sham PE) arm. All arms underwent 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Magnetic resonance imaging (MRI) volumetric analyses and regional and statistical parametric mapping (SPM) analysis on 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) were performed. Results MRI analyses (n = 198 patients) of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group (p < 0.05 in 3 structures vs. 4 to 9 in other groups). The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. SPM 18FDG-PET analyses (n = 213 patients) showed a worsening of metabolic activity in the specific areas affected in AD (posterior cingulate, precuneus, and parieto-temporal regions). The high-albumin + IVIG treatment group showed the greatest metabolic stability over the course of the study, i.e., the smallest percent decline in metabolism (MaskAD), and least progression of defect compared to placebo. Conclusions PE with albumin replacement was associated with fewer deleterious changes in subcortical structures and less metabolic decline compared to the typical of the progression of AD. This effect was more marked in the group treated with high albumin + IVIG.The AMBAR study is sponsored by Grifols, a manufacturer of therapeutic human serum albumin and intravenous immune globulin. GC-B, IR, JC-C, DP, MBo, and OLL received direct or indirect funding from Grifols to carry out the study and the preparation of the manuscript

Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer's disease : additional results from the AMBAR study

This study was designed to detect structural and functional brain changes in Alzheimer's disease (AD) patients treated with therapeutic plasma exchange (PE) with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial. Mild-to-moderate AD patients were randomized into four arms: three arms receiving PE with albumin (one with low-dose albumin, and two with low/high doses of albumin alternated with IVIG), and a placebo (sham PE) arm. All arms underwent 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Magnetic resonance imaging (MRI) volumetric analyses and regional and statistical parametric mapping (SPM) analysis on 18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) were performed. MRI analyses (n = 198 patients) of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group (p < 0.05 in 3 structures vs. 4 to 9 in other groups). The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. SPM 18 FDG-PET analyses (n = 213 patients) showed a worsening of metabolic activity in the specific areas affected in AD (posterior cingulate, precuneus, and parieto-temporal regions). The high-albumin + IVIG treatment group showed the greatest metabolic stability over the course of the study, i.e., the smallest percent decline in metabolism (MaskAD), and least progression of defect compared to placebo. PE with albumin replacement was associated with fewer deleterious changes in subcortical structures and less metabolic decline compared to the typical of the progression of AD. This effect was more marked in the group treated with high albumin + IVIG. (AMBAR trial registration: EudraCT#: 2011-001,598-25; ClinicalTrials.gov ID: NCT01561053). The online version contains supplementary material available at 10.1007/s00259-022-05915-

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study

Migranya crònica; Gruix cortical; NeuroimatgeMigraña crónica; Espesor cortical; NeuroimagenChronic migraine; Cortical thickness; NeuroimagingBackground To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC). Methods This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient’s age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis. Results Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant). Conclusions CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.The project leading to these results has received funding The Headache Study Group Grant 2016 of Spanish Neurological Society and Mutual Medica Grant 2016 and “La Caixa” Foundation under the project code LCF/PR/PR16/151110005

Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT

Cardiovascular risk; Myocardial insulin resistance; Type 2 diabetesRisc cardiovascular; Resistència miocàrdica a la insulina; Diabetis tipus 2Riesgo cardiovascular; Resistencia miocárdica a la insulina; Diabetes tipo 2Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. Methods: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic–euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81–44.06] vs. 30.82 [21.48–38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.This research was funded by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064 and PI20/01588) and AGAUR (2017SGR1303 and 2017SGR1144)

The valve uptake index : improving assessment of prosthetic valve endocarditis and updating [ 18 F]FDG PET/CT(A) imaging criteria

Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)−mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE. Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the 'definite' PVE group vs. the 'rejected' group, respectively (mean ± SD; P 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria. The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA

The valve uptake index: improving assessment of prosthetic valve endocarditis and updating [18F]FDG PET/CT(A) imaging criteria

Infective endocarditis; Nuclear imaging; Positron emission tomographyEndocarditis infecciosa; Imagen nuclear; Tomografía de emisión de positronesEndocarditis infecciosa; Imatge nuclear; Tomografia per emissió de positronsAims Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)−mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE. Methods and results Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the ‘definite’ PVE group vs. the ‘rejected’ group, respectively (mean ± SD; P 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria. Conclusions The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer's Disease Patients Treated with Plasma Exchange with 5% Human Albumin

Altres ajuts: This study was funded by Grifols. [...] James T. Becker (Department of Psychiatry, Neurology and Psychology. University of Pittsburgh, Pittsburgh PA, USA) read and commented on an earlier draft of the manuscript. Jordi Bozzo PhD, CMPP (Grifols) is acknowledged for medical writing and editorial assistance in the preparation of the manuscript.Recently, modifications of Aβ levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. Patients received between 3 and 18 PE with albumin (Albutein ® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam ®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion

Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice

Cardiovascular risk; Myocardial insulin resistance; Non-alcoholic fatty liver diseaseRiesgo cardiovascular; Resistencia a la insulina del miocardio; Enfermedad del higado graso no alcoholicoRisc cardiovascular; Resistència a la insulina del miocardi; Malaltia del fetge gras no alcohòlicBackground: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. Methods: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic–euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. Results: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. Conclusions: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.This work was supported by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064, PI20/01588) and the Agency for Management of University and Research Grants (AGAUR) of Catalonia (2017SGR1303)