Radiomics analysis of bone marrow biopsy locations in [18F]FDG PET/CT images for measurable residual disease assessment in multiple myeloma.

The combination of visual assessment of whole body [18F]FDG PET images and evaluation of bone marrow samples by Multiparameter Flow Cytometry (MFC) or Next-Generation Sequencing (NGS) is currently the most common clinical practice for the detection of Measurable Residual Disease (MRD) in Multiple Myeloma (MM) patients. In this study, radiomic features extracted from the bone marrow biopsy locations are analyzed and compared to those extracted from the whole bone marrow in order to study the representativeness of these biopsy locations in the image-based MRD assessment. Whole body [18F]FDG PET of 39 patients with newly diagnosed MM were included in the database, and visually evaluated by experts in nuclear medicine. A methodology for the segmentation of biopsy sites from PET images, including sternum and posterior iliac crest, and their subsequent quantification is proposed. First, starting from the bone marrow segmentation, a segmentation of the biopsy sites is performed. Then, segmentations are quantified extracting SUV metrics and radiomic features from the [18F]FDG PET images and are evaluated by Mann-Whitney U-tests as valuable features differentiating PET+/PET- and MFC+ /MFC- groups. Moreover, correlation between whole bone marrow and biopsy sites is studied by Spearman ρ rank. Classification performance of the radiomics features is evaluated applying seven machine learning algorithms. Statistical analyses reveal that some images features are significant in PET+/PET- differentiation, such as SUVmax, Gray Level Non-Uniformity or Entropy, especially with a balanced database where 16 of the features show a p value < 0.001. Correlation analyses between whole bone marrow and biopsy sites results in significant and acceptable coefficients, with 11 of the variables reaching a correlation coefficient greater than 0.7, with a maximum of 0.853. Machine learning algorithms demonstrate high performances in PET+/PET- classification reaching a maximum AUC of 0.974, but not for MFC+/MFC- classification. The results demonstrate the representativeness of sample sites as well as the effectiveness of extracted features (SUV metrics and radiomic features) from the [18F]FDG PET images in MRD assessment in MM patients.The author E.M. received financial support through a predoctoral Fellowship (ayuda del Programa Propio de I+D+i 2020) from Universidad Politecnica de Madrid. The project was partially supported by COVITECH-CM (Plataforma cientifico-tecnologica para alerta, diagnostico, pronostico, terapia y seguimiento de la enfermedad COVID19 y futuras pandemias) and REACT-UE through the European Regional Development Fund (ERDF), the European Social Fund (EFS) and the Fund for European Aid to the Most Deprived (FEAD).Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The authors declare that no funds, grants, or other support were received during the preparation of this manuscriptS

CASSIA (cardiology software suite for image analysis): a potential new tool for the evaluation of [18F]FDG PET/CT in the setting of infective endocarditis.

Due to the high morbidity and mortality of infective endocarditis (IE), medical imaging techniques are combined to ensure a correct diagnosis. [18F]FDG PET/CT has demonstrated the ability to improve diagnostic accuracy compared with the conventional modified Duke criteria in patients with suspected IE, especially those with prosthetic valve infective endocarditis (PVIE). The aim of this study is to provide an adjunctive diagnostic tool to improve the diagnostic accuracy in cardiovascular infections, specifically PVIE. A segmentation tool to extract quantitative measures of [18F]FDG PET/CT image studies of prosthetic heart valve regions was developed and validated in 20 cases of suspected PVIE, of which 9 were confirmed. For that, Valvular Heterogeneity Index (VHI) and Ring-to-Center Ratio (RCR) were defined. Results show an overall increase in the metabolic uptake of the prosthetic valve ring in the studies with confirmed PVIE diagnosis (SUVmax from 1.70 to 3.20; SUVmean from 0.86 to 1.50). The VHI and RCR showed areas under the curve of 0.727 and 0.808 in the receiver operating characteristics curve analyses, respectively, for PVIE diagnosis. Mann-Whitney U tests showed statistically significant differences between groups for RCR (p = 0.02). Visual analyses and clinical reports were concordant with the extracted quantitative metrics. The proposed new method and presented software solution (CASSIA) provide the capability to assess quantitatively myocardial metabolism along the prosthetic valve region in routine [18F]FDG PET/CT scans for evaluating heart valve infectious processes. VHI and RCR are proposed as new potential adjunctive measures for PVIE diagnosis.The project was partially funded by Sociedad Española de Cardiología (SEC/FEC-INVBAS 21/022). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.S

Texture-Based Analysis of 18F-Labeled Amyloid PET Brain Images

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [18F]florbetapir (FBP) or [18F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, the reference region could present high variability in longitudinal studies. Texture features based on the grey-level co-occurrence matrix, also called Haralick features (HF), are evaluated in this study to discriminate between amyloid-positive and negative cases. A retrospective study cohort of 66 patients with amyloid PET images (30 [18F]FBP and 36 [18F]FMM) was selected and SUVRs and 6 HFs were extracted from 13 cortical volumes of interest. Mann–Whitney U-tests were performed to analyze differences of the features between amyloid positive and negative cases. Receiver operating characteristic (ROC) curves were computed and their area under the curve (AUC) was calculated to study the discriminatory capability of the features. SUVR proved to be the most significant feature among all tests with AUCs between 0.692 and 0.989. All HFs except correlation also showed good performance. AUCs of up to 0.949 were obtained with the HFs. These results suggest the potential use of texture features for the classification of amyloid PET image

Late Holocene archaeobotanical evolution of the Canale di Imbocco (Roman imperial port of Portus, Central Italy)

The Roman port of Portus was the most important in the Mediterranean during the imperial period (27 BC–476 AD). It wasmade up of an outer port or Claudius basin and an inner hexagon or Trajan's port, joined by the Canale di Imbocco. The archaeobotanical record obtained in a continuos sediment core taken in this channel ismade up of 19 types of plant macroremains, with a predominance of fibers of the seagrass Posidonia oceanica L., replaced by fluvial sediments in the upper part of the core. Seeds, fruits and thorns of aquatic species frommarine or brackish waters, halophyte species, edible species, freshwater riparian vegetation and remains of charcoal and wood also appear regularly. According to the inferred palaeoenviromental evolution of this core, Portus was an area of fluvial-marine interaction during the Roman Empire, with brackish water conditions interrupted by stormy periods deduced from the record of P. oceanica. The archaeobotanical and sedimentary evolution points to a restriction of marine contributions and a final implantation of a fluvial environment. In this evolution, a specific interval with abundant charcoal and caryopses of Triticum could correspond to a fire, which was followed by a possible period of greater construction activity linked with large fragments of wood.This paper was jointly supported by the following projects: a) project DGYCIT CTM2006-06722/MAR; b) DGYCIT project CGL2006-01412; c) “From the Atlantic to the Mediterranean (DEATLANTIR): Research in the infrastructures of Portus-Ostia Antica: the Lanterna wharf” (Programme of Archeology Projects Abroad, Ministry of Culture and Sports); d) From the Atlantic to the Tyrrhenian. Hispanic ports and their commercial relations with Ostia Antica (DEATLANTIR II - HAR2017-89154-P - (National R&D Plan)); and e) FEDER project 2014-2020 UHU-1260298. Other funds come from the research groups HUM-132, RNM-238 and RNM-293 (P.A.I.D.I). It is a contribution to the Center for Research in Historical, Cultural and Natural Heritage of the University of Huelva. The archaeobotanical record is deposited in the Laboratory of Paleontology and Applied Ecology of the University of Huelva

Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-beta (A beta) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Findings: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. Interpretation: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.This study was supported by Dr. Carro grants from Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01). This study was also supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF201785310-R to Dr. Cantero, PSI2017-85311-P to Dr. Atienza); International Centre on ageing CENIE-POCTEP (0348_CIE_6_E to Dr. Atienza); and CIBERNED (CB06/05/1111 to Dr. Cantero). Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021, PI17/01799). The H2H-Spain Study was supported in Spain by grant PIE16/00021 from Instituto Carlos III, Ministry of Science, Innovation and Universities, and additional funds from the Centro Nacional de Investigaciones Cardiovasculares (CNIC). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). The funders had no role in the conceptualisation, study design, data collection analysis and preparation of this manuscript

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Automatic Diagnosis of Chronic Thromboembolic Pulmonary Hypertension Based on Volumetric Data from SPECT Ventilation and Perfusion Images

Chronic thromboembolic pulmonary hypertension (CTEPH) is confirmed by visual analysis of single-photon emission computer tomography (SPECT) ventilation and perfusion (V/Q) images. Defects in the perfusion image discordant with the ventilation image indicate obstructed segments and the positive diagnosis of CTEPH. A quantitative metric and classification algorithm are proposed based on volumetric data from SPECT V/Q images. The difference in ventilation and perfusion volumes (VV-P) is defined as a quantitative metric to identify discordant defects in the SPECT images. The algorithm was validated with 22 patients grouped according to their diagnosis: (1) CTEPH and (2) respiratory pathology. Volumetric data from SPECT perfusion images was also compared before and after treatment for CTEPH. CTEPH was detected with a sensitivity of 0.67 and specificity of 0.80. The performance of volumetric data from SPECT perfusion images for the evaluation of treatment response was studied for two cases and improvement of pulmonary perfusion was observed in one case. This study uses volumetric data from SPECT V/Q images for the diagnosis of CTEPH and its differentiation from respiratory pathologies. The results indicate that the defined metric is a viable option for a quantitative analysis of SPECT V/Q images.S

Static first-minute-frame (FMF) PET imaging after 18F-labeled amyloid tracer injection is correlated to [18F]FDG PET in patients with primary progressive aphasia.

OBJECTIVE To study the correlation between a static PET image of the first-minute-frame (FMF) acquired with 18F-labeled amyloid-binding radiotracers and brain [18F]FDG PET in patients with primary progressive aphasia (PPA). MATERIAL AND METHODS The study cohort includes 17 patients diagnosed with PPA with the following distribution: 9 nonfluent variant PPA, 4 logopenic variant PPA, 1 semantic variant PPA, 3 unclassifiable PPA. Regional SUVRs are extracted from FMFs and their corresponding [18F]FDG PET images and Pearson's correlation coefficients are calculated. RESULTS SUVRs of both images show similar patterns of regional cerebral alterations. Intrapatient correlation analyses result in a mean coefficient of r=0.94±0.06. Regional interpatient correlation coefficients of the study cohort are greater than 0.81. Radiotracer-specific and variant-specific subcohorts show no difference in the similarity between the images. CONCLUSIONS The static FMF could be a valid alternative to dynamic early-phase amyloid PET proposed in the literature, and a neurodegeneration biomarker for the diagnosis and classification of PPA in amyloid PET studies.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.S