Visualizing Convolutional Networks for MRI-based Diagnosis of Alzheimer's Disease

Visualizing and interpreting convolutional neural networks (CNNs) is an important task to increase trust in automatic medical decision making systems. In this study, we train a 3D CNN to detect Alzheimer's disease based on structural MRI scans of the brain. Then, we apply four different gradient-based and occlusion-based visualization methods that explain the network's classification decisions by highlighting relevant areas in the input image. We compare the methods qualitatively and quantitatively. We find that all four methods focus on brain regions known to be involved in Alzheimer's disease, such as inferior and middle temporal gyrus. While the occlusion-based methods focus more on specific regions, the gradient-based methods pick up distributed relevance patterns. Additionally, we find that the distribution of relevance varies across patients, with some having a stronger focus on the temporal lobe, whereas for others more cortical areas are relevant. In summary, we show that applying different visualization methods is important to understand the decisions of a CNN, a step that is crucial to increase clinical impact and trust in computer-based decision support systems.Comment: MLCN 201

Tooth Cementum Thickness as a Method of Age Estimation in the Forensic Context

Estimating age at death is a key element in the process of human identification of skeletal remains. The interest in dental cementum stems from its increase in thickness throughout life and, at the same time, from the fact it should not be affected by remodeling processes. Since the age assessment is particularly difficult in adults when using traditional anthropological methods on the skeleton, we tested a dental method based on maximum cementum thickness and developed new regression equations. We microscopically analyzed the histological sections of dental roots from a sample of 108 permanent teeth with known age and sex. Age at the time of dental extraction was in the range of 18–84 years. Our findings show that there were no differences in thickness between sexes, dental arch, and mono-and pluriradicular teeth. Separate regression equations were developed for individuals in the whole age range and individuals under 45 years. The equations were then tested on a hold-out sample from the same Mediterranean population demonstrating higher reliability for the equation developed for those under 45. Conversely, due to the increased error in age estimation in individuals over 45, this method should be used with caution in the forensic con-text when skeletal remains presumably belong to elderly individuals

Age estimation using tooth cementum annulations: bias and sources of inaccuracy

Background: Counting the tooth cementum annulations (TCA) is a method for estimating the age at death of adults by sections of their tooth root. The objective of this study was to assess the precision of counting the cementum incremental lines and the congruence between known age and age estimates. Possible factors affecting the accuracy of the estimate were also analyzed. Methods: A sample of 67 permanent teeth extracted from individuals with known age (18 84 years) and sex was analyzed to calculate the dental age. Results: Results demonstrate an excellent inter- and intra-observer reliability of annuli counting, with dissimilarities within the limits of agreement. A moderate positive correlation was found between chronological age and TCA. Our results showed that age congruence rates differed across age groups (85% congruence in individuals <= 30 years; 75% in individuals aged 31-60 years; 60% in the over 60s). Considering the bias, this method showed a clear tendency to underestimate age in specimens from old people. After age 43, the TCA estimate is highly inaccurate exceeding the underestimation of 10 years, on average, in comparison to the chronological age. Both chronological age and dental arch seem to influence the accuracy of estimates, unlike sex and the tooth root number. Conclusions: TCA analysis is characterized by high precision and low accuracy, decreasing with age. Therefore, its applicability is limited in elderly subjects. The choice of methods for age estimation in adult skeletal remains should take into account the particular age range of individuals. We recommend using different age estimation methods to verify the reliability of the performed assessments

Forensic Diagnosis of Freshwater or Saltwater Drowning Using the Marker Aquaporin 5: An Immunohistochemical Study

Background and Objectives: Aquaporins are a family of water channel proteins. In this study, the renal and intrapulmonary expression of aquaporin-5 (AQP5) was examined in forensic autopsy cases to evaluate it as a drowning marker and to differentiate between freshwater drowning and saltwater drowning. Materials and Methods: Cases were classified into three groups: freshwater drowning (FWD), saltwater drowning (SWD), and controls (CTR). Samples were obtained from forensic autopsies at less than 72 h postmortem (15 FWD cases, 15 SWD cases, and 17 other cases) and were subjected to histological and immunohistochemical investigations. Results: In FWD group, intrapulmonary AQP5 expression was significantly suppressed compared with SWD and CTR; there was no significant difference in AQP5 expression among the other two groups. The same differences in expression were also observed in the kidney. Conclusions: These observations suggest that AQP5 expression in alveolar cells was suppressed by hypotonic water to prevent hemodilution. Moreover, it is possible to hypothesize that in the kidney, with the appearance of hypo-osmotic plasma, AQP5 is hypo-expressed, as a vital reaction, to regulate the renal reabsorption of water. In conclusion, the analysis of renal and intrapulmonary AQP5 expression would be forensically useful for differentiation between FWD and SWD, or between FWD and death due to other causes

Preliminary evaluations of the environmental impact for the production of 99Mo by fusion neutrons

AbstractENEA is developing an accelerator-driven 14 MeV neutron source exploiting the deuterium–tritium fusion reaction to produce 99Mo medical radioisotope as an alternative production route not based on fission reactors. It is expected that, during normal operation, a number of radionuclides, generated by means of neutron irradiation on the raw material (natural Molybdenum), will be produced and managed. The present manuscript, as foreseen by national law, discusses a hypothetical scenario to test the environmental screening models, in turn evaluating the mechanisms and parameters which affect and control the path of liquid effluents potentially released during normal operation of the facility. The aim is to estimate the amount of radioactivity to be operated and the fraction potentially discharged in this hypothetical scenario, so as to ensure that the radioactive material can be managed without any risk for the population and the environment, according to national regulations and thoroughly fulfilling the international guidelines

Volumetric Differences in Mapped Hippocampal Regions Correlate with Increase of High Alpha Rhythm in Alzheimer's Disease

Objective. The increase of high alpha relative to low alpha power has been recently demonstrated as a reliable EEG marker of hippocampal atrophy conversion of patients with mild cognitive impairment (MCI) in Alzheimer's disease (AD). In the present study we test the reliability of this EEG index in subjects with AD. Methods. Correlation between EEG markers and volumetric differences in mapped hippocampal regions was estimated in AD patients. Results. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of mapped hippocampal regions in Alzheimer's disease. Conclusions. The findings confirm the possible diagnostic role of EEG markers

Multiple RF classifier for the hippocampus segmentation: method and validation on EADC-ADNI harmonized hippocampal protocol

AbstractThe hippocampus has a key role in a number of neurodegenerative diseases, such as Alzheimer's Disease. Here we present a novel method for the automated segmentation of the hippocampus from structural magnetic resonance images (MRI), based on a combination of multiple classifiers. The method is validated on a cohort of 50 T1 MRI scans, comprehending healthy control, mild cognitive impairment, and Alzheimer's Disease subjects. The preliminary release of the EADC-ADNI Harmonized Protocol training labels is used as gold standard. The fully automated pipeline consists of a registration using an affine transformation, the extraction of a local bounding box, and the classification of each voxel in two classes (background and hippocampus). The classification is performed slice-by-slice along each of the three orthogonal directions of the 3D-MRI using a Random Forest (RF) classifier, followed by a fusion of the three full segmentations. Dice coefficients obtained by multiple RF (0.87 ± 0.03) are larger than those obtained by a single monolithic RF applied to the entire bounding box, and are comparable to state-of-the-art. A test on an external cohort of 50 T1 MRI scans shows that the presented method is robust and reliable. Additionally, a comparison of local changes in the morphology of the hippocampi between the three subject groups is performed. Our work showed that a multiple classification approach can be implemented for the segmentation for the measurement of volume and shape changes of the hippocampus with diagnostic purposes

The New Sorgentina Fusion Source-NSFS: 14 MeV neutrons for fusion and beyond

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A European Academy of Neurology guideline on medical management issues in dementia

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow‐up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk–benefit ratio should be performed at regular intervals. Regular, preplanned medical follow‐up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non‐pharmacological measures have been proven to be without benefit or in the case of severe self‐harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first‐line therapy (Good Practice statement). CONCLUSION: This GRADE‐based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas