Automatic multispectral MRI segmentation of human hippocampal subfields: an evaluation of multicentric test–retest reproducibility

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test–retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal (“long_T1s” and “long_T1s_FLAIR”) and one cross-sectional (“long_T1s_FLAIR_crossT2”). Volume reproducibility was quantified in magnitude (reproducibility error—RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4–3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1–7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm3 had better RE (1–2%) and DICE (0.7–0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements

Clinical utility of FDG PET in Parkinson\u2019s disease and atypical parkinsonism associated with dementia

Purpose: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson\u2019s disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. Methods: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. Results: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. Conclusion: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe

INTRODUCTION Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond

Quantitative appraisal of the Amyloid Imaging Taskforce appropriate use criteria for amyloid-PET

We test the hypothesis that amyloid-positron emission tomography prescriptions, considered appropriate based on the Amyloid Imaging Taskforce (AIT) criteria, lead to greater clinical utility than AIT-inappropriate prescriptions

Assessing FDG-PET diagnostic accuracy studies to develop recommendations for clinical use in dementia

FDG-PET is frequently used as a marker of synaptic damage to diagnose dementing neurodegenerative disorders. We aimed to adapt the items of evidence quality to FDG-PET diagnostic studies, and assess the evidence available in current literature to assist Delphi decisions for European recommendations for clinical use

Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework

Purpose The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer's disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. Methods A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. Results PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand's diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. Conclusion Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties

Automated assessment of FDG-PET for differential diagnosis in patients with neurodegenerative disorders

PURPOSE: To review literature until November 2015 and reach a consensus on whether automatic semi-quantification of brain FDG-PET is useful in the clinical setting for neurodegenerative disorders. METHODS: A literature search was conducted in Medline, Embase, and Google Scholar. Papers were selected with a lower limit of 30 patients (no limits with autopsy confirmation). Consensus recommendations were developed through a Delphi procedure, based on the expertise of panelists, who were also informed about the availability and quality of evidence, assessed by an independent methodology team. RESULTS: Critical outcomes were available in nine among the 17 papers initially selected. Only three papers performed a direct comparison between visual and automated assessment and quantified the incremental value provided by the latter. Sensitivity between visual and automatic analysis is similar but automatic assessment generally improves specificity and marginally accuracy. Also, automated assessment increases diagnostic confidence. As expected, performance of visual analysis is reported to depend on the expertise of readers. CONCLUSIONS: Tools for semi-quantitative evaluation are recommended to assist the nuclear medicine physician in reporting brain FDG-PET pattern in neurodegenerative conditions. However, heterogeneity, complexity, and drawbacks of these tools should be known by users to avoid misinterpretation. Head-to-head comparisons and an effort to harmonize procedures are encouraged.status: publishe

Medial temporal lobe atrophy and posterior atrophy scales normative values

The medial temporal lobe atrophy (MTA) and the posterior atrophy (PA) scales allow to assess the degree hippocampal and parietal atrophy from magnetic resonance imaging (MRI) scans. Despite reliable, easy and widespread employment, appropriate normative values are still missing. We aim to provide norms for the Italian population