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The article discusses the use of positron emission tomography (PET) in the diagnosis and management of functional pituitary neuroendocrine tumors (PitNETs). PitNETs are common intracranial tumors that can cause significant health issues. While magnetic resonance imaging (MRI) is the primary diagnostic method, it has limitations in detecting certain types of PitNETs. PET imaging with radiolabeled amino acids, such as [11C]MET and [18F]FET, shows promise in accurately detecting and localizing functional PitNETs. However, further research and larger studies are needed to determine the accuracy and clinical indications of PET imaging in this context. [Extracted from the article]

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities. [ABSTRACT FROM AUTHOR]

The article discusses the perspectives of the European Association of Nuclear Medicine on the role of artificial intelligence (AI) in molecular brain imaging. The authors highlight the potential of AI in advancing research and clinical practice in the field of molecular brain imaging. They emphasize the need for standardization of clinical brain image recording and imaging protocols, as well as the importance of annotated images and additional data for feeding AI algorithms. The article also explores the applications of AI in image acquisition, segmentation and registration, interpretability analysis, and specific clinical areas such as epilepsy, neurodegenerative and movement disorders, neuro-oncology, and psychiatric disorders. The authors acknowledge the challenges and limitations in implementing AI in these areas, including the need for large datasets, validation studies, and harmonization of AI algorithms. Overall, the article provides a comprehensive overview of the current state and future potential of AI in molecular brain imaging. [Extracted from the article]

Background: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. Methods: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). Results: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5–46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. Conclusions: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination. [ABSTRACT FROM AUTHOR]

Introduction: There is overwhelming evidence that focal lesions cause structural, metabolic, functional, and electrical disconnection of regions directly and indirectly connected with the site of injury. Unfortunately, methods to study disconnection (positron emission tomography, structural and functional magnetic resonance imaging, electroencephalography) have been applied primarily in isolation without capturing their interaction. Moreover, multi-modal imaging studies applied to focal lesions are rare. Case report: We analyzed with a multi-modal approach the case of a patient presenting with borderline cognitive deficits across multiple domains and recurrent delirium. A post-surgical focal frontal lesion was evident based on the brain anatomical MRI. However, we were able to acquire also simultaneous MRI (structural and functional) and [18F]FDG using a hybrid PET/MRI scan along with EEG recordings. Despite the focality of the primary anatomical lesion, structural disconnection in the white matter bundles extended far beyond the lesion and showed a topographical match with the cortical glucose hypometabolism seen both locally and remotely, in posterior cortices. Similarly, a right frontal delta activity near/at the region of structural damage was associated with alterations of distant occipital alpha power. Moreover, functional MRI revealed even more widespread local and distant synchronization, involving also regions not affected by the structural/metabolic/electrical impairment. Conclusion: Overall, this exemplary multi-modal case study illustrates how a focal brain lesion causes a multiplicity of disconnection and functional impairments that extend beyond the borders of the anatomical irrecoverable damage. These effects were relevant to explain patient's behavior and may be potential targets of neuro-modulation strategies. [ABSTRACT FROM AUTHOR]

Although the hypometabolic long COVID brain profile described above seems consistent with hypotheses and findings obtained for other viruses before the COVID-19 outbreak, with symptoms reported by patients with long COVID, and with results obtained from other diagnostic approaches assessing long COVID, the significance of these metabolic abnormalities in the individual patients remains to be determined. 2 Axial slices of a brain FDG PET scan of a patient with a hypometabolic long COVID pattern (A) and in a patient with a normal brain scan (B). Here, in 143 patients diagnosed in accordance with the current WHO definition of post-COVID syndrome, a hypometabolic long COVID pattern was observed in 47% of patients presenting persistent symptoms at an average of 10.9 months after COVID-19 [[28]]. [Extracted from the article]

Pediatric soft tissue sarcomas are rare tumors with rhabdomyosarcoma being the most frequent histotype. Diagnostic imaging plays a significant role in the evaluation of this type of tumors. Thus, aim of this study was to assess the prognostic and diagnostic value of radiomic features extracted from axial T2w images of the primary lesion in children with soft tissue sarcomas examined by PET/MR for staging. Using an open source software, each lesion was segmented and 33 radiomic features then extracted. Factor and logistic regression analyses were applied to select highly correlating features and evaluate their prognostic role, respectively. Differences in radiomic, demographics, metabolic, and laboratory variables according to tumor grade and histotype were investigated by the Students' and Chi-square tests. In case of differences the diagnostic value of the variable/s was assessed by receiver operating curves. Eighteen children (11 female; mean age 7.8 ± 4.6-year-old) matched the inclusion criteria. The factor analysis allowed the selection of five highly correlating features which, according to regression analysis, did not influence the outcome (p > 0.05, each). The feature lmc1 was significantly higher in low grade lesions (p = 0.045) and showed 70.4% accuracy in classifying high grade tumors while the feature variance was significantly lower in rhabdomyosarcomas (p = 0.008) and showed 83.3% accuracy for this histotype. In conclusion, our preliminary results suggest that specific radiomic features may act as biomarkers of pediatric soft tissue sarcoma grade and histotype. [ABSTRACT FROM AUTHOR]

The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations. [ABSTRACT FROM AUTHOR]

The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan–Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival. [ABSTRACT FROM AUTHOR]

The use of amyloid PET imaging as surrogate outcome measure of the effect of anti-AD drugs is a more complex matter and has been less explored. This article is part of the Topical Collection on Neurology On June 7th, 2021, for the first time since 2003, a novel drug against Alzheimer's disease (AD), aducanumab (Aduhelm™), has been approved in the USA by the Food and Drug Administration (FDA). We will focus here on two main aspects directly concerning our clinical and research practice: (1) using amyloid PET imaging as eligibility criterion and anticipating the associated needs, and (2) evaluating amyloid PET readout changes as surrogate outcome measures in clinical trials. SUVr is a biased measure for assessment of reduction of amyloid load after a pharmacotherapeutic intervention, as it shows a "reduction" in amyloid load over time in AD patients that in fact is an artefact linked with the perfusion reduction in cortical areas that occurs in AD patients over time [[24]]. [Extracted from the article]

Purposes: We present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)–targeting radioligand (+)-[18F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[18F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer's disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding; and whether (+)-[18F]Flubatine binding and cognitive test data respective β-amyloid radiotracer accumulation were correlated. Methods: We examined 11 HCs and 9 mild AD patients. All subjects underwent neuropsychological testing and [11C]PiB PET/MRI examination. (+)-[18F]Flubatine PET data were evaluated using full kinetic modeling and regional as well as voxel-based analyses. Results: With 270-min p.i., the unchanged parent compound amounted to 97 ± 2%. Adequate fits of the time-activity curves were obtained with the 1 tissue compartment model (1TCM). (+)-[18F]Flubatine distribution volume (binding) was significantly reduced in bilateral mesial temporal cortex in AD patients compared with HCs (right 10.6 ± 1.1 vs 11.6 ± 1.4, p = 0.049; left 11.0 ± 1.1 vs 12.2 ± 1.8, p = 0.046; one-sided t tests each). PVE correction increased not only (+)-[18F]Flubatine binding of approximately 15% but also standard deviation of 0.4–70%. Cognitive test data and (+)-[18F]Flubatine binding were significantly correlated in the left anterior cingulate, right posterior cingulate, and right parietal cortex (r > 0.5, p < 0.05 each). In AD patients, (+)-[18F]Flubatine binding and [11C]PiB standardized uptake value ratios were negatively correlated in several regions; whereas in HCs, a positive correlation between cortical (+)-[18F]Flubatine binding and [11C]PiB accumulation in the white matter was found. No adverse event related to (+)-[18F]Flubatine occurred. Conclusion: (+)-[18F]Flubatine is a safe and stable PET ligand. Full kinetic modeling can be realized by 1TCM without metabolite correction. (+)-[18F]Flubatine binding affinity was high enough to detect group differences. Of interest, correlation between white matter β-amyloid PET uptake and (+)-[18F]Flubatine binding indicated an association between white matter integrity and availability of α4β2 nAChRs. Overall, (+)-[18F]Flubatine showed favorable characteristics and has therefore the potential to serve as α4β2 nAChR–targeting PET ligand in further clinical trials. [ABSTRACT FROM AUTHOR]

Aim Of the Study: Skeletal muscle metastases (SMM) are a rare entity, mainly detected at autopsy. Nevertheless, radiological and nuclear medicine imaging can contribute to the diagnosis with a significant impact on the treatment and prognosis of neoplastic patients. This study aimed to systematically review the features of SMM at imaging considering the primary tumors and the sites of occurrence.Materials and Methods: We conducted a systematic search of three electronic database (i.e., PubMed, Science Direct, and Web of Science) up to May 2019, without any language or time interval restriction. Two reviewers performed the search and selection process, data extraction, and synthesis. We resolved disagreements by consensus and/or involving a third reviewer. The included studies have been classified according to the Oxford Centre for Evidence Based Medicine (CEBM) grading system.Results: Out of 8598 and 1077 articles respectively for radiological and hybrid imaging, 29 papers were included. According to CEBM, twelve were level 4. Computed tomography (CT) is mainly applied and, despite the existence of CT and magnetic resonance-based classifications, these are rarely used. Positron emission tomography/CT allowed the detection of small and subtle lesion also in the extremities. Muscles of the trunk were mostly affected and mainly respiratory tumors are associated with this type of metastatic spread.Conclusion: Radiological and hybrid imaging allow a precise characterization of SMM. However, a more systematic approach, including also the application of available classification systems, may increase the diagnostic accuracy for this rare type of metastases.Key Points: • Skeletal muscle metastases have heterogeneous characteristics at imaging but mostly abscess-like features and high metabolic activity are described. • Skeletal muscle metastases mainly affect the muscles of the trunk. • Pulmonary, urological, and gastrointestinal cancers are the most frequent cause of skeletal muscle metastases. [ABSTRACT FROM AUTHOR]

Background: The pathological processes underlying cognitive impairment in Parkinson's disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease.Objective: To investigate regional [18F]florbetaben binding to amyloid-β (Aβ) and its contribution to cognitive dysfunction in early stage PD.Methods: A multicenter cohort of 48 PD patients from the Parkinson's Progression Marker Initiative (PPMI) underwent [18F]florbetaben positron emission tomography (PET) scanning. Clinical features, including demographic characteristics, motor severity, cerebrospinal fluid (CSF), and cognitive testing were systematically assessed according to the PPMI study protocol. For the purpose of this study, we analyzed various neuropsychological tests assessing all cognitive functions.Results: There were 10/48 (21%) amyloid positive PD patients (PDAβ+). Increased [18F]florbetaben uptake in widespread cortical and subcortical regions was associated with poorer performance on global cognition, as assessed by Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit Modality test (SDMT). Further, we found that PDAβ+ patients had higher CSF total-tau/Aβ1 - 42 (p = 0.001) and phosphorylated-tau/Aβ1 - 42 in (p = 0.002) compared to amyloid-negative PD.Conclusion: These findings suggest that multiple disease processes are associated with PD cognitive impairment and amyloid deposits may be observed already in early stages. However, prevalence of amyloid positivity is in the range of literature age-matched control population. Increased cortical and subcortical amyloid is associated with poor performance in attentive-executive domains while cognitive deficits at MoCA and SDMT may identify amyloid-related dysfunction in early PD. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common malignancy worldwide, and rectal cancer (RC) accounts for 29% of all cases. Local staging of RC is crucial for the purposes of addressing patients appropriately to surgery alone or to preoperative chemoradiotherapy (pCRT) followed by total mesorectal excision (TME). Combined pCRT and TME may negatively affect rectal function, so rectum-sparing approaches such as transanal local excision have been proposed as an alternative to TME for patients showing a major or complete clinical response on restaging after pCRT. Magnetic resonance imaging (MRI) has a fundamental role in the local staging and restaging of RC, with or without positron emission tomography (PET). PET/MRI enables a multiplanar high-resolution morphological study of the pelvis, providing important information on cell density and metabolic activity with diffusion-weighted imaging (DWI) and 18 F fluorodeoxyglucose uptake respectively. This article offers a pictorial review of the MRI anatomy of the ano-rectal region and an update on local RC staging with a hybrid 18 F-FDG PET/MRI scan. [ABSTRACT FROM AUTHOR]

Secondly, although the radiotracer activity used by Soinio et al. was presumably similar to that used by O'Shea et al. and Burton et al., the PET images acquisition protocol differed markedly. Published by Bioscientifica Ltd. Printed in Great Britain © 2021 European Society of Endocrinology https://eje.bioscientifica.com https://doi.org/10.1530/EJE-20-1402 European Journal of Endocrinology 184:3 L9-L10 F Crimì and others Imaging by 11 C-metomidate PET Functional imaging by 11 C-metomidate PET: a really useless technique for primary aldosteronism subtyping?. [Extracted from the article]

Owing to the frequent observation of poverty of movements, facial hypomimia and balance impairment, amyotrophic lateral sclerosis (ALS) variant with predominance of upper motor neuron involvement (UMN-ALS) is prone to be diagnosed with Parkinsonism. A clinical assessment, including the velocity-dependent stretch response test to differentiate between pyramidal and extrapyramidal stiffness; the Unified Parkinson's Disease Rating Scale and the Berg Balance Scale to assess degree of bradykinesia and postural instability; and 123I-FP-CIT scintigraphy evaluation to investigate the nigrostriatal circuit involvement, were carried out to characterize Parkinson-like features in UMN-ALS patients. Sixteen UMN-ALS patients were included in the study. The velocity-dependent stretch response indicated spasticity in all the muscles tested. The degree of stiffness was found to be related to bradykinesia and postural instability. Eleven patients (70%) showed a reduction in striatal 123I-FP-CIT uptake found to be related to disease duration and patients' ages but not to scores of the functional scales. Slowness of movements and postural instability noted in our patients could be mostly attributed to spasticity. The lack of any correlation between UPDRS or BBS scores and the degree of nigrostriatal impairment on DaTSCAN seems to disprove nigrostriatal circuit involvement in these extrapyramidal-like features. [ABSTRACT FROM AUTHOR]

Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%-15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography-computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach is currently based on a patient's clinical, biochemical, and morphological characteristics. The latest published International Consensus Guidelines (ICG) make no mention of the role of metabolic assessments of IPMNs. The aim of this study was to review the current literature, examining the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in IPMN management. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 10 articles were analyzed in detail, focusing on the value of PET as opposed to other standard imaging criteria. Data were retrieved on 419 patients. The 18-FDG-PET proved more sensitive, specific, and accurate than the ICG criteria in detecting malignant IPMNs (reaching 80%, 95%, and 87% vs. 67%, 58%, and 63%, respectively). Metabolic assessments may be used as an additional tool for the appropriate management of patients with doubtful imaging findings. [ABSTRACT FROM AUTHOR]

Infectious and inflammatory pulmonary diseases are a leading cause of morbidity and mortality worldwide. Although infrequently used in this setting, molecular imaging may significantly contribute to their diagnosis using techniques like single photon emission tomography (SPET), positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI) with the support of specific or unspecific radiopharmaceutical agents. 18F-Fluorodeoxyglucose (18F-FDG), mostly applied in oncological imaging, can also detect cells actively involved in infectious and inflammatory conditions, even if with a low specificity. SPET with nonspecific (e.g., 67Gallium-citrate (67Ga citrate)) and specific tracers (e.g., white blood cells radiolabeled with 111Indium-oxine (111In) or 99mTechnetium (99mTc)) showed interesting results for many inflammatory lung diseases. However, 67Ga citrate is unfavorable by a radioprotection point of view while radiolabeled white blood cells scan implies complex laboratory settings and labeling procedures. Radiolabeled antibiotics (e.g., ciprofloxacin) have been recently tested, although they seem to be quite unspecific and cause antibiotic resistance. New radiolabeled agents like antimicrobic peptides, binding to bacterial cell membranes, seem very promising. Thus, the aim of this narrative review is to provide a comprehensive overview about techniques, including PET/MRI, and tracers that can guide the clinicians in the appropriate diagnostic pathway of infectious and inflammatory pulmonary diseases. [ABSTRACT FROM AUTHOR]

The article focuses on advancing the biological definitions of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) through novel biomarker-driven frameworks like SyNeurGe and NSD-ISS, analogous to the ATN system in Alzheimer's disease. Topics include the integration of α-synucleinopathy detection using seed amplification assays in cerebrospinal fluid and skin, alongside neurodegeneration and dopaminergic deficit assessments via imaging biomarkers.