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Brain Sciences
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The Role of Multimodal Imaging in Assessing the Biology and...
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The Role of Multimodal Imaging in Assessing the Biology and Staging of Neurodegenerative Disorders

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2385

Special Issue Editor

Prof. Dr. Andrea Varrone

E-Mail Website
Guest Editor
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institute and Stockholm Health Services, BioClinicum, J4-14, Akademiska Stråket 1, 17176 Solna, Sweden
Interests: molecular imaging; PET; neurodegenerative disorders; Parkinson's disease; movement disorders; alpha-synuclein; neuroinflammation; synaptic density

Special Issue Information

Dear Colleagues,

The development and validation of fluid and imaging biomarkers for Alzheimer's disease (AD) have changed the view on how patients with suspected dementia of the Alzheimer's type are evaluated and have contributed to the establishment of research criteria for the diagnosis and staging of AD. Neuroimaging tools such as amyloid and tau PET, FDG PET and MR imaging are included as biomarkers for the assessment of A, T and N pathological changes in AD. More recently, two biological staging systems for neuronal synucleinopathies (Parkinson's disease—PD; dementia with Lewy bodies—DLB) have been proposed, leveraging the development of assays to detect synuclein pathology and established imaging biomarkers of neurodegeneration. Multimodal imaging with PET and MRI offers the opportunity to detect and measure in vivo different pathological processes. Changes in blood flow, metabolism, protein misfolding and neurodegeneration, but also peripheral markers such as cardiac denervation, can support early diagnosis of AD, PD and DLB and their biological characterization. This Special Issue aims to summarize the current status and recent advances in neuroimaging tools for in vivo biological characterization of these disorders.

Prof. Dr. Andrea Varrone
Guest Editor

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Keywords

  • amyloid beta
  • phosphorylated tau
  • alpha-synuclein
  • neuronal loss
  • neuromelanin
  • iron content
  • cardiac denervation
  • dopaminergic cell loss

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Published Papers (2 papers)

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Review

13 pages, 4314 KB  
Review
Combined Striatal Dopaminergic and Cardiac Sympathetic Imaging in Parkinson’s Disease
by Louis Versweyveld, Greet Vanderlinden, Wim Vandenberghe, Aline Delva and Koen Van Laere
Brain Sci. 2026, 16(5), 484; https://doi.org/10.3390/brainsci16050484 - 30 Apr 2026
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Abstract
Background/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson’s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in [...] Read more.
Background/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson’s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in PD and (2) the comparative and combined diagnostic accuracy of striatal dopaminergic and cardiac sympathetic imaging in PD. Methods: We searched PubMed (October 2025) for studies assessing both a striatal dopaminergic and a cardiac sympathetic imaging biomarker in the same PD cohort, supplemented by citation chaining. Diagnostic accuracy studies were evaluated using QUADAS-2. Results: Nineteen studies met the inclusion criteria. Ten studies examined within-subject associations; six reported significant correlations ranging from weak to strong (ρ ~0.2–0.8). Two studies observed a significant correlation for the akinetic-rigid subtype but not for the tremor-dominant subtype of PD. Ten studies compared diagnostic accuracies, five of which used pre-defined thresholds and consistently found higher sensitivity for [123I]FP-CIT SPECT (78–100%) compared to [123I]MIBG scintigraphy (65–82%), but higher specificity for [123I]MIBG (range 75–100%) than for [123I]FP-CIT (range 11–73%). Adding [123I]MIBG scintigraphy to [123I]FP-CIT SPECT generally increased specificity but had inconsistent effects on overall accuracy. QUADAS-2 revealed substantial risks of patient selection bias, data-driven thresholds, and limited blinding. Conclusions: Reported correlations between nigrostriatal dopaminergic degeneration and cardiac sympathetic denervation in PD are inconsistent, likely reflecting both methodological heterogeneity and real variation between phenotypes. There may be a stronger correlation in the akinetic-rigid phenotype. Dopaminergic imaging is more sensitive in early PD, while cardiac sympathetic imaging is more specific for differentiating PD from atypical Parkinsonian syndromes. However, study designs greatly restrict the generalizability of reported diagnostic accuracies. Full article
(This article belongs to the Special Issue The Role of Multimodal Imaging in Assessing the Biology and Staging of Neurodegenerative Disorders)
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25 pages, 1634 KB  
Review
Correlation and Interchangeability of Amyloid, Tau, and Glucose Metabolism PET in Mild Cognitive Impairment and Alzheimer: A Review
by Emile Balot, Stefaan Vandenberghe, Tim Van Langenhove, Valerie De Meulenaere, Yves D’Asseler and Donatienne Van Weehaeghe
Brain Sci. 2025, 15(12), 1271; https://doi.org/10.3390/brainsci15121271 - 26 Nov 2025
Cited by 1 | Viewed by 1601
Abstract
Positron emission tomography (PET) allows for minimally invasive in vivo localization of amyloid and tau deposition, and visualization of glucose metabolism using amyloid PET, tau PET, and FDG PET. Clinically, these scans are used to determine A, T, and N (amyloid-β plaques, tau [...] Read more.
Positron emission tomography (PET) allows for minimally invasive in vivo localization of amyloid and tau deposition, and visualization of glucose metabolism using amyloid PET, tau PET, and FDG PET. Clinically, these scans are used to determine A, T, and N (amyloid-β plaques, tau tangles, and neurodegeneration) status in Alzheimer’s disease. In light of the recent anti-amyloid therapies, determination of the A, and the associated T and N status is increasingly important. This review explores the potential of a single PET scan to define multiple biomarkers. A literature search using the PubMed database and an additional citation search using Google Scholar identified 76 relevant publications up to 30 July 2025. Original work reporting amyloid, tau or FDG PET to determine two or more ATN-related biomarkers were included. Non-English, animal, and non-dementia related studies were excluded. For each study, quantitative outcomes such as correlations and ROC AUC scores were extracted and compared. Early phase amyloid and tau PET (n = 58) were consistently found to be good indicators of N status with a median (IQR) correlation of 0.82 (0.76–0.86). Limited research (n = 7) was performed for amyloid or tau PET to infer both A and T status, with tau-based studies having slightly higher ROC AUC scores (0.88–0.99) than amyloid-based studies (0.84–0.9). Initial results are promising (median ROC AUC scores of 0.88 (0.81–0.96)) but need to be validated. FDG PET was found to be less accurate for A or T status (n = 12) prediction (median ROC AUC scores of 0.83 (0.80–0.87)). Among the modalities, tau PET seems to be the most promising candidate for a single tracer approach to predict all three biomarkers. Full article
(This article belongs to the Special Issue The Role of Multimodal Imaging in Assessing the Biology and Staging of Neurodegenerative Disorders)
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