Quantification of Blood Flow-Dependent Component in Estimates of Beta-Amyloid Load Obtained Using Quasi-Steady-State Standardized Uptake Value Ratio

Cselényi, Zsolt; Farde, Lars

doi:10.1038/jcbfm.2015.66

Cited by 29 publications

(34 citation statements)

References 39 publications

(104 reference statements)

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“…AV-1451 scans were collected within 3 months of the participant's last PIB scan. AV-1451 standardized uptake value ratio (SUVR) images were created based on mean uptake over 80 -100 min postinjection (Shcherbinin et al, 2016;Baker et al, 2017;Wooten et al, 2017) normalized by mean inferior cerebellar gray matter uptake (Maass et al, 2017). SUVR images were coregistered and resliced to the structural MRI closest in time to AV-1451 PET scanning (mean delay, 2.3 months).…”

Section: Methodsmentioning

confidence: 99%

“…Because individuals with AD have evidence of A␤ deposition decades before they are destined for symptoms (Bateman et al, 2012;Villemagne et al, 2013), the issue of exactly when A␤ deposition begins to exert harmful neurological effects is crucial and also tractable with studies using imaging methods. Most studies have classified participants as "amyloid positive" or "amyloid negative"; while this is useful for categorizing an individual for a potential clinical trial or predicting decline, it results in considerable loss of information (Villeneuve et al, 2015) and neglects the potential importance of early A␤ deposition and accumulation in revealing disease mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Subthreshold Amyloid Predicts Tau Deposition in Aging

et al. 2018

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Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as "positive" or "negative" for biomarkers related to the core pathology of β-amyloid (Aβ). However, the accumulation of Aβ begins slowly, years before biomarkers become abnormal. We used longitudinal [C] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans ( = 71; mean age 75 years; 35% male). We used [F] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample ( = 37). We found evidence for an inverted-U relationship between baseline Aβ levels and Aβ slope in asymptomatic older adults, suggesting a slowing of Aβ accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of Aβ predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of Aβ increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative. The progressive nature of Alzheimer's disease (AD) necessitates the earliest possible detection of pathological or cognitive change if disease progression is to be slowed. We examined cognitively normal older adults in whom AD pathology is starting to develop, with the goal of early detection of AD pathology or cognitive changes. We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition. Further, it appears that rates of amyloid accumulation already begin to slow in preclinical AD, suggesting that it is a relatively late stage of AD progression. Thus, it is crucial to examine older adults early, before amyloid levels have saturated, to intervene to slow disease progression.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Subthreshold Amyloid Predicts Tau Deposition in Aging

et al. 2018

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“…We note that because the time required for the overall system to reach steady-state is much larger than the time needed for steady-state concentration gradients to be generated within the μ Lane system alone. Thus, the operation of the system is ‘best’ described as ‘quasi-steady-state’ (5, 10, 40, 68, 71, 73) . However, because this work focuses exclusively on smaller time scales of the microchannel only, the term steady-state would be used for simplicity.…”

Section: Methodsmentioning

confidence: 99%

EGF as a New Therapeutic Target for Medulloblastoma Metastasis

et al. 2015

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Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cell-derived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates that MB-derived cells respond strongly to EGF in a dosage and gradient-dependent manner with increased EGF-R activation, and show that high EGF gradient fields cause an increased number of cells to migrate longer directed distances. Our results provide evidence that EGF and its receptor play an important role than previously documented in MB chemotactic migration than previously documented and should be considered for developing migration-target therapies against MB metastasis.

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“…However, since this estimate is derived from a single time point, variations in blood flow, which influence the delivery and washout of the tracer, cannot be accounted for. Consequently SUVR measures become biased, confounding results in longitudinal studies where, in conditions such as Alzheimer's Disease (AD), there will be both changes in blood flow and the abundance of the biological target [1].…”

Section: Introductionmentioning

confidence: 99%

Short Acquisition Time PET Quantification Using MRI-Based Pharmacokinetic Parameter Synthesis

Scott

Jiao

Cardoso

et al. 2017

Lecture Notes in Computer Science

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Positron Emission Tomography (PET) with pharmacokinetic (PK) modelling is a quantitative molecular imaging technique, however the long data acquisition time is prohibitive in clinical practice. An approach has been proposed to incorporate blood flow information from Arterial Spin Labelling (ASL) Magnetic Resonance Imaging (MRI) into PET PK modelling to reduce the acquisition time. This requires the conversion of cerebral blood flow (CBF) maps, measured by ASL, into the relative tracer delivery parameter (R1) used in the PET PK model. This was performed regionally using linear regression between population R1 and ASL values. In this paper we propose a novel technique to synthesise R1 maps from ASL data using a database with both R1 and CBF maps. The local similarity between the candidate ASL image and those in the database is used to weight the propagation of R1 values to obtain the optimal patient specific R1 map. Structural MRI data is also included to provide information within common regions of artefact in ASL data. This methodology is compared to the linear regression technique using leave one out analysis on 32 subjects. The proposed method significantly improves regional R1 estimation (p < 0.001), reducing the error in the pharmacokinetic modelling. Furthermore, it allows this technique to be extended to a voxel level, increasing the clinical utility of the images.

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Quantification of Blood Flow-Dependent Component in Estimates of Beta-Amyloid Load Obtained Using Quasi-Steady-State Standardized Uptake Value Ratio

Cited by 29 publications

References 39 publications

Subthreshold Amyloid Predicts Tau Deposition in Aging

Subthreshold Amyloid Predicts Tau Deposition in Aging

EGF as a New Therapeutic Target for Medulloblastoma Metastasis

Short Acquisition Time PET Quantification Using MRI-Based Pharmacokinetic Parameter Synthesis

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