Intrastriatal gradient analyses of 18F-FDOPA PET scans for differentiation of Parkinsonian disorders

Stormezand, Gilles N.; Chaves, Lumi T.; García, David Vállez; Doorduin, Janine; Jong, Bauke M. de; Leenders, Klaus L.; Kremer, Berry; Dierckx, Rudi

doi:10.1016/j.nicl.2019.102161

Cited by 31 publications

(21 citation statements)

References 16 publications

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“…18 F-DOPA применяется также для дифференциальной диагностики атипичного паркинсонизма и идиопатического синдрома паркинсонизма. При этом последний отличается прежде всего более линейным снижением метаболизма ДА от передней к задней части путамена [10].…”

Section: неврологияunclassified

Determination of Parameter Reference Values for 18F-DOPA PET Imaging of the Brain (Based on Using Data from Healthy Subjects)

Abramov¹,

Khoroshavina²,

Tutsenko³

et al. 2020

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Study Objective: To determine, based on data from examination of apparently healthy subjects, parameter reference values for 18F-DOPA positron emission tomography (PET) of the brain. Study Design: This was a prospective study. Materials and Methods: Apparently healthy subjects (n = 33) underwent 18F-DOPA PET of the brain using a Discovery PET/CT 600 scanner. Data were processed using standard statistical methods. The Shapiro-Wilk test was used to test data distribution for normality, and Pearson and Spearman covariance and correlation matrices were calculated. The key components were analyzed to assess combined scattering (explained variance). Study Results: For absolute parameters, the following reference levels were determined for radioactivity concentration (median [1st quartile; 3rd quartile]): 2.24 [2.02; 2.80] kBq/mL in the right putamen, 2.26 [2.02; 2.75] kBq/mL in the left putamen, 2.11 [1.78; 2.55] kBq/mL in the right caudate nucleus (CN), 2.01 [1.74; 2.49] kBq/mL in the left caudate nucleus, and 0.81 [0.71; 1.00] and 0.81 [0.74; 1.02] kBq/mL in the right and left occipital cortices (OC), respectively. For relative parameters, the following reference values were determined (mean ± standard deviation): 2.66 ± 0.52 for the right corpus striatum/OC, 2.68 ± 0.53 for the left corpus striatum/OC, 2.36 ± 0.48 for the right CN/OC, 2.34 ± 0.47 for the left CN/OC, 1.09 ± 0.21 for the right corpus striatum/CN, and 1.11 ± 0.21 for the left corpus striatum/CN. Conclusion: The paper presents reference values for radioactivity concentration in 18F-DOPA PET of the brain. This is the first report of such data. Keywords: neurodegenerative disorders, dopamine metabolism, population norm.

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Section: неврологияunclassified

Determination of Parameter Reference Values for 18F-DOPA PET Imaging of the Brain (Based on Using Data from Healthy Subjects)

Abramov¹,

Khoroshavina²,

Tutsenko³

et al. 2020

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“…This degeneration is characterized by the depletion of dopaminergic innervation to the striatum, due to the patients' loss of dopaminergic neurons in the substantia nigra pars compacta (1). Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies in PD patients demonstrate the decrease of dopamine intake in the striatum (20)(21)(22)(23). Striatal deterioration, in turn, affects motor function, leading to a range of movement impairments (1,24).…”

Section: Introductionmentioning

confidence: 99%

Mapping microstructural gradients of the human striatum in normal aging and Parkinson’s disease

2022

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Mapping structural spatial change (i.e., gradients) in the striatum is essential for understanding the function of the basal ganglia in both health and disease. We developed a method to identify and quantify gradients of microstructure in the single human brain in vivo. We found spatial gradients in the putamen and caudate nucleus of the striatum that were robust across individuals, clinical conditions, and datasets. By exploiting multiparametric quantitative MRI, we found distinct, spatially dependent, aging-related alterations in water content and iron concentration. Furthermore, we found cortico-striatal microstructural covariation, showing relations between striatal structural gradients and cortical hierarchy. In Parkinson’s disease (PD) patients, we found abnormal gradients in the putamen, revealing changes in the posterior putamen that explain patients’ dopaminergic loss and motor dysfunction. Our work provides a noninvasive approach for studying the spatially varying, structure-function relationship in the striatum in vivo, in normal aging and PD.

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“…32 This feature is helpful to differentiate idiopathic PD from atypical PD forms. 33 Putamen dopaminergic dysfunction has been shown to be the best predictive risk factor for the rapid eye movement (REM) sleep behavior phenoconversion to the overt synucleinopathy. 34 Moreover, a greater reduction in the Putamen dopaminergic binding in relation to the caudate has been shown to be specific for the PD compared to the traumatic brain injury.…”

Section: Discussionmentioning

confidence: 99%

Non-reference genome transposable elements (TEs) have a significant impact on the progression of the Parkinson’s disease

Kõks

Pfaff

Singleton

et al. 2022

Exp Biol Med (Maywood)

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The pathophysiology of Parkinson’s disease (PD) is a complex process of the interaction between genetic and environmental factors. Studies on the genetic component of PD have predominantly focused on single nucleotide polymorphisms (SNPs) using a cross-sectional case–control design in large genome-wide association studies. This approach while giving insight into a significant portion of the genetics of PD does not fully account for all the genetic components resulting in missing heritability. In this study, we approached this problem by focusing on the non-reference genome transposable elements (TEs) and their impact on the progression of PD using a longitudinal study design within the Parkinson’s progression markers initiative (PPMI) cohort. We analyzed 2886 Alu repeats, 360 LINE1 and 128 SINE-VNTR-Alus (SVAs) that were called from the whole-genome sequence data which are not within the reference genome. The presence or absence of these non-reference TE variants is known as a retrotransposon insertion polymorphism, and measuring this polymorphism describes the impact of TEs on the traits. The variations for the presence or absence of the non-reference TE elements were modeled to align with the changes in the 114 outcome measures during the five-year follow-up period of the PPMI cohort. Linear mixed-effects models were used, and many TEs were found to have a highly significant effect on the longitudinal changes in the clinically important PD outcomes such as UPDRS subscale II, UPDRS total scores, and modified Schwab and England ADL scale. In addition, the progression of several imaging and functional measures, including the Caudate/Putamen ratio and levodopa equivalent daily dose (LEDD) were also significantly affected by the TEs. In conclusion, this study identified the overwhelming effect of the non-reference TEs on the progression of PD and is a good example of the impact the variations in the “junk DNA” have on complex diseases.

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Intrastriatal gradient analyses of 18F-FDOPA PET scans for differentiation of Parkinsonian disorders

Cited by 31 publications

References 16 publications

Determination of Parameter Reference Values for 18F-DOPA PET Imaging of the Brain (Based on Using Data from Healthy Subjects)

Determination of Parameter Reference Values for 18F-DOPA PET Imaging of the Brain (Based on Using Data from Healthy Subjects)

Mapping microstructural gradients of the human striatum in normal aging and Parkinson’s disease

Non-reference genome transposable elements (TEs) have a significant impact on the progression of the Parkinson’s disease

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