Effects of the interaction between ferric iron and L‐dopa melanin on T1 and T2 relaxation times determined by magnetic resonance imaging

Tosk, Jeffrey M.; Holshouser, Barbara A.; Aloia, Roland C.; Hinshaw, David B.; Hasso, Anton N.; MacMurray, James P.; Will, Albrecht; Bozzetti, Louis P.

doi:10.1002/mrm.1910260105

Cited by 47 publications

(35 citation statements)

References 42 publications

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“…7,10,15,17,24 These differences may be related to the scanner type, magnetic field strength, sequence parameters, image-processing methods, partial volume effect on 2D imaging, or ROI selection methods. 29 Within this context, qualitative measurements such as visual assessment of NM-sensitive images or DNH appear interesting.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Pyatigorskaya

Magnin

Mongin

et al. 2018

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 99%

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Pyatigorskaya

Magnin

Mongin

et al. 2018

AJNR Am J Neuroradiol

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“…Interestingly, l -DOPA is associated with shortening of T 1 (and T 2 ) relaxation time in vitro , although this may be influenced by the presence of iron (42). This raises the possibility that changes in T 1 in the human brain after l -DOPA administration may lead to an adjustment in the number of voxels that are attributed to gray matter.…”

Section: Levodopa Gray Matter and Magnetic Resonance Imaging Signalmentioning

confidence: 99%

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

2014

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Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson’s disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID.

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“…It also interacts with proteins, including α-synuclein, which is a precursor of Lewy bodies that binds with neuromelanin during the early stage of Parkinson's disease (PD) [11]. Neuromelanin can function as a paramagnetic agent on combining with metals such as iron and copper [12]. In vitro experiments have revealed the concentration-dependent T1-shortening effects of the melanin pigment on T1-weighted images (T1WI); its longitudinal and transverse relaxivities, i.e., R1 and R2, have been reported to be 1.02 mM -1 s -1 and 1.32 mM -1 s -1 , respectively, at 0.47 T under the condition of 10% iron [13].…”

Section: What Is Neuromelanin?mentioning

confidence: 99%

Neuromelanin-Sensitive MRI

et al. 2008

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The basics and the technique of magnetic resonance imaging (MRI) for visualizing the neuromelanin present in dopaminergic and noradrenergic nuclei in the substantia nigra pars compacta (SNc) and locus caeruleus (LC) are introduced. Neuromelanin, a black pigment produced during catecholamine synthesis, has paramagnetic T1-shortening effects. Conventional MRI techniques fail to depict the contrast generated by neuromelanin, but neuromelanin-sensitive T1-weighted fast spin echo technique at 3 T allows the direct visualization of the SNc and LC as hyperintense areas. In Parkinson's disease, neuromelanin-related signals from the SNc and LC are diminished, suggesting neuronal degeneration in both the nuclei. In depression and schizophrenia, signals from the LC are reduced while those from the SNc are augmented, suggesting monoamine and dopamine hypotheses, respectively. Neuromelanin-sensitive MRI is a promising technique to elucidate the pathologic or functional changes in the catecholamine neurons of the brain stem that occur in degenerative and psychiatric diseases. ZusammenfassungDie Grundlagen und die Technik der Kernspintomographie (MRT) zur Visualisierung des in den dopaminergen und noradrenergen Nuklei in der Pars compacta der Substantia nigra (SNc) und im Locus caeruleus (LC) vorhandenen Neuromelanins werden vorgestellt. Neuromelanin, ein schwarzes Pigment, welches durch die Katecholaminsynthese entsteht, hat eine paramagnetische, T1-verkürzende Wirkung. Konventionelle MRT-Techniken sind nicht in der Lage, den durch das Neuromelanin generierten Kontrast darzustellen. Eine neuromelaninsensitive, T1-gewichtete, schnelle Spinechotechnik bei 3 T hingegen erlaubt eine unmittelbare Visualisierung der SNc und des LC als hyperintense Areale. Bei der Parkinson-Krankheit sind die neuromelaninbedingten Signale aus der SNc und dem LC vermindert und lassen auf eine neuronale Degeneration in beiden Nuklei schließen. Bei Depressionen und Schizophrenie sind die Signale aus dem LC vermindert, während die Signale aus der SNc erhöht sind und auf eine monoamine bzw. dopamine Hypothese hindeuten. Die neuromelaninsensitive MRT ist eine vielversprechende Technik zur Klärung der bei degenerativen und psychiatrischen Krankheiten vorkommenden pathologischen oder funktionellen Veränderungen der katecholaminen Neuronen des Hirnstamms. IntroductionIt is widely known that some catecholamine neurons in the human brain stem, such as those of the substantia nigra pars compacta (SNc) and locus caeruleus (LC), contain a black pigment called neuromelanin [1]. These neuromelanin-containing nuclei can be easily identified as black areas in gross specimens. However, these nuclei have remained invisible on magnetic resonance imaging (MRI), and the neuromelanin-generated contrast has hardly been studied. Recently, we proposed a new MRI technique that can depict the neuromelanin-related contrast generated by these nuclei and demonstrate pathologic changes occurring in some degenerative and psychiatric diseases [2][3][4][5]. In this review, we introduce...

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Effects of the interaction between ferric iron and L‐dopa melanin on T1 and T2 relaxation times determined by magnetic resonance imaging

Cited by 47 publications

References 42 publications

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

Neuromelanin-Sensitive MRI

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