Increased iron‐related MRI contrast in the substantia nigra in Parkinson's disease

Gorell, Jay M.; Ordidge, Roger J.; Brown, Garth G.; Deniau, J. C.; Buderer, Nancy; Helpern, Joseph A.

doi:10.1212/wnl.45.6.1138

Cited by 293 publications

(232 citation statements)

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“…Hill and Switzer [24] demonstrated the distribution of iron was overlapped with gamma-aminobutyric acid (GABA), enkephalin and lutenizing hormone releasing hormone (LHRH) in the rat brain. The increase of iron concentration in the brain was also detected in several neurological disorders, such as multiple sclerosis, Shy-drager syndrome, Parkinson's disease, and abnormal movement disorders [15,21,33,35]. It was widely accepted that iron generated oxygen free radicals, resulted in neurological cell death [32,36] and also disturbance of neuronal functions in human with age advanced [39].…”

Section: Discussionmentioning

confidence: 99%

Changes of Magnetic Resonance Imaging on the Brain in Beagle Dogs with Aging

Kimotsuki

Nagaoka

Yasuda

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Age-associated changes of magnetic resonance imaging (MRI) on the brain were evaluated in 19 beagle dogs aged from 8-month-to 16-year-old. A significant correlation of the volume of lateral ventricle space was observed in the dogs with age advanced, however, no correlation was found between hippocampus size and the aging. The hypo-intensity areas on T2-weighted MRI were detected in globus pallidus and substantia nigra with a significant correlation of both intensity ratios to lateral ventricle with age advanced. These areas were coincided with the accumulation of iron in the slice of the brain with Perls' staining. In addition, hyperintensity area, suggesting perivascular demyelination with fluid-filled space, was also observed in white matter surrounding the lateral ventricle on T2-weighted MRI. These results suggested that age-associated changes of T2-weighted MRI were developed in the dog brain, especially in globus pallidus, substantia nigra, and white matter surrounding lateral ventricle, like as those reported in the human brain KEY WORDS: age-associated change, brain, canine, hypo-and hyper-intensity, MRI.J. Vet. Med. Sci. 67(10): 961-967, 2005 Magnetic resonance imaging (MRI) has been used as a noninvasive and useful diagnostic technique for evaluating age related brain disorders, such as Alzheimer's disease, Parkinson's disease, and dementia, indicating severe atrophy of the brain, hippocampus, amygdala, and temporal lobe, gray matter, and dilatation of ventricle space, and cortical sulci, [9,17,26,28,34]. However, age-associated similar changes of MRI was also observed in the clinically healthy human brain, indicating brain atrophy, dilatation of ventricle space and cortical sulci, hypo-intensity area in globus pallidus and substantia nigra, and hyper-intensity area in white matter [7,16,20,31]. In addition, age-associated pathological changes of the brain, including developments of senile plaque, decrease number of neuronal cell, deposit of lipofuscin, and activation of astrocyte, have also been well documented [8,12,23,38]. Therefore, it is necessary for diagnose of age related degenerative diseases to evaluate age-associated changes in the brain. Various age-associated changes were detected in aged dogs with occasionally abnormal behaviors [4,6,10,27,30], like as those reported in human [13]. Although MRI has been applied in veterinary clinics and experimental medicine, several reports were on clinical cases and few reports on age-associated changes in the dog brain [5,37]. This study deals with ageassociated changes in MRI on the brain, especially lateral ventricle space, hippocampus size, and hypo-and hyperintensity area, in beagle dogs with age advanced. MATERIALS AND METHODS Animals:Clinically healthy 19 beagle dogs (8 male and 11 female), aged from 8-month-to 16-year-old, were used. All the dogs were bred, reared, and kept in Medicinal Safety Research Laboratories, Sankyo Co., Ltd. under the condition of circumstance temperature at 22 ± 2°C. The air extraction was designed to be 10...

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Section: Discussionmentioning

confidence: 99%

Changes of Magnetic Resonance Imaging on the Brain in Beagle Dogs with Aging

Kimotsuki

Nagaoka

Yasuda

et al. 2005

The Journal of Veterinary Medical Science

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“…The R2' increase better reflects histological data that consistently demonstrates excessive iron deposition in the substantia nigra in PD. Other groups 33,38,41 have also shown that R2' estimates iron concentration more accurately than R2. Many other researchers 36,42,43 demonstrated that both R2 and R2' are affected by iron.…”

Section: Relaxometrymentioning

confidence: 99%

“…In a study involving 20 patients with PD, Atasoy et al 99 demonstrated a correlation between T2 hypointensity of the substantia nigra pars compacta and clinical severity. In a study of 13 patients with PD, using 3T MRI and iron relaxometry techniques, Gorell et al 41 demonstrated elevated iron levels in the substantia nigra compared to normal controls. There was also a strong association between iron concentration and motor performance.…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…There was also a strong association between iron concentration and motor performance. 41 Using the partially refocused interleaved multiple echo MRI sequence, Graham et al 38 showed an increase in R2' and R2* in the substantia nigra of PD patients when compared with normal controls. However, R2' and R2* did not correlate with clinical impairment.…”

Section: Parkinson's Diseasementioning

confidence: 99%

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Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

et al. 2007

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Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

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“…It has been shown that these quantitative MRI techniques based on magnitude changes of the MRI signal partially correlate with iron content within a limited range of iron concentration, as seen in an aging brain (17,18). The qualitatively observable increases of iron deposition have been described in various chronic neurological diseases such as in multiple sclerosis, Alzheimer's disease, Parkinson's disease, and PKAN; however, no quantitative iron concentration estimates have been reported based on MRI signal magnitude measurements (1,15,(19)(20)(21). Moreover, at present there appears to be lack of consensus on the most desirable MRI method based on signal magnitude for accurately estimating iron content in the brain (2).…”

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confidence: 99%

Measurement of brain iron distribution in Hallevorden‐Spatz syndrome

Szumowski

Bas

Gaarder

et al. 2010

Magnetic Resonance Imaging

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Purpose: To investigate spatial distribution of iron accumulation in the globus pallidus (GP) in patients with Hallevorden-Spatz syndrome (HSS) using phase imaging. We compared sensitivity of a phase imaging technique to relaxation rate measurement methods (R1,R2,R2*) for iron quantification.Materials and Methods: R1, R2, and R2* were measured in GP structure of the brain of eight pantothenate kinaseassociated neurodegeneration (PKAN) patients and a healthy volunteer using a 3T magnetic resonance imaging (MRI) scanner. The phase of gradient-echo images was preprocessed to eliminate phase 2p wrapping and filtered to remove phase background variations. Phase gap across GP structure was used as a metric for iron effects quantification.Results: Among the relaxation rates the most sensitive to iron accumulation was the R2* rate. The R1 and R2 rates demonstrated only small variations in this group of subjects. Up to an order of magnitude phase gap changes were measured between one PKAN patient and an agematched healthy volunteer. Assuming that phase gap differences scale linearly with iron concentration we estimate that up to 2 mg Fe/g ww accumulates in GP of these patients.Conclusion: Our results demonstrate significantly higher sensitivity of the phase measurements for quantitative assessment of iron concentration compared to the relaxation rate measurements. Phase measurements could potentially be used for monitoring a progression and a response to therapy in PKAN.

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Increased iron‐related MRI contrast in the substantia nigra in Parkinson's disease

Cited by 293 publications

References 0 publications

Changes of Magnetic Resonance Imaging on the Brain in Beagle Dogs with Aging

Changes of Magnetic Resonance Imaging on the Brain in Beagle Dogs with Aging

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

Measurement of brain iron distribution in Hallevorden‐Spatz syndrome

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