Determination of transverse relaxation rate for estimating iron deposits in central nervous system

Hikita, Tachio; Abe, Kazuo; Sakoda, Saburo; Tanaka, Hisashi; Murase, Kenya; Fujita, Norihiko

doi:10.1016/j.neures.2004.09.006

Cited by 33 publications

(51 citation statements)

References 14 publications

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“…Therefore, the embalming solution was not drastically influencing tissue relaxation times. Relaxation times of our embalmed samples were similar to those of fresh tissues reported in the literature (22,27,28). Samples were removed with ceramic knives and plastic claws; the use of any metallic instrument was prohibited to avoid contamination.…”

Section: Samplesmentioning

confidence: 60%

Variable‐field relaxometry of iron‐containing human tissues: a preliminary study

Hocq

Brouette

Saussez

et al. 2009

Contrast Media & Molecular

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Excess iron is found in brain nuclei from neurodegenerative patients (with Parkinson's, Alzheimer's and Huntington's diseases) and also in the liver and spleen of cirrhosis, hemochromatosis and thalassaemia patients. Ferritin, the iron-storing protein of mammals, is known to darken T(2)-weighted MR images. Understanding NMR tissue behavior may make it possible to detect those diseases, to follow their evolution and finally to establish a protocol for non-invasive measurement of an organ's iron content using MRI methods. In this preliminary work, the MR relaxation properties of embalmed iron-containing tissues were studied as well as their potential correlation with the iron content of these tissues. Relaxometric measurements (T(1) and T(2)) of embalmed samples of brain nuclei (caudate nucleus, dentate nucleus, globus pallidus, putamen, red nucleus and substantia nigra), liver and spleen from six donors were made at different magnetic fields (0.00023-14 T). The influence of the inter-echo time on transverse relaxation was also studied. Moreover, iron content of tissues was determined by inductively coupled plasma atomic emission spectroscopy. In brain nuclei, 1/T(2) increases quadratically with the field and depends on the inter-echo time in CPMG sequences at high fields, both features compatible with an outer sphere relaxation theory. In liver and spleen, 1/T(2) increases linearly with the field and depends on the inter-echo time at all fields. In our study, a correlation between 1/T(2) and iron concentration is observed. Explaining the relaxation mechanism for these tissues is likely to require a combination of several models. The value of 1/T(2) at high field could be used to evaluate iron accumulation in vivo. In the future, confirmation of those features is expected to be achieved from measurements of fresh (not embalmed) human tissues.

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Section: Samplesmentioning

confidence: 60%

Variable‐field relaxometry of iron‐containing human tissues: a preliminary study

Hocq

Brouette

Saussez

et al. 2009

Contrast Media & Molecular

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“…One method is the measurement of phase shift by using susceptibility-weighted imaging which uses local phase differences to map the iron [8,9] , but the phase shift is affected by the background field effects caused by air-tissue interfaces that lead to signal loss in tissues adjacent to these areas. Another method is the measurement of transverse relaxation rates R2 and R2 * (R2=1/T2, R2 * =1/T2 * ) or transverse relaxation time T2 and T2 * [10][11][12][13][14][15][16][17] . Though they are strongly affected by iron concentration, pathologic water content because of neuronal damage also influences R2 and R2 * , which can cause signal loss unrelated to the internal iron content of the tissue [8,12,18] .…”

mentioning

confidence: 99%

Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitative MR R2′ mapping

Qin

Zhu

Zhan

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Brain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2' measurements. Fifteen patients with AD, 15 age- and sex-matched healthy controls, and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2' (R2'=R2*-R2). We statistically analyzed the R2' and iron concentrations of bilateral hippocampus (HP), parietal cortex (PC), frontal white matter (FWM), putamen (PU), caudate nucleus (CN), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) of the cerebellum for the correlation with the severity of dementia. Two-tailed t-test, Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis. In 30 healthy volunteers, the R2' values of bilateral SN, RN, PU, CN, globus pallidus (GP), TH, and FWM were measured. The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2' and brain iron concentration. The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed. Regional R2' was positively correlated with regional brain iron concentration in normal adults (r=0.977, P<0.01). Iron concentrations in bilateral HP, PC, PU, CN, and DN of patients with AD were significantly higher than those of the controls (P<0.05); Moreover, the brain iron concentrations, especially in parietal cortex and hippocampus at the early stage of AD, were positively correlated with the severity of patients' cognitive impairment (P<0.05). The higher the R2' and iron concentrations were, the more severe the cognitive impairment was. Regional R2' and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients' cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.

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“…44 So in essence, R2 can be rendered somewhat insensitive by the water content in the brain, whereas R2* is susceptible to contributors other than iron, and R2' may have limited sensitivity. Sequences such as the gradient echo sampling of free induction decay and echo (GESFIDE) [45][46][47] and partially refocused interleaved multiple echo (PRIME) 38 allow the derivation of R2, R2*, and R2' from a single-pulse sequence. The GESFIDE sequence consists of two echo trains, the first after an excitation pulse, the second after a 180-degree refocusing pulse.…”

Section: Relaxometrymentioning

confidence: 99%

“…The GESFIDE sequence consists of two echo trains, the first after an excitation pulse, the second after a 180-degree refocusing pulse. Hikita et al 47 studied various MRI sequences to see which of the metrics most accurately reflected brain iron, and they concluded that R2 obtained by GESFIDE sequence and R2 obtained by multiple spin echoes fitted to a single relaxation curve showed higher correlations with brain iron than R2' obtained by GESFIDE sequences. Yablonskiy et al 48 has proposed a variation on the GES-FIDE sequence called gradient echo sampling of the spin echo that samples only the rephasing and dephasing spin echo signal components, which they purport to have a lower signal-to-noise ratio compared to GESFIDE.…”

Section: Relaxometrymentioning

confidence: 99%

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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Determination of transverse relaxation rate for estimating iron deposits in central nervous system

Cited by 33 publications

References 14 publications

Variable‐field relaxometry of iron‐containing human tissues: a preliminary study

Variable‐field relaxometry of iron‐containing human tissues: a preliminary study

Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitative MR R2′ mapping

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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