The relation between brain iron and NMR relaxation times: An in <i>vitro</i> study

Vymazal, Josef; Brooks, Rodney A.; Baumgarner, Charles D.; Vu, Tran Anh; Katz, David A.; Bulte, Jeff W.M.; Bauminger, E. R.; Chiro, Giovanni Di

doi:10.1002/mrm.1910350108

Cited by 156 publications

(189 citation statements)

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“…However, the presence of conditions that increase macromolecules in sites which show negative correlations with age is less likely. Basal ganglia structures show hemosiderin deposition with age (8), and increased levels of hemosiderin reduce T2-relaxation values (12), perhaps resulting in the negative correlations found here. Whether age-related changes in iron deposition occur in the pons is unclear; however, the negative correlations may result from iron deposition in a neighboring brain site, the substantia nigra, which does show increased hemosiderin deposition with age in healthy adults (8,26).…”

Section: Discussionmentioning

confidence: 70%

“…T2-relaxation values increase with increased free tissue water content (9), in the absence of diamagnetic and paramagnetic substances; values decrease in those sites with hemosiderin deposition (12). Increased free water content typically reflects cellular and axonal loss or membrane breakdown, with such breakdown accompanying cellular and myelin changes with age (6,7) and certain pathological processes.…”

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confidence: 99%

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Age‐related regional brain T2‐relaxation changes in healthy adults

Kumar

Delshad

Woo

et al. 2011

Magnetic Resonance Imaging

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Purpose: To determine normal T2-relaxation values from different brain areas in healthy adults, assess age-related T2-relaxation changes in those sites, and evaluate potential gender-related T2-relaxation value differences. Materials and Methods:We performed proton-density and T2-weighted imaging in 60 healthy adults (male: 38, age range ¼ 31-64 years, mean age 6 SD ¼ 46.1 6 9.3 years; female: 22, age range ¼ 37-66 years, mean age 6 SD ¼ 49.5 6 8.3 years), using a 3.0 Tesla MRI scanner. T2-relaxation values were calculated voxel-by-voxel from proton-density and T2-weighted images, and whole-brain T2-relaxation maps were constructed and normalized to a common space. A set of regions-of-interest were outlined within the basal ganglia, limbic, frontal, parietal, temporal, occipital, thalamic, hypothalamic, cerebellar, and pontine regions using mean background images derived from normalized and averaged T2-weighted images of all individuals, and regional T2-relaxation values were determined from these regions-of-interest and normalized T2-relaxation maps. Pearson's correlations were calculated between T2-relaxation values and age, and male-female differences evaluated with independent-samples t-tests.Results: T2-relaxation values typically increased with age in multiple brain sites; only a few regions showed declines, including the putamen and ventral pons. Sexrelated differences in T2-relaxation values appeared in basal ganglia, frontal, temporal, occipital, and cerebellar regions; males showed higher values over females in these sites.Conclusion: Establishment of normative adult T2-relaxation values over different brain areas, with age and sex as co-factors, offers baseline values against which diseaserelated tissue changes can be assessed. NONINVASIVE ASSESSMENT OF adult human brain changes resulting from neurologic, neuropsychological, and neurocognitive pathologies against normal age-related changes remains difficult (1-3). Myelin and neurons undergo slow degradation with age in adults (4,5), and these normative changes, as well as neurodegenerative processes inducing myelin and neuronal loss (6,7), increase free tissue water content. However, certain deep brain structures, including the basal ganglia, are known to show iron deposition with age in adult subjects (8), which can alter indications of normal progression of tissue changes in these sites. Pathological and treatment-related brain tissue alterations can be assessed accurately, but only after controlling for age-related changes, which mandates determination of normative values from gray and white matter regions over wide-spread brain areas.MR T2-relaxometry provides a quantitative surrogate marker of brain tissue changes in both health and disease by assessing free tissue water content (9) in the absence of diamagnetic and paramagnetic substances, which differs during pediatric development over normal patterns of aging in adult controls (5,10), and increases with disease processes (11). T2-relaxation values increase with increased free tissue water cont...

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

Age‐related regional brain T2‐relaxation changes in healthy adults

Kumar

Delshad

Woo

et al. 2011

Magnetic Resonance Imaging

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“…Supposing that the interregional differences in the parenchymal R 2app values are caused only by paramagnetic brain iron, the proportionality factor ␤ can be calculated using values of the iron concentration reported for different tissues (20). It was shown previously (7,21) that the influence of iron on T 2 depends on the interecho time and that, as a consequence, the published ␤ values vary over a wide range. We therefore use an average value of 0.312 sec Ϫ1 /mg/100g, which is obtained from four studies (4,5,7,9) with interecho times of 20 -25 msec, which are close to our value of 25 msec.…”

Section: Effect Of Brain Ironmentioning

confidence: 99%

“…As such, it is useful to accurately map T 2 of various normal and abnormal tissues. Several studies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) have shown that T 2 varies across brain regions and during different stages of brain maturation and aging (5,10). Numerous studies in normal adults at multiple field strengths (2)(3)(4)9) have concluded that T 2 of cortical gray matter (GM) is longer than that of white matter (WM).…”

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confidence: 99%

Inverse T₂ contrast at 1.5 Tesla between gray matter and white matter in the occipital lobe of normal adult human brain

Zhou

Golay

Zijl

et al. 2001

Magnetic Resonance in Med

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T 2 of cortical gray matter is generally assumed to be longer than that of white matter. It is shown here that this is not the case in the occipital lobe, but that this effect is often obscured at lower resolution and concealed in standard T 2 -weighted images. Using a high-resolution (1 ؋ 1.3 ؋ 2 mm 3 ) segmented EPI CarrPurcell-Meiboom-Gill sequence, T 2 relaxation times of the brain were measured at 1.5 T for eight healthy adult volunteers. The average T 2 values of cortical gray and white matter were found to be 88 ؎ 2 and 84 ؎ 3 msec in the frontal lobe, 84 ؎ 2 and 83 ؎ 3 msec in the parietal lobe, and 79 ؎ 1 and 87 ؎ 3 msec in the occipital lobe, respectively. This unexpected occipital T 2 contrast between gray and white matter is attributed to regional differences in iron concentration. The transverse relaxation time T 2 is one of the most commonly employed MRI contrast parameters. We have recently shown that absolute T 2 values can be used to quantify cerebral hemodynamics and oxygen extraction (1). As such, it is useful to accurately map T 2 of various normal and abnormal tissues. Several studies (2-11) have shown that T 2 varies across brain regions and during different stages of brain maturation and aging (5,10). Numerous studies in normal adults at multiple field strengths (2-4,9) have concluded that T 2 of cortical gray matter (GM) is longer than that of white matter (WM). On the contrary, gray matter T 2 was found to be shorter than that of WM in the brains of newborns (10) and in spinal cord (12). Several factors are likely to contribute to the heterogeneity of T 2 values. Among these may be regional variations in brain iron concentration, as well as variations in the microarchitecture of the cellular constituents and myelin structure (cytoarchitecture and myeloarchitecture, respectively). Recently, investigators examining the superior temporal gyrus and primary auditory cortex region have shown that the T 2 -weighted signal intensities can vary appreciably even between neighboring regions of the cortex (11). We found a similar pattern in our studies of the visual cortex, where typically an oblique slice through the calcarine fissure is studied. In order to better quantify the T 2 contrast between GM and WM in this location, we used very-high spatial resolution absolute T 2 measurements to minimize the likelihood of including WM and CSF (cerebrospinal fluid) in voxels nominally occupied by GM. MATERIALS AND METHODSMeasurements were performed on a 1.5 T ACS-NT clinical MRI scanner (Philips Medical Systems, Best, Netherlands). A body coil was used for RF transmission and a head coil was used for signal reception. Eight normal adult volunteers (four male, four female, age range 22-44 years, mean 32 Ϯ 8 SD years) were studied in accordance with institutional guidelines. A multiecho Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with 13-shot segmented EPI acquisition was utilized at an echo-spacing of 25 msec. A single slice was acquired with 30 averages at the level of the dorsal-most aspects of the ...

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“…The rate, R2' was developed to improve specificity for tissue iron by reducing the known R2 and R2* signal losses associated with local field inhomogeneity. 27 Many in-vitro 28,29 and invivo 30 -38 studies have demonstrated a strong correlation between R2 and iron concentration as determined by histological studies of brain gray matter. A weaker cor- and E-H are from a 47-year-old normal control.…”

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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The relation between brain iron and NMR relaxation times: An in vitro study

Cited by 156 publications

References 10 publications

Age‐related regional brain T2‐relaxation changes in healthy adults

Age‐related regional brain T2‐relaxation changes in healthy adults

Inverse T₂ contrast at 1.5 Tesla between gray matter and white matter in the occipital lobe of normal adult human brain

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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The relation between brain iron and NMR relaxation times: An in vitro study

Cited by 156 publications

References 10 publications

Age‐related regional brain T2‐relaxation changes in healthy adults

Age‐related regional brain T2‐relaxation changes in healthy adults

Inverse T2 contrast at 1.5 Tesla between gray matter and white matter in the occipital lobe of normal adult human brain

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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Inverse T₂ contrast at 1.5 Tesla between gray matter and white matter in the occipital lobe of normal adult human brain