High-field Magnetic Resonance Imaging of Brain Iron in Alzheimer Disease

Schenck, John F.; Zimmerman, Earl A.; Li, Zhu; Adak, Sudeshna; Saha, Angshuman; Tandon, Reeti; Fish, Kenneth; Belden, Clifford J.; Gillen, Robert W.; Barba, Anne; Henderson, David L.; Neil, William P; O'keefe, Timothy

doi:10.1097/01.rmr.0000245455.59912.40

Cited by 64 publications

(56 citation statements)

References 82 publications

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“…20) and was confirmed with an iron extraction study (22). However, contributions from other sources have prevented the quantification of tissue iron content directly from the MRI measures.…”

Section: Discussionmentioning

confidence: 59%

“…One way to address this question is to selectively manipulate tissue iron content and observe the effects on MRI contrast. Using a biochemical process to extract iron from postmortem tissue, Schenck and coworkers previously found that iron substantially affects R 2 * relaxation in much of the brain (22). Applying their protocol to primary visual cortex, we observed an almost complete extinction of intracortical R 2 * and frequency contrasts ( Fig.…”

Section: Reduction Of Mri Contrast After Chemical Extraction Of Tissumentioning

confidence: 63%

“…Although it has been recognized that iron is responsible for much of the MRI susceptibility-based contrast in iron-rich brain regions such as the subcortical nuclei (19)(20)(21)(22), very little is known about the element's distribution in the cortex or its possible role in the laminar variation of MRI contrast. To explore the potential contribution of iron in MRI, correlative MRI with histochemical staining was performed on postmortem human brain tissue.…”

Section: Resultsmentioning

confidence: 99%

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Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Fukunaga

Gelderen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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384

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Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region's myeloarchitecture and forms the dominant source of the observed MRI contrast. myelin | ferritin | laminar variation | brain structure | magnetic susceptibility M uch of the human cerebral cortex is organized in a network of functionally specialized regions. This understanding forms the basis of studies that attempt to expose the brain's inner workings using modern functional imaging techniques such as PET and MRI (1, 2). Some of this functional specialization is reflected in the local cortical architecture, and may be observed in postmortem brain samples from the laminar and columnar variation in a number of tissue properties including cell shape (3), myelin content (4), metabolic state (5), neurochemical profile (6), and receptor density (7).One of the most striking examples of this structure-function relationship is in the primary visual cortex (V1, or Brodmann area 17), which is involved in the early stages of visual information processing. Visual area V1 can be readily identified with postmortem tissue analysis based on the prominence of myelinated fibers in layer IVb, known as the line of Gennari. Many other brain areas show characteristic myelination patterns (8, 9), and systematic analyses of this type of structural information may provide important clues about the brain's functional organization. Whole-brain postmortem studies of cellular distributions and myelin content in human brain sections at high resolution have previously been described (8, 10).A number of attempts have been made to reveal laminar cortical structure in vivo with structural MRI, by exploiting contrast based on the altered density and NMR relaxation times of water protons in myelin-rich environments (11)(12)(13)(14)(15). Although these studies have had some success, their impact has not been widespread as a result of the rather limited contrast and resolution available with conventional MRI. Nevertheless, much progress has been made over the last few years. Recent developments in high-field MRI (≥7 T) have increased spatial resolution to less than 300 μm (16-18), and improved the ability to detect subtle variations in the magnetic susceptibility of tissue. These variations are reflected in a number of intrinsic MRI parameters, including the longitudinal relaxation rate R 1 , the transverse relaxation rates R 2 and R 2 *, and the NMR resonance frequency. R 2 * indicates th...

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Section: Discussionmentioning

confidence: 59%

Section: Reduction Of Mri Contrast After Chemical Extraction Of Tissumentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

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Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Fukunaga

Gelderen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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384

409

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“…One way to establish quantitatively the contribution of iron would be to perform MR imaging before and after chemical extraction of iron. We and others have done this in normal tissue for gray matter and WM ( 28,29 ). Despite the lack of these derived measures of tissue iron ( 12,20 ), have suggested that iron and myelin are the main compounds that contribute to the R2* and phase contrast in WM and cortical gray matter.…”

Section: Neuroradiology: High-field-strength Mr Imaging Of Chronic Mumentioning

confidence: 99%

“…This hypothesized diamagnetic shift associated with myelin proposed in our model is consistent with recent high-fi eld-strength MR imaging observations in the line of Gennari, a myelin-rich layer in human primary visual cortex ( 28 ), and the absence of phase contrast between cerebrospinal fl uid and WM in this and previous work ( 11 ), despite the strongly different iron and myelin concentrations of the two substances. Results of number of recent studies, including iron extraction studies ( 28,29 ), demyelinating animal models with shiverer mice ( 30 ) and cuprizone-treated mice ( 31 ), and correlative studies between MR imaging and histochemically This heterogeneity was present across and in some cases within lesions. Consistent with previous work ( 9 ), lesions with and without pronounced rim contrast were observed.…”

Section: Neuroradiology: High-field-strength Mr Imaging Of Chronic Mumentioning

confidence: 99%

Chronic Multiple Sclerosis Lesions: Characterization with High-Field-Strength MR Imaging

Yao¹,

Bagnato²,

Matsuura³

et al. 2012

Radiology

116

124

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Purpose:To elucidate the mechanism of magnetic resonance (MR) imaging contrast in multiple sclerosis (MS) lesion appearance by using susceptibility-weighted imaging and to assess with histologic correlation the role of iron and myelin in generating this MR imaging contrast. Materials and Methods:Each patient provided written consent to a human subject protocol approved by an institutional review board. Highspatial-resolution susceptibility-weighted 7.0-T MR images were obtained in 21 patients with MS. Contrast patterns in quantitative phase and R2* images, derived from 7.0-T data, were investigated in 220 areas defi ned as chronic MS lesions on conventional T2-weighted fl uid-attenuated inversion recovery, T2-weighted, and T1-weighted spin-echo images. The presence of positive or negative phase shifts (ie, decreased or increased MR frequency, respectively) was assessed in each lesion. In addition, postmortem MR imaging was performed at 7.0 T and 11.7 T, and its results were correlated with those of immunohistochemical staining specifi c for myelin, iron, and ferritin. Results:The majority (133 [60.5%] of 220) of the identifi ed lesions had a normal phase and reduced R2*. A substantial fraction of the lesions (84 [38.2%] of 220) had negative phase shift, either uniformly or at their rim, and a variety of appearances on R2* maps. These two lesion contrast patterns were reproduced in the postmortem MR imaging study. Comparison with histologic fi ndings showed that, while R2* reduction corresponded to severe loss of both iron and myelin, negative phase shift corresponded to focal iron deposits with myelin loss. Conclusion:Combined analysis of 7.0-T R2* and phase data may help in characterizing the pathologic features of MS lesions. The observed R2* decreases suggest profound myelin loss, whereas negative phase shifts suggest a focal iron accumulation.q RSNA, 2011Supplemental material : http://radiology.rsna.org/lookup /suppl

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Iron Accumulation in the Substantia Nigra of Patients With Alzheimer Disease and Parkinsonism

Brar

Henderson²,

Schenck³

et al. 2009

Arch Neurol

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Background: Preliminary studies have shown an increase in iron accumulation in the substantia nigra but not in the hippocampus in patients with Parkinson disease without dementia and the reverse in patients with Alzheimer disease (AD) and no parkinsonism.Objective: To determine whether iron levels (measured as T2 shortening on magnetic resonance images) are greater in the substantia nigra of patients with AD who have parkinsonism than in those with AD alone.

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High-field Magnetic Resonance Imaging of Brain Iron in Alzheimer Disease

Cited by 64 publications

References 82 publications

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Chronic Multiple Sclerosis Lesions: Characterization with High-Field-Strength MR Imaging

Iron Accumulation in the Substantia Nigra of Patients With Alzheimer Disease and Parkinsonism

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