Quantitative susceptibility mapping to evaluate the early stage of Alzheimer's disease

Kim, Hyug-Gi; Park, Soonchan; Rhee, Hak Young; Lee, Kyung Mi; Ryu, Chang‐Woo; Rhee, Sun Jung; Lee, Soo Yeol; Wang, Yi; Jahng, Geon‐Ho

doi:10.1016/j.nicl.2017.08.019

Cited by 100 publications

(103 citation statements)

References 40 publications

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“…Quantitative susceptibility mapping and R2* have been used to quantify the amount of iron present in the brains of healthy individuals and in patients with Parkinson disease, Alzheimer disease, and multiple sclerosis (13)(14)(15)(16)(17)21). Our results are consistent with these studies, two of which were postmortem examinations (14,17), and it shows a reliable correlation between both susceptibility and R2* and iron-rich regions in the brain.…”

Section: Discussionsupporting

confidence: 88%

Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

et al. 2019

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Content codes:Purpose: To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods:In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 4003 magnification highpower fields with iron-containing macrophages.Results: Ten adults (four male participants [mean age, 65 years 6 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years 6 12 years; age range, 32-65 years]; mean age of all participants, 58 years 6 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P , .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells.Conclusion: MRI measurements of susceptibility, R2*, and R2' (R2* -R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas.

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Section: Discussionsupporting

confidence: 88%

Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

et al. 2019

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“…As the magnetic properties of tissue can be affected by both the cellular composition and arrangement of fiber bundles (39,40), combining DTI with QSM to detect axonal damage and demyelination can potentially lead to new insights and more robust identification of white matter pathology post-injury. To date, QSM has provided additional insight into white matter pathologies in multiple sclerosis and Alzheimer's disease (36,(41)(42)(43). Yet there has been a lag in the acceptance of the method for the analysis of traumatic axonal injury.…”

Section: Introductionmentioning

confidence: 99%

Combined Diffusion Tensor Imaging and Quantitative Susceptibility Mapping Discern Discrete Facets of White Matter Pathology Post-injury in the Rodent Brain

Soni

Vegh

et al. 2020

Front. Neurol.

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Early loss of white matter microstructure integrity is a significant cause of long-term neurological disorders following traumatic brain injury (TBI). White matter abnormalities typically involve axonal loss and demyelination. In-vivo imaging tools to detect and differentiate such microstructural changes are not well-explored. This work utilizes the conjoint potential offered by advanced magnetic resonance imaging techniques, including quantitative susceptibility mapping (QSM) and diffusion tensor imaging (DTI), to discern the underlying white matter pathology at specific time points (5 h, 1, 3, 7, 14, and 30 days) post-injury in the controlled cortical impact mouse model. A total of 42 animals were randomized into six TBI groups (n = 6 per group) and one sham group (n = 6). Histopathology was performed to validate in-vivo findings by performing myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) immunostaining for the assessment of changes to myelin and astrocytes. After 5 h of injury radial diffusivity (RD) was increased in white matter without a significant change in axial diffusivity (AxD) and susceptibility values. After 1 day post-injury RD was decreased. AxD and susceptibility changes were seen after 3 days post-injury. Susceptibility increases in white matter were observed in both ipsilateral and contralateral regions and persisted for 30 days. In histology, an increase in GFAP immunoreactivity was observed after 3 days post-injury and remained high for 30 days in both ipsilateral and contralateral white matter regions. A loss in MBP signal was noted after 3 days post-injury that continued up to 30 days. In conclusion, these results demonstrate the complementary ability of DTI and QSM in discerning the micro-pathological processes triggered following TBI. While DTI revealed acute and focal white matter changes, QSM mirrored the temporal demyelination in the white matter tracts and diffuse regions at the chronic state.

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“…Many clinical studies of QSM analysis have reported estimates of subtle susceptibility changes in the brain that occur with neuroinflammatory and neurodegenerative diseases . For example, regional iron deposition associated with amyloid‐β aggregation has been observed in the cortical and deep gray matter (GM) and white matter (WM) in Alzheimer's disease (AD) . Similarly, the susceptibility value in the substantia nigra (SN) has been found to be increased in Parkinson's disease (PD) progression and has been correlated with symptoms related to dopaminergic neurodegeneration .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the evaluation of brain atrophy and iron aggregation may be valuable for the early diagnosis and staging of these diseases. At the present time, several studies have attempted anatomical standardization of the susceptibility map in order to perform statistical voxel‐based analysis via whole brain or atlas‐based analyses . Kim et al have reported that the susceptibility value was better able to differentiate AD and mild cognitive impairment by using dual voxel‐based and region of interest (ROI)‐based analyses, and they found that this can aid in the early diagnosis of AD .…”

Section: Introductionmentioning

confidence: 99%

Simultaneous voxel‐based magnetic susceptibility and morphometry analysis using magnetization‐prepared spoiled turbo multiple gradient echo

et al. 2020

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This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel-based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T 1 -weighted and multi-echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP-QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP-spoiled gradient echo (MP-GRE) in healthy volunteers to validate the availability of MP-QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel-based comparisons of susceptibility and morphometry in MP-QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP-QSM, MP-GRE, and mGRE were 0.14 ± 0.011, 0.17 ± 0.015, and 0.045 ± 0.010, respectively.Segmented GM and WM volumes in the MP-QSM closely coincided with those in the MP-GRE. Region of interest analyses indicated that the mean susceptibility values in MP-QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP-QSM sequence makes it possible to acquire acceptable-quality images for simultaneous analysis and determine brain Abbreviations: AD, Alzheimer's disease; CSF, cerebrospinal fluid; CU, caudate nucleus; DN, dentate nucleus; FWE, family-wise error; GM, gray matter; GP, globus pallidus; IC, internal capsule; ME-MP2RAGE, multi-echo magnetization-prepared two rapid gradient echo; mGRE, multiple spoiled gradient echo; MNI, Montreal Neurological Institute; MP-GRE, magnetization-prepared spoiled turbo gradient echo; MP-QSM, magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM; NFT, neurofibrillary tangle; PD, Parkinson's disease; PU, putamen; QSM, quantitative susceptibility mapping; RMSE, root mean-square error; RN, red nucleus; ROI, region of interest; SN, substantia nigra; SPM12, Statistical Parametric Mapping 12; SSIM, structural similarity index; VBM, voxel-based morphometry; VBMSM, voxel-based magnetic susceptibility and morphometry; VOI, volume of interest; VSHARP, variable-kernel sophisticated harmonic artifact reduction for phase data; WM, white matter.

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Quantitative susceptibility mapping to evaluate the early stage of Alzheimer's disease

Cited by 100 publications

References 40 publications

Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

Combined Diffusion Tensor Imaging and Quantitative Susceptibility Mapping Discern Discrete Facets of White Matter Pathology Post-injury in the Rodent Brain

Simultaneous voxel‐based magnetic susceptibility and morphometry analysis using magnetization‐prepared spoiled turbo multiple gradient echo

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