Methodologic Concerns on the Reported Values for Assessing Permeability of the Blood-Brain Barrier in the Hippocampus

Lim, Changmok; Moon, Won-Jin

doi:10.3174/ajnr.a6228

Cited by 4 publications

(6 citation statements)

References 8 publications

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“…45 In addition, we selected the hippocampal ROI carefully using a polygonal shape and checked the individual pixel values to avoid the inclusion of arteries and CSF, as these elements may produce spurious high K trans values . 46 Third, our DCE imaging acquisition time was only 10 min, which is relatively short compared to recent recommendations. 11 For the range of small BBB permeability (1 − 2 × 10 −3 min −1 ) as in our study, scanning longer than 15 min would be more ideal with the highest contrast-to-noise ratio.…”

Section: Discussionmentioning

confidence: 97%

Hippocampal blood–brain barrier permeability is related to the APOE4 mutation status of elderly individuals without dementia

Moon

Lim

et al. 2020

J Cereb Blood Flow Metab

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Blood–brain barrier (BBB) disruption, modulated by APOE4 mutation, is implicated in the pathogenesis of cognitive decline. We determined whether BBB permeability differed according to cognitive functioning and APOE4 status in elderly subjects without dementia. In this prospective study, 33 subjects with mild cognitive impairment (MCI) and 33 age-matched controls (normal cognition [NC]) underwent 3 T brain magnetic resonance imaging. The Patlak model was used to calculate tissue permeability (Ktrans). A region-of interest analysis of Ktrans was performed to compare relevant brain regions. Effects of Ktrans on cognitive functioning were evaluated with linear regression analysis adjusted for confounding factors. NC and MCI groups did not differ in terms of vascular risk factors or hippocampal Ktrans, except for hippocampal volume. Hippocampal Ktrans was significantly higher in APOE4 carriers than in non-carriers ( p = 0.007). Factors which predicted cognitive functioning included hippocampal volume (beta=−0.445, standard error [SE]=0.137, p = 0.003) and hippocampal BBB permeability (beta = 0.142, SE = 0.050, p = 0.008) after correcting for age, education, and APOE4 status. This suggests that hippocampal BBB permeability is associated with APOE4 mutation, and may predict cognitive functioning. BBB permeability imaging represents a distinct imaging biomarker for APOE4 mutations in NC and MCI subjects and for determining the degree of APOE4-related pathology.

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Section: Discussionmentioning

confidence: 97%

Hippocampal blood–brain barrier permeability is related to the APOE4 mutation status of elderly individuals without dementia

Moon

Lim

et al. 2020

J Cereb Blood Flow Metab

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“…A consensus recommendation regarding acquisition protocols in MRI of BBB permeability has only recently been suggested [ 14 ]. However, these previous studies may not have followed this recommendation, as some predate it, while others did not report a detailed acquisition scheme (including information on DCE- and T1-weighted MRI measurements, image preprocessing, selection of vessel input function, model fitting, formulas used, generation of the region and tissue mask, and post-processing and statistical analysis of data) as recommended [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…The difficulty in manually selecting correct ROIs within the hippocampal area while excluding the choroid plexus may explain the conflicting findings in the hippocampus between manual and automated methods. Spatial resolution and slice thickness are other important aspects of correct K trans measurement, as the hippocampal artery and its branches can be included in sections 5 mm thick [ 32 ]. This aspect of assessment is important, as contamination with the choroid plexus or inclusion of arteries can result in unexpectedly high K trans values [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Spatial resolution and slice thickness are other important aspects of correct K trans measurement, as the hippocampal artery and its branches can be included in sections 5 mm thick [ 32 ]. This aspect of assessment is important, as contamination with the choroid plexus or inclusion of arteries can result in unexpectedly high K trans values [ 32 ]. Inadvertent inclusion of small vessels within the contour of the target anatomy may occur in both manual and automatic methods.…”

Section: Discussionmentioning

confidence: 99%

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Regional Differences in Blood-Brain Barrier Permeability in Cognitively Normal Elderly Subjects: A Dynamic Contrast-Enhanced MRI-Based Study

Lim

Kim

et al. 2021

Korean J Radiol

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Objective This study aimed to determine whether there are regional differences in the blood-brain barrier (BBB) permeability of cognitively normal elderly participants and to identify factors influencing BBB permeability with a clinically feasible, 10-minute dynamic contrast-enhanced (DCE) MRI protocol. Materials and Methods This IRB-approved prospective study recruited 35 cognitively normal adults (26 women; mean age, 64.5 ± 5.6 years) who underwent DCE T1-weighted imaging. Permeability maps (K trans ) were coregistered with masks to calculate the mean regional values. The paired t test and Friedman test were used to compare Ktrans between different regions. The relationships between K trans and the factors of age, sex, education, cognition score, vascular risk burden, vascular factors on imaging, and medial temporal lobar atrophy were assessed using Pearson correlation and the Spearman rank test. Results The mean permeability rates of the right and left hippocampi, as assessed with automatic segmentation, were 0.529 ± 0.472 and 0.585 ± 0.515 (K trans , × 10 −3 min −1 ), respectively. Concerning the deep gray matter, the K trans of the thalamus was significantly greater than those of the putamen and hippocampus ( p = 0.007, p = 0.041). Regarding the white matter, the K trans value of the occipital white matter was significantly greater than those of the frontal, cingulate, and temporal white matter ( p < 0.0001, p = 0.0007, p = 0.0002). The variations in K trans across brain regions were not related to age, cognitive score, vascular risk burden, vascular risk factors on imaging, or medial temporal lobar atrophy in the study group. Conclusion Our study demonstrated regional differences in BBB permeability (K trans ) in cognitively normal elderly adults using a clinically acceptable 10-minutes DCE imaging protocol. The regional differences suggest that the integrity of the BBB varies across the brains of cognitively normal elderly adults. We recommend considering regional differences in K trans values when evaluating BBB permeability in patients with neurodegenerative diseases.

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“…BBB 투과도 측정은 큰 혈관이 있는 부위는 Ktrans가 과대평가될 수 있어서, 이는 전체 뇌분석 혹은 관심영역분석 모두에서 문제점이 될 수 있다( 57 ). 또한 연구자들이 Ktrans의 두 가지 단위 표기를 혼용함으로써 생긴 오류까지 더해져서 후속 연구 및 연구자들에게 혼란을 주고 있다( 57 ).…”

Section: Dce 영상의 문제점 및 개선방안unclassified

Alzheimer Dementia and Microvascular Pathology: Blood-Brain Barrier Permeability Imaging

문¹

2020

J Korean Soc Radiol

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최근의 연구들은 알츠하이머병의 병리가 단순히 아밀로이드와 타우단백질의 축적만이 아닌, 혈액뇌장벽(blood brain barrier; 이하 BBB) 이상과 같은 미세혈관병리와 밀접한 관련이 있음을 밝히고 있다. BBB 투과도 변화는 아밀로이드 및 타우 단백질 축적뿐 아니라 신경염증과 신경 퇴행성변화를 일으킴으로써 결국 임상 치매를 야기한다. 최근에는 알츠하이머 및 관련 질환의 BBB 이상을 보기 위한 MR 영상의 이용이 증가하고 있다. 이 종설에서는 알츠하이머병에서 BBB와 관련된 병리를 소개하고, BBB 투과도 변화에 대한 MR 영상 연구들을 소개할 것이다. 또한 BBB 투과도 측정을 위한 MR 방법론 개요와 문제점들을 제시할 것이다.

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Methodologic Concerns on the Reported Values for Assessing Permeability of the Blood-Brain Barrier in the Hippocampus

Cited by 4 publications

References 8 publications

Hippocampal blood–brain barrier permeability is related to the APOE4 mutation status of elderly individuals without dementia

Hippocampal blood–brain barrier permeability is related to the APOE4 mutation status of elderly individuals without dementia

Regional Differences in Blood-Brain Barrier Permeability in Cognitively Normal Elderly Subjects: A Dynamic Contrast-Enhanced MRI-Based Study

Alzheimer Dementia and Microvascular Pathology: Blood-Brain Barrier Permeability Imaging

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