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8. Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI: Considerations

Author

Van De Haar, Harm J., Jansen, Jacobus F.A., Jeukens, Cécile R.L.P.N., Burgmans, Saartje, Van Buchem, Mark A., Muller, Majon, Hofman, Paul A.M., Verhey, Frans R.J., Van Osch, Matthias J.P., Backes, Walter H., APH - Aging & Later Life, ACS - Atherosclerosis & ischemic syndromes, and Internal medicine

Abstract

Purpose: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE-MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored. Methods: Dual-time resolution DCE-MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki) and volume fraction of detectable leaking tissue (vL) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic Ki histograms, mimicking the strong effect of noise and variation in Ki values, were performed to understand the influence of scan time on the estimated leakage. Results: The mean Ki was very low (order of 10-4 min-1) and highly influenced by noise, causing the Ki to be increasingly overestimated at shorter scan times. In the white matter, the Ki was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, vL proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min. Conclusions: Several ways to improve the sensitivity of a DCE-MRI experiment to subtle BBB leakage were presented. We have provided vL as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate Ki. Recommendations on group size and scan time are made based on statistical power calculations to aid future research.

Published
2017
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10. The Relationship between Cerebral Small Vessel Disease, Hippocampal Volume and Cognitive Functioning in Patients with COPD: An MRI Study

Author

Cleutjens, Fiona A. H. M., primary, Ponds, Rudolf W. H. M., additional, Spruit, Martijn A., additional, Burgmans, Saartje, additional, Jacobs, Heidi I. L., additional, Gronenschild, Ed H. B. M., additional, Staals, Julie, additional, Franssen, Frits M. E., additional, Dijkstra, Jeanette B., additional, Vanfleteren, Lowie E. G. W., additional, Hofman, Paul A., additional, Wouters, Emiel F. M., additional, and Janssen, Daisy J. A., additional

Published
2017
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11. Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI

Author

van de Haar, Harm J., van de Haar, Harm J., Jansen, Jacobus F. A., Jeukens, Cecile R. L. P. N., Burgmans, Saartje, van Buchem, Mark A., Muller, Majon, Hofman, Paul A. M., Verhey, Frans R. J., van Osch, Matthias J. P., Backes, Walter H., van de Haar, Harm J., van de Haar, Harm J., Jansen, Jacobus F. A., Jeukens, Cecile R. L. P. N., Burgmans, Saartje, van Buchem, Mark A., Muller, Majon, Hofman, Paul A. M., Verhey, Frans R. J., van Osch, Matthias J. P., and Backes, Walter H.

Abstract

Purpose: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE-MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored.Methods: Dual-time resolution DCE-MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (K-i) and volume fraction of detectable leaking tissue (v(L)) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic K-i histograms, mimicking the strong effect of noise and variation in K-i values, were performed to understand the influence of scan time on the estimated leakage.Results: The mean K-i was very low (order of 10(-4) min(-1)) and highly influenced by noise, causing the K-i to be increasingly overestimated at shorter scan times. In the white matter, the K-i was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, v(L) proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min.Conclusions: Several ways to improve the sensitivity of a DCE-MRI experiment to subtle BBB leakage were presented. We have provided v(L) as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate K-i. Recommendations on group size and scan time are

Published
2017

12. White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-beta

Author

Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., LeARN Project, Freeze, Whitney M., Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., and LeARN Project

Abstract

Cerebral small vessel disease (cSVD) and amyloid-beta (A beta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and A beta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. A beta pathologywas assessed as cerebrospinal fluid-derived A beta(1-42) levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and A beta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal A beta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, A beta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF A beta(42) levels, but not in individuals with normal CSF A beta(42) levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal A beta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.

Published
2017

15. eScience Infrastructure for sharing neuroimaging data and running validated analysis pipelines on a high performance cloud

Author

Vrenken Hugo, H E Tiesinga Paul, Versteeg Adriaan, Koek Marcel, Ranguelova Elena, De Leeuw Frank-Erik, P J Van Boxtel Martin, Bakker Rembrandt, J Niessen Wiro, Burgmans Saartje, Ivanova Milena, T De Boer Piter, Meulenbroek Olga, and Van Der Lijn Fedde

Subjects
World Wide Web, Pipeline transport, Neuroimaging, business.industry, Computer science, Biomedical Engineering, Neuroscience (miscellaneous), Cloud computing, business, Data science, Computer Science Applications
Published
2013
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16. Age differences in speed of processing are partially mediated by differences in axonal integrity

Author

Burgmans, Saartje, Gronenschild, Ed H B M, Fandakova, Yana, Shing, Yee Lee, van Boxtel, Martin P J, Vuurman, Eric F P M, Uylings, Harry B M, Jolles, Jelle, and Raz, Naftali

Subjects
Aging, Cognition, DTI, White matter, MRI
Abstract

Advanced age is associated with declines in brain structure and in cognitive performance, but it is unclear which aspects of brain aging mediate cognitive declines. We inquired if individual differences in white matter integrity contribute to age differences in two cognitive domains with established vulnerability to aging: executive functioning and speed of processing. The participants were healthy volunteers aged 50-81, some of whom had elevated blood pressure, a known vascular risk factor. Using latent variable analyses, we examined whether age differences in regional white matter integrity mediated age-related differences in executive functions and speed of processing. Although diffusion-related latent variables showed stronger age differences than white matter volumes and white matter hyperintensity volumes, only one of them was significantly associated with cognitive performance. Smaller linear anisotropy partially mediated age-related reduction in speed of processing. The effect was significant in posterior (temporal-parietal-occipital) but not anterior (frontal) region, and appeared stronger for cognitive rather than reaction time measures of processing speed. The presence of hypertensive participants did not affect the results. We conclude that in healthy adults, deterioration of axonal integrity and ensuing breech of connectivity may underpin age-related slowing of information processing.

Published
2011

17. Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI.

Author

Haar, Harm J., Jansen, Jacobus F.A., Jeukens, Cécile R.L.P.N., Burgmans, Saartje, Buchem, Mark A., Muller, Majon, Hofman, Paul A.M., Verhey, Frans R.J., Osch, Matthias J.P., and Backes, Walter H.

Subjects
ALZHEIMER'S disease, BLOOD-brain barrier, MAGNETIC resonance imaging, DIAGNOSTIC imaging, CONTRAST-enhanced magnetic resonance imaging
Abstract

Purpose Dynamic contrast-enhanced ( DCE) MRI can be used to measure blood-brain barrier ( BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE- MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored. Methods Dual-time resolution DCE- MRI was performed in 16 patients with early Alzheimer's disease ( AD) and 17 healthy controls. The leakage rate (Ki) and volume fraction of detectable leaking tissue ( vL) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic Ki histograms, mimicking the strong effect of noise and variation in Ki values, were performed to understand the influence of scan time on the estimated leakage. Results The mean Ki was very low (order of 10−4 min−1) and highly influenced by noise, causing the Ki to be increasingly overestimated at shorter scan times. In the white matter, the Ki was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, vL proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min. Conclusions Several ways to improve the sensitivity of a DCE- MRI experiment to subtle BBB leakage were presented. We have provided vL as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate Ki. Recommendations on group size and scan time are made based on statistical power calculations to aid future research. [ABSTRACT FROM AUTHOR]

Published
2017
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21. White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-β.

Author

Freeze, Whitney M., Jacobs, Heidi I. L., Gronenschild, Ed H., Jansen, Jacobus F. A., Burgmans, Saartje, Aalten, Pauline, Clerx, Lies, Vos, Stephanie J., van Buchem, Mark A., Barkhof, Frederik, van der Flier, Wiesje M., Verbeek, Marcel M., Rikkert, Marcel Olde, Backes, Walter H., Verhey, Frans R., and LeARN project

Subjects
LEUKOENCEPHALOPATHIES, HIPPOCAMPUS (Brain), AMYLOIDOSIS diagnosis, NEURODEGENERATION, MAGNETIC resonance imaging, ALZHEIMER'S disease, ANTHROPOMETRY, BRAIN, CEREBRAL hemorrhage, COGNITION, NEUROPSYCHOLOGICAL tests, PEPTIDES, SENSORY perception, REGRESSION analysis, CROSS-sectional method, CEREBRAL small vessel diseases
Abstract

Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present. [ABSTRACT FROM AUTHOR]

Published
2017
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34. Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

Author

Haar, Harm J. van de, Burgmans, Saartje, Jansen, Jacobus F. A., Osch, Matthias J. P. van, Buchem, Mark A. van, Muller, Majon, Hofman, Paul A. M., Verhey, Frans R. J., and Backes, Walter H.

Abstract

MR imaging was used to show global, diffusely distributed leakage of the blood-brain barrier in patients with early Alzheimer disease, which suggests that a compromised blood-brain barrier is part of the early pathology of Alzheimer disease and might be part of a cascade of pathologic events that eventually lead to cognitive decline.

Published
2016
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