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834 results on '"Giessen, E."'

3. Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol

Author

Padrela, B., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., David Zhu, Y., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B. M., Giessen, E. M., Muller, M., Fjell, A., Walhovd, K., Bjørnerud, A., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., Mutsaerts, H. J. M. M., Padrela, B., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., David Zhu, Y., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B. M., Giessen, E. M., Muller, M., Fjell, A., Walhovd, K., Bjørnerud, A., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., and Mutsaerts, H. J. M. M.

Abstract

Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and ADrelated pathologies. Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Published
2024

7. Stiffening of semiflexible biopolymers and cross-linked networks

Author

Van Dillen, T., Onck, P. R., and Van der Giessen, E.

Subjects
Physics - Biological Physics
Abstract

We study the mechanical stiffening behavior in two-dimensional (2D) cross-linked networks of semiflexible biopolymer filaments under simple shear. Filamental constituents immersed in a fluid undergo thermally excited bending motions. Pulling out these undulations results in an increase in the axial stiffness. We analyze this stiffening behavior of 2D semiflexible filaments in detail: we first investigate the average, {static} force-extension relation by considering the initially present undulated configuration that is pulled straight under a tensile force, and compare this result with the average response in which undulation dynamics is allowed during pulling, as derived earlier by MacKintosh and coworkers. We will show that the resulting mechanical behavior is rather similar, but with the axial stiffness being a factor 2 to 4 larger in the dynamic model. Furthermore, we study the stretching contribution in case of extensible filaments and show that, for 2D filaments, the mechanical response is dominated by {enthalpic} stretching. Based on the single-filament mechanics, we develop a 2D analytical model describing the mechanical behavior of biopolymer networks under simple shear, adopting the affine deformation assumption. These results are compared with discrete, finite-element (FE) calculations of a network consisting of semiflexible filaments. The FE calculations show that local, nonaffine filament reorientations occur that induce a transition from a bending-dominated response at small strains to a stretching-dominated response at larger strains. Stiffening in biopolymer networks thus results from a combination of stiffening in individual filaments and changes in the network topography.

Published
2006

8. The origin of stiffening in cross-linked semiflexible networks

Author

Onck, P. R., Koeman, T., Van Dillen, T., and Van der Giessen, E.

Subjects
Condensed Matter - Soft Condensed Matter
Abstract

Strain stiffening of protein networks is explored by means of a finite strain analysis of a two-dimensional network model of cross-linked semiflexible filaments. The results show that stiffening is caused by non-affine network rearrangements that govern a transition from a bending dominated response at small strains to a stretching dominated response at large strains. Thermally-induced filament undulations only have a minor effect; they merely postpone the transition., Comment: 5 pages, 5 figures

Published
2005
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18. PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study.

Author

Lith, S.A.M. van, Pruis, I.J., Tolboom, N., Snijders, T.J., Henssen, D.J.H.A., Laan, M. ter, Dorsthorst, Maarten Te, Leenders, W.P.J., Gotthardt, M., Nagarajah, J., Robe, P.A., Witt Hamer, P. De, Hendrikse, H., Oprea-Lager, D.E., Yaqub, M., Boellaard, R., Wesseling, P., Balvers, R.K., Verburg, F.A., Harteveld, A.A., Smits, Marion, Bent, M. van den, Zanten, S.E.M.V. van, Giessen, E. van de, Lith, S.A.M. van, Pruis, I.J., Tolboom, N., Snijders, T.J., Henssen, D.J.H.A., Laan, M. ter, Dorsthorst, Maarten Te, Leenders, W.P.J., Gotthardt, M., Nagarajah, J., Robe, P.A., Witt Hamer, P. De, Hendrikse, H., Oprea-Lager, D.E., Yaqub, M., Boellaard, R., Wesseling, P., Balvers, R.K., Verburg, F.A., Harteveld, A.A., Smits, Marion, Bent, M. van den, Zanten, S.E.M.V. van, and Giessen, E. van de

Abstract

Item does not contain fulltext, Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [(68)Ga]Ga-PSMA-11 (n = 7), 200 MBq of [(18)F]DCFpyl (n = 3), or 200 MBq of [(18)F]PSMA-1007 (n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n = 40), determined using immunohistochemistry (n = 35) or RNA sequencing (n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUV(max), 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUV(max) of tumor by SUV(max) of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodol

Published
2023

19. DEveloping BBB-ASL as non-Invasive Early biomarker of Alzheimer’s Disease (DEBBIE-AD): Study design

Author

Padrela, B. E., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., Zhu, Y. D., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B., Giessen, E., Muller, M., Fjell, A. M., Walhovd, K. B., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., Mutsaerts, H. J. M. M., Padrela, B. E., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., Zhu, Y. D., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B., Giessen, E., Muller, M., Fjell, A. M., Walhovd, K. B., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., and Mutsaerts, H. J. M. M.

Abstract

Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesized to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Arterial spin labeling (ASL) perfusion MRI has recently been adapted to map the BBB permeability non-invasively. This article outlines the study design of the DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium, focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods: DEBBIE-AD consists of 13 cohorts enrolling participants from subjective cognitive decline to AD, as well as healthy controls across the lifespan. The reproducibility and accuracy of BBB-ASL will be evaluated in healthy participants, and its clinical value will be evaluated with both established and novel AD biomarkers. Expected endpoints: DEBBIE-AD aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies, which may provide new targets for treatment.

Published
2023

20. Reproducibility of 3T APT-CEST in healthy volunteers and brain glioma patients

Author

Wamelink, I. J. H. G., Kuijer, J. P. A., Padrela, B. E., Zhang, Y., Barkhof, F., Mutsaerts, H. J. M. M., (0000-0002-3201-6002) Petr, J., Giessen, E., Keil, V. C., Wamelink, I. J. H. G., Kuijer, J. P. A., Padrela, B. E., Zhang, Y., Barkhof, F., Mutsaerts, H. J. M. M., (0000-0002-3201-6002) Petr, J., Giessen, E., and Keil, V. C.

Abstract

BACKGROUND Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications in patients with brain tumors. PURPOSE To investigate whether cerebral APT-CEST is sufficiently reproducible in healthy tissue and glioma for clinical use at 3T. STUDY TYPE Prospective, longitudinal SUBJECTS Twenty-one healthy volunteers (M:F = 10:11; age 39±11 years) and six glioma patients (M:F = 3:3; age 50±17 years: four glioblastomas, one oligodendroglioma, one suspected low-grade glioma). FIELD STRENGTH/SEQUENCE 3T, SPACE-CEST ASSESSMENT APT-CEST measurement reproducibility was assessed within-session (glioma patients, healthy volunteers), and between-sessions and between-days (healthy volunteers). The standard deviation of the within-subject difference (SDdiff) was calculated in tumor regions of interest (ROI), and eight ROIs at relevant locations including a whole-brain ROI. STATISTICAL TESTS Brown-Forsythe tests and variance component analyses (VCA) were used to assess the reproducibility of ROIs for the three reproducibility time intervals. Intraclass correlation coefficient (ICC) was used to assess agreement between the ROIs for the three reproducibility time intervals. RESULTS APT-CEST magnetization transfer ratio asymmetry (MTRasym) was 0.89±0.96% on average in healthy brain tissue and 1.59±0.67% in tumor tissue. Intratumoral mean MTRasym was significantly higher than MTRasym in healthy-appearing tissue in patients (0.5±0.46%; P< 0.001). The APTCEST difference between GBMs and contralateral tissue was 1.11%. The average within-session, between-sessions, and between-days SDdiff of healthy control brains was 0.2%. The within-session SDdiff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. The orbitofrontal gyri were the ROI with the highest within-session SDdiff (0.61%). Within-session reproducibility of ROIs did not differ significantly from between-sessions or

Published
2023

21. Genetic, vascular, and amyloid determinants of cerebral blood flow in a preclinical population

Author

Padrela, B. E., Lorenzini, L., Collij, L. E., Vállez García, D., Coomans, E., Ingala, S., Tomassen, J., Deckers, Q., Shekari, M., Geus, E. J. C., Giessen, E., Ten Kate, M., Jelle Visser, P., Barkhof, F., Petr, J., Den Braber, A., and Mutsaerts, H. J. M. M.

Abstract

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. General estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC>0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

Published
2023

39. A unified scenario for the morphology of crack paths in two-dimensional disordered solids

Author

Ponson, L., Shabir, Z., Abdulmajid, M., Van Der Giessen, E., Simone, A., Institut Jean Le Rond d'Alembert (DALEMBERT), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Delft University of Technology (TU Delft), University of Groningen [Groningen], Department of Mechanical Engineering [Padova], Department of Industrial Engineering [Padova], and Universita degli Studi di Padova-Universita degli Studi di Padova

Subjects
roughening processes, [PHYS]Physics [physics], scaling properties, fracture mechanisms, numbers: Crack path
Abstract

International audience; A combined experimental and numerical investigation of the roughness of intergranular cracks in two-dimensional disordered solids is presented. We focus on brittle materials for which the characteristic length scale of damage is much smaller than the grain size. Surprisingly, brittle cracks do not follow a persistent path with a roughness exponent ζ ≈ 0.6-0.7 as reported for a large range of materials. Instead, we show that they exhibit mono-affine scaling properties characterized by a roughness exponent ζ = 0.5 ± 0.05, which we explain theoretically from linear elastic fracture mechanics. Our findings support the description of the roughening process in two-dimensional brittle disordered solids by a random walk. Furthermore, they shed light on the failure mechanism at the origin of the persistent behavior with ζ ≈ 0.6-0.7 observed for fractures in other materials, suggesting a unified scenario for the geometry of cracks paths in two-dimensional disordered solids.

Published
2021

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