Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters... Show moreBiological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, we assessed the relationship between 92 plasma proteins from the Olink® cardiovascular III panel and normal-appearing grey matter CBF, using affinity propagation and hierarchical clustering algorithms, and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up using Spearman correlation and logistic regression. Thirteen proteins were associated with CBF (ρSpearman range: −0.10 to −0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (ρSpearman 0.42, p < 0.001) and cardiovascular events (OR 2.05, p < 0.01). In conclusion, we identified a cluster of plasma proteins related to CBF, reflecting extracellular matrix organization processes, that is also related to future cardiovascular events in patients with CVD, representing potential targets to preserve CBF and mitigate cardiovascular risk in patients with CVD. Show less
Chappell, M.A.; McConnell, F.A.K.; Golay, X.; Gunther, M.; Hernandez-Tamames, J.A.; Osch, M.J. van; Asllani, I. 2021
The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE),... Show moreThe mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, 'uncorrected', images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods. Show less
Berkhout-Byrne, N.; Kallenberg, M.H.; Gaasbeek, A.; Rabelink, T.J.; Hammer, S.; Buchem, M.A. van; ... ; Buren, M. van 2017
Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six... Show moreIntra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P<0.05). Pseudo-continuous ASL and multi TI PASL varied least between sites. Variability maps of all methods showed most variability near brain-feeding arteries within sessions and in gray matter between sessions. On the basis of the results of this study, one could consider the use of reference values in clinical routine, with whole-brain p-CASL perfusion varying <20% over repeated measurements within the same individuals considered to be normal. Knowledge on regional variability allows for the use of perfusion-weighted images in the assessment of local cerebral pathology. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1706-1715; doi:10.1038/jcbfm.2011.10; published online 9 February 2011 Show less
Emmer, B.J.; Osch, M.J. van; Wu, O.; Steup-Beekman, G.M.; Steens, S.C.; Huizinga, T.W.; ... ; Grond, J. van der 2010
Purpose: To use perfusion weighted MR to quantify any perfusion abnormalities and to determine their contribution to neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE).... Show morePurpose: To use perfusion weighted MR to quantify any perfusion abnormalities and to determine their contribution to neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE). Materials and methods: We applied dynamic susceptibility contrast (DSC) perfusion MRI in 15 active NPSLE, 26 inactive NPSLE patients. and 11 control subjects. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were reconstructed and regions of interest were compared between groups. In addition, the effect of SLE criteria, NPSLE syndromes. immunological coagulation disorder, and medication on CBF. CBV, and MTT was investigated. Results: No significant differences were found between the groups in CBF, CBV, and MTT. No significant influence of SLE criteria or NPSLE syndromes on CBF, CBV, or MTT was found. No significant influence of anti-cardiolipin antibodies, lupus anti-coagulant, the presence of anti-phospholipid syndrome (APS), or medication on CBF, CBV. or MTT was found. Conclusion: Our findings suggest CBF. CBV, and MTT in the white and the gray matter in SLE patients is not significantly different from healthy controls or between patients with and without specific symptoms or with and without immunological disorder involving coagulation. Show less
