Duchenne muscular dystrophy (DMD) affects besides muscle also the brain, resulting in memory and behavioral problems. The consequences of dystrophinopathy on gross macroscopic alterations are... Show moreDuchenne muscular dystrophy (DMD) affects besides muscle also the brain, resulting in memory and behavioral problems. The consequences of dystrophinopathy on gross macroscopic alterations are unclear. To elucidate the effect of full-length dystrophin expression on brain morphology, we used high-resolution post-mortem MRI in mouse models that either express 0% (mdx), 100% (BL10) or a low amount of full-length dystrophin (mdx-Xist(Delta hs)). While absence or low amounts of full-length dystrophin did not significantly affect whole brain volume and skull morphology, we found differences in volume of individual brain structures. The results are in line with observations in humans, where whole brain volume was found to be reduced only in patients lacking both full-length dystrophin and the shorter isoform Dp140. Show less
Kogelman, B.; Khmelinskii, A.; Verhaart, I.; Vliet, L. van; Bink, D.I.; Aartsma-Rus, A.; ... ; Weerd, L. van der 2018
The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification.... Show moreThe cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time-encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal-to-noise ratio (SNR) and shorter scan time than multi-delay arterial spin labeling (ASL). In this study, we show that time-encoded pseudo-continuous arterial spin labeling (te-pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub-boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 +/- 11 ms) and the auditory/visual cortex showed the longest (284 +/- 16 ms). Furthermore, ATT was found to be preserved in old wild-type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te-pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time-efficient manner. Show less
Mulder, I.A.; Khmelinskii, A.; Dzyubachyk, O.; Jong, S. de; Wermer, M.J.H.; Hoehn, M.; ... ; Maagdenberg, A.M.J.M. van den 2017
In pre-clinical research, whole-body small-animal imaging is widely used for in vivo visualization of functional and anatomical information to study cancer, neurological and cardiovascular diseases... Show moreIn pre-clinical research, whole-body small-animal imaging is widely used for in vivo visualization of functional and anatomical information to study cancer, neurological and cardiovascular diseases and help with a faster development of new drugs. Functional information is provided by imaging modalities such as PET, SPECT and specialized MRI. Structural imaging modalities like CT, MRI and ultrasound provide detailed depictions of anatomy. Optical imaging modalities, such as BLI and near-infrared-fluorescence offer a high sensitivity in visualizing molecular processes in vivo. Combining these modalities enables to follow the subject(s) and molecular processes in time, in living animals. With these advances in image acquisition, the problem has shifted from data acquisition to data processing: organization, analysis and interpretation of this heterogeneous whole-body imaging data has become a demanding task. Here, our data processing approach is based on an articulated whole-body atlas as a common reference to normalize the geometric heterogeneity caused by postural and anatomical differences between individuals and geometric differences between imaging modalities. Mapping to this atlas has the advantage that all the different imaging modalities can be registered to a common anatomical reference; postural variations can be corrected, and the different animals can be scaled properly while allowing for proper management of this high-throughput data. Show less
Khmelinskii, A.; Groen, H.C.; Baiker, M.; Jong, M. de; Lelieveldt, B.P.F. 2012
Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as... Show moreOptical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and mu CT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals. (C) 2010 Elsevier Inc. All rights reserved. Show less
Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as... Show moreOptical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and μCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals. Show less
