scholarly journals Deciphering the scopolamine challenge rat model by preclinical functional MRI

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gergely Somogyi ◽  
Dávid Hlatky ◽  
Tamás Spisák ◽  
Zsófia Spisák ◽  
Gabriella Nyitrai ◽  
...  

AbstractDuring preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.

2020 ◽  
Author(s):  
Gergely Somogyi ◽  
Dávid Hlatky ◽  
Tamás Spisák ◽  
Zsófia Spisák ◽  
Gabriella Nyitrai ◽  
...  

AbstractDuring preclinical drug testing, the systemic administration scopolamine (SCO), a cholinergic antagonist, is widely used. However, it has limited predictive validity partly due to its peripheral side-effects. Therefore, objective neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.Significance StatementRodent functional MRI (fMRI) is a powerful and promising tool for translational research, as it bridges the gap between animal experiments and human neuroimaging. Scopolamine (SCO) is a standard reference drug for inducing experimental cognitive impairment in both animals and humans, however, it has limited predictive validity partly due to its peripheral side-effects. We measured whisker-stimulation induced fMRI activation after injecting SCO or its peripherally acting analog with different fMRI sequences in two different anesthesia type and analyzed the data with different statistical inferences. We deciphered that the likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.


NeuroImage ◽  
2008 ◽  
Vol 43 (2) ◽  
pp. 288-296 ◽  
Author(s):  
C.J.C. Bouwman ◽  
J.T. Wilmink ◽  
W.H. Mess ◽  
W.H. Backes

2019 ◽  
Author(s):  
Mahdi Khajehim ◽  
Thomas Christen ◽  
J. Jean Chen

AbstractPurposeTo introduce a novel magnetic-resonance fingerprinting (MRF) framework with single-shot echo-planar imaging (EPI) readout to simultaneously estimate tissue T2, T1 and T2*, and integrate B1 correction.MethodsSpin-echo EPI is combined with gradient-echo EPI to achieve T2 estimation as well as T1 and T2* quantification. In the dictionary matching step, the GE-EPI data segment provides estimates of tissue T1 and T2* with additional B1 information, which are then incorporated into the T2-matching step that uses the SE-EPI data segment. In this way, biases in T2 and T2* estimates do not affect each other.ResultsAn excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches in both phantom and human scans. In the phantom scan, a linear relationship with R2>0.96 was found for all parameter estimates. The maximum error in the T2 estimate was found to be below 6%. In the in-vivo scan, similar contrast was noted between MRF and standard approaches, and values found in a small region of interest (ROI) located in the grey matter (GM) were in line with previous measurements (T2MRF=88±7ms vs T2Ref=89±11ms, T1MRF=1153±154ms vs T1Ref=1122±52ms, T2*MRF=56±4ms vs T2*Ref=53±3ms).ConclusionAdding a spin echo data segment to EPI based MRF allows accurate and robust measurements of T2, T1 and T2* relaxation times. This MRF framework is easier to implement than spiral-based MRF. It doesn’t suffer from undersampling artifacts and seems to require a smaller dictionary size that can fasten the reconstruction process.


Author(s):  
Christoph A. Rettenmeier ◽  
Danilo Maziero ◽  
V. Andrew Stenger

2017 ◽  
Vol 27 (3) ◽  
pp. 193-201 ◽  
Author(s):  
Fabian Hilbert ◽  
Tobias Wech ◽  
Henning Neubauer ◽  
Simon Veldhoen ◽  
Thorsten Alexander Bley ◽  
...  

NeuroImage ◽  
2003 ◽  
Vol 19 (2) ◽  
pp. 412-421 ◽  
Author(s):  
Christine Preibisch ◽  
Ulrich Pilatus ◽  
Jürgen Bunke ◽  
Frank Hoogenraad ◽  
Friedhelm Zanella ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document