High resolution pCASL mapping of perfusion in a mouse model of stroke
Poster No:
2594
Submission Type:
Abstract Submission
Authors:
Sara Monteiro1,2, Lydiane Hirschler3, Emmanuel Barbier4, Patricia Figueiredo2, Noam Shemesh1
Institutions:
1Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal, 2Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal, 3C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, 4Université Grenoble Alpes, Inserm, Grenoble Institut des Neurosciences, Grenoble, France
First Author:
Sara Monteiro
Champalimaud Research, Champalimaud Foundation|Instituto Superior Técnico, Universidade de Lisboa
Lisbon, Portugal|Lisbon, Portugal
Champalimaud Research, Champalimaud Foundation|Instituto Superior Técnico, Universidade de Lisboa
Lisbon, Portugal|Lisbon, Portugal
Co-Author(s):
Lydiane Hirschler
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center
Leiden, Netherlands
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center
Leiden, Netherlands
Emmanuel Barbier
Université Grenoble Alpes, Inserm, Grenoble Institut des Neurosciences
Grenoble, France
Université Grenoble Alpes, Inserm, Grenoble Institut des Neurosciences
Grenoble, France
Introduction:
pCASL enables efficient perfusion mapping in-vivo without injection of contrast agents.1 Despite its great potential, state-of-the-art pCASL in preclinical settings is still characterized by low spatial resolution and high variability in CBF maps.1-3 Compared to rats, pCASL measurements are particularly challenging in mice due to mouse-specific anatomical constraints that limit labeling efficiency due to the way carotids are placed.4 Here, we address this gap and develop a novel experimental setup that optimizes carotid placement and further harnesses dramatic SNR increases from cryogenic coils5 to achieve high-resolution and reliable pCASL imaging in mice at 9.4 T and test our approach in an animal model of stroke.
Methods:
All animal experiments received proper ethical approval.
Experimental Setup: A custom-built ramp was designed for better animal positioning (Fig.1A).
Animal Preparation: Female C57BL/g mice (N=16, ~12 weeks old, weights 20–25g) were sedated using ~2% isoflurane. In N=3 animals, a photothrombotic stroke6 was induced. The animals were scanned using the ramp at t=0h, 24h and 5days after stroke.
MRI experiments: Experiments were conducted on a 9.4 T Bruker Biospec Scanner using an unbalanced pCASL sequence7 (labelling plane (LP) positioned at the mouse neck (~8mm below the isocenter), labeling duration of 3s, post-labelling delay of 300ms, TR/TE=4000/17ms, 30 repetitions). N=7 animals were scanned with a LP tilt of 0º (no ramp 0º) and 45º (no ramp 45º) and N=6 animals were scanned with the LP angle of 0º and on top of a ramp (Fig.1A), both at low and high-resolution.
Low-resolution pCASL acquisitions: FOV=14x14mm2, slice thickness=1mm, slice gap=0.2mm, matrix=96x96 resulting in a spatial resolution of 146x146μm2. For high-resolution pCASL: FOV=12x12mm2, slice thickness=0.5mm, slice gap=0.35mm, matrix=120x120 resulting in a spatial resolution of 100x100μm2. For cerebral blood flow (CBF) quantification, the T1 map was obtained from an inversion recovery sequence7. A pCASL encoded FLASH was employed to estimate the inversion efficiency (IE) 3mm above the LP (PLD=0ms, LD=200ms).7
Data Analysis: CBF (ml/100g/min) was calculated from the relative ASL signal difference between control and label images (rASL).8 In the rASL and CBF high-resolution maps, two ROIs were defined (cortical and thalamic) and used for averaging rASL and CBF. The IE was calculated by manually drawing a ROI in each carotid.
Experimental Setup: A custom-built ramp was designed for better animal positioning (Fig.1A).
Animal Preparation: Female C57BL/g mice (N=16, ~12 weeks old, weights 20–25g) were sedated using ~2% isoflurane. In N=3 animals, a photothrombotic stroke6 was induced. The animals were scanned using the ramp at t=0h, 24h and 5days after stroke.
MRI experiments: Experiments were conducted on a 9.4 T Bruker Biospec Scanner using an unbalanced pCASL sequence7 (labelling plane (LP) positioned at the mouse neck (~8mm below the isocenter), labeling duration of 3s, post-labelling delay of 300ms, TR/TE=4000/17ms, 30 repetitions). N=7 animals were scanned with a LP tilt of 0º (no ramp 0º) and 45º (no ramp 45º) and N=6 animals were scanned with the LP angle of 0º and on top of a ramp (Fig.1A), both at low and high-resolution.
Low-resolution pCASL acquisitions: FOV=14x14mm2, slice thickness=1mm, slice gap=0.2mm, matrix=96x96 resulting in a spatial resolution of 146x146μm2. For high-resolution pCASL: FOV=12x12mm2, slice thickness=0.5mm, slice gap=0.35mm, matrix=120x120 resulting in a spatial resolution of 100x100μm2. For cerebral blood flow (CBF) quantification, the T1 map was obtained from an inversion recovery sequence7. A pCASL encoded FLASH was employed to estimate the inversion efficiency (IE) 3mm above the LP (PLD=0ms, LD=200ms).7
Data Analysis: CBF (ml/100g/min) was calculated from the relative ASL signal difference between control and label images (rASL).8 In the rASL and CBF high-resolution maps, two ROIs were defined (cortical and thalamic) and used for averaging rASL and CBF. The IE was calculated by manually drawing a ROI in each carotid.
Results:
The IE was calculated for each setup: no ramp 0º=0.57±0.20, no ramp 45º=0.80±0.63 and ramp=0.78±0.04. Note the dramatically smaller variance in the ramp setup. Additionally, only the ramp setup reveals the expected linear relationship between rASL and IE (Fig.1C). Figure 2A shows CBF maps from the mice scanned at the low and high-resolution for the 3 conditions. In controls, only the acquisitions using the ramp present the expected CBF patterns in the healthy mouse brain, with little variability across animals both at low- and high-resolution. In the high-resolution images, differences in perfusion within different hippocampal layers, descending cortical vessels can be discerned (Fig.2A). In the stroke model, we detected CBF impairments across the brain that were changing over time (Fig.2C).
Conclusions:
By using a novel experimental setup, we managed to increase state-of-the-art resolution2 of pCASL perfusion images of the mouse brain by a factor of 15 and obtain highly reliable CBF maps. Our findings include enhanced stability of the images acquired with the ramp (lower standard deviation in the IE measure) and a better delineation of brain areas including in an animal model of stroke, unveiling pCASL's potential to detect alterations in CBF in mouse models of disease or healthy longitudinal processes. Our findings bode well for future applications of CBF mapping in mice.
Modeling and Analysis Methods:
Methods Development 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Novel Imaging Acquisition Methods:
Imaging Methods Other
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 1
Keywords:
ANIMAL STUDIES
Cerebral Blood Flow
Cerebrovascular Disease
Development
MRI
Other - Perfusion MRI
1|2Indicates the priority used for review
·Figure 1. Setups for mouse positioning in the scanner when using a cryogenic coil
·Figure 2. CBF mapping in the mouse brain
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