fMRI & phMRI Studies
Changes in brain tissue activity in response to stimuli, such as by a compound or sensory stimulus, can be quantitatively measured with MRI-based applications to provide evidence of neuronal engagement. Neurovascular activity and coupling (hemodynamic response to metabolic activity) may be detected utilizing blood oxygenation level-dependent (BOLD) effect in functional MRI (fMRI) studies. Fast imaging sequences detect well-localized activations (e.g., at somatosensory cortex after forepaw stimulation). Cerebral activity following drug administration and CNS adaptation to medication may be detected using BOLD paradigm or relative cerebral blood volume (rCBV) via contrast enhancement methods, such as superparamagnetic iron oxide MION for MRI-based activity measurement. Results provide insight into brain physiology and neuropharmacological mechanisms.
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Pharmacological MRI (phMRI) is a technique that allows researchers to noninvasively map brain function in response to the hemodynamic changes brought on by the introduction of pharmaceutical stimuli. Analogous to fMRI but employing pharmacological methods of simulation, phMRI maps the time course and neurological response to specific pharmacological stimuli and gives insight into the pharmacokinetic and pharmacodynamic properties of drugs aimed at neurological, psychiatric, and neuromuscular diseases.
fMRI Case Study
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Objective
Using noninvasvive functional MRI to detect seizures in a PTZ seizure model.
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Model
Pentylenetetrazol (PTZ) is a GABA-A receptor stimulant that induces acute convulsive seizures that are antagonized using AEDs including diazepam.
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Experimental Results
PTZ injection (i.p.) caused a strong BOLD fMRI signal increase in majority of brain areas measured. Readouts taken in 0.4 mm in-plan, 1.2 mm slices at 3 s time resolution.
Longitudinal measurements of BOLD fMRI signal post PTZ injection that is antagonized using diazepam.
Mapping of the individual seizure progression using dynamic sliding window SPM analysis
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Conclusion
PTZ evokes strong measurable seizures in rat brains that are negated by diazepam. BOLD fMRI is translational and noninvasive method to measure seizure induction and diazepam induced reduction in signal.
fMRI and phMRI Frequently Asked Questions (FAQs)
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What is the preferred method of anesthesia for phMRI studies?
We have access to several anesthetics but preferentially use medetomidine, urethane, or isoflurane.
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Are there resolution differences between brain and non-brain MRI imaging?
While the measured organ, surrounding tissue environment, and imaging sequence can make a difference, it is possible to achieve high resolution brain and non-brain tissue MRI data. The brain does have the advantage of minimum motion that allows higher resolution compared to other organs.
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What are Charles River’s capabilities around fMRI?
Functional MRI capabilities are currently being developed at Charles River. A few pilot studies using gold standard methods such as forepaw stimulation have been successfully completed and the imaging team is in the process of collecting more validation data.
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What species are you able to perform MRI on?
Currently at the Charles River site in Kuopio, Finland, MRI imaging is performed on rats and mice and the Charles River site in Sherbrooke, Canada can image dogs and non-human primates.
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Which software does Charles River use for brain volumetric analysis?
Currently, we use MATLAB based software that was developed in-house and for brain volumetry analysis, the freely available IDIS software package is used.