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

  • Objective

    Using noninvasvive functional MRI to detect seizures in a PTZ seizure model.

  • Model

    Pentylenetetrazol (PTZ) is a GABA-A receptor stimulant that induces acute convulsive seizures that are antagonized using AEDs including diazepam.

  • 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.

    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.

    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

     

  • 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.

 

BOLD activation mapping of the amphetamine-induced signal change
Figure 1: BOLD activation mapping of the amphetamine-induced signal change

phMRI analysis of a 6-hydroxydopamine Parkinson’s disease rat model
Figure 2: phMRI analysis of a 6-hydroxydopamine Parkinson’s disease rat model

 

fMRI and phMRI FAQs