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The power of using functional fMRI on small rodents to study brain pharmacology and disease.

Jonckers E, Shah D, Hamaide J, Verhoye M, Van der Linden A - Front Pharmacol (2015)

Bottom Line: Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner.The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder.In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations.

View Article: PubMed Central - PubMed

Affiliation: Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp Antwerp, Belgium.

ABSTRACT
Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal's physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations.

No MeSH data available.


Related in: MedlinePlus

Overview of the physiological basis of fMRI situating the different techniques reviewed in this paper.
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Figure 1: Overview of the physiological basis of fMRI situating the different techniques reviewed in this paper.

Mentions: A variety of MRI pulse sequences exist which exploit different features of water protons in tissue. The most widely used MRI contrasts are found in T1-, T2-, T2∗- and proton density weighted images. The resulting images provide superior anatomical contrast allowing qualitative and quantitative assessment of overall brain anatomy. To study brain functioning the sequence is adapted to acquire the BOLD contrast which is based on the differential magnetic properties of oxygenated (diamagnetic) and deoxygenated (paramagnetic) hemoglobin. Upon neural activation, changes in local CBF, CBV, and CMRO2, i.e., the hemodynamic response leads to a locally increased ratio of oxygenated over deoxygenated hemoglobin, resulting in an enhancement in T2(∗)-weighted signal intensity (cfr. Figure 1). BOLD fMRI is thus an indirect measure of neuronal activity. For a more detailed description please consult (Buxton and Frank, 1997; Logothetis and Wandell, 2004).


The power of using functional fMRI on small rodents to study brain pharmacology and disease.

Jonckers E, Shah D, Hamaide J, Verhoye M, Van der Linden A - Front Pharmacol (2015)

Overview of the physiological basis of fMRI situating the different techniques reviewed in this paper.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612660&req=5

Figure 1: Overview of the physiological basis of fMRI situating the different techniques reviewed in this paper.
Mentions: A variety of MRI pulse sequences exist which exploit different features of water protons in tissue. The most widely used MRI contrasts are found in T1-, T2-, T2∗- and proton density weighted images. The resulting images provide superior anatomical contrast allowing qualitative and quantitative assessment of overall brain anatomy. To study brain functioning the sequence is adapted to acquire the BOLD contrast which is based on the differential magnetic properties of oxygenated (diamagnetic) and deoxygenated (paramagnetic) hemoglobin. Upon neural activation, changes in local CBF, CBV, and CMRO2, i.e., the hemodynamic response leads to a locally increased ratio of oxygenated over deoxygenated hemoglobin, resulting in an enhancement in T2(∗)-weighted signal intensity (cfr. Figure 1). BOLD fMRI is thus an indirect measure of neuronal activity. For a more detailed description please consult (Buxton and Frank, 1997; Logothetis and Wandell, 2004).

Bottom Line: Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner.The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder.In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations.

View Article: PubMed Central - PubMed

Affiliation: Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp Antwerp, Belgium.

ABSTRACT
Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal's physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations.

No MeSH data available.


Related in: MedlinePlus