Molecular Imaging and Biology

, Volume 20, Issue 2, pp 171–182 | Cite as

Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic Calcium Recordings and Optogenetic Control

  • Franziska Albers
  • Lydia Wachsmuth
  • Timo Mauritz van Alst
  • Cornelius Faber
Review Article


Recent developments of optogenetic tools and fluorescence-based calcium recording techniques enable the manipulation and monitoring of neural circuits on a cellular level. Non-invasive imaging of brain networks, however, requires the application of methods such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), which is commonly used for functional neuroimaging. While BOLD fMRI provides brain-wide non-invasive reading of the hemodynamic response, it is only an indirect measure of neural activity. Direct observation of neural responses requires electrophysiological or optical methods. The latter can be combined with optogenetic control of neuronal circuits and are MRI compatible. Yet, simultaneous optical recordings are still limited to fiber-optic-based approaches. Here, we review the integration of optical recordings and optogenetic manipulation into fMRI experiments. As a practical example, we describe how BOLD fMRI in a 9.4-T small animal MR scanner can be combined with in vivo fiber-optic calcium recordings and optogenetic control in a multimodal setup. We present simultaneous BOLD fMRI and calcium recordings under optogenetic control in rat. We outline details about MR coil configuration, choice, and usage of opsins and chemically and genetically encoded calcium sensors, fiber implantation, appropriate light power for stimulation, and calcium signal detection, to provide a glimpse into challenges and opportunities of this multimodal molecular neuroimaging approach.

Key Words

fMRI Optogenetics Fiber-based calcium recordings Opsin Calcium indicator Small-animal fMRI 



We thank Ofer Yizhar for his presentation and all participants of the study group meeting for the lively discussion. We thank Florian Schmid for his pioneering work and essential contribution to establishing the described experimental setup in our lab, Albrecht Stroh for his close collaboration with many discussions and intense scientific exchange, and Xin Yu for valuable advice during this period.

Funding Information

This work was in part supported by the German Research Foundation (DFG: Fa474/5, SFB1009-Z02, and EXC1003) and the Medical Faculty Münster (MedK program).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  1. 1.Department of Clinical RadiologyUniversity Hospital MünsterMünsterGermany

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