Background & Aims

Functional MRI (fMRI) is a key tool in CNS research, particularly for the study of brain activity. Recently, we have extended its application to the study of the dorsal root ganglia (DRG) to gain insight into pain processing and neural activity at the DRG level. This novel approach uses blood oxygen level-dependent (BOLD) contrast to detect and quantify the neurovascular coupling of the DRG to external painful stimuli. By monitoring the BOLD response of the DRG in vivo, this method promises a new understanding of pain (patho)physiology. The primary aim is to unravel the complexity of pain processing mechanisms at the DRG organ level. The objective of the study is to demonstrate the proof-of-principle of DRG fMRI by developing a non-invasive imaging method to examine DRG function in various pain syndromes. As such, DRG fMRI as an in vivo imaging biomarker represents a potential clinical endpoint in longitudinal (drug) studies.

Methods

In this study, we used a specific fMRI protocol to investigate the neurovascular coupling of the bilateral S1 DRG to painful stimuli (8/10 on NRS). Twelve healthy volunteers were examined using a T2*-weighted (BOLD) fMRI sequence with a temporal resolution of 0.625 s and a spatial resolution of 1.8 mm. During the MRI acquisition, participants received periodic painful electrical stimuli targeted to the S1 dermatome, specifically designed to supramaximal activate A?-, A?- and C-fibers. Stimulation was delivered via a surface electrode placed over the sural nerve, which had been previously localized and tested by electrophysiological examination. The pain paradigm consisted of a baseline rest period, followed by 10 seconds of stimulation, followed by a 50-second rest period. This one-minute paradigm was repeated 10 times in each session and for both sides per subject. To ensure consistency of results, the entire procedure was repeated a subsequent session.

Results

The results of the study showed that peripheral electrical surface stimulation of the S1 dermatome resulted in an immediate increase in T2*-weighted signal of the ipsilateral DRG level S1. This increase was significant compared to both baseline (p < 0.001) and the non-stimulated contralateral side (p < 0.001). The observed overall increase in T2*-weighted signal reached up to 7% compared to the non-stimulated contralateral side (p < 0.001). In addition to an immediate BOLD effect, the longitudinal course shows a concomitant, primarily systemic DRG increased perfusion both ipsi- and contralaterally. These results indicate a direct and quantifiable neurovascular coupling of the DRG to peripheral pain stimuli and demonstrate the efficacy of the fMRI protocol used to detect and measure DRG neurovascular coupling as a potential in vivo biomarker of pain processing at the organ level.

Conclusions

This study demonstrates the feasibility of characterizing DRG neurovascular coupling as surrogate markers of neuronal activity in primary sensory dorsal root ganglia neurons at the organ level. Our results demonstrate that it’s possible to reliably detect and quantify BOLD responses by DRG fMRI, providing a novel method to characterize physiological pain processing. Furthermore, this new method offers a new avenue for investigating different pain syndromes and potentially identifying impairments at the DRG level. DRG fMRI is emerging as a promising non-invasive biomarker that allows the objective and longitudinal study of pain disorders. This approach has significant potential for studying pain resolution, pain chronification, and the effects of (pain) medication. The ability to quantitatively assess pain processing in DRGs could improve our understanding of pain conditions and their underlying mechanisms.

References

1.Devor M. Unexplained peculiarities of the dorsal root ganglion. Pain. 1999;Suppl 6:S27-S35.
2.Godel T, Pham M, Heiland S, Bendszus M, Bäumer P. Human dorsal-root-ganglion perfusion measured in-vivo by MRI. Neuroimage. 2016;141:81-87.
3.Kim SG, Ogawa S. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab. 2012;32(7):1188-1206.
4.Logothetis NK, Wandell BA. Interpreting the BOLD signal. Annu Rev Physiol. 2004;66:735-769.

Presenting Author

Magnus Schindehütte

Poster Authors

Magnus Schindehütte

MD

Neuroradiologie Universitätsklinikum Würzburg

Lead Author

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Simon Weiner

University Hospital Würzburg

Lead Author

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Christopher Nauroth-Kreß

University Hospital Wuerzburg, Neuroradiology

Lead Author

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Thomas Kampf

University Hospital Wuerzburg, Neuroradiology

Lead Author

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György A. Homola

Dr. rer. nat

Institute for neuroradiology, university hospital Würzburg, Germany

Lead Author

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Mirko Pham

Prof. Dr. MD

Institute for neuroradiology, university hospital Würzburg, Germany

Lead Author

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Topics

  • Pain Imaging