Table 2.
Imaging changes/potential imaging biomarkers in response to various neurostimulation methods for chronic pain.
| DBS Implant | ||
|---|---|---|
| Area of Interest | Imaging Method | Imaging Changes |
| Periaqueductal gray | [11C]diprenorphine (DPN)—PET | DBS activation caused a focal reduction in [11C]DPN VT in the PAG, consistent with stimulation-evoked release of endogenous opioids [142]. |
| Thalamus | [15O]H2O PET | Changes in rCBF during thalamic DBS revealed stimulation-related increases within the ACC, the globus pallidus, and a region lateral to the thalamus identified as the internal capsule [143]. |
| VS/ALIC | fMRI | In response to pain, patients in the DBS OFF state showed significant activation in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p < 0.001) in the hippocampi when painful stimulation was applied to the affected side [144]. |
| Non-specific | MRI DTI | Patients for whom the DBS electrodes were within the DTI targets experienced better outcomes than those for whom the electrodes were not [145]. |
| VPL and PVG areas | SPECT | DBS consistently increased perfusion in the posterior subcortical region between VPL and PVG, regardless of the site of stimulation. Thalamic and dual-target DBS increased thalamic perfusion, yet PVG DBS decreased perfusion in the PVG-containing midbrain region and thalamus. Dual-target stimulation decreased anterior cingulate and insular cortex perfusion [146]. |
| ACC | MEG | Long-term functional brain changes as a result of continuous DBS over one year led to specific changes in the activity in the dissociable regions of caudal and rostral ACC [147]. |
| SCS implant | ||
| Imaging method | Imaging changes | |
| fMRI, PET, SPECT, H-MRS | Increased activity in frontal regions of the cortex, as well as identifying the ACC and thalamus as mediators of the pain experience and potentially key components determining the influence of SCS at supraspinal levels. Prior to stimulation, poor responders to SCS showed increased thalamic activation, whereas good responders showed almost no activation in the thalamus [148]. | |
| [15O]H2O PET | Comparison of rCBF before and after SCS showed significant rCBF increases in the right thalamus, right orbitofrontal cortex (BA11), left inferior parietal lobule (BA7), right superior parietal lobule (BA7), left anterior cingulate cortex (ACC) (BA24), and left lateral prefrontal cortex (BA10) [107]. | |
| [18F]FDG-PET | Burst stimulation modulated the dorsal ACC (i.e., medial pain pathway) more than tonic stimulation [149]. | |
| DRG stimulation | ||
| Imaging method | Imaging changes | |
| fMRI BOLD | During noxious paw stimulation, ganglionic field stimulation (GFS) attenuates the BOLD signal in brain regions composing the ascending neospinothalamic system, specifically the contralateral thalamic VPL/VPM nuclei and cortical S1 and S2. This ascending sensory pathway subserves the sensory–discriminative dimension of pain, composed of immediate pain awareness and spatial attentiveness to painful stimuli [150]. | |
| MCS implant | ||
| Imaging method | Imaging changes | |
| [15O]H2O PET | Compared to baseline, turning on the stimulator was associated with CBF increase in the contralateral (anterior) midcingulate cortex (aMCC, BA24 and 32) and in the dorsolateral prefrontal (BA10) cortex. The most important changes in CBF were observed in the 75 min after discontinuation of MCS (OFF). This poststimulation period was associated with CBF increases in a large set of cortical and subcortical regions (from posterior MCC (pMCC) to pregenual (pg) ACC, orbitofrontal cortex, putamen, thalami, posterior cingulate, and prefrontal areas, and in the brainstem. CBF changes in the poststimulation period correlated with pain relief [151]. | |
| [18F]FDG micro-PET (mPET) | Changes in brain activity were observed in the striatum, thalamic area, and cerebellum [152]. | |
| TENS | ||
| Area of interest | Imaging method | Imaging changes |
| Carpal tunnel syndrome |
fMRI | Within 0 to 25 minutes after TENS treatment, significant fMRI signal decrease for digit 2 was observed in the secondary somatosensory regions, ipsilateral primary motor cortex (M1), contralateral supplementary motor cortex (SMA), contralateral parahippocampal gyrus, contralateral lingual gyrus, and bilateral superior temporal gyrus. Within 30 to 35 minutes after TENS treatment, a significant fMRI signal decrease for digit 3 was detected in the contralateral M1 and contralateral SMA only in the TENS group [153]. |
| rTMS | ||
| Area of interest | Imaging method | Imaging changes |
| Primary motor cortex | MRI DTI | The rTMS-effective group had a higher delineation ratio of the corticospinal tract (CST) (p = 0.02) and the thalamocortical tract (TCT) (p = 0.005) than the rTMS-ineffective group. Results suggest that the TCT also plays a role in pain reduction via rTMS of the primary motor cortex, and that the efficacy of rTMS is predictable by fiber tracking [154]. |
DBS, deep brain stimulation; MCS, motor cortex stimulation; SCS, spinal cord stimulation; DRG, dorsal root ganglion; TENS, transcutaneous electrical nerve stimulation; rTMS, repetitive transcranial magnetic stimulation; VS/ALIC, ventral striatum/anterior limb of the internal capsule; VPL, ventroposterolateral thalamic nucleus; VPM, ventral posteromedial nucleus; PVG, periventricular gray area; ACC, anterior cingulate cortex; VT, ventral tuberal nucleus; DPN, [11C]diprenorphine; PET, positron emission tomography; mPET, micropositron emission tomography; FDG, fluorodeoxyglucose; fMRI, functional magnetic resonance imaging; MEG, magnetoencephalography; MRI, magnetic resonance imaging; DTI, diffusion tensor imaging; BOLD, blood-oxygenation-level-dependent; SPECT, single-photon emission computer tomography; H-MRS, proton magnetic resonance spectroscopy; rCBF, regional cerebral blood flow; GABA, gamma-aminobutyric acid; GFS, ganglionic field stimulation; aMCC/pMCC, anterior/posterior midcingulate cortex; SMA, supplementary motor cortex; CST, corticospinal tract; TCT, thalamocortical tract.