PET/MRI Reproducibly Discriminates Between Individuals With and Without Chronic Low Back Pain
Key findings
- In 2015, Massachusetts General Hospital researchers demonstrated that patients with chronic low back pain showed increased thalamic uptake of [11C]-PBR28, a radioligand that binds to the translocator protein (TSPO), on PET/MRI
- This replication study demonstrated the same thalamic neuroinflammation signature on PET/MRI was greater in an independent cohort of 15 patients with chronic low back pain than in 18 controls
- Pooled analyses of the original and replication datasets confirmed that the mean thalamic TSPO signal discriminates between pain patients and controls, but other features had comparable impact (e.g., maximum, kurtosis, entropy and energy)
- Exploration of a full set of radiomic features, including those from additional brain regions, might improve the ability to identify patients with chronic low back pain
- The observations also support investigation of neuroinflammation as a therapeutic target for chronic pain
In 2015, Massachusetts General Hospital researchers were the first to demonstrate in humans what numerous animal studies previously suggested: a role for neuroinflammation in chronic pain. In Brain, they reported that a small number of patients with chronic low back pain showed increased thalamic uptake of [11C]-PBR28, a radioligand that binds to the translocator protein (TSPO), on integrated positron emission tomography/magnetic resonance imaging (PET/MRI).
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Expression of TSPO is low in the healthy central nervous system but becomes dramatically upregulated during neuroinflammatory responses.
Subsequently, Mass General researchers reported similar results for patients with other pain conditions, including fibromyalgia and migraine with aura. Now, Marco L. Loggia, PhD, director of the Pain and Neuroinflammation Imaging Lab at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Angel Torrado-Carvajal, PhD, a former postdoctoral fellow in the lab, and colleagues have replicated the prior results in chronic low back pain. In Pain, they also present results suggesting the radiomic features of the TSPO signal deserve full exploration.
Replication Study
Replication data came from 15 patients with chronic low back pain and 18 controls without a history of back pain who underwent brain PET/MRI with administration of [11C]-PBR28. Both region-of-interest and voxel-wise analyses replicated the original observation of thalamic TSPO signal elevations in back pain patients compared with controls (P<0.05).
Imaging Feature Assessment
The distribution of the elevated TSPO signal is different across subtypes of chronic pain patients, Mass General researchers have found. For example, although chronic low back pain was linked to thalamic neuroinflammation, patients with migraine or fibromyalgia demonstrated cortical increases in TSPO signal, with little or no involvement of subcortical structures.
These findings suggest a tantalizing possibility: perhaps region-specific TSPO imaging could be used to develop objective biomarkers for different pain conditions. As a preliminary step toward this goal, the current study assessed whether features beside the mean uptake in PET signal could discriminate patients with chronic low back pain from controls.
The researchers pooled the original and replication cohorts, a total of 25 patients with chronic low back pain and 27 controls. They used a radiomics approach to extract various image features from the full dataset, then used novel methods to rank feature importance.
These analyses confirmed that the mean thalamic TSPO signal discriminated between back pain patients and controls, but other features had comparable or even slightly greater impact (e.g., maximum, kurtosis, entropy and energy). Classification methods that included features other than the mean had an accuracy of 70%, sensitivity of 80% and specificity of 80%.
Looking Ahead
This research suggests that the thalamic TSPO signal contains a richness of information that the mean fails to capture completely. It seems likely that exploring a full set of radiomic features, including those from additional brain regions, would improve the ability to identify patients with chronic low back pain.
The observations also support exploration of immunomodulatory therapies as a therapeutic approach for chronic pain.
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