Functional MRI, single-photon emission computed tomography, PET, and magnetic resonance spectroscopy have identified brain structures activated by pain. These include the primary and secondary somatosensory cortices, the insula, the anterior cingulate, the thalamus, the dorsal lateral prefrontal cortex, and the basal ganglia.
Similar studies have indicated fibromyalgia patients have abnormal activation in these regions, both at baseline and in response to painful stimuli.
Diffusion-weighted imaging (DWI) measures the restriction of water diffusion (the apparent diffusion coefficient or ADC) in the brain. Diffusion tensor imaging (DTI) measures the directional diffusion properties of water (fractional anisotropy or FA), and therefore, the integrity of organized tissue microstructures.
Dr. Pia C. Sundgren and Dr. Daniel J. Clauw, with colleagues at the University of Michigan in Ann Arbor, used DWI and DTI to look for cerebral abnormalities in fibromyalgia patients, versus healthy controls (Acad. Radiol. 2007;14:839–46).
The researchers studied 19 fibromyalgia patients (16 women), aged 20–57 years, and 25 pain-free controls (19 women). All subjects underwent MRI (1.5 T) including pre- and postcontrast enhanced axial and sagittal T1-weighted images, axial T-2 weighted images (with fat saturation), axial fluid attenuated inversion recovery (FLAIR) images, diffusion-weighted images, and postcontrast coronal T1-weighted images. The images were evaluated for brain volume loss, abnormal signal, abnormal contrast enhancement, abnormal diffusion, the presence of hemorrhage or mineralization, or other abnormalities.
First, the researchers developed whole-brain, gray matter-only, and white matter-only ADC histograms for each patient and control. Then histograms by group (fibromyalgia patients and controls) were calculated. ADC and FA maps also were calculated. Both ADC and FA are quantitative, with normal brain values of ADC around 0.7 × 10–3 mm
DTI maps were registered with postcontrast axial T1-weighted images. Standardized 50 mm
Clinical pain was assessed immediately before the DWI and DTI scans using a 10-cm visual analog scale. Pressure pain threshold was assessed before the DWI and DTI scans. Discrete pressure stimuli were applied to the subject's left thumbnail. Pain intensity ratings were recorded. Patients with fibromyalgia also were given the Center for Epidemiologic Studies Depression Scale questionnaire and the Spielberger's State-Trait Personality Inventory anxiety questionnaire. Specific cognitive beliefs about pain and control over pain were assessed using the Beliefs About Pain Control Questionnaire.
FA values were significantly less in the right thalamus for fibromyalgia patients, compared with controls. No differences were found in any other locations.
The differences in FA in the thalamus prompted the researchers to examine the relationship between the severity of fibromyalgia and FA within the group. Patients with more severe pain had lower FA values. Fibromyalgia patients tend to attribute their pain to an external event like minor trauma. The investigators found a negative correlation between the belief in an “external” cause of their pain and the FA values. This indicates these low right-thalamic values also were tied to a cognition known to be negatively associated with prognosis in chronic pain. Lower right-thalamic FA values also were tied to greater numbers of tender points, higher levels of depression, and a low pain threshold.
“The abnormalities that we've identified using this technique are actually less pronounced than what you'd find with [functional MRI] or PET or proton spectroscopy or other modalities. All of those modalities identify objective differences between fibromyalgia patients and controls with respect to pain processing regions,” said Dr. Clauw. “What you really find with all of those functional imaging techniques—this one included—they all give you different and somewhat complementary information. … There really is something wrong going on in the brains of these patients with fibromyalgia,” said Dr. Clauw.
The focal nature of these findings suggest these abnormalities are caused by ongoing demyelination or axonal injury but are rather due to neuronal dysfunction.
“If the tissue is less organized or the axons are dysfunctional, it might be seen as a reduction in the main directionality combined with alterations in the other diffusion directions resulting in a more round and less sphere/ellipsoid appearance of the diffusion directionality as can be seen in a more isotropic environment. This idea can be supported by the normal ADC value found here in the same region,” they wrote.
ADC and FA maps (top left and right) of a fibromyalgia patient: On the same FA map (bottom left), red white matter tracts indicate greater anisotropy. On another FA map (bottom right), there is less anisotropy in the dorsomedial aspect of right thalamus. IMAGES COURTESY DR. PIA C. SUNDGREN
