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. 2015 Jan 19;7:409-14.
doi: 10.1016/j.nicl.2015.01.009. eCollection 2015.

Increased in Vivo Glial Activation in Patients With Amyotrophic Lateral Sclerosis: Assessed With [(11)C]-PBR28

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Free PMC article

Increased in Vivo Glial Activation in Patients With Amyotrophic Lateral Sclerosis: Assessed With [(11)C]-PBR28

Nicole R Zürcher et al. Neuroimage Clin. .
Free PMC article

Abstract

Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p FWE < 0.05). Region of interest analysis revealed increased [(11)C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [(11)C]-PBR28 as a marker of treatments that target neuroinflammation.

Keywords: ALS, amyotrophic lateral sclerosis; ALSFRS-R, amyotrophic lateral sclerosis functional rating scale revised; Amyotrophic lateral sclerosis; FWE, family-wise error rate; MR, magnetic resonance; Microglia; Motor cortex; Neuroinflammation; PBR-28, peripheral benzodiazepine receptor 28; PET, positron emission tomography; Positron emission tomography; SUV, standardized uptake value; TSPO, 18 kDa translocator protein; UMNB, upper motor neuron burden scale; VC, vital capacity.; [11C]PBR-28.

Figures

Fig. 1
Fig. 1
[11C]-PBR28 SUVR60–90 min images and statistical maps for between-group differences. A. [11C]-PBR28 SUVR60–90 min for 10 individual ALS patients and 10 age- and binding affinity-matched healthy controls. SUVR60–90 min data are projected onto the MNI template in radiological orientation and shown at MNI coordinate z = +64. B. Mean [11C]-PBR28 SUVR60–90 min images for the ALS and control groups, including comparisons between limb- and bulbar-onset patients, shown at MNI coordinates x = −2, y = −20, and z = +64. C. Brain regions that exhibit significantly higher binding in ALS compared to the control group in the voxelwise whole brain analysis, pFWE < 0.05, shown at MNI coordinates x = −8, y = −20, and z = +64.
Fig. 2
Fig. 2
Increased glial activation in primary motor cortex in ALS. Boxplots for [11C]-PBR28 SUVR60–90 min for the precentral gyrus a priori ROI for individuals with ALS and healthy controls. Patients with ALS exhibit significantly increased binding in the motor cortex compared to healthy controls, *p < 0.05.
Fig. 3
Fig. 3
Correlation between glial activation and ALS disease severity. Significant correlations between [11C]-PBR28 binding in the primary motor cortex and ALS disease severity assessed using UMNB and ALSFRS-R were observed. A. Patients with higher UMNB show increased binding in the motor cortex as shown by a positive correlation between UMNB scores and SUVR60–90 min in the right precentral gyrus a priori ROI. B. A negative correlation between the ALSFRS-R and SUVR60–90 min in the right precentral gyrus reflects the fact that patients with a higher disability (lower ALSFRS-R score) show increased PBR28 binding in the motor cortex.

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