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Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28.

Zürcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, Akeju O, Catana C, Rosen BR, Cudkowicz ME, Hooker JM, Atassi N - Neuroimage Clin (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

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.

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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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f0015: 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.

Mentions: Compared to controls, individuals with ALS exhibited significantly increased binding in the bilateral precentral gyri, a priori identified region of interest. ALS (median, range): 1.15, 1.05–1.30, controls: 1.03, 0.99–1.18, p < 0.05 (Fig. 2). In ALS patients, SUVR60–90 min of the right precentral gyrus was positively correlated with UMNB scores, r = 0.69, p < 0.05 (Fig. 3A) and negatively correlated with functional status measured by ALSFRS-R, r = –0.66, p < 0.05 (Fig. 3B). Disease duration did not correlate with SUVR60–90 min in the precentral gyrus.


Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28.

Zürcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, Akeju O, Catana C, Rosen BR, Cudkowicz ME, Hooker JM, Atassi N - Neuroimage Clin (2015)

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.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310932&req=5

f0015: 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.
Mentions: Compared to controls, individuals with ALS exhibited significantly increased binding in the bilateral precentral gyri, a priori identified region of interest. ALS (median, range): 1.15, 1.05–1.30, controls: 1.03, 0.99–1.18, p < 0.05 (Fig. 2). In ALS patients, SUVR60–90 min of the right precentral gyrus was positively correlated with UMNB scores, r = 0.69, p < 0.05 (Fig. 3A) and negatively correlated with functional status measured by ALSFRS-R, r = –0.66, p < 0.05 (Fig. 3B). Disease duration did not correlate with SUVR60–90 min in the precentral gyrus.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

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.

Show MeSH
Related in: MedlinePlus