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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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[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.
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f0005: [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.

Mentions: Visual inspection of SUVR60–90 min images revealed regional increase in the precentral gyrus in patients with ALS with limb-onset, and not in the patients with ALS with bulbar-onset disease. See Fig. 1A for individual data projected onto the MNI template and Fig. 1B for means for the ALS group, including comparisons between limb- and bulbar-onset patients, and the control group. Patients with limb-onset weakness showed increased binding in the precentral gyri and patients with bulbar-onset weakness showed increased binding in the brainstem (Fig. 1B, top two rows).


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)

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

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

f0005: [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.
Mentions: Visual inspection of SUVR60–90 min images revealed regional increase in the precentral gyrus in patients with ALS with limb-onset, and not in the patients with ALS with bulbar-onset disease. See Fig. 1A for individual data projected onto the MNI template and Fig. 1B for means for the ALS group, including comparisons between limb- and bulbar-onset patients, and the control group. Patients with limb-onset weakness showed increased binding in the precentral gyri and patients with bulbar-onset weakness showed increased binding in the brainstem (Fig. 1B, top two rows).

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