Neuroinflammatory pathways have been implicated in a variety of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), but the vast majority of this evidence is from animal or ex vivo human studies. In vivo measurement of the 18 kDa translocator protein (TSPO) has become possible with [11C]-PBR28 PET imaging. Briefly, TSPO expression is increased when microglial are activated. Cross-sectional studies have demonstrated that [11C]-PBR28 uptake is elevated in ALS compared to controls, is correlated with upper motor neuron severity, and that microglial activation is associated with more severe upper motor neuron disease and faster disease progression. We are only aware of a single 6-month study of 10 patients evaluating longitudinal change of [11C]-PBR28 in ALS. We hypothesize that we will observe increased [11C]-PBR28 uptake over a 6-month period in motor cortex and prefrontal cortex in ALS. This portion of the study will be performed at UPenn only.

A dose of ≤ 20 mCi (approximate range for most studies is anticipated to be 5-20 mCi) of [11C]-PBR28 will be administered by IV injection to the patient under the direct supervision of a Nuclear Medicine Authorized User. A lesser activity may be injected if, in the opinion of a nuclear medicine authorized user complete imaging data could be generated.

Subjects will undergo an approximately 90 minute dynamic PET/CT scan over the brain starting at approximately the same time as the [11C]-PBR-28 injection. Scans will be acquired using a Philips PET/CT time-of-flight Ingenuity scanner (Philips Healthcare, Cleveland, OH, USA). At the end of the dynamic imaging the participant will be allowed to get off the scanner.

Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.

Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.

Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.

Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.

Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.

Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.

[18F]-FDG signal measurement (Standard Uptake Value or SUV) of [18F]-FDG PET for ALS patients at PENN only.