PET imaging with oxygen-15 indirectly measures blood flow to the brain. In this method, increased radioactivity signal indicates increased blood flow which is assumed to correlate with increased brain activity. Because of its 2-minute half-life, oxygen-15 must be piped directly from a medical cyclotron for such uses, which is difficult.
PET imaging with FDG takes advantage of the fact that the brain is normally a rapid user of glucose. Standard FDG PET of the brain measures regional glucose use and can be used in neuropathological diagnosis.
Brain pathologies such as Alzheimers disease (AD) greatly decrease brain metabolism of both glucose and oxygen in tandem.  Therefore FDG PET of the brain may also be used to successfully differentiate Alzheimers disease from other dementing processes, and also to make early diagnoses of Alzheimers disease. The advantage of FDG PET for these uses is its much wider availability. Some fluorine-18 based radioactive tracers used for Alzheimers include florbetapir, flutemetamol, Pittsburgh compound B (PiB) and florbetaben, which are all used to detect amyloid-beta plaques, a potential biomarker for Alzheimer's in the brain.
PET imaging with FDG can also be used for localization of "seizure focus". A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [C]raclopride, [F]fallypride and [F]desmethoxyfallypride for dopamine D/D receptors; [C]McN5652 and [C]DASB for serotonin transporters; [F]mefway for serotonin 5HT receptors; and [F]Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses.
PET may also be used for the diagnosis of hippocampal sclerosis, which causes epilepsy. FDG, and the less common tracers flumazenil and MPPF have been explored for this purpose. If the sclerosis is unilateral (right hippocampus or left hippocampus), FDG uptake can be compared with the healthy side. Even if the diagnosis is difficult with MRI, it may be diagnosed with PET.
The development of a number of novel probes for non-invasive, in-vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging close to clinical use. The earliest amyloid imaging probes included [F]FDDNP developed at the University of California, Los Angeles and Pittsburgh compound B (PiB)developed at the University of Pittsburgh. These probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [C]polymethylpentene (PMP) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for premortem diagnoses of AD and help to monitor AD treatments. Avid Radiopharmaceuticals has developed and commercialized a compound called florbetapir that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.