Clinical and Technical Considerations for Brain PET Imaging for Dementia

Cerebral Glucose Metabolism

The brain metabolizes glucose, and ¹⁸F-FDG is a glucose analog. The cerebral metabolic rate is an indicator of normal versus declining brain function. In patients with cognitive impairment, detection of decreased cerebral metabolic rate can be valuable, and an ¹⁸F-FDG scan may allow members of the health-care team to follow and manage patients as they progress from mild cognitive impairment to dementia (2). ¹⁸F-FDG scanning plays an important role in all brain imaging applications and serves as a valuable marker to differentiate AD from other causes of dementia, such as frontotemporal dementia, because an ¹⁸F-FDG scan can indicate the brain regions with a decreased cerebral metabolic rate (Fig. 1) (5).

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FIGURE 1.

Normal (column 1) and abnormal (column 2) ¹⁸F-FDG PET findings and normal (column 3) and abnormal (column 4) ¹⁸F-florbetapir PET findings.

Amyloid Protein Imaging

It has been suggested that deposition of amyloid protein in the brain (β-amyloid accumulation) is a slow process and may extend for decades before clinical symptoms are detected (4). Currently, investigational drugs to treat AD are focused mainly on arresting the progression of amyloid protein deposition, which is why it is so important to have a way to image β-amyloid accumulation over time. Over the last few decades, several radiopharmaceuticals have been developed with the ability to detect amyloid in the brain. The first was ¹¹C-Pittsburgh compound B. The biggest limitation for this radiopharmaceuticals was the short half-life of ¹¹C (20 min) and the need for an onsite cyclotron (6). More recently, 3 radiopharmaceuticals that use ¹⁸F as the radioactive label have been developed (half-life of 110 min) and have received Food and Drug Administration approval. The first to receive approval was ¹⁸F-florbetapir (Amyvid; Eli Lilly), the next was ¹⁸F-flutemetamol (Vizamyl; GE Healthcare), and the last was ¹⁸F-florbetaben (Neuraceq; Piramal). It is important to remember, with these imaging studies, that just because radiopharmaceutical uptake may be observed in the brain does not mean the patient has AD. However, negative findings on an amyloid scan suggest a low likelihood that the cognitive impairment is caused by AD (Fig. 1) (2). With any PET radioligand, off-target uptake may be observed. Thus, the reader must be adequately trained in the interpretation of images from these specific compounds.

Tau Protein Imaging

The presence of neurofibrillary tangles of hyperphosphorylated tau proteins is also a hallmark of AD (4). In the healthy brain, tau proteins should bind to microtubules inside neurons to help support those cells and their functions; however, in AD, changes to the chemistry of the brain can result in tau protein aggregation rather than binding to the microtubules. Over time, these aggregates form neurofibrillary tangles that disrupt communication between neurons (7). More recent work suggests that these tau tangles may disrupt communication between the nucleus and the body of neurons in the brain, adding to possible communication disruption mechanisms and further exacerbating neurodegeneration (8). Imaging with tau PET agents has shown a correlation between the severity of dementia and tau pathology (9).

Both amyloid and tau imaging agents have corroborated well with the Braak and Braak stages of amyloid protein and tau protein deposition of AD, starting from the medial temporal regions in the early stages of the disease and moving to more widespread neocortical accumulation in the later stages (10). Currently, several tau PET radiopharmaceuticals are being studied in clinical trials, but none has been approved by the Food and Drug Administration or is being used routinely in clinical practice.

Patient Preparation

Patient preparation before a brain PET scan for clinically suspected dementia should start with a detailed conversation with the patient and family members. Issues to be discussed include patient history, symptoms, patient or physician concerns, and instructions on how the scanning will be performed. Through this discussion, the technologist will be able to assess the brain function of the patient and have an idea of how well the patient can cooperate during imaging. This also gives family members a chance to express their concerns and raise questions. Depending on the type of imaging ordered, specific guidelines may need to be followed for patient preparation.

For an ¹⁸F-FDG brain PET/CT scan, the patient’s environment before scanning is important. The patient needs to be in a quiet room with low ambient light and few stimuli for at least 30 min before radiopharmaceutical injection and throughout the 30- to 60-min uptake time. An intravenous line needs to be placed at least 10 min before the radiopharmaceutical injection, and a blood glucose test should be performed (i.e., a blood glucose level under 200 mg/dL is recommended before injection of the radiopharmaceutical). The patient must have had nothing to eat or drink for at least 4 h before the study (other than water and daily medication taken with water) (11).

When brain PET/CT is done using amyloid radiopharmaceuticals, little patient preparation is needed. An intravenous line should be established and the patient made comfortable. Environmental stimulation is not a concern, and patients may move freely in the uptake room as desired. They may also read or watch television. There are no food restrictions, and all daily medication may be taken.

Injection of Radiopharmaceuticals and Uptake Time Guidelines

After an intravenous line is in place, the shortest intravenous extension line available should be used when injecting the radiopharmaceuticals. The radiopharmaceutical should not be injected if any particulate matter is present. All radiopharmaceuticals should be injected as a slow bolus (within 40 s) followed by a 10- to 20-mL saline flush of the intravenous line. Of note, unlike ¹⁸F-FDG, radiopharmaceuticals targeting amyloid do not allow for volume adjustment or flushing of the radiopharmaceutical syringe with saline. Details on the activity to administer and the uptake time are presented in Table 1. Once the injection is complete, the intravenous line can be removed.

Patient Positioning

At the end of the uptake time, the patient is asked to void. The mental status of the patient should be kept in mind and plenty of time allowed for use of the restroom and positioning of the patient on the scanner. The PET scan should be started on time to optimize the workflow in the PET center.

Proper head positioning for brain imaging is truly important. Before patients are positioned on the table, all items should be removed from their pockets, jewelry should be removed from the neck up, and hearing aids should be removed. The appropriate radiolucent head holder should be installed, as mild rotation or movement of the head can interfere with image interpretation. The patient is positioned supine on the table with the arms cross over the chest. The vertex of the head should reach the most superior point of the head holder. A foam wedge is used under the knees for lower back support, an arm strap to help stabilize the arms, and any other accessories needed to make the patient as comfortable as possible. Taking the time to complete these steps is essential to reduce body movement during the scan.

The laser lights on the PET/CT scanner are used to carefully position the head such that there is no rotation. The canthomeatal line should be oriented in the vertical position. Once the head is in the desired position, rolled washcloths or foam wedges are used to fill any gaps between the patient’s head and the head holder. A head strap is secured across the forehead and the positioning rechecked with the laser lights (Fig. 2). The whole brain and cerebellum need to be positioned in the field of view. Finally, the vertical placement of the table is checked to ensure that the brain is centrally located in the field of view. The patient should be given clear, detailed instructions on what to expect and the importance of remaining as still as possible.

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FIGURE 2.

Proper head positioning using radiolucent holder with stabilizing accessories.

Imaging

Depending on the imaging equipment available and the clinical indication, a single-field-of-view static image or a multiple sequential images of the same field of view, known as dynamic imaging, are performed. Static imaging is useful when the SUV is of interest. To calculate SUV, the technologist must document the patient’s accurate weight, height, and the actual amount of radiopharmaceutical that was injected into the patient. Dynamic imaging is useful when quantification of the regional metabolic rate is of interest (11). When dynamic imaging is available, it is the preferred method; however, it is generally used in research settings because the scan can take up to 180 min, with imaging starting at the time of injection. PET brain images typically are reconstructed into a 128 × 128 or 256 × 256 matrix. Iterative reconstruction is routinely used. Other reconstruction settings can be set according to institutional and camera manufacturing guidelines. Table 2 presents scan durations for each radiopharmaceutical. Often, multiple acquisitions are obtained during the scan. For example, 2 static images of the brain lasting 5 min each are typically acquired for each ¹⁸F-florbetapir scan.