The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer's Disease-Review of Literature and Interesting Images

Abstract

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer's disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided.

Keywords: 18F-FDG; Alzheimer’s disease; PET; diagnostic imaging; molecular imaging; neurocognitive disorder; nuclear medicine; precision medicine; quantification.

Figure 1

Normal study. Sixty-seven year old female patient with deteriorating cognition and multiple vascular risk factors for assessment for vascular dementia. (a) and (b) [18F]FBP shows good contrast between grey and white matter in all sections of the brain with no obvious evidence of beta amyloid plaque disease. This suggests that the diagnosis/development of Alzheimer’s disease is less likely. (c) MRI brain scan (multiplanar and multi sequence acquisitions) shows no significant T2 signal abnormality or restricted diffusion to suggest space occupying lesion, infarction, or ischemic change. (figures are courtesy RLBUHT Hospital database).

Figure 2

Normal study. Fifty-seven year old female patient memory problems/loss and confusion with a query of Alzheimer’s disease. (a) and (b) Technetium-99m HMPAO-SPECT brain Scan [^99mTc]HMPAO-SPECT brain scan. Brain scan showed mildly reduced perfusion to both temporal and both parietal lobes (yellow arrows) with relatively better perfusion anteriorly. Reduction of cerebral blood flow in these regions is commonly seen in patients with early Alzheimer’s dementia rather than vascular dementia. However, in view of the subtle nature of the appearances on the [^99mTc]HMPAO-SPECT brain scan, the [¹⁸F]FBP brain scan was performed to identify beta amyloid plaque disease and to give a higher confidence for AD diagnosis or suggest vascular aetiology. (c) Color coded [¹⁸F]FBP scan. (d) Grey scale [¹⁸F]FBP scan shows good contrast between grey and white matter in sections of the brain and no obvious evidence of beta amyloid plaque disease. This means that the likelihood of developing AD is low and as such the overall findings are more suggestive of vascular aetiology rather than early AD. (Figures are courtesy RLBUHT Hospital database).

Figure 3

Abnormal study. Seventy-four year old male patient with a history of short term memory problems/gradual memory decline for some time and a query of dementing pathology. (a) and (b) [18F]FBP shows loss of contrast between grey and white matter in all sections of the brain. The scan is suggestive of beta-amyloid plaque deposition and in a patient with the above clinical presentation is suggestive of early AD. (c) MRI brain scan (multiplanar and multi sequence acquisitions) with some motion artefact shows generalised age appropriate cerebral atrophy, proportionate symmetrical temporal lobe atrophy, and corresponding dilatation of the cerebrospinal fluid (CSF) spaces. Moderate to marked periventricular T2 white matter hyperintensities likely to represent chronic small vessel ischemic changes. No diffusion restriction or space occupying lesions were identified. (Figures are courtesy RLBUHT Hospital database.).

Figure 4

Abnormal study. Sixty-eight year old female patient with speech difficulties, deficits in memory, and visuospatial abilities. (a) [^99mTc]HMPAO-SPECT brain scan shows asymmetrical heterogenous reduced perfusion to both parietal and temporal lobes (worse on the left side) as with involvement of the frontal lobes identified by the yellow arrows. Normal areas of temporal perfusion were noted in between the abnormal parietal and frontal areas. In a patient with cognitive impairment, the findings indicate patterns of cerebral blood flow commonly seen in patients with mixed dementia, i.e., Alzheimer’s disease with vascular dementia. (b) Color coded [¹⁸F]FBP scan. (c) Grey scale [¹⁸F]FBP scans show loss of contrast between grey and white matter in all sections of the brain suggestive of beta-amyloid plaque deposition/disease. In conjunction with the [^99mTc]HMPAO-SPECT brain scan, the overall findings are again suggestive of vascular as well as beta amyloid plaque disease (early AD), making the diagnosis mixed type AD. (Figures are courtesy RLBUHT Hospital database).