Simplified quantification of PIB amyloid imaging PET studies

Image-Derived Input Function for Brain PET Studies: Many Challenges and Few Opportunities

“…In these studies, IDIF was simply the raw carotid time-activity curve obtained by placing ROIs (regions-of-interest) over the carotid arteries, without any correction for partial volume effect artifacts. Comparing to the total distribution volume (V T ) obtained with arterial sampling in [ 11 C]-PIB PET study, Lopresti et al (2005) found an overestimation of V T by a factor of two with the use of the raw carotid time-activity curves without correction for partial volume effect.…”

Impact of amyloid imaging on drug development in Alzheimer's disease

“…Note that the MCI group displays DVR values ranging from control-like (<1.4) to AD-like (>2.0) with a few MCI subjects displaying intermediate DVR values (between 1.5 and 2.0). Adapted from [22]. Schematic of the production of Aβ and Aβ (1-42) peptides from amyloid precursor protein (APP) via sequential β-and γ-secretase cleavages.…”

“…Thus from an AD diagnostic perspective, one would look for the presence of Aβ deposits or the binding of an Aβ imaging agent in specific brain regions, and the absence of binding in other regions. However, the presence of significant Aβ deposits in specific brain regions does not necessarily indicate the presence or severity of clinical AD, as some control and MCI subjects contain concentrations of Aβ plaques in their brains as high as contained in the brains of AD subjects (Fig 5) [14,22,23]. The coincidence of high Aβ loads and the absence or lack of extensive cognitive deficits in some subjects could be interpreted as high resistance to Aβ damage (i.e., a high cognitive reserve) or could indicate that excessive Aβ has not been present for a sufficiently long time in some subjects to cause as much damage as in AD subjects.…”

“…PiB binding requires an extended β-pleated sheet structure found in Aβ fibrils and plaques in order to bind with high affinity. Hence if one wishes to follow the amount of insoluble Aβ in AD brain tissue, a radiotracer such as [ 11 C]PiB with a high selectivity for insoluble Aβ likely would prove useful in vivo in human brain [16,22].…”

“…Imaging technologies such as [ 11 C]PiB that can detect Aβ deposits are under development by several groups [16,90,91,92]. The exact point in the evolution of Aβ pathology at which these imaging technologies will become useful remains to be determined, but early evidence suggests that detection of extensive Aβ deposition is possible during the mild cognitive impairment (MCI) stage [22] and perhaps prior to the onset of symptoms (Fig 5) [14,23]. …”