Head-to-Head Comparison of PET and ASL-MRI BBB Permeability measurements for Dementia Imaging: Study Protocol


Head-to-Head Comparison of PET and ASL-MRI BBB Permeability measurements for Dementia Imaging: Study Protocol

Moyaert, P.; Oyeniran, O.; Dassanayake, P.; Liu, L.; Petr, J.; Achten, E.; Mutsaerts, H.; Hicks, J.; Guenther, M.; Anazodo, U.

Aim/Introduction: Blood-brain barrier (BBB) breakdown has been suggested to be an early biomarker of cognitive dysfunction. Currently, PET using [15O]-water and [11C]-Butanol is the standard for measuring BBB permeability. Arterial Spin Labeling (ASL) MRI is a promising alternative as no exogenous contrast is used. This study will validate BBB-ASL MRI by comparing it with PET and assess if BBB-ASL indeed robustly quantifes BBB permeability. Here we present our protocol and preliminary results using image-derived input function (IDIF) to quantify BBB-PET, noninvasively. Materials and Methods: Integrated PET/MR imaging provides a unique opportunity to assess - for the frst time - the ability of ASL to noninvasively image BBB permeability by comparing it to PET in the same subjects and under the same conditions. First, the BBBASL (1) sensitivity in pigs will be investigated by mimicking BBB dysfunction using an Aquaporin-4 inhibitor that will block the fow of water (2). Absolute BBB measurements (as obtained by arterial sampling) will be compared to BBB-ASL measurements. Second, to determine whether any changes in BBB permeability measured by MRI translate to humans, permeability measured by PET and MRI in 10 ischemic stroke patients will be compared. Third, the accuracy of BBB-ASL will be assessed in humans with subtle BBB dysfunction in 12 patients with Alzheimer’s disease, 12 with mild cognitive impairment and 12 age-matched controls. Results: While the preclinical validation studies are underway, we evaluated our PET/MRI IDIF approach (3) for absolute PET quantifcation to eliminate the need for arterial sampling in the two clinical studies. In three pigs, the [15O]-water PET/MR IDIFs were similar to arterial-sampled input functions with area-under-the-curve ratio (IDIF/AIF) of 1.03 - 1.1, demonstrating the potential of IDIF for BBB permeability estimates. Conclusion: The goal of this work is twofold. On one hand, it will demonstrate the potential of ASL measurements as a reliable imaging approach for assessing BBB permeability changes, particularly for early dysfunction detection in otherwise healthy individuals. On the other hand, it will optimize PET for clinical use by integrating IDIF for quantifcation, thereby representing a clinically viable alternative to arterial blood sampling.

  • Contribution to proceedings
    Annual Congress of the European Association of Nuclear Medicine, 15.09.2022, Barcelona, Spain, 550-550
    DOI: 10.1007/s00259-022-05924-4
  • Poster
    Annual Congress of the European Association of Nuclear Medicine, 15.09.2022, Barcelona, Spain

Permalink: https://www.hzdr.de/publications/Publ-35415
Publ.-Id: 35415