Simultaneous FDG-PET/MRI detects hippocampal subfield metabolic differences in AD/MCI

Abstract

The medial temporal lobe is one of the most well-studied brain regions affected by Alzheimer's disease (AD). Although the spread of neurofibrillary pathology in the hippocampus throughout the progression of AD has been thoroughly characterized and staged using histology and other imaging techniques, it has not been precisely quantified in vivo at the subfield level using simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI). Here, we investigate alterations in metabolism and volume using [ 18 F]fluoro-deoxyglucose (FDG) and simultaneous time-offlight (TOF) PET/MRI with hippocampal subfield analysis of AD, mild cognitive impairment (MCI), and healthy subjects. We found significant structural and metabolic changes within the hippocampus that can be sensitively assessed at the subfield level in a small cohort. While no significant differences were found between groups for whole hippocampal SUVr values (p = 0.166), we found a clear delineation in SUVr between groups in the dentate gyrus (p = 0.009). Subfield analysis may be more sensitive for detecting pathological changes using PET-MRI in AD compared to global hippocampal assessment. The medial temporal lobe (MTL), which includes the hippocampus and adjacent entorhinal and perirhinal cortices, is critical to memory formation and retrieval and well known to be involved in most forms of Alzheimer's disease (AD) 1. Neurodegeneration within the MTL thus leads to memory impairments in both AD and amnestic mild cognitive impairment (MCI) 2. This neurodegeneration results in atrophy that can be measured using structural MRI 3 and a reduction in metabolism of [ 18 F]fluoro-deoxyglucose (FDG) in PET imaging 4. The hippocampus is divided into subfields distinct in cytoarchitecture, connectivity, and function in both health and disease 5-9. From external to internal, relevant MTL subregions include perirhinal cortex (PRC), entorhinal cortex (ERC), subiculum (SUB), cornu ammonis fields 1-4 (CA1-4), and dentate gyrus (DG) (Fig. 1). ERC connects the neocortex to the hippocampus by primarily projecting to DG, which in turn projects to CA3, then to CA1 and to SUB, and back to ERC 10. AD neurofibrillary pathology spreads through the hippocampus as disease progresses. In the earliest stages of AD, neurofibrillary pathology is limited to the transentorhinal (part of PRC) and entorhinal cortices 11. As AD progresses, hippocampal involvement begins with neuron loss and tau tangles in CA1/2, progresses to CA3/4 and then to SUB and DG 12,13. AD symptoms are strongly correlated with the extent of hippocampal neurofibrillary involvement 14,15. Thus, image-based subfield measurements could be non-invasive biomarkers for diagnosis and staging of AD. Several MRI studies have shown that hippocampal subfield morphological measurements detect sensitive differences between AD, MCI, and healthy subjects. Some studies have found that CA1 and DG volume is reduced in AD subjects compared to MCI subjects 14,16 and may be a biomarker of presymptomatic AD 17-23. Development...

Hippocampal subfield imaging and fractional anisotropy show parallel changes in Alzheimer's disease tau progression using simultaneous tau‐PET/MRI at 3T

“…FA/MD was similarly computed across the subfields and PHG. We have previously validated these methods with analysis of FDG‐PET and volume measures across hippocampal subfields in a separate AD cohort 14 (Figure 1).…”

“…18 Our prior work has used simultaneous PET-MR and hippocampal segmentation techniques to analyze subfield-specific measures of volume and glucose metabolism. 14 However, few studies have investigated tau uptake in vivo on a hippocampal subfield-specific level in concert with volumetric and microstructural measurements whichgiven the characteristic progression of tau with disease severity-is important for the study of onset and real-time progression of AD.…”

“…12,13 Here, we use time-of-flight (TOF) imaging capability, 2D erosion for minimizing partial volume effects, and a custom hippocampal atlas to enable subfield segmentation of PET images. 14 Diffusion tensor imaging (DTI) MRI has also been used to study connectivity and white matter degradation in the brain, complementary to structural MRI volume reductions in AD. 15,16 DTI is important to study in the context of AD to evaluate white matter connectivity within functionally connected regions of the medial temporal lobe.…”

The use of positron emission tomography/magnetic resonance imaging in dementia: A literature review

“…Limited studies have investigated hippocampal structural and metabolic changes using PET/MRI. Carlson et al 40 . employed 18 F‐FDG‐PET/MRI and automated hippocampal subfield‐segmentation in AD/MCI patients, finding significantly lower dentate gyrus and cornu ammonis volumes, and reduced dentate gyrus FDG‐SUVr compared to controls.…”

“…58 Limited studies have investigated hippocampal structural and metabolic changes using PET/MRI. Carlson et al 40 affecting individual baseline values. 59 Additionally, AD/MCI patients were grouped together to increase statistical power, which may influence the applicability of these findings to patients at varying disease stages.…”