INTRODUCTION

Motivation:

• Olfactory and memory-related regions (i.e., the entorhinal cortex, piriform cortex, amygdala, and hippocampus) are among the earliest affected regions in Alzheimer's disease (AD).
• Iron accumulation and myelin alteration within these regions may contribute to AD progression.

Challenge:

• Few studies have examined these regions together, and conventional MRI cannot separately evaluate iron accumulation from myelin degeneration in vivo.

Solution:

• Use source-separated quantitative susceptibility mapping (QSM) to independently quantify iron- and myelin-sensitive susceptibility changes throughout olfactory and memory-related regions across the AD spectrum.

MRI ACQUISITION

Cohort:

66 ADRC human volunteers

• 7 Alzheimer's disease (AD)
• 5 mild cognitive impairment (MCI)
• 21 amyloid-positive healthy controls (A+HC)
• 24 amyloid-negative healthy controls (A−HC)
• 9 Parkinson's disease (PD)

MRI sequences analyzed:

• Sagittal T1-weighted → anatomical reference, amygdala segmentation
• Coronal T2-weighted → hippocampal, entorhinal-perirhinal segmentation
• Multi-echo gradient echo → QSM, source separation

MRI PROCESSING

Anatomical segmentations:

• Registered QSM maps to T2 segmentation space

Regions of interest:

• Entorhinal-perirhinal cortices
• Piriform-periamygdaloid cortex (PAC)
• Amygdala
• Whole hippocampus

Source-separated QSM:

• Compared regional median QSM, QSM-χ⁺, and QSM-χ⁻ across diagnostic groups using nonparametric testing.

RESULTS & DISCUSSION

• QSM increased with AD severity (AD→MCI→HC) in the entorhinal-perirhinal (p=0.0067) and amygdala (p=0.0026).
• QSM-χ⁺ increased with AD severity only in the entorhinal-perirhinal cortices (p=0.017).
  • ⇒ suggestive of localized iron accumulation
• QSM-χ⁻ demonstrated significant ordinal changesacross all four olfactory- and memory-related regions.
  • ⇒ suggestive of widespread myelin alteration
• Piriform-PAC QSM-χ⁻ distinguished amyloid-positive and amyloid-negative healthy controls.

CONCLUSION

• We found increased QSM in the entorhinal-perirhinal cortices and amygdala in vivo in AD.
• Source-separated QSM identified localized iron-sensitive susceptibility changes in the entorhinal and perirhinal cortices.
  • ⇒ suggestive of regional iron accumulation
• We found widespread myelin-sensitive susceptibility changes in all four regions (i.e., entorhinal-perirhinal, piriform-PAC, amygdala, whole hippocampus).
  • ⇒ suggesting myelin alteration may be a major contributor to susceptibility changes in early AD
• In all four regions, myelin-associated signal is decreasing (i.e., approaching zero) with AD severity.
  • ⇒ suggestive of possible myelin loss
• QSM-χ⁻ identified significant differences between A+HC and A−HC participants in the piriform-PAC.
• ⇒ indicating sensitivity to early AD pathology
• Source-separated QSM extends beyond conventional QSM, providing improved biological interpretation of susceptibility changes in vivo.