Quantitative PET/MRI Framework to Identify LATE

An abstract on LATE describes a quantitative 18F-FDG PET– and MRI-volumetry–based framework intended to help identify LATE and differentiate it from Alzheimer’s disease, with outputs including stereotactic surface projection (3D-SSP) templates, z-score maps, and z-score product indices.

The report presents the approach as using imaging biomarkers to support an objective, pattern-based categorization. The framework was applied to a retrospective clinical series to categorize cases as probable LATE, probable mixed LATE+AD, or probable AD.

The pipeline is described as beginning with autopsy-confirmed datasets for LATE neuropathologic change (n = 6) and Alzheimer’s disease neuropathologic change (n = 32), from which 3D-SSP PET templates were created. Z-score maps were generated relative to 20 amyloid PET–negative control cases. Using the autopsy-derived z-score maps, z-score product indices were generated and applied to 944 clinical 18F-FDG PET studies referred from cognitive disorder clinics in a tertiary care center. Quantitative MRI volumetry comparisons were performed across the resulting groups. As described, the workflow pairs autopsy-derived pattern templates with quantitative PET/MRI measures to support probabilistic classification in a routine-referral cohort.

Within the clinical series, 13% of cases were characterized as probable LATE, subdivided into 2.4% labeled as pure LATE and 10.6% labeled as LATE with Alzheimer’s disease. It also reports that 23.7% of cases were characterized as probable Alzheimer’s disease without LATE. A smaller pure LATE-labeled subgroup sits alongside a larger mixed-pathology-labeled subgroup under the same classification framework.

For MRI volumetry, the report describes differing regional patterns across LATE-labeled subgroups, stating that the medial temporal lobe was most affected in pure LATE cases. In contrast, the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE and Alzheimer’s disease cases. Subgroup analysis of the probable LATE+AD group demonstrated additive or synergistic effects, with approximately three quarters of cases exhibiting concordant lateralized metabolic brain changes—predominantly left-sided—based on LATE and AD z-score products. A similar pattern of left-dominant brain atrophy was observed on MRI volumetry. These MRI observations are presented as part of how the framework distinguishes a pure pattern from a mixed-pattern presentation.

On potential utility, the PET and MRI patterns identified in the study could serve as a practical tool to detect potential LATE pathology in patients with cognitive impairment and to support further investigation of LATE. It again ties PET template construction to autopsy-confirmed datasets and describes applying the resulting quantitative indices to the clinical series, with MRI volumetry comparisons across groups.

Key Takeaways:

• The report describes a combined 18F-FDG PET and MRI volumetry framework built around 3D-SSP templates, z-score maps, and z-score product indices derived from autopsy-confirmed datasets and compared against amyloid-negative controls.
• In the clinical series, a minority of cases were categorized as probable LATE (including both pure and mixed LATE+AD labels), while a separate fraction was categorized as probable AD without LATE.
• MRI volumetry patterns were reported to differ by subgroup, with medial temporal involvement highlighted in pure LATE, orbitofrontal and lateral temporal involvement highlighted in mixed cases, and predominantly left-sided concordant hemispheric involvement noted in mixed LATE+AD cases.