{"paper":{"title":"When Brains Disagree: Biological Ambiguity Underlies the Challenge of Amyloid PET Synthesis from Structural MRI","license":"http://creativecommons.org/licenses/by/4.0/","headline":"Biological ambiguity from decoupled brain processes makes MRI-to-amyloid PET synthesis inherently inconsistent.","cross_cats":[],"primary_cat":"cs.CV","authors_text":"David M. Cash, Hojjat Azadbakht, Hui Zhang, Louise E. G. Baron, Philip S. J. Weston, Ross Callaghan","submitted_at":"2026-05-12T09:47:44Z","abstract_excerpt":"Structural MRI-to-amyloid PET synthesis has been proposed as a non-invasive alternative for amyloid assessment in Alzheimer's disease (AD). However, reported performance of identical models varies widely across studies, and increasingly complex architectures have not led to consistent gains. This inconsistency is thought to be caused by a fundamental biological ambiguity: MRI captures neurodegeneration, while PET measures amyloid pathology - two processes that are often temporally decoupled in AD. As a result, similar MRI patterns may correspond to different amyloid states, creating ambiguous "},"claims":{"count":4,"items":[{"kind":"strongest_claim","text":"limited and inconsistent performance in MRI-to-amyloid PET synthesis is explained by intrinsic biological ambiguity, and that stable, meaningful progress requires multimodal integration rather than architectural complexity.","source":"verdict.strongest_claim","status":"machine_extracted","claim_id":"C1","attestation":"unclaimed"},{"kind":"weakest_assumption","text":"That stratifying paired MRI-PET data by amyloid and neurodegeneration status cleanly isolates unambiguous mappings without introducing selection bias or unmeasured confounders that could explain the performance collapse.","source":"verdict.weakest_assumption","status":"machine_extracted","claim_id":"C2","attestation":"unclaimed"},{"kind":"one_line_summary","text":"Biological ambiguity between neurodegeneration on MRI and amyloid on PET makes one-to-one synthesis ill-posed, but stratifying data or adding plasma biomarkers restores performance.","source":"verdict.one_line_summary","status":"machine_extracted","claim_id":"C3","attestation":"unclaimed"},{"kind":"headline","text":"Biological ambiguity from decoupled brain processes makes MRI-to-amyloid PET synthesis inherently inconsistent.","source":"verdict.pith_extraction.headline","status":"machine_extracted","claim_id":"C4","attestation":"unclaimed"}],"snapshot_sha256":"c184feab3c1bde718ae62cd4361319868d32b44bfd6c25b487bf92fc8e284503"},"source":{"id":"2605.11867","kind":"arxiv","version":2},"verdict":{"id":"a97b6433-cd33-4765-acdf-14edb207eb9b","model_set":{"reader":"grok-4.3"},"created_at":"2026-05-13T07:17:28.735835Z","strongest_claim":"limited and inconsistent performance in MRI-to-amyloid PET synthesis is explained by intrinsic biological ambiguity, and that stable, meaningful progress requires multimodal integration rather than architectural complexity.","one_line_summary":"Biological ambiguity between neurodegeneration on MRI and amyloid on PET makes one-to-one synthesis ill-posed, but stratifying data or adding plasma biomarkers restores performance.","pipeline_version":"pith-pipeline@v0.9.0","weakest_assumption":"That stratifying paired MRI-PET data by amyloid and neurodegeneration status cleanly isolates unambiguous mappings without introducing selection bias or unmeasured confounders that could explain the performance collapse.","pith_extraction_headline":"Biological ambiguity from decoupled brain processes makes MRI-to-amyloid PET synthesis inherently inconsistent."},"integrity":{"clean":true,"summary":{"advisory":0,"critical":0,"by_detector":{},"informational":0},"endpoint":"/pith/2605.11867/integrity.json","findings":[],"available":true,"detectors_run":[{"name":"ai_meta_artifact","ran_at":"2026-05-26T16:42:02.415892Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"doi_title_agreement","ran_at":"2026-05-20T18:31:27.269987Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"doi_compliance","ran_at":"2026-05-20T12:46:24.977838Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"claim_evidence","ran_at":"2026-05-20T03:22:00.392503Z","status":"completed","version":"1.0.0","findings_count":0}],"snapshot_sha256":"d786c2e78d74a95d3f73a30be5eb86d9b5184dce2779b2418244478c9523f8bc"},"references":{"count":0,"sample":[],"resolved_work":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","internal_anchors":0},"formal_canon":{"evidence_count":2,"snapshot_sha256":"9f578ca143f27c58f0d25c60e8d759c31a8c869ee149f51d4e53e91a4b5d58f7"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"}