Periventricular white matter hyperintensities co‐localize with deep intramedullary venules, sparing compact fiber tracts and can increase or decrease over time in Alzheimer's disease
Bibliographic record
Abstract
BACKGROUND: Periventricular white matter hyperintensities (pWMH), commonly thought to be ischemic and demyelinating in origin, are prevalent in Alzheimer's disease (AD). However, occlusive collagenosis of deep medullary veins (DMVs), a venulopathy has been implicated in pWMH. Not only leakage, but also perivascular lymphatic system stasis may lead to chronic excessive extracellular fluid accumulation. In vivo, we investigated collocation of confluent pWMH with DMVs and radiological evidence of pWMH edema in AD, in conjunction with pathological correlation. METHOD: 88 AD and 33 controls (age=76) with confluent pWMH on T2/FLAIR were included. DMVs were defined as linear streaks on T1/inverted-T2 radiating from the subependymal region of the lateral ventricle. Spatial relationships of confluent pWMH was measured by counting the number of DMVs in each confluent pWMH. Radiological signs of edema were determined by whether compact white matter tracts (including optic radiation, fronto-occipital fasciculus, thalamofrontal tract and u-fibers) were spared within or around pWMH. Also pWMH changes over time were analyzed, assuming WMH would exhibit dynamic changes if they are edema related. Perivascular spaces and lacunes were also quantified. Thirteen imaging-pathological correlations were available to validate imaging findings. RESULT: DMVs were identified in 283 discrete confluent pWMH across all participants. Significant associations were demonstrated between pWMH volume and total number of DMVs depicted within pWMH. Co-location of pWMH with DMVs appeared to be unique by comparing them to regions without pWM. Compact fiber tracts were spared by confluent pWMH in 95% overall, and 24% of pWMH volumes decreased over time. Pathologically, using trichrome staining, venous collagenosis (wall thickening, stenosis or occlusion) of large (p = 0.012) and smaller venules (p = 0.036) were significant predictors of pWMH. Demyelination using luxol blue contributed but did not survive multiple regression. CONCLUSION: Confluent pWMH clearly mapped to visualizable DMVs, suggesting venous insufficiency due to collagenosis. Compact fiber tract sparing and reversible progression of pWMH provided in vivo evidence of chronic edema. Our findings support the notion that venous insufficiency of DMVs is the main substrate of pWMH, reflecting vasogenic edema induced from increased venous pressure and extracellular fluid accumulation from reduced interstitial fluid circulation along the glymphatic perivenous spaces.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".