Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy

TL;DR

This study introduces a new method to measure brain perivascular spaces in a rare amyloid disease and finds increased volume in early stages.

Contribution

A novel whole-brain semi-automated method for quantifying perivascular space volume in Dutch-type Cerebral Amyloid Angiopathy.

Findings

Symptomatic D-CAA patients had significantly higher baseline PVSvf compared to younger and older controls.

Pre-symptomatic D-CAA carriers also showed increased PVSvf compared to younger controls.

No longitudinal changes in PVSvf were observed over four years between D-CAA and control groups.

Abstract

•Novel whole-brain semi-automated perivascular space segmentation-method in D-CAA.•Cross-sectional and longitudinal perivascular space volume fraction (PVSvf) in D-CAA.•Increased PVSvf in early stages of Dutch-type Cerebral Amyloid Angiopathy (D-CAA)•No difference in PVSvf-change over 4 yr follow-up between D-CAA and control subjects.

Novel whole-brain semi-automated perivascular space segmentation-method in D-CAA.

Cross-sectional and longitudinal perivascular space volume fraction (PVSvf) in D-CAA.

Increased PVSvf in early stages of Dutch-type Cerebral Amyloid Angiopathy (D-CAA)

No difference in PVSvf-change over 4 yr follow-up between D-CAA and control subjects.

Enlarged perivascular spaces (PVS) in the centrum semiovale are an important marker of Cerebral Amyloid Angiopathy (CAA) and are thought to reflect brain clearance dysfunction. However, the current golden standard for assessing PVS is limited to a unilateral, single slice, qualitative analysis, which has the disadvantage of a strong ceiling effect. We aim to introduce a whole-brain PVS volume fraction (PVSvf) measurement to assess cross-sectional and longitudinal PVSvf differences between pre-symptomatic and symptomatic Dutch-type CAA (D-CAA) mutation carriers and similar-age controls. PVSvf was assessed with a Frangi-vesselness filter-based, segmentation tool developed in-house and was compared cross-sectionally in 70 participants (28 symptomatic D-CAA, 17 pre-symptomatic D-CAA, 10 controls > 50 years, 17 controls ≤ 50 years) and longitudinally in 40 participants (16 symptomatic D-CAA, 13 pre-symptomatic D-CAA, 11 controls combined from both age groups). We found a higher baseline PVSvf in symptomatic D-CAA compared to controls ≤ 50 years (p < 0.0001, 95% CI [−0.051, −0.025]) and controls > 50 years (p < 0.0001, 95% CI [-0.042, −0.016]), in pre-symptomatic D-CAA compared to controls ≤ 50 years (p = 0.023, 95% CI [−0.035, −0.002]), and in controls > 50 years compared to controls ≤ 50 years (p < 0.001, 95% CI [0.004, 0.014]). We found no group differences in PVSvf change over time. The introduction of this quantitative measure of PVS volume in D-CAA showed cross-sectional differences already in pre-symptomatic D-CAA, indicating increased PVSvf in the early stages of D-CAA. We did not observe longitudinal differences over a four-year follow-up when analyzed at group level.

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