NAIF 2.0 - COGNIFY

ConditionsDural Arteriovenous Fistula Glymphatic System

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18-99

SponsorHospital Universitari Vall d'Hebron Research Institute

About this trial

The goal of this observational study is to learn whether intracranial dural arteriovenous fistulae, abnormal connections between arteries and veins in the covering of the brain, may affect a brain's waste-clearance system, known as the glymphatic system.

The main question it aims to answer is: "Does glymphatic system function change after routine endovascular embolization of an intracranial dural arteriovenous fistula?" Participants who are already scheduled to receive endovascular embolization as part of their regular medical care will undergo advanced brain MRI before treatment and again about 6 months after treatment. Researchers will compare the MRI findings before and after embolization to explore whether treatment is associated with changes in glymphatic-related brain imaging markers.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant is willing and able to give informed consent for participation in the study.

Male or Female, aged 18 to 99 years.

Angiographically confirmed diagnosis of unruptured intracranial dAVF.

Candidate for endovascular embolization treatment with curative intent.

Disqualifiers

Contraindication to angiographic embolization procedures.

Acute intracranial haemorrhage secondary to dAVFs rupture and/or venous hypertension.

Any significant disease or disorder which, in the opinion of the investigator, might influence the participant's ability to participate in the study, other contraindications to MRI such as certain metallic implants.

Trial population

Patients with angiographically confirmed diagnosis of unruputred intracranial dAVFs, aged 18-99 years, candidate for endovascular embolization treatment with curative intent.

Trial design

Design model

Other

Time perspective

Prospective

Treatments tested in this trial

Brain MRI
Diagnostic test
Participants will undergo a brain MRI on a 3T scanner at baseline assessment and approximately 6 months after endovascular embolization. The MRI protocol includes routinary morphologic sequences (e.g., 3D T1-weighted imaging, T2-weighted FLAIR, susceptibility-weighted imaging), as well as a multi-shell diffusion MRI with multiple b-values and gradient directions. These sequences will be used to assess conventional brain findings and diffusion-derived metrics potentially related to glymphatic function, including DTI-ALPS, DKI-MK and FW imaging. The main otcome of the study is to evaluate changes in these metrics in relation to treatment.

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: dAVF patients1 intervention

Trial outcomes

Primary outcomes

Mean DTI-ALPS Index at Baseline and 6 Months After Endovascular Embolization

The diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index will be calculated from directional diffusivities measured in prespecified projection- and association-fiber regions of interest (ROIs). The regional measurements will be combined according to the prespecified DTI-ALPS calculation to obtain one DTI-ALPS index per participant at each time point. DTI-ALPS values will be summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. Lower DTI-ALPS values indicate greater lower diffusivity along the perivascular-space direction, suggestive of a glymphatic system impairment. The DTI-ALPS index is unitless.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Mean MK at Baseline and 6 Months After Endovascular Embolization

Mean Kurtosis (MK) will be derived from multi-shell diffusion MRI. Voxelwise mean kurtosis values within white matter ROIs covering the whole brain will be calculated and summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. Higher mean kurtosis values indicate a greater degree of non-Gaussian water diffusion, suggestive of a glymphatic system impairment. MK is unitless.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Mean FW at Baseline and 6 Months After Endovascular Embolization

Free-water (FW) will be estimated from multi-shell diffusion MRI using a free-water imaging model. Voxelwise FW values within white matter ROIs covering the whole brain will be calculated and summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. FW is a unitless volume fraction ranging from 0 to 1, with higher values indicating a greater proportion of extracellular free water, suggestive of a glymphatic system impairment.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Secondary outcomes

Spearman Rank Correlation Between Cognard Grade and Baseline DTI-ALPS Index

dAVF severity will be assessed by digital subtraction angiography using the Cognard classification and treated as an ordinal variable. The DTI-ALPS index will be derived from diffusion MRI and expressed as a unitless index. The association between Cognard grade and baseline DTI-ALPS index will be assessed using Spearman's rank correlation coefficient. Results will be reported as Spearman's rho with a 95% confidence interval.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Spearman Rank Correlation Between Cognard Grade and Baseline MK

dAVF severity will be assessed by digital subtraction angiography using the Cognard classification and treated as an ordinal variable. MK will be derived from multi-shell diffusion kurtosis imaging and expressed as a unitless value. The association between Cognard grade and baseline mean kurtosis will be assessed using Spearman's rank correlation coefficient. Results will be reported as Spearman's rho with a 95% confidence interval.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization

Spearman Rank Correlation Between Cognard Grade and Baseline FW

dAVF severity will be assessed by digital subtraction angiography using the Cognard classification and treated as an ordinal variable. FW will be derived from multi-shell diffusion MRI and expressed as a unitless fraction ranging from 0 to 1. The association between Cognard grade and baseline free-water fraction will be assessed using Spearman's rank correlation coefficient. Results will be reported as Spearman's rho with a 95% confidence interval.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Other outcomes

Mean DTI-ALPS Index According to Prespecified Clinical and Angiographic Characteristic

The DTI-ALPS index will be derived from diffusion MRI and expressed as a unitless index. DTI-ALPS values will be summarized separately according to prespecified clinical and angiographic characteristics, including clinical presentation, dAVF location and angiographic treatment response. Each characteristic will be evaluated separately. Analyses will be considered exploratory and will be performed only when the number of participants in the relevant categories is sufficient.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Mean MK According to Prespecified Clinical and Angiographic Characteristics

MK will be derived from multi-shell diffusion kurtosis imaging and expressed as a unitless value. MK values will be summarized separately according to prespecified clinical and angiographic characteristics, including clinical presentation, dAVF location and angiographic treatment response. Each characteristic will be evaluated separately. Analyses will be considered exploratory and will be performed only when the number of participants in the relevant categories is sufficient.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Mean FW According to Prespecified Clinical and Angiographic Characteristics

FW will be derived from multi-shell diffusion MRI and expressed as a unitless fraction ranging from 0 to 1. FW will be summarized separately according to prespecified clinical and angiographic characteristics, including clinical presentation, dAVF location and angiographic treatment response. Each characteristic will be evaluated separately. Analyses will be considered exploratory and will be performed only when the number of participants in the relevant categories is sufficient.

Time frame

Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.