Branch atheromatous disease (BAD)-related stroke is an important subtype of acute ischemic stroke involving penetrating arteries and is associated with early neurological deterioration. Early recognition and standardized diagnosis remain challenging in routine clinical practice because clinical symptoms are often non-specific and the diagnosis requires integrated clinical and imaging assessment.

This multicenter prospective observational study will collect demographic, clinical, laboratory, electrocardiographic, ultrasound, and multimodal neuroimaging data from adults with acute ischemic stroke within 1 week of symptom onset. Participants will receive routine clinical care determined by their treating physicians; no treatment or management strategy will be assigned by the study protocol. An independent central clinical-imaging adjudication committee will classify participants as BAD-related stroke or non-BAD acute ischemic stroke according to predefined diagnostic criteria. The study aims to develop and externally validate artificial intelligence-assisted screening and diagnostic models for BAD-related stroke and to evaluate their discrimination, calibration, and potential clinical utility.

Branch atheromatous disease (BAD)-related stroke has been increasingly recognized as a clinically meaningful subtype of acute ischemic stroke. It typically presents as a single subcortical infarction in the territory of penetrating arteries, especially the lenticulostriate arteries and paramedian pontine arteries. Because BAD-related stroke is not well captured by conventional etiologic classification systems and because its early diagnosis requires standardized interpretation of clinical and neuroimaging features, delayed or inconsistent recognition may limit subsequent precision-management research.

This study is designed as a multicenter, prospective, observational cohort study. Eligible adults with acute ischemic stroke will be enrolled within 1 week after symptom onset or last known well time. Multisource data will be collected, including demographics, vascular risk factors, baseline neurological assessments, laboratory tests, electrocardiography, carotid/cardiac ultrasound, routine brain MRI, intracranial vascular imaging by MRA/CTA/DSA when available, high-resolution vessel wall MRI when available, ASL perfusion imaging when available, acute-phase treatment information, early neurological deterioration, and 90-day functional outcomes.

The study will include two predefined diagnostic cohorts: participants with BAD-related stroke and participants with non-BAD acute ischemic stroke. BAD-related stroke will be adjudicated by an independent central clinical-imaging committee according to predefined imaging and etiologic criteria. The reference diagnosis will be based on baseline and follow-up clinical information, neuroimaging, vascular imaging, cardiac evaluation, and 90-day follow-up information when applicable.

Artificial intelligence-assisted models will be developed and validated to support early screening and diagnostic classification of BAD-related stroke. The early screening model will use non-imaging or routinely available acute-phase clinical information, whereas the diagnostic model will integrate multisource clinical and imaging information. Model performance will be evaluated in an external validation cohort using discrimination, sensitivity, specificity, accuracy, calibration, and decision curve analysis. The study protocol does not assign any therapeutic intervention, diagnostic procedure beyond routine or protocol-specified observational assessments, or clinical management strategy. All treatments will be determined by the treating physicians according to local practice and applicable guidelines.

Inclusion Criteria:

• Age 18 to 80 years.
• Diagnosis of acute ischemic stroke.
• Time from symptom onset to enrollment ≤ 1 week; if the onset time is unknown, time from last known well to enrollment ≤ 1 week.
• Availability of required baseline clinical and neuroimaging assessments according to the study protocol.
• Written informed consent provided by the participant or legally authorized representative.

Participants will be classified into the BAD-related stroke cohort if they meet all predefined BAD-related stroke diagnostic criteria, including:

• A single isolated deep subcortical infarct on diffusion-weighted imaging.
• The presumed culprit perforating artery is the lenticulostriate artery or the paramedian pontine artery.
• For lenticulostriate artery territory infarction: a comma-shaped lesion extending from inferior to superior direction on coronal DWI or involvement of ≥3 axial DWI slices with 5-7 mm slice thickness.
• For paramedian pontine artery territory infarction: a lesion extending from the deep pons to the ventral surface of the pons on axial DWI.
• No ≥50% stenosis of the corresponding parent artery, confirmed by MRA, CTA, or DSA.

Participants with acute ischemic stroke who do not meet BAD-related stroke criteria will be classified into the non-BAD acute ischemic stroke cohort.

Exclusion Criteria:

General exclusion criteria for all participants:

• Intracranial hemorrhage, vascular malformation, aneurysm, brain abscess, malignant intracranial mass, or other non-ischemic intracranial lesion on baseline CT, MRI, MRA, CTA, or DSA.
• Pre-stroke modified Rankin Scale score ≥2.
• Life expectancy ≤6 months.
• Unable to tolerate MRI examination.
• Pregnancy or breastfeeding.
• Participation in another clinical study within 3 months before informed consent or current participation in another clinical study that may interfere with this study.

Additional criteria that preclude classification as BAD-related stroke:

• Ipsilateral extracranial tandem artery stenosis ≥50%.
• Definite cardioembolic source, including atrial fibrillation, myocardial infarction, clinically significant valvular heart disease, dilated cardiomyopathy, infective endocarditis, atrioventricular conduction disease, or heart rate <50 beats/min as defined in the protocol.
• Receipt of or planned acute-phase endovascular treatment after stroke onset.
• Stroke due to other determined causes, such as moyamoya disease, arterial dissection, or vasculitis.

The study population will include adults aged 18 to 80 years with acute ischemic stroke who present within 1 week after symptom onset or last known well time at participating stroke centers. Participants will be classified as BAD-related stroke or non-BAD acute ischemic stroke according to predefined diagnostic criteria and independent central clinical-imaging adjudication.

Individual participant data will not be shared because the study involves sensitive multicenter clinical and multimodal neuroimaging data from patients with acute ischemic stroke, with residual re-identification risks even after de-identification. Data sharing is restricted by informed consent, ethics approvals, multicenter data-use agreements, institutional policies, and applicable privacy and cybersecurity regulations. Aggregate study results or study-specific questions may be directed to the corresponding author, but participant-level data access is not included in the current IPD sharing plan.