Microclots and Neutrophil Activation as Potential Indicators for Stroke Risk and Reperfusion Failure

Summary

Stroke remains a major health burden worldwide. Many patients are severely disabled and stay in need of care. Mechanical thrombectomy has dramatically improved outcomes for stroke patients with large vessel occlusions, yet 40-50% of patients with successful recanalization remain severely disabled despite successful recanalization, a scenario called "futile recanalization". One of the causes for this lack of treatment effect is capillary obstruction, or "no reflow", potentially resulting from activated neutrophils and micrometer-sized blood clots. To address this issue, we employ digital holotomographic and atomic force microscopy to investigate the structural and chemical characteristics of blood and clot material in stroke patients and individuals at high risk of developing a stroke. Our study elucidates the association of activated neutrophils and microclots with stroke risk, and may be associated with clinical outcome, stroke ethology and reperfusion failure in patients with stroke. Leveraging label-free microscopy tools, could potentially lead to the discovery of new biomarkers for individualized stroke treatment and prevention, ultimately offering rapid identification of at risk patients and improving clinical outcomes

Conditions

• Ischemic Stroke

Interventions

DIAGNOSTIC_TEST

3D rotational digital tomography

DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.

DIAGNOSTIC_TEST

Atomic Force Microscopy

The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots

DIAGNOSTIC_TEST

Micro-Computertomography

Micro-CT is a 3D imaging technique utilizing X-rays to see inside an object, slice by slice. Micro-CT, also called microtomography or micro computed tomography, is similar to hospital CT or "CAT" scan imaging but on a small scale with greatly increased resolution. Samples can be imaged with pixel sizes as small as 100 nanometers and objects can be scanned as large as 200 millimeters in diameter. We will use micro-CT to analyze blood clots from patients with large vessel occlusion.

Sponsors & Collaborators

• University of Zurich

  lead OTHER

• Empa, Swiss Federal Laboratories for Materials Science and Technology

  collaborator OTHER

Principal Investigators

• Susanne Wegener, Prof. · University Hospital Zurich, department Neurology

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-02-01

Primary Completion

2030-09-01

Completion

2030-12-01

Countries

• Switzerland

Study Locations