Quantitative photoacoustic evaluation of graded ischemic stroke and the therapeutic efficacy of low-intensity transcranial ultrasound stimulation
Rui Hu, Li Liu, Zijian Hua, Jingxian Wang, Ying Li, Dean Ta
Biomedical Optics Express 2026 · 10.1364/boe.593436
Abstract
Ischemic stroke represents a leading cause of global mortality and long-term disability. Consequently, rapid quantification of cerebral damage severity, coupled with timely neuromodulatory intervention, is imperative for improving clinical prognosis. In this study, we present a label-free quantitative monitoring framework utilizing optical-resolution photoacoustic microscopy (OR-PAM) to assess microvascular alterations and evaluate the therapeutic efficacy of low-intensity transcranial ultrasound stimulation (LITUS). A graded ischemic stroke model was established by modulating photothrombotic irradiation duration (3, 5, and 10 min) to validate system sensitivity. Subsequently, a Hessian filter-based segmentation pipeline was employed to extract quantitative vascular metrics. Five key morphological and functional parameters, including the photoacoustic (PA) signal intensity, vessel area fraction (VAF), average vessel diameter (AVD), branch-point number (BN), and perfused vessel density (PVD), were extracted to characterize the severity of ischemic injury. Our analysis revealed a strong negative correlation between irradiation duration and vascular perfusion-related metrics, which was further confirmed by ex vivo 2,3,5-triphenyltetrazolium chloride (TTC) staining showing duration-dependent infarct expansion. Applying this quantitative framework to the established model, we further demonstrated that acute LITUS treatment significantly alleviated microvascular hypoperfusion and promoted rapid hemodynamic recovery by restoring both functional perfusion and vascular morphology via vasodilation. These findings highlight the potential of a PAM-based quantitative framework for accurate grading of ischemic severity and evaluation of ultrasound-based neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: LITUS of photothrombotic lesion, left cortex
Target: cerebral cortex — “cortical target coordinates (AP = -2.0 mm, ML = -2.0 mm)”
Device: other named manufacturer · Siansonic · AQ20-1020 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 1,160 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.45 | ✓✓✓ |
PRF 1 kHz, duty cycle 20%, sonication duration 300 ms; total treatment duration 10 min starting 23 min after the photothrombotic procedure.
Flags from extraction
n_subjects— 35 mice enrolled across two cohorts; only the PT + LITUS group (five animals) received ultrasound.blinding— Only image acquisition and quantitative analysis stated blinded.exposures[0].timing.pulse_duration_ms— Pulse duration not stated; not derived from duty cycle and PRF.exposures[0].unspecified_domain.pressure_kpa— 1.16 MPa described as measured peak negative pressure; medium not stated.exposures[0].target.terms— Target given only as stereotaxic coordinates AP -2.0, ML -2.0 mm in the left cortex.anaesthesia— Isoflurane stated for stroke induction; anaesthesia during LITUS not stated explicitly.exposures[0].timing.sonication_duration_s— 300 ms sonication within a 10 min total treatment; inter-sonication interval not stated.