Focused ultrasound-microbubble treatment arrests the growth and formation of cerebral cavernous malformations.

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Tác giả: Victoria R Breza, Tanya Cruz, Anna C Debski, Delaney G Fisher, Catherine M Gorick, Matthew R Hoch, John R Lukens, James W Mandell, G Wilson Miller, David Moore, Richard J Price, Joshua D Samuels, David Schlesinger, Ishaan M Shah, Khadijeh A Sharifi, Jason P Sheehan, Petr Tvrdik

Ngôn ngữ: eng

Ký hiệu phân loại: 547.596 *Fused heterocyclic compounds

Thông tin xuất bản: England : Nature biomedical engineering , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 745722

Cerebral cavernous malformations (CCMs) are vascular lesions within the central nervous system that cause debilitating neurological symptoms. Currently, surgical excision and stereotactic radiosurgery, the primary treatment options, pose risks to some patients. Here we tested whether pulsed, low intensity, focused ultrasound-microbubble (FUS-MB) treatments control CCM growth and formation in a clinically representative Krit1 null murine model. FUS-MB under magnetic resonance imaging (MRI) guidance opened the blood-brain barrier, with gadolinium contrast agent deposition most evident at perilesional boundaries. Longitudinal MRI revealed that, at 1 month after treatment, FUS-MB halted the growth of 94% of treated CCMs. In contrast, untreated CCMs grew ~7-fold in volume. FUS-MB-treated CCMs exhibited a marked reduction in Krit1 null endothelial cells. In mice receiving multiple FUS-MB treatments with fixed peak-negative pressures, de novo CCM formation was reduced by 81%, indicating a prophylactic effect. Our findings support FUS-MB as a minimally invasive treatment modality that can safely arrest murine CCM growth and prevent de novo CCM formation in mice. If proven safe and effective in clinical trials, FUS-MB treatment may enhance therapeutic options for CCM patients.
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