雙模經顱聚焦超音波引發腦刺激之低頻血流分析

Abstract

近年來，超快速超音波成像技術在醫學影像領域取得了顯著突破。除了實現即時資訊偵測，還能通過超快速成像的演進獲取更精細的影像。目前的高頻超音波探頭能夠觀測腦部微血管的細微影像，並隨著奇異值分解濾波技術的發展，提供更穩定且豐富的血流影像資訊，也在神經變化的觀察中有了新的進展。此外，超音波還能實現熱燒灼和血腦屏障開啟等功能，成為診斷與治療合一的工具。然而，由於超音波在穿透物質上會造成能量衰減，若需要藉由高頻影像探頭獲得腦部造影，除了透過較薄的區域進行照射外，目前尚無人進行直接對頭顱的照射。因此，本研究利用0.5MHz頻率探頭進行穿顱腦部實驗，藉由血腦屏障開啟作為治療方法，並基於相同頻率進行造影，以評估單一設備的治療及造影能力。本研究首先通過仿體實驗確認0.5MHz一維探頭的影像解析度及其對流體的偵測能力。接著在大鼠的動物實驗中，利用低頻影像觀察血腦屏障開啟的效果，並設計實驗序列比較血腦屏障開啟前後的情況。為實現超快速成像，設計了針對曲面探頭的延遲曲線以達到平面波的發射。基於低頻超音波對頭顱的穿透性，大鼠在實驗中不開顱進行超音波影像，並使用微氣泡顯影。通過超快速成像設計，在短時間內獲取足夠的影像資訊，應用於奇異值分解中進行訊號分離，觀察不同強度刺激下的血流變化。根據實驗結果，觀察到在血腦屏障開啟後，腦部區域出現血液抑制的現象，這與過去利用功能性磁振造影(fMRI)觀察血氧濃度相依對比(BOLD)訊號的趨勢相近。施打後在實驗組半腦也發現血流量下降，證實0.5MHz探頭在觀察血流變化方面的能力。

In recent years, ultrafast ultrasound imaging technology has achieved significant breakthroughs in medical imaging. In addition to real-time information detection, advancements in ultrafast imaging have enabled the acquisition of more detailed images. Current high-frequency ultrasound transducers can capture the information of cerebral microvessels, with the development of singular value decomposition (SVD) filtering, more stable and rich blood flow imaging information has become available, providing new progress in the observation of neural changes. Furthermore, ultrasound can facilitate procedures such as thermal ablation and blood-brain barrier (BBB) disruption, making it an integrated tool for diagnostic and therapeutic applications. However, due to the attenuation of ultrasound energy when penetrating materials, obtaining brain imaging with high-frequency transducers typically requires targeting thinner regions, and direct transcranial ultrasound has not been widely attempted. Therefore, this study utilized a 0.5 MHz transducer for transcranial brain experiments, using BBB opening as a treatment method and performing imaging at the same frequency to evaluate the therapeutic and imaging capabilities of a single device. Initially, phantom experiments were conducted to confirm the image resolution and flow detection capability of the 0.5 MHz one-dimensional transducer. Subsequently, animal experiments on rats were performed, using low-frequency imaging to observe the effects of BBB opening and designing experimental sequences to compare conditions before and after BBB opening. To achieve ultrafast imaging, delay curves were designed for the curved transducer for plane wave emission. Given the penetrative capability of low-frequency ultrasound, the rats were imaged without craniotomy, and microbubbles were used as contrast agents. Through the ultrafast imaging design, sufficient information was obtained within a short time frame, which was applied to SVD for signal separation and the observation of blood flow changes under different intensities of stimulation. According to the experimental results, the brain region subjected to BBB opening displayed blood suppression, a trend that aligns with previous observations using functional magnetic resonance imaging (fMRI) to monitor blood-oxygen-level-dependent (BOLD) signals. The reduction in blood flow was observed in the experimental hemisphere, confirming the ability of the 0.5 MHz transducer to detect changes in blood flow.