Ponomarchuk Ekaterina, Tsysar Sergey, Kadrev Alexey, Kvashennikova Anastasia, Chupova Daria, Pestova Polina, Papikyan Liliya, Karzova Maria, Danilova Natalia, Malkov Pavel, Chernyaev Andrey, Buravkov Sergey, Sapozhnikov Oleg, Khokhlova Vera
Physics Faculty, Lomonosov Moscow State University, Moscow, Russia.
Physics Faculty, Lomonosov Moscow State University, Moscow, Russia.
Ultrasound Med Biol. 2025 Feb;51(2):312-320. doi: 10.1016/j.ultrasmedbio.2024.10.006. Epub 2024 Oct 30.
Non-invasive surgical approaches, including boiling histotripsy (BH), are currently being developed for the treatment of brain disorders aiming to avoid craniotomy and exposure of intervening tissues, and, thus, minimize associated complications. This work aimed to demonstrate the feasibility of BH for mechanical fractionation of human brain tissues ex vivo under B-mode guidance, with preliminary measurements of tissue stiffness via shear wave elastography.
Young's moduli of 25 human autopsy brain samples obtained from de-identified patients of 51-91 y old (median 77 y old) were measured via shear wave elastography prior to BH sonication. Seventeen volumetric BH lesions (1-4 layers of 5 × 5 points with a 1- mm step) were produced near brain surface (n = 10), in white matter (n = 3), in thalamus (n = 2), and globus pallidus (n = 2) using 12 element 1.5 MHz sector transducer under B-mode guidance with 10 ms or 2 ms pulses delivered 10 or 15 times per sonication point with 1% duty cycle. After treatment, the lesions were evaluated grossly through bisection, histologically with hematoxylin and eosin staining, and ultrastructurally via scanning and transmission electron microscopy.
Young's moduli of autopsy brain samples were lower in older patients (from 32.9 ± 6.6 kPa in 51 y olds to 10 ± 2 kPa in 91 y olds) and at higher temperature (6%-50% lower at 37°С vs 23°С), and were within the range observed clinically. All tested BH treatments performed near the brain surface (i.e., mostly in gray matter) resulted in formation of well-demarcated rectangular lesions with homogenized content and sharp boundaries, with majority of residual fragments below 100 microns. The use of shorter pulses (2 ms vs 10 ms) accelerated the treatment at least threefold, and the highest liquefaction rate was 568 mm/min. White matter was more resistant to BH vs gray matter: at least 15 pulses of 2 ms duration were required per each sonication point, and the liquefaction rate was three times lower. The ability of BH to produce lesions in thalamus and globus pallidus was also confirmed.
This work presents the first demonstration of BH proof-of-concept in human brain tissues ex vivo under B-mode guidance with clinically relevant treatment rates.
目前正在开发包括沸腾组织粉碎术（BH）在内的非侵入性手术方法，用于治疗脑部疾病，旨在避免开颅手术和避免中间组织暴露，从而将相关并发症降至最低。这项工作旨在证明在B模式引导下，BH在体外对人脑组织进行机械破碎的可行性，并通过剪切波弹性成像对组织硬度进行初步测量。
在进行BH超声处理之前，通过剪切波弹性成像测量从51-91岁（中位数77岁）身份不明的患者获取的25个人体尸检脑样本的杨氏模量。在B模式引导下，使用12阵元1.5MHz扇形换能器，以1%的占空比，在每个超声点以10ms或2ms的脉冲发射10次或15次，在脑表面附近（n = 10）、白质（n = 3）、丘脑（n = 2）和苍白球（n = 2）产生17个体积性BH病变（5×5点的1-4层，步长为1mm）。处理后，通过对半切开进行大体评估，用苏木精和伊红染色进行组织学评估，并通过扫描和透射电子显微镜进行超微结构评估。
尸检脑样本的杨氏模量在老年患者中较低（从51岁患者的32.9±6.6kPa降至91岁患者的10±2kPa），在较高温度下也较低（37℃时比23℃时低6%-50%），且在临床观察范围内。所有在脑表面附近进行的测试BH处理（即主要在灰质中）均导致形成边界清晰的矩形病变，内容物均匀且边界清晰，大多数残留碎片小于100微米。使用较短脉冲（2ms对10ms）至少将处理速度提高了三倍，最高液化率为568mm/min。白质比灰质对BH更具抗性：每个超声点至少需要15个持续2ms的脉冲，液化率低三倍。BH在丘脑和苍白球中产生病变的能力也得到了证实。
这项工作首次展示了在B模式引导下，BH在体外人脑组织中具有临床相关治疗速率的概念验证。
