PDF(Pubmed)
Abstract：
OBJECTIVE: We previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase (eNOS) in mouse models of Alzheimer\'s disease (AD). In a randomized, double-blind, placebo-controlled pilot trial, we demonstrated that whole-brain LIPUS therapy is safe and tends to suppress the cognitive decline in early AD patients. We herein report the findings of our basic experiments that we performed for the pilot trial in order to apply whole-brain LIPUS therapy to humans, as well.
METHODS: First, we examined the relationship between bone density/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures.
RESULTS: There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05-0.5 MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz.
CONCLUSIONS: We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.
METHODS: First, we examined the relationship between bone density/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures.
RESULTS: There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05-0.5 MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz.
CONCLUSIONS: We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.
摘要：
目的：我们以前开发了一种新的低强度脉冲超声（LIPUS）疗法，通过上调阿尔茨海默病（AD）小鼠模型中内皮型一氧化氮合酶（eNOS）来改善认知功能下降。在一个随机的，双盲,安慰剂对照试点试验，我们证明了全脑LIPUS治疗是安全的,并且倾向于抑制早期AD患者的认知功能下降.我们在此报告了我们的基础实验的结果，我们进行了试点试验，以便将全脑LIPUS治疗应用于人类，也是。
方法：首先，我们使用人颞骨检查了骨密度/厚度与超声透射率之间的关系。接下来,根据超声波透射的结果，我们进一步检查了VEGF的mRNA表达，FGF2和eNOS响应于可变的超声频率，占空比,和声压。
结果：骨厚度与透射率之间存在显着相关性（1.0MHz，P<0.001)，而骨密度与透光率之间没有显著相关性(1.0MHz，P=0.421）。在0.5MHz的频率下，最佳占空比被认为是高达20%。当组织振幅在0.05-0.5MPa范围内时,VEGF,LIPUS显著上调FGF2和eNOS。因此，LIPUS治疗人脑的必要条件被确定为声压刚好低于探头1.3MPa（组织振幅0.15MPa），占空比5%,和频率0.5MHz。
结论：我们成功确定了AD患者LIPUS治疗的最佳治疗条件。
方法：首先，我们使用人颞骨检查了骨密度/厚度与超声透射率之间的关系。接下来,根据超声波透射的结果，我们进一步检查了VEGF的mRNA表达，FGF2和eNOS响应于可变的超声频率，占空比,和声压。
结果：骨厚度与透射率之间存在显着相关性（1.0MHz，P<0.001)，而骨密度与透光率之间没有显著相关性(1.0MHz，P=0.421）。在0.5MHz的频率下，最佳占空比被认为是高达20%。当组织振幅在0.05-0.5MPa范围内时,VEGF,LIPUS显著上调FGF2和eNOS。因此，LIPUS治疗人脑的必要条件被确定为声压刚好低于探头1.3MPa（组织振幅0.15MPa），占空比5%,和频率0.5MHz。
结论：我们成功确定了AD患者LIPUS治疗的最佳治疗条件。
