無創(chuàng)開放血腦屏障是定位入腦的有效方法，RK系列產(chǎn)品是的臨床前用聚焦超聲技術(shù)開放血腦屏障的系統(tǒng)。

產(chǎn)品描述

產(chǎn)品介紹：

RK-50：臺式聚焦超聲系統(tǒng)
這一聚焦超聲系統(tǒng)能夠完成定向大腦暴露，而不需要并發(fā)的成像。
RK-50是獨(dú)立的全能型臨床前系統(tǒng)，可以利用聚焦超聲的各種用途。通過傳統(tǒng)的立體定位方法的使用，RK-50能夠透過嚙齒類動物大腦的頭蓋骨向細(xì)小的結(jié)構(gòu)發(fā)射劑量的聚焦超聲。該系統(tǒng)還能夠自動?xùn)鸥窕幌盗芯劢钩晛砀采w任意大小的體積。其應(yīng)用包括切除、血腦屏障毀壞和神經(jīng)調(diào)制。

技術(shù)參數(shù)：
· 快速的三維定位系統(tǒng)；
· 計劃軟件幫助立體定位目標(biāo)選擇和暴露劑量控制（在配備的PC上運(yùn)行）；
· 在線性、格柵和環(huán)形劑量暴露中多點(diǎn)定位都是切實(shí)可行的；
· 聚集超聲的劑量設(shè)定可以輕易地調(diào)控用于任何用途；
· 利用校準(zhǔn)的聚焦超聲轉(zhuǎn)換器可以調(diào)節(jié)到一定范圍內(nèi)的頻率。

RK-100：影像導(dǎo)航的聚焦超聲系統(tǒng)
這一可兼容核磁共振成像的影像導(dǎo)航聚焦超聲系統(tǒng)由一套電腦控制的高精度三維定位系統(tǒng)和高能的聚焦超聲轉(zhuǎn)換器組成。
定位系統(tǒng)能夠精準(zhǔn)地向毫米大小的區(qū)域輸送聚焦超聲能量到軟組織。這一系統(tǒng)專門用于研究從小到大的動物模型，從而探究超聲-組織相互作用，在用于人體之前評價方法的性，可匹配臨床MR和CT掃描儀從而完成影像導(dǎo)航的計劃和遞送。該系統(tǒng)完全無磁性，因而可以與高場核磁成像儀共同工作，還可匹配X射線CT成像。

這一無磁性定位系統(tǒng)能夠在成像時沿著任意3D路徑調(diào)動轉(zhuǎn)換器；超聲劑量的遞送用通過MRI或者CT的影像實(shí)現(xiàn)，具體依賴系統(tǒng)的配置；實(shí)時監(jiān)控前進(jìn)方向，轉(zhuǎn)換器接收反射的電能從而保證一致的能量傳輸。
該系統(tǒng)能夠遞送從軟組織熱凝結(jié)的高能連續(xù)聲波降解，到適用于例如組織裂解、傳輸或者血管透化等用途的脈沖聲波降解所需的劑量。因為該系統(tǒng)設(shè)計用于研究，所以非常靈活，用戶可以根據(jù)需要自由設(shè)置。

RK-300：小口徑影像導(dǎo)航聚焦超聲系統(tǒng)
RK-300專門設(shè)計針對小型動物模型，特別適用于血腦屏障毀壞研究，它包括影像導(dǎo)航定位軟件，一臺電腦控制的高精度兩軸定位系統(tǒng)和校準(zhǔn)的聚焦超聲轉(zhuǎn)換器。RK-300是世界上一款能夠進(jìn)行無創(chuàng)過高熱、切除和血腦屏障開放等功能的臨床前成像系統(tǒng)。

技術(shù)參數(shù)：
· 校準(zhǔn)的聚焦超聲轉(zhuǎn)換器可以提供750kHz到5MHz的基本頻率（提供常用焦距）；
· 兩軸空間定位（20mm行進(jìn)，0.25mm精度）；
· 可提供脈沖和連續(xù)超聲；
· 基于影像的計劃軟件；
· 綜合的無線電表面線圈；
· 兼容孔徑小至70mm。

應(yīng)用范圍：
1. 開放血腦屏障：
無創(chuàng)開放血腦屏障是定位入腦的有效方法，RK系列產(chǎn)品是的臨床前用聚焦超聲技術(shù)開放血腦屏障的系統(tǒng)。

2. 切除
聚焦超聲技術(shù)能夠快速無創(chuàng)切除組織結(jié)構(gòu)，RK100能夠在無論大還是小動物模型上完成組織切除。

3. 超高熱
溫和的加熱已經(jīng)在過去數(shù)十年被證明能夠使得腫瘤對放射和化療敏感，并進(jìn)而為熱激活的脂質(zhì)體和分子相互作用提供機(jī)會。配備核磁共振的RK產(chǎn)品能夠在通過核磁共振反饋調(diào)節(jié)加熱。

4. 基因和聲孔效應(yīng)
聚焦超聲能量能夠瞬時增加血管和細(xì)胞對分子化合物的通透性。RK系列產(chǎn)品能夠傳輸必要的劑量達(dá)到這些生物學(xué)效應(yīng)。

5. 空穴作用
RK-100能夠產(chǎn)生必要的壓力以在體內(nèi)生成空穴作用，從而造成組織裂解和分解。

應(yīng)用案例：
1. 聚焦超聲傳輸拉曼納米粒子穿越血腦屏障：定向?qū)嶒災(zāi)X腫瘤的可能性

Diaz, Roberto Jose, et al. “Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors.” Nanomedicine: Nanotechnology, Biology and Medicine 10.5 (2014): 1075-1087.

在近紅外范圍內(nèi)使用表面增強(qiáng)型拉曼散射能量進(jìn)行納米粒子的光譜映射是一項新興的分子成像技術(shù)。我們使用核磁共振成像導(dǎo)航的跨顱聚焦超聲技術(shù)，可逆的破壞大鼠內(nèi)臨近腦腫瘤邊際的血腦屏障。膠質(zhì)瘤細(xì)胞被發(fā)現(xiàn)吸收了50nm到120nm大小的拉曼散射納米粒子。血腦屏障的破壞使得50或120nm的拉曼散射金納米粒子可達(dá)到腫瘤區(qū)域。
因此，具有拉曼散射成像能力的納米粒子能夠通過核磁共振成像導(dǎo)航的跨顱聚焦超聲技術(shù)被無創(chuàng)傳輸?shù)侥[瘤區(qū)域，這有著用于光學(xué)追蹤惡性腦腫瘤侵襲前沿的藥劑的可能性。

圖1：使用跨顱聚焦超聲定向跨越血腦屏障傳遞金納米粒子（GNP）

圖2：使用內(nèi)化的金納米粒子追蹤GBM細(xì)胞

2. 小鼠模型的阿爾茲海默癥：核磁共振成像導(dǎo)航的聚焦超聲定位海馬開放血腦屏障，并改善病理異常和行為
Burgess, Alison, et al. “Alzheimer disease in a mouse model: MR imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.” Radiology 273.3 (2014): 736-745.
這個實(shí)驗?zāi)康氖菫榱俗C實(shí)反復(fù)定位海馬體的核磁共振成像導(dǎo)航的聚焦超聲，能否調(diào)節(jié)阿爾茲海默癥小鼠模型的病理異常、適應(yīng)性和行為。
結(jié)果表明，核磁共振成像導(dǎo)航的聚焦超聲能夠改善阿爾茲海默癥小鼠模型的空間記憶，這些改變可能是由減少淀粉體病理異常和增加的神經(jīng)適應(yīng)性導(dǎo)致的。

圖1. 核磁共振成像導(dǎo)航的聚焦超聲誘導(dǎo)雙邊海馬體的血腦屏障通透性

圖2. 經(jīng)聚焦超聲的小鼠在Y迷宮中表現(xiàn)更好

Studies using FUS Instruments’ Systems

Moyer, Linsey C., et al. “High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles.” Journal of Therapeutic Ultrasound 3.1 (2015): 7.

Ellens, N. P. K., et al. “The targeting accuracy of a preclinical MRI-guided focused ultrasound system.” Medical physics 42.1 (2015): 430-439.

Burgess, Alison, et al. “Alzheimer disease in a mouse model: MR imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.”Radiology 273.3 (2014): 736-745.

Diaz, Roberto Jose, et al. “Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors.” Nanomedicine: Nanotechnology, Biology and Medicine 10.5 (2014): 1075-1087.

Nance, Elizabeth, et al. “Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood? brain barrier using MRI-guided focused ultrasound.” Journal of Controlled Release 189 (2014): 123-132.

Oakden, Wendy, et al. “A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles.” Journal of neuroscience methods 235 (2014): 92-100.

.
Phillips, Linsey C., et al. “Dual perfluorocarbon nanodroplets enhance high intensity focused ultrasound heating and extend therapeutic window in vivo.” The Journal of the Acoustical Society of America 134.5 (2013): 4049-4049.

.
Alkins, Ryan D., et al. “Enhancing drug delivery for boron neutron capture therapy of brain tumors with focused ultrasound.” Neuro-oncology (2013): not052.

Alkins, Ryan, et al. “Focused ultrasound delivers targeted immune cells to metastatic brain tumors.” Cancer research 73.6 (2013): 1892-1899.

Huang, Yuexi, Natalia I. Vykhodtseva, and Kullervo Hynynen. “Creating brain lesions with low-intensity focused ultrasound with microbubbles: a rat study at half a megahertz.” Ultrasound in medicine & biology 39.8 (2013): 1420-1428.

Jord?o, Jessica F., et al. “Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound.” Experimental neurology 248 (2013): 16-29.

Scarcelli, Tiffany, et al. “Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in *** mice.” Brain stimulation 7.2 (2013): 304-307.

Etame, Arnold B., et al. “Enhanced delivery of gold nanoparticles with therapeutic potential into the brain using MRI-guided focused ultrasound.” Nanomedicine: Nanotechnology, Biology and Medicine 8.7 (2012): 1133-1142.

Thévenot, Emmanuel, et al. “Targeted delivery of self-complementary adeno-associated virus serotype 9 to the brain, using magnetic resonance imaging-guided focused ultrasound.” Human gene therapy 23.11 (2012): 1144-1155.

Staruch, Robert, Rajiv Chopra, and Kullervo Hynynen. “Hyperthermia in Bone Generated with MR Imaging–controlled Focused Ultrasound: Control Strategies and Drug Delivery.” Radiology 263.1 (2012): 117-127.

Burgess, Alison, et al. “Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier.” PLoS One 6.11 (2011): e27877.

Jord?o, Jessica F., et al. “Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the TgCRND8 mouse model of Alzheimer’s disease.” PloS one 5.5 (2010): e10549.

Blood-Brain Barrier Disruption Studies

Leinenga, Gerhard, and Jürgen G?tz. “Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model.” Science translational medicine 7.278 (2015): 278ra33-278ra33.

Wang, S., et al. “Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus.” Gene Therapy 22.1 (2015): 104-110.

McDannold, Nathan, et al. “Temporary disruption of the blood–brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.” Cancer research 72.14 (2012): 3652-3663.

Treat, Lisa H., et al. “Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma.” Ultrasound in medicine & biology 38.10 (2012): 1716-1725.
.

Kinoshita, Manabu, et al. “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood–brain barrier disruption.” Proceedings of the National Academy of Sciences 103.31 (2006): 11719-11723.

Kinoshita, Manabu, et al. “Targeted delivery of antibodies through the blood–brain barrier by MRI-guided focused ultrasound.” Biochemical and biophysical research communications 340.4 (2006): 1085-1090.
.

Relevant Review Papers

Burgess, Alison, and Kullervo Hynynen. “Drug delivery across the blood-brain barrier using focused ultrasound.”Expert opinion on drug delivery 11.5 (2014): 711-721.

O’Reilly, Meaghan A., and Kullervo Hynynen. “Ultrasound enhanced drug delivery to the brain and central nervous system.” International Journal of Hyperthermia 28.4 (2012): 386-396.
.

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Studies using FUS Instruments’ Systems
	Moyer, Linsey C., et al. “High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles.” Journal of Therapeutic Ultrasound 3.1 (2015): 7.
	Ellens, N. P. K., et al. “The targeting accuracy of a preclinical MRI-guided focused ultrasound system.” Medical physics 42.1 (2015): 430-439.
	Burgess, Alison, et al. “Alzheimer disease in a mouse model: MR imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.”Radiology 273.3 (2014): 736-745.
	Diaz, Roberto Jose, et al. “Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors.” Nanomedicine: Nanotechnology, Biology and Medicine 10.5 (2014): 1075-1087.
	Nance, Elizabeth, et al. “Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood? brain barrier using MRI-guided focused ultrasound.” Journal of Controlled Release 189 (2014): 123-132.
	Oakden, Wendy, et al. “A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles.” Journal of neuroscience methods 235 (2014): 92-100.
.	Phillips, Linsey C., et al. “Dual perfluorocarbon nanodroplets enhance high intensity focused ultrasound heating and extend therapeutic window in vivo.” The Journal of the Acoustical Society of America 134.5 (2013): 4049-4049.
.	Alkins, Ryan D., et al. “Enhancing drug delivery for boron neutron capture therapy of brain tumors with focused ultrasound.” Neuro-oncology (2013): not052.
	Alkins, Ryan, et al. “Focused ultrasound delivers targeted immune cells to metastatic brain tumors.” Cancer research 73.6 (2013): 1892-1899.
	Huang, Yuexi, Natalia I. Vykhodtseva, and Kullervo Hynynen. “Creating brain lesions with low-intensity focused ultrasound with microbubbles: a rat study at half a megahertz.” Ultrasound in medicine & biology 39.8 (2013): 1420-1428.
	Jord?o, Jessica F., et al. “Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound.” Experimental neurology 248 (2013): 16-29.
	Scarcelli, Tiffany, et al. “Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in * mice.” Brain stimulation 7.2 (2013): 304-307.
	Etame, Arnold B., et al. “Enhanced delivery of gold nanoparticles with therapeutic potential into the brain using MRI-guided focused ultrasound.” Nanomedicine: Nanotechnology, Biology and Medicine 8.7 (2012): 1133-1142.
	Thévenot, Emmanuel, et al. “Targeted delivery of self-complementary adeno-associated virus serotype 9 to the brain, using magnetic resonance imaging-guided focused ultrasound.” Human gene therapy 23.11 (2012): 1144-1155.
	Staruch, Robert, Rajiv Chopra, and Kullervo Hynynen. “Hyperthermia in Bone Generated with MR Imaging–controlled Focused Ultrasound: Control Strategies and Drug Delivery.” Radiology 263.1 (2012): 117-127.
	Burgess, Alison, et al. “Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier.” PLoS One 6.11 (2011): e27877.
	Jord?o, Jessica F., et al. “Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the TgCRND8 mouse model of Alzheimer’s disease.” PloS one 5.5 (2010): e10549.
Blood-Brain Barrier Disruption Studies
	Leinenga, Gerhard, and Jürgen G?tz. “Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model.” Science translational medicine 7.278 (2015): 278ra33-278ra33.
	Wang, S., et al. “Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus.” Gene Therapy 22.1 (2015): 104-110.
	McDannold, Nathan, et al. “Temporary disruption of the blood–brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.” Cancer research 72.14 (2012): 3652-3663.
	Treat, Lisa H., et al. “Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma.” Ultrasound in medicine & biology 38.10 (2012): 1716-1725. .
	Kinoshita, Manabu, et al. “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood–brain barrier disruption.” Proceedings of the National Academy of Sciences 103.31 (2006): 11719-11723.
	Kinoshita, Manabu, et al. “Targeted delivery of antibodies through the blood–brain barrier by MRI-guided focused ultrasound.” Biochemical and biophysical research communications 340.4 (2006): 1085-1090. .
Relevant Review Papers
	Burgess, Alison, and Kullervo Hynynen. “Drug delivery across the blood-brain barrier using focused ultrasound.”Expert opinion on drug delivery 11.5 (2014): 711-721.
	O’Reilly, Meaghan A., and Kullervo Hynynen. “Ultrasound enhanced drug delivery to the brain and central nervous system.” International Journal of Hyperthermia 28.4 (2012): 386-396. .

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開放血腦屏障聚焦超聲系統(tǒng)

無創(chuàng)開放血腦屏障是**定位入腦的有效方法，RK系列產(chǎn)品是**的臨床前用聚焦超聲技術(shù)開放血腦屏障的系統(tǒng)。

無創(chuàng)開放血腦屏障是定位入腦的有效方法，RK系列產(chǎn)品是的臨床前用聚焦超聲技術(shù)開放血腦屏障的系統(tǒng)。