“FUS Instruments的使命是降低聚焦超聲研究的技術壁壘，從而加速這一激動人心的醫(yī)藥領域的發(fā)展。” FUS Instruments是的臨床前聚焦超聲技術公司，因為由有超過30年經(jīng)驗的研究者創(chuàng)立，F(xiàn)US Instruments的系統(tǒng)可以滿足研究者的需求。FUS Instruments的聚焦超聲系統(tǒng)包括從為入門者量身定制的整體解決方案，到可供用戶超越聚焦超聲技術限制的可更改系統(tǒng)。高精度的聚焦超聲技術可以幫助全世界科學家探索新的輸送和開發(fā)，以及為腫瘤學、神經(jīng)科學和心血管研究新的方法。基因和聲孔效應聚焦超聲能量能夠瞬時增加血管和細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到這些生物學效應。

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小的結構發(fā)射劑量的聚焦超聲。該系統(tǒng)還能夠自動柵格化一系列聚焦超聲來覆蓋任意大小的體積。其應用包括切除、血腦屏障毀壞和神經(jīng)調(diào)制。

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

RK-100：影像導航的聚焦超聲系統(tǒng)
這一可兼容核磁共振成像的影像導航聚焦超聲系統(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換器組成。
定位系統(tǒng)能夠精準地向毫米大小的區(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)動轉換器；超聲劑量的遞送用通過MRI或者CT的影像實現(xiàn)，具體依賴系統(tǒng)的配置；實時監(jiān)控前進方向，轉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)設計用于研究，所以非常靈活，用戶可以根據(jù)需要自由設置。

RK-300：小口徑影像導航聚焦超聲系統(tǒng)
RK-300專門設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)和校準的聚焦超聲轉換器。RK-300是世界上一款能夠進行無創(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)。

技術參數(shù)：
· 校準的聚焦超聲轉換器可以提供750kHz到5MHz的基本頻率（提供常用焦距）；
· 兩軸空間定位（20mm行進，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開放血腦屏障的系統(tǒng)。

2. 切除
聚焦超聲技術能夠快速無創(chuàng)切除組織結構，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，并進而為熱激活的脂質體和分子相互作用提供機會。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
聚焦超聲能量能夠瞬時增加血管和細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到這些生物學效應。

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。

應用案例：
1. 聚焦超聲傳輸拉曼納米粒子穿越血腦屏障：定向實驗腦腫瘤的可能性

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)使用表面增強型拉曼散射能量進行納米粒子的光譜映射是一項新興的分子成像技術。我們使用核磁共振成像導航的跨顱聚焦超聲技術，可逆的破壞大鼠內(nèi)臨近腦腫瘤邊際的血腦屏障。膠質瘤細胞被發(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航的跨顱聚焦超聲技術被無創(chuàng)傳輸?shù)侥[瘤區(qū)域，這有著用于光學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細胞

2. 小鼠模型的阿爾茲海默癥：核磁共振成像導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.
這個實驗目的是為了證實反復定位海馬體的核磁共振成像導航的聚焦超聲，能否調(diào)節(jié)阿爾茲海默癥小鼠模型的病理異常、適應性和行為。
結果表明，核磁共振成像導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)適應性導致的。

圖1. 核磁共振成像導航的聚焦超聲誘導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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fus instruments品牌基因**和聲孔效應聚焦超聲系統(tǒng)