跳到主要內容

臺灣博碩士論文加值系統

(18.97.9.169) 您好!臺灣時間:2025/02/18 20:04
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:許育弘
研究生(外文):Yu-Hone Hsu
論文名稱:探討聚焦超音波開啟血腦障蔽及熱療作用以增強腦部藥物之傳輸
論文名稱(外文):Investigating focused ultrasound-induced blood-brain barrier opening and low-dose hyperthermia to enhance drug delivery to the brain
指導教授:林文澧林文澧引用關係
口試日期:2017-07-13
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:112
中文關鍵詞:血腦障蔽腦瘤腦藥物傳輸聚焦超音波黏多醣症奈米藥超音波熱療
外文關鍵詞:Blood-brain barrierBrain drug deliveryBrain tumorEvans blue dyeFocused ultrasoundMucopolysaccharidosis type INanodrugUltrasound hyperthermiaRecombinant human alpha-L-iduronidase.
相關次數:
  • 被引用被引用:0
  • 點閱點閱:189
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
聚焦超音波結合微氣泡使用可開啟血腦障蔽。但關於超音波施打參數對血腦障蔽開啟的影響、超音波開啟血腦障蔽後藥物傳輸的「時間-反應」關係及「劑量-反應」關係、血腦障蔽開啟的持續時間、不同超音波施打流程對血腦障蔽開啟的效果等問題,過去的相關研究並不多。於實驗一我們探討以上問題。我們用弱聚焦超音波來開啟小鼠 (C57/B6 mice) 的血腦障蔽,並以伊凡式藍 (Evans blue) 做為追蹤分子以監測血腦障蔽的開啟。以聲壓0.56 MPa及脈衝重覆頻率1 Hz為固定參數,探討突發時長 (burst length) ,微氣泡劑量及超音波施打時間對於血腦障蔽開啟的影響。我們於超音波開啟血腦障蔽後的1、4、24小時測量腦內伊凡式藍的沉積量,以探討超音波對於腦藥物傳輸的「時間-反應」關係;我們施打不同劑量的伊凡式藍並以超音波開啟血腦障蔽,以探討血腦障蔽開啟後對於腦藥物傳輸的「劑量-反應」關係。我們於超音波開啟血腦障蔽後的不同時間點注射伊凡式藍以探討血腦障蔽開啟的持續時間。我們以超音波施打一次及兩次來開啟血腦障蔽,探討不同的超音波施打流程對於血腦障蔽開啟的效果。實驗結果顯示弱聚焦超音波可廣泛的開啟血腦障蔽。突發時長越長及微氣泡劑量越大,血腦障蔽開啟的效果就越大;超音波施打時間超過60秒並不會增加血腦障蔽開啟的程度;施打超音波後的1小時,伊凡式藍在腦的沉積量最高,24小時後伊凡式藍在腦的沉積量仍保有尖峰量的81%;在血腦障蔽已開啟的狀況下,伊凡式藍的注射量與腦內沉積量呈現高度正相關;超音波施打後,隨著時間過去,血腦障蔽開啟的程度會下降,開啟的效果可維持6小時。超音波施打兩次比施打一次多了74.8%的伊凡式藍腦沉積量。組織切片顯示弱聚焦超音波對腦部造成的傷害輕微 。伊凡式藍在血漿中會與白蛋白結合形成一個83 kDa的聚合體,這個實驗的結果可模擬一個83 kDa的巨分子藥物藉由超音波開啟血腦障蔽後傳輸到腦組織的動力學。
黏多醣症第一型是致殘率極高的遺傳性疾病,主要病因是自身無法製造alpha-L-iduronidase (IDUA),導致身體無法代謝糖胺聚醣 (glycosaminoglycans)。糖胺聚醣在身體每個細胞不當累積,造成嚴重心智障礙及各個器官的功能障礙。目前唯一有效的治療方式是酵素替代療法,也就是定期施打recombinant human alpha-L-iduronidase (rhIDU)。酵素替代療法有效的改善了許多器官的功能但是卻無法改善腦功能,因為血腦障蔽阻絕了rhIDU進入腦組織。於實驗二,我們利用弱聚焦超音波搭配微氣泡使用以開啟黏多醣症第一型小鼠的血腦障蔽,將注射入血液的rhIDU送入腦部。我們將黏多醣症第一型小鼠分成四組:1) 對照組;2) rhIDU酵素替代治療組;3) rhIDU酵素替代治療+聚焦超音波施打一次;4) rhIDU酵素替代治療+聚焦超音波施打二次。所有的聚焦超音波都施打於左腦。比較這四組左右腦部rhIDU的活性量,並利用伊凡式藍模擬rhIDU在腦部的分佈。實驗結果顯示,以聚焦超音波搭配微氣泡使用開啟左腦血腦障蔽,左腦的rhIDU活性量高達右腦的7.81倍,達到正常值的75.84%。伊凡式藍模擬顯示藥物廣泛分佈於腦內。超音波施打二次的藥物輸送效率高於超音波施打一次。這個方式未來有機會成為黏多醣症的治療方式之一。
在腦瘤的治療上,因BBB阻擋大分子進入腦部,使得化療對於腦瘤的治療效果不如其他部位的腫瘤。於實驗三,我們探討低強度聚焦超音波熱療 (low-dose focused ultrasound hyperthermia, UH)是否能夠增強奈米化療藥物pegylated liposomal doxorubicin (PLD)在腦腫瘤的傳輸。我們將小鼠乳癌細胞4T1-luc2植入小鼠腦內以建立腦轉移瘤的動物模型,並以活體影像系統 (IVIS) 觀察腦轉移瘤的生長,於腫瘤細胞植入後6天進行治療。我們將治療小鼠分為五組:1) 對照組 (control);2) Pulsed-wave focused ultrasound hyperthermia組(pUH);3) PLD注射組 (PLD);4) PLD + continuous-wave focused ultrasound hyperthermia組 (PLD+cUH);5) PLD + pulsed-wave focused ultrasound hyperthermia組 (PLD+pUH)。其中pUH及cUH使用相同的acoustic power (2.2-Watt)及sonication duration (10分鐘)。我們利用fluorometry測量doxorubicin在腦瘤組織及正常腦組織的沉積量,以及利用免疫螢光染色法來觀察PLD在腦組織的分佈及細胞凋亡 (apoptosis) 現象。結果顯示pUH可有效的強化PLD在腦瘤組織的沉積量,pUH+PLD有效抑制腦瘤的生長,並且不會對正常腦組織造成傷害。此結果顯示低強度聚焦超音波熱療可選擇性有效增強奈米藥在腦瘤組織的傳輸,並改善腦瘤的治療成效。
Pulsed ultrasound can disrupt blood-brain barrier (BBB) temporarily, but it is not clear about the effectiveness of different ultrasound parameters on BBB disruption, time-response and dose-response relationship on brain drug delivery after BBB disruption, dynamics of BBB disruption, and the effectiveness of different sonication schemes on BBB disruption. In the first portion, we investigated sonication parameter and sonication scheme effectiveness on BBB disruption. We used pulsed weakly focused ultrasound to open the BBB of C57/B6 mice. Evans blue dye (EBD) was used to determine the degree of BBB disruption. Acoustic pressure 0.56 MPa, pulse repetitive frequency 1 Hz, burst length 10 to 50 ms, microbubble dose 100 to 300 μl/kg and sonication time 60 to 150 s were used to open BBB for parameter study; brain EBD accumulation was measured at 1, 4, 24 hours after sonication for time-response relationship study; EBD 100 to 200 mg/kg was administered for dose-response relationship study; EBD injection 0 to 6 hours after sonication was performed for BBB disruption dynamic study; brain EBD accumulation induced by one-spot and two-spot sonication was investigated to study the effectiveness on BBB disruption; histology study was performed for brain tissue damage evaluation. The results showed that pulsed weakly focused ultrasound opened BBB extensively. Longer burst length and larger microbubble dose resulted in higher degree of BBB disruption; sonication time longer than 60 s did not increase BBB disruption; brain EBD accumulation peaked at 1 hour after sonication and remained 81% of peak level at 24 hours after sonication; EBD dose administered correlated to brain EBD accumulation; BBB disruption decreased as time went on after sonication and lasted for 6 hours at least; brain EBD accumulation induced by two-spot sonication increased 74.8% of that induced by one-spot sonication. There was limited adverse effect associated with sonication including petechial hemorrhages and mild neuronal degeneration. We conclude that BBB can be opened extensively and reversibly by pulsed weakly focused ultrasound with limited brain tissue damage. Since EBD combines with albumin in plasma to form a conjugate of 83 kDa, these results may represent ultrasound induced brain delivery of therapeutic molecules of this size scale.
Mucopolysaccharidosis type I (MPS I) is a debilitating hereditary disease characterized by alpha-L-iduronidase (IDUA) deficiency and consequent inability to degrade glycosaminoglycans. The pathological accumulation of glycosaminoglycans systemically results in severe mental retardation and multiple organ dysfunction. Enzyme replacement therapy with recombinant human alpha-L-iduronidase (rhIDU) improves the function of some organs but not neurological deficits owing to its exclusion from the brain by the blood-brain barrier (BBB). In the second portion, we tried to deliver rhIDU to MPS I mice brain by FUS induced BBB opening technique. We divided MPS I mice into control group, enzyme replacement group with rhIDU 2.9 mg/kg injection, enzyme replacement with one-spot ultrasound treatment group, and enzyme replacement with two-spot ultrasound treatment group, and compared treatment effectiveness among the groups. All ultrasound treatments were applied on left side brain. Evans blue was used to simulate the distribution of rhIDU in the brain. The result showed that transcranial pulsed weakly focused ultrasound combined with microbubbles facilitated brain rhIDU delivery in MPS I mice receiving systemic enzyme replacement therapy. With intravenously injected rhIDU 2.9 mg/kg, the IDUA enzyme activity on the ultrasound treated side of the cerebral hemisphere raised to 7.81-fold that on the untreated side and to 75.84% of its normal value. Evans blue simulation showed the distribution of the delivered drug was extensive, involving a large volume of the treated cerebral hemisphere. Two-spot ultrasound treatment scheme was more efficient for brain rhIDU delivery than one-spot ultrasound treatment scheme.
The clinical application of chemotherapeutics for brain tumors remains a challenge due to limitation of blood-brain barrier/blood-tumor barrier (BBB/BTB). In the third portion, we investigated the effects of low-dose focused ultrasound hyperthermia (UH) on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer cells (4T1-luc2) expressing firefly luciferase were implanted into mouse striatum as a brain tumor model. The mice were intravenously injected with PLD with/without transcranial pulsed-wave/continuous-wave UH (pUH/cUH) treatment on day-6 after tumor implantation. pUH was conducted under equal acoustic power and sonication duration as cUH. The amounts of doxorubicin accumulated in the normal brain and tumor tissues were measured with fluorometry. The tumor growth of the control, pUH, PLD, PLD+cUH, and PLD+pUH groups were evaluated with IVIS. The PLD distribution and cell apoptosis were assessed with immunofluorescence staining. The results showed that pUH significantly enhanced the PLD delivery into brain tumors and the tumor growth was further inhibited by PLD+pUH without damaging the sonicated normal brain tissues. This indicates that low-dose transcranial pUH is a promising method to selectively enhance nanodrug delivery and improve the brain tumor treatment
口試委員會審定書 I
致謝 II
中文摘要: III
Abstract VI
Abbreviation list IX
Contents XI
Chapter 1 Introduction 1
1.1 Overview of the dissertation 1
1.2 The blood-brain barrier 2
1.3 The development of focused ultrasound 5
1.4 The mechanism of BBB opening induced by focused ultrasound 7
1.5 Pegylated liposomal doxorubicin and free doxorubicin 7
1.6 Aims 9
Figures 10
Figure 1. Cross section view of the BBB. 10
Figure 2. Mechanism of BBB opening induced by FUS combined with microbubbles. 11
References 12
Chapter 2 Influence of acoustic parameters and sonication schemes on transcranial blood-brain barrier disruption induced by pulsed weakly focused ultrasound 15
2.1 Introduction 15
2.2 Materials and Methods 19
2.2.1 Animal preparation 19
2.2.2 Ultrasound equipment 19
2.2.3 Study arrangement 20
2.2.4 Animal procedures 21
2.2.5 EBD quantification 22
2.2.6 Statistical analysis 23
2.2.7 Histology study 23
2.3 Results 24
2.3.1 Ultrasound parameters, time-response relationship, and dose-response relationship 24
2.3.2 BBBD dynamics 25
2.3.3 Efficiency of different sonication schemes 26
2.3.4 Histology study 26
2.4 Discussion 27
2.5 Summary 33
Tables and Figures 34
Table 1. Experimental conditions of parameter study. 34
Table 2. Histology study for brain tissue damage evaluation. 35
Figure 1. Ultrasound equipment setup and sonication locations. 36
Figure 2. Sonication procedures. 37
Figure 3. Brain slices of BBBD induced by one-spot sonication and two-spot sonication in sonication scheme study. 38
Figure 4. The result of the first part study. 39
Figure 5. Duration of BBBD. 40
Figure 6. Comparision of BBBD induced by one-spot and two-spot sonication. 41
Figure 7. Tissue sections of brain parenchyma with hematoxylin and eosin stain. 42
References 43
Chapter 3 Transcranial pulsed ultrasound facilitates brain uptake of laronidase in enzyme replacement therapy for Mucopolysaccharidosis type I disease 48
3.1 Introduction 48
3.2 Materials and Methods 50
3.2.1 Animal preparation 50
3.2.2 Ultrasound equipment 50
3.2.3 Experimental arrangement 51
3.2.4 Animal procedures 53
3.2.5 Evans blue quantification 54
3.2.6 IDUA enzyme activity assay 54
3.2.7 Statistical analysis 55
3.3 Results 56
3.3.1 Laronidase delivery to the brain of MPS I mice 56
3.3.2 Drug distribution simulated by Evans blue distribution 56
3.4 Discussion 58
Figures 65
Figure 1. Experimental setup for BBB opening. 65
Figure 2. Procedures of ultrasound treatment in MPS I mice and B6 mice. 66
Figure 3. Locations of ultrasound exposure on MPS I mice and B6 mice. 67
Figure 4. Plasma IDUA enzyme activity assay of MPS I mice. 68
Figure 5. The liver IDUA activity of MPS-I and B6 mice. 69
Figure 6. Brain laronidase delivery. 70
Figure 7. Brain EB delivery in B6 mice. 71
References 72
Chapter 4 Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer 77
4.1 Introduction 77
4.2 Materials and Methods 81
4.2.1 Pegylated liposomal doxorubicin (PLD) 81
4.2.2 In vitro investigation of PLD accumulation in cancer cells enhanced by ultrasound 81
4.2.3 Preparation of tumor cells and the brain tumor model 83
4.2.4 Focused ultrasound (FUS) system and pulsed-waved FUS hyperthermia 83
4.2.5 Experimental grouping 84
4.2.6 Quantification of PLD entering the normal brain and tumor tissues 84
4.2.7 Measurement of tumor growth by in vivo imaging system (IVIS) and mouse survival 85
4.2.8 Immunofluorescence and PLD distribution 86
4.2.9 TUNEL assay 87
4.2.10 Statistical analysis 87
4.3 Results 88
4.3.1 Pulsed-wave ultrasound better enhances PLD delivery into tumor cells 88
4.3.2 Low-dose pulsed-wave ultrasound hyperthermia enhances the antitumor action in brain tumors 88
4.3.3 PLD delivery to normal brain and tumor tissues by low-dose pulsed-wave/continuous-wave ultrasound hyperthermia 90
4.3.4 Immunofluorescence detection of PLD deposition 90
4.3.4 TUNEL staining for apoptotic cancer cells in the tumors 91
4.4 Discussion 92
Tables and Figures 97
Table 1. Ultrasound parameters used in the in vivo experiments to perform continuous-wave ultrasound hyperthermia (cUH) or pulsed-wave ultrasound hyperthermia (pUH). 97
Figure 1. Experimental grouping 98
Figure 2. Immunofluoresence staining for in vitro investigation of pegylated liposomal doxorubicin (PLD) up-taken by 4T1 breast tumor cells with or without ultrasound sonication. 99
Figure 3. Low-dose pulsed-wave ultrasound hyperthermia enhances the antitumor action in brain tumors 100
Figure 4. PLD delivery to normal brain and tumor tissues by low-dose pulsed-wave/continuous-wave ultrasound hyperthermia 101
Figure 5. Immunofluorescence staining in the tumor regions after different therapeutics. 102
Figure 6. TUNEL staining was used to detect apoptotic cells in tumor tissues. 103
References 104
Chapter 5 Conclusion and Future work 107
References 110
Publication list 111
Ch1
Bakay L, Ballantine HT, Jr., Hueter TF, and Sosa D. 1956. Ultrasonically produced changes in the blood-brain barrier. AMA Arch Neurol Psychiatry 76:457-467.
Ballantine HT, Jr., Bell E, and Manlapaz J. 1960. Progress and problems in the neurological applications of focused ultrasound. J Neurosurg 17:858-876. 10.3171/jns.1960.17.5.0858
Barnard JW, Fry WJ, Fry FJ, and Krumins RF. 1955. Effects of high intensity ultrasound on the central nervous system of the cat. J Comp Neurol 103:459-484.
Dobrakowski PP, Machowska-Majchrzak AK, Labuz-Roszak B, Majchrzak KG, Kluczewska E, and Pierzchala KB. 2014. MR-guided focused ultrasound: a new generation treatment of Parkinson''s disease, essential tremor and neuropathic pain. Interv Neuroradiol 20:275-282. 10.15274/NRJ-2014-10033
10.15274/INR-2014-10033
Etame AB, Diaz RJ, Smith CA, Mainprize TG, Hynynen K, and Rutka JT. 2012. Focused ultrasound disruption of the blood-brain barrier: a new frontier for therapeutic delivery in molecular neurooncology. Neurosurg Focus 32:E3. 10.3171/2011.10.FOCUS11252
Gabizon A, and Martin F. 1997. Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs 54 Suppl 4:15-21.
Gabizon A, Shmeeda H, and Barenholz Y. 2003. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet 42:419-436. 10.2165/00003088-200342050-00002
Gabizon AA. 1992. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Res 52:891-896.
Gallay MN, Moser D, Rossi F, Pourtehrani P, Magara AE, Kowalski M, Arnold A, and Jeanmonod D. 2016. Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy. J Ther Ultrasound 4:5. 10.1186/s40349-016-0049-8
Hsiao YH, Kuo SJ, Tsai HD, Chou MC, and Yeh GP. 2016. Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy. J Cancer 7:225-231. 10.7150/jca.13906
Hynynen K. 2008. Ultrasound for drug and gene delivery to the brain. Adv Drug Deliv Rev 60:1209-1217. 10.1016/j.addr.2008.03.010
Hynynen K, McDannold N, Vykhodtseva N, and Jolesz FA. 2001. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640-646. 10.1148/radiol.2202001804
Jahangiri A, Chin AT, Flanigan PM, Chen R, Bankiewicz K, and Aghi MK. 2017. Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies. J Neurosurg 126:191-200. 10.3171/2016.1.JNS151591
Jain KK. 2012. Nanobiotechnology-based strategies for crossing the blood-brain barrier. Nanomedicine (Lond) 7:1225-1233. 10.2217/nnm.12.86
Kobus T, Vykhodtseva N, Pilatou M, Zhang Y, and McDannold N. 2016. Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound. Ultrasound Med Biol 42:481-492. 10.1016/j.ultrasmedbio.2015.10.009
La-Beck NM, Zamboni BA, Gabizon A, Schmeeda H, Amantea M, Gehrig PA, and Zamboni WC. 2012. Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol 69:43-50. 10.1007/s00280-011-1664-2
Lesniak MS, Upadhyay U, Goodwin R, Tyler B, and Brem H. 2005. Local delivery of doxorubicin for the treatment of malignant brain tumors in rats. Anticancer Res 25:3825-3831.
Meairs S. 2015. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles. Pharmaceutics 7:275-293. 10.3390/pharmaceutics7030275
Mitrasinovic S, Appelboom G, Detappe A, and Sander Connolly E, Jr. 2016. Focused ultrasound to transiently disrupt the blood brain barrier. J Clin Neurosci 28:187-189. 10.1016/j.jocn.2015.12.011
Pardridge WM. 2002. Drug and gene delivery to the brain: the vascular route. Neuron 36:555-558.
Peschillo S, Caporlingua A, Diana F, Caporlingua F, and Delfini R. 2016. New therapeutic strategies regarding endovascular treatment of glioblastoma, the role of the blood-brain barrier and new ways to bypass it. J Neurointerv Surg 8:1078-1082. 10.1136/neurintsurg-2015-012048
Pestalozzi BC, and Brignoli S. 2000. Trastuzumab in CSF. J Clin Oncol 18:2349-2351. 10.1200/JCO.2000.18.11.2349
Poon C, McMahon D, and Hynynen K. 2017. Noninvasive and targeted delivery of therapeutics to the brain using focused ultrasound. Neuropharmacology 120:20-37. 10.1016/j.neuropharm.2016.02.014
U.S. Food and Drug Administration. 2016. FDA approves first MRI-guided focused ultrasound device to treat essential tremor. FDA news release https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510595.htm
von Holst H, Knochenhauer E, Blomgren H, Collins VP, Ehn L, Lindquist M, Noren G, and Peterson C. 1990. Uptake of adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas. Acta Neurochir (Wien) 104:13-16.
Voulgaris S, Partheni M, Karamouzis M, Dimopoulos P, Papadakis N, and Kalofonos HP. 2002. Intratumoral doxorubicin in patients with malignant brain gliomas. Am J Clin Oncol 25:60-64.
Vykhodtseva N, McDannold N, and Hynynen K. 2008. Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. Ultrasonics 48:279-296. 10.1016/j.ultras.2008.04.004
Zaaroor M, Sinai A, Goldsher D, Eran A, Nassar M, and Schlesinger I. 2017. Magnetic resonance-guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson''s disease and essential tremor cases. J Neurosurg:1-9. 10.3171/2016.10.JNS16758
Ch2
Beccaria K, Canney M, Goldwirt L, Fernandez C, Adam C, Piquet J, Autret G, Clement O, Lafon C, Chapelon JY, and Carpentier A. 2013. Opening of the blood-brain barrier with an unfocused ultrasound device in rabbits. J Neurosurg 119:887-898. 10.3171/2013.5.JNS122374
Chen H, and Konofagou EE. 2014. The size of blood-brain barrier opening induced by focused ultrasound is dictated by the acoustic pressure. J Cereb Blood Flow Metab 34:1197-1204. 10.1038/jcbfm.2014.71
Choi JJ, Selert K, Gao Z, Samiotaki G, Baseri B, and Konofagou EE. 2011. Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies. J Cereb Blood Flow Metab 31:725-737. 10.1038/jcbfm.2010.155
Chopra R, Vykhodtseva N, and Hynynen K. 2010. Influence of exposure time and pressure amplitude on blood-brain-barrier opening using transcranial ultrasound exposures. ACS Chem Neurosci 1:391-398. 10.1021/cn9000445
Doolittle ND, Miner ME, Hall WA, Siegal T, Jerome E, Osztie E, McAllister LD, Bubalo JS, Kraemer DF, Fortin D, Nixon R, Muldoon LL, and Neuwelt EA. 2000. Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors. Cancer 88:637-647.
Etame AB, Diaz RJ, Smith CA, Mainprize TG, Hynynen K, and Rutka JT. 2012. Focused ultrasound disruption of the blood-brain barrier: a new frontier for therapeutic delivery in molecular neurooncology. Neurosurg Focus 32:E3. 10.3171/2011.10.FOCUS11252
Guillaume DJ, Doolittle ND, Gahramanov S, Hedrick NA, Delashaw JB, and Neuwelt EA. 2010. Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors: results of a phase I study. Neurosurgery 66:48-58; discussion 58. 10.1227/01. NEU.0000363152.37594. F7
Horodyckid C, Canney M, Vignot A, Boisgard R, Drier A, Huberfeld G, Francois C, Prigent A, Santin MD, Adam C, Willer JC, Lafon C, Chapelon JY, and Carpentier A. 2016. Safe long-term repeated disruption of the blood-brain barrier using an implantable ultrasound device: a multiparametric study in a primate model. J Neurosurg:1-11. 10.3171/2016.3.JNS151635
Howles GP, Bing KF, Qi Y, Rosenzweig SJ, Nightingale KR, and Johnson GA. 2010. Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound. Magn Reson Med 64:995-1004. 10.1002/mrm.22411
Howles GP, Qi Y, and Johnson GA. 2010. Ultrasonic disruption of the blood-brain barrier enables in vivo functional mapping of the mouse barrel field cortex with manganese-enhanced MRI. Neuroimage 50:1464-1471. 10.1016/j.neuroimage.2010.01.050
Hynynen K. 2008. Ultrasound for drug and gene delivery to the brain. Adv Drug Deliv Rev 60:1209-1217. 10.1016/j.addr.2008.03.010
Hynynen K, McDannold N, Sheikov NA, Jolesz FA, and Vykhodtseva N. 2005. Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 24:12-20. 10.1016/j.neuroimage.2004.06.046
Hynynen K, McDannold N, Vykhodtseva N, and Jolesz FA. 2001. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640-646. 10.1148/radiol.2202001804
Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz FA, and Sheikov N. 2006. Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery. J Neurosurg 105:445-454. 10.3171/jns.2006.105.3.445
Jacobson O, Kiesewetter DO, and Chen X. 2016. Albumin-Binding Evans Blue Derivatives for Diagnostic Imaging and Production of Long-Acting Therapeutics. Bioconjug Chem. 10.1021/acs.bioconjchem.6b00487
Jahangiri A, Chin AT, Flanigan PM, Chen R, Bankiewicz K, and Aghi MK. 2016. Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies. J Neurosurg:1-10. 10.3171/2016.1.JNS151591
Kelly JM, Bradbury A, Martin DR, and Byrne ME. 2016. Emerging therapies for neuropathic lysosomal storage disorders. Prog Neurobiol. 10.1016/j.pneurobio.2016.10.002
Kim HJ, Kim YW, Choi SH, Cho BM, Bandu R, Ahn HS, and Kim KP. 2016. Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents. Neurosurgery 78:726-733. 10.1227/NEU.0000000000001104
Kinoshita M, McDannold N, Jolesz FA, and Hynynen K. 2006. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption. Proc Natl Acad Sci U S A 103:11719-11723. 10.1073/pnas.0604318103
Kobus T, Vykhodtseva N, Pilatou M, Zhang Y, and McDannold N. 2016. Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound. Ultrasound Med Biol 42:481-492. 10.1016/j.ultrasmedbio.2015.10.009
McDannold N, Arvanitis CD, Vykhodtseva N, and Livingstone MS. 2012. Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res 72:3652-3663. 10.1158/0008-5472.CAN-12-0128
McDannold N, Vykhodtseva N, and Hynynen K. 2008. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol 34:834-840. 10.1016/j.ultrasmedbio.2007.10.016
McDannold N, Vykhodtseva N, and Hynynen K. 2008. Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol 34:930-937. 10.1016/j.ultrasmedbio.2007.11.009
McDannold N, Vykhodtseva N, Raymond S, Jolesz FA, and Hynynen K. 2005. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. Ultrasound Med Biol 31:1527-1537. 10.1016/j.ultrasmedbio.2005.07.010
Meairs S. 2015. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles. Pharmaceutics 7:275-293. 10.3390/pharmaceutics7030275
Medel R, Monteith SJ, Elias WJ, Eames M, Snell J, Sheehan JP, Wintermark M, Jolesz FA, and Kassell NF. 2012. Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications. Neurosurgery 71:755-763. 10.1227/NEU.0b013e3182672ac9
Mitrasinovic S, Appelboom G, Detappe A, and Sander Connolly E, Jr. 2016. Focused ultrasound to transiently disrupt the blood brain barrier. J Clin Neurosci 28:187-189. 10.1016/j.jocn.2015.12.011
Morel DR, Schwieger I, Hohn L, Terrettaz J, Llull JB, Cornioley YA, and Schneider M. 2000. Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. Invest Radiol 35:80-85.
Neuwelt EA, Howieson J, Frenkel EP, Specht HD, Weigel R, Buchan CG, and Hill SA. 1986. Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma. Neurosurgery 19:573-582.
Pardridge WM. 2002. Drug and gene delivery to the brain: the vascular route. Neuron 36:555-558.
Pestalozzi BC, and Brignoli S. 2000. Trastuzumab in CSF. J Clin Oncol 18:2349-2351. 10.1200/jco.2000.18.11.2349
Poon C, McMahon D, and Hynynen K. 2016. Noninvasive and targeted delivery of therapeutics to the brain using focused ultrasound. Neuropharmacology. 10.1016/j.neuropharm.2016.02.014
Schad H, Haider M, and Brechtelsbauer H. 1987. [Determination of plasma volume with indocyanine green]. Anaesthesist 36:608-614.
Schlachetzki F, Zhang Y, Boado RJ, and Pardridge WM. 2004. Gene therapy of the brain: the trans-vascular approach. Neurology 62:1275-1281.
Sheikov N, McDannold N, Jolesz F, Zhang YZ, Tam K, and Hynynen K. 2006. Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier. Ultrasound Med Biol 32:1399-1409. 10.1016/j.ultrasmedbio.2006.05.015
Sheikov N, McDannold N, Sharma S, and Hynynen K. 2008. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol 34:1093-1104. 10.1016/j.ultrasmedbio.2007.12.015
Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, and Hynynen K. 2007. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer 121:901-907. 10.1002/ijc.22732
Vykhodtseva N, McDannold N, and Hynynen K. 2008. Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. Ultrasonics 48:279-296. 10.1016/j.ultras.2008.04.004
Williams PC, Henner WD, Roman-Goldstein S, Dahlborg SA, Brummett RE, Tableman M, Dana BW, and Neuwelt EA. 1995. Toxicity and efficacy of carboplatin and etoposide in conjunction with disruption of the blood-brain tumor barrier in the treatment of intracranial neoplasms. Neurosurgery 37:17-27; discussion 27-18.
Xie F, Boska MD, Lof J, Uberti MG, Tsutsui JM, and Porter TR. 2008. Effects of transcranial ultrasound and intravenous microbubbles on blood brain barrier permeability in a large animal model. Ultrasound Med Biol 34:2028-2034. 10.1016/j.ultrasmedbio.2008.05.004
Yang FY, Fu WM, Yang RS, Liou HC, Kang KH, and Lin WL. 2007. Quantitative evaluation of focused ultrasound with a contrast agent on blood-brain barrier disruption. Ultrasound Med Biol 33:1421-1427. 10.1016/j.ultrasmedbio.2007.04.006
Yao L, Song Q, Bai W, Zhang J, Miao D, Jiang M, Wang Y, Shen Z, Hu Q, Gu X, Huang M, Zheng G, Gao X, Hu B, Chen J, and Chen H. 2014. Facilitated brain delivery of poly (ethylene glycol)-poly (lactic acid) nanoparticles by microbubble-enhanced unfocused ultrasound. Biomaterials 35:3384-3395. 10.1016/j.biomaterials.2013.12.043
Yen LF, Wei VC, Kuo EY, and Lai TW. 2013. Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats. PLoS One 8:e68595. 10.1371/journal.pone.0068595
Ch3
Beccaria K, Canney M, Goldwirt L, Fernandez C, Adam C, Piquet J, Autret G, Clement O, Lafon C, Chapelon JY, and Carpentier A. 2013. Opening of the blood-brain barrier with an unfocused ultrasound device in rabbits. J Neurosurg 119:887-898. 10.3171/2013.5.JNS122374
Belichenko PV, Dickson PI, Passage M, Jungles S, Mobley WC, and Kakkis ED. 2005. Penetration, diffusion, and uptake of recombinant human alpha-L-iduronidase after intraventricular injection into the rat brain. Mol Genet Metab 86:141-149. 10.1016/j.ymgme.2005.04.013
Chen A, Vogler C, McEntee M, Hanson S, Ellinwood NM, Jens J, Snella E, Passage M, Le S, Guerra C, and Dickson P. 2011. Glycosaminoglycan storage in neuroanatomical regions of mucopolysaccharidosis I dogs following intrathecal recombinant human iduronidase. APMIS 119:513-521. 10.1111/j.1600-0463.2011.02760.x
Chen H, and Konofagou EE. 2014. The size of blood-brain barrier opening induced by focused ultrasound is dictated by the acoustic pressure. J Cereb Blood Flow Metab 34:1197-1204. 10.1038/jcbfm.2014.71
Choi JJ, Wang S, Tung YS, Morrison B, 3rd, and Konofagou EE. 2010. Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo. Ultrasound Med Biol 36:58-67. 10.1016/j.ultrasmedbio.2009.08.006
Chopra R, Vykhodtseva N, and Hynynen K. 2010. Influence of exposure time and pressure amplitude on blood-brain-barrier opening using transcranial ultrasound exposures. ACS Chem Neurosci 1:391-398. 10.1021/cn9000445
Chu PC, Chai WY, Hsieh HY, Wang JJ, Wey SP, Huang CY, Wei KC, and Liu HL. 2013. Pharmacodynamic analysis of magnetic resonance imaging-monitored focused ultrasound-induced blood-brain barrier opening for drug delivery to brain tumors. Biomed Res Int 2013:627496. 10.1155/2013/627496
Dickson P, McEntee M, Vogler C, Le S, Levy B, Peinovich M, Hanson S, Passage M, and Kakkis E. 2007. Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol Genet Metab 91:61-68. 10.1016/j.ymgme.2006.12.012
El-Amouri SS, Dai M, Han JF, Brady RO, and Pan D. 2014. Normalization and improvement of CNS deficits in mice with Hurler syndrome after long-term peripheral delivery of BBB-targeted iduronidase. Mol Ther 22:2028-2037. 10.1038/mt.2014.152
Etame AB, Diaz RJ, Smith CA, Mainprize TG, Hynynen K, and Rutka JT. 2012. Focused ultrasound disruption of the blood-brain barrier: a new frontier for therapeutic delivery in molecular neurooncology. Neurosurg Focus 32:E3. 10.3171/2011.10.FOCUS11252
Fleischhack G, Jaehde U, and Bode U. 2005. Pharmacokinetics following intraventricular administration of chemotherapy in patients with neoplastic meningitis. Clin Pharmacokinet 44:1-31. 10.2165/00003088-200544010-00001
Groothuis DR. 2000. The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro Oncol 2:45-59.
Horodyckid C, Canney M, Vignot A, Boisgard R, Drier A, Huberfeld G, Francois C, Prigent A, Santin MD, Adam C, Willer JC, Lafon C, Chapelon JY, and Carpentier A. 2016. Safe long-term repeated disruption of the blood-brain barrier using an implantable ultrasound device: a multiparametric study in a primate model. J Neurosurg:1-11. 10.3171/2016.3.JNS151635
Howles GP, Bing KF, Qi Y, Rosenzweig SJ, Nightingale KR, and Johnson GA. 2010. Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound. Magn Reson Med 64:995-1004. 10.1002/mrm.22411
Howles GP, Qi Y, and Johnson GA. 2010. Ultrasonic disruption of the blood-brain barrier enables in vivo functional mapping of the mouse barrel field cortex with manganese-enhanced MRI. Neuroimage 50:1464-1471. 10.1016/j.neuroimage.2010.01.050
Hynynen K. 2008. Ultrasound for drug and gene delivery to the brain. Adv Drug Deliv Rev 60:1209-1217. 10.1016/j.addr.2008.03.010
Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz FA, and Sheikov N. 2006. Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery. J Neurosurg 105:445-454. 10.3171/jns.2006.105.3.445
Jahangiri A, Chin AT, Flanigan PM, Chen R, Bankiewicz K, and Aghi MK. 2016. Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies. J Neurosurg:1-10. 10.3171/2016.1.JNS151591
Jameson E, Jones S, and Remmington T. 2016. Enzyme replacement therapy with laronidase (Aldurazyme((R))) for treating mucopolysaccharidosis type I. Cochrane Database Syst Rev 4:CD009354. 10.1002/14651858.CD009354.pub4
Janson CG, Romanova LG, Leone P, Nan Z, Belur L, McIvor RS, and Low WC. 2014. Comparison of Endovascular and Intraventricular Gene Therapy With Adeno-Associated Virus-alpha-L-Iduronidase for Hurler Disease. Neurosurgery 74:99-111. 10.1227/NEU.0000000000000157
Kakkis E, McEntee M, Vogler C, Le S, Levy B, Belichenko P, Mobley W, Dickson P, Hanson S, and Passage M. 2004. Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I. Mol Genet Metab 83:163-174. 10.1016/j.ymgme.2004.07.003
Kim HJ, Kim YW, Choi SH, Cho BM, Bandu R, Ahn HS, and Kim KP. 2016. Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents. Neurosurgery 78:726-733. 10.1227/NEU.0000000000001104
Kinoshita M, McDannold N, Jolesz FA, and Hynynen K. 2006. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption. Proc Natl Acad Sci U S A 103:11719-11723. 10.1073/pnas.0604318103
Kobus T, Vykhodtseva N, Pilatou M, Zhang Y, and McDannold N. 2016. Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound. Ultrasound Med Biol 42:481-492. 10.1016/j.ultrasmedbio.2015.10.009
McDannold N, Arvanitis CD, Vykhodtseva N, and Livingstone MS. 2012. Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res 72:3652-3663. 10.1158/0008-5472.CAN-12-0128
McDannold N, Vykhodtseva N, and Hynynen K. 2008. Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol 34:930-937. 10.1016/j.ultrasmedbio.2007.11.009
McDannold N, Vykhodtseva N, Raymond S, Jolesz FA, and Hynynen K. 2005. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. Ultrasound Med Biol 31:1527-1537. 10.1016/j.ultrasmedbio.2005.07.010
Meairs S. 2015. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles. Pharmaceutics 7:275-293. 10.3390/pharmaceutics7030275
Medel R, Monteith SJ, Elias WJ, Eames M, Snell J, Sheehan JP, Wintermark M, Jolesz FA, and Kassell NF. 2012. Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications. Neurosurgery 71:755-763. 10.1227/NEU.0b013e3182672ac9
Mitrasinovic S, Appelboom G, Detappe A, and Sander Connolly E, Jr. 2016. Focused ultrasound to transiently disrupt the blood brain barrier. J Clin Neurosci 28:187-189. 10.1016/j.jocn.2015.12.011
Ou L, Herzog T, Koniar BL, Gunther R, and Whitley CB. 2014. High-dose enzyme replacement therapy in murine Hurler syndrome. Mol Genet Metab 111:116-122. 10.1016/j.ymgme.2013.09.008
Poon C, McMahon D, and Hynynen K. 2016. Noninvasive and targeted delivery of therapeutics to the brain using focused ultrasound. Neuropharmacology. 10.1016/j.neuropharm.2016.02.014
Rawson RA. 1943. The binding of T-1824 and structurally related diazo dyes by the plasma proteins. American Journal of Physiology 138:0708-0717.
Raymond SB, Skoch J, Hynynen K, and Bacskai BJ. 2007. Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo. J Cereb Blood Flow Metab 27:393-403. 10.1038/sj.jcbfm.9600336
Sheikov N, McDannold N, Jolesz F, Zhang YZ, Tam K, and Hynynen K. 2006. Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier. Ultrasound Med Biol 32:1399-1409. 10.1016/j.ultrasmedbio.2006.05.015
Sheikov N, McDannold N, Sharma S, and Hynynen K. 2008. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol 34:1093-1104. 10.1016/j.ultrasmedbio.2007.12.015
Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, and Hynynen K. 2007. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer 121:901-907. 10.1002/ijc.22732
Vite CH, Wang P, Patel RT, Walton RM, Walkley SU, Sellers RS, Ellinwood NM, Cheng AS, White JT, O''Neill CA, and Haskins M. 2011. Biodistribution and pharmacodynamics of recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis type I-affected cats following multiple intrathecal administrations. Mol Genet Metab 103:268-274. 10.1016/j.ymgme.2011.03.011
Wolf DA, Lenander AW, Nan Z, Belur LR, Whitley CB, Gupta P, Low WC, and McIvor RS. 2011. Direct gene transfer to the CNS prevents emergence of neurologic disease in a murine model of mucopolysaccharidosis type I. Neurobiol Dis 43:123-133. 10.1016/j.nbd.2011.02.015
Wraith JE, and Jones S. 2014. Mucopolysaccharidosis type I. Pediatr Endocrinol Rev 12 Suppl 1:102-106.
Xie F, Boska MD, Lof J, Uberti MG, Tsutsui JM, and Porter TR. 2008. Effects of transcranial ultrasound and intravenous microbubbles on blood brain barrier permeability in a large animal model. Ultrasound Med Biol 34:2028-2034. 10.1016/j.ultrasmedbio.2008.05.004
Yao L, Song Q, Bai W, Zhang J, Miao D, Jiang M, Wang Y, Shen Z, Hu Q, Gu X, Huang M, Zheng G, Gao X, Hu B, Chen J, and Chen H. 2014. Facilitated brain delivery of poly (ethylene glycol)-poly (lactic acid) nanoparticles by microbubble-enhanced unfocused ultrasound. Biomaterials 35:3384-3395. 10.1016/j.biomaterials.2013.12.043
Yen LF, Wei VC, Kuo EY, and Lai TW. 2013. Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats. PLoS One 8:e68595. 10.1371/journal.pone.0068595
Ch4
Ashush H, Rozenszajn LA, Blass M, Barda-Saad M, Azimov D, Radnay J, Zipori D, and Rosenschein U. 2000. Apoptosis induction of human myeloid leukemic cells by ultrasound exposure. Cancer Res 60:1014-1020.
Buldakov MA, Hassan MA, Jawaid P, Cherdyntseva NV, and Kondo T. 2015. Cellular effects of low-intensity pulsed ultrasound and X-irradiation in combination in two human leukaemia cell lines. Ultrason Sonochem 23:339-346. 10.1016/j.ultsonch.2014.08.018
Buldakov MA, Hassan MA, Zhao QL, Feril LB, Jr., Kudo N, Kondo T, Litvyakov NV, Bolshakov MA, Rostov VV, Cherdyntseva NV, and Riesz P. 2009. Influence of changing pulse repetition frequency on chemical and biological effects induced by low-intensity ultrasound in vitro. Ultrason Sonochem 16:392-397. 10.1016/j.ultsonch.2008.10.006
Feril LB, Jr., and Kondo T. 2004. Biological effects of low intensity ultrasound: the mechanism involved, and its implications on therapy and on biosafety of ultrasound. J Radiat Res 45:479-489.
Feril LB, Jr., Kondo T, Cui ZG, Tabuchi Y, Zhao QL, Ando H, Misaki T, Yoshikawa H, and Umemura S. 2005. Apoptosis induced by the sonomechanical effects of low intensity pulsed ultrasound in a human leukemia cell line. Cancer Lett 221:145-152. 10.1016/j.canlet.2004.08.034
Feril LB, Jr., Kondo T, Zhao QL, and Ogawa R. 2002. Enhancement of hyperthermia-induced apoptosis by non-thermal effects of ultrasound. Cancer Lett 178:63-70.
Frenkel V. 2008. Ultrasound mediated delivery of drugs and genes to solid tumors. Adv Drug Deliv Rev 60:1193-1208. 10.1016/j.addr.2008.03.007
Guzman HR, Nguyen DX, Khan S, and Prausnitz MR. 2001. Ultrasound-mediated disruption of cell membranes. II. Heterogeneous effects on cells. J Acoust Soc Am 110:597-606.
Hahn GM, Braun J, and Har-Kedar I. 1975. Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation. Proc Natl Acad Sci U S A 72:937-940.
Hassan MA, Buldakov MA, Ogawa R, Zhao QL, Furusawa Y, Kudo N, Kondo T, and Riesz P. 2010. Modulation control over ultrasound-mediated gene delivery: evaluating the importance of standing waves. J Control Release 141:70-76. 10.1016/j.jconrel.2009.08.020
Husseini GA, and Pitt WG. 2008. Micelles and nanoparticles for ultrasonic drug and gene delivery. Adv Drug Deliv Rev 60:1137-1152. 10.1016/j.addr.2008.03.008
Hynynen K. 2008. Ultrasound for drug and gene delivery to the brain. Adv Drug Deliv Rev 60:1209-1217. 10.1016/j.addr.2008.03.010
Jernberg A, Edgren MR, Lewensohn R, Wiksell H, and Brahme A. 2001. Cellular effects of high-intensity focused continuous wave ultrasound alone and in combination with X-rays. Int J Radiat Biol 77:127-135.
Lejbkowicz F, and Salzberg S. 1997. Distinct sensitivity of normal and malignant cells to ultrasound in vitro. Environ Health Perspect 105 Suppl 6:1575-1578.
Liu Y, Cho CW, Yan X, Henthorn TK, Lillehei KO, Cobb WN, and Ng KY. 2001. Ultrasound-Induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells. Pharm Res 18:1255-1261.
Lizzi FL, and Ostromogilsky M. 1987. Analytical modelling of ultrasonically induced tissue heating. Ultrasound Med Biol 13:607-618.
Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, Adkins CE, Roberts A, Thorsheim HR, Gaasch JA, Huang S, Palmieri D, Steeg PS, and Smith QR. 2010. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res 16:5664-5678. 10.1158/1078-0432.CCR-10-1564
Loverock P, and ter Haar G. 1991. Synergism between hyperthermia, ultrasound and gamma irradiation. Ultrasound Med Biol 17:607-612.
May JP, and Li SD. 2013. Hyperthermia-induced drug targeting. Expert Opin Drug Deliv 10:511-527. 10.1517/17425247.2013.758631
Mayer CR, and Bekeredjian R. 2008. Ultrasonic gene and drug delivery to the cardiovascular system. Adv Drug Deliv Rev 60:1177-1192. 10.1016/j.addr.2008.03.004
McDannold N, Vykhodtseva N, Jolesz FA, and Hynynen K. 2004. MRI investigation of the threshold for thermally induced blood-brain barrier disruption and brain tissue damage in the rabbit brain. Magn Reson Med 51:913-923. 10.1002/mrm.20060
Mitragotri S. 2005. Healing sound: the use of ultrasound in drug delivery and other therapeutic applications. Nat Rev Drug Discov 4:255-260. 10.1038/nrd1662
Muller OJ, Katus HA, and Bekeredjian R. 2007. Targeting the heart with gene therapy-optimized gene delivery methods. Cardiovasc Res 73:453-462. 10.1016/j.cardiores.2006.09.021
Nelson JL, Roeder BL, Carmen JC, Roloff F, and Pitt WG. 2002. Ultrasonically activated chemotherapeutic drug delivery in a rat model. Cancer Res 62:7280-7283.
Ogilvie GK, Reynolds HA, Richardson BC, Badger CW, Goss SA, and Burdette EC. 1990. Performance of a multi-sector ultrasound hyperthermia applicator and control system: in vivo studies. Int J Hyperthermia 6:697-705.
Pitt WG, Husseini GA, and Staples BJ. 2004. Ultrasonic drug delivery--a general review. Expert Opin Drug Deliv 1:37-56. 10.1517/17425247.1.1.37
Speed CA. 2001. Therapeutic ultrasound in soft tissue lesions. Rheumatology (Oxford) 40:1331-1336.
Stringham SB, Viskovska MA, Richardson ES, Ohmine S, Husseini GA, Murray BK, and Pitt WG. 2009. Over-pressure suppresses ultrasonic-induced drug uptake. Ultrasound Med Biol 35:409-415. 10.1016/j.ultrasmedbio.2008.09.004
Suit HD, and Shwayder M. 1974. Hyperthermia: potential as an anti-tumor agent. Cancer 34:122-129.
Tabuchi Y, Ando H, Takasaki I, Feril LB, Jr., Zhao QL, Ogawa R, Kudo N, Tachibana K, and Kondo T. 2007. Identification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt-4. Cancer Lett 246:149-156. 10.1016/j.canlet.2006.02.011
Tang W, Liu Q, Wang X, Wang P, Cao B, Mi N, and Zhang J. 2008. Involvement of caspase 8 in apoptosis induced by ultrasound-activated hematoporphyrin in sarcoma 180 cells in vitro. J Ultrasound Med 27:645-656.
Thanou M, and Gedroyc W. 2013. MRI-Guided Focused Ultrasound as a New Method of Drug Delivery. J Drug Deliv 2013:616197. 10.1155/2013/616197
Wang N, Tytell JD, and Ingber DE. 2009. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10:75-82. 10.1038/nrm2594
Wu SK, Chiang CF, Hsu YH, Lin TH, Liou HC, Fu WM, and Lin WL. 2014. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer. Int J Nanomedicine 9:4485-4494. 10.2147/IJN.S68347
Yoshida T, Kondo T, Ogawa R, Feril LB, Jr., Zhao QL, Watanabe A, and Tsukada K. 2008. Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells. Cancer Chemother Pharmacol 61:559-567. 10.1007/s00280-007-0503-y
Zhong W, Sit WH, Wan JM, and Yu AC. 2011. Sonoporation induces apoptosis and cell cycle arrest in human promyelocytic leukemia cells. Ultrasound Med Biol 37:2149-2159. 10.1016/j.ultrasmedbio.2011.09.012
Ch5
Hynynen K, McDannold N, Vykhodtseva N, and Jolesz FA. 2001. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640-646. 10.1148/radiol.2202001804
Ostermann S, Csajka C, Buclin T, Leyvraz S, Lejeune F, Decosterd LA, and Stupp R. 2004. Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients. Clin Cancer Res 10:3728-3736. 10.1158/1078-0432.CCR-03-0807
Patel M, McCully C, Godwin K, and Balis FM. 2003. Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates. J Neurooncol 61:203-207.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊