JP3819845B2 - 流体で充填された空洞内の局所物理パラメータの改善された測定方法 - Google Patents
流体で充填された空洞内の局所物理パラメータの改善された測定方法 Download PDFInfo
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- G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
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Description
a)流体で充填された空洞に、安定化された又はカプセル化された気泡を投与するステップと、
b)該流体で充填された空洞に、第1の超音波パルス波もしくはパルス波列をトランスデューサにより適用して、該安定化された又はカプセル化された気泡を破壊し、遊離気泡を発生させるステップと、
c)該泡のサブおよび/またはウルトラハーモニック応答を励起するために特異的に選択される周波数の第2の超音波パルス波もしくはパルス波列をトランスデューサにより適用するステップと、
d)平均応答時間を決定するステップと、
e)ステップd)の該応答時間に基づき局所物理パラメータについての値を決定するステップとを含んで成る方法を提供する。
a)カプセル化された又は安定化された気泡を含む流体物質を被験体に投与するステップと、
b)第1の超音波パルス波もしくはパルス波列をトランスデューサにより適用して、遊離気泡を発生させるステップと、
c)該泡のサブおよび/またはウルトラハーモニック応答を励起するために特異的に選択される周波数付近の第2の超音波パルス波もしくはパルス波列をトランスデューサにより適用するステップと、
d)平均応答時間を決定するステップと、
e)ステップd)の該応答時間に基づき局所物理パラメータについての値を決定するステップとを含んで成り、
ステップc)の該サブおよび/またはウルトラハーモニック応答が、連続する超音波パルスにより時間の関数としてモニターされ、この関数が測定される該物理パラメータのインジケータ(表示)であることを特徴とする方法を提供する。
R=泡の半径
t=時間
D=拡散定数
Ci/Co =飽和濃度に対する溶解ガス濃度の比
σ=表面張力
P0 =大気圧
L=オストワルド係数
pov =過剰圧力
図4は、コンピュータシミュレーションにより得られた、2.2μmの半径をもった空気泡について時間の関数としてのサブおよびウルトラハーモニックエネルギー曲線(それぞれ上および下)を示す。明細書に記載されるように、これらの曲線は周囲液体圧力の異なる値について計算された。この液体圧力は過剰圧力すなわち760mmHgの大気圧を超える圧力値により示されている。過剰圧力の値は0、50、100および200mmHgである。異なる線はそれぞれのエネルギー曲線を示す。これらの曲線から、式(2)に従って平均応答時間が計算され、平均サブおよびウルトラハーモニック応答時間についての値が表1の第3および第4欄にそれぞれ与えられる。参照として、空気泡が完全に消失するための時間が過剰圧力の関数として式(1)により計算され、第2欄に与えられる。当該新たな方法では、異なる圧力(行と行の間の差)に対するサブおよびウルトラハーモニック応答時間(第3および第4欄)の差を見ることによって、消失時間を測定するよりも高いか又は類似の感度を得ることができることが明らかである。さらに、当該新たな方法の有意な利点は、全消失時間(第2欄)を測定するための取得時間と比較して取得時間が遥かに短い(2〜3倍)ことであり、これは当該方法のリアルタイム用途にとって重要である。
この実施例は、コンピュータシミュレーションにより得られた、2.2μmの半径をもった空気泡について10mmHgの臨床関連圧力差を測定するための当該新たな方法の感度を示す。この実施例の結果を表2に示す。過剰圧力は10mmHgずつ80ないし120mmHgまでの範囲にある。消失時間(表2の第2欄)の差は10mmHgの圧力変化当たり1.2ないし1.4msの範囲にある。サブハーモニック(表2の第3欄)についての平均応答時間の差は1.7ないし2.7msの範囲にある。ウルトラハーモニック(表2の第4欄)についての平均応答時間の差は2.1ないし2.8msの範囲にある。このことは、当該新たな方法を用いることにより、気泡の完全消失を考慮する方法と比較して感度が40〜100%も増大したことを意味する。
Claims (6)
- 安定化された又はカプセル化された気泡が投与される、流体で充填された空洞内の局所物理パラメータを遠隔的に決定するための非侵襲的測定方法を実施するための装置であって、
a)該安定化された又はカプセル化された気泡を破壊し、遊離気泡を発生させるために、流体で充填された空洞に、第1の超音波パルス波もしくはパルス波列を適用するための、そして、発生された遊離気泡のサブおよび/またはウルトラハーモニック応答を励起するために特異的に選択される周波数の第2の超音波パルス波もしくはパルス波列を適用するための少なくとも1つの送信トランスデューサと、
b)連続する超音波パルスにより、該サブおよび/またはウルトラハーモニック応答をモニターするための手段と、
c)該遊離気泡の平均サブおよび/またはウルトラハーモニック応答時間を決定するための手段と、
d)該応答時間に基づき局所物理パラメータについての値を決定するための手段と、
を含む装置。 - 第1の超音波パルス波もしくはパルス波列は、放出される遊離気泡のサイズがサブハーモニックサイズよりも大きくなるようにして調整されることを特徴とする、請求項1に記載の装置。
- 第1の超音波パルス波もしくはパルス波列の周波数および振幅が第2の超音波パルス波もしくはパルス波列とは独立して選択できることを特徴とする、請求項1または請求項2に記載の装置。
- 第2の超音波パルス波もしくはパルス波列の周波数および振幅が第1の超音波パルス波もしくはパルス波列とは独立して選択できることを特徴とする、請求項1に記載の装置。
- 第1の超音波パルス波もしくはパルス波列を適用するために使用されるトランスデューサは、第2の超音波パルス波もしくはパルス波列を適用するために使用されるトランスデューサと同一のもの又は別個のものとすることができる、請求項1に記載の装置。
- 局所パラメータが圧力、温度およびガス濃度から成る群より選択される、請求項1、請求項2、請求項3、請求項4または請求項5のいずれか一項に記載の装置。
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WO2005032523A1 (en) * | 2003-09-30 | 2005-04-14 | Acusphere, Inc. | Injectable, oral, or topical sustained release pharmaceutical formulations |
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-
2002
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- 2002-04-05 AU AU2002253454A patent/AU2002253454A1/en not_active Abandoned
- 2002-04-05 WO PCT/IB2002/001229 patent/WO2002080774A2/en active IP Right Grant
- 2002-04-05 DE DE60223239T patent/DE60223239T2/de not_active Expired - Lifetime
- 2002-04-05 EP EP02722575A patent/EP1387637B1/en not_active Expired - Lifetime
- 2002-04-05 AT AT02722575T patent/ATE376803T1/de not_active IP Right Cessation
- 2002-04-05 US US10/474,134 patent/US6962071B2/en not_active Expired - Fee Related
Also Published As
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AU2002253454A1 (en) | 2002-10-21 |
DE60223239T2 (de) | 2008-08-14 |
US20040129082A1 (en) | 2004-07-08 |
DE60223239D1 (de) | 2007-12-13 |
WO2002080774A2 (en) | 2002-10-17 |
WO2002080774A3 (en) | 2003-02-27 |
US6962071B2 (en) | 2005-11-08 |
EP1387637B1 (en) | 2007-10-31 |
JP2004529697A (ja) | 2004-09-30 |
EP1387637A2 (en) | 2004-02-11 |
ATE376803T1 (de) | 2007-11-15 |
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