光學(xué)：超級透視

1、光學(xué)：超級透視【按】2015為國際光學(xué)年, 著名期刊上有很多相關(guān)的內(nèi)容. Optics: Super vision, Nature 518, 158-160 (12 February 2015) doi:10.1038/518158a 就是其中的一篇新聞綜述報道. 科學(xué)網(wǎng)上有相應(yīng)的摘譯 可見光也能”透視”肉身, 但忽略了一些內(nèi)容. 我根據(jù)原文對紅楓原來譯文進行了修正和補譯, 供感興趣的人參考.可見光也能”透視”肉身科學(xué)家欲把天文光學(xué)技術(shù)用于活體組織透視成像你可能會說我的想法很瘋狂, 但我認(rèn)為, 我們最終能運用光學(xué)技術(shù)對整個身體器官進行成像.It seemed too good to be tr

2、ue, says Allard Mosk. It was 2007, and he was working with Ivo Vellekoop, a student in his group at the University of Twente in Enschede, the Netherlands, to shine a beam of visible light through a solid wall-a glass slide covered with white paint-and then focus it on the other side. They did not ha

3、ve a particular application in mind. “I really just wanted to try this because it had never been done before,” Mosk says. And in truth, the two researchers did not expect to pick up much more than a faint blur.聽起來似乎好得令人難以置信, Allard Mosk說. 2007年, 身為荷蘭特文特大學(xué)恩斯赫德分校教授的他和自己團隊里的一名學(xué)生Ivo Vellekoop一起工作時, 用一束可

4、見光穿透了一面”固體墻”表面覆蓋著白色油漆的載玻片然后讓這些光聚焦在載玻片的另一邊. 當(dāng)時他們對于如何應(yīng)用這一現(xiàn)象并沒有產(chǎn)生確切的想法. “我只是想試一試, 因為之前從沒有人這樣做過.” Mosk說. 可以說, 當(dāng)時兩位研究人員頭腦中除了一點模糊的影子, 并沒有其他的想法.But as it turned out, their very first attempt1 produced a sharp pinprick of light a hundred times brighter than they had hoped for. “This just doesnt happen on th

5、e first day of your experiment,” exclaims Mosk. “We thought wed made a mistake and there must be a hole in our slide letting the light through!”然而, 實驗結(jié)果表明, 他們第一次實驗1得到的清晰光斑比他們希望的要亮100倍. “這樣的好運你不會一開始實驗就撞上.” Mosk吃驚地說. “我們想可能是自己犯了什么錯誤, 載玻片上一定有一個孔可以讓光通過. “But there was no hole. Instead, their experiment

6、became the first of two independent studies1, 2 that were carried out that year pioneering ways to see through opaque barriers. So far it is still a laboratory exercise. But progress has been rapid. Researchers have now managed to obtain good-quality images through thin tissues such as mouse ears3,

7、and are working on ways to go deeper. And if they can meet the still-daunting challenges, such as dealing with tissues that move or stretch, potential applications abound. Visible-light images obtained from deep within the body might eliminate the need for intrusive biopsies, for example. Or laser l

8、ight could be focused to treat aneurysms in the brain or target inoperable tumours without the need for surgery.但載玻片上沒有任何孔. 而他們的實驗也成為了當(dāng)年開啟”透視”不透明物質(zhì)的兩項獨立實驗12中的第一項. 到目前為止, 這項工作仍處于實驗室階段, 但相關(guān)進展非常迅速. 研究人員現(xiàn)已設(shè)法對一些薄的身體組織, 如老鼠耳朵3等進行優(yōu)質(zhì)成像, 而且不斷進行深入研究. 如果他們可以戰(zhàn)勝許多棘手的挑戰(zhàn), 如找到應(yīng)對活動或是伸展組織的方法, 就會推動其潛在應(yīng)用. 比如, 如果可以利用從身體

9、組織深層獲得的可見光影像, 將不再需要侵入性的活體組織檢查; 或者可以在不進行外科手術(shù)的情況下, 用激光集中治療大腦動脈瘤等不宜手術(shù)的腫瘤.“Just ten years ago, we couldnt imagine high-resolution imaging down to even 1 centimetre in the body with optical light, but now that has now become a reality,” says Lihong Wang, a biomedical engineer at Washington University in

10、St. Louis, Missouri. “Call me crazy, but I believe that we will eventually be doing whole-body imaging with optical light.”“10年前, 我們甚至難以想象利用光學(xué)對身體組織進行精度為1厘米的高分辨率影像成像, 但現(xiàn)在這些已經(jīng)成為事實.” 美國密蘇里州華盛頓大學(xué)圣路易斯分校的生物工程學(xué)家Lihong Wang說, “你可能會說我的想法很瘋狂, 但我認(rèn)為, 我們最終會用光學(xué)技術(shù)對整個身體器官進行成像.”豐富來源 Rich sourceIt is already possible

11、 to peer inside the body with X-rays and ultrasound. But the images produced by such tools are crude compared with those that should be possible with visible light. Partly this is because visible-light images tend to have higher resolution, says Wang. But it is also because optical wavelengths inter

12、act strongly with organic molecules, so the reflected light is packed with information about biochemical changes, cellular anomalies and glucose and oxygen levels in the blood.目前, 已經(jīng)可以用X射線和超聲波窺探到身體內(nèi)部, 但如果與可見光可能獲得的影像相比, 這些手段獲取的影像都過于粗糙. Wang表示, 部分原因是可見光影像傾向于擁有更高的分辨率. 但也因為光學(xué)波長與有機分子的相互作用更強, 因此反射出的光荷載著生物

13、化學(xué)變化, 細(xì)胞異常和血液中的葡萄糖, 氧氣含量等信息.However, those interactions also make visible light prone to scattering and absorption. Absorption will scupper any imaging attempt: the information the photons pick up is lost as they are absorbed into the material. Scattering, however, preserves a ray of hope. Many mate

14、rials, such as skin, white paint or fog, are opaque only because photons passing through them ricochet until they are thoroughly scrambled. But they are not lost-so in principle, the scrambling can be reversed.然而, 這些相互作用也使得可見光易于發(fā)生散射與吸收. 吸收會破壞任何企圖成像的嘗試: 由于光子被材料吸收, 它們攜帶的信息也會丟失. 然而, 散射仍然保存著一線希望. 很多材料如皮

15、膚, 白色油漆或霧, 都是”不透明”的, 這只是因為光子會彈跳著通過它們直到被完全置亂. 但這些光子沒有丟失因此在原則上, 這種置亂是可逆的.Astronomers have already solved a version of this scattering problem using a technology called adaptive optics, which allows them to undo the distortions imposed on images of stars, planets and galaxies by the scattering of light

16、 in the atmosphere (see Nature 517, 430-432; 2015). The basic idea is to collect light from a bright reference star and use an algorithm to calculate how the atmosphere has smeared and blurred its point-like image. The algorithm then controls a special deformable mirror that cancels out the atmosphe

17、ric distortions, turns the guide-star image into a point, and at the same time brings other distant objects into sharp focus.天文學(xué)家已經(jīng)使用一種叫作自適應(yīng)光學(xué)的技術(shù)解決了這類散射問題中的一個問題, 這讓他們可以糾正因大氣層中的光散射造成的恒星, 行星和星系圖像的變形(參見Nature 517, 430-432; 2015). 其基本思路是從一顆明亮的參考恒星收集光線, 并用一個算法計算大氣如何使得恒星的點狀圖像模糊變形. 這個算法事實上控制著一個特殊的”可變形”的鏡子,

18、 用以抵消大氣扭曲, 將”吉他”狀的恒星圖像恢復(fù)成點, 同時還能將其他遠距離的天體清晰聚焦.Unfortunately, this technique is tough to use in the body. Targets deep inside biological tissues do not shine the way that stars do-they have to be illuminated from the outside-and the scatterers are much more densely packed than those that scatter ligh

19、t in the atmosphere. “Youd need the equivalent of a deformable mirror with billions of moving parts to compensate for the scattering caused by an egg shell,” says Ori Katz, an optical physicist at the Langevin Institute in Paris. That is why Mosk and Vellekoop were not too hopeful of success when th

20、ey started. Still, the pair took heart from the advance of technology. “Until recently it had been preposterous to think you could control a million pixels, but, by 2007, every smartphone could do it,” says Mosk.不幸的是, 這種技術(shù)很難在生物體內(nèi)使用. 生物組織深處目標(biāo)的閃光方式與恒星不同必須從外部照亮它們而且散射體比大氣層中光的散射體密集得多. “你需要一個擁有上百億活動部件的等價的

21、可變形鏡子才能補償一個雞蛋殼產(chǎn)生的散射.” 法國巴黎勞厄·朗之萬研究所的光物理學(xué)家Ori Katz說. 這就是Mosk和Vellekoop開始時對成功沒有抱太大希望的原因. 然而, 二人依然從技術(shù)進步中得到了鼓勵. “直到最近, 可以控制一百萬像素一直都曾被認(rèn)為是荒謬的, 但到2007年, 所有的智能手機能做到這一點.” Mosk說.They therefore made use of a spatial light modulator: a device similar to an LCD smartphone display that can control the transm

22、ission of different parts of a laser beam by delaying one part relative to another. They fired their laser through the modulator towards the painted glass slide, placed a detector beyond the slide and used a computer to monitor how much light the detector picked up. The computer then added and subtr

23、acted delays at each pixel of the modulator, going through a process of trial and error to see what changes minimized the scattering of the laser light as it passed through the slide. In effect, it was trying to give the incoming light a distortion that the opaque barrier would exactly cancel out. M

24、osk and Vellekoop ran the algorithm for more than an hour, and when it was done they had a result that beat all their expectations: a focus that was a thousand times more intense than the background signal1.他們因此采用了一種”空間光調(diào)制器”: 一個與LCD智能手機顯示器類似的設(shè)備, 通過對激光的一部分相對另一部分進行延遲, 它可以控制一束激光不同部分的傳播. 他們通過調(diào)制器將激光照向涂了油

25、漆的載玻片, 把一個探測器放在載玻片的另一側(cè), 并用計算機監(jiān)測探測器收集到多少光. 然后, 計算機會加上或減掉調(diào)制器每個像素的延遲, 通過試錯過程, 觀察當(dāng)激光通過載玻片時, 哪些改變會讓其散射最小化. 實質(zhì)上, 它試圖對入射光進行扭曲, 以便精確地抵消不透明的屏障. Mosk和Vellekoop將這個算法運行了一個多小時, 當(dāng)完成后得到了一個完全超出預(yù)期的結(jié)果: 聚焦的光強是背景信號強度的1000倍1.“The Mosk experiment was an eye-opener,” says Katz. “It changed the paradigm of what could be do

26、ne with optical light.”“Mosk的實驗讓人大開眼界,” Katz說, “它改變了光學(xué)適用的范圍模式. “Soon after his succcess, Mosk learned of similar work being done by bioengineer Changhuei Yang and his team at the California Institute of Technology in Pasadena.在獲得成功之后, Mosk很快了解到帕薩迪納市加州理工學(xué)院的Changhuei Yang與其團隊也進行了相似的工作.These researcher

27、s had used a different technique to focus scattered optical light, and a different opaque substance: a thin slice of chicken breast2. But they, too, were surprised by how easy it was to do. “I had thought well spend six months on this, and when it doesnt work, well chalk it up as a learning experien

28、ce,” says Yang. “But actually it wasnt that hard.”這些研究人員使用了一種不同的技術(shù)來聚焦散射光, 也采用了一種不同的不透明物質(zhì): 一片雞胸切片2. 但實現(xiàn)這種技術(shù)的容易程度也同樣讓他們感到驚訝. “此前我認(rèn)為, 我們可能要在這項研究上花費6個月, 如果不可行, 我們打算把它作為一次學(xué)習(xí)經(jīng)歷.” Yang說, “但實際上它并沒有那么難.”Soon after the two papers were published, the field exploded as other physicists rushed to join in. One of

29、 them was optical physicist Jacopo Bertolotti, who came to work with Mosk in 2010. Bertolotti, now at the University of Exeter, UK, says that he was drawn both by the “beauty of the experiment” and by the potential it offered for medical imaging. But he could see that that goal was still a long way

30、off.這兩篇論文發(fā)表后不久, 隨著其他物理學(xué)家的迅速介入, 該領(lǐng)域的研究呈現(xiàn)出爆炸式的增長. 光物理學(xué)家Jacopo Bertolotti就是其中之一. 曾在2010年加入Mosk的工作團隊, 現(xiàn)在英國埃克塞特大學(xué)工作的Bertolotti表示, 他為”這項實驗的漂亮”及其展現(xiàn)出的醫(yī)療成像潛力所吸引, 但是他也表示, 實現(xiàn)這一目標(biāo)依然有很長的路要走.The first issue that Bertolotti faced was that Mosks original set-up required a camera to be placed behind the opaque surfa

31、ce. That is a problem for medical applications because placing a camera under the skin would involve surgery, which would be invasive, dangerous and rarely worth the risk. In 2012, however, Bertolotti, Mosk and their colleagues devised a way to put both the laser light source and the detector in fro

32、nt of the surface4.Bertolotti面臨的首個問題是, Mosk的原始設(shè)備需要將攝像機放置在不透明表面的后面. 對于醫(yī)療應(yīng)用來說這是個問題, 因為在皮膚下放置攝像機需要動手術(shù), 這可能是侵入式的, 危險且存在一定風(fēng)險. 然而, 在2012年, Bertolotti, Mosk與同事設(shè)計了一種把激光源和探測器都放置在載玻片前的方法4.Their target was a fluorescent Greek letter just 50 micrometres across hidden behind a thin opaque screen. As such, the ta

33、rget was roughly the same size as a cell and analogous with medical techniques that involved injecting fluorescent dyes into living tissue to aid in imaging. When the laser was switched on, the photons would bounce their way through the screen and produce a diffuse illumination of the fluorescent .

34、The light reflected from the letter would then make its way back through the screen and produce a blurry speckled pattern on the other side. It was like trying to see the symbol through a shower curtain.他們的目標(biāo)是一個僅有50微米大小的熒光希臘字母, 字母被隱藏在一層不透明薄片之后. 這樣, 目標(biāo)與一個細(xì)胞的大小大致相同, 類似于向活體組織注射熒光染料幫助成像的醫(yī)療技術(shù). 當(dāng)打開激光后, 光子

35、會跳躍著通過屏幕, 并使熒光字母產(chǎn)生一種漫射照明. 從字母反射的光會反向通過屏幕, 并在屏幕的另一面產(chǎn)生模糊的斑點圖案. 這就像試圖透過浴簾看見符號那樣.Yet the shape of the letter was still encoded in the scattered light. To retrieve that shape, the team recorded the speckle pattern, moved the laser to shine at a different angle, then recorded the new speckle pattern4. By

36、repeating this many times and comparing the patterns point by point, a computer could work out how the patterns were correlated-and from that, work backwards to reconstruct the hidden letter .然而, 這個字母的形狀依然被編碼在散射光中. 為了恢復(fù)其形狀, 該團隊記錄了斑點模型, 把激光移動到不同的角度進行照射, 然后記錄這些新斑點4. 通過重復(fù)這一過程多次, 以及對圖案進行點對點的對比, 計算機可以計算出

37、這些圖案之間是如何關(guān)聯(lián)的, 并基于此進行逆向運算, 重建隱藏的字母.That was progress, says Bertolotti, but it still was not good enough. “It only works if the object to be imaged is on the other side of the scattering medium,” he says. For many medical applications, such as seeing inside the brain, or within a blood vessel, the tar

38、get is buried within tissue.Bertolotti表示, 這是一個進步, 卻仍然不夠理想. “它只有當(dāng)要成像的物體位于散射介質(zhì)背面時才起作用.” 他說. 對很多醫(yī)療應(yīng)用來說, 如觀察大腦內(nèi)部或是血管內(nèi)部, 目標(biāo)都掩藏在組織內(nèi)部.透視內(nèi)部 Inside outThe challenge of imaging inside the scattering medium has been taken up by a number of groups, including Yangs and Wangs. In 2013, for instance, Yangs team ac

39、hieved this feat with unprecedented resolution by picking out a fluorescent bead just one micrometre across sandwiched between two artificial opaque layers5.目前, 已有多個研究組在嘗試解決散射介質(zhì)內(nèi)部成像這一挑戰(zhàn), 其中就包括Yang和Wang的團隊. 例如, 在2013年, 通過識別出放在兩片不透明人工薄片之間, 僅有1微米大小的熒光微球, Yang的團隊以前所未有的分辨率展示了他們高超的技術(shù)5.Yang, together with

40、biologist Benjamin Judkewitz and the rest of his team did this by illuminating the medium and letting the light bounce its way through to the other side, then reflecting it back with a time-reversing mirror, which effectively forces every light ray to exactly retrace its steps. Time-reversing all th

41、e rays would simply undo all the scattering, however. So instead, the team focused an ultrasound beam-which is not easily scattered-at one point in the medium, knowing that any optical light that happened to pass through that point would undergo a slight shift in frequency. Then on the far side, the

42、 researchers set up the time-reversing mirror tuned so that it would send back only the light that had experienced that frequency shift. The result was a thin, time-reversed beam that would automatically pass back through the focus and add its energy to the light from the first pass. This turned the

43、 ultrasound focus into a spot of comparatively high radiation intensity-“a torch inside the wall”, says Judkewitz, who is now at the Charité University Hospital in Berlin. Better still, the ultrasound focus could be moved around within the medium. And when it passed over the bead, the bead fluo

44、resced (see Light and sound).Yang, 再加上生物學(xué)家Benjamin Judkewitz及其團隊成員所采用的方法是, 先對介質(zhì)進行照明, 讓光以彈跳的方式通向另一側(cè), 再使用時間反轉(zhuǎn)鏡將其反射回來, 從而有效地迫使每一束光線精確地回溯其路徑. 然而, 對所有光線進行時間反轉(zhuǎn)只會簡單地消除所有散射. 因此, 作為替代, 團隊將超聲波束它不容易散射聚焦于介質(zhì)中的一點, 這樣任何通過該點的光其頻率都會發(fā)生很小的偏移. 然后在另一邊, 研究人員設(shè)置了時間反轉(zhuǎn)鏡, 并將其調(diào)整得只能傳回那些有頻移的光. 結(jié)果得到了一個薄的, 時間反轉(zhuǎn)的光束, 它自動通過焦點傳回并將其能量添

45、加到第一次通過的光. 這樣就將超聲聚焦變成了一個具有較高輻射強度的點“墻中火炬”, 柏林Charité大學(xué)附屬醫(yī)院的Judkewitz說. 更好的是, 超聲聚焦可在介質(zhì)中移動. 當(dāng)它穿過微球時, 微球就會發(fā)出熒光(參見”光與聲”).However, the technique was still a long way from seeing into deep layers of tissue, which pose another, much tougher challenge: they tend to move constantly as a result of blood f

46、low and breathing. “We are still not so close to medical applications because these techniques tend to work only if the scattering medium is perfectly frozen in time,” says Mathias Fink, a physicist at Langevin who pioneered a version of the time-reversal technique in the 1990s that used ultrasound

47、alone6. Most groups have reduced the timing from Mosks original hour or so to just tens of seconds, says Katz, and that is fine for imaging a bead or a letter , but not for imaging a tumour in the body.然而, 這種技術(shù)距離觀察深層活體組織還有很長的路要走, 這也提出了另一個更加艱難的挑戰(zhàn): 由于血液的流動與呼吸作用, 組織經(jīng)常處于移動之中. “我們還沒有很接近醫(yī)療應(yīng)用, 因為這些技術(shù)往往只有當(dāng)散

48、射介質(zhì)完全靜止時才能起作用,” Mathias Fink說. 他是朗之萬研究所的一名物理學(xué)家, 曾在上世紀(jì)90年代率先提出了僅僅使用超聲波的一種時間反轉(zhuǎn)技術(shù)6. 大多數(shù)研究組都已經(jīng)將處理時間從Mosk原本的一小時左右減少到幾十秒, Katz說, 這對微球或字母成像是可以的, 但還不適合用于體內(nèi)腫瘤的成像.But last year, a team led by Sylvain Gigan, a physicist at the Kastler Brossel Laboratory in Paris, and including Katz and Fink, demonstrated a way

49、 to reconstruct the image of the hidden object in just one camera shot7. “Its a bit like magic when you see the algorithm converge on the final image,” Gigan says. 然而在去年, 一個由巴黎卡斯特勒·布羅塞爾實驗室物理學(xué)家Sylvain Giga領(lǐng)導(dǎo)的團隊, 還有Katz和Fink, 展示了一種僅用單次攝影構(gòu)建隱藏物體影像的方法7. “當(dāng)看到算法收斂到最終的影像時, 你會覺得有點兒像變魔術(shù).” Gigan說.Wang agr

50、ees that speed is of the essence. “Everything is in motion and we only have a millisecond-scale window to make an image,” he says. In a paper published in January3, Wang and his team managed to get the speed down to 5.6 milliseconds, “which is fast enough for selected in vivo imaging”, he says. Furt

51、hermore, their target was made from ink-stained gelatin and sandwiched between the ear of an anaesthetized mouse and a ground-glass diffuser. Getting success with a live mouse is impressive, says Bertolotti-although he points out that “moving from a mouse ear, which is relatively thin, to imaging hu

52、man skin and flesh will still take a lot of extra work”.Wang表示, 速度是關(guān)鍵. “一切都在運動, 而我們只有毫秒級別的時間窗口進行成像,” 他說. 在一月份發(fā)表的一篇論文中3, Wang及其團隊成功地將成像時間縮短到5.6毫秒, “對于體內(nèi)成像這已經(jīng)足夠快了”, 他說. 此外, 他們的目標(biāo)用墨水染色的明膠制成, 放置于麻醉小鼠的耳朵和毛玻璃散射器之間. 對活體小鼠取得成功令人印象深刻, Bertolotti說但他指出, “從相對較薄的小鼠耳朵, 到對人體皮膚和血肉進行成像仍將需要很多的額外工作.”As of today, Berto

53、lotti adds, there is still no imaging approach that stands out above the rest. Each has its advantages and disadvantages. “Rather than developing one technique thats good for everything, I think well develop a suite of techniques that could one day all be combined into the same piece of apparatus,”

54、he says. “I dont know how quickly that might happen, but this is a young and fast-moving community, so it could be within a few years.”截至今日, Bertolotti補充說, 還沒有一種成像方法脫穎而出, 每中方法都有其優(yōu)點和缺點. “與其開發(fā)一種適用于一切的好技術(shù), 我認(rèn)為我們應(yīng)該開發(fā)一套技術(shù), 所有這些技術(shù)有一天可能會被運用到同一個設(shè)備中,” 他說. “我不知道這多快會發(fā)生, 但這是一個新的, 快速發(fā)展的領(lǐng)域, 所以可能在幾年之內(nèi)就會發(fā)生.”The tec

55、hniques now being pioneered by bioengineers and physicists for medicine could also be put to a range of other purposes. Mosk, for example, believes that these methods could be a tool for art restoration. “Most painters build up works in several layers, and the layers below can influence the chemical and physical ageing of the painting, so its of some significance that you know what is in there if you want to preserve it,” he says. Methods that in effect unscatter light could also help th