CN101400313B - Apparatus for controlling at least one of at least two sections of at least one fiber - Google Patents

Abstract

An apparatus for applying a plurality of electro-magnetic radiations to a sample is provided. In one exemplary embodiment, the apparatus can include an arrangement which has a specific portion with a plurality of channels. One of channels can facilitate a first radiation of the radiations to be forwarded to the sample that is within an anatomical structure, and another one of the channels can facilitate a second radiation of the radiations to be forwarded to the sample. The first radiation may have a first wavelength band, and the second radiation may have a second wavelength band. The first wavelength band may be substantially different from the second wavelength band. According to another exemplary embodiment, the first radiation can be adapted to be delivered to a first area of the sample, and the second radiation may be capable of being delivered to a second area of the sample. The first area may be substantially enclosed by the second area. According to yet another exemplary embodiment of the present invention, each of the channels can facilitate at least one particular radiation of the radiations to be forwarded to the sample that is within an anatomical structure of the sample, the radiations being delivered to different areas of the sample. Centers of every one of the areas may be provided substantially along a line.

Description

Be used for device that at least one part of at least two parts of at least one optical fiber is controlled

The cross reference of related application

The serial number that the application submitted to based on February 1st, 2006 is 60/764, the serial number that 622 U.S. Patent application and on June 1st, 2006 submit to is 60/810,867 U.S. Patent application, and require the priority of these U.S. Patent applications, the full content of these U.S. Patent applications is incorporated herein by reference.

Statement about federal sponsored research

The present invention is the 17-02-2-0006 contract of authorizing according to US military cooperation agreement department (DAMD), finishes under U.S. government supports.Therefore, U.S. government enjoys some right of the present invention.

Background technology

Laser is used for ablating or heat damage illing tissue is known, and, is preferred sometimes therefore mainly due to the accurate partial result that may realize that collateral damage is minimum.Yet in practice, the use of laser therapy in using such as the specific clinical of handling early stage epithelial cancer and forerunner (precursor) thereof etc. is so not desirable.One of the problem that is used for the laser therapy of these application is can't control exactly and the boot process degree of depth, thereby causes palindromia owing to imperfect treatment or with excessive invasive processing complications associated with arterial system.

Epithelial cancer: diagnosis and processing

Generally seek to be used for discerning in early days and handling the method and the technology of cancer, so that remarkable minimizing and the possibility that shifts relevant M ﹠ M are provided.Since epithelial cancer and forerunner's pathological changes usually be focus and may on big visual field (wide field), distribute unevenly, therefore sensitive diagnosis requires high.Should diagnose with unicellular other size scale of level in may be more than the visual field of 1,000,000,000 cells comprising.

Epithelial cancer has also proposed challenge to treatment.Because they are epidermises, so usually can come near epithelial lesion by using Wicresoft's conduit or endoscope.Yet treatment challenge is to kill all sidedly, excise or ablates whole pathological changes and do not damage that underlie or contiguous tissue.Why challenging especially this be because the degree of depth of disease and even the thickness of normal epithelial layer may alter a great deal.In addition, the epithelial tissue compliance is strong and therapeutic equipments can cause obvious compression.Therefore, be designed to function of organization to the treatment of constant depth is had the undertreatment of the recurrence of causing or can cause the risk of the excess processes of severe complication.

Barrett esophagus

Described in the publication 1 of sign hereinafter, the importance of Barrett esophagus (BE) mainly based on popular, its incidence rate of this disease increase rapidly and for the patient's who suffers from severe paraplasm and adenocarcinoma pessimistic prognosis.Current common opinion (described in the publication 2 and 3 that identifies hereinafter) thinks that the BE under controlled way destroys comprehensively and anti-reflux processing causes squamous regeneration, and thinks that lasting anti-current control has stoped the recurrence of BE.Challenge is to realize comprehensive removal of pathology mucosa, keeps the tissue that underlies of esophageal wall simultaneously.Incomplete processing can cause the phosphorus shape undue growth of covering the pathology that underlies.Excessive invasive treatment can cause the narrow of esophageal wall or perforation.The information relevant with treatment with the examination of BE hereinafter is provided.

Examination

The multiple mode of the esophagus examination that is used for the BE management process is investigated.Brush cytology (described in the publication 4 and 5 of sign hereinafter) and can be independent of splanchnoscopy and be used such as the use of the biological marker of the disappearance of 17p (p53) gene and/or variation etc., but the spatial mappings of disease can not be provided.The high power video-endoscope is checked (described in the publication 8 of sign hereinafter), fluorescence spectroscopy (described in the publication 9 of sign hereinafter) and light scattering spectroscopy (described in the publication 10 of sign hereinafter), and each has all provided the assurance to a diagnosis, but provides about insufficient information of surface microstructure and be not verified as yet for the examination of big visual field.High-resolution endoscope ultrasound wave and pigment splanchnoscopy (as respectively hereinafter described in the publication 11 and 12 of sign) all can be applied to big visual field, but lock into muting sensitivity and specificity.

Optical coherence tomography (OCT) system, method and technology (described in the publication 13 and 14 that identifies hereinafter) have been developed.As submit in the International Patent Application PCT/US2004/029148 that submitted in 8th JIUYUE in 2004, on July 9th, 2004 the 10/501st, No. 276 U.S. Patent applications and hereinafter described in the publication 15-17 of sign have been developed the specific DC of OCT accurately for special intestinalization life (specialized intestinal metaplasia), paraplasm and adenocarcinoma.For example, described in the publication 18-20 of sign hereinafter, the OCT technology is development to some extent, this show wavelength domain (with time domain comparatively speaking) in gather the image taking speed improvement that the OCT signal can provide a plurality of orders of magnitude, keep the excellent images quality simultaneously.Described in the 11/266th, No. 779 U.S. Patent application of submitting on November 2nd, 2005 and the publication 21 that hereinafter identifies, developed a kind of so exemplary second filial generation imaging technique, for example optical frequency domain imaging (OFDI).Utilize OFDI method, technology and system, can disturb, in tissue, carry out high-resolution ratio range finding (publication 22 of the sign that for example vide infra) by the spectral resolution that in tuning source wavelength, detects between tissue samples and reference.Provided in the publication 23 as sign hereinafter, OFDI method, technology and system can catch (for example 10 μ m) 3 voxels with the speed of about per second 4,000 ten thousand times at present, and image taking speed might surpass twice in the near future.As what provided in the publication 24 that identifies hereinafter, the sensitive OFDI method of phase place, technology and system have been used for imaging stream in addition.

Controlled treatment

Handle (having or not paraplasm) and assessed specific intracavity mode, photodynamic therapy (PDT) (as what provide in the list of references 25 that identifies hereinafter) is provided at SIM, laser (532nm and 1064nm) (as what provide in the list of references 26 that identifies hereinafter), multipolar electrocoagulation knot (as what provide in the list of references 27 that identifies hereinafter), argon plasma condense (providing in the list of references 28 as sign hereinafter), splanchnoscopy mucous membrane resection (as what provide in the list of references 29 that identifies hereinafter), radio frequency is ablated (as what provide in the list of references 30 that identifies hereinafter) and is used the low temperature of liquid nitrogen to ablate (as what provide in the list of references 31 that identifies hereinafter).Though every kind in these technology all shows very successfully, great majority research has been described and may have been caused lasting SIM or undue non-homogeneous treatment of deeply ablating potentially, and this has caused narrow or perforation.To surpassing in 100 patients' the research, PDT may cause 30% stenosis rate with regard to single processing, and 50% stenosis rate (providing in the list of references 32 as sign hereinafter) may be provided with regard to a plurality of processing.The exemplary reason of failure still imperfectly understands, but can actively start because of comprise that these are hand-held, the manual high surface area of the character relevant of many equipment, needs processing and for the intrinsic preference (providing) of the visual processes end points of determining by the doctor that is used for handling in sight devices as the list of references 3 and 30 that identifies hereinafter with the operator.In addition, may there be high transmutability in the thickness of mucous layer in patient self and between the patient, and has observed directly the obvious compression of esophagus soft tissue.Yet existing therapeutic modality is not considered the transmutability of layer thickness or the compressibility of esophageal wall.

Thereby need overcome the deficiency of describing hereinbefore here.

Summary of the invention

In order to solve and/or to overcome the problems referred to above and/or be not enough to and other deficiency, can be provided for the example embodiment of device that at least one part at least two parts of at least one optical fiber is controlled.

Can utilize example embodiment of the present invention to solve such deficiency.In an exemplary embodiment of the present invention, can provide a kind of device that at least one part of at least two parts of at least one optical fiber is controlled of being used for.This device can comprise the first that can be arranged on the specific jointed fiber in the described optical fiber and the device between the second portion.Can with the vertical specific direction of the extension of particular fiber on specific part in first and the second portion is set.Described device can be controlled particular fiber, makes that the specific part in the described part can be with respect at least 360 ° of specific direction rotations.Described device can comprise another device, described another device can twine described particular fiber at least in part and control described particular fiber around second device, makes that the specific part in the described part can rotate with respect to specific direction during the transmission of electromagnetic radiation.

For example, the specific part in the described part can be with respect at least 1800 ° or 3600 ° of described specific direction rotations.Described optical fiber can comprise a plurality of optical fiber.Described device can be arranged between the first and second portion of each optical fiber in described specific jointed fiber in the described optical fiber and another jointed fiber.Can with the vertical specific direction of extension of respective specific optical fiber and another optical fiber on first and the first of first specific part in the second portion and described another optical fiber and second specific part in the second portion of described particular fiber are set.Described device can be controlled described particular fiber and described another optical fiber, makes that first specific part and second specific part in the described part can be with respect at least 360 ° of corresponding specific direction rotations.First specific part and second specific part in the described part can rotate simultaneously.

According to another example embodiment of the present invention, described device can comprise another device, and described device can twine particular fiber at least in part around described another device.Described another device can be the cylinder device.Described another device can be arranged on and be configured to twine in the structure of particular fiber in order to limit around described another device.Described another device can be positioned near the structure, makes described another device and/or described structure to rotate with respect to another one, so that twine particular fiber around described another device.Described particular fiber can be that optical fiber, single-mode fiber, multimode fibre, fibre ribbon and/or fibre bundle are kept in polarization.

When reading the following specifically describes of the embodiment of the invention in conjunction with claims, it is clear that these and other objects of the present invention, feature and advantage will become.

Description of drawings

More purposes of the present invention, feature and advantage will become clear from the following specifically describes with the accompanying drawing that exemplary embodiment of the present is shown is bonded, in the accompanying drawings:

Figure 1A is the sketch map of OFDI balloon catheter according to an exemplary embodiment of the present invention;

Figure 1B is the photo of the OFDI balloon catheter shown in Figure 1A;

Fig. 2 A is to use the example images of the perspective view of the pig feed pipe that OFDI balloon catheter according to an exemplary embodiment of the present invention obtained;

Fig. 2 B is the example images of top view of the pig feed pipe of Fig. 2 A;

Fig. 2 C is the example images of side view of esophageal wall of the pig feed pipe of Fig. 2 A;

The exemplary OFDI image that Fig. 3 is to use BE technology according to an exemplary embodiment of the present invention to gather in human subjects;

Fig. 4 is used to according to an exemplary embodiment of the present invention handle and monitors the exemplary means of tissue and the sketch map of use thereof;

Fig. 5 is to use a plurality of exemplary m mould OFDI phase image group that exemplary means and corresponding organizational structure obtained of Fig. 4;

Fig. 6 A-6D is the example images that is associated with the OFDI data of being gathered at the translation sample according to an exemplary embodiment of the present invention;

Fig. 7 A is the preceding OFDI image of exemplary laser treatment that utilizes exemplary embodiment of the present to obtain;

Fig. 7 B is the preceding birefringence images of exemplary laser treatment of utilizing exemplary embodiment of the present to obtain;

Fig. 7 C utilizes OFDI image after the exemplary laser treatment that exemplary embodiment of the present obtains;

Fig. 7 D utilizes birefringence images after the exemplary laser treatment that exemplary embodiment of the present obtains;

Fig. 8 is the image of the exemplary vessel graph extracted of the comprehensive data centralization that obtains from pig feed pipe live body that can utilize that exemplary embodiment of the present obtains;

Fig. 9 is the exemplary live body doppler flow image that utilizes the pig feed pipe of exemplary embodiment of the present acquisition;

Figure 10 is the figure as the water absorption coefficient of the function of wavelength and corresponding penetration depth that utilizes that exemplary embodiment of the present obtains;

Figure 11 is the sketch map of the two beam guide tubes probe of another exemplary embodiment according to the present invention;

Figure 12 is the diagrammatic side view and the front view of the three beam guide tubes probe of the another exemplary embodiment according to the present invention;

Figure 13 is the perspective view of watch spring (watch-spring) multichannel optics rotary engaging member according to an exemplary embodiment of the present invention;

Figure 14 is the design reproduction that the image of feedback can be provided to the user that utilizes exemplary embodiment of the present to obtain;

Figure 15 is the block diagram of OFDI systematic sample arm of the introducing optical switch of the another exemplary embodiment according to the present invention;

Figure 16 is the block diagram of OFDI systematic sample arm of the introducing optical branching device of the another exemplary embodiment according to the present invention;

Figure 17 is the block diagram of OFDI systematic sample arm of the single wavelength division multiplexer of introducing of the another exemplary embodiment according to the present invention;

Figure 18 is the block diagram of the OFDI systematic sample arm of the introducing cladding mode bonder of the another exemplary embodiment according to the present invention and doubly clad optical fiber;

Figure 19 is the block diagram of three port rotary couplers and conduit according to an exemplary embodiment of the present invention;

Figure 20 be according to the present invention another exemplary embodiment to the treatment follow-up demultiplexing of light and can make the block diagram of imaging single fiber rotary coupler along separate routes;

Figure 21 is the sketch map and the use of interior (in-line) conduit probe of two bunch according to an exemplary embodiment of the present invention;

Figure 22 is the front view and the side view of three beam guide tubes probes and balloon catheter according to an exemplary embodiment of the present invention;

Figure 23 is that described device can generate the treatment bundle and the fast scan imaging bundle that can slowly rotate according to an exemplary embodiment of the present invention based on the side view of the device of micro machine;

Figure 24 is the block diagram in the source for the treatment of according to an exemplary embodiment of the present invention, and the low-power tunable source of following the broadband booster amplifier is introduced in described treatment source;

Figure 25 is the block diagram in the treatment source of the introducing different wave length of another exemplary embodiment according to the present invention and polarising a plurality of laser diode (LD);

Figure 26 introduces the tunable wave length treatment source of laser diode bar and the result's that generates thus diagram according to an exemplary embodiment of the present invention;

Figure 27 is the side view that comprises another exemplary embodiment of the system of galvanometric scanners and use thereof, and this galvanometric scanners can allow the scanning repeatedly on the surface of tissue of OFDI bundle;

Figure 28 is the sketch map according to the another exemplary embodiment of OFDI of the present invention system, and the another exemplary embodiment of this OFDI system can be used for being detected as picture and supervisory signal via acousto-optic frequency shifters;

Figure 29 A is the flow chart that is used to obtain with the exemplary embodiment of the method for the information of at least one part correlation connection of sample according to of the present invention;

Figure 29 B is the flow chart according to another exemplary embodiment of the method for the Temperature Distribution that is used for controlling sample of the present invention; And

Figure 29 C is the flow chart of another exemplary embodiment of at least one part that is used for to biological structure according to the present invention method of applying laser emission.

In institute's drawings attached, unless otherwise, otherwise same numeral and character all are used for representing similar features, element, parts or the part of illustrated embodiment.In addition, although describe the theme invention now with reference to accompanying drawing, this finishes in conjunction with exemplary embodiment.Being intended to can be under the situation of true scope that does not break away from the invention of theme as defined by the appended claims and spirit, and described embodiment is changed and revises.

The specific embodiment

According to of the present invention be used to control with the exemplary embodiment of the system and method for locating therapy can be based on the thermal excitation of carrying by the spacescan laser beam of routine.For example, described in the publication 33 of sign hereinafter, when not having photochemistry or phase transition process, the laser energy that is absorbed by tissue can be basically or is fully converted temperature to and rise.Described in the publication 34 that identifies hereinafter, for the length of exposure greater than about 10ms, how the temperature persistent period that surpasses 60-70 ℃ generally all may cause irreversible protein denaturation and cell death.When energy was absorbed, it can be subjected to the space redistribution because of thermal diffusion.In nineteen eighty-three, described in the publication 35 that identifies hereinafter, described following exemplary design, this conceives proposition, can come the limited microsurgery effect in implementation space (the optionally photo-thermal effect of separating) by using the laser explosure shorter than the feature thermal diffusion time of the volume that is heated.For big relatively (〉 1mm) laser beam of diameter and the optical maser wavelength of about 1450nm, at this feature diffusion time of biological tissue can be about 1 second.Under these conditions, the temperature increase can be according to following formula, by laser power density P _d, absorptance μ _aAnd time of exposure t determines (described in the publication 33 and 34 that identifies hereinafter):

$\mathrm{\ΔT}(t,r,z)\≈\frac{P_{d}t{\mathrm{\μ}}_a}{\mathrm{\ρc}}\exp (-{\mathrm{\μ}}_{a}z-\frac{2r^2}{W^2})$ Equation 1

Wherein ρ is that tissue density, c are thermal capacity, and r is and radius W is a radial distance between the center of Gaussian laser beam of 1/e2.Though this is approximate has ignored the scattering of laser when it propagates in the tissue, the model (described in the publication 36 that hereinafter identifies) that comprises scattering significantly shows that under the described conditions the deviation with equation 1 is less than 10%.

Because absorptance is relevant with wavelength, so equation 1 shows laser parameter P _d, t and wavelength can be used for controlling the degree of depth of heat injury and minimize collateral damage to the tissue that underlies.Why operation in spectrographic visible part has challenge, is because absorb and controlled by chromophore, and described chromophoric concentration alters a great deal because of different tissues and pathological conditions.By relatively, near the absorption spectrum of the biological tissue the 1.45 μ m is leading by water, and therefore can be in the scope of organization constant.In addition, tuning by in the appropriate wave-length coverage from 1375nm to 1430nm for example, carrying out, can the range of choice from more than the absorption length of 2mm to 300 μ m.This exemplary range is matched with the depth characteristic of epithelial lesion well.

Exemplary supervision

Investigated multiple mode, comprised analysis (described in the publication 37 that identifies hereinafter) the acoustics transition that in ablation process, generates at the monitoring laser treatment, organize the variation (described in the publication 38 and 39 that identifies hereinafter) of reflectance, be used to distinguish the fluorescence spectroscopy (described in the publication 40 that identifies hereinafter) of mottle and blood vessel wall, in order to the plasma spectroscopy of difference skeleton and nervous tissue (described in the publication 41 of sign hereinafter) and to the cavity analysis of dynamics (described in the publication 42 that identifies hereinafter) of the top end of the laser optics probe that in operation for glaucoma, is used for controlled scleral perforation.Except the process of in publication 38 and 39, describing, in every kind of such method, only striden the border of particular tissue type and just caused supervisory signal after changing in the heat injury district based on reflectance.There is not a kind of method can determine the degree of depth of heat injury or the spatial relationship of damaged tissues and adjacent active tissue.By monitoring that the laser part be not organized absorption realizes the spatial resolution of specific degrees.Insert optical fiber by passing pin, can collect laser, and can measure the scattering variation (as the publication 43 that hereinafter identify described in) relevant with temperature from the volume different angles on every side of being heated.Also visual at the physical removal that will change by the scattering that the ablative laser irradiation causes and organize, verified the high-resolution original position imaging (described in the publication 44 that identifies hereinafter) of more direct mode.

Can utilize and the information relevant according to the exemplary embodiment of surveillance of the present invention, method and technology the known tissue response of heat injury.These exemplary response can include but not limited to can by LASER HEATING cause and can be in being low to moderate 45 ℃ temperature range observed microdeformation (described in the publication 33 of sign hereinafter) and scattering change (described in the publication 36,38 and 45 of sign hereinafter), birefringence (described in the publication 46 of sign hereinafter) and blood flow (described in the publication 47 that identifies hereinafter).An illustrative aspects of the exemplary embodiment of the method according to this invention and technology is and can detects and present these thermal responses with the cross sectional image form with heterogeneous microstructure with high spatial resolution.

The exemplary policy that is used for the conformal laser therapy

According to exemplary embodiment of the present invention, can provide can examination and system, the apparatus and method of the laser therapy of accurate guiding are provided.Because preferably can be used for the characteristic length scale of comprehensive examination and treatment comprehensively may be different, so might carry out these targets respectively.For example, (for example may be performed) examination as first step and can utilize a kind of or a plurality of comprehensive imaging technique of resolution for the cell size scale.This example process can be used for discerning the zone that is used for successive treatment.After carrying out the examination process, endoscope probe can refer to get back to the appointed area, and can carry out treatment under instructing in real time, thereby handles all diseases and minimize collateral damage.The risk that this example results can reduce complication simultaneously by the effectiveness that for example improves treatment is improved the management to the Barrett esophagus patient.

Though the processing of junctional epithelium cancer is described, go for any application of laser treatment according to the exemplary embodiment of system of the present invention, technology and method, include but not limited to the application in the dermatological for example.Relevant epithelial cancer of some that exemplary embodiment of the present invention solved and precancerous lesion can include but not limited to larynx, cervix uteri and ovary, bladder, oral cavity and lung.In addition, exemplary embodiment of the present invention goes for monitoring photodynamic therapy, radio frequency ablation and cold therapy field, to provide the degree of depth of treatment and the control of spatial dimension.

Exemplary big visual field examination

In order to carry out effective examination process, preferably carry out the comprehensive inspection and the aligning of big surf zone are made a definite diagnosis the application of the criterion of breaking, so that discern the particular pathologies district.Described in the publication 15-17 that identifies hereinafter, develop and verified various OCT DCs for special intestinalization life, paraplasm and adenocarcinoma.For example, described in the publication 16 that identifies hereinafter,, be identified for diagnosing the sensitivity of SIM and specificity (with all other top GI pipeline tissues contrasts) to be respectively about 97% and 92% at 288 slicers that obtain from 121 patients.Yet as of late, described exemplary OCT technology still too slowly and can't be to big mucous membrane surface regional imaging.As discussing hereinafter, following progress has been arranged: can overcome this matter of time, and the preliminary identification to comprehensive esophagus living imaging is provided here.

Optimal frequency domain imaging (OFID)

As mentioned above, the publication 21 that hereinafter identifies has been described the development of the OFDI technology of a kind of alternative technology of using as the OCT technology.Though light source (as what discuss in the publication 22 and 23 that identifies hereinafter) and the detection principle of OFDI are useful, contrast, resolution and cross sectional image present to be equal to approx or the contrast, resolution and the cross sectional image that are provided by OCT are provided and present.One of advantage of OFDI is that OFDI has higher detection sensitivity, therefore realize image acquisition speed obvious increase and without detriment to picture quality.Described in the publication 24 that identifies hereinafter, the system that is used for these preliminary study be for endoscopic imaging custom-designed, and provide in the acquisition rate, tissue of 10,000 depth scan of per second (A capable (A-line)) axial resolution of 8 μ m and the range finding degree of depth of 3.5mm.The image taking speed of this example system just is subject to data could transmit and store into hard disk drive on the bus of computer speed.

Exemplary balloon catheter

In order to carry out comprehensive esophagus imaging, the exemplary embodiment of OFDI conduit can be provided according to the present invention, this OFDI conduit can utilize the Air sac cover shown in Figure 1A and Figure 1B and in esophagus intracavity placed in the middle.This exemplary catheter can comprise scanning probe instrument 2000, and this scanning probe instrument can rotate and can retract interior light core 2010.Inner core 2010 can be closed in the transparent sheath 2020.At the far-end of conduit, air bag 2040 can make the image optics device placed in the middle when expanding.Become video beam 2030 can be focused on the esophagus surface 2050.Can scan this one-tenth video beam 2030 to realize comprehensive imaging.Air bag 2040 can have the swell diameter of 1.8cm, and can allow the vertical imaging on 4.5cm length and need not to reorientate.The light core 2010 of conduit can comprise optical fiber, be used for the sept of extensible beam, the gradient-index lens that is used to focus on and be used for will bundle vertically guiding into the corner cube prism of the longitudinal axis of conduit.Small-sized cylindrical lens is made into built-in, and should be placed on the prismatical second surface by small-sized cylindrical lens.The astigmatism that this lens compensation is caused by plastic sheath and on tissue surface, cause diffraction limited bundle (30 μ m diameter).In use, can rotate exemplary catheter by the speed that about per second 4 changes, this allows 2500 axially collections of scanning of every circular cross section.This exemplary OFDI system can record coding device signal, with the rotation of accurately following the tracks of conduit with retract.When rebuilding 3 dimension data collection, use this information.

The imaging of preliminary pig feed pipe

Can in the pig of the about 50kg in two, carry out the esophagus imaging technique.Though in discrete figure, can not show complete 20GB data set, among Fig. 2 A-2C information content has been shown.For example in the perspective view of Fig. 2 A, image 2100 provides the 3D of whole imaging esophagus to reproduce.In the front view of Fig. 2 B, image 2110 illustrates the single cross section of imaging esophagus.In Fig. 2 C, image 2120 shows the amplification cross sectional image of at least one part of esophagus.Resolution is 10 μ m * 20 μ m * 30 μ m (r, θ, z) sampling can produce comprehensive microscopic data set, this data set can be shown as the image 2100 of Fig. 2 A on volume, be used for mapping and direction, perhaps in the high-resolution cross sectional image that whole esophageal wall can be visualized as the image 2110 among Fig. 2 B, show.The expanded view of the image 2120 of Fig. 2 C has been described the architecture of mucous layer.

Preliminary human esophagus imaging

Figure 3 illustrates exemplary single image rotating 2150.Wherein show flag sign (the disorderly epithelium system of patient's SIM with irregular surface; There is big epithelial gland).Diagnosis has BE before this patient, and carries out imaging before PDT.

These preliminary study have verified that a) OFDI microcosmic living imaging is feasible comprehensively, architecture that b) can visual whole esophageal wall, and c) can utilize air bag centering probe to detect SIM diagnosis in the human subjects.

The monitoring laser heat injury

Histone and collagen may be because of the heating degeneration, and this causes microdeformation (describing in Biao Shi the publication 33 hereinafter), scattering to increase the birefringence (describing in Biao Shi the publication 46 hereinafter) of (describing in Biao Shi the publication 36,38 and 45 hereinafter), minimizing and the blood flow (describing in Biao Shi the publication 47 hereinafter) that reduces.Below describing to provide is used to utilize exemplary OFDI to monitor the method for these variations according to an exemplary embodiment of the present invention.In exemplary authentication separately, the pig feed pipe sample and the duodenum sample (as the media of SIM) that utilize the microscope cover glass just to have obtained are placed on the epithelial surface, thereby can simulate the approximate pressure and the heat conductivity of balloon catheter.

Figure 4 illustrates according to the equipment of collection OFDI signal during laser irradiation and the exemplary embodiment of use thereof of being used for of the present invention.For example, by prover 2200 transport process light.Carry imaging by second prover 2220.Handle bundle 2210 and becomes video beam 2230 arrive organize 2270 o'clock overlapping, organize 2270 to be coated with heavy sheet glass cover plate 2260, and be shelved on the backing 2280.This tissue is by motorized precision translation stage 2290 translations.Become video beam to focus on by lens 2250.Provide and described to restraint eclipsed top-down image 2250.For thermal excitation, can use the high power Gaussian laser beam (diameter=1.1mm for example of calibration; Wavelength=1450nm; Power=400mW).OFDI sampling bundle can be focused into for example 1/e of 23 μ m at tissue surface ²Intensity diameter and being aligned to makes it and laser facula overlapping, as shown in Figure 4.During data collection, sample can remain on the fixed position and/or utilize motorized stage by translation.

Exemplary microdeformation

When laser energy was deposited in the tissue, the temperature increase that brings can make protein and collagenous degeneration.Can show these by microdeformation and change, wherein can utilize OFDI to measure this microdeformation phase sensitive.Following data verification this ability.

Fixed point---for such exemplary experiment, sample remains on the fixed position.Speed with about 10kHz is gathered the OFDI depth scan constantly, while 1450nm laser turn-on, and the firm power maintenance predetermined lasting time with 400mW turn-offs then.The representative data of three different laser explosure persistent period is expressed as " M mould " image in the curve chart of Fig. 5, wherein vertical axes 2300a, 2300b, 2300c represent the in-house degree of depth, trunnion axis 2310a, 2310b, 2310c express time, and the value that utilizes color lookup table 2320 to show to record phase shift (red=positive phase shift, blueness=negative moves).At the red horizontal line 2330a at each phase shifted images top, the interval that 2330b, 2330c represent laser turn-on.When initial laser is exposed, overlay on above the zone moved of negative, below with regard to the surf zone of observing positive phase shift.Along with laser irradiation continues, phase place is covered phase shift from just changing into the minus degree of depth little by little to deepen value reduces.After laser shutdown, detect less than measurable phase shift.Protein denaturation causes local microstructure change and local deformation focus, and this local deformation focus is detected as the phase shift of interferometry signal.Along with the continuation of laser explosure, active denatured areas along with on cover tissue and become complete degeneration and on the degree of depth, spread.Deep identification when shift direction is reverse the focus center of active degeneration.

In order to verify these results, after laser explosure, obtain organizational structure section (histologicalsection), and (nitro-blue tetrazolium chloride, NBTC) degree of damage from laser is assessed in dyeing to use the chlorination nitro blue tetrazolium.NBTC is positive for dyeing for the lactic acid dehydrogenase (LDH) of thermo-labile enzyme; The active loss of LDH takes place rapidly after the cell injury that heat is brought out, and relevant with cell lethality (described in the publication 48 and 49 that identifies hereinafter).Therefore, selected to be unstained the degree of depth on the border between tissue and the dyeing tissue as the degree of depth of damage from laser.Corresponding phase shift data and organizational structure have been shown in 2340a, 2340b, 2340c.Border between preliminary discovery demonstration thermal denaturation tissue and the survival tissue is corresponding to the flex point of the phase shift of measuring with OFDI.Quantitatively, the depth derivates of phase shift is determined at each A-is capable, and will be injured the negative peak point that the degree of depth is defined as this derivative.The degree of depth of Que Dinging is provided as the vertical curve adjacent with each M mould image in Fig. 5 in this way, and shows good corresponding with tissue morphology measurement.

The translation point---by add the treatment laser beam to existing OFDI conduit, make the scanning simultaneously of laser and OFDI bundle can help laser treatment to big epithelial surface zone.Preliminary imaging research has verified that the OFDI bundle is of a size of comprehensive esophagus imaging of 30 μ m.Obtain by continuous rotation sweep therefore the accurate aligning of 1mm diameter laser beam should be attainable.For simulation monitoring in scanning, can sample speed be transformed into 0.9mm/s from 1.8mm/s with being controlled to repeatedly by computer-controlled translation stage 2290 (referring to Fig. 4).

In Fig. 6 A, illustrated and do not had the OFDI intensity image 2400 gathered under the laser irradiation situation.For the image shown in Fig. 6 B, 6C and the 6D 2410,2420 and 2430, the 1450nm laser power is about 400mW respectively.The translation of sample in exposure process causes the damage from laser line on the sample surface.Because thermal energy deposition can proportional with time of exposure (square journey 1), so the damage from laser degree of depth can change along this line according to the inverse of point-to-point speed.From fast and the zone of translation at a slow speed obtain and direction cut into slices with the vertical organizational structure of this line and show the laser hazard degree of depth of 0.41mm and 0.69mm respectively.The phase shift data corresponding with the image 2410 of Fig. 6 B is illustrated as image 2420 in Fig. 6 C.Under the consistent basically situation of the measurement of learning with tissue morphology measurement, by the definite lesion depths of phase shift data (maximum negative derivative) fast with can be respectively 0.40mm and 0.67mm in the zone at a slow speed.

The speckle decorrelation

Speckle (speckle) is a general observed phenomenon when utilizing coherent illumination to carry out imaging, and shows as high strength and the low intensive graininess pattern that does not seem relevant with microstructure.In tissue, speckle is generally caused by the interference between the photon that passes different paths in the communication process in sample.If in-house scattering object is moving, even then might see also that in the microcosmic scale speckle pattern fluctuates rapidly.Therefore measurement to speckle pattern differentiation in time can provide seeing clearly microscopic motion in the sample.This example technique has been provided for biomechanical characterization (described in the publication 50 that identifies hereinafter) and the thermal excitation of investigating in the biological tissue (described in the publication 51 that identifies hereinafter).Having looked back these designs are expanded to utilizes OFDI that the interactional deep decomposition of laser tissue is monitored.

Check that the OFDI image table that is organized in during the laser explosure understands that the potential of this example technique may.When no laser explosure, observed speckle pattern keeps constant with respect to the degree of depth and the range of image in OFDI.Under laser irradiation, observe speckle pattern fluctuation rapidly in the regional area of laser beam.When motion is checked slowly, observe the speckle fluctuation and near tissue surface, begin, and diffusion downwards in time.In order to quantize these observed results, determined the speckle decorrelation rate of each depth point of the image 2410 shown in Fig. 6 B.Particularly, determined the width relevant of the time autocorrelation function of OFDI strength signal with the degree of depth.Then by utilizing the gray scale look-up table to show that the self correlation width generates speckle decorrelation image.The image 2430 of Fig. 6 D be respectively with image 2410 and the 2420 corresponding speckle decorrelation images of Fig. 6 B and 6C.Can observe, the degree of depth of peak value decorrelation 2431 rates (black vaginal discharge shown in the arrow among Fig. 6 D) changes accordingly with the rate of translation of sample and the damage from laser degree of depth shown in the organizational structure.This discovery has confirmed that for the concordance of esophagus and duodenum sample but the degree of depth of peak value decorrelation rate is the quantitative measurement that is used for determining the laser hazard degree of depth.

Birefringence

When light was propagated in material, if the refractive index non-isotropy, then polarized state of light can change.This effect is called birefringence.Many tissues, especially muscle and collagen show very strong birefringence, can lose this birefringence (as described in the publication 46) when heating and degeneration.Polarization-Sensitive OCT (PS-OCT) technology, the method and system (publication 52 and 53 of the sign that vide infra) that are used for quantizing by the measurement result of birefringence loss depth of burn have been described.In PS-OCT, two detector channels can be configured in order to receive the orthogonal polarization state of the light that returns from sample.The birefringence sample causes the rotation relevant with the degree of depth of polarization state, and this causes the percentage ratio of detected sample light in each passage to change.If the ratio of two passages is shown as gray scale in the cross sectional image, then birefringence is observed as the feature strip pattern.

For example, as shown in Figure 27, the equipment of Fig. 4 can be changed into and comprise galvanometric scanners, makes the OFDI bundle to scan repeatedly on the surface of tissue, and the while sample is maintained fixed and the 1450nm laser facula remains secured to the center.As shown in Figure 27, can pass through first prover, 2500 transport process light, described prover 2500 is provided at incident processing bundle 2510 on the tissue 2550, and described tissue 2550 covers and supporting backing 2560 by cover plate 2540.Imaging can be provided by second prover 2570, and described prover 2570 produces into video beam 2580, and described one-tenth video beam 2580 guides scioptics 2530 by galvanometer mirror 2520.This device can be the exemplary embodiment that is applicable to the treatment surveillance of dermatosis application.During laser irradiation, gather the OFDI image or the video of esophagus and duodenum tissue.

Fig. 7 A-7D shows the image of representative data.In the frame of before laser irradiation, being gathered, can in intensity image 2450 (referring to Fig. 7 A), observe stratified esophagus structure, and can in the polarization image 2460 (referring to Fig. 7 B) of correspondence, observe feature birefringence band.In the frame of being gathered during laser explosure, the epithelium scattering strength can significantly increase (referring to Fig. 7 C) in 1.1mm laser facula 2470, and the birefringence band in the polarization image 2480 of correspondence (referring to Fig. 7 D) has loss.Check that the polarization when moving slowly moves image, can observe the zone that refractive index reduces can begin and diffusion downwards near surface.These observed results are consistent with the downward diffusion zone of degeneration tissue usually.Measurement to the birefringence percent loss is the quantisation metric that is used for the monitoring laser hot injury.

Scattering

The variation of the tissue microstructure that heat is brought out can change optical scattering.Because the signal among the OFDI is caused by scattering and can detect little variation in big dynamic range, so investigate scatterometry is used to monitor that the tissue that heat is brought out changes.Observed scattering changes the preliminary observation that can represent duodenum and esophagus sample in the image 2460 of Fig. 7 B.Under specific circumstances, determine the obvious scattering variation to be arranged and in the tissue that underlies of muscle mucosa and muscle itself (muscularispropria), change relative less at last Intradermal.For example, can from scatterometry, obtain to be used for two potential quantisation metric of damage from laser: the variation of the variation of deep decomposition scattering strength and degree of depth integral scattering intensity.

Blood flow

Laser therapy can change blood vessel and capillary tube, causes blood flow to reduce (described in the publication 54 that identifies hereinafter).Because esophagus mucosa vascularity is many, change the additional method that can be provided for the monitoring laser treatment so monitor blood flow.The image 2490 of the Fig. 8 that gathers in nearest research process to pig has illustrated pig feed pipe vascularity on figure.By launching the tubular type view data to show that epithelial surface generates this example images 2490, just as vertically opening esophagus and being fixed smooth.On the degree of depth, intensity data is integrated into tissue.Though the big scale of this class is visual is the convenient manner of mapping blood vessel, might use sensitiveer and blood flow is measured by quantitative methods/technology/system.Doppler OCT (described in the publication 55 and 56 that identifies hereinafter) has been verified the blood flow that is used for tissue and has carried out visual and quantification, and has been studied the device (described in the publication 57 that identifies hereinafter) that is used for assessment stream after laser therapy as a kind of.Describe the Doppler measurement (described in the publication 24 that identifies hereinafter) that utilizes OFDI, and checked the probability of measuring live body structure and stream simultaneously.

The viewgraph of cross-section of the example images 2590 of Fig. 9 is to gather in the esophagus of live hog, and intensity is shown as gray scale and Doppler is shown as the stack color.(r θ) has been mapped to cartesian coordinate (vertically, level) in the hope of showing simply to the coordinate of these data.The observation of these result's representative a plurality of positions in the pig of two.In addition, in the time series of doppler image, clearly observe pulsating flow.

Based on described preliminary study, the measurement that is proposed may be complementary: and the phase shift and the speckle decorrelation that only just are suitable for during laser irradiation can be sensitiveer, and bigger spatial resolution is provided.The variation of birefringence, scattering and stream is persistent, and goes for the tracking imaging after the laser treatment.

Exemplary control

Except the monitoring laser heat injury, effectively the conformal laser therapy also can be used the accurate control to the volume of processed tissue.A kind of exemplary approach in order to the control treatment degree of depth is to operate in the condition that is used for thermal confinement (thermal confinement), so that minimize collateral damage and control optical maser wavelength, power and the time of exposure degree of depth with the control heat injury.On (along epithelial surface) breadth wise dimension, can be by using through raster scanning, controlling heat injury through the bundle of spatial calibration.Diameter with edge of suitable qualification is that the flat-top bundle of 1-3mm can allow spatial control, also allows simultaneously to treat big epithelium zone by raster scanning.Exemplary laser controlling parameter is hereinafter described in the context of equation 1.The Temperature Distribution of equation 1 is general only just to be suitable under the restriction of weak scattering.

Wavelength

According to the Temperature Distribution of equation 1, obvious μ _aIt may be the optimized parameter that is used to control the laser hazard degree of depth.Though μ _aBe the feature rather than the external controllable parameter of sample, but in the present invention, utilize μ _aDependence to wavelength realizes degree of depth control.In the present invention, be target to absorb the absorptance that accounts for leading longer wavelength at water.Because water content is constant approx in epithelial tissue, so can critically regulate the heat injury degree of depth by a small amount of change optical maser wavelength.Near water absorption band near 1.45 μ m, in narrow spectral region (1375nm is to 1430nm), absorption length (referring to the curve chart 2595 of Figure 10) scope from 0.3mm to surpassing 2mm.These length are well corresponding to the characteristic length scale that is suitable for handling epithelial diseases.Near can work 1450nm water absorption band tunable laser can be used for controlling treatment by wavelength tuning.

Wavelength

When checking equation 1, absorptance is not only the index depth attenuation of control Temperature Distribution; For example it also can span of control limit of control.Because the amplitude item also depends on power density and length of exposure,, allow to change absorptance simultaneously so these variablees can be used for making amplitude normalization.

Process duration

When estimating the new therapy that is proposed, may importantly estimate preferred process time and estimate this estimation in emulative mode and under specially at the constraint background of clinical setting and patient's acceptance.PDT is applied to the processing that endoscope is provided with middle BE at present, and requires about 20 minutes process time.For exemplary conformal laser therapy technology, can come the estimation procedure time of implementation according to 2At/ (π rv), wherein At is a processing area, r is the laser facula radius, and v is the laser facula sweep speed.For the epithelium treated length of 60mm and the epithelium diameter of 20mm.

According to exemplary embodiment of the present invention, a kind of combined system can be provided, this combined system can allow controlled laser excitation.In one exemplary embodiment, can example system be used in endoscopic mode can the overall treatment epithelial lesion and make the minimized conformal laser therapy of adjacent tissue collateral damage.

The example system design

According to exemplary embodiment of the present invention, can provide a kind of system that is used for carrying out epithelial diseases conformal laser therapy by the combination that monitors and control.Because laser beam is easy to shaping and scanning spatially, and, be to limit and adjust the degree of depth of damage from laser so realize the main challenge of the accurate control of laser therapy because the nargin in the transverse plane (along the surface of esophagus) is so crucial.Based on above-mentioned modeling and analysis, might utilize optical maser wavelength and power and scanning speed to change the damage from laser degree of depth in the important clinically scope, and don't obviously change horizontal injury scope.

The exemplary treatment laser aid

Optical maser wavelength between about 1375nm and 1430nm can provide scope from surpassing 2mm to the absorption length that is less than 0.3mm.Semiconductor laser can be worked in this spectral region.Since such laser instrument can be compactness and aspect environment, be stable, so these laser instrument can be used in the clinical practice effectively.Yet the material that is suitable for this particular range of wavelengths may be nonstandard.Can pass through solid-state laser modulator material tetravalence chromium doping YAG (Cr4+:YAG), be provided for the lower alternative of expense according to the early stage test phase of the exemplary embodiment of the inventive method.For example, can realize the tunability (as the publication 58 and 59 that hereinafter identify described in) of this material in this spectral region of 1340nm-1570nm.The exemplary design and the structure of the tunable solid laser instrument of working in the near infrared light spectral limit have been described among Biao Shi the publication 60-65 hereinafter.Dynamo-electric shield in the laser resonator outside can be used for connecting/closing exemplary laser.

Exemplary operation platform system

Exemplary embodiment according to workbench optical system of the present invention can be provided, this workbench optical system can with shown in Fig. 4 and Figure 27 with system class as described herein seemingly.For example, OFDI sampling bundle can be focused the diameter of about 25 μ m on sample.The axial location of this focus can utilize standard z scanning technique to determine, and can be registered in the OFDI cross sectional image.The follow-up axial location of sample in the OFDI image window can guarantee constant focal position to all samples.Can collect data with fixed two bundles relative to each other, and simultaneously sample perpendicular to laser beam axis ground by translation.

The exemplary location and the registration of laser instrument and OFDI bundle

According to exemplary embodiment of the present invention, the skew between the center of OFDI bundle and laser facula is not crucial for supervision.Can collect OFDI data (as shown in 4) to determine to produce the skew of maximum heat injury indicated depth at various skews.This skew can be used in all follow-up studies and can be registered according to following process.Can on the surface of sample, bring out short epithelium burn of little lower powered persistent period, make sample be maintained fixed (not translation) simultaneously.As shown in Figure 7, can in OFDI, easily observe the increase of epithelium scattering, and spatially locate the increase of epithelium scattering according to the qualification of laser beam profile.Though not shown in Fig. 4, the galvanometer that OFDI bundle can be by providing two-dimensional scan to and passed on (relay) to condenser lens.Galvanometer can be with the positive OFDI image that generates sample, and the epithelium burn can show as the circle of the scattering that has increased.Can locate then and fixing galvanometer, make the OFDI bundle be positioned (as schematically illustrating among Fig. 4) with required skew.

The exemplary wavelength convergent-divergent

One of purpose of this experiment is that test is used to realize that according to of the present invention the exemplary wavelength of the clinical associated change of the damage from laser degree of depth changes and power normalization technology and method.Keep under the constant situation at laser spot size and scanning speed, optical maser wavelength can change to 1405nm from about 1375nm with the step-length of 2nm.For every kind of wavelength, can adjust laser power and make product in the equation 1 Can keep constant.This should produce the line of constant width, and the lesion depths scope is from about 0.25mm to 1.5mm.

Exemplary scan speed convergent-divergent

An exemplary embodiment that is used to influence the treatment degree of depth according to the present invention can comprise adjusts sweep speed in proportion.For example, the treatment beam scan velocity can change from 1mm/s to 5mm/s.Slower scanning speed has been reserved the dark zone required time of conduction of heat to tissue, thereby causes more deep treatment.

The exemplary location and the registration of laser and OFDI bundle

In order to guarantee to treat accurately supervision, can control the spatial relationship between OFDI sampling bundle and the laser facula.

Exemplary endoscope probe design

One exemplary embodiment of the present invention can comprise the endoscope probe that is used for comprehensive volume determination imaging and laser therapy simultaneously, as shown in Figure 11.For example, can use two bundles to pass on optics 2640a and 2640b, one of them transmits imaging 2640b and another transmits treatment light 2640a.These pass on optics and are positioned in the shell 2630, and described shell is closed in first transparent sheath 2600.Air bag centering machine (as mentioned above) 2620 can be used for keeping the constant distance between optic probe 2630 and the tissue surface 2610.Can come transmission laser bundle and OFDI bundle by isolating optical fiber 2641a and 2641b.Each optical fiber can have its optics that passes on, to produce independent controlled spot size.Another exemplary embodiment of the present invention can comprise and is designed to pass on optics in order to these that overlap hot spot.Optical fiber and distal end optical device can be contained in the coiling driving shaft, and are placed on the air bag centering probe inside identical with Air sac cover.

Can utilize be attached to the driving shaft near-end encourage longitudinal scanning by computer-controlled translation stage.This exemplary means can be identical with the device that retracts the esophagus imaging in the preliminary study that can be used in the applicant.The same with the automatization's rotation that utilizes the exemplary rotary coupler 2900 shown in Figure 13, the artificial rotation of driving shaft also is possible.In one exemplary embodiment of the present invention, the endoscope detecting system is visual field ground examination disease greatly, the accurately interaction of monitoring laser and tissue, and accurately control laser therapy.One of application of such exemplary embodiment can be to epithelial cancer and forerunner's thereof identification and processing.In another exemplary embodiment, described system can introduce process and the software module that examination, supervision and control can be contacted directly.

In another exemplary embodiment, described system can be with the high-resolution 3 dimension figure that generate whole distal esophagus, to help treatment plan.Subsequently as shown in Figure 14, can present ' work, the cross sectional image that comprises three sections to the user.The right cut sheet 2700 of image can be at the tissue that was right after before treatment laser, and the center 2730 of image can be the laser position with sign 2740, this sign indication treatment region, and the left cut sheet 2710 of image can be treated tissue.Because three bundles can continue scanning, move so tissue can show as along with the renewal of image from right to left.User (for example doctor of endoscope) can operate the control servomechanism and begin/stop to handle and increase or reduce to treat the degree of depth.By checking the untreated tissue 2700 of treatment region 2710 and eyes front, the user can handle the laser therapy district and make it consistent with re-set target.

Figure 12 illustrates the exemplary embodiment that is used for being undertaken the endoscope probe of imaging, supervision and laser therapy according to of the present invention by the centering air bag.This exemplary probe can rotate with at the neighboring scan esophagus, and can with than the slow rate longitudinal translation to be defined for the part of treatment.This probe can comprise for example three or more optical channels: be used for the third channel 2800a that before laser irradiation tissue carried out the first passage 2800c of imaging, the second channel 2800b that is used to handle and is used to monitor.Each optical fiber can laterally be imaged onto on the esophageal wall discretely by air bag.The aligning of gained output bundle can become video beam to lead over fully and handle bundle, thereby can sample to the tissue that is untreated so that when rotating in the clockwise direction.Monitor to restraint to be aligned to and fall in the laser facula.After the initial alignment of three bundles, optics can be used epoxy resin bonding, and described aligning can be fixed.

Exemplary rotary engaging member

Shown in Figure 13 according to the exemplary rotary coupler that the triple channel conduit can be connected to the OFDI system of the present invention, described rotary coupler can be called as " watch spring " rotary engaging member (because it can rest on two concentric spools).For example, when inner reel 2900 rotated in one direction, optical fiber was wound on the inner reel 2900 from outer roller 2910.When making direction reverse, optical fiber can launch from inner reel.Can use ribbon fiber, and two parallel-plates 2920 of gap and bandwidth coupling can guarantee that coil keeps smooth and do not tighten.Described plate can be sufficiently large to and make for example might reach 100 rotations before requiring the phase despining.With regard to the 1mm laser facula, can be 60 commentaries on classics to sectional the processing fully of the long esophagus of 6cm.Can use board diameter less than 10cm.Except holding three optical channels, can also avoid the loss and the back reflection that cause because of kidney joint according to this exemplary embodiment of device of the present invention and system.

Exemplary high speed acquisition and processing

Another exemplary embodiment according to system of the present invention and device can be utilized for example high speed imaging system.The exemplary embodiment of digital collection and processing system can be based on the VME bus hardware, so that gather in real time, handle and storage OFDI signal.The such example system and the example components of device can comprise the VME chassis, and this chassis comprises high-speed figure transducer (digitizer) that resides on the single board computer and the optical fiber link that leads to the RAID storage array.Can control this example system and device via primary processor (for example personal computer).It is signal digitalized to use the broadband reception device (for example 12,210MS/s) with integrated field programmable gate array (FPGA) processor will simulate OFDI.Inherent disposal ability may be important on the collection plate, because for two channel of polarization of OFDI system, raw data rate can be 800MB/s.The FPGA processor can be configured or programme in order to become to represent luminance factor that the degree of depth contained 1024 cellular arraies (an A line) from frequency domain transform each channel of polarization.These data can be passed to single board computer, so that carry out subsequent treatment and these two passages of combination before final data being sent to the RAID array of being made up of hard disk drive.The final data memory rate can for example be 400MB/s.By the data itemize is distributed on a plurality of hard disk drives, can keep this data rate constantly.

Software on the blood processor can allow the control of user to example system according to an exemplary embodiment of the present invention, and can realize that following in real time sampling rate comes display image.For example, can be under two exemplary patterns the usage example system: the continuous mode of the burst mode of full data rate and half data speed.Exemplary endoscope detecting system and device can comprise above-mentioned parts and software, and can provide additional process (for example software), with to the programming of FPGA processor and single board computer, thereby help the real-time calculating of phase shift, birefringence, speckle and Doppler signal.Vertex4ProFPGA and quad G4 single board computer can be enough to show in real time supervisory signal.

Exemplary laser

Utilize equation 1, when keeping constant scanning speed, can spot size be doubled by utilizing laser power to increase by 3 times, so that the steady temperature of keeping in the tissue distributes.At the constant light spot size scanning speed is doubled and to use the laser power of twice.An exemplary embodiment according to laser aid of the present invention can be utilized single transmit device semiconductor laser diode.Previous equipment has utilized the design of easy external cavity, provides laser power more than 3W in this spectral region, and described external cavity design comprises the diffraction grating that is used for wavelength control.Can control laser power and wavelength via the primary processing unit of OFDI system based on from potentiometric analogue signal.Described potentiometer can be that user (for example doctor of endoscope) can use so that increase or reduce the hand-held dial plate of the damage from laser degree of depth.

Exemplary user interfaces

The exemplary embodiment of system and a method according to the invention can provide the user interface of the cross sectional image that comprises tissue to the operator.Described image can continue to be updated, and can comprise that handled and the view tissue that is untreated on the horizon and for the appointment of the determined laser treated region of monitoring process.User interface can be programmed on primary processing unit, and can use the result of calculation from FPGA processor and single board computer.Image and laser parameter can be stored on the RADI array.

In another exemplary embodiment of the present invention, imaging system/device 100 can utilize optical switch 115 and be connected to three fibre-optical probes, as shown in the block diagram of Figure 15.Exemplary probe such as the probe of describing above with reference to Figure 12, can comprise two imaging fibres and a treatment optical fiber.Switch 115 can alternately be coupled to one of two imaging fibre 120a, 120b with imaging, and described imaging fibre can be used for gathering treats image and for example imaging during the treatment again.Treatment light source 105 can be directly connected to treatment optical fiber 125c.These optical fiber can be connected to conduit 130, and described conduit can be the exemplary catheter shown in Figure 12 for example.Can control the state of optical switch 115 from the signal of imaging system 100.

Shown in Figure 16 in accordance with a further exemplary embodiment of the present invention in, exemplary imaging system/device 200 can be coupled to exemplary three port catheter via optical splitters 215, such as the conduit shown in Figure 12, described optical splitters 215 can will couple light to two imaging fibre 220a, 220b.This exemplary imaging system can utilize the path coding techniques to separate picture signal from each optical fiber.In order to generate different paths, can in an optical fiber 220b or a plurality of optical fiber, optical delay devices 235 be set.Treatment light source 205 can be coupled, either directly or indirectly, to the treatment optical fiber 225c of conduit.

In the another exemplary embodiment shown in Figure 17, can utilize single wavelength division multiplexer 810 with light and 805 combinations of treatment source according to exemplary imaging system of the present invention/device 800.Light through combination can be coupled to the single fiber rotary coupler, is coupled to exemplary single fiber conduit then, such as the conduit shown in Figure 21.

In the another exemplary embodiment shown in Figure 18 according to imaging system of the present invention/device 900, can utilize the cladding mode bonder with light and 905 combinations of treatment light, described cladding mode bonder is coupled to the single-mode core of doubly clad optical fiber 911 with the light of imaging system 900 from single-mode fiber 901, and will treat light is coupled to doubly clad optical fiber 911 from multimode fibre 906 cladding mode.

Figure 19 shows via multichannel rotary coupler 410, such as the bonder shown in Figure 13, the exemplary connection between the system 400 with three output optical fibre 405a, 405b, 405c (such as the system that in for example Figure 15 and 16, schematically shows) and three port catheter 415 (such as the conduit shown in Figure 12).

Figure 20 shows the sketch map according to example system 300 of the present invention, and in this system, the single fiber 305 that holds imaging and treatment light can be coupled to single channel rotary coupler 310.For example, after rotary coupler 310, light can be opened by wavelength division multiplexer (WDM) in 330 minutes, and this WDM330 is separated to imaging on first optical fiber 332 and will treats light and is separated on second optical fiber 331.Can also utilize optical splitters 335 further separate imaging light, described optical splitters 335 has two imaging port 336a and 336b.Optical fiber 31,336a, 336b can be connected to 325 these designs of three port catheter, such as the conduit shown in Figure 12.Thereby duct portion 320 can be the flexible endoscope that allows to be inserted, and the part that comprises WDM330 and shunt 335 can be closed in the rigid pipe 315 to protect these parts.

Figure 21 shows the side view according to the exemplary embodiment of distal end optical device of the present invention, and this device can produce single one-tenth video beam 1125 and isolating treatment bundle 1120 from single-mode fiber 1101.For example, the light from the optical fiber that holds imaging and treatment light can be focused on by first grin lens 1100 earlier.Described light is passed in the wavelength-division multiplex prism 1105 then, this wavelength-division multiplex prism can upwards draw treatment Shu Bochang, to produce treatment bundle 1120, and the imaging wavelength sent to second grin lens 1110, this second grin lens is focal imaging light and guide imaging into final prism 1115 alternately, and described final prism will become video beam 1125 upwards to draw.Prism 1105 and 1115 angle can be to make the suitable distance eclipsed angle of bundle at distance equipment.

Figure 22 shows according to the side view of the exemplary embodiment of three port catheter of the present invention and front view.Described exemplary catheter can comprise three optical fiber 1005, and these optical fiber are connected to three groups of focusing optics 1035 that comprise in the V groove 1020 in the shell 1040.Described focusing optics can provide bundle to focus on.Microprism 1025 is redirected light beam for upwards passing through cylindrical lens 1030, and 1030 pairs of transparent sheath of described cylindrical lens, 1000 caused astigmatism are proofreaied and correct.Air bag 1010 centering machines can be used for keeping optics 1035 placed in the middle in interior cavity tissue 1015.In end-view, can see and monitor bundle 1050c, treatment bundle 1050b and preformation video beam 1050a.Shell 1040 goes for rotating such as the bonder shown in Figure 13 by the multichannel rotary coupler.

Figure 23 shows the side view according to the exemplary embodiment of conduit of the present invention, and described conduit can utilize micro-machine 1260 to be embodied as the rotation of video beam.For example, motor 1260 can be closed in the transparent sheath 1235.The rotation of motor shaft can rotary prism 1220.Imaging can be coupled to the distal end optical device via optical fiber 1210, and wherein said imaging can be focused on by focusing optics 1215, and is reflexed on the prism 1220 by reflector 1225.The neighboring scan that is rotated in of prism 1220 becomes video beam.Can realize that motor is electrically connected by the tube chamber identical with optical fiber 1210.Treatment couples light to the distal end optical device on the optical fiber 1200.This treatment light can utilize focusing optics 1250 to focus on, and to guide the side with respect to the fixed anglec of rotation of interior cover into by prism 1245.Become therefore inswept fixed treatment hot spot of video beam.Realize treating the translation of hot spot by the rotation of cover 1235 in overcoat 1240 in whole.Can realize this exemplary rotation such as the bonder shown in Figure 13 by using the multichannel rotary coupler.Conduit can be used for air bag 1255 the placed in the middle of light core 1230.

Figure 24 shows the block diagram according to the exemplary embodiment in the laser therapy source with tunable wave length of the present invention, this laser therapy source has utilized low-power tunable wave length source 600, and after this tunable wave length source is in order to increase the broadband booster amplifier 605 of luminous power.

Figure 25 shows the functional block diagram of the exemplary embodiment of introducing the laser therapy source be in different wave length and polarising a plurality of laser diode 500a, 500b, 500c, 500d and in order to implement the example process of such device.For example, light can be combined to single-mode fiber 515 by palarization multiplexing device 505a, 505b and wavelength division multiplexer 510.Alternatively, light can be coupled to multimode fibre 520.Mode scrambler 525 can be used for very fast speed the horizontal mould pattern from multimode fibre output being carried out scrambling fast.Other source apparatus that can export light on single-mode fiber can use similar design will couple light to multimode fibre.

Figure 26 shows the exemplary embodiment according to treatment light source of the present invention and use thereof.For example, laser diode bar 700 can be used with a plurality of wavelength 701a-g.Each waveguide can scioptics device 705 and grating 710 and partial reflection end mirror and be coupled to the free space laser cavity.Because the wavelength dispersion of grating, the formed laser instrument of each waveguide sends laser at different wave length.Therefore, by adjusting drive current, can adjust the power and the spectral shape of laser output 720 to each waveguide 701a-g.

In in accordance with a further exemplary embodiment of the present invention, single OFDI system can be modified as and help by using acousto-optic frequency shifters to be detected as image signal and supervisory signal, as shown in Figure 28.For example, length scanning lasing light emitter 3000 can be separated to produce sample arm path and reference arm path by first shunt 3020.The sample arm path is further separated by second shunt 3030, and wherein first of this shunt output is drawn towards first frequency shifter 3061 and second output is drawn towards second frequency shifter 3060.Each frequency shifter can be driven with independent frequency.Can be coupled to the imaging fibre 3072 of the three optical fiber rotary couplers 3110 similar by optical circulator 3071 to bonder shown in Figure 13 from the light of first frequency shifter 3061.Can be coupled to the monitoring fiber 3073 of same rotary coupler by circulator 3070 from the light of second frequency shifter 3060.

Independent treatment laser 3010 can be coupled to the 3rd treatment optical fiber.Back light on imaging fibre 3072 and the monitoring fiber 3073 can reconfigure on optical combiner 2080, and mixes with reference arm light at second combiner 3090, and wherein output is drawn towards detector set 3100.Because frequency shifter, the photogenic interfering signal of imaging is encoded with different carrier frequencies with the photogenic interfering signal of supervision, and can separate by conventional frequency domain technique.

Figure 29 A shows the flow chart that is used to obtain with the exemplary embodiment of the method for the information of at least one part correlation connection of sample according to of the present invention.For example, in step 3100, can in the described part of sample, cause variations in temperature.In step 3110, at least one first electromagnetic radiation can be forwarded to the section near the described part described part of sample or sample.In step 3120, the rate of change of the phase place of at least one second electromagnetic radiation that can provide from section according to (i) and/or the phase place of (ii) second electromagnetic radiation and/or amplitude is discerned the distortion of section.

Figure 29 B shows the flow chart according to another exemplary embodiment of the method that is used for controlling the sample Temperature Distribution of the present invention.For example, in step 3130, can provide electromagnetic radiation with the section of specific wavelength in sample.In step 3140, when can tangential section providing electromagnetic radiation, can control Temperature Distribution by the specific wavelength that changes electromagnetic radiation.

Figure 29 C is the flow chart of another exemplary embodiment of at least one part that is used for to biological structure according to the present invention method of applying laser emission.For example, in step 3150, can provide laser radiation beam to described part, and the cross-sectional area of described bundle be described at least one part whole area about at the most 1/10.In step 3160, can (I) in the radiating wavelength of modulated laser and/or (III) apply described bundle when applying the degree of depth in that monitoring laser is radiating based on predetermined pattern, (II).

The exemplary reference document

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Above only illustrate principle of the present invention.Based on the instruction here, will be tangible to those skilled in the art to the various modifications and variations of described embodiment.In fact, install according to an exemplary embodiment of the present invention, system and method can with any OCT system, the OFDI system, any OCT system is used and/or implemented to SD-OCT system or other imaging system together, the OFDI system, SD-OCT system or other imaging system, and the International Patent Application PCT/US2004/029148 that proposed in 8th with JIUYUE in 2004 for example, the 11/266th of submission on November 2nd, 2005, the 10/501st of No. 779 U.S. Patent applications and submission on July 9th, 2004, the system of describing in No. 276 U.S. Patent applications uses together, and the disclosure of these patent applications is incorporated into this by reference on the whole.Therefore will recognize, not illustrate or described, implemented principle of the present invention and so within the spirit and scope of the present invention many systems, apparatus and method here clearly though those skilled in the art can design.In addition, the prior art knowledge that does not have hereinbefore to be incorporated into this by reference clearly also is incorporated into this clearly on the whole.All publications that above are incorporated in this are incorporated into this by reference on the whole.

Claims (26)

1. one kind is used for equipment that at least one part of at least two parts of at least one optical fiber is controlled, comprising:

Be arranged on the first of the specific jointed fiber in the described optical fiber and the device between the second portion, wherein with the vertical specific direction of the extension of described specific jointed fiber in described first and the second portion specific one is set, and wherein said device can be controlled described specific jointed fiber, make in described first and the second portion described specific one can be with respect at least 360 ° of described specific direction rotations.

2. equipment according to claim 1, described specific one in wherein said first and the second portion can be rotated at least 1800 ° with respect to described specific direction.

3. equipment according to claim 1, described specific one in wherein said first and the second portion can be rotated at least 3600 ° with respect to described specific direction.

4. equipment according to claim 1, wherein:

Described at least one optical fiber of ■ comprises a plurality of optical fiber,

The described device of ■ is arranged between the described first and described second portion of each optical fiber in described specific jointed fiber in the described optical fiber and another jointed fiber,

■ with the vertical specific direction of extension of described respective specific jointed fiber and another jointed fiber in the described first of first specific and described another jointed fiber in the described first of described specific jointed fiber and the second portion and the second portion second specific one is set, and

The described device of ■ can be controlled described specific jointed fiber and another jointed fiber, makes specific one and second specific one of described first in described first and the second portion rotate at least 360 ° with respect to described respective specific direction.

5. equipment according to claim 4, specific one and second specific one of described first in wherein said first and the second portion can rotate simultaneously.

6. equipment according to claim 1, wherein said device comprises another device, and wherein said device can twine described specific jointed fiber at least in part around described another device.

7. equipment according to claim 6, wherein said another device is the cylinder device.

8. equipment according to claim 6, wherein said another device are arranged on and are configured to twine in the structure of described specific jointed fiber in order to limit around described another device.

9. equipment according to claim 8, wherein said another device is positioned near the described structure, make in described another device or the described structure at least one to rotate, so that twine described specific jointed fiber around described another device with respect to another one.

10. equipment according to claim 1, wherein said specific jointed fiber are that at least a in optical fiber, single-mode fiber or the multimode fibre kept in polarization.

11. equipment according to claim 1, wherein said device comprises another device, described another device can twine described specific jointed fiber at least in part around described device, and control described specific jointed fiber, make in described first and second parts described specific one can be with respect to described specific direction rotation during the transmission of electromagnetic radiation.

12. equipment according to claim 1, wherein, described specific jointed fiber extends through described first, described device and described second portion continuously.

13. equipment according to claim 1, wherein, described specific part is around the cylinder axis rotation of the described specific jointed fiber in the described specific part.

14. equipment according to claim 1, wherein, described specific jointed fiber is at least a in fibre ribbon or the fibre bundle.

15. an equipment that is used for transmitting electromagnetic radiation between at least two parts of at least one optical fiber comprises:

First device, described first device is arranged between the first and second portion of the specific jointed fiber in the described optical fiber, wherein with the vertical specific direction of the extension of described specific jointed fiber in described first and the second portion specific one is set, described first device comprises second device, can twine described specific jointed fiber at least in part around described second device, and control described specific jointed fiber, make in described first and the second portion described specific one during the transmission of described electromagnetic radiation with respect to described specific direction rotation.

16. equipment according to claim 15, wherein said first device can be controlled described specific jointed fiber, make in described first and the second portion described specific one can be with respect at least 360 ° of described specific direction rotations.

17. equipment according to claim 16, described specific one in wherein said first and the second portion can be rotated at least 1800 ° with respect to described specific direction.

18. equipment according to claim 16, described specific one in wherein said first and the second portion can be rotated at least 3600 ° with respect to described specific direction.

19. equipment according to claim 15, wherein

Described at least one optical fiber of ■ comprises a plurality of optical fiber,

The described device of ■ is arranged between the described first and described second portion of each optical fiber in described specific jointed fiber in the described optical fiber and another jointed fiber,

■ with the vertical specific direction of extension of described respective specific jointed fiber and another jointed fiber in the described first of first specific and described another jointed fiber in the described first of described specific jointed fiber and the second portion and the second portion second specific one is set, and

The described device of ■ can be controlled described specific jointed fiber and another jointed fiber, make in described first and second parts described first specific one and described second specific one with respect at least 360 ° of described respective specific direction rotations.

20. equipment according to claim 19, specific one and described second specific one of described first in wherein said first and second parts can be rotated simultaneously.

21. equipment according to claim 15, wherein said first device comprises the 3rd device, and wherein said first device can twine described specific jointed fiber at least in part around described the 3rd device.

22. equipment according to claim 21, wherein said the 3rd device is the cylinder device.

23. being arranged on, equipment according to claim 21, wherein said the 3rd device is configured to twine in the structure of described specific jointed fiber in order to limit around described second device.

24. equipment according to claim 23, wherein said the 3rd device is positioned near the described structure, make in described the 3rd device or the described structure at least one to rotate, so that twine described specific jointed fiber around described the 3rd device with respect to another one.

25. being polarization, equipment according to claim 15, wherein said specific jointed fiber keeps at least a in optical fiber, single-mode fiber or the multimode fibre.

26. equipment according to claim 15, wherein, described specific jointed fiber is at least a in fibre ribbon or the fibre bundle.

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