CN101400299B - Apparatus for applying a plurality of electro-magnetic radiations to a sample - 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 applying to sample the equipment of a plurality of electromagnetic radiation

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 60/810,868 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), completes under U.S. government supports.Therefore, U.S. government enjoys some right of the present invention.

Technical field

The present invention relates to the equipment controlled at least one part of at least two parts of at least one optical fiber, in particular to the equipment that can comprise a plurality of passages.

Background technology

Laser is used for ablation or heat damage illing tissue is known, and mainly due to the accurate partial result that may realize that collateral damage is minimum, is therefore preferred sometimes.Yet in practice, the use of laser therapy in using such as the specific clinical of processing 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 that control and guidance is processed the degree of depth exactly, thereby because imperfect treatment or the complication relevant with excessive invasive processing cause palindromia.

Epithelial cancer: diagnosis and processing

Generally seek for the method for identifying in early days and process cancer and technology, in order to remarkable minimizing and the possibility that shifts relevant M ﹠ M are provided.Due to epithelial cancer and precursor lesion be usually focus and may distribute unevenly on large visual field (wide field), 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, thus usually can by with Wicresoft's conduit or endoscope near epithelial lesion.Yet treatment challenge is to kill all sidedly, excision or the whole pathological changes of ablation and do not damage that underlie or contiguous tissue.This why challenging especially 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 simultaneously the tissue that underlies of esophageal wall.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 various ways 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 checks that each has provided the assurance to a diagnosis, but has been to provide about insufficient information of surface microstructure and not yet is verified for (described in the publication 8 that identifies hereinafter), fluorescence spectroscopy (described in the publication 9 that identifies hereinafter) and light scattering spectroscopy (described in the publication 10 that identifies hereinafter) for the examination of large 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 large 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 specifically OCT DC accurately for special intestinalization life (specialized intestinal metaplasia), paraplasm and adenocarcinoma.For example, described in the publication 18-20 that identifies 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 simultaneously good picture quality.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 by the spectral resolution that detects in tuning source wavelength between tissue samples and reference, carry out high-resolution ratio range finding (publication 22 of the sign that for example vide infra) in tissue.Provide in 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.Provide in the publication 24 of sign in addition as hereinafter, OFDI method, technology and the system of phase sensitive has been used for imaging stream.

Controllable therapeutic

process (having or not paraplasm) and assessed specific intracavity mode for SIM, photodynamic therapy (PDT) (as what provide in the list of references 25 that identifies hereinafter) is provided, 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 ablation (as what provide in the list of references 30 that identifies hereinafter) and the low temperature ablation (as what provide in the list of references 31 that identifies hereinafter) of using liquid nitrogen.Although every kind in these technology all shows very successfully, the non-homogeneous treatment that may cause potentially lasting SIM or too go deep into ablation has been described in great majority research, and this has caused narrow or perforation.To in surpassing 100 patients' 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 the character relevant with the operator that comprises many equipment in these hand-held, manual sight devices, need high surface area to be processed and for determined by the doctor for the treatment of the intrinsic preference (as what provide in the list of references 3 and 30 that identifies hereinafter) of visual processes end points.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 to 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, provide the exemplary embodiment that is used at least one part of at least two parts of at least one optical fiber is controlled and comprised the equipment of a plurality of passages.

Can use exemplary embodiment of the present invention to solve such deficiency.In one exemplary embodiment of the present invention, can provide a kind of for apply the equipment of a plurality of electromagnetic radiation to sample.This equipment can comprise the device with specific part, and described specific part has a plurality of passages.A passage in described passage can help the first radiation in described radiation to be forwarded to the interior sample of anatomical structure, and another passage in described passage can help the second radiation in described radiation to be forwarded to described sample.The first radiation can have the first wave band, and the second radiation can have the second wave band.The first wave band can be different from the second wave band basically.

For example, described passage can comprise at least one optical fiber.Described optical fiber can be double clad and/or twin-core.Another device can be provided, and this another device can have the single passage of at least two passage optical communication in passage with described specific part.This another device can be fused optic fiber wavelength division multiplexer, membrane wave division multiplexer, grating and/or dichroic mirror.

According to another exemplary embodiment, the first radiation can be suitable for being transported to the first area of sample, and the second radiation can be transported to the second area of sample.Described first area can be basically by described second area sealing.Another passage in described passage can help the 3rd radiation to be forwarded to described sample.The 3rd radiation can be transported to the 3rd zone of described sample, and the 3rd zone of described sample is basically different from first area and second area.Can provide the another device with single passage, at least two special modality optical communication in the passage of this single passage and described specific part.Can have the first optical distance via the path of a special modality from described single passage to sample in special modality, and can have the second optical distance via the path of another special modality in special modality from described single passage to sample.The first optical distance can differ at least about 0.5mm and/or about 8mm at the most with the second optical distance.

In accordance with a further exemplary embodiment of the present invention, each passage in described passage can help at least one particular radiation in described radiation to be forwarded to the interior sample of anatomical structure of sample, and these radiation are transported to the zones of different of sample.In described zone, each regional center can be basically along the line setting.This line can be arranged to be arranged essentially parallel to the scanning direction of radiation.

When reading the following specifically describes of the embodiment of the present 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 from be combined with the accompanying drawing that exemplary embodiment of the present is shown the following specifically describes become clear, in the accompanying drawings:

Figure 1A is the schematic diagram 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 the example images of using the perspective view of the pig feed pipe that OFDI balloon catheter according to an exemplary embodiment of the present invention obtains;

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;

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

Fig. 4 be according to an exemplary embodiment of the present invention for the treatment of with the exemplary means that monitors tissue and the schematic diagram of use thereof;

Fig. 5 uses the exemplary means of Fig. 4 and a plurality of exemplary m mould OFDI phase image group that corresponding organizational structure obtains;

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

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

Fig. 7 B is the front 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 that the comprehensive data that obtains from pig feed pipe live body that can utilize that exemplary embodiment of the present obtains is concentrated the exemplary vessel graph of extracting;

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 schematic diagram of the two beam guide tube probes of another exemplary embodiment according to the present invention;

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

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

Figure 14 be utilize that exemplary embodiment of the present obtains can provide the design of the image of feedback to reproduce to the user;

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 schematic diagram and the use of interior (in-line) conduit probe of two bunch according to an exemplary embodiment of the present invention;

Figure 22 is 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 according to an exemplary embodiment of the present invention based on the side view of the device of micro machine, but described device can generate treatment bundle and the fast scan imaging bundle of slow circumvolve;

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 broadband booster amplifier is followed in described treatment source introducing;

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

Figure 26 introduces the tunable wave length treatment source of laser diode bar and the diagram of the result that generates thus 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 schematic diagram 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 according to the exemplary embodiment of the method for the information for obtaining to be associated with at least one part of sample of the present invention;

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

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

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 completes in conjunction with exemplary embodiment.Be intended to and in the situation that do not break away from true scope and the spirit of the invention of theme as defined by the appended claims, described embodiment changed and to revise.

The specific embodiment

According to of the present invention for controlling and the exemplary embodiment of the system and method for locating therapy can be based on the thermal excitation by the spacescan laser beam conveying of routine.For example, described in the publication 33 of sign hereinafter, when there is no 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 of sign hereinafter, for greater than about length of exposure of 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 subject 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 (optionally photo-thermal solution effect) by using the laser explosure shorter than the feature thermal diffusion time of the volume that is heated.For relatively large (〉 1mm) laser beam of diameter and the about optical maser wavelength of 1450nm, for this feature diffusion time of biological tissue can be approximately 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 radial distance between the center of Gaussian laser beam of 1/e2.Although this is approximate has ignored the scattering of laser when it propagates in tissue, the model (described in the publication 36 that hereinafter identifies) that comprises significantly scattering shows that under the described conditions the deviation with equation 1 is less than 10%.

Because absorptance is relevant with wavelength, can be used for controlling the degree of depth of heat injury and minimizes collateral damage to the tissue that underlies so equation 1 shows laser parameter Pd, t and wavelength.Why operation in the visible part of spectrum 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 1.45 μ m is leading by water, and therefore can be in the scope of organization constant.In addition, tuning by carrying out in the appropriate wave-length coverage from 1375nm to 1430nm for example, 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 various ways for monitoring laser therapy, comprise the analysis (described in the publication 37 that identifies hereinafter) to the acoustics transition that generates in ablation process, organize the variation (described in the publication 38 and 39 that identifies hereinafter) of reflectance, be used for distinguishing the fluorescence spectroscopy (described in the publication 40 that identifies hereinafter) of mottle and blood vessel wall, in order to the plasma spectroscopy of distinguishing skeleton and nervous tissue (described in the publication 41 of sign hereinafter) and to the analysis of the Bubble dynamics of the top end of the laser optics probe that is used for controlled scleral perforation in operation for glaucoma (described in the publication 42 of sign hereinafter).Except the process based on reflectance of describing, in every kind of such method, only after having changed across the border of particular tissue type, the heat injury district just causes supervisory signal in publication 38 and 39.Do not have a kind of method can determine the degree of depth of heat injury or the spatial relationship of damaged tissues and adjacent active tissue.The laser part that has not been absorbed by tissue by supervision is realized the spatial resolution of specific degrees.Insert optical fiber by passing pin, can collect laser from the volume different angles on every side of being heated, and can measure the scattering variation (as the publication 43 that hereinafter identify described in) relevant with temperature.Also the scattering that causes changes and the physical removal of tissue is visual for being shone by ablative laser, has verified the high-resolution in situ imaging (described in the publication 44 that identifies hereinafter) of more direct mode.

Can utilize and the information relevant to the known tissue response of heat injury according to the exemplary embodiment of surveillance of the present invention, method and technology.The microdeformation that these exemplary response can include but not limited to be caused and can be observed in being low to moderate the temperature range of 45 ℃ by LASER HEATING (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 together 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 the characteristic length scale that preferably can be used for comprehensive examination and treatment comprehensively may be different, so might carry out respectively these targets.For example, (for example may be performed as first step) examination can utilize resolution to be a kind of or a plurality of comprehensive imaging technique of cell size scale.This example process can be used for identifying the zone 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 real-time instruction, thereby processes all diseases and minimize collateral damage.This example results can be by for example improving treatment effectiveness simultaneously the risk of complication improve management to the Barrett esophagus patient.

Although 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 dermatological for example.Some relevant epithelial cancers and precancerous lesion that exemplary embodiment of the present invention solves 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 for the treatment of and the control of spatial dimension.

Exemplary large visual field examination

In order to carry out effective examination process, preferably carry out to comprehensive inspection of large surf zone with to the application of Accurate Diagnosis criterion, so that identification 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, for 288 slicers that obtain from 121 patients, be identified for diagnosing the sensitivity of SIM and specificity (contrasting with all other top GI pipeline tissues) to be respectively approximately 97% and 92%.Yet as of late, described exemplary OCT technology still too slowly and can't be to large 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.Although 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 can transmit and store into the speed of hard disk drive on the bus of computer.

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 smooth core 2010.Inner core 2010 can be closed in 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 onto on 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, is used for the sept of extensible beam, is used for the gradient-index lens that focuses on and the corner cube prism that is used for restrainting the longitudinal axis of vertically guiding conduit into.The Small Cylindrical lens are made into built-in, and these Small Cylindrical lens are placed on the second surface of prism.The astigmatism that this lens compensation is caused by plastic sheath and cause diffraction limited bundle (30 μ m diameter) on tissue surface.In use, the speed rotation exemplary catheter that can turn by about per second 4, 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.Use this information when rebuilding 3 dimension data collection.

Preliminary pig feed pipe imaging

Can approximately carry out the esophagus imaging technique in the pig of 50kg at two.Although can not show complete 20GB data set in discrete figure, in 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 orientation, perhaps show in the high-resolution cross sectional image of the image 2110 in whole esophageal wall can being visualized as Fig. 2 B.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 with irregular surface of patient's SIM; There is large epithelial gland).Before this patient, diagnosis has BE, 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 human subjects.

The injury of supervision LASER HEAT

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

Figure 4 illustrates according to of the present invention for collect the equipment of OFDI signal and the exemplary embodiment of use thereof during laser irradiation.For example, by prover 2200 transport process light.Carry imaging by the second prover 2220.Process 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 backing 2280.This tissue is by motorized precision translation stage 2290 translations.Become video beam to be focused on by lens 2250.Provide and described to restraint overlapping 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).The OFDI sample beam 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 deposition was in tissue, the temperature increase that brings can make protein and collagenous degeneration.Can show these by microdeformation and change, wherein can utilize the OFDI to phase sensitive to measure this microdeformation.Following data verification this ability.

Fixed point---for such exemplary experiment, sample remains on the fixed position.Gather constantly the OFDI depth scan with the about speed of 10kHz, 1450nm laser turn-on simultaneously keeps predetermined lasting time with the firm power of 400mW, then turn-offs.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, above the zone that below overlaying on regard to the surf zone of observing positive phase shift, negative moves.Along with laser irradiation continues, phase place is covered phase shift from just changing into the negative degree of depth little by little to deepen value reduces.Can't detect measurable phase shift after laser shutdown.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 spread on the degree of depth.Deep identification when shift direction is reverse the focus center of active degeneration.

In order to verify these results, obtain organizational structure section (histologicalsection) after laser explosure, and use NBT (nitro-blue tetrazolium chloride, NBTC) dyeing to assess the degree of damage from laser.NBTC is positive for dyeing for the lactic acid dehydrogenase (LDH) of thermo-labile enzyme; The loss of LDH activity occurs rapidly after the cell injury that heat is brought out, and relevant to 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 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.Preliminary discovery demonstration thermal denaturation tissue and the border between the survival tissue are corresponding to the flex point of the phase shift of measuring with OFDI.Quantitatively, the depth derivates of phase shift is determined for 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 determining in this way is provided as the vertical curve adjacent with each M mould image in Fig. 5, 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 the laser treatment to large epithelial surface zone.Preliminary imaging research has verified that the OFDI bundle is of a size of comprehensive esophagus imaging of 30 μ m.Scanning acquisition by continuous rotation〉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).

Illustrated in Fig. 6 A and there is no the OFDI intensity image 2400 that gathers in the laser irradiation situation.Respectively for the image 2410 shown in Fig. 6 B, 6C and 6D, 2420 and 2430,1450nm laser power be about 400mW.The translation of sample in exposure process causes the damage from laser line on 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 show respectively fast the laser hazard degree of depth of 0.41mm and 0.69mm with the zone acquisition and the organizational structure section that orientation is vertical with this line of translation at a slow speed.The phase shift data corresponding with the image 2410 of Fig. 6 B is illustrated as image 2420 in Fig. 6 C.In the situation that the measurement of learning with tissue morphology measurement is basically consistent, can be respectively 0.40mm and 0.67mm by the definite lesion depths of phase shift data (maximum negative derivative) in zone fast and at a slow speed.

The speckle decorrelation

Speckle (speckle) is the phenomenon of generally observing when utilizing coherent illumination to carry out imaging, and shows as high strength and the low intensive graininess pattern that does not seem relevant to 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 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 sample.This example technique has been provided for biomechanical characterization (described in the publication 50 that identifies hereinafter) and the thermal excitation (described in the publication 51 that identifies hereinafter) of investigating in biological tissue.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 laser explosure understands that the potential of this example technique may.Without laser explosure the time, the speckle pattern of observing in OFDI keeps constant with respect to the depth ﹠ wideth of image.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 begin near tissue surface, 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 with the degree of depth of the time autocorrelation function of OFDI strength signal.Then by utilizing 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 arrow in Fig. 6 D) changes accordingly with the rate of translation of sample and the damage from laser degree of depth shown in 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 for the quantitative measurement of determining the laser hazard degree of depth.

Birefringence

When light was propagated in material, if the refractive index non-isotropy, 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 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 that birefringence loses depth of burn have been described.In PS-OCT, two detector channels can be configured 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 the sample light that detects in each passage to change.If the ratio of two passages is shown as gray scale in cross sectional image, 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 keeps fixing and the 1450nm laser facula remains secured to the center.As shown in Figure 27, can pass through the first prover 2500 transport process light, described prover 2500 is provided at the processing bundle 2510 of incident on tissue 2550, and described tissue 2550 is by cover plate 2540 coverings and against backing 2560.Imaging can be provided by the 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/system can be the exemplary embodiment that is applicable to the treatment surveillance of dermatosis application.Gather OFDI image or the video of esophagus and Duodenal Tissues during laser irradiation.

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

Scattering

The variation of the tissue microstructure that heat is brought out can change optical scattering.Because the signal in OFDI is caused by scattering and little variation can be detected in large dynamic range, so investigate, scatterometry is used for monitoring that the tissue that heat is brought out changes.The scattering of observing in the image 2460 of Fig. 7 B changes the preliminary observation that can represent duodenum and esophagus sample.Under specific circumstances, determine have obvious scattering to change and change less in the tissue that underlies of muscle mucosa and muscle itself (muscularispropria) at upper Intradermal.For example, can obtain to be used for two potential quantisation metric of damage from laser from scatterometry: 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 Oligemia (described in the publication 54 that identifies hereinafter).Because the Esophageal Mucosa vascularity is many, so monitor that blood flow changes the additional method that can be provided for monitoring laser therapy.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 open esophagus and be fixed smooth.On the degree of depth, intensity data is integrated into tissue.Be the convenient manner of mapping blood vessel although the large scale of this class is visual, might measure blood flow with sensitiveer and quantitative method/technology/system.Doppler OCT (described in the publication 55 and 56 that identifies hereinafter) has been verified for the blood flow to tissue and has carried out visual and quantize, and studied as a kind of device (described in the publication 57 that identifies hereinafter) for assessment stream after laser therapy.Describe the Doppler measurement (described in the publication 24 that identifies hereinafter) that utilizes OFDI, and checked the probability of measuring simultaneously live body structure and stream.

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.It is simple in the hope of showing that the coordinate (r, θ) of these data has been mapped to cartesian coordinate (vertically, level).The observation of this result representative a plurality of positions in the pig of two.In addition, clearly observe pulsating flow in the time series of doppler image.

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

Exemplary control

Except monitoring the LASER HEAT injury, effectively the conformal laser therapy also can be used the accurate control to the volume of processed tissue.A kind of is to operate within being used for the condition of thermal confinement (thermal confinement) in order to control the exemplary approach of processing the degree of depth, in order to minimize collateral damage and control optical maser wavelength, power and time of exposure to control the degree of depth of 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 restriction is that the flat-top bundle of 1-3mm can allow spatial control, also allows simultaneously to treat large 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 applicable under the restriction of weak scattering.

Wavelength

According to the Temperature Distribution of equation 1, obvious μ _aMay be for the optimized parameter of controlling the laser hazard degree of depth.Although μ _aBe feature rather than the outside controllable parameter of sample, but in the present invention, utilize μ _aDependence to wavelength realizes severity control.In the present invention, account for the absorptance of leading longer wavelength as target to absorb 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 the 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 is from 0.3mm to surpassing 2mm.These length are well corresponding to the characteristic length scale that is suitable for processing 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 who controls 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, so these variablees can be used for making amplitude normalization, allow simultaneously to change absorptance.

Process duration

When estimating the new therapy that proposes, may importantly estimate preferred process time and estimate this estimation in emulative mode and under specially for the constraint background of clinical setting and patient's acceptance.PDT is applied to the processing that endoscope arranges middle BE at present, and requires the approximately process time of 20 minutes.For exemplary conformal laser therapy technology, can come the estimation procedure time of implementation according to 2At/ (π rv), wherein At is 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 for carry out the system of epithelial diseases conformal laser therapy by the combination of monitoring and controlling.Because laser beam is easy to be shaped and spatially scanning, and because the nargin in transverse plane (along the surface of esophagus) is so crucial, so realize that the accurate main challenge of controlling of laser therapy is to limit and adjust the degree of depth of damage from laser.Based on above-mentioned modeling and analysis, utilize optical maser wavelength and power and scanning speed to change the damage from laser degree of depth in might be clinically important scope, and don't obviously change horizontal scope of damage.

The exemplary treatment laser device

Can provide scope from surpassing 2mm to the absorption length that is less than 0.3mm in the about optical maser wavelength between 1375nm and 1430nm.Semiconductor laser can be worked in this spectral region.Due to such laser instrument can be compactness and be stable aspect environment, so these laser instrument can be used in clinical practice effectively.Yet the material that is suitable for this particular range of wavelengths may be nonstandard.Can be by solid-state laser 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.Exemplary design and the structure of the tunable solid laser instrument of working in the near infrared light spectral limit have been described in the publication 60-65 of sign 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, the OFDI sample beam can be focused onto the approximately diameter of 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 two relative to each other fixing bundles, and simultaneously sample perpendicular to laser beam axis ground by translation.

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 for various skews.This skew can be used in all follow-up studies and can be registered according to following process.Can bring out short epithelium burn of little lower powered persistent period on the surface of sample, make simultaneously sample keep fixing (not translation).As shown in Figure 7, can easily observe the increase of epithelium scattering in OFDI, and spatially locate the increase of epithelium scattering according to the restriction of laser beam profile.Although 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 used for generating the positive OFDI image of sample, and epithelium burn can show as the circle of the scattering that has increased.Then can locate and fixing galvanometer, make the OFDI bundle be positioned (as schematically illustrating in Fig. 4) with required skew.

The exemplary wavelength convergent-divergent

One of purpose of this experiment is that test is according to exemplary wavelength variation and power normalization technology and the method for the clinical associated change be used to realizing the damage from laser degree of depth of the present invention.In the situation that laser spot size and scanning speed keep is constant, 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 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.

The exemplary scan rate scaling

An exemplary embodiment for the impact 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 reserved the dark zone required time of conduction of heat to tissue, thereby causes more deep treatment.

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 sample beam and laser facula.

Exemplary endoscope probe design

One exemplary embodiment of the present invention can comprise the endoscope probe 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 shell 2630, and described shell is closed in the 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 tissue surface 2610.Can come transmission laser bundle and OFDI bundle by optical fiber 2641a and the 2641b that separates.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 that these that be designed to overlap hot spot pass on optics.Optical fiber and distal end optical device can be contained in the coiling driving shaft, and it is inner to be placed on the air bag centering probe 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 is also possible.In one exemplary embodiment of the present invention, the endoscope detecting system is visual field ground examination disease greatly, accurately monitors the interaction of laser and tissue, and accurately controls 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, monitoring and controlling can be contacted directly.

In another exemplary embodiment, described system can be used for generating the high-resolution 3 dimension figure of whole distal esophagus, to help treatment plan.Subsequently as shown in Figure 14, can present ' living ' 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, so can showing as from right to left along with the renewal of image, moves in tissue.User (for example doctor of endoscope) can operate the control servomechanism and begin/stop to process and increase or reduce to treat the degree of depth.By checking the untreated tissue 2700 for the treatment of region 2710 and eyes front, the user can handle the laser therapy district and make it consistent with re-set target.

Figure 12 illustrates according to of the present invention for carry out the exemplary embodiment of the endoscope probe of imaging, supervision and laser therapy 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 for the treatment of.This probe can comprise for example three or more optical channels: be used for before laser irradiation to tissue carry out imaging first passage 2800c, for the treatment of the third channel 2800a that monitors of second channel 2800b and being used for.Each optical fiber can laterally be imaged onto on esophageal wall discretely by air bag.The aligning of gained output bundle can so that when rotate in the clockwise direction, become video beam to lead over fully and process bundle, thereby can sample to the tissue that is untreated.Monitor to restraint to be aligned to and fall in 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 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 make and might reach for example 100 rotations before requiring the phase despining.With regard to the 1mm laser facula, can be 60 to turn to the processing fully of the long esophagus segmentation of 6cm.Can use the 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

Can utilize for example high speed imaging system according to the another exemplary embodiment of system of the present invention and device.The exemplary embodiment of digital collection and processing system can be based on the VME bus hardware, so that Real-time Collection, processing and storage OFDI signal.Such example system and the example components of device can comprise the VME chassis, and this chassis comprises the high-speed figure transducer (digitizer) that resides on 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).Can use the broadband reception device (for example 12,210MS/s) with integrated field programmable gate array (FPGA) processor will simulate OFDI signal digitalized.On collection plate, intrinsic disposal ability may be important, 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 each channel of polarization is become to represent that from frequency domain transform luminance factor contains 1024 cellular arraies (an A line) to the degree of depth.These data can be passed to single board computer, in order to carry out subsequent treatment and these two passages of combination before final data being sent to the RAID array that is comprised of hard disk drive.The final data memory rate can be for example 400MB/s.By the data itemize is distributed on a plurality of hard disk drives, can keep constantly this data rate.

Software on blood processor can allow the user to the control of example system according to an exemplary embodiment of the present invention, and can realize that following sampling rate is come the displayed map picture in real time.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.Vertex 4 ProFPGA 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 tissue distributes.At the constant light spot size, scanning speed is doubled and to use the laser power of twice.Can utilize single-shot emitter semiconductor laser diode according to an exemplary embodiment of laser aid of the present invention.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 for wavelength control.Can be based on from potentiometric analogue signal, control laser power and wavelength via the primary processing unit of OFDI system.Described potentiometer can be that user (for example doctor of endoscope) can use in order to 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 to the operator user interface of the cross sectional image that comprises tissue.Described image can continue to be updated, and can comprise that processed 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 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 via optical splitters 215 exemplary three port catheter, such as the conduit shown in Figure 12, described optical splitters 215 can couple light into 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 according to exemplary imaging system of the present invention/device 800 shown in Figure 17, can utilize single wavelength division multiplexer 810 with light and treatment source 805 combinations.Light through combination can be coupled to the single fiber rotary coupler, then is coupled to exemplary single fiber conduit, such as the conduit shown in Figure 21.

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

Figure 19 shows via multipassage rotary bonder 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 schematically shows in for example Figure 15 and 16) and three port catheter 415 (such as the conduit shown in Figure 12).

Figure 20 shows the schematic diagram 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 Rolling bonder 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 the first optical fiber 332 and will treats light and is separated on the second optical fiber 331.Can also utilize the further separate imaging light of optical splitters 335, described optical splitters 335 has two imaging port 336a and 336b.Optical fiber 31,336a, 336b can be connected to three port catheter 325 these designs, 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 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 the treatment bundle 1120 that separates from single-mode fiber 1101.For example, the light from the optical fiber that holds imaging and treatment light can first be focused on by the first grin lens 1100.Then described light be passed in wavelength-division multiplex prism 1105, this wavelength-division multiplex prism can upwards draw treatment Shu Bochang, to produce treatment bundle 1120, and the imaging wavelength is sent to the 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 bundle in the overlapping angle of the suitable distance of 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 interior V groove 1020 of 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 caused astigmatism of transparent sheath 1000 of described cylindrical lens are proofreaied and correct.Air bag 1010 centering machines can be used for keeping optics 1035 interior placed in the middle at interior cavity tissue 1015.Can see in end-view and monitor bundle 1050c, treatment bundle 1050b and preformation video beam 1050a.Shell 1040 goes for by the multipassage rotary bonder such as the bonder shown in Figure 13 rotates.

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 transparent sheath 1235.The rotation of motor shaft can rotary prism 1220.Imaging can be coupled to via optical fiber 1210 the distal end optical device, and wherein said imaging can be focused on by focusing optics 1215, and is reflexed on 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 to by the tube chamber identical with optical fiber 1210.Treatment couples light to the distal end optical device on optical fiber 1200.This treatment light can utilize focusing optics 1250 to focus on, and guides the side with the anglec of rotation fixing with respect to inner sleeve into by prism 1245.Become therefore inswept fixing treatment hot spot of video beam.Realize treating the translation of hot spot by the rotation of whole inner sleeve 1235 in overcoat 1240.Can by with the multipassage rotary bonder such as the bonder shown in Figure 13 is realized this exemplary rotation.Conduit can be used for the placed in the middle of light core 1230 with air bag 1255.

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 the broadband booster amplifier 605 that increases luminous power.

Figure 25 show the laser therapy source of introducing a plurality of laser diode 500a be in different wave length and polarization, 500b, 500c, 500d exemplary embodiment functional block diagram 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 designs to couple light into 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 together with a plurality of wavelength 701a-g.Each waveguide can scioptics device 705 and grating 710 and part reflect end mirror and be coupled to the free space laser cavity.Due to the wavelength dispersion of grating, the formed laser instrument of each waveguide sends laser at different wave length.Therefore, by adjusting the drive current to each waveguide 701a-g, can adjust power and the spectral shape of Laser output 720.

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

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

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

Figure 29 B shows the flow chart according to another exemplary embodiment of the method for controlling the sample Temperature Distribution of the present invention.For example, in step 3130, can provide electromagnetic radiation to the section in sample with specific wavelength.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 according to another exemplary embodiment of the method that applies laser emission at least one part to biological structure of the present invention.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 at the most approximately 1/10.In step 3160, can (I) based on predetermined pattern, (II) in the wavelength of modulated laser radiation and/or (III) monitor laser emission apply the degree of depth in apply described bundle.

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Above only illustrate principle of the present invention.Based on the instruction here, will be obvious 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 for example proposed in 8th with JIUYUE in 2004, 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, the disclosure of these patent applications is incorporated into this by reference on the whole.Therefore will recognize, not illustrate clearly 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 although those skilled in the art can design.In addition, the prior art knowledge that does not have hereinbefore to be incorporated into clearly by reference this 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 (22)

1. equipment that is used for applying to sample the signal that a plurality of electromagnetic radiation and detection be associated with described sample comprises:

A. the first device that has specific part, described specific part has a plurality of passages,

A passage in wherein said passage helps the first radiation in described radiation to be forwarded to the interior sample of anatomical structure, and another passage in described passage helps the second radiation in described radiation to be forwarded to described sample, described the first radiation has the first wave band and described the second radiation has the second wave band, and

Wherein said first wave section is different from described the second wave band basically; And

B. second detection device, described second detection device is configured to receive the 3rd radiation from described sample via at least one in described first passage or described second channel, and wherein said the 3rd radiation is associated with described the first radiation and described the second radiation.

2. equipment according to claim 1, wherein said passage comprises at least one optical fiber.

3. equipment according to claim 2, wherein said at least one optical fiber are at least a in doubly clad optical fiber or twin-core fiber.

4. equipment according to claim 1, also comprise the another device with single passage, at least two passage optical communication in the described passage of described single passage and described specific part.

5. equipment according to claim 4, wherein said another device are at least a in fused optic fiber wavelength division multiplexer, membrane wave division multiplexer, grating or dichroic mirror.

6. equipment according to claim 1, wherein said the first radiation is suitable for being transported to the first area of described sample, and described the second radiation can be transported to the second area of described sample, and wherein said first area is basically by described second area sealing.

7. equipment according to claim 1, each passage in wherein said passage helps at least one particular radiation in described radiation to be forwarded to the interior described sample of anatomical structure, described radiation is transported to the zones of different of described sample, and in wherein said zone each regional center basically along the line setting.

8. equipment that is used for applying to sample the signal that a plurality of electromagnetic radiation and detection be associated with described sample comprises:

A. the first device that has specific part, described specific part has a plurality of passages,

A passage in wherein said passage helps the first radiation in described radiation to be forwarded to the interior described sample of anatomical structure, and another passage in described passage helps the second radiation in described radiation to be forwarded to described sample, described the first radiation is transported to the first area of described sample, and described the second radiation is transported to the second area of described sample, and

Wherein said first area is basically by described second area sealing; And

B. second detection device, described second detection device is configured to receive the 3rd radiation from described sample via at least one in described first passage or described second channel, and wherein said the 3rd radiation is associated with described the first radiation and described the second radiation.

9. equipment according to claim 8, another passage in wherein said passage helps the 3rd radiation in described radiation to be forwarded to described sample, and wherein said the 3rd radiation is transported to the 3rd zone of described sample, and separate with second area with described first area basically in described the 3rd zone.

10. equipment according to claim 8 also comprises:

Another device with single passage, at least two passage optical communication in the described passage of described single passage and described specific part,

Wherein has the first optical distance via the path of a passage from described single passage to described sample in described special modality, and have the second optical distance via the path of another passage in described special modality from described single passage to described sample, and

Wherein said the first optical distance and described the second optical distance differ (i) at least about 0.5mm or (ii) about at least one in 8mm at the most.

11. equipment according to claim 8, wherein said the first radiation has the first wave band and described the second radiation has the second wave band, and wherein said first wave section is different from described the second wave band basically.

12. equipment according to claim 8, each passage in wherein said passage helps at least one particular radiation in described radiation to be forwarded to the interior described sample of anatomical structure, described radiation is transported to the zones of different of described sample, and in wherein said zone each regional center basically along the line setting.

13. an equipment that is used for applying to sample the signal that a plurality of electromagnetic radiation and detection be associated with described sample comprises:

A. the first device that has specific part, described specific part has a plurality of passages,

Each passage in wherein said passage helps at least one first particular radiation in described radiation to be forwarded to the interior described sample of anatomical structure, and described radiation is transported to the zones of different of described sample, and

In wherein said zone, each regional center is basically along the line setting; And

Second detection device, described second detection device are configured to receive the second radiation from described sample via at least one passage in described passage, and wherein said the second radiation is associated with described at least one first particular radiation.

14. equipment according to claim 13, wherein said line is configured to be arranged essentially parallel to the scanning direction of described radiation.

15. equipment according to claim 13, wherein said at least one first particular radiation comprises the 3rd radiation and the 4th radiation, described the 3rd radiation has the first wave band and described the 4th radiation has the second wave band, and wherein said first wave section is different from described the second wave band basically.

16. equipment according to claim 13, wherein said at least one first particular radiation comprises the 3rd radiation and the 4th radiation, described the 3rd radiation is suitable for being transported to the first area of described sample, and described the 4th radiation can be transported to the second area of described sample, and wherein said first area is basically by described second area sealing.

17. equipment according to claim 8, wherein said passage comprises at least one optical fiber.

18. equipment according to claim 17, wherein said at least one optical fiber are at least a in doubly clad optical fiber or twin-core fiber.

19. an equipment that is used for applying to sample a plurality of electromagnetic radiation comprises:

A. the first device that has specific part, described specific part has a plurality of passages,

A passage in wherein said passage helps the first radiation in described radiation to be forwarded to the interior described sample of anatomical structure, and another passage in described passage helps the second radiation in described radiation to be forwarded to described sample, described the first radiation has the first wave band and described the second radiation has the second wave band, and

Wherein said first wave section is different from described the second wave band basically; And

B. the another device that has single passage, at least two passage optical communication in the described passage of described single passage and described specific part, wherein said first device is arranged in optical path between described another device and described sample.

20. equipment according to claim 19, wherein said another device are at least a in fused optic fiber wavelength division multiplexer, membrane wave division multiplexer, grating or dichroic mirror.

21. equipment according to claim 19, wherein said the first radiation is suitable for being transported to the first area of described sample, and described the second radiation can be transported to the second area of described sample, and wherein said first area is basically by described second area sealing.

22. equipment according to claim 19, each passage in wherein said passage helps at least one particular radiation in described radiation to be forwarded to the interior described sample of anatomical structure, described radiation is transported to the zones of different of described sample, and in wherein said zone each regional center basically along the line setting.

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