Patent Application: US-68096207-A

Abstract:
an apparatus and method according to the present invention can be provided , e . g ., for a cell specific laser therapy of atherosclerotic plaques , particularly to systems and methods for targeting endogenous light absorbers present within plaque macrophages and exogenous nanoparticle targeting . in one exemplary embodiment , an electro - magnetic radiation can be forwarded to an anatomical structure . the electromagnetic radiation may have at least one property configured to modify at least one characteristic of at least one first cell , and minimize any modification of and / or modify at least one characteristic of at least second cell . the first and second cells may be different from one another , the characteristics of the first and second cells can be different from one another , and the first cell and / or the second cell may have at least one macrophage feature , and the characteristic of the at least one first cell and / or the at least one second cell can be temperature . according to still another exemplary embodiment , a location associated with the first cell and the second cell can be determined . for example , the electromagnetic radiation can be forwarded in a vicinity of the location .

Description:
a chromophore is a molecule that absorbs light . in the absence of photochemical effects , the absorption of light can cause heating . an endogeous chromophore is a biological light absorbing molecule that is intrinsic to or resident within the cell . these molecules may absorb photons 200 which can heat the cell . certain examples of endogenous chromophores can be water molecules , lipid , cell pigments etc . cell death and irreversible protein denaturation can occur at temperatures above 6070 ° c . to 70 ° c . as described in a . l . mckenzie , “ physics of thermal processes in laser - tissue interaction ,” phys med biol . 1990 ; 35 , pp . 1175 - 209 . in the absence of photochemical or vaporization processes , the energy absorbed by tissues in response to laser irradiation may be converted to heat , as described in a . vogel et al ., “ mechanisms of pulsed laser ablation of biological tissues ,” chem rev . 2003 ; 103 , pp . 577 - 644 . when energy is absorbed , heat transfer from the target to its cooler surroundings occurs by thermal diffusion . depending on the laser parameters , different thermally induced effects can occur . when temperatures of 60 ° c . are reached , coagulation and irreversible denaturation of proteins 205 may occur which can causing cell death . at high temperatures over 100 ° c ., vaporization likely occurs . when energy is absorbed , it can be spatially redistributed by thermal diffusion . the time it may take for this energy to be conducted can depend on the thermal relaxation time of the target chromophores . depending on laser parameters a zone of thermal damage 205 , 210 , and 307 and 310 ( shown in fig2 and 3 , respectively ) may occur around the region of laser ablation and the absorbed energy may be spatially redistributed by thermal conduction , as shown in fig2 . based on these principles , previously , a technique labeled as laser angioplasty was introduced to open up stenosed arteries . ( see w . h . ahmed et al ., “ excimer laser coronary angioplasty ,” cardiol clin . 1994 ; 12 , pp . 585 - 93 ). in this conventional method , the debulking of the plaque was performed by the laser ablation , and subsequent vaporization of the plaque in coronary arteries . laser angioplasty resulted in high restenosis rates in patients possibly due to endothelial damage caused by the non - specfic tissue heating during laser ablation , initiating the process of smc proliferation , neo - intimal thickening and restenosis . exemplary embodiment of the present invention relate to systems and methods for cell specific therapy by causing laser - induced thermal damage in atherosclerotic plaque macrophages by targeting endogenous ( e . g ., lipids ) and exogenous ( such as nanoparticles and microparticles ) light absorbers . the sample approaches used according to exemplary embodiments of the present invention may not be to conduct ablation of the plaque as was previously done with the laser angioplasty , and to induce cell - specific thermal damage preferably only within macrophages , e . g ., confining the zone of damage 307 and 310 ( see fig3 ), and thereby maintain the health of the endothelium and surrounding tissues 215 , 220 ( see fig2 ) and tissues 320 , 305 ( see fig3 ). an exemplary cell specific laser therapy may be performed as a stand alone procedure or in conjunction with oct , ofdi , sd - oct , raman and ir spectroscopy , laser speckle imaging ( lsi ), angioscopy , fluorescence , fluorescence spectroscopy , time resolved fluorescence , intravascular ultrasound ( ivus ) systems / procedures , or any other imaging systems / procedures known in the art . the exemplary embodiment of the present invention can be associated with an observation that the optimized selection of laser parameters may be used to cause a cell specific thermal damage . previously , a concept of selective photothermolysis to achieve spatially confined localization of heat in tissues has been described . using this exemplary method , selective thermal damage can be induced when the wavelength of the laser 300 ( shown in fig3 ) may be preferentially absorbed by the target chromophore 307 , the required or preferable fluence is high enough to heat the chromophore , and the pulse duration of the laser exposure is shorter than the thermal relaxation time of the chromophore . ( see r . r . anderson et al ., “ selective photothermolysis : precise microsurgery by selective absorption of pulsed radiation ,” science . 1983 ; 220 , pp . 524 - 7 ). the pulse duration , ( t d ), of the exposure can influence the specificity or confinement of thermal damage , and may be determined from the thermal relaxation time ( t r ) of the target chromophore . the transition from specific to non - specific thermal damage can occur when the ratio is as follows : ( t d / t r )≧ 1 . ( see see r . r . anderson et al ., “ selective photothermolysis : precise microsurgery by selective absorption of pulsed radiation ,” science . 1983 ; 220 , pp . 524 - 7 ). for spheres of diameter , d , and thermal diffusivity , κ , the thermal relaxation time can be provided by t r =( d 2 / 27k )). to induce targeted thermal damage in specific cells while maintaining the integrity of the surrounding tissue , it is preferable is that the target chromophores have greater optical absorption at a given laser wavelength than their surrounding tissue . according to an exemplary embodiment of the present invention , a thermal confinement within specific cell populations may be achieved by targeting various endogenous absorbers present in macrophages such as lipid droplets and cholesterol esters as light absorbers . ( see c . m . pitsillides et al ., “ selective cell targeting with light - absorbing microparticles and nanoparticles ,” biophys j . 2003 ; 84 , pp . 4023 - 32 ). as shown in fig1 , plaque macrophages 105 may contain an abundance of lipid , which may provide an endogenous chromophore for selective heating and destruction of these cells while maintaining viability of the surrounding supportive cells and matrix . by targeting an endogenous absorber such as lipid , cholesterol or cholesterol esters , selective thermal damage can be induced in plaque macrophages . according to certain exemplary embodiments of the present invention , the targeting of endogenous chromophores for inducing macrophage cell death can preclude the requirement or preference for administering exogenous agents or chromophores . confined energy deposition in lipid laden macrophages can be achieved by using laser energy at a wavelength that may be strongly absorbed by lipid and not by the surrounding aqueous tissue , and with a laser pulse duration that can be less than t , to reduce heat transfer from the absorbing lipid rich macrophages . by using spectro - photometric measurements , as shown in the exemplary graph of fig4 , at 915 nm ( 400 ), 1205 nm ( 410 ), 1715 nm ( 420 ) and 2305 nm ( 430 ) in the near and mid ir spectrum , lipid rich tissue may have a higher absorption than aqueous tissue . ( see d . manstein et al ., “ selective photothermolysis of lipid rich tissue ,” annual meeting of lasers in surgery and medicine . 2001 ; supplement 13 : abs no 17 ). it may be possible to utilize a 1206 nm laser to induce selective thermal damage in subcutaneous fat , while maintaining the health of the overlying epidermis . in this exemplary embodiment of the present invention , laser wavelengths in the vicinity of absorption bands of endogenous chomophores , such as low density lipoprotein ( ldl ), free cholesterol , cholesterol esters , etc ., may be used for inducing selective thermal damage of plaque macrophages . in one exemplary embodiment for achieving the goal of cell specific laser therapy according to the present invention can include an exemplary treatment delivery system to enable selective thermal confinement , as shown in fig5 a . for example , a laser source 510 having wavelengths in the vicinity of the absorption bands of target chromophores ( e . g ., lipid , cholesterol , cholesterol esters , etc .) within macrophages can be utilized for cell specific therapy . an output 505 of the laser 510 can be controlled to achieve macrophage cell death . to perform a laser - induced thermal confinement , the laser source can be configured to illuminate the tissue 520 . the laser source 510 can be configured to permit pulsed operation by incorporating optical shutter , acousto - optical modulators 507 to facilitate a delivery of short laser pulses . the laser pulse duration , ( t d ), can be adjusted such that the ratio , ( t d / t r )≦ 1 , where t r is the thermal relaxation time . according to one exemplary exemplary embodiment of the present invention , a 100 μm region comprising of lipid - filled macrophages can be used , and t r may be approximately equal to 2 ms . pulsed laser systems which can permit shorter pulse durations (˜ 10 μs ) can provide for the targeting of single macrophages ( e . g ., t r = 20 μs ). this exemplary process can be monitored by a direct thermal visualization using an exemplary thermal camera or other measurement device 510 , or by another diagnostic imaging technique / procedure such as laser speckle imaging or optical frequency domain imaging . for example , as shown in fig5 b , a visible aiming beam from a helium - neon ( 632 nm ) source 540 can be utilized to coincide with a center of the collimated treatment laser beam , as shown in fig5 . laser speckle can be recorded using , e . g ., a lens 515 and camera 510 . a temporal modulation of the speckle pattern may be correlated to the temperature of the tissue 520 undergoing an exemplary selective laser ablation . an exemplary identification of an appropriate wavelengths and exposure times for selective laser ablation can be determined using , e . g ., cell culture experiments . cell cultures can be conducted to evaluate laser induced thermal damage of lipid rich macrophages . macrophage cells can be cultured in 75 ml flasks with dmem , 0 . 1 m hepes , 1 % penicillin streptomycin and 10 % fetal calf serum , and incubated at 10 % co 2 . the cells can be cultured until they reach confluence and then scraped off the flasks with cell scrapers . the cells can be cultured with a 1 in 10 dilution in fresh medium to prevent macrophage activation . the cells can be counted with a hemocytometer and transferred to ten 6 well culture plates . for example , in five plates , low density lipoprotein labeled with fitc ( e . g ., molecular probes , eugene , oreg .) can be added followed by incubation for , e . g ., up to 4 days . the uptake of fluorescently - labeled ldl by macrophages can be assessed by fluorescence microscopy . it is possible to utilize , e . g ., two control cell populations for the review : a ) macrophages not be incubated with ldl , and b ) human coronary smooth muscle cell lines ( hcasmc - c ) can be grown in culture and not incubated with ldl . the macrophage and control cell culture plates can be exposed to laser irradiation using the pulsed laser ablation system described above . laser therapy can be conducted by scanning a focused laser beam or illuminating a large area using a collimated laser beam . the laser pulse duration and number of pulses can be varied to evaluate the influence of these parameters on laser induced cell necrosis . after the exemplary laser treatment , cell viability assays ( such as propiodine iodide ) can be used to evaluate cell death following thermal damage . the cells can be assessed using microscopy and the percentage of cell death can be quantified by cell counting using a flow cytometer . the percentage of cell death in the ldl ingested macrophage population can be compared with the control cell populations . the correlation of percent cell death with laser exposure parameters may be evaluated using the regression analysis . freshly harvested samples of human carotid , coronary , iliac and aortic arteries obtained at autopsy can be used to evaluate the cell specificity of thermal confinement . the specimens can be opened longitudinally and pinned to expose the luminal side . the tissue specimens can be then irradiated using the pulsed laser ablation system described above . the laser pulse duration and number of pulses can be varied to evaluate the influence of these parameters on thermal confinement within macrophage rich regions in atherosclerotic plaques . following treatment laser exposure , the specimens can then be grossly sectioned and prepared for histological processing . the specimes can be stained using hematoxylin eosin , and cd68 for macrophages . nitro blue tetrazolium chloride ( nbtc ) staining can be used to assess the extent of thermal damage . nbtc stains positive for lactate dehydrogenase ( ldh ), which is a thermolabile enzyme . a loss of ldh activity ensues rapidly upon heat induced cell damage and is correlated with cell lethality . ( see m . h . khan et al ., “ intradermally focused infrared laser pulses : thermal effects at defined tissue depths ,” lasers surg med . 2005 ; 36 , pp . 270 - 280 ). the region of the border between unstained and stained tissue can be morphometrically measured to evaluate the area of thermal damage . the cd68 stained sections can be co - registered with nbtc stained sections to evaluate cell specificity of laser treatment . a metric for cell specificity of necrosis can be estimated by measuring the ratio between the areas of cd 68 staining to loss of ldh staining . the correlation of the cell specificity metric with laser pulse duration and number of pulses can be determined . the optimum laser parameters that achieve a cell specificity metric close to unity can be determined . thus , the optimal treatment laser parameters for subsequent development of an intracoronary real - time screening and therapy device can be determined that may identify macrophage - rich regions and selectively destroy them with laser energy . this exemplary development can fill the needed gap between the detection of unstable plaque and local therapy of these lesions . such exemplary embodiments may furthermore provide the foundation for cell specific laser therapy in a variety of other diseases , where endogenous absorbers can be targeted to effect selective damage of the abnormal cells while maintaining the viability of surrounding normal cells . another exemplary embodiment of the system and method according to the present invention can include the administration of exogenous metal or noble metal nanoparticles via subcutaneous , oral or intravenous arrangement . the nanoparticles of appropriate size , e . g ., preferably & lt ; about 5 nm , may penetrate the vascular endothelium and can be taken up by macrophages resident in the tissue of interest . these nanoparticles can be capable of then being irradiated by light . direct absorption or surface plasmon resonance associated with these nanoparticles , can cause local and specific heating that will thermally damage the cells containing the nanoparticles . according to yet another exemplary embodiment of the present invention , these nanoparticles may be imaged by techniques including but not limited to those mentioned in this document , in such a manner as to determine the appropriate locations for administration of selective laser therapy light . still another exemplary exemplary embodiment of the system and method according to the present invention can be provided for image - guided cell - specific laser therapy . in these exemplary system and method , high - resolution volumetric screening of tissue can be conducted using imaging techniques such as optical frequency domain imaging ( ofdi ) to detect tissue macrophages and enable simultaneous guidance of therapeutic laser irradiation to induce macrophage cell death by probing exogenous chromophores phagocytosed by macrophages . the exemplary ofdi techniques , systems and procedures can be used for comprehensive volumetric screening of tissue which enables the identification of tissue macrophages in situ . ( see , e . g ., b . d . macneill et al ., “ focal and multi - focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease ,” j am coll cardiol . 2004 ; 44 , pp . 972 - 9 . exemplary system , catheter and method according to the present invention can be provided for simultaneous macrophage detection and delivery of therapeutic laser energy . exogenous chromophores administered can include nobel metal nanoparticles , biodegradable nanoparticles or iron oxide microparticles to cause laser induced thermal confinement within macrophages while maintaining the health of the surrounding tissue . an exemplary emboidment of a laser treatment system and method can be provided that may utilize a laser source configured with an acouto - optic modulator to permit pulsed operation to enable thermal confinement . the wavelength of the light source can be provided depending on the chromophore under investigation . macrophage cells ( j774 cell line ) may be cultured in 75 ml flasks using a growth medium . to mimic plaque macrophages , the cultured cells can be separately incubated for , e . g ., up to four days with fluorescently labeled low density lipoprotein ( ldl ) ( e . g ., molecular probes , eugene , oreg .). the uptake of ldl may be evaluated using fluorescence microscopy . as for endogenous selective cell therapy , the proper exposure and power preferences for effecting cell damage may determined using cell culture studies . a population of ldl ingested macrophages will be separately incubated with nobel metal nanoparticles , biodegradable nanoparticles or iron oxide microparticles tuned to the treatment laser wavelength . for example , two control cell populations can be used : i ) macrophages that would not be incubated with ldl or exogenous chromophores , and ii ) human coronary smooth muscle cell lines ( hcasmc - c ) may be grown in culture and not incubated with ldl or nanoparticles . most or all culture plates can be exposed to laser irradiation and the percentage of cell death may be quantified using propidium iodide assays . the laser pulse duration , incident power and number of pulses will be varied to evaluate the influence of these parameters on laser induced cell death in all cell populations . animal studies may also be utilized to determine biodistribution of nanoparticles as well as proper exposure and power parameters for cell specific laser therapy . according to one exemplary embodiment of the present invention , it may be preferable to determine the distribution of gold , silver and uspio nanoparticles in hyperlipidemic animal atherosclerotic plaques . for example , each of the three nanoparticles , gold , silver and uspios can be tested independently using a similar study design . this can be done for each nanoparticle by a daily intravenous administration of the agent to , e . g ., 15 watanabe heritable hyperlipidemic ( whhl ) rabbits ( see p . m . mccabe et al . “ social environment influences the progression of atherosclerosis in the watanabe heritable hyperlipidemic rabbit ,” circulation , 2002 ; 105 , pp . 354 - 9 ; s . ojio et al . “ considerable time from the onset of plaque rupture and / or thrombi until the onset of acute myocardial infarction in humans : coronary angiographic findings within 1 week before the onset of infarction ,” circulation , 2000 ; 102 , pp . 2063 - 9 ; and k . yokoya et al . “ process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis : a study based on four serial coronary arteriograms per year ,” circulation , 1999 ; 100 , pp . 903 - 9 ), which may develop active aortic plaques at 6 months of age , and to 5 new zealand white ( nzw ) rabbit that will act as a control for each agent . five additional whhl rabbits can be investigated without the administration of any agent to provide diseased controls for each group . for example , most or all rabbits can be approximately one - year - old . nanoparticle agents may be administered daily for up to 5 days through auricular veins during sedation with isoflurane ( 1 %), at doses of 1 - 2 mg / kg . whhl rabbits receiving nanoparticle agents will be euthanized on days 2 , 3 , and 4 ( 3 rabbits per time point ). the control rabbits can be euthanized on day 4 . perfusion fixation will be performed prior to aortic harvest . serial histological sections will be cut at 5 microns and stained with hematoxylin - eosin , masson &# 39 ; s trichrome , cd 68 immunoperoxidase and prussian blue . the patterns of nanoparticle distribution may be correlated with histological determinants of plaque vulnerability , namely lipid core and cap 100 thickness . further , 2 mm sections of each aortic specimen will be subjected to electron microscopic evaluation to determine precisely the intracellular site and ultrastructural morphology and intracellular distribution of nanoparticle deposition . according to another exemplary embodiment of the present invention , it may be preferable to measure the optical signature associated with nanoparticle uptake in hyperlipidemic animal atherosclerotic plaques . for example , after euthanization and prior to perfusion fixation of the rabbit aortas described above , optical coherence tomography ( oct ) technique ( s ) and angioscopic imaging may be conducted using automatic pullback at a rate of 0 . 5 mm / second from the iliac artery to the aortic arch . the aortas may then be opened and reflectance confocal microscopy will be conducted along the length of each vessel . for each agent and time point , images obtained from the treated rabbits can be morphometrically and spectroscopically compared to images acquired from the control rabbits . a quantitative analysis of signal intensities in regions of interest within the plaque , including the cap shoulder , the body of the cap and the lipid rich core may be assessed to evaluate the quantitative distribution of each agent within atherosclerotic plaque . tissue locations with unique optical signatures relative to control rabbit measurements will be selectively taken and processed for histology and electron microscopy . according to still another exemplary embodiment of the present invention , it may be preferable to demonstrate a quantification of nanoparticle - labeled macrophages in vivo . the nanoparticle metal achieving the greatest optical contrast can be administered to 10 whhl rabbits ( 1 - year - old ) at a dose of 2 mg / kg . for example , five additional whhl rabbits not receiving the nanoparticle agent may be used as controls . on the optimal day following nanoparticle administration ( determined as provided above ), exemplary oct imaging technique can be performed and the rabbits may be sacrificed . for example , im injection of ketamine ( 35 mg / kg )/ xylazine ( 7 mg / kg ) can be administered with local anesthesia ( lidocaine ) in the inguinal region . a continuous assessment of the rabbits response to corneal and jaw reflexes will be used to monitor the level of anesthesia . the left iliac artery may be exposed and isolated via a cutdown procedure . a 6f introducer may be placed in the left iliac artery . a 0 . 014 ″ guidewire can be advanced into the aorta . under fluoroscopic guidance , the oct catheter ( 3f ) may be advanced through the introducer , over the guidewire and into the aorta . the exemplary oct imaging of the aorta and iliac arteries may be performed using anatomic landmarks for image registration . after imaging , the animals may be sacrificed . histologic sections can be taken from plaques adjacent to the anatomic landmarks identified while imaging with oct under fluoroscopic guidance . the tissue can be processed in a routine fashion . four - micron sections may be cut at the oct imaging sites and stained with hematoxylin and eosin ( h & amp ; e ) and masson &# 39 ; s trichrome . to visualize the presence of macrophages , a mouse - antirabbit cd68 monoclonal antibody may be used ( dako corporation ). immunohistochemical detection of the preferred epitopes can be performed according to the indirect horseradish peroxidase technique . using both digitized histology and oct techniques , measurements of macrophage density may be obtained using a 500 × 125 μm ( lateral × axial ) region of interest ( roi ), located in the center of each plaque . the area percentage of cd68 + staining can be quantified ( at 100 × magnification ) using automatic bimodal color segmentation within the corresponding roi &# 39 ; s of the digitized immunohistochemically stained slides . the oct signal intensity and standard deviation within each plaque may then be compared with immunohistochemical staining from slides obtained from corresponding locations using linear regression . cell specific laser therapy may be conducted as a standalone technique / procedure or in conjunction with imaging or spectroscopic techniques / procedures for diagnosis for target atherosclerotic plaques and guidance of therapy . techniques such as laser speckle imaging ( e . g ., as shown in fig5 ), angioscopy , fluorescence , fluorescence spectroscopy , time - resolved fluorescence , oct , ofdi , sdoct , raman or ir spectroscopy , ivus , intra - vascular mri etc may be used to detect culprit plaques and guide cell specific laser therapy . one exemplary embodiment for image - guided cell specific therapy involves the use of oct and / or next generation oct methods such as ofdi or spectral - domain oct ( sd - oct ) for detection of macrophage rich plaques to target therapy . this exemplary embodiment can include a design for a standalone approach for comprehensive cell specific laser therapy without the use of image guidance ( fig6 ). in this exemplary embodiment , light from the pulsed laser source can be coupled to the proximal end of an optical fiber 600 . the optical fiber can be housed in an outer sheath 615 . the fiber can be terminated by beam focusing and / or beam redirecting optics 605 to direct and focus the light 610 at a pre - determined location on the artery wall . laser light at the distal end can be collimated or focused by a lens , which can be a micro - lens , grin lens or the like . the fiber can be configured to scan the beam in at least one of a rotational 616 or longitudinal 617 or another direction along the vessel wall 620 . for this embodiment , therapy can be conducted with flushing the vessel lumen 618 in order to maintain good beam quality and avoid scattering and absorption of therapy light by blood . in another exemplary embodiment as shown in fig7 , the therapy fiber 700 can be configured to contact or be near contact to the vessel wall 710 . the fiber can be scanned in at least one of a rotational 716 or longitudinal 717 or other direction to treat a segment of the artery . in still another exemplary embodiment illustrated in fig8 , the therapy fiber can reside within a balloon 818 . the balloon 818 can be inflated in the area of the vessel wall 820 requiring treatment , and the fiber 800 can scan in at least one of a rotational direction 816 , longitudinal direction 817 or another direction to treat the area of interest . according to a further exemplary embodiment of the present invention as shown in fig9 , the light 910 associated with a target chromophore can be diffused over a large area of the artery wall 920 using a balloon , diffusing optic 905 or the like . even though the specificity of the chromophore may allow selective destruction of the cells of interest , if the absorption coefficient differential between target and surrounding tissue is not large enough , collateral damage at the surface of the tissue may occur , resulting in damaged endothelium . in order to avoid this possibly untoward effect , the surface of the endothelium may be cooled by use of cooled saline , water , d 2 o , blood or other cooled liquid during the therapy laser irradiation . this procedure can maintain viability of endothelium while safely applying cell - specific laser irradiation deeper into the vessel wall . therefore , the catheter can be associated with a mechanism for flushing the vessel with coolant . in one exemplary embodiment of the present invention , this mechanism can include a guide catheter that may contain the therapy catheter therein . in another exemplary embodiment , the therapy catheter may contain a flushing port . in still another embodiment , the catheter can contain a balloon , which may be filled with said coolant . this exemplary embodiment of the present invention can include a probe design for comprehensive volumetric diagnosis and screening for target atherosclerotic plaque and simultaneous cell specific laser therapy of macrophages in atherosclerotic plaques , as shown in fig1 . the exemplary probe 1000 illustrated in fig1 can be configured to scan across the luminal surface of the artery in at least one of an axial direction 1003 , a radial direction 1005 or another direction . therapeutic laser light 1015 and optical diagnostic arrangement 1010 ( e . g ., laser speckle imaging , angioscopy , oct , ofdi , sdoct , raman or ir spectroscopy , fluorescence , fluorescence spectroscopy , time - resolved fluorescence arrangement ) beams can be delivered through the same or separate optical fibers . for distinct diagnosis and therapy fibers , each optical fiber may have its own distal optics to produce its own optical diagnosis and therapy beam diameters on the target tissue . in one embodiment , the optical fibers and distal optics are housed in a drive shaft and placed inside a catheter sheath 1020 . the proximal end of the catheter may be coupled to a rotary junction and mounted on a motorized pull back unit . rotation of the inner components of the catheter and pullback will enable simultaneous diagnosis and therapy . in another exemplary embodiment of the present invention , the diagnosis and therapy catheters can be configured to be in contact with the artery wall 1025 . the fibers can be scanned along the endothelium to diagnose and provide cell - specific therapy at the contact point . certain exemplary embodiments for cell specific therapy methods according to the present invention are described below and shown in exemplary flow diagrams of fig1 - 13 . for example , fig1 shows an exemplary flow diagram of an exemplary embodiment of an endogenous therapy method according to the present invention , whereby the catheter can be started ( step 1100 ) and inserted in to an artery ( step 1105 ) and laser irradiation with appropriate wavelength , exposure parameters , and power density may be directed into the artery ( step 1110 ). the wavelength may be selected to obtain a large differential absorption between plaque macrophages and surrounding tissues . the exposure and power parameters can be selected to affect thermal confinement to these cells . blood may or may not be removed prior to laser irradiation . the artery is exposed by the light for a pre - determined time . the catheter may move in at least one of a circumferential , longitudinal or other direction ( step 1115 ) to scan the entire treatment area . alternatively or in addition , the light may diffuse throughout the artery without beam scanning . in step 1120 , it may be determined whether the exemplary procedure is completed , and if not , the procedure may be repeated ( step 1122 ). fig1 depicts a flow diagram of an exemplary embodiment of an exogenous therapy method according to the present invention , whereby the procedure is started in step 1200 , and an exogenous substance such as noble metal nanoparticles may be administered to the patient ( step 1205 ). following an appropriate time period ( step 1210 ), the catheter is inserted into an artery ( step 1215 ), and laser irradiation with appropriate wavelength , exposure parameters , and power density may be directed into the artery ( step 1225 ). the wavelength is selected to obtain a large differential absorption between plaque macrophages and surrounding tissues . the exposure and power parameters are selected to affect thermal confinement to these cells . blood may or may not be removed prior to the laser irradiation . the artery is exposed to therapy light for a pre - determined time . the catheter may move in at least one of a circumferential , longitudinal or other direction ( step 1230 ) to scan the entire treatment area . alternatively or in addition , the therapy light may be diffused throughout the artery without scanning . the procedure may be repeated ( step 1232 ). fig1 shows a flow diagram of an exemplary embodiment of a general cell specific therapy method according to the present invention that may utilize image guidance to determine the target location for therapy and or determine when the therapy has completed . this exemplary method can be implemented for endogenous absorbers ( e . g ., without elements provided in box 1307 ) or exogenous absorbers ( e . g ., with elements provided in box 1307 ). the procedure may be started in step 1300 , the exogenous agent can be administered in step 1305 , and then it is possible to wait ( step 1310 ). the catheter may be inserted into an artery ( step 1315 ) and information can be retrieved from the artery wall to determine if therapeutic laser irradiation should be deployed ( step 1320 ). at appropriate exemplary locations , e . g ., determined by an exemplary diagnostic method , the light irradiates the wall with appropriate wavelength , exposure parameters , and power density ( step 1325 ). the exposure and power parameters are selected to affect thermal confinement to these cells . the artery may be exposed to therapy light for a pre - determined time or a time determined by feedback to the same or another exemplary diagnostic method ( step 1330 ). the catheter may move in at least one of a circumferential , longitudinal or other direction to scan the entire treatment area ( step 1335 ). the procedure may be repeated ( step 1332 ). 1 . chambers a f , naumov g n , varghese h j , nadkarni k v , macdonald i c , groom a c . critical steps in hematogenous metastasis : an overview . surg oncol clin n am . 2001 ; 10 : 243 - 55 , vii . 2 . chambers a f . the metastatic process : basic research and clinical implications . oncol res . 1999 ; 11 : 161 - 8 . 3 . tabas i . consequences and therapeutic implications of macrophage apoptosis in atherosclerosis : the importance of lesion stage and phagocytic efficiency . arterioscler thromb vasc biol . 2005 ; 25 : 2255 - 64 . 4 . brinkmann r , huttmann g , rogener j , roider j , birngruber r , lin c p . origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen . lasers surg med . 2000 ; 27 : 451 - 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