Apparatus, method, and computer-accessible medium for in situ three-dimensional reconstruction of luminal structures

Abstract

To provide apparatus and methods, including embodiments of instrumentation, probes, and algorithms, for measuring the three-dimensional shape of a luminal structure, including in vivo.SOLUTION: An apparatus for determining a shape of a luminal sample includes: a catheter disposed within a strain-sensing sheath 140 such that a lens rotates and translates; a structural imaging system 110 and a strain-sensing system 120 that are optically coupled to the catheter; and a controller coupled to the strain-sensing system and the structural imaging system. The controller determines: a first position of the catheter relative to the luminal sample at a first location within the strain-sensing sheath; a second position of the catheter relative to the luminal sample at a second location within the strain-sensing sheath; a first strain of the strain-sensing sheath at the first location; a second strain of the strain-sensing sheath at the second location; a local curvature of the luminal sample relative to the catheter; a local curvature of the catheter; and a local curvature of the luminal sample.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 475,304, entitled "Apparatus, Method, and Computer-Accessible Medium for In Situ Three-Dimensional Reconstruction of Luminal Structures," filed March 23, 2017, which is incorporated herein by reference in its entirety. [Background technology]

[0002] The present disclosure relates to three-dimensional imaging and reconstruction, and more particularly to exemplary embodiments of apparatus, methods, and computer-accessible media for imaging cylindrical structures, and more particularly for imaging luminal structures, such as the vasculature and digestive tract of the human body.

[0003] Faithful three-dimensional (3D) reconstruction is a desirable feature for several applications, such as measuring endothelial shear stress (ESS) to diagnose the progression of coronary artery disease or sleep apnea in the airway lumen. The 3D anatomical structure of the airway has been successfully reconstructed using magnetic sensors. However, due to the large size of magnetic sensor catheters, cardiologists have had to rely on biplane angiography images to reconstruct the 3D shape of coronary arteries. Intravascular ultrasound (IVUS) imaging and biplane angiography have been applied in several studies to calculate ESS, but the repeated use of angiography is often undesirable due to complications such as the ionizing potential of the X-rays used in this process. Furthermore, ESS measurements are obtained through labor-intensive and time-consuming post-processing procedures, making them unsuitable for online applications. Another approach to determining the 3D shape of arteries is proposed: using a shape-sensing catheter employing optical frequency-domain reflectometry (OFDR) with either multiple fibers or a single fiber with multiple cores containing a distributed fiber Bragg grating. This technique requires an additional optical fiber, which increases the diameter of the catheter and makes the rotary joint and imaging system more complex.

[0004] There is a need to find alternative minimally invasive techniques with high-resolution imaging and 3D reconstruction capabilities. Summary of the Invention

[0005] Optical coherence tomography (OCT) has emerged as a new imaging modality, providing images similar to IVUS but with much higher resolution. When applied to luminal structures, OCT captures high-resolution images of the surface and luminal substructure. However, OCT does not provide the overall three-dimensional shape of the lumen, so an alternative methodology is desired that can provide accurate 3D shape reconstruction information and provide high-resolution OCT images of the lumen and microstructure. Carbon nanotube-based composite coatings have recently been used to measure material strain. Therefore, by measuring local strain-induced spectroscopic information from carbon nanotube-based strain sensors, this technique can be applied to measure 3D shape, and relatedly, the curvature of the sheath typically used to house OCT catheters during intraluminal imaging. Strain-sensitive OCT is employed in various embodiments disclosed herein, avoiding the time-consuming process of registering angiograms with intravascular imaging data while also measuring their own shape.

[0006] This invention describes a dual-channel (e.g., OCT plus strain measurement) system that can measure 3D luminal geometry while acquiring high-resolution cross-sectional images. This method can be applied to obtain the 3D geometry of luminal or tubular structures, including but not limited to coronary arteries, other blood vessels, or endoluminal organs, including but not limited to lymphatic vessels, esophagus, ducts, intestines, ureters, pulmonary airways, and the pharynx, or non-biological tubular structures, such as pipes, ducts, and tunnels. Additionally, structural information may be obtained by imaging modalities other than OCT (e.g., polarization-sensitive OCT, 1 micron high-resolution OCT, various embodiments of OCT such as ultrasound, intravascular ultrasound (IVUS), photoacoustic ultrasound, etc.), including stereo imaging, imaging from motion or blur, computed tomography, radiography, projection tomography, magnetic resonance imaging, etc. Systems and concepts of this work are disclosed herein.

[0007] Accordingly, in one aspect, the present invention provides an apparatus comprising: at least one optical waveguide that emits electromagnetic radiation; a scanning arrangement that rotates and / or translates to guide the electromagnetic radiation; a strain-sensing sheath that at least partially surrounds the at least one optical waveguide and the scanning arrangement and comprises a strain-sensing system optically coupled to the at least one waveguide; and a controller coupled to the strain-sensing system. The controller uses the strain-sensing system to determine a first strain in the strain-sensing sheath at a first location and a second strain in the strain-sensing sheath at a second location different from the first location. The controller further determines a curvature of the sheath between the first and second locations based on determining the first and second strains in the strain-sensing sheath.

[0008] In another aspect, the present invention provides an apparatus including a catheter including a lens, a strain-sensing system, and a controller. The catheter is disposed within the strain-sensing sheath such that the lens rotates and translates within the strain-sensing sheath. The strain-sensing system is optically coupled to the catheter. The controller is connected to the strain-sensing system. The controller uses the strain-sensing system to determine a first strain in the strain-sensing sheath at a first location and a second strain in the strain-sensing sheath at a second location different from the first location. The controller further determines a curvature of the catheter between the first and second locations based on determining the first and second strains in the strain-sensing sheath.

[0009] In yet another aspect, the present invention provides a method comprising providing a catheter optically coupled to a strain sensing system, including a lens, and positioned within the strain sensing sheath such that the lens rotates and translates within the strain sensing sheath; determining, with a controller in communication with the strain sensing system, a first strain of the strain sensing sheath in the xz plane and the yz plane at a first location within the strain sensing sheath, determining a second strain of the strain sensing sheath in the xz plane and the yz plane at a second location within the strain sensing sheath that is different from the first location, and determining a curvature of the catheter between the first location and the second location based on the determination of the first strain and the second strain of the strain sensing sheath.

[0010] In yet another aspect, the present invention provides an apparatus for determining a shape of a luminal sample, the apparatus comprising: a lens; a catheter disposed within the strain-sensing sheath such that the lens rotates and translates within the strain-sensing sheath; a structural imaging system optically coupled to the catheter; a strain-sensing system optically coupled to the catheter; and a controller coupled to the strain-sensing system and the structural imaging system, wherein the controller uses the structural imaging system to determine a first position of the catheter relative to the luminal sample at a first location within the strain-sensing sheath and to determine a second position of the catheter relative to the luminal sample at a second location within the strain-sensing sheath that is different from the first position. The controller uses the strain sensing system to determine a first strain of the strain sensing sheath at a first location, determine a second strain of the strain sensing sheath at a second location, and further determine a first local curvature of the lumen sample relative to the catheter between the first and second locations based on determining a first and second position of the catheter relative to the lumen sample, determine a second local curvature of the catheter between the first and second locations based on determining the first and second strains of the strain sensing sheath, and determine a third local curvature of the lumen sample between the first and second locations based on determining the first and second local curvatures.

[0011] In yet another aspect, the invention provides a method for determining a shape of a lumen sample, the method including providing a catheter optically coupled to a structural imaging system and a strain sensing system, the catheter including a lens and positioned within the strain sensing sheath such that the lens rotates and translates within the strain sensing sheath, and a controller coupled to the strain sensing system and the structural imaging system determines a first position of the catheter relative to the lumen sample at a first location within the strain sensing sheath, determines a second position of the catheter relative to the lumen sample at a second location within the strain sensing sheath different from the first location, determines a first strain of the strain sensing sheath at the first location, determines a second strain of the strain sensing sheath at the second location, determines a first local curvature of the lumen sample relative to the catheter between the first and second locations based on the determination of the first and second strains of the strain sensing sheath, and determines a third local curvature of the lumen sample between the first and second locations based on the determination of the first and second local curvatures.

[0012] The foregoing and other aspects and advantages of the present invention will become apparent from the following description, in which reference is made to the accompanying drawings, which form a part hereof and which show, by way of illustration, preferred embodiments of the invention. Such embodiments do not necessarily represent the full scope of the invention, and reference is therefore made to the claims herein for interpreting the scope of the invention.

[0013] Further objects, features, and advantages of the present disclosure will become apparent from the following detailed description, taken in conjunction with the accompanying drawings illustrating exemplary embodiments of the present disclosure. [Brief explanation of the drawings]

[0014] [Figure 1] 1 is a schematic block diagram of an exemplary embodiment of an apparatus used to reconstruct the 3D shape of a luminal structure. [Figure 2A]FIG. 1 is a schematic diagram of an exemplary embodiment of an optical strain-sensing probe using a single sheath, showing strain-sensing molecules attached to the outer sheath wall. [Figure 2B] FIG. 1 illustrates strain-sensing molecules attached to the inner sheath wall. [Figure 2C] FIG. 1 shows strain-sensing molecules embedded within the sheath wall. [Figure 2D] FIG. 1 shows an optical strain sensing probe with a guide wire. [Figure 3] FIG. 1 is a schematic diagram of a strain-sensing optical probe with a molecular strain sensor embedded in the exterior of an inner sheath inside an outer sheath. [Figure 4A-B] FIG. 1 is a schematic diagram of a strain-sensing optical probe in which molecular strain sensors are embedded as thin wires placed outside a sheath. [Figure 5] FIG. 1 shows an exemplary emission spectrum obtained from a straight, undistorted coronary catheter whose exterior surface is coated with SWCNTs. [Figure 6] FIG. 10 depicts data on wavelength shifts in the emission spectra of single-walled carbon nanotubes embedded in a polyurethane-coated intracoronary catheter sheath sampled in-plane and perpendicular to the plane of a 45° bend. [Figure 7] FIG. 10 illustrates a strain-sensing sheath with bends in which light is collected at 0°, 90°, 180°, and 270°. [Figure 8A-C] 10 is a series of graphs of peak frequency versus frame number as a function of pullback position and rotation angle. [Figure 9] 1 is a block diagram of an exemplary embodiment of an apparatus for reconstructing the 3D shape of a luminal object, such as a blood vessel, in accordance with the present disclosure. [Figure 10] FIG. 1 is a schematic diagram of an exemplary process for reconstructing the three-dimensional shape of a luminal object from a combination of OCT and spectroscopic data acquired at known pullback positions and rotation angles. [Figure 11]FIG. 1 is a schematic diagram of the RT-ESS catheter and imaging console, where ECG: electrocardiogram, DCF: double-clad fiber, CFO: computational fluid dynamics, HCT: hematocrit, ESS: endothelial shear stress, OCT: optical coherence tomography, NIRF: near-infrared fluorescence, SWCNT: single-walled carbon nanotubes, Fluor: fluorescence. [Figure 12A] FIG. 10 shows the fluorescence spectra of (7,5) and (7,6) SWCNTs on a catheter sheath at curvatures of 0 (solid line) and 0.08 mm (dotted line) showing the blue and red wavelength shifts induced by compressive strain. [Figure 12B] FIG. 13 shows a scatter plot of (7,5) and (7,6) peak separation versus sheath curvature. [Figure 13A] Figure 1 shows the 3D shape of the human right coronary artery lumen 3D printed to create a physical phantom. [Figure 13B] FIG. 1 shows a 3D image of a phantom reconstructed by a SWCNT catheter. [Figure 13C] FIG. 10 shows the centerline of the 3D reconstruction relative to the X, Y, and Z axes. [Figure 14] Schematic diagram of the RT-ESS console, where RJ: rotary junction, C: circulator, BS: beam splitter, WDM: wavelength division multiplexer, PC: power combiner, REF: reference arm, DB-PD: both balanced polarization diversities, ADC: analog-to-digital converter, CPU: central processing unit, GPU: graphical processing unit. [Figure 15] 1 is a flowchart of an exemplary process for determining the shape of a luminal sample. [Figure 16] 1 is a flowchart of an exemplary process for determining the shape of a catheter disposed within a sheath. DETAILED DESCRIPTION OF THE INVENTION

[0015] Thus, disclosed herein are devices and methods, including embodiments of instruments, probes, and algorithms, for measuring the three-dimensional geometry of luminal structures, including in vivo. Exemplary embodiments disclosed herein can be applied to intracoronary imaging and provide input to computational models that estimate endothelial shear stress on arterial walls. Nevertheless, the techniques and devices disclosed herein can be used to determine information about other luminal structures in addition to coronary vessels.

[0016] A particular feature of the present disclosure is that the three-dimensional geometry of luminal structures such as coronary arteries can be reconstructed using structural data obtained from a structural imaging system, such as an optical coherence tomography, and a fluorescent light-emitting strain-sensing system based on, for example, single-walled carbon nanotubes attached to a sheath. The present disclosure provides a method that can be embodied in a clinical device, an intracoronary catheter, and used to reconstruct the 3D geometry of a coronary artery (or other luminal structure) in real time, and further provides a real-time 3D coronary geometry computational fluid dynamics model that uses this input to estimate endothelial shear stress (ESS) in patients undergoing percutaneous coronary intervention in real time.

[0017] The diagnosis and treatment of coronary artery disease (CAD) are hindered by an inability to investigate the fundamental pathobiological processes that lead to the progression and destabilization of human coronary atherosclerotic plaques. A key mechanism responsible for plaque behavior is the local shear stress experienced by endothelial cells, which is governed by the vessel geometry and the resulting local pattern of blood flow. In areas of low shear stress, endothelial cells respond by increasing their permeability to protein complexes such as LDL, further initiating various proatherogenic, proinflammatory, and prothrombotic processes at the site. This low shear stress environment is what uniquely determines the pathobiological endothelial response and atherosclerotic plaque progression / destabilization.

[0018] Recently, a method for calculating the ESS of human coronary arteries in vivo has been developed. Reconstruction of the 3D anatomy of each coronary artery is performed by registering intracoronary optical coherence tomography (OCT) or intravascular ultrasound (IVUS) imaging data to specially acquired angiograms. 3D anatomical data from coronary arteries is input into computational fluid dynamics (CFD) models that calculate ESS at the luminal surface of the coronary arteries. These techniques are currently used in natural history clinical studies, with results showing that low ESS is the most powerful predictor of future coronary events. However, ESS cannot currently be acquired in real time in the cardiac catheterization laboratory because image data registration, 3D reconstruction, and CFD modeling are time-consuming and must be performed offline. These limitations mean that it can take several hours to calculate an ESS map for each artery in a given patient.

[0019] Thus, the disclosed methods and devices may help improve patient outcomes and guide personalized management of CAD by enabling real-time ESS (RT-ESS) measurements during routine cardiac catheterization. The simplicity, efficiency, and accuracy offered by the proposed RT-ESS technology greatly enhances the ability to use ESS information in research and clinical practice.

[0020] Accordingly, this disclosure describes the development of RT-ESS technology for clinical CAD patient management. Shape-sensing OCT-NIRF (near-infrared fluorescence) imaging catheters and automated image processing algorithms enable accurate and rapid reconstruction of coronary arteries without the need for angiography. In various embodiments, the inner surface of the RT-ESS catheter's sheath may be coated with single-walled carbon nanotubes (SWCNTs), which have a strain-dependent NIR fluorescence spectrum. As the catheter's optics are helically scanned, fluorescence spectra from the sheath are acquired and analyzed to provide the catheter's shape (centerline). OCT images of the arterial wall, acquired simultaneously with the fluorescence spectra, are automatically segmented and mapped to the catheter's centerline to provide a faithful 3D representation of the arterial lumen.

[0021] In various embodiments, the 3D arterial geometry can be used to generate a 3D mesh for CFD modeling. Patient-specific blood viscosity and artery-specific blood flow velocities can be used to perform flow simulations on the mesh via highly parallel CPU workstations running a pressure-based coupled parallel solver.

[0022] 1 is a schematic block diagram of an exemplary embodiment of a 3D shape sensing apparatus including a shape sensing probe according to the present disclosure. This exemplary device can include a structural imaging system 110 that generates images of the microstructure of a luminal object 160, a strain sensing system 120 that generates data from which the 3D shape of the luminal object 160 can be reconstructed, and a structural output. Provided are an imaging system output 115, a strain sensing system output 125, a dual-modality rotary junction unit 130, a strain sensing probe 135 with a sheath 140, a data acquisition system 145, and a data processing and storage unit 150. It will be understood that multiples of each of these described systems, arrangements, and elements can be included in and / or implemented with the exemplary apparatus.

[0023] The structural imaging system 110 is designed to collect back-reflected signals, which may be optical or mechanical in nature, from the luminal structure 160 to obtain information about the luminal surface and underlying microstructure. Exemplary structures are tissue, particularly coronary arteries. Depth-resolved microstructural images obtained from the structural imaging system 110 may include features associated with the luminal surface and subsurface as well as the probe sheath 140.

[0024] In an exemplary embodiment, the structural imaging system 110 performs optical coherence tomography (OCT) or other OCT-related modalities to generate depth-resolved microstructural images, including optical frequency domain imaging (OFDI), polarization-sensitive optical coherence tomography (ps-OCT), and other forms of high-resolution OCT, also known as μOCT, which use distal optical designs to extend the depth of focus while maintaining a sub-10 μm lateral spot size. Embodiments are included.

[0025] In another embodiment, the structural imaging system can perform intravascular ultrasound (IVUS) or photoacoustic ultrasound imaging to investigate tissue microstructure. Similar to OCT, both techniques produce transverse images that are automatically registered to strain measurements.

[0026] The strain sensing system 120 includes instruments and components that enable either fluorescence spectroscopy, Raman spectroscopy, or absorption spectroscopy. Local material strain is encoded in the central wavelength of a molecular spectrum. While the instrument is specific to the spectroscopic technique used, each spectroscopic technique generally requires a light source to interrogate the molecular signature, a dispersive element to separate the returning spectroscopic signal, such as a prism, grating, spectrometer, or spectrograph, and an optical detector to record the molecular signal. In another embodiment, the light source wavelength is scanned as a function of time, and similar information can be obtained by detecting the light spectroscopically without the need for a dispersive element in the detection path.

[0027] The structural imaging system 110 can be connected to the dual-modality rotary junction 130 via a single-mode fiber 115, while the strain-sensing system 120 can be connected with a double-clad fiber (DCF) 125 or a combination of single-mode and / or multimode fiber. The dual-modality rotary junction 130 can combine two optical beams from different modalities and act as an interface between a stationary imaging platform and a helical-scanning (rotational and translational) probe 135. Combining and splitting the optical beams at the dual-modality rotary junction can be achieved using a dichroic mirror, beam splitter, or an arrangement of dispersive elements. A transparent strain-sensing sheath 140 can be used to protect the probe 135 and can include molecular strain sensors that report the local curvature of the strain-sensing sheath 140 during helical scanning of luminal structures. Light beams 155 from the structural imaging 110 and strain sensing 120 modalities are delivered by a double-clad fiber within the probe 135, allowing for the investigation of the sheath and microstructure of lumens, such as coronary arteries. An advantage of a DCF-based mechanically scanned OCT fluorescence catheter is that the double-clad fiber within the probe allows for simultaneous collection of co-localized and essentially co-registered OCT from the fluorescence from the lumen and the probe sheath at each scan location. Light reflected from the lumen wall and fluorescence emission from the sheath are collected by the optical probe and transmitted to the dual-modality rotary junction, where back-reflected structural (e.g., OCT) light is separated and transmitted back to the structural imaging system 110, and spectroscopic signals (i.e., from the strain sensing sheath 140) are transmitted back to the strain sensing system 120 for spectral analysis and detection. The resulting structural (e.g., OCT) and spectroscopic data are recorded by the data acquisition system 145, and these signals are analyzed and processed to reconstruct the three-dimensional shape of the luminal structure by the data processing and storage unit 150.

[0028] 2A-2D show exemplary schematic diagrams of several strain-sensing sheaths designed for side-viewing multi-modality optical probes. Figure 2A illustrates an embodiment of a strain-sensing sheath 200 in which strain-sensing molecules can be disposed on the outer sheath wall. The dual-modality optical probe includes an optical fiber 202 that transmits and receives broadband light from the structural imaging system 110 and excitation light from the strain sensing system 120. The distal end of the optical fiber is terminated with an optical system 204 that focuses and collects OCT and spectroscopy signals. The preferred optical fiber 202 used in this embodiment is a double-clad fiber (DCF). The double-clad fiber's structure incorporates a central core surrounded by inner and outer claddings. The core is designed to transmit single-mode light, while the inner cladding collects light similar to a multimode fiber. Structural imaging light (e.g., OCT) is transmitted and received through the single-mode core, excitation light is focused into either the core or the inner cladding of the DCF, and returning radiation is collected by the inner cladding. The double clad fiber 202 is threaded onto a torque transmitting drive shaft 206, and the assembly is then enclosed in a thin-walled flexible sheath 202 that conforms to the shape of the luminal structure. 2A, the molecular strain sensor 210 is applied to the exterior of the sheath 208, which is in direct contact with the luminal structure (e.g., tissue). The materials of the sheath 208 and external coating / strain sensor 210 are selected to be optically transparent to the broadband OCT light and spectroscopic signals. In a preferred spectroscopic embodiment (e.g., fluorescence), excitation light is focused by the distal optics 204, exciting the molecular strain sensor, which emits red-shifted light that is collected by the distal optics and directed by the optical fiber 202 to the rotary junction 130, which separates the optical signals and transmits them to the respective structural optics 110 and strain sensing 120 systems.

[0029] FIG. 2B shows an exemplary schematic diagram of another embodiment of a strain-sensing optical probe 220 in which a molecular sensor 210 is applied to the inner wall of a sheath 208. This is a preferred embodiment because the molecular sensor is isolated from the luminal surface by the sheath material, thereby avoiding direct contact with the lumen (e.g., tissue and bodily fluids). In an ideal case, the coating containing the molecular sensor is thin and supports free and uniform rotation of the drive shaft. FIG. 2C shows an exemplary schematic diagram of yet another embodiment of a strain-sensing optical probe 230 in which the molecular sensor is embedded in the sheath material during sheath extrusion. A second polymer, lacking the molecular sensor, is coextruded outside the inner strain-sensing polymer to isolate the lumen (e.g., tissue and bodily fluids) from direct exposure to the sensor. Referring to FIG. 2D, the disclosed embodiments (including those of FIGS. 2A-2C, 3, and 4A-4B) may include a guidewire feed 252 that includes a guidewire pathway (openings 254 and 256 for guidewire entry and exit). Additionally, the guidewire delivery 252 may include a radiopaque tip marker 258 to aid in locating the probe 200 within the subject, for example, using fluoroscopy. Furthermore, each embodiment (including those of FIGS. 2A-2C, 3, and 4A-4B) optionally includes a radiopaque lens marker 212, as shown in FIG. 2D, to aid in locating the probe 200 within the subject, for example, using fluoroscopy.

[0030] A second exemplary embodiment of a strain-sensing optical probe 300 is shown in Figure 3. In this embodiment, a smaller diameter second inner sheath 302 can be coated with strain-sensing molecules 210 and then threaded inside the larger outer sheath 208. The optical fiber / drive shaft assembly is then threaded into the smaller diameter sheath 302. This embodiment has the advantage of not changing the properties of the outer sheath 208.

[0031] Accurate reconstruction of the 3D shape of the luminal structure relies on uniform rotation and pullback of the drive shaft through the strain-sensing sheath. Non-uniform rotational distortion (NURD) can adversely affect 3D reconstruction. Compensation for NURD or torsion-induced fluorescence can be identified and corrected for by adding fiducial markers to the sheath that can be detected by both modalities. In a third exemplary embodiment of the strain-sensing sheath, strain-sensing molecules can be incorporated into thin threads or wires 402 embedded in the sheath, as shown in FIGS. 4A and 4B. FIG. 4A shows a side cross-sectional view, and FIG. 4B shows a cross-sectional end view of the optical probe 400. In this particular embodiment, four sensing wires 402 are embedded within the sheath at 90° radial angles to each other. In a preferred embodiment, wires coated with strain-sensing molecules can be embedded into the sheath 210 during the extrusion process. In another embodiment, the strain-sensing wires 402 can be attached to the exterior of the sheath 210 and sealed in place by a polymer oversheath or a thin coating of a curable polymer material. In various embodiments, fewer or more than four wires may be used. Typically, the wires are evenly spaced around the circumference of the sheath.

[0032] Molecular strain sensors are molecules or polymers whose electronic structure changes predictably in response to changes in strain when the host material is subjected to compression or elongation. An exemplary strain-sensing material is the single-walled carbon nanotube (SWCNT). SWCNTs are a class of nanoscale tubes composed entirely of covalently bonded carbon atoms. Each SWCNT contains a distinct structure characterized by a pair of integers (n,m) that specify the tube diameter and roll-up angle of the SWCNT. SWCNTs have a well-defined molecular structure. The physical structure of SWCNTs controls their electronic structure and, therefore, the spectral transitions they undergo. Axial stretching and compression of individual SWCNTs produces predictable changes in their electronic structure, which systematically perturbs the molecular structure and shifts the spectral transitions, resulting in shifts in the frequency (wavelength) of fluorescence, absorption, or Raman spectra when the nanotubes are strained. The literature has established that for SWCNTs with different elastic moduli (nm,3), the direction of strain-induced spectral shifts occurs in opposite directions. For example, in some embodiments, the peak emission wavelength shift in the fluorescence spectrum can be large enough to detect axial strains as low as 0.1%.

[0033] In an exemplary embodiment 200, as shown in Figure 2A, a coating 210 containing SWCNTs can be applied to the exterior of a coronary catheter sheath 208. The strain-sensing coating was prepared by dispersing single-walled nanotubes grown using the CoMoCAT process in a mixture of poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) and toluene. The solution was tip-sonicated at 1 W / ml for 30 minutes and then centrifuged for 30 minutes. The clear supernatant containing the isolated nanotubes was removed. According to literature, the solubility of nanotubes is low in almost all solvents. Due to the strong noncovalent interaction between PFO and SWCNTs, single-wrapped nanotubes with separated chiralities (7,5) and (7,6) were obtained. After centrifugation, the clear solution containing the concentrated (7,5) and (7,6) nanotubes was mixed 1:1 with a commercially available oil-based polyurethane (Minwax FastDrying SemiGloss Polyurethane). The exterior of a coronary catheter sheath 208 was dip-coated with a SWCNT polymer solution and cured. To optimize the fluorescent signal, multiple layers can be deposited along the 10 cm long distal segment. For this exemplary coating, the average coating thickness of 36 μm varied by only ±6 μm. Due to the thin coating, the catheter sheath flexibility was maintained within 5% as assessed by a standard gravity-induced deflection test.

[0034] Another exemplary method for achieving high concentrations of individually dispersed (7,5) and (7,6) nanotubes involves suspending the nanotubes in an aqueous solution of sodium dodecyl sulfate (SDS) and using sonication to achieve separation and purification of a single chirality. After sonication, the SWCNT suspension can be ultracentrifuged to remove aggregates, and the SWCNT solution can be subjected to multistage gel chromatography. This method can result in a nanotube concentration in solution of approximately 1 μg / ml, which is several orders of magnitude greater than that used in the examples disclosed herein. The concentrated nanotube solution can be mixed with a curable polymer coating according to embodiments 200, 220, and 230, or mixed with a polymer feedstock prior to extrusion according to embodiments 300 and 400.

[0035] Figure 5 shows an exemplary emission spectrum acquired from a straight, undistorted coronary catheter whose outer surface was coated with SWCNTs 200. Fluorescence excitation light at 660 nm was coupled into the optical core of a double-clad fiber 201 and focused onto the SWCNT-coated sheath by an angle-polished ball lens 202 positioned at the end of the dual-clad fiber. Fluorescence emission from the nanotubes was collected through the inner cladding of the same double-clad fiber 201 and focused into an optical spectrometer equipped with a linear InGaAs array detector. The emission spectrum was recorded in the 950-1170 nm range and shows two prominent peaks at approximately 1050 nm (515) and 1135 nm (520), attributed to emission from (7,5) and (7,6) nanotubes, respectively; the fitted portions of each peak are separated by horizontal tick marks. The peak emission wavelength can be precisely determined by fitting the individual emission peaks to a spectral line shape, such as a log-normal distribution 510, Gaussian, or other known linear function. Single or multiple functions may be required to represent the acquired line shape. Polynomial fitting can also be used to determine the peak emission wavelength. Spectral fitting allows for sub-pixel accuracy in determining small distortions. The wavelength can be determined.

[0036] Figure 6 shows exemplary emission spectra acquired from the strain-sensing sheath. Spectra were acquired every 90°, corresponding to the excitation beam being in the plane of the bend (0° and 180°) and orthogonal to the plane of the bend (90° and 270°) (see Figure 7). At the inward curvature (0°), compressive strain was induced in the sheath (nanotube), resulting in a shift in the spectral emissions from the (7,5) and (7,6) nanotubes to shorter (blue-shifted) and longer (red-shifted) wavelengths, respectively. At the outward curvature (180°), tensile strain was applied to the sheath, resulting in a shift in the spectral emissions of the (7,5) and (7,6) nanotubes in opposite directions. Spectra acquired at orthogonal out-of-plane angles (90° and 270°) were nearly identical, with no visible shift in emission wavelength.

[0037] Fluorescence spectra from the strain-sensitive sheath were acquired as the probe helically scanned the sheath, which followed a well-defined bending radius. The emission spectra were spectrally fitted to a linear function to determine the peak emission wavelength as a function of pullback position and rotation angle, as shown in the example data in Figures 8A and 8C. Frame number (labeled on the horizontal axis) is a function of pullback distance and rotation angle. Figures 8A and 8B show the extracted emission wavelengths for chiralities (7,5) and (7,6), respectively, while Figure 8C shows their difference (7,6)-(7,5). For the first 200 frames, the coronary catheter is relatively straight, with little rotational variation in the emission wavelength during the scan. Around frame 400, the catheter experiences a constant bending radius of 12 mm, and its peak wavelength cycles to generate a periodic function between maximum tensile and compressive strain. The curvature-dependent wavelength is obtained by averaging multiple cycles.

[0038] Calibration curves relating spectral shift to the chirality of a nanotube or nanotubes can be constructed by extracting the mean emission wavelength for either compressive or tensile strain as a function of curvature. Note that mathematical combination of chiralities can increase strain sensitivity, as strain-induced spectral shifts can act in opposite directions under the same stress, as observed for the difference between (7,6) and (7,5) emission wavelengths. Figure 12B (discussed below) shows a calibration curve mapping spectral shift (peak separation) to radius of curvature. As shown in Figure 12B and discussed further below, this relationship is linear and sensitive over the range of curvatures required to detect the 3D shape of the catheter.

[0039] Figure 9 is a schematic diagram of an exemplary embodiment of a 3D shape sensing system consisting of two subunits: (1) an optical frequency domain imaging (OFDI) engine for acquiring tissue microstructure images, and (2) a fluorescence engine for providing shape sensing capabilities. The OFDI system is built around an Axsun Technologies Swept Source Engine. The OCT Axsun engine includes a 100 kHz swept laser as well as high-speed data acquisition electronics optimized for OFDI data acquisition using an Ethernet interface. The swept-wavelength light from the Axsun laser is coupled into a single-mode (SM) fiber-based beam splitter (BS1), which directs 90% of the signal to the sample arm and 10% to the reference arm. After passing through a circulator (C), the sample arm light is combined with the fluorescence excitation beam using a wavelength-division multiplexer (WDM) unit. The combined excitation and OCT laser beams are coupled into a double-clad (DC) fiber coupler (FC) attached to a custom-fabricated rotary junction. A DC fiber catheter is attached to the rotating part of a rotary junction (RJ). At the end of the catheter, a ball lens is machined and polished to direct the optical signal to the sample. In one particular embodiment, the custom fiber catheter is placed inside a flexible transparent sheath. In a particular embodiment, strain sensing For example, the outside of the sheath is coated with carbon nanotubes for strain sensing, although in other embodiments the strain sensing material may have a different location (e.g., embedded in the sheath material or inside the sheath). During imaging, the catheter is rotated and the rotating catheter is pulled back into the sheath to generate a helical scan.

[0040] For OFDI imaging, the back-reflected light from the sample surface and reference surface is directed by the corresponding circulator (C) to the beam splitter (BS2), where these signals interfere with each other. The use of polarizing beam splitters (PBS1, PBS2) and a polarization controller (PC) after the beam splitter BS2 allows for the implementation of a polarization-diverse detection scheme, which avoids image artifacts that may arise from polarization changes induced by the rotating optical fiber inside the rotating catheter. Light from the polarization-maintaining (PM) fiber is detected using two balanced detectors consisting of four diode receivers. The digitized signal from the photodiodes is processed on a field-programmable gate array (FPGA) board, including wavelength remapping and Fourier transformation, to obtain depth-resolved OFDI signals (A-lines). The A-lines collected at each rotation of the optical beam are compressed into JPEG format by the Axsun engine and transferred via an Ethernet cable to a workstation for real-time circumferential display and data storage.

[0041] On the strain sensing side, the fluorescent signal from the carbon nanotubes is collected through the sheath of the catheter's DC fiber. After passing through the RJ, this signal is transmitted to a spectrometer by a fiber coupler. In one embodiment, the spectrometer includes an input slit, guiding optics, a grating, or a supercooled, low-noise, linear-response camera. The signal from the spectrometer is used to determine the strain within the sheath.

[0042] FIG. 10 illustrates a 3D reconstruction algorithm using one of the exemplary embodiments. In various embodiments, the complete 3D reconstruction is based on input from two channels: a structural optics (e.g., OFDI) imaging channel and a strain sensing channel. First, an image analysis algorithm is used to manually, semi-automatically, or automatically determine the position of the catheter relative to the arterial wall, detecting its position at two different locations, Z1 and Z2, in two different planes, xz and yz. These values are used to calculate the curvature of the catheter relative to the arterial wall. Furthermore, fluorescence data from the carbon nanotubes is used to calculate strain in the same planes (xz and yz) as the curvature calculated from the OFDI data, and the measured strain values are converted to curvature using calibration data. This process results in the curvature of the catheter itself in two planes. The actual curvature of the artery in different orthogonal planes can be calculated by adding the curvature of the catheter in these planes and the curvature of the artery relative to the catheter. Once the curvature of the artery in two planes is known, a 2D shape in the orthogonal plane is calculated. The 3D geometry can be generated from the geometry of two orthogonal planes using software such as the commercially available IVUSAngio tool.

[0043] The process of measuring ESS from these data is very time-consuming and requires unique catheterization lab processes and biomedical engineering expertise. To accurately reconstruct the artery in 3D, angiograms must be acquired using a biplane / isocentric configuration, which is impractical in most PCI labs. 3D reconstruction is cumbersome because the arterial centerline must be obtained from the angiogram, and the OCT or IVUS lumen must be segmented and the lumen centroid registered to the centerline. This disclosure provides a method and apparatus that circumvents the resource and time constraints of ESS calculation by providing a single device that can automatically and in real time determine the 3D structure of the arterial lumen, calculate detailed regional ESS patterns, and display them in conjunction with OCT anatomical characterization. This breaks down the barriers to ESS calculation, enabling real-time reconstruction in the catheterization lab. By providing a practical means of obtaining this measurement in real time or near real time, this advancement makes it possible, for the first time, to use ESS to guide coronary interventions to provide optimal CAD management at the point of care.

[0044] These data can be processed to automatically determine the 3D centerline of the catheter. Combined with automated lumen segmentation, this technique allows rapid mapping of the lumen contour to the catheter centerline to reconstruct an anatomically correct 3D representation of the coronary arteries.

[0045] Figure 11 shows a high-level schematic of an embodiment of the RT-ESS system and catheter. In some embodiments, the catheter may be identical to an existing clinical 2.6F intracoronary DCF-based OCT-NIRF catheter; in certain embodiments, the inner surface of the outer sheath may be functionalized with a thin layer of fluorescent SWCNTs, whose emission spectrum shifts when strained. OCT (1310 ± 50 nm) and SWCNT fluorescence excitation light (660 nm) can penetrate the core of the DCF within the multimodality catheter. Under radiographic guidance, the catheter can be advanced over a guidewire through the guiding catheter until its imaging tip is located distal to the target coronary artery location. A non-occlusive radiocontrast flush can be injected through the guiding catheter to expel blood from the arterial imaging field. Next, light from the focusing optics at the distal tip of the catheter is helically scanned through a high-speed DCF rotary junction (in one embodiment, the rotation speed is 800 kHz and the translation speed ranges from 10 to 20 cm / s) and can be gated to diastole in synchronization with real-time ECG. OCT light from the arterial wall returns through the core of the DCF. NIR SWCNT fluorescence (1000-1200 nm) from the entire catheter sheath can be simultaneously collected through the larger inner cladding of the DCF. OCT and fluorescence are separated within the RT-ESS console and individually detected and digitized. OCT images are automatically segmented to extract the lumen of each cross-section. Automatic processing of the peak shift in the SWCNT fluorescence spectrum determines the 3D centerline of the catheter. An anatomically correct 3D arterial model is then reconstructed by essentially locating the lumen on the centerline of the co-registered catheter. To calculate arterial-specific flow, a known amount of contrast agent can be injected through the guide catheter and another OCT scan can be acquired. The time between the OCT images of the leading and trailing edges of the bolus can be used to estimate blood flow. Blood viscosity can be determined from the patient's hematocrit (HCT). The 3D arterial model, blood flow, and blood viscosity can be input into a highly optimized parallel CFD simulation, the output of which can provide an ESS map.

[0046] In certain embodiments, OCT is employed as the intravascular anatomical imaging technique because it is the standard imaging technique for assessing plaque morphology and stent deployment adequacy in the catheterization laboratory. Furthermore, its high resolution and contrast provide the most accurate geometry and detailed ESS maps. Because OCT images are acquired with a non-occlusive radiocontrast flash, which removes blood from the field of view, these images are also highly amenable to automated analysis. Recent studies have shown that OCT measurements of plaque extent and free wall arc are highly correlated with IVUS measurements of plaque burden.

[0047] The fluorescence spectra of catheters coupled with strain-sensitive sheaths (prepared by applying SWCNTs to the sheath as described above) were measured at various curvatures to determine the relationship between curvature and SWCNT fluorescence peak separation, as shown in Figures 12A-12B. Fluorescence excitation light (660 nm) was coupled into the DCF core of the catheter and focused onto the coated sheath by an angle-polished ball lens at the end of the fiber. Fluorescence emission from the nanotubes was collected through the inner cladding of the DCF and detected by a spectrofluorometer. Figure 12A (solid line) shows the fluorescence spectra of (7,5) and (7,6) SWCNT coatings on a straight catheter. The fluorescence spectrum shows two NIR emission peaks at approximately 1050 nm and 1140 nm, respectively. The catheter was then bent and its optics oriented to collect in-plane fluorescence at the bend away from the inner curvature of the sheath. At this position, the nanotubes underwent compressive strain, broadening the fluorescence peaks and causing them to spectrally separate from each other (Figure 12A, dotted lines). An opposite shift occurred with tensile strain (not shown). The (7,5) and (7,6) peak separation was measured as a function of varying sheath curvature by fitting the individual peaks with Gaussian linear functions. As shown in Figure 12B, this relationship was linear and sensitive over the range of curvatures required to detect the 3D shape of the catheter. This data demonstrates that carbon nanotube fluorescence can be used to detect the curvature of an RT-ESS catheter.

[0048] SWCNT catheter-based shape sensing and 3D arterial reconstruction To test the principle of SWCNT catheter-based shape sensing for 3D reconstruction of coronary arteries, we connected the aforementioned catheter to an OCT-NIRF system via a DCF rotary junction and modified it with custom wavelength separation optics and NIR fluorescence spectral detection. The catheter was then inserted into a phantom of a coronary artery lumen, 3D printed using a lumen centerline from a human dataset (Figure 13A). The catheter's internal optics were helically scanned (1 mm / s pullback and 1 Hz rotation) along the phantom's lumen, simultaneously acquiring OCT A-lines and fluorescence spectra from the catheter sheath at all angles (θ) and lateral positions (z). The OCT dataset was processed by segmenting the lumen. The fluorescence spectra were fitted and peak separation was used to create curvature maps at each θ-z scan position. The catheter curvature map was converted to a 3D catheter centerline by solving a modified Frenet-Serret equation. The OCT lumen in each frame was then superimposed on the catheter centerline, converted to a 3D mesh, and rendered (Figure 13B). The 3D centerline of the lumen of the phantom artery measured using the SWCNT catheter (Figure 13B) correlated well with the phantom artery with a Pearson correlation coefficient (PCC) of 0.84. The calculated centerline of the coronary artery was approximately consistent with the known 3D centerline of the coronary artery. Figure 13C shows the centerline of the 3D reconstruction relative to the X, Y, and Z axes. This data demonstrates that the 3D shape of the coronary artery can be measured automatically and accurately using OCT-NIRF and the SWCNT catheter.

[0049] SWCNT fluorescence efficiency To recover the shape of the catheter, embodiments of a clinical RT-ESS system may require acquiring at least eight spectra per circumferential scan of the catheter's optics. Assuming a frame rate of 800 Hz, the spectra should be approximately 6.5 kHz ( The SWCNTs are then digitized at a 150 μs integration time. This is facilitated by the use of a high-speed imaging spectrograph. Using a relatively coarse, low-concentration SWCNT formulation, adequate fluorescence signal intensities of approximately 2000 counts were achieved with a 100 ms integration time at 10 mW optical power at the sheath. Applying SNR analysis and assuming a safe excitation power of 50 mW, in various embodiments, approximately 100-fold higher SWCNT fluorescence intensities may be required to facilitate faster acquisition speeds, factors that may be obtained by increasing nanotube density and alignment as described below. These results demonstrate the feasibility of achieving the SWCNT fluorescence intensities required to measure catheter geometry at RT-ESS acquisition rates.

[0050] While the data disclosed herein demonstrate that SWCNT-functionalized mechanically scanned OCT catheters can create accurate 3D coronary artery models, in various embodiments, improved devices suitable for human use may be provided. In one embodiment, nanotubes can be coated on the inside of a sheath to protect the SWCNTs from body fluids, which may be difficult if the catheter includes a closed distal tip. In other embodiments, nanotubes may be coated at higher concentrations than used in the example above, and the nanotubes can be dispersed to preserve their fluorescent properties, or the nanotubes can be placed inside the catheter. The coating can be aligned along the axis of the ter to optimize emission intensity and strain sensitivity. In a further embodiment, the coating can be thin, tightly toleranced, and robust so as not to be affected by the rotating drive shaft.

[0051] In various embodiments, the RT-ESS console performs the following functions: 1) high-speed OCT image acquisition; 1) detecting and digitizing SWCNT fluorescence spectra; and 2) rapidly processing these signals to calculate the ESS. The target time from acquiring the OCT data to arriving at the ESS is 1 minute (optimal) to 3 minutes (minimum), both of which are short enough to be completed during a catheterization lab procedure. Figure 14 shows a schematic diagram of an embodiment of the RT-ESS console.

[0052] The OCT light can be provided by a wavelength-tunable laser using a MEMS-based Fabry-Perot cavity, sweeping a bandwidth of approximately 100 nm at an A-line rate of 200 kHz with a 50% duty cycle. To acquire cross sections at 800 Hz (512 A-lines / image), the A-line frequency can be doubled to 400 kHz by buffering the laser (2x) using an optical fiber delay line terminated with a Faraday mirror. A buffer optical amplifier can be used to normalize the output power. The OCT interferometer can use a standard circulator-based Mach-Zehnder configuration with a computer-controlled reference arm optical path length. The 660 nm SWCNT pump light can be combined with the OCT sample arm light via a WDM, and then both can be coupled into the core of the DCF via a power combiner.

[0053] Fluorescence from the sheath returning through the DCF's inner cladding may be diverted via a power combiner to the MMF, which illuminates a high-speed NIRF (6000 spectra / sec) InGaAs imaging spectrograph. OCT spectral interference signals can be detected using a dual-balanced polarization-diversity detection unit. The detector output is digitized at 12 bits and sampled by a 2x k-clock provided by the laser. The interferometric OCT data is transferred to a GPU, where it is converted, processed, displayed, and stored on a high-speed solid-state drive (SSD).

[0054] In various embodiments, a rotational junction, such as those used in multi-modality DCF-based devices, can be used, and its use has been clinically demonstrated. To avoid motion artifacts in the OCT dataset, the image acquisition and catheter rotation speeds are increased so that the entire pullback can be achieved during a single diastolic cycle while the catheter and artery are stationary. The start of the helical scan of the catheter can be synchronized to the diastolic trigger of the real-time ECG recording. Assuming a maximum heart rate of 100 bpm and diastole approximately 50% of the cardiac cycle, an average 5 cm pullback takes approximately 0.3 seconds. The image interval is 200 μm. In this case, a rotation speed of approximately 800 Hz is required to capture a 250-second image in 0.3 seconds. do.

[0055] The acquired spectra were fitted to a Gaussian function to determine the (7,5) and (7,6) SWCNT fluorescence peak separation, which can be converted to curvature at each θ-z scan position. The centerline can be calculated by solving the Frenet-Serret equation, which describes the 3D catheter path.

[0056] Thus, in various embodiments, the present invention includes an apparatus for determining the shape of a luminal sample. The apparatus includes a catheter disposed within a strain-sensing sheath. The strain-sensing sheath is associated with strain-sensing molecules such that changes in the shape of the strain-sensing sheath result in a strain in the sheath that can be detected spectroscopically. The catheter / sheath combination can be inserted into a luminal structure such as an artery, and the shape of the artery can be determined by measuring differences in strain along the sheath. In particular, a lens associated with the catheter can be rotated inside the sheath and simultaneously paralleled. The lens may be moved (e.g., using a pullback) to generate a helical translation. While the lens is moving (e.g., helically), data indicative of distortion from the sheath (e.g., from molecular spectroscopy data) may be collected, as well as structural information (e.g., OCT) that can be used to determine the 3D shape of the luminal sample. Combining the spectroscopic data from the sheath with the structural information can determine the overall shape of the luminal sample, essentially creating a wireframe model of the central axis of the luminal sample.

[0057] The strain-sensing molecules associated with the sheath are selected based on having a detectable spectral shift in response to changes in strain. Thus, in certain embodiments, the strain-sensing sheath has nanotubes (e.g., single-walled carbon nanotubes, SWCNTs) associated with it, which undergo a spectral shift as a result of changes in strain.

[0058] To detect the spectral shift of the strain-sensing molecules, the catheter has a lens (e.g., a ball lens) attached to its end, which is configured to rotate and translate within the strain-sensing sheath. To facilitate lens rotation, the catheter in some embodiments is optically coupled to the structural optics system and the molecular spectroscopy system using a rotary junction. The lens is configured to transmit light at an angle (e.g., perpendicular) to the longitudinal axis of the catheter, so that light is emitted and collected from the sidewalls of the sheath and the luminal structure into which the sheath is inserted.

[0059] As the lens rotates and translates the sheath, light is emitted from and collected by the lens to determine strain and gather data to determine structural information. Light from the molecular spectroscopy system is emitted from the lens and interacts with strain-sensing molecules associated with the sheath, and light returning from the sheath (e.g., in the form of fluorescence) is collected by the lens.

[0060] The returning light is analyzed spectroscopically to identify spectral shifts indicative of changes in strain. The strain is determined at two different locations along the axis of the sample (Z1 and Z2, see e.g., Figure 10), e.g., determining the strain at each location in the x-z and y-z planes. From this information, the local curvature of the catheter and sheath can be determined (with reference to calibration information). Molecular spectroscopy systems may be based on fluorescence spectroscopy, Raman spectroscopy, or absorption spectroscopy.

[0061] Light from the structure optical system (e.g., OCT) is also emitted from the lens as the lens / catheter moves (e.g., helically) through the sheath. Light returning from the sample is collected by the lens and directed toward the structure optical system. The returning light is used to determine the position of the catheter, for example, in the x-z and y-z planes for each position Z1 and Z2. From this, the local curvature of the luminal structure relative to the catheter can be determined (to the extent that the catheter does not exactly follow the contours of the luminal structure).

[0062] The operation of the catheter and the optical data collection are performed by one or more controllers, e.g., computer systems, each including one or more processors / microprocessors, memory, storage, input, output, and communication capabilities. The controllers control operations such as rotating the lens, emitting and collecting light from the lens, and processing the data. The controllers may be coupled to, e.g., in communication with, the structural optical system and / or the molecular spectroscopy system and perform functions related to these systems. In particular, the controllers may perform steps to perform operations according to embodiments disclosed herein.

[0063] In various embodiments, the sheath includes a sheath wall. The sheath wall may be associated with strain-sensing molecules (e.g., SWCNTs). In various embodiments, the strain-sensing molecules may be on the inner surface of the sheath wall, the outer surface of the sheath wall, or embedded within the sheath wall. In embodiments, the strain sensing molecules may be associated with one or more wires that are then attached to the sheath wall, e.g., the outer surface. In certain embodiments, the strain sensing sheath may be disposed within another outer sheath (e.g., if the strain sensing molecules are disposed on the outer wall of the strain sensing sheath and the strain sensing sheath is then disposed within another outer sheath, this keeps the strain sensing molecules away from the luminal sample, i.e., away from the subject's body).

[0064] FIG. 15 is a flowchart of an exemplary process 1500 for determining the shape of a luminal sample. Process 1500 includes providing a catheter optically coupled to a structural imaging system and a strain sensing system (step 1510). The catheter may include a lens, and the catheter may be disposed within a strain sensing sheath such that the lens rotates and translates within the strain sensing sheath. Process 1500 may also include determining a first position of the catheter relative to the luminal sample at a first location within the strain sensing sheath (step 1520). This and other steps may be performed by a controller coupled to the molecular spectroscopy system and the structural optical system. Process 1500 may further include determining a second position of the catheter relative to the luminal sample at a second location within the strain sensing sheath (step 1530), the first location being different from the second location. Process 1500 may also include determining a first strain in the strain sensing sheath at the first location (step 1540) and a second strain in the strain sensing sheath at the second location (step 1550). Process 1500 may also include determining a first local curvature of the lumen sample relative to the catheter between the first and second locations based on determining the first and second positions of the catheter (step 1560). Process 1500 may further include determining a second local curvature of the catheter between the first and second locations based on determining the first and second strains of the strain-sensing sheath (step 1570). Process 1500 may further include determining a third local curvature of the lumen sample between the first and second locations based on determining the first and second local curvatures of the strain-sensing sheath (step 1580). Process 1500 of FIG. 15 may be used with the methods and apparatus disclosed herein.

[0065] FIG. 16 is a flowchart of an exemplary process 1600. Process 1600 includes providing a catheter optically coupled to a strain-sensing system (step 1610). The catheter may include a lens, and the catheter may be disposed within a strain-sensing sheath such that the lens rotates and translates within the strain-sensing sheath. Process 1600 may also include determining a first strain of the strain-sensing sheath in the x-z and y-z planes at a first location within the strain-sensing sheath (step 1620). This and other steps may be performed by a controller coupled to the molecular spectroscopy system. Process 1600 may further include determining a second strain of the strain-sensing sheath in the x-z and y-z planes at a second location within the strain-sensing sheath (step 1630), the first location being different from the second location. Process 1600 may also include determining a catheter curvature between the first and second locations based on determining the first and second strains of the strain-sensing sheath (step 1640). The process 1600 of FIG. 16 may be used in conjunction with the methods and apparatus disclosed herein.

[0066] It will be apparent to those skilled in the art that numerous changes and modifications can be made in the specific embodiments of the invention described above without departing from the scope of the invention, and therefore the whole of the foregoing description should be interpreted in an illustrative rather than a limiting sense.

Claims

1. 1. An apparatus for determining the shape of a luminal sample, comprising: a catheter including a lens disposed within the strain-sensing sheath for rotational and translational movement within the strain-sensing sheath; a structural imaging system optically coupled to the catheter; a strain sensing system optically coupled to the catheter; a controller coupled to the strain sensing system and the structural imaging system; Equipped with The controller uses the structural imaging system to: determining a first position of the catheter relative to the luminal sample at a first location within the strain sensing sheath; configured to determine a second position of the catheter relative to the luminal sample within the strain-sensing sheath at a second location different from the first location; The controller uses the strain sensing system to: determining a first strain in the strain-sensing sheath at the first location based on fluorescence spectroscopy of a first strain-sensing molecule associated with the strain-sensing sheath; determining a second strain in the strain-sensing sheath at the second location based on fluorescence spectroscopy of a second strain-sensing molecule associated with the strain-sensing sheath; The controller further comprises: determining a first local curvature of the lumen sample relative to the catheter between the first location and the second location based on determining the first and second locations of the catheter relative to the lumen sample; determining a second local curvature of the catheter between the first location and the second location based on the determination of the first strain and the second strain of the strain sensing sheath; An apparatus configured to perform a three-dimensional (3D) reconstruction of the luminal sample.

2. 2. The apparatus of claim 1, wherein performing the three-dimensional reconstruction of the lumen sample includes segmenting one or more images generated by the structural imaging system and creating a curvature map from the first location and the second location of the lumen sample.

3. The apparatus of claim 2 , wherein the one or more images are generated while the lens is moved through the strain-sensing sheath and along the luminal sample.

4. The device described in claim 1, wherein a first fluorescence spectrum and a second fluorescence spectrum having an angular position and a lateral position corresponding to each location are respectively obtained at the first location and the second location.

5. The apparatus of claim 2 , wherein the curvature map is converted to a 3D catheter centerline by solving a modified Frenet-Serret equation.

6. The apparatus of claim 5 , wherein the one or more images are superimposed onto the centerline of the catheter and converted into a 3D mesh.

7. The apparatus of claim 1 , wherein the structural imaging system comprises an optical coherence tomography (OCT) system.

8. The device of claim 1 , wherein the strain-sensing sheath comprises a sheath wall.

9. The apparatus of claim 8 , wherein the first strain-sensing molecule and the second strain-sensing molecule are associated with the sheath wall.

10. The apparatus of claim 9 , wherein the first strain-sensing molecule and the second strain-sensing molecule are associated with an inner surface of the sheath wall.

11. The device of claim 9 , wherein the first strain-sensing molecule and the second strain-sensing molecule are embedded within the sheath wall.

12. The apparatus of claim 9 , wherein the first strain sensing molecule and the second strain sensing molecule are associated with an outer surface of the sheath wall.

13. The apparatus of claim 12 , wherein the first strain sensing molecule and the second strain sensing molecule are associated with a plurality of wires attached to the outer surface of the sheath wall.

14. The apparatus of claim 9 , wherein the first strain-sensing molecule and the second strain-sensing molecule comprise single-walled carbon nanotubes (SWCNTs).

15. The controller When determining the first distortion, further comprising: transmitting a first light toward the strain sensing sheath; obtaining second light from the strain sensing sheath; determining the first distortion based on the acquisition of the second light; When determining the second strain, further transmitting a third light toward the strain sensing sheath; obtaining a fourth light from the strain sensing sheath; and determining the second distortion based on the acquisition of the fourth light.

10. The apparatus of claim 1.

16. When the controller determines the first distortion, the controller further determines the first distortion based on detecting a spectral shift of the second light; The apparatus of claim 15 , wherein the controller, when determining the second distortion, is configured to determine the second distortion based on detecting a spectral shift of the fourth light.

17. When the controller determines the first strain, the controller further determines the first strain based on at least one of fluorescence spectroscopy, Raman spectroscopy, or absorption spectroscopy; The apparatus of claim 1 , wherein the controller, when determining the second strain, is further configured to determine the second strain based on at least one of fluorescence spectroscopy, Raman spectroscopy, or absorption spectroscopy.

18. The apparatus of claim 1 , wherein the strain sensing system and the structural imaging system are optically coupled to the catheter by a rotary joint.

19. The apparatus of claim 1 , wherein the luminal sample comprises a coronary artery.

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