Radiofrequency ablation procedures, such as pulmonary vein isolation for patients with atrial fibrillation, require detailed anatomical mapping of atrial structural substrate to identify AF substrate. Identification of structural substrates, such as scar tissue, pulmonary vein, collagen and adipose tissue can provide helpful guidance of RFA procedures. We demonstrate mapping of atrial substrates using optical spectral signatures from near-infrared spectroscopy. Using position tracking and interpolation algorithm, we assess the capability of NIRS to distinguish various tissue structures on a reconstructed 3D spatial maps of ex-vivo swine and human atriums.
Patients with cardiac arrythmia most commonly require radiofrequency ablation to destroy arrhythmogenic electrical pathways and restore normal heart rhythm. However, arrhythmia resurgence exists from limited means to directly confirm the extent of lesion progression during RFA procedure. Optical spectroscopy is sensitive to tissue optical properties and changes in biomolecular composition. We propose a simplified optical spectroscopy through a single fiber integrated catheter to predict irrigated endocardial lesion progression using deep neural network model on ex-vivo model.
Radiofrequency ablation is the most common procedure to treat cardiac arrythmias, such as atrial fibrillation. Catheter ablation isolates or eradicates abnormal electrical activity to maintain sinus rhythm. However, inadequate lesion formation permits arrhythmia resurgence. Optical spectroscopic signatures can detect biomolecular and tissue structural changes and can potentially serve as a tool to evaluate lesion quality. In this work, we introduce a near-infrared spectroscopy through fiber-optic integrated catheter to assess contact and predict lesion size using artificial neural network model on both ex-vivo porcine model and non-survival in-vivo pilot experiments in pigs.
KEYWORDS: Tissue optics, Optical spectroscopy, Spectroscopy, Near infrared spectroscopy, Heart, 3D metrology, Tissues, Reflectance spectroscopy, Monte Carlo methods, In vitro testing
Epicardial catheter ablation has been increasingly recognized as an important adjunct in treating ventricular arrhythmias unamenable by endocardial ablation alone. The presence of epicardial adipose tissue (EAT) is a primary cause for ineffective ablation energy delivery and electrogram misinterpretation. To address this need, we propose a catheter-based near-infrared spectroscopic technique for mapping EAT and lesion deposition, and validate it within excised human donor hearts. We introduce a new parameter, the adipose contrast index (ACI), for rapid lipid assessment. Strong correspondence was observed between values derived from interpolated 3-dimensional ACI maps and histologically-determined EAT layer thickness (Pearson’s, R = 0.903).
Radiofrequency ablation (RFA) therapy is commonly used to treat cardiac arrythmias. To restore sinus rhythm, areas of myocardium that triggers abnormal electrical activity are ablated. However, patients require multiple procedures for treatment. Clinicians currently lack the intraoperative surgical tools to visualize and assess tissue during ablation. Real-time visualization of myocardial tissue and lesion formation in vivo could potentially help reduce relapses. In this work, a combined multispectral fiber bundle-RFA catheter is introduced to assess contact and directly visualize lesion formation during and after ablation.
An important parameter that affects the quality of radiofrequency ablation lesions that are produced is the contact angle and contact orientation. Both are challenging to determine in vivo, and a method to classify that information and provide feedback in real time could potentially titrate the energy dose and increase the success rates of this treatment.
In our work, a grin lens-terminated single mode fiber was integrated into a commercial RFA catheter to allow for M-mode OCT imaging at the catheter tip. Ventricular wedges were dissected from four fresh swine hearts and submerged in whole blood. M-mode imaging was performed in four different orientations: non-contact, 30 degrees, 60 degrees, and 90 degrees.
One contact classifier with two sub-classifiers was developed to classify whether the catheter is in proper contact with the tissue and the angle of the catheter when it is in contact. This classifier is based on convolutional neural networks and used keras as developing framework with tensorflow backend.
We achieved 98.51% accuracy in the "contact" or "noncontact" classifier and 91.21% in the orientation classifier with 30 degrees, 60 degrees and 90 degrees as outputs. We successfully tested the contact quality classifier in real time and achieved high accuracy in 0.0053 seconds for a group of 20 A-lines. These results support the potential of having the guidance of catheter placement during the RFA therapy using OCT image and pre-trained classifiers. Future experiments will further test M-mode OCT and our processing algorithm within a larger sample size and demonstrate the utility in vivo.
Pulmonary vein (PV) isolation is a critical procedure for the treatment and termination of atrial fibrillation (AF). The success of such treatment depends on the extent of tissue damage, where partial lesions can allow abnormal electrical conduction and risk relapse of AF. Proper evaluation of lesion delivery and ablation line continuity remains challenging with current techniques and in part limit procedural efficacy. A tool for direct visualization of endo-myocardial lesions in vivo could potentially reduce ambiguity in treatment location and extent and improve the overall fidelity of lesion sets. In this work, we introduce a method for wide-field visualization of myocardial tissue including the discernment of ablated and non-ablated regions using an endoscopic multispectral imaging system (EMIS). The system was designed to fit the working channel of most commercial sheathes (<4 Fr) and supported quadruple-wavelength reflectance imaging through a flexible fiber-bundle. A total of 50 endocardial lesions were created and imaged on nine swine hearts, ex vivo in addition to 15 lesions on human LA samples near PV regions. A pixel-wise linear discriminant analysis algorithm was developed to classify regions of ablation treatment based on calibrated EMI maps. Results show good agreement of treatment severity and spatial extent compared to post-hoc tissue vital staining.
In non-pharmacological treatment of cardiac arrhythmias such as catheter ablation therapy, long-term treatment effectiveness is related in part to the quality of lesion generation. Superficial lesions may lead to arrhythmia recurrence by allowing recovery along conduction channels for arrhythmic impulses to propagate; conversely transmural lesions inhibit conduction. Conventional techniques rely on measurement of surrogate parameters such as change in bioelectrical impedance, or electrogram amplitude dampening as a qualitative assessment for lesion size. In previous work, we’ve demonstrated a relationship between lesion dimensions and spectroscopic parameters extracted using an optically-integrated ablation catheter. Though these metrics present some trend, a method to directly assess lesion transmurality maybe better suited. In this work, we report a method for direct recovery of lesion depth in cardiac tissue using diffusely reflected optical measurements and present initial in silico validation.
Photon transport throughout a heterogeneous volume was simulated for a series of source-detector pairs and optical properties using a GPU-based Monte Carlo (MC) code. Results were used to generate a multi-dimensional look-up table for each collection geometry for partial to transmural lesions. A genetic algorithm-based two-step inversion method was employed to extract lesion transmurality. MC simulated optical measurements for various lesion sizes were generated using optical properties for ablated and normal cardiac tissue found in literature and were fitted using our algorithm. Recovered lesion depths ranged between 2-10% for lesions less than 3mm and were within 20% for lesions greater than 4mm. These results support the application of this technique for lesion validation for atrial tissue.
Electroanatomical mapping (EAM) is an invaluable tool for guiding cardiac radiofrequency ablation (RFA) therapy. The principle roles of EAM is the identification of candidate ablation sites by detecting regions of abnormal electrogram activity and lesion validation subsequent to RF energy delivery. However, incomplete lesions may present interim electrical inactivity similar to effective treatment in the acute setting, despite efforts to reveal them with pacing or drugs, such as adenosine. Studies report that the misidentification and recovery of such lesions is a leading cause of arrhythmia recurrence and repeat procedures. In previous work, we demonstrated spectroscopic characterization of cardiac tissues using a fiber optic-integrated RF ablation catheter. In this work, we introduce OSAM (optical spectroscopic anatomical mapping), the application of this spectroscopic technique to obtain 2-dimensional biodistribution maps. We demonstrate its diagnostic potential as an auxiliary method for lesion validation in treated swine preparations.
Endocardial lesion sets were created on fresh swine cardiac samples using a commercial RFA system. An optically-integrated catheter console fabricated in-house was used for measurement of tissue optical spectra between 600-1000nm. Three dimensional, Spatio-spectral datasets were generated by raster scanning of the optical catheter across the treated sample surface in the presence of whole blood. Tissue optical parameters were recovered at each spatial position using an inverse Monte Carlo method. OSAM biodistribution maps showed stark correspondence with gross examination of tetrazolium chloride stained tissue specimens. Specifically, we demonstrate the ability of OSAM to readily distinguish between shallow and deeper lesions, a limitation faced by current EAM techniques. These results showcase the OSAMs potential for lesion validation strategies for the treatment of cardiac arrhythmias.
Using light-based catheters for radiofrequency ablation (RFA) therapies grants the ability to accurately derive tissue
properties such as lesion depth and overtreatment from spectroscopic information. However, this information is heavily
reliant on contact quality with the treatment area and the orientation of the catheter. Thus to improve assessments of
tissue properties, this work utilizes Bayesian modelling to classify whether the catheter is indeed in proper contact with
the tissue. Initially in-laboratory experiments were conducted with ten fresh swine hearts submerged in blood. A total of
1555 unique near infrared spectra were collected from a spectrometer using a light-based catheter and manually tagged
as “full perpendicular contact,” “angled contact,” and “no contact,” between the catheter and heart tissue. Three features
were prominent in all spectra for distinguishing purposes: area underneath the spectra, an intensity “valley” between 730
nm and 800 nm, along with the slope between 850 nm and 1150 nm. A classifier featuring bootstrapping, adaboost, and
k-means techniques was thus created and achieved a 96.05% accuracy in classifying full contact, 98.33% accuracy in
classifying angled contact, and 100% accuracy in classifying no contact.
Despite considerable advances in guidance of radiofrequency ablation (RFA) therapies for atrial fibrillation, success rates have been hampered by an inability to intraoperatively characterize the extent of permanent injury. Insufficient lesions can elusively create transient conduction blockages that eventually reconduct. Prior studies suggest significantly greater met-myoglobin (Mmb) concentrations in the lesion core than those in the healthy myocardium and may serve as a marker for irreversible tissue damage. In this work, we present real-time monitoring of permanent injury through spectroscopic assessment of Mmb concentrations at the catheter tip. Atrial wedges (n=6) were excised from four fresh swine hearts and submerged under pulsatile flow of warm (37oC) phosphate buffered saline. A commercial RFA catheter inserted into a fiber optic sheath allowed for simultaneous measurement of tissue diffuse reflectance (DR) spectra (500-650nm) during application of RF energy. Optical measurements were continuously acquired before, during, and post-ablation, in addition to healthy neighboring tissue. Met-myoglobin, oxy-myoglobin, and deoxy-myoglobin concentrations were extracted from each spectrum using an inverse Monte Carlo method. Tissue injury was validated with Masson’s trichrome and hematoxylin and eosin staining. Time courses revealed a rapid increase in tissue Mmb concentrations at the onset of RFA treatment and a gradual plateauing thereafter. Extracted Mmb concentrations were significantly greater post-ablation (p<0.0001) as compared to healthy tissue and correlated well with histological assessment of severe thermal tissue destruction. On going studies are aimed at integrating these findings with prior work on near infrared spectroscopic lesion depth assessment. These results support the use of spectroscopy-facilitated guidance of RFA therapies for real-time permanent injury estimation.
We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.
Cardiac tissue from swine and canine hearts were assessed using diffuse reflectance near-infrared spectroscopy (NIRS) ex vivo. Slope measured between 800-880 nm reflectance was found to reveal differences between epicardial fat and normal myocardium tissue. This parameter was observed to increase monotonically from measurements obtained from the onset of radiofrequency ablation (RFA). A sheathe-style fiber optic catheter was then developed to allow real-time sampling of the zone of resistive heating during RFA treatment. A model was developed and used to extract changes in tissue absorption and reduced scattering based on the steady-state diffusion approximation. It was found that key changes in tissue optical properties occur during application of RF energy and can be monitored using NIRS. These results encourage the development of NIRS integrated catheters for real-time guidance of the cardiac ablation treatment.
It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.
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