A tissue-mimicking prostate phantom for 980 nm laser interstitial thermal therapy.

Purpose: To develop a phantom with optical and thermal properties matched to human prostate. This phantom will provide a platform for the development and characterization of 980 nm laser interstitial thermal therapy (LITT) systems. Methods: A polyacrylamide gel was doped with Naphthol Green B, Intralipid, and Bovine Serum Albumin (BSA). The necessary concentration of each ingredient was determined by measuring the optical properties via fluence measurements and light diffusion theory. LITT was then performed under the same conditions as a previous clinical trial in which temperature was monitored via a thermal probe. The thermal data and induced coagulation zone were compared to clinical data to illustrate the similarity between the phantom and patient. LITT was also performed under magnetic resonance thermometry (MRT). Results: The requisite concentrations of Naphthol Green B, Intralipid and BSA were found to be 0.144% (w/v), 8.06% (v/v) and 31.4% (v/v) respectively. In the native state, the absorption coefficient and reduced scattering coefficient ( µs' ) were found to be 0.66 ± 0.06 cm-1 and 8.27 ± 0.50 cm-1 respectively, with µs' increasing to 17.63 ± 1.41 cm-1 after coagulation. The thermal response of the phantom was similar to that observed clinically with maximum thermal probe measurements of 64.2 °C and 66.9 °C respectively. The shape of the induced coagulation zone was qualitatively and quantitatively similar to the MRT zone of elevated temperature and the coagulation zone observed clinically. Conclusions: A phantom which simulates optical and thermal response to 980 nm LITT was constructed and demonstrated to be similar to human prostate.

Biaxial sensing suture breakage warning system for robotic surgery.

The number of procedures performed with robotic surgery may exceed one million globally in 2018. The continual lack of haptic feedback, however, forces surgeons to rely on visual cues in order to avoid breaking sutures due to excessive applied force. To mitigate this problem, the authors developed and validated a novel grasper-integrated system with biaxial shear sensing and haptic feedback to warn the operator prior to anticipated suture breakage. Furthermore, the design enables facile suture manipulation without a degradation in efficacy, as determined via measured tightness of resulting suture knots. Biaxial shear sensors were integrated with a da Vinci robotic surgical system. Novice subjects (n = 17) were instructed to tighten 10 knots, five times with the Haptic Feedback System (HFS) enabled, five times with the system disabled. Seven suture failures occurred in trials with HFS enabled while seventeen occurred in trials without feedback. The biaxial shear sensing system reduced the incidence of suture failure by 59% (p = 0.0371). It also resulted in 25% lower average applied force in comparison to trials without feedback (p = 0.00034), which is relevant because average force was observed to play a role in suture breakage (p = 0.03925). An observed 55% decrease in standard deviation of knot quality when using the HFS also indicates an improvement in consistency when using the feedback system. These results suggest this system may improve outcomes related to knot tying tasks in robotic surgery and reduce instances of suture failure while not degrading the quality of knots produced.

An examination of the elastic properties of tissue-mimicking phantoms using vibro-acoustography and a muscle motor system.

Tissue hardness, often quantified in terms of elasticity, is an important differentiating criterion for pathological identity and is extensively used by surgeons for tumor localization. Delineation of malignant regions from benign regions is typically performed by visual inspection and palpation. Although practical, this method is highly subjective and does not provide quantitative metrics. We have previously reported on Vibro-Acoustography (VA) for tumor delineation. VA is unique in that it uses the specific, non-linear properties of tumor tissue in response to an amplitude modulated ultrasound beam to generate spatially resolved, high contrast maps of tissue. Although the lateral and axial resolutions (sub-millimeter and sub-centimeter, respectively) of VA have been extensively characterized, the relationship between static stiffness assessment (palpation) and dynamic stiffness characterization (VA) has not been explicitly established. Here we perform a correlative exploration of the static and dynamic properties of tissue-mimicking phantoms, specifically elasticity, using VA and a muscle motor system. Muscle motor systems, commonly used to probe the mechanical properties of materials, provide absolute, quantitative point measurements of the elastic modulus, analogous to Young's modulus, of a target. For phantoms of varying percent-by-weight concentrations, parallel VA and muscle motor studies conducted on 18 phantoms reveal a negative correlation (p < - 0.85) between mean signal amplitude levels observed with VA and calculated elastic modulus values from force vs. indentation depth curves. Comparison of these elasticity measurements may provide additional information to improve tissue modeling, system characterization, as well as offer valuable insights for in vivo applications, specifically surgical extirpation of tumors.

A Multielement Tactile Feedback System for Robot-Assisted Minimally Invasive Surgery.

A multi-element tactile feedback (MTF) system has been developed to translate the force distribution, in magnitude and position, from 3times2 sensor arrays on surgical robotic end-effectors to the fingers via 3times2 balloon tactile displays. High detection accuracies from perceptual tests (> 96%) suggest that MTF may be an effective means to improve robotic control.

Tactile Feedback Induces Reduced Grasping Force in Robot-Assisted Surgery.

Robot-assisted minimally invasive surgery has gained widespread use over the past decade, but the technique is currently operated in the absence of haptic feedback during tissue manipulation. We have developed a complete tactile feedback system, consisting of a piezoresistive force sensor, control system, and pneumatic balloon tactile display, and mounted directly onto a da Vinci surgical robotic system. To evaluate the effect of tactile feedback on robotic manipulation, a group of novices (n = 16) and experts ( n = 4) were asked to perform three blocks of peg transfer tasks with the tactile feedback system in place. Force generated at the end-effectors was measured in all three blocks, but tactile feedback was active only during the middle block. All subjects used higher force when the feedback system was inactive. When active, subjects immediately used substantially less force and still maintained appropriate grip during the task. After the system was again turned off, grip force increased significantly to prefeedback levels. These results demonstrate that robotic manipulations without tactile feedback are done with more force than needed to grasp objects. Therefore, the addition of tactile feedback allows the surgeon to grasp with less force, and may improve control of the robotic system and handling of tissues and other objects.

Reflective terahertz imaging of porcine skin burns.

A reflective pulsed terahertz imaging system based on direct detection was developed and used to obtain high-resolution images of a porcine skin specimen with superficial partial-thickness (second-degree) burns. Images were also obtained of the sample through ten layers of dry medical (cotton) gauze with minimal image degradation. The burned and unburned regions of skin had large differences in terahertz reflectivity, displaying clear delineation [20 dB signal-to-noise ratio (SNR) difference signal] between both regions in the images. The terahertz images also exhibited a "halo" surrounding the burn areas that may correlate to the extent of burn injury. The system operated at a center frequency of 500 GHz with 125 GHz of 3 dB bandwidth and used whiskbroom scanning to generate images with a spatial resolution of 1.5 mm. Each pixel was acquired with a 16 ms integration time, resulting in a 40 dB postdetection SNR. The simplicity and high SNR of the reflective terahertz system are promising steps toward real-time terahertz medical imaging.

Excimer laser (308 nm) recanalisation of in-stent restenosis: thermal considerations.

Excimer laser recanalisation of in-stent restenosis may be a viable modality for improving coronary patency. However, the presence of arterial stents modifies the thermal properties of the irradiated area and may alter temperature patterns generated during ablation. The goal of this study was to evaluate, in vitro, temperature changes during excimer laser ablation of stented vessels and compare them with those obtained from unstented (control) vessels. Six different stent types (AVE Microstent-II, AVE-GFX, ACS Multi-link, JJ Palmaz-Schatz, JJ Crown, and NIR) were deployed in freshly excised porcine coronary vessels. Three control unstented samples were also measured. Blood or saline was infused through the vessels, while the tissue environment was kept at approximately 37 degrees C. A 308 nm excimer laser (Spectranetics, CVX300) with an eccentric 2.0 mm laser catheter (Spectranetics, EII) delivered two trains of 200 pulses each, 10 s apart, at 60 mJ/mm2, and 40 Hz, simulating maximum clinical exposure. The catheter was positioned midway in the stent, first coaxially parallel to the vessel wall, and then at an angle against the stent and vessel wall. Temperature measurements (n= 168 for blood, n=96 for saline) were performed with a approximately 210 microm diameter, fast-response thermocouple with 0.1 degrees C resolution. The probe was positioned to within approximately 250 microm from the inner surface of the vessels. Tissue temperature was measured at the catheter tip and at the distal and proximal edges of the stents. Maximum recorded temperatures for coaxial and angular alignment, did not exceed 42.2 degrees C (approximately 6 degrees C above baseline) and 54.2 degrees C (approximately 18.1 degrees C above baseline) respectively, for all stents types tested, controls, and all probe locations. Both stented and unstented vessels exhibited comparable temperature gradients. The observed maximum temperatures, obtained under extreme lasing conditions, indicated that 308 nm ablation, in the presence of stents under blood or saline infusion, produces clinically acceptable temperatures.

Excimer laser (308 nm) based transmyocardial laser revascularization: effects of the lasing parameters on myocardial histology.

BACKGROUND AND OBJECTIVE: The effect of the excimer laser (308 nm) parameters on transmyocardial revascularization (TMR) channels is not well defined. This study investigates the influence of the pulse repetition rate, the size of the delivery catheter and its advancement speed on the morphology of TMR channels in vivo. STUDY DESIGN/MATERIALS AND METHODS: Myocardial ablation was performed in a porcine model (N = 27) using multifiber catheters of 1.0 and 1.4 mm in diameter. The catheters were advanced into the myocardium at different speeds (1.27 and 2.54 mm/sec) while ablating at various repetition rates (10-80 Hz). The radiant exposure was kept at 35 mJ/mm(2) throughout the experiments. The channel histology was quantified by digital microscopy. RESULTS: The channel cross-sectional area and the extent of the thermal damage decrease as the catheter advancement speed exceeds the ablation speed and vice versa. Within the parameters tested, advancement speed of about 1.3 mm/sec and pulse repetition rates of 40 Hz produce channels of size comparable to the catheter's diameter with moderate thermomechanical damage. CONCLUSIONS: The repetition rate, catheter size, and catheter advancement speed are closely intertwined and crucial to the histological outcome of excimer laser based TMR.

Ablation spectra of the human cornea.

Ablation of human corneal tissue with 193 nm excimer laser energy generates fluorescence in the near ultraviolet and visible regions of the spectrum. The fluorescence spectra from five human corneas were collected during ablation in vitro. We find that the fluorescence spectrum changes continuously as the cornea is ablated from the epithelial surface towards the endothelium. We reduced the dimensionality of the large data set resulting from each cornea by a principal components analysis. The three most significant principal component eigenvectors suffice to describe the observed spectral evolution, and independent analysis of each tissue sample produces a similar set of eigenvectors. The evolution of the calculated eigenvector weighting factors during ablation then corresponds to the observed spectral evolution. In fact, this evolution is qualitatively consistent between corneas. We suggest that this spectral evolution offers promise as a real-time surgical feedback tool.

Discrimination of human coronary artery atherosclerotic lipid-rich lesions by time-resolved laser-induced fluorescence spectroscopy.

Lesion composition plays a significant role in atherosclerotic lesion instability and rupture. Current clinical techniques cannot fully characterize lesion composition or accurately identify unstable lesions. This study investigates the use of time-resolved fluorescence spectroscopy for unstable atherosclerotic lesion diagnosis. The fluorescence of human coronary artery samples was induced with nitrogen laser and detected in the 360- to 510-nm wavelength range. The samples were sorted into 7 groups according to the AHA classification: normal wall and types I, II(a) (fatty streaks), III (preatheroma), IV (atheroma), V(a) (fibrous), and V(b) (calcified) lesions. Spectral intensities and time-dependent parameters [average lifetime tau(f); decay constants: tau(1) (fast-term), tau(2) (slow-term), A(1) (fast-term amplitude contribution)] derived from the time-resolved spectra of coronary samples were used for tissue characterization. We determined that a few intensity values at longer wavelengths (>430 nm) and time-dependent parameters at peak emission region (390 nm) discriminate between all types of arterial samples except between normal wall and type I lesions. The lipid-rich lesions (more unstable) can be discriminated from fibrous lesions (more stable) on the basis of time-dependent parameters (lifetime and fast-term decay). We inferred that features of lipid fluorescence are reflected on lipid-rich lesion emission. Our results demonstrate that analysis of the time-resolved spectra may be used to enhance the discrimination between different grades of atherosclerotic lesions and provide a means of discrimination between lipid-rich and fibrous lesions.

Time-resolved fluorescence of human aortic wall: use for improved identification of atherosclerotic lesions.

BACKGROUND AND OBJECTIVE: This study characterized aortic time-resolved fluorescence spectra for stratified levels of atherosclerosis and proposed interpretation of spectrotemporal variations in terms of histologic changes. STUDY DESIGN/MATERIALS AND METHODS: Fluorescence emission transients were measured at 370-510 nm (337 nm excitation) on 94 excised human aortic samples, ranging from normal to advanced fibrous atherosclerotic lesion. Global analysis yielded a three-exponential approximation of the time-resolved spectra from which average lifetime and decay-associated spectra were derived. RESULTS: Average lifetime at 390 nm gradually increased from 2.4+/-0.1 nsec (normal aorta) to 3.9+/-0.1 nsec (advanced lesion). Fluorescence intensity was markedly decreased above 430 nm in intermediate and advanced lesions. Spectral intensity associated with the intermediate decay increased at 470-490 nm for early and intermediate lipid-rich lesions. CONCLUSION: Time-resolved fluorescence spectra of aortic samples presented distinctive features for each atherosclerotic lesion type, which could serve as characteristic markers for optical analysis of the aortic wall.

Consequences of scattering for spectral imaging of turbid biologic tissue.

Spectral imaging permits two-dimensional mapping of the backscattering properties of biological systems. Such mapping requires broadband illumination of the entire area of interest. However, imaging of turbid biological media under these conditions often involves mean photon path lengths that exceed the pixel size. Using a numerical Monte Carlo model, we have studied the effects of photon scattering in a hemoglobin-bearing model system. We find that photon migration and the resulting wavelength-dependent optical coupling between pixels can complicate the analysis of imaging spectroscopy data. In fact, the wavelength dependence of photon trajectories also alters the distribution of photon exit angles at the tissue surface. We therefore find that the finite optical field of view of an imaging spectrometer can affect the measured spectra in the absence of chromatic aberrations.

Laser tissue interaction in direct myocardial revascularization.

This investigation examines the various laser choices used for transmyocardial laser revascularization (TMLR) with emphasis on the laser-tissue interaction. A series of in vivo (porcine model, n=27) and in vitro experiments were performed to study the effects of CO(2), holmium:YAG, and XeCl excimer lasers on the histological outcome of TMR channels. Computerized histopathological analysis has revealed that the CO(2) and holmium:YAG lasers produce substantial unpredictable thermal damage and differ predominantly in the amount of the mechanical injury or tissue shredding. In comparison, the excimer laser appears to produce the most uniform tissue ablation with the least thermal and shockwave damage.

Laser induced fluorescence attenuation spectroscopy: detection of hypoxia.

The development of a new laser-induced fluorescence (LIF) spectroscopy technique for the measurement of the attenuation spectrum of tissue is described. The technique, termed laser-induced fluorescence attenuation spectroscopy (LIFAS), has been applied to study the effects of hypoxia on the in vivo optical properties of renal and myocardial tissue in the 350-600-nm band. Excimer laser (Xe-Cl) is used to excite a small volume of the tissue (rabbit model, N = 20) and induce autofluorescence. The emitted LIF is monitored fiberoptically at two locations that are unevenly displaced about the fluorescing volume. The optical attenuation of the tissue is calculated from the dual LIF measurements by assuming an exponential decay of the fluorescence with distance. The results indicate that hypoxia modulates the attenuation spectrum leading to characteristic changes in its shape. Primarily, the spectral profile becomes more concave between 455 nm and 505 nm and two spectral peaks at about 540 and 580 nm disappear leaving in their place a single peak at about 555 nm. The attenuation spectra of normoxic and hypoxic tissue are used to train partial least squares multivariate model for spectral classification. The model detected acute renal and myocardial hypoxia with an accuracy greater than 90% (range: 90%-96%) and 74% (range: 74%-90%), respectively.

Time-resolved fluorescence spectra of arterial fluorescent compounds: reconstruction with the Laguerre expansion technique.

The time-resolved fluorescence spectra of the main arterial fluorescent compounds were retrieved using a new algorithm based on the Laguerre expansion of kernels technique. Samples of elastin, collagen and cholesterol were excited with a pulsed nitrogen laser and the emission was measured at 29 discrete wavelengths between 370 and 510 nm. The expansion of the fluorescence impulse response function on the Laguerre basis of functions was optimized to reproduce the observed fluorescence emission. Collagen lifetime (5.3 ns at 390 nm) was substantially larger than that of elastin (2.3 ns) and cholesterol (1.3 ns). Two decay components were identified in the emission decay of the compounds. For collagen, the decay components were markedly wavelength dependent and hydration dependent such that the emission decay became shorter at higher emission wavelengths and with hydration. The decay characteristics of elastin and cholesterol were relatively unchanged with wavelength and with hydration. The observed variations in the time-resolved spectra of elastin, collagen and cholesterol were consistent with the existence of several fluorophores with different emission characteristics. Because the compounds are present in different proportions in healthy and atherosclerotic arterial walls, characteristic differences in their time-resolved emission spectra could be exploited to assess optically the severity of atherosclerotic lesions.

Photobleaching of arterial fluorescent compounds: characterization of elastin, collagen and cholesterol time-resolved spectra during prolonged ultraviolet irradiation.

To study the photobleaching of the main fluorescent compounds of the arterial wall, we repeatedly measured the time-resolved fluorescence of elastin, collagen and cholesterol during 560 s of excitation with nitrogen laser pulses. Three fluence rate levels were used: 0.72, 7.25 and 21.75 microW/mm2. The irradiation-related changes of the fluorescence intensity and of the time-resolved fluorescence decay constants were characterized for the emission at 390, 430 and 470 nm. The fluorescence intensity at 390 nm decreased by 25-35% when the fluence delivered was 4 mJ/mm2, a common value in fluorescence studies of the arterial wall. Cholesterol fluorescence photobleached the most, and elastin fluorescence photobleached the least. Photobleaching was most intense at 390 nm and least intense at 470 nm such that the emission spectra of the three compounds were markedly distorted by photobleaching. The time-resolved decay constants and the fluorescence lifetime were not altered by irradiation when the fluence was below 4 mJ/mm2. The spectral distortions associated with photobleaching complicate the interpretation of arterial wall fluorescence in terms of tissue content in elastin, collagen and cholesterol. Use of the time-dependent features of the emission that are not altered by photobleaching should increase the accuracy of arterial wall analysis by fluorescence spectroscopy.

Safety evaluation of laparoscopically applied clips.

We have evaluated in vitro, the security of laparoscopically applied clips, through two commercially available clip appliers: the Endo Clip II (US Surgical) and the Ligaclip (Ethicon). The clip performance was tested with respect to dislodgment and leakage. Dislodgment was attempted both transversely and at 45 degrees with respect to the main axis of the tubular structures tested. The mean maximum force (N = 24) necessary to dislodge a clip applied to silicone tubing (2.1, 2.4, 3.2 mm o.d.) and porcine vascular tissue was measured. The maximum force needed to transversely dislodge a clip applied to silicone tubing, ranged from 262 +/- 9 g (2.1 mm) to 315 +/- 11 g (3.2 mm) for the Endo Clip II applier, while the values for the Ligaclip were 220 +/- 28 g (2.1 mm) and 273 +/- 11 g (3.2 mm), respectively. To achieve dislodgment at 45 degrees pull, corresponding forces of 294 +/- 8 g (2.1 mm) and 369 +/- 14 g (3.2 mm) for the Endo Clip II, and 254 +/- 14 g (2.1 mm) and 297 +/- 13 g (3.2 mm) for the Ligaclip (N = 24) were required. Transverse dislodgment forces, for clips applied to tissue, were 556 +/- 146 g for the Endo Clip II and 356 +/- 170 for the Ligaclip (N = 6). Leakage tests were also performed under pulsatile blood circulation at mean pressure of approximately 800 mm Hg. No tested clips applied to either silicone tubing or tissue allowed for any blood leakage. The dislodgment test showed that the Endo Clip II exhibits superior performance compared to the Ligaclip, based on the fact that it requires more force for transverse and semiaxial dislodgment. In the leakage test, both clip appliers performed equivalently.

Spectro-temporal studies of Xe-Cl excimer laser-induced arterial wall fluorescence.

We report on spectro-temporal fluorescence studies of cadaver femoral arterial walls at different stages in the progression of atherosclerosis. After excitation with a Xe-Cl excimer pulse, the time course of the fluorescence spectrum was recorded over time, and time-resolved multispectral analysis was performed. Then, under the assumption of linearity, we derived a linear spectro-temporal kernel (a weighting function) which describes the temporal behavior of the fluorescence process independently of the pulse width of the photoexcitation. The data analysis revealed both static and dynamic fluorescence characteristics which exhibited a good correlation with histological findings.