Comparison of holmium:yttrium-aluminium-garnet (YAG), thulium fiber laser, and pulsed thulium:YAG lasers on soft tissue: an ex vivo study.

OBJECTIVES: To assess laser-tissue interactions through ablation, coagulation, and carbonisation characteristics in a non-perfused porcine kidney model between three pulsed lasers: holmium (Ho): yttrium-aluminium-garnet (YAG), thulium fiber laser (TFL), and pulsed thulium (p-Tm):YAG. MATERIALS AND METHODS: A 150-W Ho:YAG, a 60-W TFL, and a 100-W p-Tm:YAG lasers were compared. The laser settings that can be set identically between the three lasers and be clinically relevant for prostate laser enucleation were identified and used on fresh, unfrozen porcine kidneys. Laser incisions were performed using stripped laser fibers of 365 and 550 µm, set at distances of 0 and 1 mm from the tissue surface at a constant speed of 2 mm/s. Histological analysis evaluated shape, depth, width of the incision, axial coagulation depth, and presence of carbonisation. RESULTS: Incision depths, widths, and coagulation zones were greater with Ho:YAG and p-Tm:YAG lasers than TFL. Although no carbonisation was found with the Ho:YAG and p-Tm:YAG lasers, it was common with TFL, especially at high frequencies. The shapes of the incisions and coagulation zones were more regular and homogeneous with the p-Tm:YAG laser and TFL than with Ho:YAG laser. Regardless of the laser used, short pulse durations resulted in deeper incisions than long pulse durations. Concerning the distance, we found that to be effective, TFL had to be used in contact with the tissue. Finally, 365-µm fibers resulted in deeper incisions, while 550-µm fibers led to wider incisions and larger coagulation zones. CONCLUSION: Histological analysis revealed greater tissue penetration with the p-Tm:YAG laser compared to the TFL, while remaining less than with Ho:YAG. Its coagulation properties seem interesting insofar as it provides homogeneous coagulation without carbonisation, while incisions remained uniform without tissue laceration. Thus, the p-Tm:YAG laser appears to be an effective alternative to Ho:YAG and TFL lasers in prostate surgery.

Non-Contact Irreversible Electroporation in the Esophagus With a Wet Electrode Approach.

Our objective was to develop a technique for performing irreversible electroporation (IRE) of esophageal tumors while mitigating thermal damage to the healthy lumen wall. We investigated noncontact IRE using a wet electrode approach for tumor ablation in a human esophagus with finite element models for electric field distribution, joule heating, thermal flux, and metabolic heat generation. Simulation results indicated the feasibility of tumor ablation in the esophagus using an catheter mounted electrode immersed in diluted saline. The ablation size was clinically relevant, with substantially lesser thermal damage to the healthy esophageal wall when compared to IRE performed by placing a monopolar electrode directly into the tumor. Additional simulations were used to estimate ablation size and penetration during noncontact wet-electrode IRE (wIRE) in the healthy swine esophagus. A novel catheter electrode was manufactured and wIRE evaluated in seven pigs. wIRE was performed by securing the device in the esophagus and using diluted saline to isolate the electrode from the esophageal wall while providing electric contact. Computed tomography and fluoroscopy were performed post-treatment to document acute lumen patency. Animals were sacrificed within four hours following treatment for histologic analysis of the treated esophagus. The procedure was safely completed in all animals; post-treatment imaging revealed intact esophageal lumen. The ablations were visually distinct on gross pathology, demonstrating full thickness, circumferential regions of cell death (3.52 ± 0.89 mm depth). Acute histologic changes were not evident in nerves or extracellular matrix architecture within the treatment site. Catheter directed noncontact IRE is feasible for performing penetrative ablations in the esophagus while avoiding thermal damage.

Microbial nitroreductases: A versatile tool for biomedical and environmental applications.

Nitroreductases, enzymes found mostly in bacteria and also in few eukaryotes, use nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for their activity and metabolize an enormous list of a diverse nitro group-containing compounds. Nitroreductases that are capable of metabolizing nitroaromatic and nitro heterocyclic compounds have drawn great attention in recent years owing to their biotechnological, biomedical, environmental, and human impact. These enzymes attracted medicinal chemists and pharmacologists because of their prodrug selectivity for activation/reduction of nitro compounds that wipe out pathogens/cancer cells, leaving the host/normal cells unharmed. It is applied in diverse fields of study like prodrug activation in treating cancer and leishmaniasis, designing fluorescent probes for hypoxia detection, cell imaging, ablation of specific cell types, biodegradation of nitro-pollutants, and interpretation of mutagenicity of nitro compounds. Keeping in view the immense prospects of these enzymes and a large number of research contributions in this area, the present review encompasses the enzymatic reaction mechanism, their role in antibiotic resistance, hypoxia sensing, cell imaging, cancer therapy, reduction of recalcitrant nitro chemicals, enzyme variants, and their specificity to substrates, reaction products, and their applications.

Methodology for the Implementation of Internal Standard to Laser-Induced Breakdown Spectroscopy Analysis of Soft Tissues.

The improving performance of the laser-induced breakdown spectroscopy (LIBS) triggered its utilization in the challenging topic of soft tissue analysis. Alterations of elemental content within soft tissues are commonly assessed and provide further insights in biological research. However, the laser ablation of soft tissues is a complex issue and demands a priori optimization, which is not straightforward in respect to a typical LIBS experiment. Here, we focus on implementing an internal standard into the LIBS elemental analysis of soft tissue samples. We achieve this by extending routine methodology for optimization of soft tissues analysis with a standard spiking method. This step enables a robust optimization procedure of LIBS experimental settings. Considering the implementation of LIBS analysis to the histological routine, we avoid further alterations of the tissue structure. Therefore, we propose a unique methodology of sample preparation, analysis, and subsequent data treatment, which enables the comparison of signal response from heterogenous matrix for different LIBS parameters. Additionally, a brief step-by-step process of optimization to achieve the highest signal-to-noise ratio (SNR) is described. The quality of laser-tissue interaction is investigated on the basis of the zinc signal response, while selected experimental parameters (e.g., defocus, gate delay, laser energy, and ambient atmosphere) are systematically modified.

Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.

Selective bladder denervation for overactive bladder (OAB) syndrome: From concept to healing outcomes using the ovine model.

AIMS: We evaluated a Selective Bladder Denervation (SBD) device, which uses radiofrequency ablation, for the treatment of overactive bladder syndrome in terms of its nerve denervation, ablation characteristics, and post-treatment healing. METHODS: Using the SBD device, eight fresh extirpated ovine bladder trigones were treated (90°C set point for 60 s) and nitroblue tetrazolium viability stained to characterize the ablation. In addition, 12 trigones were treated in vivo with three adjacent ablations and divided into survival cohorts: Day 7, Day 30, and Day 90 to assess the ablations and their associated healing. RESULTS: The ex vivo single trigone ablations had a 7.9 ± 0.9 mm width and 5.7 ± 1.0 mm thickness that involved the submucosa, detrusor muscle, adventitia, and vagina. Microscopic viability staining confirmed complete nerve necrosis within the targeted tissue. The in vivo Day 7 trigones supported the ex vivo ablation characteristics and showed up to minimal inflammation, granulation tissue, and collagen fibrosis. Day 30 trigones had essentially absent inflammation and granulation tissue with evolving collagen fibrosis at the ablation's periphery. Day 90 trigones had essentially absent acute inflammation, minimal chronic inflammation, essentially absent granulation tissue, and up to mild collagen fibrosis. No ureteral/urethral alterations, vesico-vaginal fistulas, or other complications were identified. CONCLUSIONS: The SBD device provided a targeted trigone ablation with resultant denervation. The tissue healing timeline followed that expected for a hyperthermic ablation and was characterized by a fibroproliferative healing response with limited inflammation and granulation tissue. The ablations did not impact the overlying bladder mucosal surface.

Theoretical model for laser ablation outcome predictions in brain: calibration and validation on clinical MR thermometry images.

PURPOSE: Neurosurgical laser ablation is experiencing a renaissance. Computational tools for ablation planning aim to further improve the intervention. Here, global optimisation and inverse problems are demonstrated to train a model that predicts maximum laser ablation extent. METHODS: A closed-form steady state model is trained on and then subsequently compared to N = 20 retrospective clinical MR thermometry datasets. Dice similarity coefficient (DSC) is calculated to provide a measure of region overlap between the 57 °C isotherms of the thermometry data and the model-predicted ablation regions; 57 °C is a tissue death surrogate at thermal steady state. A global optimisation scheme samples the dominant model parameter sensitivities, blood perfusion (ω) and optical parameter (µeff) values, throughout a parameter space totalling 11 440 value-pairs. This represents a lookup table of µeff-ω pairs with the corresponding DSC value for each patient dataset. The µeff-ω pair with the maximum DSC calibrates the model parameters, maximising predictive value for each patient. Finally, leave-one-out cross-validation with global optimisation information trains the model on the entire clinical dataset, and compares against the model naïvely using literature values for ω and µeff. RESULTS: When using naïve literature values, the model's mean DSC is 0.67 whereas the calibrated model produces 0.82 during cross-validation, an improvement of 0.15 in overlap with the patient data. The 95% confidence interval of the mean difference is 0.083-0.23 (p < 0.001). CONCLUSIONS: During cross-validation, the calibrated model is superior to the naïve model as measured by DSC, with +22% mean prediction accuracy. Calibration empowers a relatively simple model to become more predictive.

Automating neurosurgical tumor resection surgery: Volumetric laser ablation of cadaveric porcine brain with integrated surface mapping.

OBJECTIVE: Current surgical instruments for soft tissue resection including neurosurgical procedures rely on the accuracy and precision of the human operator and are fundamentally constrained by the human hand. Automated surgical action with the integration of intraoperative data sources can enable highly accurate and fast tissue manipulation using laser ablation. This study presents the first experiments with a prototype designed for automated tumor resection via laser ablation. We demonstrate targeted soft tissue resection in porcine brain with an integrated device that combines 3D scanning capabilities with a steerable surgical laser and discuss implications for future automated robotic neurosurgical procedures. STUDY DESIGN AND METHODS: A device consisting of a two-axis galvanometer for steering a cutting laser and a 3D surface profiler is used to perform volumetric removal of tissue of ex vivo porcine brain. Three-dimensional surface profiles are gathered between cuts and used to estimate ablation rate. RESULTS: Volumetric ablation of porcine brain tissue is performed and subsequently surface profiled. The average ablation rates across the area cutting areas were 2.6 mm3 /s and 3.7 mm3 /s for the initial and subsequent cuts, respectively. A Kruskal-Wallis and post-hoc Tukey test show statistical significance between the initial and subsequent cuts. Accuracy between cuts when benchmarked against a human surgeon varied from 47 to 88%. CONCLUSION: A feed-forward volumetric resection is demonstrated with sensing and cutting housed within a single device, thereby opening the potential for automated soft tissue resection as necessary during the surgical removal of pathologic tissues. High variance around target cut depths motivates future work in developing a closed-loop ablation tool as well as characterization of laser-tissue interactions for predictive modelling. Objective Lasers Surg. 50:1017-1024, 2018. © 2018 Wiley Periodicals, Inc.

A novel transcutaneous, non-focused ultrasound energy delivering device is able to induce subcutaneous adipose tissue destruction in an animal model.

BACKGROUND AND OBJECTIVES: The understanding that adipocytes are greatly influenced by thermal changes combined with the advancement of non-invasive ultrasound technologies have led to the application of ultrasound as an energy source to induce thermal fat destruction. While application of high intensity focused, ultrasound energy have been widely explored, there is far less information regarding the effects of non-focused ultrasound on adipose tissue. The purpose of this study was to characterize the effects of a novel transcutaneous, multi-elements, non-focused ultrasound energy regimen in an animal model, as a proof-of-concept of its potential to treat non-invasive subcutaneous benign tumors. MATERIALS AND METHODS: The non-invasive transcutaneous ultrasound system prototype (LUMENIS, Ltd., Yoqneam, Israel) was applied to thermally induce adipocytes' death. During treatment, the ultrasound energy was transmitted into the subcutaneous adipose tissue (SAT) of 12 domestic adult female pigs. Two modes of operation (long and short), which differ in both the acoustic energy applied to the tissue and in their time durations (i.e., differ in their power settings), were used in this study. Efficacy and safety assessments included: Temperature measurement of skin and subcutaneous adipose tissue (SAT) visual inspection and ultrasound imaging of the thermally affected areas, histopathological assessment of tissue samples using hematoxylin & eosin, and Masson's trichrome stains and in situ cell death detection kit for apoptosis assessment. RESULTS: The long and short treatment modes led to a 13.2°C and 17.8°C rise from baseline, respectively, in the SAT, whereas skin surface temperature was practically unaffected. Visual, ultrasonographic, and histopathological evaluation of the treated area showed SAT ablation. No treatment-related changes were observed in the epidermis, dermis subcutaneous muscle and nerves, or in livers and kidneys of treated animals. Additionally, no significant changes from baseline in blood- and urine-borne analytes were detected post-treatment. CONCLUSIONS: The novel transcutaneous, multi-elements, non-focused ultrasound energy regimen used in this study, proved effective in non-invasively ablating SAT in an animal model. The usage of low energy settings such as in the current study might reduce unwanted side effects related to high energy application. Lasers Surg. Med. 49:110-121, 2017. © 2016 Wiley Periodicals, Inc.

Enhanced Tissue Ablation Efficiency with a Mid-Infrared Nonlinear Frequency Conversion Laser System and Tissue Interaction Monitoring Using Optical Coherence Tomography.

We report development of optical parametric oscillator (OPO)-based mid-infrared laser system that utilizes a periodically poled nonlinear crystal pumped by a near-infrared (NIR) laser. We obtained a mid-infrared average output of 8 W at an injection current of 20 A from a quasi-phase-matched OPO using an external cavity configuration. Laser tissue ablation efficiency is substantially affected by several parameters, including an optical fluence rate, wavelength of the laser source, and the optical properties of target tissue. Dimensions of wavelength and radiant exposure dependent tissue ablation are quantified using Fourier domain optical coherence tomography and the ablation efficiency was compared to a non-converted NIR laser system.

Efficacy of Dietitian-instructed Low Iodine Diet for Radioiodine Remnant Tissue Ablation for Thyroid Cancer.

We evaluated the significance of dietary instruction (DI) for patients who are going on a low iodine diet (LID) as a preparation for remnant tissue ablation for thyroid cancer. DI was done by a dietarian using a dedicated handbook we have developed. To assess the effect of LID on depleting body iodine, urinary iodine concentration (UIC) in patients with post-surgical papillary thyroid cancer was measured twice, before and after LID. UIC on the day of radioiodine administration was compared with radioiodine uptake (RU) in the remnant tissue. Additionally, the association between clinical and lifestyle-related features of patients and the outcome of LID were investigated. A questionnaire survey was conducted to determine whether the DI helped patients go on LID. The mean value of UIC after the one-week LID was decreased to about 15% of the baseline value. There was a significant inverse correlation between UIC and RU (r= -0.694). Age and UIC before the start of LID were linked to successful outcome of LID. In the questionnaire survey, 84% of the participants answered that the handbook helped them go on a LID. Likewise, 80% answered that they could manage their LID without using the boil-in-the-bag low iodine food. LID successfully decreased UIC in patients undergoing remnant tissue ablation. DI by a dietitian may make a practice of LID easier.

A Ten-Year Kuala Lumpur Review on Laser Posterior Cordectomy for Bilateral Vocal Fold Immobility.

Bilateral vocal fold immobility (BVFI) is commonly caused by injury to the recurrent laryngeal nerve (RLN) and leads to stridor and dyspnea of varying onsets. A retrospective study was done at the Department of Otorhinolaryngology of Universiti Kebangsaan Malaysia Medical Centre on laser microsurgical posterior cordectomy for BVFI. The objectives were to identify the average duration of onset of stridor from the time of insult and to evaluate the outcome of laser posterior cordectomy as a surgical option. From 1997 to 2007, a total of 31 patients with BVFI were referred for surgery. Twelve patients had tracheostomy done prior to the procedure, whereas 19 patients were without tracheostomy. Ten patients were successfully decannulated, and only 4 patients had complications related to the procedure. The minimum onset of stridor was 7 months, maximum onset of stridor was 28 years, and the mean onset of stridor was 8.7 years. The commonest complication observed was posterior glottic adhesion following bilateral posterior cordectomy. Laser endolaryngeal posterior cordectomy is an excellent surgical option as it enables successful decannulation or avoidance of tracheostomy in patients with BVFI. The onset of stridor took years after the insult to the recurrent laryngeal nerves.

Electrical breakdown in tissue electroporation.

Electroporation, the permeabilization of the cell membrane by brief, high electric fields, has become an important technology in medicine for diverse application ranging from gene transfection to tissue ablation. There is ample anecdotal evidence that the clinical application of electroporation is often associated with loud sounds and extremely high currents that exceed the devices design limit after which the devices cease to function. The goal of this paper is to elucidate and quantify the biophysical and biochemical basis for this phenomenon. Using an experimental design that includes clinical data, a tissue phantom, sound, optical, ultrasound and MRI measurements, we show that the phenomenon is caused by electrical breakdown across ionized electrolysis produced gases near the electrodes. The breakdown occurs primarily near the cathode. Electrical breakdown during electroporation is a biophysical phenomenon of substantial importance to the outcome of clinical applications. It was ignored, until now.

Parametric study of irreversible electroporation with different needle electrodes: electrical and thermal analysis.

PURPOSE: Irreversible electroporation (IRE) is a new tumour ablation method used in cancer treatment procedures. In a successful IRE treatment it is crucial to impose minimum thermal damage to the tumour and its surrounding healthy tissue, while subjecting the entire tumour to a strong electric field. METHOD: Here we present a 3D model of a subcutaneous tumour in a four-layer skin using a geometry-based finite element approach. Four common needle electrode configurations were studied in this paper. The study evaluated six essential factors which are important in the electrical and thermal distributions in tumour and normal tissue. RESULTS: The results revealed that a hexagonal 3 × 3 geometry provides the maximum electrical coverage of the tumour, compared to other electrode configurations. However, in some cases the hexagonal 2 × 2 geometry can ablate the entire tumour with less damage to normal tissue. We found that the deeper insertion of 2- and 4-electrode geometries can lead to more damage to healthy tissue. The results also indicate that the insertion of the electrodes into tumour tissue can increase thermal damage dramatically due to existing large electrical conductivity. CONCLUSION: These findings suggest that needle electrodes should not be placed within the tumour tissue if the goal is to prevent thermal damage. This method can be used as a trade-off between electric field coverage in tumour tissue and thermal damage to both tumour and normal tissue.

Tissue Ablation: Applications and Perspectives.

Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics.

Advancing laser ablation assessment in hyperspectral imaging through machine learning.

Hyperspectral imaging (HSI) is gaining increasing relevance in medicine, with an innovative application being the intraoperative assessment of the outcome of laser ablation treatment used for minimally invasive tumor removal. However, the high dimensionality and complexity of HSI data create a need for end-to-end image processing workflows specifically tailored to handle these data. This study addresses this challenge by proposing a multi-stage workflow for the analysis of hyperspectral data and allows investigating the performance of different components and modalities for ablation detection and segmentation. To address dimensionality reduction, we integrated principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) to capture dominant variations and reveal intricate structures, respectively. Additionally, we employed the Faster Region-based Convolutional Neural Network (Faster R-CNN) to accurately localize ablation areas. The two-stage detection process of Faster R-CNN, along with the choice of dimensionality reduction technique and data modality, significantly influenced the performance in detecting ablation areas. The evaluation of the ablation detection on an independent test set demonstrated a mean average precision of approximately 0.74, which validates the generalization ability of the models. In the segmentation component, the Mean Shift algorithm showed high quality segmentation without manual cluster definition. Our results prove that the integration of PCA, t-SNE, and Faster R-CNN enables improved interpretation of hyperspectral data, leading to the development of reliable ablation detection and segmentation systems.

Real-Time Monitoring of Thermal Phenomena during Femtosecond Ablation of Bone Tissue for Process Control.

Femtosecond (fs) laser technology is currently being considered in innovative fields such as osteotomy and treatment of hard tissue thanks to the achievable high resolution and ability to prevent tissue damage. In a previous study, suitable process parameters were obtained to achieve competitive ablation rates on pork femur processing. Nevertheless, a better control of thermal accumulation in the tissue during laser ablation could further improve the postoperative regeneration of the treated bone compared with conventional procedures and push forward the exploitation of such technology. This study presents methods for real time analyses of bone tissue temperature and composition during fs laser ablation and highlights the importance of implementing an efficient cooling method of bone tissue in order to achieve optimized results. Results show that it is possible to achieve a larger process window for bone tissue ablation where bone tissue temperature remains within the protein denaturation temperature in water-based processing environment. This is a key outcome towards a clinical exploitation of the presented technology, where higher process throughputs are necessary. The effects of process parameters and environments on bone tissue were confirmed by LIBS technique, which proved to be an efficient method by which to record real-time variation of bone tissue composition during laser irradiation.

Advances in Tumor Management: Harnessing the Potential of Histotripsy.

Tissue ablation techniques have long been used in clinical settings to treat various oncologic diseases. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is a noninvasive, nonionizing, nonthermal tissue ablation technique that has the potential to replace surgical interventions in various clinical settings. Histotripsy works by delivering high-intensity focused ultrasound waves to target tissue. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tissue into acellular debris that is subsequently absorbed by the body's immune system. Preclinical and clinical studies have demonstrated the efficacy of histotripsy in treating a range of diseases, including liver, pancreatic, renal, and prostate tumors. Safety outcomes of histotripsy have been generally favorable, with minimal adverse effects reported. However, further studies are needed to optimize the technique and understand its long-term effects. This review aims to discuss the importance of histotripsy as a noninvasive tissue ablation technique, the preclinical and clinical literature on histotripsy and its safety, and the potential applications of histotripsy in clinical practice. Keywords: Tumor Microenvironment, Ultrasound-High-Intensity Focused (HIFU), Ablation Techniques, Abdomen/GI, Genital/Reproductive, Nonthermal Tissue Ablation, Histotripsy, Clinical Trials, Preclinical Applications, Focused Ultrasound © RSNA, 2024.

Feasibility test of a sapphire cryoprobe with optical monitoring of tissue freezing.

This article describes a sapphire cryoprobe as a promising solution to the significant problem of modern cryosurgery that is the monitoring of tissue freezing. This probe consists of a sapphire rod manufactured by the edge-defined film-fed growth technique from Al2 O3 melt and optical fibers accommodated inside the rod and connected to the source and the detector. The probe's design enables detection of spatially resolved diffuse reflected intensities of tissue optical response, which are used for the estimation of tissue freezing depth. The current type of the 12.5-mm diameter sapphire probe cooled down by the liquid nitrogen assumes a superficial cryoablation. The experimental test made by using a gelatin-intralipid tissue phantom shows the feasibility of such concept, revealing the capabilities of monitoring the freezing depth up to 10 mm by the particular instrumentation realization of the probe. This justifies a potential of sapphire-based instruments aided by optical diagnosis in modern cryosurgery.

Design and test of a rigid endomicroscopic system for multimodal imaging and femtosecond laser ablation.

Significance: Conventional diagnosis of laryngeal cancer is normally made by a combination of endoscopic examination, a subsequent biopsy, and histopathology, but this requires several days and unnecessary biopsies can increase pathologist workload. Nonlinear imaging implemented through endoscopy can shorten this diagnosis time, and localize the margin of the cancerous area with high resolution. Aim: Develop a rigid endomicroscope for the head and neck region, aiming for in-vivo multimodal imaging with a large field of view (FOV) and tissue ablation. Approach: Three nonlinear imaging modalities, which are coherent anti-Stokes Raman scattering, two-photon excitation fluorescence, and second harmonic generation, as well as the single photon fluorescence of indocyanine green, are applied for multimodal endomicroscopic imaging. High-energy femtosecond laser pulses are transmitted for tissue ablation. Results: This endomicroscopic system consists of two major parts, one is the rigid endomicroscopic tube 250 mm in length and 6 mm in diameter, and the other is the scan-head (10×12×6 cm3 in size) for quasi-static scanning imaging. The final multimodal image accomplishes a maximum FOV up to 650 µm, and a resolution of 1 µm is achieved over 560 µm FOV. The optics can easily guide sub-picosecond pulses for ablation. Conclusions: The system exhibits large potential for helping real-time tissue diagnosis in surgery, by providing histological tissue information with a large FOV and high resolution, label-free. By guiding high-energy fs laser pulses, the system is even able to remove suspicious tissue areas, as has been shown for thin tissue sections in this study.