Assessing the Outcomes of Focused Heating of the Skin by a Long-Pulsed 1064 nm Laser with an Integrated Scanner, Infrared Thermal Guidance, and Optical Coherence Tomography.

BACKGROUND AND OBJECTIVE: Long-term benefits can be predicted by the incorporation of more intelligent systems in lasers and other devices. Such systems can produce more reliable zones of thermal injury when used in association with non-invasive monitoring and precise laser energy delivery. The more classical endpoint of tumor destruction with radiofrequency or long-pulsed (LP) 1064 nm laser is the non-specific appearance of tissue graying and tissue contraction. Herein we discuss combining non-invasive LP 1064 nm Nd:YAG treatment with the assistance of optical coherence tomography (OCT) and the forward-looking infrared (FLIR) thermal camera while testing literature-based formulae for thermal destruction. STUDY DESIGN/MATERIALS AND METHODS: The skin on the forearm and back of two consenting volunteers was marked and anesthetized with lidocaine with epinephrine. The parameters of a scanner-equipped LP 1064 nm Nd:YAG laser were adjusted to achieve an epidermal/superficial dermal heating of between 50°C and 60°C over a specified time course. Experimental single treatments examined various adjusted parameters including, fluence, pulse overlap, pulse duration, scan size, and pulse rate. A FLIR camera was used to record skin temperature. Outcome measures included skin temperature, post-treatment appearance, and OCT assessment of skin and vascular damage. The clinical response of each treatment was followed daily for 4 weeks. RESULTS: Optimal protocols initially raised the skin temperature to between 55°C and 60°C, which was carefully maintained using subsequent laser passes over a 60-second time course. Immediately post laser, clinical responses included erythema, edema, and blistering. Immediate OCT revealed increased vascularity with intact, dilated blood vessels. Prolonged exposure above 60°C resulted in sub-epidermal blistering and an absence of blood flow in the treatment area with prolonged healing. CONCLUSION: The LP 1064 nm laser can be used to achieve heat-related tissue injury, though the narrow parameters necessary for the desired endpoint require the assistance of IR thermal regulation to avoid unacceptable outcomes. The use of the laser scanner ensures precise energy delivery over a defined treatment area. Future studies might explore this as a selective hyperthermic method for the treatment of non-melanoma skin cancer. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Clinical Feasibility of a High-Resolution Thermal Monitoring Sheet for Superficial Hyperthermia in Breast Cancer Patients.

Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition patterns and applicator efficiency (1-2%), the reduced heat transfer of the water boluses (51-56%) could be compensated by adjusting the water bolus flow. Skin surface temperatures were monitored reliably, and no alteration of thermal toxicity was observed compared to standard Amsterdam UMC thermometry. Conclusion: Clinical application of the TMS is feasible. Power deposition patterns and applicator efficiency were not affected. Surface temperatures were monitored reliably.

Association between Serum Indoxyl Sulfate Levels and Endothelial Function in Non-Dialysis Chronic Kidney Disease.

Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were obtained from 110 patients with stages 3-5 CKD. The endothelial function, represented by vascular reactivity index (VRI), was measured non-invasively using digital thermal monitoring. Serum IS levels were determined using liquid chromatography-mass spectrometry. Twenty-one (19.1%), 36 (32.7%), and 53 (48.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. By univariate linear regression analysis, a higher prevalence of smoking, advanced age, higher systolic, and diastolic blood pressure (DBP), elevated levels of serum phosphorus, blood urea nitrogen, creatinine, and IS were negatively correlated with VRI values, but estimated glomerular filtration rate negatively associated with VRI values. After being adjusted by using multivariate stepwise linear regression analysis, DBP and IS levels were significantly negatively associated with VRI values in CKD patients. We concluded that IS level associated inversely with VRI values and had a modulating role in endothelial function in patients with stages 3-5 CKD.

Theoretical and experimental modeling of interstitial laser hyperthermia with surface cooling device using Nd3+-doped nanoparticles.

To improve methods of laser hyperthermia for the treatment of bulk malignant neoplasms, an urgent task is the development of techniques and devices that automatically control heating at a given tissue depth and ensure its uniformity. The article proposes the concept of a system for performing hyperthermia with real-time spectroscopic temperature control and surface cooling, which allows to record spectra of diffusely scattered radiation and fluorescent signal from various depths of biological tissues by the means of the variation of the angle and distance between the fiber source of laser radiation and the receiving fiber. Theoretical and experimental modeling of the spatial distribution of diffusely scattered radiation and temperature inside the tissue with a fiber optic device providing surface cooling of the irradiated tissue, and recording spectral information from a given depth in real time, is presented. Simulation of radiation propagation in biological tissues, depending on the distance between the source and the receiver and the angle of their tilt, was carried out using the Monte Carlo method. Modeling of the temperature distribution inside the tissues was carried out by means of a numerical solution of the heat conduction equation. Experimental modeling was carried out on phantoms of biological tissues simulating their scattering properties as well as accumulation of the investigated nanoparticles doped with Nd3+ ions. It was shown that inorganic nanoparticles doped with rare-earth Nd3+ ions can be used as temperature labels for feedback to the therapeutic laser. According to the results of the theoretical simulation, optimal configurations of the relative arrangement of the fibers were chosen, as well as the optimum surface cooling temperatures for the given power densities. The heating of the phantom of the neoplasm containing the investigated nanoparticles doped with Nd3+ ions by laser radiation with an 805-nm wavelength and power density of 1 W/cm2 up to 42 °C at a depth of 1 cm while maintaining the surface temperature within the limits of the norm was demonstrated.

Ultrasound-guided percutaneous microwave ablation assisted by a three-dimensional visualization preoperative treatment planning system for larger adrenal metastasis (D ≥ 4 cm): Preliminary results.

OBJECTIVE: The objective of this study is to assess the clinical effect and safety of ultrasound-guided percutaneous microwave ablation (US-PMWA) assisted by three-dimensional (3D) visualization operative treatment planning system in larger adrenal metastasis (LAM) (D ≥ 4 cm). MATERIALS AND METHODS: From Dec 2011 to Dec 2017, 12 consecutive LAM patients with pathologically proven with a mean diameter of 5.2±1.3cm (range 4.1-7.6) were treated. Artificial ascites and thermal monitoring system as ancillary technique were used. The patients were followed up with imagings and complications were recorded. RESULTS: The median follow-up period was 31 months (ranged 6-52 m). All LAM achieved completely ablation according to the 3D planning preoperation. Complete ablation was achieved in 10 (10/12, 83.3%) patients by one session and 2 patients (2/12, 16.7%) by two sessions. Recurrence was detected at the treated site in 3 patients (3/12, 25.0%) at 5, 9, and 13 months after ablation and received another ablation. Progression of metastasis disease at extra-adrenal sites occurred in 9 patients (9/12, 75%). Seven (7/12, 58.3%) patients died during the follow-up period. Therefore, the 1-, 2-, and 3-year local tumor control rates were 83.3%, 75.0%, and 75.0%, and 1-, 2-, 3- and 4-year overall survival rates were 91.7%, 75.0%, 50.0%, and 41.7%, respectively. No severe complications related to ablation occurred, except 3 (3/12, 25%) patients developed hypertension during ablation. CONCLUSIONS: US-PMWA assisted by 3D visualization preoperative treatment planning system maybe a safe and efficient therapy for LAM, which could promote ablation precision, improve the clinical outcomes.

Ultrasound thermal monitoring with an external ultrasound source for customized bipolar RF ablation shapes.

PURPOSE: Thermotherapy is a clinical procedure which delivers thermal energy to a target, and it has been applied for various medical treatments. Temperature monitoring during thermotherapy is important to achieve precise and reproducible results. Medical ultrasound can be used for thermal monitoring and is an attractive medical imaging modality due to its advantages including non-ionizing radiation, cost-effectiveness and portability. We propose an ultrasound thermal monitoring method using a speed-of-sound tomographic approach coupled with a biophysical heat diffusion model. METHODS: We implement an ultrasound thermometry approach using an external ultrasound source. We reconstruct the speed-of-sound images using time-of-flight information from the external ultrasound source and convert the speed-of-sound information into temperature by using the a priori knowledge brought by a biophysical heat diffusion model. RESULTS: Customized treatment shapes can be created using switching channels of radio frequency bipolar needle electrodes. Simulations of various ablation lesion shapes in the temperature range of 21-59 [Formula: see text]C are performed to study the feasibility of the proposed method. We also evaluated our method with ex vivo porcine liver experiments, in which we generated temperature images between 22 and 45 [Formula: see text]C. CONCLUSION: In this paper, we present a proof of concept showing the feasibility of our ultrasound thermal monitoring method. The proposed method could be applied to various thermotherapy procedures by only adding an ultrasound source.

Target visualisation and microwave hyperthermia monitoring using nanoparticle-enhanced transmission ultrasound (NETUS).

PURPOSE: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment. METHODS: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored. RESULTS: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5 °C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p < 0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia profile significantly. In the breast mimicking phantom, NETUS yielded accurate detection of the target region as well as thermal monitoring of the microwave heating procedure. CONCLUSIONS: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast.

Optical flow and image segmentation analysis for noninvasive precise mapping of microwave thermal ablation in X-ray CT scans - ex vivo study.

PURPOSE: To develop image processing algorithms for noninvasive mapping of microwave thermal ablation using X-ray CT. METHODS: Ten specimens of bovine liver were subjected to microwave ablation (20-80 W, 8 min) while scanned by X-ray CT at 5 s intervals. Specimens were cut and manually traced by two observers. Two algorithms were developed and implemented to map the ablation zone. The first algorithm utilises images segmentation of Hounsfield units changes (ISHU). The second algorithm utilises radial optical flow (ROF). Algorithm sensitivity to spatiotemporal under-sampling was assessed by decreasing the acquisition rate and reducing the number of acquired projections used for image reconstruction in order to evaluate the feasibility of implementing radiation reduction techniques. RESULTS: The average radial discrepancy between the ISHU and ROF contours and the manual tracing were 1.04±0.74 and 1.16±0.79mm, respectively. When diluting the input data, the ISHU algorithm retained its accuracy, ranging from 1.04 to 1.79mm. By contrast, the ROF algorithm performance became inconsistent at low acquisition rates. Both algorithms were not sensitive to projections reduction, (ISHU: 1.24±0.83mm, ROF: 1.53±1.15mm, for reduction by eight fold). Ablations near large blood vessels affected the ROF algorithm performance (1.83±1.30mm; p < 0.01), whereas ISHU performance remained the same. CONCLUSION: The two suggested noninvasive ablation mapping algorithms can provide highly accurate contouring of the ablation zone at low scan rates. The ISHU algorithm may be more suitable for clinical practice as it appears more robust when radiation dose reduction strategies are employed and when the ablation zone is near large blood vessels.

Body Mass Index Is Associated With Microvascular Endothelial Dysfunction in Patients With Treated Metabolic Risk Factors and Suspected Coronary Artery Disease.

BACKGROUND: Obesity is key feature of the metabolic syndrome and is associated with high cardiovascular morbidity and mortality. Obesity is associated with macrovascular endothelial dysfunction, a determinant of outcome in patients with coronary artery disease. Here, we compared the influence of obesity on microvascular endothelial function to that of established cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolemia, and smoking in patients with suspected coronary artery disease. METHODS AND RESULTS: Endothelial function was assessed during postocclusive reactive hyperemia of the brachial artery and downstream microvascular beds in 108 patients who were scheduled for coronary angiography. In all patients, microvascular vasodilation was assessed using peripheral arterial tonometry; laser Doppler flowmetry and digital thermal monitoring were performed. Body mass index was significantly associated with decreased endothelium-dependent vasodilatation measured with peripheral arterial tonometry (r=0.23, P=0.02), laser Doppler flowmetry (r=0.30, P<0.01), and digital thermal monitoring (r=0.30, P<0.01). In contrast, hypertension, hypercholesterolemia, and smoking had no influence on microvascular vasodilatation. Especially in diabetic patients, endothelial function was not significantly reduced (control versus diabetes mellitus, mean±SEM or median [interquartile range], peripheral arterial tonometry: 1.90±0.20 versus 1.67±0.20, P=0.19, laser Doppler flowmetry: 728% [interquartile range, 427-1110] versus 589% [interquartile range, 320-1067] P=0.28, and digital thermal monitoring: 6.6±1.0% versus 2.5±1.7%, P=0.08). In multivariate linear regression analysis, body mass index was the only risk factor that significantly attenuated endothelium-dependent vasodilatation using all 3 microvascular function tests. CONCLUSIONS: Higher body mass index is associated with reduced endothelial function in patients with suspected coronary artery disease, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.

Safety assessment and therapeutic efficacy of percutaneous microwave ablation therapy combined with percutaneous ethanol injection for hepatocellular carcinoma adjacent to the gallbladder.

OBJECTIVE: This study sought to evaluate the safety and efficacy of ultrasound-guided (US-guided) percutaneous microwave (MW) ablation combined with percutaneous ethanol injection (PEI) to treat liver tumours adjacent to the gallbladder. MATERIALS AND METHODS: A total of 136 patients with hepatocellular carcinoma (HCC) adjacent to the gallbladder, who underwent ultra-sonographically-guided percutaneous MW ablation, which was combined with PEI in 132 patients, were retrospectively assessed. The patient population characteristics, tumour features, local tumour progression and treatment were compared and analysed. The safety and efficacy of the therapy were assessed by clinical data and imaging in follow-up examinations. RESULTS: All patients were completely treated with two sessions; 120 patients underwent one session, 16 patients underwent two sessions. The primary technique was effective in 95.6% of the cases, according to the computed tomography (CT) or magnetic resonance imaging (MRI) in the one-month follow-up (132 of 138 sessions). PEI and other therapies were performed in the patients who had been incompletely treated (all six patients underwent PEI, and some underwent other therapies, including one transcatheter arterial chemoembolisation (TACE), one liver transplantation and two liver resections). There was a median follow-up period of 30.1 months and a range of 4 to 68 months. None of the patients had major complications. There were no treatment-related deaths. Twenty-six patients died of primary disease progression that was not directly attributable to MW ablation (19.1%, 26/136). Local tumour progression was noted in five patients (3.7%, 5/136), who had completely ablated tumours at follow-up. The patients with locally progressing tumours underwent additional therapy (three patients underwent PEI, one patient TACE, and one liver resection). CONCLUSION: Ultrasound-guided percutaneous MW ablation, in combination with percutaneous ethanol injection and thermal monitoring, is a safe and effective treatment for HCC adjacent to the gallbladder.