Influence of vitamins and food on the fluorescence spectrum of human urine.

OBJECTIVES: Fluorescence spectroscopy of human urine is a method with the potential to gain importance as a diagnostic tool in the medical field, e.g., for measuring Coproporphyrin III (CPIII) as an indicator of cancer and acute types of porphyria. Food can change human urine's color, which could influence the urine fluorescence spectrum and the detection of CPIII in urine. To determine if there is a noticeable influence on the urine fluorescence spectrum or on the detection of CPIII in urine, 16 vitamin supplements, and three food items were tested. Such investigation may also prevent false interpretation of measured data. METHODS: Urine samples were collected before and after (overnight, ca. 8 h) intake of each test substance. Samples were investigated by fluorescence spectrum analysis. At excitation wavelengths from 300 to 500 nm and emission wavelengths from 400 to 700 nm excitation-emission-matrices were measured. Data obtained from urine before intake were compared to the data from overnight urine. Furthermore, the investigation of any interference with the CPIII concentration was performed at an excitation wavelength of 407 ± 3 nm and emission wavelengths of 490-800 nm. RESULTS: Only vitamin B2, but none of the other tested substances, showed noticeable influence on the urine fluorescence spectrum. None of the tested substances showed noticeable interference with the recovery rate of CPIII. CONCLUSIONS: The correct interpretation of measured data by fluorescence spectroscopy is possible with the exception if vitamin B2 supplementation was performed; thus, the consumption of vitamin B2 supplements before fluorescence testing of the patient's urine should be avoided and/or must be requested. CPIII concentrations could reliably be measured in all cases.

Hyperspectral imaging for monitoring of free flaps of the oral cavity: A feasibility study.

OBJECTIVES: Hyperspectral imaging (HSI) provides spectral information about hemoglobin, water and oxygen supply and has thus great potential in perfusion monitoring. The aim of the present study was to investigate the feasibility of HSI in the postoperative monitoring of intraoral free flaps. METHODS: The 14 patients receiving reconstructive head and neck surgery with a radial forearm free flap were included. HSI was performed intraoperatively (t0), on Day 1 (t1), 2 (t2), 3-6 (t3), 7-9 (t4), 10-11 (t5) and 12-15 (t6) postoperatively. Flap tissue perfusion was assessed on defined regions of interest by calculating the perfusion indices Tissue Hemoglobin Index (THI), hemoglobin oxygenation (StO2 ), Near Infrared Perfusion Index (NIR Perfusion Index) and Tissue Water Index (TWI). RESULTS: Image quality varied depending on location of the flap and time of measurement. StO2 was >50 intraoperatively and >40 on t1 for all patients. A significant difference was found solely for TWI between t0 and t2 and t0 and t4. No flap loss occurred. CONCLUSIONS: The use of HSI in the monitoring of intraoral flaps is feasible and might become a valuable addition to the current clinical examination of free flaps.

Investigations on correlations between changes of optical tissue properties and NMR relaxation times.

BACKGROUND: Accurate light dosimetry is a complex remaining challenge in interstitial photodynamic therapy (iPDT) for malignant gliomas. The light dosimetry should ideally be based on the tissue morphology and the individual optical tissue properties of each tissue type in the target region. First investigations are reported on using NMR information to estimate changes of individual optical tissue properties. METHODS: Porcine brain tissue and optical tissue phantoms were investigated. To the porcine brain, supplements were added to simulate an edema or high blood content. The tissue phantoms were based on agar, Lipoveneous, ink, blood and gadobutrol (Gd-based MRI contrast agent). The concentrations of phantom ingredients and tissue additives are varied to compare concentration-dependent effects on optical and NMR properties. A 3-tesla whole-body MRI system was used to determine T1 and T2 relaxation times. Optical tissue properties, i.e., the spectrally resolved absorption and reduced scattering coefficient, were obtained using a single integrating sphere setup. The observed changes of NMR and optical properties were compared to each other. RESULTS: By adjusting the NMR relaxation times and optical tissue properties of the tissue phantoms to literature values, recipes for human brain tumor, white matter and grey matter tissue phantoms were obtained that mimic these brain tissues simultaneously in both properties. For porcine brain tissue, it was observed that with increasing water concentration in the tissue, both NMR-relaxation times increased, while µa decreased and µs' increased at 635 nm. The addition of blood to porcine brain samples showed a constant T1, while T2 shortened and the absorption coefficient at 635 nm increased. CONCLUSIONS: In this investigation, by changing sample contents, notable changes of both NMR relaxation times and optical tissue properties have been observed and their relations examined. The developed dual NMR/optical tissue phantoms can be used in iPDT research, clinical training and demonstrations.

Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors.

Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors. Results: NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 µmol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 µmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors. Conclusion: NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future.

Prospects of Endovenous Laser Ablation (EVLA) Standardization-Mid-Term Results of a Four-Zone Dosimetry Guiding Tool for 1940 nm Laser.

BACKGROUND: Heterogeneity regarding dosimetry and reporting of endovenous laser ablation (EVLA) mandates the development of a standardized protocol. This study presents the mid-term results of EVLA with 1940 nm-laser and radial-fibre, supported by a four-zone dosimetry tool. MATERIALS AND METHODS: Four anatomical dosimetry zones for great saphenous veins (GSV) and two for small saphenous veins (SSV) were defined with set power levels. Zone-1G (4 W) extended from the inguinal ligament to the apex of femoral triangle, Zone-2G (4 W) from the apex of femoral triangle to the upper border of patella. Zone-3G (3 W) from the patella to the tibial tuberosity. Zone-4G (2 W) extended from the tibial tuberosity to the ankle. Zone-1S from the sapheno-popliteal junction to the tibial tuberosity. Zone-2S from the tibial tuberosity to the ankle. Power was increased by 1 W for veins >10 mm and decreased by 1 W when fibre sticking was encountered. Pullback-velocity was max. 1 mm/s. RESULTS: A total of 152 consecutive patients (185 procedures) were recruited. Mean follow-up time was 11.9 months. Mean linear endovenous energy density for GSV was Zone-1G:42 J/cm, Zone-2G:33 J/cm, Zone-3G:27 J/cm, Zone-4G:22 J/cm, Zone-1S:34 J/cm, Zone-2S:27 J/cm. Occlusion rates were 98.9% (1-month) and 93.7% (12-months). Complications at 1 M were low, namely laser-induced paraesthesia (LIP) 2.2% and endovenous heat-induced thrombosis (EHIT) 1.6%. Persistent LIP (12 M) was observed in 0.5%. CONCLUSION: The proposed four-zone guiding tool is a step towards standardizing dosimetry and documentation for EVLA with 1940 nm. This strategy shows good mid-term results with minimal complications. Long-term follow-up and application in further centres are necessary to prove its reproducibility. Such a guiding tool could improve the ability to analyse, compare and review different EVLA wavelengths and fibre types.

Interstitial Photodynamic Therapy of Glioblastomas: A Long-Term Follow-up Analysis of Survival and Volumetric MRI Data.

BACKGROUND: The treatment of glioblastomas, the most common primary malignant brain tumors, with a devastating survival perspective, remains a major challenge in medicine. Among the recently explored therapeutic approaches, 5-aminolevulinic acid (5-ALA)-mediated interstitial photodynamic therapy (iPDT) has shown promising results. METHODS: A total of 16 patients suffering from de novo glioblastomas and undergoing iPDT as their primary treatment were retrospectively analyzed regarding survival and the characteristic tissue regions discernible in the MRI data before treatment and during follow-up. These regions were segmented at different stages and were analyzed, especially regarding their relation to survival. RESULTS: In comparison to the reference cohorts treated with other therapies, the iPDT cohort showed a significantly prolonged progression-free survival (PFS) and overall survival (OS). A total of 10 of 16 patients experienced prolonged OS (≥ 24 months). The dominant prognosis-affecting factor was the MGMT promoter methylation status (methylated: median PFS of 35.7 months and median OS of 43.9 months) (unmethylated: median PFS of 8.3 months and median OS of 15.0 months) (combined: median PFS of 16.4 months and median OS of 28.0 months). Several parameters with a known prognostic relevance to survival after standard treatment were not found to be relevant to this iPDT cohort, such as the necrosis-tumor ratio, tumor volume, and posttreatment contrast enhancement. After iPDT, a characteristic structure (iPDT remnant) appeared in the MRI data in the former tumor area. CONCLUSIONS: In this study, iPDT showed its potential as a treatment option for glioblastomas, with a large fraction of patients having prolonged OS. Parameters of prognostic relevance could be derived from the patient characteristics and MRI data, but they may partially need to be interpreted differently compared to the standard of care.

Interstitial photodynamic therapy for newly diagnosed glioblastoma.

PURPOSE: Innovative, efficient treatments are desperately needed for people with glioblastoma (GBM). METHODS: Sixteen patients (median age 65.8 years) with newly diagnosed, small-sized, not safely resectable supratentorial GBM underwent interstitial photodynamic therapy (iPDT) as upfront eradicating local therapy followed by standard chemoradiation. 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX was used as the photosensitizer. The tumors were irradiated with light at 635 nm wavelength via stereotactically implanted cylindrical diffuser fibers. Outcome after iPDT was retrospectively compared with a positively-selected in-house patient cohort (n = 110) who underwent complete tumor resection followed by chemoradiation. RESULTS: Median progression-free survival (PFS) was 16.4 months, and median overall survival (OS) was 28.0 months. Seven patients (43.8%) experienced long-term PFS > 24 months. Median follow-up was 113.9 months for the survivors. Univariate regression revealed MGMT-promoter methylation but not age as a prognostic factor for both OS (p = 0.04 and p = 0.07) and PFS (p = 0.04 and p = 0.67). Permanent iPDT-associated morbidity was seen in one iPDT patient (6.3%). Patients treated with iPDT experienced superior PFS and OS compared to patients who underwent complete tumor removal (p < 0.01 and p = 0.01, respectively). The rate of long-term PFS was higher in iPDT-treated patients (43.8% vs. 8.9%, p < 0.01). CONCLUSION: iPDT is a feasible treatment concept and might be associated with long-term PFS in a subgroup of GBM patients, potentially via induction of so far unknown immunological tumor-controlling processes.

Comprehensive Investigation of Parameters Influencing Fluorescence Lifetime Imaging Microscopy in Frequency- and Time-Domain Illustrated by Phasor Plot Analysis.

Having access to fluorescence lifetime, researchers can reveal in-depth details about the microenvironment as well as the physico-chemical state of the molecule under investigation. However, the high number of influencing factors might be an explanation for the strongly deviating values of fluorescent lifetimes for the same fluorophore reported in the literature. This could be the reason for the impression that inconsistent results are obtained depending on which detection and excitation scheme is used. To clarify this controversy, the two most common techniques for measuring fluorescence lifetimes in the time-domain and in the frequency-domain were implemented in one single microscopy setup and applied to a variety of fluorophores under different environmental conditions such as pH-value, temperature, solvent polarity, etc., along with distinct state forms that depend, for example, on the concentration. From a vast amount of measurement results, both setup- and sample-dependent parameters were extracted and represented using a single display form, the phasor-plot. The measurements showed consistent results between the two techniques and revealed which of the tested parameters has the strongest influence on the fluorescence lifetime. In addition, quantitative guidance as to which technique is most suitable for which research task and how to perform the experiment properly to obtain consistent fluorescence lifetimes is discussed.

Endovenous laser ablation using laser systems emitting at wavelengths > 1900 nm: a systematic review.

The aim of this systematic review was to summarize the currently available literature reporting clinical application of endovenous laser ablation (EVLA) by means of laser systems emitting at wavelengths > 1900 nm, pertaining dosimetry, intraoperative parameters, postoperative outcomes, and efficacy based on occlusion rates, recanalization, and postoperative complications. A literature search was conducted in PubMed, Cochrane Library, Embase, OVID, and Web of Science for publications since the year 2000 until December 2021. Case series, prospective trials, retrospective studies, and randomized controlled trials describing the application of a 1920/1940-nm wavelength laser for EVLA in humans with a minimum of one postoperative follow-up visit were included in the study. Four case series and one randomized controlled trial with a total of 509 EVLA procedures (396 great saphenous veins and 113 small saphenous veins) were identified, meeting the inclusion criteria. The studies were heterogenous in their documentation, EVLA, and duplex ultrasound protocol and result reporting. Overall, the applied average cumulative LEED values ranged from 17.8 to 53 J/cm. Complications observed were pigmentation (0-9.75%), paresthesia (2.5-7.3%), thrombophlebitis (0-5%), EHIT Class 2 (2.26-2.4%), and EHIT Class 1 (1.2-2.4%). Four cases of recanalizations were observed in one study cohort within the first month after treatment. Follow-up at 12 months was available for 3 studies (procedures n = 218) with recanalizations in 8 limbs. Follow-up at 24-36 months was available for 2 studies (procedures n = 126) showing recanalizations in 5 limbs. Recanalizations were asymptomatic and incidental findings on follow-up duplex ultrasound. Pooled occlusion rates were 99.2% at 1 M, 96.3% at 12 M, and 96% at 24 M. Overall, patients undergoing EVLA with long wavelength laser systems > 1900 nm show high occlusion rates, significant improvement in VCSS, low postoperative complication rate, low pain levels, low analgesic requirement, and early convalescence. Apart from persistent paresthesia, all the complications regressed spontaneously within 6 months. EVLA by means of 1920/1940 nm shows promising clinical results with high efficacy and low complication rates. Heterogeneity still exists regarding ideal protocol for duplex ultrasound examination and documentation of anatomical parameters (e.g., vein diameter, ideal stump length and status of accessory veins) and light dosimetry for EVLA.

The role of Shikonin in improving 5-aminolevulinic acid-based photodynamic therapy and chemotherapy on glioblastoma stem cells.

Glioblastoma multiforme is a malignant neoplasia with a median survival of less than two years and without satisfactory therapeutic options. The so-called glioblastoma stem cells escape the established radio- and chemotherapies and lead to tumor recurrence in most cases. The alkaloid Shikonin with its various anti stem cell properties and the interstitial photodynamic therapy with 5-aminolevulinic acid seem to be promising new options in the therapy of glioblastoma. In this study, in vitro investigations were performed to observe the influence of Shikonin on viability, proliferation, induction of apoptosis and the capability of forming tumor spheres in U-87 MG and the primary glioblastoma cell line GB14. The combined effect with the chemotherapeutic temozolomide and photodynamic treatment on the mRNA expression of glioma specific stem cell markers and further examined intracellular protoporphyrin IX accumulation under Shikonin treatment was analyzed. Shikonin effectively inhibited the capability of forming tumor spheres and enhanced temozolomide effectiveness in the reduction of proliferation and in the induction of apoptosis. Additionally, Shikonin increased the mRNA expression of the tumor suppressing Neurofibromatosis type 1 (NF1) gene and showed modulating effects on intracellular protoporphyrin IX.

Development of a microstructured tissue phantom with adaptable optical properties for use with microscopes and fluorescence lifetime imaging systems.

OBJECTIVES: For the development and validation of diagnostic procedures based on microscopic methods, knowledge about the imaging depth and achievable resolution in tissue is crucial. This poses the challenge to develop a microscopic artificial phantom focused on the microscopic instead of the macroscopic optical tissue characteristics. METHODS: As existing artificial tissue phantoms designed for image forming systems are primarily targeted at wide field applications, they are unsuited for reaching the formulated objective. Therefore, a microscopy- and microendoscopy-suited artificial tissue phantom was developed and characterized. It is based on a microstructured glass surface coated with fluorescent beads at known depths covered by a scattering agent with modifiable optical properties. The phantom was examined with different kinds of microscopy systems in order to characterize its quality and stability and to demonstrate its usefulness for instrument comparison, for example, regarding structural as well as fluorescence lifetime analysis. RESULTS: The analysis of the manufactured microstructured glass surfaces showed high regularity in their physical dimensions in accordance with the specifications. Measurements of the optical parameters of the scattering medium were consistent with simulations. The fluorescent beads coating proved to be stable for a respectable period of time (about a week). The developed artificial tissue phantom was successfully used to detect differences in image quality between a research microscope and an endoscopy based system. Plausible causes for the observed differences could be derived based on the well known microstructure of the phantom. CONCLUSIONS: The artificial tissue phantom is well suited for the intended use with microscopic and microendoscopic systems. Due to its configurable design, it can be adapted to a wide range of applications. It is especially targeted at the characterization and calibration of clinical imaging systems that often lack extensive positioning capabilities such as an intrinsic z-stage.

Development and pre-clinical test of a phosphorous-32 containing polyetheretherketone foil aiming at urethral stricture prevention by low-dose-rate brachytherapy.

Purpose: Primary or recurrent urethral stenoses are common clinical problems. The aim of this feasibility study was development and application test of a novel radioactive catheter for potential use in low-dose-rate (LDR) brachytherapy to prevent urethral stenosis. Material and methods: A beta radiation emitting phosphorous-32 (32P)-foil was developed and integrated in indwelling catheter, which is usually inserted after surgical intervention in the urethra. Activity and dose distribution were measured after neutron activation of the phosphorus-31 (31P)-foil component with scintillation techniques as well as radiochromic films, and compared to MC simulations. Practicability and radiation safety of this new applicator were tested on male rabbits, which, before catheter application, had undergone a new method of stricture induction by radial laser light irradiation. Results: Measured dose distributions of catheters with 32P-foils were found to be in good agreement with MC simulations. Wash-out tests confirmed the radioactive catheter setup to be inside permitted limits of a sealed source. Strictures could be induced by laser light in all animals, surgically treated by slitting and irradiation with a 7-day dose of 15 Gy or 30 Gy, without adverse effects of radiation during a 4-week observation time. Conclusions: This proof-of-concept study presents a safe and technically simple approach to LDR brachytherapy intending to prevent urethral stenosis. The prescribed irradiation dose can be administered in a reproducible and precise manner using a urethral catheter as a carrier of beta radiating foil. The study duration of 63 days was too short to make statistically significant stricture-related conclusions. This approach may be considered for similar problems in other hollow organs and in cases regarding superficial hyper-proliferation.

Clinical Evaluation of Single-Use, Fiber-Optic, and Digital Ureterorenoscopes in the Treatment of Kidney Stones.

INTRODUCTION: Indication of ureteroscopy for the treatment of urolithiasis has expanded immensely over the last decade. Fiber-optic and digital reusable instruments present the standard in clinical practice, but various newly available single-use devices might offer an exciting alternative. To date, the evidence is limited to clinical evaluation and efficacy of single-use ureteroscopes (URS) compared to standard instruments. Therefore, we evaluate a single-use instrument's clinical characteristics and efficacy in direct comparison with a fiber-optic and digital device. METHODS: A prospective study was conducted for patients undergoing endoscopic therapy for urolithiasis at a tertiary care center. We evaluated the different instruments' clinical performance in categories of visibility, the stability of visibility, irrigation flow, and surgeon's satisfaction. Statistical analyses were performed by SPSS using the Chi-Quadrat and Kruskal-Wallis test. A p value of p ≤ 0.05 was defined as statistically significant. RESULTS: A total number of 77 patients were included and distributed as follows: 35 (46.7%) single-use, 19 (25.3%) digital, and 23 (28%) fiber-optic URS. Patients' characteristics were homogenous over the three cohorts in sex, stone amount, and localization. The stone-free rate was equal in all three cohorts (p = 0.31). We identify stability of visibility, irrigation flow, and satisfaction were equal in all cohorts (p = 0.73; p = 0.20; p = 0.20). We report a significant difference in visibility, with 100% rated excellent in the digital URS group (p = 0.028). DISCUSSION/CONCLUSIONS: Single-use URS achieve comparable clinical outcomes with equal stone-free rates in direct comparison with fiber-optic and digital reusable instruments. Accordingly, single-use devices present an adequate alternative for endoscopic therapy of urolithiasis.

Homogeneously Emitting, Mechanically Stable, and Efficient fs-Laser-Machined Fiber Diffusers for Medical Applications.

BACKGROUND AND OBJECTIVES: Light delivery is an essential part of therapy forms like photodynamic therapy (PDT), laser-induced thermotherapy, and endovenous laser therapy. While there are approaches to the light application for all three therapies, there is no diffuser that can be used for all three approaches. This diffuser must meet the following criteria: Homogeneous radiation profile over a length of 40 mm, efficient light extraction in the diffuser area, mechanical breakage resistance as well as thermal stability when applying high power. STUDY DESIGN/MATERIALS AND METHODS: An ultrashort pulse laser was used to inscribe inhomogeneities into the core of a fused-silica fiber core while scanning the laser focus within a linear arrangement of cuboids centered around the fiber axis. The manufactured diffuser was optically and mechanically characterized and examined to determine the maximum power that can be applied in a tissue environment. RESULTS: Based on the analysis of all examined diffusers, the manufactured diffuser exhibits an emission efficiency ε = (81.5 ± 5.9)%, an intensity variability of (19 ± 5)% between distal and proximal diffuser end, and a minimum bending radius Rb = (15.4 ± 1.5) mm. It was taken advantage of the fact that the outer areas of the fiber core do not undergo any structural changes due to the machining and therefore do not suffer a major loss of stability. Tissue experiments revealed that a maximal power of 15 W was deliverable from the diffuser without harming the diffuser itself. CONCLUSIONS: It could be shown that a diffuser manufactured by ultrafast-laser processing can be used for low power applications as well as for high power applications. Further tests have to show whether the mechanical stability is still maintained after the application of high power in a tissue environment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Evaluation of hyperspectral imaging to quantify perfusion changes during the modified Allen test.

OBJECTIVES: To evaluate the capability of hyperspectral imaging (HSI), a contact-less and noninvasive technology, to monitor perfusion changes of the hand during a modified Allen test (MAT) and cuff occlusion test. Furthermore, the study aimed at obtaining objective perfusion parameters of the hand. METHODS: HSI of the hand was performed on 20 healthy volunteers with a commercially available HSI system during a MAT and a cuff occlusion test. Besides gathering red-green-blue (RGB) images, the perfusion parameters tissue hemoglobin index (THI), (superficial tissue) hemoglobin oxygenation (StO2), near-infrared perfusion (NIR), and tissue water index (TWI) were calculated for four different regions of interest on the hand. For the MAT, occlusion (OI; the ratio between the condition during occlusion and before occlusion) and reperfusion (RI; the ratio between the non-occlusion state and the prior occlusion state) indices were calculated for each perfusion parameter. All data were correlated to the clinical findings. RESULTS: False-color images showed visible differences between the various perfusion conditions during the MAT and cuff occlusion test. THI, StO2, and NIR behaved as expected from physiology, while TWI did not in the context of this study. During rest, mean THI, StO2, and NIR of the hand were 34 ± 2, 72 ± 9, and 61 ± 6, respectively. The RI for THI showed a roundabout threefold increase after reperfusion of both radial and ulnar artery and was thus, distinctly pronounced when compared with StO2 and NIR (~1.25). The OI was lowest for THI when compared with StO2 and NIR. CONCLUSIONS: HSI with its parameters THI, StO2, and NIR proved to be suitable to evaluate perfusion of the hand. By this, it could complement visual inspection during the MAT for evaluating the functionality of the superficial palmary arch before radial or ulnar artery harvest. The presented RI might deliver useful comparative values to detect pathological perfusion disorders at an early stage. As microcirculation monitoring is crucial for many medical issues, HSI shows potential to be used, besides further applications, in the monitoring of (free) flaps and transplants and microcirculation monitoring of critically ill patients.

Safety and efficacy of endovenous laser ablation (EVLA) using 1940 nm and radial emitting fiber: 3-year results of a prospective, non-randomized study and comparison with 1470 nm.

OBJECTIVES: To evaluate the safety, efficacy and ≥36 months outcomes of endovenous laser ablation (EVLA) by means of 1940 nm laser with radial fiber for the treatment of truncal vein insufficiency and compare the results to a historical cohort, obtained via reviewing the literature. METHODS: This prospective, non-randomized, single-center clinical study included 139 consecutive patients with 177 incompetent great saphenous (GSV, n = 135) and short saphenous veins (SSV, n = 42). The maximum laser power (Pmax. 10 W) and pullback velocity were adjusted individually (Vmax = 1 mm/s). The laser fiber was placed at the junction to the deep vein under duplex monitoring. Simultaneous phlebectomies were performed on all the patients. Regular follow up with clinical and duplex ultrasound examination (DUS) were carried out postoperatively at 1 month (1 M), 6 months (6 M), 12 months (12 M), 24 months (24 M), 36 months, and after that (≥36 M). The results were compared with three cohorts (total 616 EVLA procedures with 1470 nm laser and radial fiber) from literature (criteria: >100 procedures, follow-up of ≥2 years). RESULTS: The follow-up rate was 100%, 91%, 73%, 48%, and 23% of the truncal veins at 1, 6, 12, 24, and ≥36 M, respectively. In comparison to the literature using 1470, a lower average linear endovenous energy density (LEED) (53 vs. 77-82 J/cm) resulted in 100% (6 M) and 96.5% (24 M) occlusion rates, reduced local ecchymosis (2.2% vs. 3.2%-18.7%) and reduced average postoperative pain levels (1.3 vs. 2.18). Regarding adverse events, induration (1.1% vs. 1.8%), skin burns (0% vs. 0.45%), endovenous heat-induced thrombus propagation (EHIT) in the deep veins (2.3% vs. 1.8%) and laser-induced persistent paresthesia (2.2% vs. 0.5%-2.9%) were comparable. Recanalizations observed in this study (GSV 0, SSV 3) were asymptomatic and required no treatment. At ≥36 M reflux in the accessory veins was observed in 5% versus 10.5% of patients. Reintervention was required in none (0% vs. 21%). At >36 M, short average stump lengths of 1 cm (GSV) and 0.3 cm (SSV) were observed. CONCLUSION: EVLA with 1940 nm laser with radial emitting fiber is as safe and effective as 1470 nm laser for the treatment of truncal vein insufficiency. Lower postoperative pain, low analgesic requirements, short convalescence add to patients' comfort. EVLA with 1940 nm laser-guided by intraoperative DUS permits reproducible placement of the radial fiber at the saphenofemoral and saphenopopliteal junction, enabling further studies to assess the effect of shorter stump length on patterns and frequency of recurrence without increased risk of EHIT.

Bioenergetic Alterations of Metabolic Redox Coenzymes as NADH, FAD and FMN by Means of Fluorescence Lifetime Imaging Techniques.

Metabolic FLIM (fluorescence lifetime imaging) is used to image bioenergetic status in cells and tissue. Whereas an attribution of the fluorescence lifetime of coenzymes as an indicator for cell metabolism is mainly accepted, it is debated whether this is valid for the redox state of cells. In this regard, an innovative algorithm using the lifetime characteristics of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) to calculate the fluorescence lifetime induced redox ratio (FLIRR) has been reported so far. We extended the FLIRR approach and present new results, which includes FLIM data of the various enzymes, such as NAD(P)H, FAD, as well as flavin mononucleotide (FMN). Our algorithm uses a two-exponential fitting procedure for the NAD(P)H autofluorescence and a three-exponential fit of the flavin signal. By extending the FLIRR approach, we introduced FLIRR1 as protein-bound NAD(P)H related to protein-bound FAD, FLIRR2 as protein-bound NAD(P)H related to free (unbound) FAD and FLIRR3 as protein-bound NAD(P)H related to protein-bound FMN. We compared the significance of extended FLIRR to the metabolic index, defined as the ratio of protein-bound NAD(P)H to free NAD(P)H. The statistically significant difference for tumor and normal cells was found to be highest for FLIRR1.

Single center retrospective analysis of fifty-two prostate cancer patients with customized MR-guided transurethral ultrasound ablation (TULSA).

OBJECTIVES: MR-guided transurethral ultrasound ablation (TULSA) has primarily been investigated for whole-gland prostate ablation, even though the technology is also well-suited for partial gland treatment. The objectives were to perform a clinical service evaluation of partial to whole-gland TULSA for patients with localized prostate cancer (CaP). TULSA was also evaluated as a combined therapy for a subset of patients presenting with both cancer and concurrent benign prostate hyperplasia (BPH). SUBJECTS AND METHODS: This retrospective, consecutive clinical service evaluation included men with histopathologically-confirmed CaP who underwent TULSA either as primary or salvage treatment. The planned ablation was dependent on the individual tumor characteristics, concurrent BPH and patient preferences. The Clavien-Dindo classification was used to record complications. Surgeon-assessed functional outcomes were reported. Early treatment success was defined by negative multiparametric MRI (mpMRI) and lack of prostate specific antigen (PSA) recurrence. RESULTS: Fifty-two consecutive patients (47 treatment-naïve and 5 salvage) were included, with median follow-up of sixteen months and a max of thirty-six months. Baseline median (IQR) age and PSA were 67 years (63-76) and 8.0 ng/ml (5.2-13), respectively. Two Grade IIIa adverse events were observed, with no bowel-related complications. For urinary continence outcomes, 1 patient worsened to 1 pad per day. All patients who were previously potent maintained erectile potency. Of the patient subgroup also seeking treatment for BPH, 83% reported symptom improvement. Median (IQR) PSA nadir after primary treatment was 1.1 ng/ml (0.5-2.1). Early treatment success was 88%. Nine patients underwent a single repeat TULSA. CONCLUSION: Customized prostate ablation with TULSA offers flexible ablation according to patients' disease characteristics and treatment expectations, providing favorable safety and promising early MRI and PSA results. TULSA is a feasible combination therapy for patients with both cancer and concurrent BPH.

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences.

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4-87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)-isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)-for their second, 9 (20.5%)-for the third or further recurrence. The median iPDT target volume was 3.34 cm3 (range, 0.50-22.8 cm3). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4-9.8) months and the median PRS was 13.0 (95% CI, 9.2-16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.