Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity.

Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm2. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.

Pennes' bioheat equation vs. porous media approach in computer modeling of radiofrequency tumor ablation.

The objective of this study was to compare three different heat transfer models for radiofrequency ablation of in vivo liver tissue using a cooled electrode and three different voltage levels. The comparison was between the simplest but less realistic Pennes' equation and two porous media-based models, i.e. the Local Thermal Non-Equilibrium (LTNE) equations and Local Thermal Equilibrium (LTE) equation, both modified to take into account two-phase water vaporization (tissue and blood). Different blood volume fractions in liver were considered and the blood velocity was modeled to simulate a vascular network. Governing equations with the appropriate boundary conditions were solved with Comsol Multiphysics finite-element code. The results in terms of coagulation transverse diameters and temperature distributions at the end of the application showed significant differences, especially between Pennes and the modified LTNE and LTE models. The new modified porous media-based models covered the ranges found in the few in vivo experimental studies in the literature and they were closer to the published results with similar in vivo protocol. The outcomes highlight the importance of considering the three models in the future in order to improve thermal ablation protocols and devices and adapt the model to different organs and patient profiles.

Effects of nitrite and far-red light on coagulation.

Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due to its ability to reduce platelet activation and due to the central role of platelet activation and adhesion in device thrombosis. Nitrite is a unique NO donor that reduces platelet activation in that it's activity requires the presence of red blood cells whereas NO activity of other NO donors is blunted by red blood cells. Interestingly, we have previously shown that red blood cell mediated inhibition of platelet activation by adenosine diphosophate (ADP) is dramatically enhanced by illumination with far-red light that is likely due to photolysis of red cell surface bound NO congeners. We now report the effects of nitrite, far-red light, and their combination on several measure of blood coagulation using a variety of agonists. We employed turbidity assays in platelet rich plasma, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, multiplate impedance-based platelet aggregometry, and assessment of platelet adhesion to collagen coated flow-through microslides. In all cases, the combination of far-red light and nitrite treatment decreased measures of coagulation, but in some cases mono-treatment with nitrite or light alone had no effect. Perhaps most relevant to device thrombosis, we observed that platelet adhesions was inhibited by the combination of nitrite and light treatment while nitrite alone and far-red light alone trended to decrease adhesion, but the results were mixed. These results support the potential of combined far-red light and nitrite treatment for preventing thrombosis in extra-corporeal or shallow-tissue depth devices where the far-red light can penetrate. Such a combined treatment could be advantageous due to the localized treatment afforded by far-red light illumination with minimal systemic effects. Given the role of thrombosis in COVID 19, application to treatment of patients infected with SARS Cov-2 might also be considered.

Effects of Intercept pathogen reduction treatment on extended cold storage of apheresis platelets.

BACKGROUND: Platelets pose the greatest transfusion-transmitted infectious risk among blood products. Refrigeration of platelets can mitigate bacterial contamination and extend platelet shelf life. Implementation of pathogen reduction technologies (PRTs) at blood banks has become increasingly popular to protect against emerging and reemerging infectious diseases. In this study, we sought to evaluate the effects of Intercept PRT on platelets collected on different platforms and cold-stored for up to 21 days in plasma and platelet additive solution (PAS). METHODS: Double-dose apheresis platelets were collected with use of a Trima or Amicus system into either 100% plasma or 65% InterSol PAS/35% plasma and split equally between two bags. One bag served as control, while the other received Intercept PRT treatment. Bags were stored unagitated in the cold and evaluated on Days 1, 7, 14, and 21 to assess platelet metabolism, activation, aggregation, and clot formation and retraction. RESULTS: By Day 14 of storage, lactate levels reached approximately 13 mmol/L for all samples irrespective of Intercept treatment. Mean clot firmness dropped from the 62.2- to 67.5-mm range (Day 1) to the 28.4- to 51.3-mm range (Day 21), with no differences observed between groups. Clot weights of Intercept-treated Trima/plasma samples were significantly higher than control by Day 14 of storage (P = .004), indicating a reduced clot retraction function. Intercept treatment caused a higher incidence of plasma membrane breakdown in plasma-stored platelets (P = .0013; Trima/plasma Day 14 Control vs Intercept). CONCLUSIONS: Intercept treatment of platelets and subsequent cold storage, in plasma or PAS, results in comparable platelet metabolism platelets for up to 14 days of storage but altered clotting dynamics. Pathogen-reduced platelets with an extended shelf life would be beneficial for the deployed setting and would greatly impact transfusion practice among civilian transfusion centers.

Radiation synergizes with antitumor activity of CD13-targeted tissue factor in a HT1080 xenograft model of human soft tissue sarcoma.

BACKGROUND: Truncated tissue factor (tTF) retargeted by NGR-peptides to aminopeptidase N (CD13) in tumor vasculature is effective in experimental tumor therapy. tTF-NGR induces tumor growth inhibition in a variety of human tumor xenografts of different histology. To improve on the therapeutic efficacy we have combined tTF-NGR with radiotherapy. METHODS: Serum-stimulated human umbilical vein endothelial cells (HUVEC) and human HT1080 sarcoma cells were irradiated in vitro, and upregulated early-apoptotic phosphatidylserine (PS) on the cell surface was measured by standard flow cytometry. Increase of cellular procoagulant function in relation to irradiation and PS cell surface concentration was measured in a tTF-NGR-dependent Factor X activation assay. In vivo experiments with CD-1 athymic mice bearing human HT1080 sarcoma xenotransplants were performed to test the systemic therapeutic effects of tTF-NGR on tumor growth alone or in combination with regional tumor ionizing radiotherapy. RESULTS: As shown by flow cytometry with HUVEC and HT1080 sarcoma cells in vitro, irradiation with 4 and 6 Gy in the process of apoptosis induced upregulation of PS presence on the outer surface of both cell types. Proapoptotic HUVEC and HT1080 cells both showed significantly higher procoagulant efficacy on the basis of equimolar concentrations of tTF-NGR as measured by FX activation. This effect can be reverted by masking of PS with Annexin V. HT1080 human sarcoma xenografted tumors showed shrinkage induced by combined regional radiotherapy and systemic tTF-NGR as compared to growth inhibition achieved by either of the treatment modalities alone. CONCLUSIONS: Irradiation renders tumor and tumor vascular cells procoagulant by PS upregulation on their outer surface and radiotherapy can significantly improve the therapeutic antitumor efficacy of tTF-NGR in the xenograft model used. This synergistic effect will influence design of future clinical combination studies.

Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates.

Purpose: Evaluation of the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS).Materials and methods: Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on Day 1) or repeat dose (5.0 mg/kg on Days 1 and 8), pegfilgrastim alone as a repeat dose (0.3 µg/kg on Day 1 and 8), or a combination of both agents (romiplostim 5.0 mg/kg on Day 1; pegfilgrastim 0.3 µg/kg on Days 1 and 8). Clinical outcome, hematological parameters and PK were assessed throughout the 45 d study period post-irradiation.Results: Administration of romiplostim, pegfilgrastim or the combination of both resulted in significant improvements in hematological parameters, notably prevention of severe thrombocytopenia, compared with irradiated, vehicle control-treated NHPs. The largest hematologic benefit was observed when romiplostim and pegfilgrastim were administered as a combination therapy with much greater effects on both platelet and neutrophil recovery following irradiation compared to single agents alone.Conclusions: These results indicate that romiplostim alone or in combination with pegfilgrastim is effective at improving hematological parameters in an NHP model of ARS. This study supports further study of romiplostim as a medical countermeasure to improve primary hemostasis and survival in ARS.

Carbon debris and fiber cleaving: Effects on potassium-titanyl-phosphate laser energy and chorioallantoic membrane model vessel coagulation.

OBJECTIVES/HYPOTHESIS: Photoangiolytic precision afforded by the 532-nm potassium-titanyl-phosphate (KTP) laser relies on predictable energy delivery. Inadequate energy output can cause vessel rupture, and excessive energy can cause thermal damage. The quality of the cleaved surface and carbon deposits from ablated tissue are two factors that could negatively impact fiber performance. The effects of these on energy output and blood vessel coagulation were assessed using a chorioallantoic membrane (CAM) model. STUDY DESIGN: Comparative analysis. METHODS: Laser fibers with carbon debris, optimal fiber cleaving, and suboptimal cleaving were inspected at three times magnification, and the light dispersion pattern of each fiber was rated. The average energy output from consecutive pulses through each fiber configuration was recorded. The effect of these fiber conditions on clinical efficacy was estimated by measuring vessel coagulation versus rupture in the CAM model. Repeated measures analysis of variance compared results. RESULTS: Carbon debris and suboptimal cleaving resulted in decreased energy output in comparison to optimal cleaving ([-Δ244 mJ, d = 4.31, P < .001] and [-Δ195 mJ, d = 6.04, P < .001]). Optimal cleaving resulted in immediate coagulation of vessels. Fibers with suboptimal cleaving and carbon debris had unpredictable outcomes, requiring multiple pulses for coagulation or causing vessel rupture. CONCLUSIONS: KTP laser fiber function is significantly affected by fiber tip condition. Carbon debris and suboptimal cleaving create significant attenuation of energy, which results in an unpredictable angiolytic effect, as demonstrated by increased vessel rupture in the CAM model. Optimal recleaving of KTP laser fibers restores prior energy output and predictable coagulation. Care should be taken to avoid carbon debris on laser-fiber tips and to cleave fibers properly. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2244-2248, 2019.

Endothelial Microparticles and Blood Coagulation Activation in Head and Neck Cancer Patients Undergoing Radiotherapy or Radiochemotherapy.

BACKGROUND/AIM: Endothelial microparticles (EMP) are small vesicles which are released from the endothelium and contribute to blood coagulation activation in various clinical settings. The aim of this study was to examine whether EMP influence blood coagulation activation in cancer patients during radiotherapy/radiochemotherapy (RT/RCT). MATERIALS AND METHODS: Sixteen head and neck cancer (HNC) patients undergoing RT/RCT and 10 controls were examined. EMP and thrombin-antithrombin complex (TAT) were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Tissue factor-positive EMP (TF+EMP) were defined as CD31+/CD142+/CD42b- Results: TF+EMP were significantly elevated in HNC patients before RT/RCT (T0) (1299±1154/µl), one day after RT/RCT (T1d) (1257±603/µl) and 3 months after RT/RCT (T3m) (1289±372/µl) compared to controls (688±647/µl). TF+EMP levels at T0/T1d and T0, as well as at T1d and T3m were not significantly different. TAT levels at T0 and T1d did not differ significantly but at T3m were significantly lower compared to T0 and T1d TF+EMP and TAT concentrations were not significantly correlated at T0 (r=0.058; p=0.828), T1d (r=0.373, p=0.154) and T3m (r=-0.302, p=0.204). CONCLUSION: TF+EMP may not contribute to hemostatic abnormalities in HNC patients.

Coagulation parameters in hyperthyroid cats before and after radioiodine treatment compared with healthy controls.

OBJECTIVES: The aim of the study was to describe the coagulatory state of hyperthyroid cats before and after successful radioiodine therapy (RIT) compared with healthy age-matched controls, using classical coagulation parameters and thromboelastogram (TEG) as a global assessment method. The differences in coagulation activity after RIT, depending on the thyroid hormone (normal vs low total thyroxine [T4]) state, were also evaluated. METHODS: Fifteen hyperthyroid cats and 10 healthy age-matched controls were recruited. Hyperthyroid cats that remained hyperthyroid 14 days after RIT were excluded. Haematology, biochemistry, T4, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and TEG were assessed in control cats and hyperthyroid cats before and 7 and 14 days after RIT. Two weeks after successful RIT, further comparisons were made between cats with normal T4 vs those with low T4. RESULTS: Fourteen days after successful RIT, 7/15 cats had normal T4 and 8/15 had low T4. Thrombocytosis was noted in 6/15 cats after treatment. Fibrinogen was significantly higher (P <0.001) and PT shorter (P <0.01) in the hyperthyroid cats compared with the healthy controls and these changes persisted after RIT. Persistent increases in fibrinogen, PT, TEG maximal amplitude and TEG clot rigidity, reflecting clot stability, after RIT primarily occurred in the cats with normal T4. TEG-K (time until preset amplitude of 20 mm is reached) and alpha (α) angle reflected impaired fibrin cross-linking ability prior to RIT, which significantly increased after therapy (P <0.05). CONCLUSIONS AND RELEVANCE: Based on some of the coagulation parameters, cats with hyperthyroidism showed hypercoagulable tendencies, which were mildly increased after RIT, possibly due to transient radiation-induced thyroiditis.

Immediate laser-induced hemostasis in anticoagulated rats subjected to oral soft tissue surgery: a double-blind study.

Given the growing trend towards medical indications for continuous use of anticoagulants, the number of patients on these medications continues to rise. The management of patients on oral anticoagulants requiring oral surgical procedures has aroused much controversy. Changes in an anticoagulation regimen are associated with an increased risk of thromboembolism. However, it seems logical and advantageous for the patients' health if surgery could be performed without any change to the anticoagulation therapy. In dentistry, high-power lasers have been poorly explored in this field. The hemostatic properties of high-power lasers could be helpful during oral soft tissue surgeries in anticoagulated patients. The aim of this study was to compare bleeding time in anticoagulated rats after lingual frenectomy performed with a scalpel or diode laser with bleeding time in healthy animals. Twenty-four male Wistar rats were assigned to four groups (n = 6): (CS) Control-Scalpel Surgery; (AS) Anticoagulated-Scalpel Surgery; (CL) Control-Laser (diode laser 810 nm/1.5 W) Surgery; and (AL) Anticoagulated-Laser Surgery (diode laser 810 nm/1.5 W). Warfarin administration was used to induce anticoagulation. Blood was blotted every 30 seconds with filter paper until bleeding stopped to verify bleeding time. Two blinded researchers performed the surgeries and collected the bleeding time data. Diode laser surgery led to complete hemostasis in rats during and after lingual frenectomy. Zero bleeding was assessed during surgeries and after diode laser surgeries in anticoagulated rats. Laser-induced hemostasis offered an alternative solution to the controversial issue of intraoperative and postoperative bleeding control in patients on anticoagulation therapy.

Plasma temperature during methylene blue/light treatment influences virus inactivation capacity and product quality.

BACKGROUND: Photodynamic treatment using methylene blue (MB) and visible light is in routine use for pathogen inactivation of human plasma in different countries. Ambient and product temperature conditions for human plasma during production may vary between production sites. The influence of different temperature conditions on virus inactivation capacity and plasma quality of the THERAFLEX MB-Plasma procedure was investigated in this study. METHODS: Plasma units equilibrated to 5 ± 2°C, room temperature (22 ± 2°C) or 30 ± 2°C were treated with MB/light and comparatively assessed for the inactivation capacity for three different viruses, concentrations of MB and its photoproducts, activity of various plasma coagulation factors and clotting time. RESULTS: Reduced solubility of the MB pill was observed at 5 ± 2°C. Photocatalytic degradation of MB increased with increasing temperature, and the greatest formation of photoproducts (mainly azure B) occurred at 30 ± 2°C. Inactivation of suid herpesvirus, bovine viral diarrhoea virus and vesicular stomatitis virus was significantly lower at 5 ± 2°C than at higher temperatures. MB/light treatment affected clotting times and the activity of almost all investigated plasma proteins. Factor VIII (-17·7 ± 8·3%, 22 ± 2°C) and fibrinogen (-14·4 ± 16·4%, 22 ± 2°C) showed the highest decreases in activity. Increasing plasma temperatures resulted in greater changes in clotting time and higher losses of plasma coagulation factor activity. CONCLUSIONS: Temperature conditions for THERAFLEX MB-Plasma treatment must be carefully controlled to assure uniform quality of pathogen-reduced plasma in routine production. Inactivation of cooled plasma is not recommended.

Numerical study to establish relationship between coagulation volume and target tip temperature during temperature-controlled radiofrequency ablation.

The present study aims at proposing a relationship between the coagulation volume and the target tip temperature in different tissues (viz., liver, lung, kidney, and breast) during temperature-controlled radiofrequency ablation (RFA). A 20-min RFA has been modelled using commercially available monopolar multi-tine electrode subjected to different target tip temperatures that varied from 70°C to 100°C with an increment of 10°C. A closed-loop feedback proportional-integral-derivative (PID) controller has been employed within the finite element model to perform temperature-controlled RFA. The coagulation necrosis has been attained by solving the coupled electric field distribution, the Pennes bioheat and the first-order Arrhenius rate equations within the three-dimensional finite element model of different tissues. The computational study considers temperature-dependent electrical and thermal conductivities along with the non-linear piecewise model of blood perfusion. The comparison between coagulation volume obtained from the numerical and in vitro experimental studies has been done to evaluate the aptness of the numerical models. In the present study, a total of 20 numerical simulations have been performed along with 12 experiments on tissue-mimicking phantom gel using RFA device. The study revealed a strong dependence of the coagulation volume on the pre-set target tip temperature and ablation time during RFA application. Further, the effect of target tip temperature on the applied input voltage has been studied in different tissues. Based on the results attained from the numerical study, statistical correlations between the coagulation volume and treatment time have been developed at different target tip temperatures for each tissue.

Dual-wavelength-assisted thermal hemostasis for treatment of benign prostate hyperplasia.

Laser treatment on a large size of prostate gland often encounters significant bleeding that can prolong the entire procedure and cause urinary complications. The current study investigates the feasibility of dual-wavelength (532 and 980 nm) application to achieve rapid hemostasis for 532-nm laser prostatectomy. Porcine kidney and bleeding phantom models were tested to quantify the degree of the irreversible tissue coagulation and to estimate the time for the complete hemostasis, respectively. The ex vivo kidney testing verifies that the dual-wavelength created up to 40% deeper and 25% wider coagulation regions than a single wavelength does. The bleeding phantom testing demonstrates that due to the enhanced thermal effects, the simultaneous irradiation yields the complete photocoagulation (~11 seconds) whereas 532 or 980 nm hardly stops bleeders. Numerical simulations validate that the combined optical-thermal characteristics of both the wavelengths account for the augmented thermal coagulation. The dual-wavelength-assisted coagulation can be a feasible treatment to entail the rapid hemostasis and to facilitate the laser prostatectomy in an effective manner.

Immediate laser-induced hemostasis in anticoagulated rats subjected to oral soft tissue surgery: a double-blind study

Abstract Given the growing trend towards medical indications for continuous use of anticoagulants, the number of patients on these medications continues to rise. The management of patients on oral anticoagulants requiring oral surgical procedures has aroused much controversy. Changes in an anticoagulation regimen are associated with an increased risk of thromboembolism. However, it seems logical and advantageous for the patients' health if surgery could be performed without any change to the anticoagulation therapy. In dentistry, high-power lasers have been poorly explored in this field. The hemostatic properties of high-power lasers could be helpful during oral soft tissue surgeries in anticoagulated patients. The aim of this study was to compare bleeding time in anticoagulated rats after lingual frenectomy performed with a scalpel or diode laser with bleeding time in healthy animals. Twenty-four male Wistar rats were assigned to four groups (n = 6): (CS) Control-Scalpel Surgery; (AS) Anticoagulated-Scalpel Surgery; (CL) Control-Laser (diode laser 810 nm/1.5 W) Surgery; and (AL) Anticoagulated-Laser Surgery (diode laser 810 nm/1.5 W). Warfarin administration was used to induce anticoagulation. Blood was blotted every 30 seconds with filter paper until bleeding stopped to verify bleeding time. Two blinded researchers performed the surgeries and collected the bleeding time data. Diode laser surgery led to complete hemostasis in rats during and after lingual frenectomy. Zero bleeding was assessed during surgeries and after diode laser surgeries in anticoagulated rats. Laser-induced hemostasis offered an alternative solution to the controversial issue of intraoperative and postoperative bleeding control in patients on anticoagulation therapy.

Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study.

OBJECTIVE: This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD) assisted sonolysis in both the in vitro and in vivo clots. METHODS: Therapeutic ultrasound (TUS) and lipid microbubbles (MBs) were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI) and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT) in rabbits. FAT were dyed with H&E. RESULTS: The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both P < 0.05). Clots had different pathological changes. Recanalization rates and flow scores in TUS + MB group were significantly higher than the control and TUS group. Flow scores and recanalization ratios were grade 0 in 0% of the control group, grade I in 25% of TUS group, and grade II or higher in 87.5% of TUS + MB group after 30 min sonolysis. CONCLUSIONS: Both the in vitro and in vivo sonolysis can be significantly augmented by the introduction of MBs without thrombolytic agents, which might be induced by the enhanced cavitation via UMMD.

Paediatric laser dentistry. Part 2: Hard tissue laser applications.

AIM: Erbium lasers can provide effective and minimally invasive caries removal in children. The bonding phase remains a critic step as well as the choice of material. Glass ionomers exhibits lower bonding properties in laser irradiated teeth compared to the conventional method or to composite and resin modified glass ionomer. Laser can also provide effective decontamination and coagulation effects in vital and non vital pulp therapy of primary teeth, improving and simplifying the cleaning and disinfecting steps.

Hemolinfangioma como causa de hemorragia de origen obscura evidente. Presentación de un caso / Hemolymphangioma as a cause of overt obscure gastrointestinal bleeding: a case report

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Nd:YAG laser-induced morphology change and photothermal conversion of gold nanorods with potential application in the treatment of port-wine stain.

Based on the principle of selective photothermolysis, 1064 nm Nd:YAG laser has great potential for the treatment of deeper and larger PWS. However, the clinical effectiveness is limited because of the weak absorption of blood to Nd:YAG laser. The aim of this study is to obtain the optimal irradiation conditions to effectively destroy vascular lesions with the assistance of PEG-modified gold NRs to enhance blood absorption of Nd:YAG laser. In our study, PEG-modified gold NRs were prepared by the seeded growth method. Gold NRs after exposure to Nd:YAG laser were characterized using absorption spectra and transmission electron microscope images. The tissue-like phantom containing a glass capillary with blood was prepared and exposed to Nd:YAG laser to investigate the laser energy density and pulse number required for blood coagulation before and after the addition of gold NRs in blood. The results show that the millisecond Nd:YAG laser irradiation does not result in the shape change of gold NRs. After injection of gold NRs into the bloodstream (4.60 mg/kg), the absorbance of blood at 1064 nm increased 3.9 times. The threshold energy density for the treatment of PWS decreased by 33% (from 30 to 20 J/cm2). Our findings provide an experimental guide for choosing laser parameters and gold NRs concentration for the treatment of deeper and larger PWS with the assistance of PEG-modified gold NRs in vivo in the future.

Noninvasive thrombolysis using microtripsy: a parameter study.

Histotripsy fractionates soft tissue by well-controlled acoustic cavitation using microsecond-long, high-intensity ultrasound pulses. The feasibility of using histotripsy as a noninvasive, drug-free, and image-guided thrombolysis method has been shown previously. A new histotripsy approach, termed microtripsy, has recently been investigated for the thrombolysis application to improve treatment accuracy and avoid potential vessel damage. In this study, we investigated the effects of pulse repetition frequency (PRF) on microtripsy thrombolysis. Microtripsy thrombolysis treatments using different PRFs (5, 50, and 100 Hz) and doses (20, 50, and 100 pulses) were performed on blood clots in an in vitro vessel flow model. To quantitatively evaluate the microtripsy thrombolysis effect, the location of focal cavitation, the incident rate of pre-focal cavitation on the vessel wall, the size and location of the resulting flow channel, and the generated clot debris particles were measured. The results demonstrated that focal cavitation was always well confined in the vessel lumen without contacting the vessel wall for all PRFs. Pre-focal cavitation on the front vessel wall was never observed at 5Hz PRF, but occasionally observed at PRFs of 50 Hz (1.2%) and 100 Hz (5.4%). However, the observed pre-focal cavitation was weak and did not significantly affect the focal cavitation. Results further demonstrated that, although the extent of clot fractionation per pulse was the highest at 5 Hz PRF at the beginning of treatment (<20 pulses), 100 Hz PRF generated the largest flow channels with a much shorter treatment time. Finally, results showed fewer large debris particles were generated at a higher PRF. Overall, the results of this study suggest that a higher PRF (50 or 100 Hz) may be a better choice for microtripsy thrombolysis to use clinically due to the larger resulting flow channel, shorter treatment time, and smaller debris particles.

Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode.

Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.