Corrigendum to "Assessing pripherally inserted central catheter tip location in multiple postures: A case report" [Asia-Pacific J Oncol Nurs 10 (2023) 100238].

[This corrects the article DOI: 10.1016/j.apjon.2023.100238.].

Assessing pripherally inserted central catheter tip location in multiple postures: A case report.

This report presents a case involving a 21-year-old male patient with acute promyelocytic leukemia, where the peripherally inserted central catheter (PICC) tip location was diagnosed differently using ultrasound and computed tomography. The PICC was inserted into the left upper arm via the basilic vein. Echocardiography performed in the left lateral recumbent position suggested the PICC tip to be in the right atrium, deepest at the level of the tricuspid annulus. However, trans-catheter contrast-enhanced echocardiography, performed with a different posture involving left shoulder abduction and slight external rotation, revealed the tip to be at the cavo-atrial junction. Additionally, chest computed tomography, conducted in the supine position with raised arms, indicated the tip to be located at the upper one-third of the superior vena cava. These contradictory diagnoses can be attributed to the use of different body postures during the assessments. Considering the clinical efficacy and safety, it is crucial to fully consider the influence of multiple postures on PICC tip location during placement and determination. We recommend incorporating at least two opposite extreme daily postures to assess the nearest and farthest positions of the tip, ensuring effective and safe PICC placement and reducing the risk of complications.

The effectiveness of portable ultrasound-guided resuscitative endovascular balloon occlusion of the aorta for stopping iliac artery hemorrhage during first aid pre-hospital: a randomized control animal trial.

PURPOSE: This study aimed at to comparing the effectiveness of portable ultrasound guided REBOA vs. traditional manual extracorporeal compression in stopping iliac artery hemostasis. METHODS: Twelve swine were included in this study (treatment group vs. control group, 6:6). A biopsy device was used to create an iliac artery rupture and hemorrhage in each swine. After 30 s of bleeding, the treatment group received REBOA under the guidance of ultrasound, whereas the control group received traditional manual extracorporeal compression. General physiological conditions were recorded at 0 s (baseline, T1), 30 s (initiation of therapies to stop bleeding, T2), 10 min (T3) and 30 min (T4) after bleeding. Intraperitoneal and retroperitoneal hemorrhage and specimens of iliac artery were collected after all swine were euthanized. RESULTS: One swine was excluded because of accidental death not related to the experiment; thus, 11 swine were analyzed in this study. The general physiological characteristics of the two groups showed no difference at T1. Hemorrhagic shock occurred in both groups. After the hemostatic procedure was performed, systolic pressure, diastolic pressure and heart rate first increased significantly between T2 and T3, and then became stable between T3 and T4; these indicators in the control group deteriorated over time. The total blood loss in the treatment group (1245.23 ± 190.07 g) was much significantly less than that in the control group (2605.63 ± 291.67 g) with p < 0.001. CONCLUSIONS: Performing REBOA under the guidance of portable ultrasound is an effective way to stop bleeding. It suggests a potential alternative method for iliac artery hemostasis in the pre-hospital setting.

Inverse association between periumbilical fat and longevity mediated by complement C3 and cardiac structure.

Although abdominal obesity plays a fundamental role in the onset of immune and inflammatory reactions leading to cardiac abnormalities and premature mortality, the potential association between periumbilical fat and longevity mediated by the antibody-complement system and/or cardiac structure and function remains unclear. To address this issue, we collected biochemical and morphological data from 419 centenarians and 491 non-centenarian oldest-old individuals from the China Hainan Centenarian Cohort Study. Centenarians had lower waist circumference (WC), periumbilical fat thickness (PFT), serum complement C3 level, right atrium end-systolic diameter (RAESD), left atrium end-systolic diameter (LAESD), and left ventricular end-diastolic diameter (LVEDD) than non-centenarians (P<0.05 for all comparisons). WC, PFT, complement C3 levels, RAESD, LAESD, and LVEDD were inversely associated with centenarians (P<0.05 for all variables). Complement C3 level, LAESD, and LVEDD were positively associated with PFT and WC (P<0.05 for all variables). RAESD was positively associated with WC and complement C3 level (P<0.05 for both variables). Centenarians had less periumbilical fat, a weaker complement system, and smaller cardiac structure than non-centenarians. Importantly, periumbilical fat was inversely associated with longevity mediated by complement C3 and cardiac structure. This study suggests that successful aging can be promoted by increased efforts to prevent abdominal obesity.

Pilot Study of Robot-Assisted Teleultrasound Based on 5G Network: A New Feasible Strategy for Early Imaging Assessment During COVID-19 Pandemic.

Early diagnosis is critical for the prevention and control of the coronavirus disease 2019 (COVID-19). We attempted to apply a protocol using teleultrasound, which is supported by the 5G network, to explore the feasibility of solving the problem of early imaging assessment of COVID-19. Four male patients with confirmed or suspected COVID-19 were hospitalized in isolation wards in two different cities. Ultrasound specialists, located in two other different cities, carried out the robot-assisted teleultrasound and remote consultation in order to settle the problem of early cardiopulmonary evaluation. Lung ultrasound, brief echocardiography, and blood volume assessment were performed. Whenever difficulties of remote manipulation and diagnosis occurred, the alternative examination was repeated by a specialist from another city, and in sequence, remote consultation was conducted immediately to meet the consensus. The ultrasound specialists successfully completed the telerobotic ultrasound. Lung ultrasound indicated signs of pneumonia with varying degrees in all cases and mild pleural effusion in one case. No abnormalities of cardiac structure and function and blood volume were detected. Remote consultation on the issue of manipulation practice, and the diagnosis in one case was conducted. The cardiopulmonary information was delivered to the frontline clinicians immediately for further treatment. The practice of teleultrasound protocol makes early diagnosis and repeated assessment available in the isolation ward. Ultrasound specialists can be protected from infection, and personal protective equipment can be spared. Quality control can be ensured by remote consultations among doctors. This protocol is worth consideration as a feasible strategy for early imaging assessment in the COVID-19 pandemic.

Contrast Transthoracic Echocardiography Using 50% Glucose as a Contrast Agent for Screening of a Patent Foramen Ovale.

A patent foramen ovale (PFO) is considered a risk factor for neurologic events. The goal of the study described here was to assess the feasibility, advantages, diagnostic sensitivity and accuracy of contrast transthoracic echocardiography examination (cTTE) using 50% glucose as a contrast agent in comparison with the use of agitated saline as contrast to screen for PFO. In our study, we found that the peak time, effective duration and duration of microbubbles produced by 50% glucose were all longer than those produced by the physiologic saline. The sensitivities for detection of PFO with cTTE using physiologic saline and 50% glucose as contrast were 83% (20/24) and 100% (24/24), respectively. TEE suggested a PFO in 24 patients in two groups. Use of 50% glucose as a contrast agent in cTTE examination enables ultrasound technicians to easily observe the right-to-left shunt across the PFO. However, the sensitivities for detection of PFO with cTTE using 50% glucose did not statistically significantly differ from those for physiologic saline.

Thyroid nodules in centenarians: prevalence and relationship to lifestyle characteristics and dietary habits.

BACKGROUND: Thyroid nodules (TNs) are common thyroid lesions in older population. Few studies have focused on the prevalence of TNs and their relationship to lifestyle characteristics and dietary habits in centenarians. The current study aimed at determining the prevalence of TNs in Chinese centenarians by using high-resolution ultrasound (US) equipment and at investigating its relationship to lifestyle characteristics and dietary habits. PARTICIPANTS AND METHODS: The current study was part of the China Hainan Centenarian Cohort Study that was conducted in Hainan, an iodine-sufficient region in People's Republic of China. A total of 874 permanent residents aged ≥100 years (mean age =102.8±2.8 years) without any missing data were included in the analysis. RESULTS: Among the participants, 649 of them were detected at least one TN under the US examinations. The overall prevalence rate of TNs was 74.3%. The prevalence of TNs was higher in participants who were women, had hypertension, had diabetes, and were underweight compared with their counterparts. Multivariate logistic regression analyses showed that being female, hypertensive, and diabetic; betel quid consumption; and red meat consumption were independent risk factors, while being underweight and nut consumption were independent protective factors for TNs. CONCLUSION: Our findings indicate that the presence of TNs was highly prevalent in Chinese centenarians, particularly in women. In addition to gender, having hypertension, having diabetes, and being underweight, the presence of TNs was independently associated with betel quid, red meat, and nut consumption. Further prospective studies are warranted to verify these associations in populations from different age strata, races, cultures, and iodine supplementation.

Disruption of Prostate Microvasculature by Combining Microbubble-Enhanced Ultrasound and Prothrombin.

Previous studies have shown a unique method to disrupt tumor vasculature using pulsed, high-pressure amplitude therapeutic ultrasound combined with microbubbles. In this study, we attempted to destroy the prostate vasculature of canine prostates using microbubble-enhanced ultrasound (MEUS) and prothrombin. The prostates of 43 male mongrel canines were surgically exposed. Twenty-two prostates were treated using MEUS (n = 11) or MEUS and prothrombin (PMEUS, n = 11). The other 21 prostates, which were treated using microbubbles (n = 7), ultrasound (n = 7) or prothrombin (n = 7) only, served as the controls. Prothrombin was intravenously infused at 20 IU/kg. MEUS was induced using a therapeutic ultrasound device at a peak negative pressure of 4.47 MPa and a microbubble injection. Contrast-enhanced ultrasound was performed to assess the blood perfusion of the prostates. Then, the prostate tissue was harvested immediately after treatment and at 48 hours later for pathological examination. The contrast-enhanced ultrasound peak value of the prostate decreased significantly from 36.2 ± 5.6 to 27.1 ± 6.3 after treatment in the PMEUS group, but it remained unchanged in the other groups. Histological examination found severe microvascular rupture, hemorrhage and thrombosis in both MEUS- and PMEUS-treated prostates immediately after treatment, while disruption in the PMEUS group was more severe than in the MEUS group. Forty-eight hours after treatment, massive necrosis and infiltration of white blood cells occurred in the PMEUS group. This study demonstrated that PMEUS disrupted the normal microvasculature of canine prostates and induced massive necrosis. PMEUS could potentially become a new noninvasive method used for the treatment of benign prostatic hyperplasia.

Enhanced Homing of CXCR-4 Modified Bone Marrow-Derived Mesenchymal Stem Cells to Acute Kidney Injury Tissues by Micro-Bubble-Mediated Ultrasound Exposure.

Although the curative effects of bone marrow stromal cells (BMSCs) for acute kidney injury (AKI) have been recognized, their in vivo reparative capability is limited by the low levels of targeted homing and retention of intravenous injected cells. Stromal cell-derived factor-1 (SDF-1) plays an important role in stem cell homing and retention through interaction with its specific functional receptor, CXCR4, which is presumably related to the poor homing in AKI therapy. However, most of the functional CXCR4 chemokine receptors are lost upon in vitro culturing. Ultrasound-targeted micro-bubble destruction (UTMD) has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve BMSC homing to AKI kidneys, we isolated and cultured rat BMSCs to third passage and enhanced CXCR-4 transfection efficiency in vitro by applying UTMD and polyethylenimine. Transwell migration assay showed that the migration ability of CXCR4-modified BMSCs was nine-fold higher than controls. Then, mercuric chloride-induced AKI rats were injected with transfected BMSCs through their tail veins. We showed that enhanced homing and retention of BMSCs were observed in the CXCR-4 modified group compared with other groups at 1, 2 and 3 d post-treatment. Collectively, our data indicated that UTMD was an effective method to increase BMSCs' engraftment to AKI kidney tissues by increasing CXCR-4 expression.

Effects of diagnostic ultrasound-targeted microbubble destruction on the homing ability of bone marrow stromal cells to the kidney parenchyma.

OBJECTIVES: Bone marrow stromal cells (BMSC) transplantation proves successful in treating kidney disease and injury in many studies. However, their reparative capacity is limited by the poor homing ability in vivo, which is decided mainly by the local expression of chemoattractants. Our study explored the mechanical effects of ultrasound targeted microbubble destruction (UTMD) on BMSCs homing ability in treated kidney tissues. METHODS: Rats were injected with red fluorescent protein (RFP)-labelled BMSCs and sonicated with microbubble-mediated ultrasound. Then, we tested kidney micro-environment changes induced and their influence on stem cell homing ability. RESULTS: The results showed that the mechanical effects of UTMD would increase local and transient levels of chemoattractants (i.e. cytokines, integrins and growth factors) in targeted kidney tissues. Transmission electron microscopy showed that vascular endothelial cell was discontinuous in the UTMD group post-treatment, becoming smooth 72 h later. Confocal laser scanning microscopy and RT-PCR showed up to eight times more stem cells in the peritubular regions of experimental kidneys on days 1 and 3 post-treatment compared with the contralateral kidney. CONCLUSIONS: These results confirmed that renal micro-environment changes caused by appropriate UTMD may promote BMSC homing ability toward treated kidney tissues without renal toxicity and cell damage. KEY POINTS: • This experiment showed a feasible strategy in promoting stem cell homing ability. • The treatment uses diagnostic ultrasound during enhancement with IV microbubbles. • A suitable micro-environment was important for targeted stem cell homing and retention. • The method is effective for stem cell homing to kidney diseases. • More work is required with larger animals before potential human trials.

Enhanced Homing Ability and Retention of Bone Marrow Stromal Cells to Diabetic Nephropathy by Microbubble-Mediated Diagnostic Ultrasound Irradiation.

Bone marrow stromal cell (BMSC) transplantation can successfully treat diabetic nephropathy (DN), but the lack of a specific homing place for intravenously injected cells limits the effective implementation of stem cell therapies. The migration and survival of transplanted BMSCs are determined by inflammatory reactions in the local kidney micro-environment. We tested the hypothesis that microbubble-mediated diagnostic ultrasound irradiation could provide a suitable micro-environment for BMSC delivery and retention in DN therapy. In this study, red fluorescent protein-labeled BMSCs were administered combined with microbubbles to streptozotocin-induced DN rats 4 wk after diabetes onset. We observed enhanced BMSC homing and retention in microbubble-mediated diagnostic ultrasound-irradiated kidneys compared with the contralateral kidneys on days 1 and 3 post-treatment. The results from immunohistochemical analysis, Western blot and enzyme-linked immunosorbent assay indicated that the local and transient expression of various chemo-attractants (i.e., cytokines, integrins and trophic factors) found to promote BMSC homing was much higher than observed in non-treated kidneys. The local capillary endothelium rupture observed by transmission electron microscopy may account for local micro-environment changes. Histopathologic analysis revealed no signs of kidney damage. These results confirmed that renal micro-environment changes caused by appropriate microbubble-mediated diagnostic ultrasound irradiation may promote BMSC homing ability to the diabetic kidney without renal toxicity and cell damage. This non-invasive and effective technique may be a promising method for BMSC transplantation therapy.

Ultrasound-Targeted Microbubble Destruction Improves the Migration and Homing of Mesenchymal Stem Cells after Myocardial Infarction by Upregulating SDF-1/CXCR4: A Pilot Study.

Mesenchymal stem cell (MSC) therapy shows considerable promise for the treatment of myocardial infarction (MI). However, the inefficient migration and homing of MSCs after systemic infusion have limited their therapeutic applications. Ultrasound-targeted microbubble destruction (UTMD) has proven to be promising to improve the homing of MSCs to the ischemic myocardium, but the concrete mechanism remains unclear. We hypothesize that UTMD promotes MSC homing by upregulating SDF-1/CXCR4, and this study was aimed at exploring this potential mechanism. We analyzed SDF-1/CXCR4 expression after UTMD treatment in vitro and in vivo and counted the number of homing MSCs in MI areas. The in vitro results demonstrated that UTMD not only led to elevated secretion of SDF-1 but also resulted in an increased proportion of MSCs that expressed surface CXCR4. The in vivo findings show an increase in the number of homing MSCs and higher expression of SDF-1/CXCR4 in the UTMD combined with MSCs infusion group compared to other groups. In conclusion, UTMD can increase SDF-1 expression in the ischemic myocardium and upregulate the expression of surface CXCR4 on MSCs, which provides a molecular mechanism for the homing of MSCs assisted by UTMD via SDF-1/CXCR4 axis.

Hypoxic Preconditioning Combined with Microbubble-Mediated Ultrasound Effect on MSCs Promote SDF-1/CXCR4 Expression and its Migration Ability: An In Vitro Study.

Our objective is to investigate the promoting effect of hypoxic preconditioning combined with microbubble (MB)-mediated ultrasound (US) on the SDF-1/CXCR4 expression and the migration ability of mesenchymal stem cells (MSCs). Based on the uniform design, the parameters of MB-mediated US, such as the total treatment time (T), acoustic intensity (Q), and the dosage of MBs, were optimized firstly. The results were assessed by regression analysis. Using the optimum irradiation parameters, the concentration of SDF-1 in the supernatant, the expression levels of membrane CXCR4, and the cell viability of hypoxic MSCs or normoxic MSCs were compared. The in vitro transwell migration assay was performed as well. The best combination of parameters for more SDF-1 secretion and less MSCs death was T = 30 s, A = 0.6 W/cm(2), and MB = 10(6)/ml. After 24 h of hypoxic preconditioning, the expression of SDF-1 and surface CXCR4 was increased in the hypoxic MSC group as compared to the normoxic MSC group (P < 0.05). On the basis of that, MB-mediated US could further upregulate the expression of SDF-1/CXCR4 with the optimum parameters (P < 0.05), while the cell viability was only decreased by about 9-10 % compared to the untreated groups. The number of successfully migrated cells was also the largest in the hypoxic preconditioning combined with MB-mediated US group than all the other groups. The results obtained indicate the combination of hypoxic preconditioning, and MB-mediated US can upregulate the SDF-1/CXCR4 expression and improve the migration ability in MSCs.

Transfection of CXCR-4 using microbubble-mediated ultrasound irradiation and liposomes improves the migratory ability of bone marrow stromal cells.

Bone marrow stromal cells (BMSCs) have proven useful for the treatment of various human diseases and injuries. However, their reparative capacity is limited by their poor migration and homing ability, which are primarily dependent on the SDF-1/CXCR4 axis. Most subcultured BMSCs lack CXCR4 receptor expression on the cell surface and exhibit impaired migratory capacity. To increase responsiveness to SDF-1 and promote cell migration and survival of cultured BMSCs, we used a combination of ultrasound-targeted microbubble destruction (UTMD) and liposomes to increase CXCR4 expression in vitro. We isolated and cultured rat BMSCs to their third passage and transduced them with recombinant plasmid pDsRed-CXCR4 using microbubble-mediated ultrasound irradiation and liposomes. Compared to some viral vectors, the method we employed here resulted in significantly better transfection efficiency, CXCR4 expression, and technical reproducibility. The benefits of this approach are likely due to the combination of "sonoporation" caused by shockwaves and microjet flow resulting from UTMD-generated cavitation. Following transfection, we performed a transwell migration assay and found that the migration ability of CXCR4-modified BMSCs was 9-fold higher than controls. The methods we describe here provide an effective, safe, non-viral means to achieve high levels of CXCR4 expression. This is associated with enhanced migration of subcultured BMSCs and may be useful for clinical application as well.

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.

Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

Effects of ultrasound-combined microbubbles on hippocampal AchE fibers in rats.

OBJECTIVE: To investigate the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholinesterase (AchE) fibers in rats. METHODS: According to random digits table, 60 SD rats were divided into two groups, marrow stromal cells (MSCs) intracranial transplantation group and MSCs intracranial transplantation + ultrasonic microbubbles group. Marrow stromal cells were cultivated and isolated in vitro; 12 weeks after transplantation, spatial learning and memorizing abilities of rats were assessed by Morris water maze; AchE staining method was used to observe changes in density and appearance of AchE staining positive fibers in hippocampal CA1 region. RESULTS: There was a significant increase in spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group. Hippocampal AchE staining suggested an increase in the density of AchE staining positive fibers in MSCs intracranial transplantation group; the fibers were regular, intact and dense. Density of hippocampal AchE positive fibers was negatively correlated with the escape latent period and was positively correlated with percentage of the time needed to cross each platform quadrant. CONCLUSIONS: Better promotion of spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group may be related with the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholine fibers.

Ultrasound-microbubble transplantation of bone marrow stromal cells improves neurological function after forebrain ischemia in adult mice.

In this study, bone marrow stromal cells (MSCs) were transplanted into the brain of adult rats after forebrain ischemia induced by 4VO. SD rats (n = 60) were randomly divided into three groups: (I) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region using ultrasound-microbubble method, (2) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region (n = 20), and (3) 4VO alone (n = 20). Rats were sacrificed 28 days after treatment. Neurological functions of rats were evaluated by Morris Water Maze. The current findings suggest that the ultrasound microbubble transplanted MSCs survived in the ischemic brain and significantly improved functional recovery of adult rats compared to regular transplantation.

Impact of microbubble-enhanced ultrasound on liver ethanol ablation.

Ethanol ablation (EA) is a safe and effective method for treating small liver cancer. However, the ethanol is rapidly washed out by blood perfusion, preventing its accumulation within tumors. Microbubble-enhanced ultrasound (MEUS) is capable of disrupting tumor and liver circulation. We hypothesized that this disruption could be used to enhance EA of normal liver tissue. We treated surgically exposed rabbit liver with a combination of MEUS and EA. The controls were treated with only MEUS or 0.05 mL EA. MEUS treatment was administered with a high-pressure-amplitude, pulsed therapeutic ultrasound device and intra-venous injection of microbubbles. Therapeutic ultrasound was delivered at an acoustic pressure of 4.3 MPa and a duty cycle of 0.22%. Contrast-enhanced ultrasound was performed to estimate liver blood perfusion. Livers were harvested for necrotic volume measurements 48 h after treatment. Contrast-enhanced ultrasound demonstrated that liver perfusion was temporally arrested, with a significant peak intensity decline from -46.9 ± 3.8 to -64.0 ± 3.3 dB, after MEUS treatment. The mean volume ablated in MEUS + EA-treated livers (3.3 ± 2.3 cm(3)) was more than 10 times larger than that in livers treated only with EA (0.3 ± 0.2 cm(3)). The volume of liver ablated by MEUS treatment alone was minor, scattered and immeasurable. These results indicate that MEUS disruption of the liver circulation can greatly promote EA of liver.

Disruption of splenic circulation using microbubble-enhanced ultrasound and prothrombin: a preliminary study.

The spleen is a solid organ in which splenomegaly frequently develops and to which abdominal blunt trauma occurs. In this study, we demonstrated the potential therapeutic effect of microbubble-enhanced ultrasound (MEUS) combined with prothrombin to disrupt splenic circulation. A high-pressure-amplitude therapeutic ultrasound (TUS) device was used to treat 36 surgically exposed spleens in healthy New Zealand rabbits. Eighteen spleens were treated with either MEUS (n = 9) or MEUS combined with prothrombin (n = 9). The other 18 spleens were treated with TUS only or sham ultrasound exposure and served as the controls. The TUS was operated at a frequency of 831 kHz and a peak negative pressure of 4.8 MPa. Prothrombin was administered intravenously at 20 IU/kg. Contrast-enhanced ultrasound (CEUS) and acoustic quantification were performed to assess splenic blood perfusion. We found significant blood perfusion slowdown and drop-off in the MEUS-treated spleens. The peak intensity dropped from 20.2 ± 2.70 dB to 11.6 ± 4.58 dB immediately after treatment. The spleens treated with the combination of MEUS and prothrombin showed consistently poor perfusion within 1 h. In histologic examination of the MEUS-treated spleens, we found significant dilatation of splenic sinuses, hemorrhage, interstitial edema and thrombosis. This study demonstrated that the vascular effects induced by microbubble-enhanced, high-pressure ultrasound can slow down or block blood perfusion in the rabbit spleen. Prothrombin helps to enhance and extend the effects for up to 1 h.

[Destruction of Walker-256 tumor vasculature by a novel ultrasound cavitation technique].

OBJECTIVE: To explore the feasibility of disrupting tumor microcirculation by the cavitation of microbubbles enhanced ultrasound (US) and analyze its pathological mechanism. METHODS: Twenty-four SD male rats with subcutaneously transplanted Walker-256 tumor were divided into 3 groups, i.e. ultrasound plus microbubbles group (US + MB), US group and sham group. Pulsed US was delivered to tumor for 3 minutes during an intravenous infusion of microbubbles at 0.2 ml/kg in the US + MB group. The control groups received only the US exposure or the MB injection. Tumor perfusion was visualized with contrast enhanced ultrasound before and 0 min after treatment. Finally the pathological examination was performed. RESULTS: The contrast perfusion of Walker-256 tumors vanished immediately after treatment in the US + MB group and the gray scale value (GSV) decreased from 121 ± 12 (pre-treatment) to 81 ± 9 (post-treatment, P < 0.01). There was no significant difference of GSV before and after treatment in two control groups (P > 0.05). The GSV values were 112 ± 14 and 111 ± 12 pre-treatment and 113 ± 14 and 103 ± 13 post-treatment in the sham and US groups. The pathological examination showed remarkable hemorrhage, endothelial injuries, increased intercellular edema and in situ thrombosis. CONCLUSION: Microbubble-enhanced ultrasound can significantly disrupt tumor vasculature and block its circulation. And it may become a novel physical anti-angiogenetic therapy for tumor.