Contrast-enhanced US for the Interventional Radiologist: Current and Emerging Applications.

US is a powerful and nearly ubiquitous tool in the practice of interventional radiology. Use of contrast-enhanced US (CEUS) has gained traction in diagnostic imaging given the recent approval by the U.S. Food and Drug Administration (FDA) of microbubble contrast agents for use in the liver, such as sulfur hexafluoride lipid-type A microspheres. Adoption of CEUS by interventional radiologists can enhance not only procedure guidance but also preprocedure patient evaluation and assessment of treatment response across a wide spectrum of oncologic, vascular, and nonvascular procedures. In addition, the unique physical properties of microbubble contrast agents make them amenable as therapeutic vehicles in themselves, which can lay a foundation for future therapeutic innovations in the field in drug delivery, thrombolysis, and vascular flow augmentation. The purpose of this article is to provide an introduction to and overview of CEUS aimed at the interventional radiologist, highlighting its role before, during, and after frequently practiced oncologic and vascular interventions such as biopsy, ablation, transarterial chemoembolization, detection and control of hemorrhage, evaluation of transjugular intrahepatic portosystemic shunts (TIPS), detection of aortic endograft endoleak, thrombus detection and evaluation, evaluation of vascular malformations, lymphangiography, and percutaneous drain placement. Basic physical principles of CEUS, injection and scanning protocols, and logistics for practice implementation are also discussed. Early adoption of CEUS by the interventional radiology community will ensure rapid innovation of the field and development of future novel procedures. Online supplemental material is available for this article. ©RSNA, 2020.

Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score-Matched Study.

PURPOSE: To compare segmental radioembolization with segmental chemoembolization for localized, unresectable hepatocellular carcinoma (HCC) not amenable to ablation. MATERIALS AND METHODS: In a single-center, retrospective study (2010-2015), 101 patients with 132 tumors underwent segmental radioembolization, and 77 patients with 103 tumors underwent segmental doxorubicin-based drug-eluting embolic or conventional chemoembolization. Patients receiving chemoembolization had worse performance status (Eastern Cooperative Oncology Group 0, 76% vs 56%; P = .003) and Child-Pugh class (class A, 65% vs 52%; P = .053); patients receiving radioembolization had larger tumors (32 mm vs 26 mm; P < .001), more infiltrative tumors (23% vs 9%; P = .01), and more vascular invasion (18% vs 1%; P < .001). Toxicity, tumor response, tumor progression, and survival were compared. Analyses were weighted using a propensity score (PS). RESULTS: Toxicity rates were low, without significant differences. Index and overall complete response rates were 92% and 84% for radioembolization and 74% and 58% for chemoembolization (P = .001 and P < .001). Index tumor progression at 1 and 2 years was 8% and 15% in the radioembolization group and 30% and 42% in the chemoembolization group (P < .001). Median progression-free and overall survival were 564 days and 1,198 days in the radioembolization group and 271 days and 1,043 days in the chemoembolization group (PS-adjusted P = .002 and P = .35; censored by transplant PS-adjusted P < .001 and P = .064). CONCLUSIONS: Segmental radioembolization demonstrates higher complete response rates and local tumor control compared with segmental chemoembolization for HCC, with similar toxicity profiles. Superior progression-free survival was achieved.

Yttrium-90 Radioembolization as a Salvage Treatment following Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To determine safety and efficacy of yttrium-90 ((90)Y) transarterial radioembolization (TARE) in patients who have undergone chemoembolization for hepatocellular carcinoma. MATERIALS AND METHODS: A retrospective study identified 40 patients (median age 61 y; range, 44-84 y) who underwent (90)Y mapping angiography and had undergone ≥ one prior chemoembolizations. There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1-11.6 cm). The most common indications for changing to TARE were tumor progression (35/40; 86%) and development of portal vein thrombus (15/40; 37.5%). RESULTS: Of 40 patients, 29 (72.5%) underwent TARE; the most common reasons for not undergoing TARE were attenuated hepatic arteries (5/11), high pulmonary shunt (4/11), and poor arterial flow (2/11). Patients who underwent ≤ 4 chemoembolizations to the TARE target tended to be more likely to undergo TARE after mapping than patients who had > 4 chemoembolizations (P = .056). Most common grade ≥ 3 toxicities were fatigue (9/29; 31%) and biochemical alterations (bilirubin [3/29; 10.3%], albumin [4/29; 13.8%], aspartate aminotransferase [5/29; 17.2%]). Of 27 patients treated with TARE with follow-up, responses were 11 (41%) complete response, 5 (19%) partial response, 2 (7%) stable disease, and 9 (33%) progressive disease. Median progression-free survival and overall survival were 90 days and 257 days. CONCLUSIONS: TARE is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone > 4 chemoembolizations to the (90)Y target, feasibility of TARE tends to be decreased.

Superselective yttrium-90 radioembolization for hepatocellular carcinoma yields high response rates with minimal toxicity.

PURPOSE: To assess the safety and efficacy of yttrium-90 ((90)Y) radioembolization when performed in a superselective fashion for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 20 patients with unresectable HCC. Median Model for End-Stage Liver Disease score was 10.5 (range, 6-25), with 8 of 20 patients (40%) classified Child-Pugh class B and 1 of 20 patients (5%) classified class C cirrhosis. Segmental tumor-associated portal vein thrombus was present in 12 patients (60%), and a transjugular intrahepatic portosystemic shunt was present in 4 patients (20%). Median tumor diameter was 3.9 cm (range, 2.5-7.1 cm). All patients underwent superselective (90)Y radioembolization targeted to a single liver segment using glass microspheres. RESULTS: Median dose to the treated segment was 254 Gy, and median dose to the tumor was 536 Gy. No grade 3-4 hepatotoxicity occurred. The most common clinical toxicities were fatigue (30%), abdominal pain (10%), and postembolization syndrome (10%). Follow-up imaging demonstrated complete European Association for the Study of the Liver response of the index tumor in 19 of 20 patients (95%) and stable disease in 1 of 20 patients (5%). In patients with complete response, local tumor recurrence rate was 5.3% (1 of 19 patients). Median time to progression was 319 days. Overall survival was 90% (18 of 20 patients) with a median follow-up period of 275 days (range, 32-677 d). CONCLUSIONS: When performed in a segmental fashion, (90)Y radioembolization demonstrates high response rates and low local tumor recurrence rates. Complete imaging response can be achieved in patients with locally aggressive disease. This study demonstrates no clinically significant hepatotoxicity, despite moderate liver dysfunction in many patients.

Ultrasound backscatter microscopy for imaging of oral carcinoma.

OBJECTIVES: Ultrasound backscatter microscopy (UBM), or ultrasound biomicroscopy, is a noninvasive, label-free, and ionizing radiation-free technique allowing high-resolution 3-dimensional structural imaging. The goal of this study was to evaluate UBM for resolving anatomic features associated with squamous cell carcinoma of the oral cavity. METHODS: The study was conducted in a hamster buccal pouch model. A carcinogen was topically applied to cheeks of 14 golden Syrian hamsters. Six additional hamsters served as healthy controls. A high-frequency (41 MHz, 6-mm focal depth, lateral and axial resolutions of 65 and 37 µm, respectively) UBM system was used for scanning the oral cavity after 14 weeks of carcinogen application. Histologic analyses were conducted on scanned regions. RESULTS: The histologic structure of buccal tissue and microvasculature networks could be visualized from the UBM images. Epithelial and mucosal hypertrophy and neoplastic changes were identified in animals subjected to the carcinogen. In animals with invasive squamous cell carcinoma, lesion development and destruction of the structural integrity of tissue layers were noted. CONCLUSIONS: In this pilot study, UBM generated sufficient contrast for morphologic features associated with oral carcinoma compared to healthy tissue. This modality may present a practical technique for detection of oral neoplasms that is potentially translatable to humans.

Development of a Three-Dimensional Multi-Modal Perfusion-Thermal Electrode System for Complete Tumor Eradication.

Background: Residual viable tumor cells after ablation at the tumor periphery serve as the source for tumor recurrence, leading to treatment failure. Purpose: To develop a novel three-dimensional (3D) multi-modal perfusion-thermal electrode system completely eradicating medium-to-large malignancies. Materials and Methods: This study included five steps: (i) design of the new system; (ii) production of the new system; (iii) ex vivo evaluation of its perfusion-thermal functions; (iv) mathematic modeling and computer simulation to confirm the optimal temperature profiles during the thermal ablation process, and; (v) in vivo technical validation using five living rabbits with orthotopic liver tumors. Results: In ex vivo experiments, gross pathology and optical imaging demonstrated the successful spherical distribution/deposition of motexafin gadolinium administered through the new electrode, with a temperature gradient from the electrode core at 80 °C to its periphery at 42 °C. An excellent repeatable correlation of temperature profiles at varying spots, from the center to periphery of the liver tumor, was found between the mathematic simulation and actual animal tumor models (Pearson coefficient ≥0.977). For in vivo validation, indocyanine green (ICG) was directly delivered into the peritumoral zones during simultaneous generation of central tumoral lethal radiofrequency (RF) heat (>60 °C) and peritumoral sublethal RF hyperthermia (<60 °C). Both optical imaging and fluorescent microscopy confirmed successful peritumoral ICG distribution/deposition with increased heat shock protein 70 expression. Conclusion: This new 3D, perfusion-thermal electrode system provided the evidence on the potential to enable simultaneous delivery of therapeutic agents and RF hyperthermia into the difficult-to-treat peritumoral zones, creating a new strategy to address the critical limitation, i.e., the high incidence of residual and recurrent tumor following thermal ablation of unresectable medium-to-large and irregular tumors.

Nanotechnology development and utilization: a primer for diagnostic and interventional radiologists.

The term nanotechnology refers to the design, creation, and manipulation of structures on the nanometer scale. Much of the ongoing research and development of nanotechnology is focused on the development of novel methods of imaging and delivery of therapeutics through minimally invasive means. Multifunctional nanoparticles offer great promise for molecular imaging and directing novel therapeutics to molecular targets, which was never before possible. Nanoparticle-based contrast agents have been developed for all imaging modalities. A rapidly increasing number of companies and government funding initiatives have led to a large number of novel agents in various stages of development, ranging from in vitro and in vivo animal studies to clinical use. However, barriers to the delivery of nanoparticles for tumor imaging and therapy exist. Interventional radiologists may circumvent these barriers by using imaging to guide delivery of nanoparticles.

Contrast-enhanced dedicated breast CT: initial clinical experience.

PURPOSE: To quantify contrast material enhancement of breast lesions scanned with dedicated breast computed tomography (CT) and to compare their conspicuity with that at unenhanced breast CT and mammography. MATERIALS AND METHODS: Approval of the institutional review board and the Radiation Use Committee and written informed consent were obtained for this HIPAA-compliant study. Between September 2006 and April 2009, 46 women (mean age, 53.2 years; age range, 35-72 years) with Breast Imaging Reporting and Data System category 4 or 5 lesions underwent unenhanced breast CT and contrast material-enhanced breast CT before biopsy. Two radiologists independently scored lesion conspicuity for contrast-enhanced breast CT versus mammography and for contrast-enhanced breast CT versus unenhanced breast CT. Mean lesion voxel intensity was measured in Hounsfield units and normalized to adipose tissue intensity on manually segmented images obtained before and after administration of contrast material. Regression models focused on conspicuity and quantified enhancement were used to estimate the effect of pathologic diagnosis (benign vs malignant), lesion type (mass vs calcifications), breast density, and interradiologist variability. RESULTS: Fifty-four lesions (25 benign, 29 malignant) in 46 subjects were analyzed. Malignant lesions were seen significantly better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) or mammography (P < .001). Malignant calcifications (malignant lesions manifested mammographically as microcalcifications only, n = 7) were seen better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) and were seen similarly at contrast-enhanced breast CT and mammography. Malignant lesions enhanced 55.9 HU +/- 4.0 (standard error), whereas benign lesions enhanced 17.6 HU +/- 6.1 (P < .001). Ductal carcinoma in situ (n = 5) enhanced a mean of 59.6 HU +/- 2.8. Receiver operating characteristic curve analysis of lesion enhancement yielded an area under the receiver operating characteristic curve of 0.876. CONCLUSION: Conspicuity of malignant breast lesions, including ductal carcinoma in situ, is significantly improved at contrast-enhanced breast CT. Quantifying lesion enhancement may aid in the detection and diagnosis of breast cancer.

Maximizing parameters for tissue ablation by using an internally cooled electrode.

PURPOSE: To compare an algorithm of gradually ramped-up power to a full-power-level technique to determine which technical parameters maximized tissue coagulation by using a saline-perfused electrode. MATERIALS AND METHODS: Institutional review board approval was not necessary and animal committee approval was unnecessary because an ex vivo bovine liver model was used and the animals were not specifically killed for this study. This four-part experiment utilized multiple ablations of ex vivo bovine liver with a standard radiofrequency (RF) generator and an internally cooled needle. First, 10 RF ablations were performed at 20-60 W for 12 minutes. Second, ablation volumes obtained from an algorithm of eight ablations performed at 50 W were compared with those obtained from an algorithm of eight ablations that were gradually ramped-up to 50 W, until full impedance. Third, volumes obtained from 10 ablations performed at impedance control power levels were compared with those obtained from 10 ablations performed with a gradual ramp-up of power that started at 50 W, terminating at full impedance. Last, the third part was repeated, but with 11 ablations continuing past full impedance for 12 minutes each. RESULTS: In the first part, maximum measurements of tissue coagulation seemed to plateau from 40 to 60 W. The second part produced significantly larger measurements of tissue coagulation than did the use of a constant power level of 50 W. The third and final parts produced larger measurements of tissue coagulation than did utilizing full power for 12 minutes. Larger measurements and volumes were obtained from repeat ablations after the generator reached impedance level than were obtained from ablations stopped at maximum impedance. CONCLUSION: A gradual ramp-up of power and repeating ablations after power impedance level is reached are the two methods that increased tissue ablation in this ex vivo experiment.

Radiographic and histologic response to neoadjuvant radiotherapy in patients with soft tissue sarcoma.

BACKGROUND: Limited data exist regarding the radiographic and histologic response of soft tissue sarcoma (STS) to neoadjuvant radiotherapy (RT). METHODS: Between February 2000 and January 2009, a total of 25 patients aged >16 years with intermediate- or high-grade primary STS of all sites were treated with neoadjuvant RT followed by definitive resection. Patients receiving chemoradiotherapy were excluded. Cross-sectional images obtained before and after RT as well as pathologic specimens were reviewed for maximal change in tumor diameter and percentage tumor necrosis, respectively. Clinicopathologic variables were analyzed for their association with pathologic and radiographic response. RESULTS: There were 18 extremity (72%) and 7 retroperitoneal (28%) tumors. Median maximal tumor size was 9 cm (range, 3.3-35 cm), and 88% were of high grade. There were 21 R0 resections (84%) and 4 R1 resections (16%). Radiographically, the median percentage change in tumor diameter was 0% (range, -25 to +86%). By Response Evaluation Criteria in Solid Tumors (RECIST), 5 patients demonstrated progressive disease, 20 demonstrated stable disease, and 0 demonstrated partial/complete response. The median pathologic percentage tumor necrosis was 30% (range, 5-100%). Two tumors (8%) demonstrated near-complete pathologic response (≥95% necrosis). Near-complete pathologic response was associated with favorable oncologic outcomes, although these associations were not statistically significant. CONCLUSIONS: Radiologic and near-complete pathologic responses are rare events after preoperative RT for STS. Near-complete pathologic response may be a potentially meaningful surrogate marker for disease outcome and is not predicted by RECIST response. Knowledge of these historical response rates is important for the evaluation of novel neoadjuvant therapies for patients with STS.

Semiautomated segmentation for volumetric analysis of intratumoral ethiodol uptake and subsequent tumor necrosis after chemoembolization.

OBJECTIVE: Linear measurements, such as those described by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, may be limited for assessment of response after transarterial chemoembolization (TACE). The purpose of this pilot study was to show intra- and interobserver reproducibility of volumetric measurements of Ethiodol (ethiodized oil) seen within tumor 24 hours after TACE and of necrotic and viable tumor 1 month after treatment. Volumetric measurements are compared with linear measurements and survival outcomes. MATERIALS AND METHODS: Between 2006 and 2009, 37 consecutive TACE procedures were performed in 27 patients with hepatic malignancies. CT images obtained 24 hours and 1 month after TACE were retrospectively analyzed. Three observers measured volumes twice. Intraoperator reproducibility was determined using Wilcoxon's signed rank test to assess whether the difference in each volumetric measurement approaches zero. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to determine interoperator reproducibility. Survival data were retrospectively obtained from the electronic medical record. RESULTS: Good intraobserver reproducibility and interobserver reproducibility (p > 0.05, ICC > 0.9, respectively) were shown for Ethiodol, whole tumor, and necrotic tumor volumes. The volume of Ethiodol correlated with subsequent necrotic tumor volume (p = 0.009), reduction in whole tumor volume (p = 0.004), and patient survival (p = 0.029). Kaplan-Meier curves suggest that Ethiodol accumulation in more than 50% of the tumor and a 10% or greater increase in the volume of necrotic tumor correlated with survival (p = 0.028 and 0.047, respectively). CONCLUSION: Semiautomated volumetric analysis can be performed with good intra- and interobserver reproducibility. The volume of Ethiodol accumulated in the tumor after TACE correlates with subsequent necrosis. These early measurements may predict survival outcomes.

Virtual-Reality Guided Versus Fluoroscopy-Guided Transseptal Puncture in a Cardiac Phantom.

OBJECTIVES: We compared virtual-reality guided versus fluoroscopy-guided transseptal puncture by novice and experienced operators in a cardiac phantom. Outcome measures included accuracy, time, transseptal path distance, and a survey of the operator experience. METHODS: A transseptal simulator was created using a Plexiglas case and a 3D-printed cardiac phantom with a replaceable fossa ovalis, a customized support, and an electromagnetic tracking system. A precisely registered virtual-reality rendering was constructed. To display the transseptal instruments in virtual reality, we attached electromagnetic sensors to standard transseptal instruments, including the needle, dilator, and sheath. Each subject completed 6 simulated transseptal punctures (3 fluoroscopy-guided and 3 virtual-reality guided). We measured the distance traversed by the transseptal needle, accuracy, and time for each simulated transseptal puncture. Operators were then surveyed regarding their experience. RESULTS: A total of 8 subjects (6 faculty, 2 fellows) completed the trial. We found that virtual-reality guidance resulted in significantly more accurate puncture site selection and, subjectively, was more intuitive for the operator, particularly for novices. None of the participants experienced negative symptoms in virtual reality that required cessation of the procedure. CONCLUSIONS: Virtual reality compared with fluoroscopic guidance for transseptal puncture shows considerable promise, particularly for novice trainees, where it could lessen the learning curve. Current barriers to widespread implementation are discussed.

Percutaneous Extra-Anatomic Lymphovenous Bypass Creation: Toward Treatment of Central Conducting Lymphatic Obstructions.

INTRODUCTION: Protein-losing enteropathy manifests as a loss of serum proteins through the gastrointestinal tract, resulting in hypoproteinemia, extravascular fluid retention, and edema. Management consists of nutritional maintenance in conjunction with interventions targeted at treating the underlying etiology. MATERIALS AND METHODS: This report describes a patient with protein-losing enteropathy from a central conducting lymphatic obstruction who was treated with percutaneous extra-anatomic lymphovenous bypass creation. RESULTS: A modified gun-sight technique was used to create a lymphovenous bypass between an occluded terminal thoracic duct and the left internal jugular vein. CONCLUSION: A percutaneous technique to reconstruct the terminal thoracic duct via lymphovenous bypass creation was feasible.

Congenital single, pelvic iliac artery: a case report.

Congenital vascular anomalies of pelvis and lower limb arteries are rare. During embryologic development, the sciatic artery represents the dominant supplier of blood to the lower limb. The external iliac and femoral arteries appear later in the process and take over as the sciatic artery regresses. Failure of the sciatic artery to regress creates a persistent sciatic artery malformation. Failure of the external iliac artery to properly bud may lead to similar vascular malformations. The authors present a patient with atresia of the left external iliac artery with an associated atresia of the left common iliac vein, duplication of the infrarenal inferior vena cava, and absence of the left S1 bony arch. The left-sided single iliac artery supplies both pelvic structures and the lower limb. The "pelvic" external iliac artery may result from embryologic budding at a lower segmental level than the usual fifth lumbar segmental artery. This combination of anomalies suggests an abnormality of segmentation on left at the first sacral level.

Inactivation of Planktonic Escherichia coli by Focused 1-MHz Ultrasound Pulses with Shocks: Efficacy and Kinetics Upon Volume Scale-Up.

This study addresses inactivation of E. coli in either 5- or 10-mL volumes, which were 50- to 100-fold greater than used in an earlier study (Brayman et al. 2017). Cells were treated with 1-MHz pulsed high-intensity focused ultrasound (10 cycles, 2-kHz repetition frequency, +65/-12.8 MPa focal pressures). The surviving fraction was assessed by coliform assay, and inactivation demonstrated curvilinear kinetics. The reduction of surviving fraction to 50% required 2.5 or 6 min in 5- or 10-mL samples, respectively. Exposure of 5 mL for 20 min reduced the surviving fraction to ∼1%; a similar exposure of 10-mL samples reduced the surviving fraction to ∼10%. Surviving cells from 5-min exposures appeared normal under light microscopy, with minimal debris; after 20 min, debris dominated. Transmission electron microscopy images of insonated samples showed some undamaged cells, a few damaged but largely intact cells and comminuted debris. Cellular damage associated with substantive but incomplete levels of inactivation can be variable, ranging from membrane holes tens of nanometers in diameter to nearly complete comminution.

Dual-balloon infusion microcatheter for selective drug-eluting bead transarterial chemoembolization: initial feasibility study.

PURPOSE: We aimed to demonstrate feasibility of the use of a dual-balloon infusion microcatheter for segmental/subsegmental drug-eluting bead transarterial chemoembolization (DEB-TACE). METHODS: Over a 16-month period, 15 segmental and 21 subsegmental DEB-TACE procedures were attempted using a dual-balloon anti-reflux microcatheter (IsoFlow™ microcatheter, Vascular Designs Inc.) in 21 patients (15 males; median age, 61 years; range, 49-82 years) with hepatocellular carcinoma (Barcelona clinic liver cancer stage A [n=4]; B [n=12]; C [n=5]) with one to three tumors, median size of 3.4 cm (1.2-9 cm). Follow-up enhanced computed tomography or magnetic resonance imaging was obtained at one month then subsequently every three months for one year. Technical success was evaluated. Modified RECIST criteria was used for target tumor response assessment. Safety was evaluated by assessing for arterial injury and hepatic injury at the time of the procedure and subsequent evidence of complications and liver toxicity. RESULTS: In 26 of the procedures, the segmental/subsegmental arteries were thought not to be easily selected with standard microcatheters due to the arterial branches being severely tortuous/angulated or atretic from prior TACE or anti-angiogenic therapy or could not be catheterized. Radiologic response assessment of treated tumors demonstrated 32% complete response, 19% partial response, 34% stable disease, and 15% progressive disease. No complications occurred. The median time to progression for the targeted tumors was 7 months (range, 3-12 months). CONCLUSION: DEB-TACE, using this dual-balloon anti-reflux infusion microcatheter is feasible and safe.

Inactivation of Planktonic Escherichia coli by Focused 2-MHz Ultrasound.

This study was motivated by the desire to develop a non-invasive means to treat abscesses, and represents the first steps toward that goal. Non-thermal, high-intensity focused ultrasound (HIFU) was used to inactivate Escherichia coli (∼1 × 109 cells/mL) in suspension. Cells were treated in 96-well culture plate wells using 1.95-MHz ultrasound and incident focal acoustic pressures as high as 16 MPa peak positive and 9.9 MPa peak negative (free field measurements). The surviving fraction was assessed by coliform culture and the alamarBlue assay. No biologically significant heating was associated with ultrasound exposure. Bacterial inactivation kinetics were well described by a half-life model, with a half-time of 1.2 min. At the highest exposure levels, a 2log inactivation was typically achieved within 10 min. The free field-equivalent peak negative acoustic pressure threshold for inactivation was ∼7 MPa. At the highest acoustic pressures used, inactivation efficacy was insensitive to reciprocal changes in pulse length and pulse repetition frequency at constant duty factor. Although treated volumes were very small, proof of principle was provided by these experiments.

Initial clinical use of a novel mechanical thrombectomy device, XCOILTM, in hemodialysis graft and fistula declot procedures.

PURPOSE: We aimed to evaluate the safety and effectiveness of a novel catheter-based mechanical thrombectomy device, XCOILTM, as a first line therapy to restore patency of thrombosed dialysis grafts and fistulae. METHODS: In 2010, 18 consecutive/sequential patients (11 male, 7 female; median age, 52 years; age range, 32-69 years) with occluded arteriovenous grafts (n=15) or fistulae (n=3) were treated with XCOILTM (NexGen Medical Systems Inc.) without adjunctive thrombolytic drugs. XCOILTM was advanced distal to the thrombus within the outflow vein as well as distal to the arterial inflow platelet thrombin plug, using a 4F angiographic catheter. The percentage of thrombus cleared, primary patency, procedure time, and XCOILTM performance were documented. RESULTS: Thrombosis occurred 1-30 days prior to the procedure. Thrombosed segments of graft/fistula measured 10-50 cm. Pre- and postprocedure angiography demonstrated that in 15 of 18 cases (83%) XCOILTM removed 80%-100% of the venous outflow thrombus. In 11 of 14 cases (79%), the platelet thrombin plug was also removed. Thrombectomy procedure time averaged 8 min, with one to three passes with the XCOILTM required. No evidence of distal embolization or graft/vessel injury was found on angiography following clot removal. In four cases in whom patency was not restored with XCOILTM, subsequent use of other clot removal devices also failed to restore patency. In one case with severe venous stenosis, the device failed to deploy and the thrombus was not captured. No intraprocedural complications related to XCOILTM use occurred. CONCLUSION: XCOILTM is an effective and safe first-line therapy option for the treatment of thrombosed hemodialysis grafts/fistulae. Rapid removal of intact thrombus and platelet thrombin plug can be achieved without adjunctive thrombolytics.

Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability.

Induction of vascular hyperpermeability is one of the early vascular responses to radiation exposure and is considered to contribute to subsequent fibrosis and tissue injuries. However, the mechanism underlying radiation-induced hyperpermeability has not yet been clearly elucidated. Here, we provide experimental evidence indicating that mast cells contribute to the increase in vascular permeability for albumin in normal mouse skin after irradiation. Vascular permeability in the skin of C3H mice increased after 2, 15 and 50 Gy irradiation, peaked at 24 h after irradiation and gradually decreased thereafter to the baseline level within 3-10 days. Both the extent and duration of hyperpermeability were dose dependent. We found significant degranulation of mast cells in the skin after 15 Gy irradiation. To further investigate the role of mast cells in the radiation-induced increase in vascular permeability, we measured vascular permeability in the skin of mast cell-deficient mice (WW(v)) and their wild-type littermates at 24 h after irradiation. Vascular permeability in WW(v) mice did not change, whereas that in wild-type mice significantly increased after irradiation. There were no appreciable changes in the total tissue levels of vascular endothelial growth factor or endothelial nitric oxide synthase after 15 Gy irradiation and there was no detectable expression of inducible nitric oxide synthase. Collectively, these results show that exposure to radiation induces vascular hyperpermeability in a dose-dependent manner and that mast cells contribute to this process.

Histotripsy Liquefaction of Large Hematomas.

Intra- and extra-muscular hematomas result from repetitive injury as well as sharp and blunt limb trauma. The clinical consequences can be serious, including debilitating pain and functional deficit. There are currently no short-term treatment options for large hematomas, only lengthy conservative treatment. The goal of this work was to evaluate the feasibility of a high intensity focused ultrasound (HIFU)-based technique, termed histotripsy, for rapid (within a clinically relevant timeframe of 15-20 min) liquefaction of large volume (up to 20 mL) extra-vascular hematomas for subsequent fine-needle aspiration. Experiments were performed using in vitro extravascular hematoma phantoms-fresh bovine blood poured into 50 mL molds and allowed to clot. The resulting phantoms were treated by boiling histotripsy (BH), cavitation histotripsy (CH) or a combination in a degassed water tank under ultrasound guidance. Two different transducers operating at 1 MHz and 1.5 MHz with f-number = 1 were used. The liquefied lysate was aspirated and analyzed by histology and sized in a Coulter Counter. The peak instantaneous power to achieve BH was lower than (at 1.5 MHz) or equal to (at 1 MHz) that which was required to initiate CH. Under the same exposure duration, BH-induced cavities were one and a half to two times larger than the CH-induced cavities, but the CH-induced cavities were more regularly shaped, facilitating easier aspiration. The lysates contained a small amount of debris larger than 70 µm, and 99% of particulates were smaller than 10 µm. A combination treatment of BH (for initial debulking) and CH (for liquefaction of small residual fragments) yielded 20 mL of lysate within 17.5 minutes of treatment and was found to be most optimal for liquefaction of large extravascular hematomas.