Effect of Thrombin and Incubation Time on Porcine Whole Blood Clot Elasticity and Recombinant Tissue Plasminogen Activator Susceptibility.

Deep vein thrombosis is a major source of morbidity and mortality worldwide. Catheter-directed thrombolytics are the frontline approach for vessel recanalization, though fibrinolytic efficacy is limited for stiff, chronic thrombi. Although thrombin has been used in preclinical models to induce thrombosis, the effect on lytic susceptibility and clot stiffness is unknown. The goal of this study was to explore the effect of bovine thrombin concentration and incubation time on lytic susceptibility and stiffness of porcine whole blood clots in vitro. Porcine whole blood was allowed to coagulate at 37°C in glass pipets primed with 2.5 or 15 U/mL thrombin for 15 to 120 min. Lytic susceptibility to recombinant tissue plasminogen activator (rt-PA, alteplase) over a range of concentrations (3.15-107.00 µg/mL) was evaluated using percentage clot mass loss. The Young's moduli and degrees of retraction of the clots were estimated using ultrasound-based single-track-location shear wave elasticity and B-mode imaging, respectively. Percentage mass loss decreased and clot stiffness increased with the incubation period. Clots formed with 15 U/mL and incubated for 2 h exhibited properties similar to those of highly retracted clots: Young's modulus of 2.39 ± 0.36 kPa and percentage mass loss of 8.69 ± 2.72% when exposed to 3.15 µg/mL rt-PA. The histological differences between thrombin-induced porcine whole blood clots in vitro and thrombi in vivo are described.

Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model.

Adjuvant ultrasound at 2 MHz with or without an ultrasound contrast agent improves the rate of thrombus resolution by recombinant tissue plasminogen activator (rt-PA) in laboratory and clinical studies. A sub-megahertz approach can further expand this therapy to a subset of patients with an insufficient temporal bone window, improving efficacy in unselected patient populations. The aim of this study was to determine if a clinical ultrasound contrast agent (UCA), Definity, and 220 kHz pulsed ultrasound accelerated rt-PA thrombolysis in a preclinical animal model of vascular occlusion. The effect of Definity and ultrasound on thrombus clearance was first investigated in vitro and subsequently tested in a xenographic porcine cerebral thromboembolism model in vivo. Two different microcatheter designs (end-hole, multi-side-hole) were used to infuse rt-PA and Definity at the proximal edge or directly into clots, respectively. Sonothrombolysis with Definity increased clot mass loss relative to saline or rt-PA alone in vitro, only when rt-PA was administered directly into clots via a multi-side-hole microcatheter. Combined treatment with rt-PA, Definity, and ultrasound in vivo increased the rate of reperfusion up to 45 min faster than clots treated with rt-PA or saline. In this porcine cerebral thromboembolism model employing retracted human clots, 220 kHz ultrasound, in conjunction with Definity increased the probability of early successful reperfusion with rt-PA.

Diffuse reflectance spectroscopy for breach detection during pedicle screw placement: a first in vivo investigation in a porcine model.

BACKGROUND: The safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery, emphasizing the need for intraoperative guidance techniques. Diffuse reflectance spectroscopy (DRS) is an optical sensing technology that may provide intraoperative guidance in pedicle screw placement. PURPOSE: The study presents the first in vivo minimally invasive procedure using DRS sensing at the tip of a Jamshidi needle with an integrated optical K-wire. We investigate the effect of tissue perfusion and probe-handling conditions on the reliability of fat fraction measurements for breach detection in vivo. METHODS: A Jamshidi needle with an integrated fiber-optic K-wire was gradually inserted into the vertebrae under intraoperative image guidance. The fiber-optic K-wire consisted of two optical fibers with a fiber-to-fiber distance of 1.024 mm. DRS spectra in the wavelength range of 450 to 1600 nm were acquired at several positions along the path inside the vertebrae. Probe-handling conditions were varied by changing the amount of pressure exerted on the probe within the vertebrae. Continuous spectra were recorded as the probe was placed in the center of the vertebral body while the porcine specimen was sacrificed via a lethal injection. RESULTS: A typical insertion of the fiber-optic K-wire showed a drop in fat fraction during an anterior breach as the probe transitioned from cancellous to cortical bone. Fat fraction measurements were found to be similar irrespective of the amount of pressure exerted on the probe (p = 0.65). The 95% confidence interval of fat fraction determination was found in the narrow range of 1.5-3.6% under various probe-handling conditions. The fat fraction measurements remained stable during 70 min of decreased blood flow after the animal was sacrificed. DISCUSSIONS: These findings indicate that changes in tissue perfusion and probe-handling conditions have a relatively low measureable effect on the DRS signal quality and thereby on the determination of fat fraction as a breach detection signal. CONCLUSIONS: Fat fraction quantification for intraoperative pedicle screw breach detection is reliable, irrespective of changes in tissue perfusion and probe-handling conditions.

Validation of diffuse reflectance spectroscopy with magnetic resonance imaging for accurate vertebral bone fat fraction quantification.

Safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery. The diffuse reflectance spectroscopy (DRS) technique may offer the possibility of intra-operative guidance for pedicle screw placement. Currently, Magnetic Resonance Imaging (MRI) is one of the most accurate techniques used to measure fat concentration in tissues. Therefore, the purpose of this study is to compare the accuracy of fat content measured invasively in vertebrae using DRS and validate it against the Proton density fat fraction (PDFF) derived via MRI. Chemical shift-encoding-based water-fat imaging of the spine was first performed on six cadavers. PDFF images were computed and manually segmented. 23 insertions using a custom-made screw probe with integrated optical fibers were then performed under cone beam computer tomography (CBCT). DR spectra were recorded at several positions along the trajectory as the optical screw probe was inserted turn by turn into the vertebral body. Fat fractions determined via DRS and MRI techniques were compared by spatially correlating the optical screw probe position within the vertebrae on CBCT images with respect to the PDFF images. The fat fraction determined by DRS was found to have a high correlation with those determined by MRI, with a Pearson coefficient of 0.950 (P< 0.001) as compared with PDFF measurements calculated from the MRI technique. Additionally, the two techniques were found to be comparable for fat fraction quantification within vertebral bodies (R2 = 0.905).

Machine learning for automated 3-dimensional segmentation of the spine and suggested placement of pedicle screws based on intraoperative cone-beam computer tomography.

OBJECTIVE: The goal of this study was to develop and validate a system for automatic segmentation of the spine, pedicle identification, and screw path suggestion for use with an intraoperative 3D surgical navigation system. METHODS: Cone-beam CT (CBCT) images of the spines of 21 cadavers were obtained. An automated model-based approach was used for segmentation. Using machine learning methodology, the algorithm was trained and validated on the image data sets. For measuring accuracy, surface area errors of the automatic segmentation were compared to the manually outlined reference surface on CBCT. To further test both technical and clinical accuracy, the algorithm was applied to a set of 20 clinical cases. The authors evaluated the system's accuracy in pedicle identification by measuring the distance between the user-defined midpoint of each pedicle and the automatically segmented midpoint. Finally, 2 independent surgeons performed a qualitative evaluation of the segmentation to judge whether it was adequate to guide surgical navigation and whether it would have resulted in a clinically acceptable pedicle screw placement. RESULTS: The clinically relevant pedicle identification and automatic pedicle screw planning accuracy was 86.1%. By excluding patients with severe spinal deformities (i.e., Cobb angle > 75° and severe spinal degeneration) and previous surgeries, a success rate of 95.4% was achieved. The mean time (± SD) for automatic segmentation and screw planning in 5 vertebrae was 11 ± 4 seconds. CONCLUSIONS: The technology investigated has the potential to aid surgeons in navigational planning and improve surgical navigation workflow while maintaining patient safety.

Diffuse reflectance spectroscopy, a potential optical sensing technology for the detection of cortical breaches during spinal screw placement.

Safe and accurate placement of screws remains a critical issue in open and minimally invasive spine surgery. We propose to use diffuse reflectance (DR) spectroscopy as a sensing technology at the tip of a surgical instrument to ensure a safe path of the instrument through the cancellous bone of the vertebrae. This approach could potentially reduce the rate of cortical bone breaches, thereby resulting in fewer neural and vascular injuries during spinal fusion surgery. In our study, DR spectra in the wavelength ranges of 400 to 1600 nm were acquired from cancellous and cortical bone from three human cadavers. First, it was investigated whether these spectra can be used to distinguish between the two bone types based on fat, water, and blood content along with photon scattering. Subsequently, the penetration of the bone by an optical probe was simulated using the Monte-Carlo (MC) method, to study if the changes in fat content along the probe path would still enable distinction between the bone types. Finally, the simulation findings were validated via an experimental insertion of an optical screw probe into the vertebra aided by x-ray image guidance. The DR spectra indicate that the amount of fat, blood, and photon scattering is significantly higher in cancellous bone than in cortical bone (p < 0.01), which allows distinction between the bone types. The MC simulations showed a change in fat content more than 1 mm before the optical probe came in contact with the cortical bone. The experimental insertion of the optical screw probe gave similar results. This study shows that spectral tissue sensing, based on DR spectroscopy at the instrument tip, is a promising technology to identify the transition zone from cancellous to cortical vertebral bone. The technology therefore has the potential to improve the safety and accuracy of spinal screw placement procedures.

The management of pediatric renovascular hypertension: a single center experience and review of the literature.

INTRODUCTION: Renal artery occlusive disease is poorly characterized in children; treatments include medications, endovascular techniques, and surgery. We aimed to describe the course of renovascular hypertension (RVH), its treatments and outcomes. METHODS: We performed literature review and retrospective review (1993-2014) of children with renovascular hypertension at our institution. Response to treatment was defined by National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents at most-recent follow-up. RESULTS: We identified 39 patients with RVH. 54% (n=21) were male, with mean age of 6.93 ± 5.27 years. Most underwent endovascular treatment (n=17), with medication alone (n=12) and surgery (n=10) less commonly utilized. Endovascular treatment resulted in 18% cure, 65% improvement and 18% failure; surgery resulted in 30% cure, 50% improvement and 20% failure. Medication alone resulted in 0% cure, 75% improvement and 25% failure. 24% with endovascular treatment required secondary endovascular intervention; 18% required secondary surgery. 20% of patients who underwent initial surgery required reoperation for re-stenosis. Mean follow-up was 52.2 ± 58.4 months. CONCLUSIONS: RVH treatment in children includes medications, surgical or endovascular approaches, with all resulting in combined 79% improvement in or cure rates. A multidisciplinary approach and individualized patient management are critical to optimize outcomes. TYPE OF STUDY: Retrospective comparative study LEVEL OF EVIDENCE: Level III.

CT-guided localization of pulmonary nodules in children prior to video-assisted thoracoscopic surgical resection utilizing a combination of two previously described techniques.

BACKGROUND: Pulmonary nodules in pediatric oncology patients can present a diagnostic and treatment dilemma. Imaging findings are often nonspecific and tissue diagnosis may be required for appropriate treatment. The smaller subpleural nodules may not be visualized and cannot be palpated during video-assisted thoracoscopic surgical (VATS) resection. Preoperative localization has been beneficial in obtaining an adequate pathological specimen. OBJECTIVE: This study presents experience in a large pediatric hospital using CT-guided preoperative localization of pulmonary nodules combining two previously utilized techniques, hook wire and methylene blue blood patch localization. MATERIALS AND METHODS: A search of the electronic medical record utilizing a medical record search application was performed to identify all patients who underwent preoperative lung nodule localization during a 12.5-year period (July 1999 through January 2012). A retrospective chart review of these patients was then performed. Pre- and postoperative imaging, interventional radiology procedural images and reports, surgical reports, and pathology reports were obtained and evaluated. RESULTS: Thirty-five patients, with 40 nodules, who underwent preoperative CT-guided lung nodule localization were identified. Patients ranged in age from 8 months to 21 years. The pulmonary nodules ranged in size from 1.4 mm to 18 mm. Twelve nodules were localized using a Kopans breast lesion localization needle with hook wire, 4 were localized using a methylene blue blood patch, and 24 were localized using the combination of these two techniques. The technical success rate of all procedures was 100%. A pathological diagnosis was determined in 39 patients (97.5%). There were 6 (15.0%) minor complications and no major complications. CONCLUSION: CT-guided lung nodule localization using the combined techniques of methylene blue blood patch and hook wire is safe, technically feasible and successful in children. Using this combination of techniques will consistently yield a pathological diagnosis, is currently the preferred technique at our tertiary pediatric hospital and could be considered the new best practice.

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients.

Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.Experimental Design: We delivered a single dose of 105 to 107 infectious units of HSV1716 via computed tomography-guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on 18fluorine-deoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 23(14); 3566-74. ©2017 AACR.

Augmented Reality on a C-Arm System: A Preclinical Assessment for Percutaneous Needle Localization.

Purpose To compare the navigational accuracy and radiation dose during needle localization of targets for augmented reality (AR) with and without motion compensation (MC) versus those for cone-beam computed tomography (CT) with real-time fluoroscopy navigation in a pig model. Materials and Methods This study was approved by the Institutional Animal Care and Use Committee. Three operators each localized 15 targets (bone fragments) approximately 7 cm deep in the paraspinal muscles of nine Yorkshire pigs by using each of the three modalities (AR with and without MC and cone-beam CT with fluoroscopy). Target depth, accuracy (distance between needle tip and target), and radiation dose (dose-area product [DAP]) were recorded for each procedure. Correlation between accuracy and depth of target was assessed by using the Pearson correlation coefficient. Two-way analysis of variance was used for differentiating accuracy and DAPs across navigation techniques and operator backgrounds. Results There was no correlation between depth of target and accuracy. There was no significant difference in accuracy between modalities (mean distance, 3.0 mm ± 1.9 [standard deviation] for cone-beam CT with fluoroscopy, 2.5 mm ± 2.0 for AR, and 3.2 mm ± 2.7 for AR with MC [P = .33]). There was, however, a significant difference in fluoroscopy radiation dose (10.4 Gy · cm(2) ± 10.6 for cone-beam CT fluoroscopy, 2.3 Gy · cm(2) ± 2.4 for AR, and 3.3 Gy · cm(2) ± 4.6 for AR with MC [P < .05]) and therefore in total procedural radiation dose (20.5 Gy · cm(2) ± 13.4 for cone-beam CT fluoroscopy, 12.6 Gy · cm(2) ± 5.3 for AR, 13.6 Gy · cm(2) ± 7.4 for AR with MC [P < .05]). Conclusion Use of an AR C-arm system reduces radiation dose while maintaining navigational accuracy compared with cone-beam CT fluoroscopy during image-guided percutaneous needle placement in a pig model. (©) RSNA, 2016 Online supplemental material is available for this article.

Comparison of complications between pediatric peripherally inserted central catheter placement techniques.

BACKGROUND: Peripherally inserted central catheter (PICC) is among the most common procedures performed in children in the hospital setting. PICC insertion can be simplified with the use of a sheathed needle as an alternative to the modified Seldinger technique. OBJECTIVE: To retrospectively evaluate PICC placement for the technique used and the incidence of complications at a large pediatric tertiary care center. MATERIALS AND METHODS: We retrospectively reviewed all PICC placements at a single institution over a 4-year period. We reviewed patient records for demographic data, PICC placement technique, catheter size and number of lumens, and the incidence of complications (i.e. multiple attempted puncture sites, phlebitis and vessel thrombosis). We analyzed complication rates between two placement techniques using a chi-square test. RESULTS: We identified 8,816 successful PICC placements, 4,749 (53.9%) in males and 4,067 (46.1%) in females. The average age of the patients for which a line was placed was 5.6 years (range 1 day to 45 years). A direct sheathed needle puncture technique was used in 8,362 (94.9%) placements and a modified Seldinger technique was used in 454 (5.1%). Complications occurred in 312 (3.7%) of direct sheathed needle puncture placements versus 17 (3.7%) of modified Seldinger placements (P = 0.99). Multiple puncture sites were required in 175 (2.1%) attempted direct sheathed needle puncture placements compared with 8 (1.7%) attempted modified Seldinger placements (P = 0.63). Phlebitis occurred in 94 (1.1%) direct sheathed needle puncture lines versus 5 (1.1%) modified Seldinger placed lines (P = 0.96). Vessel thrombosis occurred in 43 (0.5%) direct sheathed needle puncture lines versus 4 (0.9%) modified Seldinger placed lines (P = 0.30). CONCLUSION: The direct peel-away sheathed needle vessel puncture technique and the modified Seldinger technique used to place PICC lines in children have similar complication rates.

Use of cone-beam CT and live 3-D needle guidance to facilitate percutaneous nephrostomy and nephrolithotripsy access in children and adolescents.

BACKGROUND: Gaining access into non-dilated renal collecting systems for percutaneous nephrolithotripsy, particularly in patients with prohibitive body habitus and/or scoliosis, is often challenging using conventional techniques. OBJECTIVE: To evaluate the feasibility of cone-beam CT for percutaneous nephrostomy placement for subsequent percutaneous nephrolithotripsy in children and adolescents. MATERIALS AND METHODS: A retrospective review of percutaneous nephrostomy revealed use of cone-beam CT and 3-D guidance in 12 percutaneous nephrostomy procedures for 9 patients between 2006 and 2015. All cone-beam CT-guided percutaneous nephrostomies were for pre-lithotripsy access and all 12 were placed in non-dilated collecting systems. RESULTS: Technical success was 100%. There were no complications. CONCLUSION: Cone-beam CT with 3-D guidance is a technically feasible technique for percutaneous nephrostomy in children and adolescents, specifically for nephrolithotripsy access in non-dilated collecting systems.

Ultrasound-Guided Botulinum Toxin Type A Salivary Gland Injection in Children for Refractory Sialorrhea: 10-Year Experience at a Large Tertiary Children's Hospital.

BACKGROUND: Sialorrhea is problematic for neurologically impaired children, and botulinum toxin A salivary gland injection has been reported as effective in reducing sialorrhea. This article assesses the success and safety of ultrasound-guided weight-based botulinum toxin A injection for the management of sialorrhea in children. METHODS: A total of 111 patients (63 males; 48 females; average age 7 years) with refractory sialorrhea were treated with ultrasound-guided botulinum toxin type A salivary gland injections (144 procedures) from July 1, 2004, to July 1, 2014, using a single weight-based protocol. Patient history, procedural records, and clinical follow-up documents were retrospectively reviewed. Clinical data were compared with reported effectiveness and complications using odds ratios. RESULTS: A total of 144 procedures were performed in 111 patients with refractory sialorrhea. Cerebral palsy was the most common underlying etiology for sialorrhea (29%), whereas others included encephalopathy (5%), anoxic brain injury (4%), and a variety of chromosomal anomalies (5%). There was a 100% technical success rate. Overall treatment effectiveness was 68%. Repeat injections were not associated with increased clinical success. No procedure-related deaths or major complications were identified; the minor complication rate was less than 2%. CONCLUSIONS: The protocol used for ultrasound-guided injection of botulinum toxin A proved to be safe and effective in children suffering from sialorrhea. Image guidance technique may lead to a reduction in rates of adverse events reported in other series. Subsequent procedures do not improve upon initial efficacy.

Comparison of pediatric radiation dose and vessel visibility on angiographic systems using piglets as a surrogate: antiscatter grid removal vs. lower detector air kerma settings with a grid - a preclinical investigation.

The purpose of this study was to reduce pediatric doses while maintaining or improv-ing image quality scores without removing the grid from X-ray beam. This study was approved by the Institutional Animal Care and Use Committee. Three piglets (5, 14, and 20 kg) were imaged using six different selectable detector air kerma (Kair) per frame values (100%, 70%, 50%, 35%, 25%, 17.5%) with and without the grid. Number of distal branches visualized with diagnostic confidence relative to the injected vessel defined image quality score. Five pediatric interventional radiologists evaluated all images. Image quality score and piglet Kair were statistically compared using analysis of variance and receiver operating curve analysis to define the preferred dose setting and use of grid for a visibility of 2nd and 3rd order vessel branches. Grid removal reduced both dose to subject and imaging quality by 26%. Third order branches could only be visualized with the grid present; 100% detector Kair was required for smallest pig, while 70% detector Kair was adequate for the two larger pigs. Second order branches could be visualized with grid at 17.5% detector Kair for all three pig sizes. Without the grid, 50%, 35%, and 35% detector Kair were required for smallest to largest pig, respectively. Grid removal reduces both dose and image quality score. Image quality scores can be maintained with less dose to subject with the grid in the beam as opposed to removed. Smaller anatomy requires more dose to the detector to achieve the same image quality score.

Isolated Upper Extremity Posttransplant Lymphoproliferative Disorder in a Child.

Posttransplant lymphoproliferative disorder (PTLD) is a well-described complication of solid organ and bone marrow transplants. The most common presentation is intra-abdominal lymphadenopathy or single or multiple intraparenchymal masses involving the liver, spleen, or kidneys. Here we describe the imaging and pathology findings of an unusual case of PTLD appearing as an intramuscular forearm lesion in a pediatric male. The manifestation of PTLD as an isolated upper extremity mass in a pediatric patient has to our knowledge not been described.

Estimates of diagnostic reference levels for pediatric peripheral and abdominal fluoroscopically guided procedures.

OBJECTIVE: The objective of our study was to survey radiation dose indexes of pediatric peripheral and abdominal fluoroscopically guided procedures from which estimates of diagnostic reference levels (DRLs) can be proposed for both a standard fluoroscope and a novel fluoroscope with advanced image processing and lower radiation dose rates. MATERIALS AND METHODS: Radiation dose structured reports were retrospectively collected for 408 clinical pediatric cases: Half of the procedures were performed with a standard imaging technology and half with a novel x-ray technology. Dose-area product (DAP), air Kerma (AK), fluoroscopy time, number of digital subtraction angiography images, and patient mass were collected to calculate and normalize radiation dose indexes for procedures completed with the standard and novel fluoroscopes. RESULTS: The study population was composed of 180 and 175 patients who underwent procedures with the standard and novel technology, respectively. The 21 different types of pediatric peripheral and abdominal interventional procedures produced 408 total studies. Median ages, mass and body mass index, fluoroscopy time per procedure, and total number of recorded images for the standard and novel technologies were not statistically different. The area of the x-ray beams was square at the level of the patient with a dimension of 10-13 cm. The dose reduction achieved with the novel fluoroscope ranged from 18% to 51% of the dose required with the standard fluoroscope. The median DAP and AK patient dose indexes were 0.38 Gy · cm(2) and 4.00 mGy, respectively, for the novel fluoroscope. CONCLUSION: Estimates of dose indexes of pediatric peripheral and abdominal fluoroscopically guided, clinical procedures should assist in the development of DRLs to foster management of radiation doses of pediatric patients.

Endovascular thrombolysis to salvage central venous access in children with catheter-associated upper extremity deep vein thrombosis: technique and initial results.

Nine patients (average age 8.3 years, range 20 days to 17 years; average weight 31 kg, range 2.7-79 kg) with catheter-associated UE-DVT underwent upper extremity venous thrombolysis with the goal of access salvage. Catheter directed therapy with alteplase (tPA), balloon angioplasty, and mechanical thrombectomy was used in all cases. The mean total dose of TPA was 15 mg (range 1-40 mg). Venous access was ultimately preserved in all patients. No stents or superior vena cava filters were used. There was one episode of symptomatic clinically suspected pulmonary embolism managed by systemic tPA and heparin without long term sequaele. Mean imaging and clinical follow-up was 351 ± 208 and 613 ± 498 days respectively. Endovenous thrombolysis for catheter-associated upper-extremity DVT in children may be safe and effective and could be considered particularly in patients in whom long-term venous access is needed.

Real-Time In Vivo Characterization of Primary Liver Tumors With Diffuse Optical Spectroscopy During Percutaneous Needle Interventions: Feasibility Study in Woodchucks.

OBJECTIVE: This study presents the first in vivo real-time optical tissue characterization during image-guided percutaneous intervention using near-infrared diffuse optical spectroscopy sensing at the tip of a needle. The goal of this study was to indicate transition boundaries from healthy tissue to tumors, namely, hepatic carcinoma, based on the real-time feedback derived from the optical measurements. MATERIALS AND METHODS: Five woodchucks with hepatic carcinoma were used for this study. The woodchucks were imaged with contrast-enhanced cone beam computed tomography with a flat panel detector C-arm system to visualize the carcinoma in the liver. In each animal, 3 insertions were performed, starting from the skin surface toward the hepatic carcinoma under image guidance. In 2 woodchucks, each end point of the insertion was confirmed with pathologic examination of a biopsy sample. While advancing the needle in the animals under image guidance such as fluoroscopy overlaid with cone beam computed tomography slice and ultrasound, optical spectra were acquired at the distal end of the needles. Optical tissue characterization was determined by translating the acquired optical spectra into clinical parameters such as blood, water, lipid, and bile fractions; tissue oxygenation levels; and scattering amplitude related to tissue density. The Kruskal-Wallis test was used to study the difference in the derived clinical parameters from the measurements performed within the healthy tissue and the hepatic carcinoma. Kurtoses were calculated to assess the dispersion of these parameters within the healthy and carcinoma tissues. RESULTS: Blood and lipid volume fractions as well as tissue oxygenation and reduced scattering amplitude showed to be significantly different between the healthy part of the liver and the hepatic carcinoma (P < 0.05) being higher in normal liver tissue. A decrease in blood and lipid volume fractions and tissue oxygenation as well as an increase in scattering amplitude were observed when the tip of the needle crossed the margin from the healthy liver tissue to the carcinoma. The kurtosis for each derived clinical parameter was high in the hepatic tumor as compared with that in the healthy liver indicating intracarcinoma variability. CONCLUSIONS: Tissue blood content, oxygenation level, lipid content, and tissue density all showed significant differences when the needle tip was guided from the healthy tissue to the carcinoma and can therefore be used to identify tissue boundaries during percutaneous image-guided interventions.

Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients.

Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven tumor-specific immunity. Pexa-Vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. We sought to determine the safety of intratumoral administration in pediatric patients. In a dose-escalation study using either 10(6) or 10(7) plaque-forming units per kilogram, we performed one-time injections in up to three tumor sites in five pediatric patients and two injections in one patient. Ages at study entry ranged from 4 to 21 years, and their cancer diagnoses included neuroblastoma, hepatocellular carcinoma, and Ewing sarcoma. All toxicities were ≤ grade 3. The most common side effects were sinus fever and sinus tachycardia. All three patients at the higher dose developed asymptomatic grade 1 treatment-related skin pustules that resolved within 3-4 weeks. One patient showed imaging evidence suggestive of antitumor biological activity. The two patients tested for cellular immunoreactivity to vaccinia antigens showed strong responses. Overall, our study suggests Pexa-Vec is safe to administer to pediatric patients by intratumoral administration and could be studied further in this patient population.