A Study of Postoperative Complications Occurring at Home With Pediatric Gastrostomy Feeding Tubes.

OBJECTIVE: Gastrostomy tubes (G-tubes) provide long-term feeding assistance to children with severe feeding dysfunction. Although there are a host of complications that occur at home with current pediatric G-tube feeding, their prevalences and outcomes remain relatively unstudied. This study aims to identify and describe such complications. METHODS: A dual-round survey was administered to 98 participants through the Feeding Tube Awareness Foundation, a 501(c)(3) organization that supports parents and caretakers of G-tube-fed children. Information was collected broadly regarding G-tube complications, causes, and attitudes toward such complications. RESULTS: Infection (56%), itching/irritation/redness (52%), and leakage (51%) were the leading G-tube related complications. The average time that G-tubes were replaced was 3.4 ± 1.2 months as compared to the typical recommended period of up to 6 months. Of the caretakers who had not experienced G-tube displacement, 7.9% wanted to see a change in current G-tubes to address the issue, compared with 75% of those who had experienced displacement. This 67.1% differential in caretakers' attitudes toward G-tubes based on their prior experience with a particular complication was the largest gap among all other listed complications. CONCLUSIONS: G-tube complications are prevalent and varied. A sizable portion of G-tube users experience complications severe enough to require intervention. Of these, G-tube displacement is particularly critical and frequently precedes other prevalent complications, namely gastric leakage, infection, and tissue granulation.

Are Current Technical Exclusion Criteria for Clinical Trials of Magnetic Resonance-Guided High-Intensity Focused Ultrasound Too Restrictive?: Early Experiences at a Pediatric Hospital.

Certain technical criteria must be met to ensure the treatment safety of magnetic resonance-guided high-intensity focused ultrasound. We retrospectively reviewed how our enrollment criteria were applied from 2014 to 2017 in a clinical trial of magnetic resonance-guided high-intensity focused ultrasound ablation of recurrent malignant and locally aggressive benign solid tumors. Among the 36 screened patients between 2014 and 2017, more than one-third were excluded for technical exclusion criteria such as the anatomic location and proximity to prosthetics. Overall, patients were difficult to accrue for this trial, given the incidence of these tumors. To increase potential accrual, screening exclusion criteria could be more generalized and centered on the ability to achieve an acceptable treatment safety margin, rather than specifically excluding on the basis of general anatomic areas.

Ultrasound-detected venous changes associated with peripheral intravenous placement in children.

HIGHLIGHTS: Ultrasound shows several venous changes in pediatric PIV-containing veins. Changes were visualized by ultrasound in the absence of physical exam findings. Venous luminal narrowing, wall thickening, and thrombosis may explain PIV failure. BACKGROUND: Peripheral intravenous catheters (PIVs) are routinely used for venous access in hospitalized pediatric patients to administer fluids and medications and to aspirate blood. Unfortunately, PIVs do not remain functional for the entire duration of intravascular need. We hypothesized that PIV malfunction may be related to venous changes that can be visualized with ultrasound (US) imaging. The purpose of this study was to describe and document such changes in pediatric patients. METHODS: This Institutional Review Board-approved study was performed at a tertiary pediatric medical center. Patients underwent US scans of their PIV-containing veins, documenting venous characteristics such as depth, diameter, wall thickness, blood flow, valves, branch points, and presence of thrombus. Patient demographics and PIV characteristics were also recorded. RESULTS: Data from 30 patients including 12 males and 18 females with a mean age of 11 years were analyzed. Mean venous depth and diameter were 2.07 ± 0.13 and 2.02 ± 0.18 mm, respectively. Mean PIV dwell time at time of evaluation was 3.3 days. PIV-associated venous changes were seen in 73% of accessed veins and included lumen narrowing (47%), wall thickening (33%), presence of thrombus (20%), and absence of blood flow around the PIV tip (40%). CONCLUSION: PIV-associated venous changes are seen with US in the majority of pediatric patients with indwelling PIVs but are not necessarily appreciated on physical exam. These changes may help explain the high rate of pediatric PIV device failure. Given the small sample size, further investigation is needed to better characterize PIV-associated venous changes in children.

Catheter-Related Venous Thrombosis in Hospitalized Pediatric Patients with Inflammatory Bowel Disease: Incidence, Characteristics, and Role of Anticoagulant Thromboprophylaxis with Enoxaparin.

OBJECTIVE: To describe the incidence and characteristics of central venous catheter (CVC)-related thrombosis in hospitalized pediatric patients with active inflammatory bowel disease (IBD) and report the potential usefulness of anticoagulant thromboprophylaxis (AT). STUDY DESIGN: We conducted a retrospective study of patients who were admitted to our children's hospital in the last 2 years with active IBD and required a CVC and identified all patients with an objectively confirmed symptomatic CVC-related thrombosis. To assess the usefulness of a recently implemented institutional AT protocol, we compared the frequency of CVC-related thrombosis, nadir hemoglobin, and red blood cell transfusion requirements in patients who received AT with those who did not during the study period. RESULTS: A total of 40 patients with IBD who required 47 consecutive hospitalizations were included. AT was administered during 24 of 47 hospitalizations (51%). Patients who received AT were similar to those who did not receive AT with regard to demographics, IBD phenotypes, extent of colonic involvement, and thrombotic risk factors. CVC-related thrombosis occurred in 5 of 23 hospitalizations (22%) in which AT was withheld compared with 0 of 24 hospitalizations (0%) in which patients received AT (P = .02). The red blood cell transfusion requirements and nadir hemoglobin were not significantly different between the 2 groups. CONCLUSIONS: We observed a high incidence of CVC-related thrombosis in hospitalized children with IBD. Administration of AT in our population was associated with significant reduction in CVC-related thrombosis without evidence of increased bleeding.

Bench-to-clinic development of imageable drug-eluting embolization beads: finding the balance.

This review describes the historical development of an imageable spherical embolic agent and focuses on work performed in collaboration between Biocompatibles UK Ltd (a BTG International group company) and the NIH to demonstrate radiopaque bead utility and bring a commercial offering to market that meets a clinical need. Various chemistries have been investigated and multiple prototypes evaluated in search of an optimized product with the right balance of handling and imaging properties. Herein, we describe the steps taken in the development of DC Bead LUMI™, the first commercially available radiopaque drug-eluting bead, ultimately leading to the first human experience of this novel embolic agent in the treatment of liver tumors.

Mechanical fractionation of tissues using microsecond-long HIFU pulses on a clinical MR-HIFU system.

PURPOSE: High intensity focussed ultrasound (HIFU) can non-invasively treat tumours with minimal or no damage to intervening tissues. While continuous-wave HIFU thermally ablates target tissue, the effect of hundreds of microsecond-long pulsed sonications is examined in this work. The objective of this study was to characterise sonication parameter-dependent thermomechanical bioeffects to provide the foundation for future preclinical studies and facilitate clinical translation. METHODS AND MATERIALS: Acoustic power, number of cycles/pulse, sonication time and pulse repetition frequency (PRF) were varied on a clinical magnetic resonance imaging (MRI)-guided HIFU (MR-HIFU) system. Ex vivo porcine liver, kidney and cardiac muscle tissue samples were sonicated (3 × 3 grid pattern, 1 mm spacing). Temperature, thermal dose and T2 relaxation times were quantified using MRI. Lesions were histologically analysed using H&E and vimentin stains for lesion structure and viability. RESULTS: Thermomechanical HIFU bioeffects produced distinct types of fractionated tissue lesions: solid/thermal, paste-like and vacuolated. Sonications at 20 or 60 Hz PRF generated substantial tissue damage beyond the focal region, with reduced viability on vimentin staining, whereas H&E staining indicated intact tissue. Same sonication parameters produced dissimilar lesions in different tissue types, while significant differences in temperature, thermal dose and T2 were observed between the parameter sets. CONCLUSION: Clinical MR-HIFU system was utilised to generate distinct types of lesions and to produce targeted thermomechanical bioeffects in ex vivo tissues. The results guide HIFU research on thermomechanical tissue bioeffects, inform future studies and advice sonication parameter selection for direct tumour ablation or immunomodulation using a clinical MR-HIFU system.

Comparison of Noninvasive High-Intensity Focused Ultrasound with Radiofrequency Ablation of Osteoid Osteoma.

OBJECTIVE: To evaluate clinical feasibility and safety of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) treatment of symptomatic osteoid osteoma and to compare clinical response with standard of care treatment. STUDY DESIGN: Nine subjects with radiologically confirmed, symptomatic osteoid osteoma were treated with MR-HIFU in an institutional review board-approved clinical trial. Treatment feasibility and safety were assessed. Clinical response was evaluated in terms of analgesic requirement, visual analog scale pain score, and sleep quality. Anesthesia, procedure, and recovery times were recorded. This MR-HIFU group was compared with a historical control group of 9 consecutive patients treated with radiofrequency ablation. RESULTS: Nine subjects (7 male, 2 female; 16 ± 6 years) were treated with MR-HIFU without technical difficulties or any serious adverse events. There was significant decrease in their median pain scores 4 weeks within treatment (6 vs 0, P < .01). Total pain resolution and cessation of analgesics were achieved in 8 of 9 patients after 4 weeks. In the radiofrequency ablation group, 9 patients (8 male, 1 female; 10 ± 6 years) were treated in routine clinical practice. All 9 demonstrated complete pain resolution and cessation of medications by 4 weeks with a significant decrease in median pain scores (9 vs 0, P < .001). One developed a second-degree skin burn, but there were no other adverse events. Procedure times and treatment charges were comparable between the 2 groups. CONCLUSION: This pilot study shows that MR-HIFU treatment of osteoid osteoma refractory to medical therapy is feasible and can be performed safely in pediatric patients. Clinical response is comparable with standard of care treatment but without any incisions or exposure to ionizing radiation. TRIAL REGISTRATION: ClinicalTrials.govNCT02349971.

Multimodality Imaging of Ethiodized Oil-loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors.

Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor-bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70-150-µm radiopaque microspheres in saline (radiopaque microsphere group), 70-150-µm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70-150-µm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone-beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement. For the group with nonradiopaque microspheres and contrast material, retained tumoral contrast remained qualitatively visible with all modalities except for micro-CT, which demonstrated soluble contrast material washout over time. Conclusion Radiopaque microspheres were visible with all imaging modalities and helped increase conspicuity of the tumor as well as its feeding arteries after TAE in a rabbit VX2 liver tumor model. (©) RSNA, 2015.

Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization.

PURPOSE: To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. MATERIALS AND METHODS: Rabbit Vx2 liver tumors were embolized with 100-300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3-5 per group; 18 total). RESULTS: Mean microvascular density was 70 vessels/mm(2) ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31(+) structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. CONCLUSIONS: Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy.

Preparation of Radiopaque Drug-Eluting Beads for Transcatheter Chemoembolization.

PURPOSE: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. MATERIALS AND METHODS: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. RESULTS: Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. CONCLUSIONS: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.

DC BeadM1™: towards an optimal transcatheter hepatic tumour therapy.

Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 µm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100-300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100-300 µm beads. Radiopaque versions of 70-150 and 100-300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70-150 µm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100-300 µm beads.

Direct Quantification and Comparison of Intratumoral Hypoxia following Transcatheter Arterial Embolization of VX2 Liver Tumors with Different Diameter Microspheres.

PURPOSE: To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors. MATERIALS AND METHODS: Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 µm, 100-300 µm, or 300-500 µm in diameter. RESULTS: Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 µm diameters compared with 70-150 µm diameters (P < .05). CONCLUSIONS: In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions.

Temperature-sensitive liposome-mediated delivery of thrombolytic agents.

BACKGROUND: Clinical efficacy of thrombolytic drugs is limited by lack of specific delivery and requires large therapeutic doses which increase toxicity. Encapsulating these drugs in temperature-sensitive liposomes and applying hyperthermia to deliver thrombolytic agents locally to thrombus might theoretically favourably alter the therapeutic window. The objectives of this study were to formulate liposomes encapsulating thrombolytics and assess thrombolytic activity following hyperthermia. METHODS: Three liposome formulations were investigated: temperature-sensitive liposome (TSL, DPPC:DSPE-PEG2000 (mol% 95:5)), low temperature-sensitive liposome (LTSL, DPPC:MSPC:DSPE-PEG2000 (mol% 85.3:9.7:5)), and traditional temperature-sensitive liposome (TTSL, DPPC:HSPC:Chol:DSPE-PEG2000 (mol% 55:25:15:5)). To characterise temperature-dependent release of high molecular weight cargo from each formulation, fluorescein-conjugated dextrans (70 kDa) were loaded and release was quantified via spectrophotometry. Staphylokinase (SAK), urokinase, and tissue-type plasminogen activator were also loaded individually into each liposome formulation. Leakage at 37 °C and release at 38-44 °C were quantified via chromogenic enzymatic activity assay. Clot lysis was evaluated by measuring mass of blood clots before and after thrombolytic liposome treatment. RESULTS: The LTSL formulation had optimal release characteristics with maximum release at 41.3 °C. Release of dextrans from LTSLs was observed to be 11.5 ± 1.5%, 79.7 ± 1.6%, and 93.6 ± 3.7% after 15 min in plasma at 37°, 39°, and 41.3 °C, respectively. The SAK LTSL had the highest release/leakage ratio and demonstrated greater clot lysis. CONCLUSIONS: The SAK LTSL achieves significant clot lysis in vitro. When combined with local hyperthermia, the SAK LTSL potentially produces sufficient thrombolysis while minimising systemic side effects.

Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization.

Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead(®)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead(®) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1'-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.

Design and Evaluation of a Spoke-Based Double-Lumen Pediatric Gastrostomy Tube.

Gastrostomy tubes (G-tubes) are the gold standard for feeding assistance for children with feeding dysfunction. Current G-tubes pose complications that interrupt the delivery of feed, including tube displacement and difficulty of at-home use. This study details an alternative, spoke-based, double-lumen G-tube design and preliminary validation of its function and usability. Pull force testing was performed on spoke G-tube models across three sizes and two classifications (hard/soft). Preliminary models were evaluated against market standards. Though the pull force of the spoke model was found to be lower than that of both market standards, hard modifications to the spoke model improved retentive force. Ease of use was tested amongst users unfamiliar with G-tube placement. The spoke design required 12.3 ± 4.7 s to deploy, less than half the time required for market standards. However, balloon G-tubes were still perceived to be easiest to use by 70% of participants, with indications that a spoke design may be easier to use if sized similarly to current G-tubes, with auxiliary improvements to factors such as grip. While there is a need for improvements in the material properties and manufacturing of the proposed design, this study provides early validation of the potential to address complications of existing G-tubes.

Assessing the Effect of Augmented Reality on Procedural Outcomes During Ultrasound-Guided Vascular Access.

OBJECTIVE: Augmented reality devices are increasingly accepted in health care, though most applications involve education and pre-operative planning. A novel augmented reality ultrasound application, HoloUS, was developed for the Microsoft HoloLens 2 to project real-time ultrasound images directly into the user's field of view. In this work, we assessed the effect of using HoloUS on vascular access procedural outcomes. METHODS: A single-center user study was completed with participants with (N = 22) and without (N = 12) experience performing ultrasound-guided vascular access. Users completed a venipuncture and aspiration task a total of four times: three times on study day 1, and once on study day 2 between 2 and 4 weeks later. Users were randomized to use conventional ultrasound during either their first or second task and the HoloUS application at all other times. Task completion time, numbers of needle re-directions, head adjustments and needle visualization rates were recorded. RESULTS: For expert users, task completion time was significantly faster using HoloUS (11.5 s, interquartile range [IQR] = 6.5-23.5 s vs. 18.5 s, IQR = 11.0-36.5 s; p = 0.04). The number of head adjustments was significantly lower using the HoloUS app (1.0, IQR = 0.0-1.0 vs. 3.0, IQR = 1.0-5.0; p < 0.0001). No significant differences were identified in other measured outcomes. CONCLUSION: This is the first investigation of augmented reality-based ultrasound-guided vascular access using the second-generation HoloLens. It demonstrates equivalent procedural efficiency and accuracy, with favorable usability, ergonomics and user independence when compared with traditional ultrasound techniques.

Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine.

PURPOSE: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 µm or 100-300 µm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). MATERIALS AND METHODS: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. RESULTS: MicroCT demonstrated that 70-150-µm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 µm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-µm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. CONCLUSIONS: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine.

Comparison of Smartphone Augmented Reality, Smartglasses Augmented Reality, and 3D CBCT-guided Fluoroscopy Navigation for Percutaneous Needle Insertion: A Phantom Study.

PURPOSE: To compare needle placement performance using an augmented reality (AR) navigation platform implemented on smartphone or smartglasses devices to that of CBCT-guided fluoroscopy in a phantom. MATERIALS AND METHODS: An AR application was developed to display a planned percutaneous needle trajectory on the smartphone (iPhone7) and smartglasses (HoloLens1) devices in real time. Two AR-guided needle placement systems and CBCT-guided fluoroscopy with navigation software (XperGuide, Philips) were compared using an anthropomorphic phantom (CIRS, Norfolk, VA). Six interventional radiologists each performed 18 independent needle placements using smartphone (n = 6), smartglasses (n = 6), and XperGuide (n = 6) guidance. Placement error was defined as the distance from the needle tip to the target center. Placement time was recorded. For XperGuide, dose-area product (DAP, mGy*cm2) and fluoroscopy time (sec) were recorded. Statistical comparisons were made using a two-way repeated measures ANOVA. RESULTS: The placement error using the smartphone, smartglasses, or XperGuide was similar (3.98 ± 1.68 mm, 5.18 ± 3.84 mm, 4.13 ± 2.38 mm, respectively, p = 0.11). Compared to CBCT-guided fluoroscopy, the smartphone and smartglasses reduced placement time by 38% (p = 0.02) and 55% (p = 0.001), respectively. The DAP for insertion using XperGuide was 3086 ± 2920 mGy*cm2, and no intra-procedural radiation was required for augmented reality. CONCLUSIONS: Smartphone- and smartglasses-based augmented reality reduced needle placement time and radiation exposure while maintaining placement accuracy compared to a clinically validated needle navigation platform.

Development of "imageable" beads for transcatheter embolotherapy.

PURPOSE: To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intraprocedural fluoroscopy and computed tomography (CT) imaging and to evaluate their spatial distribution inside target tissues during and after transcatheter embolization. MATERIALS AND METHODS: Polyvinyl alcohol hydrogel microspheres were loaded with Lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intraprocedural fluoroscopy and CT. Ex vivo evaluation was performed with light microscopy and micro-CT. RESULTS: In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose-dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution. CONCLUSIONS: Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intraprocedural fluoroscopy and CT. These radiopaque microspheres provided the three-dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time intraprocedural feedback for the interventional radiologist. These microspheres may be useful for demonstrating the influence of material and technical variability in transcatheter embolization in addition to providing intraprocedural identification of tissue at risk of undertreatment.

Emerging hyperthermia applications for pediatric oncology.

Local application of hyperthermia has a myriad of effects on the tumor microenvironment as well as the host's immune system. Ablative hyperthermia (typically > 55 °C) has been used both as monotherapy and adjuvant therapy, while mild hyperthermia treatment (39-45 °C) demonstrated efficacy as an adjuvant therapy through enhancement of both chemotherapy and radiation therapy. Clinical integration of hyperthermia has especially great potential in pediatric oncology, where current chemotherapy regimens have reached maximum tolerability and the young age of patients implies significant risks of late effects related to therapy. Furthermore, activation of both local and systemic immune response by hyperthermia suggests that hyperthermia treatments could be used to enhance the anticancer effects of immunotherapy. This review summarizes the state of current applications of hyperthermia in pediatric oncology and discusses the use of hyperthermia in the context of other available treatments and promising pre-clinical research.