Image-Guided Transbronchial Pulmonary Cryoablation with a Flexible Cryoprobe in Swine: Performance and Radiology-Pathology Correlation.

PURPOSE: To evaluate the performance of a prototype flexible transbronchial cryoprobe compared with that of percutaneous transthoracic cryoablation and to define cone-beam computed tomography (CT) imaging and pathology cryolesion features in an in vivo swine model. MATERIALS AND METHODS: Transbronchial cryoablation was performed with a prototype flexible cryoprobe (3 central and 3 peripheral lung ablations in 3 swine) and compared with transthoracic cryoablation performed with a commercially available rigid cryoprobe (2 peripheral lung ablations in 1 swine). Procedural time and cryoablation success rates for endobronchial navigation and cryoneedle deployment were measured. Intraoperative cone-beam CT imaging features of cryolesions were characterized and correlated with gross pathology and hematoxylin and eosin-stained sections of the explanted cryolesions. RESULTS: The flexible cryoprobe was successfully navigated and delivered to each target through a steerable guiding sheath (6/6). At 4 minutes after ablation, 5 of 6 transbronchial and 2 of 2 transthoracic cryolesions were visible on cone-beam CT. The volumes on cone-beam CT images were 55.5 cm3 (SE ± 8.0) for central transbronchial ablations (n = 2), 72.5 cm3 (SE ± 8.1) for peripheral transbronchial ablations (n = 3), and 79.5 cm3 (SE ±11.6) for peripheral transthoracic ablations (n = 2). Pneumothorax developed in 1 animal after transbronchial ablation and during ablation in the transthoracic cryoablation. Images of cryoablation zones on cone-beam CT correlated well with the matched gross pathology and histopathology sections of the cryolesions. CONCLUSIONS: Transbronchial cryoablation with a flexible cryoprobe, delivered through a steerable guiding sheath, is feasible. Transbronchial cryoablation zones are imageable with cone-beam CT, with gross pathology and histopathology similar to those of transthoracic cryoablation.

Morphometric characterization and temporal temperature measurements during hepatic microwave ablation in swine.

PURPOSE: Heat-induced destruction of cancer cells via microwave ablation (MWA) is emerging as a viable treatment of primary and metastatic liver cancer. Prediction of the impacted zone where cell death occurs, especially in the presence of vasculature, is challenging but may be achieved via biophysical modeling. To advance and characterize thermal MWA for focal cancer treatment, an in vivo method and experimental dataset were created for assessment of biophysical models designed to dynamically predict ablation zone parameters, given the delivery device, power, location, and proximity to vessels. MATERIALS AND METHODS: MWA zone size, shape, and temperature were characterized and monitored in the absence of perfusion in ex vivo liver and a tissue-mimicking thermochromic phantom (TMTCP) at two power settings. Temperature was monitored over time using implanted thermocouples with their locations defined by CT. TMTCPs were used to identify the location of the ablation zone relative to the probe. In 6 swine, contrast-enhanced CTs were additionally acquired to visualize vasculature and absence of perfusion along with corresponding post-mortem gross pathology. RESULTS: Bench studies demonstrated average ablation zone sizes of 4.13±1.56cm2 and 8.51±3.92cm2, solidity of 0.96±0.06 and 0.99±0.01, ablations centered 3.75cm and 3.5cm proximal to the probe tip, and temperatures of 50 ºC at 14.5±13.4s and 2.5±2.1s for 40W and 90W ablations, respectively. In vivo imaging showed average volumes of 9.8±4.8cm3 and 33.2±28.4cm3 and 3D solidity of 0.87±0.02 and 0.75±0.15, and gross pathology showed a hemorrhagic halo area of 3.1±1.2cm2 and 9.1±3.0cm2 for 40W and 90W ablations, respectfully. Temperatures reached 50ºC at 19.5±9.2s and 13.0±8.3s for 40W and 90W ablations, respectively. CONCLUSION: MWA results are challenging to predict and are more variable than manufacturer-provided and bench predictions due to vascular stasis, heat-induced tissue changes, and probe operating conditions. Accurate prediction of MWA zones and temperature in vivo requires comprehensive thermal validation sets.

HoloLens augmented reality system for transperineal free-hand prostate procedures.

Purpose: An augmented reality (AR) system was developed to facilitate free-hand real-time needle guidance for transperineal prostate (TP) procedures and to overcome the limitations of a traditional guidance grid. Approach: The HoloLens AR system enables the superimposition of annotated anatomy derived from preprocedural volumetric images onto a patient and addresses the most challenging part of free-hand TP procedures by providing real-time needle tip localization and needle depth visualization during insertion. The AR system accuracy, or the image overlay accuracy ( n = 56 ), and needle targeting accuracy ( n = 24 ) were evaluated within a 3D-printed phantom. Three operators each used a planned-path guidance method ( n = 4 ) and free-hand guidance ( n = 4 ) to guide needles into targets in a gel phantom. Placement error was recorded. The feasibility of the system was further evaluated by delivering soft tissue markers into tumors of an anthropomorphic pelvic phantom via the perineum. Results: The image overlay error was 1.29 ± 0.57 mm , and needle targeting error was 2.13 ± 0.52 mm . The planned-path guidance placements showed similar error compared to the free-hand guidance ( 4.14 ± 1.08 mm versus 4.20 ± 1.08 mm , p = 0.90 ). The markers were successfully implanted either into or in close proximity to the target lesion. Conclusions: The HoloLens AR system can provide accurate needle guidance for TP interventions. AR support for free-hand lesion targeting is feasible and may provide more flexibility than grid-based methods, due to the real-time 3D and immersive experience during free-hand TP procedures.

Imaging and Pathologic Evaluation of Cryoablation of Woodchuck (Marmota monax) Hepatocellular Carcinoma.

We characterized cryoablation as a mode of clinical intervention in adult woodchucks with hepatocellular carcinoma (HCC). Woodchucks (n = 4) were infected with woodchuck hepatitis virus at birth and developed LI-RADS-5 hypervascular HCC. At 21 mo of age, they underwent ultrasound (US), contrast-enhanced CT (CECT) imaging, and US-guided subtotal cryoablation (IcePearl 2.1 CX, Galil, BTG) of their largest tumor (Mean HCC volume of 49 ± 9 cm³). Cryoablation was performed using two 10-min freeze cycles, each followed by an 8-min thaw cycle. The first woodchuck developed significant hemorrhage after the procedure and was euthanized. In the other 3 woodchucks, the probe track was cauterized and all 3 completed the study. Fourteen days after ablation, CECT was performed, and woodchucks were euthanized. Explanted tumors were sectioned using subject-specific, 3D-printed cutting molds. Initial tumor volume, the size of the cryoablation ice ball, gross pathology and hematoxylin and eosin-stained tissue sections were evaluated. On US, the edges of the solid ice balls were echogenic with dense acoustic shadowing and average dimensions of 3.1 ± 0.5 × 2.1 ± 0.4 cm and cross-sectional area of 4.7 ± 1.0 cm². On day 14 after cryoablation, CECT of the 3 woodchucks showed devascularized hypo-attenuating cryolesions with dimensions of 2.8 ± 0.3 × 2.6 ± 0.4 × 2.93 ± 0.7 cm and a cross sectional area of 5.8 ± 1.2 cm². Histopathologic evaluation showed hemorrhagic necrosis with a central amorphous region of coagulative necrosis surrounded by a rim of karyorrhectic debris. A rim of approximately 2.5 mm of coagulative necrosis and fibrous connective tissue clearly demarcated the cryolesion from adjacent HCC. Partial cryoablation of tumors produced coagulative necrosis with well-defined ablation margins at 14 d. Cauterization appeared to prevent hemorrhage after cryoablation of hypervascular tumors. Our findings indicate that woodchucks with HCC may provide a predictive preclinical model for investigating ablative modalities and developing new combination therapies.

In-line miniature 3D-printed pressure-cycled ventilator maintains respiratory homeostasis in swine with induced acute pulmonary injury.

The COVID-19 pandemic demonstrated the need for inexpensive, easy-to-use, rapidly mass-produced resuscitation devices that could be quickly distributed in areas of critical need. In-line miniature ventilators based on principles of fluidics ventilate patients by automatically oscillating between forced inspiration and assisted expiration as airway pressure changes, requiring only a continuous supply of pressurized oxygen. Here, we designed three miniature ventilator models to operate in specific pressure ranges along a continuum of clinical lung injury (mild, moderate, and severe injury). Three-dimensional (3D)-printed prototype devices evaluated in a lung simulator generated airway pressures, tidal volumes, and minute ventilation within the targeted range for the state of lung disease each was designed to support. In testing in domestic swine before and after induction of pulmonary injury, the ventilators for mild and moderate injury met the design criteria when matched with the appropriate degree of lung injury. Although the ventilator for severe injury provided the specified design pressures, respiratory rate was elevated with reduced minute ventilation, a result of lung compliance below design parameters. Respiratory rate reflected how well each ventilator matched the injury state of the lungs and could guide selection of ventilator models in clinical use. This simple device could help mitigate shortages of conventional ventilators during pandemics and other disasters requiring rapid access to advanced airway management, or in transport applications for hands-free ventilation.

Woodchuck Hepatic Anatomy and Vascular Alterations Due to Hepatocellular Carcinoma with Angiographic Atlas of the Abdomen and Pelvis.

PURPOSE: To characterize the hepatic and abdominal angiographic anatomy of woodchucks and vascular changes associated with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-nine woodchucks (23 with viral-associated HCC, 6 without) underwent multiphasic computed tomography (CT). Fourteen woodchucks (8 with HCC) also underwent diagnostic angiography. Hepatic arterial diameters were measured on the CT scans. Woodchucks were divided into 3 groups: non-tumor-bearing, largest tumor supplied by the right hepatic artery (RHA), and largest tumor supplied by the left hepatic artery (LHA). Statistical analysis with a repeated measures model was performed to determine the effects of tumor location (right, left), vessel measured (RHA, LHA), and interaction between the 2 on vessel diameter. Lobar arteries supplying HCC were compared with those that did not. RESULTS: CT anatomy and normal and variant vascular anatomy were defined. In woodchucks with HCC, LHA and RHA supplying tumors had mean diameters of 2.0 mm ± 0.3 and 1.6 mm ± 0.3 versus 1.5 mm ± 0.3 and 1.1 mm ± 0.2 for non-tumor-supplying arteries (P = .0002 and P < .0001), respectively. Lobar arteries supplying tumors were similarly ectatic. The right lateral lobe artery had the most profound increase in the mean diameter when supplying tumors, measuring 1.7 mm ± 0.1 versus 1.0 mm ± 0.1 in the non-tumor-supplying artery (P < .0001). There were no differences in the diameters of the aorta and celiac, common, and proper hepatic arteries between tumor- and non-tumor-bearing woodchucks. An angiographic atlas of the abdominal vessels was generated. CONCLUSIONS: HCC tumoral vasculature in woodchucks was ectatic compared with normal vasculature. This phenomenon recapitulates human HCC and may facilitate investigation of transcatheter and drug delivery therapies in an HCC animal model.

Endovascular steerable and endobronchial precurved guiding sheaths for transbronchial needle delivery under augmented fluoroscopy and cone beam CT image guidance.

BACKGROUND: Endobronchial navigation is performed in a variety of ways, none of which are meeting all the clinicians' needs required to reach diagnostic success in every patient. We sought to characterize precurved and steerable guiding sheaths (GS) in endobronchial targeting for lung biopsy using cone beam computed tomography (CBCT) based augmented fluoroscopy (AF) image guidance. METHODS: Four precurved GS (EdgeTM 45, 90, 180, 180EW, Medtronic) and two steerable GS [6.5 F Destino Twist (DT), Oscor; 6 F Morph, BioCardia] were evaluated alone and in combination with an electromagnetic tracking (EM) guide and biopsy needles in three experimental phases: (I) bench model to assess GS deflection and perform biopsy simulations; (II) ex vivo swine lung comparing 2 steerable and 2 precurved GS; and (III) in vivo male swine lung to deliver a needle (n=2 swine) or to deliver a fiducial marker (n=2 swine) using 2 steerable GS. Ex vivo and in vivo image guidance was performed with either commercial or prototype AF image guidance software (Philips) based on either prior CT or procedural CBCT. Primary outcomes were GS delivery angle (θGS) and needle delivery angle (θN) in bench evaluation and needle delivery error (mm) (mean ± se) for ex vivo and in vivo studies. RESULTS: The steerable DT had the largest range of GS delivery angles (θN: 0-114°) with either the 21 G or 19 G biopsy needle in the bench model. In ex vivo swine lung, needle delivery errors were 8.7±0.9 mm (precurved Edge 90), 5.4±1.9 mm (precurved Edge 180), 4.7±1.2 mm (steerable DT), and 5.6±2.4 mm (steerable Morph). In vivo, the needle delivery errors for the steerable GS were 6.0±1.0 mm (DT) and 15±7.0 mm (Morph). In vivo marker coil delivery was successful for both the steerable DT and morph GS. A case report demonstrated successful needle biopsy with the steerable DT. CONCLUSIONS: Endobronchial needle delivery with AF guidance is feasible without a bronchoscope with steerable GS providing comparable or improved accuracy compared to precurved GS.

Electromagnetic Tracking and Optical Molecular Imaging Guidance for Liver Biopsy and Point-of-Care Tissue Assessment in Phantom and Woodchuck Hepatocellular Carcinoma.

PURPOSE: To evaluate an integrated liver biopsy platform that combined CT image fusion, electromagnetic (EM) tracking, and optical molecular imaging (OMI) of indocyanine green (ICG) to target hepatocellular carcinoma (HCC) lesions and a point-of-care (POC) OMI to assess biopsy cores, all based on tumor retention of ICG compared to normal liver, in phantom and animal model. MATERIAL: A custom CT image fusion and EM-tracked guidance platform was modified to integrate the measurement of ICG fluorescence intensity signals in targeted liver tissue with an OMI stylet or a POC OMI system. Accuracy was evaluated in phantom and a woodchuck with HCC, 1 day after administration of ICG. Fresh biopsy cores and paraffin-embedded formalin-fixed liver tissue blocks were evaluated with the OMI stylet or POC system to identify ICG fluorescence signal and ICG peak intensity. RESULTS: The mean distance between the initial guided needle delivery location and the peak ICG signal was 5.0 ± 4.7 mm in the phantom. There was complete agreement between the reviewers of the POC-acquired ICG images, cytology, and histopathology in differentiating HCC-positive from HCC-negative biopsy cores. The peak ICG fluorescence intensity signal in the ex vivo liver blocks was 39 ± 12 and 281 ± 150 for HCC negative and HCC positive, respectively. CONCLUSION: Biopsy guidance with fused CT imaging, EM tracking, and ICG tracking with an OMI stylet to detect HCC is feasible. Immediate assessment of ICG uptake in biopsy cores with the POC OMI system is feasible and correlates with the presence of HCC in the tissue.

Imaging, Pathology, and Immune Correlates in the Woodchuck Hepatic Tumor Model.

BACKGROUND: Woodchucks chronically infected with woodchuck hepatitis virus (WHV), which resembles human hepatitis B virus, develop spontaneous hepatic tumors and may be an important biological and immunological model for human HCC. Nonetheless, this model requires further validation to fully realize its translational potential. METHODS: Woodchucks infected at birth with WHV that had developed HCC (n=12) were studied. Computed tomography, ultrasound, and magnetic resonance imaging were performed under anesthesia. LI-RADS scoring and correlative histologic analysis of sectioned tissues were performed. For immune characterization of tumors, CD3 (T cells), CD4 (T helpers), NCAM (Natural killers), FOXP3 (T-regulatory), PDL-1 (inhibitory checkpoint protein), and the human hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP) immunohistochemical stains were performed. RESULTS: Forty tumors were identified on imaging of which 29 were confirmed to be HCC with 26 categorized as LR-4 or 5. The remainder of the tumors had benign histology including basophilic foci, adenoma, and lipidosis as well as pre-malignant dysplastic foci. LR-4 and LR-5 lesions showed high sensitivity (90%) and specificity (100%) for malignant and pre-malignant tumors. Natural killers count was found to be 2-5 times lower in tumors relative to normal parenchyma while other immune cells were located in the periphery of tumors. Tumors expressed AFP and did not express PD-L1. CONCLUSION: Woodchucks chronically infected with WHV developed diverse hepatic tumor types with diagnostic imaging, pathology, and immune patterns comparable to that in humans. This unique animal model may provide a valuable tool for translation and validation of novel image-guided and immune-therapeutic investigations.

Endobronchial Navigation Guided by Cone-Beam CT-Based Augmented Fluoroscopy without a Bronchoscope: Feasibility Study in Phantom and Swine.

PURPOSE: To evaluate the accuracy of cone-beam computed tomography (CT)-based augmented fluoroscopy (AF) image guidance for endobronchial navigation to peripheral lung targets. METHODS: Prototypic endobronchial navigation AF software that superimposed segmented airways, targets, and pathways based on cone-beam CT onto fluoroscopy images was evaluated ex vivo in fixed swine lungs and in vivo in healthy swine (n = 4) without a bronchoscope. Ex vivo and in vivo (n = 3) phase 1 experiments used guide catheters and AF software version 1, whereas in vivo phase 2 (n = 1) experiments also used an endovascular steerable guiding sheath, upgraded AF software version 2, and lung-specific low-radiation-dose protocols. First-pass navigation success was defined as catheter delivery into a targeted airway segment solely using AF, with second-pass success defined as reaching the targeted segment by using updated AF image guidance based on confirmatory cone-beam CT. Secondary outcomes were navigation error, navigation time, radiation exposure, and preliminary safety. RESULTS: First-pass success was 100% (10/10) ex vivo and 19/24 (79%) and 11/15 (73%) for in vivo phases 1 and 2, respectively. Phase 2 second-pass success was 4/4 (100%). Navigation errors were 2.2 ± 1.2 mm ex vivo and 4.9 ± 3.2 mm and 4.0 ± 2.6 mm for in vivo phases 1 and 2, respectively. No major device-related complications were observed in the in vivo experiments. CONCLUSIONS: Endobronchial navigation is feasible and accurate with cone-beam CT-based AF image guidance. AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy.

Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit Preclinical Model.

PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70-150 µm, DC Bead LUMI™, Biocompatibles UK Ltd-Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post-TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076-0.105 mL) and 1.99 mg/kg (1.51-2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within 2 weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m2) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Tracked Foley catheter for motion compensation during fusion image-guided prostate procedures: a phantom study.

BACKGROUND: Uncorrected patient or prostate motion may impair targeting prostate areas during fusion image-guided procedures. We evaluated if a prototype "tracked Foley catheter" (TFC) could maintain fusion image alignment after simulated organ motion. METHODS: A pelvic phantom model underwent magnetic resonance imaging (MRI), and the prostate was segmented. The TFC was placed in the phantom. MRI/ultrasound (US) fusion was performed. Four trials were performed varying motion and TFC presence/absence: (1) TFC/no-motion, (2) TFC/motion, (3) no-TFC/no-motion, and (4) no-TFC/motion. To quantify image alignment, screen captures generated Dice similarity coefficient (DSC) and offset distances (ODs) (maximal US-to-MRI distance between edges on fusion images). Three anatomical targets were identified for placement of a needle under fusion guidance. A computed tomography scan was used to measure system error (SE), i.e., the distance from needle tip to intended target. RESULTS: The TFC presence improved MRI/US alignment by DSC 0.88, 0.88, 0.74, and 0.61 in trials 1, 2, 3, and 4, respectively. Both OD (trial 2 versus trial 4, 4.85 ± 1.60 versus 25.29 ± 6.50 mm, p < 0.001) and SE (trial 2 versus trial 4, 6.35 ± 1.31 versus 32.16 ± 6.50 mm, p < 0.005) were significantly lower when the TFC was present after artificial motion, and significantly smaller OD when static (trial 1 versus trial 3, 4.29 ± 1.24 versus 6.42 ± 2.29 mm, p < 0.001). CONCLUSION: TFC provided better image alignment with or without simulated motion. This may overcome system limitations, allowing for more accurate fusion image alignment during fusion-guided biopsy, ablation, or robotic prostatectomy.

Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma.

PURPOSE: To assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Nine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0-2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70-150-µm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin. RESULTS: The tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm3 ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor. CONCLUSIONS: Woodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic-pathologic correlations.

Feasibility and Acute Safety Study of Radiofrequency Energy Delivery to the Vena Caval Wall via an IVC Filter in Swine.

Retrievable inferior vena cava (IVC) filters are self-expanding metallic devices implanted in the IVC to prevent migration of thrombi from the deep veins of the legs and pelvis to the lungs. The risk of complications from the filters increases with duration of implantation, but retrieval may be difficult due to intimal hyperplasia around the components of the filter. In this study, the potential for delivery of radiofrequency (RF) energy to the IVC wall via the filter was investigated. IVC filters were deployed in 4 swine while attached to a snare connected to a 480 kHz RF generator. Energy ranging from 0 to 48 kJ was applied via the filter followed by re-sheathing and withdrawal of the filter while connected to a force measurement device. Resheathing forces for the 0-energy cohort and pooled data from the 6-24 kJ cohorts were 4.50±0.70 N and 4.50±0.75 N, respectively. Petechial hemorrhages and variable non-occlusive thrombi were noted in some cohorts including the 0-energy cohort, consistent with delivery and acute retrieval of an IVC filter. Histologically, the extent of RF-induced injury was subtle at 6 kJ with focal areas of homogenized collagen while the 12 kJ cohort showed segmental tissue charring with coagulation necrosis which was more extensive for the 24 kJ cohort. The 48 kJ energy caused more extensive and non-target organ damage. The study demonstrated feasibility of delivery of RF to the IVC wall via a deployed filter, supporting further study of the ability of local RF heating of the IVC wall to inhibit the neointimal hyperplasia or as an aid in retrieval.

Template for MR Visualization and Needle Targeting.

To improve the targeting accuracy and reduce procedure time in magnetic resonance imaging (MRI)-guided procedures, a 3D-printed flexible template was developed. The template was printed using flexible photopolymer resin FLFLGR02 in Form 2 printer® (Formlabs, Inc., Somerville, MA). The flexible material gives the template a unique advantage by allowing it to make close contact with human skin and provide accurate insertion with the help of the newly developed OncoNav software. At the back of the template, there is a grid comprised of circular containers filled with contrast agent. At the front of the template, the guide holes between the containers provide space and angular flexibility for needle insertion. MRI scans are initially used to identify tumor position as well as the template location. The OncoNav software then pre-selects a best guide hole for targeting a specific lesion and suggests insertion depth for the physician A phantom study of 13 insertions in a CT scanner was carried out for assessing needle placement accuracy. The mean total distance error between planned and actual insertion is 2.7 mm, the maximum error was 4.78 mm and standard deviation was 1.1 mm. The accuracy of the OncoNav-assisted and template-guided needle targeting is comparable to the robot-assisted procedure. The proposed template is a low-cost, quickly-deployable and disposable medical device. The presented technology will be further evaluated in prostate cancer patients to quantify its accuracy in needle biopsy.

Mapping Drug Dose Distribution on CT Images Following Transarterial Chemoembolization with Radiopaque Drug-Eluting Beads in a Rabbit Tumor Model.

Purpose To correlate bead location and attenuation on CT images with the quantity and distribution of drug delivered to the liver following transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEB) in a rabbit tumor model. Materials and Methods All procedures were performed with a protocol approved by the Institutional Animal Care and Use Committee. TACE was performed in rabbits (n = 4) bearing VX2 liver tumors by using radiopaque DEB (70-150 µm) loaded with doxorubicin (DOX). Livers were resected 1 hour after embolization, immediately frozen, and cut by using liver-specific three-dimensional-printed molds for colocalization of liver specimens and CT imaging. DOX penetration into tissue surrounding beads was evaluated with fluorescence microscopy. DOX levels in liver specimens were predicted by using statistical models correlating DOX content measured in tissue with bead volume and attenuation measured on CT images. Model predictions were then compared with actual measured DOX concentrations to assess the models' predictive power. Results Eluted DOX remained in close proximity (<600 µm) to beads in the liver 1 hour after TACE. Bead volume and attenuation measured on CT images demonstrated positive linear correlations (0.950 and 0.965, respectively) with DOX content in liver specimens. DOX content model predictions based on CT images were accurate compared with actual liver DOX levels at 1 hour. Conclusion CT may be used to estimate drug dose delivery and distribution in the liver following transarterial chemoembolization (TACE) with doxorubicin-loaded radiopaque drug-eluting beads (DEB). Although speculative, this informational map might be helpful in planning and understanding the spatial effects of TACE with DEB. © RSNA, 2018.

"Super-active surveillance": MRI ultrasound fusion biopsy and ablation for less invasive management of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has allowed clinicians to better visualize and target suspicious lesions during biopsy. Targeted prostate biopsies give a more accurate representation of the true cancer volume and stage so that appropriate treatment or active surveillance can be selected. Advances in technology have led to the development of MRI and ultrasound fusion platforms used for targeted biopsies, monitoring cancer progression, and more recently for the application of focal therapy. Lesions visualized on mpMRI can be targeted for ablation with a variety of energy sources employed under both local and general anesthesia. Focal ablation may offer an alternative option for treating prostate cancer as compared to the well-established interventions of whole-gland radiation or prostatectomy. Focal ablation may also be an option for patients on active surveillance who wish to be even more "active" in their surveillance. In this review, we describe the advancements and development of fusion biopsies, the rationale behind focal therapy, and introduce focal ablative techniques for indolent prostate cancers ("super-active surveillance"), including cryoablation and focal laser ablation (FLA) and the subsequent MRI/biopsy surveillance.

Distribution and Detection of Radiopaque Beads after Hepatic Transarterial Embolization in Swine: Cone-Beam CT versus MicroCT.

PURPOSE: To determine the true distribution of radiopaque beads (ROBs) after hepatic embolization in swine as imaged by micro-computed tomography (microCT) compared with in vivo cone-beam computerized tomography (CT) imaged at different kVp settings. MATERIALS AND METHODS: Swine (n = 3) underwent hepatic transarterial embolization (n = 6) with the use of 70-150-µm ROBs under fluoroscopic guidance. After stasis, in vivo cone-beam CT was performed at 120, 100, and 80 kVp. The animal was euthanized, the liver resected, and microCT with 17 µm resolution performed on embolized tissue samples. The resulting cone-beam CT and microCT data were segmented and registered. Total vessel length, minimum volume-enclosing ellipsoid (MVEE), and number of independent volumes were measured. Maximum-intensity projections (MIPs) were generated for each cone-beam CT. RESULTS: Metrics for all cone-beam CT segmentations differed significantly from microCT segmentations. Segmentations at 80 kVp presented significantly greater vessel length, MVEE, and number of independent volumes compared with 100 kVp and 120 kVp. In addition, 100 kVp segmentations presented significantly greater vessel length than 120 kVp. MIPs presented greater visualization than cone-beam CT segmentations and improved as kVp decreased. CONCLUSIONS: The full ROB distribution was more extensive than was apparent on cone-beam CT. Quantitative measures of embolic distribution demonstrated significantly better correlation with microCT with decreasing kVp. Similarly, qualitative analysis of MIPs showed improved visualization of beads with decreasing kVp. These findings demonstrate the clinical value of 80 kVp and 100 kVp protocols in the imaging of radiopaque embolizations compared with 120 kVp. However, considerations on X-ray penetration and dose may favor use of 100 kVp imaging over 80 kVp.

Lyso-thermosensitive liposomal doxorubicin for treatment of bladder cancer.

PURPOSE: To evaluate lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox®) in combination with loco-regional mild hyperthermia (HT) for targeted drug delivery to the bladder wall and potential treatment of bladder cancer. MATERIAL AND METHODS: Porcine in vivo studies were performed with the following groups: (i) intravenous (IV) LTLD with hyperthermia (LTLD + HT); (ii) IV doxorubicin (DOX) with hyperthermia (IV DOX + HT) and (iii) IV LTLD without hyperthermia (LTLD - HT). Drug formulations were delivered via 30 min IV infusion coinciding with 1-h bladder irrigation (45 °C water for HT groups, 37 °C for non-HT group), followed by immediate bladder resection. DOX concentrations were measured in consecutive sections parallel to the bladder lumen by liquid chromatography following drug extraction. Computer models were developed to simulate tissue heating and drug release from LTLD. RESULTS: Comparing mean DOX concentrations at increasing depths from the lumen to outer surface of the bladder wall, the ranges for LTLD + HT, IV DOX + HT and LTLD - HT, respectively, were 20.32-3.52 µg/g, 2.34-0.61 µg/g and 2.18-0.51 µg/g. The average DOX concentrations in the urothelium/lamina and muscularis, respectively, were 9.7 ± 0.67 and 4.09 ± 0.81 µg/g for IV LTLD + HT, 1.2 ± 0.39 and 0.86 ± 0.24 µg/g for IV DOX + HT, and 1.15 ± 0.38 and 0.62 ± 0.15 µg/g for LTLD - HT. Computational model results were similar to measured DOX levels and suggest adequate temperatures were reached within the bladder wall for drug release from LTLD. CONCLUSIONS: Doxorubicin accumulation and distribution within the bladder wall was achieved at concentrations higher than with free IV doxorubicin by mild bladder hyperthermia combined with systemic delivery of LTLD.

Antenatal betamethasone improves postnatal transition in late preterm lambs with persistent pulmonary hypertension of the newborn.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is associated with increased oxidative stress in pulmonary arteries (PAs). Betamethasone decreases the oxidative stress and improves antioxidant balance in PPHN. We investigated whether antenatal betamethasone improves pulmonary vasodilation and postnatal oxygenation in late preterm lambs with PPHN. METHODS: PPHN was induced by constriction of fetal ductus arteriosus from 128 to 136 d gestation. Ewes were given two intramuscular doses of betamethasone or saline at 24 and 12 h before cesarean-section delivery at 136 d gestation, simulating late preterm birth. Newborn lambs were mechanically ventilated for 8 h with monitoring of blood gas and hemodynamic variables. Lungs were harvested postmortem to determine oxidative stress markers and in vitro responses of PAs. RESULTS: Postnatal arterial partial pressure of oxygen and pH were higher and the oxygenation index and arterial partial pressure of carbon dioxide were lower in betamethasone-treated lambs. PA pressure was lower and systemic pressure higher in lambs treated with betamethasone. Betamethasone decreased the oxidative stress markers and increased endothelial nitric oxide synthase expression in ventilated PPHN lungs. CONCLUSION: Antenatal betamethasone decreases oxidative stress and improves postnatal transition in late preterm lambs with PPHN. This study suggests a potential benefit for antenatal betamethasone in late preterm births.