Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics.

Advanced-stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced-stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long-term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients.

Multi-Functional Biomaterial for the Treatment and Prevention of Central Line-Associated Bloodstream Infections.

Central venous catheters are among the most used medical devices in hospitals today. Despite advances in modern medicine, catheter infections remain prevalent, causing significant morbidity and mortality worldwide. Here, SteriGel is reported, which is a multifunctional hydrogel engineered to prevent and treat central line-associated bloodstream infections (CLABSI). The mechanical properties of SteriGel are optimized to ensure appropriate gelation kinetics, bio-adhesiveness, stretchability, and recoverability to promote durability upon application and to provide persistent protection against infection. In vitro assays demonstrated that SteriGel exhibits long-term antimicrobial efficacy and has bactericidal effects against highly resistant patient-derived pathogens known to be frequently associated with CLABSI. SteriGel outperformed Biopatch, which is a clinically used device for CLABSI, in ex vivo cadaver studies that simulate clinical scenarios. Furthermore, SteriGel has biocompatible, pro-healing, and anti-inflammatory properties in vitro and in a rat subcutaneous injection model, suggesting a potential synergistic effect in the prevention and treatment of CLABSI. SteriGel is a multifunctional adherent biomaterial with potent antimicrobial effects for sustained sterility while promoting healing of the catheter incision site to protect against infection.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Biocompatible Liquid Embolic for the Treatment of Microvascular Hemorrhage.

Persistent or recurrent bleeding from microvessels inaccessible for direct endovascular intervention is a major problem in medicine today. Here, an innovative catheter-directed liquid embolic (P-LE) is bioengineered for rapid microvessel embolization to treat small vessel hemorrhage. Tested in rodent, porcine, and canine animal models under normal and coagulopathic conditions, P-LE outperformed clinically used embolic materials in both survival and non-survival experiments, effectively occluding vessels as small as 40 microns with no signs of recanalization. P-LE occlusion is independent of the coagulation cascade, and its resistance to displacement is ≈ 8 times greater than systolic blood pressure. P-LE is also found to be biocompatible and x-ray visible and does not require polymerization or a chemical reaction to embolize. To simulate the clinical scenario, acute microvascular hemorrhage is created in the pig kidney, liver, or stomach; these are successfully treated with P-LE achieving immediate hemostasis. Furthermore, P-LE is found to be bactericidal to highly resistant patient-derived bacteria, suggesting that P-LE may also protect against infectious complications that may occur following embolization procedures. P-LE is safe, easy to use, and effective in treating -microvessel hemorrhage.

Aging of deep venous thrombosis in-vivo using polarization sensitive optical coherence tomography.

Deep venous thrombosis (DVT) is a medical condition with significant post-event morbidity and mortality coupled with limited treatment options. Treatment strategy and efficacy are highly dependent on the structural composition of the thrombus, which evolves over time from initial formation and is currently unevaluable with standard clinical testing. Here, we investigate the use of intravascular polarization-sensitive optical coherence tomography (PS-OCT) to assess thrombus morphology and composition in a rat DVT model in-vivo, including changes that occur over the thrombus aging process. PS-OCT measures tissue birefringence, which provides contrast for collagen and smooth muscle cells that are present in older, chronic clots. Thrombi in the inferior vena cava of two cohorts of rats were imaged in-vivo with intravascular PS-OCT at 24 hours (acute, nrats = 3, 73 cross-sections) or 28 days (chronic, nrats = 4, 41 cross-sections) after thrombus formation. Co-registered histology was labelled by an independent pathologist to establish ground-truth clot composition. Automated analysis of OCT cross-sectional images differentiated acute and chronic thrombi with 97.6% sensitivity and 98.6% specificity using a linear discriminant model comprised of both polarization and conventional OCT metrics. These results support PS-OCT as a highly sensitive imaging modality for the assessment of DVT composition to differentiate acute and chronic thrombi. Intravascular PS-OCT imaging could be integrated with advanced catheter-based treatment strategies and serve to guide therapeutic decision-making and deployment, by offering an accurate assessment of DVT patients in real time.

Safety and effectiveness of transsplenic access for portal venous interventions: a single-center retrospective study.

PURPOSE: To assess the safety and effectiveness of percutaneous transsplenic access (PTSA) for portal vein (PV) interventions among patients with PV disease. MATERIALS AND METHODS: Adult patients with PV disease were enrolled if they required percutaneous catheterization for PV angioplasty, embolization, thrombectomy, variceal embolization, or transjugular intrahepatic portosystemic shunt (TIPS) placement for a difficult TIPS or recanalization of a chronically occluded PV. The procedures were performed between January 2018 and January 2023. Patients were excluded if they had an active infection, had a chronically occluded splenic vein malignant infiltration of the needle tract, had undergone splenectomy, or were under age 18 years. RESULTS: Thirty patients (15 women, 15 men) were enrolled. Catheterization of the PV through PTSA succeeded for 29 of 30 patients (96.7%). The main adverse effect recorded was flank pain in 5 of 30 cases (16.7%). No bleeding events from the spleen, splenic vein, or percutaneous access point were recorded. Two cases (6.7%) each of hepatic bleeding and rethrombosis of the PV were reported, and a change in hemoglobin levels (mean [SD], - 0.5 [1.4] g/dL) was documented in 14 cases (46.7%). CONCLUSION: PTSA as an approach to accessing the PV is secure and achievable, with minimal risk of complications. Minimal to no bleeding is possible by using tract closure methods.

Tissue Ablation: Applications and Perspectives.

Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics.

Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation.

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non-survival and survival porcine experiments, successful PVE is achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug-resistant patient-derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.

Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization.

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient-derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo- and immunotherapy response in solid tumors.

Single-arm prospective study comparing ablation zone volume between time zero and 24 h after microwave ablation of liver tumors.

PURPOSE: Percutaneous thermal ablation is an effective treatment for primary and metastatic liver tumors and is a recommended local therapy for early-stage hepatocellular carcinoma (HCC). Reported evidence shows an increase in the ablation zone volume over the first 24-h post-liver ablation. This report compares ablation zone volumes immediately at the completion (T = 0) of 26 microwave ablations of liver tumors to 24-h post-procedure (T = 24) volumes. MATERIALS AND METHODS: 20 patients, 13 (65%) males, underwent a total of 26 hepatic microwave ablations (MWA) under ultrasound guidance. Contrast-enhanced CT (CECT) or MRI was performed immediately and another CECT 24 h post operatively. Evaluation of the ablation zone and comparison of the two post-operative scans were done using BioTrace software. The expansion of ablation zones on post-op CECTs was matched point by point per direction. The distance between each 2 points was measured and grouped by distance. The incidence of each specific distance was then converted into a percentage, first for each case separately, then for all cases altogether. Data were tested by a matched paired one-sided t test. RESULTS: The median lesion diameter was 1.5 cm (range 0.5-3.3) with 16 (62%) HCC cases and 9 hepatic metastases (4 neuroendocrine carcinoma, 4 colorectal carcinomas, 1 breast carcinoma, 1 pancreatic cancer). The data show a consistent volume expansion greater than 30% (p = 7.7e-5) 24-h post-ablation, where the median expansion is 57%. Distances between T = 0 and T = 24 equal to 3-7 mm occur in over 35% of the cases. CONCLUSION: The ablation zone expansion at 24-h post-op was not uniform. The final ablation zone is difficult to predict at the time of the procedure. The awareness of the ablation zone expansion is important when treating near-critical structures, managing the heat sink effect, and preserving liver parenchyma.

Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

Treatment of Ruptured Wide-Necked Aneurysms using a Microcatheter Injectable Biomaterial.

Ruptured wide-neck aneurysms (WNAs), especially in a setting of coagulopathy, are associated with significant morbidity and mortality. It is shown that by trapping a sub-millimeter clinical catheter inside the aneurysm sac using a flow diverter stent (FDS), instant hemostasis can be achieved by filling the aneurysm sac using a novel biomaterial, rescuing catastrophic bleeding in large-animal models. Multiple formulations of a biomaterial comprising gelatin, nanoclay (NC), and iohexol are developed, optimized, and extensively tested in vitro to select the lead candidate for further testing in vivo in murine, porcine, and canine models of WNAs, including in a subset with aneurysm rupture. The catheter-injectable and X-ray visible versions of the gel embolic agent (GEA) with the optimized mechanical properties outperform control groups, including a subset that receive a clinically used liquid embolic (Onyx, Medtronic), with and without aneurysm rupture. A combinatorial approach to ruptured WNAs with GEA and FDS may change the standard of medical practice and save lives.

Percutaneous Transesophageal Gastrostomy: Procedural Technique and Outcomes.

PURPOSE: To demonstrate the safety and effectiveness of percutaneous transesophageal gastrostomy (PTEG) as a palliative option in patients with malignant bowel obstructions (MBOs), and provide a comprehensive review of PTEG indications, placement technique, and short- and long-term outcomes. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent a PTEG procedure attempt from 2014 to 2022 were included in this analysis. Clinical indications, method of placement, technical and clinical success, adverse events, including procedure-related mortality, and effectiveness were assessed. Technical success was defined as placement of a PTEG. Clinical success was defined as improvement in clinical symptoms following PTEG placement. RESULTS: Of the 38 patients who underwent PTEG, 19 (50%) were men and 19 (50%) were women (median age, 58 years; range, 21-75 years). Three (8%) PTEG placements were performed with the patients under moderate sedation, whereas the remainder (92%) were performed with the patients under general anesthesia. Technical success was achieved in 35 of the 38 (92%) patients. The mean catheter duration was 61 days (median, 29 days; range, 1-562 days), with 5 of the 35 patients requiring tube exchanges after initial placement. Moreover, 7 of the 35 patients with successful PTEG placement experienced an adverse event, including 1 case of non-procedure-related mortality. All patients with successful PTEG placement experienced improvement in clinical symptoms. CONCLUSIONS: PTEG is an effective and safe option for patients with contraindications to traditional percutaneous gastrostomy tube placement in the setting of MBO. PTEG is an effective means of providing palliation and improving the quality of life.

Society of Interventional Radiology Foundation Funding to National Institutes of Health Funding: Report from the Society of Interventional Radiology Foundation/National Institutes of Health Task Force.

The Society of Interventional Radiology Foundation (SIRF) aims to support interventional radiology (IR) investigators by awarding numerous grants to promote the advancement of scientific knowledge in IR. Over the last 19 years, SIRF has awarded 227 research grants, amounting to more than $4.7 million. To increase the engagement of interventional radiologists and IR scientists with the National Institutes of Health (NIH), SIRF created a SIRF/NIH taskforce in 2020. Over the past couple of years, the task force has been working to assess the return on investment of SIRF grants in terms of NIH funding because this metric is an effective measure of assessing the early success of foundation funding. The objectives of this report are to assess SIRF funding from 2002 to 2020 and investigate the conversion of this funding into NIH grants by the same investigators. During the study period, more than $37.6 million in NIH funds were awarded to SIRF awardees, which shows a return of 8 NIH dollars for every 1 SIRF dollar invested.

Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.

Establishing a telemedicine program for interventional radiology: a study of patient opinion and experience.

PURPOSE The COVID-19 pandemic forced healthcare officials to implement new policies, such as the use of virtual consultations over office-based medical appointments, to reduce the transmission of the virus. The purpose of this study is to quantitatively compare patients' experiences with virtual outpatient telemedicine encounters at a single academic institution in Interventional Radiology (IR) and in-person visits during the course of the COVID-19 pandemic. METHODS The TeleENT Satisfaction Questionnaire and the Medical Communication Competence Scale (MCCS) were used to survey patients' satisfaction with both in-person and virtual office visits. RESULTS Ninety respondents (38 in-person, 52 virtual) acknowledged numerous benefits of virtual visits versus in-person office visits including reductions in time, cost, and potential viral transmission risk during the COVID-19 pandemic. No statistically significant difference was noted, based on a Likert scale from 1 to 7, between in-person and virtual visits (all p > 0.05) for scheduling related factors. No statistically significant difference was noted in any of the MCCS subscales between the two cohorts in regards to medical information communication (all p > 0.05). A majority of patients with virtual encounters (82.7%) stated that it was easy to obtain an electronic device for use during the telemedicine visit, and 73.1% of patients felt that setting up the telemedicine encounter was easy. CONCLUSION This study demonstrates that telemedicine is an acceptable alternative to in-office appointments and could increase access to IR care outside of the traditional physician-patient interaction. With telemedicine visits, patients can communicate their concerns and obtain information from the doctor with noninferior communication compared to in-person visits.

Interventional Radiology Management of Adult Liver Transplant Complications.

Liver transplant remains the definitive therapy for patients with end-stage liver disease. Outcomes have continued to improve, in part owing to interventions used to treat posttransplant complications involving the hepatic arteries, portal vein, hepatic veins or inferior vena cava (IVC), and biliary system. Significant hepatic artery stenosis can be treated with angioplasty or stent placement to prevent thrombosis and biliary ischemic complications. Hepatic arterioportal fistula and hepatic artery pseudoaneurysm are rare complications that can often be treated with endovascular means. Treatment of hepatic artery thrombosis can have mixed results. Portal vein stenosis can be treated with venoplasty or more commonly stent placement. The rarer portal vein thrombosis can also be treated with endovascular techniques. Hepatic venous outflow stenosis of the hepatic veins or IVC is amenable to venoplasty or stent placement. Complications of the bile ducts are the most encountered complication after liver transplant. When not amenable to endoscopic intervention, biliary stricture, bile leak, and ischemic cholangiopathy can be treated with percutaneous transhepatic cholangiography with biliary drainage and other interventions. New techniques have further improved care for these patients. Transsplenic portal vein recanalization has improved transplant candidacy for patients with chronic portal vein thrombosis. Spontaneous splenorenal shunt and splenic artery steal syndrome (nonocclusive hepatic artery hypoperfusion syndrome) remain complicated topics, and the role of endovascular embolization is developing. When patients have recurrence of cirrhosis after transplant, most commonly due to viral hepatitis, transjugular intrahepatic portosystemic shunt (TIPS) may be required to treat symptoms of portal hypertension. Online supplemental material is available for this article. ©RSNA, 2022.

Interventional Management of Acquired Lymphatic Disorders.

The lymphatic system is a complex network of tissues, vessels, and channels found throughout the body that assists in fluid balance and immunologic function. When the lymphatic system is disrupted related to idiopathic, iatrogenic, or traumatic disorders, lymphatic leaks can result in substantial morbidity and/or mortality. The diagnosis and management of these leaks is challenging. Modern advances in lymphatic imaging and interventional techniques have made radiology critical in the multidisciplinary management of these disorders. The authors provide a review of conventional and clinically relevant variant lymphatic anatomy and recent advances in diagnostic techniques such as MR lymphangiography. A detailed summary of technical factors related to percutaneous lymphangiography and lymphatic intervention is presented, including transpedal and transnodal lymphangiography. Traditional transabdominal access and retrograde access to the central lymph nodes and thoracic duct embolization techniques are outlined. Newer techniques including transhepatic lymphangiography and thoracic duct stent placement are also detailed. For both diagnostic and interventional radiologists, an understanding of lymphatic anatomy and modern diagnostic and interventional techniques is vital to the appropriate treatment of patients with acquired lymphatic disorders. ©RSNA, 2022.