Prospective comparison of positron emission tomography (PET)/magnetic resonance and PET/computed tomography dosimetry in hepatic malignant neoplastic disease after 90Y radioembolization treatment.

Background: 90Y radioembolization is an established treatment modality for hepatic malignancies. Successful radioembolization requires optimal dose delivery to tumors while minimizing dosages to parenchyma. Post-treatment positron emission tomography (PET)/computed tomography (CT) dosimetry is the established benchmark, whereas PET/magnetic resonance (MR) is an emerging modality. The goal of this study was to assess the intermodality agreement between PET/MR and PET/CT 90Y dosimetry. Methods: In this single-institution study, 18 patients (20 treatment sessions) with a primary or metastatic hepatic malignancy underwent both PET/MR and PET/CT after 90Y radioembolization. Patients were randomized to undergo one modality first, followed by the other. The region of interest was delineated using MR images and tumor and liver dosimetry was calculated. Intermodality agreement was assessed using the Bland-Altman method. A generalized linear model was used to assess the effect of baseline variables on intermodality dose differences. Results: PET/MR underestimated tumor and liver absorbed doses when compared to PET/CT by -3.7% (P=0.042) and -5.8% (P=0.029), respectively. A coverage probability plot demonstrated that 80% and 90% of tumor dose measurements fell within intermodality differences of 11% and 18%, respectively. PET/MR underestimated tumor dose at both low (<1 GBq) and high (>3 GBq) injected activity levels (P<0.001) by -22.3 [standard deviation (SD) =13.5] and -24.3 (SD =18.7), respectively. Conclusions: Although PET/MR significantly underestimated the absorbed dose when compared to PET/CT, the intermodality agreement was high and the degree of underestimation was better than previously reported. Intermodality differences were more pronounced at low and high injected doses. Additional studies are required to assess the clinical implications of these findings.

Factors predicting the active treatment of renal angiomyolipoma: 30 years of experience in two tertiary referral centers.

Introduction and objective: This study aimed to identify clinical features representing predictive factors of active treatment (AT) compared to active surveillance (AS) for renal angiomyolipoma (AML). Patients and methods: From 1990 to 2020, patients referred to two institutions for a renal mass and diagnosed with an AML based on typical features on CT were included in the analysis. The study population was divided into two groups based on the treatment received: active surveillance (AS) or active treatment (AT). Age, gender, tuberous sclerosis syndrome, tumor size, contralateral kidney disease, renal function, year of diagnosis, and symptoms at presentation were assessed as potential predictive factors of active treatment using a logistic regression model in univariate and multivariate analyses. Results: In total, 253 patients (mean age 52.3 ± 15.7 years; 70% women; 70.9% incidentally diagnosed) were included in the analysis. One hundred and nine (43%) received AS, whereas 144 (57%) were actively treated. For univariate analysis, age, tuberous sclerosis complex syndrome, tumor size, symptoms at presentation, and contralateral kidney disease were found to be predictors of AT. Only tumor size (p < 0.001) and the year of diagnosis (p < 0.001) remained significant for multivariable analyses. The likelihood of being managed with AS evolved over the study period and was 50% and 75% when diagnosed before and after 2010, respectively. With respect to size, 4-cm and 6-cm tumors had a probability of 50% and 75% of being treated with AS, respectively. Conclusion: The present analysis from a high-volume institution provides evidence that the management of renal masses with typical radiological features of AML has markedly changed over the last three decades with a trend toward AS over AT. Tumor size and the year of diagnosis were significant factors for the treatment strategies.

Role of stenting for maintenance of the extremity fistula/graft overview.

Dialysis access interventions have undergone significant developments over the last few decades. Angioplasty has been the mainstay of therapy since the early interventions in the 1980s and 1990s, but poor long-term patency and early loss of access has led investigators to assess other devices to treat stenoses associated with dialysis access failure. Multiple retrospective studies of stents for treatment of stenoses that did not respond to angioplasty demonstrated that the long-term outcomes were not improved over angioplasty alone. Cutting balloons have been studied in a prospective randomized fashion but also showed no long-term improvement over angioplasty alone. Prospective randomized trials have demonstrated that stent-grafts have superior primary patency of the access and the target lesions than angioplasty. The purpose of this review is to summarize the current state of knowledge regarding stent and stent graft use in dialysis access failure. We will discuss the early observational data related to stent use in dialysis access failure including the earliest reports of stent use in dialysis access failure. This review will then focus the review on the prospective randomized data that supports the use of stent-grafts in specific areas of access failure. These include venous outflow stenosis related to grafts, cephalic arch stenoses, native fistula intervention, and the use of stent-grafts to revise in-stent restenosis. Each of these applications will be summarized and the current status of the data will be reviewed.

Semiautomatic Cone-Beam Computed Tomography Virtual Hepatic Volumetry for Intra-Arterial Therapies.

PURPOSE: To evaluate a software simulating the perfused liver volume from virtual selected embolization points on proximal enhanced cone-beam computed tomography (CT) liver angiography data set using selective cone-beam CT as a reference standard. MATERIALS AND METHODS: Seventy-eight selective/proximal cone-beam CT couples in 46 patients referred for intra-arterial liver treatment at 2 recruiting centers were retrospectively included. A reference selective volume (RSV) was calculated from the selective cone-beam CT by manual segmentation and was used as a reference standard. The virtual perfusion volume (VPV) was then obtained using Liver ASSIST Virtual Parenchyma software on proximal cone-beam CT angiography using the same injection point as for selective cone-beam CT. RSV and VPV were then compared as absolute, relative, and signed volumetric errors (ABSErr, RVErr, and SVErr, respectively), whereas their spatial correspondence was assessed using the Dice similarity coefficient. RESULTS: The software was technically successful in automatically computing VPV in 74 of 78 (94.8%) cases. In the 74 analyzed couples, the median RSV was not significantly different from the median VPV (394 mL [196-640 mL] and 391 mL [192-620 mL], respectively; P = .435). The median ABSErr, RVErr, SVErr, and Dice similarity coefficient were 40.9 mL (19.9-97.7 mL), 12.8% (5%-22%), 9.9 mL (-49.0 to 40.4 mL), and 80% (76%-84%), respectively. No significant ABSErr, RVErr, SVErr, and Dice similarity coefficient differences were found between the 2 centers (P = .574, P = .612, P = .416, and P = .674, respectively). CONCLUSIONS: Perfusion hepatic volumes simulated on proximal enhanced cone-beam CT using the virtual parenchyma software are numerically and spatially similar to those manually obtained on selective cone-beam CT.

Increased incidence of venous thromboembolism associated with inferior vena cava filter placement in patients diagnosed with isolated calf deep vein thrombosis after intracranial hemorrhage or intracranial operation.

In this study, we sought to investigate the effectiveness of inferior vena cava (IVC) filter placement in reducing the incidence of venous thromboembolism (VTE) in patients diagnosed with isolated calf deep vein thrombosis (DVT) after an intracranial hemorrhage or intracranial operation. A retrospective chart review (January 2000-December 2019) was performed to identify patients diagnosed with calf DVT after intracranial hemorrhage or intracranial operation. A total of 100 patients met the study criteria and were divided into groups based on treatment: IVC filter placement (n = 22), prophylactic anticoagulation (n = 42), or imaging surveillance (n = 36). Treatment-related complications were identified, and differences between groups in the primary endpoint (VTE occurrence after DVT diagnosis) were assessed using logistic regression. VTE occurred in 15 patients after calf DVT diagnosis. The rate of VTE was higher in the IVC filter group (9/22; 41%) than in the anticoagulation (2/42; 5%; p = 0.002) and surveillance (4/36; 11%; p = 0.013) groups. These treatment effects remained significant after adjustments were made for baseline characteristics (IVC filter vs anticoagulation, p = 0.009; IVC filter vs surveillance, p = 0.019). There was a single occurrence of pulmonary embolism in the surveillance group (3%). A single case of IVC filter thrombus was identified; no anticoagulation-related complications were reported. The findings of this study do not support IVC filter placement as a primary and solitary treatment for isolated calf DVT occurring after intracranial hemorrhage or intracranial operation.

Percutaneous-Reinforced Osteoplasty: A Review of Emerging Treatment Strategies for Bone Interventions.

Percutaneous-reinforced osteoplasty is currently being investigated as a possible therapeutic procedure for fracture stabilization in high-risk patients, primarily in patients with bone metastases or osteoporosis. For these patients, a percutaneous approach, if structurally sound, can provide a viable method for treating bone fractures without the physiologic stress of anesthesia and open surgery. However, the low strength of fixation is a common limitation that requires further refinement in scaffold design and selection of materials, and may potentially benefit from tissue-engineering-based regenerative approaches. Scaffolds that have tissue regenerative properties and low inflammatory response promote rapid healing at the fracture site and are ideal for percutaneous applications. On the other hand, preclinical mechanical tests of fracture-repaired specimens provide key information on restoration strength and long-term stability and enable further design optimization. This review presents an overview of percutaneous-reinforced osteoplasty, emerging treatment strategies for bone repair, and basic concepts of in vitro mechanical characterization.

Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Artificial Intelligence in Interventional Radiology: From Code to Bedside.

Artificial intelligence (AI)-based technologies are the most rapidly growing field of innovation in healthcare with the promise to achieve substantial improvements in delivery of patient care across all disciplines of medicine. Recent advances in imaging technology along with marked expansion of readily available advanced health information, data offer a unique opportunity for interventional radiology (IR) to reinvent itself as a data-driven specialty. Additionally, the growth of AI-based applications in diagnostic imaging is expected to have downstream effects on all image-guidance modalities. Therefore, the Society of Interventional Radiology Foundation has called upon 13 key opinion leaders in the field of IR to develop research priorities for clinical applications of AI in IR. The objectives of the assembled research consensus panel were to assess the availability and understand the applicability of AI for IR, estimate current needs and clinical use cases, and assemble a list of research priorities for the development of AI in IR. Individual panel members proposed and all participants voted upon consensus statements to rank them according to their overall impact for IR. The results identified the top priorities for the IR research community and provide organizing principles for innovative academic-industrial research collaborations that will leverage both clinical expertise and cutting-edge technology to benefit patient care in IR.

Mathematical Models for Blood Flow Quantification in Dialysis Access Using Angiography: A Comparative Study.

Blood flow rate in dialysis (vascular) access is the key parameter to examine patency and to evaluate the outcomes of various endovascular interve7ntions. While angiography is extensively used for dialysis access-salvage procedures, to date, there is no image-based blood flow measurement application commercially available in the angiography suite. We aim to calculate the blood flow rate in the dialysis access based on cine-angiographic and fluoroscopic image sequences. In this study, we discuss image-based methods to quantify access blood flow in a flow phantom model. Digital subtraction angiography (DSA) and fluoroscopy were used to acquire images at various sampling rates (DSA-3 and 6 frames/s, fluoroscopy-4 and 10 pulses/s). Flow rates were computed based on two bolus tracking algorithms, peak-to-peak and cross-correlation, and modeled with three curve-fitting functions, gamma variate, lagged normal, and polynomial, to correct errors with transit time measurement. Dye propagation distance and the cross-sectional area were calculated by analyzing the contrast enhancement in the vessel. The calculated flow rates were correlated versus an in-line flow sensor measurement. The cross-correlation algorithm with gamma-variate curve fitting had the best accuracy and least variability in both imaging modes. The absolute percent error (mean ± SEM) of flow quantification in the DSA mode at 6 frames/s was 21.4 ± 1.9%, and in the fluoroscopic mode at 10 pulses/s was 37.4 ± 3.6%. The radiation dose varied linearly with the sampling rate in both imaging modes and was substantially low to invoke any tissue reactions or stochastic effects. The cross-correlation algorithm and gamma-variate curve fitting for DSA acquisition at 6 frames/s had the best correlation with the flow sensor measurements. These findings will be helpful to develop a software-based vascular access flow measurement tool for the angiography suite and to optimize the imaging protocol amenable for computational flow applications.

Research Priorities for Percutaneous Arteriovenous Fistula Creation in Patients with End-Stage Renal Disease: Proceedings and Recommendations from a Multidisciplinary Research Consensus Panel.

Recently developed endovascular techniques to create percutaneous arteriovenous fistulas are an alternative to surgical arteriovenous fistula creation, although there is currently a lack of high-level evidence regarding their creation, maturation, utilization, and long-term function. Recognizing this, the Society of Interventional Radiology Foundation sponsored a Research Consensus Panel and Summit for the prioritization of a research agenda to identify and address the gaps in current knowledge.

Acute pulmonary embolism multimodality imaging prior to endovascular therapy.

The manuscript discusses the application of CT pulmonary angiography, ventilation-perfusion scan, and magnetic resonance angiography to detect acute pulmonary embolism and to plan endovascular therapy. CT pulmonary angiography offers high accuracy, speed of acquisition, and widespread availability when applied to acute pulmonary embolism detection. This imaging modality also aids the planning of endovascular therapy by visualizing the number and distribution of emboli, determining ideal intra-procedural catheter position for treatment, and signs of right heart strain. Ventilation-perfusion scan and magnetic resonance angiography with and without contrast enhancement can also aid in the detection and pre-procedural planning of endovascular therapy in patients who are not candidates for CT pulmonary angiography.

Screening of Polymer-Based Drug Delivery Vehicles Targeting Folate Receptors in Triple-Negative Breast Cancer.

PURPOSE: To compare cellular uptake and cytotoxicity of fluorescein (FL)-labeled polyethylene glycols (PEGs) carrying 2 folate groups (targeted delivery vehicles [TDVs]) to non-PEGylated molecules with 1 or 2 folate groups. MATERIALS AND METHODS: Three PEGylated TDVs and 2 non-PEGylated folic acid (FA)-fluorescein (FL) conjugates (FA-FL and FA-FL-FA) were synthesized. Two triple-negative breast cancer cell lines (MDA-MB-231and MDA-MB-468) were cultured to 70% confluency and incubated for 2 h in a folate-depleted medium. Folate receptor (FR) expression was confirmed by immunocytochemistry. Cellular uptake and cytotoxicity of compounds were measured by flow cytometry. Intracellular localization was confirmed using confocal microscopy. RESULTS: MDA-MB-231 demonstrated 40% more FR staining than MD-MB-468. Intracellular localization of the 2 non-PEGylated molecules (FA-FL and FA-FL-FA) and the 3 PEGylated TDVs was confirmed with confocal microscopy. Cellular uptake was independent of concentration for FA-FL, but there was 26.8% more cytotoxicity at 30 µg/mL compared with no treatment (P ≤ .05). Uptake was > 90% for FA-FL-FA at 10 µg/mL and 30 µg/mL without significant cytotoxicity (P ≤ .005). Cellular uptake was > 80% for all TDVs. The molecule containing monodispersed PEG with Mn = 1,000 g/mol had the highest uptake in both cell lines without cytotoxicity. Maximum toxicity was demonstrated by the molecule containing PEG2,000 only at the highest dose of 30 µg/mL (8.66% ± 3.94% cytotoxicity; cut-off was 20%). CONCLUSIONS: The molecule containing monodispersed PEG with Mn = 1,000 g/mol and 2 FA targeting groups demonstrated better targetability and cellular uptake as a TDV.

Thoracic Central Vein Occlusion in the Dialysis Patient: An Interventional Perspective.

Thoracic central venous occlusion in hemodialysis patients can cause significant disability from arm and facial swelling and can lead to worsening function of dialysis access. Current techniques for managing thoracic central venous occlusion and some of the newer techniques for achieving dialysis access when all central veins are occluded. Techniques for dealing with acute superior vena cava thrombosis will also be covered as will the complications of central venous recanalization techniques.

Inferior vena cava filter - comprehensive overview of current indications, techniques, complications and retrieval rates.

Inferior vena cava (IVC) filter has been used to manage patients with pulmonary embolism and deep venous thrombosis. Its ease of use and the expansion of relative indications have led to a dramatic increase in IVC filter placement. However, IVC filters have been associated with a platitude of complications. Therefore, there exists a need to examine the current indications and identify the patient population at risk. In this paper, we comprehensively reviewed the current indications and techniques of IVC filter placement. Further, we examined the various complications associated with either permanent or retrievable IVC filters. Lastly, we examined the current data on filter retrieval.

Pharmacological induction of selective endoplasmic reticulum retention as a strategy for cancer therapy.

The integrated stress response (ISR) converges on eIF2α phosphorylation to regulate protein synthesis. ISR is activated by several stress conditions, including endoplasmic reticulum (ER) stress, executed by protein kinase R-like endoplasmic reticulum kinase (PERK). We report that ER stress combined with ISR inhibition causes an impaired maturation of several tyrosine kinase receptors (RTKs), consistent with a partial block of their trafficking from the ER to the Golgi. Other proteins mature or are secreted normally, indicating selective retention in the ER (sERr). sERr is relieved upon protein synthesis attenuation and is accompanied by the generation of large mixed disulfide bonded complexes, including ERp44. sERr was pharmacologically recapitulated by combining the HIV-protease inhibitor nelfinavir with ISRIB, an experimental drug that inhibits ISR. Nelfinavir/ISRIB combination is highly effective to inhibit the growth of RTK-addicted cell lines and hepatocellular (HCC) cells in vitro and in vivo. Thus, pharmacological sERr can be utilized as a modality for cancer treatment.

Blood flow quantification in dialysis access using digital subtraction angiography: A retrospective study.

BACKGROUND AND OBJECTIVE: Vascular access is the "lifeline" of end-stage renal disease patients, which is surgically constructed to remove blood-waste and return artificially filtered blood into circulation. The arteriovenous shunting causes an abrupt change in blood flow and results in increased fluidic stress, which predisposes to access stenosis and thrombosis. While access flow is crucial to evaluate interventional endpoint, application to measure flow using digital angiogram is not yet available. The goal of this study was to determine the feasibility of flow quantification in dialysis access using a software tool and to guide the design of an imaging protocol. METHODS: 173 digital subtraction angiographic (DSA) images were retrospectively analyzed to evaluate access flow in a custom-programming environment. Four bolus transit time algorithms and a distance calculation method were assessed for flow computation. Gamma variate function was applied to remove secondary flow and intensity outliers in the bolus time-intensity curves and evaluated for enhancement in computational accuracy. The percent deviations of flow rates computed from dilution of iodinated radio-contrast material were compared with in situ catheter-based flow measurement. RESULTS: Among the implemented bolus transit time algorithms, quantification error (mean ± standard error) of cross-correlation algorithm without and with gamma variate curve fitting was 35 ± 1% and 22 ± 1%, respectively. All other algorithms had quantification error >27%. The bias and limits of agreement of the cross-correlation algorithm with gamma variate curve fit was -94 ml/min and [-353, 165] mL/min, respectively. CONCLUSIONS: The cross-correlation algorithm with gamma variate curve fit had the best accuracy and reproducibility for image-based blood flow computation. To further enhance accuracy, images may need to be acquired with a dedicated injection protocol with predetermined parameters such as the duration, rate and mode of bolus injection, and the acquisition frame rate.

Quiescent hepatic stellate cells induce toxicity and sensitivity to doxorubicin in cancer cells through a caspase-independent cell death pathway: Central role of apoptosis-inducing factor.

Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy.

Percutaneous reinforced osteoplasty for long bone metastases: a feasibility study.

OBJECTIVE: While percutaneous osteoplasty is common for the treatment of vertebral fractures, low strength of fixation remains a major challenge for use in metastatic weight-bearing bones. With stent, wire, and cement augmentation, this study explores the feasibility of percutaneous reinforced osteoplasty for use in correcting long bone fractures. MATERIALS AND METHODS: Fifteen explanted swine femora were randomly assigned into three groups. Group 1 (n = 5) was native (intact) bones without any intervention (control), group 2 (n = 5) received cementoplasty, and group 3 (n = 5) received stent and wire scaffolding ("rebar") in addition to cementoplasty. All treatment procedures were performed under fluoroscopic guidance. Mechanical strength of fracture fixation was quantified by peak load to failure, stiffness, work done to fracture, and fatigue testing with four-point bend test. RESULTS: Percutaneous osteoplasty with or without reinforcement was successfully achieved in all specimens. The respective peak load at failure, flexural stiffness, and work done to fracture (mean ± SEM) for group 1 was 2245 ± 168 N, 14.77 ± 1.3 Nm/degree, and 4854 ± 541 Nmm; group 2 was 468 ± 81 N, 3.9 ± 0.5 Nm/degree, and 401 ± 56 Nmm; and group 3 was 594 ± 90 N, 4.42 ± 0.4 Nm/degree, and 522 ± 54 Nmm. The mean cyclic displacement for groups 1, 2, and 3 were 0.15, 0.58, and 0.48 mm, respectively, at 220-240 N loading. CONCLUSIONS: While percutaneous reinforced osteoplasty with stent, wire, and cement augmentation resulted in improved mechanical strength in restored bones, it did not differ significantly from specimens that underwent exclusive cementoplasty. With the improvement of fracture strength, the concept may be applicable for prevention or treatment of pathological fractures.