Adding non-contrast and delayed phases increases the diagnostic performance of arterial CTA for suspected active lower gastrointestinal bleeding.

OBJECTIVES: When assessing for lower gastrointestinal bleed (LGIB) using CTA, many advocate for acquiring non-contrast and delayed phases in addition to an arterial phase to improve diagnostic performance though the potential benefit of this approach has not been fully characterized. We evaluate diagnostic accuracy among radiologists when using single-phase, biphasic, and triphasic CTA in active LGIB detection. METHOD AND MATERIALS: A random experimental block design was used where 3 blinded radiologists specialty trained in interventional radiology retrospectively interpreted 96 CTA examinations completed between Oct 2012 and Oct 2017 using (1) arterial only, (2) arterial/non-contrast, and (3) arterial/non-contrast/delayed phase configurations. Confirmed positive and negative LGIB studies were matched, balanced, and randomly ordered. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive and negative predictive values, and time to identify the presence/absence of active bleeding were examined using generalized estimating equations (GEE) with sandwich estimation assuming a binary distribution to estimate relative benefit of diagnostic performance between phase configurations. RESULTS: Specificity increased with additional contrast phases (arterial 72.2; arterial/non-contrast 86.1; arterial/non-contrast/delayed 95.1; p < 0.001) without changes in sensitivity (arterial 77.1; arterial/non-contrast 70.2; arterial/non-contrast/delayed 73.1; p = 0.11) or mean time required to identify bleeding per study (s, arterial 34.8; arterial/non-contrast 33.1; arterial/non-contrast/delayed 36.0; p = 0.99). Overall agreement among readers (Kappa) similarly increased (arterial 0.47; arterial/non-contrast 0.65; arterial/non-contrast/delayed 0.79). CONCLUSION: The addition of non-contrast and delayed phases to arterial phase CTA increased specificity and inter-reader agreement for the detection of lower gastrointestinal bleeding without increasing reading times. KEY POINTS: • A triphasic CTA including non-contrast, arterial, and delayed phase has higher specificity for the detection of lower gastrointestinal bleeding than arterial-phase-only protocols. • Inter-reader agreement increases with additional contrast phases relative to single-phase CTA. • Increasing the number of contrast phases did not increase reading times.

Pressure-Enabled Drug Delivery Approach in the Pancreas with Retrograde Venous Infusion of Lipiodol with Ex Vivo Analysis.

PURPOSE: To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach. METHODS: Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands. RESULTS: A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5-2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia. CONCLUSIONS: PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study.

HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery.

In recent years, cell therapy technologies have resulted in impressive results in hematologic malignancies. Treatment of solid tumors with chimeric antigen receptor T-cells (CAR-T) has been less successful. Solid tumors present challenges not encountered with hematologic cancers, including high intra-tumoral pressure and ineffective CAR-T trafficking to the site of disease. Novel delivery methods may enable CAR-T therapies for solid tumor malignancies. A patient with liver metastases secondary to pancreatic adenocarcinoma received CAR-T targeting carcinoembryonic antigen (CEA). Previously we reported that Pressure-Enabled Drug Delivery (PEDD) enhanced CAR-T delivery to liver metastases 5.2-fold. Three doses of anti-CEA CAR-T were regionally delivered via hepatic artery infusion (HAI) using PEDD technology to optimize the therapeutic index. Interleukin-2 was systemically delivered by continuous intravenous infusion to support CAR-T in vivo. HAI of anti-CEA CAR-T was not associated with any serious adverse events (SAEs) above grade 3 and there were no on-target/off-tumor SAEs. Following CAR-T treatment, positron emission tomography-CT demonstrated a complete metabolic response within the liver, which was durable and sustained for 13 months. The response was accompanied by normalization of serum tumor markers and an abundance of CAR+ cells found within post-treatment tumor specimens. The findings from this report exhibit biologic activity and safety of regionally infused CAR-T for an indication with limited immune-oncology success to date. Further studies will determine how HAI of CAR-T may be included in multidisciplinary treatment plans for patients with liver metastases. ClinicalTrials.gov number, NCT02850536.

HITM-SIR: phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA+ liver metastases.

Effective chimeric antigen receptor-modified T-cell (CAR-T) therapy for liver metastases (LM) will require innovative solutions to ensure efficient delivery and minimization of systemic toxicity. We previously demonstrated the safety of CAR-T hepatic artery infusions (HAI). We subsequently conducted the phase 1b HITM-SIR trial, in which six patients (pts) with CEA+ LM received anti-CEA CAR-T HAIs and selective internal radiation therapy (SIRT). The primary endpoint was safety with secondary assessments of biologic activity. Enrolled pts had a mean LM size of 6.4 cm, 4 pts had >10 LM, and pts received an average of two lines of prior systemic therapy. No grade 4 or 5 toxicities were observed, and there were no instances of severe cytokine-release syndrome (CRS) or neurotoxicity. The mean transduction efficiency was 60.4%. Following CAR-T HAI, reduced levels of GM-CSF-R, IDO, and PD-L1 were detected in LM, and serum CEA levels were stable or decreased in all subjects. Median survival time was 8 months (mean 11, range 4-31). Anti-CEA CAR-T HAI with subsequent SIRT was well tolerated, and biologic responses were demonstrated following failure of conventional therapy. HAI of CAR-T was once again confirmed not to be associated with severe CRS or neurotoxicity.

Challenges in assessing solid tumor responses to immunotherapy.

With the advent of immunotherapy as an integral component of multidisciplinary solid tumor treatment, we are confronted by an unfamiliar and novel pattern of radiographic responses to treatment. Enlargement of tumors or even new lesions may not represent progression, but rather reflect what will ultimately evolve into a clinically beneficial response. In addition, the kinetics of radiographic changes in response to immunotherapy treatments may be distinct from what has been observed with cytotoxic chemotherapy and radiation. The phenomenon of pseudoprogression has been documented in patients receiving immunotherapeutic agents, such as checkpoint inhibitors and cellular therapies. Currently, there are no clinical response guidelines that adequately account for pseudoprogression and solid tumor responses to immunotherapy in general. Even so, response criteria have evolved to account for the radiographic manifestations of novel therapies. The evolution of World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), along with the emergence of immune-related response criteria (irRC) and the immune Response Evaluation Criteria in Solid Tumors (iRECIST) reflect the need for new frameworks. This review evaluates the relationship between pseudoprogression, clinical outcomes, and our current understanding of the biology of pseudoprogression. To achieve our goal, we discuss unusual response patterns in patients receiving immunotherapy. We seek to develop a deeper understanding of radiographic responses to immunotherapy such that clinical benefit is not underappreciated in individual patients and during clinical investigation.

Acute Lower Gastrointestinal Bleeding: Temporal Factors Associated With Positive Findings on Catheter Angiography After (99m)Tc-Labeled RBC Scanning.

OBJECTIVE: The objective of the study was to determine if time to positive (TTP), defined as the time from the start of (99m)Tc-labeled RBC scanning to the appearance of a radionuclide blush (considered to be a positive finding for acute lower gastrointestinal bleeding [LGIB]), and lag time (LT), defined as the time from the appearance of a radionuclide blush to the start of catheter angiography (CA), affected the yield of CA for the detection of acute LGIB. MATERIALS AND METHODS: TTP and LT were retrospectively evaluated in 120 patients who had positive findings for acute LGIB on (99m)Tc-labeled RBC scanning and subsequently underwent CA for the diagnosis and localization of gastrointestinal bleeding. Two nuclear medicine fellowship-trained radiologists independently reviewed the (99m)Tc-labeled RBC scans. Two fellowship-trained interventional radiologists independently reviewed the angiograms. All data were analyzed using SAS software. RESULTS: When a TTP threshold of ≤ 9 minutes was used, the sensitivity, specificity, positive predictive value, and negative predictive value for a positive CA study were 92%, 35%, 27%, and 94%, respectively. In addition, the odds of detecting bleeding on CA increased 6.1-fold with a TTP of ≤ 9 minutes relative to a TTP of > 9 minutes (p = 0.020). A significant inverse relationship was found between LT and a positive CA study (p = 0.041). CONCLUSION: TTP and LT impact the rate of positive CA studies. A TTP threshold of ≤ 9 minutes allows the detection of almost all patients who would benefit from CA for treatment and allows a reduction in unnecessary negative CA studies. The likelihood of positive findings on CA decreases with a delay in the performance of CA.

Fenoldopam for the prevention of contrast-induced nephropathy (CIN)-do we need more trials? A meta-analysis.

We conducted a pooled analysis of clinical trials comparing intravenous Fenoldopam (FP) with Saline/Placebo/N-acetyl cysteine (NAC) for the prevention of contrast-induced nephropathy (CIN). Five studies were eligible. Quantitative analyses were done with Review Manager (RevMan version 5.2.). A total of 85 out of 353 patients in Fenoldopam group while 73 among 366 in the control group were affected due to CIN. The risk ratio for the development of CIN in the Fenoldopam group was 1.19 compared to the control group. This was not statistically significant. Fenoldopam is no better than Placebo/Saline or NAC in preventing CIN, but more studies are required.

The preclose technique in percutaneous endovascular aortic repair: a systematic literature review and meta-analysis.

PURPOSE: To establish the efficacy and safety of the preclose technique in total percutaneous endovascular aortic repair (PEVAR). METHODS: A systematic literature search of Medline database was conducted for series on PEVAR published between January 1999 and January 2012. RESULTS: Thirty-six articles comprising 2,257 patients and 3,606 arterial accesses were included. Anatomical criteria used to exclude patients from undergoing PEVAR were not uniform across all series. The technical success rate was 94 % per arterial access. Failure was unilateral in the majority (93 %) of the 133 failed PEVAR cases. The groin complication rate in PEVAR was 3.6 %; a minority (1.6 %) of these groin complications required open surgery. The groin complication rate in failed PEVAR cases converted to groin cutdown was 6.1 %. A significantly higher technical success rate was achieved when arterial access was performed via ultrasound guidance. Technical failure rate was significantly higher with larger sheath size (≥20F). CONCLUSION: The preclose technique in PEVAR has a high technical success rate and a low groin complication rate. Technical success tends to increase with ultrasound-guided arterial access and decrease with larger access. When failure occurs, it is unilateral in the majority of cases, and conversion to surgical cutdown does not appear to increase the operative risk.

Basic neuroangiography: review of technique and perioperative patient care.

Neuroangiography (NA) is an important part of diagnosis and treatment of patients with neurological disease. Although NA may be performed for diagnostic purposes, in many instances NA is performed with the intent to treat. Indications for NA range from extracranial diseases (vertebrobasilar insufficiency from subclavian steal, extracranial carotid stenosis, cavernous-carotid fistula, neck trauma, epistaxis, tumor invasion of the carotid artery, and tumor embolization) to intracranial diseases (nontraumatic subarachnoid hemorrhage, cerebral aneurysms, cerebral arteriovenous malformations, cerebral vasospasm, acute stroke, tumor embolization, and WADA test). Similar to peripheral angiography, appropriate preprocedural assessment and postprocedural care, along with understanding of anatomy, catheter technique, and disease processes, are vital to successful outcomes. This article will review the basic technique, equipment, and patient management in NA. With appropriate skill and knowledge, interventional radiologists can perform NA with safe and successful results.

Basic vascular neuroanatomy of the brain and spine: what the general interventional radiologist needs to know.

This article is intended to provide a review of clinically relevant neurovascular anatomy. A solid understanding of the vascular anatomy of the brain and spine are essential for the safe and effective performance of neurointerventional radiology. Key concepts to master include collateral pathways and anastomoses between the external and internal carotid circulation, the Circle of Willis as a route to otherwise inaccessible intracranial vascular distributions, and the origin of spinal arterial blood supply. These concepts will be highlighted using clinical angiographic examples with discussion of relevant embryology and pathology as needed.

Interventional management of vertebral body metastases.

Metastases to the vertebral column are often due to hypervascular primary tumors, the most common of which is renal cell carcinoma. Clinical symptoms attributed to vertebral body metastases include localized pain, mechanical instability of the vertebral column, and neurologic deficits resulting from mass effect. Treatment options include targeted radiotherapy, percutaneous vertebral augmentation with or without thermal ablation, and surgical resection with subsequent fusion. Overall, surgical resection of the tumor and stabilization of the vertebral column provide the best prognosis for the patient in terms of symptomatic improvement and long-term survival; however, resection of hypervascular vertebral body metastases can result in significant intraoperative blood loss that can add to the morbidity of the procedure. Preoperative embolization of hypervascular metastases of the vertebral column has been shown to significantly reduce intraoperative blood loss at the time of surgery. The goal of this manuscript is to describe the role of embolization therapy in the management of patients with vertebral body metastases.

Intra-arterial Stroke Management.

Acute ischemic stroke is a leading cause of death and the leading cause of disability in the United States. Cerebral neuronal death begins within minutes after threshold values of blood oxygen saturation are crossed. Prompt restoration of oxygenated blood flow into ischemic tissue remains the common goal of reperfusion strategies. This article provides a brief overview of acute ischemic stroke, a summary of the major intra-arterial stroke therapy trials, and comments on current training requirements for the performance of intra-arterial therapies.

Carotid artery stenting: review of technique and update of recent literature.

Stroke is the fourth leading cause of death and the number one cause of long-term disability in the United States. Carotid stenosis is an important cause of ischemic strokes, accounting for 20 to 25%. Previous studies have established carotid endarterectomy as standard of care of symptomatic patients with > 50% stenosis and asymptomatic patients with > 60% stenosis; recently, carotid artery stenting has emerged as an alternative treatment for carotid stenosis. Several studies have been published comparing carotid artery stenting with endarterectomy with mixed results. In this article, the authors discuss carotid artery stenting technique, the results from the most recent trials, and future directions.

Interventional spine procedures for management of chronic low back pain-a primer.

Chronic low back pain is a common clinical condition. Percutaneous fluoroscopic-guided interventions are safe and effective procedures for the management of chronic low back pain, which can be performed in an outpatient setting. Interventional radiologists already possess the technical skills necessary to perform these interventions effectively so that they may be incorporated into a busy outpatient practice. This article provides a basic approach to the evaluation of patients with low back pain, as well as a review of techniques used to perform the most common interventions using fluoroscopic guidance.

Catheter-based arterial sympathectomy: hypertension and beyond.

Transluminal ablation of renal artery sympathetic nerves has been shown to provide a significant and durable reduction in blood pressure with very low complication rates. Additional publications have documented improvement in insulin sensitivity, obstructive sleep apnea indices, and frequency and severity of congestive heart failure in subgroups undergoing the procedure. This technology may provide effective management of other diseases in which there is autonomic imbalance. Available data are reviewed with the intent to provoke interest within the interventional radiology community in this novel technology, which may allow minimally invasive treatment of many important chronic medical conditions.

Angiographically documented hemorrhagic conversion of a left middle cerebral artery embolic stroke during intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: The clinical benefits of intra-arterial thrombolysis for ischemic stroke must be weighed against the risks, including hemorrhagic conversion. SUMMARY OF CASE: A case of angiographically documented hemorrhagic conversion of an ischemic stroke during intra-arterial thrombolysis is presented. Discussion focuses on recognition and management of risk factors for hemorrhagic conversion during performance of stroke thrombolysis. CONCLUSIONS: Recognition and modification of risk factors for hemorrhagic conversion may not prevent this complication during stroke thrombolysis. Identification of the angiographic appearance of hemorrhagic conversion should alert the interventionalist to the likelihood of a poor clinical outcome regardless of vessel patency status.

The prevalence and clinical significance of noncardiac findings on cardiac MRI.

OBJECTIVE: This study aims to evaluate the prevalence, nature, and clinical significance of noncardiac findings (NCFs) at cardiac MRI. MATERIALS AND METHODS: We retrospectively reviewed 240 consecutive, clinically indicated cardiac MRI examinations conducted over a 21-month period. All noncardiac findings (NCFs) were recorded. Those findings that were included in the report impressions were regarded as clinically important (INCF). Electronic medical records and related imaging studies were then reviewed for all patients having INCFs to determine their actual clinical significance. A finding was significant (SNCF) if it was associated with a new diagnosis, treatment, or intervention. The prevalences of findings in the neck, chest, and abdomen were determined. RESULTS: We found 162 NCFs in 104 studies (43%), of which 94 (58%) were INCFs, and 16 (10%) were SNCFs. There was at least one INCF in 65 studies (27%)--67% of which were new--and at least one SNCF in 13 studies (5%). Compared with younger patients, patients 60 years and older were much more likely to have INCFs (43% vs 17%) and SNCFs (12% vs 1%). Overall, 29% of NCFs were in the abdomen, 70% in the chest, and 1% in the neck. The most common INCFs were pleural effusion (n = 26), air-space disease or atelectasis (n = 13), and adenopathy (n = 9). Five new cases of cancer were diagnosed, including lung (n = 2), lymphoma (n = 2), and thyroid (n = 1). CONCLUSION: NCFs are commonly encountered on cardiac MRI studies, many of which are clinically relevant. Proper recognition of NCFs is critical to the comprehensive management of patients referred for cardiac MRI.