Protein-based polymer liquid embolics for cerebral aneurysms.

Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achieving >90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. STATEMENT OF SIGNIFICANCE: Unruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments.

Impact of Implicit Abdominal Aortic Aneurysm Screening in the Veterans Affairs Health Care System Over 10 Years.

Background Abdominal aortic aneurysm (AAA) screening programs have been active in the United States since 2005, but are not the only way AAAs are detected. AAA management and outcomes have not been investigated broadly in the context of "implicit AAA screening," whereby radiologic examinations not intended for focused screening can identify AAAs. Methods and Results We examined the association between imaging-based AAA screening, both explicit and implicit, and various outcomes for ≈1.6 million veterans in the Veterans Affairs health care system from 2005 to 2015. Screened-positive, screened-negative, and unscreened veterans were identified in the overall cohort and within a subgroup of veterans aged 65 years in 2005. The yearly composite screening rate increased over 10 years, from 11.7% to 18.3%, whereas the screened-positive rate decreased from 7.3% to 4.9%. Only 12.9% of screening examinations were explicit AAA screening ultrasounds. The subgroup's composite screening rate was 74% within its 10-year eligibility window, with implicit screening accounting for 91.8% of examinations. In the 2005 subgroup, all-cause mortality and Charlson comorbidity scores were higher for veterans who underwent screening compared with those unscreened (31.2% versus 23.1% and 0.47 versus 0.25, respectively; P<0.001). AAA rupture rates were similar between those unscreened and screened-negative individuals. Conclusions Accounting for both explicit and implicit screening, AAA screening in the Veterans Affairs population has moderate reach. Efforts to expand explicit AAA screening are not likely to impact either all-cause mortality or AAA rupture on the population scale as significantly as a careful accounting for and use of implicit screening data.

Colonic lipomas revisited on CT colonography.

PURPOSE: CT colonography (CTC) is growing in its utilization as a nationally approved colorectal cancer screening test. After colonic polyps, lipomas are the second most common colonic lesions and their accurate and rapid recognition are important. METHODS: This retrospective Institutional Review Board approved study was performed at two large academic university-based institutions. 1044 patients underwent CTC at Institution A from 2010 to 2018 and 1094 patients underwent CTC at Institution B from 2003 to 2015. All CTC examinations with at least one colonic lipoma in their report were evaluated by a fellowship-trained abdominal imaging radiologist. 47 CTC examinations containing 59 colonic lipomas were detected and included. Segmental location, sessile versus pedunculated morphology, multiplicity, average attenuation, and largest lesion diameter were evaluated. A review of the current literature on colonic lipomas is entailed. RESULTS: The overall incidence of colonic lipoma was 2.2% in women and 2.3% in men. Mean age for detection of colonic lipomas on CTC was 66.9 years. Segmental locations of colonic lipomas include ascending colon (39%), transverse colon (19%), ileocecal valve (12%), cecum (12%), descending colon (10%), and rectosigmoid (8%). 9% of colonic lipomas were multiple, 42% were pedunculated, and 58% were sessile. The mean (range) size of detected lipomas was 19 (6-59) mm. The mean (range) attenuation was - 132 (- 41 to - 258) HU. CONCLUSION: Most colonic lipomas are located in the ascending colon. Although they are typically solitary, just under 10% are multiple, and although they are most often sessile, slightly under half are pedunculated mimicking polyps. CTC detects smaller lipomas than optical colonoscopy.

Translational Development of a Silk-Elastinlike Protein Polymer Embolic for Transcatheter Arterial Embolization.

Locally blocking blood flow to tumors with embolic materials is the key to transcatheter arterial embolization for treating hepatocellular carcinoma. Current microparticle agents do not deeply penetrate target tissues and are compatible with a very limited selection of therapeutic agents. Silk-elastinlike protein polymers (SELPs) combine the solubility of elastin and the strength of silk to create an easily injected liquid embolic that transition into a solid depot amenable to loading with drugs, gene therapy agents, or biologics. SELP, injected as liquid solution, penetrates the vasculature before transitioning to a solid hydrogel. The objective of this manuscript is to evaluate SELP embolization, stability, and biocompatibility at 7-, 30-, and 90-day survival intervals in a porcine model. SELP embolics selectively block blood flow in the kidneys and livers, with no off-target infarctions. As assessed with angiography, SELP renal embolization exhibits decreasing persistence for the duration of the 90-day study period. There is an increased presence of microscopic SELP emboli in the renal setting, compared to Embosphere. Histologically scored inflammatory reactions to SELP are decreased in both the renal and hepatic implantations compared to Embosphere. In conclusion, a bioresorbable SELP liquid embolic system deeply penetrates target tissue and selectively embolizes blood vessels in vivo.

Percutaneous embolization of post traumatic splenic pseudoaneurysm.

Management of splenic pseudoaneurysms in hemodynamically stable patients has shifted toward nonoperative management, including watchful waiting and endovascular embolization. Standard of treatment does not include percutaneous embolization for splenic pseudoaneurysm repair. In this case report, we document a successful percutaneous embolization of a post traumatic splenic pseudoaneurysm with thrombin. Percutaneous embolization of splenic pseudoaneurysms can be considered a viable technique in patients who fail endovascular embolization or have lesions inaccessible to endovascular repair.

Imaging of the Postoperative Colon.

Recognition of postoperative complications is important for the immediate diagnosis and treatment needed for appropriate patient care. Identification of postoperative complications from colon surgery requires not only knowledge of the type of procedure, but also the expected normal postoperative appearance. The purpose of this article is to discuss and review the expected anatomic changes after colorectal surgery, and the appearance of the most common postoperative complications.

Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma.

PURPOSE: In this study, we compare an abbreviated screening MRI protocol (aMRI), utilizing only dynamic contrast-enhanced images, to a conventional liver MRI (cMRI) for the characterization of observations in at-risk patients. MATERIALS AND METHODS: 164 consecutive HCC screening MRIs were retrospectively analyzed. Two sets of de-identified image sets were created: one with all acquired sequences including T2- and diffusion-weighted sequences (cMRI), and one with only T1-weighted precontrast and dynamic post-contrast images utilizing an extracellular gadolinium contrast agent (aMRI). Three readers assigned a LI-RADS score based on the lesion with the highest LI-RADS category using the aMRI and cMRI datasets during separate reads. RESULTS: There was no change between the aMRI and cMRI LI-RADS categorization in 93%, 96%, and 96% of cases for readers 1, 2, and 3, respectively. In the majority of the discrepant cases, the score increased from LI-RADS 3 to LI-RADS 4 due to the presence of ancillary features on T2 and DWI. Kappa values for interobserver variability demonstrated fair-to-moderate LI-RADS agreement among the 3 readers. CONCLUSION: There was strong agreement between the abbreviated T1-only MRI protocol and a full liver MRI, with only 5% of cases changing LI-RADS categorization due to the inclusion of T2 and DWI. The estimated time to run this abbreviated MRI is approximately 7-10 min, possibly allowing for a more cost-effective screening MRI than our cMRIs.

The Role of PET/MR Imaging in Precision Medicine.

Fluorodeoxyglucose PET and PET/computed tomography have gained acceptance in the evaluation of disease. Nontargeted tracers have been used in the diagnosis of certain malignancies but may not be sensitive or specific enough to become standard of care. Newer targeted PET tracers have been developed that target disease-specific biomarkers, and allow accurate and sensitive detection of disease. Combined with the capabilities of MR imaging to evaluate soft tissue, precision imaging with PET/MR imaging can change the diagnosis. This article discusses specific areas in which precision imaging with nontargeted and targeted diagnostic agents can change the diagnosis and treatment.

Application of 3-Dimensional Printing in a Case of Osteogenesis Imperfecta for Patient Education, Anatomic Understanding, Preoperative Planning, and Intraoperative Evaluation.

BACKGROUND: The techniques and applications of 3-dimensional (3D) printing have progressed at a fast pace. In the last 10 years, there has been significant progress in applying this technology to medical applications. We present a case of osteogenesis imperfecta in which treatment was aided by prospectively using patient-specific, anatomically accurate 3D prints of the calvaria. The patient-specific, anatomically accurate 3D prints were used in the clinic and in the operating room to augment patient education, improve surgical decision making, and enhance preoperative planning. CASE DESCRIPTION: A 41-year-old woman with osteogenesis imperfecta and an extensive neurosurgical history presented for cranioplasty revision. Computed tomography (CT) data obtained as part of routine preoperative imaging were processed into a 3D model. The 3D patient-specific models were used in the clinic for patient education and in the operating room for preoperative visualization, planning, and intraoperative evaluation of anatomy. The patient reported the 3D models improved her understanding and comfort with the planned surgery when compared with discussing the procedure with the neurosurgeon or viewing the CT images with a neuroradiologist. The neurosurgeon reported an improved understanding of the patient's anatomy and potential cause of patient symptoms as well as improved preoperative planning compared with viewing the CT imaging alone. The neurosurgeon also reported an improvement in the planned surgical approach with a better intraoperative visualization and confirmation of the regions of planned calvarial resection. CONCLUSIONS: The use of patient-specific, anatomically accurate 3D prints may improve patient education, surgeon understanding and visualization, preoperative decision making, and intraoperative management.

Polymeric materials for embolic and chemoembolic applications.

Percutaneous transcatheter embolization procedures involve the selective occlusion of blood vessels. Occlusive agents, referred to as embolics, vary in material characteristics including chemical composition, mechanical properties, and the ability to concurrently deliver drugs. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives, in situ gelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackable in vivo. This article reviews commercially available materials used for embolization as well as polymeric materials that are under investigation.

Advances in PET Imaging of Degenerative, Cerebrovascular, and Traumatic Causes of Dementia.

In this review we present the most recent advances in nuclear medicine imaging as a diagnostic and management tool for dementia. The clinical diagnosis of dementia syndromes can be challenging for physicians, particularly in the early stages of disease. Given the growing number of individuals affected by dementia, early and accurate diagnosis can lead to improved clinical management of patients. Although tests are available for exclusion of certain causes of cognitive impairment, the results rarely allow the clinician to make a definitive diagnosis. For this reason, information obtained from imaging ("imaging biomarkers") is playing an increasingly important role in the workup of patients with suspected dementia. Imaging biomarkers also provide indispensable tools for clinical and preclinical studies of dementing illnesses to elucidate their pathophysiology and to develop better therapies. A wide range of imaging has been used to diagnose and investigate neurodegenerative disorders including structural, cerebral perfusion, glucose metabolism, neurochemical, and molecular imaging. In the first section, we discuss the imaging methods used in clinical practice to diagnose dementia as well as explore additional experimental modalities that are currently used as research tools. In the second section, a comprehensive review covering the myriad aspects of vascular disease as a cause of dementia is presented and illustrated with MRI- and PET-focused case examples. In the third section, advances in imaging Alzheimer disease pathology are emphasized by reviewing current approaches for PET imaging with ß-amyloid imaging agents. We provide an outline for the appropriate use criteria for ß-amyloid imaging agents in dementia. In addition, the recognition of the importance of neocortical neurofibrillary tangles as related to Alzheimer disease progression has led to the development of promising tau imaging agents such as [(18)F]T807. The last section provides a history brain trauma as a cause of chronic traumatic encephalopathy. Although the recognition of cognitive deficits from brain trauma dates back to the early part of last century, recent advances in our understanding of the neurobiology has led to the hope of developing molecular imaging methods for earlier diagnoses and treatment. This has become increasingly important given the raised public and physician awareness of the high incidence of this pathology in military conflicts and sports-related injuries. Overall advancements in nuclear medicine imaging have led to an improvement in the detection and accurate identification of dementia and its underlying causes. With both primary and secondary causes of dementia demonstrating often overlapping presentations, nuclear medicine imaging can play a key role not only in the diagnosis but the understanding of dementia. With earlier diagnosis and better understanding comes the hope of improved treatments or possibly someday a cure.

In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization.

Hepatocellular carcinoma annually affects over 700,000 people worldwide and trends indicate increasing prevalence. Patients ineligible for surgery undergo loco-regional treatments such as transarterial chemoembolization (TACE) to selectively target tumoral blood supply. Using a microcatheter, chemotherapeutics are infused followed by an embolic agent, or the drug is encapsulated by the embolic moiety; simultaneously inducing stasis while delivering localized chemotherapy. Presently, several products are used, but no universally accepted system is promoted because very disparate limitations exist. The goal of this investigation was to design and develop in situ gelling recombinant silk-elastinlike protein polymers (SELPs) for TACE. Two SELP compositions, SELP-47K and SELP-815K, with varying lengths of silk and elastin blocks, were investigated to formulate a new embolic that was injectable through commercially available microcatheters. The goal was to develop a composition providing maximal permeation of tumor vasculature while exhibiting effective embolic activity. The SELPs evaluated remain soluble until reaching 37 °C, when irreversible transition ensues forming a solid hydrogel network. SELP-815K formulated at 12% w/w with shear processing demonstrated acceptable rheological properties and clear embolic capability under flow conditions in vitro. A rabbit model showed feasibility of embolization in vivo allowing selective occlusion of lobar hepatic arterial branches.

Chemical shift MR imaging methods for the quantification of transcatheter lipiodol delivery to the liver: preclinical feasibility studies in a rodent model.

PURPOSE: To demonstrate the feasibility of using chemical shift magnetic resonance (MR) imaging fat-water separation methods for quantitative estimation of transcatheter lipiodol delivery to liver tissues. MATERIALS AND METHODS: Studies were performed in accordance with institutional Animal Care and Use Committee guidelines. Proton nuclear MR spectroscopy was first performed to identify lipiodol spectral peaks and relative amplitudes. Next, phantoms were constructed with increasing lipiodol-water volume fractions. A multiecho chemical shift-based fat-water separation method was used to quantify lipiodol concentration within each phantom. Six rats served as controls; 18 rats underwent catheterization with digital subtraction angiography guidance for intraportal infusion of a 15%, 30%, or 50% by volume lipiodol-saline mixture. MR imaging measurements were used to quantify lipiodol delivery to each rat liver. Lipiodol concentration maps were reconstructed by using both single-peak and multipeak chemical shift models. Intraclass and Spearman correlation coefficients were calculated for statistical comparison of MR imaging-based lipiodol concentration and volume measurements to reference standards (known lipiodol phantom compositions and the infused lipiodol dose during rat studies). RESULTS: Both single-peak and multipeak measurements were well correlated to phantom lipiodol concentrations (r(2) > 0.99). Lipiodol volume measurements were progressively and significantly higher when comparing between animals receiving different doses (P < .05 for each comparison). MR imaging-based lipiodol volume measurements strongly correlated with infused dose (intraclass correlation coefficients > 0.93, P < .001) with both single- and multipeak approaches. CONCLUSION: Chemical shift MR imaging fat-water separation methods can be used for quantitative measurements of lipiodol delivery to liver tissues.

Unexplained renal colic: what is the utility of IV contrast?

PURPOSE: The aim of this study was to evaluate the benefit of intravenous (IV) contrast in patients with suspected renal colic and unremarkable unenhanced MDCT. MATERIALS AND METHODS: One thousand two hundred and four patients with suspected ureterolithiasis were evaluated with unenhanced MDCT. Seven hundred and eight patients that had additional imaging following IV contrast were our study group. RESULTS: Of the patients, 9.4% (67/708) had abnormalities seen only on contrast-enhanced exams. In 53.1% (376/708) of the patients, no additional finding was identified after IV contrast. CONCLUSION: IV contrast in patients with renal colic is rarely helpful.