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2.
AJR Am J Roentgenol ; 219(4): 634-646, 2022 10.
Article in English | MEDLINE | ID: mdl-35583424

ABSTRACT

The most challenging and time-consuming step of TIPS procedures is obtaining appropriate portal vein (PV) access. Given the lack of real-time direct target visualization, conventional fluoroscopic guidance requires multiple passes, contributing to complications. In comparison, intravascular ultrasound (IVUS) guidance during TIPS procedures provides direct visualization of hepatic structures and real-time guidance for PV puncture. IVUS guidance during TIPS creation improves procedural metrics such as radiation dose, contrast agent volume, procedure time, and technical success rate and is particularly beneficial in technically challenging cases (e.g., in patients portal vein thrombosis, small or variant portal vein anatomy, Budd-Chiari syndrome, or liver masses). The purpose of this review is to summarize current IVUS technology, describe the technical aspects of IVUS-guided TIPS creation, and discuss the clinical indications for and benefits of using IVUS for TIPS creation, while presenting available evidence supporting the technique's use. Given the improved safety profile and overall success rate in comparison with conventional guidance methods, IVUS guidance has the future potential to become the standard practice for TIPS placement.


Subject(s)
Portasystemic Shunt, Transjugular Intrahepatic , Contrast Media , Humans , Portal Vein/diagnostic imaging , Portasystemic Shunt, Transjugular Intrahepatic/methods , Punctures , Treatment Outcome , Ultrasonography, Interventional
3.
Eur Heart J Case Rep ; 6(4): ytac113, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35481254

ABSTRACT

Background: CardioMEMS heart failure (HF) system is an implantable wireless pressure sensor that is placed in a branch of the pulmonary artery (PA) for remote monitoring of PA pressures in patients with HF. Pulmonary artery injury/haemoptysis can occur during the sensor placement. Case summary: An 80-year-old male patient with HF with reduced ejection fraction (20%) underwent CardioMEMS HF system implantation for recurrent shortness of breath. He developed haemoptysis and dyspnoea during the procedure, which was managed with furosemide. The patient's computerized tomographic angiography showed a 3.4 cm pseudoaneurysm with active extravasation from the superior segmental branch of the left PA due to injury during device placement. The decision to embolize the pseudoaneurysm was made after a multi-disciplinary team meeting and discussion with the patient. The embolization procedure was carried out successfully with the final left pulmonary angiogram showed complete stasis and no further filling of the pseudoaneurysm sac. Discussion: The incidence of mortality in patients with PA injury from CardioMEMS devices is high, and therefore prompt diagnosis and management are critical. Pulmonary artery pseudoaneurysms are uncommon and present with haemoptysis. Transcatheter embolization has been shown to be a practical, effective, and safe therapeutic option in stable patients.

5.
Prostate ; 82(6): 695-705, 2022 05.
Article in English | MEDLINE | ID: mdl-35167141

ABSTRACT

BACKGROUND: Prostate cancer (PCa) models in mice and rats are limited by their size and lack of a clearly delineated or easily accessible prostate gland. The canine PCa model is currently the only large animal model which can be used to test new preclinical interventions but is costly and availability is sparse. As an alternative, we developed an orthotopic human prostate tumor model in an immunosuppressed New Zealand White rabbit. Rabbits are phylogenetically closer to humans, their prostate gland is anatomically similar, and its size allows for clinically-relevant testing of interventions. METHODS: Rabbits were immunosuppressed via injection of cyclosporine. Human PC3pipGFP PCa cells were injected into the prostate via either (a) laparotomy or (b) transabdominal ultrasound (US) guided injection. Tumor growth was monitored using US and magnetic resonance imaging (MRI). Contrast-enhanced ultrasound (CEUS) imaging using nanobubbles and Lumason microbubbles was also performed to examine imaging features and determine the optimal contrast dose required for enhanced visualization of the tumor. Ex vivo fluorescence imaging, histopathology, and immunohistochemistry analyses of the collected tissues were performed to validate tumor morphology and prostate-specific membrane antigen (PSMA) expression. RESULTS: Immunosuppression and tumor growth were, in general, well-tolerated by the rabbits. Fourteen out of 20 rabbits, with an average age of 8 months, successfully grew detectable tumors from Day 14 onwards after cell injection. The tumor growth rate was 39 ± 25 mm2 per week. CEUS and MRI of tumors appear hypoechoic and T2 hypointense, respectively, relative to normal prostate tissue. Minimally invasive US-guided tumor cell injection proved to be a better method compared to laparotomy due to the shorter recovery time required for the rabbits following injection. Among the rabbits that grew tumors, seven had tumors both inside and outside the prostate, three had tumors only inside the prostate, and four had tumors exclusively outside of the prostate. All tumors expressed the PSMA receptor. CONCLUSIONS: We have established, for the first time, an orthotopic PCa rabbit model via percutaneous US-guided tumor cell inoculation. This animal model is an attractive, clinically relevant intermediate step to assess preclinical diagnostic and therapeutic compounds.


Subject(s)
Prostatic Neoplasms , Animals , Castration , Disease Models, Animal , Dogs , Humans , Male , Mice , Microbubbles , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Rabbits , Rats , Ultrasonography/methods
6.
Indian J Radiol Imaging ; 31(Suppl 1): S21-S30, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33814758

ABSTRACT

The COVID-19 pandemic has affected every sector of healthcare. Interventional Radiology in many instances continues to provide frontline care during this pandemic. The purpose of this article is to assist Interventional Radiologists in their preparation to face the challenges, by summarizing global experiences and guidelines. We provide a basic framework that can be used to prepare institue specific guidelines in coordination with multidisciplinary teams and hospital administration.

7.
AJR Am J Roentgenol ; 216(6): 1452-1461, 2021 06.
Article in English | MEDLINE | ID: mdl-33787298

ABSTRACT

OBJECTIVE. No studies or guidelines exist to direct management of ureteroarterial fistula (UAF) after ileal conduit urinary diversion in which the possible risks and complications associated with stent-graft infection from the conduit flora must be reconciled with those of open surgical repair. This study seeks to characterize the clinical presentation, pathogenesis, and optimal diagnostic and therapeutic management of this entity through a systematic review of the literature. MATERIALS AND METHODS. A systematic search of the English-language literature using the PubMed, Scopus, and ScienceDirect databases was performed: 264 abstracts were identified. From those abstracts, 32 studies comprising 40 patients with 43 UAFs were selected for analysis. Data points including demographics, clinical presentation, UAF specifications, procedural details, postprocedural complications, and clinical outcomes were reviewed. RESULTS. Predisposing factors included female sex, chronic ureteral stent placement, and past surgical intervention and irradiation for pelvic malignancy. Fistulization was overwhelmingly unilateral (95.0% of patients) and included the common iliac artery (90.7% of UAFs). Combined endovascular and endoureteral modalities presented similar outcomes compared with surgical approaches in terms of UAF-related mortality (7.1% vs 13.3%, respectively) and complication rates (28.6% vs 26.7%) during a similar median follow-up period (9.5 vs 14.0 months). Endovascular stent-graft infections were present in 14.3% of cases and represented a leading indication for reintervention after endovascular management (50.0%). CONCLUSION. Short- and intermediate-term outcomes of combined endovascular and endoureteral techniques compare favorably with those of surgical approaches in the treatment of UAF after ileal conduit urinary diversion. Although there is a relatively low stent-graft infection rate, close follow-up within the first year after the procedure is required given the propensity of complications to develop during this window. The use of postprocedural antibiotics is uncertain but is likely prudent.


Subject(s)
Postoperative Complications/etiology , Ureteral Diseases/etiology , Urinary Diversion/adverse effects , Urinary Diversion/methods , Urinary Fistula/etiology , Vascular Fistula/etiology , Female , Humans , Male , Treatment Outcome
8.
AJR Am J Roentgenol ; 217(4): 921-932, 2021 10.
Article in English | MEDLINE | ID: mdl-33470838

ABSTRACT

Management of acute pancreatitis is challenging in the presence of local complications that include pancreatic and peripancreatic collections and vascular complications. This review, targeted for interventional radiologists, describes minimally invasive endoscopic, image-guided percutaneous, and surgical procedures for management of complicated pancreatitis and provides insight into the procedures' algorithmic application. Local complications are optimally managed in a multidisciplinary team setting that includes advanced endoscopists; pancreatic surgeons; diagnostic and interventional radiologists; and specialists in infectious disease, nutrition, and critical care medicine. Large symptomatic or complicated sterile collections and secondary infected collections warrant drainage or débridement. The drainage is usually delayed for 4-6 weeks unless clinical deterioration warrants early intervention. If collections are accessible by endoscopy, endoscopic procedures are preferred to avoid pancreaticocutaneous fistulas. Image-guided percutaneous drainage is indicated for symptomatic collections that are not accessible for endoscopic drainage or that present in the acute setting before developing a mature wall. Peripancreatic arterial pseudoaneurysms should be embolized before necrosectomy procedures to prevent potentially life-threatening hemorrhage. Surgical procedures are reserved for symptomatic collections that persist despite endoscopic or interventional drainage attempts. Understanding these procedures facilitates their integration by interventional radiologists into the complex longitudinal care of patients with complicated pancreatitis.


Subject(s)
Pancreatitis/diagnostic imaging , Pancreatitis/surgery , Radiography, Interventional , Acute Disease , Algorithms , Biopsy, Fine-Needle , Debridement , Drainage , Endoscopy, Digestive System/methods , Humans , Necrosis/surgery , Pancreatitis/complications , Pancreatitis/pathology , Patient Care Team , Stents , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiology
9.
Abdom Radiol (NY) ; 46(3): 1163-1170, 2021 03.
Article in English | MEDLINE | ID: mdl-32940757

ABSTRACT

In the setting of portal hypertension, intractable bleeding from anorectal varices is a rare occurrence. In this review, clinical presentation and management of this dilemma are presented in a case-based fashion. Bleeding may occur in the absence of prior history of cirrhosis or gastroesophageal varices and measurement of hepatic venous pressure gradient and liver biopsy could help to establish the diagnosis. Successful treatment outcome necessitates tailoring treatment to the patient's anatomy and imaging findings. A multidisciplinary algorithmic approach is also proposed to aid clinicians in this regard.


Subject(s)
Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Varicose Veins , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/therapy , Humans , Hypertension, Portal/complications , Hypertension, Portal/diagnostic imaging , Radiology, Interventional , Varicose Veins/complications , Varicose Veins/diagnostic imaging , Varicose Veins/therapy
10.
Clin Imaging ; 72: 31-36, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33202292

ABSTRACT

BACKGROUND: To evaluate Interventional Radiology (IR) procedural volume changes at a large Midwest health system between March 17, 2020 and April 30, 2020 following a state-mandated shutdown of nonessential procedures during the initial phase of COVID-19. METHODS: IR procedural volumes were compiled, stratified by location and compared with Diagnostic Radiology (DR) volumes during the same timeframe. Procedure volume was categorized by type, including oncology, dialysis interventions, and drainage procedures with comparisons made using Z-score test for proportions. IR and system-wide surgical procedural volume was compared with baseline values. RESULTS: System-wide IR procedural volume decreased by 35%, with a 41% decrease in outpatient and a 25% decrease in inpatient volume during the state-mandated order. DR volume decreased by 45%, with a 57% decrease in outpatient and a 22% decrease in inpatient volume. Total IR procedural volume during the mandate was 1077 versus 1518 during the preceding six weeks. The proportion of Interventional Oncology and dialysis interventions showed no significant change (p > 0.05) while that of drainage procedures increased (p < 0.05). Compared to baseline values, system-wide procedural volumes for IR, Vascular Surgery, Urology, General Surgery, Gastroenterology and Gynecology decreased by 3%, 11%, 25%, 20%, 38% and 31% in March 2020 and 25%, 47%, 68%, 63%, 79% and 73% in April 2020 respectively. CONCLUSION: Outpatient IR volumes were less impacted compared to DR during the initial phase of COVID-19. Oncology, dialysis and drainage interventions may be considered essential procedures due to their stability. IR volumes were less affected compared to other procedural specialties.


Subject(s)
COVID-19 , Radiology, Interventional , Humans , Inpatients , Radiography , SARS-CoV-2
12.
Indian J Radiol Imaging ; 29(2): 219-222, 2019.
Article in English | MEDLINE | ID: mdl-31367096

ABSTRACT

Congenital extrahepatic portosystemic shunt (CEPS) is a rare splanchnic venous malformation, wherein the portal venous outflow drains into the systemic venous circulation via a pathologic shunt. CEPS exhibits heterogeneous clinical behavior and angiography is the gold standard for evaluation of the portomesenteric communication to systemic vasculature. The potential severity of complications necessitates shunt closure. Here, we present two cases of CEPS. The first patient presented with an asymptomatic hyperammonemia and was found to have a Type 1 CEPS with absence of intrahepatic portal system. The second patient was asymptomatic and was incidentally found to have a Type 2 CEPS on imaging with normal intrahepatic portal system. Both patients were successfully treated with endovascular occlusion of the CEPS.

13.
Int J Cardiovasc Imaging ; 35(7): 1365-1377, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30830527

ABSTRACT

Heart failure is a clinical condition that is associated with significant morbidity and mortality. With the advent of left ventricular assist device (LVAD), an increasing number of patients have received an artificial heart both as a bridge-to-therapy and as a destination therapy. Clinical trials have shown clear survival benefits of LVAD implantation. However, the increased survival benefits and improved quality of life come at the expense of an increased complication rate. Common complications include perioperative bleeding, infection, device thrombosis, gastrointestinal bleeding, right heart failure, and aortic hemodynamic changes. The LVAD-associated complications have unique pathophysiology. Multiple imaging modalities can be employed to investigate the complications, including computed tomography (CT), positron emission tomography-computed tomography (PET-CT), catheter angiography and echocardiography. Imaging studies not only help ascertain diagnosis and evaluate the severity of disease, but also help direct relevant clinical management and predict prognosis. In this article, we aim to review the common LVAD complications, present the associated imaging features and discuss the role of imaging in their management.


Subject(s)
Cardiac Imaging Techniques , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Postoperative Complications/diagnostic imaging , Postoperative Complications/therapy , Prosthesis Implantation/adverse effects , Prosthesis Implantation/instrumentation , Ventricular Function, Left , Adult , Aged , Female , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Humans , Male , Middle Aged , Postoperative Complications/etiology , Predictive Value of Tests , Prosthesis Design , Risk Factors , Treatment Outcome
14.
ACS Biomater Sci Eng ; 5(4): 1849-1856, 2019 Apr 08.
Article in English | MEDLINE | ID: mdl-33405558

ABSTRACT

In this study, we have developed a tunable polymer vascular embolic implant (TPVEI) with adjustable precipitation rates allowing for personalized, controlled vascular occlusion depths. We hypothesized that reducing the water miscibility of the solvent would result in slower TPVEI precipitation, leading to distal vascular occlusion. To investigate homogeneous vascular distribution and occlusion control, the TPVEI was directly injected into the portal vein of a rat and imaged with microCT. Changing the solvent ratio of NMP/BB from 100/0 to 50/50 showed a significant (p < 0.05) decrease in vessel size occluded from 675 ± 20 to 170 ± 25 µm, respectively. The 60/40 (NMP/BB) formulation was able to occlude several branches throughout the whole liver, displaying a homogeneous vasculature distribution. Broadband Doppler ultrasound validated that there was complete portal vein occlusion after embolization with all materials. These findings suggest that adjusting the solvent polarity allows embolization control and with appropriate optimization, phase-inverting embolics could be used better to control depth of occlusion for endovascular therapies.

15.
J Vasc Surg Venous Lymphat Disord ; 7(3): 413-419, 2019 May.
Article in English | MEDLINE | ID: mdl-30477980

ABSTRACT

OBJECTIVE: The objective of this study was to assess the safety, feasibility, and effectiveness of endobronchial forceps-assisted retrieval of inferior vena cava (IVC) filters when standard retrieval techniques fail. METHODS: An Institutional Review Board-approved single-center retrospective review during a 6-year period identified 60 consecutive patients (23 men and 37 women; mean age, 49.3 years; range, 19-77 years) in whom rigid endobronchial forceps were required for IVC filter retrieval after standard techniques failed. Factors affecting retrieval success, including an embedded or tilted filter, overall dwell time, filter fracture, and caval penetration, were recorded, as were success rates, procedural details, and complications. RESULTS: Mean dwell time between filter placement and removal was 565 days (range, 15-7366 days). Various IVC filters were encountered: 33 Option (Argon Medical, Frisco, Tex), 8 Celect (Cook Medical, Bloomington, Ind), 9 Günther Tulip (Cook Medical), 4 G2 and 3 Eclipse (Bard, Murray Hill, NJ), 2 OptEase (Cordis, Bridgewater, NJ), and 1 Simon Nitinol (Bard). Imaging before retrieval showed grade 1 (3/60), grade 2 (44/60), and grade 3 (13/60) filter interaction with IVC wall. The degree of secondary tilt as assessed on images acquired before attempted retrieval was <10 degrees (n = 22; 36.7%), 10 to 20 degrees (n = 26; 43.3%), and >20 degrees (n = 12; 20%), with an average tilt of 13.8 degrees (range, 0-48.9 degrees). Of the 60 filters, 58 were retrieved successfully (96.7%). Two of these required a second attempt (one because of migration into the right atrium and the other because of extreme discomfort of the patient requiring subsequent general anesthesia). Five of 60 procedures were forceps-assisted loop snare retrievals in which the forceps were used to dissect the embedded hook free from surrounding hyperplastic caval venous endothelium. Mean fluoroscopy retrieval time was 33.2 minutes (range, 10-76.9 minutes). Intraprocedural inconsequential filter fracture was observed in 10 patients. There were four complications: one retroperitoneal hemorrhage, one IVC dissection flap, and two filter fractures with subsequent migration of filter components to the right side of the heart and to the right pulmonary artery. The first two complications required hospital admission and conservative management; in the last two, the fractured and migrated filter limbs were retrieved successfully using a snare device. CONCLUSIONS: Rigid endobronchial forceps can be safely and reliably used to remove embedded, fractured, or tilted retrievable IVC filters from patients in whom standard retrieval techniques are unsuccessful. There is a high success rate and minimal complications. We propose that the degree of filter tilt, caval penetration, and filter fracture are predictive of the need for the use of forceps as a first-line retrieval technique.


Subject(s)
Device Removal/instrumentation , Foreign-Body Migration/therapy , Prosthesis Failure , Prosthesis Implantation/instrumentation , Surgical Instruments , Vena Cava Filters , Adult , Aged , Cross-Sectional Studies , Device Removal/adverse effects , Equipment Design , Feasibility Studies , Female , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/etiology , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
16.
Tech Vasc Interv Radiol ; 20(1): 31-37, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28279407

ABSTRACT

Autogenous arteriovenous fistulae are the best method for prolonged, successful dialysis access. However, a substantial limitation of dialysis fistulae is their high primary failure rate, estimated to be as high as 70% for radiocephalic fistulae. Fistula maturation is influenced by demographic risk factors as well as anatomical barriers, the latter of which can be readily identified by noninvasive ultrasound imaging and physical examination. These barriers can be categorized as inflow problems (native arterial disease, arteriovenous anastomotic stenosis, and juxta-anastomotic stenosis) or outflow problems (proximal venous stenosis or collateral veins). Venous stenoses represent the most commonly observed barrier to fistula maturation. By treating these barriers with a systematic approach, interventionalists can significantly improve the likelihood of a fistula's usability for dialysis.


Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Graft Occlusion, Vascular/epidemiology , Graft Occlusion, Vascular/therapy , Renal Dialysis , Angiography , Blood Flow Velocity , Collateral Circulation , Graft Occlusion, Vascular/diagnosis , Graft Occlusion, Vascular/physiopathology , Humans , Predictive Value of Tests , Radiography, Interventional , Regional Blood Flow , Risk Factors , Treatment Outcome , Vascular Patency
17.
J Vasc Interv Radiol ; 27(8): 1228-35, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27363299

ABSTRACT

PURPOSE: To evaluate intraarterial catheter-directed thrombolysis for prediction and prevention of delayed surgical amputation as part of multidisciplinary management of frostbite injury. MATERIALS AND METHODS: A retrospective review was performed of 13 patients (11 men, 2 women; median age, 33.4 y; range, 8-62 y) at risk of tissue loss secondary to frostbite injury and treated with catheter-directed tissue plasminogen activator (t-PA) thrombolysis. Amputation data were assessed on follow-up (mean, 23 mo; range, 9-83 mo). Angiographic findings were classified into complete, partial, and no angiographic response and assessed for association with follow-up amputation rates. Correlation between amputation outcome and duration of cold exposure (mean, 23 h; range, 5-96 h), time between exposure and rewarming therapy (mean, 25.5 h; range, 7-95 h), and time between exposure and t-PA thrombolysis (mean, 32 h; range, 12-96 h) was assessed. Complications were recorded. RESULTS: Of 127 digits at risk on baseline angiography that were treated with catheter-directed thrombolysis, complete recovery was seen in 106 (83.4%). Total mean t-PA dose per extremity was 27.5 mg (range, 12-48 mg) over a mean period of 34 hours (range, 12-72 h). Patients with complete angiographic response (8 patients; 79.5% of digits) did not require amputations; 4 of 5 patients (80%) with partial angiographic response (20.5% of digits) underwent amputation (P = .007). There was no significant correlation between amputation rates and duration of cold exposure (P = .9), time to rewarming therapy (P = .88), and time to thrombolysis (P = .56). Femoral access site bleeding in 2 patients was managed conservatively. One patient underwent surgical exploration for brachial artery hematoma. CONCLUSIONS: Intraarterial catheter-directed thrombolysis should be included in initial management of frostbite injury, as it may prevent delayed amputations. The degree of angiographic response to thrombolysis can potentially predict amputation outcomes.


Subject(s)
Catheterization, Peripheral , Fibrinolytic Agents/administration & dosage , Fingers/blood supply , Frostbite/therapy , Patient Care Team , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Toes/blood supply , Adolescent , Adult , Amputation, Surgical , Angiography, Digital Subtraction , Catheterization, Peripheral/adverse effects , Child , Combined Modality Therapy , Female , Fibrinolytic Agents/adverse effects , Frostbite/diagnostic imaging , Frostbite/physiopathology , Humans , Infusions, Intra-Arterial , Limb Salvage , Male , Middle Aged , Radiography, Interventional , Retrospective Studies , Rewarming , Risk Factors , Thrombolytic Therapy/adverse effects , Time Factors , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , Young Adult
18.
Cardiovasc Diagn Ther ; 6(6): 623-631, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28123982

ABSTRACT

Post-thrombotic syndrome (PTS) is a venous stress disorder that develops from long-term effects from a previous deep venous thrombosis (DVT). The morbidity associated with PTS may be significant and patients can present with edema, chronic pain, swelling, skin changes, and heaviness of the affected limb. PTS can eventually lead to a decreased quality of life and to a marked burden for the healthcare system. This article elaborates on clinical aspects of PTS including the pathophysiology, diagnostic work-up and management of the disease with a particular focus on endovascular options.

19.
Radiology ; 276(2): 518-25, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25811427

ABSTRACT

PURPOSE: To determine whether (a) stem cells loaded with DNA-carrying microbubbles (MBs) can be transfected in vivo, (b) the cells remain alive to express the gene, and (c) gene expression is sufficiently robust to be detected in vivo. MATERIALS AND METHODS: The study was approved by the Institutional Animal Care and Use Committee. Cationic MBs were prepared, characterized, and loaded with pLuciferase green fluorescent protein (GFP) plasmid. Loading was confirmed with SYBR Gold staining (Life Technologies, Carlsbad, Calif). C17.2 cells were loaded with the DNA-carrying MBs. Two hundred thousand cells suspended in 20 µL phosphate-buffered saline were mixed with 200 µL Matrigel (BD Biosciences, San Jose, Calif) and injected in both flanks of eight nude mice. One of the Matrigel (BD Biosciences) injections contained 50 000 cells pretransfected in vitro by using lipofectamine as a positive control. Nine flanks were exposed to 2.25-MHz ultrasonic pulses at 50% duty cycle for 1 minute at 1 W/cm(2) (n = 3) or 2 W/cm(2) (n = 6), and six flanks served as the negative control. Two days later, bioluminescent images were acquired in each mouse every 3 minutes for 1 hour after the intraperitoneal injection of d-luciferin (Perkin Elmer, Waltham, Mass). Differences between groups were assessed by using the nonparametric Kruskal-Wallis test with Wilcoxon rank sum tests for follow-up comparisons. Mice were then killed, plugs were explanted, and alternate sections were stained with hematoxylin-eosin or stained for GFP expression. RESULTS: Mean DNA-loaded MB diameter ± standard deviation was 2.87 µm ± 1.69 with the DNA associated with the MB shell. C17.2 cells were associated with 2-4 MBs each, and more than 90% were viable. Peak background subtracted bioluminescent signal was fourfold higher when cells were exposed to 2 W/cm(2) pulses as compared with 1 W/cm(2) pulses (P = .02) and negative controls (P = .002). Histologic examination showed cells within the Matrigel (BD Biosciences) with robust GFP expression only after 2 W/cm(2) ultrasound exposure and lipofectamine transfection. CONCLUSION: Stem cells loaded with DNA-carrying MBs can be transfected in vivo with ultrasonic pulses and remain alive to demonstrate robust gene expression.


Subject(s)
DNA/administration & dosage , Gene Expression , Microbubbles , Stem Cells , Transfection/instrumentation , Transfection/methods , Animals , Cells, Cultured , Mice , Mice, Nude
20.
Biomaterials ; 34(21): 4926-35, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23578557

ABSTRACT

Tracking neuroprogenitor cells (NPCs) that are used to target tumors, infarction or inflammation, is paramount for cell-based therapy. We employed ultrasound imaging that can detect a single microbubble because it can distinguish its unique signal from those of surrounding tissues. NPCs efficiently internalized positively charged microbubbles allowing a clinical ultrasound system to detect a single cell at 7 MHz. When injected intravenously, labeled NPCs traversed the lungs to be imaged in the left ventricle and the liver where they accumulated. Internalized microbubbles were not only less sensitive to destruction by ultrasound, but remained visible in vivo for days as compared to minutes when given free. The extended longevity provides ample time to allow cells to reach their intended target. We were also able to transfect NPCs in vitro when microbubbles were preloaded with GFP plasmid only when cells were insonated. Transfection efficiency and cell viability were both greater than 90%.


Subject(s)
Contrast Media , Diagnostic Imaging/methods , Microbubbles , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Staining and Labeling , Ultrasonics/methods , Animals , Bromodeoxyuridine/metabolism , DNA , Fluorescent Antibody Technique , Limit of Detection , Liver/pathology , Mice , Mice, Nude , Optical Phenomena , Transfection
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