-
[show abstract]
[hide abstract]
ABSTRACT: Barium sulfate powder used for radiopacity of experimental blood clots (EBCs) for testing mechanical thrombectomy devices (MTD) has negative effects on EBCs mechanical properties. and exploration was performed to determine if the iodine based contrast medium will have less negative effects on the EBCs than barium.
Fresh blood from 2 swine was used to create fibrinogen enhanced and thrombin initiated EBC in tubes. Iodine radiopacity was achieved by mixing the blood with 65% Iohexol or by soaking the EBCs for 2 or 24 hours in Iohexol. The EBCs opacified with barium served as controls study: The EBCs were subjected to four tests, manual elongation, catheter injection, radiopacity and contrast wash out tests. study: The common carotid arteries of 2 swine were embolized by either barium EBC or EBC soaked for 24 hours in Iohexol. The duration of radiopacity of the different EBCs was compared.
The EBCs opacified with Iohexol initially had higher radiopacity than the barium opacified EBCs. However, their opacity rapidly decreased with saline soaking and, particularly, after they were embolized in live animals. The mechanical properties of Iohexol opacified EBCs were inferior to barium opacified EBCs. The Iohexol mixed EBCs were less firm and elastic and half of them fragmented during catheter injection. The Iohexol soaked EBCs exhibited decreased tensile strength and elasticity compared to the barium EBCs.
Compared to barium, iodine based contrast medium does not offer any advantage for opacifying EBCs.
Radiology and Oncology 03/2013; 47(1):14-8. · 0.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore if addition of fibrinogen to the most commonly used experimental blood clot (EBC) model would improve its mechanical properties and histologic structure.
Fresh blood from three swine was used to create four EBC types. The Gralla model of thrombin-induced barium-opaque EBC served as the control. In three other EBC types, 50 mg, 100 mg, and 200 mg of bovine fibrinogen were added. Evaluation of EBCs was done with three tests: manual elongation, injection through an 8-F catheter, and an opacity test. Thirty EBCs of each type were evaluated with each test. Histologic evaluation followed.
The control EBCs had low tensile strength and broke at 165% elongation. However, they were elastic and returned to their original length after catheter injection. The EBCs with fibrinogen exhibited increased tensile strength with increasing fibrinogen doses and withstood elongation to 213% (P < .01). Their elasticity decreased with increased tensile strength, and they remained elongated after catheter injection (P < .01 for EBC with 100 mg and 200 mg fibrinogen). Histologic examination showed more thorough mixing of blood with barium and a significantly increased amount of fibrin after addition of fibrinogen.
Addition of fibrinogen to a Gralla EBC model changes its mechanical properties proportionately to the fibrinogen dose. Fibrinogen increases EBC tensile strength but decreases its elasticity. Fibrinogen also significantly increases the binding of blood cells with fibrin on histologic slides.
Journal of vascular and interventional radiology: JVIR 06/2012; 23(8):1077-83. · 1.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the long-term effectiveness and safety of a new Double BioDisk (DBD) device for closure of atrial septal defect (ASD). MATERIALS AND METHODS.: ASD was created with transeptal needle (TS) followed by balloon dilatation in 12 sheep weighing 40.1 to 64 kg (mean 55.2 ± 7.1). The ASD diameters were measured after creation and two weeks later before DBD implantation. The DBDs consists of two nitinol rings 18 to 28 mm in diameter connected with small cannulas and covered with a porcine small intestinal submucosa (SIS). They were implanted via a 10 Fr sheath. DBD effectiveness was evaluated by angiocardiography and by intra-cardiac echogram (ICE) with Doppler studies. Two animals were acute, two were followed for 6 weeks, three for 3 months, three for 6 months and two for 12 months.
TS punctures were successful in 10 sheep. In two sheep ASD was created by existing PFO dilation. The ASD size ranged from 13-15 mm (mean 14.1± 0.73 mm) after initial balloon dilation and from 9-13 mm (mean 10.06 ± 1.37 mm) after two weeks. In all animals none of the successfully implanted DBDs spontaneously embolized on release or on follow up. ICE demonstrated no shunting around the DBDs during follows ups. Macroscopic and histologic evaluation of the 6, 12, 24 and 52 weeks animals showed that DBDs were well incorporated in the atrial septum with complete shunt closure. The SIS showed progressive remodeling with the host cells, including endothelization of the DBD devices.
ASD closure with the Double BioDisk is safe and effective in adult sheep.
Radiology and Oncology 06/2012; 46(2):89-96. · 0.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the feasibility of one-step implantation of a new type of stent-based mechanical aortic disc valve prosthesis (MADVP) above and across the native aortic valve and its short-term function in swine with both functional and dysfunctional native valves.
The MADVP consisted of a folding disc valve made of silicone elastomer attached to either a nitinol Z-stent (Z model) or a nitinol cross-braided stent (SX model). Implantation of 10 MADVPs (6 Z and 4 SX models) was attempted in 10 swine: 4 (2 Z and 2 SX models) with a functional native valve and 6 (4 Z and 2 SX models) with aortic regurgitation induced either by intentional valve injury or by MADVP placement across the native valve. MADVP function was observed for up to 3 hr after implantation.
MADVP implantation was successful in 9 swine. One animal died of induced massive regurgitation prior to implantation. Four MADVPs implanted above functioning native valves exhibited good function. In 5 swine with regurgitation, MADVP implantation corrected the induced native valve dysfunction and the device's continuous good function was observed in 4 animals. One MADVP (SX model) placed across native valve gradually migrated into the left ventricle.
The tested MADVP can be implanted above and across the native valve in a one-step procedure and can replace the function of the regurgitating native valve. Further technical development and testing are warranted, preferably with a manufactured MADVP.
CardioVascular and Interventional Radiology 04/2012; 29(1):114-9. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To introduce a new transseptal (TS) needle assembled in our laboratory--the coaxial TS (CTS) needle--and describe our experience with it in creating experimental atrial septal defects (ASD) in adult sheep.
With commercially available TS needles, we were not able to consistently perform TS puncture at the fossa ovalis in adult sheep.
Ten adult sheep with a mean weight of 63.5 kg were used. The CTS needle consists of four components: a 9F Teflon catheter, a 14-gauge blunt curved-tip metal cannula, a 4F tapered catheter, and a 20-gauge open needle. A transjugular 5F pigtail catheter was used to display the septal anatomy by angiocardiography and was left in place to mark the level of the fossa ovalis. The septum was then probed by a transfemoral 5F curved-tip end-hole catheter. The CTS needle was aligned with the tip of the transjugular catheter, and the TS puncture was performed under fluoroscopic guidance. After documenting a left atrial position, a balloon angioplasty catheter was used for creation of the ASD.
A small patent foramen ovale was discovered by septal probing in one sheep. All sheep underwent successful TS punctures without complications. The ASD size ranged from 13 to 15 mm. In eight sheep, the ASD was in fossa ovalis. In the first two sheep where the needle was not well aligned with the marking catheter, the ASD was in the septum secundum. No damage to the atrial or other heart structures was found at necropsy.
The CTS needle is a suitable needle for TS puncture and ASD creation in adult sheep. Proper alignment of the CTS needle with a catheter marking the fossa ovalis is essential for successful puncture.
CardioVascular and Interventional Radiology 06/2011; 34(3):620-5. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate feasibility of a twin valve caval stent (TVCS) for functional replacement of an incompetent tricuspid valve (TV) in an acute animal study.
One swine and three sheep were used in the study. TVCS placement was tested in a swine with a normal TV. TVCS function was tested in three sheep with TV regurgitation created by papillary muscle avulsion. Cardiac angiograms and pressure measurements were used to evaluate TVCS function. Two sheep were studied after fluid overload.
TVCS was percutaneously placed properly at the central portions of the superior vena cava (SVC) and inferior vena cava (IVC) in the swine. Papillary muscle avulsion in three sheep caused significant tricuspid regurgitation with massive reflux into the right atrium (RA) and partial reflux into the SVC and IVC. TVCS placement eliminated reflux into the SVC and IVC. After fluid overload, there was enlargement of the right ventricle and RA and significant increase in right ventricle, RA, SVC, and IVC pressures, but no reflux into the IVC and SVC.
The results of this feasibility study justify detailed evaluation of TVCS insertion for functional chronic replacement of incompetent TV.
CardioVascular and Interventional Radiology 02/2011; 34(1):174-9. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Swine are commonly used as a model to study congenital cardiovascular defects that occur in humans and these models have been both spontaneous and experimentally induced. Ventricular septal defect, patent ductus arteriosus, and atrial septal defect (ASD) are examples of experimentally induced models. Absence of caudal/inferior vena cava (CVC/IVC) with azygos/hemiazygos continuation is an uncommon vascular anomaly.
The vascular anomaly presented in this case report was an incidental finding on a pig that was evaluated for experimental percutaneous atrial septal defect creation and its closure using a percutaneous femoral vein approach. Absence of CVC/IVC was confirmed by venography and necropsy.
To the best of the investigators knowledge, this is the first report of absence of CVC/IVC with azygos/hemiazygos continuation in the swine.
Radiology and Oncology 09/2010; 44(3):149-52. · 0.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Most of the presently used percutaneous arterial closure devices (PACD) for hemostasis after interventional vascular procedures are effective, but carry risk of complications by deposition of a foreign body. A new promising externally applied PACD - chitosan-based HemCon Bandage (HCB) was explored in sheep. The HCB hemostatic efficacy and complications occurring with its use were compared to those with the standard manual compression (SMC).
Both superficial femoral arteries (SFA) of 9 heparinized sheep were catheterized with an 8F sheath for 5 minutes. After the sheath withdrawal, hemostasis with the HCB was compared with hemostasis achieved with SMC in the contralateral SFA. Iliac angiograms performed by carotid artery approach determined the hemostasis time.
The HCB use shortened time to hemostasis with a mean time of 6.9 ± 3.9 minutes versus 10.8 ± 2.8 minutes for the SMC (P-value 0.019). Seven SFAs in the HCB group and only 1 SFA in the SMC group exhibited hemostasis in 5 minutes. All nine SFAs using the HCB showed femoral artery patency and demonstrated less hematoma (2/9) than in the SMC group (8/9). No complications developed in the HCB group, one SFA occlusion was seen in the SMC group.
The externally applied HCB in heparinized sheep was safe and effective. It significantly shortened time to hemostasis at the SFA access sites following 8F sheath removal. Proper application of the HCB was necessary to shorten hemostasis and prevent hematoma formation. The HCB should be tested in a clinically controlled study to evaluate its efficacy in humans.
Radiology and Oncology 06/2010; 44(2):86-91. · 0.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to evaluate efficacy of a plug made of small intestinal submucosa (SIS) for closure of dilated nephrostomy tract in the kidney after nephroscopy. Ten kidneys in 5 swine had nephrostomy tracts dilated up to 8 mm. The SIS plug was placed into the dilated renal cortex under nephroscopic control. Follow-up arteriograms, retrograde pyelograms, and macroscopic and histologic studies at 24 h (n = 4), 6 weeks (n = 2), and 3 months (n = 4) were performed to evaluate the efficacy of the plug. The SIS plug effectively closed the dilated nephrostomy tract. Follow-up studies showed minimal changes of the kidneys, except for 1 small infarction, regarding inflammatory and foreign-body reactions and progressive scarring of the SIS. SIS plug is effective for occlusion of dilated nephrostomy tract after nephroscopy. Its efficacy should be compared with other therapeutic options.
CardioVascular and Interventional Radiology 06/2010; 33(3):596-600. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the feasibility, effectiveness, and safety of a porcine small intestinal submucosa (SIS)-covered Biodisk (BD) for the closure of patent foramen ovale (PFO) in swine.
Twelve piglets (9-30 kg) with PFO ranging in size from 6 to 12 mm were used for the in vivo testing. The BD device consisted of two basic nitinol wire components covered with platinum coil, a flexible SIS-covered ring, and an anchor. The BD was advanced through an 8-Fr sheath from the femoral vein. Nine acute animals were used to test the BD for deployment, stability, immediate shunt closure, and device repositioning before or after its detachment. To assess retrievability, four devices were deployed and intentionally embolized into the RA (n = 2) and LA (n = 2). The effectiveness of the device was evaluated by angiocardiography. EKG was recorded before and after PFO closure for 3 hr. From the 12 animals, nine were acute and three were followed; one for 6 weeks, one for 12 weeks, and one for 16 weeks.
Successful device implantation was achieved in all animals with no shunting of contrast media observed during follow-up in. One animal needed to have device repositioned for complete PFO occlusion because of suboptimal placement at the first attempt. The device was easily placed and retrieved before detachment in all nine animals in the acute study. None of the BDs spontaneously embolized during release or on follow-up. EKG did not demonstrate arrhythmias during or after treatment. Four intentionally embolized BDs were easily retrieved with an Amplatz goose neck snare. Macroscopic and histologic evaluation of the three long-term animals showed that devices were well incorporated in the atrial septum with complete shunt closure. The SIS showed progressive remodeling with the host cells. There was also progressive endothelization of the BD device.
The BD device deployment is feasible, safe, and effective. Long-term studies are needed to evaluate its long-term effectiveness.
Catheterization and Cardiovascular Interventions 05/2010; 75(6):861-7. · 2.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Disclosure: No potential conflicts of interest were disclosed. Background. Swine are commonly used as a model to study congenital cardiovascular defects that occur in hu-mans and these models have been both spontaneous and experimentally induced. Ventricular septal defect, patent ductus arteriosus, and atrial septal defect (ASD) are examples of experimentally induced models. Absence of caudal/ inferior vena cava (CVC/IVC) with azygos/hemiazygos continuation is an uncommon vascular anomaly. Case report. The vascular anomaly presented in this case report was an incidental finding on a pig that was evalu-ated for experimental percutaneous atrial septal defect creation and its closure using a percutaneous femoral vein approach. Absence of CVC/IVC was confirmed by venography and necropsy. Conclusions. To the best of the investigators knowledge, this is the first report of absence of CVC/IVC with azygos/ hemiazygos continuation in the swine.
Radiol Oncol. 01/2010; 44:149-152.
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled period of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.
CardioVascular and Interventional Radiology 10/2009; 33(2):330-5. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to evaluate the angiographic and histopathologic changes in the superficial femoral artery (SFA) in heparinized sheep shortly after catheterization with an 8-Fr sheath and manual compression hemostasis either with standard manual compression (SMC) or with the use of a procoagulant chitosan-based HemCon Bandage. The evaluation was done in 38 SFAs of 19 heparinized (100 mg/kg) sheep. After a 5-min catheterization with an 8-Fr sheath, a 5-min compression was applied. Follow-up angiograms to evaluate hemostasis were done immediately after release of compression and then at 2.5-min intervals until no extravasation was present. Compression was reapplied between angiograms. Final angiograms were performed approximately 30 min after hemostasis and after 3 min of passive flexion and extension of sheep hind limbs. Sheep were then euthanized and SFA specimens with surrounding tissues excised for histopathologic evaluation. Both types of compression caused similar changes in the catheterized SFAs. Follow-up angiograms showed mild arterial narrowing in 14 SFAs and intraluminal clots in 9 SFAs. Histology revealed periarterial hematoma in all 38 specimens. Intraluminal thrombi consisting predominantly of platelets and fibrin were present in 32 SFAs. Their size varied from superficial elevations (8 arteries) to medium-sized, 1- to 2-mm, polypoid protrusions (15 arteries) to large polypoid clots, 3-4 mm long (9 arteries). In six SFAs, the arterial access sites were not included in the obtained specimens. In conclusion, hemostasis with manual compression is achieved in the acute phase by formation of a predominantly platelet-fibrin thrombus occluding the arterial wall access site and often extending significantly into the arterial lumen. The healing process of arterial access sites should be explored several days after catheterization.
CardioVascular and Interventional Radiology 09/2009; 33(2):321-9. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to report the longitudinal angiographic evaluation of prefabricated lyophilized small-intestinal submucosa (SIS) grafts placed in ovine carotid arteries and to demonstrate a variety of complications that developed. A total of 24 grafts, 10 cm long and 6 mm in diameter, were placed surgically as interposition grafts. Graft patency at 1 week was evaluated by Doppler ultrasound, and angiography was used for follow-up at 1 month and at 3 to 4 months. A 90% patency rate was found at 1 week, 65% at 1 month, and 30% at 3 to 4 months. On the patent grafts, angiography demonstrated a variety of changes, such as anastomotic stenoses, graft diffuse dilations and dissections, and aneurysm formation. These findings have not been previously demonstrated angiographically by other investigators reporting results with small-diameter vessel grafts made from fresh small-intestinal submucosa (SIS). The complications found were partially related to the graft construction from four SIS layers. Detailed longitudinal angiographic study should become an essential part of any future evaluation of small-vessel SIS grafting.
CardioVascular and Interventional Radiology 11/2008; 32(1):106-13. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An optional inferior vena cava (IVC) filter prototype was evaluated for safety and long-term retrievability as an initial feasibility study in an animal model. This filter has four centering struts that have the ability to disengage from the filtering cone portion, allowing the legs to slide out of endothelial growth. Retrieval of six filters in three animals was successful up to 27 weeks. There was no substantial filter tilt, migration, or IVC damage. In conclusion, this filter design may help overcome some of the shortcomings in currently approved optional IVC filters, including long-term retrieval difficulties, tilting, or migration.
Journal of vascular and interventional radiology: JVIR 11/2008; 19(12):1772-6. · 1.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The ovine superficial femoral artery was used for testing the efficacy of percutaneous arterial closure devices (PACDs) in their developmental stage. Two topical devices containing chitostan, one staple-mediated PACD and a porcine small intestinal submucosa plug, were tested by follow-up angiography in 37 sheep. Absence or presence of bleeding and time to bleeding cessation were the main criteria for evaluation of PAVD efficacy. The results of these tests directed modification of individual PACDs and improved their efficacy.
CardioVascular and Interventional Radiology 10/2008; 32(2):313-6. · 2.09 Impact Factor
-
Journal of Vascular and Interventional Radiology 08/2008; 19(7):1123-4. · 2.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lower extremity chronic deep venous insufficiency (CDVI) is common and remains a major health problem worldwide. Selected patients benefited from direct deep vein valve surgical repair or valve transplantation. A major limitation of this approach is that most of the patients are not candidates for these procedures due to obstructions or residual thrombus throughout the vein. The past 15 years have witnessed experimental efforts at catheter-based management of CDVI. This review describes the initial designs and experimental evolution of a mechanical and bioprosthetic venous valve that can be implanted by using a transcatheter technique. These valves consisted of single, double, or triple cusp leaflets made of synthetic or biological materials attached to a carrier or frame. All described devices for percutaneous transcatheter valve placement rely on some form of a vascular stent for valve attachment.
Vascular Medicine 03/2008; 13(1):75-84. · 1.46 Impact Factor
-
Hanno Hoppe,
Won-Kyu Park,
Luiz O Correa,
Wie Lu,
Long Liu,
Hans A Timmermanns, Dusan Pavcnik,
Barry T Uchida,
Howard K Song,
Josef Rösch,
John A Kaufman
[show abstract]
[hide abstract]
ABSTRACT: This study was conducted to create an animal model for thoracic aortic transection that is suitable for thoracic endograft research.
Percutaneous aortic transection creation was attempted in 12 sheep. A custom collapsible circumferential cutting device was inserted into the proximal descending thoracic aorta via a femoral approach with an 11-F delivery catheter. The device was deployed 2 cm distal to the left subclavian artery origin and rotated 20 times to create aortic transection. Aortic diameters, mean aortic pressures, and heart rates were tested for degrees of difference between measurements before and after the creation of transection. On necropsy, the extent of aortic damage was classified as none, nontransmural, or transmural, and aortic transection was classified as none, partial, or circumferential.
On angiography, creation of transmural thoracic aortic transection was successful in 91.7% (11/12) of animals. Aortic transection was circumferential in 54.4% (6/11) of animals and partial in 45.6% (5/11) of animals. Mean aortic diameter was 19.6 +/- 3.4 mm (range 12-24 mm) pre-transection and 25.8 +/- 4.5 mm (range 17.8-33 mm) post-transection (P = .0003). Pre-transection, mean aortic pressure was 79 +/- 13.8 mmHg, and 64.6 +/- 15.8 mmHg 15 min post-transection (P = .041). Pre-transection, mean heart rate was 94.5 +/- 17.2 beats per minute (bpm), and 105.8 +/- 17.2 bpm 15 min post-transection (P = .0057).
Thoracic aortic transection was successfully created percutaneously in most animals. The animals remained in hemodynamically stable condition for as long as 240 minutes after the creation of aortic injury. This percutaneous animal model is straightforward and may be of potential value for future thoracic endograft research.
Journal of Vascular and Interventional Radiology 02/2008; 19(1):105-10. · 2.08 Impact Factor
-
Won Kyu Park, Dusan Pavcnik,
Brad Shirley,
Wei Lu,
Barry T Uchida,
Qiang Yin,
Hanno Hoppe,
Man Kim Duck,
Long Liu,
Frederick S Keller,
Josef Rösch
[show abstract]
[hide abstract]
ABSTRACT: To compare two techniques used to create a larger animal model of venous valve incompetence.
To achieve vein dilatation as the primary cause of valve incompetence, common carotid jugular vein (JV) fistulas were created and optional filters were placed into the JV of sheep. Altogether, nine inferior vena cava filters were placed in three sheep in two stages. Six filters were placed caudal to the most caudal JV valve in three sheep and removed 6 weeks later. Then, three filters were placed across the most caudal valve in two sheep with competent valves and removed 3 weeks later. A common carotid artery-JV fistula was created in three sheep and followed-up for 1-3 weeks. Ascending and descending venograms were obtained to determine the JV sizes and function of their valves. The JVs removed at necropsy were studied with venoscopy.
Only one of the six JVs with filters caudal to the most caudal valve had incompetent valves after filter removal at 6 weeks. In addition, only one of three JVs with the filter across the valve had incompetent valves after filter removal at 3 weeks. At 1-3-week follow-up of the group with common carotid artery-JV fistula, all three JVs had incompetent valves in the cephalad vein portion, but only one JV had an incompetent valve in its caudal portion. At venoscopy, the incompetent valves showed various degrees of damage ranging from shortening to the destruction of valve leaflets.
Dilation of the valve annulus with a removable vena cava filter failed to produce valve incompetence. The promising results with the common carotid artery-JV fistula justify further detailed research.
Journal of Vascular and Interventional Radiology 10/2007; 18(9):1169-75. · 2.08 Impact Factor
