S34 Ultrasound in Medicine and Biology Volume 35, Number 8S, 2009

exposure protocols were determined. The effects of sonication andUTMD parameters on three different DNA plasmids (DsRed, pEGFP-C1, and pVEGF) were investigated.Results: A series of experiments indicated that cell viability main-tained at the near normal level (�80%) when the ultrasound inten-sity of 0.4 W/cm2 or 1.0 W/cm2 and low duty cycle (10% or 20%).Under an appropriate condition, transfection efficiency could beenhanced with limited cell toxicity. pCMV-LUC reporter gene hadsimilar results as DsRed plasmid. The result of agarose gel electro-phoresis showed that the structural integrity of different plasmidDNA were unaffected by the optimal sonication conditions em-ployed.Conclusions: The best conditions of UTMD parameters in this studycould increase transfection in the absence of significant cell death andDNA damage. This novel, noninvasive transgenic technology repre-sents a useful, non-viral tool for gene transduction.

0280

Ultrasound Exposure Enhances Gene Delivery with PLGA-BasedNanoparticlesHai Zhang, The First Metropolitan Hospital and The AffiliatedHospital of Jinan University School of Medicine, Shenzhen,Guangdong 528001, ChinaJianxi Tang, The University of Kansas Medical Center, Kansas City,Kansas 66106, USA, United StatesYing Li, The First Metropolitan Hospital and The Affiliated Hospitalof Jinan University School of Medicine, Shenzhen, Guangdong528001, ChinaYong Dai, The First Metropolitan Hospital and The AffiliatedHospital of Jinan University School of Medicine, Shenzhen,Guangdong 528001, ChinaLi Sheng Wang, The First Metropolitan Hospital and The AffiliatedHospital of Jinan University School of Medicine, Shenzhen,Guangdong 528001, ChinaBen Yi Li, The University of Kansas Medical Center, Kansas City,Kansas 66106, USA, United States

Purpose: Although PLGA polymers are biodegradable, The effect ofultrasound exposure and enhance release naked DNA with PLGA-based nanoparticles on gene expression inside cells will be tested.Methods: PLGA polymers were used to fabricate nanoparticles. Mean-while, red fluorescent dye or green fluorescent protein (GFP)-express-ing plasmid vectors were encapsulated into the nanoparticle. Humanprostate cancer cel line C4-2 were used for testing in cell culture andnude mouse xenograft models.Results: In test tubes, applying ultrasound field to the nanoshell-containing solution resulted in destruction of more than 85% PLGAnanoshells (180-220 nm in diameter), as evidenced by an increase ofDNA contents in the supernatant of nanoparticle solution. In a cellculture model, without ultrasound exposure, GFP expression appearedon day 5 after addition of the nanoshells into cultured human prostatecancer C4-2 cells. In contrast, applying ultrasound exposure led to earlyexpression of GFP protein on day 3 after addition of nanoshells intocultured cells. Consistantly, in a mouse xenograft model with the cells,ultrasound exposure also dramatically enhanced GFP expression, asevidenced by GFP appearence in 3-5 days comparing to the control onday 7 after intratumoral injection of the GFP vector-encapsulatednanoparticles.Conclusion: Our data confirmed our hypothesized that acoustic wavesdestroy PLGA polymer nanoshells and subsequently promote encap-sulated reagents from the nanoparticles. These results suggest thatcombining the use of nanoparticles with acoustic power provides

additional benefits in gene delivery from nanocarriers, which has tre-

mendous potential for targeted anti-cancer therapy by fairly non-inva-sive means.

0281

Sonography of the ThyroidAlan Daneman, Toronto Children’s Hospital, Canada

In pediatrics the thyroid can be easily depicted with sonography at allages including neonates. We have found incidental abnormalities of thethyroid in 18% of children having sonography of the neck for nonthyroid related reasons. Almost 70% of these abnormalities are cystsmeasuring under 1 cm in size and in many they are multiple. Thesecond commonest incidental abnormality has been the unexpectedfinding of hypoechoic nodules, often with a stippled echogenicity,similar to thymus and which represent intrathyroid ectopic thymus. Ininfants with hypothyroidism thyroid sonography is valuable to deter-mine the presence or abscence of the thyroid gland and to determinewhether it is ectopic in position. In older children thyroid sonographyis important to characterize palpable nodules - cysts are invariablebenign but it may be difficult to differentiate benign from malignantlesions in many complex and echogenic lesions. Fine calcification ischaracteristic of papillary carcinoma. Thyroid sonography is invaluableto differentiate single (palpable) from multiple nodules and to diffreen-tiate multinodular glands from those with diffuse disease. Multinodularcystic changes in the thyroid are characteristicly seen in children withMcCune-Albright syndrome.

0282

Ultrasound of the SpineIn-One Kim, Seoul National University Hospital, Korea

US is useful in the imaging of the spine, although MRI is the modalityof choice, especially in young infants because posterior neural arch isincompletely ossified and US can image the spinal canal and itscontents. Spinal dysraphism or postoperative neural arch defect alsoprovides acoustic window to visualize the internal structures. Highfrequency linear array transducers are usually preferred and scanning isperformed in prone position creating a kyphotic curvature to facilitatethe acoustic window. Images are obtained in transverse and sagittalplanes. Spinal cord shows as a relatively hypoechoic tubular structurewith central echogenic linear structure. The cord gradually tapers toform a conus medullaris at the level between T12 and L1 or L2.Echogenic cauda equina surround the filum terminale that penetratesdural sac at the level of S1-2. Abnormally thickened or echogenic filumterminale can be visualized in case of tight filum terminale or thickenedfatty filum with cord tethering. US shows abnormal low position of thespinal cord in spinal dysraphism. Lipomatous tissue connecting thesubcutaneous tissue and spinal cord is seen as an echogenic massextending through the dysraphic spinal canal in lipomyelomeningocele.Hydromyelia is readily visible. Dorsal dermal sinus is visualized as ahyper-or hypoechoic tract extending from the skin surface. A low levelof conus medullaris indicates tethered cord with dermal sinus extendingto the spinal canal or spinal cord. Sacrococcygeal teratoma, frequentlybenign cystic mass in the neonate, can be diagnosed with US showingthe internal architecture and extent of the mass. Other developmentalanomalies of the spinal cord will be discussed.

0283

3D and 4D in Contrast Enhanced UltrasoundMichel Claudon, Service de Radiologie, France

Contrast-enhanced ultrasound appears now as a well-assessed tech-nique for the real-time evaluation of macro-and microvasculature of

many organs, mainly including the liver, the kidney, the pancreas, the

Abstracts S35

spleen and the heart. 3D acquisitions are usually performed by me-chanical probe with a sector ranging from approximately 10 to 70degrees, which allow appropriately covering of most organs. Compa-nies now introduce specific contrast-modes on these probes, allowingevaluating a portion of or the whole organ vasculature at successivephases of enhancement. 4D acquisitions can be obtained by the repe-tition of 3D acquisitions, or directly by using matrix probes which workwithout any motion of elements and allow higher frame rates but withlower spatial resolution at the time. Post-treatment is an essential, oftentime-consuming phase to allow reconstruction in any plane, includingthose which could not be obtained from 2D modes. Quantitative studiesinclude enhancement profiles analysis based on time-intensity curvesand calculation of volume of focal lesions or any portion of an organ.Potential clinical applications include most of the indications that havealready been developed with 2D imaging as a complement or poten-tially in the future as the contrast-enhanced ultrasound mode. Examplesof lesions of the liver, kidney, spleen and pancreas will be shown toillustrate the potential of these techniques.

0284

Congenital Intrahepatic Portosystemic Venous Shunt BetweenPortal Vein and Hepatic Vein: Perinatal UltrasonographicDetection and Follow-upByoung Hee Han, Department of Radiology, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaMi Jin Song, Department of Radiology, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaMin Hwan Moon, Department of Radiology, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaYoung-Ho Lee, Department of Radiology, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaJee Yeon Min, Department of Pediatrics, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaKyung Ah Kim, Department of Pediatrics, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, KoreaYeon Kyung Lee, Department of Pediatrics, Kwandong UniversityCollege of Medicine, Cheil General Hospital & Women’s HealthcareCenter, Korea

Objective: To show variable fetal and neonatal ultrasonographic find-ings of IPVS and the results of follow-up.Methods: We detected and followed up 6 congenital IPVS by fetal andneonatal US.Results: On fetal US, IPVS were detected in 2. There were abnormalintrahepatic tubular structure in 1, prominent hepatic vein in 1 and con-gestive heart failure(CHF) in 1. Other findings were intrauterine growthretardation(IUGR) in 4, echogenic bowel in 2, placentomegally in 2, smallamniotic fluid in 1, single umbilical artery in 1 and persistent rightumbilical vein in 1. Neonatal US showed abnormal communication of abranch of Lt. portal vein with a hepatic vein in 5 and communication oftwo branches of Lt. portal vein with two hepatic veins in 1 There wascoincidental shunt between hepatic artery and portal vein in 1. Four of thesix congenital IPVS were spontaneously closed on follow-up US (2-11months), one of them was treated with coil embolization during neonatalperiod, and the last one is not closed until now.Conclusions: US demonstrated congenital IPVS in just two fetuses.However, we suggest that if the secondary findings such as abnormal

tubular structure, prominent hepatic vein, and CHF are detected, IPVS

should be suspected. IUGR is nonspecific but the most common asso-ciated finding. Neonatal US is useful for the confirmation, detection ofprenatally undetected congenital IPVS, and classification. Clinical ob-servation and follow-up with US until closure are the first choice formanagement of congenital IPVS.

0286

Live Scanning Workshop: Basic Fetal HeartJo Lennox, Ultrasound Care

Congenital heart disease is a major cause of perinatal morbidity andmortality. Antenatal diagnosis of CHD facilitates specialist prenatalcare and optimizes post natal management. The fetal heart is recog-nized as one of the most difficult areas of a fetus to image.Good quality cardiac assessment is a vital part of the screening obstetricultrasound at 19 weeks gestation. It requires a sound knowledge of normalfetal cardiac anatomy and congenital heart abnormalities. Familiarity withand reproduction of standard imaging techniques dramatically increasesthe ability of the sonographer to detect the abnormal fetal heart.In this session, we will discuss:� The normal fetal cardiac anatomy� The fetal circulation� The basic views required to complete a fetal cardiac screeningexamination� The importance of fetal position� Normal fetal heart rates and rhythms� Examples of fetal cardiac abnormalities.This will be followed by hands on scanning session and question time.

0290

Plenary Presentation: Molecular Imaging and Assessment ofAngiogenesis with Contrast UltrasoundJonathan R Lindner, Oregon Health & Science University, UnitedStates

Contrast-enhanced ultrasound (CEU) relies on the acoustic detection ofmicrobubble or gas-containing nano-scale contrast agents. It is possibleto target ultrasound microbubble contrast agents to disease-relatedcellular and molecular processes that are amenable to pure-intravascu-lar tracers. Targeting relies on conjugating specific ligands to thesurface of the microbubbles. This talk will focus on some of the recentadvances in molecular imaging with targeted ultrasound contrast agentsin angiogenesis and how they can be paired with perfusion and vascularanatomic information available on CEU.A popular strategy for molecular imaging of adaptive or pathologic an-giogenesis has been to target endothelial integrins that participate invasculogenesis or remodeling. Molecular imaging probes have been tar-geted to matrix-binding integrins that signal endothelial cell migration,proliferation and survival such as av- and a5-integrins. These agents havebeen used to examine temporal development of tumor angiogenesis, andendogenous and therapeutic angiogenesis in models of chronic limb isch-emia. CEU molecular imaging has also been able to detect key growthfactor receptors, such as VEGFR-2, that play a key role in tumor andischemia-mediated vascular remodeling. The immune response plays acritical role in angiogenesis and arteriogenesis, in part by providing asource for pro-angiogenic growth factors, cytokines, and proteases. Tar-geted contrast ultrasound imaging of monocyte recruitment and endothe-lial cell adhesion molecule expression has recently been shown to heraldvasculogenesis and vascular remodeling in limb ischemia prior to anysignificant flow recovery. This strategy also has been used to detectimmune response dysfunction associated with impaired arteriogenesis,

such as in diabetes mellitus.