Ultrasound in Medicine and Biology - Articles in Press

Sonodynamically induced apoptosis by Protoporphyrin IX on Hepatoma-22 cells in vitro - Corrected Proof

2010-03-08

Abstract: The synergistic effect of ultrasound and certain chemicals on cells is known as sonodynamic therapy (SDT). It has been reported that the direct sonochemical and subsequent redox reactions induced by SDT treatment can lead to apoptotic cell death. However, the detailed biologic mechanism about it is not well understood until now. In this study the effect of low-intensity ultrasound on Hepatoma-22 cells (H22) in the presence of the sonosensitizing drug protoporphyrin IX (PpIX) was evaluated at different incubation times after sonication. Trypan blue exclusion was used to detect cell viability. The presence of apoptotic cells was identified by 4'-6-diamidino-2-phenylindole (DAPI) nuclear staining and transmission electric microscope (TEM) observation. An inverted confocal laser scanning microscope was used to detect the release of mitochondrial protein cytochrome c (Cyt c) and the redistribution of Bcl-2 family proteins Bid and Bax. Additionally, the generation of intracellular reactive oxygen species (ROS) and the loss of mitochondria membrane potential (MMP) were quantificationally measured by a fluorescence microplate reader. The results indicated that the synergistic cytotoxicity of PpIX and ultrasound increased in a time-dependent manner and the mitochondria damage may be the main factor for sonodynamically induced apoptosis by PpIX in H22 cells. (E-mail: lshaof@snnu.edu.cn)

Detection of MPTP-Induced Substantia Nigra Hyperechogenicity in Rhesus Monkeys by Transcranial Ultrasound - Corrected Proof

Thyagarajan Subramanian, Christopher A. Lieu, Kumaraswamy Guttalu, Daniela Berg — 2010-03-08

Abstract: Detection of substantia nigra (SN) hyperechogenicity by transcranial ultrasound has been proposed as a putative biomarker to differentiate between idiopathic Parkinson's disease (PD) and other forms of parkinsonism. In the present study, we evaluated the feasibility of using transcranial ultrasound to detect SN echogenicity in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated Rhesus monkeys, a well-established model of PD. All animals had natural temporal bone windows for transcranial sonography. We could show that it is possible to visualize major brain landmarks including the “butterfly shaped” midbrain, basal cisterns, third and lateral ventricles in all animals by transcranial ultrasound. Blinded assessments showed that all normal monkeys had no SN hyperechogenicity. Bilaterally parkinsonian (overlesioned) monkeys showed hyperechogenicity of both SN, whereas right hemiparkinsonian monkeys only showed left nigral hyperechogenicity. These findings confirm the feasibility of transcranial ultrasound to detect SN hyperechogenicity in MPTP-treated Rhesus monkeys and suggest that this animal model may provide a platform for understanding the pathophysiologic basis of nigral hyperechogenicity. (E-mail: tsubram@yahoo.com)

Quantitative Ultrasound of the Calcaneus in Hemodialysis Patients - Corrected Proof

Chiung-Wen Kuo, Shang-Yun Ho, Tung-Hao Chang, Tieh-Chi Chu — 2010-03-08

Abstract: The aim of this study was to investigate the bone status of hemodialysis patients and identify factors that have influence on bone quality. Four hundred eighty-nine subjects (213 males and 276 females) on maintenance hemodialysis and 696 healthy subjects (309 men, 387 women) were enrolled in this study. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) were assessed by quantitative ultrasound (QUS) at the right calcaneus in both groups. Serum levels of intact parathyroid (iPTH), total alkaline phosphatase (ALP), calcium and phosphate were measured to determine their influence on bone status in hemodialysis patients. All QUS parameters were significantly lower in hemodialysis patients than in controls (p < 0.0001). Stepwise multiple linear regression analysis in male patients indicated that age, weight, calcium-phosphate product and ALP were significant predictors of QUS parameters (adjusted R2 = 0.15 in SOS; adjusted R2 = 0.17 in BUA and QUI). In female patients, same findings including number of parity were observed in SOS only (adjusted R2 = 0.25 in SOS). In postmenopausal patients, the duration of menopause was significant negatively correlated with all QUS parameters (p < 0.01). In conclusion, patients on maintenance hemodialysis had additional risk of bone loss. Advanced age, low body weight, high calcium-phosphate product and high ALP level were important risk factors for deterioration of bone quality. (E-mail: tcchu@mx.nthu.edu.tw)

An Acoustic Backscatter-Based Method for Localization of Lesions Induced by High-Intensity Focused Ultrasound - Corrected Proof

Xinliang Zheng, Shahram Vaezy — 2010-03-08

Abstract: Ultrasound B-mode visualization of lesions produced in soft tissues using high-intensity focused ultrasound (HIFU) has been shown to be challenging when there is no cavitation activity and, therefore, no hyperechogenecity in the focal region. We investigated a method for the visualization and localization of HIFU-induced lesions after HIFU delivery was complete based on the change in backscattered radio-frequency (RF) signals. A HIFU transducer was used with focal dimension of 8 mm by 2 mm working at 5 MHz. HIFU was applied at different intensities to produce lesions in ex vivo chicken breast, with or without the generation of hyperecho in B-mode images. We compared lesion locations obtained from our RF-processing method, from measurement of physical lesions after exposure and from the B-mode images, if exposures had resulted in hyperecho. The results showed that the RF amplitude decreased as a function of time immediately after stopping the HIFU exposure. The lesions were clearly visualized in two-dimensional (2-D) images of the decay rate of RF amplitude, no matter with or without hyperecho. In experiments with hyperecho, when comparing to physical lesion locations, there was no statistically significant difference in the localization accuracy between the RF-based and the hyperecho-based method (p = 0.76). In cases without hyperecho, the distance between RF-based locations and measured lesion locations was 3.37 ± 1.59 mm (mean ± standard deviation). The axial and lateral difference were 2.00 ± 2.31 mm and 0.85 ± 2.15 mm, respectively, and no statistically significant difference was found between lesion coordinates (axial: p = 0.37 and lateral: p = 0.15). We demonstrated the feasibility of our proposed RF-based method for the localization of HIFU-induced lesions immediately after HIFU treatment. Using the decay rate in RF amplitude as the signature of lesion formation, our method can detect lesion locations even without the appearance of hyperecho. (E-mail: xlzheng@u.washington.edu)