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The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRL However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI. blood-brain barrier | brain drug delivery | focused ultrasound | magnetic nanoparticles | magnetic targeting doi/ 10.1073/pnas.1003388107

The objective of this research is to prospectively evaluate the feasibility of vibroacoustography (VA) imaging in monitoring prostate cryotherapy in an ex vivo model. Baseline scanning of an excised human prostate is accomplished by a VA system apparatus in a tank of degassed water. Alcohol and dry ice mixture are used to freeze two prostate tissue samples. The frozen prostates are subsequently placed within the water tank at 27[degrees]C and rescanned. VA images were acquired at prescribed time intervals to characterize the acoustic properties of the partially frozen tissue. The frozen prostate tissue appears in the images as hypoemitting signal. Once the tissue thaws, previously frozen regions show coarser texture than prior to freezing. The margin of the frozen tissue is delineated with a well-defined rim. The thawed cryolesions show a different contrast compared with normal unfrozen prostate. In conclusion, this pilot study shows that VA produces clear images of a frozen prostate at different temperature stages. The frozen tissue appears as a uniform region with well-defined borders that are readily identified. These characteristic images should allow safer and more efficient application of prostatic cryosurgery. These results provide substantial motivation to further investigate VA as a potential modality to monitor prostate cryotherapy intraoperatively. Index Terms--Cryosurgery, prostate cancer, ultrasound, vibroacoustography (VA).

The purpose of this paper is to demonstrate a prototype design of a low-frequency multiple-channel hemispherical focused-ultrasound phased-array system for transcranial disruption of the blood-brain barrier (BBB). A 32-channel ultrasound driving system tunable in the frequency range from 200 to 400 kHz was designed for producing a suitable ultrasound output for BBB disruption. The driving system includes a microcontroller/field-programmable gate-array-based control kernel with multiple-channel driving circuits implemented by a high-voltage switching/LC-resonance/impedance-matching circuit module. Three hemispherical phased arrays comprising 22, 31, and 80 elements were fabricated and tested. The pressure distributions at the geometric center and at off-center positions were tested experimentally. The focal performance of the different hemispherical arrays was also evaluated theoretically. The results showed that the developed phased-array system can successfully drive the hemispherical array with multiple-channel ultrasound signals with independent phase control at 8-bit resolution. Good focusing abilities were evident both at the geometric center and at specific off-center target positions. Preliminary animal experiments show that the BBB in rat can be locally disrupted successfully. The system will serve as a reference platform for developing a focused-ultrasound system for clinical use in brain drug delivery applications. Index Terms--Biomedical ultrasonics, brain, drug delivery systems.

In freehand 3-D ultrasound (US), the relative positions of US images are usually measured using a position tracking device despite its cumbersome nature. The probe trajectory can instead be estimated from image data, using registration techniques to recover in-plane motion and speckle decorrelation to recover out-of-plane transformations. The relationship between speckle decorrelation and elevational separation is typically represented by a single curve, estimated from calibration data. Distances read off such a curve are corrupted by bias and uncertainty, and only provide an absolute estimate of elevational displacement. This paper presents a probabilistic model of the relationship between correlation measurements and elevational separation. This representation captures the skewed distribution of distance estimates based on high correlations and the uncertainties attached to each measurement. Multiple redundant correlation measurements can then be integrated within a maximum likelihood estimation framework. This paper also introduces a new method based on the traveling salesman problem for resolving sign ambiguities ill data sets resulting from nonmonotonic probe motion and frame intersections. Experiments with real and synthetic US data show that by combining these new methods, out-of-plane US probe motion is recovered with improved accuracy over baseline methods using a deterministic model and fewer measurements. Index Terms--Acoustics, image reconstruction, maximum entropy methods, maximum likelihood estimation, traveling salesman problems.

We recovered a novel mouse mutant exhibiting neonatal lethality associated with severe fetal cardiac hypertrophy and with some adult mice dying suddenly with left ventricular hypertrophic cardiomyopathy. Using Doppler echocardiography, we screened surviving adult mice in this mutant line for cardiac hypertrophy. Cardiac dimensions were obtained either from two-dimensional images collected using a novel ECG-gated ultra-high-frequency ultrasound system or by traditional M-mode imaging on a clinical ultrasound system. These analyses identified, among the littermates, two populations of mice: those with apparent cardiac hypertrophy with hypercontractile function characterized by ejection fraction of 75-80%, and normal littermates with ejection fraction of 53-55%. Analysis of the ECG-gated two-dimensional cines indicated that the hypertrophy was of the nonobstructive type. Further analysis of heart-to-body weight ratio confirmed the ultrasound diagnosis of left ventricular hypertrophic cardiomyopathy. Histopathology showed increased ventricular wall thickness, enlarged myocyte size, and mild myofiber disarray. Ultrastructural analysis by electron microscopy revealed mitochondria hyperproliferation and dilated sarcoplasmic reticulum. Genome scanning using microsatellite DNA markers mapped the mutation to the X chromosome. DNA sequencing showed no mutations in the coding regions of several candidate genes on the X chromosome, including several known to be associated with left ventricular hypertrophic cardiomyopathy. These findings suggest that this mouse line may harbor a mutation in a novel gene causing X-linked cardiomyopathy. echocardiography; X-linked cardiomyopathy; hypertrophic cardiomyopathy; ultrasound

The dynamics of bubble clouds induced by histotripsy are discussed. Findings reveal that the bubble clouds share the same evolutionary trend.

Ultrasound (US) is among the most popular diagnostic techniques today. It is non-invasive, fast, comparably cheap, and does not require ionizing radiation. US is commonly used to examine the size, and structure of the thyroid gland. In clinical routine, thyroid imaging is usually performed by means of 2-D US. Conventional approaches for measuring the volume of the thyroid gland or its nodules may therefore be inaccurate due to the lack of 3-D information. This work reports a semi-automatic segmentation approach for the classification, and analysis of the thyroid gland based on 3-D US data. The images are scanned in 3-D, pre-processed, and segmented. Several pre-processing methods, and an extension of a commonly used geodesic active contour level set formulation are discussed in detail. The results obtained by this approach are compared to manual interactive segmentations by a medical expert in five representative patients. Our work proposes a novel framework for the volumetric quantification of thyroid gland lobes, which may also be expanded to other parenchymatous organs. Index Terms--Geodesic active contour, level set, segmentation, thyroid gland, three-dimensional (3-D) ultrasound.

Previous studies have demonstrated that mutation in the forkhead domain of the forkhead box P2 (FOXP2) protein (R553H) causes speech-language disorders. To further analyze FOXP2 function in speech learning, we generated a knockin (KI) mouse for Foxp2 (R552H) [Foxp2 (R552H)-KI], corresponding to the human FOXP2 (R553H) mutation, by homologous recombination. Homozygous Foxp2 (R552H)-KI mice showed reduced weight, immature development of the cerebellum with incompletely folded folia, Purkinje cells with poor dendritic arbors and less synaptophysin immunoreactivity, and achieved crisis stage for survival 3 weeks after birth. At postnatal day 10, these mice also showed severe ultrasonic vocalization (USV) and motor impairment, whereas the heterozygous Foxp2 (R552H)-KI mice exhibited modest impairments. Similar to the wild-type protein, Foxp2 (R552H) localized in the nuclei of the Purkinje cells and the thalamus, striatum, cortex, and hippocampus (CA1) neurons of the homozygous Foxp2 (R552H)-KI mice (postnatal day 10), and some of the neurons showed nuclear aggregates of Foxp2 (R552H). In addition to the immature development of the cerebellum, Foxp2 (R552H) nuclear aggregates may further compromise the function of the Purkinje cells and cerebral neurons of the homozygous mice, resulting in their death. In contrast, heterozygous Foxp2 (R552H)-KI mice, which showed modest impairment of USVs with different USV qualities and which did not exhibit nuclear aggregates, should provide insights into the common molecular mechanisms between the mouse USV and human speech learning and the relationship between the USV and motor neural systems. KE family | nuclear aggregation | autism | endoplasmic reticulum stress

The designing of binary codes suitable for high-frequency applications of coded excitation in medical ultrasound instead of the traditional base sequence by improving the signal-to-noise ratio (SNR) is studied. This approach searches all the codes that match the transducer passband and show improved SNR.

A strategy is proposed to enhance the cavitation-induced tissue erosion, wherein tissue erosion is initiated by a short, high-intensity sequence of pulses and sustained by lower intensity pulses. Results show that the initiating sequence increases the probability of erosion occurrence and the erosion rate with only slight overall increases in propagated energy, and if extinguished and reinitiated, the sustained cavitation period becomes shorter after each initiation.

A review of progress and the challenges remaining in biomedical ultrasound exposimetry are described. A wide array of topics that include devices and techniques, method of calibration, progress in standardization, and current problem areas, including the effects of noncolinear propagation are illustrated.

A new laser optoacoustic imaging system is described and discussed.

Samarium- and manganese-doped lead titanate ceramic fibers are prepared using a sol-gel method.

A miniaturized ultrasonic transducer, based on fiber optic technology, is proposed.

A procedure is described for quantitatively analyzing sinoatrial nodes (SAN) using doppler tissue images (DTI).

Mechanical properties of polyvinyl alcohol (PVA) cryogel are investigated in order to show its usefulness for intravascular elasography.

High-intensity, focused ultrasound (HIFU) surgical applicators are described and discussed.

Research is described involving use of stabilized microbubbles for aiding tissue ablation during ultrasound therapy.

A method for deconvolution of high-frequency ultrasound skin images is described and discussed.

It is shown that the thermoeleastic effect in black polydimethylsiloxane (PDMS) is a viable alternative to piezoelectricity for configuring arrays in the 100 MHz regime.

A guide is presented for use of statistical procedures for specifying acoustic output values and measurement uncertainties of ultrasound devices.

It is shown that the spatial coherence of backscatter for the nonlinearly generated second harmonic differs from the spatial coherence of backscatter for the fundamental. The application of the pulse-echo version of the Van Cittert-Zernike theorem is extended to the nonlinearly generated second harmonic.

A multiparameter approach involving classification of breast masses in ultrasonic B-scan images is described and discussed.

An algorithm for obtaining a second-order Volterra filter (SVF) for separating linear and quadratic components from echo signals is proposed and discussed.

Use of ultrasonic backscatter from cancellous bone as a predictor of osteoporotic fracture risk is examined and discussed.

Research is described that involves control over thermal damage caused by interstitial ultrasound heating applications.

An innovative procedure for directional velocity estimation is described and discussed.

An innovative procedure for directional velocity is described and discussed.

An innovative approach for acquiring flow images using synthetic aperture techniques in medical ultrasound is described and discussed.

It is shown, for bandwidth and sample volume depths examined, that the normal range of medium absorption has little effect on Doppler sensitivity.

A strain-flow imaging procedure for investigating vascular dynamics and tumor biology is described and discussed.

A coded excitation procedure, based on spectrum inversion, is described and discussed.

A class of ultrasound phase aberration correction/autofocusing algorithms is described and discussed.

Force-free images can provide diagnostic information unavailable in other image types.

Performance of an ultrasono-therapy transducer with contact detection is examined and reported.

A numerical algorithm for computing the full harmonic pressure field radiated from phased-array transducers is described and discussed.

Performance effects of a preclassification stage that subdivides tissue regions of interest (ROI) and classifies subregions based on scatterer structure types are examined and reported.

Acoustic radiation force impulse (ARFI) imaging is investigated and discussed.

A linear systems frameworkis described. It is based on a solution to the wave equation for inhomogeneous media.

An ultrasound-based procedure for cortical thickness measurement is described and discussed.

Use of u ltrasound biomicroscopy (UBM)-guided Doppler ultrasound for analyzing cardiovascular phenotypes of developing mouse embryos is described and discussed.

The Doppler power from porcine bollod is examined in a mock flow loop> Cyclic and radial variation is observed during pulsatile cyclics.

A new method is proposed that uses the wavelet frame and soft-thresholding algorithm to denoise quadrature Doppler signals from bi-directional blood flow.

Optical observations of freely flowing, oscillating microbubbles from an experimental ultrasound contrast agent (UCA) are examined and reported.