Publications by Year: 2008

2008
Lee J-H, O'Leary HM, Park HW, Jolesz FA, Yoo S-S. Atlas-based multichannel monitoring of functional MRI signals in real-time: automated approach. Hum Brain Mapp. 2008;29 (2) :157-66.Abstract
We report an automated method to simultaneously monitor blood-oxygenation-level-dependent (BOLD) MR signals from multiple cortical areas in real-time. Individual brain anatomy was normalized and registered to a pre-segmented atlas in standardized anatomical space. Subsequently, using real-time fMRI (rtfMRI) data acquisition, localized BOLD signals were measured and displayed from user-selected areas labeled with anatomical and Brodmann's Area (BA) nomenclature. The method was tested on healthy volunteers during the performance of hand motor and internal speech generation tasks employing a trial-based design. Our data normalization and registration algorithm, along with image reconstruction, movement correction and a data display routine were executed with enough processing and communication bandwidth necessary for real-time operation. Task-specific BOLD signals were observed from the hand motor and language areas. One of the study participants was allowed to freely engage in hand clenching tasks, and associated brain activities were detected from the motor-related neural substrates without prior knowledge of the task onset time. The proposed method may be applied to various applications such as neurofeedback, brain-computer-interface, and functional mapping for surgical planning where real-time monitoring of region-specific brain activity is needed.
McDannold N, Vykhodtseva N, Hynynen K. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol. 2008;34 (5) :834-40.Abstract
This work investigated the effect of ultrasonic frequency on the threshold for blood-brain barrier (BBB) disruption induced by ultrasound pulses combined with an ultrasound contrast agent. Experiments were performed in rabbits using pulsed sonications at 2.04 MHz with peak pressure amplitudes ranging from 0.3 to 2.3 MPa. BBB disruption was evaluated using contrast-enhanced magnetic resonance imaging. The threshold for BBB disruption was estimated using probit regression. Representative samples with similar amounts of contrast enhancement were examined in light microscopy. Results from these experiments were compared with data from previous studies that used ultrasound frequencies between 0.26 and 1.63 MHz. We found that the BBB disruption threshold (value where the probability for disruption was estimated to be 50%) expressed in terms of the peak negative pressure amplitude increased as a function of the frequency. It appeared to be constant, however, when the exposures were expressed as a function of the mechanical index (peak negative pressure amplitude estimated in situ divided by square root of frequency). Regression of data from all frequencies resulted in an estimated mechanical index threshold of 0.46 (95% confidence intervals: 0.42 to 0.50). Histologic examination of representative samples with similar amounts of blood-brain barrier disruption found that the number of regions containing extravasated red blood cells per unit area was substantially lower on average for lower ultrasound frequencies. This data suggests that the mechanical index is a meaningful metric for ultrasound-induced blood-brain barrier disruption, at least for when other parameters that are not taken into account by the mechanical index are not varied. It also suggests that lower frequency sonication produces less red blood cell extravasation per unit area.
Lee J-H, Lee T-W, Jolesz FA, Yoo S-S. Independent vector analysis (IVA): multivariate approach for fMRI group study. Neuroimage. 2008;40 (1) :86-109.Abstract
Independent component analysis (ICA) of fMRI data generates session/individual specific brain activation maps without a priori assumptions regarding the timing or pattern of the blood-oxygenation-level-dependent (BOLD) signal responses. However, because of a random permutation among output components, ICA does not offer a straightforward solution for the inference of group-level activation. In this study, we present an independent vector analysis (IVA) method to address the permutation problem during fMRI group data analysis. In comparison to ICA, IVA offers an analysis of additional dependent components, which were assigned for use in the automated grouping of dependent activation patterns across subjects. Upon testing using simulated trial-based fMRI data, our proposed method was applied to real fMRI data employing both a single-trial task-paradigm (right hand motor clenching and internal speech generation tasks) and a three-trial task-paradigm (right hand motor imagery task). A generalized linear model (GLM) and the group ICA of the fMRI toolbox (GIFT) were also applied to the same data set for comparison to IVA. Compared to GLM, IVA successfully captured activation patterns even when the functional areas showed variable hemodynamic responses that deviated from a hypothesized response. We also showed that IVA effectively inferred group-activation patterns of unknown origins without the requirement for a pre-processing stage (such as data concatenation in ICA-based GIFT). IVA can be used as a potential alternative or an adjunct to current ICA-based fMRI group processing methods.
Talos I-F, Rubin DL, Halle M, Musen M, Kikinis R. A prototype symbolic model of canonical functional neuroanatomy of the motor system. J Biomed Inform. 2008;41 (2) :251-63.Abstract
Recent advances in bioinformatics have opened entire new avenues for organizing, integrating and retrieving neuroscientific data, in a digital, machine-processable format, which can be at the same time understood by humans, using ontological, symbolic data representations. Declarative information stored in ontological format can be perused and maintained by domain experts, interpreted by machines, and serve as basis for a multitude of decision support, computerized simulation, data mining, and teaching applications. We have developed a prototype symbolic model of canonical neuroanatomy of the motor system. Our symbolic model is intended to support symbolic look up, logical inference and mathematical modeling by integrating descriptive, qualitative and quantitative functional neuroanatomical knowledge. Furthermore, we show how our approach can be extended to modeling impaired brain connectivity in disease states, such as common movement disorders. In developing our ontology, we adopted a disciplined modeling approach, relying on a set of declared principles, a high-level schema, Aristotelian definitions, and a frame-based authoring system. These features, along with the use of the Unified Medical Language System (UMLS) vocabulary, enable the alignment of our functional ontology with an existing comprehensive ontology of human anatomy, and thus allow for combining the structural and functional views of neuroanatomy for clinical decision support and neuroanatomy teaching applications. Although the scope of our current prototype ontology is limited to a particular functional system in the brain, it may be possible to adapt this approach for modeling other brain functional systems as well.
Maddah M, Grimson EWL, Warfield SK, Wells WM. A unified framework for clustering and quantitative analysis of white matter fiber tracts. Med Image Anal. 2008;12 (2) :191-202.Abstract
We present a novel approach for joint clustering and point-by-point mapping of white matter fiber pathways. Knowledge of the point correspondence along the fiber pathways is not only necessary for accurate clustering of the trajectories into fiber bundles, but also crucial for any tract-oriented quantitative analysis. We employ an expectation-maximization (EM) algorithm to cluster the trajectories in a gamma mixture model context. The result of clustering is the probabilistic assignment of the fiber trajectories to each cluster, an estimate of the cluster parameters, i.e. spatial mean and variance, and point correspondences. The fiber bundles are modeled by the mean trajectory and its spatial variation. Point-by-point correspondence of the trajectories within a bundle is obtained by constructing a distance map and a label map from each cluster center at every iteration of the EM algorithm. This offers a time-efficient alternative to pairwise curve matching of all trajectories with respect to each cluster center. The proposed method has the potential to benefit from an anatomical atlas of fiber tracts by incorporating it as prior information in the EM algorithm. The algorithm is also capable of handling outliers in a principled way. The presented results confirm the efficiency and effectiveness of the proposed framework for quantitative analysis of diffusion tensor MRI.
Jolesz FA, McDannold N. Current status and future potential of MRI-guided focused ultrasound surgery. J Magn Reson Imaging. 2008;27 (2) :391-9.Abstract
The combination of the imaging abilities of magnetic resonance imaging (MRI) with the ability to delivery energy to targets deep in the body noninvasively with focused ultrasound presents a disruptive technology with the potential to significantly affect healthcare. MRI offers precise targeting, visualization, and quantification of temperature changes and the ability to immediately evaluate the treatment. By exploiting different mechanisms, focused ultrasound offers a range of therapies, ranging from thermal ablation to targeted drug delivery. This article reviews recent preclinical and tests clinical of this technology.
Sheikov N, McDannold N, Sharma S, Hynynen K. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol. 2008;34 (7) :1093-104.Abstract
Previous studies have investigated a potential method for targeted drug delivery in the central nervous system that uses focused ultrasound bursts combined with an ultrasound contrast agent to temporarily disrupt the blood-brain barrier (BBB). The purpose of this work was to investigate the integrity of the tight junctions (TJs) in rat brain microvessels after this BBB disruption. Ultrasound bursts (1.5-MHz) in combination with a gas contrast agent (Optison) was applied at two locations in the brain in 25 rats to induce BBB disruption. Using immunoelectron microscopy, the distributions of the TJ-specific transmembrane proteins occludin, claudin-1, claudin-5, and of submembranous ZO-1 were examined at 1, 2, 4, 6 and 24 h after sonication. A quantitative evaluation of the protein expression was made by counting the number of immunosignals per micrometer in the junctional clefts. BBB disruption at the sonicated locations was confirmed by the leakage of i.v. administered horseradish peroxidase (HRP, m.w. 40,000 Da) and lanthanum chloride (La(3+), m.w. approximately 139 Da). Leakage of these agents was observed at 1 and 2 h and, in a few vessels, at 4 h after ultrasound application. These changes were paralleled by the apparent disintegration of the TJ complexes, as evidenced by the redistribution and loss of the immunosignals for occludin, claudin-5 and ZO-1. Claudin-1 seemed less involved. At 6 and 24 h after sonication, no HRP or lanthanum leakage was observed and the barrier function of the TJs, as indicated by the localization and density of immunosignals, appeared to be completely restored. This study provides the first direct evidence that ultrasound bursts combined with a gas contrast agent cause disassembling of the TJ molecular structure, leading to loss of the junctional barrier functions in brain microvessels. The BBB disruption appears to last up to 4 h after sonication and permits the paracellular passage of agents with molecular weights up to at least 40 kDa. These promising features can be exploited in the future development of this method that could enable the delivery of drugs, antibodies or genes to targeted locations in the brain.
McDannold N, Vykhodtseva N, Hynynen K. Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol. 2008;34 (6) :930-7.Abstract
Previously, it was shown that low-intensity focused ultrasound pulses applied along with an ultrasound contrast agent results in temporary blood-brain barrier (BBB) disruption. This effect could be used for targeted drug delivery in the central nervous system. This study examined the effects of burst length, pulse repetition frequency (PRF), and ultrasound contrast agent dose on the resulting BBB disruption. One hundred nonoverlapping brain locations were sonicated through a craniotomy in experiments in 26 rabbits (ultrasound frequency: 0.69 MHz, burst: 0.1, 1, 10 ms, PRF: 0.5, 1, 2, 5 Hz, duration: 20 s, peak negative pressure amplitude: 0.1 to 1.5 MPa, Optison dosage 50, 100, 250 microl/kg). For each sonication, BBB disruption was evaluated using contrast-enhanced magnetic resonance imaging. The BBB disruption threshold (the pressure amplitude yielding a 50% probability for BBB disruption) was determined using probit regression for the three burst lengths tested. Tissue effects were examined in light microscopy for representative locations with similar amounts of contrast enhancement from each group. While changing the PRF or the Optison dosage did not result in a significant difference in the magnitude of the BBB disruption (p > 0.05), reducing the burst length resulted in significantly less contrast enhancement (p < 0.01). The BBB disruption thresholds were estimated to be 0.69, 0.47 and 0.36 MPa for 0.1, 1 and 10 ms bursts, respectively. No difference was detected in histology between any experimental groups. This data suggests that over the range of parameters tested, BBB disruption is not affected by PRF or ultrasound contrast agent dose. However, both the BBB disruption magnitude and its threshold depend on the burst length.
Farny CH, Clement GT. Feasibility of ultrasound phase contrast for heating localization. J Acoust Soc Am. 2008;123 (3) :1773-83.Abstract
Ultrasound-based methods for temperature monitoring could greatly assist focused ultrasound visualization and treatment planning based on sound speed-induced change in phase as a function of temperature. A method is presented that uses reflex transmission integration, planar projection, and tomographic reconstruction techniques to visualize phase contrast by measuring the sound field before and after heat deposition. Results from experiments and numerical simulations employing a through-transmission setup are presented to demonstrate feasibility of using phase contrast methods for identifying temperature change. A 1.088-MHz focused transducer was used to interrogate a medium with a phase contrast feature, following measurement of the baseline reference field with a hydrophone. A thermal plume in water and a tissue phantom with multiple water columns was used in separate experiments to produce a phase contrast. The reference and phase contrast field scans were numerically backprojected and the phase difference correctly identified the position and orientation of the features. The peak temperature reconstructed from the phase shift was within 0.2 degrees C of the measured temperature in the plume. Simulated results were in good agreement with experimental results. Finally, employment of reflex transmission imaging techniques for adopting a pulse-echo arrangement was simulated, and its future experimental application is discussed.
Tang SC, Clement GT. A harmonic cancellation technique for an ultrasound transducer excited by a switched-mode power converter. IEEE Trans Ultrason Ferroelectr Freq Control. 2008;55 (2) :359-67.Abstract
The aim of this study is to evaluate the feasibility of using harmonic cancellation for a therapeutic ultrasound transducer excited by a switched-mode power converter without an additional output filter. A switching waveform without the third harmonic was created by cascading two switched-mode power inverter modules at which their output waveforms were pi/3 phase shifted from each other. A PSPICE simulation model for the power converter output stage was developed. The simulated results were in good agreement with the measurement. The waveform and harmonic contents of the acoustic pressure generated by a 1-MHz, self-focused piezoelectric transducer with and without harmonic cancellation have been evaluated. Measured results indicated that the acoustic third harmonicto- fundamental ratio at the focus was small (-48 dB) with harmonic cancellation, compared to that without harmonic cancellation (-20 dB). The measured acoustic levels of the fifth harmonic for both cases with and without harmonic cancellation also were small (-46 dB) compared to the fundamental. This study shows that it is viable to drive a piezoelectric ultrasound transducer using a switched-mode power converter without the requirement of an additional output filter in many high-intensity focused ultrasound (HIFU) applications.
Chen N-kuei, Oshio K, Panych LP. Improved image reconstruction for partial Fourier gradient-echo echo-planar imaging (EPI). Magn Reson Med. 2008;59 (4) :916-24.Abstract
The partial Fourier gradient-echo echo planar imaging (EPI) technique makes it possible to acquire high-resolution functional MRI (fMRI) data at an optimal echo time. This technique is especially important for fMRI studies at high magnetic fields, where the optimal echo time is short and may not be achieved with a full Fourier acquisition scheme. In addition, it has been shown that partial Fourier EPI provides better anatomic resolvability than full Fourier EPI. However, the partial Fourier gradient-echo EPI may be degraded by artifacts that are not usually seen in other types of imaging. Those unique artifacts in partial Fourier gradient-echo EPI, to our knowledge, have not yet been systematically evaluated. Here we use the k-space energy spectrum analysis method to understand and characterize two types of partial Fourier EPI artifacts. Our studies show that Type 1 artifact, originating from k-space energy loss, cannot be corrected with pure postprocessing, and Type 2 artifact can be eliminated with an improved reconstruction method. We propose a novel algorithm, that combines images obtained from two or more reconstruction schemes guided by k-space energy spectrum analysis, to generate partial Fourier EPI with greatly reduced Type 2 artifact. Quality control procedures for avoiding Type 1 artifact in partial Fourier EPI are also discussed.
Morrison PR, Silverman SG, Tuncali K, Tatli S. MRI-guided cryotherapy. J Magn Reson Imaging. 2008;27 (2) :410-20.Abstract
Over the last decade the focus of published research on MRI-guided cryotherapy has switched from the study of experimental models to the clinical treatment of patients. The latter reports attest to the safety and feasibility of treating lesions in the liver, kidney, and other sites throughout the body. Further, the published images and initial results speak to the utility of MRI for the task of monitoring this specific procedure. This clinical utility is a realization of the promise of the earlier experimental work that showed the clarity with which interstitial ice is seen under MRI under various pulse sequence parameters. Early adopters have taken advantage of access to the patient that is provided by low and mid-field open scanners; the near future will test the suitability of higher field systems. It has been critical that an FDA-approved cryotherapy system and suitably thin probes were customized for the MRI environment a decade ago by which percutaneous cryotherapy could be performed. There is still work to be done to expand the role of percutaneous cryotherapy, to understand various tissue responses, and to optimize visualization of therapeutic isotherms. Also, long-term outcomes need to be assessed. Overall, in a worldwide environment in which the practice of ablation is growing and an appreciation for such therapies is on the rise, the work of these recent years provides sound footing for the advances that lay ahead for clinical MRI-guided cryotherapy.
Tang AM, Kacher DF, Lam EY, Wong KK, Jolesz FA, Yang ES. Simultaneous ultrasound and MRI system for breast biopsy: compatibility assessment and demonstration in a dual modality phantom. IEEE Trans Med Imaging. 2008;27 (2) :247-54.Abstract
Simultaneous capturing of ultrasound (US) and magnetic resonance (MR) images allows fusion of information obtained from both modalities. We propose an MR-compatible US system where MR images are acquired in a known orientation with respect to the US imaging plane and concurrent real-time imaging can be achieved. Compatibility of the two imaging devices is a major issue in the physical setup. Tests were performed to quantify the radio frequency (RF) noise introduced in MR and US images, with the US system used in conjunction with MRI scanner of different field strengths (0.5 T and 3 T). Furthermore, simultaneous imaging was performed on a dual modality breast phantom in the 0.5 T open bore and 3 T close bore MRI systems to aid needle-guided breast biopsy. Fiducial based passive tracking and electromagnetic based active tracking were used in 3 T and 0.5 T, respectively, to establish the location and orientation of the US probe inside the magnet bore. Our results indicate that simultaneous US and MR imaging are feasible with properly-designed shielding, resulting in negligible broadband noise and minimal periodic RF noise in both modalities. US can be used for real time display of the needle trajectory, while MRI can be used to confirm needle placement.
Tokuda J, Morikawa S, Haque HA, Tsukamoto T, Matsumiya K, Liao H, Masamune K, Dohi T. Adaptive 4D MR imaging using navigator-based respiratory signal for MRI-guided therapy. Magn Reson Med. 2008;59 (5) :1051-61.Abstract
For real-time 3D visualization of respiratory organ motion for MRI-guided therapy, a new adaptive 4D MR imaging method based on navigator echo and multiple gating windows was developed. This method was designed to acquire a time series of volumetric 3D images of a cyclically moving organ, enabling therapy to be guided by synchronizing the 4D image with the actual organ motion in real time. The proposed method was implemented in an open-configuration 0.5T clinical MR scanner. To evaluate the feasibility and determine optimal imaging conditions, studies were conducted with a phantom, volunteers, and a patient. In the phantom study the root mean square (RMS) position error in the 4D image of the cyclically moving phantom was 1.9 mm and the imaging time was approximately 10 min when the 4D image had six frames. In the patient study, 4D images were successfully acquired under clinical conditions and a liver tumor was discriminated in the series of frames. The image quality was affected by the relations among the encoding direction, the slice orientation, and the direction of motion of the target organ. In conclusion, this study has shown that the proposed method is feasible and capable of providing a real-time dynamic 3D atlas for surgical navigation with sufficient accuracy and image quality.
Kazanzides P, Xia T, Baird C, Jallo G, Hayes K, Nakajima N, Hata N. A cooperatively-controlled image guided robot system for skull base surgery. Stud Health Technol Inform. 2008;132 :198-203.Abstract
We created an image-guided robot system to assist with skull base drilling by integrating a robot, a commercial navigation system, and an open source visualization platform. The objective of this procedure is to create a cavity in the skull base to allow access for neurosurgical interventions. The motivation for introducing an image-guided robot is to improve safety by preventing the surgeon from accidentally damaging critical structures during the drilling procedure. Our approach is to attach the cutting tool to the robot end-effector and operate the robot in a cooperative control mode, where robot motion is determined from the forces and torques applied by the surgeon. We employ "virtual fixtures" to constrain the motion of the cutting tool so that it remains in the safe zone that was defined on a preoperative CT scan. This paper presents the system design and the results of phantom and cadaveric experiments. Both experiments have demonstrated the feasibility of the system, with average overcut error at about 1 mm and maximum errors at 2.5 mm.
Wong SH, Watkins RD, Kupnik M, Pauly KB, Khuri-Yakub BT. Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT. IEEE Trans Ultrason Ferroelectr Freq Control. 2008;55 (4) :811-8.Abstract
In the last decade, high intensity focused ultrasound (HIFU) has gained popularity as a minimally invasive and noninvasive therapeutic tool for treatment of cancers, arrhythmias, and other medical conditions. HIFU therapy is often guided by magnetic resonance imaging (MRI), which provides anatomical images for therapeutic device placement, temperature maps for treatment guidance, and postoperative evaluation of the region of interest. While piezoelectric transducers are dominantly used for MR-guided HIFU, capacitive micromachined ultrasonic transducers (CMUTs) show competitive advantages, such as ease of fabrication, integration with electronics, improved efficiency, and reduction of self-heating. In this paper, we will show our first results of an unfocused CMUT transducer monitored by MR-temperature maps. This 2.51 mm by 2.32 mm, unfocused CMUT heated a HIFU phantom by 14 degrees C in 2.5 min. This temperature rise was successfully monitored by MR thermometry in a 3.0 T General Electric scanner.
Hata N, Tokuda J, Hurwitz S, Morikawa S. MRI-compatible manipulator with remote-center-of-motion control. J Magn Reson Imaging. 2008;27 (5) :1130-8.Abstract
PURPOSE: To develop and assess a needle-guiding manipulator for MRI-guided therapy that allows a physician to freely select the needle insertion path while maintaining remote center of motion (RCM) at the tumor site. MATERIALS AND METHODS: The manipulator consists of a three-degrees-of-freedom (DOF) base stage and passive needle holder with unconstrained two-DOF rotation. The synergistic control keeps the Virtual RCM at the preplanned target using encoder outputs from the needle holder as input to motorize the base stage. RESULTS: The manipulator assists in searching for an optimal needle insertion path which is a complex and time-consuming task in MRI-guided ablation therapy for liver tumors. The assessment study showed that accuracy of keeping the virtual RCM to predefined position is 3.0 mm. In a phantom test, the physicians found the needle insertion path faster with than without the manipulator (number of physicians = 3, P = 0.001). However, the alignment time with the virtual RCM was not shorter when imaging time for planning were considered. CONCLUSION: The study indicated that the robot holds promise as a tool for accurately and interactively selecting the optimal needle insertion path in liver ablation therapy guided by open-configuration MRI.
Vykhodtseva N, McDannold N, Hynynen K. Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. Ultrasonics. 2008;48 (4) :279-96.Abstract
Advances in neuroscience have resulted in the development of new diagnostic and therapeutic agents for potential use in the central nervous system (CNS). However, the ability to deliver the majority of these agents to the brain is limited by the blood-brain barrier (BBB), a specialized structure of the blood vessel wall that hampers transport and diffusion from the blood to the brain. Many CNS disorders could be treated with drugs, enzymes, genes, or large-molecule biotechnological products such as recombinant proteins, if they could cross the BBB. This article reviews the problems of the BBB presence in treating the vast majority of CNS diseases and the efforts to circumvent the BBB through the design of new drugs and the development of more sophisticated delivery methods. Recent advances in the development of noninvasive, targeted drug delivery by MRI-guided ultrasound-induced BBB disruption are also summarized.
Raymond SB, Treat LH, Dewey JD, McDannold NJ, Hynynen K, Bacskai BJ. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models. PLoS One. 2008;3 (5) :e2175.Abstract
Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9-26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.
Warfield SK, Zou KH, Wells WM. Validation of image segmentation by estimating rater bias and variance. Philos Trans A Math Phys Eng Sci. 2008;366 (1874) :2361-75.Abstract
The accuracy and precision of segmentations of medical images has been difficult to quantify in the absence of a 'ground truth' or reference standard segmentation for clinical data. Although physical or digital phantoms can help by providing a reference standard, they do not allow the reproduction of the full range of imaging and anatomical characteristics observed in clinical data. An alternative assessment approach is to compare with segmentations generated by domain experts. Segmentations may be generated by raters who are trained experts or by automated image analysis algorithms. Typically, these segmentations differ due to intra-rater and inter-rater variability. The most appropriate way to compare such segmentations has been unclear. We present here a new algorithm to enable the estimation of performance characteristics, and a true labelling, from observations of segmentations of imaging data where segmentation labels may be ordered or continuous measures. This approach may be used with, among others, surface, distance transform or level-set representations of segmentations, and can be used to assess whether or not a rater consistently overestimates or underestimates the position of a boundary.

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