Publications

2007
Wittek A, Miller K, Kikinis R, Warfield SK. Patient-specific model of brain deformation: application to medical image registration. J Biomech. 2007;40 (4) :919-29.Abstract
This contribution presents finite element computation of the deformation field within the brain during craniotomy-induced brain shift. The results were used to illustrate the capabilities of non-linear (i.e. accounting for both geometric and material non-linearities) finite element analysis in non-rigid registration of pre- and intra-operative magnetic resonance images of the brain. We used patient-specific hexahedron-dominant finite element mesh, together with realistic material properties for the brain tissue and appropriate contact conditions at boundaries. The model was loaded by the enforced motion of nodes (i.e. through prescribed motion of a boundary) at the brain surface in the craniotomy area. We suggest using explicit time-integration scheme for discretised equations of motion, as the computational times are much shorter and accuracy, for practical purposes, the same as in the case of implicit integration schemes. Application of the computed deformation field to register (i.e. align) the pre-operative images with the intra-operative ones indicated that the model very accurately predicts the displacements of the tumour and the lateral ventricles even for limited information about the brain surface deformation. The prediction accuracy improves when information about deformation of not only exposed (during craniotomy) but also unexposed parts of the brain surface is used when prescribing loading. However, it appears that the accuracy achieved using information only about the deformation of the exposed surface, that can be determined without intra-operative imaging, is acceptable. The presented results show that non-linear biomechanical models can complement medical image processing techniques when conducting non-rigid registration. Important advantage of such models over the previously used linear ones is that they do not require unrealistic assumptions that brain deformations are infinitesimally small and brain stress-strain relationship is linear.
Yoo S-S, Hu PT, Gujar N, Jolesz FA, Walker MP. A deficit in the ability to form new human memories without sleep. Nat Neurosci. 2007;10 (3) :385-92.Abstract
Evidence indicates that sleep after learning is critical for the subsequent consolidation of human memory. Whether sleep before learning is equally essential for the initial formation of new memories, however, remains an open question. We report that a single night of sleep deprivation produces a significant deficit in hippocampal activity during episodic memory encoding, resulting in worse subsequent retention. Furthermore, these hippocampal impairments instantiate a different pattern of functional connectivity in basic alertness networks of the brainstem and thalamus. We also find that unique prefrontal regions predict the success of encoding for sleep-deprived individuals relative to those who have slept normally. These results demonstrate that an absence of prior sleep substantially compromises the neural and behavioral capacity for committing new experiences to memory. It therefore appears that sleep before learning is critical in preparing the human brain for next-day memory formation-a worrying finding considering society's increasing erosion of sleep time.
Alayón S, Robertson R, Warfield SK, Ruiz-Alzola J. A fuzzy system for helping medical diagnosis of malformations of cortical development. J Biomed Inform. 2007;40 (3) :221-35.Abstract
Malformations of the cerebral cortex are recognized as a common cause of developmental delay, neurological deficits, mental retardation and epilepsy. Currently, the diagnosis of cerebral cortical malformations is based on a subjective interpretation of neuroimaging characteristics of the cerebral gray matter and underlying white matter. There is no automated system for aiding the observer in making the diagnosis of a cortical malformation. In this paper a fuzzy rule-based system is proposed as a solution for this problem. The system collects the available expert knowledge about cortical malformations and assists the medical observer in arriving at a correct diagnosis. Moreover, the system allows the study of the influence of the various factors that take part in the decision. The evaluation of the system has been carried out by comparing the automated diagnostic algorithm with known case examples of various malformations due to abnormal cortical organization. An exhaustive evaluation of the system by comparison with published cases and a ROC analysis is presented in the paper.
Rolls HK, Yoo S-S, Zou KH, Golby AJ, Panych LP. Rater-dependent accuracy in predicting the spatial location of functional centers on anatomical MR images. Clin Neurol Neurosurg. 2007;109 (3) :225-35.Abstract
OBJECTIVES: The determination of eloquent cortex is essential when planning neurosurgical approaches to brain lesions. This study examined the abilities of medical personnel of various backgrounds to predict the location of functional cortex using anatomical information provided by MR imaging. PATIENTS AND METHODS: Neurosurgeons, neuroscientists, neuroradiologists, medical students and MR technologists viewed anatomical MR images acquired from patients with brain tumors and healthy controls. These five groups of raters were then asked to locate the primary motor hand, supplementary motor and primary auditory areas and their predictions were compared to fMRI data acquired from the same subjects. RESULTS: The overall mean distance from the center of the fMRI activation was 2.38 cm. The neuroscientists performed the best and MR technologists performed the worst (mean distance from center of 1.83 and 3.04 cm, respectively, p<0.05). The difference between patients and controls was not significant. The mean distance by ROI was primary motor hand 2.03 cm, auditory area 2.06 cm and supplementary motor area 3.18 cm (p<0.05). Raters also performed best in the medial-lateral direction, compared to superior-inferior and anterior-posterior directions (mean distances from center 0.42, 1.04 and 1.81 cm, respectively). Finally, the approximate minimum fields of view necessary to capture the entire fMRI activations using the raters' predictions ranged from 5 to 15 cm, or 3 to 12 cm larger than the fMRI activations. CONCLUSION: Medical personnel of various training perform poorly when using only anatomical information to predict the location of functional areas of cortex.
Zou KH, O'Malley JA, Mauri L. Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation. 2007;115 (5) :654-7.
Clement GT. Two-dimensional ultrasound detection with unfocused frequency-randomized signals. J Acoust Soc Am. 2007;121 (1) :636-47.Abstract
A method is described for detecting scattering in two-dimensions using an unfocused ultrasound field created from a continuously driven source array. The frequency of each element on the array is unique, resulting in a field that is highly variant as a function of both time and position. The scattered signal is then received by a single receiving line. The method, as currently written, is valid under the first order Born approximation. To demonstrate the approach, a series of simulations within the frequency range of 0.10-1.25 MHz are performed and compared with a simulated B-Scan in the same frequency range. The method is found to be superior in resolving closely spaced objects, discerning 1.4 mm separation in the radial and 0.5-mm separation in the axial direction. The method was also better able to determine object size, resolving scatters less than 10% of wavelength associated with the center frequency.
Yoo S-S, O'Leary HM, Lee J-H, Chen N-kuei, Panych LP, Jolesz FA. Reproducibility of trial-based functional MRI on motor imagery. Int J Neurosci. 2007;117 (2) :215-27.Abstract
The investigation of the reproducibility in functional MRI (fMRI) is an important step in the quantification and analysis of paradigm-related brain activation. This article reports on reproducibility of cortical activation characterized by repeated fMRI runs (10 times) during the performance of a motor imagery and a passive auditory stimulation as a control task. Two parameters, the size of activation and BOLD signal contrast, were measured from regions-of-interest for 10 subjects across different threshold conditions. The variability of these parameters was normalized with respect to the mean obtained from 10 runs, and represented as the intrasession variability. It was found that the variability was significantly lower in the measurement of BOLD signal contrast as compared to the measurement of the size of activation. The variability of the activation volume measurement was greater in the motor imagery task than in the auditory tasks across all thresholds. This task-dependent difference was not apparent from the measurement of the BOLD signal contrast. The presence of threshold dependence in the variability measurement was also examined, but no such dependency was found. The results suggest that a measurement of BOLD signal itself is a more reliable indicator of paradigm-related brain activation during repeated fMRI scans.
DiMaio SP, Pieper S, Chinzei K, Hata N, Haker SJ, Kacher DF, Fichtinger G, Tempany CM, Kikinis R. Robot-assisted needle placement in open MRI: system architecture, integration and validation. Comput Aided Surg. 2007;12 (1) :15-24.Abstract
In prostate cancer treatment, there is a move toward targeted interventions for biopsy and therapy, which has precipitated the need for precise image-guided methods for needle placement. This paper describes an integrated system for planning and performing percutaneous procedures with robotic assistance under MRI guidance. A graphical planning interface allows the physician to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's registered pre-operative and pre-procedural MR images, immediately prior to the intervention in an open-bore MRI scanner. All image-space coordinates are automatically computed, and are used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Automatic alignment of real-time intra-operative images aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided.
McDannold N, Vykhodtseva N, Hynynen K. Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: a feasibility study. Ultrasound Med Biol. 2007;33 (4) :584-90.Abstract
We have developed a method to use low-intensity focused ultrasound pulses combined with an ultrasound contrast agent to produce temporary blood-brain barrier disruption (BBBD). This method could provide a means for the targeted delivery of drugs or imaging agents into the brain. In all our previous work, we used Optison as the ultrasound contrast agent. The purpose of this study was to test the feasibility of using the contrast agent Definity for BBBD. A total of 36 non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (four locations per rabbit; ultrasound [US] frequency: 0.69 MHz; burst: 10 ms; pulse repetition frequency (PRF): 1 Hz; duration: 20 s). The peak negative pressure amplitude ranged from 0.2 to 1.5 MPa. An additional 11 locations were sonicated using Optison at pressure amplitude of 0.5 MPa. Definity and Optison dosages were the same as those used clinically for ultrasound imaging: 10 and 50 microl/kg, respectively. The probability for BBBD (determined using MRI contrast agent enhancement) as a function of pressure amplitude was similar to that found earlier with Optison. For both agents, the probability was estimated to be 50% at 0.4 MPa using probit regression. Histologic examination revealed small, isolated areas of extravasated erythrocytes in some locations. At 0.8 MPa and higher, these areas were sometimes accompanied by tiny (dimensions of 100 microm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (signal enhancement: 13.3% +/- 4.4% vs. 8.4% +/- 4.9%; p = 0.04). In addition, more areas with extravasated erythrocytes were observed with Optison (5.0 +/- 3.5 vs. 1.4 +/- 1.9 areas with extravasation in histology section with largest effect; p = 0.03). We concluded that BBBD is possible using Definity at the dosage of contrast agent and the acoustic parameters tested in this study. The probability for BBBD as a function of pressure amplitude and the type of acute tissue effects were similar to what has been observed using Optison. However, under the experimental conditions used in this study, Optison produced a larger effect for the same acoustic pressure amplitude.
Talos I-F, Zou KH, Kikinis R, Jolesz FA. Volumetric assessment of tumor infiltration of adjacent white matter based on anatomic MRI and diffusion tensor tractography. Acad Radiol. 2007;14 (4) :431-6.Abstract
RATIONALE AND OBJECTIVES: To perform a retrospective, quantitative assessment of the anatomic relationship between intra-axial, supratentorial, primary brain tumors, and adjacent white matter fiber tracts based on anatomic and diffusion tensor magnetic resonance imaging (MRI). We hypothesized that white matter infiltration may be common among different types of tumor. MATERIAL AND METHODS: Preoperative, anatomic (T1- and T2-weighted), and LINESCAN diffusion tensor MRI were obtained in 12 patients harboring supratentorial gliomas (World Health Organization [WHO] Grades II and III). The two imaging modalities were rigidly registered. The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Statistical methods included summary statistics to examine the fraction of tumor volume infiltrating adjacent white matter. RESULTS: There were five patients with low-grade oligodendroglioma (WHO Grade II), one with low-grade mixed oligoastrocytoma (WHO Grade II), one with ganglioglioma, two with low-grade astrocytoma (WHO Grade II), and three with anaplastic astrocytoma (WHO Grade III). We identified white matter tracts infiltrated by tumor in all 12 cases. The median tumor volume (+/- standard deviation) in our patient population was 42.5 +/- 28.9 mL. The median tumor volume (+/- standard deviation) infiltrating white matter fiber tracts was 5.2 +/- 9.9 mL. The median percentage of tumor volume infiltrating white matter fiber tracts was 21.4% +/- 9.7%. CONCLUSIONS: The information provided by diffusion tensor imaging combined with anatomic MRI might be useful for neurosurgical planning and intraoperative guidance. Our results confirm previous reports that extensive white matter infiltration by primary brain tumors is a common occurrence. However, prospective, large population studies are required to definitively clarify this issue, and how infiltration relates to histologic tumor type, tumor size, and location.
Mulkern RV, Haker SJ, Maier SE. Complimentary aspects of diffusion imaging and fMRI: II. Elucidating contributions to the fMRI signal with diffusion sensitization. Magn Reson Imaging. 2007;25 (6) :939-52.Abstract
Tissue water molecules reside in different biophysical compartments. For example, water molecules in the vasculature reside for variable periods of time within arteries, arterioles, capillaries, venuoles and veins, and may be within blood cells or blood plasma. Water molecules outside of the vasculature, in the extravascular space, reside, for a time, either within cells or within the interstitial space between cells. Within these different compartments, different types of microscopic motion that water molecules may experience have been identified and discussed. These range from Brownian diffusion to more coherent flow over the time scales relevant to functional magnetic resonance imaging (fMRI) experiments, on the order of several 10s of milliseconds. How these different types of motion are reflected in magnetic resonance imaging (MRI) methods developed for "diffusion" imaging studies has been an ongoing and active area of research. Here we briefly review the ideas that have developed regarding these motions within the context of modern "diffusion" imaging techniques and, in particular, how they have been accessed in attempts to further our understanding of the various contributions to the fMRI signal changes sought in studies of human brain activation.
Von Spiczak J, Samset E, DiMaio S, Reitmayr G, Schmalstieg D, Burghart C, Kikinis R. Device connectivity for image-guided medical applications. Stud Health Technol Inform. 2007;125 :482-4.Abstract
The integration of medical devices with software applications is crucial for image-guided medical applications. This work describes a general device interface that has been designed for high-frequency streaming of multi-modal events, thus providing maximum performance and flexibility for such applications. Several sample applications and performance tests are provided to demonstrate the usability of the concept.
Mewes AUJ, Zöllei L, Hüppi PS, Als H, McAnulty GB, Inder TE, Wells WM, Warfield SK. Displacement of brain regions in preterm infants with non-synostotic dolichocephaly investigated by MRI. Neuroimage. 2007;36 (4) :1074-85.Abstract
Regional investigations of newborn MRI are important to understand the appearance and consequences of early brain injury. Previously, regionalization in neonates has been achieved with a Talairach parcellation, using internal landmarks of the brain. Non-synostotic dolichocephaly defines a bi-temporal narrowing of the preterm infant's head caused by pressure on the immature skull. The impact of dolichocephaly on brain shape and regional brain shift, which may compromise the validity of the parcellation scheme, has not yet been investigated. Twenty-four preterm and 20 fullterm infants were scanned at term equivalent. Skull shapes were investigated by cephalometric measurements and population registration. Brain tissue volumes were calculated to rule out brain injury underlying skull shape differences. The position of Talairach landmarks was evaluated. Cortical structures were segmented to determine a positional shift between both groups. The preterm group displayed dolichocephalic head shapes and had similar brain volumes compared to the mesocephalic fullterm group. In preterm infants, Talairach landmarks were consistently positioned relative to each other and to the skull base, but were displaced with regard to the calvarium. The frontal and superior region was enlarged; central and temporal gyri and sulci were shifted comparing preterm and fullterm infants. We found that, in healthy preterm infants, dolichocephaly led to a shift of cortical structures, but did not influence deep brain structures. We concluded that the validity of a Talairach parcellation scheme is compromised and may lead to a miscalculation of regional brain volumes and inconsistent parcel contents when comparing infant populations with divergent head shapes.
Nain D, Haker S, Bobick A, Tannenbaum A. Multiscale 3-D shape representation and segmentation using spherical wavelets. IEEE Trans Med Imaging. 2007;26 (4) :598-618.Abstract
This paper presents a novel multiscale shape representation and segmentation algorithm based on the spherical wavelet transform. This work is motivated by the need to compactly and accurately encode variations at multiple scales in the shape representation in order to drive the segmentation and shape analysis of deep brain structures, such as the caudate nucleus or the hippocampus. Our proposed shape representation can be optimized to compactly encode shape variations in a population at the needed scale and spatial locations, enabling the construction of more descriptive, nonglobal, nonuniform shape probability priors to be included in the segmentation and shape analysis framework. In particular, this representation addresses the shortcomings of techniques that learn a global shape prior at a single scale of analysis and cannot represent fine, local variations in a population of shapes in the presence of a limited dataset. Specifically, our technique defines a multiscale parametric model of surfaces belonging to the same population using a compact set of spherical wavelets targeted to that population. We further refine the shape representation by separating into groups wavelet coefficients that describe independent global and/or local biological variations in the population, using spectral graph partitioning. We then learn a prior probability distribution induced over each group to explicitly encode these variations at different scales and spatial locations. Based on this representation, we derive a parametric active surface evolution using the multiscale prior coefficients as parameters for our optimization procedure to naturally include the prior for segmentation. Additionally, the optimization method can be applied in a coarse-to-fine manner. We apply our algorithm to two different brain structures, the caudate nucleus and the hippocampus, of interest in the study of schizophrenia. We show: 1) a reconstruction task of a test set to validate the expressiveness of our multiscale prior and 2) a segmentation task. In the reconstruction task, our results show that for a given training set size, our algorithm significantly improves the approximation of shapes in a testing set over the Point Distribution Model, which tends to oversmooth data. In the segmentation task, our validation shows our algorithm is computationally efficient and outperforms the Active Shape Model algorithm, by capturing finer shape details.
Odille F, Pasquier C, Abächerli R, Vuissoz P-A, Zientara GP, Felblinger J. Noise cancellation signal processing method and computer system for improved real-time electrocardiogram artifact correction during MRI data acquisition. IEEE Trans Biomed Eng. 2007;54 (4) :630-40.Abstract
A system was developed for real-time electrocardiogram (ECG) analysis and artifact correction during magnetic resonance (MR) scanning, to improve patient monitoring and triggering of MR data acquisitions. Based on the assumption that artifact production by magnetic field gradient switching represents a linear time invariant process, a noise cancellation (NC) method is applied to ECG artifact linear prediction. This linear prediction is performed using a digital finite impulse response (FIR) matrix, that is computed employing ECG and gradient waveforms recorded during a training scan. The FIR filters are used during further scanning to predict artifacts by convolution of the gradient waveforms. Subtracting the artifacts from the raw ECG signal produces the correction with minimal delay. Validation of the system was performed both off-line, using prerecorded signals, and under actual examination conditions. The method is implemented using a specially designed Signal Analyzer and Event Controller (SAEC) computer and electronics. Real-time operation was demonstrated at 1 kHz with a delay of only 1 ms introduced by the processing. The system opens the possibility of automatic monitoring algorithms for electrophysiological signals in the MR environment.
Nakajima N, Wada J, Miki T, Haraoka J, Hata N. Surface rendering-based virtual intraventricular endoscopy: retrospective feasibility study and comparison to volume rendering-based approach. Neuroimage. 2007;37 Suppl 1 :S89-99.Abstract
OBJECTIVE: Virtual endoscopic simulations using volume rendering (VR) have been proposed as a tool for training and understanding intraventricular anatomy. It is not known whether surface rendering (SR), an alternative to VR, can visualize intraventricular and subependymal structures better and thus making the virtual endoscope more useful for simulating the intraventricular endoscopy. We sought to develop SR-virtual endoscopy and compared the visibility of anatomical structures in SR and VR using retrospective cases. MATERIALS AND METHODS: Fourteen patients who underwent endoscopic intraventricular surgery of third ventricle enrolled the study. SR-virtual endoscopy module was developed in open-source software 3D Slicer and virtual endoscopic scenes from the retrospective cases were created. VR virtual endoscopy of the same cases was prepared in commercial software. Three neurosurgeons scored the visibility of substructures in lateral and third ventricle, arteries, cranial nerves, and other lesions Results: We found that VR and SR-virtual endoscopy performed similarly in visualization of substructures in lateral and third ventricle (not significant statistically). However, the SR was statistically significantly better in visualizing subependymal arteries, cranial nerves, and other lesions (p<0.05, respectively). CONCLUSIONS: We concluded that SR-virtual endoscopy is a promising tool to visualize critical anatomical structures in simulated endoscopic intraventricular surgery. The results lead us to propose a hybrid technique of volume and surface rendering to balance the strength of surface rendering alone in visualizing arteries, nerves and lesions, with fast volume rendering of third and lateral ventricles.
Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer. 2007;121 (4) :901-7.Abstract
The clinical application of chemotherapy to brain tumors has been severely limited because antitumor agents are typically unable to penetrate an intact blood-brain barrier (BBB). Although doxorubicin (DOX) has been named as a strong candidate for chemotherapy of the central nervous system (CNS), the BBB often prevents cytotoxic levels from being achieved. In this study, we demonstrate a noninvasive method for the targeted delivery of DOX through the BBB, such that drug levels shown to be therapeutic in human tumors are achieved in the normal rat brain. Using MRI-guided focused ultrasound with preformed microbubbles (Optison) to locally disrupt the BBB and systemic administration of DOX, we achieved DOX concentrations of 886 +/- 327 ng/g tissue in the brain with minimal tissue effects. Tissue DOX concentrations of up to 5,366 +/- 659 ng/g tissue were achieved with higher Optison doses, but with more significant tissue damage. In contrast, DOX accumulation in nontargeted contralateral brain tissue remained significantly lower for all paired samples (p < 0.001). These results suggest that targeted delivery by focused ultrasound may render DOX chemotherapy a viable treatment option against CNS tumors, despite previous accessibility limitations. In addition, MRI signal enhancement in the sonicated region correlated strongly with tissue DOX concentration (r = 0.87), suggesting that contrast-enhanced MRI could perhaps indicate drug penetration during image-guided interventions. Our technique using MRI-guided focused ultrasound to achieve therapeutic levels of DOX in the brain offers a large step forward in the use of chemotherapy to treat patients with CNS malignancies.
Fennessy FM, Tempany CM, McDannold NJ, So MJ, Hesley G, Gostout B, Kim HS, Holland GA, Sarti DA, Hynynen K, et al. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology. 2007;243 (3) :885-93.Abstract
PURPOSE: To prospectively assess patient response (after 12 months) to magnetic resonance (MR) imaging-guided focused ultrasound surgery in treatment of uterine leiomyomas by using two treatment protocols. MATERIALS AND METHODS: This prospective clinical trial was approved by institutional review boards and was HIPAA compliant. After giving informed consent, patients with symptomatic leiomyomas were consecutively enrolled and treated at one of five U.S. centers by using an original or a modified protocol. Outcomes were assessed with the symptom severity score (SSS) obtained at baseline and 3, 6, and 12 months after treatment. Adverse events (AEs) were recorded. Statistical analysis included Student t test, Fisher exact test, analysis of covariance, Spearman correlation, and logistic regression. RESULTS: One hundred sixty patients had a mean SSS of 62.1 +/- 16.3 (standard deviation) at baseline, which decreased to 35.5 +/- 19.5 at 3 months (P<.001) and to 32.3 +/- 19.8 at 6 months (P<.001) and was 32.7 +/- 21.0 at 12 months (P<.001). Ninety-six patients (mean age, 46.0 years +/- 4.6) were treated with an original protocol, and 64 (mean age, 45.9 years +/- 3.9) were treated with a modified protocol. Patients in the modified group had a significantly greater SSS decrease at 3 months (P=.037) than those in the original group, and 73% of those in the original group and 91% of those in the modified group reported a significant decrease in SSS (of 10 points or greater) at 12 months. No serious AEs were recorded. Fewer AEs were reported in the modified group than in the original group (25% vs 13% reporting no event). Of evaluable patients, fewer in the modified group chose alternative treatment (28%) than in the original group (37%). CONCLUSION: MR imaging-guided focused ultrasound surgery results in symptomatic improvement, sustained to 12 months after treatment. Treatment with a modified protocol results in greater clinical effectiveness and fewer AEs.
Pohl KM, Kikinis R, Wells WM. Active mean fields: solving the mean field approximation in the level set framework. Inf Process Med Imaging. 2007;20 :26-37.Abstract
We describe a new approach for estimating the posterior probability of tissue labels. Conventional likelihood models are combined with a curve length prior on boundaries, and an approximate posterior distribution on labels is sought via the Mean Field approach. Optimizing the resulting estimator by gradient descent leads to a level set style algorithm where the level set functions are the logarithm-of-odds encoding of the posterior label probabilities in an unconstrained linear vector space. Applications with more than two labels are easily accommodated. The label assignment is accomplished by the Maximum A Posteriori rule, so there are no problems of "overlap" or "vacuum". We test the method on synthetic images with additive noise. In addition, we segment a magnetic resonance scan into the major brain compartments and subcortical structures.
Sassaroli E, Hynynen K. Cavitation threshold of microbubbles in gel tunnels by focused ultrasound. Ultrasound Med Biol. 2007;33 (10) :1651-60.Abstract
The investigation of inertial cavitation in micro-tunnels has significant implications for the development of therapeutic applications of ultrasound such as ultrasound-mediated drug and gene delivery. The threshold for inertial cavitation was investigated using a passive cavitation detector with a center frequency of 1 MHz. Micro-tunnels of various diameters (90 to 800 microm) embedded in gel were fabricated and injected with a solution of Optison(trade mark) contrast agent of concentrations 1.2% and 0.2% diluted in water. An ultrasound pulse of duration 500 ms and center frequency 1.736 MHz was used to insonate the microbubbles. The acoustic pressure was increased at 1-s intervals until broadband noise emission was detected. The pressure threshold at which broadband noise emission was observed was found to be dependent on the diameter of the micro-tunnels, with an average increase of 1.2 to 1.5 between the smallest and the largest tunnels, depending on the microbubble concentration. The evaluation of inertial cavitation in gel tunnels rather than tubes provides a novel opportunity to investigate microbubble collapse in a situation that simulates in vivo blood vessels better than tubes with solid walls do.

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