Publications

2007
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.
Hynynen K, Clement G. Clinical applications of focused ultrasound-the brain. Int J Hyperthermia. 2007;23 (2) :193-202.Abstract
This paper provides a historic and contemporary overview of the use of focused ultrasound for treating brain disorders.
Dauguet J, Peled S, Berezovskii V, Delzescaux T, Warfield SK, Born R, Westin C-F. Comparison of fiber tracts derived from in-vivo DTI tractography with 3D histological neural tract tracer reconstruction on a macaque brain. Neuroimage. 2007;37 (2) :530-8.Abstract
Since the introduction of diffusion weighted imaging (DWI) as a method for examining neural connectivity, its accuracy has not been formally evaluated. In this study, we directly compared connections that were visualized using injected neural tract tracers (WGA-HRP) with those obtained using in-vivo diffusion tensor imaging (DTI) tractography. First, we injected the tracer at multiple sites in the brain of a macaque monkey; second, we reconstructed the histological sections of the labeled fiber tracts in 3D; third, we segmented and registered the fibers (somatosensory and motor tracts) with the anatomical in-vivo MRI from the same animal; and last, we conducted fiber tracing along the same pathways on the DTI data using a classical diffusion tracing technique with the injection sites as seeds. To evaluate the performance of DTI fiber tracing, we compared the fibers derived from the DTI tractography with those segmented from the histology. We also studied the influence of the parameters controlling the tractography by comparing Dice superimposition coefficients between histology and DTI segmentations. While there was generally good visual agreement between the two methods, our quantitative comparisons reveal certain limitations of DTI tractography, particularly for regions at remote locations from seeds. We have thus demonstrated the importance of appropriate settings for realistic tractography results.
Zöllei L, Jenkinson M, Timoner S, Wells W. A marginalized MAP approach and EM optimization for pair-wise registration. Inf Process Med Imaging. 2007;20 :662-74.Abstract
We formalize the pair-wise registration problem in a maximum a posteriori (MAP) framework that employs a multinomial model of joint intensities with parameters for which we only have a prior distribution. To obtain an MAP estimate of the aligning transformation alone, we treat the multinomial parameters as nuisance parameters, and marginalize them out. If the prior on those is uninformative, the marginalization leads to registration by minimization of joint entropy. With an informative prior, the marginalization leads to minimization of the entropy of the data pooled with pseudo observations from the prior. In addition, we show that the marginalized objective function can be optimized by the Expectation-Maximization (EM) algorithm, which yields a simple and effective iteration for solving entropy-based registration problems. Experimentally, we demonstrate the effectiveness of the resulting EM iteration for rapidly solving a challenging intra-operative registration problem.
Petrovich Brennan NM, Whalen S, de Morales Branco D, O'shea JP, Norton IH, Golby AJ. Object naming is a more sensitive measure of speech localization than number counting: Converging evidence from direct cortical stimulation and fMRI. Neuroimage. 2007;37 Suppl 1 :S100-8.Abstract
Using direct cortical stimulation to map language function during awake craniotomy is a well-described and useful technique. However, the optimum neuropsychological tasks to use have not been detailed. We used both functional MRI (fMRI) and direct cortical stimulation to compare the sensitivity of two behavioral paradigms, number counting and object naming, in the demonstration of eloquent cortical language areas. Fifteen patients with left hemisphere lesions and seven healthy control subjects participated. Patients had both preoperative fMRI at 3 T and direct cortical stimulation. Patients and controls performed object naming and number counting during fMRI at 3 T. Laterality indices were calculated from the fMRI maps for the Number-counting>Object-naming and Object-naming>Number-counting contrasts. The same number-counting and object-naming paradigms were tested during awake craniotomy and assessed for sensitivity to speech disruption. In all patients during intraoperative cortical stimulation, speech disruption occurred at more sites during object naming than during number counting. Subtle speech errors were only elicited with the object-naming paradigm, whereas only speech arrest and/or hypophonia were measured using the number counting paradigm. In both patients and controls, fMRI activation maps demonstrated greater left lateralization for object naming as compared to number counting in both frontal and temporal language areas. Number counting resulted in a more bihemispheric distribution of activations than object naming. Both cortical stimulation testing and fMRI suggest that automated speech tasks such as number counting may not fully engage putative language networks and therefore are not optimal for language localization for surgical planning.
Maddah M, Wells WM, Warfield SK, Westin C-F, Grimson EWL. Probabilistic clustering and quantitative analysis of white matter fiber tracts. Inf Process Med Imaging. 2007;20 :372-83.Abstract
A novel framework for joint clustering and point-by-point mapping of white matter fiber pathways is presented. Accurate clustering of the trajectories into fiber bundles requires point correspondence determined along the fiber pathways. This knowledge is 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, and point correspondences along the trajectories. 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. Probabilistic assignment of the trajectories to clusters is controlled by imposing a minimum threshold on the membership probabilities, to remove outliers in a principled way. The presented results confirm the efficiency and effectiveness of the proposed framework for quantitative analysis of diffusion tensor MRI.
Kindlmann G, Tricoche X, Westin C-F. Delineating white matter structure in diffusion tensor MRI with anisotropy creases. Med Image Anal. 2007;11 (5) :492-502.Abstract
Geometric models of white matter architecture play an increasing role in neuroscientific applications of diffusion tensor imaging, and the most popular method for building them is fiber tractography. For some analysis tasks, however, a compelling alternative may be found in the first and second derivatives of diffusion anisotropy. We extend to tensor fields the notion from classical computer vision of ridges and valleys, and define anisotropy creases as features of locally extremal tensor anisotropy. Mathematically, these are the loci where the gradient of anisotropy is orthogonal to one or more eigenvectors of its Hessian. We propose that anisotropy creases provide a basis for extracting a skeleton of the major white matter pathways, in that ridges of anisotropy coincide with interiors of fiber tracts, and valleys of anisotropy coincide with the interfaces between adjacent but distinctly oriented tracts. The crease extraction algorithm we present generates high-quality polygonal models of crease surfaces, which are further simplified by connected-component analysis. We demonstrate anisotropy creases on measured diffusion MRI data, and visualize them in combination with tractography to confirm their anatomic relevance.
Honda Y, Hata N. Dynamic imaging of swallowing in a seated position using open-configuration MRI. J Magn Reson Imaging. 2007;26 (1) :172-6.Abstract
PURPOSE: To assess the feasibility of dynamic MRI of swallowing in a seated position using an open-configuration MRI scanner, and to compare its capacity for motion analysis around the pharyngeal wall with that of videofluorography. MATERIALS AND METHODS: Six healthy individuals (four women and two men, mean age = 31.4 +/- 7.5 years) were examined with an open-configuration MRI system using a fast spoiled gradient-recalled echo (SPGR) sequence. Dynamic imaging was performed while the subjects were in a seated position after they swallowed oral contrast medium from a cup. An oral and maxillofacial radiologist measured the motion of six structures: the hyoid bone (HB), larynx (LX), upper oropharynx (UOP), lower oropharynx (LOP), pharyngoesophageal segment (PES) behind the vocal folds, and upper esophagus (ESO). The measured motions were compared with reported values from videofluorography-based observations. RESULTS: Open-configuration MRI depicted the anatomic structures related to swallowing (lip, tongue, soft palate, mandible, pharynx, HB, LX, and PES), and the course of the mylohyoid muscle (MM). The vertical and anteroposterior displacements of these structures did not differ significantly from those measured by videofluorography. CONCLUSION: Dynamic imaging of swallowing using open-configuration MRI provides image information comparable to that obtained from videofluorography.
Lokken PR, Gervais DA, Arellano RS, Tuncali K, Morrison PR, Tatli S, Mueller PR, Silverman SG. Inflammatory nodules mimic applicator track seeding after percutaneous ablation of renal tumors. AJR Am J Roentgenol. 2007;189 (4) :845-8.Abstract
OBJECTIVE: The objective of our study was to report the occurrence of benign inflammatory nodules that develop in or near applicator tracks after percutaneous radiofrequency ablation and cryoablation of renal tumors. CONCLUSION: Benign inflammatory nodules occur rarely after percutaneous ablation of renal tumors and may mimic tumor seeding of the applicator track.
Pohl KM, Fisher J, Bouix S, Shenton M, McCarley RW, Grimson EWL, Kikinis R, Wells WM. Using the logarithm of odds to define a vector space on probabilistic atlases. Med Image Anal. 2007;11 (5) :465-77.Abstract
The logarithm of the odds ratio (LogOdds) is frequently used in areas such as artificial neural networks, economics, and biology, as an alternative representation of probabilities. Here, we use LogOdds to place probabilistic atlases in a linear vector space. This representation has several useful properties for medical imaging. For example, it not only encodes the shape of multiple anatomical structures but also captures some information concerning uncertainty. We demonstrate that the resulting vector space operations of addition and scalar multiplication have natural probabilistic interpretations. We discuss several examples for placing label maps into the space of LogOdds. First, we relate signed distance maps, a widely used implicit shape representation, to LogOdds and compare it to an alternative that is based on smoothing by spatial Gaussians. We find that the LogOdds approach better preserves shapes in a complex multiple object setting. In the second example, we capture the uncertainty of boundary locations by mapping multiple label maps of the same object into the LogOdds space. Third, we define a framework for non-convex interpolations among atlases that capture different time points in the aging process of a population. We evaluate the accuracy of our representation by generating a deformable shape atlas that captures the variations of anatomical shapes across a population. The deformable atlas is the result of a principal component analysis within the LogOdds space. This atlas is integrated into an existing segmentation approach for MR images. We compare the performance of the resulting implementation in segmenting 20 test cases to a similar approach that uses a more standard shape model that is based on signed distance maps. On this data set, the Bayesian classification model with our new representation outperformed the other approaches in segmenting subcortical structures.
Archip N, Jolesz FA, Warfield SK. A validation framework for brain tumor segmentation. Acad Radiol. 2007;14 (10) :1242-51.Abstract
RATIONALE AND OBJECTIVES: We introduce a validation framework for the segmentation of brain tumors from magnetic resonance (MR) images. A novel unsupervised semiautomatic brain tumor segmentation algorithm is also presented. MATERIALS AND METHODS: The proposed framework consists of 1) T1-weighted MR images of patients with brain tumors, 2) segmentation of brain tumors performed by four independent experts, 3) segmentation of brain tumors generated by a semiautomatic algorithm, and 4) a software tool that estimates the performance of segmentation algorithms. RESULTS: We demonstrate the validation of the novel segmentation algorithm within the proposed framework. We show its performance and compare it with existent segmentation. The image datasets and software are available at http://www.brain-tumor-repository.org/. CONCLUSIONS: We present an Internet resource that provides access to MR brain tumor image data and segmentation that can be openly used by the research community. Its purpose is to encourage the development and evaluation of segmentation methods by providing raw test and image data, human expert segmentation results, and methods for comparing segmentation results.
O'Donnell LJ, Westin C-F. Automatic tractography segmentation using a high-dimensional white matter atlas. IEEE Trans Med Imaging. 2007;26 (11) :1562-75.Abstract
We propose a new white matter atlas creation method that learns a model of the common white matter structures present in a group of subjects. We demonstrate that our atlas creation method, which is based on group spectral clustering of tractography, discovers structures corresponding to expected white matter anatomy such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate fasciculus, and corona radiata. The white matter clusters are augmented with expert anatomical labels and stored in a new type of atlas that we call a high-dimensional white matter atlas. We then show how to perform automatic segmentation of tractography from novel subjects by extending the spectral clustering solution, stored in the atlas, using the Nystrom method. We present results regarding the stability of our method and parameter choices. Finally we give results from an atlas creation and automatic segmentation experiment. We demonstrate that our automatic tractography segmentation identifies corresponding white matter regions across hemispheres and across subjects, enabling group comparison of white matter anatomy.
Lesniak J, Tokuda J, Kikinis R, Burghart C, Hata N. A device guidance method for organ motion compensation in MRI-guided therapy. Phys Med Biol. 2007;52 (21) :6427-38.Abstract
Organ motion compensation in image-guided therapy is an active area of research. However, there has been little research on motion tracking and compensation in magnetic resonance imaging (MRI)-guided therapy. In this paper, we present a method to track a moving organ in MRI and control an active mechanical device for motion compensation. The method proposed is based on MRI navigator echo tracking enhanced by Kalman filtering for noise robustness. We also developed an extrapolation scheme to resolve any discrepancies between tracking and device control sampling rates. The algorithm was tested in a simulation study using a phantom and an active mechanical tool holder. We found that the method is feasible to use in a clinical MRI scanner with sufficient accuracy (0.36 mm to 1.51 mm depending on the range of phantom motion) and is robust to noise. The method proposed may be useful in MRI-guided targeted therapy, such as focused ultrasound therapy for a moving organ.
Kindlmann G, Ennis DB, Whitaker RT, Westin C-F. Diffusion tensor analysis with invariant gradients and rotation tangents. IEEE Trans Med Imaging. 2007;26 (11) :1483-99.Abstract
Guided by empirically established connections between clinically important tissue properties and diffusion tensor parameters, we introduce a framework for decomposing variations in diffusion tensors into changes in shape and orientation. Tensor shape and orientation both have three degrees-of-freedom, spanned by invariant gradients and rotation tangents, respectively. As an initial demonstration of the framework, we create a tunable measure of tensor difference that can selectively respond to shape and orientation. Second, to analyze the spatial gradient in a tensor volume (a third-order tensor), our framework generates edge strength measures that can discriminate between different neuroanatomical boundaries, as well as creating a novel detector of white matter tracts that are adjacent yet distinctly oriented. Finally, we apply the framework to decompose the fourth-order diffusion covariance tensor into individual and aggregate measures of shape and orientation covariance, including a direct approximation for the variance of tensor invariants such as fractional anisotropy.
Yoo S-S, Lee J-H, O'Leary H, Lee V, Choo S-E, Jolesz FA. Functional magnetic resonance imaging-mediated learning of increased activity in auditory areas. Neuroreport. 2007;18 (18) :1915-20.Abstract
Our earlier study indicated that functional magnetic resonance imaging (fMRI)-based detection and feedback of regional cortical activity from the auditory area enabled a group of individuals to increase the level of activation mediated by auditory attention during sound stimulation. The long-term ability to maintain an increased level of cortical activation, extending to a time period of a few weeks, however, has not been investigated. We used real-time fMRI to confirm the utility of fMRI in forming a basis for the regulation of brain function to increase the activation in the auditory areas, and demonstrated that the learned ability could be retained after a 2-week period, with additional involvement of an attention-related neural network.

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