Publications

2007
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.
Tang AM, Kacher DF, Lam EY, Brodsky M, Jolesz FA, Yang ES. Multimodal imaging: simultaneous MRI and ultrasound imaging for carotid arteries visualization. Conf Proc IEEE Eng Med Biol Soc. 2007;2007 :2603-6.Abstract
The purpose of this study is to examine the feasibility of simultaneous Magnetic Resonance Imaging (MRI) and Ultrasound (US) imaging in visualizing anatomical structures and functions in human carotid arteries. US has high frame rate in visualizing dynamic changes while high resolution MRI is capable of capturing volumetric structures with the best tissue contrast. Concurrent multi-modal image acquisition allows fusion of US Doppler flow measurement with volumetric MRI. We present a method for acquiring MR images in a known orientation with respect to US image by passive fiducial tracking and demonstrate concurrent real-time imaging in the right Common Carotid Artery (CCA) in both modalities. Preliminary results suggest that US and MRI can operate concurrently with proper shielding. Dispensability measurements are feasible on both modalities at the co-incident plane.
Peled S. New perspectives on the sources of white matter DTI signal. IEEE Trans Med Imaging. 2007;26 (11) :1448-55.Abstract
A minimalist numerical model of white matter is presented, the objective of which is to help provide a biological basis for improved diffusion tensor imaging (DTI) analysis. Water diffuses, relaxes, and exchanges in three compartments-intracellular, extracellular, and myelin sheath. Exchange between compartments is defined so as to depend on the diffusion coefficients and the compartment sizes. Based on the model, it is proposed that an additive "baseline tensor" that correlates with intraaxonal water volume be included in the computation. Anisotropy and tortuosity calculated from such analysis may correspond better to tract ultrastructure than if calculated without the baseline. According to the model, reduced extracellular volume causes increased baseline and reduced apparent diffusion. Depending on the pulse sequence, reduced permeability can cause an increase in both the baseline and apparent diffusion.
O'Donnell LJ, Westin C-F, Golby AJ. Tract-based morphometry. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :161-8.Abstract
Multisubject statistical analyses of diffusion tensor images in regions of specific white matter tracts have commonly measured only the mean value of a scalar invariant such as the fractional anisotropy (FA), ignoring the spatial variation of FA along the length of fiber tracts. We propose to instead perform tract-based morphometry (TBM), or the statistical analysis of diffusion MRI data in an anatomical tract-based coordinate system. We present a method for automatic generation of white matter tract arc length parameterizations, based on learning a fiber bundle model from tractography from multiple subjects. Our tract-based coordinate system enables TBM for the detection of white matter differences in groups of subjects. We present example TBM results from a study of interhemispheric differences in FA.
Kindlmann G, San José Estépar R, Niethammer M, Haker S, Westin C-F. Geodesic-loxodromes for diffusion tensor interpolation and difference measurement. Med Image Comput Comput Assist Interv. 2007;10 (Pt 1) :1-9.Abstract
In algorithms for processing diffusion tensor images, two common ingredients are interpolating tensors, and measuring the distance between them. We propose a new class of interpolation paths for tensors, termed geodesic-loxodromes, which explicitly preserve clinically important tensor attributes, such as mean diffusivity or fractional anisotropy, while using basic differential geometry to interpolate tensor orientation. This contrasts with previous Riemannian and Log-Euclidean methods that preserve the determinant. Path integrals of tangents of geodesic-loxodromes generate novel measures of over-all difference between two tensors, and of difference in shape and in orientation.
Fan AC, Fisher JW, Wells WM, Levitt JJ, Willsky AS. MCMC curve sampling for image segmentation. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :477-85.Abstract
We present an algorithm to generate samples from probability distributions on the space of curves. We view a traditional curve evolution energy functional as a negative log probability distribution and sample from it using a Markov chain Monte Carlo (MCMC) algorithm. We define a proposal distribution by generating smooth perturbations to the normal of the curve and show how to compute the transition probabilities to ensure that the samples come from the posterior distribution. We demonstrate some advantages of sampling methods such as robustness to local minima, better characterization of multi-modal distributions, access to some measures of estimation error, and ability to easily incorporate constraints on the curve.
White PJ, Clement GT. Two-dimensional localization with a single diffuse ultrasound field excitation. IEEE Trans Ultrason Ferroelectr Freq Control. 2007;54 (11) :2309-17.Abstract
Traditional ultrasound imaging methods rely on the bandwidth and center frequency of transduction to achieve axial and radial image resolution, respectively. In this study, a new modality for spatially localizing scattering targets in a two-dimensional field is presented. In this method, the bandwidth of field excitation is high, and the center frequency is lowered such that the corresponding wavelengths are substantially larger than the target profiles. Furthermore, full two-dimensional field measurements are obtained with single send-receive sequences, demonstrating a substantial simplification of the traditional scanning techniques. Field reconstruction is based on temporal-spectral cross-correlations between measured backscatter data and a library of region of interest (ROI) backscatter data measured a priori. The transducer design is based upon a wedge-shaped geometry, which was shown to yield spatially frequency-separated bandwidths of up to 156% with center frequencies of 1.38 MHz. Initial results with these send-and-receive transducer parameters and cylindrical reflection targets in a 10-mm x 10-mm ROI demonstrate two-dimensional target localization to within 0.5 mm. Spatial localization of point scatterers is demonstrated for single and multiple scattering sites.
Hata N, Piper S, Jolesz FA, Tempany CM, Black PM, Morikawa S, Iseki H, Hashizume M, Kikinis R. Application of open source image guided therapy software in MR-guided therapies. Med Image Comput Comput Assist Interv. 2007;10 (Pt 1) :491-8.Abstract

We present software engineering methods to provide free open-source software for MR-guided therapy. We report that graphical representation of the surgical tools, interconnectively with the tracking device, patient-to-image registration, and MRI-based thermal mapping are crucial components of MR-guided therapy in sharing such software. Software process includes a network-based distribution mechanism by multi-platform compiling tool CMake, CVS, quality assurance software DART. We developed six procedures in four separate clinical sites using proposed software engineering and process, and found the proposed method is feasible to facilitate multicenter clinical trial of MR-guided therapies. Our future studies include use of the software in non-MR-guided therapies.

DiMaio S, Kapur T, Cleary K, Aylward S, Kazanzides P, Vosburgh KG, Ellis R, Duncan J, Farahani K, Lemke H, et al. Challenges in image-guided therapy system design. Neuroimage. 2007;37 Suppl 1 :S144-51.Abstract

System development for image-guided therapy (IGT), or image-guided interventions (IGI), continues to be an area of active interest across academic and industry groups. This is an emerging field that is growing rapidly: major academic institutions and medical device manufacturers have produced IGT technologies that are in routine clinical use, dozens of high-impact publications are published in well regarded journals each year, and several small companies have successfully commercialized sophisticated IGT systems. In meetings between IGT investigators over the last two years, a consensus has emerged that several key areas must be addressed collaboratively by the community to reach the next level of impact and efficiency in IGT research and development to improve patient care. These meetings culminated in a two-day workshop that brought together several academic and industrial leaders in the field today. The goals of the workshop were to identify gaps in the engineering infrastructure available to IGT researchers, develop the role of research funding agencies and the recently established US-based National Center for Image Guided Therapy (NCIGT), and ultimately to facilitate the transfer of technology among research centers that are sponsored by the National Institutes of Health (NIH). Workshop discussions spanned many of the current challenges in the development and deployment of new IGT systems. Key challenges were identified in a number of areas, including: validation standards; workflows, use-cases, and application requirements; component reusability; and device interface standards. This report elaborates on these key points and proposes research challenges that are to be addressed by a joint effort between academic, industry, and NIH participants.

Tang SC, Clement GT, Hynynen K. A Computer-controlled Ultrasound Pulser-receiver System for Transkull Fluid Detection using a Shear Wave Transmission Technique. IEEE Trans Ultrason Ferroelectr Freq Control. 2007;54 (9) :1772-83.Abstract

The purpose of this study was to evaluate the performance of a computer-controlled ultrasound pulser-receiver system incorporating a shear mode technique for transskull fluid detection. The presence of fluid in the sinuses of an ex vivo human skull was examined using a pulse-echo method by transmitting an ultrasound beam through the maxilla bone toward the back wall on the other side of the sinus cavity. The pulser was programmed to generate bipolar pulse trains with 5 cycles at a frequency of 1 MHz, repetition frequency of about 20 Hz, and amplitude of 100 V to drive a 1-MHz piezoelectric transducer. Shear and longitudinal waves in the maxilla bone were produced by adjusting the bone surface incident angle to 45 degrees and 0 degrees, respectively. Computer tomography (CT) scans of the skull were performed to verify the ultrasound experiment. Using the shear mode technique, the echo waveform clearly distinguishes the presence of fluid, and the estimated distance of the ultrasound traveled in the sinus is consistent with the measurement from the CT images. Contrarily, using the longitudinal mode, no detectable back wall echo was observed under the same conditions. As a conclusion, this study demonstrated that the proposed pulser-receiver system with the shear mode technique is promising for transskull fluid detecting, such as mucus in a sinus.

DiMaio SP, Samset E, Fischer G, Iordachita I, Fichtinger G, Jolesz FA, Tempany CM. Dynamic MRI scan plane control for passive tracking of instruments and devices. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :50-8.Abstract

This paper describes a novel image-based method for tracking robotic mechanisms and interventional devices during Magnetic Resonance Image (MRI)-guided procedures. It takes advantage of the multi-planar imaging capabilities of MRI to optimally image a set of localizing fiducials for passive motion tracking in the image coordinate frame. The imaging system is servoed to adaptively position the scan plane based on automatic detection and localization of fiducial artifacts directly from the acquired image stream. This closed-loop control system has been implemented using an open-source software framework and currently operates with GE MRI scanners. Accuracy and performance were evaluated in experiments, the results of which are presented here.

Tharin S, Golby AJ. Functional brain mapping and its applications to neurosurgery. Neurosurgery. 2007;60 (4 Suppl 2) :185-201; discussion 201-2.Abstract

Functional brain mapping may be useful for both preoperative planning and intraoperative neurosurgical decision making. "Gold standard" functional studies such as direct electrical stimulation and recording are complemented by newer, less invasive techniques such as functional magnetic resonance imaging. Less invasive techniques allow more areas of the brain to be mapped in more subjects (including healthy subjects) more often (including pre- and postoperatively). Expansion of the armamentarium of tools allows convergent evidence from multiple brain mapping techniques to bear on pre- and intraoperative decision making. Functional imaging techniques are used to map motor, sensory, language, and memory areas in neurosurgical patients with conditions as diverse as brain tumors, vascular lesions, and epilepsy. In the future, coregistration of high resolution anatomic and physiological data from multiple complementary sources will be used to plan more neurosurgical procedures, including minimally invasive procedures. Along the way, new insights on fundamental processes such as the biology of tumors and brain plasticity are likely to be revealed.

Yoo S-S, Gujar N, Hu P, Jolesz FA, Walker MP. The Human Emotional Brain without Sleep - A Prefrontal Amygdala Disconnect. Curr Biol. 2007;17 (20) :R877-8.
Nguyen PL, Chen M-H, D'Amico AV, Tempany CM, Steele GS, Albert M, Cormack RA, Carr-Locke DL, Bleday R, Suh WW. Magnetic Resonance Image-guided Salvage Brachytherapy after Radiation in Select Men who Initially Presented with Favorable-risk Prostate Cancer: A Prospective Phase 2 Study. Cancer. 2007;110 (7) :1485-92.Abstract

BACKGROUND: The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate-specific antigen (PSA) control of magnetic resonance imaging (MRI)-guided brachytherapy used as salvage for radiation therapy (RT) failure. METHODS: From October 2000 to October 2005, 25 men with a rising PSA level and biopsy-proven, intraprostatic cancer at least 2 years after initial RT (external beam in 13 men and brachytherapy in 12 men) who had favorable clinical features (Gleason score < or =7, PSA < 10 ng/mL, negative pelvic and bone imaging studies), received MRI-guided salvage brachytherapy to a minimum peripheral dose of 137 gray on a phase 1/2 protocol. Estimates of toxicity and cancer control were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 47 months. The 4-year estimate of grade 3 or 4 GI or GU toxicity was 30%, and 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval < 4.5 years between RT courses was associated with both outcomes with a hazard ratio of 12 (95% confidence interval [95% CI], 1.4-100; P = .02) for grade 3 or 4 toxicity and 25 (95% CI, 1.1-529; P = .04) for colostomy and/or urostomy. PSA control (nadir +2 definition) was 70% at 4 years. CONCLUSIONS: The current results indicated that MRI-guided salvage brachytherapy in men who are selected based on presenting characteristics and post-failure PSA kinetics can achieve high PSA control rates, although complications requiring surgical intervention may occur in 10% to 15% of patients. Prospective randomized studies are needed to characterize the relative cancer control and toxicity after all forms of salvage local therapy.

Archip N, Clatz O, Whalen S, Kacher D, Fedorov A, Kot A, Chrisochoides N, Jolesz FA, Golby AJ, Black PM, et al. Non-rigid alignment of pre-operative MRI, fMRI, and DT-MRI with intra-operative MRI for enhanced visualization and navigation in image-guided neurosurgery. Neuroimage. 2007;35 (2) :609-24.Abstract

OBJECTIVE: The usefulness of neurosurgical navigation with current visualizations is seriously compromised by brain shift, which inevitably occurs during the course of the operation, significantly degrading the precise alignment between the pre-operative MR data and the intra-operative shape of the brain. Our objectives were (i) to evaluate the feasibility of non-rigid registration that compensates for the brain deformations within the time constraints imposed by neurosurgery, and (ii) to create augmented reality visualizations of critical structural and functional brain regions during neurosurgery using pre-operatively acquired fMRI and DT-MRI. MATERIALS AND METHODS: Eleven consecutive patients with supratentorial gliomas were included in our study. All underwent surgery at our intra-operative MR imaging-guided therapy facility and have tumors in eloquent brain areas (e.g. precentral gyrus and cortico-spinal tract). Functional MRI and DT-MRI, together with MPRAGE and T2w structural MRI were acquired at 3 T prior to surgery. SPGR and T2w images were acquired with a 0.5 T magnet during each procedure. Quantitative assessment of the alignment accuracy was carried out and compared with current state-of-the-art systems based only on rigid registration. RESULTS: Alignment between pre-operative and intra-operative datasets was successfully carried out during surgery for all patients. Overall, the mean residual displacement remaining after non-rigid registration was 1.82 mm. There is a statistically significant improvement in alignment accuracy utilizing our non-rigid registration in comparison to the currently used technology (p<0.001). CONCLUSIONS: We were able to achieve intra-operative rigid and non-rigid registration of (1) pre-operative structural MRI with intra-operative T1w MRI; (2) pre-operative fMRI with intra-operative T1w MRI, and (3) pre-operative DT-MRI with intra-operative T1w MRI. The registration algorithms as implemented were sufficiently robust and rapid to meet the hard real-time constraints of intra-operative surgical decision making. The validation experiments demonstrate that we can accurately compensate for the deformation of the brain and thus can construct an augmented reality visualization to aid the surgeon.

Archip N, Tatli S, Morrison P, Jolesz FA, Warfield SK, Silverman S. Non-rigid registration of pre-procedural MR images with intra-procedural unenhanced CT images for improved targeting of tumors during liver radiofrequency ablations. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :969-77.Abstract

In the United States, unenhanced CT is currently the most common imaging modality used to guide percutaneous biopsy and tumor ablation. The majority of liver tumors such as hepatocellular carcinomas are visible on contrast-enhanced CT or MRI obtained prior to the procedure. Yet, these tumors may not be visible or may have poor margin conspicuity on unenhanced CT images acquired during the procedure. Non-rigid registration has been used to align images accurately, even in the presence of organ motion. However, to date, it has not been used clinically for radiofrequency ablation (RFA), since it requires significant computational infrastructure and often these methods are not sufficient robust. We have already introduced a novel finite element based method (FEM) that is demonstrated to achieve good accuracy and robustness for the problem of brain shift in neurosurgery. In this current study, we adapt it to fuse pre-procedural MRI with intra-procedural CT of liver. We also compare its performance with conventional rigid registration and two non-rigid registration methods: b-spline and demons on 13 retrospective datasets from patients that underwent RFA at our institution. FEM non-rigid registration technique was significantly better than rigid (p < 10-5), non-rigid b-spline (p < 10-4) and demons (p < 10-4) registration techniques. The results of our study indicate that this novel technology may be used to optimize placement of RF applicator during CT-guided ablations.

Sierra R, DiMaio SP, Wada J, Hata N, Székely G, Kikinis R, Jolesz FA. Patient specific simulation and navigation of ventriculoscopic interventions. Stud Health Technol Inform. 2007;125 :433-5.Abstract

In this paper a comprehensive framework for pre-operative planning, procedural skill training, and intraoperative navigation is presented. The goal of this system is to integrate surgical simulation with surgical planning in order to improve the individual treatment of patients. Various surgical approaches and new, more complex procedures can be assessed using a safe and objective platform that will allow the physicians to explore and discuss possible risks and benefits prior to the intervention. A simulation environment extends the pre-operative planning in a natural way, as it allows for direct evaluation of the surgical approach envisioned for each case. In addition, by providing intraoperative navigation based on this simulation, surgeons can carry out the previously optimized plan with higher precision and greater confidence.

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