Publications

2008
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.
Wang M, Rohling R, Duzenli C, Clark B, Archip N. Evaluation of targeting errors in ultrasound-assisted radiotherapy. Ultrasound Med Biol. 2008;34 (12) :1944-56.Abstract
A method for validating the start-to-end accuracy of a 3-D ultrasound (US)-based patient positioning system for radiotherapy is described. A radiosensitive polymer gel is used to record the actual dose delivered to a rigid phantom after being positioned using 3-D US guidance. Comparison of the delivered dose with the treatment plan allows accuracy of the entire radiotherapy treatment process, from simulation to 3-D US guidance, and finally delivery of radiation, to be evaluated. The 3-D US patient positioning system has a number of features for achieving high accuracy and reducing operator dependence. These include using tracked 3-D US scans of the target anatomy acquired using a dedicated 3-D ultrasound probe during both the simulation and treatment sessions, automatic 3-D US-to-US registration and use of infrared LED (IRED) markers of the optical position-sensing system for registering simulation computed tomography to US data. The mean target localization accuracy of this system was 2.5 mm for four target locations inside the phantom, compared with 1.6 mm obtained using the conventional patient positioning method of laser alignment. Because the phantom is rigid, this represents the best possible set-up accuracy of the system. Thus, these results suggest that 3-D US-based target localization is practically feasible and potentially capable of increasing the accuracy of patient positioning for radiotherapy in sites where day-to-day organ shifts are greater than 1 mm in magnitude.
Xia T, Baird C, Jallo G, Hayes K, Nakajima N, Hata N, Kazanzides P. An integrated system for planning, navigation and robotic assistance for skull base surgery. Int J Med Robot. 2008;4 (4) :321-30.Abstract
BACKGROUND: We developed an image-guided robot system to provide mechanical assistance for skull base drilling, which is performed to gain access for some neurosurgical interventions, such as tumour resection. The motivation for introducing this robot was to improve safety by preventing the surgeon from accidentally damaging critical neurovascular structures during the drilling procedure. METHODS: We integrated a Stealthstation navigation system, a NeuroMate robotic arm with a six-degree-of-freedom force sensor, and the 3D Slicer visualization software to allow the robotic arm to be used in a navigated, cooperatively-controlled fashion by the surgeon. We employed virtual fixtures to constrain the motion of the robot-held cutting tool, so that it remained in the safe zone that was defined on a preoperative CT scan. RESULTS: We performed experiments on both foam skull and cadaver heads. The results for foam blocks cut using different registrations yielded an average placement error of 0.6 mm and an average dimensional error of 0.6 mm. We drilled the posterior porus acusticus in three cadaver heads and concluded that the robot-assisted procedure is clinically feasible and provides some ergonomic benefits, such as stabilizing the drill. We obtained postoperative CT scans of the cadaver heads to assess the accuracy and found that some bone outside the virtual fixture boundary was cut. The typical overcut was 1-2 mm, with a maximum overcut of about 3 mm. CONCLUSIONS: The image-guided cooperatively-controlled robot system can improve the safety and ergonomics of skull base drilling by stabilizing the drill and enforcing virtual fixtures to protect critical neurovascular structures. The next step is to improve the accuracy so that the overcut can be reduced to a more clinically acceptable value of about 1 mm.
McDannold N, Maier SE. Magnetic resonance acoustic radiation force imaging. Med Phys. 2008;35 (8) :3748-58.Abstract
Acoustic radiation force impulse imaging is an elastography method developed for ultrasound imaging that maps displacements produced by focused ultrasound pulses systematically applied to different locations. The resulting images are "stiffness weighted" and yield information about local mechanical tissue properties. Here, the feasibility of magnetic resonance acoustic radiation force imaging (MR-ARFI) was tested. Quasistatic MR elastography was used to measure focal displacements using a one-dimensional MRI pulse sequence. A 1.63 or 1.5 MHz transducer supplied ultrasound pulses which were triggered by the magnetic resonance imaging hardware to occur before a displacement-encoding gradient. Displacements in and around the focus were mapped in a tissue-mimicking phantom and in an ex vivo bovine kidney. They were readily observed and increased linearly with acoustic power in the phantom (R2=0.99). At higher acoustic power levels, the displacement substantially increased and was associated with irreversible changes in the phantom. At these levels, transverse displacement components could also be detected. Displacements in the kidney were also observed and increased after thermal ablation. While the measurements need validation, the authors have demonstrated the feasibility of detecting small displacements induced by low-power ultrasound pulses using an efficient magnetic resonance imaging pulse sequence that is compatible with tracking of a dynamically steered ultrasound focal spot, and that the displacement increases with acoustic power. MR-ARFI has potential for elastography or to guide ultrasound therapies that use low-power pulsed ultrasound exposures, such as drug delivery.
Maddah M, Zöllei L, Grimson EWL, Wells WM. Modeling of Anatomical Information in Clustering of White Matter Fiber Trajectories Using Dirichlet Distribution. Proc Workshop Math Methods Biomed Image Analysis. 2008;2008 :1-7.Abstract
In this work, we describe a white matter trajectory clustering algorithm that allows for incorporating and appropriately weighting anatomical information. The influence of the anatomical prior reflects confidence in its accuracy and relevance. It can either be defined by the user or it can be inferred automatically. After a detailed description of our novel clustering framework, we demonstrate its properties through a set of preliminary experiments.
Hoge SW, Brooks DH. Using GRAPPA to improve autocalibrated coil sensitivity estimation for the SENSE family of parallel imaging reconstruction algorithms. Magn Reson Med. 2008;60 (2) :462-7.Abstract
Two strategies are widely used in parallel MRI to reconstruct subsampled multicoil image data. SENSE and related methods employ explicit receiver coil spatial response estimates to reconstruct an image. In contrast, coil-by-coil methods such as GRAPPA leverage correlations among the acquired multicoil data to reconstruct missing k-space lines. In self-referenced scenarios, both methods employ Nyquist-rate low-frequency k-space data to identify the reconstruction parameters. Because GRAPPA does not require explicit coil sensitivities estimates, it needs considerably fewer autocalibration signals than SENSE. However, SENSE methods allow greater opportunity to control reconstruction quality though regularization and thus may outperform GRAPPA in some imaging scenarios. Here, we employ GRAPPA to improve self-referenced coil sensitivity estimation in SENSE and related methods using very few auto-calibration signals. This enables one to leverage each methods' inherent strength and produce high quality self-referenced SENSE reconstructions.
Poynton C, Jenkinson M, Whalen S, Golby AJ, Wells W. Fieldmap-free retrospective registration and distortion correction for EPI-based functional imaging. Med Image Comput Comput Assist Interv. 2008;11 (Pt 2) :271-9.Abstract
We describe a method for correcting the distortions present in echo planar images (EPI) and registering the EPI to structural MRI. A fieldmap is predicted from an air / tissue segmentation of the MRI using a perturbation method and subsequently used to unwarp the EPI data. Shim and other missing parameters are estimated by registration. We obtain results that are similar to those obtained using fieldmaps, however neither fieldmaps, nor knowledge of shim coefficients is required.
Tricoche X, Kindlmann G, Westin C-F. Invariant crease lines for topological and structural analysis of tensor fields. IEEE Trans Vis Comput Graph. 2008;14 (6) :1627-34.Abstract
We introduce a versatile framework for characterizing and extracting salient structures in three-dimensional symmetric second-order tensor fields. The key insight is that degenerate lines in tensor fields, as defined by the standard topological approach, are exactly crease (ridge and valley) lines of a particular tensor invariant called mode. This reformulation allows us to apply well-studied approaches from scientific visualization or computer vision to the extraction of topological lines in tensor fields. More generally, this main result suggests that other tensor invariants, such as anisotropy measures like fractional anisotropy (FA), can be used in the same framework in lieu of mode to identify important structural properties in tensor fields. Our implementation addresses the specific challenge posed by the non-linearity of the considered scalar measures and by the smoothness requirement of the crease manifold computation. We use a combination of smooth reconstruction kernels and adaptive refinement strategy that automatically adjust the resolution of the analysis to the spatial variation of the considered quantities. Together, these improvements allow for the robust application of existing ridge line extraction algorithms in the tensor context of our problem. Results are proposed for a diffusion tensor MRI dataset, and for a benchmark stress tensor field used in engineering research.
Tokuda J, Fischer GS, Csoma C, Dimaio SP, Gobbi DG, Fichtinger G, Tempany CM, Hata N. Software strategy for robotic transperineal prostate therapy in closed-bore MRI. Med Image Comput Comput Assist Interv. 2008;11 (Pt 2) :701-9.Abstract
A software strategy to provide intuitive navigation for MRI-guided robotic transperineal prostate therapy is presented. In the system, the robot control unit, the MRI scanner, and open-source navigation software are connected to one another via Ethernet to exchange commands, coordinates, and images. Six states of the system called "workphases" are defined based on the clinical scenario to synchronize behaviors of all components. The wizard-style user interface allows easy following of the clinical workflow. On top of this framework, the software provides features for intuitive needle guidance: interactive target planning; 3D image visualization with current needle position; treatment monitoring through real-time MRI. These features are supported by calibration of robot and image coordinates by the fiducial-based registration. The performance test shows that the registration error of the system was 2.6 mm in the prostate area, and it displayed real-time 2D image 1.7 s after the completion of image acquisition.
Maier SE, Mulkern RV. Biexponential Analysis of Diffusion Related Signal Decay in Normal Human Cortical and Deep Gray Matter. Magn Reson Imaging. 2008;26 (7) :897-904.Abstract

Diffusion imaging with high-b factors, high spatial resolution and cerebrospinal fluid signal suppression was performed in order to characterize the biexponential nature of the diffusion-related signal decay with b-factor in normal cortical gray and deep gray matter (GM). Integration of inversion pulses with a line scan diffusion imaging sequence resulted in 91% cerebrospinal fluid signal suppression, permitting accurate measurement of the fast diffusion coefficient in cortical GM (1.142+/-0.106 microm2/ms) and revealing a marked similarity with that found in frontal white matter (WM) (1.155+/-0.046 microm2/ms). The reversal of contrast between GM and WM at low vs high b-factors is shown to be due to a significantly faster slow diffusion coefficient in cortical GM (0.338+/-0.027 microm2/ms) than in frontal WM (0.125+/-0.014 microm2/ms). The same characteristic diffusion differences between GM and WM are observed in other brain tissue structures. The relative component size showed nonsignificant differences among all tissues investigated. Cellular architecture in GM and WM are fundamentally different and may explain the two- to threefold higher slow diffusion coefficient in GM.

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