Publications

2009
Fischer K, McDannold NJ, Zhang Y, Kardos M, Szabo A, Szabo A, Reusz GS, Jolesz FA. Renal ultrafiltration changes induced by focused US. Radiology. 2009;253 (3) :697-705.Abstract
PURPOSE: To determine if focused ultrasonography (US) combined with a diagnostic microbubble-based US contrast agent can be used to modulate glomerular ultrafiltration and size selectivity. MATERIALS AND METHODS: The experiments were approved by the animal care committee. The left kidney of 17 healthy rabbits was sonicated by using a 260-kHz focused US transducer in the presence of a microbubble-based US contrast agent. The right kidney served as the control. Three acoustic power levels were applied: 0.4 W (six rabbits), 0.9 W (six rabbits), and 1.7 W (five rabbits). Three rabbits were not treated with focused US and served as control animals. The authors evaluated changes in glomerular size selectivity by measuring the clearance rates of 3000- and 70,000-Da fluorescence-neutral dextrans. The creatinine clearance was calculated for estimation of the glomerular filtration rate. The urinary protein-creatinine ratio was monitored during the experiments. The authors assessed tubular function by evaluating the fractional sodium excretion, tubular reabsorption of phosphate, and gamma-glutamyltransferase-creatinine ratio. Whole-kidney histologic analysis was performed. For each measurement, the values obtained before and after sonication were compared by using the paired t test. RESULTS: Significant (P < .05) increases in the relative (ratio of treated kidney value/nontreated kidney value) clearance of small- and large-molecule agents and the urine flow rates that resulted from the focused US treatments were observed. Overall, 1.23-, 1.23-, 1.61-, and 1.47-fold enhancement of creatinine clearance, 3000-Da dextran clearance, 70 000-Da dextran clearance, and urine flow rate, respectively, were observed. Focal tubular hemorrhage and transient functional tubular alterations were observed at only the highest (1.7-W) acoustic power level tested. CONCLUSION: Glomerular ultrafiltration and size selectivity can be temporarily modified with simultaneous application of US and microbubbles. This method could offer new opportunities for treatment of renal disease.
Wang X, Grimson EWL, Westin C-F. Tractography segmentation using a hierarchical Dirichlet processes mixture model. Inf Process Med Imaging. 2009;21 :101-13.Abstract
In this paper, we propose a new nonparametric Bayesian framework to cluster white matter fiber tracts into bundles using a hierarchical Dirichlet processes mixture (HDPM) model. The number of clusters is automatically learnt from data with a Dirichlet process (DP) prior instead of being manually specified. After the models of bundles have been learnt from training data without supervision, they can be used as priors to cluster/classify fibers of new subjects. When clustering fibers of new subjects, new clusters can be created for structures not observed in the training data. Our approach does not require computing pairwise distances between fibers and can cluster a huge set of fibers across multiple subjects without subsampling. We present results on multiple data sets, the largest of which has more than 120, 000 fibers.
Farny CH, Clement GT. Ultrasound phase contrast thermal imaging with reflex transmission imaging methods in tissue phantoms. Ultrasound Med Biol. 2009;35 (12) :1995-2006.Abstract
Thermal imaging measurements using ultrasound phase contrast have been performed in tissue phantoms heated with a focused ultrasound source. Back projection and reflex transmission imaging principles were used to detect sound speed-induced changes in the phase caused by an increase in the temperature. The temperature was determined from an empirical relationship for the temperature dependence on sound speed. The phase contrast was determined from changes in the sound field measured with a hydrophone scan conducted before and during applied heating. The lengthy scanning routine used to mimic a large two-dimensional array required a steady-state temperature distribution within the phantom. The temperature distribution in the phantom was validated with magnetic resonance (MR) thermal imaging measurements. The peak temperature was found to agree within 1 degrees C with MR, and good agreement was found between the temperature profiles. The spatial resolution was 0.3x0.3x0.3mm, comparing favorably with the 0.625x0.625x1.5-mm MR spatial resolution.
Madore B, White JP, Thomenius K, Clement GT. Accelerated focused ultrasound imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 2009;56 (12) :2612-23.Abstract
One of the most basic trade-offs in ultrasound imaging involves frame rate, depth, and number of lines. Achieving good spatial resolution and coverage requires a large number of lines, leading to decreases in frame rate. An even more serious imaging challenge occurs with imaging modes involving spatial compounding and 3-D/4-D imaging, which are severely limited by the slow speed of sound in tissue. The present work can overcome these traditional limitations, making ultrasound imaging many-fold faster. By emitting several beams at once, and by separating the resulting overlapped signals through spatial and temporal processing, spatial resolution and/or coverage can be increased by many-fold while leaving frame rates unaffected. The proposed approach can also be extended to imaging strategies that do not involve transmit beamforming, such as synthetic aperture imaging. Simulated and experimental results are presented where imaging speed is improved by up to 32-fold, with little impact on image quality. Object complexity has little impact on the method's performance, and data from biological systems can readily be handled. The present work may open the door to novel multiplexed and/or multidimensional protocols considered impractical today.
Lee J-H, Oh S, Jolesz FA, Park HW, Yoo S-S. Application of independent component analysis for the data mining of simultaneous Eeg-fMRI: preliminary experience on sleep onset. Int J Neurosci. 2009;119 (8) :1118-36.Abstract
The simultaneous acquisition of electroencephalogram (EEG) and functional MRI (fMRI) signals is potentially advantageous because of the superior resolution that is achieved in both the temporal and spatial domains, respectively. However, ballistocardiographic artifacts along with ocular artifacts are a major obstacle for the detection of the EEG signatures of interest. Since the sources corresponding to these artifacts are independent from those producing the EEG signatures, we applied the Infomax-based independent component analysis (ICA) technique to separate the EEG signatures from the artifacts. The isolated EEG signatures were further utilized to model the canonical hemodynamic response functions (HRFs). Subsequently, the brain areas from which these EEG signatures originated were identified as locales of activation patterns from the analysis of fMRI data. Upon the identification and subsequent evaluation of brain areas generating interictal epileptic discharge (IED) spikes from an epileptic subject, the presented method was successfully applied to detect the theta and alpha rhythms that are sleep onset-related EEG signatures along with the subsequent neural circuitries from a sleep-deprived volunteer. These results suggest that the ICA technique may be useful for the preprocessing of simultaneous EEG-fMRI acquisitions, especially when a reference paradigm is unavailable.
Ou W, Nummenmaa A, Golland P, Hamalainen MS. Multimodal functional imaging using fMRI-informed regional EEG/MEG source estimation. Conf Proc IEEE Eng Med Biol Soc. 2009;2009 :1926-9.Abstract
We propose a novel method, fMRI-Informed Regional Estimation (FIRE), which utilizes information from fMRI in E/MEG source reconstruction. FIRE takes advantage of the spatial alignment between the neural and the vascular activities, while allowing for substantial differences in their dynamics. Furthermore, with the regional approach, FIRE can be efficiently applied to a dense grid of sources. Inspection of our optimization procedure reveals that FIRE is related to the re-weighted minimum-norm algorithms, the difference being that the weights in the proposed approach are computed from both the current estimates and fMRI data. Analysis of both simulated and human fMRI-MEG data shows that FIRE reduces the ambiguities in source localization present in the minimum-norm estimates. Comparisons with several joint fMRI-E/MEG algorithms demonstrate robustness of FIRE in the presence of sources silent to either fMRI or E/MEG measurements.
Kindlmann GL, San José Estépar R, Smith SM, Westin C-F. Sampling and visualizing creases with scale-space particles. IEEE Trans Vis Comput Graph. 2009;15 (6) :1415-24.Abstract
Particle systems have gained importance as a methodology for sampling implicit surfaces and segmented objects to improve mesh generation and shape analysis. We propose that particle systems have a significantly more general role in sampling structure from unsegmented data. We describe a particle system that computes samplings of crease features (i.e. ridges and valleys, as lines or surfaces) that effectively represent many anatomical structures in scanned medical data. Because structure naturally exists at a range of sizes relative to the image resolution, computer vision has developed the theory of scale-space, which considers an n-D image as an (n+1)-D stack of images at different blurring levels. Our scale-space particles move through continuous four-dimensional scale-space according to spatial constraints imposed by the crease features, a particle-image energy that draws particles towards scales of maximal feature strength, and an inter-particle energy that controls sampling density in space and scale. To make scale-space practical for large three-dimensional data, we present a spline-based interpolation across scale from a small number of pre-computed blurrings at optimally selected scales. The configuration of the particle system is visualized with tensor glyphs that display information about the local Hessian of the image, and the scale of the particle. We use scale-space particles to sample the complex three-dimensional branching structure of airways in lung CT, and the major white matter structures in brain DTI.
Tang SC, Clement GT. Acoustic Standing Wave Suppression using Randomized Phase-shift-keying Excitations. J Acoust Soc Am. 2009;126 (4) :1667-70.Abstract

Recent papers have demonstrated that acoustic standing waves can be inhibited by frequency-modulated spread-spectrum excitation. An alternative method is studied here that is designed to be more practical for implementation in phased arrays. The method operates using phase-shift-keying (PSK), which introduces phase shifts into the driving signal to break wave symmetry. Sequential and random binary-PSK (BPSK) and quadrature-PSK (QPSK) excitations are studied in water, using a carrier frequency of 250 kHz and a time segment of 10 cycles. The resulting acoustic field is measured with a transducer inside a plastic-walled chamber and compared with continuous wave excitation. Results indicate that both the random BPSK and QPSK methods can reduce time-averaged spatial intensity variation caused by standing waves by approximately six times.

Poynton C, Jenkinson M, Wells III WM. Atlas-based improved prediction of magnetic field inhomogeneity for distortion correction of EPI data. Med Image Comput Comput Assist Interv. 2009;12 (Pt 2) :951-9.Abstract

We describe a method for atlas-based segmentation of structural MRI for calculation of magnetic fieldmaps. CT data sets are used to construct a probabilistic atlas of the head and corresponding MR is used to train a classifier that segments soft tissue, air, and bone. Subject-specific fieldmaps are computed from the segmentations using a perturbation field model. Previous work has shown that distortion in echo-planar images can be corrected using predicted fieldmaps. We obtain results that agree well with acquired fieldmaps: 90% of voxel shifts from predicted fieldmaps show subvoxel disagreement with those computed from acquired fieldmaps. In addition, our fieldmap predictions show statistically significant improvement following inclusion of the atlas.

Toews M, Wells III WM. Bayesian registration via local image regions: information, selection and marginalization. Inf Process Med Imaging. 2009;21 :435-46.Abstract

We propose a novel Bayesian registration formulation in which image location is represented as a latent random variable. Location is marginalized to determine the maximum a priori (MAP) transform between images, which results in registration that is more robust than the alternatives of omitting locality (i.e. global registration) or jointly maximizing locality and transform (i.e. iconic registration). A mathematical link is established between the Bayesian registration formulation and the mutual information (MI) similarity measure. This leads to a novel technique for selecting informative image regions for registration, based on the MI of image intensity and spatial location. Experimental results demonstrate the effectiveness of the marginalization formulation and the MI-based region selection technique for ultrasound (US) to magnetic resonance (MR) registration in an image-guided neurosurgical application.

Colucci V, Strichartz G, Jolesz FA, Vykhodtseva N, Hynynen K. Focused Ultrasound Effects on Nerve Action Potential in Vitro. Ultrasound Med Biol. 2009;35 (10) :1737-47.Abstract

Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661 MHz and 1.986 MHz) and to heated Ringer's solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently.

Mulkern RV, Haker SJ, Maier SE. On High b Diffusion Imaging in the Human Brain: Ruminations and Experimental Insights. Magn Reson Imaging. 2009;27 (8) :1151-62.Abstract

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber "tractography" results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,"ruminations," which have been proposed to account for the nonmonoexponentiality to date.

Jagannathan J, Sanghvi NT, Crum LA, Yen C-P, Medel R, Dumont AS, Sheehan JP, Steiner L, Jolesz FA, Kassell NF. High-intensity focused ultrasound surgery of the brain: part 1--A historical perspective with modern applications. Neurosurgery. 2009;64 (2) :201-10; discussion 210-1.Abstract

The field of magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

Shen S-H, Fennessy FM, McDannold N, Jolesz FA, Tempany CM. Image-guided Thermal Therapy of Uterine Fibroids. Semin Ultrasound CT MR. 2009;30 (2) :91-104.Abstract

Thermal ablation is an established treatment for tumors. The merging of newly developed imaging techniques has allowed precise targeting and real-time thermal mapping. This article provides an overview of the image-guided thermal ablation techniques in the treatment of uterine fibroids. Background on uterine fibroids, including epidemiology, histology, symptoms, imaging findings, and current treatment options, is first outlined. After describing the principle of magnetic resonance thermal imaging, we introduce the applications of image-guided thermal therapies, including laser ablation, radiofrequency ablation, cryotherapy, and in particular, magnetic resonance-guided focused ultrasound surgery, and how they apply to uterine fibroid treatment.

White JP, Whalen S, Tang SC, Clement GT, Jolesz FA, Golby AJ. An intraoperative brain shift monitor using shear mode transcranial ultrasound: preliminary results. J Ultrasound Med. 2009;28 (2) :191-203.Abstract

OBJECTIVE: Various methods of intraoperative structural monitoring during neurosurgery are used to localize lesions after brain shift and to guide surgically introduced probes such as biopsy needles or stimulation electrodes. With its high temporal resolution, portability, and nonionizing mode of radiation, ultrasound has potential advantages over other existing imaging modalities for intraoperative monitoring, yet ultrasound is rarely used during neurosurgery largely because of the craniotomy requirement to achieve sufficiently useful signals. METHODS: Prompted by results from recent studies on transcranial ultrasound, a prototype device that aims to use the shear mode of transcranial ultrasound transmission for intraoperative monitoring was designed, constructed, and tested with 10 human participants. Magnetic resonance images were then obtained with the device spatially registered to the magnetic resonance imaging (MRI) reference coordinates. Peaks in both the ultrasound and MRI signals were identified and analyzed for both spatial localization and signal-to-noise ratio (SNR). RESULTS: The first results aimed toward validating the prototype device with MRI showed an excellent correlation (n = 38; R(2) = 0.9962) between the structural localization abilities of the two modalities. In addition, the overall SNR of the ultrasound backscatter signals (n = 38; SNR = 25.4 +/- 5.2 dB, mean +/- SD) was statistically equivalent to that of the MRI data (n = 38; SNR = 22.5 +/- 4.8 dB). CONCLUSIONS: A statistically significant correlation of localized intracranial structures between intraoperative transcranial ultrasound monitoring and MRI data was achieved with 10 human participants. We have shown and validated a prototype device incorporating transcranial shear mode ultrasound for clinical monitoring applications.

Oguro S, Tokuda J, Elhawary H, Haker S, Kikinis R, Tempany CM, Hata N. MRI signal intensity based B-spline nonrigid registration for pre- and intraoperative imaging during prostate brachytherapy. J Magn Reson Imaging. 2009;30 (5) :1052-8.Abstract

PURPOSE: To apply an intensity-based nonrigid registration algorithm to MRI-guided prostate brachytherapy clinical data and to assess its accuracy. MATERIALS AND METHODS: A nonrigid registration of preoperative MRI to intraoperative MRI images was carried out in 16 cases using a Basis-Spline algorithm in a retrospective manner. The registration was assessed qualitatively by experts' visual inspection and quantitatively by measuring the Dice similarity coefficient (DSC) for total gland (TG), central gland (CG), and peripheral zone (PZ), the mutual information (MI) metric, and the fiducial registration error (FRE) between corresponding anatomical landmarks for both the nonrigid and a rigid registration method. RESULTS: All 16 cases were successfully registered in less than 5 min. After the nonrigid registration, DSC values for TG, CG, PZ were 0.91, 0.89, 0.79, respectively, the MI metric was -0.19 +/- 0.07 and FRE presented a value of 2.3 +/- 1.8 mm. All the metrics were significantly better than in the case of rigid registration, as determined by one-sided t-tests. CONCLUSION: The intensity-based nonrigid registration method using clinical data was demonstrated to be feasible and showed statistically improved metrics when compare to only rigid registration. The method is a valuable tool to integrate pre- and intraoperative images for brachytherapy.

Pilatou MC, Stewart EA, Maier SE, Fennessy FM, Hynynen K, Tempany CM, McDannold N. MRI-based thermal dosimetry and diffusion-weighted imaging of MRI-guided focused ultrasound thermal ablation of uterine fibroids. J Magn Reson Imaging. 2009;29 (2) :404-11.Abstract

PURPOSE: To investigate tissue changes observed in diffusion-weighted imaging (DWI) and its relation to contrast imaging, thermal dosimetry, and changes in the apparent diffusion coefficient (ADC) after MRI-guided focused ultrasound surgery (MRgFUS) of uterine fibroids. MATERIALS AND METHODS: Imaging data were analyzed from 45 fibroids in 42 women treated with MRgFUS. The areas of the hyperintense regions in DWI and of nonperfused regions in T1-weighted contrast enhanced imaging (both acquired immediately after treatment) were compared with each other and to thermal dosimetry based estimates. Changes in ADC were also calculated. RESULTS: Hyperintense regions were observed in 35/45 fibroids in DWI. When present, the areas of these regions were comparable on average to the thermal dose estimates and to the nonperfused regions, except for in several large treatments in which the nonperfused region extended beyond the treated area. ADC increased in 19 fibroids and decreased in the others. CONCLUSION: DWI changes, which includes changes in both in T2 and ADC, may be useful in many cases to delineate the treated region resulting from MRgFUS. However, clear DWI changes were not always observed, and in some large treatments, the extent of the nonperfused region was under estimated. ADC changes immediately after MRgFUS were unpredictable.

Tokuda J, Fischer GS, Papademetris X, Yaniv Z, Ibanez L, Cheng P, Liu H, Blevins J, Arata J, Golby AJ, et al. OpenIGTLink: An Open Network Protocol for Image-guided Therapy Environment. Int J Med Robot. Int J Med Robot. 2009;5 (4) :423-34.Abstract

BACKGROUND: With increasing research on system integration for image-guided therapy (IGT), there has been a strong demand for standardized communication among devices and software to share data such as target positions, images and device status. METHOD: We propose a new, open, simple and extensible network communication protocol for IGT, named OpenIGTLink, to transfer transform, image and status messages. We conducted performance tests and use-case evaluations in five clinical and engineering scenarios. RESULTS: The protocol was able to transfer position data with submillisecond latency up to 1024 fps and images with latency of <10 ms at 32 fps. The use-case tests demonstrated that the protocol is feasible for integrating devices and software. CONCLUSION: The protocol proved capable of handling data required in the IGT setting with sufficient time resolution and latency. The protocol not only improves the interoperability of devices and software but also promotes transitions of research prototypes to clinical applications.

Nguyen PL, Chen RC, Clark JA, Cormack RA, Loffredo M, McMahon E, Nguyen AU, Suh WW, Tempany CM, D'Amico AV. Patient-reported Quality of Life after Salvage Brachytherapy for Radio-recurrent Prostate Cancer: A Prospective Phase II Study. Brachytherapy. 2009;8 (4) :345-52.Abstract

BACKGROUND: Patient-reported quality of life (QOL) after salvage brachytherapy for radiorecurrent prostate cancer has not been well-characterized prospectively. METHODS: We examined 25 men who recurred after primary radiotherapy for prostate cancer and received MRI-guided salvage brachytherapy as part of a prospective Phase II study. These patients received prospectively a validated patient-reported QOL questionnaire to fill out at baseline, as well as 3, 15, and 27 months after re-irradiation to determine the degree of sexual, bowel, and urinary dysfunction (maximum dysfunction score=100). RESULTS: On average, sexual function continued to decline with time, and patients had significantly worse sexual function scores at 27 months than baseline (p=0.01). Although bowel and urinary symptoms worsened acutely at 3 or 15 months, they showed on average some improvement by 27 months, and there were no significant differences between baseline and 27-month urinary or bowel scores. An interval to re-irradiation less than 4.5 years and prior brachytherapy were each associated significantly with the largest decrements in bowel function (p=0.035). CONCLUSION: Similar to the patterns seen in the de novo setting, patients who receive salvage brachytherapy report a worsening of bowel and urinary symptoms followed by some improvement by 27 months, while sexual function steadily declines over time. Interval to re-irradiation and type of prior radiation received may be used to counsel and optimize selection of men for salvage brachytherapy with regard to QOL endpoints.

Suarez RO, Whalen S, Nelson AP, Tie Y, Meadows M-E, Radmanesh A, Golby AJ. Threshold-independent Functional MRI Determination of Language Dominance: A Validation Study Against Clinical Gold Standards. Epilepsy Behav. 2009;16 (2) :288-97.Abstract

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.

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