Publications by Year: 2012

2012
Tina Kapur, Clare M. Tempany, and Ferenc A. Jolesz. 2012. “Proceedings of the 5th Image Guided Therapy Workshop.” Image Guided Therapy Workshop 5, Pp. 1-70. 2012 IGT Workshop Proceedings
Tina Kapur, Ferenc A Jolesz, Jonathan S Lewin, and Thomas Kahn. 2012. “Proceedings of the 9th Interventional MRI Symposium.” 9th Interventional MRI Symposium 9, Pp. 1-156. 2012 iMRI Symposium Proceedings
Andriy Fedorov, Reinhard Beichel, Jayashree Kalpathy-Cramer, Julien Finet, Jean-Christophe Fillion-Robin, Sonia Pujol, Christian Bauer, Dominique Jennings, Fiona M Fennessy, Milan Sonka, John Buatti, Stephen Aylward, James V Miller, Steve Pieper, and Ron Kikinis. 2012. “3D Slicer as an image computing platform for the Quantitative Imaging Network.” Magn Reson Imaging, 30, 9, Pp. 1323-41.Abstract

Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open-source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer.

Tina Kapur, Jan Egger, Antonio Damato, Ehud J Schmidt, and Akila N Viswanathan. 2012. “3T MR-guided Brachytherapy for Gynecologic Malignancies.” Magn Reson Imaging, 30, 9, Pp. 1279-90.Abstract

Gynecologic malignancies are a leading cause of death in women worldwide. Standard treatment for many primary and recurrent gynecologic cancer cases includes external-beam radiation followed by brachytherapy. Magnetic resonance (MR) imaging is beneficial in diagnostic evaluation, in mapping the tumor location to tailor radiation dose and in monitoring the tumor response to treatment. Initial studies of MR guidance in gynecologic brachytherapy demonstrate the ability to optimize tumor coverage and reduce radiation dose to normal tissues, resulting in improved outcomes for patients. In this article, we describe a methodology to aid applicator placement and treatment planning for 3 Tesla (3-T) MR-guided brachytherapy that was developed specifically for gynecologic cancers. This methodology has been used in 18 cases from September 2011 to May 2012 in the Advanced Multimodality Image Guided Operating (AMIGO) suite at Brigham and Women's Hospital. AMIGO comprises state-of-the-art tools for MR imaging, image analysis and treatment planning. An MR sequence using three-dimensional (3D)-balanced steady-state free precession in a 3-T MR scanner was identified as the best sequence for catheter identification with ballooning artifact at the tip. 3D treatment planning was performed using MR images. Items in development include software designed to support virtual needle trajectory planning that uses probabilistic bias correction, graph-based segmentation and image registration algorithms. The results demonstrate that 3-T MR image guidance has a role in gynecologic brachytherapy. These novel developments have the potential to improve targeted treatment to the tumor while sparing the normal tissues.

Jennifer Pursley, Petter Risholm, Andriy Fedorov, Kemal Tuncali, Fiona M Fennessy, William M Wells III, Clare M Tempany, and Robert A Cormack. 2012. “A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization.” Med Phys, 39, 11, Pp. 6858-67.Abstract

PURPOSE: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measure of the associated registration uncertainty. METHODS: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. RESULTS: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was ≤3 mm (95th percentiles within ±4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of ≤5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. CONCLUSIONS: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance.

Hatsuho Mamata, Junichi Tokuda, Ritu R Gill, Robert F Padera, Robert E Lenkinski, David J Sugarbaker, James P Butler, and Hiroto Hatabu. 2012. “Clinical application of pharmacokinetic analysis as a biomarker of solitary pulmonary nodules: dynamic contrast-enhanced MR imaging.” Magn Reson Med, 68, 5, Pp. 1614-22.Abstract
The purpose of this study is to evaluate perfusion indices and pharmacokinetic parameters in solitary pulmonary nodules (SPNs). Thirty patients of 34 enrolled with SPNs (15-30 mm) were evaluated in this study. T1 and T2-weighted structural images and 2D turbo FLASH perfusion images were acquired with shallow free breathing. B-spline nonrigid image registration and optimization by χ² test against pharmacokinetic model curve were performed on dynamic contrast-enhanced MRI. This allowed voxel-by-voxel calculation of k(ep) , the rate constant for tracer transport to and from plasma and the extravascular extracellular space. Mean transit time, time-to-peak, initial slope, and maximum enhancement (E(max) ) were calculated from time-intensity curves fitted to a gamma variate function. After blinded data analysis, correlation with tissue histology from surgical resection or biopsy samples was performed. Histologic evaluation revealed 25 malignant and five benign SPNs. All benign SPNs had k(ep) < 1.0 min⁻¹. Nineteen of 25 (76%) malignant SPNs showed k(ep) > 1.0 min⁻¹. Sensitivity to diagnose malignant SPNs at a cutoff of k(ep) = 1.0 min⁻¹ was 76%, specificity was 100%, positive predictive value was 100%, negative predictive value was 45%, and accuracy was 80%. Of all indices studied, k(ep) was the most significant in differentiating malignant from benign SPNs.
Daniel A Orringer, David R Vago, and Alexandra J Golby. 2012. “Clinical Applications and Future Directions of Functional MRI.” Semin Neurol, 32, 4, Pp. 466-75.Abstract

First described for use in mapping the human visual cortex in 1991, functional magnetic resonance imaging (fMRI) is based on blood-oxygen level dependent (BOLD) changes in cortical regions that occur during specific tasks. Typically, an overabundance of oxygenated (arterial) blood is supplied during activation of brain areas. Consequently, the venous outflow from the activated areas contains a higher concentration of oxyhemoglobin, which changes the paramagnetic properties of the tissue that can be detected during a T2-star acquisition. fMRI data can be acquired in response to specific tasks or in the resting state. fMRI has been widely applied to studying physiologic and pathophysiologic diseases of the brain. This review will discuss the most common current clinical applications of fMRI as well as emerging directions.

Giovanna S Danagoulian, Lei Qin, Krishna S Nayak, Rivka R Colen, Srinivasan Mukundan, Mitchell B Harris, Ferenc A Jolesz, Ajit Shankaranarayanan, William A Copen, and Ehud J Schmidt. 2012. “Comparison of wideband steady-state free precession and T₂-weighted fast spin echo in spine disorder assessment at 1.5 and 3 T.” Magn Reson Med, 68, 5, Pp. 1527-35.Abstract
Wideband steady-state free precession (WB-SSFP) is a modification of balanced steady-state free precession utilizing alternating repetition times to reduce susceptibility-induced balanced steady-state free precession limitations, allowing its use for high-resolution myelographic-contrast spinal imaging. Intertissue contrast and spatial resolution of complete-spine-coverage 3D WB-SSFP were compared with those of 2D T₂-weighted fast spin echo, currently the standard for spine T₂-imaging. Six normal subjects were imaged at 1.5 and 3 T. The signal-to-noise ratio efficiency (SNR per unit-time and unit-volume) of several tissues was measured, along with four intertissue contrast-to-noise ratios; nerve-ganglia:fat, intradural-nerves:cerebrospinal fluid, nerve-ganglia:muscle, and muscle:fat. Patients with degenerative and traumatic spine disorders were imaged at both MRI fields to demonstrate WB-SSFP clinical advantages and disadvantages. At 3 T, WB-SSFP provided spinal contrast-to-noise ratios 3.7-5.2 times that of fast spin echo. At 1.5 T, WB-SSFP contrast-to-noise ratio was 3-3.5 times that of fast spin echo, excluding a 1.7 ratio for intradural-nerves:cerebrospinal fluid. WB-SSFP signal-to-noise ratio efficiency was also higher. Three-dimensional WB-SSFP disadvantages relative to 2D fast spin echo are reduced edema hyperintensity, reduced muscle signal, and higher motion sensitivity. WB-SSFP's high resolution and contrast-to-noise ratio improved visualization of intradural nerve bundles, foraminal nerve roots, and extradural nerve bundles, improving detection of nerve compression in radiculopathy and spinal-stenosis. WB-SSFP's high resolution permitted reformatting into orthogonal planes, providing distinct advantages in gauging fine spine pathology.
Byung Kwan Park, Paul R Morrison, Servet Tatli, Usha Govindarajulu, Kemal Tuncali, Phil Judy, Paul B Shyn, and Stuart G Silverman. 2012. “Estimated effective dose of CT-guided percutaneous cryoablation of liver tumors.” Eur J Radiol, 81, 8, Pp. 1702-6.Abstract
PURPOSE: To estimate effective dose during CT-guided cryoablation of liver tumors, and to assess which procedural factors contribute most to dose. MATERIALS AND METHODS: Our institutional review board approved this retrospective, HIPAA-compliant study. A total of 20 CT-guided percutaneous liver tumor cryoablation procedures were performed in 18 patients. Effective dose was determined by multiplying the dose length product for each CT scan obtained during the procedure by a conversion factor (0.015mSv/mGy-cm), and calculating the sum for each phase of the procedure: planning, targeting, monitoring, and post-ablation survey. Effective dose of each phase was compared using a repeated measures analysis. Using Spearman correlation coefficients, effective doses were correlated with procedural factors including number of scans, ratio of targeting distance to tumor size, anesthesia type, number of applicators, performance of ancillary procedures (hydrodissection and biopsy), and use of CT fluoroscopy. RESULTS: Effective dose per procedure was 72±18mSv. The effective dose of targeting (37.5±12.5mSv) was the largest component compared to the effective dose of the planning phase (4.8±2.2mSv), the monitoring phase (25.5±6.8mSv), and the post-ablation survey (4.1±1.9mSv) phase (p<0.05). Effective dose correlated positively only with the number of scans (p<0.01). CONCLUSIONS: The effective dose of CT-guided percutaneous cryoablation of liver tumors can be substantial. Reducing the number of scans during the procedure is likely to have the greatest effect on lowering dose.
Lauren J O'Donnell, Laura Rigolo, Isaiah Norton, William M Wells III, Carl-Fredrik Westin, and Alexandra J Golby. 2012. “fMRI-DTI modeling via landmark distance atlases for prediction and detection of fiber tracts.” Neuroimage, 60, 1, Pp. 456-70.Abstract

The overall goal of this research is the design of statistical atlas models that can be created from normal subjects, but may generalize to be applicable to abnormal brains. We present a new style of joint modeling of fMRI, DTI, and structural MRI. Motivated by the fact that a white matter tract and related cortical areas are likely to displace together in the presence of a mass lesion (brain tumor), in this work we propose a rotation and translation invariant model that represents the spatial relationship between fiber tracts and anatomic and functional landmarks. This landmark distance model provides a new basis for representation of fiber tracts and can be used for detection and prediction of fiber tracts based on landmarks. Our results indicate that the measured model is consistent across normal subjects, and thus suitable for atlas building. Our experiments demonstrate that the model is robust to displacement and missing data, and can be successfully applied to a small group of patients with mass lesions.

Subashini Srinivasan, Peng Hu, Kraig V Kissinger, Beth Goddu, Lois Goepfert, Ehud J Schmidt, Sebastian Kozerke, and Reza Nezafat. 2012. “Free-breathing 3D whole-heart black-blood imaging with motion sensitized driven equilibrium.” J Magn Reson Imaging, 36, 2, Pp. 379-86.Abstract
PURPOSE: To assess the efficacy and robustness of motion sensitized driven equilibrium (MSDE) for blood suppression in volumetric 3D whole-heart cardiac MR. MATERIALS AND METHODS: To investigate the efficacy of MSDE on blood suppression and myocardial signal-to-noise ratio (SNR) loss on different imaging sequences, seven healthy adult subjects were imaged using 3D electrocardiogram (ECG)-triggered MSDE-prep T(1) -weighted turbo spin echo (TSE), and spoiled gradient echo (GRE), after optimization of MSDE parameters in a pilot study of five subjects. Imaging artifacts, myocardial and blood SNR were assessed. Subsequently, the feasibility of isotropic spatial resolution MSDE-prep black-blood was assessed in six subjects. Finally, 15 patients with known or suspected cardiovascular disease were recruited to be imaged using a conventional multislice 2D double inversion recovery (DIR) TSE imaging sequence and a 3D MSDE-prep spoiled GRE. RESULTS: The MSDE-prep yielded significant blood suppression (75%-92%), enabling a volumetric 3D black-blood assessment of the whole heart with significantly improved visualization of the chamber walls. The MSDE-prep also allowed successful acquisition of black-blood images with isotropic spatial resolution. In the patient study, 3D black-blood MSDE-prep and DIR resulted in similar blood suppression in left ventricle and right ventricle walls but the MSDE-prep had superior myocardial signal and wall sharpness. CONCLUSION: MSDE-prep allows volumetric black-blood imaging of the heart.
Xinyang Liu, Kemal Tuncali, William M Wells III, Paul R Morrison, and Gary P Zientara. 2012. “Fully automatic 3D segmentation of iceball for image-guided cryoablation.” Conf Proc IEEE Eng Med Biol Soc, 2012, Pp. 2327-30.Abstract

The efficient extraction of the cryoablation iceball from a time series of 3D images is crucial during cryoablation to assist the interventionalist in determining the coverage of the tumor by the ablated volume. Conventional semi-automatic segmentation tools such as ITK-SNAP and 3D Slicer's Fast Marching Segmentation can attain accurate iceball segmentation in retrospective studies, however, they are not ideal for intraprocedure real time segmentation, as they require time-consuming manual operations, such as the input of fiducials and the extent of the segmented region growth. In this paper, we present an innovative approach for the segmentation of the iceball during cryoablation, that executes a fully automatic computation. Our approach is based on the graph cuts segmentation framework, and incorporates prior information of iceball shape evolving in time, modeled using experimentally-derived iceball growth parameters. Modeling yields a shape prior mask image at each timepoint of the imaging time series for use in the segmentation. Segmentation results of our method and the ITK-SNAP method are compared for 8 timepoints in 2 cases. The results indicate that our fully automatic approach is accurate, robust and highly efficient compared to manual and semi-automatic approaches.

Andriy Fedorov, Kemal Tuncali, Fiona M Fennessy, Junichi Tokuda, Nobuhiko Hata, William M Wells III, Ron Kikinis, and Clare M Tempany. 2012. “Image registration for targeted MRI-guided transperineal prostate biopsy.” J Magn Reson Imaging, 36, 4, Pp. 987-92.Abstract

PURPOSE: To develop and evaluate image registration methodology for automated re-identification of tumor-suspicious foci from preprocedural MR exams during MR-guided transperineal prostate core biopsy. MATERIALS AND METHODS: A hierarchical approach for automated registration between planning and intra-procedural T2-weighted prostate MRI was developed and evaluated on the images acquired during 10 consecutive MR-guided biopsies. Registration accuracy was quantified at image-based landmarks and by evaluating spatial overlap for the manually segmented prostate and sub-structures. Registration reliability was evaluated by simulating initial mis-registration and analyzing the convergence behavior. Registration precision was characterized at the planned biopsy targets. RESULTS: The total computation time was compatible with a clinical setting, being at most 2 min. Deformable registration led to a significant improvement in spatial overlap of the prostate and peripheral zone contours compared with both rigid and affine registration. Average in-slice landmark registration error was 1.3 ± 0.5 mm. Experiments simulating initial mis-registration resulted in an estimated average capture range of 6 mm and an average in-slice registration precision of ±0.3 mm. CONCLUSION: Our registration approach requires minimum user interaction and is compatible with the time constraints of our interventional clinical workflow. The initial evaluation shows acceptable accuracy, reliability and consistency of the method.

Lisa H Treat, Nathan McDannold, Yongzhi Zhang, Natalia Vykhodtseva, and Kullervo Hynynen. 2012. “Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma.” Ultrasound Med Biol, 38, 10, Pp. 1716-25.Abstract
The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment (p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.
Junichi Tokuda, Kemal Tuncali, Iulian Iordachita, Sang-Eun Song, Andriy Fedorov, Sota Oguro, Andras Lasso, Fiona M Fennessy, Clare M Tempany, and Nobuhiko Hata. 2012. “In-bore Setup and Software for 3T MRI-guided Transperineal Prostate Biopsy.” Phys Med Biol, 57, 18, Pp. 5823-40.Abstract

MRI-guided prostate biopsy in conventional closed-bore scanners requires transferring the patient outside the bore during needle insertion due to the constrained in-bore space, causing a safety hazard and limiting image feedback. To address this issue, we present our custom-made in-bore setup and software to support MRI-guided transperineal prostate biopsy in a wide-bore 3 T MRI scanner. The setup consists of a specially designed tabletop and a needle-guiding template with a Z-frame that gives a physician access to the perineum of the patient at the imaging position and allows the physician to perform MRI-guided transperineal biopsy without moving the patient out of the scanner. The software and Z-frame allow registration of the template, target planning and biopsy guidance. Initially, we performed phantom experiments to assess the accuracy of template registration and needle placement in a controlled environment. Subsequently, we embarked on our clinical trial (N = 10). The phantom experiments showed that the translational errors of the template registration along the right-left (RP) and anterior-posterior (AP) axes were 1.1 ± 0.8 and 1.4 ± 1.1 mm, respectively, while the rotational errors around the RL, AP and superior-inferior axes were (0.8 ± 1.0)°, (1.7 ± 1.6)° and (0.0 ± 0.0)°, respectively. The 2D root-mean-square (RMS) needle-placement error was 3 mm. The clinical biopsy procedures were safely carried out in all ten clinical cases with a needle-placement error of 5.4 mm (2D RMS). In conclusion, transperineal prostate biopsy in a wide-bore 3T scanner is feasible using our custom-made tabletop setup and software, which supports manual needle placement without moving the patient out of the magnet.

Jan Egger, Junichi Tokuda, Laurent Chauvin, Bernd Freisleben, Christopher Nimsky, Tina Kapur, and William M Wells III. 2012. “Integration of the OpenIGTLink Network Protocol for Image-guided Therapy with the Medical Platform MeVisLab.” Int J Med Robot, 8, 3, Pp. 282-90.Abstract

BACKGROUND: OpenIGTLink is a new, open, simple and extensible network communication protocol for image-guided therapy (IGT). The protocol provides a standardized mechanism to connect hardware and software by the transfer of coordinate transforms, images, and status messages. MeVisLab is a framework for the development of image processing algorithms and visualization and interaction methods, with a focus on medical imaging. METHODS: The paper describes the integration of the OpenIGTLink network protocol for IGT with the medical prototyping platform MeVisLab. The integration of OpenIGTLink into MeVisLab has been realized by developing a software module using the C++ programming language. RESULTS: The integration was evaluated with tracker clients that are available online. Furthermore, the integration was used to connect MeVisLab to Slicer and a NDI tracking system over the network. The latency time during navigation with a real instrument was measured to show that the integration can be used clinically. CONCLUSIONS: Researchers using MeVisLab can interface their software to hardware devices that already support the OpenIGTLink protocol, such as the NDI Aurora magnetic tracking system. In addition, the OpenIGTLink module can also be used to communicate directly with Slicer, a free, open source software package for visualization and image analysis.

Lawrence P Panych, Joseph R Roebuck, Nan-kuei Chen, Yi Tang, Bruno Madore, Clare M Tempany, and Robert V Mulkern. 2012. “Investigation of the PSF-choice method for reduced lipid contamination in prostate MR spectroscopic imaging.” Magn Reson Med, 68, 5, Pp. 1376-82.Abstract
The purpose of this work was to evaluate a previously proposed approach that aims to improve the point spread function (PSF) of MR spectroscopic imaging (MRSI) to avoid corruption by lipid signal arising from neighboring voxels. Retrospective spatial filtering can be used to alter the PSF; however, this either reduces spatial resolution or requires extending the acquisition in k-space at the cost of increased imaging time. Alternatively, the method evaluated here, PSF-choice, can modify the PSF localization to reduce the contamination from adjacent lipids by conforming the signal response more closely to the desired MRSI voxel grid. This is done without increasing scan time or degrading SNR of important metabolites. PSF-choice achieves improvements in spatial localization through modifications to the radiofrequency excitation pulses. An implementation of this method is reported for MRSI of the prostate, where it is demonstrated that, in 13 of 16 pilot prostate MRSI scans, intravoxel spectral contamination from lipid was significantly reduced when using PSF-choice. Phantom studies were also performed that demonstrate, compared with MRSI with standard Fourier phase encoding, out-of-voxel signal contamination of spectra was significantly reduced in MRSI with PSF-choice.
Juyoung Park, Yongzhi Zhang, Natalia Vykhodtseva, Ferenc A Jolesz, and Nathan J McDannold. 2012. “The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound.” J Control Release, 162, 1, Pp. 134-42.Abstract
Focused ultrasound (FUS) combined with a circulating microbubble agent is a promising strategy to non-invasively disrupt the blood-brain barrier (BBB) and could enable targeted delivery of therapeutics that normally do not leave the brain vasculature. This study investigated the kinetics of the BBB permeability using dynamic contrast-enhanced MRI (DCE-MRI) and the resulting payload of the chemotherapy agent, doxorubicin (DOX). We also investigated how the disruption and drug delivery were affected by a double sonication (DS) with two different time intervals (10 or 120 min). Two locations were sonicated transcranially in one hemisphere of the brain in 20 rats using a 690 kHz FUS transducer; the other hemisphere served as a control. For BBB disruption, 10 ms bursts were applied at 1 Hz for 60s and combined with IV injection of a microbubble ultrasound contrast agent (Definity; 10 μl/kg). DOX was injected immediately after the second location was sonicated. The transfer coefficient (K(trans)) for an MRI contrast agent (Gd-DTPA) was estimated serially at 4-5 time points ranging from 30 min to 7.5 hrs after sonication using DCE-MRI. After a single sonication (SS), the mean K(trans) was 0.0142 ± 0.006 min(-1) at 30 min and was two or more orders of magnitude higher than the non-sonicated targets. It decreased exponentially as a function of time with an estimated half-life of 2.22 hrs (95% confidence intervals (CI): 1.06-3.39 hrs). Adding a second sonication increased K(trans), and with a 120 min interval between sonications, prolonged the duration of the BBB disruption. Mean K(trans) estimates of 0.0205 (CI: 0.016-0.025) and 0.0216 (CI: 0.013-0.030) min(-1) were achieved after DS with 10 and 120 min delays, respectively. The half-life of the K(trans) decay that occurred as the barrier was restored was 1.8 hrs (CI: 1.20-2.41 hrs) for a 10 min interval between sonications and increased to 3.34 hrs (CI: 0.84-5.84 hrs) for a 120 min interval. DOX concentrations were significantly greater than in the non-sonicated brain for all experimental groups (p<0.0001), and 1.5-fold higher for DS with a 10 min interval between sonications. A linear correlation was found between the DOX concentration achieved and the K(trans) measured at 30 min after sonication (R: 0.7). These data suggest that one may be able to use Gd-DTPA as a surrogate tracer to estimate DOX delivery to the brain after FUS-induced BBB disruption. The results of this study provide information needed to take into account the dynamics BBB disruption over time after FUS.
Yun Jing, Tianren Wang, and Greg T Clement. 2012. “A k-space method for moderately nonlinear wave propagation.” IEEE Trans Ultrason Ferroelectr Freq Control, 59, 8, Pp. 1664-73.Abstract
A k-space method for moderately nonlinear wave propagation in absorptive media is presented. The Westervelt equation is first transferred into k-space via Fourier transformation, and is solved by a modified wave-vector time-domain scheme. The present approach is not limited to forward propagation or parabolic approximation. One- and two-dimensional problems are investigated to verify the method by comparing results to analytic solutions and finite-difference time-domain (FDTD) method. It is found that to obtain accurate results in homogeneous media, the grid size can be as little as two points per wavelength, and for a moderately nonlinear problem, the Courant-Friedrichs-Lewy number can be as large as 0.4. Through comparisons with the conventional FDTD method, the k-space method for nonlinear wave propagation is shown here to be computationally more efficient and accurate. The k-space method is then employed to study three-dimensional nonlinear wave propagation through the skull, which shows that a relatively accurate focusing can be achieved in the brain at a high frequency by sending a low frequency from the transducer. Finally, implementations of the k-space method using a single graphics processing unit shows that it required about one-seventh the computation time of a single-core CPU calculation.
Ricky Medel, Stephen J Monteith, Jeffrey W Elias, Matthew Eames, John Snell, Jason P Sheehan, Max Wintermark, Ferenc A Jolesz, and Neal F Kassell. 2012. “Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications.” Neurosurgery, 71, 4, Pp. 755-63.Abstract
Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

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