Publications

2012
Mei C-S, Mulkern RV, Oshio K, Chen N-kuei, Madore B, Panych LP, Hynynen K, McDannold NJ. Ultrafast 1D MR thermometry using phase or frequency mapping. MAGMA. 2012;25 (1) :5-14.Abstract
OBJECT: To develop an ultrafast MRI-based temperature monitoring method for application during rapid ultrasound exposures in moving organs. MATERIALS AND METHODS: A slice selective 90° - 180° pair of RF pulses was used to solicit an echo from a column, which was then sampled with a train of gradient echoes. In a gel phantom, phase changes of each echo were compared to standard gradient-echo thermometry, and temperature monitoring was tested during focused ultrasound sonications. Signal-to-noise ratio (SNR) performance was evaluated in vivo in a rabbit brain, and feasibility was tested in a human heart. RESULTS: The correlation between each echo in the acquisition and MRI-based temperature measurements was good (R = 0.98 ± 0.03). A temperature sampling rate of 19 Hz was achieved at 3T in the gel phantom. It was possible to acquire the water frequency in the beating heart muscle with 5-Hz sampling rate during a breath hold. CONCLUSION: Ultrafast thermometry via phase or frequency monitoring along single columns was demonstrated. With a temporal resolution around 50 ms, it may be possible to monitor focal heating produced by short ultrasound pulses.
Wu W, Rigolo L, O'Donnell LJ, Norton I, Shriver S, Golby AJ. Visual pathway study using in vivo diffusion tensor imaging tractography to complement classic anatomy. Neurosurgery. 2012;70 (1 Suppl Operative) :145-56; discussion 156.Abstract
BACKGROUND: Knowledge of the individual course of the optic radiations (ORs) is important to avoid postoperative visual deficits. Cadaveric studies of the visual pathways are limited because it has not been possible to separate the OR from neighboring tracts accurately and results may not apply to individual patients. Diffusion tensor imaging studies may be able to demonstrate the relationships between the OR and neighboring fibers in vivo in individual subjects. OBJECTIVE: To use diffusion tensor imaging tractography to study the OR and the Meyer loop (ML) anatomy in vivo. METHODS: Ten healthy subjects underwent magnetic resonance imaging with diffusion imaging at 3 T. With the use of a fiducial-based diffusion tensor imaging tractography tool (Slicer 3.3), seeds were placed near the lateral geniculate nucleus to reconstruct individual visual pathways and neighboring tracts. Projections of the ORs onto 3-dimensional brain models were shown individually to quantify relationships to key landmarks. RESULTS: Two patterns of visual pathways were found. The OR ran more commonly deep in the whole superior and middle temporal gyri and superior temporal sulcus. The OR was closely surrounded in all cases by an inferior longitudinal fascicle and a parieto/occipito/temporo-pontine fascicle. The mean left and right distances between the tip of the OR and temporal pole were 39.8 ± 3.8 and 40.6 ± 5.7 mm, respectively. CONCLUSION: Diffusion tensor imaging tractography provides a practical complementary method to study the OR and the Meyer loop anatomy in vivo with reference to individual 3-dimensional brain anatomy.
Mamata H, Tokuda J, Gill RR, Padera RF, Lenkinski RE, Sugarbaker DJ, Butler JP, Hatabu H. Clinical application of pharmacokinetic analysis as a biomarker of solitary pulmonary nodules: dynamic contrast-enhanced MR imaging. Magn Reson Med. 2012;68 (5) :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.
Danagoulian GS, Qin L, Nayak KS, Colen RR, Mukundan S, Harris MB, Jolesz FA, Shankaranarayanan A, Copen WA, Schmidt EJ. 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. 2012;68 (5) :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.
Srinivasan S, Hu P, Kissinger KV, Goddu B, Goepfert L, Schmidt EJ, Kozerke S, Nezafat R. Free-breathing 3D whole-heart black-blood imaging with motion sensitized driven equilibrium. J Magn Reson Imaging. 2012;36 (2) :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.
Madore B, Meral CF. Reconstruction algorithm for improved ultrasound image quality. IEEE Trans Ultrason Ferroelectr Freq Control. 2012;59 (2) :217-30.Abstract
A new algorithm is proposed for reconstructing raw RF data into ultrasound images. Previous delay-and-sum beamforming reconstruction algorithms are essentially one-dimensional, because a sum is performed across all receiving elements. In contrast, the present approach is two-dimensional, potentially allowing any time point from any receiving element to contribute to any pixel location. Computer-intensive matrix inversions are performed once, in advance, to create a reconstruction matrix that can be reused indefinitely for a given probe and imaging geometry. Individual images are generated through a single matrix multiplication with the raw RF data, without any need for separate envelope detection or gridding steps. Raw RF data sets were acquired using a commercially available digital ultrasound engine for three imaging geometries: a 64-element array with a rectangular field-of- view (FOV), the same probe with a sector-shaped FOV, and a 128-element array with rectangular FOV. The acquired data were reconstructed using our proposed method and a delay- and-sum beamforming algorithm for comparison purposes. Point spread function (PSF) measurements from metal wires in a water bath showed that the proposed method was able to reduce the size of the PSF and its spatial integral by about 20 to 38%. Images from a commercially available quality-assurance phantom had greater spatial resolution and contrast when reconstructed with the proposed approach.
Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, Rathi Y, Vu M-A, Purohit MP, Helmer K, Koerte I, et al. A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging Behav. 2012;6 (2) :137-92.Abstract
Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.
Egger J, Kapur T, Dukatz T, Kolodziej M, Zukić D, Freisleben B, Nimsky C. Square-cut: a segmentation algorithm on the basis of a rectangle shape. PLoS One. 2012;7 (2) :e31064.Abstract
We present a rectangle-based segmentation algorithm that sets up a graph and performs a graph cut to separate an object from the background. However, graph-based algorithms distribute the graph's nodes uniformly and equidistantly on the image. Then, a smoothness term is added to force the cut to prefer a particular shape. This strategy does not allow the cut to prefer a certain structure, especially when areas of the object are indistinguishable from the background. We solve this problem by referring to a rectangle shape of the object when sampling the graph nodes, i.e., the nodes are distributed non-uniformly and non-equidistantly on the image. This strategy can be useful, when areas of the object are indistinguishable from the background. For evaluation, we focus on vertebrae images from Magnetic Resonance Imaging (MRI) datasets to support the time consuming manual slice-by-slice segmentation performed by physicians. The ground truth of the vertebrae boundaries were manually extracted by two clinical experts (neurological surgeons) with several years of experience in spine surgery and afterwards compared with the automatic segmentation results of the proposed scheme yielding an average Dice Similarity Coefficient (DSC) of 90.97±2.2%.
Egger J, Freisleben B, Nimsky C, Kapur T. Template-cut: a pattern-based segmentation paradigm. Sci Rep. 2012;2 :420.Abstract
We present a scale-invariant, template-based segmentation paradigm that sets up a graph and performs a graph cut to separate an object from the background. Typically graph-based schemes distribute the nodes of the graph uniformly and equidistantly on the image, and use a regularizer to bias the cut towards a particular shape. The strategy of uniform and equidistant nodes does not allow the cut to prefer more complex structures, especially when areas of the object are indistinguishable from the background. We propose a solution by introducing the concept of a "template shape" of the target object in which the nodes are sampled non-uniformly and non-equidistantly on the image. We evaluate it on 2D-images where the object's textures and backgrounds are similar, and large areas of the object have the same gray level appearance as the background. We also evaluate it in 3D on 60 brain tumor datasets for neurosurgical planning purposes.
Treat LH, McDannold N, Zhang Y, Vykhodtseva N, Hynynen K. Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol. 2012;38 (10) :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.
Panych LP, Roebuck JR, Chen N-kuei, Tang Y, Madore B, Tempany CM, Mulkern RV. Investigation of the PSF-choice method for reduced lipid contamination in prostate MR spectroscopic imaging. Magn Reson Med. 2012;68 (5) :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.
Park J, Zhang Y, Vykhodtseva N, Jolesz FA, McDannold NJ. The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound. J Control Release. 2012;162 (1) :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.
Medel R, Monteith SJ, Elias JW, Eames M, Snell J, Sheehan JP, Wintermark M, Jolesz FA, Kassell NF. Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications. Neurosurgery. 2012;71 (4) :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.
Tokuda J, Song S-E, Fischer GS, Iordachita II, Seifabadi R, Cho NB, Tuncali K, Fichtinger G, Tempany CM, Hata N. Preclinical evaluation of an MRI-compatible pneumatic robot for angulated needle placement in transperineal prostate interventions. Int J Comput Assist Radiol Surg. 2012;7 (6) :949-57.Abstract
PURPOSE: To evaluate the targeting accuracy of a small profile MRI-compatible pneumatic robot for needle placement that can angulate a needle insertion path into a large accessible target volume. METHODS: We extended our MRI-compatible pneumatic robot for needle placement to utilize its four degrees-of-freedom (4-DOF) mechanism with two parallel triangular structures and support transperineal prostate biopsies in a closed-bore magnetic resonance imaging (MRI) scanner. The robot is designed to guide a needle toward a lesion so that a radiologist can manually insert it in the bore. The robot is integrated with navigation software that allows an operator to plan angulated needle insertion by selecting a target and an entry point. The targeting error was evaluated while the angle between the needle insertion path and the static magnetic field was between -5.7° and 5.7° horizontally and between -5.7° and 4.3° vertically in the MRI scanner after sterilizing and draping the device. RESULTS: The robot positioned the needle for angulated insertion as specified on the navigation software with overall targeting error of 0.8 ± 0.5mm along the horizontal axis and 0.8 ± 0.8mm along the vertical axis. The two-dimensional root-mean-square targeting error on the axial slices as containing the targets was 1.4mm. CONCLUSIONS: Our preclinical evaluation demonstrated that the MRI-compatible pneumatic robot for needle placement with the capability to angulate the needle insertion path provides targeting accuracy feasible for clinical MRI-guided prostate interventions. The clinical feasibility has to be established in a clinical study.
Yuan J, Mei C-S, Panych LP, McDannold NJ, Madore B. Towards fast and accurate temperature mapping with proton resonance frequency-based MR thermometry. Quant Imaging Med Surg. 2012;2 (1) :21-32.Abstract
The capability to image temperature is a very attractive feature of MRI and has been actively exploited for guiding minimally-invasive thermal therapies. Among many MR-based temperature-sensitive approaches, proton resonance frequency (PRF) thermometry provides the advantage of excellent linearity of signal with temperature over a large temperature range. Furthermore, the PRF shift has been shown to be fairly independent of tissue type and thermal history. For these reasons, PRF method has evolved into the most widely used MR-based thermometry method. In the present paper, the basic principles of PRF-based temperature mapping will be reviewed, along with associated pulse sequence designs. Technical advancements aimed at increasing the imaging speed and/or temperature accuracy of PRF-based thermometry sequences, such as image acceleration, fat suppression, reduced field-of-view imaging, as well as motion tracking and correction, will be discussed. The development of accurate MR thermometry methods applicable to moving organs with non-negligible fat content represents a very challenging goal, but recent developments suggest that this goal may be achieved. If so, MR-guided thermal therapies may be expected to play an increasingly-important therapeutic and palliative role, as a minimally-invasive alternative to surgery.
Jing Y, Wang T, Clement GT. A k-space method for moderately nonlinear wave propagation. IEEE Trans Ultrason Ferroelectr Freq Control. 2012;59 (8) :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.
Fennessy FM, Fedorov A, Gupta SN, Schmidt EJ, Tempany CM, Mulkern RV. Practical considerations in T1 mapping of prostate for dynamic contrast enhancement pharmacokinetic analyses. Magn Reson Imaging. 2012;30 (9) :1224-33.Abstract
There are many challenges in developing robust imaging biomarkers that can be reliably applied in a clinical trial setting. In the case of dynamic contrast-enhanced (DCE) MRI, one such challenge is to obtain accurate precontrast T(1) maps for subsequent use in two-compartment pharmacokinetic models commonly used to fit the MR enhancement time courses. In the prostate, a convenient and common approach for this task has been to use the same 3D spoiled gradient-echo sequence used to collect the DCE data, but with variable flip angles (VFAs) to collect data suitable for T(1) mapping prior to contrast injection. However, inhomogeneous radiofrequency conditions within the prostate have been found to adversely affect the accuracy of this technique. Herein we demonstrate the sensitivity of DCE pharmacokinetic parameters to precontrast T(1) values and examine methods to improve the accuracy of T(1) mapping with flip angle-corrected VFA SPGR methods, comparing T(1) maps from such methods with "gold standard" reference T(1) maps generated with saturation recovery experiments performed with fast spin-echo (FSE) sequences.
Bonmassar G, Fujimoto K, Golby AJ. PTFOS: flexible and absorbable intracranial electrodes for magnetic resonance imaging. PLoS One. 2012;7 (9) :e41187.Abstract
Intracranial electrocortical recording and stimulation can provide unique knowledge about functional brain anatomy in patients undergoing brain surgery. This approach is commonly used in the treatment of medically refractory epilepsy. However, it can be very difficult to integrate the results of cortical recordings with other brain mapping modalities, particularly functional magnetic resonance imaging (fMRI). The ability to integrate imaging and electrophysiological information with simultaneous subdural electrocortical recording/stimulation and fMRI could offer significant insight for cognitive and systems neuroscience as well as for clinical neurology, particularly for patients with epilepsy or functional disorders. However, standard subdural electrodes cause significant artifact in MRI images, and concerns about risks such as cortical heating have generally precluded obtaining MRI in patients with implanted electrodes. We propose an electrode set based on polymer thick film organic substrate (PTFOS), an organic absorbable, flexible and stretchable electrode grid for intracranial use. These new types of MRI transparent intracranial electrodes are based on nano-particle ink technology that builds on our earlier development of an EEG/fMRI electrode set for scalp recording. The development of MRI-compatible recording/stimulation electrodes with a very thin profile could allow functional mapping at the individual subject level of the underlying feedback and feed forward networks. The thin flexible substrate would allow the electrodes to optimally contact the convoluted brain surface. Performance properties of the PTFOS were assessed by MRI measurements, finite difference time domain (FDTD) simulations, micro-volt recording, and injecting currents using standard electrocortical stimulation in phantoms. In contrast to the large artifacts exhibited with standard electrode sets, the PTFOS exhibited no artifact due to the reduced amount of metal and conductivity of the electrode/trace ink and had similar electrical properties to a standard subdural electrode set. The enhanced image quality could enable routine MRI exams of patients with intracranial electrode implantation and could also lead to chronic implantation solutions.
Park J, Zhang Y, Vykhodtseva N, Akula JD, McDannold NJ. Targeted and reversible blood-retinal barrier disruption via focused ultrasound and microbubbles. PLoS One. 2012;7 (8) :e42754.Abstract
The blood-retinal barrier (BRB) prevents most systemically-administered drugs from reaching the retina. This study investigated whether burst ultrasound applied with a circulating microbubble agent can disrupt the BRB, providing a noninvasive method for the targeted delivery of systemically administered drugs to the retina. To demonstrate the efficacy and reversibility of such a procedure, five overlapping targets around the optic nerve head were sonicated through the cornea and lens in 20 healthy male Sprague-Dawley rats using a 690 kHz focused ultrasound transducer. For BRB disruption, 10 ms bursts were applied at 1 Hz for 60 s with different peak rarefactional pressure amplitudes (0.81, 0.88 and 1.1 MPa). Each sonication was combined with an IV injection of a microbubble ultrasound contrast agent (Definity). To evaluate BRB disruption, an MRI contrast agent (Magnevist) was injected IV immediately after the last sonication, and serial T1-weighted MR images were acquired up to 30 minutes. MRI contrast enhancement into the vitreous humor near targeted area was observed for all tested pressure amplitudes, with more signal enhancement evident at the highest pressure amplitude. At 0.81 MPa, BRB disruption was not detected 3 h post sonication, after an additional MRI contrast injection. A day after sonication, the eyes were processed for histology of the retina. At the two lower exposure levels (0.81 and 0.88 MPa), most of the sonicated regions were indistinguishable from the control eyes, although a few tiny clusters of extravasated erythrocytes (petechaie) were observed. More severe retinal damage was observed at 1.1 MPa. These results demonstrate that focused ultrasound and microbubbles can offer a noninvasive and targeted means to transiently disrupt the BRB for ocular drug delivery.
Park E-J, Zhang Y-Z, Vykhodtseva N, McDannold N. Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model. J Control Release. 2012;163 (3) :277-84.Abstract
Trastuzumab has shown positive results in many patients with metastatic HER2-positive breast cancer, but it is less effective for controlling metastases in the CNS, which remains a site of relapse. The poor prognosis for patients with brain metastases is thought to be largely due to the presence of the blood-brain barrier (BBB) that prevents delivery of most drugs to the CNS and to the heterogeneous and limited permeability of the blood-tumor barrier (BTB). Focused ultrasound (FUS) bursts combined with circulating microbubbles can temporarily permeabilize both the BBB and the BTB. This technique has been investigated as a potential noninvasive method for targeted drug delivery in the brain. Here, we investigated whether BBB/BTB permeabilization in the tumor and surrounding brain tissue induced by FUS and microbubbles can slow tumor growth and improve survival in a breast cancer brain metastases model. HER2/neu-positive human breast cancer cells (BT474) were inoculated in the brains of 41 nude (nu/nu) rats. Animals in the treatment group received six weekly treatments of BTB/BBB permeabilization under MRI guidance combined with IV administration of trastuzumab (2 mg/kg). Tumor growth and survival rates were monitored via MRI for seven weeks after sonication. Starting at week seven and continuing through the end of the study, the mean tumor volume of the FUS+trastuzumab group was significantly (P<0.05) less than those of the three control groups (no treatment, FUS alone, trastuzumab alone). Furthermore, in four out of 10 rats treated with FUS+trastuzumab, the tumor appeared to be completely resolved in MRI, an outcome which was not observed in any of the 31 rats in three control groups. Trastuzumab improved median survival by 13% compared to the no treatment group, a difference which was significant (P=0.044). Treatment with FUS+trastuzumab produced the most significant benefit compared to the no-treatment controls (P=0.0084). More than half (6/10) animals survived at the study endpoint, leading to a median survival time greater than 83 days (at least 32% longer than the untreated control group). Overall, this work suggests that BBB/BTB permeabilization induced by FUS and microbubbles can improve outcomes in breast cancer brain metastases.

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