Publications by Year: 2006

Julien Dauguet, Sharon Peled, Vladimir Berezovskii, Thierry Delzescaux, Simon K Warfield, Richard Born, and Carl-Fredrik Westin. 2006. “3D Histological Reconstruction of Fiber Tracts and Direct Comparison With Diffusion Tensor MRI Tractography.” Med Image Comput Comput Assist Interv, 9, Pt 1, Pp. 109-16.Abstract
A classical neural tract tracer, WGA-HRP, was injected at multiple sites within the brain of a macaque monkey. Histological sections of the labeled fiber tracts were reconstructed in 3D, and the fibers were segmented and registered with the anatomical post-mortem MRI from the same animal. Fiber tracing along the same pathways was performed on the DTI data using a classical diffusion tracing technique. The fibers derived from the DTI were compared with those segmented from the histology in order to evaluate the performance of DTI fiber tracing. While there was generally good agreement between the two methods, our results reveal certain limitations of DTI tractography, particularly at regions of fiber tract crossing or bifurcation.
Neculai Archip, Robert Rohling, Vincent Dessenne, Pierre-Jean Erard, and Lutz Peter Nolte. 2006. “Anatomical Structure Modeling From Medical Images.” Comput Methods Programs Biomed, 82, 3, Pp. 203-15.Abstract
Some clinical applications, such as surgical planning, require volumetric models of anatomical structures represented as a set of tetrahedra. A practical method of constructing anatomical models from medical images is presented. The method starts with a set of contours segmented from the medical images by a clinician and produces a model that has high fidelity with the contours. Unlike most modeling methods, the contours are not restricted to lie on parallel planes. The main steps are a 3D Delaunay tetrahedralization, culling of non-object tetrahedra, and refinement of the tetrahedral mesh. The result is a high-quality set of tetrahedra whose surface points are guaranteed to match the original contours. The key is to use the distance map and bit volume structures that were created along with the contours. The method is demonstrated on computed tomography, MRI and 3D ultrasound data. Models of 170,000 tetrahedra are constructed on a standard workstation in approximately 10s. A comparison with related methods is also provided.
Nan-kuei Chen, Koichi Oshio, and Lawrence P Panych. 2006. “Application of k-space energy spectrum analysis to susceptibility field mapping and distortion correction in gradient-echo EPI.” Neuroimage, 31, 2, Pp. 609-22.Abstract
Echo-planar imaging (EPI) is widely used in functional MRI studies. It is well known that EPI quality is usually degraded by geometric distortions, when there exist susceptibility field inhomogeneities. EPI distortions may be corrected if the field maps are available. It is possible to estimate the susceptibility field gradients from the phase reconstruction of a single-TE EPI image, after a successful phase-unwrapping procedure. However, in regions affected by pronounced field gradients, the phase-unwrapping of a single-TE image may fail, and therefore the estimated field maps may be incorrect. It has been reported that the field inhomogeneity may be calculated more reliably from T2*-weighted images corresponding to multiple TEs. However, the multi-TE MRI field mapping increases the scan time. Furthermore, the measured field maps may be invalid if the subject's position changes during dynamic scans. To overcome the limitations in conventional field mapping approaches, a novel k-space energy spectrum analysis algorithm is developed, which quantifies the spatially dependent echo-shifting effect and the susceptibility field gradients directly from the k-space data of single-TE gradient-echo EPI. Using the k-space energy spectrum analysis, susceptibility field gradients can be reliably measured without phase-unwrapping, and EPI distortions can be corrected without extra field mapping scans or pulse sequence modification. The reported technique can be used to retrospectively improve the image quality of the previously acquired EPI and functional MRI data, provided that the complex-domain k-space data are still available.
Robert V Mulkern, Agnieszka Szot Barnes, Steven J Haker, Yin P Hung, Frank J Rybicki, Stephan E Maier, and Clare M Tempany. 2006. “Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.” Magn Reson Imaging, 24, 5, Pp. 563-8.Abstract

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.

Nickolai Sheikov, Nathan McDannold, Ferenc A Jolesz, Yong-Zhi Zhang, Karen Tam, and Kullervo Hynynen. 2006. “Brain Arterioles Show more Active Vesicular Transport of Blood-borne Tracer Molecules than Capillaries and Venules after Focused Ultrasound-evoked Opening of the Blood-brain Barrier.” Ultrasound Med Biol, 32, 9, Pp. 1399-409.Abstract

Previously, activation of vesicular transport in the brain microvasculature was shown to be one of the mechanisms of focused ultrasound-induced blood-brain barrier (BBB) opening. In the present study, we aimed to estimate the rate of the transendothelial vesicular traffic after focused ultrasound sonication in the rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP) as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the number of HRP-containing vesicles per microm(2) of the cell cytoplasm) were 0.9 and 1.05 vesicles/microm(2) 1 h after sonication with ultrasound frequencies of 0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and 2.43 vesicles/microm(2), values 1.8 and 2.3 times higher. In control locations, the densities were 0.7 and 0.14 vesicles/microm(2) for capillaries and arterioles, respectively. A small number of HRP-positive vesicles were observed in the venules. Focal delivery of HRP tracer was also observed in light microscopy. The results indicate that the precapillary microvessels play an important role in macromolecular transcytoplasmic traffic through the ultrasound-induced BBB modulation, which should be considered in the future development of trans-BBB drug delivery strategies.

Scott W Hoge and Dana H Brooks. 2006. “On the complimentarity of SENSE and GRAPPA in parallel MR imaging.” Conf Proc IEEE Eng Med Biol Soc, 1, Pp. 755-8.Abstract
Two image reconstruction methods currently dominate parallel MR imaging: SENSE and GRAPPA. While both seek to reconstruct images from subsampled multi-channel MRI data, there exist fundamental differences between the two. In particular, SENSE reconstructs an image of the excited spin-density directly whereas GRAPPA reconstructs estimates of the fully sampled raw coil data and then combines them to obtain an image. In this work we show that these differences can be exploited such that each method can compliment the other. In the case of SENSE, which requires an estimate of the coil sensitivity map before reconstruction, one can use GRAPPA to improve the coil sensitivity estimates. Alternatively, using coil sensitivity estimates and the SENSE reconstruction equations, one can improve the GRAPPA reconstruction parameter estimation. Together, these approaches can provide higher image quality than either method alone.
Bruno Madore, Scott W Hoge, and Raymond Kwong. 2006. “Extension of the UNFOLD method to include free breathing.” Magn Reson Med, 55, 2, Pp. 352-62.Abstract
Unaliasing by Fourier-encoding the overlaps using the temporal dimension (UNFOLD) is a method to reduce the data acquisition burden in dynamic MRI. The method works by forcing aliased signals to behave in specific ways through time, so that these unwanted signals can be detected and removed. Unexpected events in time, such as displacements caused by breathing, have the potential to disturb the temporal strategy and may affect UNFOLD's ability to suppress aliasing artifacts. This work presents an extension of the UNFOLD method to accommodate temporal encoding disruptions. While the main type of disruption considered here comes from respiratory motion, other types of disruption can be envisioned, such as departures from the usual UNFOLD k-space sampling scheme. This extended version of UNFOLD was incorporated into UNFOLD-sensitivity encoding (UNFOLD-SENSE), and should also be applicable to closely related methods such as temporal SENSE (TSENSE), k-t Broaduse Linear Acquisition Speed up Technique (k-t BLAST), and k-t SENSE. Five patients were imaged with a modified version of a myocardial-perfusion sequence, and UNFOLD was used either alone or in conjunction with SENSE to obtain an acceleration of 2.0 (in three patients) or 3.0 (in two patients). In both cases this extended version of UNFOLD was able to suppress artifacts caused by the presence of breathing motion.
Sharon Peled, Ola Friman, Ferenc A Jolesz, and Carl-Fredrik Westin. 2006. “Geometrically Constrained Two-tensor Model for Crossing Tracts in DWI.” Magn Reson Imaging, 24, 9, Pp. 1263-70.Abstract

MR diffusion tensor imaging (DTI) of the brain and spine provides a unique tool for both visualizing directionality and assessing intactness of white matter fiber tracts in vivo. At the spatial resolution of clinical MRI, much of primate white matter is composed of interdigitating fibers. Analyses based on an assumed single diffusion tensor per voxel yield important information about the average diffusion in the voxel but fail to reveal structure in the presence of crossing tracts. Until today, all clinical scans assume only one tensor, causing potential serious errors in tractography. Since high angular resolution imaging remains, so far, untenable for routine clinical use, a method is proposed whereby the single-tensor field is augmented with additional information gleaned from standard clinical DTI. The method effectively resolves two distinct tract directions within voxels, in which only two tracts are assumed to exist. The underlying constrained two-tensor model is fitted in two stages, utilizing the information present in the single-tensor fit. As a result, the necessary MRI time can be drastically reduced when compared with other approaches, enabling widespread clinical use. Upon evaluation in simulations and application to in vivo human brain DTI data, the method appears to be robust and practical and, if correctly applied, could elucidate tract directions at critical points of uncertainty.

Neil I Weisenfeld, Andrea UJ Mewes, and Simon K Warfield. 2006. “Highly accurate segmentation of brain tissue and subcortical gray matter from newborn MRI.” Med Image Comput Comput Assist Interv, 9, Pt 1, Pp. 199-206.Abstract
The segmentation of newborn brain MRI is important for assessing and directing treatment options for premature infants at risk for developmental disorders, abnormalities, or even death. Segmentation of infant brain MRI is particularly challenging when compared with the segmentation of images acquired from older children and adults. We sought to develop a fully automated segmentation strategy and present here a Bayesian approach utilizing an atlas of priors derived from previous segmentations and a new scheme for automatically selecting and iteratively refining classifier training data using the STAPLE algorithm. Results have been validated by comparison to hand-drawn segmentations.
Simon P Dimaio, Neculai Archip, Nobuhiko Hata, Ion-Florin Talos, Simon K Warfield, Amit Majumdar, Nathan McDannold, Kullervo Hynynen, Paul R Morrison, William M Wells, Daniel F Kacher, Randy E Ellis, Alexandra J Golby, Peter M Black, Ferenc A Jolesz, and Ron Kikinis. 2006. “Image-guided Neurosurgery at Brigham and Women’s Hospital.” IEEE Eng Med Biol Mag, 25, 5, Pp. 67-73.
Seung-Schik Yoo, Heather M O'Leary, Ty Fairneny, Nan-kuei Chen, Lawrence P Panych, HyunWook Park, and Ferenc A Jolesz. 2006. “Increasing cortical activity in auditory areas through neurofeedback functional magnetic resonance imaging.” Neuroreport, 17, 12, Pp. 1273-8.Abstract
We report a functional magnetic resonance imaging method to deliver task-specific brain activities as biofeedback signals to guide individuals to increase cortical activity in auditory areas during sound stimulation. A total of 11 study participants underwent multiple functional magnetic resonance imaging scan sessions, while the changes in the activated cortical volume within the primary and secondary auditory areas were fed back to them between scan sessions. On the basis of the feedback information, participants attempted to increase the number of significant voxels during the subsequent trial sessions by adjusting their level of attention to the auditory stimuli. Results showed that the group of individuals who received the feedback were able to increase the activation volume and blood oxygenation level-dependent signal to a greater degree than the control group.
Natalia Vykhodtseva, Nathan McDannold, and Kullervo Hynynen. 2006. “Induction of apoptosis in vivo in the rabbit brain with focused ultrasound and Optison.” Ultrasound Med Biol, 32, 12, Pp. 1923-9.Abstract
Histologic effects of focused ultrasound (FUS) exposures combined with an ultrasound contrast agent (Optison) were investigated to examine whether the lesions were dominated by apoptosis or necrosis. The rabbit brains (n = 17) were sonicated (1.5 MHz, peak rarefactional pressure amplitude: 1.4 to 8.8 MPa) after Optison was injected intravenously (IV). MRI and light microscopy were used to examine tissue effects. To detect apoptosis, TUNEL staining based on labeling of DNA strand breaks was used. The average number of apoptotic and necrotic cells in 300 x 220 microm microscopic fields were counted in 18 representative lesions. Lesions in the rabbit brains were created at lowered acoustic power levels when FUS was combined with Optison. In histology, the lesions exhibited red blood cell extravasations and destruction of blood vessels. At 4 h after sonication, the lesions lost many cells, and the remaining cells exhibited both necrotic and apoptotic features. Overall, apoptosis dominated; there were, on average, 32.3 +/- 13.2 apoptotic cells per microscopic field compared with only 5.1 +/- 3.4 necrotic cells per field. In conclusion, FUS combined with Optison could produce lesions that are dominated by apoptosis, presumably induced primarily via ischemia after cavitation-produced damage to the brain vasculature.
James P O'shea, Stephen Whalen, Daniel M Branco, Nicole M Petrovich, Kyle E Knierim, and Alexandra J Golby. 2006. “Integrated image- and function-guided surgery in eloquent cortex: a technique report.” Int J Med Robot, 2, 1, Pp. 75-83.Abstract
The ability to effectively identify eloquent cortex in close proximity to brain tumours is a critical component of surgical planning prior to resection. The use of electrocortical stimulation testing (ECS) during awake neurosurgical procedures remains the gold standard for mapping functional areas, yet the preoperative use of non-invasive brain imaging techniques such as fMRI are gaining popularity as supplemental surgical planning tools. In addition, the intraoperative three-dimensional display of fMRI findings co-registered to structural imaging data maximizes the utility of the preoperative mapping for the surgeon. Advances in these techniques have the potential to limit the size and duration of craniotomies as well as the strain placed on the patient, but more research accurately demonstrating their efficacy is required. In this paper, we demonstrate the integration of preoperative fMRI within a neuronavigation system to aid in surgical planning, as well as the integration of these fMRI data with intraoperative ECS mapping results into a three-dimensional dataset for the purpose of cross-validation.
Joachim Kettenbach, Daniel F Kacher, Angela R Kanan, Bill Rostenberg, Janice Fairhurst, Alfred Stadler, K Kienreich, and Ferenc A Jolesz. 2006. “Intraoperative and interventional MRI: recommendations for a safe environment.” Minim Invasive Ther Allied Technol, 15, 2, Pp. 53-64.Abstract
In this paper we report on current experience and review magnetic resonance safety protocols and literature in order to define practices surrounding MRI-guided interventional and surgical procedures. Direct experience, the American College of Radiology White paper on MR Safety, and various other sources are summarized. Additional recommendations for interventional and surgical MRI-guided procedures cover suite location/layout, accessibility, safety policy, personnel training, and MRI compatibility issues. Further information is freely available for sites to establish practices to minimize risk and ensure safety. Interventional and intraoperative MRI is emerging from its infancy, with twelve years since the advent of the field and well over 10,000 cases collectively performed. Thus, users of interventional and intraoperative MRI should adapt guidelines utilizing universal standards and terminology and establish a site-specific policy. With policy enforcement and proper training, the interventional and intraoperative MR imaging suite can be a safe and effective environment.
PJ White, GT Clement, and K Hynynen. 2006. “Local Frequency Dependence in Transcranial Ultrasound Transmission.” Phys Med Biol, 51, 9, Pp. 2293-305.Abstract

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

PJ White, GT Clement, and K Hynynen. 2006. “Longitudinal and shear mode ultrasound propagation in human skull bone.” Ultrasound Med Biol, 32, 7, Pp. 1085-96.Abstract
Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.
I-F Talos, AZ Mian, KH Zou, L Hsu, D Goldberg-Zimring, S Haker, JG Bhagwat, and RV Mulkern. 2006. “Magnetic Resonance and the Human Brain: Anatomy, Function and Metabolism.” Cell Mol Life Sci, 63, 10, Pp. 1106-24.Abstract

The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth.

SP DiMaio, DF Kacher, RE Ellis, G Fichtinger, N Hata, GP Zientara, LP Panych, R Kikinis, and FA Jolesz. 2006. “Needle artifact localization in 3T MR images.” Stud Health Technol Inform, 119, Pp. 120-5.Abstract
This work explores an image-based approach for localizing needles during MRI-guided interventions, for the purpose of tracking and navigation. Susceptibility artifacts for several needles of varying thickness were imaged, in phantoms, using a 3 tesla MRI system, under a variety of conditions. The relationship between the true needle positions and the locations of artifacts within the images, determined both by manual and automatic segmentation methods, have been quantified and are presented here.
Bruno Madore, Gunnar Farnebäck, Carl-Fredrik Westin, and Alejandra Durán-Mendicuti. 2006. “A new strategy for respiration compensation, applied toward 3D free-breathing cardiac MRI.” Magn Reson Imaging, 24, 6, Pp. 727-37.Abstract
In thorax and abdomen imaging, image quality may be affected by breathing motion. Cardiac MR images are typically obtained while the patient holds his or her breath, to avoid respiration-related artifacts. Although useful, breath-holding imposes constraints on scan duration, which in turn limits the achievable resolution and SNR. Longer scan times would be required to improve image quality, and effective strategies are needed to compensate for respiratory motion. A novel approach at respiratory compensation, targeted toward 3D free-breathing cardiac MRI, is presented here. The method aims at suppressing the negative effects of respiratory-induced cardiac motion while capturing the heart's beating motion. The method is designed so that the acquired data can be reconstructed in two different ways: First, a time series of images is reconstructed to quantify and correct for respiratory motion. Then, the corrected data are reconstructed a final time into a cardiac-phase series of images to capture the heart's beating motion. The method was implemented, and initial results are presented. A cardiac-phase series of 3D images, covering the entire heart, was obtained for two free-breathing volunteers. The present method may prove especially useful in situations where breath-holding is not an option, for example, for very sick, mentally impaired or infant patients.
Manabu Kinoshita, Nathan McDannold, Ferenc A Jolesz, and Kullervo Hynynen. 2006. “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption.” Proc Natl Acad Sci U S A, 103, 31, Pp. 11719-23.Abstract
Antibody-based anticancer agents are promising chemotherapeutic agents. Among these agents, Herceptin (trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, has been used successfully in patients with breast cancer. However, in patients with brain metastasis, the blood-brain barrier limits its use, and a different delivery method is needed to treat these patients. Here, we report that Herceptin can be delivered locally and noninvasively into the mouse central nervous system through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound blood-brain barrier disruption technique. The amount of Herceptin delivered to the target tissue was correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. Histological changes attributable to this procedure were minimal. This method may represent a powerful technique for the delivery of macromolecular agents such as antibodies to treat patients with diseases of the central nervous system.