Publications

2007
Philip Blumenfeld, Nobuhiko Hata, Simon DiMaio, Kelly Zou, Steven Haker, Gabor Fichtinger, and Clare M Tempany. 2007. “Transperineal Prostate Biopsy under Magnetic Resonance Image Guidance: A Needle Placement Accuracy Study.” J Magn Reson Imaging, 26, 3, Pp. 688-94.Abstract

PURPOSE: To quantify needle placement accuracy of magnetic resonance image (MRI)-guided core needle biopsy of the prostate. MATERIALS AND METHODS: A total of 10 biopsies were performed with 18-gauge (G) core biopsy needle via a percutaneous transperineal approach. Needle placement error was assessed by comparing the coordinates of preplanned targets with the needle tip measured from the intraprocedural coherent gradient echo images. The source of these errors was subsequently investigated by measuring displacement caused by needle deflection and needle susceptibility artifact shift in controlled phantom studies. Needle placement error due to misalignment of the needle template guide was also evaluated. RESULTS: The mean and standard deviation (SD) of errors in targeted biopsies was 6.5 +/- 3.5 mm. Phantom experiments showed significant placement error due to needle deflection with a needle with an asymmetrically beveled tip (3.2-8.7 mm depending on tissue type) but significantly smaller error with a symmetrical bevel (0.6-1.1 mm). Needle susceptibility artifacts observed a shift of 1.6 +/- 0.4 mm from the true needle axis. Misalignment of the needle template guide contributed an error of 1.5 +/- 0.3 mm. CONCLUSION: Needle placement error was clinically significant in MRI-guided biopsy for diagnosis of prostate cancer. Needle placement error due to needle deflection was the most significant cause of error, especially for needles with an asymmetrical bevel.

Phillip J White and Greg T Clement. 2007. “Two-dimensional localization with a single diffuse ultrasound field excitation.” IEEE Trans Ultrason Ferroelectr Freq Control, 54, 11, Pp. 2309-17.Abstract
Traditional ultrasound imaging methods rely on the bandwidth and center frequency of transduction to achieve axial and radial image resolution, respectively. In this study, a new modality for spatially localizing scattering targets in a two-dimensional field is presented. In this method, the bandwidth of field excitation is high, and the center frequency is lowered such that the corresponding wavelengths are substantially larger than the target profiles. Furthermore, full two-dimensional field measurements are obtained with single send-receive sequences, demonstrating a substantial simplification of the traditional scanning techniques. Field reconstruction is based on temporal-spectral cross-correlations between measured backscatter data and a library of region of interest (ROI) backscatter data measured a priori. The transducer design is based upon a wedge-shaped geometry, which was shown to yield spatially frequency-separated bandwidths of up to 156% with center frequencies of 1.38 MHz. Initial results with these send-and-receive transducer parameters and cylindrical reflection targets in a 10-mm x 10-mm ROI demonstrate two-dimensional target localization to within 0.5 mm. Spatial localization of point scatterers is demonstrated for single and multiple scattering sites.
Gregory T Clement. 2007. “Two-dimensional ultrasound detection with unfocused frequency-randomized signals.” J Acoust Soc Am, 121, 1, Pp. 636-47.Abstract
A method is described for detecting scattering in two-dimensions using an unfocused ultrasound field created from a continuously driven source array. The frequency of each element on the array is unique, resulting in a field that is highly variant as a function of both time and position. The scattered signal is then received by a single receiving line. The method, as currently written, is valid under the first order Born approximation. To demonstrate the approach, a series of simulations within the frequency range of 0.10-1.25 MHz are performed and compared with a simulated B-Scan in the same frequency range. The method is found to be superior in resolving closely spaced objects, discerning 1.4 mm separation in the radial and 0.5-mm separation in the axial direction. The method was also better able to determine object size, resolving scatters less than 10% of wavelength associated with the center frequency.
Nathan McDannold, Natalia Vykhodtseva, and Kullervo Hynynen. 2007. “Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: a feasibility study.” Ultrasound Med Biol, 33, 4, Pp. 584-90.Abstract
We have developed a method to use low-intensity focused ultrasound pulses combined with an ultrasound contrast agent to produce temporary blood-brain barrier disruption (BBBD). This method could provide a means for the targeted delivery of drugs or imaging agents into the brain. In all our previous work, we used Optison as the ultrasound contrast agent. The purpose of this study was to test the feasibility of using the contrast agent Definity for BBBD. A total of 36 non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (four locations per rabbit; ultrasound [US] frequency: 0.69 MHz; burst: 10 ms; pulse repetition frequency (PRF): 1 Hz; duration: 20 s). The peak negative pressure amplitude ranged from 0.2 to 1.5 MPa. An additional 11 locations were sonicated using Optison at pressure amplitude of 0.5 MPa. Definity and Optison dosages were the same as those used clinically for ultrasound imaging: 10 and 50 microl/kg, respectively. The probability for BBBD (determined using MRI contrast agent enhancement) as a function of pressure amplitude was similar to that found earlier with Optison. For both agents, the probability was estimated to be 50% at 0.4 MPa using probit regression. Histologic examination revealed small, isolated areas of extravasated erythrocytes in some locations. At 0.8 MPa and higher, these areas were sometimes accompanied by tiny (dimensions of 100 microm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (signal enhancement: 13.3% +/- 4.4% vs. 8.4% +/- 4.9%; p = 0.04). In addition, more areas with extravasated erythrocytes were observed with Optison (5.0 +/- 3.5 vs. 1.4 +/- 1.9 areas with extravasation in histology section with largest effect; p = 0.03). We concluded that BBBD is possible using Definity at the dosage of contrast agent and the acoustic parameters tested in this study. The probability for BBBD as a function of pressure amplitude and the type of acute tissue effects were similar to what has been observed using Optison. However, under the experimental conditions used in this study, Optison produced a larger effect for the same acoustic pressure amplitude.
Kilian M Pohl, John Fisher, Sylvain Bouix, Martha Shenton, Robert W McCarley, Eric WL Grimson, Ron Kikinis, and William M Wells. 2007. “Using the logarithm of odds to define a vector space on probabilistic atlases.” Med Image Anal, 11, 5, Pp. 465-77.Abstract
The logarithm of the odds ratio (LogOdds) is frequently used in areas such as artificial neural networks, economics, and biology, as an alternative representation of probabilities. Here, we use LogOdds to place probabilistic atlases in a linear vector space. This representation has several useful properties for medical imaging. For example, it not only encodes the shape of multiple anatomical structures but also captures some information concerning uncertainty. We demonstrate that the resulting vector space operations of addition and scalar multiplication have natural probabilistic interpretations. We discuss several examples for placing label maps into the space of LogOdds. First, we relate signed distance maps, a widely used implicit shape representation, to LogOdds and compare it to an alternative that is based on smoothing by spatial Gaussians. We find that the LogOdds approach better preserves shapes in a complex multiple object setting. In the second example, we capture the uncertainty of boundary locations by mapping multiple label maps of the same object into the LogOdds space. Third, we define a framework for non-convex interpolations among atlases that capture different time points in the aging process of a population. We evaluate the accuracy of our representation by generating a deformable shape atlas that captures the variations of anatomical shapes across a population. The deformable atlas is the result of a principal component analysis within the LogOdds space. This atlas is integrated into an existing segmentation approach for MR images. We compare the performance of the resulting implementation in segmenting 20 test cases to a similar approach that uses a more standard shape model that is based on signed distance maps. On this data set, the Bayesian classification model with our new representation outperformed the other approaches in segmenting subcortical structures.
Fiona M Fennessy, Clare M Tempany, Nathan J McDannold, Minna J So, Gina Hesley, Bobbie Gostout, Hyun S Kim, George A Holland, Dennis A Sarti, Kullervo Hynynen, Ferenc A Jolesz, and Elizabeth A Stewart. 2007. “Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols.” Radiology, 243, 3, Pp. 885-93.Abstract
PURPOSE: To prospectively assess patient response (after 12 months) to magnetic resonance (MR) imaging-guided focused ultrasound surgery in treatment of uterine leiomyomas by using two treatment protocols. MATERIALS AND METHODS: This prospective clinical trial was approved by institutional review boards and was HIPAA compliant. After giving informed consent, patients with symptomatic leiomyomas were consecutively enrolled and treated at one of five U.S. centers by using an original or a modified protocol. Outcomes were assessed with the symptom severity score (SSS) obtained at baseline and 3, 6, and 12 months after treatment. Adverse events (AEs) were recorded. Statistical analysis included Student t test, Fisher exact test, analysis of covariance, Spearman correlation, and logistic regression. RESULTS: One hundred sixty patients had a mean SSS of 62.1 +/- 16.3 (standard deviation) at baseline, which decreased to 35.5 +/- 19.5 at 3 months (P<.001) and to 32.3 +/- 19.8 at 6 months (P<.001) and was 32.7 +/- 21.0 at 12 months (P<.001). Ninety-six patients (mean age, 46.0 years +/- 4.6) were treated with an original protocol, and 64 (mean age, 45.9 years +/- 3.9) were treated with a modified protocol. Patients in the modified group had a significantly greater SSS decrease at 3 months (P=.037) than those in the original group, and 73% of those in the original group and 91% of those in the modified group reported a significant decrease in SSS (of 10 points or greater) at 12 months. No serious AEs were recorded. Fewer AEs were reported in the modified group than in the original group (25% vs 13% reporting no event). Of evaluable patients, fewer in the modified group chose alternative treatment (28%) than in the original group (37%). CONCLUSION: MR imaging-guided focused ultrasound surgery results in symptomatic improvement, sustained to 12 months after treatment. Treatment with a modified protocol results in greater clinical effectiveness and fewer AEs.
Neculai Archip, Ferenc A Jolesz, and Simon K Warfield. 2007. “A validation framework for brain tumor segmentation.” Acad Radiol, 14, 10, Pp. 1242-51.Abstract
RATIONALE AND OBJECTIVES: We introduce a validation framework for the segmentation of brain tumors from magnetic resonance (MR) images. A novel unsupervised semiautomatic brain tumor segmentation algorithm is also presented. MATERIALS AND METHODS: The proposed framework consists of 1) T1-weighted MR images of patients with brain tumors, 2) segmentation of brain tumors performed by four independent experts, 3) segmentation of brain tumors generated by a semiautomatic algorithm, and 4) a software tool that estimates the performance of segmentation algorithms. RESULTS: We demonstrate the validation of the novel segmentation algorithm within the proposed framework. We show its performance and compare it with existent segmentation. The image datasets and software are available at http://www.brain-tumor-repository.org/. CONCLUSIONS: We present an Internet resource that provides access to MR brain tumor image data and segmentation that can be openly used by the research community. Its purpose is to encourage the development and evaluation of segmentation methods by providing raw test and image data, human expert segmentation results, and methods for comparing segmentation results.
Ion-Florin Talos, Kelly H Zou, Ron Kikinis, and Ferenc A Jolesz. 2007. “Volumetric assessment of tumor infiltration of adjacent white matter based on anatomic MRI and diffusion tensor tractography.” Acad Radiol, 14, 4, Pp. 431-6.Abstract
RATIONALE AND OBJECTIVES: To perform a retrospective, quantitative assessment of the anatomic relationship between intra-axial, supratentorial, primary brain tumors, and adjacent white matter fiber tracts based on anatomic and diffusion tensor magnetic resonance imaging (MRI). We hypothesized that white matter infiltration may be common among different types of tumor. MATERIAL AND METHODS: Preoperative, anatomic (T1- and T2-weighted), and LINESCAN diffusion tensor MRI were obtained in 12 patients harboring supratentorial gliomas (World Health Organization [WHO] Grades II and III). The two imaging modalities were rigidly registered. The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Statistical methods included summary statistics to examine the fraction of tumor volume infiltrating adjacent white matter. RESULTS: There were five patients with low-grade oligodendroglioma (WHO Grade II), one with low-grade mixed oligoastrocytoma (WHO Grade II), one with ganglioglioma, two with low-grade astrocytoma (WHO Grade II), and three with anaplastic astrocytoma (WHO Grade III). We identified white matter tracts infiltrated by tumor in all 12 cases. The median tumor volume (+/- standard deviation) in our patient population was 42.5 +/- 28.9 mL. The median tumor volume (+/- standard deviation) infiltrating white matter fiber tracts was 5.2 +/- 9.9 mL. The median percentage of tumor volume infiltrating white matter fiber tracts was 21.4% +/- 9.7%. CONCLUSIONS: The information provided by diffusion tensor imaging combined with anatomic MRI might be useful for neurosurgical planning and intraoperative guidance. Our results confirm previous reports that extensive white matter infiltration by primary brain tumors is a common occurrence. However, prospective, large population studies are required to definitively clarify this issue, and how infiltration relates to histologic tumor type, tumor size, and location.
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.

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