Publications by Year: 2007

Seung-Schik Yoo, Heather M O'Leary, Jong-Hwan Lee, Nan-kuei Chen, Lawrence P Panych, and Ferenc A Jolesz. 2007. “Reproducibility of trial-based functional MRI on motor imagery.” Int J Neurosci, 117, 2, Pp. 215-27.Abstract
The investigation of the reproducibility in functional MRI (fMRI) is an important step in the quantification and analysis of paradigm-related brain activation. This article reports on reproducibility of cortical activation characterized by repeated fMRI runs (10 times) during the performance of a motor imagery and a passive auditory stimulation as a control task. Two parameters, the size of activation and BOLD signal contrast, were measured from regions-of-interest for 10 subjects across different threshold conditions. The variability of these parameters was normalized with respect to the mean obtained from 10 runs, and represented as the intrasession variability. It was found that the variability was significantly lower in the measurement of BOLD signal contrast as compared to the measurement of the size of activation. The variability of the activation volume measurement was greater in the motor imagery task than in the auditory tasks across all thresholds. This task-dependent difference was not apparent from the measurement of the BOLD signal contrast. The presence of threshold dependence in the variability measurement was also examined, but no such dependency was found. The results suggest that a measurement of BOLD signal itself is a more reliable indicator of paradigm-related brain activation during repeated fMRI scans.
SP DiMaio, S Pieper, K Chinzei, N Hata, SJ Haker, DF Kacher, G Fichtinger, CM Tempany, and R Kikinis. 2007. “Robot-assisted needle placement in open MRI: system architecture, integration and validation.” Comput Aided Surg, 12, 1, Pp. 15-24.Abstract
In prostate cancer treatment, there is a move toward targeted interventions for biopsy and therapy, which has precipitated the need for precise image-guided methods for needle placement. This paper describes an integrated system for planning and performing percutaneous procedures with robotic assistance under MRI guidance. A graphical planning interface allows the physician to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's registered pre-operative and pre-procedural MR images, immediately prior to the intervention in an open-bore MRI scanner. All image-space coordinates are automatically computed, and are used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Automatic alignment of real-time intra-operative images aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided.
Jian Qing Zhang, Kevin R Loughlin, Kelly H Zou, Steven Haker, and Clare M Tempany. 2007. “Role of endorectal coil magnetic resonance imaging in treatment of patients with prostate cancer and in determining radical prostatectomy surgical margin status: report of a single surgeon's practice.” Urology, 69, 6, Pp. 1134-7.Abstract

OBJECTIVES: To evaluate the role of the combination of endorectal coil and external multicoil array magnetic resonance imaging (MRI) in the management of prostate cancer and predicting the surgical margin status in a single-surgeon practice. METHODS: We reviewed all patients referred by a single surgeon from January 1993 to May 2002 for staging prostate MRI before selecting treatment. All MRI examinations were performed using 1.5T (Signa, GE Medical Systems) with a combination of endorectal and pelvic multicoil array. The tumor size, stage, and total gland volume on MRI, prostate-specific antigen (PSA) level, and Gleason score were all compared with the pathologic stage and diagnosis of positive surgical margins (PSMs). RESULTS: A total of 232 patients were evaluated, of whom 110 underwent radical prostatectomy, all performed by one surgeon (group 1), and 122 did not (group 2). The results showed that MRI stage, PSA level, and age were all significantly different (P <0.001). In group 1, the results showed a high specificity (99%) and accuracy (91%) for MRI staging of T3 cancer. The postoperative follow-up (median 4.5 years) revealed that 90% of men had PSA levels of less than 0.1 ng/mL. The PSM rate was 16%. No significant difference was found on MRI between the PSM group and non-PSM group. A single tumor length greater than 1.8 cm was the cutpoint above which PSMs were found (P = 0.002). CONCLUSIONS: The results of our study have shown that the combined use of clinical data and endorectal MRI can help optimize patient treatment and selection for surgery and, in a single surgeon's practice, lead to successful outcomes.

Nobuyuki Nakajima, Jun Wada, Tamotsu Miki, Jo Haraoka, and Nobuhiko Hata. 2007. “Surface rendering-based virtual intraventricular endoscopy: retrospective feasibility study and comparison to volume rendering-based approach.” Neuroimage, 37 Suppl 1, Pp. S89-99.Abstract
OBJECTIVE: Virtual endoscopic simulations using volume rendering (VR) have been proposed as a tool for training and understanding intraventricular anatomy. It is not known whether surface rendering (SR), an alternative to VR, can visualize intraventricular and subependymal structures better and thus making the virtual endoscope more useful for simulating the intraventricular endoscopy. We sought to develop SR-virtual endoscopy and compared the visibility of anatomical structures in SR and VR using retrospective cases. MATERIALS AND METHODS: Fourteen patients who underwent endoscopic intraventricular surgery of third ventricle enrolled the study. SR-virtual endoscopy module was developed in open-source software 3D Slicer and virtual endoscopic scenes from the retrospective cases were created. VR virtual endoscopy of the same cases was prepared in commercial software. Three neurosurgeons scored the visibility of substructures in lateral and third ventricle, arteries, cranial nerves, and other lesions Results: We found that VR and SR-virtual endoscopy performed similarly in visualization of substructures in lateral and third ventricle (not significant statistically). However, the SR was statistically significantly better in visualizing subependymal arteries, cranial nerves, and other lesions (p<0.05, respectively). CONCLUSIONS: We concluded that SR-virtual endoscopy is a promising tool to visualize critical anatomical structures in simulated endoscopic intraventricular surgery. The results lead us to propose a hybrid technique of volume and surface rendering to balance the strength of surface rendering alone in visualizing arteries, nerves and lesions, with fast volume rendering of third and lateral ventricles.
Lisa H Treat, Nathan McDannold, Natalia Vykhodtseva, Yongzhi Zhang, Karen Tam, and Kullervo Hynynen. 2007. “Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound.” Int J Cancer, 121, 4, Pp. 901-7.Abstract
The clinical application of chemotherapy to brain tumors has been severely limited because antitumor agents are typically unable to penetrate an intact blood-brain barrier (BBB). Although doxorubicin (DOX) has been named as a strong candidate for chemotherapy of the central nervous system (CNS), the BBB often prevents cytotoxic levels from being achieved. In this study, we demonstrate a noninvasive method for the targeted delivery of DOX through the BBB, such that drug levels shown to be therapeutic in human tumors are achieved in the normal rat brain. Using MRI-guided focused ultrasound with preformed microbubbles (Optison) to locally disrupt the BBB and systemic administration of DOX, we achieved DOX concentrations of 886 +/- 327 ng/g tissue in the brain with minimal tissue effects. Tissue DOX concentrations of up to 5,366 +/- 659 ng/g tissue were achieved with higher Optison doses, but with more significant tissue damage. In contrast, DOX accumulation in nontargeted contralateral brain tissue remained significantly lower for all paired samples (p < 0.001). These results suggest that targeted delivery by focused ultrasound may render DOX chemotherapy a viable treatment option against CNS tumors, despite previous accessibility limitations. In addition, MRI signal enhancement in the sonicated region correlated strongly with tissue DOX concentration (r = 0.87), suggesting that contrast-enhanced MRI could perhaps indicate drug penetration during image-guided interventions. Our technique using MRI-guided focused ultrasound to achieve therapeutic levels of DOX in the brain offers a large step forward in the use of chemotherapy to treat patients with CNS malignancies.
Nathan McDannold, Agnieszka Szot Barnes, Frank J Rybicki, Koichi Oshio, Nan-kuei Chen, Kullervo Hynynen, and Robert V Mulkern. 2007. “Temperature mapping considerations in the breast with line scan echo planar spectroscopic imaging.” Magn Reson Med, 58, 6, Pp. 1117-23.Abstract

A line-scan echo planar spectroscopic imaging (LSEPSI) sequence was used to serially acquire spectra from 4,096 voxels every 6.4 s throughout the breasts of nine female subjects in vivo. Data from the serial acquisitions were analyzed to determine the potential of the technique to characterize temperature changes using either the water frequency alone or the water-methylene frequency difference. Fluctuations of the apparent temperature change under these conditions of no heating were smallest using the water-methylene frequency difference, most probably due to a substantial reduction of motion effects both within and without the imaged plane. The approach offers considerable advantages over other methods for temperature change monitoring in the breast with magnetic resonance but suffers from some limitations, including the unavailability of lipid and water resonances in some voxels as well as a surprisingly large distribution of water-methylene frequency differences, which may preclude absolute temperature measurement.

Lauren J O'Donnell, Carl-Fredrik Westin, and Alexandra J Golby. 2007. “Tract-based morphometry.” Med Image Comput Comput Assist Interv, 10, Pt 2, Pp. 161-8.Abstract
Multisubject statistical analyses of diffusion tensor images in regions of specific white matter tracts have commonly measured only the mean value of a scalar invariant such as the fractional anisotropy (FA), ignoring the spatial variation of FA along the length of fiber tracts. We propose to instead perform tract-based morphometry (TBM), or the statistical analysis of diffusion MRI data in an anatomical tract-based coordinate system. We present a method for automatic generation of white matter tract arc length parameterizations, based on learning a fiber bundle model from tractography from multiple subjects. Our tract-based coordinate system enables TBM for the detection of white matter differences in groups of subjects. We present example TBM results from a study of interhemispheric differences in FA.
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 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.