Publications by Year: 2003

Cotton F, Weiner HL, Jolesz FA, Guttmann CRG. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology. 2003;60 (4) :640-6.Abstract
BACKGROUND: One of the diagnostic imaging hallmarks of MS is the uptake of IV administered contrast material in new lesions in the brain, signaling blood-brain barrier breakdown and active inflammation. Many clinical drug trials are designed based on the assumption that lesion enhancement on MRI remains visible on average for 1 month. For practical reasons, few serial MRI studies of patients with MS have been performed at intervals shorter than 4 weeks. METHODS: The authors performed a year-long longitudinal study in 26 patients with relapsing-remitting MS (RRMS), which comprised an initial phase of MRI follow-up at weekly intervals for 8 weeks, followed by imaging every other week for another 16 weeks, and monthly thereafter. They present a quantitative analysis (using a supervised interactive thresholding procedure) of new enhancing lesions appearing during the first 6 weeks in this cohort and evaluated from the time of first detection until enhancement was no longer seen. RESULTS: The average duration of Gd-DTPA enhancement in individual new lesions was 3.07 weeks (median, 2 weeks). Significant correlations were demonstrated between the duration of contrast enhancement or initial growth rates and lesion volumes. Different lesions in the same patient appeared to develop largely independent of each other and demonstrated a large range in the duration of enhancement during the acute phase of their evolution. CONCLUSIONS: The average duration of blood-brain barrier impairment in RRMS is shorter than earlier estimates. Early lesion growth parameters may predict final lesion size. Within-patient heterogeneity of lesion evolution suggests that individual lesions develop independently.
Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Lee C-U, Ciszewski AA, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. Am J Psychiatry. 2003;160 (1) :156-64.Abstract
OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions. CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.
Soman S, Chung ACS, Grimson EWL, Wells WM. Rigid Registration of Echoplanar and Conventional Magnetic Resonance Images by Minimizing the Kullback-Leibler Distance. Biomed Image Registration. 2003;2717 :181-190.Abstract
Functional Magnetic Resonance Imaging (fMRI) studies are derived from a time series of Echo-Planar images (EPIs). Compared to conventional Magnetic Resonance Images (MRIs), EPIs are of relatively poor quality for discerning anatomic features and are often registered with corresponding MRIs to map brain activity to neuroanatomy. In this paper we demonstrate the utility of a technique to register an EPI-MRI pair by minimizing the discrepancy between its joint intensity probability mass function (PMF) and a previously learned one for a properly registered EPI-MRI pair, using the Kullback-Leibler Distance (KLD). In probing experiments Joint Entropy (JE) and Mutual Information showed significant bias relative to KLD along the axial direction and JE along a rotation axis. A comparison of searches using random starting poses showed KLD to have lower final pose errors than JE. Results of variation on parameters of the KLD based EPI-MRI registration technique are also presented.
Hunt RW, Warfield SK, Wang H, Kean MJ, Volpe JJ, Inder TE. Assessment of the Impact of the Removal of Cerebrospinal Fluid on Cerebral Tissue Volumes by Advanced Volumetric 3D-MRI in Posthaemorrhagic Hydrocephalus in a Premature Infant. J Neurol Neurosurg Psychiatry. 2003;74 (5) :658-60.Abstract
Current clinical practice in the premature infant with posthaemorrhagic ventricular dilatation (PHVD) includes drainage of cerebrospinal fluid (CSF). This case study used advanced volumetric three dimensional magnetic resonance imaging to document the impact of CSF removal on the volume of regional brain tissues in a premature infant with PHVD. The removal of a large volume of CSF was associated with an identical reduction in CSF volume, but more dramatically with a significant increase in the regional volumes of cortical grey matter and myelinated white matter. The alterations in cerebral cortical grey matter and myelinated white matter volumes may provide insight into the established association of PHVD with deficits in cognitive and motor functions.
Kasai K, Shenton ME, Salisbury DF, Onitsuka T, Toner SK, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis. Arch Gen Psychiatry. 2003;60 (11) :1069-77.Abstract
CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. SETTING: Inpatient units at a private psychiatric hospital. PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated. RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes. CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.
Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Onitsuka T, Spencer MH, Yurgelun-Todd DA, Kikinis R, Jolesz FA, McCarley RW. Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry. 2003;60 (8) :766-75.Abstract
BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.
Tsai A, Yezzi A, Wells W, Tempany CM, Tucker D, Fan A, Grimson EWL, Willsky A. A Shape-based Approach to the Segmentation of Medical Imagery using Level Sets. IEEE Trans Med Imaging. 2003;22 (2) :137-54.Abstract

We propose a shape-based approach to curve evolution for the segmentation of medical images containing known object types. In particular, motivated by the work of Leventon, Grimson, and Faugeras, we derive a parametric model for an implicit representation of the segmenting curve by applying principal component analysis to a collection of signed distance representations of the training data. The parameters of this representation are then manipulated to minimize an objective function for segmentation. The resulting algorithm is able to handle multidimensional data, can deal with topological changes of the curve, is robust to noise and initial contour placements, and is computationally efficient. At the same time, it avoids the need for point correspondences during the training phase of the algorithm. We demonstrate this technique by applying it to two medical applications; two-dimensional segmentation of cardiac magnetic resonance imaging (MRI) and three-dimensional segmentation of prostate MRI.

Park H-J, Kubicki M, Shenton ME, Guimond A, McCarley RW, Maier SE, Kikinis R, Jolesz FA, Westin C-F. Spatial normalization of diffusion tensor MRI using multiple channels. Neuroimage. 2003;20 (4) :1995-2009.Abstract
Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the detection of brain abnormalities in diseases characterized by compromised neural connectivity. To quantify diffusion tensor abnormalities based on voxel-based statistical analysis, spatial normalization is required to minimize the anatomical variability between studied brain structures. In this article, we used a multiple input channel registration algorithm based on a demons algorithm and evaluated the spatial normalization of diffusion tensor image in terms of the input information used for registration. Registration was performed on 16 DT-MRI data sets using different combinations of the channels, including a channel of T2-weighted intensity, a channel of the fractional anisotropy, a channel of the difference of the first and second eigenvalues, two channels of the fractional anisotropy and the trace of tensor, three channels of the eigenvalues of the tensor, and the six channel tensor components. To evaluate the registration of tensor data, we defined two similarity measures, i.e., the endpoint divergence and the mean square error, which we applied to the fiber bundles of target images and registered images at the same seed points in white matter segmentation. We also evaluated the tensor registration by examining the voxel-by-voxel alignment of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear warping using six independent tensor components as input channels showed the best performance in effectively normalizing the tract morphology and tensor orientation. We also present a nonlinear method for creating a group diffusion tensor atlas using the average tensor field and the average deformation field, which we believe is a better approach than a strict linear one for representing both tensor distribution and morphological distribution of the population.
Zou KH, Warfield SK, Fielding JR, Tempany CM, William WM, Kaus MR, Jolesz FA, Kikinis R. Statistical Validation Based on Parametric Receiver Operating Characteristic Analysis of Continuous Classification Data. Acad Radiol. 2003;10 (12) :1359-68.Abstract

RATIONALE AND OBJECTIVES: The accuracy of diagnostic test and imaging segmentation is important in clinical practice because it has a direct impact on therapeutic planning. Statistical validations of classification accuracy was conducted based on parametric receiver operating characteristic analysis, illustrated on three radiologic examples, MATERIALS AND METHODS: Two parametric models were developed for diagnostic or imaging data. Example 1: A semi-automated fractional segmentation algorithm was applied to magnetic resonance imaging of nine cases of brain tumors. The tumor and background pixel data were assumed to have bi-beta distributions. Fractional segmentation was validated against an estimated composite pixel-wise gold standard based on multi-reader manual segmentations. Example 2: The predictive value of 100 cases of spiral computed tomography of ureteral stone sizes, distributed as bi-normal after a non-linear transformation, under two treatment options received. Example 3: One hundred eighty cases had prostate-specific antigen levels measured in a prospective clinical trial. Radical prostatectomy was performed in all to provide a binary gold standard of local and advanced cancer stages. Prostate-specific antigen level was transformed and modeled by bi-normal distributions. In all examples, areas under the receiver operating characteristic curves were computed. RESULTS. The areas under the receiver operating characteristic curves were: Example 1: Fractional segmentation of magnetic resonance imaging of brain tumors: meningiomas (0.924-0.984); astrocytomas (0.786-0.986); and other low-grade gliomas (0.896-0.983). Example 3: Ureteral stone size for treatment planning (0.813). Example 2: Prostate-specific antigen for staging prostate cancer (0.768). CONCLUSION: All clinical examples yielded fair to excellent accuracy. The validation metric area under the receiver operating characteristic curves may be generalized to evaluating the performances of several continuous classifiers related to imaging.

Goldberg-Zimring D, Achiron A, Guttmann CRG, Azhari H. Three-dimensional analysis of the geometry of individual multiple sclerosis lesions: detection of shape changes over time using spherical harmonics. J Magn Reson Imaging. 2003;18 (3) :291-301.Abstract
PURPOSE: To suggest a quantitative method for assessing the temporal changes in the geometry of individual multiple sclerosis (MS) lesions in follow-up studies of MS patients. MATERIALS AND METHODS: Computer simulated and in vivo magnetic resonance (MR) imaged MS lesions were studied. Ten in vivo MS lesions were identified from sets of axial MR images acquired from a patient scanned consecutively for 24 times during a one-year period. Each of the lesions was segmented and its three-dimensional surface approximated using spherical harmonics (SH). From the obtained SH polynomial coefficients, indices of shape were defined, and analysis of the temporal changes in each lesion's geometry throughout the year was performed by determining the mean discrete total variation of the shape indices. RESULTS: The results demonstrate that most of the studied lesions undergo notable geometrical changes with time. These changes are not necessarily associated with similar changes in size/volume. Furthermore, it was found that indices corresponding to changes in lesion shape could be 1.4 to 8.0 times higher than those corresponding to changes in the lesion size/volume. CONCLUSION: Quantitative three-dimensional shape analysis can serve as a new tool for monitoring MS lesion activity and study patterns of MS lesion evolution over time.
Meier DS, Guttmann CRG. Time-series analysis of MRI intensity patterns in multiple sclerosis. Neuroimage. 2003;20 (2) :1193-209.Abstract
In progressive neurological disorders, such as multiple sclerosis (MS), magnetic resonance imaging (MRI) follow-up is used to monitor disease activity and progression and to understand the underlying pathogenic mechanisms. This article presents image postprocessing methods and validation for integrating multiple serial MRI scans into a spatiotemporal volume for direct quantitative evaluation of the temporal intensity profiles. This temporal intensity signal and its dynamics have thus far not been exploited in the study of MS pathogenesis and the search for MRI surrogates of disease activity and progression. The integration into a four-dimensional data set comprises stages of tissue classification, followed by spatial and intensity normalization and partial volume filtering. Spatial normalization corrects for variations in head positioning and distortion artifacts via fully automated intensity-based registration algorithms, both rigid and nonrigid. Intensity normalization includes separate stages of correcting intra- and interscan variations based on the prior tissue class segmentation. Different approaches to image registration, partial volume correction, and intensity normalization were validated and compared. Validation included a scan-rescan experiment as well as a natural-history study on MS patients, imaged in weekly to monthly intervals over a 1-year follow-up. Significant error reduction was observed by applying tissue-specific intensity normalization and partial volume filtering. Example temporal profiles within evolving multiple sclerosis lesions are presented. An overall residual signal variance of 1.4% +/- 0.5% was observed across multiple subjects and time points, indicating an overall sensitivity of 3% (for axial dual echo images with 3-mm slice thickness) for longitudinal study of signal dynamics from serial brain MRI.
Jaume S, Ferrant M, Macq B, Hoyte L, Fielding JR, Schreyer A, Kikinis R, Warfield SK. Tumor detection in the bladder wall with a measurement of abnormal thickness in CT scans. IEEE Trans Biomed Eng. 2003;50 (3) :383-90.Abstract
Virtual cystoscopy is a developing technique for bladder cancer screening. In a conventional cystoscopy, an optical probe is inserted into the bladder and an expert reviews the appearance of the bladder wall. Physical limitations of the probe place restrictions on the examination of the bladder wall. In virtual cystoscopy, a computed tomography (CT) scan of the bladder is acquired and an expert reviews the appearance of the bladder wall as shown by the CT. The task of identifying tumors in the bladder wall has often been done without extensive computational aid to the expert. We have developed an image processing algorithm that aids the expert in the detection of bladder tumors. Compared with an expert observer reading the CT, our algorithm achieves 89% sensitivity, 88% specificity, 48% positive predictive value, and 98% negative predictive value.
Tsai A, Wells III WM, Tempany CM, Grimson EWL, Willsky AS. Coupled Multi-shape Model and Mutual Information for Medical Image Segmentation. Inf Process Med Imaging. 2003;18 :185-97.Abstract

This paper presents extensions which improve the performance of the shape-based deformable active contour model presented earlier in [9]. In contrast to that work, the segmentation framework that we present in this paper allows multiple shapes to be segmented simultaneously in a seamless fashion. To achieve this, multiple signed distance functions are employed as the implicit representations of the multiple shape classes within the image. A parametric model for this new representation is derived by applying principal component analysis to the collection of these multiple signed distance functions. By deriving a parametric model in this manner, we obtain a coupling between the multiple shapes within the image and hence effectively capture the co-variations among the different shapes. The parameters of the multi-shape model are then calculated to minimize a single mutual information-based cost functional for image segmentation. The use of a single cost criterion further enhances the coupling between the multiple shapes as the deformation of any given shape depends, at all times, upon every other shape, regardless of their proximity. We demonstrate the utility of this algorithm to the segmentation of the prostate gland, the rectum, and the internal obturator muscles for MR-guided prostate brachytherapy.

Fan A, Wells III WM, Fisher JW, Cetin M, Haker S, Mulkern R, Tempany CM, Willsky AS. A Unified Variational Approach to Denoising and Bias Correction in MR. Inf Process Med Imaging. 2003;18 :148-59.Abstract

We propose a novel bias correction method for magnetic resonance (MR) imaging that uses complementary body coil and surface coil images. The former are spatially homogeneous but have low signal intensity; the latter provide excellent signal response but have large bias fields. We present a variational framework where we optimize an energy functional to estimate the bias field and the underlying image using both observed images. The energy functional contains smoothness-enforcing regularization for both the image and the bias field. We present extensions of our basic framework to a variety of imaging protocols. We solve the optimization problem using a computationally efficient numerical algorithm based on coordinate descent, preconditioned conjugate gradient, half-quadratic regularization, and multigrid techniques. We show qualitative and quantitative results demonstrating the effectiveness of the proposed method in producing debiased and denoised MR images.