Publications by Year: 2004


Brun A, Knutsson H, Park HJ, Shenton ME, Westin CF. Clustering Fiber Traces Using Normalized Cuts. Med Image Comput Comput Assist Interv. 2004;3216/2004(3216):368–375.
In this paper we present a framework for unsupervised segmentation of white matter fiber traces obtained from diffusion weighted MRI data. Fiber traces are compared pairwise to create a weighted undirected graph which is partitioned into coherent sets using the normalized cut (N cut) criterion. A simple and yet effective method for pairwise comparison of fiber traces is presented which in combination with the N cut criterion is shown to produce plausible segmentations of both synthetic and real fiber trace data. Segmentations are visualized as colored stream-tubes or transformed to a segmentation of voxel space, revealing structures in a way that looks promising for future explorative studies of diffusion weighted MRI data.
Wei X, Guttmann CRG, Warfield SK, Eliasziw M, Mitchell R. Has your patient’s multiple sclerosis lesion burden or brain atrophy actually changed?. Mult Scler. 2004;10(4):402–6.
Changes in mean magnetic resonance imaging (MRI)-derived measurements between patient groups are often used to determine outcomes in therapeutic trials and other longitudinal studies of multiple sclerosis (MS). However, in day-to-day clinical practice the changes within individual patients may also be of interest In this paper, we estimated the measurement error of an automated brain tissue quantification algorithm and determined the thresholds for statistically significant change of MRI-derived T2 lesion volume and brain atrophy in individual patients. Twenty patients with MS were scanned twice within 30 min. Brain tissue volumes were measured using the computer algorithm. Brain atrophy was estimated by calculation of brain parenchymal fraction. The threshold of change between repeated scans that represented statistically significant change beyond measurement error with 95% certainty was 0.65 mL for T2 lesion burden and 0.0056 for brain parenchymal fraction. Changes in lesion burden and brain atrophy below these thresholds can be safely (with 95% certainty) explained by measurement variability alone. These values provide clinical neurologists with a useful reference to interpret MRI-derived measures in individual patients.
Zou KH, Wells WM, Kikinis R, Warfield SK. Three validation metrics for automated probabilistic image segmentation of brain tumours. Stat Med. 2004;23(8):1259–82.
The validity of brain tumour segmentation is an important issue in image processing because it has a direct impact on surgical planning. We examined the segmentation accuracy based on three two-sample validation metrics against the estimated composite latent gold standard, which was derived from several experts’ manual segmentations by an EM algorithm. The distribution functions of the tumour and control pixel data were parametrically assumed to be a mixture of two beta distributions with different shape parameters. We estimated the corresponding receiver operating characteristic curve, Dice similarity coefficient, and mutual information, over all possible decision thresholds. Based on each validation metric, an optimal threshold was then computed via maximization. We illustrated these methods on MR imaging data from nine brain tumour cases of three different tumour types, each consisting of a large number of pixels. The automated segmentation yielded satisfactory accuracy with varied optimal thresholds. The performances of these validation metrics were also investigated via Monte Carlo simulation. Extensions of incorporating spatial correlation structures using a Markov random field model were considered.
Goldberg-Zimring D, Achiron A, Warfield SK, Guttmann CRG, Azhari H. Application of spherical harmonics derived space rotation invariant indices to the analysis of multiple sclerosis lesions’ geometry by MRI. Magn Reson Imaging. 2004;22(6):815–25.
In the longitudinal study of multiple sclerosis (MS) lesions, varying position of the patient inside the MRI scanner is one of the major sources of assessment errors. We propose to use analytical indices that are invariant to spatial orientation to describe the lesions, rather than focus on patient repositioning or image realignment. Studies were made on simulated lesions systematically rotated, from in vitro MS lesions scanned on different days, and from in vivo MS lesions from a patient that was scanned five times the same day with short intervals of time between scans. Each of the lesions’ 3D surfaces was approximated using spherical harmonics, from which indices that are invariant to space rotation were derived. From these indices, an accurate and highly reproducible volume estimate can be derived, which is superior to the common approach of 2D slice stacking. The results indicate that the suggested approach is useful in reducing part of the errors that affect the analysis of changes of MS lesions during follow-up studies. In conclusion, our proposed method circumvents the need for precise patient repositioning and can be advantageous in MRI longitudinal studies of MS patients.
Ratiu P, Talos IF, Haker S, Lieberman D, Everett P. The tale of Phineas Gage, digitally remastered. J Neurotrauma. 2004;21(5):637–43.
The injury of Phineas Gage has fueled research on and fascination with the localization of cerebral functions in the past century and a half. Most physicians and anatomists believed that Gage sustained a largely bilateral injury to the frontal lobes. However, previous studies seem to have overlooked a few less obvious, but essential details. This has led us to reanalyze the injury using three-dimensional reconstruction and quantitative computer-aided techniques and to propose a new biomechanical model, in order to determine the location and extent of the injury and explain Gage’s improbable survival. Unlike previous studies on this subject, our findings are based on computer-generated three-dimensional reconstructions of a thin-slice computed tomography scan (CAT) of Phineas Gage’s skull. The results of our image analysis were corroborated with the clinical findings, thoroughly recorded by Dr. Harlow in 1848, as well as with a systematic examination of the original skull specimen. Our results show that the cerebral injury was limited to the left frontal lobe, did not extend to the contralateral side, did not affect the ventricular system, and did not involve vital intracranial vascular structures. Although modern neuroscience has perhaps outgrown the speculations prompted by this famous case, it is still a living part of the medical folklore and education. Setting the record straight based on clinical reasoning, observation of the physical evidence, and sound quantitative computational methods is more than mere minutia and of interest for the broad medical community.
Levitt JJ, Westin CF, Nestor PG, Estepar RSJ, Dickey CC, Voglmaier MM, Seidman LJ, Kikinis R, Jolesz FA, McCarley RW, Shenton ME. Shape of Caudate Nucleus and its Cognitive Correlates in Neuroleptic-Naive Schizotypal Personality Disorder. Biol Psychiatry. 2004;55(2):177–84.
BACKGROUND: We measured the shape of the head of the caudate nucleus with a new approach based on magnetic resonance imaging (MRI) in schizotypal personality disorder (SPD) subjects in whom we previously reported decreased caudate nucleus volume. We believe MRI shape analysis complements traditional MRI volume measurements. METHODS: Magnetic resonance imaging scans were used to measure the shape of the caudate nucleus in 15 right-handed male subjects with SPD, who had no prior neuroleptic exposure, and in 14 matched normal comparison subjects. With MRI processing tools, we measured the head of the caudate nucleus using a shape index, which measured how much a given shape deviates from a sphere. RESULTS: In relation to comparison subjects, neuroleptic never-medicated SPD subjects had significantly higher (more "edgy") head of the caudate shape index scores, lateralized to the right side. Additionally, for SPD subjects, higher right and left head of the caudate SI scores correlated significantly with poorer neuropsychological performance on tasks of visuospatial memory and auditory/verbal working memory, respectively. CONCLUSIONS: These data confirm the value of measuring shape, as well as volume, of brain regions of interest and support the association of intrinsic pathology in the caudate nucleus, unrelated to neuroleptic medication, with cognitive abnormalities in the schizophrenia spectrum.
Zou KH, Warfield SK, Bharatha A, Tempany CM, Kaus MR, Haker SJ, Wells WM, Jolesz FA, Kikinis R. Statistical Validation of Image Segmentation Quality Based on a Spatial Overlap Index: Scientific Reports. Acad Radiol. 2004;11(2):178–89.
RATIONALE AND OBJECTIVES: To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy. MATERIALS AND METHODS: The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA). RESULTS: Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other mixed gliomas (0.490-0.899). CONCLUSION: The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks.
, Mewes AUJ, Alcañiz M, Kikinis R, Warfield SK. Improved watershed transform for medical image segmentation using prior information. IEEE Trans Med Imaging. 2004;23(4):447–58.
The watershed transform has interesting properties that make it useful for many different image segmentation applications: it is simple and intuitive, can be parallelized, and always produces a complete division of the image. However, when applied to medical image analysis, it has important drawbacks (oversegmentation, sensitivity to noise, poor detection of thin or low signal to noise ratio structures). We present an improvement to the watershed transform that enables the introduction of prior information in its calculation. We propose to introduce this information via the use of a previous probability calculation. Furthermore, we introduce a method to combine the watershed transform and atlas registration, through the use of markers. We have applied our new algorithm to two challenging applications: knee cartilage and gray matter/white matter segmentation in MR images. Numerical validation of the results is provided, demonstrating the strength of the algorithm for medical image segmentation.
Park HJ, Levitt J, Shenton ME, Salisbury DF, Kubicki M, Kikinis R, Jolesz FA, McCarley RW. An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls. Neuroimage. 2004;22(3):1231–46.
We created a spatial probability atlas of schizophrenia to provide information about the neuroanatomic variability of brain regions of patients with the disorder. Probability maps of 16 regions of interest (ROIs) were constructed by taking manually parcellated ROIs from subjects’ magnetic resonance images (MRIs) and linearly transforming them into Talairach space using the Montreal Neurological Institute (MNI) template. ROIs included temporal, parietal, and prefrontal cortex subregions, with a principal focus on temporal lobe structures. Subject Ns ranged from 11 to 28 for the different ROIs. Our global measure of the spatial distribution of the transformed ROI was the sum of voxels with 50% overlap among subjects. The superior temporal gyrus (STG) and fusiform gyrus (FG) had lower values for schizophrenic subjects than for normal controls, suggestive of greater spatial variability for these ROIs in schizophrenic subjects. For the computation of statistical significance of group differences in portions of the ROI, we used voxel-wise comparisons and Fisher’s exact test. First-episode schizophrenic patients compared with controls showed lower probability (P
Tolsa CB, Zimine S, Warfield SK, Freschi M, Rossignol AS, Lazeyras F, Hanquinet S, Pfizenmaier M, Hüppi PS. Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res. 2004;56(1):132–8.
Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 +/- 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights