Robert P. Velthuizen

MRI segmentation: methods and applications.

The current literature on MRI segmentation methods is reviewed. Particular emphasis is placed on the relative merits of single image versus multispectral segmentation, and supervised versus unsupervised segmentation methods. Image pre-processing and registration are discussed, as well as methods of validation. The application of MRI segmentation for tumor volume measurements during the course of therapy is presented here as an example, illustrating problems associated with inter- and intra-observer variations inherent to supervised methods.

A comparison of neural network and fuzzy clustering techniques in segmenting magnetic resonance images of the brain

Magnetic resonance (MR) brain section images are segmented and then synthetically colored to give visual representations of the original data with three approaches: the literal and approximate fuzzy c-means unsupervised clustering algorithms, and a supervised computational neural network. Initial clinical results are presented on normal volunteers and selected patients with brain tumors surrounded by edema. Supervised and unsupervised segmentation techniques provide broadly similar results. Unsupervised fuzzy algorithms were visually observed to show better segmentation when compared with raw image data for volunteer studies. For a more complex segmentation problem with tumor/edema or cerebrospinal fluid boundary, where the tissues have similar MR relaxation behavior, inconsistency in rating among experts was observed, with fuzz-c-means approaches being slightly preferred over feedforward cascade correlation results. Various facets of both approaches, such as supervised versus unsupervised learning, time complexity, and utility for the diagnostic process, are compared.

MRI: Stability of three supervised segmentation techniques

Supervised segmentation methods from three families of pattern recognition techniques were used to segment multispectral MRI data. Studied were the maximum likelihood method (MLM), k-nearest neighbors (k-NN), and a back-propagation artificial neural net (ANN). Performance was measured in terms of execution speed, and stability for the selection of training data, namely, region of interest (ROI) selection, and interslice and interpatient classifications. MLM proved to have the smallest execution times, but demonstrated the least stability. k-NN showed the best stability for training data selection. To evaluate the segmentation techniques, multispectral images were used of normal volunteers and patients with gliomas, the latter with and without MR contrast material. All measures applied indicated that k-NN provides the best results.

Application of fuzzy c-means segmentation technique for tissue differentiation in MR images of a hemorrhagic glioblastoma multiforme.

The application of a raw data-based, operator-independent MR segmentation technique to differentiate boundaries of tumor from edema or hemorrhage is demonstrated. A case of a glioblastoma multiforme with gross and histopathologic correlation is presented. The MR image data set was segmented into tissue classes based on three different MR weighted image parameters (T1-, proton density-, and T2-weighted) using unsupervised fuzzy c-means (FCM) clustering algorithm technique for pattern recognition. A radiological examination of the MR images and correlation with fuzzy clustering segmentations was performed. Results were confirmed by gross and histopathology which, to the best of our knowledge, reports the first application of this demanding approach. Based on the results of neuropathologic correlation, the application of FCM MR image segmentation to several MR images of a glioblastoma multiforme represents a viable technique for displaying diagnostically relevant tissue contrast information used in 3D volume reconstruction. With this technique, it is possible to generate segmentation images that display clinically important neuroanatomic and neuropathologic tissue contrast information from raw MR image data.

Comparison of supervised MRI segmentation methods for tumor volume determination during therapy

Two different multispectral pattern recognition methods are used to segment magnetic resonance images (MRI) of the brain for quantitative estimation of tumor volume and volume changes with therapy. A supervised k-nearest neighbor (kNN) rule and a semi-supervised fuzzy c-means (SFCM) method are used to segment MRI slice data. Tumor volumes as determined by the kNN and SFCM segmentation methods are compared with two reference methods, based on image grey scale, as a basis for an estimation of ground truth, namely: (a) a commonly used seed growing method that is applied to the contrast enhanced T1-weighted image, and (b) a manual segmentation method using a custom-designed graphical user interface applied to the same raw image (T1-weighted) dataset. Emphasis is placed on measurement of intra and inter observer reproducibility using the proposed methods. Intra- and interobserver variation for the kNN method was 9% and 5%, respectively. The results for the SFCM method was a little better at 6% and 4%, respectively. For the seed growing method, the intra-observer variation was 6% and the interobserver variation was 17%, significantly larger when compared with the multispectral methods. The absolute tumor volume determined by the multispectral segmentation methods was consistently smaller than that observed for the reference methods. The results of this study are found to be very patient case-dependent. The results for SFCM suggest that it should be useful for relative measurements of tumor volume during therapy, but further studies are required. This work demonstrates the need for minimally supervised or unsupervised methods for tumor volume measurements.

On the statistical nature of mammograms.

We show that digitized mammograms can be considered as evolving from a simple process. A given image results from passing a random input field through a linear filtering operation, where the filter transfer function has a self-similar characteristic. By estimating the functional form of the filter and solving the corresponding filtering equation, the analysis shows that the input field gray value distribution and spectral content can be approximated with parametric methods. The work gives a simple explanation for the variegated image appearance and multimodal character of the gray value distribution common to mammograms. Using the image analysis as a guide, a simulated mammogram is generated that has many statistical characteristics of real mammograms. Additional benefits may follow from understanding the functional form of the filter in conjunction with the input field characteristics that include the approximate parametric description of mammograms, showing the distinction between homogeneously dense and nondense images, and the development of mass analysis methods.

MONITORING BRAIN TUMOR RESPONSE TO THERAPY USING MRI SEGMENTATION

The performance evaluation of a semi-supervised fuzzy c-means (SFCM) clustering method for monitoring brain tumor volume changes during the course of routine clinical radiation-therapeutic and chemo-therapeutic regimens is presented. The tumor volume determined using the SFCM method was compared with the volume estimates obtained using three other methods: (a) a k nearest neighbor (kNN) classifier, b) a grey level thresholding and seed growing (ISG-SG) method and c) a manual pixel labeling (GT) method for ground truth estimation. The SFCM and kNN methods are applied to the multispectral, contrast enhanced T1, proton density, and T2 weighted, magnetic resonance images (MRI) whereas the ISG-SG and GT methods are applied only to the contrast enhanced T1 weighted image. Estimations of tumor volume were made on eight patient cases with follow-up MRI scans performed over a 32 week interval during treatment. The tumor cases studied include one meningioma, two brain metastases and five gliomas. Comparisons with manually labeled ground truth estimations showed that there is a limited agreement between the segmentation methods for absolute tumor volume measurements when using images of patients after treatment. The average intraobserver reproducibility for the SFCM, kNN and ISG-SG methods was found to be 5.8%, 6.6% and 8.9%, respectively. The average of the interobserver reproducibility of these methods was found to be 5.5%, 6.5% and 11.4%, respectively. For the measurement of relative change of tumor volume as required for the response assessment, the multi-spectral methods kNN and SFCM are therefore preferred over the seedgrowing method.

Review and evaluation of MRI nonuniformity corrections for brain tumor response measurements

Current MRI nonuniformity correction techniques are reviewed and investigated. Many approaches are used to remedy this artifact, but it is not clear which method is the most appropriate in a given situation, as the applications have been with different MRI coils and different clinical applications. In this work four widely used nonuniformity correction techniques are investigated in order to assess the effect on tumor response measurements (change in tumor volume over time): a phantom correction method, an image smoothing technique, homomorphic filtering, and surface fitting approach. Six brain tumor cases with baseline and follow-up MRIs after treatment with varying degrees of difficulty of segmentation were analyzed without and with each of the nonuniformity corrections. Different methods give significantly different correction images, indicating that rf nonuniformity correction is not yet well understood. No improvement in tumor segmentation or in tumor growth/shrinkage assessment was achieved using any of the evaluated corrections.

Spectral analysis of full field digital mammography data.

The spectral content of mammograms acquired from using a full field digital mammography (FFDM) system are analyzed. Fourier methods are used to show that the FFDM image power spectra obey an inverse power law; in an average sense, the images may be considered as 1/f fields. Two data representations are analyzed and compared (1) the raw data, and (2) the logarithm of the raw data. Two methods are employed to analyze the power spectra (1) a technique based on integrating the Fourier plane with octave ring sectioning developed previously, and (2) an approach based on integrating the Fourier plane using rings of constant width developed for this work. Both methods allow theoretical modeling. Numerical analysis indicates that the effects due to the transformation influence the power spectra measurements in a statistically significant manner in the high frequency range. However, this effect has little influence on the inverse power law estimation for a given image regardless of the data representation or the theoretical analysis approach. The analysis is presented from two points of view (1) each image is treated independently with the results presented as distributions, and (2) for a given representation, the entire image collection is treated as an ensemble with the results presented as expected values. In general, the constant ring width analysis forms the foundation for a spectral comparison method for finding spectral differences, from an image distribution sense, after applying a nonlinear transformation to the data. The work also shows that power law estimation may be influenced due to the presence of noise in the higher frequency range, which is consistent with the known attributes of the detector efficiency. The spectral modeling and inverse power law determinations obtained here are in agreement with that obtained from the analysis of digitized film-screen images presented previously. The form of the power spectrum for a given image is approximately l/f2beta with beta approximately 1.4-1.5.

A statistical methodology for mammographic density detection

A statistical methodology is presented based on a chi-square probability analysis that allows the automated discrimination of radiolucent tissue (fat) from radiographic densities (fibroglandular tissue) in digitized mammograms. The method is based on earlier work developed at this facility that shows mammograms may be considered as evolving from a linear filtering operation where a random input field is passed through a 1/f filtering process. The filtering process is reversible which allows the solution of the input field with knowledge obtained from the raw image (the output). The input field solution is analogous to a prewhitening technique or deconvolution. This field contains all the information of the raw image in a much simplified format that can be approximated and analyzed with parametric methods. In the work presented here evidence indicates that there are two random events occurring in the input field with differing variances: (1) one relating to fat tissue with the smaller variance, and (2) the second relating to all other tissue with the larger variance. A statistical comparison of the variances is made by scanning the image with a small search window. A relaxation method allows for making a reliable estimate of the smaller variance which is considered as the global reference. If a local variance deviates significantly from the reference variance, based on chi-square analysis, it is labeled as nonfat; otherwise it is labeled as fat. This statistical test procedure results in a region by region continuous labeling of fat and nonfat tissue across the image. In the work presented here, the emphasis is on the methodology development with supporting preliminary results that are very encouraging. It is widely accepted that mammographic density is a breast cancer risk factor. An important application of this work is to incorporate density-based risk analysis into the ongoing statistical-based detection work developed at this facility. Additional applications include risk analysis dependent on either percentages or total amounts of fat or dense tissue. This work may be considered as the initial step in introducing many of the known breast cancer risk factors into the actual image data analysis.