Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Magnetic Resonance Imaging (MRI) provides very sensitive indication of the presence and extent of the lesions of Multiple Sclerosis (MS). As a result, quantifying changes in the number and extent of lesions in MR images has been used to indicate disease activity in clinical trials of new therapies. However, lesion quantification is long, arduous, and subject to variability between and within operators. These factors limit the application of quantitative techniques and increase the duration, and thus cost, of clinical trials which rely on their measurements to assess therapeutic effect.;A computerised system was developed for assisted 3-D quantification and analysis of MS lesions in standard spin-echo MR exams. Manual and assisted quantification were compared using repeated measurements of lesions in MR exams of a phantom and MS patient. Results indicate that assisted quantification reduced inter-operator variability by 1/3, and reduced intra-operator variability by 1/2. The minimum significant change between two successive measurements of lesion volume by the same operator, was 0.64 cm{dollar}\sp3{dollar} for manual quantification, and 0.42 cm{dollar}\sp3{dollar} for assisted quantification. For two different operators making successive measurements, the minimum significant change was 0.94 cm{dollar}\sp3{dollar} for manual quantification, but only 0.47 cm{dollar}\sp3{dollar} for assisted quantification.;Repeated measurements were also used to determine the impact on operator variability of: (a) lesion quantification in high-field (1.5T) versus mid-field (0.5T) exams; and, (b) an anisotropic diffusion filter algorithm which reduces image noise without blurring or moving object boundaries. Results suggest that inter- and intra-operator variability are reduced by anisotropic filtering, and by quantification in 0.5T exams. Reduced operator variabilities may result from higher detail signal-to-noise ratios (dSNR's) in 0.5T and filtered exams.;Finally, pathological change may occur within a lesion without a corresponding change in volume. Therefore, a new technique was developed to provide lesion composition information from MR exam intensities. Analysis of serial exams of 3 MS patients revealed changes in the intensity spectra within lesions, even when their volume remained constant. Together, assisted lesion quantification and analysis may provide additional insight into disease activity, and improve the sensitivity of clinical trials of new therapies.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.