• A poster by Zhang Y. et al. was presented at the annual Americas MS research and treatment meeting (ACTRIMS) held in Chicago, USA on October 8th, 2006. The theme of this meeting was on "Biomarkers in MS".
• A parallel meeting was also undertaken in Madrid, Spain on Septeber 27-30, 2006 organized by the European MS committee (ECTRIMS).

Multiple sclerosis (MS) is an autoimmune disease that affects the brain and spinal cord. The disease destroys myelin, a fatty protective neuron coating that aids in nerve signal propagation, in patches throughout the central nervous system. As a result, neuron signal pathways can be delayed or destroyed. The location of MS attacks is unpredictable, resulting with a plethora of symptoms including changes in perception, visual problems, weakness, and difficulties in coordination and speech.

Healthy subject

People with multiple sclerosis

MS has four main disease types: benign; relapsing-remitting (RR); secondary progressive (SP); and, primary progressive (PP). Relapsing-remitting is characterized by unpredictable attacks followed by durations of disease inactivity where the patient might recover slightly, known as remission. Primary progressive MS is characterized by a steady increase of disability following the initial MS attack; there are no periods of remission. Secondary progressive MS is characterized by initial RR disease suddenly changing into PP.

More information on MS can be found at the MS Society of Canada website.

If you are interested in our research, please check out the following publications:

Papers

• The clinical response to minocycline in MS is accompanied by beneficial immune changes: A pilot study. RK Zabad, LM Metz, T Todoruk, Y Zhang, JR Mitchell, M Yeung, D Patry, RB Bell, VW Yong. Multiple Sclerosis 2006, in press.
  
• A Novel MRI Texture Analysis of Demyelination and Inflammation in Relapsing-remitting Experimental Allergic Encephalomyelitis. Zhang Y, Wells J, Buist R, Peeling J, Yong VW, Mitchell JR. Lecture Notes in Computer Science, 2006.
  
• Characterization of the NMR behavior of white matter in bovine brain. Bjarnason TA, Vavasour IM, Chia CLL, MacKay AL. Magnetic Resonance in Medicine, 54(5); 1072-81 (2005). PMID: 16200557, doi: 10.1002/mrm.20680
• Minocycline Reduces Gadolinium-enhancing MRI Lesions in Multiple Sclerosis. Metz LM, Zhang Y, Yeung M, Patry DG, Bell RB, Stoian CA, Yong VW, Patten SB, Duquette P, Antel JP, Mitchell JR. Annals of Neurology, 55(5):756 (2004). PMID: 15122721, doi: 10.1002/ana.20119
• Posterior fossa lesion volume and slowed information processing in multiple sclerosis. Archibald CJ, Wei X, Scott JN, Wallace CJ, Zhang Y, Metz LM, Mitchell JR. Brain, 127(7):1526-34 (2004). PMID: 15090476, doi: 10.1093/brain/awh167
• Texture Analysis of MR Images of Minocycline Treated MS Patients. Y Zhang, H Zhu, R Ferrari, X Wei, M Eliasziw, LM Metz, JR Mitchell. Lecture Notes in Computer Science, 2003, Volume 2878, Pages 786-793.
• Magnetization Transfer and Multi-component T2 Relaxation Measurments with Histopathological Correaltion in an Experimental Model of MS. Gareau PJ, Rutt BK, Karlik SJ, Mitchell JR. Journal of Magnetic Resonance Imaging, 11(6):586-95 (2000). PMID: 10862056, doi: 10.1002/1522-2586(200006)11:6<586::AID-JMRI3>3.0.CO;2-V
• Computer assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain. Mitchell JR, Karlik SJ, Lee DH, Fenster A. Journal of Magnetic Resonance Imaging, 4(2):197-208 (1994). PMID: 8180461, DOI: 10.1002/jmri.1880040218

Abstracts

• ‘Black T2’ at 3T MRI: A biomarker for Disability in Multiple Sclerosis? Zhang Y, Metz LM, Zabad R, Mitchell JR. Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), Oct 8, 2006.
  
• Serial texture analysis in deep gray matter of patients with multiple sclerosis treated with minocycline. Y Zhang, LM Metz, H Zhu, VW Yong, JR Mitchell. Berlex Canada MS Research Award at the Canadian Journal of Neurological Sciences, June 13-17, 2006. 

• T2 Hypointensity at 3 T Correlates with Expanded Disability Status Scale in Multiple Sclerosis. Zhang Y, Metz LM, Zabad R, Lauzon LM, Wei X, Frayne R, Mitchell JR. Proceedings of the International Society for Magnetic Resonance in Medicine, 13; 1052 (2005).

• In vivo MRI quantification of mouse spinal cord with Relapsing Remitting EAE: Disability and imaging correlates. Zhang Y, Wells J, Buist T, Sun X, Peeling J, Yong WV, Mitchell JR. Proceedings of the International Society for Magnetic Resonance in Medicine, 13; 1094 (2005).
• Correlation of diffusion measures with multicomponent T2-relaxation data in Multiple Sclerosis lesions and normal appearing white matter. Kolind SH, Laule C, Bjarnason TA, Vavasour IM, Traboulsee AL, Li DK, MacKay AL. Proceedings of the International Society for Magnetic Resonance in Medicine, 13; 314 (2005)
• Proton signal characterisation in white matter: a four pool model. Bjarnason TA, Vavasour IM, Chia CLL, MacKay AL. Proceedings of the International Society for Magnetic Resonance in Medicine, 12; 2706 (2004)

Highlights

• A new Mac OS X application for rapid measurement of brain blood flow in acute stroke patients. Drabycz S and Mitchell JR. Poster presentation by S Drabycz at the Apple Worldwide Developers Conference (WWDC), San Francisco, California (2006). pdf

Description

Blood flow map of an ischemic stroke patient shows reduced blood flow in the right hemisphere of the brain (left side of the image)

Ischemic stroke is caused by the obstruction of cerebral blood vessels. Without acute treatment stroke usually results in permanent neurological damage. Stroke neurologists can inject “clot-busting” drugs to help dissolve obstructions and restore blood flow to brain tissue at risk of infarction.  However, studies have shown that, on average, after three hours from the onset of stroke the risks of hemorrhage associated with drug therapy begin to outweigh the benefits.  The ability to make quantitative measures of local blood flow to brain tissue (perfusion) has the potential to provide precise knowledge of the extent of brain tissue that can be salvaged and extend this three-hour window.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) measures the concentration of a bolus of contrast material as it passes through the cerebral vessels.  This allows non-invasive visualization of blood flow through the brain. The University of Calgary Stroke Program is at the forefront of stroke research to develop quantitative DSC-MRI techniques in order to predict the extent of brain tissue at risk in ischemic stroke.

Ongoing stroke related projects at the centre include: improving DSC-MRI, fast visualization for clinicians of CT and MR stroke data and prediction of stroke evolution in hyperacute patients.

More information about stroke can be found at the Canadian Heart & Stroke Foundation website.

Papers

• Separate Grey and White Matter Cerebral Blood Flow Analysis for Improved Stroke Outcome Prediction. Simon JE, Bristow MS, Lu H, Lauzon ML, Brown R, Manjon JV, Eliasziw M, Frayne R, Buchan AM, Demchuk AM, Mitchell JR. Journal of Cerebral Blood-Flow and Metabolism, doi: 10.1038/sj.jcbfm.9600130 (2005).
• Perfusion and Diffusion in Acute Stroke: Human Gray and White Matter Have Different Thresholds for Infarction. Bristow MS, Simon JE, Brown RA, Eliasziw M, Hill MD, Coutts S, Frayne R, Demchuk AM, Mitchell JR. Journal of Cerebral Blood-Flow and Metabolism, doi: 10.1038/sj.jcbfm.9600135 (2005).
• Maximum entropy deconvolution for dynamic susceptibility contrast magnetic resonance imaging. Drabycz S, Brown RA, Law AG, Mitchell JR. Proc. 5th IASTED International Conference on Visualization, Imaging, and Image Processing (VIIP).  Benidorm, Spain. ACTA Press, 480(114):442-447 (2005).

Abstracts

• Real-time generation of quantitative cerebral perfusion maps to improve acute ischemic stroke management. Drabycz S, Brown RA, O’Brien B, Kmech J, Mitchell JR. Stroke 37(2):703 (2006). International Stroke Conference Poster Presentation P284.
• A fast regularization algorithm to generate absolute maps of brain blood flow. Drabycz S, Brown RA, O’Brien B, Mitchell JR.  Oral presentation by S Drabycz at the 6th Alberta Biomedical Engineering Conference, Banff, Alberta, Canada (2005). Most Outstanding Oral Presentation – First Prize
• Maximum entropy deconvolution for MR perfusion imaging. Drabycz S, Brown RA, Mitchell JR. Oral presentation by S Drabycz at the 2nd University of Calgary Engineering Graduate Student Conference, Calgary, Alberta, Canada (2005).
• A Novel Method for Deriving Grey and White Matter CBF Using Multi-Spectral MR. Brown RA, Simon JE, Lu H, Lauzon ML, Frayne R, Mitchell JR. Oral presentation by RA Brown at the 11th annual International Society of Magnetic Resonance in Medicine Scientific Meeting and Exhibition, Toronto, Ontario, Canada (2003).
  

Invited Talks

• Improving the speed and accuracy of quantitative perfusion imaging. Drabycz S. Universidad Politécnica de Valencia, Valencia, Spain (2005).

Brain cancer is a devastating disease.  Primary central nervous system (CNS) tumors, though rare, are responsible for approximately 2% of cancer deaths.  In addition, they result in 7% of the years of life lost due to cancer as they often affect children or people in middle age -- brain tumors account for 20% of malignant tumors diagnosed in children under 15.  Standard treatment for most malignant brain tumors consists of surgical resection followed by radiation therapy.

Imaging techniques, particularly magnetic resonance (MR) imaging, allow precise localization of tumors.  This enables surgeons to perform minimally invasive stereotactic biopsies and image guided surgery, resulting in more complete resection.  The Seaman Family MR Research Centre is home to the first mobile intra-operative MR scanner.  This scanner has proven its worth for surgical treatment of brain tumors, allowing more accurate and complete resection.

Imaging also allows detection of abnormalities much earlier in their development.  MR is a very sensitive diagnostic test (abnormalities are reliably detected) but is often not specific (the nature of the abnormality is ambiguous).  In the case of brain tumors, it is usually very difficult to make a firm diagnosis of tumor type based solely on imaging.  A biopsy is generally required to obtain samples for histologic or genetic investigation but this is an extremely invasive procedure.  Some of our research projects are aimed at developing imaging based tests that are capable of reliably identifying and classifying brain tumors.

Papers

• Texture Analysis for Non-Invasive Identification of Brain Tumor Genotype from MRI. Brown RA, Zlatescu MC, Cairncross JG, Mitchell JR. Proceedings of the Fifth IASTED International Conference on Visualization, Imaging, and Image Processing (VIIP). Benidorm, Spain. ACTA Press, 480(116):459-464 (2005).

Invited Talks

Time domain signal containing two sine functions and two bursts of noise	Frequency domain of the signal generated from the Fourier Transform	Time-Frequency domain of the signal generated from the S-Transform

The Stockwell transform ( ST)  combines the time–frequency representation of the Gabor Transform with the multi-scaling feature of the Wavelet Transform. It provides a unique time–frequency representation of a signal by adapting the FT to analyze the localized signal, using frequency-dependent time-scaling windows. The interpretation in a time–frequency domain becomes much easier and the multi-resolution analysis allows the ST to detect subtle Fourier spectral changes over time. In addition, the Fourier and Stockwell spectra are intimately related; they can be readily converted from one to the other. This close connection suggests the possibility of pre-processing image data in the Stockwell domain for Fourier-based imaging modalities (in particular, MRI and CT). Thus, the properties of the ST make it a potentially valuable processing tool for medical imaging.

Projects at the centre related to time-frequency analysis include texture analysis in both multiple sclerosis and cancer patients, the development of new transforms, the formulation of an efficient (fast) ST and development of a general theoretical framework to describe time-frequency transforms and analysis.

Patents

• Local Multi-Scale Fourier Analysis for MRI. Mitchell JR, Fong C, Zhu H, Goodyear BG, Brown R. US patent #6,850,062 (issued Feb 1 2005).

Papers

• Texture Analysis for Non-Invasive Identification of Brain Tumor Genotype from MRI. Brown RA, Zlatescu MC, Cairncross JG, Mitchell JR. Proceedings of the Fifth IASTED International Conference on Visualization, Imaging, and Image Processing (VIIP). Benidorm, Spain. ACTA Press, #480-116 pg. 459-464 (2005).
  
• Distributed Vector Processing of a New Local Multi-Scale Fourier Transform For Medical Imaging Applications. Brown RA, Zhu H, Mitchell JR. IEEE Transactions on Medical Imaging, 24(5):689-91 (2005).
• 3D MRI Progressive Imaging: Data- and Transform-Space Strategies. Brown RA, Baeza I, Mitchell JR, Villanueva RJ, Zhu H, Villanueva-Oller J, Law AG. CCCT in-press.
• 3D Progressive Imaging with Feature Selection. Brown RA, Zhu H, Mitchell JR, Law AG. Proceedings of the 2004 International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences (METMBS). Valafar FH, Arabnia HR, He M, Sinha U (Eds); CSREA Press, ISBN 1-932415-43-2, 216-219 (2004).
  
• A New Local Multiscale Fourier Analysis for Medical Imaging. Zhu H, Goodyear BG, Lauzon ML, Brown RA, Mayer G, Law AG, Mansinha L, Mitchell JR. Medical Physics, 30:1134-1141 (2003).

Invited Talks

• "Applications of time frequency analysis in medicine and geiophysics." Adler DH, Bjarnason TA, Drabycz S, Mitchell JR. ISAAC Workshop on Pseudo-Differential Operators: Partial Differential Equations and Time-Frequency Analysis, Toronto, ON. December 11-15, 2006. (Podcast)
• Time/frequency analysis of medical images. Mitchell JR, Brown RA, Drabycz S. Pacific Institute for the Mathematical Sciences Workshop on Time-Frequency Analysis and Non-Stationary Filtering, Banff, Alberta, Canada (2005).
• Texture Analysis for Non-Invasive Identification of Brain Tumor Genotype from MRI. Brown RA, Zlatescu MC, Cairncross JG, Mitchell JR. Universidad Politécnica de Valencia, Valencia, Spain (2005).

Abstracts

• A 2D local frequency analysis approach using the S-transform. Drabycz S and Mitchell JR. Poster presentation by S Drabycz at the upcoming CAIMS/MITACS Joint Annual Conference, Toronto, Ontario (2006).

• Time/frequency analysis in magnetic resonance imaging. Drabycz S, Mitchell JR. Oral presentation at the Applied Mathematics Graduate Student Conference, Simon Fraser University, Vancouver, BC, Canada (2006).

• Progressive Imaging: A Transform Space Approach. Brown RA, Baeza I, Zhu H, Villanueva RJ, Mitchell JR, Law AG. Poster at the Society for Industrial and Applied Mathematics Conference, Salt Lake City, Utah (2004).
  

Keywords

The Imaging Informatics research group is at the forefront of translational research, developing algorithms that allow advanced, real-time image processing and analysis for clinical applications.

We have developed a novel algorithm and software to correct for MR field inhomogeniety (known as non-uniformity bias correction).  Our group has created a unique, real-time implementation of an advanced edge-preserving noise filter (known as anisotropic diffusion filtering).  We are also developing novel time-frequency analysis techniques and transforms to perform advanced noise filtering and artifact removal, and to extract new information about spatial-frequency content of images (ie. texture).

One of our key strengths is the development of simple, robust software for real-time clinical image analysis.  The links below describe software we have developed for: real-time 3D visualization and surface rendering of medical images (Resolution MD); and, interactive generation of blood flow maps for acute stroke diagnosis (perFusion).

For more information about our algorithms and software:

• AnalyzeNNLS
  
• Non-Uniformity Correction
  
• Anisotropic Diffusion Filtering
• Time-Frequency Analysis

• Interactive 3D Volume Visualization
  
• perFusion
• Software Commercialization