Timothy J. Scholl, Scientist
I have always had an innate interest in understanding “how things work”. As a budding scientist, my parents claim that there was never a pen in the house that still included its spring. Pieces from my Meccano set were cannibalized and shaped into custom parts - sacrificed in the development of new “inventions”. These childhood interests ultimately led to my graduate training in experimental physics where I designed and constructed novel experimental apparatus to measure basic properties of atoms and molecules and test physical theories. Eventually, an opportunity arose to apply my physics training in the field of Medical Biophysics where my recent research is concentrated on magnetic resonance imaging (MRI). I am presently an Investigator with the Ontario Institute for Cancer Research, embedded as an Imaging Scientist at Robarts Research and Assistant Professor of Medical Biophysics at Western University.
Molecular imaging is a rapidly developing field, which non-invasively visualizes cellular function such as metabolism. My research at Robarts Research Institute has been focused on development of novel molecular imaging probes and methods for MRI with a specific emphasis on applications to cancer imaging. Therapeutic choice for an individual cancer patient relies on invasive tumour sampling. For many targeted agents, molecular assessment is particularly important in order to apply these agents to cancers that are most likely to respond and avoid treatments that are unlikely to be effective. Sadly, predictive biomarkers are not perfect prognosticators of therapeutic response or failure for a given agent in a particular patient and treatment assessment often relies on longitudinal measurements of changes in tumour size. Significant changes in tumour size can take months to become apparent if at all. Molecular imaging has the potential to non-invasively assess subtle changes in tumour biology to help understand the evolution of the tumour microenvironment, determine the potential for tumour proliferation and, perhaps most importantly, provide prompt evidence for early responses versus non-responses during ongoing treatment.
Since MRI is a valuable diagnostic imaging tool capable of morphological and functional imaging with high spatial resolution and is the standard of care for assessment of most solid tumours, the added capability to assess molecular function is an important development, particularly for cancer research. In collaboration with other imaging scientists, chemists, cancer biologists and oncologists, my research group is tackling the challenges of developing molecular imaging probes of the tumour microenvironment for use with MRI. We expect that these probes will be useful for:
- non-invasive measurement of tumour aggressiveness;
- providing early assessment of cancer treatment;
- reduction of the overtreatment of cancer.
My research is concentrated into three general areas (see below) that have attracted funding through the Investigator and Smarter Imaging Programs of the Ontario Institute for Cancer Research (OICR), the Cancer Imaging Network of Ontario (CINO) and the NSERC Discovery Research Program. The hypothesis central to all this work is that molecular imaging of tumours can provide biomarkers of the tumour environment that are important for understanding changes in the tumour biology as it evolves and undergoes treatment.
Can hyperpolarized imaging probes measure early metabolic changes in tumours in response to treatment?
Magnetic resonance spectroscopic imaging is used to assess properties of the tumour environment by following the metabolic fate of hyperpolarized 13C-enriched endogenous compounds after injection in an animal model of cancer therapy. This is a very sensitive method, which allows us to map regional changes of tumour hypoxia, pH and eventual cell death by following the metabolic fate of these molecules. Our preclinical research using hyperpolarized endogenous probes of tumour metabolism is demonstrating the ability to measure changes in tumour metabolism as soon as one day after initiation of therapy. We are working to establish whether these changes are predictive of longer-term treatment response. With the advent of hyperpolarization apparatus compatible for human use, this research will have immediate clinical application.
Does sodium concentration in prostate tumours correlate with tumour grade and aggressiveness?
Increased sodium concentration in breast and brain tumours has been previously investigated; however, significant difficulties associated with producing high contrast MR images of the prostate and the lower signals inherent with sodium MRI makes this imaging a challenge for prostate cancer. My research group has developed very sensitive MRI hardware, which has been optimized for imaging sodium in the prostate. Working with other researchers at Robarts and clinician scientists at our hospitals and cancer program, we have recently begun to collect sodium images from volunteers with biopsy-proven prostate cancer. Post-surgical histology of sections from their prostates has been compared with multi-parametric MRI and our sodium imaging data. Our preliminary measurements of tissue sodium concentration show a significant positive correlation with tumour grade and aggressiveness. Further research is underway to establish if sodium MRI might provide a non-invasive method to assist with risk-stratification decisions for treatment of prostate cancer and prove to be a valuable tool for active surveillance of indolent prostate tumours.
Can field-cycling magnetic resonance imaging increase the specificity of magnetic resonance contrast agents for detection and assessment of cancer?
Targeted contrast agents are being developed for MRI that are preferentially taken up by cancer cells or bind to a specific receptor or protein that is over-expressed on their surfaces. These agents have the potential to improve the detection of small lesions or be used to probe tumour heterogeneity. We have developed a novel MRI method known as delta relaxation enhanced magnetic resonance (dreMR), which uses magnetic field-cycling to increase the target specificity of these contrast agents. We are using dreMR with Ablavar, a clinical contrast agent, which binds to human serum album to investigate albumin trafficking in xenografted breast tumour models.
Tumour associated macrophages (TAMs) are associated with poor outcome for breast cancer. TAMs actively take up iron particles such as those present after injection of Feraheme, an iron-based therapy approved to treat chronic kidney disease. We are investigating the use of dreMR to increase the detection specificity for iron-laden TAMs in preclinical models of breast cancer in order to map their infiltration of these tumours. This research may ultimately establish if non-invasive quantification of TAMS will be a predictor for prognosis of this disease and useful as a biomarker for its treatment.
B.Sc. Physics (Hons), University of Windsor, 1983
M.Sc. Physics, Western University, 1985
Ph.D. Physics, Western University, 1988
Postdoctoral Fellow, Department of Physics and Astronomy, Western University, 1989-92.
New Investigator Award, Ontario Institute for Cancer Research, 2010-2014
Investigator Award Renewal, Ontario Institute for Cancer Research, 2015-2019
Farag A, Peterson J, Szekeres T, Bauman G, Chin J, Romagnoli C, Bartha R, and Scholl TJ, Unshielded Asymmetric Transmit-Only and Endorectal Receive-Only RF Coil for 23Na MRI of the Prostate at 3 Tesla. Journal of Magnetic Resonance Imaging, 2014. (article first published online: 19 November 2014).
Lim H, Thind K, Alejski A, Martínez F, and Scholl TJ, Construction and Evaluation of a Switch-Tuned 13C - 1H Birdcage Radiofrequency Coil for Imaging the Metabolism of Hyperpolarized 13C-Enriched Compounds. Journal of Magnetic Resonance Imaging, 2014. 40(5): p. 1082-1090.
Harris CT, Handler WB, Araya Y, Martínez-Santiesteban F, Alford JK, Dalrymple B, Van Sas F, Chronik BA, and Scholl TJ, Development and optimization of hardware for delta relaxation enhanced MRI. Magnetic Resonance in Medicine, 2014. 72(4): p. 1182-1190.
Scholl TJ, Rehse SJ, Holt RA, and Rosner SD, Absolute wave-number measurements in 130Te2: reference lines spanning the 420.9-464.6-nm region. Journal of the Optical Society of America B-Optical Physics, 2005. 22(5): p. 1128-1133.
Scholl TJ, Holt RA, and Rosner SD, Precision measurement of the 1s2s 1S0 1s2p 1P1 interval in heliumlike beryllium. Physical Review A, 1989. 39(3): p. 1163-1169.
Timothy J. Scholl, PhD
Scientist, Imaging Research Laboratories
Robarts Research Institute
Phone: 519-931-5777 ext. 20019
Darlene Goodine, Administrative Assistant
Phone: 519-931-5777 ext. 25251