Principal Investigator
Timothy J. Scholl, Ph.D.
Why I Became a Scientist
I have always been fascinated with understanding how things work. For me, framing complex systems in terms of physical principles and mathematics provides a great challenge as well as personal satisfaction as a problem is unraveled. My graduate training involved experimental atomic and molecular physics where very detailed physical models can be used to accurately describe various parameters of these systems. My research interests have since shifted to medical physics with a focus on application of a new technology for imaging metabolic function with magnetic resonance imaging. Much of the basis of this technology is grounded in the type of atomic physics research with which I was familiar and was partly responsible for this attraction. As a medical physicist in the Imaging Research Laboratories, at the Robarts Research Institute, I have found a new challenge to develop novel methods of visualizing and quantifying disease and then translate that technology from research to clinical practice that will impact healthcare.
Research Summary
Dr. Scholl’s interests at the Robarts Research Institute will concentrate on the development and use of advanced molecular probes for cancer imaging with magnetic resonance. These probes will include hyperpolarized endogenous compounds and targeted paramagnetic contrast agents.
1) Hyperpolarized probes for metabolic imaging
Magnetic resonance spectroscopy (MRS) has been a powerful tool for biomedical research. Its main weakness is its relatively low sensitivity even for ubiquitous protons found in water molecules. The poor sensitivity arises mainly due to the small degree of magnetic alignment of nuclear spins achievable at body temperature even at magnetic fields greater than 3T. Other biologically interesting nuclei, such as ¹³C and 15N, are even more difficult to detect for a number of reasons and, as a result, are rarely imaged without any special effort. However, once magnetized, certain molecular compounds containing 13C and 15N can remain magnetized as long as tens of seconds – even inside a living animal.
This aspect, combined with hyperpolarization techniques that can profoundly enhance the magnetization of compounds containing these rare nuclei by factors of ~100,000, make MR imaging with these nuclei feasible with similar or even better SNR than that of protons. Furthermore, 13C nuclei ordinarily present at natural abundance are below the detection limit of normal MRSI. Therefore, only the signal from hyperpolarized 13C-enriched substances is detected leading to extremely high contrast-to-noise ratio. As a result of these factors, endogenous substances containing highly enriched fractions of these nuclei are proving to be important probes for metabolic imaging research using MRS.
For example, with specialized equipment now installed at the Robarts Research Institute, 13C enriched pyruvate is now routinely hyperpolarized to better than 20% in our dynamic nuclear polarization laboratory for use as an endogenous contrast agent (CA) to probe fluxes in metabolic processes such as glycolysis and the citric cycle. MRS imaging of injected hyperpolarized pyruvate and its metabolites produces spatial and temporal information about cellular metabolism. With funding from the Ontario Institute for Cancer Research, work by the group led by Dr. Scholl will have a primary focus on cancer imaging using hyperpolarized probes for
- Early cancer detection,
- Tumor and tissue characterization, and
- Monitoring tumor response to treatment.
Research Questions and Disease Implications
Can one use hyperpolarized metabolic probes such as 13C-enriched pyruvate to characterize and stage a tumour?
This group intends to examine a range of cell lines to examine whether it is possible to establish biomarkers based on a metabolic probe such as hyperpolarized pyruvate to establish the malignancy of an unknown growth. Furthermore, it would be very significant if a biomarker could be established that also indicates the likelihood of metastasis of the cancer. Such information would be vital for cancer treatment to indicate the type and immediacy of treatment.
Can tumour response to treatment be quantified using hyperpolarized metabolic probes at an early stage of treatment?
As oncology moves to develop more individualized cancer treatment, molecular imaging will be come a valuable tool to characterized tumours and their response to a specific therapy. Recent pre-clinical research using hyperpolarized 13C1 - pyruvate has demonstrated that it is possible to detect brain tumour response to a standard chemotherapeutic drug in a rat model much earlier than with standard methods. If this research can be extended to other forms of cancers and other treatments such as immunotherapy, it will establish a very important tool for oncologists to follow the course of treatment and to make changes based on the efficacy of treatment measured using this unique form of molecular imaging.
Education
Ph.D. Physics
1985-1988
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
M.Sc. Physics
1983-1985
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
Hons. B.Sc. Physics
1979-1983
The University of Windsor
Department of Physics
Windsor Ontario, Canada
Training
Research Associate - Medical Physics
2004-2009
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
Research Associate - Atomic and Molecular Physics
1991-2004
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
Postdoctoral Fellow - Atomic and Molecular Physics
1989-1990
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
Graduate Student
1983-1988
The University of Western Ontario
Department of Physics and Astronomy
London Ontario, Canada
Awards
- The University of Western Ontario1983 - 1988, Special University Scholarship.
- The University of Western Ontario1983 - 1987, Natural Sciences and Engineering Research Council Postgraduate Scholarship.
- The University of Western Ontario
- 1983, University of Western Ontario Entrance Scholarship.
- The University of Windsor
- 1983, Governor's Medal in Physics.
- The University of Windsor
- 1981 - 1983, Natural Sciences and Engineering Research Council Summer Research Award.
- The University of Windsor
- 1980 - 1983, President's Roll.
- The University of Windsor
- 1979 - 1983, Nora Cleary Scholarship.
Selected Publications
- Alford JK, Rutt BK, Scholl TJ, Handler WB, Chronik BA. Delta relaxation enhanced MR: obtaining order of magnitude increases in the activation-specificity of molecular probes through R1 dispersion imaging. Magn Reson Med. 2009; 61:796-802. [PDF]
- Alford JK, Scholl TJ, Handler WB, Chronik BA. Design, construction, interfacing and benchmarking of a prototype high-power B0 insert coil for field-cycled imaging in a 1.5T superconducting MRI system. Concepts in Magn Reson B: Magn Res Eng. 2009; 35B:1-10. [PDF]
- Bindseil GA, Handler WB, Scholl TJ, Gilbert KM, Chronik BA. First hybrid images from a combined PET and field-cycled MRI system. Proceedings of the ISMRM 17th Scientific Meeting, Honolulu. 2009:590.
- Gilbert KM, Scholl TJ, Handler WB, Alford JK, Chronik BA. Evaluation of a positron emission tomography (PET) - compatible field-cycled MRI (FCMRI) scanner. Magn Reson Med. 2009; 62:1017-1025. [PDF]
- Recoskie BJ, Scholl TJ, Chronik BA. Discrepancy between human peripheral nerve chronaxie times as measured using magnetic and electric field stimuli: relevance to MRI gradient coil safety. Phys Med Biol. 2009; 54:5965-5979. [PDF]
Contact Information
Mailing Address
Imaging Research Laboratories
Robarts Research Institute
1151 Richmond Street, North
London, Ontario
Canada N6A 5B7
Phone: 519-663-5777, ext. 20019
Administrative Assistant
Sherri Couto
Phone: 519-931-5290
Email: scholl@uwo.ca
