A. Personal Statement

As a neuroradiologist with a strong academic background in clinical neuroradiology, advanced neuroimaging research, and neuromodulation devices (e.g. deep brain stimulation (DBS)), I have acquired a unique combination of expertise that aligns closely with the objectives of this project assessing potential new imaging biomarkers for crucial circuit-based neurological disorders. My work has been dedicated to bridging the gap between clinical practice and research, with a specific focus on improving the safety and expanding the clinical applications of MRI for patients with neuromodulation devices. I have the expertise, leadership, and motivation necessary to successfully contribute to the proposed work.

I am particularly interested in using unique brain features to predict outcomes and evolution of treatments. Advanced brain imaging techniques such as resting-state fMRI (rsfMRI) and diffusion-weighted diffusion tensor imaging (DTI) can capture patients’ unique brain circuitry. Using multimodal advanced neuroimaging, I focus on generating biomarkers of treatment response for functional neurosurgery patients undergoing DBS and MRguided Focused Ultrasound, and patients with neurodegenerative disorders. Ultimately, my priority is the clinical translation of these tools to improve patient outcomes while providing a foundation for further advancements.

In my clinical practice, I have firsthand experience with the challenges and limitations of current neuroimaging techniques including in patients with DBS systems and other neuromodulation devices. This perspective has fueled my research efforts, leading to significant advancements in the safety and utility of MRI in these patients. 

My research has improved our understanding of the MRI safety of DBS systems, enabling the expansion of MRI usage in this population. At our institution, we now routinely perform 3T functional MRI (fMRI) in these patients, which is becoming a powerful tool guiding the fine tuning of the stimulation, a methodology now under clinical trial funded by the National Institutes of Health (NIH). Moreover, the safety work has addressed critical clinical needs by enabling spine MRI for patients with both DBS systems and spinal conditions, who previously required invasive CT myelograms. This shift to MRI, following comprehensive safety testing, has provided a more accurate and less invasive diagnostic tool for these patients, enhancing clinical outcomes.

My collaborations with local and international experts in neuromodulation safety and advanced imaging have resulted in seminal publications over the past five years, further solidifying my reputation in the field. As a coinvestigator on several grants, I successfully administered projects (e.g., leadership, staffing, budget), and collaborated with other researchers. As a result of these previous experiences, I am aware of the importance of frequent communication among project members and ensuring a realistic research plan, timeline, and budget. I have 50% protected research time to ensure successful and timely completion of the deliverables, leveraging my clinical insights, research experience, and collaborative network to develop this new dual-field MRI method to probe the brain in DBS patients. In summary, the current application builds logically on my prior work and acquired skills related to advanced imaging techniques. I have a demonstrated record of accomplished and productive research projects in an area of high relevance for patients, and my expertise and experience have prepared me to contribute to the proposed project.

Ongoing synergistic grants that I like to highlight include:
R01NS133433-01
Boutet (Co-I)
10/15/23-10/15/28
Functional Magnetic Resonance Imaging and Deep Learning to Improve Deep Brain Stimulation Therapy

Representative publications:
1. Boutet A, Rashid T, Hancu I, Elias GJB, Gramer RM, Germann J, et al. Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients. Radiology. 2019;293(1):174-83. doi: 10.1148/radiol.2019190546. PMID: 31385756
2. Boutet A, Hancu I, Saha U, Crawley A, Xu DS, Ranjan M, et al. 3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences. Journal of Neurosurgery. 2019;132(2):586- 94. doi: 10.3171/2018.11.JNS181338. PMID: 30797197
3. Hancu I, Boutet A, Fiveland E, Ranjan M, Prusik J, Dimarzio M, et al. On the (Non-) equivalency of monopolar and bipolar settings for deep brain stimulation fMRI studies of Parkinson’s disease patients. Journal of Magnetic Resonance Imaging. 2019;49(6):1736-49. doi: 10.1002/jmri.26321. PMID: 30552842
4. Elias GJB*, Boutet A*, Joel SE, Germann J, Gwun D, Neudorfer C, et al. Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy. Ann Neurol. 2021 Mar;89(3):426-443. doi: 10.1002/ana.25975. Epub 2020 Dec 21. PubMed PMID: 33252146.
5. Boutet A, Chow CT, Narang K, Elias GJB, Neudorfer C, Germann J, et al. Improving Safety of MRI in Patients with Deep Brain Stimulation Devices. Radiology. 2020;296(2):250-62. Epub 2020/06/24. doi: 10.1148/radiol.2020192291. PMID: 32573388.

B. Positions, Scientific Appointments and Honors

Positions and Scientific Appointments
2025-Present Slaight Neuroradiology Research Lead, University Health Network
2024-Present Clinician Investigator, Krembil Research Institute, University Health Network
2024-Present Co-lead Krembil Brain Institute (KBI) Neurosciences Rounds, University Health Network
2023-Present Neuroradiologist, University Health Network
2023-Present Assistant Professor, University of Toronto
2021-Present American Journal of Neuroradiology Editorial Fellow
2021-Present Review Editor, Frontiers in Neuro-Oncology and Neurosurgical Oncology
2020-Present Member, American Society of Neuroradiology, 100422
2020-Present Reviewer, Stereotactic and Functional Neurosurgery
2013-Present Member, Radiological Society of North America, 00661289
2022-2023 Diagnostic Neuroradiology Fellow, University of Toronto, Toronto, ON
2013-2022 Diagnostic Radiology Resident, University of Toronto, Toronto, ON
2011-2012 Co-Editor-in-Chief, McGill Journal of Medicine, McGill University, Montreal, QC

Honors
2022 Gordon Potts Best Resident Award, University of Toronto, Toronto, ON
2021 The RSNA Roentgen Resident/Fellow Research Award, University of Toronto, Toronto, ON
2020 CSCI/CIHR Best Resident Research Prize, Ottawa, ON
2013 Lieutenant Governor Youth Medal, Quebec city, QC
2008-13 Dean’s Honour List, Faculty of Medicine, McGill University, Montreal, QC
2005 Canada Governor General Bronze Medal, Ottawa, ON

C. Contribution to Science

1. Translational neuroimaging for precision medicine in functional neurosurgery. My unique skillset as a neuroradiologist investigator has allowed me to build a neuroimaging program at Toronto Western Hospital aiming at incorporating imaging into the clinical workflow of functional neurosurgeries (e.g. deep brain stimulation surgeries and MR-guided Focused ultrasound). We have shown that stimulation can be personalized to target symptom-specific circuitopathies for DBS patients. Similarly, we have defined optimal lesioning target for MR-guided Focused ultrasound thalamotomies taking into account inter-individual differences in thalamus morphology. The goal is provide patients with individualized therapies based on their unique brain features to improve clinical outcomes and streamline the workflow.
a. Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, et al. Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain. 2018;141(12):3405-14. Epub 2018/11/20. doi: 10.1093/brain/awy278. PMID: 30452554.
b. Boutet A, Loh A, Chow CT, Taha A, Elias GJ, Neudorfer C, et al. A literature review of magnetic resonance imaging sequence advancements in visualizing functional neurosurgery targets. Journal of Neurosurgery. 2021;26;135(5):1445-1458. DOI: 10.3171/2020.8.JNS201125. PMID: 33770759
c. Boutet A*, Elias GJ*, Joel SE, Germann J, Gwun D, Neudorfer C, et al. Probabilistic mapping of deep brain stimulation: insights from 15 years of therapy. Annals of Neurology. 2021;89(3):426-43. DOI: 10.1002/ana.25975. PMID: 33252146 d. Krauss JK, Lipsman N, Aziz T, Boutet A, Brown P, Chang JW, et al. Technology of deep brain stimulation: current status and future directions. Nature Reviews Neurology. 2021;17(2):75-87. DOI: 10.1038/s41582-020-00426-z. PMID: 33244188
e. Boutet A*, Germann J*, Gwun D, Loh A, Elias GJ, Neudorfer C, et al. Sign-specific stimulation ‘hot’and ‘cold’spots in Parkinson’s disease validated with machine learning. Brain Communications. 2021;3(2):fcab027. doi: 10.1093/braincomms/fcab027. PMID: 33870190
2. Advanced imaging techniques to develop network biomarkers in DBS.  Fine tuning the DBS stimulation for each patient is a cumbersome and costly process requiring multiple clinical visits over several months. My research has demonstrated that in vivo fMRI acquired in DBS patients can be used as a rapid biomarker of success. The fMRI pattern obtained upon DBS activation can be used
to predict the clinical outcomes. Promising results have been obtained in movement and psychiatric disorders.
a. Boutet A, Rashid T, Hancu I, Elias GJB, Gramer RM, Germann J, et al. Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients. Radiology. 2019;293(1):174-83. Epub 2019/08/07. doi: 10.1148/radiol.2019190546. PMID: 31385756
b. Boutet A, Madhavan R, Elias GJB, Joel SE, Gramer R, Ranjan M, et al. Predicting optimal deep brain stimulation parameters for Parkinson’s disease using functional MRI and machine learning. Nature Communications. 2021;12(1):3043. doi: 10.1038/s41467-021-23311-9. PubMed PMID: 34031407.
c. Elias GJ, Germann J, Boutet A, Loh A, Li B, Pancholi A, et al. 3 T MRI of rapid brain activity changes driven by subcallosal cingulate deep brain stimulation. Brain. 2022;145(6):2214-2226. doi: 10.1093/brain/awab447. PMID: 34919630
d. Loh A, Elias GJB, Germann J, Boutet A, Gwun D, Yamamoto K, et al. Neural Correlates of Optimal Deep Brain Stimulation for Cervical Dystonia. Annals of Neurology. 2022 Sep;92(3):418–24. doi: 10.1002/ana.26450. PMID: 35785489
3. Lesioning with intracranial MR-guided focused ultrasound (MrgFUS). MRgFUS is a novel minimally invasive treatment creating tiny lesions in the brain to disrupt dysfunctional brain circuits. Most commonly, a small lesion is done in the thalamus for tremor disorders. However, controversy remains regarding the precise lesion location for maximal tremor benefits. My research has characterized the optimal area to ablate and the optimal skull characteristics, which can be used to improve accuracy for each treatment.
a. Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, et al. Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain. 2018;141(12):3405-14. Epub 2018/11/20. doi: 10.1093/brain/awy278. PMID: 30452554.
b. Meng Y, Solomon B, Boutet A, Llinas M, Scantlebury N, Huang Y, et al. Magnetic resonance–guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study. Movement Disorders. 2018;33(10):1647-50. doi: 10.1002/mds.99. PMID: 30288794
c. Ranjan M, Boutet A, Bhatia S, Wilfong A, Hader W, Lee MR, et al. Neuromodulation beyond neurostimulation for epilepsy: scope for focused ultrasound. Expert review of neurotherapeutics. 2019;19(10):937-43. doi: 10.1080/14737175.2019.1635013. PMID: 31232614
d. Boutet A, Gwun D, Gramer R, Ranjan M, Elias GJ, Tilden D, et al. The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound. Journal of Neurosurgery. 2019;132(6):1785-91. doi: 10.3171/2019.2.JNS182571. PMID: 31051458
e. Vetkas A, Boutet A, Sarica C, Germann J, Gwun D, Yamamoto K, et al. Successful magnetic resonance–guided focused ultrasound treatment of tremor in patients with a skull density ratio of 0.4 or less. Journal of Neurosurgery. 2023 Sep 1;1–9. doi: 10.3171/2023.6.JNS23171. PMID: 37657095
4. Understanding Huntington’s Disease through neurotrophins. Huntington’s disease is a fatal neurodegenerative disorder. Striatal degeneration is the pathological hallmark. A lack of neurotrophins such as brain-derived neurotrophic factor (BDNF) has been implicated in various neurodegenerative disorders. This research project assessed the relationship between the quantity of BDNF in the striatal afferents, and the behavioral as well as histological changes in a mouse model of Huntington’s Disease. The results showed a temporal relationship between decreasing BDNF in striatal afferents, and the behavioral and histological manifestations of Huntington’s Disease. I was the principal graduate student leading this project in collaboration with a post-doctoral fellow. As the second author, I contributed to the data acquisition and analysis.
a. Samadi P, Boutet A, Rymar V, Rawal K, Maheux J, Kvann J.C, Beaubien F, Wang Q, Cloutier J.F, Levesques D, Sadikot A.F. Relationships between BDNF expression in major striatal afferents, stratum morphology and motor behaviour in the R6/2 mouse model of Huntington’s disease. Genes Brain Behav. 2013 Feb;12(1):108-24. DOI: 10.1111/j.1601-183X.2012.00858.x. PMID: 23006318

Complete List of Published Work in My Bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/alexandre.boutet.2/bibliography/public/