Imaging Brains and Treating Hearts: An Interview with Esmaeil Mansouri

by Mashal Ahmed.

A part-time registered nurse (RN) at St. Michael’s Hospital and a full-time Master’s student at IMS, Esmaeil Mansouri has struck a unique balance between his dual roles as a healthcare provider and clinical researcher. However, unlike many healthcare workers, for whom problems encountered on-the-job might pique interest into research, Mansouri’s journey began at the opposite end: with clinical inquiry.

After graduating from the University of Toronto in 2014 with a Bachelor of Science in Neuroscience and Chemistry, Mansouri began working at the Centre for Addiction and Mental Health (CAMH) as a research assistant. This position eventually led him into his current Master’s program, which he began in 2018. For the past six years Mansouri has worked with the Human Brain Imaging Lab under the supervision of Dr. Isabelle Boileau to better understand the biological mechanisms underlying mental illness and substance use disorders (SUDs).

SUDs impose a significant social and economic burden on society. Alcohol use disorder, for example, accounts for an average cost of $14.6 billion in Canada every year.1 Often, patients suffering from SUDs present with multiple comorbid psychiatric disorders, including bipolar disorder, major depression, antisocial personality disorder, general anxiety disorder, and dependence on other drugs,2 which further magnify mental, physical, and socioeconomic strains. Despite the prevalence of these disorders, treatments remain sub-optimal. This highlights the need to better understand the neurobiological under-pinning’s of such disorders.

Mansouri’s research has focused on using positron emission tomography (PET) and autoradiography imaging to learn more about the interaction between the brain’s cannabinoid and dopaminergic systems; both of which have been implicated in addiction and reward-related behaviours. PET is a nuclear imaging technique that uses a radioactive tracer to measure metabolic processes within the body. Mansouri’s project employs the radiotracer [C-11]-(+)-PHNO to measure in vivo dopamine D2/3 receptor binding.

Esmaeil Mansouri, BSc, RN. MSc Student, Institute of Medical Science, University of Toronto

“There is growing interest in the dopamine D3 receptor due to its pivotal role in addiction,” Mansouri explains. “Preclinical, post-mortem, and brain imaging studies have shown an upregulation of this receptor in stimulant users.3 Furthermore, a genetic variation (C385A) in an endocannabinoid system enzyme called “fatty acid amide hydrolase” (FAAH) has been associated with the same type of reward-related behaviours that are linked to dopamine D3 receptors.”

Mansouri’s imaging results demonstrate higher [C-11]-(+)-PHNO binding and D3 receptor expression in patients with the FAAH genetic variant (C385A).4 This genetic variation (C385A) results in lower FAAH activity, which has been associated with SUDs.5,6 “It’s exciting because we replicated this finding in mice as well. These results suggest that FAAH may serve as a novel therapeutic target for SUDs, which in turn, could spark interest in the employment of FAAH-targeted treatment options”, he explains. “Modulation of FAAH activity within the endocannabinoid system could have beneficial effects on the dopaminergic system, aiding in the treatment of SUDs.”

As the interview continues, we walk through the bright halls of the Research Imaging Centre at CAMH. Mansouri leads us into one of the patient prep rooms. “While preparing patients for imaging procedures I came to really enjoy the element of patient interaction; building rapport, learning uniquely different life stories, and providing emotional support when needed.” Mansouri explains. “Out of curiosity, I began talking to CAMH nurses to get a sense of their job experiences. It was these direct patient interactions and discussions that piqued my interest in clinical care and nursing. I loved my role in research, but I also wanted to make a difference on an individual basis.”

A common misconception in research as well as the medical field in general, is that one’s area of expertise should be very specific and niche. While it is true that researchers and clinicians should be knowledgeable in their field, this notion should not hinder exploration of other areas, medical or otherwise. Branching into new endeavours promotes personal growth and provides broader perspective into one’s original field of work. That was the case for Mansouri.

Mansouri completed nursing school in 2017 and began working as an RN in the Cardiovascular Intensive Care Unit (CVICU) at Toronto General Hospital in January 2018. “It was a big leap to go from working in a mental health hospital to the CVICU. A number of people questioned the seemingly great difference between my research and clinical work.” Yet for Mansouri, this was an exciting transition. “From my perspective I was bringing the patient interaction skills I had developed from working with mentally vulnerable populations and applying them to a different set of patients”, he explained.

Patients admitted to the CVICU are either suffering from acute coronary syndromes, recovering from a major cardiothoracic-related surgery, or receiving critical treatment for a chronic cardiothoracic illness. Due to the severity of their ailments, these individuals often experience a roller-coaster of emotions, ranging from depression to extreme anxiety to delirium. “Having a background in mental health helps me better connect and understand these additional challenges. In turn, this allows patients to more easily build trust and have a more comfortable hospital experience. I like to tell people ‘I learn about the brain and help treat the heart’”.

Mansouri’s experience in research also helped him understand the importance of transitioning towards evidence-based clinical practice. A few decades ago, many medical procedures were anecdotal; if they worked for a handful of patients, surely they would work for others presenting with similar symptoms, right? Today, hospitals are moving away from this form of thinking and implementing practices that are based on reliable medical research and peer-reviewed literature. “My exposure to the scientific method taught me about the importance of evidence-based medicine early in my career, and I carry this knowledge forward through my job.”

“What about vice versa? What has your role as an RN taught you about research?” I ask. “The bigger picture”, he answers almost immediately. “As graduate students, we can easily be consumed with the nitty, gritty details of our work; striving to find statistical significance in our hard-earned data. But does statistical significance equate to clinical relevance? Not always.” Mansouri continued, “Working in healthcare has taught me to step back from my research and question how this will translate to bedside. This form of thinking has also helped me keep my manuscripts and thesis focused on the main purpose: How will these findings contribute to the medical community?”

As one might expect, the workload from navigating a Master’s project and concurrently working as an RN can be overwhelming. Initially Mansouri was working fulltime, but it became very stressful to balance with the academic expectations of his program. To maintain a healthy balance with his dual roles and responsibilities, Mansouri has started working part-time as an RN. “I try to work night shifts and weekends at St. Micheal’s and come into the lab to work on my thesis project. I also make time for taking power naps, working out, and hanging out with friends. I think these breaks between school and work are essential to maintaining this busy lifestyle. There is no way to survive without it”, he laughs.

As his Master’s comes to an end this summer, Mansouri contemplates the next steps in his career. “My options are wide open. I definitely want to remain in the healthcare field. I might pursue my PhD or further my studies to becoming a nurse practitioner. But as always, I am keeping my options open!” For anyone considering a similar, unconventional route in medical research and healthcare: stay open-minded about your opportunities; you might just end up imaging brains and treating hearts.

References

  1. Rehm J, Baliunas D, Brochu S, et al. The costs of substance abuse in Canada 2002 (Highlights). Canadian Centre on Substance Use and Addiction. 2006.
  2. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the national epidemiologic survey on alcohol and related conditions. Archives of general psychiatry. 2004 Aug 1;61(8):807-16.
  3. Payer D, Balasubramaniam G, Boileau I. What is the role of the D3 receptor in addiction? A mini review of PET studies with [11C]-(+)-PHNO. Progress in neuro-psychopharmacology and biological psychiatry. 2014 Jul 3;52:4-8.
  4. Mansouri E, Nobrega JN, Hill MN, et al. D3 dopamine receptors and a missense mutation of fatty acid amide hydrolase linked in mouse and men: implication for addiction. Neuropsychopharmacology. 2019 Nov 27:1-8.
  5. Boileau I, Tyndale RF, Williams B, et al. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C] CURB. Journal of cerebral blood flow & metabolism. 2015 Aug;35(8):1237-40.
  6. Tyndale RF, Payne JI, Gerber AL, et al. The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians. American journal of medical genetics part b: Neuropsychiatric genetics. 2007 Jul 5;144(5):660-6.