Meet the Scientists: Dr Kiran Thapaliya


Dr Kiran Thapaliya

The number of times patients with Myalgic Encephalomyelitis and chronic fatigue syndrome have been dismissed as having a psychosomatic illness or worse still, a non-existent one, is something most experience at some stage. Without a biomarker, people have had a hard time being taken seriously. Finding a biomarker is a goal of Dr Kiran Thapaliya from Queensland’s National Centre for Neuroimmunology and Emerging Diseases (NCNED) at Griffith University.

By Kathy Collett

‘Meet the Scientists’ Series
‘Meet the Scientists’ is a series of interviews with researchers working on ME and chronic fatigue syndrome. We ask them about their current research and get to meet the people working to improve our health. The series introduces early career researchers through to interviewing scientists and clinicians who have been working on the problems for decades.

Dr Kiran Thapaliya is a Research Fellow working at Menzies Health Institute, NCNED. His research interest lies in developing new neuroimaging methods for the direct in vivo mapping of tissue microstructure in Myalgic Encephalomyelitis and chronic fatigue syndrome. His research focuses on understanding how changes in tissue microstructure influence MRI signals and the development of new neuroimaging methods to identify biomarkers for ME.

Dr Thapaliya’s recent paper sheds light on deep within the brain to reveal increases in TW1/TW2 in white matter. T2W sequences are used in conjunction with T1W sequences for the detection and characterisation of a variety of disease processes. The predominant information provided by T2W sequences is the presence of increased fluid in diseased tissue that results in high signal intensity. (source)

Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans’ was published in NeuroImage: Clinical.

Dr Thapaliya and the team at Griffith University tested Fukuda criteria chronic fatigue syndrome* patients and their study showed higher T1w/T2w signal intensity which is different from MS and schizophrenia shown by other studies. Although MS can be similar to ME they found their results were unique and quite separate.

The method they used was to detect changes in tissue microstructure. Using non-weighted MRI (magnetic resonance imaging) scans they found a significant increase in TW1/TW2 in white matter as well as in the basal ganglia resulting in contrasts to healthy controls and other neurodegenerative diseases such as those mentioned above. They state that with an increase in T1w/T2w in white matter and basal ganglia regions it could potentially relate to an increase in myelination in CFS. Myelination refers to an increase in the fatty sheath surrounding neuronal processes and fibres that increases the efficiency of electrical transmission. Basal ganglia are a group of structures found deep with the cerebral hemisphere.

The study included 45 people with Fukuda chronic fatigue syndrome and 27 controls.

*The Fukuda definition of chronic fatigue syndrome is a broader definition than the International Consensus Criteria for ME: NCNED found around 62% of Australians diagnosed with chronic fatigue syndrome met the Fukuda criteria, 32% met the criteria for ME.

How long have you been researching ME, and what brought you to the field?

Not very long, I started a year ago. My PhD focussed on development of neuroimaging methods to study tissue microstructure in the brain of healthy controls. When I heard that myalgic encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) has unknown aetiology, I was very excited to implement my neuroimaging methods in ME/CFS dataset. 

What was the turning point for you to start testing for brain abnormalities?

The brain is involved in almost all activities. In ME/CFS, impaired concentration and memory, visual and auditory changes, headache and autonomic manifestations, predominate its signs and symptoms and confirm primary brain involvement. Previous work from our current team has demonstrated dysfunction in brain stem as well as in many other brain regions in ME/CFS.

What is the difference between weighted and non-weighted MRIs?

T1 and T2 weighted images are the basic pulse sequences in MRI. T1 weighted images (T1w) show differences in T1 relaxation time of tissues whereas T2 weighted (T2w) demonstrates difference in the T2 relaxation time of tissue. Sometimes, T1 weighted and T2 weighted images are also written as T1 and T2 images but not sure about non T1 and T2 weighted images.  Here, we acquired clinical standard T1 and T2 weighted images to study structural changes in ME/CFS. Using the ratio of these two images, there is improvement in the tissue contrast that provides much better information about tissue pathology. This method is sensitive to changes in myelin in white matter as well as iron in deep grey matter regions. 

Why wasn’t it possible to achieve the same results with a standard MRI?

T1 and T2 weighted MRIs are standard MRI sequence but calculating ratio using T1w and T2w MRIs provide much better tissue contrast.

Why do you think the associated problems may result in an increase in myelination and what physical problems and symptoms would this cause?

This is a very interesting finding. We observed elevated T1w/T2w signal intensity in ME/CFS white matter which is the opposite of CNS disorders. We are still unsure about the associated physiology changes and symptoms. We need to confirm this finding using different methodology in larger ME/CFS cohort.

Do you feel you can advance this research by following up with more research on the brain?

At this stage, I am very confident that brain abnormalities exist in ME/CFS and we need more data to understand the pathophysiology of ME/CFS. We have also related our MRI findings in the brain with clinical parameters to understand the relationship between MRI findings and ME/CFS. We are always looking forward to collaborating with other scientists to understand brain dysfunction in ME/CFS.

Do you feel the non-weighted MRI scans will lead to a diagnostic test?

Not sure about non-weighted MRI, all T1 and T2 images are weighted, that is each is slightly affected by the other.

Do you have any potential treatments in mind?

It’s too early to say about any kind of treatment. We are currently working on a number of possible treatment options and testing them in the laboratory before we will take a step to a possible clinical trial.

Apart from the impact the brain has on the illness, are you interested in looking into damage done elsewhere in the body, created by toxins for example?

Not for now. We are very much focused on working with the brain, in part because we need to understand more about its bodily effects in ME/CFS. However, another team in our group is working on natural killer (NK) cells as a model and investigating a number of key channels that may be mirrored in other body systems.

Now that you have established problems with TW1 and TW2, do you think that it will be possible to reverse the damage done to the brain? 

Still very early to say anything about brain damage recovery. These are just the preliminary findings. We are planning to use ultra-high field 7T scanner that has a higher sensitivity to changes in brain tissue and anatomy and superior pathophysiological information. If we can reproduce these findings in a larger cohort then we can confirm these findings and possibly help specify targeted drugs that may recover brain damage.

How is technology affecting your work?

Technology has great influence in our current work. We have advanced MRI to acquire data with higher resolution. Many image processing toolboxes are available now, and better computing systems than were available 10 years ago. 

Patient recruitment has been much easier through social media like Facebook, twitter and Instagram. I have great respect to those scientists who conducted earlier research with limited resources.

What interests you about researching the brain?

The brain is one of the largest and most complex organs in the human body. When I heard that neurodegenerative diseases such as Alzheimer’s disease have no cure, that really hit me hard. Then I thought this is a very interesting area on which to focus.

Do you think Queensland is a good place to be a researcher? What is it like to be a scientist working in Australia at the moment (funding, global pandemic, any issues you think are relevant)?

Queensland is blessed with top research institutes and great scientists. This is one of the best places to conduct advanced research activities especially in my field because we have great infrastructure available and are surrounded by experts in the field. However, it is always challenging to continue in this field because of limited funding. 

What is the biggest challenge in researching ME?

ME/CFS has heterogenous symptoms and we require more data to understand pathophysiology of this disease. Our biggest challenge for now is to acquire funding and motivate participants to take part in the research. I am very thankful to all the donors who have made great contributions toward this research.

In this paper, the cohort is Fukuda criteria CFS, why was this chosen instead of the Canadian or International Consensus Criteria?

We acquired this data in 2016. At that time, we accepted subjects that met Fukuda or ICC criteria but we combined them in analysis. However, we are aware that ICC and CCC criteria would be more stringent to classify ME/CFS patients, and our future research will only accept subjects that meet ICC or CCC criteria.

What are you most proud of in your career, so far?

Being a recent graduate, I am proud that I can continue research and use all my skills and knowledge to investigate brain abnormalities in ME/CFS. I am also proud to work with the great team at NCNED with its national and international standing.

What would you like to achieve in your career?

I would like to identify a biomarker for ME/CFS that could potentially lead to targeted drug development and benefit the wider community of ME/CFS patients.

What do you enjoy doing outside of work?

Apart from research, I enjoy jogging, playing soccer and cricket, travelling, spending time with family and hanging out with friends.

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