Imaging brings treatment a step closer for children with genetic heart condition

Researchers have tracked a molecule that targets the heart using imaging techniques supported by NIF, taking them a step closer to preventing a common genetic cardiac condition. 

The researchers are developing the first therapeutic for preventing – and even reversing – hypertrophic cardiomyopathy (HCM), the leading cause of sudden cardiac death in those aged 5 to 15 years.  

They have identified a mechanism in which the powerhouse of the cell, called mitochondria, use large amounts of oxygen to enlarge the heart wall in people with HCM. 

In vivo multispectral fluorescence imaging at NIF’s Node at the Centre for Microscopy, Characterisation and Analysis (CMCA) at the University of Western Australia (UWA) tracked a molecule called AID-TAT that decreases oxygen used by the mitochondria and prevents the enlargement.  


UWA NIF Fellow, Ms Diana Patalwala said a fluorescent dye was added to the AID-TAT so it could be tracked to the heart to ensure it reached the correct site for treatment. 

AID-TAT was also tracked to the liver and kidneys so the ‘rate of clearance’ could be studied to confirm its safe removal from the body, she said. 

CMCA provided expertise to the project as part of NIF’s role in underpinning Australian research priorities, including how to handle the in vivo fluorescence imaging equipment and samples to obtain relevant results, and how best to analyse them. 

Wesfarmers, UWA and Victor Chang Cardiac Research Institute Chair in Cardiovascular Research, Professor Livia Hool, who is leading the research, said HCM was hereditary so screening at-risk family members would identify people to target for prevention. 

“Prevention is better than cure with HCM,” Professor Hool said. 

“Genetic testing is now much cheaper so it will become more common – and that will help to identify the people who will benefit from HCM prevention strategies. 

“At the moment, people don’t know they have HCM until they develop symptoms such as chest pain, shortness of breath, fatigue or going into cardiac arrest. 

“There is presently no treatment that can reverse or prevent HCM.” 

Professor Hool said the research team used the CMCA imaging to build a proof of concept for AID-TAT, to assist in moving towards preclinical trials to demonstrate safety and efficacy. 

A genetic mutation causes hypertrophic cardiomyopathy in one in 500 people and about one in every 100 of those people will have a sudden cardiac death. 

The research uses AID-TAT to control cardiac metabolic activity, which may help prevent HCM in at-risk people identified as having a genetic mutation. 

World’s first longitudinal muscle study grows understanding of cerebral palsy development

NIF infrastructure is enabling the Muscle Growth in the Lower Extremity (MUGgLE) Study, the first longitudinal study comparing muscle growth in children with cerebral palsy and typically developing children.

The project is a collaboration between Neuroscience Research Australia (NeuRA), the University of NSW (UNSW) and the Cerebral Palsy Alliance Research Institute.

The National Health and Medical Research Council-funded study is using magnetic resonance imaging (MRI) to compare muscle growth between typically developing children and children with cerebral palsy, using high-resolution measurements of the architecture of whole muscles.

Researcher Dr Bart Bolsterlee said the longitudinal study will see the lower legs of over 300 children scanned, between the ages of 0-3 months and 5-14 years.

“They will be scanned three times, with one-and-a-half years in between scans. We analyse the images to look at the individual muscles and how they change in size and structure over time,” Dr Bolsterlee said.

“The key measures we are getting out of this study are not just the volume of muscles, but also the orientations and lengths of their muscle fibres, which is a key determinant of the function of a muscle.

“We also look at the fat content which is a compositional feature of muscles that is quite different between diseased muscles and healthy muscles.

The impacts of this research have real implications for children growing up in Australia, with one-in-seven hundred babies born with cerebral palsy.

“This is very much a fundamental research study – we don’t have any direct clinical outcomes that we are assessing – but what we do know about children with cerebral palsy, the leading cause of childhood physical disability in the western world, is that outcomes can be pretty poor,” Dr Bolsterlee said.

“One-in-three children with cerebral palsy cannot walk independently, and we know this has got something to do with disordered muscle growth.

“It’s obvious from cross-sectional studies that there are quite some differences between the muscles of children with cerebral palsy and their typically developing peers, but nobody has actually studied this longitudinally, so we don’t know when these changes occur.

“We believe that information is necessary to develop new treatments.”

Currently there is no cure for cerebral palsy, and often children undergo severe interventions including complex surgical procedures with drugs to improve daily functioning. These interventions can change muscle growth, but how that affects musculoskeletal function is poorly understood.

Dr Bolsterlee is part of the team developing imaging methods and algorithms to be able to study this, and they are now generating the first data to give a comprehensive picture of how muscles develop typically – and how they develop in children with cerebral palsy.

“Many of the tools that are out there were developed for the brain – I’d say 99% of diffusion imaging software is used to reconstruct the neuronal architecture of the brain. We had to adapt the acquisition protocols as well as the imaging analysis techniques to accommodate measurement of the specific features of muscles we are interested in,” Dr Bolsterlee said.

In addition to configuring the imaging software to analyse data for the muscles, Dr Bolsterlee said there was a lot to consider when optimising scanning protocols to get the best images possible, while scanning children within a limited time.

“I’ve been working at NeuRA for the better part of eight years on this – and it’s really nice to see the first proof of principle demonstrations being taken to large-scale research – and hopefully to clinical practice as well.

“We’ve developed algorithms that several groups around the world are now using,” Dr Bolsterlee said.

This research into muscle imaging has grown the understanding of the architecture of muscles globally.

“Most anatomical knowledge comes from textbooks that are based on dissections of cadaver legs, and these are usually from older people who’ve donated their bodies to science.

“We have a rough understanding of the fibre structure within muscles and how they sit between muscles, but it’s been very difficult to get any information from living human muscles.

“Muscle is one of the most adaptable human tissues in the human body – when you exercise, they get bigger and when you’re lying in bed for too long, they get smaller very quickly.

“So, it’s very important if you want to understand how muscles respond to various stimuli, to have in-vivo imaging methods – or methods that can be applied to living humans,” Dr Bolsterlee said.

Previously, researchers were limited to ultrasound in living patients, which was 2D and only able to capture muscles superficial to the skin because the ultrasonic waves have limited penetration depth.

The MRI diffusion imaging technique allows researchers to look at whole human muscles in 3D, which has led to discoveries in the complex fibre structure of muscles and how it changes when they contract, lengthen or are diseased.

For more information, listen to our podcast with Dr Bolsterlee and NIF Fellow, Dr Michael Green from NeuRA: The MUGgLE Study: Imaging to understand how muscles grow.

Cancer diagnosis and targeted therapies to flow from new NIF investment

Cancer research will advance and personalised treatment will come a step closer, with installation of NIF’s new nanoScan PET/MRI 3T camera for preclinical studies.  

The camera is at the Olivia Newton-John Cancer Research Institute (ONJCRI) and represents a significant national investment as part of NIF expertise and critical mass in molecular imaging and nuclear theranostics.  

Nuclear theranostics offers simultaneous imaging and therapy, enabling researchers and clinicians to see where targeted medicines go in the body in real time, identify drugs most likely to succeed and select patients who will benefit. 

It has the potential to improve quality of life and decrease health-related costs.  

NIF Fellow Dr Ingrid Burvenich from ONJCRI and La Trobe University has conducted MRI scans using the camera as part of work to develop diagnostic tools and cancer therapies. 

“We found that the high field 3T magnet has fast scanning times and high-quality images,” Dr Burvenich said.  

“We can already see that we have excellent delineation of organs and that will enable us to better identify specific tumours in the brain, abdominal organs and other cancer sites.  

“With the new camera, we will be able to explore new areas of cancer biology, metabolism and neuroscience, and also develop new imaging probes and therapeutics.  

“In our studies we answer questions such as: does the drug reach the tumour, is enough drug going into the tumour to be effective, and are there risks for toxicity?”  

Dr Burvenich’s tumour-targeting work involves collaboration with ONJCRI’s Centre for Research Excellence in Brain Cancer, focusing on research models that reflect the disease as it is seen in human patients.   

“We are very excited to try the new camera to image brain tumours to assist with developing new therapeutics.   

“Other ONJCRI collaborators are working on genetic models that develop tumours in the stomach or the intestine and surgical models for pancreatic cancer.  

“Increasing the visibility of such tumours will potentially make a difference in this research in monitoring how tumours establish, grow and respond to newly-developed therapeutics.  

“Our new camera will also assist with advancing research in heart disease, the brain and pharmaceutical drug development – especially in developing radiopharmaceuticals, medicines with radioactive isotopes that can be used as for both diagnosis and treatment.  

“We can evaluate the radiopharmaceuticals in preclinical models and then progress them into human trials.” 

NIF is investing in improved health outcomes through novel medical products, technologies and practices – including human imaging technologies, high value therapeutics and cutting-edge pharmaceutical treatments.  

Nuclear theranostics is increasingly being used for cancer imaging, detection and treatment, in clinical trials, and in research and development to counter a growing global incidence from 19.3 million new cases in 2020 to 28.4 million in 2040. 

It has a promising future, with estimated market valuations for 2021 ranging from $1.7 billion to $6 billion and annual growth ranging from 4 to 19 per cent within eight years.  

Advanced imaging collects insights into museum’s birds and their evolution

Using advanced NIF imaging techniques to study bird skulls is helping researchers understand how they see, how they evolved to hunt at night, and the best ways to protect them.

In the process, researchers are also digitising valuable museum collections, connecting communities to nature and science and unlocking possibilities for researchers to investigate our natural world.

NIF Micro-computed tomography (CT scanning) at the University of Queensland’s Centre for Advanced Imaging has been used to scan 30 raptor skulls from Australian museums, create 3D reconstructions, measure and then study the anatomy for tell-tale signs of a bird’s visual powers.

Research published in Royal Society Open Science compared the world’s only nocturnal hawk, the Australian letter-winged kite Elanus scriptus, to other hawks and falcons with differing hunting styles.

Associate Professor in Evolutionary Biology at Flinders University Vera Weisbecker said findings threw into doubt long-held views that changes to skeletal structure were needed for evolution.

The research sought to understand whether evolutionary changes to the eye-area of the skull was evidence of the kite’s adaptation to night-time hunting, Dr Weisbecker said.

“The answer is no. In fact, there are two close relatives of the letter-winged kite that have a similar bony visual system, but both hunt in daylight,” she said.

The findings have implications for the study of evolution, with researchers often deducing that changes in skeletal remains are linked to behavioural changes.

“That’s not necessarily the whole story. In this instance, there’s no difference between the eye regions in the skulls of the night-time and the day-time hunters, so if you were just looking at the skull, you’d never know.”

Dr Weisbecker said different birds had greatly adapted their vision to have excellent visual sensitivity, sharpness, colour discrimination or even UV wavelength detection.

For Australia’s letter-winged kite, it’s possible that the nocturnal bird also picks up odours and movement, as well as adjusting its hunting methods.

CT-scanning the 30 birds of prey was primarily undertaken by CAI’s Dr Karine Mardon, on NIF-funded equipment, with skulls provided by Queensland Museum.

Dr Mardon said the imaging techniques, teamed with recent advances in anatomical understanding, opened the door to a wealth of new knowledge without needing live birds or their tissues.

CAI was the ideal place to undertake the research, enabled through national investment in imaging equipment and expertise, data analysis capability, and existing relationships with the Queensland Museum and Flinders University, she said.

Dr Weisbecker said obtaining eyes and brains of rare species was generally not feasible but some aspects of their anatomy could be estimated from skulls.

“We are extremely lucky to have Australia’s amazing museum collections at our disposal to help us understand this bird without the need to find and disturb the species,” she said.

“The kinds of things you can study closely with CT scanning are the size of their eyes and their position in the skull – are they facing forward or more on the side?”

PhD student Aubrey Keirnan compared 3D reconstructions of the letter-winged kite’s skull and brain with other birds of prey in the Weisbecker lab.

“The diversity among hawks that are active during daylight is possibly the most striking between the Spotted Harrier and the Pacific Baza,” she said.

“Both are incredible predators, but one species resembles owls while the other is much more pigeon-like in appearance.

“These two species really highlight how adaptable and diverse the visual systems of birds are, even amongst species within the same family.

“You can have birds that are anatomically similar but behave differently – and species that are behaviourally similar but anatomically different. Both sides of the coin are true.”

But Dr Weisbecker said the research was not just about insights into evolution.

The Australian letter-winged kite lives in remote, arid Australia, avoids human settlements and is highly elusive. It is listed as near-threatened, with population estimates varying between 670 and 6,700, she said.

“To conserve the species, it is critical that we understand its behavioural needs and capabilities, but these are extremely difficult to observe.

“Think about fences and powerlines potentially posing a greater threat to nocturnal birds than their daytime relatives.

“For example, in an earlier study, we found that the nocturnal night parrot is likely unable to see small objects because it may trade high resolution for higher contrast. This may put it at risk of hitting with thin fence wires.”

Dr Mardon has also scanned the bones of a night parrot, a bandicoot and many Australian marsupial mammals.

“We have an excellent working relationship with Queensland Museum, who trust us with handling some of their precious items,” she said.

Later this year CAI will install a new NIF-funded CT-scanner, a Yxlon FF35CT, along with new software to increase graphics capability, such as accurate reconstructions of soft tissue around the skull.

CAI expects greater demand for scanning which contributes to research on evolution, and Australia’s native flora and fauna.

Read the article on the Australian letter-winged kite Elanus scriptus here: Not like night and day: the nocturnal letter-winged kite does not differ from diurnal congeners in orbit or endocast morphology | Royal Society Open Science (royalsocietypublishing.org)


More about National Imaging Facility (NIF)

NIF is Australia’s advanced imaging network.

We provide open access to flagship imaging equipment, expertise, tools, data and analysis. We address Australia’s strategic science and research priorities, and this benefits Australian industry and helps keep Australians healthy.

NIF provides a full suite of advanced imaging capability including preclinical and clinical, human and animal imaging, radiochemistry and imaging data analysis. We focus on health and medical innovation, and also provide highly specialised capabilities for agriculture, materials science, museums and cultural applications.

NIF assembles partnerships that produce quality-controlled and harmonised data that provides invaluable evidence to make new discoveries, validate new products and demonstrate new therapies.

We partner with people who can translate their discoveries into real-world applications. NIF has helped Australians innovate in fields such as bioengineering, clinical science, biology, medical technology, pharmaceutical and non-pharmaceutical therapies, agriculture, materials, museums and cultural collections.

More about the Centre for advanced Imaging (CAI)

The Centre for Advanced Imaging (CAI) brings together the skills of a critical mass of researchers and ‘state-of-the-art’ research imaging instruments. It is the only facility of its type in Australia, one of only a handful in the world. The 5,500 m2, $55M CAI building was funded by the Federal Education Investment Fund in 2010 and contains over $50M of imaging and spectroscopy equipment, putting The University of Queensland’s researchers at the forefront of a field that is advancing swiftly.

Our researchers work on innovations in spectroscopic and imaging technology, imaging biomarker development and in biomedical research disciplines, frequently in collaboration with clinical research sites and other local, national, and international research institutes.  Find out more here

Resources for Working from Home

NIF Central has been working from home for over 3 weeks now, and we’re just starting to find our rhythm! From daily video catchups to messaging apps, we’re keeping in touch. But this is a marathon, not a sprint, and we are always looking for ways to improve! Here is a collection of resources that I’ve found useful.

There are upsides and downsides to working from home. This Conversation article, written before the crisis, overviews some of the research into working from home generally.

It’s important to learn from those of us who came before – researchers in isolated field studies and sailors, for example.  Some tips for coping with isolation during lockdown are outlined here. Of course, they didn’t have to worry about home-schooling and childcare. Representing a suite of new challenges,  this guide for WFH with kids may give parents and carers some tips.

Some academics swear by the Pomodoro Technique to get things done. This is a time management technique that exploits deadline anxiety to overcome procrastination – if you’re having difficulty getting anything done while you work from home, this may help! Trackers such as these are also a good way to ensure you’re not working all the time.

LinkedIn has provided 16 online courses for those looking to maximise efficiency, manage the transition to work from home, and manage teamwork. These are particularly good if you’re unable to process all the reading you’ve been doing lately, as they’re video delivered!

Let’s get real for a moment – you can be forgiven if you don’t find time to put any of these ideas into practice! Even finding the energy to consume the resources provided might be enough to put you over the edge. So, I’m going to share these articles, in particular, to outline why your productivity might be down (and why that’s okay) and some steps you can take for your mental health and long-term productivity.

Are you relying on social media to get your social fix? Here are some hashtags on Twitter that you might like to follow:

#PhDChat – posts by or for PhD students

#ECRChat – posts by or for early career researchers

#AcademicChatter – posts by or for academics

#workingfromhome – posts about working from home

There are some good pieces of advice coming out on Twitter about managing your life when you work from home. See for example: Getting things done without going to the lab, WFH with kids,  and videoconference etiquette.

What hashtags and social media gurus are you following? Let us know! We’re here to help and enjoy hearing from you.

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