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.

Neuro Imaging to examine high rates of dementia in older Aboriginal Australians

Early life stress (ELS) has been linked to abnormalities in brain structure and function and may contribute to increased risk of cognitive decline and dementia later in life. ELS has also been associated with the high prevalence of dementia observed in older Aboriginal Australians.

A study at NIF’s UNSW Node, NeuRA Imaging is engaging the Australian Aboriginal community to investigate structural and pathological brain changes that underlie in high rates of dementia and cognitive decline in older Aboriginal Australians.

This will be the first study that investigates neuroimaging in cognitive impairment in older Aboriginal Australians and will inform dementia prevention, diagnosis and policy. It will also contribute to the wider literature on vascular risk in the pathogenesis of Alzheimer’s disease and associated biomedical and social risk factors.

After extensive community engagement with partnering Aboriginal communities including La Perouse, NSW, the initial consultation stage of NeuRA’s Koori Growing Old Well Study indicated that neuroimaging should be included in future dementia studies (Lavrencic et al., 2020, Int Psychogeriatr). Led by NeuRA’s, researchers including Dr Kylie Radford, Professor Tony Broe AM and Dr Louise Lavrencic, the Koori Growing Old Well Study included a community planning survey, pilot MRI study and guidance from an Aboriginal and Torres Strait Islander Steering Committee.

“NIF’s capabilities are allowing this study to investigate underlying brain changes and pathology in ageing and dementia in partnership with Aboriginal communities. The study will give greater detail and is using sophisticated and novel MRI techniques. By having the facility in-house at NeuRA it also means we can ensure a culturally safe and welcoming environment for our participants. With a rapidly ageing population and high rates of dementia, we hope that this ground breaking study will shed light on important ways to promote healthy brain ageing with Aboriginal and Torres Strait Islander peoples,” said Dr Kylie Radford, Senior Research Scientist and Group Leader, Neuroscience Research Australia.

The neuroimaging sub-study is a prospective, cross-sectional non-interventional study where participants will first complete a comprehensive interview and diagnostic assessment as part of the Koori Growing Old Well study. Consenting participants (200) aged 55+ will undergo MR scans with an expected study completion by 2023.

The outcome analyses will include identifying associations between cognitive impairment and hippocampal atrophy/volume and vascular indices on MR. Vascular pathology will be examined for cases of possible or probable Alzheimer’s disease compared to a cognitively intact control group. Correlations between MR measures and early life stress, adult risk and protective factors, cognitive function, and clinically diagnosed cognitive impairment will be investigated.

Better detection and treatment of dementia

Biogen’s Aducanumab (Aduhelm) is the first disease modifying therapy for AD approved by the The United States Food and Drug Administration (FDA). NIF’s positron emission tomography (PET) imaging facilities at the University of Melbourne, HIRF and the Hunter Medical Research Institute (HMRI) supported the Australian trial recruitment of the Biogen Phase 3 trial by screening potentially suitable participants with amyloid PET scans in collaboration with the Australian Imaging Biomarkers and Lifestyle Study of Ageing at the Florey Institute of Neuroscience and Mental Health and Austin Health.

To prescribe the treatment for prodromal and early clinical AD it will be necessary to use imaging both PET and magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF)/blood biomarkers to ensure that subjects being treated have AD and that side effects from Aduhelm are properly managed.

Alzheimer’s disease (AD) is the most common type of dementia making up 70% of all dementia. There are about 300,000 Australians currently living with the disease, with the average disease duration of 10 years equating to 30,000 new cases each year. These numbers are predicted to triple by 2050.

The degeneration within the brain begins two to three decades before overt symptoms, highlighting early detection is critical. NIF’s University of Melbourne Node and the Herston Imaging Research Facility (HIRF) have been involved in several dementia trials, studying different aspects of the disease including early biomarker detection, combining state of the art multimodality imaging, genetics and neuropsychology. NIF is working to assess novel radiotracers as a diagnostic tool for early detection of AD and the development of a national network of radiotracers for dementia screening in collaboration with QTRaCE and the Australia Dementia Network (ADNeT). This research aids the success of new preventative medicines, both through repurposing an existing drug and novel drug development and improves classification of AD subtypes, which impact treatment profiles.

NIF has played a major role in helping Australia to maintain its leadership in imaging applied to the dementias, particularly in AD. This has occurred at multiple sites around the country since 2012. The advent of disease modifying therapies for AD will cause an increase in demand for services and it will be crucial for new innovative and cost effective methods of service delivery in our increasingly ageing population.


Changes in the brain related to parenthood

Parents can tell you that having kids changes your life. Recent studies by the Cognitive Neuroimaging Team at Monash Biomedical Imaging have shown just how deep those changes go by analysing brain structure in older adults that have had children. Parenthood was shown to cause life-long changes in both mothers and fathers, with a follow-up study suggesting that motherhood can protect the ageing maternal brain.

Read More

fMRI Short Course at UQ

From Friday 20th – Sunday 22nd November 2020, a broad audience of PhD students, postdocs, associate professors, a radiographer and a clinician attended the University of Queensland (UQ) Centre for Advanced Imaging (CAI) functional Magnetic Resonance Imaging (fMRI) short course.

Read More

Creating a Lizard Brain Atlas

Until recently, reptilian evolutionary studies lacked an important resource – a lizard brain atlas. As the subject of numerous ecological and behavioural studies, the Australian tawny dragon (Agamidae: Ctenophorus decresii) was an ideal candidate for creating a high-resolution MRI atlas of a representative scaled reptile (squamata). Such data is not only a resource for studies of the genus but also informs environmental decision making through an improved understanding of animal adaptation and evolution.

Read More

CT as part of the Forensic Science SA toolkit

A post-mortem examination, or autopsy, is a forensic technique for learning about the conditions of a person’s health at the end of life. These are typically carried out as part of a coronial inquiry to establish the cause of death. A post-mortem may also provide information about undiagnosed medical problems of relevance to family members and the research community.

Read More

Understanding Feto-Placental Vasculature

Proper vascular development of the human placenta is crucial for meeting the metabolic needs of the developing fetus during pregnancy. Maternal environmental stressors such as malnutrition disrupt the elaboration of the feto-placental vasculature that, in turn, impacts on placental function and results in reduced fetal growth. The ramifications of this are not only on short-term foetal health but also on long-term health outcomes. Indeed, distortion in placental shape and size strongly associate with later adult health outcomes such as cardiovascular disease, obesity and cancer.

Read More
Privacy Settings
Youtube
Vimeo
Google Maps