Imaging enabling nanomedicine to treat aggressive brain cancer

Image: Gadolinium enhanced MRI showing the bright brain tumour (red circle) compared to the normal brain tissue (yellow circle).

‘Nanomedicine’ sounds like a term you’d hear in a futuristic novel or an episode of Doctor Who, but cutting-edge scientists from the National Imaging Facility’s Node at the University of Queensland’s Centre for Advanced Imaging are already applying it to solve complex health challenges in collaboration with the Australian Institute for Bioengineering and Nanotechnology, and the Australian Research Council’s Centre of Excellence in Convergent BioNano Science and Technology and Training Centre in Biomedical Imaging Technology.

Nanomedicine applies nanoscale materials, such as nanoparticles and nanorobots (wow!) to the prevention and treatment of disease. Nanomedicine is a promising strategy to target tumours with chemotherapy in a safe and controlled manner.

This all sounds great, but within the context of the brain things get a little more complicated. For brain tumours, the integrity of the blood brain barrier (BBB) is central to its effective use as treatment.

The BBB is a protective barrier between the blood vessels and brain tissue, providing a defence against pathogens and toxins that may be present within the blood, while at the same time allowing vital nutrients to reach the brain.

While the BBB protects the brain against pathogens and toxins that could cause infection, it also blocks medicine from crossing the barrier in many cases, which can hamper the (often urgent) treatment of tumours, among other neurological disorders.

This is where imaging comes in…

UQ researchers have undertaken studies utilising NIF’s flagship preclinical magnetic resonance –positron emission tomography (MR-PET) system to develop hybrid imaging, combining the imaging of MRI with the information of PET.

Simultaneous MR-PET imaging enables experts to measure opening of the BBB using Gadolinium (Gd) contrast agents at the same time as delivering novel PET tracers and new theranostic candidates including nanomedicine.

These tools assist in investigating the link between BBB integrity and tumour diagnosis and treatment, and ensure the development of promising new treatments such as nanomedicine that can permeate the BBB.

BBB integrity: Tumour diagnosis and treatment

The rapid growth of brain tumours requires the formation of new vessels to supply increased demands for nutrients. The new vessels are leaky compared to normal brain vessels, where the BBB tightly regulates the transfer between blood and tissue.

The team have used Gd MRI to estimate how leaky the tumour vessels are. This information is vital for understanding how tumours are developing, and when and how diagnostic or therapeutic drugs can enter the tumour tissue.

In combination with new nanomedicines, there are also exciting new techniques that allow opening of the brain for treatment without surgery, which can increase risk for patients. These new imaging methods allow the opening of the brain to be accurately monitored to ensure entry of the treatment without any unrelated damage to the brain. 

So – our takeaway message? While advances in nanomedicine alone are exciting and important, the integration of nanomedicine and advanced imaging brings opportunity for exponential synergistic innovation in healthcare, that can improve outcomes for patients and ultimately has the potential to save lives.

For more information, contact Dr Gary Cowin, Queensland Facility Fellow, UQ Centre for Advanced Imaging.

#ImagingTheFuture Week: Unlocking solutions to major health challenges

#ImagingTheFuture Week: Unlocking solutions to major health challenges


Chan Zuckerberg Initiative’s (CZI) Imaging the Future Week puts a spotlight on the significance of imaging science in biomedicine, and the importance of building a vibrant imaging community across the world to tackle these challenges at scale.

Imaging science and the highly skilled researchers behind it are vital to addressing global health challenges, and driving innovation in disease management, prevention, and cure.

The National Imaging Facility (NIF) invests in state-of-the-art equipment and partners with world-class experts to process and interpret data and apply imaging to solve challenging health problems.

CEO Prof Wojtek Goscinski said he was proud of the NIF’s partnerships which enable the translation of discoveries through to real world applications to improve the health of the population.

“Advanced imaging techniques make it possible to deepen our understanding of health and disease in the human body through visualisation,” Prof Goscinski said.

“Imaging already plays a critical role in healthcare, and the acceleration of its advancements in biomedicine are positioning us, and our colleagues world-wide to continue this work well into the future.”

“We are supportive of the efforts of CZI and I’m excited for NIF to work alongside them and our other international imaging colleagues, building a cutting-edge imaging community at the forefront of global imaging research,” Prof Goscinski said.

You can find out more about Imaging the Future Week here.

Keep scrolling to check out some of the impressive imaging work from a few of the Australian National Imaging Facility’s Nodes.

Time-of-flight angiography of the human brain using 7 Tesla MRI – courtesy of the Centre for Advanced Imaging, University of Queensland

Human Tooth CT scan – courtesy of Diana Patalwala, University of Western Australia

Angiogram scanned on the Siemens 3T Skyra magnet – courtesy of the Large Animal Research and Imaging Facility, South Australian Health and Medical Research Institute

Tractography template image of a sham rat – courtesy of David Wright, The Florey Institute of Neuroscience and Mental Health

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.

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National Preclinical PET QA

The NIF Molecular Imaging & Radiochemistry (MIR) Theme is a group of NIF Fellows, Directors, and users of NIF facilities that focus on state-of-the-art radiochemistry and molecular imaging applications using PET, SPECT, and MRI.

Integrating preclinical PET systems into a national resource requires the development of defined QA programs to monitor and integrate the data from individual systems. Hence, the MIR Theme initiated a national quality assurance (QA) program for the NIF preclinical PET instruments.

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PET training for HDR

From July 14 – 17, four CIBIT HDR students, Saikat Ghosh, Vanessa Soh, Pragalath Sadasivam and Ting Xiang Lim, attended an in-depth training session on PET imaging. Run by Dr Karine Mardon, NIF Facility Fellow and Molecular Imaging Facility Manager at the Centre for Advanced Imaging, the course covered both molecular imaging theory and practical hands-on training relevant to the students’ research projects. 

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Detecting atherothrombosis using targeted MRI

Cardiovascular disease (CVD) is responsible for more than a quarter of all deaths in Australia and remains the global leading cause of death accounting for 17.9 million deaths per year. Of all CVDs, stroke and coronary artery disease account for the majority of deaths. A common underlying cause in these conditions in atherosclerosis, characterised by the build-up of abnormal deposits inside the arteries. Atherosclerotic plaques can rupture and cause thrombosis, or blood clots, resulting in stroke and myocardial infarction. Diagnostic strategies for the detection of thrombi are currently invasive and may not be sensitive to early biomarkers such as localised coagulation and inflammation.

A/Prof Ta, of Griffith University, has teamed up with researchers across Australia and internationally to develop a new form of MRI contrast agent. These ultra-small dual positive and negative contrast iron oxide nanoparticles (DCIONs) provide both T1-positive and T2-negative contrast effects, overcoming the limitations of single modality contrast agents. This duality is particularly important for imaging intravascular thromboses, as current single-contrast nanoparticles results in a black dye against a black artery. Further, the DCIONs are monodisperse, water-soluble, and biocompatible, of critical importance to biomedical applications.

In-vivo MRI of carotid artery thrombus (green arrows) detection after injection with a conjugated DCION. Image from Ta et al 2017.

Using non-invasive MRI at the NIF QLD Node, the application of a DCION conjugated to an enzyme found in activated platelets demonstrated accurate and sensitive detection of intravascular thrombosis. Work is continuing to further optimise the early detection of thrombi, expected to allow for earlier and more effective preventative treatments and improved clinical outcomes for patients at risk of stroke and myocardial infarction.

A/Prof Ta is enthusiastic about the future applications of DCIONs beyond thrombosis diagnoses, stating that “these nanoparticles have the potential to replace traditional gadolinium-based contrast agents due to their stronger T1 contrast effect. Existing alternatives cannot do what these nanoparticles can.”

If you have any concerns about heart disease or atherosclerosis, please talk to your GP and check this website.

Nighttime vision of the Australian Night Parrot

NIF Facility Fellow Dr Karine Mardon used CT to scan the intact skull of an exceedingly rare species, the Australian Night Parrot. These scans were compared to related parrots, finding that the night parrot may not be any better at seeing in the dark than other related species. Possibly a contributing factor to its rarity, these findings have implications for Night Parrot conservation efforts in the Australian outback.

Mysterious Australian Night Parrots in natural environment. Credit: Steve Murphy, Charles Darwin University.

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Exploration of the deep foot muscles at ultra-high field

The arches of the human foot are unique structures that are important for functions like walking and running. The deep intrinsic muscles of the foot, such as the adductor halluces and interossei, are thought to play key roles in arch control; yet little is known about how they are controlled during functional tasks. The traditional measurement techniques can only provide information regarding muscle size, which is inadequate to evaluate the force-generating capacity of the muscles, assess the process of force generation by the muscles, and understand the involvement of the neural drive sent by the body to the muscles to regulate force production.

 

Using the 7T human MRI at the Centre for Advanced Imaging, a research study is currently investigating the muscle architecture of the adductor halluces and interossei. This research aims to quantify the force-generating capacities of these deep-foot muscles by measuring their MRI muscle volumes, estimate their force production by shear wave Elastography and measure their neural drive by using Electromyography.

black and white MRI images showing a cross-section of the foot with deep foot muscles outlined in colour

Deep foot muscles outlined in two cross-sections of a structural MRI scan obtained at ultra-high field: abductor halluces (green), abductor digiti minimi (pink), flexor digitorium brevis (magenta), quadrature plantae (cyan) and extensor digitorium brevis (yellow). With thanks to Dr Natalie Collins, University of Queensland

 

MRI images are obtained from male and female volunteers with no lower limb pain or injury. To date, structural MR images of deep foot muscles have been obtained using T1 VIBE 3D Transverse Oblique sequence and MRI muscle volumes have been measured. In future, diffusion tensor imaging will be performed to measure apparent diffusion coefficient and fractional anisotropy of the deep foot muscles.

 

This story was contributed by the University of Queensland, with acknowedgements to Dr Natalie Collins of the School of Health and Rehabilitation Sciences, Health and Behavioural Sciences, University of Queensland.

For further information, please contact Dr Tonima Ali.

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