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.

High-Resolution MRI for Exposing Cancer Spread in the Brain

Sunny Queensland has a high rate of skin cancer, with melanoma as the second most common cancer in Queenslanders. In the area of the head and neck, this can lead to invasion of facial nerves and spread via the base of the skull to reach the brain stem. The extent of the progression, the so-called perineural spread, defines the therapeutic approach, informing the extent of required resection, and the complexity and duration of the surgical procedure. Imaging the extent of nerve involvement is critical to guiding treatment decisions and MRI neurography is the accepted imaging modality of choice.

Standard MRI may underestimate disease extent, but a current clinical trial explores the improved resolution and sensitivity using the 7 Tesla ultra-high field MRI scanner at the Centre for Advance Imaging at UQ. This improves visualisation of cranial nerves (see Figure and insert with zoomed nerve fibres) and potentially improves the definition of the perineural spread. The clinical trial is led by Dr. Sommerville from the Royal Brisbane and Women’s Hospital, QLD, and involves a Brisbane-based multidisciplinary team of head and neck surgeons, radiologists and scientists in the UHF MR Research team (Head: Dr. Barth, NIF Fellows Dr. Bollmann and Dr. Ali) at the UQ Centre for Advanced Imaging. The first patient scan has been performed, with 20 patients more to follow after a successful funding application sponsored by the 2018 round of the RBWH Diamond Care Grants.

 

MRI images showing a slice of brain with perineural cancer spread. The images highlight a region which is blurry in 3T and well defined in 7T.

 

If you would like to know more about skin cancer, please check the Cancer Council website and speak to your GP.

 

This story was contributed by the University of Queensland. For further information, contact Dr Tonima Ali.

The First Australian Multi-Centre Study of Dementia using Ultra-High Field MRI

Australia is at the forefront of dementia research with world leading studies such as the Australian Imaging and Lifestyle study of Ageing (AIBL) led by a consortium of Australia’s leading Dementia centres, and the recently started Prospective Study of Ageing (PISA) led by the QIMR Berghofer.

The installation of the first human ultra-high field MRI scanner in the southern hemisphere at the Centre for Advance Imaging, the Qld node of the National Imaging Facility, in 2014 opened up a new era of imaging research. The Siemens 7T whole-body MRI scanner brought Australia to the forefront of ultra-high field research enabling examination of the human brain with an unprecedented level of detail.

Subsequently, a second 7T scanner was installed at the Melbourne Brain Centre providing a unique opportunity for a national multi-centre collaboration in ultra-high field MRI and the capability to explore new imaging biomarkers for diagnosis of neurodegenerative disease. A major project is underway, led by the Brisbane-based CSIRO eHealth Research Centre, co-funded by the CRC for Mental Health and in collaboration with the QIMR Berghofer, University of Melbourne and Florey Institute for Neuroscience with the broad aim of characterising new bioimaging biomarkers of neurodegeneration in the aging population. A suite of MRI methods is being applied at both sites on large cohorts of healthy aging subjects and patients diagnosed with fronto-temporal dementia. The scanning part of the project has been successfully completed with superb image quality obtained using state of the art sequences. A significant effort is now underway to analyse this valuable data which may contain a wealth of diagnostic information not otherwise available.

 

This story was contributed by The University of Queensland

Feature image: (Left) 3D MP2RAGE 0.9mm isotropic showing exceptional tissue contrast, (centre) example of a Quantitative Susceptibility Mapping (QSM), a mechanism for useful chemical identification and quantification of specific biomarkers, and (right) T2W TSE using coronal accquisition for hippocampus subfield examination. 

National Network of Trusted Data Repositories

During 2017 the National Imaging Facility (NIF) nodes at the University of Western Australia (UWA), University of Queensland (UQ), University of New South Wales (UNSW) and Monash University collaborated on a national project to enhance the quality, durability and reliability of data generated by NIF through the Trusted Data Repository project.

●        Quality pertains to a NIF user’s expectation that an animal, plant or material can be scanned and from that data reliable outcomes/characterisations can be obtained (e.g. signal, volume, morphology) over time and across NIF sites.

●        Durability refers to guaranteed long-term availability of the data.

●        Reliability means that the data is useful for future researchers, i.e. stored in one or more open data formats and with sufficient evidential metadata.

The Project, Delivering durable, reliable, high-quality image data, was jointly funded by the Australian National Data Service (ANDS) and Research Data Services (RDS). It was motivated both by NIF’s desire to enhance the quality of the data associated with the use of its facilities, and the desire of ANDS/RDS to facilitate the establishment of Trusted Data Repositories that enable access to data for at least 10 years and includes metadata that documents both the quality of the data and its provenance.

A trusted data repository service is essential for sharing data and ensures that project data created and used by researchers is “managed, curated, and archived in such a way to preserve the initial investment in collecting them” and that the data “remain useful and meaningful into the future” (https://www.coretrustseal.org).

The scope of the Project was limited to MRI data with the understanding that the developed requirements and trusted data repository services could be adapted to, or serve as a basis for other instruments/modalities.

The key outcomes from the Project include:

  1. The NIF agreed process for acquiring trusted data (NAP) – Lists the requirements that must be satisfied to obtain high-quality data, i.e. NIF-certified data, suitable for ingestion in a NIF trusted data repository service. They cover provisioning of a unique instrument identifier, instrument registration with Research Data Australia (https://researchdata.ands.org.au), quality control (QC), quality assurance measures, requisite metadata (including cross-reference to the QC data),  the process by which data is moved from the instrument to the digital repository service and the format(s) of the data.
  2. The NIF requirements for a trusted data repository service – Provides a platform-agnostic checklist of requirements that a basic NIF trusted data repository service should satisfy, including: identification of data by a unique Project identifier, ingestion of data from NIF-compliant instruments, authentication via the Australian Access Federation (https://aaf.edu.au), interoperability and easy deployment across NIF nodes.
  3. Implementations of trusted data repository services for two exemplars:
    1. Preclinical MRI data (with mouse brain data as an example) acquired across three NIF nodes—UNSW, UQ and UWA—using a Bruker BioSpec 9.4T MRI. The services have been implemented using the open source MyTardis/ImageTrove (https://www.mytardis.org) platform.
    2. Clinical ataxia MRI data acquired using a Siemens Skyra 3T MRI scanner in support of a Monash-proposed International Ataxia Imaging Repository (IAIR). The service has been Implemented using the open source XNAT (https://www.xnat.org) platform.

Software developed to support the implementation of the repository services includes: Docker (https://www.docker.com) Compose scripts to permit easy deployment at differents sites, client-side scripts for uploading NIF-certified data to ImageTrove/MyTardis and an XNAT plugin for uploading non-DICOM files.

  1. Assessments of the resulting trusted data repository services against a relevant international metric, the CoreTrustSeal (https://www.coretrustseal.org) Core Trustworthy Data Repositories Requirements.

For NIF users and the broader imaging research community the benefits and impact of this Project include:

  • Reliable and durable access to data
  • Improved reliability of research outputs and the provenance associated with it
  • Making NIF data more FAIR (Findable, Accessible, Interoperable, Reusable – https://www.ands.org.au/working-with-data/the-fair-data-principles)
  • Easier linkages between publications and data
  • Stronger research partnerships

For research institutions they include:

  • Enhanced reputation management
  • A means by which to comply with the Australian Code for the Responsible Conduct of Research
  • Enhanced ability to engage in multi-centre imaging research projects

For NIF they include

  • Improved data quality
  • Improved international reputation
  • The ability to run multi-centre trials

The transition plan post-funding includes: maintenance of existing services for 10 years; the integration of additional instruments; creation of a project web portal; planned new national and international service deployments; refinements and improvements; and CoreTrustSeal certification.

Project documents have been archived in the NIF Customer Relationship Management (CRM) system (accessible by NIF staff). Project software is hosted on GitHub and is freely available for download here: https://github.com/NIF-au/TDR. For further information please contact either the national Project Manager or NIF.

Project Manager and UWA lead: Andrew Mehnert (NIF Informatics Fellow, Centre for Microscopy, Characterisation and Analysis).
NIF lead – Graham Galloway (Chief Executive Officer, NIF)
UQ lead – Andrew Janke (NIF Informatics Fellow, Centre for Advanced Imaging)
UNSW lead – Marco Gruwel (Senior Research Associate, Mark Wainwright Analytical Centre)
Monash lead – Wojtek Goscinski (Associate Director, Monash eResearch Centre)

New diagnostic strategies to determine cardiovascular risk

Despite significant advances in diagnostic and therapeutic technologies, cardiovascular disease (CVD) remains the global leading cause of death, accounting for 17.3 million deaths per year, and is expected to grow to more than 23.6 million by 2030. Currently, the prevention of MI and stroke is limited due to the lack of sensitive imaging methods. Those available usually involve invasive procedures such as coronary angiograms, which are potentially associated with complications, including death caused by MI or bleeding. Hence, there is a great need for new diagnostic strategies to determine whether the individual patient is at risk of MI or stroke, which then would allow for effective and early preventative treatment and improved clinical outcome.

This project is a multicentre collaboration led by the University of Queensland (UQ), Australian Institute for Bioengineering and Nanotechnology (AIBN), including the Queensland nodes of the National Imaging Facility and Australian National Fabrication Facility, Monash University, Baker IDI Heart and Diabetes Institute and the SooChow University. Together this project developed novel molecular imaging nanoparticles to enhance for MRI detection of activated platelets which is associated with unstable vulnerable atherosclerotic plaques.

 

A complete description of the project, including the particles and imaging methods, is available via the a publication in Biomaterials journal.

 

The uncovered toxins in Fang Blenny fish venom could pave the way for new medications

The UQ Node of the National Imaging facility has recently helped a scientific breakthrough in the field of venom research. The 3D image of a fang blenny reef fish was produced at the Centre for Advanced Imaging using the Siemens micro CT scanner. It was part of an international study led by Professor Bryan Fry from UQ school of Biological sciences involving,  Leiden University in Netherlands, Liverpool School of Tropical Medicine in UK, Monash University and the University of Queensland in Australia. The study was recently published in Current Biology. 

The team of scientists confirm that one group of fang blenny have venom glands that contain enkephalins, an opioid hormone that works by targeting the same molecules as synthetic opioid painkillers. According to Fry, the venoms of these species may serve as a novel source of painkillers. Currently prescribed opioids have led to an epidemic of addiction, so doctors and scientists are keen to find alternatives.

You can find more about this discovery through the following online articles by New Scientists, BBC, Science, National Public Radio (NPR), New York Times, and more!

Discover Magazine

The Atlantic

Science Magazine

New Scientist

Wired

Gizmodo

BBC

New York Times

 

Collaborators: Liverpool School of Tropical Medicine, UK; Leiden University, The Netherlands; The University of Queensland, Australia; Monash University, Australia; University of Karachi, Pakistan; Leiden University Medical Centre, The Netherlands; Bangor University, UK; Anglia Ruskin University, UK

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