Centre for Advanced Bioimaging: Technology developments in bio-imaging

An image to demonstrate bio-imaging

With new technologies on the rise, such as computational scatterography and colour-image 3D scanners, the future of medical imaging innovation is heading into an exciting and unknown territory.

The imaging of biological samples, also known as bio-imaging, enables scientists to analyse tissues, cells and molecules without any physical interference. According to the Centre for Advanced Bioimaging (CAB), based in Denmark, bio-imaging can be defined as: ‘Methods that non-invasively visualise biological processes in real time [and…] aims to interfere as little as possible with life processes. Bio-imaging spans the observation of subcellular structures and entire cells over tissues up to entire multicellular organisms. Among others, it uses light, fluorescence, electrons, ultrasound, X-ray, magnetic resonance and positrons as sources for imaging.’

Computational scatterography

Internal body imaging techniques such as X-rays and ultrasounds have previously been limited by their penetration and their safety. Now, a new imaging technology has been developed in partnership with National Science Foundation at the Carnegie Mellon University, USA, which is able to see 10 times deeper than X-rays.

According to an article published on the PRNewswire website, the imaging technology is: “A camera that is able to peek much deeper beneath the skin than current technologies. The new camera combines advanced optics and computation to process light which penetrated the skin but gets scattered by internal body structures. It is believed that this will enable bio-imaging at cellular level, a feat that current technologies cannot match. With conventional bio-imaging, radiographers are only able to see a few millimetres below the skin, which is not sufficient to yield views of organs much deeper in the body.

“This development is based on a technique known as ‘computational scatterography’, which helps to gather light scattered by organs. With conventional imaging techniques, when light passes through an organ, it is scattered and contributes no further in the production of the final image. Using advanced computation, the new technique makes sense of the light by tracing the path of photons before they reach the camera.’ Associate director of this research, Srinivasa Narasimham, added to this and said: “it is possible to view five to ten times deeper using the technology we have developed.”

Overcoming the limits of invasive liver biopsies

The World Journal of Hepatology (WJH) have published a paper on the prospect of digital liver biopsy, written by Mancini and Summers et al. The WJH study investigates the development of ‘a digital biopsy for in vivo study of liver pathophysiology.’ Traditionally, invasive liver biopsies have limitations: ‘The liver biopsy specimen provides a random sampling of just 1/150000th of the liver, and as such is subject to considerable sampling errors in cases with an inhomogeneous distribution of the pathologic lesion.

‘Moreover, it is obtained by an invasive procedure, unsuitable for the repeated sampling necessary to follow the in vivo dynamics of many physiopathologic mechanisms. In addition, in the process of fixation and staining, the melting of intracellular fat results in artifactual ghost droplets. In short, histology provides a dead, isolated frame from a living film that runs throughout the liver, and this has deeply limited the advancement of knowledge regarding the physiopathology of fatty liver.’

However, the growth of functional, molecular and structural bio-imaging has led to the development of a new type of liver biopsy which will be beneficial in the treatment of diseases such as non-alcoholic fatty liver disease (NAFLD). According to the WJH study: ‘Modern biomedical imaging techniques offer an attractive non-invasive option for the in vivo study of liver physiopathology and have the capacity to provide detailed anatomical and biochemical information on the whole organ, thereby overcoming the limit of sampling error.’

‘Digital biopsies for NAFLD,’ the study adds, ‘need to be fast and easy to obtain, and consistent among operators, technologies and methods, and most importantly provide clinically relevant results. To arrive at this level, there is a need for research, development, and extensive collaboration. A number of imaging techniques are already available for [the] evaluation of fibrosis and steatosis. Wider adoption of these techniques and continued work to overcome their limitations can provide the basis for multi-centric collaboration on the optimization of imaging for fatty liver.

‘No individual centre has the breadth and depth of patients to go it alone in establishing a validated digital liver biopsy. Collaboration on imaging technique adoption should be performed in combination with establishing a cross-centre imaging biobank linked to associated conventional biobanks. An open need lays in the attraction of expertise and interest to carry out radiomics and radiogenomic studies and this follows the generation of data and the establishment of the bio-repository resources described above. Only at this point we will see the fruits of the labour, in terms of possible imaging biomarker signatures and associations with clinical and biological endpoints. Prospective studies should then compare the results obtained using images acquired at different points in time by multiple technicians, and read by both radiologists and trained non-radiologists. The next step is studying and comparing quantitative image features to unravel the relationships between the digital biopsy features and histopathologic, metabolic and genetic characteristics and building models which link them to the disease outcomes.”

Colour-image 3D scanner

As new technologies in the bio-imaging industry continue to evolve, researchers in New Zealand are developing 3D scanning technology which could potentially have a significant impact on healthcare in the future. Here, researchers that are part of the ‘MARS programme’ joint initiative are developing a spectral molecular scanner that is capable of producing colour images of objects that are inside of the body; such as soft tissues and bones. Professor Anthony Butler, who is a part of the research team, told the New Zealand website www.nzherald.co.nz that: “This spectral molecular imaging technology really is the next big medical imaging innovation, and these 3D images will provide clinicians with information that is currently not possible in CT, MRI or PET scans. The capability of this scanner will enable greater diagnosis and monitoring of many diseases and will lead to better outcomes for patients – particularly in stroke prevention, joint replacement and cancer management.”

While in some respects this is similar to X-ray-based CT systems, the new 3D scanner being developed by the MARS programme differs from standard systems as it is said to feature improved spatial resolution as well as colour imaging. The new scanner works by using two Medpix3 detectors that are bonded to high-Z sensors at 110micron pitch with eight energy bins per pixel and two ms frame readout. The two fundamental materials that make up a sample, density and atomic variation, are then able to be distinguished; the density determines the images brightness and the atomic structure determines the colour.

Arguably, this scanner offers high-resolution scans faster than traditional systems, resulting in its possibilities to change surgical procedures and medical diagnostics.
To conclude, bio-imaging already offers an alternative to traditional invasive techniques, such as X-rays and ultrasounds. Today, this field continues to grow and develop in finding new ways to further the penetration and effectiveness of bio-imaging. With new technologies on the rise, such as computational scatterography and colour-image 3D scanners, the future of medical imaging innovation is heading into an exciting and unknown territory.

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