A novel way to enhance the diagnosis of early stage of colorectal cancer through micro-computed tomography imaging
Lead Research Organisation:
University of Southampton
Department Name: Faculty of Engineering & the Environment
Abstract
Patients with long-term (>8 years) inflammatory bowel disease (IBD) have a 20% lifetime risk of developing colorectal cancer (CRC). Early diagnosis of CRC is essential as it leads to better therapy and survival. Therefore, IBD patients are currently screened by using regular surveillance colonoscopies (camera test) and biopsies (tissue sampling) for diagnosis at a pre-cancerous or early cancer stage. Despite surveillance screening and biochemical tests, advanced cancers are still reported and the value of surveillance program remains controversial. On this account, reliable markers for early diagnosis of CRC are still required for better therapy and increased survival rate.
To this end, we propose a novel way to enhance the early diagnosis of colorectal cancer through micro-computed tomography (microCT):
- AIM 1: We will use a mouse model for inflammatory-induced CRC to image the colon by microCT at different time points of CRC progression. New microstructural markers for early-stage CRC will be derived from microCT data, such as lesion textures. CRC specificity of these microstructural markers will be tested by cross-correlation with co-registered histological sections.
- AIM 2: We will develop a microCT protocol for imaging microstructures of un-contrasted colon tissue, by adapting previous work at UoS on imaging of un-contrasted lung tissue using lab-based microCT. This is aligned with our current Wellcome Pathfinder Award (2016 - 2017), where in collaboration with Nikon Metrology UK, we develop the first microCT system that is fully compatible with existing histopathological workflows.
- AIM 3: As the presence of dysplasia-associated lesion mass (DALM) is highly indicative of underlying or associated CRC, we will recruit IBD patients attending the surveillance screening program with long-term (>8 years) IBD for a small study. MicroCT results from DALM samples, non-DALM, and CRC advanced stage will be validated through proof of diagnosis, already obtained through histology, which will provide evidence for the utility of microCT imaging in CRC diagnosis.
To this end, we propose a novel way to enhance the early diagnosis of colorectal cancer through micro-computed tomography (microCT):
- AIM 1: We will use a mouse model for inflammatory-induced CRC to image the colon by microCT at different time points of CRC progression. New microstructural markers for early-stage CRC will be derived from microCT data, such as lesion textures. CRC specificity of these microstructural markers will be tested by cross-correlation with co-registered histological sections.
- AIM 2: We will develop a microCT protocol for imaging microstructures of un-contrasted colon tissue, by adapting previous work at UoS on imaging of un-contrasted lung tissue using lab-based microCT. This is aligned with our current Wellcome Pathfinder Award (2016 - 2017), where in collaboration with Nikon Metrology UK, we develop the first microCT system that is fully compatible with existing histopathological workflows.
- AIM 3: As the presence of dysplasia-associated lesion mass (DALM) is highly indicative of underlying or associated CRC, we will recruit IBD patients attending the surveillance screening program with long-term (>8 years) IBD for a small study. MicroCT results from DALM samples, non-DALM, and CRC advanced stage will be validated through proof of diagnosis, already obtained through histology, which will provide evidence for the utility of microCT imaging in CRC diagnosis.
People |
ORCID iD |
| Philipp Schneider (Primary Supervisor) | |
| Charalambos Rossides (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509747/1 | 01/10/2016 | 30/09/2021 | |||
| 1831924 | Studentship | EP/N509747/1 | 09/01/2017 | 31/12/2019 | Charalambos Rossides |
| Description | I applied a standard animal murine model that recapitulates the progression of colorectal cancer in humans. I then introduced an alternative way of chemically fixing and embedding the murine samples by preserving their native shape (colonic tube). Employed an advanced imaging technique and research facilities (synchrotron X-ray phase-contrast computed tomography) to create three-dimensional representations of the murine colons. During this process, I distilled down the minimal requirements necessary to perform X-ray phase-contrast imaging in synchrotron and laboratory environments. To study the microstructure of the murine colons I developed a software tool to digitally unrolling them. This innovation allows us to preserve the morphology of the samples, thus obtaining precise morphometric measurements of the colonic crypt shape. During the early stages of colorectal cancer, the colonic crypts undergo a branching process where their topology and dimensions change drastically. Analysing the obtained datasets I was able to quantify these changes in their native form for the first time. |
| Exploitation Route | I developed a complete workflow and the necessary tools that facilitate the study of colorectal cancer in three dimensions (3D). Specifically, I introduced X-ray imaging as a new technique to study 3D tissue deformation in colorectal cancer while keeping the samples in their native shape. This workflow and tools can now be used by biologists to perform animal studies of larger scales. A side outcome of my work is the applicability of the digital unrolling tool in versatile fields. We have already been collaborating with an international group (partners in Australia and the UK) to digitally unroll an ancient lead amulet (scroll) with Mandaic inscriptions. We have also showcased the applicability of this tool not only in biological sciences (the study of colorectal cancer and human placenta) but also in pharmaceutics (drug adhesive films) and industry (flattening of 3D-printed parts with curved geometry). |
| Sectors | Aerospace, Defence and Marine,Education,Healthcare,Manufacturing, including Industrial Biotechology,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology |
| Description | Currently working as an enterprise fellow at µVIS X-ray imaging centre, the University of Southampton, I work with industrial partners to study the microstructure of 3D-printed parts using micro-computed tomography. I have applied my digital unrolling technique to flatted such parts and facilitate non-destructive evaluation/testing for cracks and deposition defects. |
| Sector | Manufacturing, including Industrial Biotechology |
| Title | Murine colorectal cancer diseased sites |
| Description | Exceedingly high resolution (pixel size: 0.33 µm) synchrotron phase contrast X-ray micro computed tomographic data of selected sites from human and murine colons with progressive stages of colorectal cancer. This dataset was created by selecting sites of interest from formalin-fixed and paraffin embedded tissue samples with colorectal cancer in order to create 3D representations of the morphology of the tissue at the sites where disease is developing. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | This dataset allows us to study histological structures in exceedingly high resolution at locations where disease is under development. The image quality is comparable to the current state of the art (histology) in terms of structural representation while in advances the field from the 2D nature of histology to 3D representations of the tissue. |
| Title | Murine colorectal cancer overview |
| Description | Synchrotron phase contrast X-ray micro computed tomographic 3D reconstructions of murine colons fixed in formalin and embedded in paraffin wax. The colons are preserved in their native shape (deformed cylindrical shell) and the scans are such that the entire sample is in the field of view. Thus, they provide an overview of the pathology at progressive stages of colorectal cancer. The dataset spans a range of treatments, time-points and locations of the colon. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | To our knowledge, this is the first time that unstained (no special dyes used) murine colons fixed in formalin have been imaged in 3D with X-rays. This, and the fact that the samples are induced with progressive stages of colorectal cancer, provides an invaluable resource of data that represents the structural changes during the early stage of this disease that is notably the third most lethal cancer worldwide. |
| Description | Mandaic amulet |
| Organisation | Australian Nuclear Science and Technology Organisation |
| Country | Australia |
| Sector | Public |
| PI Contribution | Digital unrolling of an image stack depicting an ancient artefact (lead amulet with Mandaic inscriptions). |
| Collaborator Contribution | Imaged the lead amulet at DINGO neutron imaging beamline at ANSTO and provided the image data. |
| Impact | This collaboration is still active. The Australian collaborators have successfully imaged the artefact (a technically challenging task) using neutron imaging. We have successfully unrolled and retrieved the inscribed text (a similarly challenging task) which is currently being studied/translated by partners at Cambridge University, UK. This is a multi-disciplinary collaboration to decipher the text on an ancient artefact of prospectively high cultural heritage importance. Partners from Australia provide the technical know-how and facilities for non-destructive imaging of the lead artefact (physics, engineering). We provide the expertise of image-processing and digital unrolling of the resulting image stack (computer science, engineering). The collaborators from Cambridge University provide their expertise in linguistics to translate the Mandaic text to English. |
| Start Year | 2019 |
| Description | Mandaic amulet |
| Organisation | Macquarie University |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | Digital unrolling of an image stack depicting an ancient artefact (lead amulet with Mandaic inscriptions). |
| Collaborator Contribution | Imaged the lead amulet at DINGO neutron imaging beamline at ANSTO and provided the image data. |
| Impact | This collaboration is still active. The Australian collaborators have successfully imaged the artefact (a technically challenging task) using neutron imaging. We have successfully unrolled and retrieved the inscribed text (a similarly challenging task) which is currently being studied/translated by partners at Cambridge University, UK. This is a multi-disciplinary collaboration to decipher the text on an ancient artefact of prospectively high cultural heritage importance. Partners from Australia provide the technical know-how and facilities for non-destructive imaging of the lead artefact (physics, engineering). We provide the expertise of image-processing and digital unrolling of the resulting image stack (computer science, engineering). The collaborators from Cambridge University provide their expertise in linguistics to translate the Mandaic text to English. |
| Start Year | 2019 |
| Title | Cyclorama technique |
| Description | Script and graphical user interface used to digitally unroll three-dimensional representations (stack of images) of deformed tubes of non-unifrom thickness. I use this to digitally unroll X-ray micro-computed tomographic scans of murine colons and study their structure. The software is written in Jython and it is tightly linked to ImageJ. |
| Type Of Technology | Software |
| Year Produced | 2019 |
| Impact | This is a crucial tool for my research in the study of colorectal cancer. It can be however useful for digital unrolling of other structures both biomedical and industry-related. We are in the process of publishing the technique, which would then allow us to make the software available for other researchers to use as well. Having developed this tool allowed us to establish an international collaboration (ANSTO, Macquarie University, University of Cambridge) to decipher the text on an ancient lead amulet. |
| Title | Morphometric quantification of branching structures |
| Description | It takes a binary image stack of branching structures such as the colonic crypts and quantifies key topological and morphological characteristics. I use this to quantify the branching crypts in micro-computed tomographic image stacks of murine colons with early-stage colorectal cancer. It can, however, be used for other structures with similar topologies, such as the airways in the lung. |
| Type Of Technology | Software |
| Year Produced | 2020 |
| Impact | It allows us to objectively quantify the morphology of branching crypts in 3D with high accuracy. This has not been done in the past. |
| Description | New forest show 2018 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Part of the crew of the Wessex Medical tent in an outreach activity at the New forest show. We taught the general public, mainly kids, about the role of our immune system against intruding microorganisms. I took this chance to explain how my project tries to understand the structural changes in the colon during colorectal cancer development. I created a model tube of the colon, where kids could see how the gut wall looks like inside-out. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.newforestshow.co.uk/ |
| Description | UoS open days |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | As a representative of the µVIS imaging centre, I engaged with prospective undergraduate students and their parents to showcase the activities undertaken by the centre. About 50 people were reached and provided with a tour and a brief introduction about the centre, helping them to decide whether the university of Southampton was t a good choice for their undergraduate degree. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.southampton.ac.uk/about/visit/open-days.page |