Development of Non-invasive Advanced Diffusion Magnetic Resonance Imaging Methods for in vivo tissue microstructure profiling
Lead Research Organisation:
University of Aberdeen
Department Name: Institute of Medical Sciences
Abstract
The proposed research aims to develop a novel, non-invasive, quantitative method for measuring tissue cellular dimensions and packing density in humans based on magnetic resonance imaging (MRI). Tissue microstructure can be probed using diffusion MRI, where the Brownian motion of water and its interaction with the cellular boundaries are characterised.
In the project, the student will develop rapid q-space imaging method and validate the developed technique through multidisciplinary approaches. The proposed work is divided into three phases:
(1) basic sequence development of QSI, where the QSI sequence will be implemented on a research dedicated 3T whole body human scanner hosted at the Aberdeen Biomedical Imaging Centre and basic acquisition parameters established; Validation will be performed on phantom, porcine specimen and young healthy volunteers.
(2) optimisation of QSI, during which the QSI acquisition strategies will be examined with the assistance of numerical simulation to reduce scan time, so that a data reduction strategy can be devised. Validation will be carried out in phantom, as well as in healthy young volunteers against biopsy results.
(3) sequence integration and application trial, where QSI with data reduction strategy will be assembled. Validation will be carried out on phantom and young healthy volunteers.
During this project, the student will receive research training in a range of biomedical areas. The student will be trained to perform MRI pulse sequence programming, a specialised skill. The student will conduct extensive numerical simulation and computer programming, a high value transferable skill. Above all, the knowledge acquired on advanced diffusion MRI is probably of the highest value in enhancing employability, since there is a global shortage of MRI physicists and advanced diffusion is one of the main areas on which faculty positions are generated. The student will also be a member of ABIC, and undertake our postgraduate generic training, including writing skills, journal club, method club and regularly presenting at lab meetings. We will encourage the student to undertake an industrial internship, and our industrial partner, Philips has expressed enthusiasm in relation to this.
In the project, the student will develop rapid q-space imaging method and validate the developed technique through multidisciplinary approaches. The proposed work is divided into three phases:
(1) basic sequence development of QSI, where the QSI sequence will be implemented on a research dedicated 3T whole body human scanner hosted at the Aberdeen Biomedical Imaging Centre and basic acquisition parameters established; Validation will be performed on phantom, porcine specimen and young healthy volunteers.
(2) optimisation of QSI, during which the QSI acquisition strategies will be examined with the assistance of numerical simulation to reduce scan time, so that a data reduction strategy can be devised. Validation will be carried out in phantom, as well as in healthy young volunteers against biopsy results.
(3) sequence integration and application trial, where QSI with data reduction strategy will be assembled. Validation will be carried out on phantom and young healthy volunteers.
During this project, the student will receive research training in a range of biomedical areas. The student will be trained to perform MRI pulse sequence programming, a specialised skill. The student will conduct extensive numerical simulation and computer programming, a high value transferable skill. Above all, the knowledge acquired on advanced diffusion MRI is probably of the highest value in enhancing employability, since there is a global shortage of MRI physicists and advanced diffusion is one of the main areas on which faculty positions are generated. The student will also be a member of ABIC, and undertake our postgraduate generic training, including writing skills, journal club, method club and regularly presenting at lab meetings. We will encourage the student to undertake an industrial internship, and our industrial partner, Philips has expressed enthusiasm in relation to this.
People |
ORCID iD |
| Jiabao He (Primary Supervisor) | |
| David Lurie (Primary Supervisor) |
Publications
Cheung SM
(2019)
Metabolic and Structural Skeletal Muscle Health in Systemic Lupus Erythematosus-Related Fatigue: A Multimodal Magnetic Resonance Imaging Study.
in Arthritis care & research
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M010996/1 | 01/10/2015 | 31/03/2024 | |||
| 1654748 | Studentship | BB/M010996/1 | 01/10/2015 | 30/09/2019 |
| Description | The studentship has been completed. An advanced diffusion magnetic resonance imaging (MRI) technique (Q-space imaging) has been developed for probing tissue structural information in breast tumours, implementing the method on a human scanner system (objective 1). An ex vivo study has been completed (objective 2) to compare imaging measurements of tissue structure against measurements from existing imaging techniques and microscopy assessment of breast tumour cellularity (cell density). In addition, the repeatability of the method has been determined. The dependence of outcome measures on signal-to-noise ratio has been determined by simulation. The Q-space imaging analysis approach has been developed to extract the entropy and dispersion of cellularity in breast tumours, as key features of tumour heterogeneity. This studentship research has also developed a slide scanning microscopy analysis method to determine heterogeneity in tumour cellularity, to compare diffusion imaging measurements to underlying tissue structure. Intratumour heterogeneity obtained from diffusion imaging measurements were correlated to the underlying heterogeneity of tumour cellularity, for which the developed Q-space imaging technique had an increased measurement range compared to other diffusion imaging techniques. The knowledge and findings generated from this ex vivo research has informed development of the imaging technique for in vivo investigation of breast tumours, with a longitudinal study imaging patients with breast cancer to be completed during the studentship to assess the Q-space imaging technique for tissue structure measurements as an in vivo histology method (objective 3). |
| Exploitation Route | The findings of this research will inform investigation of different disease mechanisms using the developed imaging technique. The imaging technique will be investigated as an in vivo histology method, to measure structural information from biological tissue. The imaging technique may be developed further in industry for clinical system applications. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | This research has the aimed to develop diffusion magnetic resonance imaging (MRI) methods applicable to human scanner, for investigation of tissue structural changes resulting from disease. An advanced diffusion method has been developed for human scanner imaging of whole breast tumours, with an ex vivo study completed. This study has informed the translation of the diffusion technique for in vivo imaging of patients with breast cancer, for which a longitudinal study has been undertaken as part of this studentship. The aim of the longitudinal study is to investigate the value of the imaging technique for probing tumour tissue cellular changes resulting from treatment, as an in vivo histology imaging method. This research has the aim to ultimately inform healthcare and drug trial research through developing imaging methods sensitive to tissue structural changes and furthering understanding of disease mechanisms. |
| First Year Of Impact | 2018 |
| Sector | Healthcare |
| Impact Types | Societal |
| Description | MSc Course Update |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The MSC in Biomedical Physics and Biomedical Imaging were updated to follow the new development in the methodology. |
| Description | Endowment Research Grant 2015 |
| Amount | £11,802 (GBP) |
| Funding ID | 15/1/052 |
| Organisation | NHS Grampian |
| Department | NHS Grampian Endowment Fund |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 07/2016 |
| Description | Endowment Research Grant 2017 |
| Amount | £11,501 (GBP) |
| Funding ID | 16/11/047 |
| Organisation | NHS Grampian |
| Department | NHS Grampian Endowment Fund |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 03/2018 |
| Description | Friends of Anchor Research Grant 2017 |
| Amount | £9,744 (GBP) |
| Funding ID | 17 004 |
| Organisation | Friends of ANCHOR |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2017 |
| End | 08/2018 |
| Description | Is lipid composition mapping using magnetic resonance imaging an effective early detection tool for breast cancer in high risk populations? |
| Amount | £72,085 (GBP) |
| Funding ID | C68628/A28312 |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 11/2020 |
| Description | Tenovus Scotland Research Grant 2017 |
| Amount | £12,064 (GBP) |
| Funding ID | G16.09 |
| Organisation | Tenovus Cancer Care |
| Department | Tenovus Scotland |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 08/2018 |
| Title | Non-invasive Histology of Heterogeneity in Cellularity in Breast Cancer using Q-Space Imaging |
| Description | We demonstrated that q-space imaging (QSI) provides higher effect gradient than existing diffusion imaging methods with high fidelity to the historical heterogeneity of cellularity in breast cancer. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | We are currently conducting clinical trial of q-space imaging (QSI) in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), so that the translation into clinical practice becomes feasible. |
| Description | Preclinical Imaging |
| Organisation | Francis Crick Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My group obtained the experimental cost for clinical imaging, obtained NHS ethics and R&D approval, drafted collaboration agreement and Material Transfer Agreement (MTA) in line with the Human Tissue Authority (HTA). We further conducted patient recruitment, performed surgery, and collected surplus tumour tissues after routine histology. We arranged tissue transportation and developed protocol for preclinical imaging, as well as conducted image analysis. |
| Collaborator Contribution | The Francis Crick Institute provided access to preclinical facility and 3D histology, in-kind support for preclinical data acquisition, as well as the expertise for acquiring the data. |
| Impact | N. Senn, Y. Masannat, E. Husain, B. Siow, S. D. Heys, J. He. Q-space imaging yields a higher effect gradient to assess cellularity than conventional diffusion weighted imaging methods at 3T: A pilot study using freshly excised whole breast tumors. Radiology: Imaging Cancer. 2019 Sept; 1(1): 190008 Disciplines: Biology, Physics, Surgery, Histology, Engineering, Computer Science |
| Start Year | 2018 |
| Title | Q-Space Imaging for Breast Cancer |
| Description | We have demonstrated that q-space imaging (QSI) provides higher effect gradient compared to existing diffusion imaging, and has high fidelity to histological heterogeneity of cellularity in breast cancer. We have recently completed data acquisition of this clinical trial to examine the ability yfo QSI as a non-invasive histological approach for early sensitivity to neoadjuvant chemotherapy (NACT) response. |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2019 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | The q-space imaging (QSI) will provide early sensitivity to neoadjuvant chemotherapy (NACT) response, reducing the exposure of non-responding patients from drug toxicity and delayed surgery while reducing high healthcare cost with better targetting. |
| URL | https://clinicaltrials.gov/show/NCT03501394 |
| Description | Breast Unit Interdisciplinary Meetings |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | The studentship research has been presented at three interdisciplinary breast unit meetings at the NHS Aberdeen Royal Infirmary, informing medical practitioners of the research conducted locally. This also provides the avenue for interdisciplinary discussion of the current research being conducted in relation to medical applications. The studentship research will continue to be presented an these meetings. |
| Year(s) Of Engagement Activity | 2016,2017,2018 |
| Description | Interactive Poster Display at BCISMRM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | K.-S. Chan, S. M. Cheung, N. Senn, Y. Masannat, E. Husain, S. D. Heys, J. He. Lipid composition mapping in whole breast tumour. BCISMRM (Sheffield, UK) 2019. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Interactive Poster Display at EBCSS |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | S. M. Cheung, K. S. Chan, N. Senn, Y. Masannat, E. Husain, S. D. Heys, J. He. Lipid composition mapping in whole breast tumour using chemical shift encoded imaging. EBCSS (Edinburgh, UK) 2020. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interactive Poster Display at EBCSS |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, Y. Masannat, E. Husain, B. S. Siow, S. D. Heys, J. He. q-space imaging is more sensitive to breast tumour cellularity than conventional diffusion- weighted imaging methods at 3T. EBCSS (Edinburgh, UK) 2020 |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interactive Poster Display at ISMRM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, Y. Masannat, E. Husain, B. S. Siow, S. D. Heys, J. He. q-space imaging is more sensitive to breast tumour cellularity than conventional diffusion- weighted imaging methods at 3T. ISMRM (Sydney, Australia) 2020 |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interactive Poster Display at ISMRM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, E. Husain, Y. Masannat, S. M. Cheung, B. S. Siow, S. D. Heys, J. He. Heterogeneity of cellularity in breast cancer from diffusion q-space MRI. ISMRM (Sydney, Australia) 2020. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interactive Poster Display at ISMRM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | S. M. Cheung, K. S. Chan, N. Senn, Y. Masannat, E. Husain, S. D. Heys, J. He. Lipid composition mapping in whole breast tumour using chemical shift encoded imaging. ISMRM (Sydney, Australia) 2020. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interactive Poster Display at the NHS Grampian Research and Development Annual Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Supporters |
| Results and Impact | Research findings were presented to local NHS practitioners, local researchers and patient groups. Poster was presented, answering questions interactively. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Interactive Poster Display at the University of Aberdeen Cancer Rally Show |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | The University of Aberdeen hosted the Cancer Rally Show event, for which the research team produced an interactive display of posters, electronic posters and table items to showcase the research undertaken to investigate breast cancer imaging techniques. The research undertaken was disseminated through interactive discussions with the public and patient groups. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Interactive display: Friends of Anchor 20th anniversary celebration |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | The local charity Friends of ANCHOR held a 20th Anniversary celebration event to showcase the research being undertaken and supported. The research team constructed an interactive table display to showcase the research we undertake to investigate breast cancer. As an interactive display the patients / general public at the event were able to inform the discussion of what research is being undertaken locally. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Proffered Talk of Scientific Abstract at British Chapter - ISMRM 2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Scientific abstract talk was presented at the British Chapter ISMRM to research scientists, representatives from industry and professional practitioners. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ismrm.org.uk |
| Description | Proffered Talk of Scientific Abstract at European Conference - ESMRMB 2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Scientific abstract talk was presented at the European Society of Magnetic Resonance in Medicine and Biology (ESMRMB) to research scientists, representatives from industry and professional practitioners. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.esmrmb.org |
| Description | Proffered talk of Scientific Abstract at ISMRM 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Scientific abstract talk was presented at the ISMRM (Paris 2018) to research scientists, representatives from industry and professional practitioners. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Proffered talk of Scientific Abstract at Scottish Imaging Conference - SINAPSE 2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Scientific abstract talk was presented at the Scottish Imaging Network 2017 conference (SINAPSE) to research scientists, representatives from industry and professional practitioners. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.sinapse.ac.uk |
| Description | Talk at BCISMRM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, Y. Masannat, E. Husain, B. Siow, S. D. Heys, J. He. Q-space imaging is more sensitive to breast tumour skewness than conventional diffusion MRI. BCISMRM (Sheffield, UK) 2019. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk at ESMRMB |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, Y. Masannat, E. Husain, B. Siow, S. D. Heys, J. He. Q-space imaging is more sensitive to breast tumour heterogeneity than conventional diffusion MRI. ESMRMB (Rotterdam, Netherlands) 2019. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk at SINAPSE |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | N. Senn, Y. Masannat, E. Husain, B. Siow, S. D. Heys, J. He. Multiparametric q-space imaging provides sensitive assessment of complex breast tumour heterogeneity. SINAPSE (Dundee, UK) 2019 |
| Year(s) Of Engagement Activity | 2019 |