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  • Who are seen in TA? Symptomatic women or women recalled after abnormal screening round Relationship with MDM? MDM is more thorough, complete and includes surgeons. When TA happens, it is always before MDM, and there is no surgeon in TAP. MDM: A meeting where breast surgeons, radiologists, histopathologists and other clinicians discuss the actions to be taken for women referred after TAP or women who have already been treated for a first cancer (40%).
  • (with low-level, not computationally intensive properties)
  • Retrieval

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  • How e-Science may transform healthcare delivery All Hands Meeting, September 2004 Professor Sir Michael Brady FRS FREng Department of Engineering Science Oxford University Founding Director, Mirada Solutions Ltd
  • “ medicine is a humanly impossible task”
    • “ It is now humanly impossible for unaided healthcare professionals to deliver patient care with the efficacy, consistency and safety that the full range of current knowledge could support” http://www.openclinical.org/
    • Exponential growth in knowledge and techniques, eg over past 20 years:
      • New imaging modalities CT, MRI, PET, fMRI, MEG
      • Entirely new drug therapies, particularly for cancer and brain disease
      • Molecular medicine
  • Data flood & information trickle
    • Surge in what information might be mobilised in patient management
    • Rise of PACS and NHS spine
    • Workstations everywhere … and used
    • Doctors are drowning in data
    • They need information to support patient management decisions
  • Staying abreast
    • Doctors are already working to their limits, and beyond, never mind staying abreast
    • Continuing education is vital yet requirements are spotty compared to the USA
  • Concentration of expertise
    • As knowledge becomes deeper and broader, expertise is becoming more widely distributed
    • ‘ Twas ever thus
      • large teaching centres in UK, USA, France, …
      • postcode medicine
    • Trend has accelerated
    • Example: mammography in the USA
  • Population expectations
    • Less and less prepared to accept, without challenge, expert pronouncements
    • Press reports fuel expectation of average treatment that cannot be satisfied by NHS, particularly for a greying population
    • More people expect more, high quality treatment, want to participate in management of their condition, want access to specialised knowledge, and they want it now!
  • Patient management
    • Increasingly a team process
      • Multidimensional meeting
      • Dialogue of the “hard of hearing”
    • The team is increasingly distributed widely
    • The team is increasingly a VO
    • The timescales are shortening
    • While medicine is becoming ever more complex
    Patient management = a highly and increasingly complex example of business-on-demand
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • On-demand epidemiology
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • Drug discovery and image-based clinical trials
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • UK Breast Screening – Today Began in 1988 Women 50-64 Screened Every 3 Years 1 View/Breast Scotland, Wales, Northern Ireland England (8 Regions) 92 Breast Screening Centres Each centre sees 5K-20K images/yr 1.5M - Screened in 2001-02 65,000 - Recalled for Assessment 8,545 – Cancers detected 300 - Lives per year Saved 230 – Radiologists “Double Reading” Film Paper Statistics from NHS Cancer Screening web site
  • UK Breast Screening – Challenges 230 - Radiologists “double Reading” 50% - Workload Increase 2,000,000 - Screened every Year 120,000 - Recalled for Assessment 10,000 - Cancers 1,250 - Lives Saved Women 50-70 Screened Every 3 Years 2 Views/Breast + Demographic Increase Scotland, Wales, Northern Ireland England (8 Regions) 92 Breast Screening Programmes Up to 50K/yr per centre Digital Digital
    • Architecture
      • IBM Hursley, Oxford eScience Centre
    • Acquisition workstation
      • Mirada Solutions
    • Teaching tool for radiologists, radiographers
      • St George’s Hospital
    • Tele-diagnosis
      • Edinburgh Breast Screening Unit, W. of Scotland
    • Algorithm development: data mining
      • Oxford medical vision, Oxford Radcliffe Breast Care Unit, Mirada
    • Epidemiology
      • Guy’s Hospital, London
    • Quality control
      • Oxford Medical Vision Laboratory, Mirada Solutions
    end-user project goals Clinicians want to use the Grid & they profoundly wish to remain ignorant about how it works
  • Functional overview
    • Key functions are:
    • Image acquisition (EDAS)
    • query – by several classes of user
    • Image retrieval – individually or as a collection
    • Diagnostic reports
    • Image processing & data mining
  • Administration Client Authorised personnel at hospital X can create and edit a worklist The images in the worklist can be owned by Hospital Y
  • Viewer Once there is a worklist created at Hospital X, DICOM images owned by Hospital Y can be viewed by an authorised person at Hospital Z, eg for second reading
  • GridView This is a view of the Grid as it would appear to the Grid maintenance centre
  • Data Acquisition Workstation
    • control digitisation of films (or input of directly digital images)
    • facilitate addition of annotations
    • attach annotations to digitised images
    • create/maintain local database
    • serve pro tem as visualisation platform
  • Reporting and Annotation
    • support entry of patient data
    • reports on location and type of lesion
    Reporting varies from centre to centre Several people contribute at different times to the report & have differing levels of authority Several people can access & use the report
    • Virtual image store
      • Each breast care unit maintains its own image store (relational database of patient data & image metadata)
    • Open standards
      • OGSA (Open Grid Services Architecture) GT3
    • OGSA-DAI
      • Data Access & Integration (UK project)
      • Enables data resources such as databases to be incorporated in OGSA
      • OGSA-DAI services represent non-image & image data
      • “ Staging” of data & creation of a worklist
    • IBM’s DB2 & Content Manager
    Architecture
  • Phase 2 – deployed in July 2004 Application Development Methodology ??? Training Services OGSA DAI Data Federation Core Services OGSA DAI Data Load Core API DB2 Content Manager CHU Core Services OGSA DAI Core API DB2 Content Manager UCL Data Load Core Services OGSA DAI Core API DB2 Content Manager UED Data Load Core Services OGSA DAI Core API DB2 Content Manager KCL Data Load Core API Training Application Training API Local Files Database OGSA DAI Core & Training API Core & Training API Core & Training API Core & Training API Training Appl Training Appl Training Appl Training Appl
    • Large data sets
      • Images
      • screening forms as DICOM Structured Report Documents
    • Multimodality
    • Data heterogeneity
    • Multi-view, temporal and bilateral sets
    • Infrastructure support
    • Security
    Data Base: key issues
  • Grid query service architecture
    • Interactions with eDiamond database via web services
      • query using XML documents
        • Ascertain the access rights of a user
        • Passed to OGSA-DAI
        • Returns an XML document (easy to translate)
    • Access attempts are logged correctly
      • Several users can be mapped to a single database account while maintaining traceability
  • DICOM: Digital Imaging and Communications in Medicine DICOM entity relationship diagram Schema to store DICOM data for eDiamond
    • Considerations
      • Ethical & legal
      • NHS network constraints
      • Current & projected IT initiatives
      • Deployment of workflow methods
    • Asset attributes
      • Confidentiality
      • Availability
      • Integrity
    Security modelling
    • human error
    • annotation error
    • software failures
    • IP rights infringed
    • data corruption
    • theft
    • natural disaster
    • hacker
    • DOS attack (eg virus)
    • Unauthorised snoop
    • impersonisation
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • Computer based diagnosis
    • Training sets
    • learn characteristic signs from positive examples (eg cancers)
    • normality from a screening population, from which abnormality = tails of the normal population density function (“novelty”)
    Regions defined by dense attenuation and significant changes in local phase Have associated descriptor of the shape of the region (left, here spiculated) Have associated texture descriptors learned from training set (textons from filter response  hidden MRF (right)
  • Training sets
    • Subtle distinctions need to be learned
    • Images are complex, with poor SNR
    • Need many feature dimensions to guarantee acceptable sensitivity/specificity
    • “ curse of dimensionality”
    • Conclude: need vastly more exemplars for learning than can ever be provided in even the largest centres
  • Can the Grid provide the required power?
    • Screening results in about 6 cancers per 1000 cases
    • A typical centre sees 10,000-15,000 screening cases annually, that is, 60-90 cancers
    • The Grid potentially provides the statistical power at acceptable bandwidth and with guarantees on secure image/data transmission
  • Image data mining: FindOneLikeIt Search features include: boundary, shape, texture inside & outside, … Query image Response 1 Response 2 Response 3 eDiamond federated database
  • Image data mining: FindOneLikeIt Search features include: boundary, shape, texture inside & outside, … Grid-enabled find-one-like-it from the Mirada EDAS
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • VirtualMammo Grid
    • VirtualMammo is a CPD tool for radiographers
      • Distributed in USA by ASRT
      • Recently made freely available for NHS staff by Mirada
    • VirtualMammo models image formation
      • User can experiment with changing tube voltage, exposure time, ...
      • Distributed with a “canned” set of cases
  • VirtualMammo SMF(x,y) = amount of non-fat tissue at (x,y) I(SMF|exp=115mAs) I(SMF|exp=66mAs) Original Image + calibration data GenerateSMF See Caryn Hughes of Mirada Solutions for a demonstration
  • Why VirtualMammo Grid ?
    • Much of medical training resembles apprenticeship
    • Examples are drawn from teacher’s personal experience to illustrate points raised in class
      • a canned set of cases is not enough
    • But most teachers only see a small percentage of the cases of interest ..
    • Need to be able to generate SMF “on demand” perhaps after data mining for suitably annotated images … ie Grid enable it
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • The application domain: breast cancer management DIAGNOSIS Diagnosis is reached after image analysis AND reasoning about image contents and patient data Joint initiative between two major projects in the UK: MI AS (Medical Image analysis) and AKT (Advanced Knowledge Technologies)
  • Ontology for breast cancer Index of key concepts and their relationships with unambiguous machine-readable semantics Based on BI-RADS lexicon for mammography
  • Ontology-mediated annotation Advanced Knowledge Technologies Image Descriptor Region-of-Interest Mammogram Shape Area Margin has-descriptor contains has-descriptor Enrichment of Region of Interests by the computer or by the user graphic-region image-id has-descriptor
  • Browser interface Advanced Knowledge Technologies FIND SIMILAR …
    • Shape: oval, tubular, lobulated, …
    • Margin: circumscribed, obscured, …
    Navigating records using a lattice browser
    • Re-express the annotations using description-logic instances
    • Use them to construct the lattice via Formal Concept Analysis
    • Nest line diagrams with regard to different features
    • Associate individual patient record with nodes on the line diagram
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • Continuous monitoring
    • 20-25% of the population in the Western world suffers from a chronic condition (diabetes, asthma or high blood pressure), yet tele-medicine has had relatively little impact on improving the management of these conditions
    • e-San and the University of Oxford have developed a new solution based on 2.5G mobile phone technology (which allows real-time interactive data transfer) for the self-monitoring and self-management of asthma and diabetes
    Ease of use Intelligent software generates trend analysis and identifies anomalous patterns Clinician alerted and brought into the loop as and when required Server Clinician
  • e-Health
    • e-Health enables monitoring and self- management of chronic conditions such as:
      • diabetes
      • asthma
      • hypertension
    • e-Health relies upon smart signal processing and mobile telecoms
    • Both intervention and control group patients are given a blood glucose meter and a GPRS phone
    The Oxford Diabetes Type 1 clinical trial
    • Blood glucose readings and patient diary (insulin dose, meal and exercise data) are transmitted by the GPRS phone to the remote server
  • What might the Grid offer?
    • Distributed power, bandwidth & security etc
    • Federated database: eDiamond
    • Statistical power
    • New approaches to CPD
    • Distributed intelligence: semantic web
    • Support for continuous monitoring
    • Personalisation
    • Coping with the mobile population
    • Accommodate massive ranges of spatiotemporal scales
    • On-demand epidemiology
    • Drug discovery and image-based clinical trials
  • Personalised diagnosis
    • Diagnosis is often made relative to an exemplar that consitutes “normality” and “normal expected variation”
    • In the case of brain disease, the examplar typically consists of an atlas that is the “average” brain computed from a set of brain images
    • Normality varies from patient to patient
  • Used to create an atlas – the “average” brain, so that differences between this brain and the average can be noted The database of brains may comprise: young/old; male vs female; normal vs (many) diseases; left vs right handed; … Can we dynamically create an atlas that is relevant for this patient? Original Data From 200 Subjects
  • Personalised diagnosis
    • Personalising the atlas
      • “ a 79 year old man who has a history of transient ischaemic attacks”
    • The Grid is crucial because:
      • The data is federated across many sites to provide the necessary statistical power
      • selection of relevant exemplars has to be computed “on demand”
      • The atlas then needs to be computed on the fly from the exemplars
      • To do this, the data needs to be aligned (geometrically and photometrically) and perhaps non-rigidly – a computationally intensive step
  • Oxford University King’s College London (Guy’s Campus) IMPERIAL COLLEGE KING’S COLLEGE LONDON Create atlas Patient scan + instructions Get reference images Personalised Atlas
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  • Major biomedical challenges spatiotemporal scales Cancer CVD Arthritis Degenerative brain disease Medical science Personalised medicine Drug discovery Image-based clinical trials No single group has all the expertise required No single institution has all the expertise required Pace of development  no fixed group of people will have the expertise Dynamic Virtual Organisations are the only effective way to tackle such problems Epidemiology – x10^3 people, years Radiology – 1-10mm, 0.1s-1hour Pathology - 1 μ , in vitro Proteomics Genomics Biochemistry – 1nm, 1 μ s Mathematical models differ at each level, and are hard to relate across levels
  • Acknowledgements and where to look for further information
    • This talk was distilled from the efforts of many scientists, all of whom I thank:
    • The eDiamond team at IBM Hursley (especially Dave Watson, Alan Knox, John Williams); Oxford eScience Centre (especially Andy Simpson, Mark Slaymaker, David Power, Eugenia Politou, Sharon Lloyd); Mirada Solutions Limited (Tom Reading, Dave McCabe, Caryn Hughes, Chris Behrenbruch); UCL & St George’s; Churchill Hospital, Oxford; Edinburgh University & Ardmillan; KCL &Guy’s
    • For VirtualMammo : Mirada Solutions Ltd (Caryn Hughes, Kranti Parekh, Hugh Bettesworth, Ralph Highnam)
    • For semantic web : the MiAKT consortium headed by Professor Nigel Shadbolt (Southampton)
    • For distributed monitoring : Professor Lionel Tarassenko (Oxford) & e-San
    • For personalised diagnosis : the iXi project, especially Professor Derek Hill (KCL, ie UCL)
    • For spatiotemporal analysis : the Integrated Biology group in Oxford led by Dr. David Gavaghan (Oxford)