ALCF Concept to Clinic Design Document

Introduction

User story: how to think about this software

Bob is 55 years old. He goes to his family doctor for a routine checkup. The family doctor notes that Bob fits the right diagnostic profile for getting a lung cancer early screening scan. Bob’s doctor schedules him for a low dose computed tomography (LDCT) scan at a teaching hospital down the street. Bob goes to this appointment a few days later where a technician helps him into the computed tomography (CT) machine and then captures imagery of his chest cavity.

Dr. Smith is a chief resident in diagnostic radiology at the hospital where Bob’s scans were taken, and works in a lab that conducts experimental research using new technologies and treatments. She is an experienced and competent professional with years of experience making diagnoses using standard Picture Archiving and Communication System (PACS) software.

Still, like most radiologists she acknowledges that there is an art to detection and diagnosis and that if several other radiologists examined the same CT scans they might all reach slightly different conclusions.

She also knows that computer aided detection (CADe)/computer aided diagnosis (CADx) technology has been advancing rapidly and she’s open to using an easy-to-use tool that will help her do her job more efficiently.

Dr. Smith has just pulled up Bob’s imagery in order to review and interpret the imagery that the CT scanner generated. In front of Dr. Smith are two computers:

  • To the left is her ordinary hospital workstation running a standard PACS software package. This is a system she uses every day, and she is extremely practiced at using this software; ever since starting residency, she has used some similar version of PACS software nearly every day. The PACS software is a highly specialized and fully featured software suite geared towards making it easy for clinicians to explore imagery. For instance, the user can pan around the image, zoom in and out of specific areas, scroll up and down the Z axis through image layers, change image brightness and contrast, and measure lengths between points.
  • To the right is a standalone laptop. The software from this project is running locally on a fresh Linux install, and a browser window is opened on the homepage of the web-based interface service. This computer is trusted and only has intranet access to the DICOM imagery server.

The key question is this: armed with recent developments in artificial intelligence and machine learning, how might we help Dr. Smith catch cancer early and give her patients a better chance of having more time with their families?

Here are some issues in the current PACS diagnosis workflow that Dr. Smith feels could be improved upon:

  • Radiologists don’t want to miss any spots with potentially concerning tissue.The current software is great at presenting imagery but doesn’t adequately help detect nodules.
  • Radiologists worry a lot about false positives because exposing patients to additional CT scan radiation or unnecessary surgical procedures carry risks of their own and can end up being more dangerous than the original nodules. The current software doesn’t adequately help minimize false positives.
  • The more accurately a nodule is measured, the more accurate the diagnosis. Right now, most radiologists just eyeball which slice looks like it has the widest diameter. Then they use the measuring tool to take one horizontal measurement in the direction that looks widest. This method is imprecise and results in a loss of useful information when a complex 3D shape having volume and surface features is reduced to a single estimated width. Additionally, not knowing the precise nodule boundaries also means it’s difficult to quantify whether and how a nodule has changed over time. The absence or presence and characteristics of such change over time is a major cancer indicator for radiologists. So the current software doesn’t adequately help measure nodule boundaries.
  • There is an existing set of best practices for what should be included in a lung cancer screening report (i.e. RSNA Standard Template For Lung Cancer Screening, http://www.radreport.org/template/0000268). Most radiologists haven’t adopted this standard yet, partially because it’s a lot of work and partially because the tools aren’t helpful in filling this out. The current software doesn’t help radiologists organize their thoughts or automatically annotate the records in ways that conform with best practices, so it doesn’t adequately help streamline reporting.

Goals and scope

This application can be thought of as a prototype in the research and development (R&D) phase that is closely focused on building and presenting features that are novel and build or improve upon existing tools for lung cancer CADe/CADx. To borrow terms from “The Lean Startup,” this application will serve as a minimum viable product (MVP) from which we can quickly gather feedback from radiologist users.

A minimum viable product is the “version of a new product which allows a team to collect the maximum amount of validated learning about customers with the least effort” — “The Lean Startup” by Eric Ries, 2014

In this MVP, we are focusing on three core predictive task areas:

  • IDENTIFICATION: Analyze CT scan images to detect and pinpoint the location of concerning nodules from background tissue.
  • CLASSIFICATION: Use what we’ve seen from nodules in the past to predict whether the identified nodules are cancerous or benign.
  • SEGMENTATION: Find the boundaries of nodules and create automatic measures to help radiologists refine and build out the computer-aided diagnosis.

We are also focusing on three ancillary but useful task areas:

  • IMPORTING: Going from DICOM formatted images on disk (or, ideally, available through a server process that mimics the DICOM servers in hospitals) and (1) loading these DICOM images into a data format that is useful for analysis, e.g. Numpy array, and (2) persisting these imported data structures to a central location for access by various services. For the purposes of this project we will simply use the local filesystem to which all processes will have access, but in the future this file abstraction could easily be extended to cover cloud storage or network files.
  • REPORTING: Present what has been found in a concise and clinically useful format that corresponds to identified best practices (such as the RSNA standard template) and evidence based risk diagnosis tools (such as the Lung-RADS™ assessment methodology).
  • EXPORTING: Allow results to be exported in a variety of sensible formats which ideally fit existing standards, align with real world usage, or at least would be easy to repurpose in other applications.

XKCD #927: Standards

Non Goals

For this proof of concept, we only want to spend time on value-added features that advance the core research and development efforts of the project. In order to focus work solely on things that are important, it helps to explicitly outline what’s not in scope for this project.

Here’s one important non-goal: we are not trying to recreate the features of a production PACS system. Millions of dollars and many engineer years have been spent creating commercial off-the-shelf (COTS) software that lets radiologists explore imagery in a fast, native application; PACS is a solved problem that we’re not tackling here.

The goal is also certainly not to create a HIPAA-compliant, cloud-ready SaaS app completely with enterprise-grade security, load balancing, SSL certificates and so forth. In other words, this project’s scope entails running on a local, trusted computer in a research clinic authorized to use non-standard applications. That means the app does not have to be ready to run in a public venue or with complicated security and privacy controls; the reasoning is not that this tool could never be put in production in such a system, it’s just that productionizing an app for privacy, security, user workflow, and so forth are all (1) largely solved problems, (2) highly specific to the application setting, and (3) not relevant to this project’s R&D focus.

So while a limited set of features common to PACS systems or SaaS applications may incidentally need to be built or incorporated if it improves our ability to demonstrate core capabilities, the following features are examples of things that aren’t relevant or do not fit within the scope of this R&D effort unless user feedback indicates otherwise:

  • User authentication, including password resets and transactional emails
  • Role based access control or file access controls
  • Service discovery and sophisticated container orchestration
  • Most types of production-centric optimization like page caching
  • Native or GPU accelerated exploration of CT images

Design goals and architecture

It’s important to remember that the overarching goals is for this project is that the models are (1) useful, and (2) able to be adapted and adopted for use in hospitals with as little modification as possible. By adopting a hypothesis-driven development model and incorporating iterative product releases and validated learning in accordance with the Lean Startup principles, we can achieve our development goals more efficiently and with reduced risk of failure.

Let’s imagine that somebody is creating a plugin that recreates our functionality on an existing COTS PACS system. Our goal is not to replace PACS, just to build on it, so this would be a great outcome. Such an implementation of this prototype would not use this software unmodified — indeed, it would use the existing PACS frontend which is unlikely to be web-based. So even though our interface will demonstrate what is possible, it needs to be loosely coupled to the trained models which are doing the core predictive tasks.

In order to preserve a bright line separation of concerns, we’ll break the overall application down into several constituent pieces. Here’s an extremely high level view of the component hierarchy:

  • The job of the prediction service (via the trained models it wraps) is to implement these core predictive tasks and expose them for use, respectively. The models themselves shouldn’t need to know about the prediction service which in turn should not need to know anything about the interface application.
  • The job of the interface backend (API) is to ferry data back and forth between the client browser and model service, handle web requests, take care of computationally intensive transformations not appropriate for frontend Javascript, and persist user-entered data to a data store. It should not need to know much about the interface frontend, but it’s main job is to relay data for frontend manipulation so it’s acceptable for this part to less abstractly generalizable than the prediction service.
  • The job of the interface frontend (UI) is to demonstrate as much value as possible by exposing functionality that the models make possible in an intuitive and attractive format. Each of these jobs to be done is described in greater detail below.

Here’s a visual representation of this architecture:

Jobs to be done

Imagery selection

Task areas: IMPORTING

Imagery - Prediction service

RESERVED

Imagery - Interface API

  1. List available DICOM images on local filesystem.
  2. Display such details as may be available (e.g. metadata) for any particular DICOM image set on local filesystem.
  3. Return a preview of the DICOM image on local filesystem as an HTML-displayable image.
  4. Allow a specific image to be selected and create a new “Case” to work on for the remainder of the steps.
  5. Items 1-3, but connecting to a DICOM server running in a separate container.

Imagery - Interface frontend

  1. List available DICOM images on local filesystem.
  2. Display such details as may be available (e.g. metadata) for any available DICOM image.
  3. Display a preview of an available DICOM image.
  4. Allow user to select a given image and start a new “Case.” This image will be used in the identification step next.

Detect and select

Task areas: IDENTIFICATION, CLASSIFICATION

Detect - Prediction service

  1. Given a pointer to a DICOM image on the local filesystem, generate a response with an array of predicted nodules (“candidates”). Each candidate in the response should indicate the centroid location tuple (X # voxels from left, Y # voxels from top, Z as slice number), and P(concerning) that each model outputs for each predicted location. Parameters that the request may include are a threshold for minimum P(concerning) to include a candidate in the response, and (2) a specific list of which models to use.
  2. If multiple models are used to make predictions, combine and deconflict the predictions in a useful way. For example, if each of the models comes up with a slightly different set of candidates (which is to be expected), try to figure out if candidates that are close together are duplicates or bona fide separate tissue locations. If this approach has some tunable sensitivity (e.g. tweaking a distance threshold at which candidate sites are assumed to be the same nodule) then look for such a parameter in the model request.
  3. Items 1 and 2, but accept an appropriate URI as the pointer to a DICOM image and implement fetching so that a DICOM server running in a separate container may be used in place of the local filesystem.

Detect - Interface API

  1. Act as the data broker for the image being worked on (selected in our current session), requesting predictions from the Prediction service along with filtering or other passed parameters and relay them back to the frontend.
  2. Provide an endpoint that can receive a payload of all nodule locations, (1) nodule centroid location tuple (X # voxels from left, Y # voxels from top, Z as slice number), (2) whether the nodule was predicted or manually added, and (3) whether the nodule was marked for further analysis or not (those manually identified by the user are presumably concerning). Persist this location list to the database attached to the current Case.

Detect - Interface frontend

  1. List all available predicted candidate sites. Allow each to be selected to view details.
  2. When a candidate is selected, show a detail view in an image viewer control. By default, show the slice containing the predicted centroid and a marker clearly indicating where the predicted centroid occurs.
  3. Allow the user to zoom, pan, and navigate through slices in the image viewer.
  4. Allow the user to window grayscale levels.
  5. Allow the user to toggle the candidate centroid marker’s visibility.
  6. Allow the user to mark any predicted candidate for further analysis.
  7. Allow the user to navigate through the imagery freestyle and mark other locations which the models missed.
  8. When the user has finished marking candidates, send all of this labeled data to the backend in the format specified above.

Annotate

Task areas: CLASSIFICATION, REPORTING

Annotate - Prediction service

RESERVED

Annotate - Interface API

  1. List nodules identified as part of the current Case for detail view.
  2. Receive and persist to the database a radiologist-supplied label for how concerning each nodule actually is.
  3. Receive and persist to the database the other fields expected for each case in the RSNA Radiology Reporting Template for CT Lung Cancer Screening (http://www.radreport.org/template/0000268) — for example, solid/semi-solid/ground glass consistency, left lung/right lung, and any freehand notes they entered in the text box.
  4. Receive and persist to the database the other fields expected for each nodule in the RSNA Radiology Reporting Template for CT Lung Cancer Screening. Namely: a choice between left lung/right lung; a choice between solid, semi-solid, and ground glass; a choice between unchanged/increased/decreased/new; and a field for text entry of notes. These should all be persisted to the database.

Annotate - Interface frontend

  1. Provide UI controls for adding sending general RSNA template notes for the case.
  2. Provide UI controls for selecting a nodule for detail view for a single nodule and display that nodule in a corresponding image viewer.
  3. In the detail view for a single nodule, provide a UI control for specific a user-supplied ground truth label for P(concerning). Also show an indication of what the predicted P(concerning) was for each nodule.
  4. In the detail view, provide UI controls for the nodule specific RSNA template data outlined above.
  5. In the detail view, enrich the image viewer with pan, zoom, and slide traversal for taking a closer look at and around nodules.

Segment

Task areas: SEGMENTATION

Segment - Prediction service

  1. Given a nodule centroid location tuple (X # voxels from left, Y # voxels from top, Z as slice number), return a 3D boolean mask with true values for voxels associated with that nodule and false values for other tissue or voids.

Segment - Interface API

  1. For any given slice of any given nodule, transform the true values in the binary mask from the Prediction service into a series of vertices defining an irregular polygon which can be displayed on the image. In the transformation to vertices, take a precision parameter which causes the transformation to use more or fewer vertices to make the polygon fit the binary mask more precisely.
  2. Given a stack of such irregular polygons, calculate a number of summary statistics of interest, to include: a new estimated centroid location tuple (X # voxels from left, Y # voxels from top, Z as slice number); a volume in cubic millimeters; a longest axial diameter.
  3. Provide an endpoint that allows the current vertices to be persisted to the database attached to the current Case and Nodule.
  4. Provide an endpoint that allows a 3D visualization of each nodule to be provided in a static image format (.png).
  5. Provide an endpoint that allows a 3D visualization of each nodule to be viewed in an interactive format.

Segment - Interface frontend

  1. Display an image view of a given slice of the selected nodule. Allow navigation between slices.
  2. Overlay the current vertices on top of the nodule image to see the predicted boundary.
  3. Allow the user to move existing vertices.
  4. Allow the user to delete existing vertices.
  5. Allow the user to add a new vertex splitting a line segment connecting two vertices.
  6. Allow the user to extend the nodule boundary along the Z axis by extending the currently terminal polygon up or down to the adjacent slice which still has unhighlighted nodule.
  7. Indicate to the user the Z axis extent of slices.

Results

Task areas: REPORTING, EXPORTING

Results - Prediction service

RESERVED

Results - Interface API

  1. Summarize all of the data from the Case, including the general notes, and details for each nodule into a single JSON report.
  2. Allow export of the whole report as an Extensible Markup Language (.xml) file.
  3. Allow export of the whole report as a Portable Document Format (.pdf) file.
  4. Allow export of the whole report as a Microsoft Word document (.docx) file.
  5. Allow export of 3D nodule reconstructions in STL format.
  6. Allow export of 3D nodule reconstructions in SHP format.

Results - Interface frontend

  1. Display all of the results from the case matching the RSNA format in a clean, organized, and hyperlinked report.
  2. Display the results
  3. Provide links to all of the export options in sensible locations throughout the report.