HIPAA - The Hippocratic Oath for Techies

As technology proliferated into healthcare, especially in the radiological practice, privacy protection once again entered the limelight as new issues concerning electronic data have been raised. In the medical imaging industry alone, which is a small subset of the healthcare sector, IXICO can testify that vast numbers of medical images exist in electronic format for compact storage, easy maintenance and rapid retrieval.

However, the convenience of data access across networks extending far beyond clinical sites or hospitals means that the patient’s personal information is potentially at risk of becoming publicly available. For example, every level of image transfer presents a potential security threat: (i) the images could be accessed by unauthorized parties at the clinical site (confidentiality) (ii) during the image transfer, images could be intercepted and modified (integrity) (iii) the intended receiver of the images might not receive them (authentication).

To meet the demands of rapidly developing technology, the US instituted in 2003 the Health Insurance Portability and Accountability Act (HIPAA) in order to set and enforce the standards for protecting the privacy and security of healthcare data. Indeed, privacy protection in the healthcare sector has always been an important issue. One part of the Hippocratic Oath, penned more than two millennia ago, stated that ‘Whatever I see or hear, professionally or privately, which ought not to be divulged, I will keep secret and tell no one’. HIPAA can be seen as the equivalent of the Hippocratic Oath for anyone dealing with electronic medical data. Non-compliance with HIPAA regulations can have severe consequences, including heavy fines and potential prison time.

Patient privacy is clearly an area of increasing focus for both the healthcare and technology industries. The difficulty for medical practitioners and clinical trial sponsors alike is that compliance with the regulations is difficult to maintain; the regulations are often not clear in their application to new and emerging technologies and individuals are often faced with rather laborious routes to compliance. The goal is to simplify the process as much as possible through automation. Many medical technology companies, including IXICO, are developing tools to help comply with HIPAA regulations through computer-based automation. Promising technologies include data encryption, virtual private networks, data embedding, and audit trails. These tools will undoubtedly improve personal data security and may potentially provide the basis for updating the laws governing the practice of medicine in the modern medical arena.

DICOM – The Industry’s Equivalent of a .pdf File

The word DICOM has a certain buzz about it in the medical imaging community. A substantial part of IXICO’s business revolves around DICOM data analysis. However, despite the large amount of information available in DICOM format, we can testify from experience that it still remains hazy to many. Below is a short description that explains how DICOM came about and its relevance to the imaging community.

DICOM stands for Digital Imaging and Communications in Medicine. It was developed in the 1980s and eventually adopted by the medical imaging community to allow for ease of communication and data transfer. DICOM can be thought of as the medical imaging field’s equivalent of a .pdf file or the lingua franca for imaging systems.

The development of a universal industry standard was imperative as digital imaging began to be widely used. Although the 1980s saw the proliferation of magnetic resonance imaging and computed tomography, both of which allowed for an unparallel level of image detail, the emphasis is now on easy connectivity and seamless communication between different imaging devices to boost efficiency and workflow.

The imaging devices were initially designed as isolated equipment with their unique printing and archiving methods. Equipment vendors were thus free to use their own propriety formats for storing imaging data. An image from one vendor could not be viewed using another’s viewer. Adding to this, it came to the point that the vendors would alter formats such that images from older devices could not be read by newer ones. Slight changes in image formats made it a nightmare for display workstations as they were forced to accommodate each new format.

DICOM was born out of the need to develop an imaging standard that would simplify data transfer and archiving between the many vendors. The DICOM format is now a universal imaging standard that is compatible with different brands, modalities, and models of imaging devices. A DICOM committee of radiologists, imaging equipment manufacturers, and engineers are tasked with periodically producing technical guidelines regarding transfer between devices, archives, printers and display workstations. Major imaging equipment manufacturers are also encouraged to produce DICOM conformance statements for their equipment.

DICOM is now the industry standard for medical images. It has made things easier for devices to communicate, raised awareness for connectivity amongst consumers, immensely enhanced collaboration between manufacturers to improve their products, and had a dramatic impact on clinical workflows.

The Rise of Image Registration

In a typical clinical trial that makes use of imaging, a subject is often scanned multiple times over a period of weeks or months. In-order to get a precise assessment of how well the drug being tested works, you need to detect subtle changes in the patient which might have been caused by the drug. While radiologists are very skilled at detecting abnormalities in images, they are not so good at measuring change precisely. This is especially true if the changes are small, as, for example, in Alzheimer's disease where the brain shrinks by a tiny fraction each year.

The first step in comparing two images is to bring them into spatial alignment, a process referred to as registration. One of the original ways of aligning the images is to simply introduce an external marker attached to the subject such that it is easily detectable in the images. Since the early 1990s, however, computer algorithms that can register the images without using markers have been developed and these are now widely used.

The founders of IXICO, Derek Hill, Jo Hajnal, David Hawkes and Daniel Rueckert, pioneered several image registration techniques in the 1990s, and demonstrated the value of image registration in diagnosis, planning treatment and monitoring disease progression.

Here’s a few words from IXICO’s CEO, Derek Hill:

“Image registration is now such an important sub-field in medical imaging that there are now conferences dedicated to it. Two important branches of image registration are simple alignment of the images to correct for position differences (often called "rigid body") and image registration that tries to exactly map one image onto another by warping (often called "non-rigid"). In rigid-body registration, if you subtract the images after the registration, you can see areas where there has been change that may be due to disease progression or drug treatment. After non-rigid registration, however, the two images look identical and it is important to analyse the valuable information in the warps to get an indication of what has changed.

Image registration is not an end in itself but a means of making more effective use of medical images, especially where precise measurements are needed. Image registration algorithms are now commonly used in many clinical trial areas as a key step in the analysis, such as measuring brain shrinkage (atrophy) and the amount of blood flowing to cancer tumours.

However, image registration can also play a role in the trials well before making measurements, by ensuring the image data is of high quality. IXICO uses image registration algorithms to check that a subject was scanned correctly (in the right place in the scanner, and imaging the correct parts of the body), to ensure that the images with the same subject label are really of the same subject (accidental mislabelling of images is, regrettably, a common feature of clinical trials), and to detect whether scanners have gone out of calibration over time. In these situations, using registration methods on the data as soon as possible after it has been collected can enable potential bad data to be detected and dealt with before it is too late.”

Trial Wire – Organizing DICOM Images in a Disorderly World

IXICO recently made available for free a tool called Trial Wire. This is a tool that is routinely used by us in-house to transfer medical image files between clinical trial sites and IXICO servers. Nearly all medical imaging scanners in hospitals can store and transfer image files as a series of slices, or cross sections, using the industry-standard DICOM format. DICOM stands for digital imaging and communications in medicine. It was adopted by the medical imaging community to allow for ease of communication and data transfer, independent of the manufacturer or type of scanner involved. You can think of DICOM as the medical imaging field’s equivalent of a .pdf file.

The DICOM format is designed for communication of image data between scanners, imaging workstations, and hospital image archive (known as Picture Archival and Communication Systems or PACS). But for research studies and clinical trials, handling of DICOM data can be painful!
Among several clever features of Trial Wire, one that is sometimes overlooked is its ability to organize DICOM files into series of sub-directories. This seemingly trivial feature is in fact very complicated for most DICOM data users.

The problem lies with the imaging systems and equipment that are made by the likes of GE, Siemens, and Philips. When a patient is given an MR or CT scan, say, the imaging system can transmit the images to a computer in either a random or systematic fashion. Although the images are still fully DICOM compliant, the manufacturers do not have a standard way of organizing the data. This can result in several image slices being stored in dozens of sub-directories in what to many users can be a very confusing fashion. To manually structure the images is tedious and time-consuming.

Trial Wire uses an algorithm that is able to specifically tackle this problem. When a directory is specified, Trial Wire searches that particular directory and any sub-directory for any DICOM data. It then automatically imposes a directory structure into one of the three options set by the user:

1. Subject/Study/Series
   In this structure, the data is organized first by subject (which can be de-identified by Trial Wire) then by study name and then by image series. This allows for easy review in a trial-centric manner, meaning that someone interested in retrieving the data can now easily search by subject, study, or series. This approach will generally appeal most to those conducting clinical trials.
2. Flat directory
   In this structure, all the files are copied into one target collection. They are also all renamed to have a unique 8-character filename and a DICOMDIR file is created to describe them. This approach will most often be used by those who want to maintain large volumes of data that can be further organized later according to changing needs.
3. Mirror the original structure
   The original directory structure will be kept. This also means that any name on the files (which may contain personal information) is kept. This approach will most likely be used in a clinical setting where patient data is a necessary part of communication between physicians, such as conferring physicians within a hospital centre.

The organizing feature offered by Trial Wire gives the option to structure its files the way our experts do it here at IXICO or preserve the original structure. This provides the maximum flexibility for end users to organize DICOM data for storage or transfer. And a key benefit is that data from different scanners can all be stored together in a coherent structure to allow for easier sharing and analysis of the data.

What's In a Name?

I thought a good place to start the conversation was to begin by telling you how IXICO’s name came about. Having surveyed a number of our competitor’s websites, I could not help but notice a striking similarity between all of their names, the word ‘imaging’, the prefix ‘bio’ or indeed any clinical related words featured quite heavily. And then of course there is IXICO. To an outsider, like me (I only joined the company two weeks ago), the name did not give the slightest clue as to what the company did. So this is what I found out.

IXICO’s journey started from a scientific project based on the Grid to create the Dynamic Brain Atlas. Derek Hill, founding CEO of IXICO and one of the key scientists behind the project, likened the Grid to a ‘turbocharged internet’. Hospitals typically produce terabytes of imaging data in a year. As image analysis is computationally expensive (a single image analysis can take hours), the Grid project enabled institutions to connect their super-computers together in order to harness their processing power to create a dynamic brain atlas. It allowed a doctor to compare a patient’s brain scan to that of a dynamically created brain atlas showing the normal range of size and shape of brain structures for a person of the same age, gender, and past medical history as the current patient.

At the time, the technology received significant press coverage and this encouraged a follow-up project called IXI, short for Information eXtraction from Imaging. The idea was to use Grid technology to do automated image analysis for drug development, including image registration and segmentation. The objective of IXI was to assess the scalability of the Dynamic Brain Atlas, extend data outside the brain and build an application interface. One application was the automatic delineation of bones. Manual delineation is extremely time consuming and expensive. IXI was able to rapidly identify the structures of inte

rest and extract useful information.

As pharmaceutical companies are keen on controlling the spiralling drug development costs and accelerate time to market, the business idea was to form IXICO and offer image analysis with the in-house developed algorithms and experience amassed from the Grid project.

Today, IXICO is a full-service Imaging CRO that provides comprehensive, technology-based solutions for the pharmaceutical and biotech industries across all therapeutic areas and clinical trials phases. IXICO works within an ISO9001:2000 certified Quality Management System, with the provenance of the data analysis results stored to provide a complete electronic audit trail.

Welcome to IXICO’s Blog

The IXICO blog is not only your source of information on the latest developments at IXICO but also a platform for us to exchange viewpoints on medical imaging for clinical trials.

We’re privileged to have clever, passionate people doing amazing things with medical images, such as measuring volume change in brains, assessing fatty liver disease, quantifying joint inflammation. Our innovative team is also committed to transforming the way that trials are run through technology solutions that are accessible to anyone with an interest in imaging trials.

This blog is designed to share with you some of the insights we’ve gained and to provide a source of information on the latest developments at IXICO. We look forward to hearing your viewpoints and welcome your ideas and feedback!