Eldon D. Lehmann

Computer-aided interpretation of SPECT images of the brain using an MRI-derived 3D neuro-anatomical atlas

Nuclear medicine images have comparatively poor spatial resolution, making it difficult to relate the functional information which they contain to precise anatomical structures. A 3D neuro-anatomical atlas has been generated from the MRI data set of a normal, healthy volunteer to assist in the interpretation of nuclear medicine scans of the brain. Region growing and edge-detection techniques were used to semi-automatically segment the data set into the major tissue types within the brain. The atlas was then labelled interactively by marking points on each 2D slice. Anatomical structures useful in the interpretation of SPECT images were labelled. Additional, more detailed information corresponding to these structures is provided via an interactive index which allows access to images, diagrams and explanations. Registration of patient SPECT studies with the atlas is accomplished by using the position of the skull vertex and four external fiducial markers attached to the skin surface. The 3D coordinates determined from these points are used to calculate the transformation required to rotate, scale and translate the SPECT data, in 3D, to match the atlas. Corresponding 2D slices from the two 3D data sets are then displayed side-by-side on a computer screen. A cursor linking the two images allows the delineation of regions of interest (ROIs) in the SPECT scan based on anatomical structures identified from the atlas. Conversely regions of abnormal isotope distribution in the SPECT image can be localized by reference to corresponding structures in the atlas.

Preliminary Work on the Interpretation of SPECT Images with the Aid of Registered MR Images and an MR Derived 3D Neuro-anatomical Atlas

This paper describes two methods to aid interpretation and quantification of SPECT or PET images. In the first method 3D SPECT or PET data sets are aligned and scaled to a 3D MRI data set of the same patient using 4 skin markers visible on each modality. Three display schemes have been implemented for viewing the aligned slices. Examples of these displays are provided. The second method uses a labelled 3D MRI reference data set from a volunteer to identify major anatomical structures. The MR reference data set is aligned with the isotope image using the same 4 markers plus a marker on the vertex of the skull. The reference data set is segmented approximately into the major tissue types - cerebrospinal fluid (CSF) and grey and white matter. Major structures are identified via labels in the 3D data set. A linked cursor aids delineation of anatomical regions on the isotope image using the outline of structures on the reference data set as a template. Directions for future research in the generation of complete digital anatomical atlases, which include inter-individual variations, are outlined.

Blood glucose prediction using artificial neural networks trained with the AIDA diabetes simulator: a proof-of-concept pilot study

Diabetes mellitus is a major, and increasing, global problem. However, it has been shown that, through good management of blood glucose levels (BGLs), the associated and costly complications can be reduced significantly. In this pilot study, Elman recurrent artificial neural networks (ANNs) were used to make BGL predictions based on a history of BGLs, meal intake, and insulin injections. Twenty-eight datasets (from a single case scenario) were compiled from the freeware mathematical diabetes simulator, AIDA. It was found that the most accurate predictions were made during the nocturnal period of the 24 hour daily cycle. The accuracy of the nocturnal predictions was measured as the root mean square error over five test days (RMSE5day) not used during ANN training. For BGL predictions of up to 1 hour a RMSE5 day of (±SD) 0.15±0.04 mmol/L was observed. For BGL predictions up to 10 hours, a RMSE5 day of (±SD) 0.14±0.16 mmol/L was observed. Future research will investigate a wider range of AIDA case scenarios, real-patient data, and data relating to other factors influencing BGLs. ANN paradigms based on real-time recurrent learning will also be explored to accommodate dynamic physiology in diabetes.

Computerised decision-support tools in diabetes care: hurdles to implementation.

In this Diabetes Information Technology & WebWatch column hurdles to the use of computerised decision-support tools in clinical diabetes care will be considered. The clinical background with respect to insulin-dependent (type 1) diabetes mellitus and the Diabetes Control and Complications Trial is reviewed, and an overview is given of various computer applications. The use of decision-support tools is discussed, and the importance of identifying the proposed user, e.g., health-care professional, student, or patient, is highlighted. Validation/evaluation issues are considered as important topics that remain to be properly addressed for many decision-support prototypes. The column concludes by highlighting that in this era of evidence-based medicine well-conducted, rigorous evaluation and validation studies are required to inform decisions about whether or not to make use of current computerised decision-support prototypes.

Research Use of the AIDA www.2aida.org Diabetes Software Simulation Program: A Review—Part 1. Decision Support Testing and Neural Network Training

The purpose of this two-part review is to overview research use of the AIDA diabetes software simulator. AIDA is a diabetes computer program that permits the interactive simulation of plasma insulin and blood glucose profiles for teaching, demonstration, and self-learning purposes. It has been made freely available, without charge, on the Internet as a noncommercial contribution to continuing diabetes education. Since its launch in 1996 over 300,000 visits have been logged at the main AIDA Website-www.2aida.org-and over 60,000 copies of the AIDA program have been downloaded free-of-charge. This review describes research projects and ventures, undertaken for the most part by other research workers in the diabetes computing field, that have made use of the freeware AIDA software. Relevant research work was identified in three main ways: (i) by personal (e-mail/written) communications from researchers, (ii) via the ISI Web of Science citation database to identify published articles that referred to AIDA-related papers, and (iii) via searches on the Internet. In a number of cases research students who had sought advice about AIDA, and diabetes computing in general, provided copies of their research dissertations/theses upon the completion of their projects. The two reviews highlight some of the many and varied research projects that have made use of the AIDA diabetes simulation software to date. A wide variety of diabetes computing topics have been addressed. In Part 1 of the review, these range from testing decision support prototypes to training artificial neural networks. In Part 2 of the review, issues surrounding dietary assessments, developing new diabetes models, and performance monitoring of closed-loop insulin delivery devices are considered. Overall, research projects making use of AIDA have been identified in Australia, Italy, South Korea, the United Kingdom, and the United States. These reviews confirm an unexpected but useful benefit of distributing medical software, like AIDA, for free via the Internet-demonstrating how it is possible to have a synergistic benefit with other researchers-facilitating their own research projects in related medical fields. The reviews highlight a variety of these projects that have benefited from the free availability of the AIDA diabetes software simulator. In a number of cases these other research projects simply would not have been possible without unrestricted access to the AIDA software and/or technical descriptions of its workings. In addition, some specific common themes begin to emerge from the research ventures that have been reviewed. These include the use of simulated blood glucose data from the AIDA program for preliminary computerlab-based testing of other decision support prototypes. Issues surrounding such use of simulated data for separate prototype testing are discussed further in Part 2 of the review.

A serious game prototype for education of medical doctors and students on insulin management for treatment of diabetes mellitus

This paper describes the construction of a serious game prototype for training doctors and medical students about insulin management for the treatment of diabetes mellitus (DM). There are a few simulators that are educationally useful for this aim, but they are little attractive for the user, so we intend to create a tool that includes game elements to make it more fun and appealing. A series of hypothetical, clinical cases with increasing complexity are used to develop a minimum curriculum for training, incorporating all the principal aspects of insulin therapy for DM in the context of primary health care. We chose to develop an Adventure game, based on a minimum curriculum of contents about insulin management. The game presents a series of clinical scenarios and asks the players to make decisions about the best diagnostic and therapeutic options for each case. After each decision, the players receive feedback, comparing their decisions with the recommendations from the best-quality medical literature, and have access to additional educational resources (texts, algorithms, links to guidelines).

Randomized Controlled Trial Design for Simulator Use in Diabetes Education: Some Issues for Consideration

We thank Dr. Biermann for his interest in the AIDA diabetes simulator.1,2 He makes various observations, which it may be useful to discuss further. As Dr. Biermann will be aware, our original protocol was published in another journal3— and covered in some detail our reasoning behind adopting the protocol that we have. However, the article ran to 17 pages, which was probably long enough for an initial description of the approach. Hopefully, we will be able to expand here. However, we recommend that these comments should be read together with the comprehensive protocol description.3 In this respect, we have considered many of the issues raised by Biermann,4 but for various reasons opted not to include these in our initial pilot studies. As the saying goes, “there are many ways to skin a cat.” Similarly, there are many ways that a software program, like AIDA, can be evaluated. However, while it is clearly useful to have a discussion—we think the most important thing is to actually get on and run some studies, and learn from the experience. Connected with this it may be worthwile to point out that there can always be a downside when designing studies in trying to do too much. Similarly, it is possible to have too many variables or parameters to measure, and/or too many components to a study. This can actually impact on one’s ability to execute such a trial— simply due to study logistics. Therefore, the old adage to “keep it simple” comes to mind. Given this, as we have highlighted before,3 we found it necessary in drawing up our protocol to balance what might be ideal versus what is practical, given limited time and resources. As such, one of us (E.D.L.) has described a “pyramid of tests” that might be applied to evaluate the educational utility of a program like AIDA (Table 1).5,6 We are working our way through this in order to try and evaluate the program as rigorously as we can. This does take time—but the end result, if the program passes each stage, should be a well-validated piece of software—with some evidence to support its wider educational use. In this respect, one possible misconception that we would like to correct early on is that a single study can (or needs to) address all the possible points that one may wish to investigate with a given piece of software and a randomized controlled trial. One study cannot, and we feel it should not, do all of this. Rather, we see there being a whole series of studies, over a period of time, that will gradually address different points of interest and which will be revised and focused on particular questions that need answering. However, our hope and intention is that these further studies, by adopting a common basic protocol,3 will have some common structure that will assist later in making comparisons between studies. Connected with this, no single study can prove efficacy. Rather, we anticipate the need for a number of studies, hopefully in increasing numbers of patients, with increasing numbers of teachers, in separate centers that will, over a period of time, both confirm the safety and establish the efficacy of using simulators in diabetes education sessions. We also expect to learn from such studies how best to apply the simulator program in different settings. Dr. Biermann has made various statements which it might be worthwhile to respond to, LETTERS TO THE EDITOR 258

Who Is Downloading the Freeware AIDA v4.3 Interactive Educational Diabetes Simulator? An Audit of 2,437 Downloads

The purpose of this paper is to report an audit of 2437 downloads of the AIDA interactive educational diabetes simulator. AIDA is a diabetes computer program that permits the interactive simulation of plasma insulin and blood glucose profiles for educational, demonstration, and self-learning purposes. It has been made freely available, without charge, on the Internet as a noncommercial contribution to continuing diabetes education. Since its launch in 1996 over 200000 visits have been logged at the AIDA Website - www.2aida.org - and over 37000 copies of the AIDA program have been downloaded free-of-charge. This report documents an audit of downloaders of the software, with the intended goals of the study being to demonstrate the use of the Internet for auditing and surveying diabetes software users and to confirm the proportion of patients with diabetes and their relatives who are actually making use of the AIDA v4.3 program. The Internet-based survey methodology was confirmed to be robust and reliable. Over a 7(1/2)-month period (from mid-July 2000 to early March 2001) 2437 responses were received. During the corresponding period 4100 actual downloads of the software were independently logged via the same route at the AIDA Website - giving a response rate to this audit of 59.4%. Responses were received from participants in 61 countries - although over half of these (n = 1533; 62.9%) originated from the United States and United Kingdom. Of these responses 1,361 (55.8%) were received from patients with diabetes and 303 (12.4%) from relatives of patients, with fewer responses from doctors, diabetes educators, students, nurses, pharmacists, and other end users. This study has confirmed the feasibility of using the Internet to survey, at no real cost, a large number of medical software downloaders/users. In addition, it has yielded up-to-date and interesting data about who are the main downloaders of the AIDA program.

Research Use of the AIDA www.2aida.org Diabetes Software Simulation Program: A Review—Part 2. Generating Simulated Blood Glucose Data for Prototype Validation

The purpose of this review is to describe research applications of the AIDA diabetes software simulator. AIDA is a computer program that permits the interactive simulation of insulin and glucose profiles for teaching, demonstration, and self-learning purposes. Since March/April 1996 it has been made freely available on the Internet as a noncommercial contribution to continuing diabetes education. Up to May 2003 well over 320,000 visits have been logged at the main AIDA Website--www.2aida.org--and over 65,000 copies of the AIDA program have been downloaded free-of-charge. This review (the second of two parts) overviews research projects and ventures, undertaken for the most part by other research workers in the diabetes computing field, that have made use of the freeware AIDA program. As with Part 1 of the review (Diabetes Technol Ther 2003;5:425-438) relevant research work was identified in three main ways: (i) by personal (e-mail/written) communications from researchers, (ii) via the ISI Web of Science citation database to identify published articles which referred to AIDA-related papers, and (iii) via searches on the Internet. Also, in a number of cases research students who had sought advice about AIDA, and diabetes computing in general, provided copies of their research dissertations/theses upon the completion of their projects. Part 2 of this review highlights some more of the research projects that have made use of the AIDA diabetes simulation program to date. A wide variety of diabetes computing topics are addressed. These range from learning about parameter interactions using simulated blood glucose data, to considerations of dietary assessments, developing new diabetes models, and performance monitoring of closed-loop insulin delivery devices. Other topics include evaluation/validation research usage of such software, applying simulated blood glucose data for prototype training/validation, and other research uses of placing technical information on the Web. This review confirms an unexpected but useful benefit of distributing a medical program, like AIDA, for free via the Internet--demonstrating how it is possible to have a synergistic benefit with other researchers--facilitating their own research projects in related medical fields. A common theme that emerges from the research ventures that have been reviewed is the use of simulated blood glucose data from the AIDA software for preliminary computer lab-based testing of other decision support prototypes. Issues surrounding such use of simulated data for separate computer prototype testing are considered further.

Who Is Downloading the Free AIDA v4.3a Interactive Educational Diabetes Computer Software? A 1-Year Survey of 3,864 Downloads

AIDA is a free diabetes computer program that permits the interactive simulation of plasma insulin and blood glucose profiles for educational, demonstration, self-learning, and research purposes. To date over 70000 copies of the software have been downloaded from the AIDA Website, www.2aida.org. This column documents a survey of downloaders of the latest release of the program (AIDA v4.3a). The Internet-based survey methodology was confirmed to be robust and reliable. Over a 1-year period (from March 2001 to February 2002) in total 3864 responses were received. During the corresponding period some 8578 actual downloads of the software were independently logged via the same route at the AIDA Website, giving a response rate for this survey of 45%. Responses were received from participants in 66 countries - over half of these (n = 2,137; 55.3%) were from the United States and the United Kingdom. There were 2318 responses (60.0%) received from patients with diabetes and 443 (11.5%) from relatives of patients, with fewer responses from doctors, students, diabetes educators, nurses, pharmacists, and other end users. This study highlights considerable interest amongst patients and their relatives to learn more about balancing insulin and diet in diabetes, as well as possibly to get more involved in self-management of insulin dosages. More computer applications that can cater for this interest in diabetes patient self-care need to be developed and made available. The Internet provides an ideal medium for the distribution of such educational tools.