Patient-Specific Controller for an Implantable Artificial Pancreas by Dr. Yvonne Ho

Supervisor’s Foreword

Artificial pancreas that can provide tight blood glucose control for a diabetic is one of the most challenging problems of engineering in medicine. This book by Dr. Yvonne Ho will be an especially useful reference book for those working on diabetes mellitus and artificial pancreas. After an introductory chapter, which includes a short summary of the background of this research topic. Chap. 2 presents a detailed description about diabetes mellitus and its related physiology. Chapter 3 presents a state-of-the-arts review of the various treatment options. The emphasis of the remaining chapters is on new results from the research and development of an implantable artificial pancreas. The implantable artificial pancreas regulates blood glucose level by delivering appropriate dosage of insulin when necessary. By sensing the blood glucose and injecting insulin directly into the vein, the implantable device aims to remove delays from subcutaneous blood glucose sensing and insulin delivery. Preliminary in vitro and in vivo experimental results suggest that the implantable approach for blood glucose control could be a clinicially viable alternative to pancreas transplant. There is deep knowledge in the modeling and control of blood glucose level as well as design of implantable devices. This book should provide a valuable addition to the library of the scientist and engineer working at the interface of engineering and medicine.

Chee-Kong Chui, January 2018

Cyber-medical system for patient-specific medical devices development

Above is the title of my invited talk in The 13th Annual IEEE International Conference on Nano/Micro Engineered and Molecular Systems (IEEE NEMS 2018), April 22-26, 2018 in Singapore.

Following is the abstract of my talk:

With rising demands for quality as well as affordable healthcare services, organizations in the medical device manufacturing industry are embracing more intelligent and responsive systems via the integration and development of dynamic digital technologies. We are proposing a Cyber-Physical System (CPS)-based production system with integrated enabling digital technologies and robot assistance. It could potentially increase productivity and sustainability, specifically for the production of patient-specific, hybrid medical devices. A hybrid medical device incorporates multiple components and materials that have to perform without fault for a long time often under the stressful conditions of the human body. Examples of hybrid medical device include artificial trachea, artificial pancreas for treatment of diabetes and information-delivering microchips. The proposed CPS-based manufacturing system utilizes an integration of enabling digital technologies including Augmented Reality (AR), Wireless Sensor Network (WSN), Internet of Things (IoT) and Artificial Intelligence (AI) for the fabrication of patient-specific medical devices. Necessary visual and haptic cues are provided to the human operator in a timely manner so that he/she can intervene in a speedy manner. Importance-driven computer graphical rendering of visual cues is embedded into physics-based simulation for haptic rendering.

The study on human centricity in an immersive and robot-assisted environment will provide unique insights on human hand-eye coordination capabilities under external influences. Interesting scientific questions include to what extent an individual learn and how the individual learn motor skill with external guidance.

Note: There is an IEEE Technical Committee (TC) on Cyber-Medical Systems under IEEE SMC. More information of the TC can be found here.

Imaging and visualization of bone tissue properties

Accurate quantitative estimation of tissue mechanical properties is a research topic. In order for the measurement to be clinical viable, it should be achieved in a non-invasive manner. Estimation of bone density from clinical CT images is reported in 2010 [1]. We are investigating the application of computational intelligent methods on multimodal medical data to aid the estimation of bone material properties from images. It has led to the development of opportunistic screening for detection and management of osteopenia [2][3].

There are few works on visualization of tissue mechanical properties. However, a spine invasive map could provide the clinicians with an intuitive representation of the underlying bone properties. Visualization of bone properties can be achieved using material sensitive transfer functions and coloring schemes that represent different properties:

A clustering-based framework for automatic generation of transfer functions for medical visualization is reported in [4].

[1] Zhang, J, CH Yan, CK Chui and SH Ong, “Accurate measurement of bone mineral density using clinical CT imaging with single energy beam spectral intensity correction”. IEEE Transactions on Medical Imaging, 29, 7 (2010): 1382-1389.
[2] Tay, WL, CK Chui, SH Ong and ACM Ng, “Osteopenia screening using areal bone mineral density estimation from diagnostic CT images”. Academic Radiology, 19, no. 10 (2012): 1273-1282.
[3] Tay, WL, CK Chui, SH Ong and ACM Ng, “Ensemble-based regression analysis of multimodal medical data for ostopenia diagnosis”. Expert Systems with Applications, 40, no. 2 (2013): 811-819.
[4] Nguyen, BP, WL Tay, CK Chui and SH Ong, “A Clustering-Based System to Automate Transfer Function Design for Medical Image Visualization”. Visual Computer, 28, no. 2 (2012): 181-191.

Robotic surgery: hand-eye coordination, cognition and biomechanics

Around 2013- 2014, I contributed an article with the above title to the then Engineering Research News (ISSN 0217-7870). The theme was “The Changing Faces of ME”. Mechanical Engineering (ME) is multi-disciplinary.

Following is an edited version:

One key research area pursued by my group is intelligent surgical robotic system, which augments and enhances the hand-eye coordination capability of the surgeon during operation so as to achieve the desired outcome and reduce invasiveness.

Hand-eye coordination refers to the ability of our vision system to coordinate and process the information received through the eyes to control, guide and direct our hands in the accomplishment of a given task. In this work, we studied hand-eye coordination to build medical simulator for surgical training and to develop medical robot that will duplicate the best surgeon’s hand-eye coordination skill.

An integrated view on surgical simulator and robot assisted surgery is adopted in our research. The former is a simulation game for surgical training and treatment planning. The latter is a single or plurality of devices assisting the surgical team to operate on the patient precisely.  With computer simulator, a patient specific surgical plan can be derived with robot manipulation included. By combining patient specific simulation with robotic execution, we can developed highly autonomous robot(s).

In an automated system, poor information feedback will remove the human operator from the decision-making role and into a supervisory role. Necessary visual, audio and haptic cues should be provided to the human in a timely manner so that he/she can intervene in a speedy manner. The study on human centricity in an immersive and robot-assisted environment will provide unique insights on human hand-eye coordination capabilities under external influences.

Cognitive engine provides a high level of intelligence in the autonomous robot to be effective collaborator with human(s). The engine possesses knowledge about relevant parts of surgery, including the dynamics of the surgery, the robot’s actions and the behavior of the biological tissue in response to the actions. The action of the surgical team has added to the dynamics and, sometimes, uncertainty to the operation. The self-learning process of the cognitive engine requires inherent knowledge of tissue biomechanics. The biological tissues within the human patient body cavity are living elements that may be preserved, repaired or destroyed using mechanical and thermal methods.

A surgery can be planned with a virtual robot in a simulator with realistic biomechanical models, and the surgery is then performed on the patient using the robot with the help of advanced man-machine interfaces.  Augmented reality technologies with intelligent visual, haptic and audio cues will provide a medium for the surgical team to have an effective control over the robot.

The figure on our architecture of an intelligent surgical robotic system with cognitive engine in the original article is still a work-in-progress. Its latest version can be found in:

Tan, X, C B Chng, B Duan, Y Ho, R Wen, X Chen, K B Lim and C K Chui, “Cognitive engine for robot-assisted radio-frequency ablation system”, Acta Polytechnica Hungarica 14, no. 1 (2017): 129-145.


Liver tissue properties and frequency-control of RF ablation

A computational model comprising an equivalent circuit of resistors and capacitors to study the changes in electrical properties of liver tissue during radio-frequency (RF) ablation is proposed in [1].  The changes in tissue mechanical properties are correlated with that of the tissue electrical properties. In addition to liver tumor treatment, RF ablation can be used to stop blood flow during liver resection. In [2], we further developed the multi-scale model to study the bioimpedance dispersion of liver tissue. The following figure from [3] compares our model with the Cole-Cole model used in Gabriel study. At high frequency region, both models fit the experimental data well. At the lower frequency region, our model can fit the data better.

With the accurate multi-scale model and a 3D finite element model, we conducted RF ablation simulations using different frequencies in [3]. The ablation region increases as the frequency increases. The frequency-control method may be more effective compared to duration-control method in RF ablation.

Our earlier and preliminary work on applying multi-scale/multi-level model for simulating molecular medicine using electroporation is reported in [4].

References: [1] W-H Huang et al. Multi-scale model for investigating the electrical properties and mechanical properties of liver tissue undergoing ablation, Int J CARS (2011) 6:601-607. [2] W-H Huang et al. A multiscale model for bioimpedance dispersion of liver tissue, IEEE Trans Biomed Eng (2012) 59(6):1593-1597. [3] B Duan and CK Chui, Multiscale modeling of liver bio-impedance and frequency control for radiofrequency ablation, 2016 IEEE Region 10 Conference (TENCON) – Proceedings of the International Conference, pp. 1532-1535, November 2016. [4] Chui et al. A medical simulation system with unified multilevel biomechanical model, Proc of 12th International Conference on Biomedical Engineering ICBME 2002, Singapore, 4-7 December 2002.

Constitutive modeling of biological soft tissue

Stress–strain curves of combined porcine liver tissue sample compression and elongation from (Journal of Biomechanics 47 (2014) 2430–2435): (a) Mean values of experimental data, standard deviations from mean values are indicated with horizontal bars; (b) Median values of experimental data; (c) Simulation using the 5-constant Mooney-Rivlin model with parameters calculated by inverse finite element method; and (d) Simulation using the 5-constant Mooney–Rivlin model with parameters calculated by curve fitting.

Both compression and elongation stress-strain data should be considered for modeling and simulation of soft tissue indentation since the tissue deformation is affected by both its compressive and tensile characteristics.

An alternative to the Mooney-Rivlin model is a combined logarithmic and polynomial model originally proposed in (Medical & Biological Engineering and Computing 42 (2004) 787-798). The combined logarithmic and polynomial model is better than the 5-constant Mooney-Rivlin model as the constitutive model for simulation of soft tissue indentation.

GPU Technology Conference (GTC) 2015 poster

This poster “Accelerated Medical Computing Toolkit and GPU Accelerated Importance-Driven Volume Visualization” was presented under the category of Medical Imaging in GPU Technology Conference (GTC 2015), Silicon Valley, 17-20 March 2015. It was modified from “GPU Accelerated Transfer Function Generation for Importance-Driven Volume Visualization” which won Best Poster Award (Grand Prize) in the GPU Technology Workshop South East Asia (GTW SEA 2014), Singapore, 10 July 2014.

Medical simulation system for catheterization

This picture of me was taken in 1990s. I was the developer of a medical simulation system for catheterization. I hung catheters on the window panel next to the door of my office.

The simulation system was a new concept in providing physicians with a real-time interactive simulation of vascular catheterization procedures to augment training and enhance pretreatment planning and design of medical devices.

Implantable artificial pancreas

A picture of our prototype implantable artificial pancreas that we have been developing. It was exhibited in National University of Singapore Science & Technology Exhibition in March 2015 and then in “The Future of Us” Exhibition organized by the Singapore Government for SG50 celebration between 1 December 2015 and 8 March 2016. This device will take many years of R&D to become a viable alternative to pancreas transplant.