Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Bioresorbable silicon electronic sensors for the brain

3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

https://iopscience.iop.org/article/10.1088/1748-6041/10/3/034002/pdf

Current progress in 3D printing for cardiovascular tissue engineering

As we shift from population-based medicine towards a more precise patient-specific regime guided by predictions of verified and well-established cardiovascular models, an urgent question arises: how sensitive are the model predictions to errors and uncertainties in the model inputs? To make our models suitable for clinical decision-making, precise knowledge of prediction reliability is of paramount importance. Efficient and practical methods for uncertainty quantification (UQ) and sensitivity analysis (SA) are therefore essential. In this work, we explain the concepts of global UQ and global, variance-based SA along with two often-used methods that are applicable to any model without requiring model implementation changes: Monte Carlo (MC) and polynomial chaos (PC). Furthermore, we propose a guide for UQ and SA according to a six-step procedure and demonstrate it for two clinically relevant cardiovascular models: model-based estimation of the fractional flow reserve (FFR) and model-based estimation of the total arterial compliance (CT ). Both MC and PC produce identical results and may be used interchangeably to identify most significant model inputs with respect to uncertainty in model predictions of FFR and CT . However, PC is more cost-efficient as it requires an order of magnitude fewer model evaluations than MC. Additionally, we demonstrate that targeted reduction of uncertainty in the most significant model inputs reduces the uncertainty in the model predictions efficiently. In conclusion, this article offers a practical guide to UQ and SA to help move the clinical application of mathematical models forward. Copyright © 2015 John Wiley & Sons, Ltd.

A guide to uncertainty quantification and sensitivity analysis for cardiovascular applications

Clinical Utility of Intravascular Imaging and Physiology in Coronary Artery Disease

Planar biaxial characterization of diseased human coronary and carotid arteries for computational modeling

Objectives The aim of this study was to assess the validity of measuring fractional flow reserve (FFR) of the left main (LM) coronary artery in the setting of concomitant left anterior descending (LAD) or left circumflex (LCX) stenoses. Background The theoretical impact of a stenosis in the LAD on the FFR assessment of intermediate LM disease with the pressure wire in an unobstructed LCX is currently unknown. Methods A previously validated in vitro model of the coronary circulation was used to create a fixed intermediate stenosis of the LM and a variable downstream LAD or LCX stenosis. The true LM FFR (FFRLM true), with no concomitant downstream disease, was compared to the apparent LM FFR (FFRLM apparent), with concomitant downstream disease measured with different degrees of LAD or LCX disease. Additionally, an equation based on a resistors model was derived to predict the effect of downstream stenosis on LM FFR (FFRLM predicted). Results In the setting of isolated moderate LM disease (FFR 0.72 ± 0.08), mild to moderate proximal LAD or LCX lesions did not significantly affect LM FFR. Lesions with a composite FFR (LM + downstream disease) ≥0.65 resulted in an FFRLM apparent that was not significantly different from FFRLM true (0.76 ± 0.06 vs. 0.76 ± 0.05, p = 0.124). Our equation for FFRLM predicted accurately modeled the effects of concomitant disease (r = 0.95, p Conclusions These data suggest that in the presence of proximal mild to moderate LAD or LCX disease, LM FFR can be reliably measured with the pressure wire placed in the uninvolved epicardial artery.

The impact of downstream coronary stenoses on fractional flow reserve assessment of intermediate left main disease

http://www.mate.tue.nl/mate/pdfs/10659.pdf

Continuous infusion thermodilution for assessment of coronary flow: Theoretical background and in vitro validation

Constitutive models describing the arterial mechanical behavior are important in the development of catheterization products, to be used in arteries with a specific radius. To prove the possible existence of a constitutive model that, provided with a generic set of material and geometric parameters, is able to predict the radius-specific mechanical behavior of a coronary artery, the passive pressure–inner radius (P–ri) and pressure–axial force change (P–ΔFz) relations of seven porcine left anterior descending coronary arteries were measured in an in-vitro set-up and fitted with the model of Driessen et al. in J Biomech Eng 127(3):494–503 (2005), Biomech Model Mechanobiol 7(2):93–103 (2008). Additionally, the collagen volume fraction, physiological axial pre-stretch, and wall thickness to inner radius ratio at physiological loading were determined for each artery. From this, two generic parameter sets, each comprising four material and three geometric parameters, were obtained. These generic sets were used to compute the deformation of each tested artery using a single radius measurement at physiological loading as an artery-specific input. Artery-specific P–ri and P–ΔFz relations were predicted with an accuracy of 32 μm (2.3%) and 6 mN (29% relative to ΔFz-range) on average compared to the relations measured in-vitro. It was concluded that the constitutive model provided with the generic parameters found in this study can well predict artery-specific mechanical behavior.

https://link.springer.com/content/pdf/10.1007%2Fs10237-010-0231-9.pdf

A generic constitutive model for the passive porcine coronary artery

The flex-to-rigid (F2R) platform allows for the fabrication of miniature and flexible sensor assemblies for minimally invasive medical instruments such as catheters and guidewires. Devices fabricated on silicon wafers are transferred onto polyimide and partially rendered flexible by means of a two-step backside silicon deep reactive ion etching. The flexibility allows for the devices to be folded into, or wrapped around the tip of the instruments. The fabrication of the whole assembly is based on standard integrated circuit manufacturing technologies so that it is possible to scale the devices down to the dimension of the smallest guidewires. Several demonstrations are presented to show the versatility of the F2R technology, and a polyimide-based flexible thermal flow sensor for application at the tip of a 360- μm diameter guidewire is introduced.

Flex-to-Rigid (F2R): A Generic Platform for the Fabrication and Assembly of Flexible Sensors for Minimally Invasive Instruments

A model describing the primary relations between the cardiac muscle and coronary circulation might be useful for interpreting coronary hemodynamics in case multiple types of coronary circulatory disease are present. The main contribution of the present study is the coupling of a microstructure-based heart contraction model with a 1D wave propagation model. The 1D representation of the vessels enables patient-specific modeling of the arteries and/or can serve as boundary conditions for detailed 3D models, while the heart model enables the simulation of cardiac disease, with physiology-based parameter changes. Here, the different components of the model are explained and the ability of the model to describe coronary hemodynamics in health and disease is evaluated. Two disease types are modeled: coronary epicardial stenoses and left ventricular hypertrophy with an aortic valve stenosis. In all simulations (healthy and diseased), the dynamics of pressure and flow qualitatively agreed with observations described in literature. We conclude that the model adequately can predict coronary hemodynamics in both normal and diseased state based on patient-specific clinical data.

/pdf/towards-patient-specific-modeling-of-coronary-hemodynamics-3ur38hzeiu.pdf

A Arjen van der Horst

Papers

The impact of downstream coronary stenoses on fractional flow reserve assessment of intermediate left main disease

Continuous infusion thermodilution for assessment of coronary flow: Theoretical background and in vitro validation

A generic constitutive model for the passive porcine coronary artery

Flex-to-Rigid (F2R): A Generic Platform for the Fabrication and Assembly of Flexible Sensors for Minimally Invasive Instruments

Towards patient-specific modeling of coronary hemodynamics in healthy and diseased state