Harnessing Q Rev B 2021 This handbook entitled Knowing Q (Flow) presents information for bioengineering students who are interested in the development of biomedical devices. Its content was developed by Transonic for the purpose of championing the importance of incorporating quantita- tive flow methodolgy into biomedical device manufacture. Following a Table of Contents, Knowing Q offers an introductory forward that proceeds sections on cardiovascular physiology, flow dynamics and principles of flow measurement. Then chapters on biomedical device design and development, and on Knowing Q research and clinical applications that employ transit-time ultrasound and indicator dilution technologies follow. The second from the last chapter in the body of the handbook presents an outline for a pilot collaborative student / academic research program with Transonic while the final chapter gives an overview of Transonic flowsensing products. Finally, an annotated bibliography of relevant publications and an extensive glossary of technology and hemodynamic terms complete the handbook. Cover photography by Kyle Re (www.kylerecreative.com) ©2021 by Transonic Systems Inc. Printed in the United States of America Transonic®, Transonic Systems Inc.®, Flow-QC®, AureFlo®, Flowsound®, Optimax®, Flow-XL® are registered trademarks of Transonic Systems Inc. This handbook is an educational service of Transonic Systems Inc., Cornelis J. Drost, publisher; John Haberstock, Martine Bosch, Margo Sosa, creators; Susan Eymann, editor. All rights reserved. No part of this handbook may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photocopying, recording, or otherwise, without permission from Transonic Systems Inc. Copies of this handbook may be ordered from Transonic Systems Inc. Tel: 1-800-353-3569 (USA); 607-257-5300; Fax: 607-257-7256; www.transonic.com. www.transonic.com Harnessing Q (OEM-700-hb) Rev B 2021 USltr 2 Table of Contents Table of Contents A. From Bench to Bedside ........................................................................ 5 B. Principles of Blood Flow Measurement: .......................................................... 7 Ultrasound ................................................................................. 7 Indicator Dilution ............................................................................ 10 Electromagnetic Induction .................................................................... 14 Radiology .................................................................................. 15 Thermal Convection .......................................................................... 16 C. Medical Device Design and Development D. Applications .................................................................................. 25 Research Applications Mock Circulatory Loops (MCL) ............................................................. 26 Specialized Models ....................................................................... 28 Pre-Clinical In Vivo Testing ................................................................ 29 Silicone Vascular Models ................................................................. 30 Early Stage Artificial Organ Development .................................................... 31 Clinical Applications Mechanical Circulatory Support (MCS) ...................................................... 20 Cardiopulmonary Bypass .............................................................. 33 Extracorporeal Membrane Oxygenation (ECMO) .......................................... 34 Ventricular Assist Devices - VADs ....................................................... 37 Total Artificial Hearts™ ............................................................... 38 Artificial Lungs .......................................................................... 39 Renal Replacement - Hemodialysis ......................................................... 40 Organ Preservation ....................................................................... 41 Medicine Delivery - Infusion Pumps ......................................................... 42 Urodynamic System / Uroflowmeter, Pediatric Hydrocephalus ................................... 43 Endometrial Ablation,Ocular Surgery ........................................................ 44 E. Working with Transonic 1. Who Is Transonic? ......................................................................... 45 2. Innovative Liquid Flow Solutions ............................................................. 46 3. Co-engineering Program .................................................................... 47 4. Transonic’s Intellectual Property Lineage ...................................................... 48 F. Transonic Flowsensing Products .................................................................. 50 Appendix Cardiovascular Physiology ..................................................................... 58 Flow Dynamics ................................................................................ 73 Bibliography .................................................................................. 79 Glossary of Terms ............................................................................. 84 Bioengineers’ Guide (OEM-700-hb) Rev A 2019 A4 3 ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ “I often say that when you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatis- factory kind; it may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of science, whatever the matter may be.” William Thomson, Lord Kelvin (1824-1907) Scottish physicist “Electrical Units of Measurement,” lecture (3 May 1883) ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ • ~ Harnessing Q (OEM-700-hb) Rev B 2021 USltr 4 From Bench to Bedside A. From Bench to Bedside Flow Is Life’s Vital Sign then carries away the metabolic wastes. By measuring true blood flow, one is Blood flow enables life. It is life’s vital sign. quantifying an essential medical parameter. When blood flow is cut off or ceases, heart Rather than relying on subjective impressions attacks and strokes occur. Life can end. or qualitative images, real numbers provide Yet, why is flow so often disregarded? Simply functional information. Just as a pilot must stated, devices and technologies to precisely learn to use instruments to fly safely, the measure blood flow were unavailable until engineer, researcher or clinician must rely on the mid-twentieth century. In their stead, real quantitative data in order to arrive at surrogate measurement modalities were accurate, objective conclusions. introduced, became established and are still being used. Pressure, used by the body to drive flow, Transonic’s Inspiration is routinely used to assess hemodynamic Transonic’s mission “To Advance Meaningful function. But it does not always correlate Measurements” has inspired, guided and with flow (see graphic on page 30). Pulses, propelled Transonic’s growth from genesis 35 visual and tactile, are felt and observed years ago to the present day where Transonic to assess blood pressure, but they do not is globally recognized as a biomedical provide adequate information about true measurement company leader. flow. Angiography is used, but it shows anatomical structure, not quantitative function. Doppler technology is also a Purpose of Handbook common measurement technique, but it The intent of this booklet is to introduce measures the velocity, not volume, of flow. bioengineers to the importance of flow All are used as surrogates for flow. They do (Q) and the measurement technologies not provide quantitative true volume flow offered used to measure flow. Transonic as measured precisely by Transonic devices. measurement technologies (transit-time Volume flow is truly the quintessential “vital ultrasound, indicator dilution, conductance, sign” of hemodynamic function. pressure and Laser Doppler) are used in a broad spectrum of applications and in the development of biomedical devices as it Why Is Flow So Important? moves from bench-top scientific research Blood flow, defined as the volume of to device development and pre-clinical blood that passes a certain point in a vessel validation to, ultimately, the manufacture of during a defined time frame, is crucial for commercial products. proper metabolism. Blood delivers oxygen and nutrients to each cell in the body, Harnessing Q (OEM-700-hb) Rev B 2021 USltr 5 From Bench to Bedside A. From Bench to Bedside cont. Typical Phases of Medical Device Development Harnessing Q (OEM-700-hb) Rev B 2021 USltr 6 Flow Principles B. Principles of Flow Measurement Testing, verification and validation is Ultrasound: Doppler key during each stage of medical device development. Measurement of blood flow To generate the Doppler effect, an oscillator by various methodologies is frequently used delivers a signal at several MHz to excite in combination with other hemodynamic a piezoelectric transducer. The difference parameters to test, validate and verify between the the original and shifted signals biomedical devices. gives the Doppler frequency. A Doppler shift is the change in frequency between the There are a myriad of methods, employed ultrasound waves emitted by the transducer by biomedical engineers to measure and the ultrasound waves