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Magnetic Resonance Imaging in Tissue Engineering provides a unique overview of the field of non-invasive MRI assessment of tissue engineering and regenerative medicine * Establish a dialogue between the tissue-engineering scientists and imaging experts and serves as a guide for tissue engineers and biomaterial developers alike * Provides comprehensive details of magnetic resonance imaging (MRI) techniques used to assess a variety of engineered and regenerating tissues and organs * Covers cell-based therapies, engineered cartilage, bone, meniscus, tendon, ligaments, cardiovascular, liver and bladder tissue engineering and regeneration assessed by MRI * Includes a chapter on oxygen imaging method that predominantly is used for assessing hypoxia in solid tumors for improving radiation therapy but has the ability to provide information on design strategies and cellular viability in tissue engineering regenerative medicine

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Magnetic Resonance Imaging in Tissue Engineering

 

 

Edited by Mrignayani Kotecha, Richard L. Magin, and Jeremy J. Mao

 

 

 

 

 

 

 

 

This edition first published 2017© 2017 John Wiley & Sons, Inc.

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The right of Mrignayani Kotecha, Richard L. Magin, and Jeremy J. Mao to be identified as the author(s) of this work has been asserted in accordance with law.

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Library of Congress Cataloguing‐in‐Publication data has been applied for

ISBN: 9781119193357

Cover image courtesy Temel Kaya YasarCover design by Wiley

List of Plates

Figure 1.3 Cell migration into a synthetic three‐dimensional (3D) scaffold. A composite 3D scaffold composed of poly(methacrylic acid) (PMMA) and poly(hydroxyethyl methacrylate) (PHEMA) was developed for cornea tissue engineering. Confocal microscopy was used to monitor migration of corneal fibroblasts into the acellular scaffold. Using a viability assay, the live or dead cells fluoresce different in different wavelengths. Because the confocal images were collected at different focal depths, reconstructed 3D images can be produced with detailed information in the direction of cell migration into the scaffold. * indicates p

Figure 1.4 Four‐color imaging of osteogenesis. Human MSCs were induced to differentiate to osteoblasts. At day 14, the cells were labeled and visualized to quantify the extent of osteogenesis. Using a multiphotom microscope (Bio‐Rad, Radiance 2000), a set of four fluorophores was selected to label and image simultaneously the nuclei (blue), osteocalcin expression (green), microtubule (yellow), and microfilament (red) organization. These four fluorophores were carefully chosen to minimize potential spectroscopic overlaps.

Figure 2.7 The calculated T1 and T2 as functions of the water molecule tumbling rate and magnetic field strength (100–700 MHz) calculated using the BPP theory of relaxation [50]. As the tissue matures, both T1 and T2 decrease, as shown by the red arrow. Most human tissues fall within the range shown by the blue ellipse. T2 is commonly used in the assessment of cartilage regeneration, as can be seen in a recent clinical trial [2, 6]. The figure shows that relaxation times are field dependent for soft tissues. The inset shows an example of how T2/T1 can be used as a unit‐free biomarker for the assessment. As shown in the inset, the control gel has the highest T2/T1, but the ratio is lowest for osteogenic constructs with chondrogenic constructs falling between the two. Data in the inset are adapted from [25, 51].

Figure 3.6 (a) Schematic of a sample preparation for MRI measurement (the black arrow indicates the sample inside a 5 mm tube). (b) A representative T2‐weighted proton MRI of an acellular scaffold. (c–e) Representative sodium MRI of chondrogenic constructs at day 7, day 14, and day 28 along with representative ROIs of the construct (bottom box) and reference media (top box). The average number of voxels in sodium images is 231 ± 22. Majumdar [23]. Reproduced with the permission of Springer.

Figure 3.8 (a) TQ signal intensity as a function of creation time for tissue‐engineered cartilage and their best fit with Equation 3.1 for 1‐day‐old engineered cartilage constructs. (b) The TQ signal of human marrow stromal cells (HMSCs) seeded in biomimetic scaffolds at week 2 and week 4. The week 4 spectrum is narrow compared to the week 2 spectrum, indicating faster motion or lower ω0τc at week 4. Reproduced with the permission from Kotecha et al. [26].

Figure 5.6 Material properties are calculated from each filtered dataset and averaged with a weight corresponding to the amplitude of the motion at each pixel.

Figure 5.7 A circular low‐pass Butterworth filter is applied on every map of material properties so that they appear smoother.

Figure 5.9 Construct development map over 4‐week period. Adipogenic (A) and osteogenic (O) constructs are shown from left to right with corresponding shear wave image, elastogram, and average shear stiffness. The colormap for the elastogram corresponds with the color scheme of the bar chart.

Figure 5.11 Shear wave images (top) and corresponding stiffness maps (bottom) in engineered constructs after 4 weeks of implantation. The displacement map shows the propagation of shear waves through constructs. Notice that, multiple waves are visible in adipose construct, indicating a lower stiffness and softer tissue structure, while for stiffer tissues—both osteogenic and chondrogenic—a full shear wave is not attained. Reconstructed elastogram on the bottom shows estimated stiffness of 2, 9, 15 kPa for adipogenic, chondrogenic, and osteogenic constructs, respectively.

Figure 5.12 Silk construct development map over 8‐week study. Shown from left to right are the magnitude image, T2 relaxation map, shear wave image, and stiffness map of the constructs. Average T2 relaxation times decreased from 91.2 67.6 ± 3.1 at week 8. Average stiffness values increased from 7.6 ± 2.0 kPa 17.2 ± 3.1 at week 8.

Figure 5.13 Collagen construct development map over 8‐week study. Shown from left to right are the magnitude image, T2 relaxation map, and stiffness map of the constructs. Average T2 relaxation times decreased from 75.2 ± 18.4 ms at week 2 to 58.4 ± 4.2 at week 8. Average stiffness values increased from 4.6 ± 1.7 kPa at week 2 to 14.7 ± 3.8 kPa at week 8.

Figure 6.1 Example of using FEA to verify the inversion algorithm in MRE. (a) The geometry of the model is that of a fluid‐filled spherical shell embedded in a stiffer medium, and a solid spherical medium with the same density as the shell embedded in the medium for comparison. (b) The wave pattern of the model under a horizontal 80‐Hz harmonic excitation. (c) The stiffness map obtained from the regular Helmholtz inversion algorithm. (d) The stiffness map obtained from an effective stiffness estimation algorithm.

Figure 6.3 Displacement amplitude results for three simulations. The top row is the displacement amplitude shown on the 3D models of (a) harmonic excitation on a 3‐mm diameter area in the vertical direction, (b) harmonic excitation on a 3‐mm diameter area in the direction normal to the excitation plane, and (c) harmonic excitation on a 6‐mm diameter area in the direction normal to the excitation plane. The bottom row is the displacement amplitude map on the short‐axis slice plane of (d) harmonic excitation on a 3‐mm diameter area in the vertical direction, (e) harmonic excitation on a 3‐mm area in the direction normal to the excitation plane, and (f) harmonic excitation on a 6‐mm are in the direction normal to the excitation plane.

Figure 7.1