Intermolecular Multiple Quantum Coherences Enable Accurate Thermal Imaging of Red Bone ...

195 Pages·2015·4.66 MB·English

Intermolecular Multiple Quantum Coherences Enable Accurate Thermal Imaging of Red
Bone Marrow During Thermal Therapy of Bone Metastases
by
Ryan M Davis
Department of Biomedical Engineering
Duke University

Date:_______________________
Approved:

___________________________
Warren S. Warren, Supervisor

___________________________
Mark W. Dewhirst

___________________________
G. Allan Johnson

___________________________
R. Tamara Branca

___________________________
Kathy Nightingale

Dissertation submitted in partial fulfillment of
the requirements for the degree of Doctor
of Philosophy in the Department of
Biomedical Engineering in the Graduate School
of Duke University

2015
ABSTRACT
Intermolecular Multiple Quantum Coherences Enable Accurate Thermal Imaging of Red
Bone Marrow During Thermal Therapy of Bone Metastases
by
Ryan M Davis
Department of Biomedical Engineering
Duke University

Date:_______________________
Approved:

___________________________
Warren S. Warren, Supervisor

___________________________
Mark W. Dewhirst

___________________________
G. Allan Johnson

___________________________
R. Tamara Branca

___________________________
Kathy Nightingale

An abstract of a dissertation submitted in partial
fulfillment of the requirements for the degree
of Doctor of Philosophy in the Department of
Biomedical Engineering in the Graduate School of
Duke University

2015
Copyright by
Ryan M Davis
2015
Abstract
Prostate and breast cancers are two of the most common types of cancer in the
United States, and those cancers metastasize to bone in more than two thirds of patients.
Recent evidence suggests that metastatic bone cancer can be effectively treated with
thermal therapy. For example, thermal therapy enables targeted drug delivery to bone,
ablation of cancer cells in bone marrow, and palliation of bone pain. Thermal therapy of
bone metastases would be greatly improved if it were possible to image the temperature
of the tissue surrounding the disease, which is usually red bone marrow (RBM).
Unfortunately, current thermal imaging techniques are inaccurate in RBM.
Here, we show that many of the difficulties with thermal imaging of RBM can be
overcome using a magnetic resonance phenomenon called an intermolecular multiple
quantum coherence (iMQC). Herein, iMQCs are detected with a magnetic resonance
imaging (MRI) pulse sequence called multi-spin-echo HOMOGENIZED with off
resonance transfer (MSE-HOT). Compared to traditional methods, MSE-HOT provided
ten-fold more accurate images of temperature change. Furthermore, MSE-HOT was
translated to a human MRI scanner, which enabled imaging of RBM temperature during
heating with a clinical focused ultrasound applicator. In summary, this dissertation
develops a MRI technique that enables thermal imaging of RBM during thermal therapy
of bone metastases.
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Contents
Abstract ......................................................................................................................................... iv
List of Tables ................................................................................................................................. xi
List of Figures .............................................................................................................................. xii
1. Introduction ............................................................................................................................... 1
1.1 The motivation for thermal imaging of red bone marrow ......................................... 3
1.2 A new method for thermal imaging in RBM ................................................................ 4
2. Review of literature: Bone metastases, thermal therapy, and thermal imaging .............. 6
2.1 Bone Metastasis ................................................................................................................. 6
2.1.1 Incidence, prognosis, and symptoms ....................................................................... 6
2.1.2 Biology of bone metastasis ......................................................................................... 7
2.1.3 Currently available therapies for bone metastasis.................................................. 9
2.1.4 The motivation for hyperthermia of bone metastases ......................................... 11
2.2 Thermal therapy of bone metastases ........................................................................... 12
2.2.1 The effects of heat on tissue ..................................................................................... 13
2.2.1.1 Hyperthermia ..................................................................................................... 13
2.2.1.2 Ablation ............................................................................................................... 14
2.2.2 Heat applicators ......................................................................................................... 15
2.2.2.1 Percutaneous heat applicators ......................................................................... 15
2.2.2.2 External heat applicators................................................................................... 16
2.2.3 Thermal therapy of bone metastases ...................................................................... 17
2.2.3.1 Palliative ablation of the bone-soft tissue interface ....................................... 17
v
2.2.3.2 Thermal therapy of cancer surrounded by cortical bone ............................. 18
2.2.4 Thermal dosimetry .................................................................................................... 21
2.2.4.1 T notation .......................................................................................................... 22
N
2.2.4.2 Cumulative effective minutes at 43 °C (CEM43) ........................................... 22
2.2.5 Evidence for a thermal dose-response relationship in clinical hyperthermia .. 23
2.2.6 The motivation for developing a method to measure the temperature of red
marrow ................................................................................................................................. 26
2.2.7 Noise, accuracy, and resolution targets for thermal imaging of red marrow .. 27
2.3 Thermal imaging of fatty tissues .................................................................................. 29
2.3.1 Non-Invasive thermal imaging ............................................................................... 30
2.3.2 A physical description of the temperature dependent resonance frequency of
hydrogen-bound protons .................................................................................................. 31
2.3.3 Thermal imaging using the PRF of water .............................................................. 34
2.3.4 Strengths of PRF thermometry ................................................................................ 36
2.3.5 Limitations and weaknesses of PRF thermometry ............................................... 38
2.3.5.1 Magnetic Field Drift ........................................................................................... 38
2.3.5.2 Magnetic susceptibility-related effects ............................................................ 39
2.3.5.3 Motion Artefacts................................................................................................. 42
2.3.5.4 Temperature dependence of tissue conductivity .......................................... 44
2.3.5.5 Presence of other peaks in the spectrum ........................................................ 45
2.3.6 Spectroscopic thermal imaging and referenced thermometry ............................ 46
2.3.6.1 The motivation or spectroscopic thermal imaging ....................................... 46
2.3.6.2 Line Scan Echo-Planar Spectroscopic Imaging .............................................. 47
vi
2.3.7 Limitations of spectroscopic thermal imaging of red bone marrow .................. 49
3. Fat-water intermolecular multiple quantum coherences .................................................. 54
3.1 Intro .................................................................................................................................. 54
3.2 Basics of the density matrix .......................................................................................... 54
3.2.1 Formal definition of the density matrix ................................................................. 55
3.2.2 Time evolution of the density matrix ..................................................................... 58
3.2.3 N-quantum coherences ............................................................................................. 60
3.2.3.1 Single quantum coherences (N=±1) ................................................................. 61
3.2.3.2 Multiple Quantum coherences (N=0,±2) ......................................................... 63
3.2.3.3. The equilibrium density matrix: the starting point for all density matrix
calculations .......................................................................................................................... 65
3.3 Intermolecular dipolar couplings in liquids ............................................................... 68
3.3.1 Dipolar couplings are zero in homogeneous, isotropic media ........................... 68
3.3.2 iZQC-CRAZED - A simple pulse sequence that establishes intermolecular
dipolar couplings in liquids .............................................................................................. 71
3.3.3 Periodically modulated z-magnetization creates a dipolar field that creates
detectable magnetization after iZQC-CRAZED ............................................................. 73
3.4 Coupled spin (density matrix) description of fat-water iMQCs: the HOT pulse
sequence ................................................................................................................................. 76
3.4.1 Case 1: l = 2m .............................................................................................................. 80
3.4.2 Case 2: l = -2n .............................................................................................................. 83
3.4.3 Comparison between the magnetization phase for l=2m and l=-2n ................... 85
3.5 Formation of spin echoes with iMQCs ........................................................................ 86
4. Intermolecular zero quantum coherences enable accurate temperature imaging in red
bone marrow ................................................................................................................................ 89
vii
4.1 Methods ........................................................................................................................... 89
4.1.1 Bone marrow samples .............................................................................................. 89
4.1.2 Imaging console ......................................................................................................... 89
4.1.3 ZQSQ-HOT imaging parameters ............................................................................ 90
4.1.4 Conversion of HOT image phase to iZQC frequency .......................................... 92
4.1.5 ZQSQ-HOT-CSI ......................................................................................................... 93
4.1.6 Point Resolved Spectroscopy (PRESS) ................................................................... 93
4.1.7 Measuring iZQC, fat and water frequencies as a function of temperature ....... 94
4.1.8 Comparison between T -iZQC and T * .................................................................. 95
2 2
4.1.9 Two dimensional spectra of red marrow using HOT .......................................... 96
4.1.10 Propagation of uncertainty in α to uncertainty in T ........................................... 97
4.1.11 Quantification of ZQSQ-HOT temperature precision ........................................ 97
4.2 Results .............................................................................................................................. 98
4.3 Discussion ...................................................................................................................... 107
4.3.1 Accuracy of thermometry in red marrow ............................................................ 107
4.3.2 The potential for absolute thermometry in red marrow .................................... 111
4.3.3 Limitations of ZQSQ-HOT ..................................................................................... 112
4.4 Conclusion ..................................................................................................................... 113
5. MSE-HOT ............................................................................................................................... 114
5.1 Methods ......................................................................................................................... 115
5.1.1 Imaging Console ...................................................................................................... 115
5.1.2 MSE-HOT pulse sequence ...................................................................................... 115
viii
5.1.3 Calculation of phase difference images ................................................................ 118
5.1.4 iZQC signal vs. time ................................................................................................ 118
5.1.5 Weighted echo averaging ....................................................................................... 120
5.1.6 CPMG experiments ................................................................................................. 121
5.1.7 CPMG simulations .................................................................................................. 121
5.1.8 Comparison of precision between SSE- and MSE-HOT .................................... 123
5.1.9 Accuracy determination ......................................................................................... 123
5.1.10 Preparation and Imaging of Emulsions ............................................................. 125
5.2 Results ............................................................................................................................ 125
5.3 Discussion ...................................................................................................................... 134
5.3.1 Precision and Accuracy of MSE-HOT .................................................................. 134
5.3.2 Suppression of J-coupling using MSE encoding ................................................. 135
5.3.3 Factors affecting the accuracy of absolute temperature measurements .......... 138
5.3.4 Difficulties and Limitations of MSE-HOT ........................................................... 140
5.3.5 Alternative applications of MSE-HOT ................................................................. 142
5.5 Conclusion ..................................................................................................................... 143
6. Thermal imaging with MSE-HOT on a clinical scanner .................................................. 144
6.1 Methods ......................................................................................................................... 144
6.1.1 Imaging console and pulse sequence development ........................................... 144
6.1.2 Preparation of Red Marrow Samples ................................................................... 146
6.1.3 HIFU and Imaging setup ........................................................................................ 147
6.1.4 Reconstruction of MSE-HOT images from raw data .......................................... 148
ix
6.1.5 Human Imaging ...................................................................................................... 152
6.2 Results ............................................................................................................................ 152
6.3 Discussion ...................................................................................................................... 158
6.3.1 Challenges with translating MSE-HOT to human scanner ........................... 159
6.3.2 On the RMSD deviation between MSE-HOT and fiberoptic temperature
measurements ................................................................................................................... 161
6.4 Conclusion ..................................................................................................................... 163
7. Summary of MSE-HOT performance ................................................................................. 164
8. Conclusion ............................................................................................................................. 166
References .................................................................................................................................. 167
Biography ................................................................................................................................... 180

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