Monitoring and Analysis of Hemodynamic Response to Cold Noxious Stimuli
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Monitoring and Analysis of Hemodynamic Response to Cold Noxious Stimuli Using Functional Near Infrared Spectroscopy A Thesis Submitted to the Faculty of Drexel University by Zeinab Barati In partial fulfillment of the requirements for the degree of Doctor of Philosophy July 2013 © Copyright 2013 Zeinab Barati. All Rights Reserved. i Dedications To my beloved parents for their unconditional love and support And to my husband for his love, patience, and encouragement ii Acknowledgements I would like to first thank my supervisor Dr. Kambiz Pourrezaei for his guidance and support in the course of completing this research. It was a great honor to work under his supervision. His support was far beyond supervising a research project. I learned life- lasting lessons through his thoughtful critiques and recommendations that will undoubtedly help me in my future career. I would like to extend my gratitude to my co-adviser Dr. Issa Zakeri who generously devoted his time educating me on advanced statistical techniques and supervised the data analyses. I am also thankful to Dr. Patricia Shewokis for her guidance in the statistical analysis during the first couple of years of this PhD research. I also thank the committee members Dr. Arye Rosen, Dr. Joshua Jacobs, and Dr. John Grothusen for their time and effort to serve on my committee and review my dissertation. I am very thankful to our lab‟s faculty members Dr. Meltem Izzetoglu and Dr. Hasan Ayaz for their help and guidance with signal processing and hardware. I also would like to thank my lab colleagues Rutvi Vyas, Kang Hee Lee, Daryl Omire- Mayor, and Esther Lim for their help in hardware and experimentation and more importantly, making the long hours of lab work much easier and enjoyable. iii I would like to appreciate all of my friends who supported me emotionally during my graduate studies in Philadelphia. My very special thanks go to Marjan Saboktakin, Saba Borujerdi, Zahra Javaheri, Sedigheh Banihashemi, Somayeh Yousefi, Shokouh Pourarian and all my friends at Mahdieh community. I would like to appreciate the financial support from the School of Biomedical Engineering, Science, and Health Systems and especially, I would like to thank Dr. Banu Onaral for her support and guidance. And at the end, I am very thankful to my family and specially my husband for their encouragement and love. iv Table of Contents List of Tables ________________________________________________________________ vii List of Figures _______________________________________________________________ viii ABSTRACT _________________________________________________________________ xiii CHAPTER 1: INTRODUCTION _________________________________________________ 1 1.1. Background __________________________________________________________ 1 1.2. Problem Statement _____________________________________________________ 5 1.3. Objectives ___________________________________________________________ 6 1.4. Specific Aims and Research Hypotheses ____________________________________ 6 1.5. Significance __________________________________________________________ 7 1.6. Outline ______________________________________________________________ 8 CHAPTER 2: HEMODYNAMIC RESPONSE TO REPEATED NOXIOUS COLD PRESSOR TESTS MEASURED BY FUNCTIONAL NEAR INFRARED SPECTROSCOPY ON FOREHEAD _________________________________________________________________ 9 2.1. Abstract _____________________________________________________________ 9 2.2. Introduction _________________________________________________________ 10 2.3. Materials and Methods _________________________________________________ 13 2.3.1 fNIRS Principles and Instrumentation _________________________________ 13 2.3.2 Subjects ________________________________________________________ 15 2.3.3 Protocol ________________________________________________________ 16 2.3.4 fNIR Data Processing _____________________________________________ 18 2.4. Results _______________________________________________________________ 19 2.4.1. The effect of a CPT on the THb concentration __________________________ 21 2.4.2. Adaptation to repeated CPTs observable in subjective pain ratings and THb ___ 24 v 2.4.3. Correlation analysis between ΔTHb and subjective pain scores _____________ 30 2.4.4. Comparing ΔTHb response at the „far channels‟ with the „near channels‟ across left and right sides of the forehead ____________________________________________ 30 2.5. Discussion __________________________________________________________ 33 2.6. Acknowledgement ____________________________________________________ 37 CHAPTER 3: FUNCTIONAL DATA ANALYSIS VIEW OF FNIRS DATA _____________ 38 3.1. Abstract ____________________________________________________________ 38 3.2. Introduction _________________________________________________________ 39 3.3. Materials and Methods _________________________________________________ 43 3.3.1. Participants ______________________________________________________ 43 3.3.2. Protocol ________________________________________________________ 43 3.3.3. Measurements ___________________________________________________ 44 3.3.4. Functional Data Analysis ___________________________________________ 45 3.4. Results _____________________________________________________________ 50 3.4.1. fNIR Data Pre-processing __________________________________________ 50 3.4.2. Results of fPCA __________________________________________________ 54 3.4.3. Rotating PCs ____________________________________________________ 58 3.4.4. Results of fCCA __________________________________________________ 62 3.5. Discussion __________________________________________________________ 64 3.6. Acknowledgment _____________________________________________________ 69 CHAPTER 4: HEMODYNAMIC RESPONSE TO COLD TOLERANCE TESTS AT DIFFERENT TEMPERATURES ________________________________________________ 70 4.1. Introduction _________________________________________________________ 70 4.2. Methods ____________________________________________________________ 71 4.2.1. Subjects ________________________________________________________ 71 4.2.2. Instrument ______________________________________________________ 72 vi 4.2.3. Protocol ________________________________________________________ 72 4.2.4. Features ________________________________________________________ 73 4.2.5. Statistical Data Analysis ___________________________________________ 74 4.3. Results _____________________________________________________________ 80 4.3.1. Analysis of maximum reported pain, pain threshold and pain tolerance _______ 80 4.3.2. Statistical Analysis of Hb and HbO2 __________________________________ 84 4.4. Discussion _________________________________________________________ 103 4.5. Conclusion ___________________________________________________________ 106 CHAPTER 5: SUMMARY, FUTURE WORK, AND CLINICAL APPLICATIONS _______ 108 5.1. Summary __________________________________________________________ 108 5.2. Future work ________________________________________________________ 110 5.3. Clinical Applications _________________________________________________ 111 List of References ___________________________________________________________ 113 VITA _____________________________________________________________________ 123 vii List of Tables 1. Results of repeated measures ANOVA on THb during the four experimental conditions: baseline, pre-stimulus, stimulus, and post-stimulus conditions……………..22 2. Pairwise condition comparisons across the Forehead Side and Channel including 95% confidence intervals and effect sizes for THb , comparing the four conditions: the baseline, 1st pre-stimulus, 1st stimulus, and 1st post-stimulus conditions…………....…23 3. Main effect of cold pressor test (CPT) trials repeated measures ANOVAs on THb ……………………………………………………………………………………...26 4. Pairwise cold pressor test (CPT) trials comparisons across the Forehead Side and Channel including 95% confidence intervals and effect sizes for THb …………………27 5. Within-subjects correlation values between self-reported pain rating scores and ΔTHb……………………………………………………………………………………..30 6. Pairwise channel pair comparisons across cold pressor test (CPT) trials including 95% confidence intervals and effect sizes for ΔTHb………………………………………….32 7. Regression Coefficients……………………………………………………..………...83 8. Type III tests of model covariates for the dependent variable delta_Hb………..…….88 9. Type III tests of model covariates for the dependent variable delta_HbO2…………..93 10. Type III tests of model covariates for the dependent variable MV……………….....98 11. Type III tests of model covariates for the dependent variable MA………………...102 viii List of Figures 1. A schematic of the fNIRS probe configuration. Photons travel from a light source to a photodetector through a banana shape pathway with a penetration depth of half the source-detector distance. Measures are approximate…………………………...………..15 2. A demonstration of the placement of fNIRS probes on a subject‟s forehead. The probes are shown reversed to illustrate the location of the light source and photodetectors……………………………………………………………………………17 3. Block diagram of the protocol…………………………………………………...……17 4A-B. The hemodynamic response to three trials of cold pressor test (CPT) averaged across 20 subjects on the right (a) and left (b) sides of the forehead. The black vertical lines represent time points at which subjects switched their hand from the tepid water to the ice water and vice versa. The pink shaded field represents the baseline period, the orange shaded fields represent the immersion