Temporal Pattern Recognition in Multiparameter ICU

Intensive Care Unit (ICU) patients are physiologically fragile and require vigilant monitoring and support. The myriad of data gathered from biosensors and clinical information systems has created a challenge for clinicians to assimilate and interpret such large volumes of data. Physiologic measurements in the ICU are inherently noisy, multidimensional, and can readily fluctuate in response to therapeutic interventions as well as evolving pathophysiologic states. ICU patient monitoring systems may potentially improve the efficiency, accuracy and timeliness of clinical decision-making in intensive care. However, the aforementioned characteristics of ICU data can pose a significant signal processing and pattern recognition challenge---often leading to false and clinically irrelevant alarms. We have developed a temporal database of several thousand ICU patient records to facilitate research in advanced monitoring systems. The MIMIC-II database includes high-resolution physiologic waveforms such as ECG, blood pressures waveforms, vital sign trends, laboratory data, fluid balance, therapy profiles, and clinical progress notes over each patient's ICU stay. We quantitatively and qualitatively characterize the MIMIC-II database and include examples of clinical studies that can be supported by its unique attributes. We also introduce a novel algorithm for identifying "similar" temporal patterns that may illuminate hidden information in physiologic time series. The discovery of multi-parameter temporal patterns that are predictive of physiologic instability may aid clinicians in optimizing care. In this thesis, we introduce a novel temporal similarity metric based on a transformation of time series data into an intuitive symbolic representation. The symbolic transform is based on a wavelet decomposition to characterize time series dynamics at multiple time scales. The symbolic transformation allows us to utilize classical information retrieval algorithms based on a vector-space model. Our algorithm is capable of assessing the similarity between multi-dimensional time series and is computationally efficient. We utilized our algorithm to identify similar physiologic patterns in hemodynamic time series from ICU patients. The results of this thesis demonstrate that statistical similarities between different patient time series may have meaningful physiologic interpretations in the detection of impending hemodynamic deterioration. Thus, our framework may be of potential use in clinical decision-support systems. As a generalized time series similarity metric, the algorithms that are described have applications in several other domains as well. Thesis Supervisor: Roger G. Mark Title: Distinguished Professor of Health Sciences and Technology Professor of Electrical Engineering and Computer Science Acknowledgments When I first came to MIT, some people told me that it would be a challenging and daunting environment. There have certainly been occasions when times were difficult--but in truth---this experience has been an enjoyable, life-altering, and blissful chapter in my life. As I am writing these acknowledgements, I fully realize that I am a wealthy man. I am wealthy because I have a circle of friends and family that have showered me with their generosity, love, and happiness. Professor Roger Mark has been a mentor, friend, and role model. He taught me a great deal about physiology, clinical medicine, and physiologic signal processing. I feel truly blessed for having met such a wonderful human being. We could just as easily converse about medicine, engineering, religion, politics, and family. His level of compassion for others and passion for educating and mentoring students is unrivaled. I wish him and his family all the joy and blessings that they so richly deserve. Professor Peter Szolovits has been a wonderful research mentor and great teacher. He has injected insightful ideas when I needed them, and gently prodded me forward with his great sense of humor when I may have tended to stagnate. Dr. Bill Long has been a valuable member of my doctoral committee, and has provided me with a great deal of practical advice as I explored different aspects of my thesis. Dr. Danny Talmor and Dr. Atul Malhotra are great colleagues to work with at BIDMC. Their insightful comments were particularly helpful in the clinical studies we developed from the MIMIC-II database. I look forward to many years of collaboration with them. The people at LCP have made my studies at MIT extremely enjoyable. There are few words that can describe my admiration and feelings for Rama Mukkamala. I feel extremely fortunate to know somebody who is so hard-working, creative, passionate, loyal, and sincere. He really brought the word "fun" into LCP. When I start a ten minute phone call with him, it usually ends two hours later because we have so much to discuss. I treasure our close friendship and I am grateful for his support over the years. Wei Zong is a constant professional in all senses of the word. He is unfailing in always providing his colleagues a helping hand. It is rewarding to know somebody who is so talented---yet so humble. I very much enjoyed every minute spent with Wei at MIT, Philips Medical Systems, and the swimming pool! Thomas Heldt has been a great colleague over the years. As my officemate, he was an intelligent, principled, and hard-working peer. Outside of the lab, he has been a loyal and supportive friend. I could always count on him to make sure that I didn't take myself too seriously with his witty zingers. Omar Abdala is a great friend and colleague. I am very proud to know somebody who can combine his level of intellect with a passion for making our greater community a better place. Matt Oefinger was great to have in the lab as a friend and colleague. His great sense of humor, positive outlook, and good nature were an integral part of LCP. Admittedly, I have yet to get over my loss to him in the LCP pizza-eating contest. George Moody has provided me with so much help over the years. As we developed the MIMIC-II database, his experience was invaluable in moving us in the right direction. His passion for facilitating research has helped to sustain LCP over the years. Andrew Reisner's wit, insight, and great sense of humor over the years were a welcome addition to LCP. I am grateful for the many times he taught me some very practical clinical medicine and pearls of wisdom about the dynamics of the medical profession. Sherman is not only a virtuoso of the violin, but also a talented student and kind friend who is great to work with. Professor George Verghese has made extremely valuable contributions to the MIMIC-II project. It is a pleasure to work with such a friendly and insightful individual. Dr. Joseph Frassica has been a valuable mentor for many years. His understanding of ICU medicine and the patient monitoring industry is amazing. Gari Clifford is an English gentleman in every respect. He is helpful to people in the lab and has a great sense of humor. Mauro, Zaid, Li-wei, Isaac, Christine Leu, Anton, Zaid, Dewang, Brian Janz, and Benjamin Moody were all great contributors to LCP and wonderful people to work with. Within the HST community, I have met many wonderful people. Ali Shoeb has been a great friend over the years. His exuberance for learning and positive attitude with respect to every activity he engages in serves as a great example of the model student. His energetic personality makes every conversation with him enjoyable and truly memorable. I first knew Lucia Madariaga as my team member in HST anatomy, and now I know her as my friend. Through the many enjoyable walks between Harvard and MIT, I came to appreciate and respect her spirituality, intelligence, and genuine kindness. I have known Nick Houstis since high school in Indiana. His great sense of humor, loyalty to his friends, and absolute brilliance make him one of the most amazing people I have ever met. Ray "L" Chan has been a great friend over the years. His unforgettable laughter and good nature always brightened my days. His positive outlook on life is an example I strive for. Quite possibly, Ying Zhang takes the title as the world's most considerate person. I remember when we had offices next to one another at Philips, she would bring me a glass of water when she heard the slightest cough out of me. You would think that somebody as kind as her is too good to be true---but she is for real! I have had the pleasure of knowing some truly gifted and wonderful people in EECS over the years. It has been an honor to know Professor Paul Gray at MIT. I enjoyed being his TA in circuit class. He was always available to render his wealth of invaluable advice to me when I needed it. It was also a pleasure serve as a TA under Professors Art Smith, Jacob White, and Jeff Lang. In the many environments I have worked in, there were always capable people making sure I didn't stray too far off the path. Marilyn Pierce of EECS at MIT was always there for any questions I had about registration, graduation, and institute policies. Patty and Linda have been so helpful over the years at the HST office. At LCP, Ken has been extremely helpful anytime I needed his expertise in document processing or filling out obscure forms. Karen at Philips was always available to help me in every thing I did when all hope seemed lost! Professor Rick Mitchell at HST has always been a great leader and advisor for me and countless other students. The first month I came to MIT as a na'ive twenty one year-old kid from Indiana, I felt out of place and longed for the comforts of home and my family. While my dorm was next to a nuclear reactor, by the grace of God, my next door neighbor happened to be Gassan AlKibsi. Since I have known him, he has been my truest friend and brother. He has been an unfailing source of support, comfort, inspiration, and optimism. Whenever I feel challenged by a situation professionally or socially, I think about how Gassan would handle it, and the answer usually presents itself. We may now be physically separated by 8000 miles, but I feel his presence in my heart everyday. Ayman Shabra is too humble of a person for even allowing me to praise him. He is the epitome of gentleness, sincerity, and thoughtfulness. Whenever I have needed his help, he has been there. For the kindness that he has shown me and his wisdom that has enlightened me, I will be in his debt for the rest of my life. Babak Ayazifar has been in every respect an older brother that I can count on for moral support, professional and spiritual guidance, and his witty sense of humor. He has shaken me when I needed shaking, and calmed me when I needed calming. The pilgrimage we made to Mecca together will always be special because he was there with me. He and his wife Sara will always be dear friends. Belal Helal has a unique ability to brighten the room with his smile. He has been a wonderful example of a man who combines intellect, loyalty to family and friends, and glowing spirituality that shines on all those who know him. The many family parties we have had over the years with Belal and his wife, Sarah, and their wonderful children have made our lives at MIT more enjoyable. Jalal Khan has always been a great role-model as a man who excels professionally while having an untiring commitment to his family and friends. I feel fortunate that such a good person is part of my life every time he calls me on the phone just to say "hi!" Every time I finish a long swim, I remember the countless hours Jalal spent in the children's pool teaching this overgrown kid how to swim with the care and patience that only he possesses. Jalal and his wife, Elie, have been pillars among our community of friends. Kashif Khan has impacted me in innumerable ways. His style of questioning and searching for the truth ---in science or religion--should be made into a course for every truth seeker to enroll in. His remarkable gift of always seeing the good in people while forgiving their shortcomings enriched our circle of friends. As my close friend, I feel his positive impact every day of my life. Kashif and his wife, Marilene, enriched all our lives. Milton (and Nausheen), Naim (and Rani), Asif (and Zaregul), Ali Merchant (and Soraya) are all dear friends that made life in Boston so enjoyable for me and my family over the years. I am humbled by how generous they have always been to us. Their friendship is a gift from the Almighty. I am grateful to Reem Al-Hashimy for the kindness she has shown to my wife and me, and the valuable insight she has given me about the importance of showing compassion to patients and their families. I will never forget the great friends I made when I was studying at Purdue University. Hasan and Haydar Syed, and Gautham Nayak have always been great friends to me. Larry Nielsen has been a great mentor for me at Philips. His has been a constant advocate for my research at Philips, and he always encouraged me to take risks and pursue my goals to the fullest extent. I have learnt a great deal from him about the practical challenges in patient monitoring as well as benefited from his wisdom in dealing with people. Greg Raber put in so much of his time to write the software that has enabled us to create the MIMIC-II database. Simply put, this work would not have been possible without him. It is a pleasure to work with such a talented engineer who is fun-loving, passionate about his work and a real maverick who gets things done. Jesus Santana and Mike Bortonne helped me every step of the way as I tried to validate the MIMIC-II system at Philips before I could use it in the hospital. Carol Russell and Steve Weisner were quite generous in supporting my research activities and academic pursuits of the many years at Philips. There are many other people that I have learnt a great deal from over the years at Philips and I thank them all: Andres Aguirre, Walid Ali, Larry Eshelman, Joanne Foster, Scott Kresge, John Wang, and Dale Wiggins. Ten years ago I married Wejdan---the love of my life. She has supported me in every endeavor I have set forth on. She is my wife, the mother of my children, and my best friend. Every day as I arrive back from work, she has filled our home with joy and happiness. She has given up so much so that I could complete my MD-PhD over the past ten years. It will take me the next 100 years to recompense her unselfishness and compassion. My daughter, Fatima, and son, Hasan, are the joys of my life. One hug from them and any worry that I have quickly vanishes. My brother Ali is the greatest brother anybody could dream for. He is gentle, unselfish, loyal, and supportive to the greatest extremes. He has been like a second father for my children and the backbone of our extended family. He is my friend, confidant, and ally. I cannot say anything else that would do him justice. The last year that he has been here at MIT has made this the most enjoyable year I could imagine. My sisters, Huda, Ziena, and Zainab have always been a source of support and love even as I studied far from home. I feel so blessed that my children will grow up having such wonderful aunts. MIT provided me with an education---but more importantly---I was blessed with a dear brother in Ihsan Djomehri. The purity and sincerity of Ihsan's heart provides me with great comfort. He has all the qualities I could ever ask for in a brother for me, husband for my sister, and uncle for my children. He has been so unselfish in showering me with his love and kindness. In short, he has been an angel. My brother-in-law Ridha has always been an older brother I could count on for support, wisdom, and love. My brother-in-law Issa has always been kind to me. I am particularly grateful for the great journey to Mecca we took together. The love and support my mother, Khaola Saeed, has always provided me is something I can never measure because it simply has no bounds. Her prayers and supplications have sustained me. She had devoted her entire life to comforting her children. Everything that I have ever accomplished is due to her struggles to care for me whenever I have needed her. My father, Mahdi Saeed is my hero. He left a war-torn country and obtained a doctoral degree and helped to raise five children at the same time. He was deeply involved in our education from childhood through college. He provided me with guidance whenever I sought it out, and he comforted me when I was at my weakest. When I was sick with the chicken pox as a young child, he slept in the same small cramped room to comfort me for a week. When I had a major surgery, he flew to Boston for several weeks to be my cook, cleaner, and comforter. Finally, I thank God for the many blessings He has given me and my family. I submit myself to Him, and seek His mercy. I ask that He protects me and my loved ones and increases my knowledge so that I can better serve mankind.