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Neurophotonics
and
Brain Mapping
Endorsements
Society for Brain Mapping & Therapeutics (SBMT)
Brain Mapping Foundation (BMF)
National Center for NanoBioElectronics (NCNBE)
Western University of Health Science College of Optometry
California Neurosurgical Institute (CNI)
California Institute of Neuroscience (CIN)
MISSION STATEMENTS
Society for Brain Mapping & Therapeutics Mission Statement

The Society for Brain Mapping & Therapeutics is a nonprofit society organized for the purpose of
encouraging basic and clinical scientists who are interested in the areas of brain mapping, engineer-
ing, stem cell, nanotechnology, imaging, and medical device to improve the diagnosis, treatment,
and rehabilitation of patients afflicted with neurological disorders.
This society promotes the public welfare and improves patient care through the translation of new
technologies/therapies into life-saving diagnostic and therapeutic procedures. The society is com-
mitted to excellence in education and scientific discovery. The society achieves its mission through
multidisciplinary collaborations with government agencies, patient advocacy groups, educational
institutes, and industries, as well as philanthropic organizations.
Brain Mapping Foundation Mission Statement

Brain Mapping Foundation (BMF) is a nonprofit 501c3 charitable organization, which is estab-
lished for the purpose of facilitating multidisciplinary brain and spinal cord research and expedit-
ing integration and translation of cutting-edge technologies into the field of neuroscience. BMF
is focused on translating state-of-the-art technologies from space and defense industries into neu-
roscience in order to bring the most advanced medicine to wounded warriors as well as civilians.
National Center for NanoBioElectronics Mission Statement

The National Center for NanoBioElectronics’s (NCNBE) mission is to establish collaborating research
laboratories and network throughout California and beyond in order to rapidly develop solutions for
neurological disorders employing advances in nanotechnology, stem cell research, and medical devices
(nanobioelectronics) while fostering biotech spin-offs for the purpose of job creation.
The NCNBE promotes public welfare and improves patient care through the translation of new
technologies into life-saving diagnostic and therapeutic procedures. The center is committed to
excellence in education and scientific discovery. The NCNBE achieves its mission through multi-
disciplinary collaborations/consortium with government agencies, patient advocacy groups, educa-
tional institutions, private sector, industries, and philanthropic organizations.
iii
Western University of Health Science College of Optometry Mission Statement
The Western University of Health Science College of Optometry’s mission is to graduate caring
and compassionate healthcare professionals who serve the need of diverse global society. The col-
lege emphasizes the rehabilitation of visual system, neuro-optometry, and interprofessional educa-
tion. The college advances the profession of optometry through innovation in healthcare education,
research, and patient care.
California Neurosurgical Institute Mission Statement

California Neurosurgical Institute is the preeminent neurosurgical practice in Los Angeles, serving
the greater part of the Los Angeles, Ventura, and Kern Counties, providing the quality neurosurgical
care to four million individuals.
Its mission is to provide the highest quality neurosurgical care to patients in their own communi-
ties by working closely with physicians in their communities and their local hospitals. The institute
strives to accomplish this by translating and integrating advances in science and technology into
people’s daily clinical practice. As an “academic department without walls,” the institute’s neuro-
surgeons have subspecialty training and interests that allow people to manage the full spectrum of
neurosurgical diseases and treatments while orienting themselves toward elevating the field through
basic science and clinical research efforts and collaborations.
California Institute of Neuroscience Mission Statement

California Institute of Neuroscience’s mission is to provide state-of-the-art diagnostics and treatment
of neurological and neurosurgical diseases and conditions involving the brain, spine, and peripheral
nerves as well as perform research and developments in the aforementioned areas.
Neurophotonics
and
Brain Mapping
Edited by
Yu Chen
Associate Professor and Associate Chair, Director of Graduate Studies, Fischell
Department of Bioengineering, Fellow of American Society for Laser Medicine
and Surgery, University of Maryland School of Engineering, College Park,
Maryland
Babak Kateb
Scientific Director and Chief Strategy Officer, California Neurosurgical Institute;
Chairman of the Board and CEO of Society for Brain Mapping and Therapeutics
(SBMT); President of Brain Mapping Foundation; Director of National Center
for NanobioElectronics (NCNBE); Director of National Brain Innovation
and Technology Park (NBITP); 8159 Santa Monica Blvd, Suite # 200, West
Hollywood, California 90046
CRC Press
Taylor & Francis Group
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© 2017 by Taylor & Francis Group, LLC

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No claim to original U.S. Government works
Printed on acid-free paper
International Standard Book Number-13: 978-1-4822-3685-9 (Hardback)
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Library of Congress Cataloging‑in‑Publication Data
Names: Chen, Yu, 1973 December 28- editor. | Kateb, Babak, editor.
Title: Neurophotonics and brain mapping / [edited by] Yu Chen & Babak Kateb.
Description: Boca Raton : Taylor & Francis, 2017. | Includes bibliographical
references and index.
Identifiers: LCCN 2016040650 | ISBN 9781482236859 (hardback : alk. paper)
Subjects: | MESH: Brain Mapping--methods | Optical Phenomena |
Neurosurgery--methods | Spectroscopy, Near-Infrared
Classification: LCC RC386.6.B7 | NLM WL 335 | DDC 612.82--dc23
LC record available at https://lccn.loc.gov/2016040650
Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com
and the CRC Press Web site at

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Dedication
This work is dedicated to our families, friends, spouse,

students, colleagues, and mentors.
This book is dedicated to Dr. Babak Kateb’s mentor, Ferenc A. Jolesz,
MD. Dr. Jolesz was B. Leonard Holman professor of radiology in Brigham
and Women’s Hospital at Harvard Medical School, recipient of 2005 Pioneer
in Medicine Award by the Society for Brain Mapping & Therapeutics.
Dr. Jolesz served as the second president of the society from 2004 to 2005.
Dr. Anna Jolesz, Dr. Ferenc Jolesz, and Dr. Babak Kateb in 2004
during the first annual meeting of Society for Brain Mapping
& Therapeutics, Westin Hotel, Pasadena, California.
This book is also dedicated to Dr. Yu Chen’s mentor, Professor Britton
Chance (1913–2010), who was a pioneer in neurophotonics and brain
mapping, for his innovation and discovery in research and his mentoring
and training of generations of scientists in this exciting field. Dr. Chance
was Eldridge Reeves Johnson University professor emeritus of biochemistry
and biophysics as well as professor emeritus of physical chemistry and
radiological physics at the University of Pennsylvania School of Medicine.
Dr. Yu Chen and Dr. Britton Chance

Contents
Preface..............................................................................................................................................xiii
Contributors......................................................................................................................................xv
Chapter 1 History of Brain Mapping and Neurophotonics: From Technological

Discoveries to Brain Initiatives.....................................................................................1
Babak Kateb, Frank Boehm, Alexandra Jalali, Vassiliy Tsytsarev,
Vicky Yamamoto, Bahram Jalali, Derek Backer, Brian Pikul, Parham Yashar,
and Yu Chen
Section I Optical Spectroscopy and Spectral Imaging of Brain
Chapter 2 Pain Assessment Using Near-Infrared Spectroscopy..................................................21

Kambiz Pourrezaei, Ahmad Pourshoghi, Zeinab Barati, and Issa Zakeri
Chapter 3 Application of Functional Near-Infrared Spectroscopy in Brain Mapping.................41

Afrouz Azari-Anderson, Fatima A. Chowdhry, Yasaman Ardeshirpour,
Nader Shahni Karamzadeh, Elizabeth G. Smith, Viktor Chernomordik,
and Amir H. Gandjbakhche
Chapter 4 Therapeutic Monitoring of Children with Attention Deficit Hyperactivity

Disorder Using fNIRS Assessment.............................................................................57
Yukifumi Monden
Chapter 5 Functional Near-Infrared Spectroscopy: In Search of the Fast Optical Signal...........77

Carlos G. Treviño-Palacios, Karla J. Sanchez-Perez, Javier Herrera-Vega,
Felipe Orihuela-Espina, Luis Enrique Sucar, Oscar Javier Zapata-Nava,
Francisco F. De-Miguel, Guillermo Hernández-Mendoza,
Paola Ballesteros-Zebadua, Javier Franco-Perez, and Miguel Ángel Celis-López
Chapter 6 Voltage-Sensitive Dye and Intrinsic Signal Optical Imaging: Advantages

and Disadvantages for Functional Brain Mapping....................................................101
Vassiliy Tsytsarev and Reha S. Erzurumlu
Chapter 7 Optical Techniques to Study Drug-Induced Neurovascular and Cellular

Changes In Vivo.........................................................................................................117
Congwu Du and Yingtian Pan
ix
x Contents
Section II B
rain Imaging and Mapping
from Micro to Macroscales
Chapter 8 Three-Dimensional Optical Coherence Microscopy Angiography and Mapping

of Angio-Architecture in the Central Nervous System.............................................141
Conor Leahy and Vivek J. Srinivasan
Chapter 9 Doppler Optical Coherence Tomography and Its Application in Measurement

of Cerebral Blood Flow.............................................................................................159
Zhongping Chen and Jiang Zhu
Chapter 10 Brain Imaging and Mapping with Multi-Contrast Optical Coherence Tomography.....177
Hui Wang and Taner Akkin
Chapter 11 Advanced Optical Imaging in the Study of Acute and Chronic Response
to Implanted Neural Interfaces..................................................................................203
Cristin G. Welle and Daniel X. Hammer
Chapter 12 Photoacoustic Neuroimaging....................................................................................235

Lihong V. Wang, Jun Xia, and Junjie Yao
Chapter 13 Perfusion Brain Mapping in the Treatment of Acute Stroke.....................................257

Michael J. Alexander and Paula Eboli
Chapter 14 Mapping the Injured Brain: Structure and Function Following Traumatic Brain Injury.......273
Chandler Sours, Jiachen Zhuo, and Rao P. Gullapalli
Section III Intraoperative Neuroimaging
Chapter 15 UV-Based Imaging Technologies for Intraoperative Brain Mapping........................299

Babak Kateb, Frank Boehm, Ray Chu, Sam Chang, Keith Black, and Shouleh Nikzad
Chapter 16 Visible Light Optical Imaging and Spectroscopy during Neurosurgery...................311

Sameer Allahabadi, Caroline Jia, and Neal Prakash
Chapter 17 Intraoperative Infrared Optical Imaging in Neurosurgery.........................................325

Michael E. Wolf, Richard P. Menger, Osama Ahmed, Shahdad Sherkat,
and Babak Kateb
Chapter 18 Autofluorescence-Guided Resection of Intracranial Tumor: Past, Present, and Future.......341

Fartash Vasefi, Zhaojun Nie, David S. Kittle, Chirag G. Patil, and Pramod Butte
Contents xi
Chapter 19 Spectro-Temporal Autofluorescence Contrast–Based Imaging for Brain Tumor

Margin Detection and Biobanking............................................................................355
Asael Papour, Zach Taylor, Linda Liau, William H. Yong, Oscar Stafsudd,
and Warren Grundfest
Chapter 20 Optical Coherence Tomography and Quantitative Optical Imaging of Brain Cancer..... 369
Carmen Kut, Jordina Rincon-Torroella, Alfredo Quinones-Hinojosa, and Xingde Li
Chapter 21 Intraoperative Optical Guidance for Neurosurgery...................................................383

Chia-Pin Liang, Cha-Min Tang, and Yu Chen
Section IV Image-Guided Intervention and Phototherapy

Chapter 22 Impact of Retinal Stimulation on Neuromodulation.................................................411
Deborah Zelinsky
Chapter 23 FUS-Mediated Image-Guided Neuromodulation of the Brain..................................443

Seung-Schik Yoo, Wonhye Lee, and Ferenc A. Jolesz
Chapter 24 Advances in Portable Neuroimaging and Their Effect on Novel Therapies.............457

Eric M. Bailey, Ibrahim Bechwati, Sonal Ambwani, Matthew Dickman,
Joseph Fonte, and Geethika Weliwitigoda
Chapter 25 The Deep Brain Connectome....................................................................................479

Ifije E. Ohiorhenuan, Vance L. Fredrickson, and Mark A. Liker
Chapter 26 Neurovascular Photonics...........................................................................................487

Nimer Adeeb, Babak Kateb, Salman Abbasi Fard, and Martin M. Mortazavi
Chapter 27 Neurophotonics for Peripheral Nerves......................................................................499

Ashfaq Ahmed, Yuqiang Bai, Jessica C. Ramella-Roman, and Ranu Jung
Chapter 28 EEG Biomarkers in Depression................................................................................513

Nevzat Tarhan, Fatma Zehra Keskin Krzan, Merve Çebi, Şehadet Ekmen,
Türker Ergüzel, Serhat Özekes, Baris Ünsalver, and Cumhur Taş
Chapter 29 fMRI as a Biomarker in Neuroimaging.....................................................................525

Asimina Lazaridou, Babak Kateb, and A. Aria Tzika
Chapter 30 Single-Neuron Recordings from Depth Electrodes with Embedded Microwires

in Epilepsy Patients: Techniques and Examples.......................................................537
Ueli Rutishauser and Adam N. Mamelak
Index...............................................................................................................................................551
Preface
Using light to determine the function of brain and malfunction of neurological diseases has been
a dream for scientists, but recent advances in bio-optics and neuroscience, imaging, and medical
devices have made such dream a reality. We have also covered advanced brain mapping techniques
and applications of such technologies in this book because neurophotonics itself is defined as the
application of optical physics for studying neuronal structures and functions for the purpose of bet-
ter understanding of the nervous system, which is inherently part of the larger and more advanced
field of brain mapping and therapeutics.
The capability to noninvasively image cells, proteins, genes, molecules, and nanoparticles for
their function and therapeutic applications is no longer a science fiction. Today, we use such tech-
nologies in the diagnosis and treatment of neurological disorders such as traumatic brain injury,
epilepsy, Alzheimer’s disease, and brain cancer. However, rapid integration, translation, and com-
mercialization of such technologies from physical sciences into clinical neuroscience/neurology/
neurosurgery and psychiatry meet many challenges from proper grant funding to proper regulatory
reviews by the Food and Drug Administration (FDA). This gap between deep understanding of sci-
entific concepts to new generation of devices and optogenetic drugs could be addressed by closer
interaction between academic scientists, clinicians, industries, and government agencies, which
could bridge the gap of knowledge between disciplines in biology, physical sciences, and medicine.
Neurophotonic is still a young and developing field with great promises for helping scientists
to track cells/genes/molecules, study their functions, and modify cellular behavior. In recent years,
we have witnessed an amazing level of scientific innovation and discovery emerging from the
integration of neurophotonics, nanotechnology, imaging devices, artificial intelligence, supercom-
puting, and cellular and stem cell therapy into “nanobioelectronics.” In this book, we have attempted
to highlight at least a few of such remarkable scientific progress in the field of neurophotonics. We
strongly believe that neurophotonics, nanoneuroscience, nanoneurosurgery, and nanobioelectronics
will revolutionize medicine and remarkably improve the prevention, diagnosis, and treatment of
neurological disorders over the next 10–20 years. In our lifetime, we will see “Internet of things”
include cellular, genomic, and molecular tracking.
Careful regulation of neurophotonic techniques, application, and ethics will ensure a healthy
development of the field, which in turn could help scientists validate the accuracy of diagnostic tests
and verify the safety and efficacy of therapies that utilize neurophotonics, including drugs, devices,
cellular therapy, and their combinations. In this book, we have tried our best to make sure such top-
ics are covered in the context of each neurophotonic technology and its application.
Thus, this book is a fine review of the latest technologies, application, and regulatory guidelines
as well as policies in the young and emerging field of neurophotonics and its correlative application
in brain mapping and therapeutics. This book is a collective teamwork among more than 100 world-
renowned scientists who have contributed 30 chapters in neurophotonic and brain mapping with
more than 2000 references. This broad coverage of neurophotonic and brain mapping technologies
and applications in diverse areas of neuroscience, neurosurgery, neuroradiology, and neurology and
the role of FDA regulation and healthcare policy provides a foundation to support and impact the
future of personalized targeted therapy of neurological disorders.
This textbook is devoted to implementing new approaches to perform less radical procedures
(surgical and nonsurgical), eventually leading to approaches with minimal or no invasiveness to treat
nervous system disorders, including brain tumors, brain and spinal cord injuries, vascular malfor-
mations, Alzheimer’s disease, and Parkinson’s disease. We hope that this book provides scientists
and physicians with helpful references as they devise successful treatments for these neurological
disorders.
xiii
xiv Preface
We thank all the contributors for their scientific contributions to this remarkable textbook. We
appreciate the visionary support of CRC/Taylor & Francis Group. Without their support, this book
would not have been possible. We thank the Brain Mapping Foundation, the National Center for
NanoBioElectronics, and the Society for Brain Mapping & Therapeutics, California Neurosurgical
Institute, the Western University School of Optometry, and California Institute for Neuroscience for
their generous support and endorsement of this truly unique book.
Finally, we thank our parents, Jabbar Kateb and Maleheh Samsame-Shirzad, and Li Chen and
Yaoshen Wu, for their years of support and personal guidance. We thank Lance Wobus (senior
editor), Jo Koster (publisher), Randy Brehm (senior editor), Laurie Oknowsky (production coor-
dinator), Robert Sims (project editor), S. Valantina Jessie (project manager), and Amanda Parida
(editorial assistant) for their tremendous support.
We trust that readers will take the ideas and methods described in this textbook to formulate novel
and more effective treatments of presently incurable diseases.
Respectfully yours,
Yu Chen
Babak Kateb
MATLAB® is a registered trademark of The MathWorks, Inc. For product information, please
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Contributors
Nimer Adeeb Afrouz Azari-Anderson
Department of Neurosurgery Section on Analytical and Functional
California Institute of Neuroscience Biophotonics
Thousand Oaks, California National Institutes of Child Health and Human
Development
Ashfaq Ahmed National Institutes of Health
Department of Biomedical Engineering Bethesda, Maryland
Florida International University
Miami, Florida Derek Backer
California Neurosurgical Institute
Osama Ahmed Valencia, California
Department of Neurosurgery
Louisiana State University of Health Sciences Yuqiang Bai
Shreveport, Louisiana Department of Biomedical Engineering
Taner Akkin Miami, Florida
Department of Biomedical Engineering
University of Minnesota
Eric M. Bailey
Minneapolis, Minnesota
NeuroLogica Corporation
Danvers, Massachusetts
Michael J. Alexander
Paola Ballesteros-Zebadua
Cedars-Sinai Medical Center
Medical Physics Laboratory
Los Angeles, California
National Institute of Neurology and
Neurosurgery
Sameer Allahabadi México City, Mexico
Rice University
Division of Neurology
City of Hope National Medical Center Zeinab Barati
Houston, Texas Institute of Arctic Biology
University of Alaska
Fairbanks, Alaska
Sonal Ambwani
St. Jude Medical
Westford, Massachusetts Ibrahim Bechwati
Samsung USA
Danvers, Massachusetts
Yasaman Ardeshirpour
Section on Analytical and Functional
Biophotonics Keith Black
National Institutes of Child Health and Human Department of Neurosurgery
Development Maxin Dunitz Neurosurgical Institute
National Institutes of Health Cedars-Sinai Medical Center
Bethesda, Maryland Beverly Hills, California
xv
xvi Contributors
Frank Boehm Fatima A. Chowdhry

Society for Brain Mapping & Therapeutics Section on Analytical and Functional
and Biophotonics
Brain Mapping Foundation National Institutes of Child Health and Human
West Hollywood, California Development
National Institutes of Health
Pramod Butte Bethesda, Maryland
Cedars-Sinai Medical Center Ray Chu
Los Angeles, California Department of Neurosurgery
Merve Çebi Beverly Hills, California
Department of Psychology
Uskudar University Francisco F. De-Miguel
İstanbul, Turkey Cellular Physiology Institute
Universidad Nacional Autónoma de
Miguel Ángel Celis-López México
Clinical Neurology and Neurosurgery Mexican Autonomous National
Department University
National Institute of Neurology México City, Mexico
and Neurosurgery
México City, Mexico Matthew Dickman
Oculus VR
Sam Chang Menlo Park, California
NASA/Jet Propulsion Laboratory
California Institute of Technology Congwu Du
Pasadena, California Department of Biomedical Engineering
Stony Brook University
Yu Chen
Stony Brook, New York
Fiscehll Department of Bioengineering
University of Maryland
Paula Eboli
College Park, Maryland
and Cedars-Sinai Medical Center
Society for Brain Mapping & Therapeutics Los Angeles, California
and
Brain Mapping Foundation Şehadet Ekmen
West Hollywood, California Department of Psychology
Uskudar University
Zhongping Chen İstanbul, Turkey
Beckman Laser Institute
Department of Biomedical Engineering Türker Ergüzel
University of California Department of Computer Engineering
Irvine, California Uskudar University
İstanbul, Turkey
Viktor Chernomordik
Section on Analytical and Functional Reha S. Erzurumlu
Biophotonics Department of Anatomy
National Institutes of Child Health and Human and Neurobiology
Development University of Maryland School
National Institutes of Health of Medicine
Bethesda, Maryland Baltimore, Maryland
Contributors xvii
Salman Abbasi Fard Javier Herrera-Vega

Department of Neurosurgery Department of Computer Science
California Institute of Neuroscience Instituto Nacional de Astrofísica, Óptica y
National Institute of Neurology Electrónica
and Neurosurgery National Institute for Astrophysics, Optics
Thousand Oaks, California and Electronics
Puebla, Mexico
Joseph Fonte
NeuroLogica Corporation Alexandra Jalali
Danvers, Massachusetts Society for Brain Mapping & Therapeutics
and
Javier Franco-Perez Brain Mapping Foundation
Reticular Formation Laboratory West Hollywood, California
National Institute of Neurology and Neurosurgery
and
México City, Mexico
Brentwood School
Vance L. Fredrickson Los Angeles, California
University of Southern California Bahram Jalali
Los Angeles, California School of Engineering
University of California, Los Angeles
Amir H. Gandjbakhche Los Angeles, California
Section on Analytical and Functional and
Biophotonics
Society for Brain Mapping & Therapeutics
Eunice Kennedy Shriver National Institutes
and
of Child Health and Human Development
Brain Mapping Foundation
National Institutes of Health
West Hollywood, California
Bethesda, Maryland
Warren Grundfest Caroline Jia

Department of Bioengineering Division of Neurology
University of California, Los Angeles University of California, Los Angeles
Los Angeles, California Los Angeles, California
Rao P. Gullapalli Ferenc A. Jolesz

Department of Diagnostic Radiology Department of Radiology
and Nuclear Medicine Brigham and Women’s Hospital
University of Maryland School of Medicine Harvard Medical School
Baltimore, Maryland Boston, Massachusetts
Daniel X. Hammer Ranu Jung

Division of Biomedical Physics Department of Biomedical Engineering
Office of Science and Engineering Laboratories Florida International University
Center for Devices and Radiological Health Miami, Florida
Food and Drug Administration
Silver Spring, Maryland Nader Shahni Karamzadeh
Section on Analytical and Functional
Guillermo Hernández-Mendoza Biophotonics
Cellular Physiology Institute National Institutes of Child Health and Human
Universidad Nacional Autónoma de México Development
Mexican Autonomous National University National Institutes of Health
México City, Mexico Bethesda, Maryland
xviii Contributors
Babak Kateb Xingde Li

California Neurosurgical Institute Department of Biomedical Engineering
Valencia, California Johns Hopkins University School of Medicine
and Baltimore, Maryland
and Chia-Pin Liang
Brain Mapping Foundation Wellman Center for Photomedicine
West Hollywood, California Massachusetts General Hospital
Harvard Medical School
and Boston, Massachusetts
Department of Neurosurgery and
Beverly Hills, California Fiscehll Department of Bioengineering
University of Maryland
David S. Kittle College Park, Maryland
Cedars-Sinai Medical Center Linda Liau
Los Angeles, California Department of Neurosurgery
University of California, Los Angeles
Fatma Zehra Keskin Krzan
Department of Psychology
Uskudar University
İstanbul, Turkey Mark A. Liker
Carmen Kut University of Southern California
Department of Biomedical Engineering Los Angeles, California
Johns Hopkins University School of Medicine
Baltimore, Maryland Adam N. Mamelak
Asimina Lazaridou Cedars-Sinai Medical Center
NMR Surgical Laboratory Los Angeles, California
Department of Surgery
Massachusetts General Hospital and Shriners
Burn Institute Richard P. Menger
Harvard Medical School Department of Neurosurgery
and Louisiana State University of Health Sciences
Athinoula A. Martinos Center of Biomedical Shreveport, Louisiana
Imaging
Department of Radiology Yukifumi Monden
Massachusetts General Hospital Department of Pediatrics
Boston, Massachusetts Jichi Medical University
Conor Leahy Shimotsuke, Japan
Neurophotonics Laboratory and
University of California, Davis Department of Pediatrics
Davis, California Jichi Medical University
Tochigi, Japan
Wonhye Lee
and
Department of Radiology
Harvard Medical School Department of Pediatrics
Brigham and Women’s Hospital International University of Health and Walfare
Boston, Massachusetts Tochigi, Japan
Contributors xix
Martin M. Mortazavi Brian Pikul

Department of Neurosurgery Department of Neurosurgery
California Institute of Neuroscience Kaiser Permanent
Thousand Oaks, California Los Angeles, California
Zhaojun Nie Kambiz Pourrezaei

Department of Neurosurgery School of Biomedical Engineering, Science
Cedars-Sinai Medical Center and Health Systems
Los Angeles, California Drexel University
Philadelphia, Pennsylvania
Shouleh Nikzad
NASA/Jet Propulsion Laboratory Ahmad Pourshoghi
California Institute of Technology School of Biomedical Engineering, Science
Pasadena, California and Health Systems
Drexel University
Philadelphia, Pennsylvania
Ifije E. Ohiorhenuan
Neal Prakash
University of Southern California
Department of Medicine
Division of Neurology
City of Hope National Medical Center
Felipe Orihuela-Espina Duarte, California
Department of Computer Science
Instituto Nacional de Astrofísica, Óptica y Alfredo Quinones-Hinojosa
Electrónica Department of Neurological Surgery
National Institute for Astrophysics, Optics Mayo Clinic Hospital
and Electronics Jacksonville, Florida
Puebla, Mexico
Jessica C. Ramella-Roman
Serhat Özekes Department of Biomedical Engineering
Department of Computer Engineering Florida International University
Uskudar University and
İstanbul, Turkey Herbert Wertheim College of Medicine
Yingtian Pan Miami, Florida
Stony Brook University Jordina Rincon-Torroella
Stony Brook, New York Department of Neurological Surgery
Johns Hopkins University School of Medicine
Baltimore, Maryland
Asael Papour
Wellman Center for Photomedicine
Massachusetts General Hospital Ueli Rutishauser
Harvard Medical School Department of Neurosurgery
Boston, Massachusetts Cedars-Sinai Medical Center
Chirag G. Patil and
Department of Neurosurgery Division of Biology and Biological Engineering
Cedars-Sinai Medical Center California Institute of Technology
Los Angeles, California Pasadena, California
xx Contributors
Karla J. Sanchez-Perez Nevzat Tarhan

Optics Department Department of Psychology
Instituto Nacional de Astrofísica, Óptica y Uskudar University
Electrónica İstanbul, Turkey
National Institute for Astrophysics, Optics
and Electronics Cumhur Taş
Puebla, Mexico Department of Psychology
Uskudar University
Shahdad Sherkat İstanbul, Turkey
Society for Brain Mapping & Therapeutics and
and Division of Cognitive Neuropsychiatry
Brain Mapping Foundation and Psychiatric Preventative Medicine
Los Angeles, California Ruhr University
Bochum, Germany
Elizabeth G. Smith
National Institutes of Mental Health Zach Taylor
National Institutes of Health Department of Bioengineering
Bethesda, Maryland University of California, Los Angeles
Chandler Sours
Department of Diagnostic Radiology Carlos G. Treviño-Palacios
and Nuclear Medicine Optics Department
University of Maryland School of Medicine Instituto Nacional de Astrofísica, Óptica y
Baltimore, Maryland Electrónica
National Institute for Astrophysics, Optics and
Vivek J. Srinivasan Electronics
Neurophotonics Laboratory Puebla, Mexico
University of California, Davis Vassiliy Tsytsarev
Davis, California Department of Anatomy and Neurobiology
University of Maryland School of Medicine
Oscar Stafsudd Baltimore, Maryland
Department of Electrical Engineering and
University of California, Los Angeles Society for Brain Mapping & Therapeutics
Los Angeles, California and
Brain Mapping Foundation
Luis Enrique Sucar West Hollywood, California
Department of Computer Science
Instituto Nacional de Astrofísica, Óptica y A. Aria Tzika
Electrónica The NMR Surgical Laboratory
National Institute for Astrophysics, Optics Department of Surgery
and Electronics Massachusetts General Hospital and Shriners
Puebla, Mexico Burns Institute
Harvard Medical School
Cha-Min Tang and
Department of Neurology Department of Radiology
University of Maryland School of Medicine Athinoula A. Martinos Center of Biomedical
and Imaging
Research Service, VA Medical Center Massachusetts General Hospital
Baltimore, Maryland Boston, Massachusetts
Contributors xxi
Baris Ünsalver Michael E. Wolf

Department of Computer Engineering NeuroCite LLC
Uskudar University Los Angeles, California
İstanbul, Turkey
Jun Xia
Fartash Vasefi Optical Imaging Laboratory
Department of Neurosurgery Department of Biomedical Engineering
Cedars-Sinai Medical Center The State University of New York
Los Angeles, California Buffalo, New York
and
Society for Brain Mapping & Vicky Yamamoto
Therapeutics Department of Otolaryngology—Head and
and Neck Surgery
Brain Mapping Foundation USC-Norris Comprehensive Cancer Center
West Hollywood, California Keck School of Medicine of USC
and
Hui Wang Brain Mapping Foundation
Athinoula A. Martinos Los Angeles, California
Center for Biomedical Imaging
Massachusetts General Hospital/Harvard
Medical School Junjie Yao
Charlestown, Massachusetts Optical Imaging Laboratory
Washington University in St. Louis
Lihong V. Wang St. Louis, Missouri
Optical Imaging Laboratory
Department of Biomedical
Engineering Parham Yashar
Washington University in St. Louis California Neurosurgical Institute
St. Louis, Missouri Valencia, California
Geethika Weliwitigoda William H. Yong

Samsung USA Brain Tumor Translational Resource
Danvers, Massachusetts University of California, Los Angeles
Cristin G. Welle
Division of Biomedical Physics Seung-Schik Yoo
Office of Science and Engineering Laboratories Department of Radiology, Brigham and
Center for Devices and Radiological Health, Women’s Hospital
Food and Drug Administration Harvard Medical School
Silver Spring, Maryland Boston, Massachusetts
and
Departments of Neurosurgery Issa Zakeri
and Bioengineering School of Public Health
University of Colorado Denver Drexel University
Aurora, Colorado Philadelphia, Pennsylvania
xxii Contributors
Oscar Javier Zapata-Nava Deborah Zelinsky

Optics Department Mind-Eye Connection
Instituto Nacional de Astrofísica, Óptica y Northbrook, Illinois
Electrónica
Jiang Zhu
National Institute for Astrophysics, Optics and
Beckman Laser Institute
Electronics
Puebla, Mexico
University of California, Irvine
and Irvine, California
Mechatronics Departments Jiachen Zhuo
Instituto Superior Tecnológico de Department of Diagnostic Radiology
Zacapoaxtla and Nuclear Medicine
Zacapoaxtla Tecnological Institute University of Maryland School of Medicine
Zacapoaxtla, Pue, Mexico Baltimore, Maryland
1 History of Brain Mapping
and Neurophotonics
From Technological Discoveries
to Brain Initiatives
Babak Kateb, Frank Boehm, Alexandra Jalali,
Vassiliy Tsytsarev, Vicky Yamamoto, Bahram Jalali,
Derek Backer, Brian Pikul, Parham Yashar, and Yu Chen
CONTENTS
Introduction.........................................................................................................................................1
Historical Milestones in Brain Mapping ............................................................................................2
X-Ray��3
Computed Tomography..................................................................................................................3
Magnetic Resonance Imaging........................................................................................................3
Positron Emission Tomography.....................................................................................................4
Historical Milestones in Neurophotonics............................................................................................4
Near-Infrared Spectroscopy and Imaging......................................................................................5
Optical Coherence Tomography.....................................................................................................5
Fluorescence Spectroscopy, Imaging, and Microscopy.................................................................6
Optogenetics...................................................................................................................................6
Photodynamic Therapy..................................................................................................................7
Intraoperative Brain Mapping.............................................................................................................8
GE Double Donut MRI..................................................................................................................9
Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite...............................9
Advanced Multimodality Image Guided Operating.....................................................................10
Brain Initiative, G20 World Brain Mapping and Therapeutics Initiative, and National
Photonic Initiative.............................................................................................................................10
SBMT-IEEE Brain Mapping Initiative.............................................................................................12
National Photonic Initiative.........................................................................................................13
Conclusion........................................................................................................................................14
References.........................................................................................................................................14
INTRODUCTION
According to the Society for Brain Mapping and Therapeutics (SBMT), brain mapping is defined
as the study and elucidation of the anatomy and functionality of the brain and spinal cord through
the use of imaging (including intraoperative, microscopic, endoscopic, molecular, and multimo-
dality imaging), immunohistochemistry, optogenetics, stem cell and cellular biology, engineering
(material, electrical, and biomedical), advanced technologies (ultrasound, photonics, etc.), neuro-
physiology, and nanotechnology (Kateb and Heiss, 2013). Diverse types of brain mapping exist,
1
2 Neurophotonics and Brain Mapping
encompassing anatomical, structural, cellular, functional, and metabolic. Cellular maps, for instance,
may comprise nanoscale imaging and may be alternately defined via genomics. This volume will
endeavor to survey and articulate the latest advances in neurophotonics. These exciting technologi-
cal advances will lead to the further enhancement of the diagnoses and treatments of myriad brain
conditions toward improved patient outcomes globally.
HISTORICAL MILESTONES IN BRAIN MAPPING

The first known written instance of the word “brain,” in addition to articulations of the meninges,
the cerebrospinal fluid, and various brain injuries, dates back to ~3000 BC in what is referred to
as The Edwin Smith Surgical Papyrus, which is an ancient medical text that was authored by the
prominent Egyptian physician Imhotep. At the time, however, the brain was thought to be an incon-
sequential organ in contrast to the heart, which was deemed to be its life force (Minagar et al., 2003).
The Greek medical theorist and dissectionist Alcmaeon of Croton (500 BC) is thought to have been
the earliest author to propose that the brain was the center of cognition and sensation. His dissection
studies of the eye led him to posit that the optic nerves “came together behind the forehead” and
comprised brain terminating “light bearing paths” (Lloyd, 1975). Democritus (460–370 BC) put for-
ward that all matter in the universe was made of various constituent atoms and that the human mind
was composed of the most rapidly motile atoms (Gross, 1995). Plato (~428–347 BC) expanded on
these musings in his Timaeus, where he states that the brain “…is the divinest part of us and lord
over all the rest” (Plato, 1959), whereas Hippocrates (460–370 BC) affirmed that mental operations
were “completely undertaken by the brain.” He also conveyed his firm belief that epilepsy originated
within the brain in his well-known essay “On the Sacred Disease” (Hippocrates, 1950; Gross, 1995).
Galen (AD 121–201) was among the first well-documented ancient scientists who provided
insights into the detailed gross anatomy of the human brain (Toga and Mazziotta, 2002). The Persian
polymath and physician Rhazes (AD 865–925) first conveyed the existence of seven cranial nerves
and 31 spinal nerves in Kitab al-Hawi fi al-tibb (The Comprehensive Book on Medicine) (Tubbs et al.,
2007). Avicenna (Abu Ali Sina AD 980–1037) conducted thorough anatomical studies of the spinal
cord, described its functionality, and identified various spinal traumas and their treatments (Ghaffari
et al., 2015). Leonardo da Vinci (AD 1452–1519) was the first individual to convey a precise depic-
tion of the brain through the fusion of art perspective with dissection (Pevsner, 2002). In 1536, the
Venetian physician Niccolo Massa initially discovered cerebrospinal fluid during the course of an
autopsy (Herbowski, 2013); the Italian neuroanatomist Costanzo Varolio, in 1573, was the first to
dissect the brain from its base (Zago and Meraviglia, 2009); and in 1586, Archangelo Piccolomini
initially distinguished the neocortex, white matter, and subcortical nuclei (Compston, 2013).
From the sixteenth till the eighteenth centuries, increasing advances in the elucidation of brain
structure and functionality were made, with some of the most prominent being the following*:
1641—Fissures on brain surfaces are revealed by Franciscus de la Boe Sylvius.

1664—Thomas Willis discovers the eleventh cranial nerve.
1695—Publication of The Anatomy of the Brain by Humphrey Ridley.
1717—Cross sections of nerve fibers are initially described by Antony van Leeuwenhoek.
1778—Classification of the twelve cranial nerves and optic chiasm (1786) are articulated by
Samuel Thomas von Soemmerring.
1809—Luigi Rolando stimulates the cortex via galvanic current.
1836—Gabriel Gustav Valentin recognizes the nucleus and nucleolus of neurons.
1836—Myelinated and unmyelinated axons are discovered by Robert Remak, who later
(1844) illustrates the six layers of the neocortex.
* Adapted from Chudler (2016).

History of Brain Mapping and Neurophotonics 3
Modern cognitive neuroscience, which couples investigative cognitive psychology with the elu-
cidation of how brain function drives mental activity, has garnered intense interest and development
over the last three decades. This research is facilitated to a great extent through functional brain
imaging/mapping that employs techniques such as positron emission tomography (PET), functional
magnetic resonance imaging (fMRI), electroencephalography (EEG), electrocorticography, and
magnetoencephalography, along with the most recent addition of optical near-infrared spectroscopy
(NIRS) imaging (Raichle, 2009).
X-Ray
German physicist Röntgen’s accidental discovery of x-rays in 1895 earned him the Nobel Prize in
Physics in 1901. While studying emission of light by cathode-ray tubes, he observed that the impact
of cathode rays on the glass vacuum tube was generating a new type of radiation that could penetrate
human tissue, wood, copper, and aluminum and could be recorded on photographic plates. Röntgen
named it the x-ray to denote the fact that it was an unknown type of radiation. Röntgen did not patent
his discovery as he was convinced that it had important medical applications and he wanted the world to
benefit from it. As a result, x-rays were quickly adopted throughout the world. In 1896, the British army
began to use x-ray machines to locate bullets and diagnose bone fractures. Also, in 1896, John Hall-
Edwards in Birmingham, England, used it to locate a needle, which was stuck in the hand of an associate
(Meggitt, 2008). While x-ray is still used for such applications, today it is primarily employed in the
context of digital radiology and computed tomography (CT) scanners, as discussed in the following text.
Computed Tomography
X-ray computed tomography (CT), otherwise known as computed axial tomography (CAT), is a scanner
that provides 3D images of the brain by taking x-ray images from different angles. It operates by passing
highly focused x-ray beams through the body and recording their attenuation. These projections from
multiple directions are fed to a tomographic reconstruction software algorithm. CT scanning is generally
used to distinguish benign and malignant tumors, as well as injuries to the brain. The information is
typically presented as a series of cross-sectional images. Referred to as planography, an earlier version
of CT imaging was reported in 1953 by B. Pollak (1953). The mathematical modeling of transverse axial
scanning was a key in the development of CT, which was due to the work of South African-born Allan
McLeod Cormack and UK scientist Godfrey Hounsfield. The modern and first commercial CT scanner
was introduced by Godfrey Hounsfield in 1971 at Atkinson Morley Hospital in London (Littleton,
2014). This revolutionary tool replaced highly invasive techniques, such as pneumoencephalography,
whereby a lumbar puncture through the skull facilitated the drainage of the cerebrospinal fluid that
surrounded the brain to be exchanged with air to enable clearer x-ray imagery. In the 1980s, the speed
of CT scanners was significantly enhanced through the addition of spiral scanning, developed by
Kalender at the University of Wisconsin. This allowed the creation of CT angiograms and the addition
of time-dependent measurements of blood perfusion through the use of a dye to enhance contrast; CT
angiography depicts vascular structures and ruptures of the blood vessels for diagnosis of brain injuries.
Hence, CT scanning has had a tremendous impact in the field of brain mapping (Castillo, 2014).
Magnetic Resonance Imaging

Magnetic resonance imaging, or MRI, is an important tool used in brain mapping that uses a magnetic
field and radio-frequency (RF) pulses to create images of the internal structure of the body. The pre-
decessor to MRI (nuclear magnetic resonance or NMR) was invented by Felix Bloch from Harvard
University and Edward Purcell from Stanford University in 1946. The next major development, in
1973, was attributed to Paul Lauterbur who invented a technique by which NMR could create images
in the same way as a CT scanner, albeit with much more detail. It was then that the system was
renamed as MRI (Raichle, 2009). The operation of MRI relies on the magnetic moment of protons
in tissues and their interaction with a magnetic field and a RF wave. In the presence of a magnetic
field, protons align in parallel with the field, which is the lowest proton energy state. When the RF
signal is turned on, its energy excites the protons to a higher energy state, which is associated with the
magnetic moment being misaligned with the magnetic field. Turning off the field allows the protons
to relax back to their original state. During this relaxation period, energy is released via the emission
of electromagnetic energy, which is detected by a coil. Since the rate of relaxation is different for
various tissues, MRI can distinguish circulatory and metabolic changes in brain activity. Functional
MRI, or fMRI, refers to the use of MRI to visualize the functionality of the brain while the subject is
performing specific tasks. The technique was introduced by Seiji Ogawa and his colleagues at AT&T
Bell Laboratories, where they studied the concentration of deoxygenated blood in the brains of living
rodents (Miyamoto et al., 2014). fMRI has emerged as the most important tool for brain mapping.
Chapters 13 and 14 review advanced MRI technologies for brain mapping.
Positron Emission Tomography

Other strategies for functional imaging comprise nuclear medicines such as single-photon emission
computerized tomography (SPECT) or PET. PET selectively highlights areas of the body with rela-
tively higher metabolic activity, characterized by high sugar or oxygen uptake.
A type of glucose (fluorodeoxyglucose, or FDG) is typically used to deliver a tracer molecule that
emits gamma rays (through positron emission) to areas with higher metabolic activity. Alternatively,
a radioactive isotope of oxygen is employed to image the volume of blood flow in different regions
of the brain. Subsequently, areas of the brain with higher than normal (cancer tissue) or lower than
normal (e.g., Alzheimer’s disease) oxygen consumption may be identified.
A modern PET imaging system was pioneered in 1975 by researchers at Washington University
in St. Louis (Phelps et al., 1975; Ter-Pogossian et al., 1975). This development benefited from the
earlier work that was done in the 1950s, which involved the use of positron emitters to localize
brain tumors at Massachusetts General Hospital (Sweet and Brownell, 1953), and in the 1960s at
Brookhaven National Laboratory (DOE report, 2010).
HISTORICAL MILESTONES IN NEUROPHOTONICS

Neurophotonics is generally defined as the use of photonic methods for the imaging and manipula-
tion of brain structure and function, spanning from the visualization of intracellular organelles and
protein assemblies to the noninvasive macroscopic investigation of cortical activity in human sub-
jects (Boas, 2014). Light has several advantages, such that it is nonionizing, has low cost, is portable,
and possesses high molecular and biochemical specificity. At the onset of the neurophotonics era,
the strategy for imaging brain function was based on slow optical changes that occurred in the neural
tissue, which allowed for visualization with good spatial and temporal resolution. The existence of
these optical changes associated with metabolic activity has been observed since the first part of
the twentieth century, when optical alterations were demonstrated in cytochromes (Kelin, 1925)
and hemoglobin (Millikan, 1937, 1942). Decades later, scientists demonstrated optical changes that
were associated with neural activity (Hill and Keynes, 1949). It has only been within the last decades
of the twentieth century that it became possible to utilize the detection of subtle optical changes for
the imaging of neural activity (Kalchenko et al., 2014). Computerization coupled with light-sensi-
tive semiconductor devices makes neurophotonics a very powerful facet of neuroscience (Grinvald
et al., 2015). Imaging methods were dramatically improved with approaches that employed voltage-
and calcium-sensitive dyes, which served to enhance spatial and temporal resolution. Following
further decades, genetically encoded fluorescent probes were introduced into the armamentarium of
experimental neuroscience. Currently, neurophotonics is experiencing rapid growth toward facilitat-
ing our understanding of brain activity under normal and pathological conditions.
History of Brain Mapping and Neurophotonics 5
Near-Infrared Spectroscopy and Imaging

The spectroscopy system was pioneered at Cambridge University (Hartridge and Roughton, 1923;
Roughton and Millikan, 1936). Since tissue is typically opaque, light absorption is disrupted by scat-
tering. In 1950, Britton Chance invented the “double beam spectrometer” using two wavelengths in
the visible region with a small spectral interval to eliminate scattering effects (Chance, 1951). The
first demonstration of near-infrared (NIR) light with human tissue in vivo was reported by Franz
Jobsis in 1977 (Jobsis, 1977). Since then, many papers have been published on the use of NIR spec-
troscopy (NIRS) for brain mapping. Many researchers use continuous-wave (CW) technology, as
the system is simple, has low cost, and is robust (Chance et al., 2005). Time-resolved spectroscopy
provided a solution for the absolute quantification of chemical concentrations in tissues (Chance
et al., 1988; Patterson et al., 1989). Alternatively, frequency-domain NIRS may be also used for
quantization (Fishkin and Gratton, 1993; Madsen et al., 1994; Chen et al., 2003).
Since Seiji Ogawa’s discovery in the early 1990s that signal changes associated with deoxyhe-
moglobin in NMR can detect brain cognition (Ogawa et al., 1990), researchers have been interested
in using NIR light to detect brain function (Chance et al., 1993; Villringer and Chance, 1997; Hoshi
et al., 2003). NIRS may quantify the concentrations of both Hb and HbO2, thereby revealing the
blood volume and oxygenation saturation changes associated with various brain functions. NIRS
may be extended to imaging mode by employing multiple source-detector channels. Images can be
formed using back-projection and interpolation algorithms, sometimes referred to as diffuse optical
topography, which may provide an estimate of the 2D spatial distribution of the optical properties
of tissues (Hielscher et al., 2002). Another approach is to perform 3D tomographic reconstruction,
which is typically referred to as diffuse optical tomography (DOT). DOT is similar to x-ray CT and
involves image reconstruction by solving the inverse problem (Arridge, 1999).
NIR imaging has found extensive applications in clinical settings (Hillman, 2007; Wolf et al.,
2007). One major research area involves the elucidation of how the brain functions. Optical imaging
offers the unique capability to noninvasively monitor functional activations in vivo without disturb-
ing the organ. Various applications such as visual responses (Takahashi et al., 2000; Zeff et al.,
2007), somatosensory responses (Becerra et al., 2009), auditory responses (Sato et al., 1999), lan-
guage stimuli (Watanabe et al., 1998; Pena et al., 2003), and problem solving (Chance et al., 2007)
have been explored. Another important area for optical brain imaging is to diagnose and monitor
conditions such as stroke (Kirkpatrick et al., 1998; Durduran et al., 2009), epilepsy (Watanabe et
al., 2002), brain injury (Kim et al., 2010), and post-traumatic stress disorder (Matsuo et al., 2003).
Optical techniques are well suited for the early detection of hemorrhage (Stankovic et al., 2000) and
to discriminate between ischemic and hemorrhagic stroke, which leads to improved management of
therapeutics for patients (Intes and Chance, 2005). Chapters 2 through 5 review the applications of
fNIRS for pain management and neurological disease monitoring. Chapters 15 through 17 review
the application of optical imaging that is based on ultraviolet (UV), visible, and infrared (IR) light
for neurosurgical guidance.
Optical Coherence Tomography

Concurrently with other photonic imaging techniques, microscopic imaging using light has been
actively pursued over the last several decades. One representative technology is optical coherence
tomography (OCT), which enables the cross-sectional imaging of tissue microstructures in situ and
in real time (Huang et al., 1991). OCT may achieve resolution at from 1 to 10 μm and a penetration
depth of 1 to 2 mm, approaching those of standard excisional biopsy and histopathology, however,
without the requirement for the removal and processing of tissue specimens (Fujimoto et al.,
1995). OCT is analogous to ultrasound imaging, except that imaging is performed by measur-
ing the echo delay time and intensity of back-reflected or backscattered light, rather than sound.
OCT imaging may be performed fiber-optically using delivery devices such as handheld probes,
endoscopes, catheters, laparoscopes, and needles that enable noninvasive or minimally invasive
internal body imaging (Yaqoob et al., 2006).
OCT is performed using a Michelson interferometer with a low coherence length (broadband)
light source. One arm of the interferometer illuminates the tissue and collects the backscattered
light (referred to as the “sample arm”). Another arm has a reference path delay, which is scanned as
a function of time (referred to as the “reference arm”). Optical interference between the light from
the sample and reference arms occurs only when the optical delays match to the coherence length of
the light source. This technique is generally referred to as “time-domain OCT.” Alternatively, OCT
interference signals may be detected in the frequency or Fourier domain. In Fourier-domain OCT,
the reference mirror position is fixed and the light scattering profile is obtained by a Fourier trans-
form of the interference spectrum. These techniques are somewhat analogous to Fourier transform
spectroscopy and have significant sensitivity and speed advantages in contrast to time-domain OCT
in that they measure the optical signals from different depths along the entire axial scan simultane-
ously, rather than sequentially (Choma et al., 2003; de Boer et al., 2003; Leitgeb et al., 2003). These
advances not only greatly improve the performance of OCT but also enable three-dimensional OCT
(3D-OCT) imaging in vivo. Time-stretch OCT is a Fourier-domain technique that delivers the high-
est imaging speed of OCT (Goda and Jalali, 2013). This novel system uses a photonic time-stretch
technology (Jalali and Coppinger, 2001) to capture images with nanosecond time resolution and
subsequently optically slows them in time so they can be digitized and analyzed by the computer
in real time. This method is very attractive in neuroimaging, as the action potentials (the electri-
cal impulses used by the brain to send signals) and physiological changes they produce occur on
millisecond time scales, which is too fast to be detected by conventional OCT techniques.
Chapters 7 through 11 review the application of OCT for imaging brain function with animal
models. Neurosurgical guidance using OCT represents another exciting application area (Jafri et al.,
2005). Chapters 20 and 21 review the development and translation of OCT imaging to intraoperative
guidance for neurosurgery.
Fluorescence Spectroscopy, Imaging, and Microscopy

Fluorescence-based brain imaging uses the emission of visible or NIR light via fluorescent dyes or pro-
teins. It visualizes processes and structures at cellular and molecular scales, that is, with much better resolu-
tion than other techniques, however, with a lower penetration depth due to the high rate of light scattering
and absorption within tissues. Fluorescence imaging is key for the reconstruction of dense neural circuits
known as connectomes (Helmstaedter, 2013) and the observation of gene and protein expressions through
genetically encoded fluorescent protein tracers. High speed is necessary in brain mapping to capture the
dynamics of action potentials. Fluorescence imaging via radio-frequency-tagged excitation (FIRE) is the
world’s fastest fluorescence imaging modality (Diebold et al., 2013). The microscope uses methods for
data multiplexing borrowed from wireless communications to acquire fluorescent images at microsecond
time intervals (see Figure 1.1). As is the case with all optical techniques, due to the low penetration depth of
photons in tissue, the creation of 3D maps of the brain via fluorescence microscopy is challenging. There
are currently two approaches to this: tissue sectioning and light-sheet/multiphoton fluorescence microscopy.
Chapter 6 reviews the use of fluorescence-based voltage-sensitive dyes for brain imaging, whereas Chapter
11 reviews the application of multiphoton microscopy for monitoring implanted neural interfaces. Chapters
18 and 19 review the application of autofluorescence-based technologies for intraoperative guidance during
neurosurgery. In addition, Chapter 12 describes another very exciting multimodal optics method referred to
as photoacoustic tomography which was pioneered by Professor Lihong Wang.
Optogenetics
Optogenetics has revolutionized neuroscience over the last few decades by allowing scientists
to activate or inhibit specific neurons and monitor neural activity using light, without the use of
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towards her, and she, seeing that I recognized her, bounded to me
with joy in every feature, and expressed her great happiness at
seeing me. All thought of slavery, color, or what might seem to
belong to the dignity of her position vanished, and the meeting was
as the meeting of friends long separated, yet still present in each
other’s memory and affection.
Amanda made haste to tell me that she agreed with me about
slavery, and that she had freed all her slaves as they had become of
age. She brought her children to me, and I took them in my arms,
with sensations which I could not if I would stop here to describe.
One explanation of the feeling of this lady towards me was, that her
mother, who died when she was yet a tender child, had been briefly
described by me in a little “Narrative of my life,” published many
years before our meeting, and when I could have had no motive but
the highest for what I said of her. She had read my story, and
learned something of the amiable qualities of her mother through
me. She also recollected that as I had had trials as a slave, she had
had her trials under the care of a stepmother, and that when she was
harshly spoken to by her father’s second wife she could always read
in my dark face the sympathy of one who had often received kind
words from the lips of her beloved mother. Mrs. Sears died three
years ago in Baltimore, but she did not depart without calling me to
her bedside, that I might tell her as much as I could about her
mother, whom she was firm in the faith that she should meet in
another and better world. She especially wished me to describe to
her the personal appearance of her mother, and desired to know if
any of her own children then present resembled her. I told her that
the young lady standing in the corner of the room was the image of
her mother in form and features. She looked at her daughter and
said, “Her name is Lucretia—after my mother.” After telling me that
her life had been a happy one, and thanking me for coming to see
her on her death-bed, she said she was ready to die. We parted to
meet no more in life. The interview touched me deeply, and was, I
could not help thinking, a strange one—another proof that “Truth is
often stranger than Fiction.”
If any reader of this part of my life shall see in it the evidence of
a want of manly resentment for wrongs inflicted upon myself and
race by slavery, and by the ancestors of this lady, so it must be. No
man can be stronger than nature, one touch of which, we are told,
makes all the world akin. I esteem myself a good, persistent hater of
injustice and oppression, but my resentment ceases when they
cease, and I have no heart to visit upon children the sins of their
fathers.
It will be noticed, when I first met Mr. Sears in Philadelphia, he
declined to talk with me, on the ground that I had been unjust to
Capt. Auld, his father-in-law. Soon after that meeting, Capt. Auld had
occasion to go to Philadelphia, and, as usual, went straight to the
house of his son-in-law, and had hardly finished the ordinary
salutations, when he said: “Sears, I see by the papers that Frederick
has recently been in Philadelphia. Did you go to hear him?” “Yes,
sir,” was the reply. After asking something more about my lecture, he
said, “Well, Sears, did Frederick come to see you?” “Yes, sir,” said
Sears. “Well, how did you receive him?” Mr. Sears then told him all
about my visit, and had the satisfaction of hearing the old man say
that he had done right in giving me welcome to his house. This last
fact I have from Rev. J. D. Long, who, with his wife, was one of the
party invited to meet me at the house of Mr. Sears, on the occasion
of my visit to Mrs. Sears.
But I must now return from this digression, and further relate my
experience in the Loyalist National Convention, and how from that
time there was an impetus given to the enfranchisement of the
freedmen, which culminated in the fifteenth amendment to the
Constitution of the United States. From the first, the members of the
convention were divided in their views of the proper measures of
reconstruction, and this division was in some sense sectional. The
men from the far South, strangely enough, were quite radical, while
those from the border States were mostly conservative, and,
unhappily, these last had control of the convention from the first. A
Kentucky gentleman was made President, and its other officers were
for the most part Kentuckians, and all opposed to colored suffrage in
sentiment. There was a “whole heap” (to use a Kentucky phrase) of
“halfness” in that State during the war for the union, and there was
much more there after the war. The Maryland delegates, with the
exception of Hon. John L. Thomas, were in sympathy with Kentucky.
Those from Virginia, except Hon. John Miner Botts, were unwilling to
entertain the question. The result was, that the convention was
broken square in two. The Kentucky President declared it adjourned,
and left the chair against the earnest protests of the friends of
manhood suffrage.
But the friends of this measure were not to be out-generaled and
suppressed in this way, and instantly reorganized, elected John M.
Botts of Virginia, President, discussed and passed resolutions in
favor of enfranchising the freedmen, and thus placed the question
before the country in such a manner that it could not be ignored. The
delegates from the Southern States were quite in earnest, and bore
themselves grandly in support of the measure; but the chief
speakers and advocates of suffrage on that occasion were Mr.
Theodore Tilton and Miss Anna E. Dickinson. Of course, on such a
question, I could not be expected to be silent. I was called forward,
and responded with all the energy of my soul, for I looked upon
suffrage to the negro as the only measure which could prevent him
from being thrust back into slavery.
From this time onward the question of suffrage had no rest. The
rapidity with which it gained strength was more than surprising to
me.
In addition to the justice of the measure, it was soon
commended by events as a political necessity. As in the case of the
abolition of slavery, the white people of the rebellious States have
themselves to thank for its adoption. Had they accepted, with
moderate grace, the decision of the court to which they appealed,
and the liberal conditions of peace offered to them, and united
heartily with the national government in its efforts to reconstruct their
shattered institutions, instead of sullenly refusing as they did, their
counsel and their votes to that end, they might easily have defeated
the argument based upon necessity for the measure. As it was, the
question was speedily taken out of the hands of colored delegations
and mere individual efforts, and became a part of the policy of the
Republican party; and President U. S. Grant, with his characteristic
nerve and clear perception of justice, promptly recommended the
great amendment to the Constitution by which colored men are to-
day invested with complete citizenship—the right to vote and to be
voted for in the American Republic.
CHAPTER XIV.
LIVING AND LEARNING.
Inducements to a political career—Objections—A newspaper enterprise—The

new National Era—Its abandonment—The Freedmen’s Savings and Trust
Company—Sad experience—Vindication.
THE adoption of the fourteenth and fifteenth amendments and their

incorporation into the Constitution of the United States opened a
very tempting field to my ambition, and one to which I should
probably have yielded, had I been a younger man. I was earnestly
urged by many of my respected fellow-citizens, both colored and
white and from all sections of the country, to take up my abode in
some one of the many districts of the South where there was a large
colored vote, and get myself elected, as they were sure I easily could
do, to a seat in Congress—possibly in the Senate. That I did not
yield to this temptation was not entirely due to my age; for the idea
did not square well with my better judgment and sense of propriety.
The thought of going to live among a people in order to gain their
votes and acquire official honors, was repugnant to my self-respect,
and I had not lived long enough in the political atmosphere of
Washington to have this sentiment sufficiently blunted to make me
indifferent to its suggestions. I do not deny that the arguments of my
friends had some weight in them, and from their stand-point it was all
right; but I was better known to myself than to them. I had small faith
in my aptitude as a politician, and could not hope to cope with rival
aspirants. My life and labors in the North had in a measure unfitted
me for such work, and I could not readily have adapted myself to the
peculiar oratory found to be most effective with the newly
enfranchised class. In the New England and Northern atmosphere I
had acquired a style of speaking which in the South would have
been considered tame and spiritless; and, consequently, he who
“could tear a passion to tatters and split the ear of groundlings,” had
far better chance of success with the masses there, than one so little
boisterous as myself.
Upon the whole, I have never regretted that I did not enter the
arena of Congressional honors to which I was invited.
Outside of mere personal considerations I saw, or thought I saw,
that in the nature of the case the sceptre of power had passed from
the old slave and rebellious States to the free and loyal States, and
that hereafter, at least for some time to come, the loyal North, with its
advanced civilization, must dictate the policy and control the destiny
of the republic. I had an audience ready made in the free States; one
which the labors of thirty years had prepared for me, and before this
audience the freedmen of the South needed an advocate as much
as they needed a member of Congress. I think in this I was right; for
thus far our colored members of Congress have not largely made
themselves felt in the legislation of the country; and I have little
reason to think I could have done any better than they.
I was not, however, to remain long in my retired home in
Rochester, where I had planted my trees and was reposing under
their shadows. An effort was being made about this time to establish
a large weekly newspaper in the city of Washington, which should be
devoted to the defence and enlightenment of the newly emancipated
and enfranchised people; and I was urged by such men as George
T. Downing, J. H. Hawes, J. Sella Martin, and others, to become its
editor-in-chief. My sixteen years’ experience as editor and publisher
of my own paper, and the knowledge of the toil and anxiety which
such a relation to a public journal must impose, caused me much
reluctance and hesitation: nevertheless, I yielded to the wishes of my
friends and counsellors, went to Washington, threw myself into the
work, hoping to be able to lift up a standard at the national capital,
for my people, which should cheer and strengthen them in the work
of their own improvement and elevation.
I was not long connected with this enterprise, before I discovered
my mistake. The coöperation so liberally promised, and the support
which had been assured, were not very largely realized. By a series
of circumstances a little bewildering as I now look back upon them, I
found myself alone, under the mental and pecuniary burden involved
in the prosecution of the enterprise. I had been misled by loud talk of
a grand incorporated publishing company, in which I should have
shares if I wished, and in any case a fixed salary for my services;
and after all these fair-seeming conditions, I had not been connected
with the paper one year before its affairs had been so managed by
the agent appointed by this invisible company or corporate body, as
to compel me to bear the burden alone, and to become the sole
owner of the printing establishment. Having become publicly
associated with the enterprise, I was unwilling to have it prove a
failure, and had allowed it to become in debt to me, both for money
loaned, and for services, and at last it seemed wise that I should
purchase the whole concern, which I did, and turned it over to my
sons Lewis and Frederic, who were practical printers, and who, after
a few years, were compelled to discontinue its publication. This
paper was the New National Era, to the columns of which the
colored people are indebted for some of the best things ever uttered
in behalf of their cause; for, aside from its editorials and selections,
many of the ablest colored men of the country made it the medium
through which to convey their thoughts to the public. A misadventure
though it was, which cost me from nine to ten thousand dollars, over
it I have no tears to shed. The journal was valuable while it lasted,
and the experiment was full of instruction to me, which has to some
extent been heeded, for I have kept well out of newspaper
undertakings since.
Some one has said that “experience is the best teacher.”
Unfortunately the wisdom acquired in one experience seems not to
serve for another and new one; at any rate, my first lesson at the
National Capital, bought rather dearly as it was, did not preclude the
necessity of a second whetstone to sharpen my wits in this my new
home and new surroundings. It is not altogether without a feeling of
humiliation that I must narrate my connection with the “Freedmen’s
Savings and Trust Company.”
This was an institution designed to furnish a place of security
and profit for the hard earnings of the colored people, especially at
the South. Though its title was “The Freedmen’s Savings and Trust
Company,” it is known generally as the “Freedmen’s Bank.”
According to its managers it was to be this and something more.
There was something missionary in its composition, and it dealt
largely in exhortations as well as promises. The men connected with
its management were generally church members, and reputed
eminent for their piety. Some of its agents had been preachers of the
“Word.” Their aim was now to instil into the minds of the untutored
Africans lessons of sobriety, wisdom, and economy, and to show
them how to rise in the world. Circulars, tracts, and other papers
were scattered like snowflakes in winter by this benevolent institution
among the sable millions, and they were told to “look” to the
Freedman’s Bank and “live.” Branches were established in all the
Southern States, and as a result, money flowed into its vaults to the
amount of millions. With the usual effect of sudden wealth, the
managers felt like making a little display of their prosperity. They
accordingly erected one of the most costly and splendid buildings of
the time on one of the most desirable and expensive sites in the
national capital, finished on the inside with black walnut, and
furnished with marble counters and all the modern improvements.
The magnificent dimensions of the building bore testimony to its
flourishing condition. In passing it on the street I often peeped into its
spacious windows, and looked down the row of its gentlemanly and
elegantly dressed colored clerks, with their pens behind their ears
and button-hole bouquets in their coat-fronts, and felt my very eyes
enriched. It was a sight I had never expected to see. I was amazed
with the facility with which they counted the money; they threw off
the thousands with the dexterity, if not the accuracy, of old and
experienced clerks. The whole thing was beautiful. I had read of this
Bank when I lived in Rochester, and had indeed been solicited to
become one of its trustees, and had reluctantly consented to do so;
but when I came to Washington and saw its magnificent brown stone
front, its towering height, and its perfect appointments, and the fine
display it made in the transaction of its business, I felt like the Queen
of Sheba when she saw the riches of Solomon, “the half had not
been told me.”
After settling myself down in Washington in the office of the New
Era, I could and did occasionally attend the meetings of the Board of
Trustees, and had the pleasure of listening to the rapid reports of the
condition of the institution, which were generally of a most
encouraging character. My confidence in the integrity and wisdom of
the management was such that at one time I had entrusted to its
vaults about twelve thousand dollars. It seemed fitting to me to cast
in my lot with my brother freedmen, and help to build up an institution
which represented their thrift and economy to so striking advantage;
for the more millions accumulated there, I thought, the more
consideration and respect would be shown to the colored people of
the whole country.
About four months before this splendid institution was compelled
to close its doors in the starved and deluded faces of its depositors,
and while I was assured by its President and by its Actuary of its
sound condition, I was solicited by some of its trustees to allow them
to use my name in the board as a candidate for its Presidency. So I
waked up one morning to find myself seated in a comfortable arm
chair, with gold spectacles on my nose, and to hear myself
addressed as President of the Freedmen’s Bank. I could not help
reflecting on the contrast between Frederick the slave boy, running
about at Col. Lloyd’s with only a tow linen shirt to cover him, and
Frederick—President of a Bank counting its assets by millions. I had
heard of golden dreams, but such dreams had no comparison with
this reality. And yet this seeming reality was scarcely more
substantial than a dream. My term of service on this golden height
covered only the brief space of three months, and these three
months were divided into two parts, during the first part of which I
was quietly employed in an effort to find out the real condition of the
Bank and its numerous branches. This was no easy task. On paper,
and from the representations of its management, its assets
amounted to three millions of dollars, and its liabilities were about
equal to its assets. With such a showing I was encouraged in the
belief that by curtailing expenses, doing away with non-paying
branches, which policy the trustees had now adopted, we could be
carried safely through the financial distress then upon the country.
So confident was I of this, that in order to meet what was said to be a
temporary emergency, I was induced to loan the Bank ten thousand
dollars of my own money, to be held by it until it could realize on a
part of its abundant securities. This money, though it was repaid,
was not done so promptly as under the supposed circumstances I
thought it should be, and these circumstances increased my fears
lest the chasm was not so easily bridged as the Actuary of the
institution had assured me it could be. The more I observed and
learned the more my confidence diminished. I found that those
trustees who wished to issue cards and publish addresses
professing the utmost confidence in the Bank, had themselves not
one dollar deposited there. Some of them, while strongly assuring
me of its soundness, had withdrawn their money and opened
accounts elsewhere. Gradually I discovered that the Bank had
sustained heavy losses at the South through dishonest agents, that
there was a discrepancy on the books of forty thousand dollars, for
which no account could be given, that instead of our assets being
equal to our liabilities we could not in all likelihoods of the case pay
seventy-two cents on the dollar. There was an air of mystery, too,
about the spacious and elegant apartments of the Bank building
which greatly troubled me, and which I have only been able to
explain to myself on the supposition that the employees, from the
Actuary and the Inspector down to the messengers, were (perhaps)
naturally anxious to hold their places, and consequently have the
business continued. I am not a violent advocate of the doctrine of the
total depravity of human nature. I am inclined, on the whole, to
believe it a tolerably good nature, yet instances do occur which
oblige me to concede that men can and do act from mere personal
and selfish motives. In this case, at any rate, it seemed not
unreasonable to conclude that the finely dressed young gentlemen,
adorned with pens and bouquets, the most fashionable and genteel
of all our colored youth, stationed behind those marble counters,
should desire to retain their places as long as there was money in
the vaults to pay them their salaries.
Standing on the platform of this large and complicated
establishment, with its thirty-four branches, extending from New
Orleans to Philadelphia, its machinery in full operation, its
correspondence carried on in cipher, its actuary dashing in and out
of the bank with an air of pressing business, if not of bewilderment, I
found the path of enquiry I was pursuing an exceedingly difficult one.
I knew there had been very lately several runs on the bank, and that
there had been a heavy draft made upon its reserve fund, but I did
not know what I should have been told before being allowed to enter
upon the duties of my office, that this reserve, which the bank by its
charter was required to keep, had been entirely exhausted, and that
hence there was nothing left to meet any future emergency. Not to
make too long a story, I was, in six weeks after my election as
president of this bank, convinced that it was no longer a safe
custodian of the hard earnings of my confiding people. This
conclusion once reached, I could not hesitate as to my duty in the
premises, and this was, to save as much as possible of the assets
held by the bank for the benefit of the depositors; and to prevent
their being further squandered in keeping up appearances, and in
paying the salaries of myself and other officers in the bank.
Fortunately, Congress, from which we held our charter, was then in
session, and its committees on finance were in daily session. I felt it
my duty to make known as speedily as possible to Hon. John
Sherman, chairman of the Senate committee on finance, and to
Senator Scott of Pennsylvania, also of the same committee, that I
regarded the institution as insolvent and irrecoverable, and that I
could no longer ask my people to deposit their money in it. This
representation to the finance committee subjected me to very bitter
opposition on the part of the officers of the bank. Its actuary, Mr.
Stickney, immediately summoned some of the trustees, a dozen or
so of them, to go before the finance committee and make a counter
statement to that made by me; and this they did. Some of them who
had assisted me by giving me facts showing the insolvency of the
bank, now made haste to contradict that conclusion and to assure
the committee that it was abundantly able to weather the financial
storm, and pay dollar for dollar to its depositors if allowed to go on.
I was not exactly thunderstruck, but I was much amazed by this
contradiction. I, however, adhered to my statement that the bank
ought to stop. The finance committee substantially agreed with me,
and in a few weeks so legislated as to bring this imposing banking
business to a close by appointing three commissioners to take
charge of its affairs.
This is a fair and unvarnished narration of my connection with
the Freedmen’s Savings and Trust Company, otherwise known as
the Freedmen’s Savings Bank, a connection which has brought upon
my head an amount of abuse and detraction greater than any
encountered in any other part of my life.
Before leaving the subject I ought in justice to myself to state
that when I found that the affairs of the bank were to be closed up, I
did not, as I might easily have done, and as others did, make myself
a preferred creditor and take my money out of the bank, but on the
contrary, I determined to take my chances with other depositors, and
left my money, to the amount of two thousand dollars, to be divided
with the assets among the creditors of the bank. And now, after
seven years have been allowed for the value of the securities to
appreciate and the loss of interests on the deposits for that length of
time, the depositors may deem themselves fortunate if they receive
sixty cents on the dollar of what they placed in the care of this fine
savings institution.
It is also due to myself to state, especially since I have seen
myself accused of bringing the Freedmen’s Bank into ruin, and
squandering in senseless loans on bad security the hardly-earned
moneys of my race, that all the loans ever made by the bank were
made prior to my connection with it as its president. Not a dollar, not
a dime of its millions were loaned by me, or with my approval. The
fact is, and all investigation shows it, that I was married to a corpse.
The fine building was there with its marble counters and black walnut
finishings, the affable and agile clerks, and the discreet and comely
colored cashier; but the Life, which was the money, was gone, and I
found that I had been placed there with the hope that by “some
drugs, some charms, some conjuration, or some mighty magic,” I
would bring it back.
When I became connected with the bank I had a tolerably fair
name for honest dealing; I had expended in the publication of my
paper in Rochester thousands of dollars annually, and had often to
depend upon my credit to bridge over immediate wants, but no man
there or elsewhere can say I ever wronged him out of a cent; and I
could, to-day, with the confidence of the converted centurion, offer
“to restore fourfold to any from whom I have unjustly taken aught.” I
say this, not for the benefit of those who know me, but for the
thousands of my own race who hear of me mostly through the
malicious and envious assaults of unscrupulous aspirants who vainly
fancy that they lift themselves into consideration by wanton attacks
upon the characters of men who receive a larger share of respect
and esteem than themselves.
CHAPTER XV.
WEIGHED IN THE BALANCE.
The Santo Domingo controversy—Decoration day at Arlington, 1871—Speech

delivered there—National colored convention at New Orleans, 1872—
Elector at large for the State of New York—Death of Hon. Henry Wilson.
THE most of my story is now before the reader. Whatever of good or ill
the future may have in store for me, the past at least is secure. As I
review the last decade up to the present writing, I am impressed with a
sense of completeness; a sort of rounding up of the arch to the point
where the key stone may be inserted, the scaffolding removed, and the
work, with all its perfections or faults, left to speak for itself. This
decade, from 1871 to 1881, has been crowded, if time is capable of
being thus described, with incidents and events which may well
enough be accounted remarkable. To me they certainly appear
strange, if not wonderful. My early life not only gave no visible promise,
but no hint of such experience. On the contrary, that life seemed to
render it, in part at least, impossible. In addition to what is narrated in
the foregoing chapter, I have to speak of my mission to Santo
Domingo, my appointment as a member of the council for the
government of the District of Columbia; my election as elector at large
for the State of New York; my invitation to speak at the monument of
the unknown loyal dead, at Arlington, on Decoration day; my address
on the unveiling of Lincoln monument, at Lincoln Park, Washington; my
appointment to bring the electoral vote from New York to the National
Capital; my invitation to speak near the statue of Abraham Lincoln,
Madison Square, New York; my accompanying the body of Vice-
President Wilson from Washington to Boston; my conversations with
Senator Sumner and President Grant; my welcome to the receptions of
Secretary Hamilton Fish; my appointment by President R. B. Hayes to
the office of Marshal of the District of Columbia; my visit to Thomas
Auld, the man who claimed me as his slave, and from whom I was
purchased by my English friends; and my visit to Lloyd’s plantation, the
home of my childhood, after an absence of fifty-six years; my
appointment by President James A. Garfield to the office of Recorder
of Deeds of the District of Columbia, are some of the matters which
belong to this decade, and may come into the chapter I am now about
to write.
Those who knew of my more than friendly relations with Hon.
Charles Sumner, and of his determined opposition to the annexation of
Santo Domingo to the United States, were surprised to find me
earnestly taking sides with Gen. Grant upon that question. Some of my
white friends, and a few of those of my own color—who, unfortunately,
allow themselves to look at public questions more through the medium
of feeling than of reason, and who follow the line of what is grateful to
their friends rather than what is consistent with their own convictions—
thought my course was an ungrateful return for the eminent services of
the Massachusetts senator. I am free to say that, had I been guided
only by the promptings of my heart, I should in this controversy have
followed the lead of Charles Sumner. He was not only the most
clearsighted, brave, and uncompromising friend of my race who had
ever stood upon the floor of the Senate, but was to me a loved,
honored, and precious personal friend; a man possessing the exalted
and matured intellect of a statesman, with the pure and artless heart of
a child. Upon any issue, as between him and others, when the right
seemed in anywise doubtful, I should have followed his counsel and
advice. But the annexation of Santo Domingo, to my understanding,
did not seem to be any such question. The reasons in its favor were
many and obvious; and those against it, as I thought, were easily
answered. To Mr. Sumner, annexation was a measure to extinguish a
colored nation, and to do so by dishonorable means and for selfish
motives. To me it meant the alliance of a weak and defenceless
people, having few or none of the attributes of a nation, torn and rent
by internal feuds, unable to maintain order at home, or command
respect abroad, to a government which would give it peace, stability,
prosperity, and civilization, and make it helpful to both countries. To
favor annexation at the time when Santo Domingo asked for a place in
our union, was a very different thing from what it was when Cuba and
Central America were sought by fillibustering expeditions. When the
slave power bore rule, and a spirit of injustice and oppression
animated and controlled every part of our government, I was for
limiting our dominion to the smallest possible margin; but since liberty
and equality have become the law of our land, I am for extending our
dominion whenever and wherever such extension can peaceably and
honorably, and with the approval and desire of all the parties
concerned, be accomplished. Santo Domingo wanted to come under
our government upon the terms thus described; and for more reasons
than I can stop here to give, I then believed, and do now believe, it
would have been wise to have received her into our sisterhood of
States.
Charles Sumner
The idea that annexation meant degradation to a colored nation,
was altogether fanciful; there was no more dishonor to Santo Domingo
in making her a State of the American union, than in making Kansas,
Nebraska, or any other territory such a State. It was giving to a part the
strength of the whole, and lifting what must be despised for its isolation
into an organization and relationship which would compel
consideration and respect.
Though I differed from Mr. Sumner in respect of this measure, and
although I told him I thought he was unjust to President Grant, it never
disturbed our friendship. After his great speech against annexation,
which occupied six hours in its delivery, and in which he arraigned the
President in a most bitter and fierce manner, being at the White House
one day, I was asked by President Grant what I “now thought of my
friend Mr. Sumner”? I replied that I believed Mr. Sumner sincerely
thought, that in opposing annexation, he was defending the cause of
the colored race as he always had done, but that I thought he was
mistaken. I saw my reply was not very satisfactory, and said: “What do
you, Mr. President, think of Senator Sumner?” He answered, with
some feeling, “I think he is mad.”
The difference in opinion on this question between these two great
men was the cause of bitter personal estrangement, and one which I
intensely regretted. The truth is, that neither one was entirely just to
the other, because neither saw the other in his true character; and
having once fallen asunder, the occasion never came when they could
be brought together.
Variance between great men finds no healing influence in the
atmosphere of Washington. Interested parties are ever ready to fan the
flame of animosity and magnify the grounds of hostility in order to gain
the favor of one or the other. This is perhaps true in some degree in
every community; but it is especially so of the National Capital, and
this for the reason that there is ever a large class of people here
dependent upon the influence and favor of powerful public men for
their daily bread.
My selection to visit Santo Domingo with the commission sent
thither, was another point indicating the difference between the old
time and the new. It placed me on the deck of an American man-of-
war, manned by one hundred marines and five hundred men-of-wars-
men, under the national flag, which I could now call mine, in common
with other American citizens, and gave me a place not in the fore-
castle, among the hands, nor in the caboose with the cooks, but in the
captain’s saloon and in the society of gentlemen, scientists, and
statesmen. It would be a pleasing task to narrate the varied
experiences and the distinguished persons encountered in this Santo
Domingo tour, but the material is too boundless for the limits of these
pages. I can only say, it was highly interesting and instructive. The
conversations at the Captain’s table (at which I had the honor of a
seat) were usually led by Messrs. Wade, Howe, and White—the three
commissioners; and by Mr. Hurlburt of the New York World; the last-
named gentleman impressed me as one remarkable for knowledge
and refinement, in which he was no whit behind Messrs. Howe and
White. As for Hon. Benj. F. Wade, he was there, as everywhere,
abundant in knowledge and experience, fully able to take care of
himself in the discussion of any subject in which he chose to take a
part. In a circle so brilliant, it is no affectation of modesty to say I was
for the most part a listener and a learner. The commander of our good
ship on this voyage, Capt. Temple, now promoted to the position of
Commodore, was a very imposing man, and deported himself with
much dignity towards us all. For his treatment to me I am especially
grateful. A son of the United States navy as he was,—a department of
our service considerably distinguished for its aristocratic tendencies, I
expected to find something a little forbidding in his manner; but I am
bound to say that in this I was agreeably disappointed. Both the
commander and the officers under him bore themselves in a friendly
manner towards me during all the voyage, and this is saying a great
thing for them, for the spectacle presented by a colored man seated at
the captain’s table was not only unusual, but had never before
occurred in the history of the United States navy. If during this voyage
there was anything to complain of, it was not in the men in authority, or
in the conduct of the thirty gentlemen who went out as the honored
guests of the expedition, but in the colored waiters. My presence and
position seemed to trouble them for its incomprehensibility; and they
did not know exactly how to deport themselves towards me. Possibly
they may have detected in me something of the same sort in respect of
themselves; at any rate we seemed awkwardly related to each other
during several weeks of the voyage. In their eyes I was Fred. Douglass
suddenly, and possibly undeservedly, lifted above them. The fact that I
was colored and they were colored had so long made us equal, that
the contradiction now presented was too much for them. After all, I
have no blame for Sam and Garrett. They were trained in the school of
servility to believe that white men alone were entitled to be waited
upon by colored men; and the lesson taught by my presence on the
“Tennessee” was not to be learned upon the instant, without thought
and experience. I refer to the matter simply as an incident quite
commonly met with in the lives of colored men who, by their own
exertions or otherwise, have happened to occupy positions of
respectability and honor. While the rank and file of our race quote with
much vehemence the doctrine of human equality, they are often
among the first to deny and denounce it in practice. Of course this is
true only of the more ignorant. Intelligence is a great leveler here as
elsewhere. It sees plainly the real worth of men and things, and is not
easily imposed upon by the dressed up emptiness of human pride.
With a colored man on a sleeping car as its conductor, the last to
have his bed made up at night, and the last to have his boots blacked
in the morning, and the last to be served in any way, is the colored
passenger. This conduct is the homage which the black man pays to
the white man’s prejudice whose wishes, like a well-trained servant, he
is taught to anticipate and obey. Time, education, and circumstances
are rapidly destroying these mere color distinctions, and men will be
valued in this country as well as in others, for what they are, and for
what they can do.
My appointment at the hands of President Grant to a seat in the
council—by way of eminence sometimes called the upper house of the
territorial legislature of the District of Columbia—at the time it was
made, must be taken as a signal evidence of his high sense of justice,
fairness, and impartiality. The colored people of the district constituted
then as now about one-third of the whole population. They were given
by Gen. Grant, three members of this legislative council—a
representation more proportionate than any that has existed since the
government has passed into the hands of commissioners, for they
have all been white men.
Commissioners to Santo Domingo.
It has sometimes been asked why I am called “Honorable.” My
appointment to this council must explain this, as it explains the
impartiality of Gen. Grant, though I fear it will hardly sustain this
prodigious handle to my name, as well as it does the former part of this
proposition. The members of this district council were required to be
appointed by the President, with the advice and consent of the United
States Senate. This is the ground, and only ground that I know of,
upon which anybody has claimed this title for me. I do not pretend that

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Neurophotonics and brain mapping 1st

Non Neuronal Mechanisms of Brain Damage and Repair

Mapping Populism Approaches and Methods 1st Edition

Mapping Human and Natural Systems 1st Edition Pete

Geographical Information System and Crime Mapping 1st

Elicitive Conflict Mapping 1st Edition Wolfgang

The Ecological Brain: Unlying the Sciences of Brain,

Cardiac Mapping 5th Edition Mohammad Shenasa

Cultural Mapping as Cultural Inquiry 1st Edition Nancy

Society for Brain Mapping & Therapeutics Mission Statement

Brain Mapping Foundation Mission Statement

National Center for NanoBioElectronics Mission Statement

California Neurosurgical Institute Mission Statement

California Institute of Neuroscience Mission Statement

© 2017 by Taylor & Francis Group, LLC

No claim to original U.S. Government works

Printed on acid-free paper

International Standard Book Number-13: 978-1-4822-3685-9 (Hardback)

Library of Congress Cataloging‑in‑Publication Data

Visit the Taylor & Francis Web site at

and the CRC Press Web site at

This work is dedicated to our families, friends, spouse,

Dr. Yu Chen and Dr. Britton Chance

Chapter 1 History of Brain Mapping and Neurophotonics: From Technological

Section I Optical Spectroscopy and Spectral Imaging of Brain

Chapter 2 Pain Assessment Using Near-Infrared Spectroscopy..................................................21

Chapter 3 Application of Functional Near-Infrared Spectroscopy in Brain Mapping.................41

Chapter 4 Therapeutic Monitoring of Children with Attention Deficit Hyperactivity

Chapter 5 Functional Near-Infrared Spectroscopy: In Search of the Fast Optical Signal...........77

Chapter 6 Voltage-Sensitive Dye and Intrinsic Signal Optical Imaging: Advantages

Chapter 7 Optical Techniques to Study Drug-Induced Neurovascular and Cellular

Chapter 8 Three-Dimensional Optical Coherence Microscopy Angiography and Mapping

Chapter 9 Doppler Optical Coherence Tomography and Its Application in Measurement

Chapter 12 Photoacoustic Neuroimaging....................................................................................235

Chapter 13 Perfusion Brain Mapping in the Treatment of Acute Stroke.....................................257

Section III Intraoperative Neuroimaging

Chapter 15 UV-Based Imaging Technologies for Intraoperative Brain Mapping........................299

Chapter 16 Visible Light Optical Imaging and Spectroscopy during Neurosurgery...................311

Chapter 17 Intraoperative Infrared Optical Imaging in Neurosurgery.........................................325

Chapter 18 Autofluorescence-Guided Resection of Intracranial Tumor: Past, Present, and Future.......341

Chapter 19 Spectro-Temporal Autofluorescence Contrast–Based Imaging for Brain Tumor

Chapter 21 Intraoperative Optical Guidance for Neurosurgery...................................................383

Section IV Image-Guided Intervention and Phototherapy

Chapter 23 FUS-Mediated Image-Guided Neuromodulation of the Brain..................................443

Chapter 24 Advances in Portable Neuroimaging and Their Effect on Novel Therapies.............457

Chapter 25 The Deep Brain Connectome....................................................................................479

Chapter 26 Neurovascular Photonics...........................................................................................487

Chapter 27 Neurophotonics for Peripheral Nerves......................................................................499

Chapter 28 EEG Biomarkers in Depression................................................................................513

Chapter 29 fMRI as a Biomarker in Neuroimaging.....................................................................525

Chapter 30 Single-Neuron Recordings from Depth Electrodes with Embedded Microwires

The MathWorks, Inc.

Frank Boehm Fatima A. Chowdhry

Salman Abbasi Fard Javier Herrera-Vega

Warren Grundfest Caroline Jia

Rao P. Gullapalli Ferenc A. Jolesz

Daniel X. Hammer Ranu Jung

Babak Kateb Xingde Li

Martin M. Mortazavi Brian Pikul

Zhaojun Nie Kambiz Pourrezaei

Karla J. Sanchez-Perez Nevzat Tarhan

Baris Ünsalver Michael E. Wolf

Geethika Weliwitigoda William H. Yong