Dr. Vincent
Tomaselli
Research Foundation of City University of New York
30 West Broadway
New York, NY 10003
Phone: 212 417 8320
Fax: 212 417 6448
E-mail: vptrf@cunyvm.cuny.edu
Number of Human Subjects projects reported: 5
"Near Infrared Spectroscopy (NIRS) in Patients with Obstructive Sleep Apnea Syndromes"
Principal Investigator: Dr. Arthur Spielman, City University of New York
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: City University of New York
Most recent approval: 04/13/00
IRB approval number: H-0002
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Fiscal Year 2000 (10/1/99-9/30/2000)
Type(s) of Human Subjects Involvement:
One of the series sleep disorder diseases is obstructive sleep apnea syndrome (OSAS). OSAS is described as a potentially lethal disease because it leads to hypoxia and hypoxemia. Since the brain is very sensitive to hypoxia, the recurrent decrease of the arterial oxygen saturation in sleep apnea could cause the patient to not get enough rest, to induce brain injury, and even to cause death during the sleep apnea status.
Conventional polysomnography detects sleep apnea in correlation to the various sleep stages and the finger pulse oximetry signal is used to determine arterial oxygen saturation, but does not provide information on brain oxygenation, especially in subjects with preexisting anatomical functional vascular pathology.
The methodology of the study of OSAS patient subjects is to investigate the brain blood dynamic changes that accompany recurrent episodes of obstructive hypopnea during sleep. Two diode lasers were used at 830 nm and 780 nm. These wavelengths were selected on each side of the isobastic point of the oxy-hemoglobin and deoxy-hemoglobin absorption spectra around ~800 nm. The beam was modulated at different low frequencies, 367 Hz and 600 Hz, respectively. The light propagates through a 1.0-mm optical fiber to the sample surface of the subject about 0.25 mw (0.1 mw for 780 nm and 0.15 mw for 830 nm) at the output point. The output power of the fiber is set below 0.32 mw for each wavelength at a level safe for human subjects. A 5-mm diameter glass fiber bundle optical waveguide will be used to collect the optical signal at a distance 3-cm away from the pump fiber. The collected optical signal is passed through a wide band filter center wavelength 800 nm to remove the environment light noise, and is then transformed to an electrical signal by a single photo multiplier tube. Two PC-board lock-in amplifiers are used for detection. The two wavelengths optical signals were detected at the chopped frequencies read out from the two lock-in amplifier outputs and recorded in a computer data file for post data processing. The optical fiber probes were placed 3 cm apart and embedded in an elastic headband with a perpendicular orientation to the surface of the forehead. Symmetrically positioned across the midline, the input probe was to the left and the detector probe to the right. Both probes were approximately equidistant from the eyebrows and hairline. Bipolar EEG signals and the NIRS signals were simultaneously recorded by connecting to a polygraph recorder and a PC computer based digital recorder. For the daytime nap experiment, the arterial blood oxygenation (SaO2) status was obtained from a finger of the subject by a finger pulse oximeter. The breath property was obtained from the nose tidal air by an end tidal CO2 monitor. The SaO2 signal, end tidal CO2 signal and the NIRS signals were simultaneously recorded by connecting to a polygraph recorder and a PC computer based digital recorder.
Procedure: The napping protocol was made from 2 to 5 p.m. Following preliminary calibrations and 3 minutes of waking recording with eyes alternatively opened and closed, the room lights were turned off, and the subject was requested to stop breathing by the order of the operator to produce an artificial apnea for comparison with sleep apnea. After three trails of the breathing holding test, the door of the sound attenuated room was closed and the subject was told to go to sleep. The nighttime sleep began around 11 p.m., the typical sleep time of the subject. An additional air mask was hooked up on the subjects face and connected to a continuous positive airway pressure (CPAP) treatment equipment to help improve the breathing quality of the subject during the night sleep. The beginning procedure is the same as the nap experiment. Following preliminary calibrations and 3 minutes of waking recording with eyes alternatively opened and closed, the room lights were turned off, and the subject was requested to stop breathing by the order of the operator to produce an artificial apnea for comparison with sleep apnea. After three trails of the breathing holding test, the door of the sound attenuated room closed and the subject was told to go to sleep. Nasal continuous positive airway pressure (NCPAP) was set at 3 cm of H2O at the start of the nocturnal polysomnogram. Shortly after falling asleep CPAP was increased to 6 cm of H2O and this resolved the mixed obstructive apneas.
The risks for human subjects associated with this study are minimal:
1. On the basis of studies that have been done there are no known risks associated with the low power near-infrared laser light used in this study. According to the standards established by the American National Standards Institute (Safe Use for Lasers, 1993) the level of light and time of exposure used in this study falls within the category that is considered to be incapable of producing damaging radiation levels.
2. Abrasions or pressure at the site of electrodes or light source or detectors may occur. If an abrasion occurs the technician on duty will have an ointment available that the human subject may use if he wishes. If the subject feels pressure from a sensor or light source the technician will make adjustments to alleviate the pressure.
The identity of the participating person(s) will remain confidential. Any publication or presentation of the results of this study will not identify the subject(s) in any way. The records of the study will be kept confidential to the extent permitted by law.
"Imaging the Brain with Near Infrared Light During Sleep"
Principal Investigator: Dr. Arthur Spielman, City University of New York
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: City University of New York
Most recent approval: 05/10/00
IRB approval number: H-0009
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Fiscal Year 2000 (10/1/99-9/30/2000)
Type(s) of Human Subjects Involvement:
Objective
Previous imaging studies have shown that cerebral metabolism is gradually reduced at the beginning of sleep. Few studies have examined the sleep state transition periods from wakefulness to sleep and sleep to wakefulness. The objective of the current study is to use the Near Infrared Spectroscopy (NIRS) technique to describe the intracerebral hemodynamics at the frontal pole in the circumscribed period between wakefulness and sleep.
Methodology
Healthy young adults were studied during afternoon naps. Optical probes were placed on the forehead and EEG electrodes on the scalp. At sleep onset oxygenated hemoglobin (oxy-Hb) was reduced (P<0.01) and deoxygenated hemoglobin (deoxy-Hb) showed a near significant reduction (P<0.063). At sleep offset there were increases in oxy-Hb (P<0.005) and deoxy-Hb (P<0.05). In 18 of 26 transition to sleep there was a coordinated fall in both NIRS parameters, we call the Switch Point, that lasted a mean of 3.6 s. In 32 of 36 transitions to wakefulness there was an analogous Switch Point that lasted a mean of 3.4 s. Before and after the Switch Point, changes were small and the relationship between oxy-Hb and deoxy-Hb was a combination of parallel and reciprocal fluctuations. A synchronized, parallel and short-lived change in oxy-Hb and deoxy-Hb is a discrete event in the transition period between wakefulness and sleep. The concentration of these light absorbing molecules is abruptly set to a new level at sleep-wake transition and probably reflects the different perfusion demand of these states.
Involvement of Human Subjects
Qualified human subjects participating in the study have spent a night sleeping in the Sleep Disorders center. At the beginning of the night a subject was awakened shortly after falling asleep on a few occasions and asked questions. The following sensors were applied to subjects head and body to make continuous measurements: face and scalp sensors to record brain waves; corner of eyes sensors to measure eye movement; chin and legs sensors to measure muscle activity; one or more belt-type devices around chest-stomach area to record breathing efforts, under nose and near mouth sensors to measure airflow and carbon dioxide, a light emitting probe on one finger to measure the oxygen level of the blood, and chest electrodes to record the heart rhythm. In addition, the near-infrared apparatus was put on the head for continuous recording.
The risks for human subjects associated with this study are minimal. On the basis of studies that have been done there are no known risks associated with the low power near-infrared laser light used in this study. According to the standards established by the American National Standards Institute (Safe Use of Lasers, 1996) the level of light and time of exposure used in this study falls within the category that is considered to be incapable of producing damaging radiation levels. The abrasions or pressure at the site of electrodes or light source or detectors may occur. If an abrasion occurs the technician on duty have an ointment available that the subject may use if he wish. If the subject feels pressure from a sensor or light source the technician makes adjustments to alleviate the pressure.
The identity of participating person will remain confidential. Any publication or presentation of the results of this study will not identify the person in any way. The records of the study will be kept confidential to the extent permitted by law.
"Breast Cancer Program: Optical Mammography"
Principal Investigator: Dr. Robert R. Alfano, City University of New York
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: City University of New York
Most recent approval: 10/29/99
IRB approval number: H9938-C
Explanation of IRB approval:
Date of most recent renewal
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2000 (10/1/99-9/30/2000)
Type(s) of Human Subjects Involvement:
The objective of the project is to develop a noninvasive non-ionizing breast cancer screening modality with diagnostic ability using near-infrared light.
The methodology of the study is based on the use of picosecond laser pulses as the probing source and an ultrafast shutter to select the earlier arrival photons with the minimum distortion. When photons migrate through a random media, such as the human breast, there are three main contributions to the transmitted light: diffusive (incoherent, scattered), ballistic (coherent, unscattered, first arriving photons, shortest time-to-flight), and snake (nearly unscattered, photons arriving during the first 10-ps). The diffusive portion of the signal travels over a much longer distance than the ballistic and snake parts which take the shorter paths through the medium within a small forward cone. The diffusive part introduces noise mixing with the undistorted signal and scrambles the information to be imaged or mapped. The ballistic and snake photons carry the least distorted image and can be measured using time-gated techniques. With the advancement of ultrashort laser pulses, a 100 micron spatial resolution of the optical image in modeled systems and human breast tissues in vitro has been achieved. Based on time-resolved imaging which restricts detection to the earliest arriving photons, 1 mm spatial resolution of the transient image of the human breast in vivo can be obtained using a ps time gate.
The procedures involving human subjects are as follows:
Human subject (woman) in this study will be asked (1) to take one section of optical imaging through her right breast at CCNY, (2) to take one conventional x-ray mammography at Memorial Sloan-Kettering Cancer Center (MSKCC), and (3) to take another section of optical imaging at CCNY after x-ray mammography. There is no intention to diagnose disease from this study. If there are any findings from the mammography, physicians at MSKCC will be responsible for informing the subject. The subject will not pay anything, except her own transportation. After the completion of the measurements, the subject will receive a $100 check in mail to compensate for her time and any expenses.
For the optical imaging study, the subject will lie on her chest on a mammography bed. One of subject's breasts will hang down through an opening in the bed and will be placed between a pair of plastic plates. The plates may be moved with respect to each other and thus to compress the breast to provide uniform thickness. There may be minor discomfort due to the low pressure compression (~ 25 lbs or 0.25 newtons/cm2) from the plates. Under any conditions, the subject can ask to stop the compression procedure. Laser light will illuminate the compressed breast through one of the plates, and the transmitted light will be collected through the second plate. Several exposures will be taken from different directions. Each exposure time should be less than ten minutes. The total experimental time will be under two hours for one session. The transmitted light will be recorded by a time gated charge couple device (CCD) camera which can store and digitize image information. The subject can withdraw at any time without penalties.
The identity of the subject as a participant in this research will remain confidential. Any publication or presentation of the results of this study will not identify the subject except in general terms such as age or race group. The records in this study will be kept confidential to the extent permitted by law. If the subject will have any questions or if any problems arise as a result of her participation in this research, she should contact the PI of the project.
The participating subject will be supplied with laser safety goggles which she will wear to protect her eyes from laser beams. There are no known risks associated with the low energy near infrared laser pulses other than the direct illumination to unprotected eyes. There will be no benefit to the participating subject directly except the $100 compensation for her time and expenses. Information obtained from her participation will help to obtain more knowledge towards developing a new methods of optical screening of breast cancer.
"Skin Subsurface Imaging Using Spectral and Polarization Imaging"
Principal Investigator: Dr. Robert R. Alfano, City University of New York
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: City University of New York
Most recent approval: 10/29/99
IRB approval number: H9939-C
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2000 (10/1/99-9/30/2000)
Type(s) of Human Subjects Involvement:
Objective
The objective of the project to employ non linear optics (second harmonic generation and two photon fluorescence) to develop noninvasive in situ and in vivo tomographic and histologic techniques to construct 3-D layered structure maps of symmetry and content of native fluorophors in human tissue. One may use these images to distinguish regions on a tissue at different states: normal, benign, pre-cancer, and cancerous.
Methodology
Research methodology is based on the sub-micron resolution and structural response from non-linear optical signals (harmonic generation and multi-photon excitation of fluorescence). 3-D images will be obtained by mapping the non linear signal generated from a focused, ultra short pulsed laser system, using depth (z) and lateral (x, y) scanning.
Involvement of human subjects
To date, no measurements have been performed on human subjects. In the future, volunteer subjects will be recruited for participation in this study.
The procedures involving human subjects will be as follows: The subject will sit on a chair and leave one of his fingers, hands, or arms on a platform to be illuminated by a light source. There should be no physical pain at all under any conditions. It may take five exposures with each exposure time less than 5 minutes. The total experimental time should be less than 2 hours and the total exposure time should be less than 30 minutes. During the exposure, if the subject will feel any symptoms of heat or burning, he can ask to stop the experiment immediately. The low energy laser pulses will be directing toward the subject's finger, hand, or arm and the emitted signal light will be recorded by a charge-couple-device (CCD) camera. The subject can withdraw at any time without penalty.
The identity of a participant in this research will remain confidential. Any publication or presentation of the results of this study will not identify the subject in any way without his prior approval. The records in this study will be kept confidential to the extent permitted by law.
If the subject will have any questions or if any problems arise as a result of his participation in this research, he should contact PI of the project. There will be no benefit to the subject directly, besides the knowledge that he will be contributing to a better understanding of imaging of skins.
Risks
To our knowledge, there is no known data to report the safety hazard at the planned excitation energy and power levels. The nonlinear processes will generate low levels of UVA radiation (320 to 400 nm). Subjects may be exposed to this radiation. It is estimated that the maximum UV exposure will be less than 3 mJ/cm2.
"Hormone Levels Probed by Fluorescence Spectroscopy of the Female Genitalia"
Principal Investigator: Dr. Robert R. Alfano, City University of New York
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: City University of New York
Most recent approval: 04/26/00
IRB approval number: H-0024
Additional IRB approvals from other institutions:
Type of Review: Full Board
Approving Institution: Yale School of Medicine
Most recent approval: 04/03/00
IRB approval number: HIC 9211
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Fiscal Year 2000 (10/1/99-9/30/2000)
Type(s) of Human Subjects Involvement:
Objectives:
Investigate the capability of using native fluorescence spectroscopy of the female genitalia for the purpose of monitoring hormone levels.
Methodology:
Perform emission and excitation fluorescence measurements from the vulva in the blue and UVA spectral regions. For three healthy volunteers fluorescence from the skin on the volar aspect of the forearm and the fourchette on the vulva was measured on a daily basis, excluding weekends, for two menstrual cycles. One volunteer measured the fluorescence on the inner aspect of the labia minora and on the gum for one additional cycle. Fluorescence measurements were performed by the subject using the Mediscience Technology CD-Scan. Basil body temperature and first morning urine were collected to measure levels of estrogen and progesterone in the urine. Spectra were analyzed to determine if the emission intensity or wavelength from collagen and other tissue fluorophores change during the patient's cycle. Variation in spectral intensity and/or profile will be corrected with hormonal changes.
Involvement of Human Subjects:
Subjects are recruited from nursing staff at the Yale New Haven Hospital. Informed consent was acquired from each subject prior to performing any measurements. Each subject was instructed in the use of the CD-Scan spectrometer by a physician, prior to initiating a cycle of measurements. Measurements are made by placing one end of a fiber optic probe in contact with the vulva using minimum pressure to maintain contact. Subjects were instructed to position the probe at the same location for each series of measurements. Data collection was controlled by the SD-Scan computer and is fully automated. The measurements consist of six scans and take about five minutes to complete. During this time, patients were exposed to approximately 0.7 millijoules/cm^2 of UVA radiation. This compares to the threshold limit value of 2900 millijoules/cm^2 at 320 nm, established by the American Conference of Governmental and Industrial Hygienists (ACGIH).
Patient confidentiality is preserved by having a unique study number assigned to each subject and only identifying scans by this number.