Ms. Montana Compton
1002 Health Sciences Rd East
Irvine, CA 92612
Phone: 949-824-9265
Fax: 949-824-8413
E-mail: mocomton@uci.edu
Number of Human Subjects projects reported: 1
| BLI-91-ER61227 | "A Center of Excellence for Laser Applications in Medicine" |
"A Center of Excellence for Laser Applications in Medicine"
Principal Investigator: Dr. Michael W. Berns, University of California Irvine
Project started in: 1991
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Beckman Laser Institute/UC Irvine
Most recent approval: 09/24/03
IRB approval number: HS 95-563
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 232
Reporting period for number of human subjects:
Fiscal Year 2003
Type(s) of Human Subjects Involvement:
Objectives:
Our goal is to move towards developing a simple, rapid, hand-held optical screening device which will yield low resolution tissue functional information that complements and enhances the detailed structural information obtained from x-ray mammography. The functional information obtained from the optical screening device should allow for distinguishing between healthy and diseased tissue by providing a description of the tissue cellular state. Most non-optical imaging technologies measure static physical structure rather than cellular state, so that while images may reflect anatomical details, they reveal nothing about the functionality of the tissue. For example, x-ray mammography often does not distinguish between healthy and dying tissues, even though such functional information may be crucial to accurate diagnosis and effective medical treatment. Hence, the broad, long-term goal of this project is to develop a novel, non-invasive optical diagnostic technique which quantitatively determines near-infrared optical absorption and scattering parameters in discrete volumes (about 0.25-0.50 cm3) of heterogeneous breast tissue.
Methodology:
Optical properties can be determined in biological tissues using Frequency-Domain Photon Migration (FDPM) by a single non-invasive measurement. In FDPM, the intensity of light aimed upon a biological material is modulated at high frequencies, and the diffusely reflected or transmitted signal is measured with a phase-sensitive detector. Intensity-modulated light propagates through a turbid medium with a coherent front, forming photon density waves. The wave dispersion is highly dependent on the optical properties of the medium and the measured parameters characterizing the wave dispersion can be used to rapidly determine these properties, namely the medium scattering and absorption parameters.
Prior studies have been conducted on tissue phantoms and have shown that accurate optical properties can be extracted regarding the medium under investigation. Ex vivo studies on bulk human and animal tissues using a "first generation" low-bandwidth (250 MHz) FDPM device have demonstrated the need for in vivo measurements using a high-bandwidth, multi-wavelength instrument. Other studies have been performed on suspensions of cells and subcellular organelles under carefully controlled environmental conditions. These experiments were conducted in order to establish a structural basis for optical properties in simple biological models. They demonstrate varied optical characteristics for different cell types and subcellular components. It is expected that these observations will allow us to gain histo/physiological diagnostic insight from the scattering and absorption parameters derived from FDPM breast tissue measurements. To address this need, Dr. Tromberg's group has developed a high-bandwidth (1 GHz) FDPM device.
Instrumentation:
The portable high-bandwidth FDPM instrument employs intensity-modulated diode lasers and conventional steady-state lamps as sources and an avalanche photodiode as the detector. A network analyzer (Hewlett Packard model 8753C), which measures reflection and transmission characteristics of devices and networks, is used to produce an RF signal swept from 300 kHz to 1 GHz superimposed on the direct current of the laser diode (SDL, Inc. model 7420). The network analyzer is driven by a computer (Dell Dimension PC), which uses custom-designed virtual instrument code to render the measurement session convenient and “user-friendly.” Different wavelengths are accessed by serially addressing an RF switch array (Hewlett Packard, model 8768K). Up to 16 unique laser wavelengths within the visible to near-infrared region are used. In some cases, a conventional light source is used to fill the gap between laser wavelengths. Each laser output is directly coupled into optical fibers which are bundled at the probe end and placed in contact with the tissue. The optical power launched into the sample (lasers or conventional sources) averages 10-50 mW (comparable to halogen-bulb household flashlights). Backscattered light is either collected by an optical fiber or coupled directly to an optical detector [avalanche photodiode detector (APD, Hamamatsu, model C5658, 12 V bias)] placed in contact with the skin. The time required to perform an FDPM measurement depends on the desired precision and number of sweeps. At present, approximately 30 to 60 seconds are needed to record data from typical tissues at a given wavelength and position. Several locations judged clinically relevant are probed. Total measurement time ranges from approximately 5 to 90 minutes, depending on the number of sites mapped and style of measurement.
Involvement of Human Subjects:
1. Procedures:
Non-invasive measurements of breast tissue optical properties will be performed on the skin surface using a specially designed FDPM measurement probe which is similar in shape to an ultrasound probe. The FDPM probe is embedded with optic fibers set at a fixed separation. The FDPM probe will be placed on different areas of the breast including areas suspected to have disease and areas appearing to be normal. The diseased location will be identified by clinical palpation. In some cases, optical measurements will be guided by co-registered ultrasound measurements for the purpose of determining lesion size and location. There are two guiding principles as to the use of ultrasound: (1) The ultrasound will ONLY be used in women who have had a breast lesion detected by a physician, and (2) the ultrasound scan will ONLY be performed in the region of the lesion, and will not be used in other areas of the breast. This ultrasound will NOT be available as a medical record for the patient; it is for research purposes only. Some mild tissue compression will be performed within comfort tolerance of the patient during the application of the FDPM probe. When the probe is in position, the laser will be activated and a measurement will be taken. Each measurement will require about 30 to 60 seconds to record the data and calculate optical properties. The probe will then be turned off and moved to a new position for further measurements. The process will be repeated until an adequate number of measurements are performed (10 to 20).
2. Risks:
The optical scan is not expected to cause any pain, burning, or discomfort during or after the exam. There may be risks, however, that are currently unforeseeable. During all measurements, the laser will be turned on only when needed. Although not required for safety, subjects may wear protective eye goggles if requested. The length of surgery and anesthesia time will be slightly longer as a result of this study, and the chance of infection may be minimally increased. However, the patient's face will be behind an opaque sheet to reduce the risk of injury to the eyes and will be monitored very closely during this time. No additional risk or discomfort is anticipated. No other instruments will be used to perform breast biopsy other than those used in conventional surgery.
3. Privacy/confidentiality/consent:
The collection and submission of medical information from this study will be accomplished with the strictest adherence to professional standards and confidentiality. An identification number for each patient will be kept on file, and all records will be filed in a locked area, accessible only to researchers listed on this protocol, authorized representatives of UC Irvine, and any other officials as required by law. Patients will be identified by initials and corresponding identification number. A locator sheet will be completed for each patient that bears the necessary information needed to contact the patient should new information about the use of the study test articles become known in the future which might adversely affect that patient's well-being. A report of the results of this study may be published; however, anonymity will be maintained and names will be known only to the investigator and his technical personnel. Informed consent for research will be obtained when the patients are scheduled for surgery and a detailed explanation of the study will be given.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Beckman Laser Institute/UC Irvine
Most recent approval: 08/05/03
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 80
Reporting period for number of human subjects:
Fiscal Year 2003
Type(s) of Human Subjects Involvement:
Objective:
The purpose of this study is to determine the degree of Port Wine Stain (PWS) lightening and the incidence of side effects during treatment with a 1,500 microsec pulsed dye laser in association with dynamic cooling (ScleroPLUS or Cbeam) at high incident light dosages.
Research Plan:
The study will be a single center study. Subjects will receive PWS treatment with the 1,500 microsec pulsed dye laser in association with CSC (ScleroPLUS) or the 450 microsec pulsed dye laser in association with CSC (Cbeam). These lasers are FDA approved for the treatment of PWS birthmarks. The PWS will be treated with a cryogen spurt of 10-100 ms, a delay of 10-60 ms, and light doses of 6-15 J/cm2. Patients will have repeat treatments every 8 to 12 weeks until the completion of the study or such time as they no longer desire treatment with the ScleroPLUS laser. Patients seeking PWS removal will receive the same treatment whether or not they choose to enter the protocol. Involvement in the protocol will involve only formal documentation of the duration of post-treatment purpura, the incidence of side effects and the comparison of non-invasive reflectance measurements, and before and after treatment photographs by an independent observer (a physician not previously involved in the study) at the completion of the study.
Subjects:
We will enroll 200 subjects who are seeking PWS removal.
Exclusion criteria:
-Pregnancy (There are no known risks of laser treatment to a fetus. Because laser light does not penetrate through the skin, the risk to a fetus is very low. However, the effect of laser light on a fetus has not been specifically studied and thus there may be unknown risks.)
-History of cutaneous photosensitivity
-History of photodermatoses or skin cancer
-Any therapy to the proposed treatment sites within the previous two months
-Current participation in any other investigational drug or device evaluation
-Concurrent use of known photosensitizing drugs
-Inability to understand and carry out subject instructions
Risks:
The study procedure involves only the collection of data and thus there is no risk directly related to the study procedure. Risks of the laser procedure (which the patients would undergo whether or not they participate in the study) will be explained and a separate consent signed for the procedure. The investigators in this clinical trial have extensive experience with the use of laser systems in dermatology. This is the most critical element in managing patient risk. Subjects will be followed closely during the course of the trial and will have access to the investigators at all times via provision of after hours telephone and/or pager numbers.
Benefit:
There is no direct benefit to the patient from participation in the research. The patient may benefit from treatment by blanching of their PWS birthmark. However, there is no guarantee that the PWS will be removed and this is clearly stated in the consent form. The study may benefit future patients desiring the treatment of PWS birthmarks.
Measures Taken to Protect the Rights and Welfare of Subjects:
Any patient interested in participating in the study will be counseled about the protocol. The attending physician, fellow patients and nurses serve as information resources for the patients. After the patient has had a chance to review all materials and has had his/her questions answered, if he/she chooses to be placed in the study, the patient is then enrolled. Each patient will also be given a copy of the consent form and Experimental Subject's Bill of Rights which will be explained to him/her and which he/she must sign in order to be enrolled. The patient may withdraw from the study at any time without penalty and this is stated in the consent form.