Project Proposal. Near-Infrared Imaging System (NIRIS) Team 4 Barbara Adu-Baffour Amir Nasser Bigdeli Albert Pham

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1 Project Proposal Near-Infrared Imaging System (NIRIS) Team 4 Barbara Adu-Baffour Amir Nasser Bigdeli Albert Pham Client Contact Qing Zhu, PhD Professor University of Connecticut, Electrical and Computer Engineering department, New InfoTech Building, Unit 2157, Storrs, CT Telephone: Qing.Zhu@uconn.edu

2 Executive Summary This project aims to create a near-infrared imaging system using laser diodes for imaging biological tissue. The device will provide multiple inputs from a probe of 10 centimeter in diameter that contains multiple laser diodes. The client wants the diodes to be able to operate at two different optical wavelengths, 780nm and 830nm, and the probe to potentially contain up to eight different laser diodes. To operate at these wavelengths the system will be operating in according to the International Commission on Illumination (CIE) at IR-A infrared radiation or near-infrared wavelengths. The proposed device will have each of the laser diodes modulated at different frequencies to enable a spatial coding system and an optical detector channel will be designed with this device to detect signals from all the laser diodes and reveal their spatial locations. The device will have a system that would be able to identify the states of the laser diodes in either an on or off state. The device will have photodetectors placed next to each laser diode to detect the back-scattering off of biological tissue, and ultimately convert that analog signal into an electrical signal. An amplifier will be incorporated into the design to strengthen the signal from the photodetectors for proper processing through a data acquisition device, which will be connected to a computer and monitored with LabVIEW software. This software will programmatically detect the states of each diode and filter any noise using a bandpass filter. The filter will be designed to sort out the specified frequencies and separate multiple frequencies that might be detected by the photodetectors, placing each separate signal on a graph that is displayed on an interactive user interface.

3 1. Introduction 1.1 Background The Near Infrared Imaging System (NIRIS) is a research based device that will help the client in her research on imaging of cancerous tissues. The client Dr. Zhu is a Professor in the Department of Electrical and Computer Engineering at the University of Connecticut in Storrs CT. Professor Zhu is a leading researcher in combining ultrasound and near infrared (NIR) imaging modalities for clinical diagnosis of breast cancers. The primary concept behind the NIRIS for imaging biological tissue stems from the discovery that the transmission and absorption of near-infrared light by biological tissue can provide information about hemoglobin concentration changes. By employing several wavelengths and time resolved (frequency or time domain) and/or spatially resolved methods, blood flow, volume, and oxygenation can be quantified. These measurements are a form of oximetry, which is used in the detection and assessment of breast tumors. Optical methods and devices have been used for a variety of biomedical applications for about twenty years for chemical analysis, such as colorimetry and spectrophotometry. More recently, instruments for direct chemical analysis in tissues have been developed. At the beginning of the twentieth century, instruments based on the use of visible light began to be used. After several years of research, it was found that the near infrared part of the electromagnetic spectrum has the ability to penetrate deeper into biological tissues compared to visible light.

4 Near-infrared imaging is a useful technique to investigate biological tissues, because in the near-infrared regions ( nm), water has a low absorption rate, while oxyhemoglobin (Hb) and deoxyhemoglobin (shbo2d) still have detectable absorption differences. As a result, near-infrared light can penetrate several centimeters of biological tissues. It is a relatively simple and a non-invasive technique that is portable, does not require a dedicated technical staff, and does not require the patient to be injected with any isotopes. It can also be very useful in probing bulk material with little or no sample preparation. This method allows achieving safe and noninvasive monitoring of important variables in a variety of clinical applications. 1.2 Purpose of the Project Techniques such as electroencephalography (EEG), positron emission tomography (PET), functional magnetic resonance imaging (fmri), or magnetoencephalography (MEG) can be used to noninvasively investigate cerebral function. Although these techniques are widely used clinically, the instruments are very expensive, require specially trained technical staff to operate, and with the exception of EEG, patients have to be moved from their ward and taken to specially constructed rooms where the investigation is carried out. In the case of PET, patients have to be injected with radioisotopes, which prevent multiple repeated studies. All of these factors make these imaging modalities unsuitable and inconvenient for imaging. A diagnostic imaging modality based on near-infrared (NIR) radiation offers several potential advantages over existing radiological techniques. First, the radiation is non-ionizing, and therefore reasonable doses can be repeatedly employed without harm to the patient. Second, optical methods offer the potential to differentiate between soft tissues, due to their different absorption or scatter at NIR wavelengths that are indistinguishable using other modalities. And

5 third, specific absorption by natural chromophores (such as oxy-hemoglobin) allows functional information to be obtained. NIR imaging research has focused on a variety of possible clinical applications. Potentially the most important is the development of a means of screening for breast cancer, particularly if a specificity and sensitivity exceeding that of x-ray mammography can be achieved. Screening demands a spatial resolution of a few millimeters or better in order that tumors can be distinguished from surrounding healthy tissue while they are still small in size before metastasis occurs and treatment becomes more difficult. Using a NIRIS will be a better and more patient-friendly method of imaging. 1.3 Previous Work Done by Others Products There has been significant research and work done in the area of NIR imaging. One product that has been designed is a portable near infrared system for topographic imaging of the brain of babies. This device provides real time temporal and spatial information about the cortical response to stimulation in unrestrained infants. This product was designed and made by Vaithianathan et al from University College London. Another product that has been created which utilizes NIR imaging is a hand-held laser breast scanner (LBS) which can accurately distinguish between malignant and benign tumors, potentially providing an easy-to-use, non-invasive technique to see whether breast tumors warrant further aggressive treatment. The scanner works by measuring metabolism in breast tumors and normal breast tissue. The LBS provides detailed functional information by measuring hemoglobin, fat, and water content, as well as tumor oxygen consumption and tissue density.

6 1.3.2 Patents Patent # : Near Infrared Chemical Imaging Microscope The system includes an illumination source which illuminates an area of a sample using light in the near infrared radiation wavelength and light in the visible wavelength. A multitude of spatially resolved spectra of transmitted, reflected and emitted near infrared wavelength radiation light from the illuminated area of the sample is collected, followed by production of a collimated beam. A near infrared imaging spectrometer is provided for selecting a near infrared radiation image of the collimated beam and the filtered images are collected by a detector for further processing. The visible wavelength light from the illuminated area of the sample is simultaneously detected providing for the simultaneous visible and near infrared chemical imaging analysis of the sample. Patent # : Device and Method for Determining Optical Characteristics of Biological Tissue This is an appliance for examining biological tissue, comprising of a light injection means for injecting visible and/or close infrared light into the biological tissue, a detector for converting light signals that exit the biological tissue into detection signals, and an output device allocated to the detector for outputting information that depends on the detection signals. Patent # : Combined Total-Internal-Reflectance and Tissue Imaging Systems and Methods The system includes an illumination source, a platen, a light detector, an optical train, and a computational unit. The platen is disposed to make contact with a skin site of an individual. The

7 optical train is disposed to provide optical paths between the illumination source and the platen, and between the platen and the light detector. The combination of the illumination source and optical train provides illumination to the platen under multispectral conditions. The computational unit is interfaced with the light detector and has instructions to generate a totalinternal-reflectance image of the skin site from a first portion of light received from the skin site, and to generate a tissue image of the skin site from a second portion of light received from the skin site. 2.0 Project Description 2.1 Objective The device at hand will be a near infrared imaging system (NIRIS) used to image biological tissues. Two different types of laser diodes will be used: one set at 780 nm, and the other at 830 nm. Both lasers will emit at frequencies which are are within the near infrared range. To correctly identify the source of data being transmitted from the device, it is necessary to detect which diode or diodes are turned on. This process incorporates a method known as spatial coding. A system will be created that will identify which diode is on and which is off, allowing the user to know which laser diode the system is collecting data from. A current driver will be used to keep the current to the diodes at a constant and predetermined frequency. Precautions must be made to ensure that the diodes will not be damaged and will be properly functioning at the time of use. If the current going through the laser diode surpasses its maximum threshold, the diode will be damaged. If it drops below the operating value, the diode will not turn on. Collecting information from the laser diodes will be done using multiple photodetectors, one for each laser diode. The type of photodetectors used will be photodiodes. This component

8 takes an optical signal from the laser diode and converts it into an electrical signal. The electrical signals will be in the form of current from the photodiode, which must be amplified before it is further processed. The amplification will be handled by a current amplifier. This will allow the data acquisition device (DAQ) to properly read the signal generated from the photodiode. The DAQ will then take the amplified signal and digitize it, turning it into a digital signal. From there, the signal will be filtered. Through the use of a software filter programed in LabVIEW, the signals from the laser diodes will be isolated and separated based on their frequency. This plays into the spatial coding aspect of the NIRIS. Isolating each signal will allow the states of the laser diodes to be read. If a signal is read that corresponds to the frequency of a laser diode, then we know that that laser diode is on. If the laser diodes frequency is not detected by the bandpass filter, it will be assumed to be off. 2.2 Methods Not taking into account the wavelength of different laser diodes, there are many different types of diodes to consider. A laser diode is formed by doping a very thin layer on the surface of a crystal wafer. The crystal is doped to create two different regions: an n-type region and a p- type region. The regions are doped one above the other resulting in a p-n junction which is a diode. Laser diodes are a part of the semiconductor p-n junction diode family. When there is a forward electrical bias from the Anode towards the cathode, this causes two species of charge carriers, holes from the p-junction and electrons from the n-junction to gather within the depletion region. This phenomenon allows the crystal to conduct current in one direction from the Anode to Cathode without any current in the reverse direction. This method of conducting current pertaining to laser diodes differentiates this type of diode from the rest and is called an injection laser diode or ILD. A second method of power laser diodes is through the use of optical

9 pimping. Optically Pumped Semiconductor Lasers or OPSL uses a III-V semiconductor chip as the gain media in conjunction with another laser diode as the light pump source. Building from injection laser diodes there are new types of diodes which have been heavily modified to improve functionality of a diode to keep up with modern technology. Specifically being examined is the double heterostructure laser diodes. The ILD described previously can be considered a homojunction laser to differentiate between the heterostructures. With the heterostructure laser diodes a low bandgap material is sandwiched between two high bandgap layers. Each junction between different bandgaps is a heterostructure these types of diodes contain two such structures thus double heterostructure. The advantage of such a laser diode is that free electrons and holes exist simultaneously in one active region. This allows for many more electron-hole pairs to form which greatly contributes to amplification of the diode signal. Figure 1 shows an example of how a double heterostructure laser diode would be layered. Figure 1. Double Heterostructure Lasers

10 Another type of laser diode that is being considered is the Quantum well lasers. If the middle layer of a diode is made thin enough it acts as a quantum well. This means that the vertical variation of the electron's wavefunction is quantized. The quantum well system concentrates electrons in energy states that will contribute to laser action. Figure 2 shows an example of how the Quantum well lasers would be layered. Figure 2. Quantum Well Lasers A specific multiple quantum well laser diode being considered is the HL8337MG from Opnext. This diode produces a laser at 830 nm which satisfies the requirements for one diode. It is created from Gallium, Arsenic, and Aluminum. It operates at a current of 75 ma with its maximum current being 100 ma. Figure 3 shows the internal circuitry of the diode and also how it is packaged. By examining the Internal Circuit, one can notice that a laser diode, unlike other diodes, contains three pins. This is because laser diodes have an internal feedback system. When emitting the laser if it is starting to emit beyond its operating range an internal photo detector portion of the laser diode detects this and reduces the operating rate. Within this particular diode,

11 HL8337MG, the photo detector portion or PD can be ignored and simply using pin 3 and 2 to power the laser diode will suffice. Figure 3. Quantum Laser Diode HL8337MG 830nm The second diode is being considered from the same family as the HL8337MG, but it only operates at 730nm instead of the specified 780nm. They both share similar operating currents so building a circuit that powers one diode should be able to effectively power the second diode. The threshold current though is different however the max for the HL8337MG lays within the threshold range for the HL7301MG so shouldn't be an issue. Another major difference is the material makeup. The HL7301MG is created from Indium, Gallium, Arsenic, and Phosphorus. The internal circuitry, as seen in Figure 4, is identical to the one seen above, and thus the orientation for one will work for the other.

12 Figure 4. Quantum Laser Diode HL7301MG 730nm Knowing the specifications of the laser diodes now allows for building of the proper foundations to operate these diodes. The next relevant component would be a current driver. A current driver takes a voltage and outputs a constant current regardless of fluctuations within the power supply. In an LED the current dictates the brightness of the display so fluctuations result in brightening or dimming of the LED. Within a laser diode these fluctuations even if in the nanosecond will compromise and have a high chance of rendering the laser diode useless. It is imperative that the current is held within operating point and does not surpass the maximum capacity of the laser diode. Currently a consideration for a constant current driver is one from STmicroelectronics. The constant current driver is the STCS1 and being considered because it can take a wide range of voltages ranging from 0 to 45 volts and output towards 1.5 amps. The current can be set with an external resistor in accordance with Equation 1 below. (1) R f is the external resistor where V FB is the feedback node the resistor will be connected to. I ld is the desired current of the laser diodes. So from examining details for the two laser

13 diodes HL8337MG and HL7301MG to properly power the two a desired operating current of 75 ma is needed. Plugging this value into Equation 1, and having a feedback voltage of 100 mv, an external resistor of 1.3 mω would be used to achieve the desired current. Figure 5 shows an example of how the STCS1 chip looks. Figure 5. Constant Current Driver STCS1 Now for consideration of a photodiode it has been decided that an Avalanche Photodiode will be used. The advantage of an Avalanche Photodiode over a common photodiode is that an avalanche photodiode provides an inner gain through avalanche multiplication. The greater the voltage applied to the diode the greater the gain. With the inner gain the signal received from the avalanche photo diode will be that much easier to amplify. This signal from the avalanche photodiode will be fed into a current amplifier. An example of a current amplifier is show in Figure 6. Two transistors are used one an NPN-type and the other a PNP-type. Using this suggested amplifier circuit the gains can be boosted between 250 and 250,000 times the input signal.

14 Figure 6. Two-Stage Current Amplifier Circuit This signal will then be fed into a National Instruments DAQ which will read the signals into a personal computer. A LabVIEW filter program will be constructed in which will read the information, filter out the noise, and isolate the individual laser diode signals. This program will be the user interface displaying all the information needed to effectively use the NIRS device. Figure 7 shows the process of how the NIRS device will function in its entirety. Figure 7. Near Infrared Imaging Flow Chart

15 3.0 Budget Due to the nature of this project, and the fact that our parts list is relatively small, it seems feasible that our project will be completed well within our budget of 1000 USD. The most expensive components are the laser diodes and photodiodes. Each part will cost anywhere from 75 to 100 dollars apiece, depending on where the part is purchased from. Our team has been busy finding the best deals from global warehouses, including local sites in the US. The table below represents our current state of cost. Table 1. Current Budget as of October 2010 One of the turning points in the early stages of our project regarding the budget was when we transitioned from the use of high-bandwidth, National Instrument photodetectors to the use of photodiodes. At the time, we were not aware of the high costs of the National Instruments photodetectors, but as we continued our research, we realized that it would not be feasible to use them as our main method of collecting light data. The reason why they were considered first was because we were trying to make communication between the circuit and our data acquisition

16 device as simple as possible. Because our data acquisition device is developed by National Instruments, using a photodector also issued by National Instruments would have made the transfer of light data from the circuit a mere plug-and-play solution. Now, with our budget in high regards, we have replaced the National Instruments photodetectors with conventional avalanche photodiodes. These photodetectors cost a fraction of the price, and will be integrated onto the circuit itself rather than be a separate body. The connection to the National Instruments data acquisition device will now be done through the use of a BNC jack which will be attached to our circuit. All other parts are very reasonably priced, including the laser diodes, which will be the main component of our circuit. In Table 1 above, Miscellaneous Circuit Components make up all the resistors, capacitors, and inductors that we will have to purchase to complete the final product. 4.0 Conclusion The Near-Infrared Imaging System will exhibit the properties of both special coding and target detection. This will be done with the use of laser diodes and photodiodes. A circuit board will have two or more laser diodes, accompanied with two or more photodiodes positioned next to our laser diodes. The laser diodes will be powered and emit light at different frequencies, and the back-scatter from this emission will be collected and turned into an electrical signal (current) by the photodiodes. The electric signal from both the photodiodes will be combined, amplified, and fed into a data acquisition device through an analog BNC connection. The DAQ will digitize the signal and convert it into a digital signal, which will be further processed programmatically through LabVIEW software.

17 Our project is unique in the sense that many of the similar designs don t utilize LabVIEW to create an interactive user interface. Our project has both a hardware and software component which will work together to produce the overall result. The hardware aspect of our project will control the laser diodes and the collection of light which results from the back-scatter. The software aspect will filter the digital signal delivered by the DAQ and deliver an interactive user interface, with graphs of the process signals, for the client to collect meaningful data from. All of this will be done well within our budget limit, as we plan to deliver a fully working prototype on the first run. At the time being, the cost of our projected prototype is less than half of our given budget. Marketing costs will run low due to the fact that this product is aimed at a very individualized sector. Our client is of course the main target of our product, but researchers in her field will definitely benefit from such an item. References Design of a portable near infrared system for topographic imaging of the brain in babies. INAK &idtype=cvips&prog=normal&doi= / A New Laser-Based Diagnostic to Detect Malignant Breast Cancer Tumors

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