This PDF file contains the front matter associated with SPIE Proceedings Volume 8214, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

Fluorescence image guided surgery (FIGS) allows intraoperative visualization of critical structures, with applications spanning neurology, cardiology and oncology. An unmet clinical need is prevention of iatrogenic nerve damage, a major cause of post-surgical morbidity. Here we describe the advancement of FIGS imaging hardware, coupled with a custom nerve-labeling fluorophore (GE3082), to bring FIGS nerve imaging closer to clinical translation. The instrument is comprised of a 405nm laser and a white light LED source for excitation and illumination. A single 90 gram color CCD camera is coupled to a 10mm surgical laparoscope for image acquisition. Synchronization of the light source and camera allows for simultaneous visualization of reflected white light and fluorescence using only a single camera. The imaging hardware and contrast agent were evaluated in rats during in situ surgical procedures.

We report on the development of a non-invasive instrument based on scanning confocal microscopy for tracking inherently fluorescent drugs and measuring spatial features in the anterior chamber of the eye. The new instrument incorporates all features of the initial instrument¹ with the addition of fluorescence detection from within the anterior chamber of the eye. We have measured the diffusion of Fluorescein with high time resolution within a cuvette, an artificial eye and ex vivo porcine eyes. Results are be presented that demonstrate the capability of the instrument to accurately measure the concentration and the location of the fluorescent drug over a given period of time along the optical axis of the eye with an axial resolution of under 200 μm and temporal resolution of < 1s. We show that the instrument has high sensitivity and can measure concentrations of < 1μM/L of compounds having a quantum yield as low as 0.01 with high specificity for the compound of interest over competing background signals. The role of the instrument in assessing the efficiency of any inherently fluorescent ophthalmic drug as well as monitoring other medication that might produce fluorescent compounds in the eye will be discussed. We furthermore believe that the instrument might also be capable of monitoring certain bodily processes which have an impact on the compounds present in the eye.

We have developed a novel label-free approach referred to as plasmonic coupling interference (PCI) nanoprobes for nucleic acid detection using surface-enhanced Raman scattering (SERS). To induce a strong plasmonic coupling effect and SERS signal, a nano-network of silver nanoparticles having the Raman label located between adjacent nanoparticles is assembled by Raman-labeled nucleic acid duplexes. The PCI method then utilizes specific nucleic acid sequences of interest as competitor elements of the Raman-labeled DNA probes to interfere the formation of the nucleic acid-crosslinked nano-networks in a competitive binding process, resulting in a reduced SERS signal. We illustrate the potential of the PCI technique for biomedical applications by detecting single-nucleotide polymorphism (SNP) and microRNA sequences involved in breast cancers. The results of this study could lead to the development of nucleic acid diagnostic tools for biomedical diagnostics and biosensing applications using SERS detection.

A modified Wiener estimation method is presented for the accurate estimation of diffuse reflectance spectra from RGB values. In this method, the original RGB values are combined with a set of synthetic optical filters to generate another new three color values by using the system matrix. A modified Wiener matrix can then be created with the RGB values and the new color values, which will yield more accurate estimation because of the new color information incorporated. This method is tested on in-vivo color measurements from 200 skin sites in 10 volunteers. The results show that the proposed method improves the accuracy of the estimated diffuse reflectance spectra significantly compared with the traditional Wiener estimation method. Because of the fast computation in Wiener estimation, this method could be potentially developed for a cost effective alternative to a spectral imager.

Diffuse reflectance spectroscopy has been previously explored as a promising method for providing real-time visual maps of tissue composition to help surgeons determine breast lumpectomy margins and to ensure the complete removal of a tumor during surgery. We present the simple design, validation, and implementation of a compact and cost-effective spectral imaging system for the application of tumor margin assessment. Our new system consists of a broadband source with bandpass filters for illumination and a fabricated custom 16-pixel photodiode imaging array for the detection of diffuse reflectance. The system prototype was characterized in tissue-mimicking phantoms and has an SNR of greater than 40 dB in phantoms, animals, and human tissue. We show proof-of-concept for performing fast, wide-field spectral imaging with a simple, inexpensive design. The strategy also allows for the scaling to higher pixel number and density in future iterations of the system.

It has been proposed a method based on Raman spectroscopy for identification of different microorganisms involved in bacterial urinary tract infections. Spectra were collected from different bacterial colonies (Gram negative: E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, E. cloacae and Gram positive: S. aureus and Enterococcus sp.), grown in culture medium (Agar), using a Raman spectrometer with a fiber Raman probe (830 nm). Colonies were scraped from Agar surface placed in an aluminum foil for Raman measurements. After pre-processing, spectra were submitted to a Principal Component Analysis and Mahalanobis distance (PCA/MD) discrimination algorithm. It has been found that the mean Raman spectra of different bacterial species show similar bands, being the S. aureus well characterized by strong bands related to carotenoids. PCA/MD could discriminate Gram positive bacteria with sensitivity and specificity of 100% and Gram negative bacteria with good sensitivity and high specificity.

Raman spectroscopy is a unique analytical probe for molecular vibration and is capable of providing specific spectroscopic fingerprints of molecular compositions and structures of biological tissues. The aim of this study is to improve the classification accuracy of cervical precancer by characterizing the variations in the normal high wavenumber (HW - 2800-3700cm^-1) Raman spectra arising from the menopausal status of the cervix. A rapidacquisition near-infrared (NIR) Raman spectroscopic system was used for in vivo tissue Raman measurements at 785 nm excitation. Individual HW Raman spectrum was measured with a 5s exposure time from both normal and precancer tissue sites of 15 patients recruited. The acquired Raman spectra were stratified based on the menopausal status of the cervix before the data analysis. Significant differences were noticed in Raman intensities of prominent band at 2924 cm^-1 (CH₃ stretching of proteins) and the broad water Raman band (in the 3100-3700 cm^-1 range) with a peak at 3390 cm^-1 in normal and dysplasia cervical tissue sites. Multivariate diagnostic decision algorithm based on principal component analysis (PCA) and linear discriminant analysis (LDA) was utilized to successfully differentiate the normal and precancer cervical tissue sites. By considering the variations in the Raman spectra of normal cervix due to the hormonal or menopausal status of women, the diagnostic accuracy was improved from 71 to 91%. By incorporating these variations prior to tissue classification, we can significantly improve the accuracy of cervical precancer detection using HW Raman spectroscopy.

Cellular histopathological melanoma screening is critical but expensive/invasive. Confocal screening is cheap/noninvasive but data interpretation remains difficult. Human terminology for biological features is insufficient to fully exploit the diagnostic value, so we propose automated quantitative morphometry. Normal diagnostic traits include a regularly organized spinous keratinocyte matrix on an underlying smooth basal keritinocyte layer. Computational identification of dark nuclei in spinous keratinocytes and bright pigmented basal keratinocytes yields two distinct regions: basal and super-basal. These independent algorithms usually yield complementary regions but occasionally overlap or leave gaps. Improved microanatomical discrimination will yield a better diagnostic map to evaluate morphology for cancer detection.

The design and realization of an optical sensor for measuring haematic pH during extracorporeal circulation is presented. It consists of a chemical sensing element in contact with the blood, an interrogation optical head to externally probe the sensing element and the front-end electronics to acquire and process the information of interest. The fluorescein O-methacrylate 97% is used as the indicator. The developed system has been tested in-vitro and on an in-vivo animal model. It showed a linear behavior in the haematic range of interest with a mean error lower than 0.01 units of pH.

Clot elastic modulus (CEM) has recently been shown to correlate with various hemostatic and thrombotic disorders and may be an important diagnostic parameter in cardiovascular diseases. Current methods of CEM measurement lack repeatability and require large sample volume. We present a novel method named resonant acoustic spectroscopy with optical vibrometry (RASOV) that has the potential to assess CEM with higher accuracy and speed, and lower sample volume. To validate RASOV, we measured the acoustic spectrum of agarose gel with varied concentrations in openfaced rectangular wells. Results showed a linear relationship between the natural resonant frequency and agarose content within a concentration range of 4 to 12 mg/mL. Furthermore, we observed that the resonant frequencies decrease with increasing transducer mass. As a highly accurate, resonance-based method, RASOV has great potential for biomechanical properties measurement, especially for human blood.

A multispectral enhancement method that preserves the natural color of the background pixels was previously proposed. In such method, the band for enhancement was identified from the N-band spectral residual-error of the objects of interest. The spectral residual-error is determined by taking the difference between the original spectrum of the pixel and its estimate using M<<N principal components in principal component analysis (PCA). However, for stained histopathology images where staining variations do exist even among tissue sections the band for enhancement could vary. In this work, we introduced a modification to the previously proposed multispectral enhancement method such that the band for enhancement could be specified independent of the spectral residualerror configurations. In the proposed modification the original spectral transmittance of the pixels at each band are shifted by the product between the spectral residual-error coefficient, which is the most dominant PC coefficient of the spectral error, of the pixel and the weighting factor assigned by the user to each band. Results of our experiments on H&E stained sections of liver tissue show that the proposed modification delivers more consistent enhancement results compared to the previously proposed methods, especially when the band for enhancement varies.

Confocal microscopy has shown potential as an imaging technique to detect precancer. Imaging cellular features throughout the depth of epithelial tissue may provide useful information for diagnosis. However, the current in vivo axial scanning techniques for confocal microscopy are cumbersome, time-consuming, and restrictive when attempting to reconstruct volumetric images acquired in breathing patients. Chromatic dispersion confocal microscopy (CDCM) exploits severe longitudinal chromatic aberration in the system to axially disperse light from a broadband source and, ultimately, spectrally encode high resolution images along the depth of the object. Hyperchromat lenses are designed to have severe and linear longitudinal chromatic aberration, but have not yet been used in confocal microscopy. We use a hyperchromat lens in a stage scanning confocal microscope to demonstrate the capability to simultaneously capture information at multiple depths without mechanical scanning. A photonic crystal fiber pumped with a 830nm wavelength Ti:Sapphire laser was used as a supercontinuum source, and a spectrometer was used as the detector. The chromatic aberration and magnification in the system give a focal shift of 140μm after the objective lens and an axial resolution of 5.2-7.6μm over the wavelength range from 585nm to 830nm. A 400x400x140μm³ volume of pig cheek epithelium was imaged in a single X-Y scan. Nuclei can be seen at several depths within the epithelium. The capability of this technique to achieve simultaneous high resolution confocal imaging at multiple depths may reduce imaging time and motion artifacts and enable volumetric reconstruction of in vivo confocal images of the epithelium.

Intraoperative 3D imaging during minimally invasive surgery (MIS) is possible using structured lighting and has applications in the quantification of tissue morphology. However, projection schemes containing various patterns and colours can be disruptive to the surgeon's field of view. In this paper, a stroboscopic system is proposed in which structured lighting and white light images are interleaved during a high-speed camera acquisition so that the patterned light is not perceived and white light can be used solely for navigation and visual assessment. A beam chopper synchronised with the camera switches rapidly between the two lighting modes while still providing video rate display. A spectrally-encoded structured lighting system is provided by an optical fibre-based probe developed in our lab and is suitable for use in endoscopic biopsy channels. In this dual acquisition mode it is possible to display an augmented view so that the centroids of the structured lighting features are visible on the white light image. Sequential acquisition of varying exposure time images with the high speed camera also allowed the generation of high dynamic range images of the wavelength-encoded structured lighting pattern. Possible applications of this work include classification of polyp morphology as an indicator of pathology.

Hand-held optical imaging devices are currently developed by several research groups as a noninvasive and non-ionizing method towards clinical imaging of breast cancer. The devices developed to date are typically utilized towards spectroscopic imaging via reflectance-based measurements. Additionally, a couple of devices have been used to perform 3D tomography with the addition of a second modality (e.g. ultrasound). A hand-held optical device that is unique in its ability to perform rapid 2D imaging and 3D tomography (without the use of a second modality) has been developed in our Optical Imaging laboratory. Herein, diffuse optical imaging studies are performed in breast cancer subjects. For these studies, the subject lay in a recliner chair and both breast tissues were imaged with the hand-held optical device which uses 785 nm laser source and an intensified CCD camera-based detector. Preliminary results demonstrate the ability to image invasive ductal carcinoma and lymphatic spread, as compared to the patient's medical records (e.g. xray, ultrasound, MRI). Multiple imaging studies with a subject undergoing chemotherapy demonstrated the potential to monitor response to treatment. Currently, studies are carried out to tomographically determine the 3D location of the tumor(s) in breast cancer subjects using the hand-held optical device.

Light-emitting diode (LED) based endoscopic illumination devices have been shown to have several benefits over arclamp systems. LEDs are energy-efficient, small, durable, and inexpensive, however their use in endoscopy has been limited by the difficulty in efficiently coupling enough light into the endoscopic light cable. We have demonstrated a highly homogenised lightpipe LED light source that combines the light from four Luminus LEDs emitting in the red, green, blue and violet using innovative dichroics that maximise light throughput. The light source spectrally combines light from highly divergent incoherent sources that have a Lambertian intensity profile to provide illumination matched to the acceptance numerical aperture of a liquid light guide or fibre bundle. The LED light source was coupled to a standard laparoscope and performance parameters (power, luminance, colour temperature) compared to a xenon lamp. Although the total illuminance from the endoscope was lower, adjustment of the LEDs' relative intensities enabled contrast enhancement in biological tissue imaging. The LED light engine was also evaluated in a minimally invasive surgery (MIS) box trainer and in vivo during a porcine MIS procedure where it was used to generate 'narrowband' images. Future work using the violet LED could enable photodynamic diagnosis of bladder cancer.

Low intensity focused ultrasound (LIFU) is now being considered as a noninvasive brain therapy for clinical applications. We maintain that LIFU can efficiently deliver energy from outside the skull to target specific brain regions, effecting localized neuromodulation. However, the underlying molecular mechanisms that drive this LIFU-induced neuromodulation are not well-defined due, in part, to our lack of understanding of how particular sets of LIFU delivery parameters affect the outcome. To efficiently conduct multiple sweeps of different parameters and determine their effects, we have developed an in-vitro system to study the effects of LIFU on different types of cells grown in culture. Presently, we are evaluating how LIFU affects the ionic flux that may underlie neuronal excitation and inhibition observed in-vivo. The results of our in-vitro studies will provide a rationale for selection of optimal LIFU parameter to be used in subsequent in-vivo applications. Thus, a prototype ultrasound cell assay system has been developed to conduct these studies, and is described in this work.

The purpose of this research is to quantify functional signals in the microvascular circulation of the plantar. Our device is based on thermal and spectral technologies that can be easily adopted in clinical and tele-screening settings. Eightytwo thousand amputations are performed annually on diabetics in the US. The cost of foot disorder diagnosis and management are estimated at $10.9 billion dollars annually. Our experiments on normal controls and diabetics assess the temperature recovery time characteristics due to cold provocation to the bottom of the foot (plantar). A difference in the nature of the recovery time between normal controls and diabetics was observed.

Optical Coherence Tomography (OCT) as emerging clinical diagnostic imaging technology for dermatology and other semitransparent tissues has shown high potential in monitoring and evaluating the inner structure of articular cartilages. Since novel therapies for the limitation of cartilage degeneration in early stages of osteoarthritis are available, the early minimal invasive diagnosis of cartilage degradation is clinically essential for further treatment options. With the advancing performance and thus diagnostic opportunities of 3D-OCT devices, we carried out a systematic study by monitoring arthrotic alterations of porcine osteochondral explants that are mechanically induced under traumatic impaction. As for in-vitro tomographic imaging we utilized two OCT devices, a Thorlabs FD-OCT device with 92KHz A-scan rate and 1310nm as central wavelength and a self-developed FD-OCT device at 840nm central wavelength. This allows the comparison in image contrast and optical penetration of cartilage tissue between these two spectral bandwidths. Further we analyzed human biopsies of articular cartilages with various degrees of osteoarthritis. The 2D and 3D OCT tomograms are characterized qualitatively regarding the inner tissue structure and quantitatively regarding the tissue absorption parameters. Therefore, we are developing image processing algorithms for the automated monitoring of cartilage tissue. A scoring system for 3D-monitoring allows the characterization of the probe volume regarding the morphological structure and tissue compactness by processing the C - scan data.

An office based Doppler and polarization sensitive swept-source optical coherence tomography (Doppler-PS-SS-OCT) was developed for diagnosis and evaluation of abnormalities of anterior eye segment in clinic. A healthy eye was measured in vivo by the Doppler PS-OCT. The results showed that the Doppler PS-OCT may have potential to identify blood vessels and discriminate fibrous tissues in abnormalities, such as scarring in bleb, and scleral inflammation.

Confocal mosaicing microscopy is a developing technology platform for imaging tumor margins directly in fresh tissue, without the processing that is required for conventional pathology. Previously, basal cell carcinoma margins were detected by mosaicing of confocal images of 12 x 12 mm² of excised tissue from Mohs surgery. This mosaicing took 9 minutes. Recently we reported the initial feasibility of a faster approach called "strip mosaicing" on 10 x 10 mm² of tissue that was demonstrated in 3 minutes. In this paper we report further advances in instrumentation and software. Rapid mosaicing of confocal images on large areas of fresh tissue potentially offers a means to perform pathology at the bedside. Thus, strip mosaicing confocal microscopy may serve as an adjunct to pathology for imaging tumor margins to guide surgery.

Metastasis is a life threatening complex physiological phenomenon that involves the movement of cancer cells from one organ to another by means of blood and lymph. An understanding about metastasis is extremely important to device diagnostic systems to detect and monitor its spread within the body. For the first time we report rapid photoacoustic detection of the induced metastatic melanoma in mice in vitro using photoacoustic flowmetry. A new photoacoustic flow system is developed, that employs photoacoustic excitation coupled with an ultrasound transducer capable of determining the presence of individual, induced mouse melanoma cells (B16/F10) within the circulating system in vitro. Tumor was induced in mice by injecting mouse melanoma cells through tail vein into the C57BL/6 mice. A luciferase based in vivo bioluminescence imaging is performed to confirm the tumor load and multiple metastases in the tumor-induced mice. 1ml of blood obtained through cardiac puncture of the induced metastasized mice was treated to lyse the red blood cells (RBC) and enriched, leaving the induced melanoma in the peripheral blood mononuclear suspension (PBMC). A photoacoustic flowsystem coupled with an ultrasound transducer is used to detect the individual circulating metastatic melanoma cells from the enriched cell suspension.

Screening cancer in excision margins may be done with confocal microscopy to save time and cost over the gold standard histopathology (H&E). However, diagnostic accuracy requires sufficient contrast. Reflectance mode enables detection of large (>500um) nodular tumors. Enhanced nuclear contrast with acridine orange fluorescence mode additionally enables detection of tiny (<50um) basal cell carcinomas. Here, we present a novel combination of three modes to detect squamous cell carcinoma (SCC). Accurate screening of SCC requires eosin fluorescence, reflectance and acridine orange fluorescence to enable contrast for cytoplasm, collagen and nuclei respectively. Combining these signals replicates H&E for rapid clinical translation.

To acquire the optical diffuse tomographic image of the cervix, a novel endoscopic rotary probe is designed and the frequency domain measurement system is developed. The finite element method and Gauss-Newton method are proposed to reconstruct the image of the phantom. In the optical diffuse tomographic imaging of the cervix, an endoscopic probe is needed and the detection of light at different separation to the irradiation spot is necessary. To simplify the system, only two optical fibers are adopted for light irradiation and collection, respectively. Two small stepper motors are employed to control the rotation of the incident fiber and the detection fiber, respectively. For one position of source fiber, the position of the detection fiber is changed from -61.875° to -50.625° and 50.625° to 61.875° to the source fiber, respectively. Then, the position of the source fiber is changed to another preconcerted position, which deviates the precious source position in an angle of 11.25°, and the detection fiber rotates within the above angles. To acquire the efficient irradiation and collection of the light, a gradient-index (GRIN) lens is connected at the head of the optical fiber. The other end of the GRIN lens is cut to 45°. With this design, light from optical fiber is reflected to the cervix wall, which is perpendicular to the optical fiber or vice versa. Considering the cervical size, the external diameter of the endoscopic probe is made to 20mm. A frequency domain (FD) near-infrared diffuse system is developed aiming at the detection of early cervical cancer, which modulates the light intensity in radio frequency and measures the amplitude attenuation and the phase delay of the diffused light using heterodyne detection. Phantom experiment results demonstrate that the endoscopic rotary scan probe and the system perform well in the endoscopic measurement.

In optical tumor detection region, there has been recently a considerable interest in simultaneously reconstructing yield and lifetime distributions of fluorescent imaging agents inside a pathologic tissue, since combined monitoring of these two parameters provides a potential means of in vivo interrogating quantitative and environmental information of specific molecules as well as accessing interactions among them. This paper describes the structure of a multi-channel time-correlated single photon counting (TCSPC) system for early breast tumor detection and how we use it to reconstruct the distribution of fluorescent parameters. By using a normalized Born appropriation algorithm, the proposed examination scheme in a transmission mode is experimentally validated to achieve simultaneous reconstruction of the fluorescent yield and lifetime distributions with reasonable accuracy. The performance of the instrument will be proved by using two targets be of different fluorescent agents embedded in solid phantom for image reconstruction.

Purpose: To study a method of the induction of dendritic cells (DCs) from rabbit peripheral blood. Methods: Peripheral blood cells were removed from rabbit, filtered through nylon mesh. Peripheral blood mononuclear cells (PBMC) were isolated from the blood cells by Ficoll-Hypaque centrifugation (density of 1.077g/cm³).To obtain DCs, PBMC were cultured in RPMI1640 medium containing 10% fetal calf serum, 50U/mL penicillin and streptomycin, referred to subsequently as complete medium, at 37°C in 5% CO₂ atmosphere for 4 hours. Nonadherent cells were aspirated, adherent cells were continued incubated in complete medium, supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF, 50ng/ml),and interleukin 4 (IL-4, 50ng/ml) for 9 days. Fluorescein labeled antibodies(anti-CD14, anti-HLA-DR, anti-CD86) were used to sign cells cultured for 3,6,9 days respectively, Then flow cytometry was performed. Results: Ratio of anti-HLA-DR and anti-CD86 labeled cells increased with induction time extension, in contrast with anti-CD14. Conclusion: Dendritic cells can be effectively induced by the method of this experiment, cell maturation status increased with induction time extension.

A combined time-domain diffuse fluorescence and optical tomographic system is proposed based on the multi-channel time-correlated single-photon counting (TCSPC) technique, aiming at enhancing the reliability of breast diffuse optical tomography. The system equipped with two pulsed laser diodes at wavelengths of 780 nm and 830 nm that are specific to the maximal excitation and emission of the FDA-approved ICG dye, and works with a 4-channel TCSPC module to acquire the temporal distributions of the light re-emissions 32 boundary sites of tissues in a tandem serial-to-parallel mode. The performance and efficacy of the system are investigated with phantom experiments for diffuse optical tomography (DOT), as well as fluorescence-guided DOT.

Diabetic foot ulceration is a major complication for patients with diabetes mellitus. Approximately 15% to 25% of patients with Type I and Type II diabetes eventually develop feet ulcers. If not adequately treated, these ulcers may lead to foot infection, and ultimately to total (or partial) lower extremity amputation, which means a great loss in health-related quality of life. The incidence of foot ulcers may be prevented by early identification and subsequent treatment of pre-signs of ulceration, such as callus formation, redness, fissures, and blisters. Therefore, frequent examination of the feet is necessary, preferably on a daily basis. However, self-examination is difficult or impossible due to consequences of the diabetes. Moreover, frequent examination by health care professionals is costly and not feasible. The objective of our project is to develop an intelligent telemedicine monitoring system that can be deployed at the patients' home environment for frequent examination of patients feet, to timely detect pre-signs of ulceration. The current paper reports the preliminary results of an implementation of a photometric stereo imaging system to detect 3D geometric abnormalities of the skin surfaces of foot soles. Using a flexible experimental setup, the system parameters such as number and positions of the illuminators have been selected so as to optimize the performance with respect to reconstructed surface. The system has been applied to a dummy foot sole. Finally, the curvature on the resulting 3D topography of the foot sole is implemented to show the feasibility of detecting the pre-signs of ulceration using photometric stereo imaging. The obtained results indicate clinical potential of this technology for detecting the pre-signs of ulceration on diabetic feet soles.

New X-ray phase contrast imaging techniques without using synchrotron radiation confront a common problem from the negative effects of finite source sizes and limited spatial resolution. These negative effects swamp the fine phase contrast fringes and make them almost undetectable. In order to alleviate this problem, deconvolution procedures should be applied to the x-ray phase contrast images. In this study, four different deconvolution techniques were applied to experimental phase contrast images of a simple geometric phantom, including Weiner deconvolution method and Tikhonov regularization techniques with their Tikhonov matrix separately set as identity matrix, first order difference operator and second order difference operator. According to the free space propagation x-ray phase contrast imaging system, the source-to-sample distance (SS) of 200cm or 180cm was used with corresponding sample-to-detector distance (SD) of 20cm or 40cm. Image contrasts of 9.8%, 52.7%, 27.6% and 31.5% were separately obtained corresponding to above mentioned four techniques with SS/SD=200cm/20cm. For the second system setting (SS/SD=180cm/40cm), image contrasts of 11.9%, 112.8%, 66.3% and 76.5% were obtained separately. The Tikhonov regularization technique with Tikhonov matrix chosen as identity matrix obtains the highest contrast among all techniques. However, under this case, most noticeable artifacts and noise were introduced simultaneously. With full consideration on noise and artifacts, the Tikhonov matrix of second order difference operator will be the best choice for Tikhonov regularization method.

Bacterial related infections are a burden on the healthcare industry. A system was built to test the efficacy of laser generated shockwaves on S. epidermidis biofilms (RP62A) grown on polystyrene surfaces. The system is based on a Qswitched, ND:YAG pulsed laser with an output wavelength of 1.064 μm that ablates titanium-coated soda-lime glass. Results show that the system is capable of generating stress profiles that can effectively delaminate biofilm structures from polymer surfaces.