Ulf Gustafsson

Sum-frequency generation with a blue diode laser for mercury spectroscopy at 254 nm

Blue diode lasers emitting 5 mW continuous-wave power around 400 nm have recently become available. We report on the use of a blue diode laser together with a 30 mW red diode laser for sum-frequency generation around 254 nm. The ultraviolet power is estimated to be 0.9 nW, and 35 GHz mode-hop-free tuning range is achieved. This is enough to perform high-resolution ultraviolet spectroscopy of mercury isotopes. The possibility to use frequency modulation in the ultraviolet is demonstrated; however, at present the ultraviolet power is too low to give advantages over direct absorption monitoring. Mercury detection at atmospheric pressure is also considered which is of great interest for environmental monitoring.

Compact fiber-optic fluorosensor using a continuous-wave violet diode laser and an integrated spectrometer

A compact fluorosensor with a fiber-optic measurement probe was developed, employing a continuous-wave violet diode laser as an exciting source and an integrated digital spectrometer for the monitoring of fluorescence signatures. The system has the dimensions 22×13×8 cm3, and features 5 nm spectral resolution and an excellent detectivity. Results from measurements on vegetation and human premalignant skin lesions are reported, illustrating the potential of the instrument.

Domain-Specific Image Analysis for Cervical Neoplasia Detection Based on Conditional Random Fields

This paper presents a domain-specific automated image analysis framework for the detection of pre-cancerous and cancerous lesions of the uterine cervix. Our proposed framework departs from previous methods in that we include domain-specific diagnostic features in a probabilistic manner using conditional random fields. Likewise, we provide a novel window-based performance assessment scheme for 2D image analysis which addresses the intrinsic problem of image misalignment. Image regions corresponding to different tissue types are indentified for the extraction of domain-specific anatomical features. The unique optical properties of each tissue type and the diagnostic relationships between neighboring regions are incorporated in the proposed conditional random field model. The validity of our method is examined using clinical data from 48 patients, and its diagnostic potential is demonstrated by a performance comparison with expert colposcopy annotations, using histopathology as the ground truth. The proposed automated diagnostic approach can support or potentially replace conventional colposcopy, allow tissue specimen sampling to be performed in a more objective manner, and lower the number of cervical cancer cases in developing countries by providing a cost effective screening solution in low-resource settings.

Frequency-modulation spectroscopy with blue diode lasers

Frequency-modulation spectroscopy provides ultrasensitive absorption measurements. The technique is especially adaptable to diode lasers, which can be modulated easily, and has been used extensively in the near-infrared and infrared spectral regions. The availability of blue diode lasers now means that the accessible wavelength region can be increased. We successfully demonstrate wavelength-modulation spectroscopy and two-tone frequency-modulation spectroscopy for the weak second resonance line of potassium at 404.8 nm and for the transition at 405.8 nm in lead, starting from the thermally populated 6(p)(2 3)P(2) metastable level. Information on the modulation parameters is obtained with a fitting procedure. Experimental signal-to-noise ratios at different absorption levels are compared with theoretical signal-to-noise ratios and show good agreement. Detection sensitivities of 2 x 10(-6) and 5 x 10(-6) for wavelength and two-tone frequency-modulation spectroscopy, respectively, for a 120-Hz bandwidth are demonstrated.

Using acetowhite opacity index for detecting cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN) exhibits certain morphologic features that can be identified during a colposcopic exam. Immature metaplastic and dysplastic cervical squamous epithelia turn white after application of acetic acid during the exam. The whitening process occurs visually over several minutes and subjectively helps to discriminate between dysplastic and normal tissue. Digital imaging technologies enable us to assist the physician in analyzing acetowhite (acetic-acid-induced) lesions in a fully automatic way. We report a study designed to measure multiple parameters of the acetowhitening process from two images captured with a digital colposcope. One image is captured before the acetic acid application, and the other is captured after the acetic acid application. The spatial change of the acetowhitening is extracted using color and texture information in the post-acetic-acid image; the temporal change is extracted from the intensity and color changes between the post-acetic-acid and pre-acetic-acid images with an automatic alignment. In particular, we propose an automatic means to calculate an opacity index that indicates the grades of temporal change. The imaging and data analysis system is evaluated with a total of 99 human subjects. The proposed opacity index demonstrates a sensitivity and specificity of 94 and 87%, respectively, for discriminating high-grade dysplasia (CIN2+) from normal and low-grade subjects, considering histology as the gold standard.

Long-path monitoring of NO2 with a 635 nm diode laser using frequency-modulation spectroscopy

In situ monitoring of traffic-generated nitrogen dioxide (NO2) emissions using long-path absorption spectroscopy is reported. High-sensitivity detection of NO2 is achieved by employing two-tone frequency-modulation spectroscopy at a visible absorption band using a tunable high-power diode laser operated around 635 nm. A real-time absorption spectrometer is accomplished by repetitively applying a rectangular current pulse to the diode-laser operating current, allowing detection of isolated NO2 absorption lines. A detection limit of 10 microg/m3 for NO2 at atmospheric pressure using a 160 m absorption path is demonstrated. Continuous monitoring of NO2 over a road intersection at peak traffic is performed.

Atomic spectroscopy with violet laser diodes

Laser spectroscopy with laser diodes can now also be performed in the violet/blue spectral region. A 5 mW commercially available CW laser diode operating at 404 nm was used to perform spectroscopy on potassium atoms with signal detection in absorption as well as fluorescence when operating on a potassium vapor cell and with optogalvanic detection on a potassium hollow cathode lamp. The 4s 2S1/2–5p 2P3/2,1/2 transitions were observed at 404.5 and 404.8 nm, respectively. The laser diode was operated with a standard laser diode driver, and with or without an external cavity. The 4s 2S1/2–4p 2P1/2 transition at 770.1 nm was also observed with a different laser diode. Here, Doppler-free saturated-absorption signals were also observed, enabling the evaluation of the ground-state hyperfine splitting of about 460 MHz. The data recorded allows an experimental verification of the theory for Doppler broadening at two widely separated wavelengths.

Reflectance and fluorescence hyperspectral elastic image registration

Science and Technology International (STI) presents a novel multi-modal elastic image registration approach for a new hyperspectral medical imaging modality. STIs HyperSpectral Diagnostic Imaging (HSDI) cervical instrument is used for the early detection of uterine cervical cancer. A Computer-Aided-Diagnostic (CAD) system is being developed to aid the physician with the diagnosis of pre-cancerous and cancerous tissue regions. The CAD system uses the fusion of multiple data sources to optimize its performance. The key enabling technology for the data fusion is image registration. The difficulty lies in the image registration of fluorescence and reflectance hyperspectral data due to the occurrence of soft tissue movement and the limited resemblance of these types of imagery. The presented approach is based on embedding a reflectance image in the fluorescence hyperspectral imagery. Having a reflectance image in both data sets resolves the resemblance problem and thereby enables the use of elastic image registration algorithms required to compensate for soft tissue movements. Several methods of embedding the reflectance image in the fluorescence hyperspectral imagery are described. Initial experiments with human subject data are presented where a reflectance image is embedded in the fluorescence hyperspectral imagery.

Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo

The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology.

In-vivo fluorescence and reflectance imaging of human cervical tissue

A hyperspectral imaging spectrograph has been used to measure the fluorescence and reflectance of cervical tissue in vivo. The instrument was employed in a clinical trial in Vilnius, Lithuania, where 111 patients were examined. The patients were initially screened by Pap smear, examined by colposcopy and a tissue sampling procedure was performed. Detailed histopathological assessments were performed on the biopsies, and these assessments were correlated with spectra and images. The results of the spectroscopic investigations show that different tissue types within one biopsy region exhibit different spectral signatures. A spectral analysis of the entire image localizes dysplastic regions in both fluorescence and reflectance, suggesting that the hyperspectral imaging technique is useful in the management of cervical malignancies.