Comparison of X-ray fluorescence and optical fluorescence measured behind scattering layers as a basis for X-ray fluorescence endoscopy.

Recent developments in the technology of capillary-fiber optics suitable for X-rays in the range of approximately 4-10keV point to the possible realization of endoscopes applicable in X-ray fluorescence analysis. A general problem is the determination of scattering and absorption processes with consideration to tissue optics, X-ray scattering and X-ray absorption in a diagnostic partial volume. Therefore comparative investigations were performed in order to answer these questions. Zinc-oxide nanoparticles configured as single particles and ZnO clusters provided the fluorescence source in cell layers. An artificial scattering material was employed, which closely approximated the tissue optical conditions and the X-ray optical application conditions in possible diagnostic situations. As a result imaging of spatially resolved X-ray contrasts was better than adequate optical fluorescence imaging by approximately one magnitude. Hence a very important precondition for realizing X-ray fluorescence endoscopy is fulfilled.

Heart tissue viability monitoring in vivo by using combined fluorescence, thermography and electrical activity measurements.

A prototype system for in vivo monitoring of the heart tissue viability by using combined measurements of fluorescence, thermography and electrical activity has been elaborated for cardiac surgery. The fluorescence imaging of nicotinamide adenine dinucleotide NAD(P)H in the blue light range (lambda=467 nm) by using UV light (lambda=347 nm) excitation was used to detect metabolic disturbances. The method of the principal component analysis was used for the processing of the fluorescence image sequences. Far infrared (lambda=7.5-13 microm) imaging was used to evaluate temperature dynamics of the tissue surface during circulation disturbances. Evaluation of the epicardial electrogram shape by using continuous wavelet transform was used to detect and evaluate ischemia-caused disturbances of the electrical activity of the tissue. The combination of temperature, fluorescence and electrical activity estimates obtained from synchronically registered parameters during the experiments on model systems and experimental animals yielded qualitatively new results for the evaluation of cardiac tissue viability and enabled to achieve a versatile evaluation of the heart tissue viability.

Evolution strategies for optical tomographic characterization of homogeneous media.

The reconstruction problem in diffuse optical tomography can be formulated as an optimization problem, in which an objective function has to be minimized. Current model-based iterative image reconstruction schemes commonly use information about the gradient of the objective function to locate the minimum. These gradient-based search algorithms often find local minima close to an initial guess, or do not converge if the gradient is very small. If the initial guess is too far from the solution, gradient-based schemes prove inefficient for finding the global minimum. In this work we introduce evolution-strategy (ES) algorithms for diffuse optical tomography. These algorithms seek to find the global minimum and are less sensitive to initial guesses and regions with small gradients. We illustrate the fundamental concepts by comparing the performance of gradient-based schemes and ES algorithms in finding optical properties (absorption coefficient microa , scattering coefficient micros , and anisotropy factor g) of a homogenous medium.

Near-infrared diffuse optical tomography.

Diffuse optical tomography (DOT) is emerging as a viable new biomedical imaging modality. Using near-infrared (NIR) light, this technique probes absorption as well as scattering properties of biological tissues. First commercial instruments are now available that allow users to obtain cross-sectional and volumetric views of various body parts. Currently, the main applications are brain, breast, limb, joint, and fluorescence/bioluminescence imaging. Although the spatial resolution is limited when compared with other imaging modalities, such as magnetic resonance imaging (MRI) or X-ray computerized tomography (CT), DOT provides access to a variety of physiological parameters that otherwise are not accessible, including sub-second imaging of hemodynamics and other fast-changing processes. Furthermore, DOT can be realized in compact, portable instrumentation that allows for bedside monitoring at relatively low cost. In this paper, we present an overview of current state-of-the -art technology, including hardware and image-reconstruction algorithms, and focus on applications in brain and joint imaging. In addition, we present recent results of work on optical tomographic imaging in small animals.

Magnetic resonance imaging-controlled laser-induced interstitial thermotherapy.

RATIONALE AND OBJECTIVES: Laser-induced interstitial thermotherapy (LITT) may become an attractive modality for minimally invasive tumor therapy. Magnetic resonance imaging (MRI) could be used to assist this procedure. METHODS: A T1-weighted turbo fast low-angle shot (FLASH) sequence for on-line monitoring of the laser-influenced region (liver, muscle) was investigated. Sequence parameters were optimized for maximal image contrast. Magnetic resonance imaging-controlled LITT was performed in vitro, in vivo (rabbits), and in 8 human investigations (6 patients). Special laser applicators were used to establish a uniform laser light distribution. RESULTS: With the MRI sequence used, the LITT region is visualized as a bright area outlined by a dark border. This dark border corresponds to an isotherm of 45 +/- 2 degrees C depending on the sequence parameters used. CONCLUSION: With the T1-weighted turbo-FLASH sequence, MRI can be used for on-line monitoring of interstitial laser-induced thermotherapy in moving organs.

The spatial variation of the refractive index in biological cells.

With a phase microscope the phase shift of cells from type L 929 fibroblast and mitochondria from liver cells was measured. Compared to the total phase shift caused by the cell relative to vacuum (approximately 1400 nm) the single phase shift of the mitochondria (approximately 180 nm) is small. Only the nucleus and the membrane of the cell give a visibly different phase shift relative to the mean value of the cell. The Fraunhofer diffraction of the measured phase object is calculated. With a simplified scattering theory, i.e. Rayleigh-Gans Scattering, different phase objects are investigated and their differential cross section is discussed.

[Phenomenological statistics of laser irradiation related metabolic changes in guinea pig livers]. / Phänomenologische Statistik der Anderungen im Stoffwechsel von Meerschweinchenleber nach biomedizinischen Laseranwendungen.

In the past, dosimetric investigations on which hyperthermal therapy radiation planning for minimally invasive treatment of tumours were based were often limited to tissue coagulation. While heatshock proteins identified by biochemical basic research provided a fundamental knowledge of the thermal processes of tissue reactions between 42 degrees C and ca. 45 degrees C, the resulting understanding was insufficient to serve as a basis for radiation planning. For this reason, the Arrhenius formalism has so far been used as a good approximation for the complex description of the hyperthermal tissue reactions, with the activation energy being employed as statistic energy threshold for irreversible tissue coagulation. Our investigations were aimed at elucidating whether this formalism could be kept reproducible for tissue damage as temporal accumulation with an implicit biochemically balanced feedback mechanism, i.e. below the coagulation threshold. In our experiments we chose the fluorescence-technical measurement of the NADH concentration as a vital parameter to obtain a more informative statement in a preliminary phenomenological approach. The two most striking differences--as compared with the vitality measurement from the Arrhenius formalism--are the negligible variations in the damage integral (as compared with the phenomenological metabolic reactions acquired by cyclic heating), and the conclusion that the Arrhenius formalism as quasi-linear correlation between metabolic dynamics and tissue damage, will not hold.

[Initial studies of the application of the linear signal transfer theory in evaluating diaphanoscopic examinations exemplified by rheumatism diagnosis]. / Erste Untersuchungen zur Anwendung der linearen Signalübertragungstheorie in der Auswertung diaphanoskopischer Untersuchungen am Beispiel der Rheumadiagnostik.

Rheumatoid arthritis affecting the small joints--in particular the fingers--has advantageous geometry for the transmission of near-infrared (NIR) light. Examination of the optical properties of tissues has revealed that as a result of changes to the capsule and synovial fluid there is a considerable increase in photon scattering already in the early stages of the disease--in particular around 685 nm. This suggests the appropriateness of analysing the photon density profile resulting from punctiform irradiation of the joint. In a first approximation, the point spread function of transmitted photon density is confirmed to be proportional to a Gauss distribution, as suggested by Arridge. In accordance with the linear signal transfer theory, therefore, it is possible to establish a virtual transfer system described by a first-order differential equation. (The tissue optical conditions mu a << mu's and mu a = constant (mu a = absorption coefficient) were assumed). The parameter mu's (= reduced scattering coefficient) was determined by linear approximation of the Gauss distribution to the calculated or measured point spread function. For selected patient data, the mu's was determined in healthy and diseased finger joints (e.g. 10.1 cm-1 and 26.8 cm-1, respectively), and the results were in good agreement with those obtained experimentally.

[The development of a finger joint phantom for the optical simulation of early inflammatory rheumatic changes]. / Entwicklung eines Fingergelenkphantoms zur optischen Simulation früher entzündlich-rheumatischer Veränderungen.

In the field of rheumatology, conventional diagnostic methods permit the detection only of advanced stages of the disease, which is at odds with the current clinical demand for the early diagnosis of inflammatory rheumatic diseases. Prompted by current needs, we developed a finger joint phantom that enables the optical and geometrical simulation of an early stage of rheumatoid arthritis (RA). The results presented here form the experimental basis for an evaluation of new RA diagnostic systems based on near infrared light. The early stage of RA is characterised mainly by a vigorous proliferation of the synovial membrane and clouding of the synovial fluid. Using a double-integrating-sphere technique, the absorption and scattering coefficients (mua, mus') are experimentally determined for healthy and pathologically altered synovial fluid and capsule tissue. Using a variable mixture of Intralipid Indian ink and water as a scattering/absorption medium, the optical properties of skin, synovial fluid or capsule can be selected individually. Since the optical and geometrical properties of bone tissue remain constant in early-stage RA, a solid material is used for its simulation. Using the finger joint phantom described herein, the optical properties of joint regions can be adjusted specifically, enabling an evaluation of their effects on an optical signal--for example, during fluorography--and the investigation of these effects for diagnostically useful information. The experimental foundation for the development of a new optical system for the early diagnosis of RA has now been laid.

First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints.

OBJECTIVE: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. METHODS: 78 SLOT images of proximal interphalangeal joints II-IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. RESULTS: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. CONCLUSION: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.

[Infrared diaphanoscopy (IRD)--a choice diagnostic procedure? Preliminary results of the clinical testing]. / Infrarotdiaphanoskopie (IRD)--ein diagnostisches Verfahren der Wahl? Erste Ergebnisse der klinischen Erprobung.

X-ray examinations of maxillary sinus represent an exposure to radiation not to be ignored especially in infancy and childhood. The diagnostic method of infrared diaphanoscopy (IRD) is described. As a method of choice it is compared with other possibilities of diagnosing inflammatory diseases of the maxillary sinus. No exposure to radiation, easy application as well as low costs and small demands on the equipment are essential advantages of this method. First results have already shown its clinical relevance.

[Uniform theory on the pathomechanism of closed renal stalk injuries--subpelvic ureteral ruptures and kidney vascular stalk lesions]. / Beitrag für eine einheitliche Theorie über den Pathomechanismus geschlossener Nierenstielverletzungen--subpelvine Harnleiterrupturen und Nierengefässstielläsionen.

There are no homogeneous opinions concerning the pathomechanism of closed renal stalk injuries. On the basis of a literary analysis of 168 renal vessel stalk lesions and 78 ruptures of the ureter the attempt is made to contribute to the clarification of the etiology of these injuries. Subpelvic ruptures of the ureter and renal vessel stalk lesions are regarded as a constituent of closed renal stalk injuries and traced back to a uniform pathomechanism. Deceleration traumas leading to cranial, caudal and ventral movements of the kidney are regarded as predominant cause of closed renal stalk injuries. In accidents with deceleration processes should more be thought of closed renal vessel stalk lesions and subpelvic injuries of the ureter, also when there are no blunt abdominal traumas.

In vitro studies and computer simulations to assess the use of a diode laser (850 nm) for laser-induced thermotherapy (LITT).

BACKGROUND AND OBJECTIVE: This study investigated the feasibility of 850 nm diode laser-induced thermotherapy (LITT), a new procedure providing local hyperthermia and photocoagulation, a minimally invasive treatment of tumors, and other disorders such as benign prostate hyperplasia. STUDY DESIGN/MATERIAL AND METHODS: An improved fiber optic diffuser inserted through a catheter was used to irradiate prostate, liver, and kidney tissue in-vitro. Experimental results were compared with predictions from mathematical simulations based on measured optical tissue parameters. RESULTS: After 10 minutes of irradiation with 2-4.6 W CW laser power, sizable coagulation diameters had been achieved. In prostate and kidney tissue, temperature rises and coagulation diameters after laser irradiation were found to be smaller than in liver tissue. Those tissues also had a higher threshold for carbonization, thus reducing the risk of damage to the delivery system. CONCLUSION: The data suggest that a low power diode laser can be recommended for use in LITT to treat prostate and kidney tissue.

Variations in cell surfaces of estrogen treated breast cancer cells detected by a combined instrument for far-field and near-field microscopy.

The response of single breast cancer cells (cell line T-47D) to 17beta-estradiol (E(2)) under different concentrations was studied by using an instrument that allows to combine far-field light microscopy with high resolution scanning near-field (AFM/SNOM) microscopy on the same cell. Different concentrations of E(2) induce clearly different effects as well on cellular shape (in classical bright-field imaging) as on surface topography (atomic force imaging) and absorbance (near-field light transmission imaging). The differences range from a polygonal shape at zero via a roughly spherical shape at physiological up to a spindle-like shape at un-physiologically high concentrations. The surface topography of untreated control cells was found to be regular and smooth with small overall height modulations. At physiological E(2) concentrations the surfaces became increasingly jagged as detected by an increase in membrane height. After application of the un-physiological high E(2) concentration the cell surface structures appeared to be smoother again with an irregular fine structure. The general behaviour of dose dependent differences was also found in the near-field light transmission images. In order to quantify the treatment effects, line scans through the normalised topography images were drawn and a rate of co-localisation between high topography and high transmission areas was calculated. The cell biological aspects of these observations are, so far, not studied in detail but measurements on single cells offer new perspectives to be empirically used in diagnosis and therapy control of breast cancers.

[Laser-induced thermotherapy of liver metastases with MRI control. Prospective results of an optimized therapy procedure]. / Laserinduzierte Thermotherapie (LITT) von Lebermetastasen unter MRT-Kontrolle. Prospektive Ergebnisse eines optimierten Therapieverfahrens.

In a prospective study MR-guided laser-induced thermotherapy (LITT) of liver metastases was optimized and the clinical parameters evaluated. Seventeen patients (4 women, 13 men) with a total of 29 lesions underwent LITT in 25 sessions through 1 March 1994. Twelve of them suffered from colorectal carcinomas, 5 from other primary tumors. Under local anesthesia a maximum of 5 lesions per patient were treated. For MR-guided LITT a neodymium yttrium aluminum garnet laser (Nd-YAG 1064 nm) with energy varying from 3 to 7.5 W was used. Energy and application time were defined through a computer program; they varied, dependent on the lesion size, location and consistency. To monitor the progress of LITT two special thermosensitive MR sequences (Thermo-Turbo-FLASH and FLASH-2D sequences) were individually optimized, whereby the increase in temperature correlates with an increase in signal loss. All procedures were well tolerated without significant early or late side effects. In only one patient was minimal air documentated in the pleural cavity with spontaneous resorption. Patients were dismissed without complaints after 24-h hospitalization. The control parameters of the contrast-enhanced dynamic MRI documented at optimal response a hypointense signal around the tip of the laser applicator, in accordance with laser-induced necrosis. In lesions 20 mm or smaller, nearly 100% tumor necrosis was achieved and in lesions larger than 20 mm, only 50%. Follow-up evaluation 6 months after treatment shows a significantly better response in lesions with a diameter of 20 mm or smaller, with a local tumor control rate of 66%. In lesions larger than 20 mm only a local tumor control rate of 35% could be achieved. Laser-induced thermotherapy (LITT) represents a new, minimally invasive technique for tumor destruction and a high response rate in small liver metastases.

Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: technique and prospective results.

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided laser-induced thermotherapy (LITT) of liver metastases. MATERIALS AND METHODS: In a phase II study, 20 patients with 33 metastases from colorectal carcinoma (75%) or other primary tumors (25%) underwent LITT. MR thermometry performed with fast low-angle shot sequences was used to monitor therapy on-line, and dynamic and static contrast material-enhanced MR images enabled estimation of the degree of resultant necrosis. Follow-up studies were performed 3 months after thermotherapy. RESULTS: The thermosequences enabled accurate on-line monitoring in 85% of lesions. In 69% of lesions 20 mm in diameter or smaller, contrast-enhanced MR images depicted substantial necrosis, with a local tumor control rate of 69% after 6 months and 44% after 12 months. Among lesions larger than 20 mm, necrosis was frequently incomplete, with a local control rate of only 41% after 6 months and 27% after 12 months. CONCLUSION: MR imaging-guided LITT of liver metastases is a safe and promising therapy for liver metastases.