Multisensor hyperspectral imaging approach for the microchemical analysis of ultramarine blue pigments.

This work presents a multisensor hyperspectral approach for the characterization of ultramarine blue, a valuable historical pigment, at the microscopic scale combining the information of four analytical techniques at the elemental and molecular levels. The hyperspectral images collected were combined in a single hypercube, where the pixels of the various spectral components are aligned on top of each other. Selected spectral descriptors have been defined to reduce data dimensionality before applying unsupervised chemometric data analysis approaches. Lazurite, responsible for the blue color of the pigment, was detected as the major mineral phase present in synthetic and good quality pigments. Impurities like pyrite were detected in lower quality samples, although the clear identification of other mineral phases with silicate basis was more difficult. There is no correlation between the spatial distribution of the bands arising in the Raman spectra of natural samples in the region 1200-1850 cm-1 and any of the transition metals or rare earth elements (REE). With this information, the previous hypothesis (based on bulk analysis) attributing these bands to luminescence emissions due to impurities of these elements must be revised. We propose the consideration of CO2 molecules trapped in the cages of the aluminosilicate structure of sodalite-type. Additionally, correlation between certain Raman features and the combined presence of Ca, P, and REE, in particular Nd, was detected for the lowest quality pigment. Our results highlight the usefulness of fusing chemical images obtained via different imaging techniques to obtain relevant information on chemical structure and properties.

Theoretical considerations of monitor unit calculations for intensity modulated beam treatment planning.

A treatment planning system to compute intensity modulated radiotherapy (IMRT) treatments using inverse planning was investigated. The system was designed to optimize the intensity patterns required to treat a specified target volume with specified normal structure constraints. A beam model that uses the convolution of pencil beams was used to compute the dose distributions. A multileaf collimator leaf-setting sequence intended to produce the intensity pattern was computed along with the monitor units required to deliver each of a number of fixed-gantry modulated fields. Computer calculations are commonly verified using an independent manual procedure. It is difficult to calculate treatment delivery monitor units for this variant of IMRT using manual methods. Since manual calculations are not feasible, it is important both to understand and to verify the calculation of treatment monitor units by the planning system algorithm. A formal analysis was made of the dose calculation model and the monitor unit calculation embedded in the algorithm. Experimental verification of the dose delivered by plans computed with the methodology demonstrated an agreement of better than 4% between the dose model and measurements.

The field-matching problem as it applies to the peacock three dimensional conformal system for intensity modulation.

PURPOSE: Intensity modulated beam systems have been developed as a means of creating a high-dose region that closely conforms to the prescribed target volume while also providing specific sparing of organs at risk within complex treatment geometries. The slice-by-slice treatment paradigm used by one such system for delivering intensity modulated fields introduces regions of dose nonuniformity where each pair of treatment slices abut. A study was designed to evaluate whether or not the magnitude of the nonuniformity that results from this segmental delivery paradigm is significant relative to the overall dose nonuniformity present in the intensity modulation technique itself. An assessment was also made as to the increase in nonuniformity that would result if errors were made in indexing during treatment delivery. METHODS AND MATERIALS: Treatment plans were generated to simulate correctly indexed and incorrectly indexed treatments of 4, 10, and 18 cm diameter targets. Indexing errors of from 0.1 to 2.0 mm were studied. Treatment plans were also generated for targets of the same diameter but of lengths that did not require indexing of the treatment couch. RESULTS: The nonuniformity that results from the intensity modulation delivery paradigm is 11-16% for targets where indexing is not required. Correct indexing of the couch adds an additional 1-2% in nonuniformity. However, a couch indexing error of as little as 1 mm can increase the total nonuniformity to as much as 25%. All increases in nonuniformity from indexing are essentially independent of target diameter. CONCLUSIONS: The dose nonuniformity introduced by the segmental strip delivery paradigm is small relative to the nonuniformity present in the intensity modulation paradigm itself. A positioning accuracy of better than 0.5 mm appears to be required when implementing segmental intensity modulated treatment plans.

MRI guided interstitial laser therapy in a rat malignant glioma model.

We have used MR monitoring to guide and evaluate the effects of the Nd:YAG interstitial laser on a well-characterized rat brain tumor model (C6). MRI was used to determine the tumor size, verify the location of the interstitial probe, and evaluate the size and location of the laser-induced lesion during and after treatment. During laser irradiation, an irreversible loss of signal intensity at the fiber tip and a reversible decrease in signal intensity around it were observed with MRI. None of the treatment protocols affected mean rat survival significantly. Although MRI-guided interstitial laser therapy appears to be safe and easy, it does not provide a curative treatment for spatially disseminated gliomas where a "target volume" cannot be adequately defined. Better results can be expected, especially in well-defined tumors, with improvements of both the imaging techniques and the laser treatment protocol.

Magnetic resonance imaging of the acute effects of interstitial neodymium:YAG laser irradiation on tissues.

RATIONALE AND OBJECTIVES: Laser irradiation therapy in deep tissues requires a monitoring method other than visual guidance. Magnetic resonance imaging (MRI) can be used for this purpose because it visualizes soft tissue structures and heat distribution. METHODS: The authors performed interstitial laser irradiations in rat livers with various laser outputs and measured the sizes of laser-induced lesions. MRI of these lesions was done ex vivo and compared with the histologic findings. Laser-induced lesions also were studied in rabbit brain, liver, and skeletal muscle to show the influences of tissue optical and thermal properties. Imaging of interstitial laser irradiation also was performed in vivo in rabbit brains. RESULTS: MRI depicted the laser-induced lesions produced with different laser outputs and tissue types. MRIs of rabbit brain in vivo effectively demonstrated the signal decrease during heating and acute tissue changes. CONCLUSION: MRI has potential for monitoring interstitial laser surgery or hyperthermia.

Effects related to temperature changes during MR imaging.

Magnetic resonance (MR) imaging has been proposed as a method of monitoring the interstitial laser heating of tissue for the clinical treatment of tumors (laser hyperthermia). The treatment causes considerable temperature changes over the time that image data are acquired, and therefore an analysis of the time-dependent effects of heating is required. The problem is expressed mathematically, and computer-simulated images are compared with those obtained from experimental heating and imaging of gel phantoms. Results show that at the rates of heating typical for laser hyperthermia and even with the relatively slow standard imaging techniques used, generation of artifact is not a major concern. It is also shown that a spatial spin signal magnitude distribution, evolving in time, is effectively sampled at the time to when the low-numbered phase-encoding steps are collected at to. It is noted, however, that substantial temperature changes during image data acquisition make accurate temperature determination difficult and place limits on MR imaging for quantitative spatial temperature mapping.

Real-time magnetic resonance imaging of laser heat deposition in tissue.

We applied diffusion-sensitive echo planar (Instascan) imaging to study thermal changes caused by a Nd:YAG laser. Images of phantom materials and normal rabbit brain tissue in vivo, acquired in 150 ms, every 2s, clearly showed the dynamics of temperature-related signal intensity changes in the regions irradiated by the laser.

CPMG imaging sequences for high field in vivo transverse relaxation studies.

Two-dimensional Fourier transform Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.9-T and 1.5-T imaging systems in order to test their ability to characterize in vivo transverse decay curves (TDCs). Both hard- and soft-pulse CPMG imaging sequences, consisting of up to 128 echoes with echo spacings of approximately 10 ms were developed, implemented, and tested. These sequences provide one of the most detailed samplings of TDCs from image data sets reported to date. Good agreement between image-extracted T2 values and spectroscopically obtained T2 values of NiCl2-doped saline solutions was found with both hard- and soft-pulse sequences. In vivo TDCs were extracted from rabbit and human image data sets. For several tissues, biexponential TDC fits provided considerable improvement over monoexponential fits and the sensitivity of the fitting parameters to positive baseline offsets was examined. With the time coverage of the relaxation decay curves available from these sequences, the TDCs from white matter in humans appear largely monoexponential while those from cortical grey matter demonstrate biexponential behavior.

Compatibility of the two-site exchange model and 1H NMR relaxation rates.

We demonstrate a formalism for determining whether 1H longitudinal and transverse magnetic relaxation decay curves are compatible with a model of proton exchange between two sites with inherently different relaxation rates. We apply the method to published data in which both decay curves have been fit to normalized biexponential functions, a prediction of the simplest two-site exchange model. The analysis is applied to relaxation data of adsorbed water vapor on silica gel (J.R. Zimmerman and J.A. Lasater, J. Phys. Chem. 62, 1157 (1958] and to relaxation data reported in mycelia of Botrytis cinerea Persoon and pupae of the tobacco cutworm (M. Yoshida and K. Nose, Agric. Biol. Chem. 51, 3399 (1987]. Exchange parameters are calculated form these data sets and the compatibility of the two-site exchange model with the data is discussed for each case. The sensitivity of the calculated exchange parameters to errors in the bioexponential fitting parameters is treated in some detail.

Response to and control of destructive energy by magnetic resonance.

Magnetic resonance imaging techniques can be used to control and monitor the deposition of destructive energy. The authors evaluated the feasibility of phosphorus-31 magnetic resonance spectroscopy for the control, monitoring, and prediction of the three-dimensional extent of tissue destruction during interstitial laser surgery. Characteristic metabolic changes were demonstrated within the lesion and in the adjacent normal tissue during the deposition of thermal energy.

The effect of gadolinium DTPA on tissue water compartments in slow- and fast-twitch rabbit muscles.

Proton T2 relaxation and its biexponential components have been determined in rabbit skeletal muscle in the presence and absence of GdDTPA. The effect of GdDTPA, which distributes only in the extracellular space, was greatest in the longer-relaxing T2 component (T22). A 27% reduction in T22 was measured for slow-twitch (red) muscle and 17% for fast-twitch (white) muscle, consistent with the larger extracellular space of the former. Magnetic resonance images demonstrated apparent contrast between red and white rabbit muscles. This contrast was instantaneously enhanced by administration of GdDTPA and returned to near normal levels after approximately 30 min. These functional changes in tissue contrast are consistent with differences in blood perfusion and biological water compartmentation between fast- and slow-twitch skeletal muscles.

Two-site exchange revisited: a new method for extracting exchange parameters in biological systems.

A new analysis is presented which links real volume fractions, relaxation rates, and intracompartmental exchange rates directly with apparent volume fractions and relaxation rates obtained from biexponential fits of transverse magnetization decay curves. The analysis differs from previous methods in that measurements from two paramagnetic doping levels are used to close the two-site exchange equations. Both the new method and one previously described by Herbst and Goldstein (HG) have been applied to paramagnetically doped whole-blood data sets. Significant differences in the calculated exchange parameters are found between the two methods. A small dependence of the intracellular relaxation rate on extracellular paramagnetic agent concentration, assumed nonexistent with the HG method, is inferred from the new analysis. The analysis was also applied to published data on perfused rat hearts, and we obtained a limited assessment of two-site exchange in this system.

MR imaging of laser-tissue interactions.

A new application of magnetic resonance (MR) imaging to map the spatial and temporal distribution of the effects of Nd:YAG lasers on tissues was studied. The temperature dependence of MR relaxation mechanisms and the high sensitivity of MR to changes in the mobility and distribution of tissue water make it particularly suitable for the demonstration and control of thermal energy deposition in tissues. In heterogeneous tissues, MR imaging does not follow changing temperatures directly because even in the case of reversible thermal interactions, there is a hysteresis in the dynamic relationship between MR signal intensity and temperature. Appropriate matching of the laser and MR pulse sequences can, however, optimize the detection of relatively small laser energy deposition, and reversible and irreversible tissue changes can be distinguished. There is a potential for the integration of MR imaging and lasers for three-dimensional control and monitoring of laser-tissue interactions.

Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.

The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.

An improved ultrasound simulation model: use in evaluating log versus linear processing for lesion detection.

This paper reports the development of an improved three-dimensional computer simulation model for evaluation of ultrasonic imaging systems. This model was used to successfully evaluate a signal processing method for improving lesion detection in ultrasound imaging. Linear processing of the rf signal amplitudes from a limited region of tissue was compared with the logarithmic compression employed by most commercial scanners. Two lesions were simulated by spherical distributions of scatterers having backscatter coefficients greater than the scatterers in the surrounding medium. Linear processing improved the differential contrast by a factor of about two. The simulation is based on the three-dimensional distribution of acoustic frequency spectra in a transducer beam and integration of scattered pulses from a corresponding three-dimensional array of scatterers. The simulation reported in previous papers depended upon physical measurement of the impulse response of a transducer. An original contribution described briefly herein, and in more detail in a companion article, is the addition of a model of the transducer's pulse waveform generation. Another new addition is the definition of a specific lesion detection task for objective assessment of a change in image quality following perturbation of some system parameter.

Breast tissue classification using diagnostic ultrasound and pattern recognition techniques: I. Methods of pattern recognition.

This paper discusses the application of statistical pattern recognition techniques to problems in diagnostic ultrasound. Using our own system as an example, we describe the concepts and specific methods that we have applied to a problem involving the computer-aided classification of breast tissue in vivo. Topics include feature generation, feature selection and classification, as well as a method which estimates the probability of error on classifying future data. An accompanying paper applies these methods to the classification of backscattered RF signals from normal and diseased breast tissue.

Breast tissue classification using diagnostic ultrasound and pattern recognition techniques: II. Experimental results.

The methods of statistical pattern recognition have been applied to the problem of in vivo ultrasonic characterization of breast disease in humans. Backscattered A-mode signals obtained from a commercial pulse imaging system were used to generate a large set of potentially useful features. Using statistical tests, a small subset of discriminatory features was selected to design a Bayes decision rule for each of two tissue classification schemes: malignant disease vs. benign disease, and malignant disease vs. (benign disease + normal tissue). Classification results obtained by the rotation method included sensitivities of 88 percent and 76 percent for the two schemes, based on data obtained from 32 women. These results are encouraging, though a definitive statement concerning the extrapolation of these numbers to the general population should only be made after obtaining results with a large data base.