The importance of neuromagnetic studies in basic research on sensory and cognitive functions is well recognized. Researchers are now exploiting more sophisticated paradigms as well as more sophisticated data analysis techniques to achieve new knowledge about the human brain. Our recent identification of characteristic time constants in human auditory cortex that well predict the behavioral lifetime of human auditory sensory memory, and developments and application of various procedures for the magnetic inverse problem have opened new areas of investigation and advanced the technical capability of MSI. With multi-disciplinary efforts from physicists, neural scientists, psychologists and physiologists, MSI is being established as an important modality for functional images.

In order to improve our ability to use electromagnetic fields to diagnose and treat disease, it would be helpful to know the electric conductivity in the interior of the body. In order to obtain this information, our group of Rensselaer has built devices, which we call Adaptive Current Tomograph (ACT) systems, that apply small currents to the body through electrodes stuck to the skin. The ACT systems measure the induced voltages, and send all the current and voltage information to the computer, which uses an algorithm to process the data and reconstruct approximate images of the conductivity and permittivity in the interior.

Electroencephalography (EEG) is the primary means of studying neocortical dynamic function in the millisecond time scales at which information is processed. However, the information content of conventional EEG is severely limited by its poor spatial resolution (approximately 6 cm). With high resolution EEG, spatial resolution can be improved by a factor of three or more (approximately 2 cm). Two categories of methods have been used to obtain high resolution EEG: surface Laplacian (i.e., 'current source density') and cortical imaging (i.e., 'spatial deconvolution'). While these methods have somewhat different theoretical bases, each essentially involves an estimate of cortical surface potential. Computer simulations involving widely distributed sources are used to demonstrate the apparent accuracy of various approaches.

Iterative reconstruction algorithms for single photon emission tomography (SPECT) have generally outperformed conventional Fourier back-projections algorithms. Since faster computers have allowed their use in clinical investigations it is important to identify the best iterative approach. In this paper, the MENT and MART (Multiplicative Algebraic Reconstruction Technique) algorithms have been compared. They are considered to be quite different and their performance are frequently compared in the literature. MENT is generally preferred because it produces a maximum entropy solution to the problem of reconstruction but it is much slower than MART. We have demonstrated that MART can be mathematically derived from MENT. MART should then be the algorithm of choice for entropy maximization.

Some phase-sensitive methods obtain a phase measurement for each voxel in an otherwise conventional image. In an alternative approach, data for a variety of flow-sensitive conditions are obtained and Fourier transformed to obtain a velocity 'spectrum'. Fourier velocity encoded data are highly accurate and are not degraded by velocity distributions within a voxel. One important application of Fourier velocity encoding is the non-invasive measurement of local vessel wall compliance. We have developed a new technique in which spin velocity information is acquired simultaneously for several stations along a vessel using a comb excitation rf pulse and Fourier velocity encoding. In the absence of pulse wave reflections, two stations separated by a sufficient distance are enough to calculate the velocity of the pressure wave, C. Once the wave velocity is known, it can be used to determine vessel wall distensibility, D, using the relationship D equals 1/((rho) C²), where (rho) is the density of blood. Preliminary data from a group of healthy volunteers suggest a strong correlation of local vessel compliance with physical fitness and age.

In this theoretical paper we study the alterations of the laser induced fluorescence spectra as a function of the spectral variations of the absorption factor μ_a(λ), the scattering factor μ_s(λ) and of the mean cosine of the scattering angle g(λ) of the medium. The calculations of the signal received by the detector are based on a Monte Carlo simulation. All media are homogeneous, with infinite length and width, depth is assumed to be infinite. The total detected fluorescence signal S(λ) may be described by: S(λ)= F(λ_e,λ) . M(μ_a(λ_e),μ_s(λ_e),g(λ_e),μ_a(λ),μ_s(λ),g(λ)) where F is proportional to the original fluorescence spectrum and M a function of the optical and geometrical properties of the medium. In order to show the importance of the scattering, absorption and anisotropy spectral dependence, we have computed M for ideal experiments. Each coefficient μ_a, μ_s and g is alternately considered to be wavelength dependent while the others are considered to be constant. Consequently, each calculation provides a different distorted transfer function M(λ_e,λ) showing the influence of the spectral dependence of each coefficient. This signal is also different if the wavelength of the excitation light is changed.

For many situations in clinical medicine and other areas, knowledge of the interior structure and properties of materials is of great practical value. Imaging schemes which employed high energy sources, such as x-rays, have been the method of choice, in part, because of the high quality images that can be produced. While the undesirable biological effects of ionizing radiation have been known for several decades, it has only been within the past 15-20 years that alternative strategies that evaluate endogenous sources or exogeneous, but non-ionizing, sources have been made available. Endogenous sources include the electrical and magnetic fields produced as a result of synaptic propagation of the chemical signals generated in neuro-muscular tissues. Electroencephalographic (EEG) [1] and magnetoencephalographic (MEG) [2] imaging methods are based on measurement of these signals. Knowledge that body tissues contain ionic species that will conduct electrical current has led to the development of elecirical impedance tomography (EIT) [3]. Within the electromagnetic spectrum, radio and microwave sources are also being explored for their suitability. When performed in the presence of a large external magnetic field, the former, has proven extremely successful in the form of magnetic resonance imaging [4,5]. The observation that mechanical energy will differentially propagate in tissue has led to acoustic imaging methods in the form of ultrasound imaging and more recently as acoustic tomography [6]. More recently, the search for identifying alternative sources for imaging studies has been extended into the near infrared range [7-9]. At these frequencies it is known that whereas light is intensely scattered by tissue, NIR photons will penetrate deeply, allowing measurements through the head of a neonate or an adult female breast [10]. The great sensitivity of optical measurements and the known relationship between tissue function and the oxygen-dependent spectral properties of hemoglobin and other heme proteins has underscored interest in this area. With the exception of MRI, the quality of images produced using these alternative sources has been significantly poorer than that achieved using high energy sources. Frequently, though, the informational value of the resultant images is not strictly dependent on an accurate mapping of anatomical structures. For example, the acquisition of signals in real-time has proven especially valuable for sonography and for BEG, MEG, and BIT imaging and the closely associated electrocardiographic imaging method. Further, the ability to directly relate the measured response to well defined physiological events has also served to extend the usefulness of these methods. 081944 1 140/931$6.OO SPIE Vol. 1887/77 While the precise reasons accounting for the image quality obtained vary with the different methods, a common aspect of all is the considerable uncertainty which can exists as to the spatial origin of, in the case of endogenous sources, or path taken by, in the case of penetrating energy, the detected signal. When electromagnetic or acoustic sources are employed, this uncertainty is a result scattering of the penetrating energy due to localized differences in permittivity that is produced as a consequence of the physiochemical and structural heterogeneity of tissues. The theoretical framework for evaluating such measurements is described by the wave equation and is the basis for Diffraction Tomography (DT) [1 1]. As general rule, problems whose detector responses are dominated by scattering are typically ill-posed as multiple descriptions of the underlying medium may be consistent with the measured data. Invariably, another attribute of these types of problems is the considerable computing effort required to produce the resultant image, especially if a map in 3-dimensions rather than 2-D is required. In practice, the cost and time constraints imposed by the computing effort dominate and is the key element in defining the application range that a particular measurement-algorithm scheme may have. Theoretically sound strategies that rely on brute force computations frequently have little practical value. The need to effectively balance the measurement-algorithm scheme with acceptable computing times has led to the development of a variety of image recovery strategies. The Born and Rytov approximations, for example, introduce the assumption that the intensity of scattered signal is small relative to the incident field thereby linearizing the problem [1 1]. Recent studies, however, have demonstrated that this approximation cannot provide sufficient accuracy in the resultant images [12,13}. Other schemes provide a nonlinear treatment of the data and obtain convergence by minimizing a specified cost functional. These methods differ in their starting points. Newton-type methods usually consider a homogeneous background and update Bom-Rytov approximations in an iterative process [12, 13]. Solutions of non-Newton methods are not dependent on employing a "good' initial first guess as to the properties of the medium [14-16]. In general, efforts to solve inverse scattering problems (ISP), especially in the 3-D case, are difficult because of the following factors: i) Ill-conditionedness; small random fluctuations in the data cause large variations in the solution; ii) inherent nonlinearity of measured data with respect to unknown coefficients; iii) very large scale computations because unkiiown coefficients essentially depend on three, rather than two spatial variables. Attempts to address these concerns invariably involve tradeoffs. For example, all of the approaches described above require minimization of some type of functional. In doing this one faces at least one of the following procedures which are rather lime consuming, even in the 2D case. i) Solution of a boundary value problem for Helmholtz-like equation; ii) computation of a large number of 2-D, or 3-D integrals on each iteration step; iii) implementation of regularization techniques that require computing multiple solutions of (i) and (ii) in order to choose a proper value of the regularization parameter; (iv) properties of minimizing cost functionals are usually not investigated theoretically, which, in principle, can lead to the presence of multiple local minimums that may further add to the computational burden for search of the global minimum, especially in the case of a large number of unknowns [17]. Clearly, the correct solution requires determining the global minimum. Overall, whereas various techniques have been successfully developed to address the issue of il-posedness, the practical applicability of these becomes increasingly problematic as the size of the computing problem grows (i.e. 3-D case) and alternative numerical strategies must be sought. Recently, a new approach for solving ISPs has been described by some of the co-authors [18-22]. We call this the Regularized Quasi-Reversibility approach (RQR). The coreof the RQR scheme consists of working directly with partial differential equations, rather than with associated integral equations (e.g. as for instance, Lippman-Schwinger integral equation). Computational efficiency is accomplished by using explicit precalculation of all needed integrals, a priori choice of the number of Fourier coefficients of the unknown function as a regularization parameter, and construction of quasisolutions ofneeded boundary value problems rather than construction of actual solutions. Alternatively, similar efficiencies are obtained through construction of a globally convex minimizing cost functional that has the attractive feature of a single minimum. Examination of the method indicates that it is computationally efficient and results presented here, and elsewhere [18,19,22] for the Helmholtz and time-dependent wave equations confirm this. For example accurate solutions in the 2-D case have been obtained for inverse problems containing 441 unknowns (solved iteratively) in less than one minute of CPU time using a YIMP-CRAY. In fact recent preliminary results (not shown) have indicated that 3-D problems involving 3,000-4,000 unknowns can be computed in less than 30 minutes. In this report we describe two versions of the RQR approach and present results demonstrating the accuracy and stability of the solutions, in the 2-D case, based on evaluation of time-independent as well as time-dependent data. We also provide a discussion which considers the potential applicability of these methods to evaluate time-resolved optical measurements from dense scattering media obtained using ultrafast laser sources operating at NIR frequencies. The compatibility of this approach with solution of the ISP based on the transport equation is also described

NIR Raman scattering and fluorescence were investigated from malignant and normal biomedical media. Raman spectra were obtained from human normal, benign and cancerous tissues of the gynecological (GYN) tracts. Comparing the differences in intensity for the different Raman modes as well as the difference between the number of Raman lines, the normal (GYN) tissues can be distinguished from the malignant tissues. The fluorescence spectra from human breast tissues that were obtained showed that the ratio of fluorescence intensities at 340 nm to 440 nm can be used to distinguish between malignant and non- malignant tissues. Separate studies from normal and malignant breast cell lines show spectral differences assigned to NADH and flavins. These studies show that various optical techniques have the potential to be useful in medical diagnostic applications.

The NMR methods for the measurement of intracellular free Na⁺, K⁺, Mg²⁺, Ca²⁺, and H⁺ are introduced. The recent literature is then presented showing applications of these methods to cells and tissues from hypertensive animal model systems, and humans with essential hypertension. The results support the hypothesis of consistent derangement of the intracellular ionic environment in hypertension. The theory that this derangement may be a common link in the disease states of high blood pressure and abnormal insulin and glucose metabolism, which are often associated clinically, is discussed.

The ability to image at optical frequencies objects embedded in a dense scattering medium has been experimentally evaluated using a previously described Progressive Expansion (PE) algorithm. Optical backscatter measurements were performed in a limited raster-type scan using a colliding pulse modelocked (CPM) femtosecond laser operating at 620 nm and streak camera. Data were collected in the presence and absence of the embedded absorber (3 mm diameter bead) located at a depth not visible from the surface, smoothed and evaluated between - - 200 ps in steps of 36 ps, using an overlapping approach contained in the PE algorithm, which is based on a linear perturbation model. Results obtained demonstrate the sensitivity of reconstructed images to variations in source and detector locations in relation to the subsurface location of the absorber.

Recent developments in Magnetic Resonance Imaging (MRI) enabling imaging of hemodynamics and metabolism hold significant promise in the noninvasive evaluation of normal and abnormal brain function. Among several methods, the most successful approach exploits the sensitivity of MRI to changes in the oxygenation status of hemoglobin (oxy/deoxyhemoglobin) in red blood cells related to local variations in blood flow and oxygen consumption in tissues. In cerebral cortex, such variations may be induced by external stimuli or internal cognitive processes. Typically, MRI signal slightly increases when brain is activated due to increase in oxygen supply (blood flow). These studies suggest that MRI may be the method of choice to study mental and cognitive processes underlying the function of the human brain.

One of the fundamental problems in theoretical electrocardiography can be characterized by an inverse problem. In this paper, we present new methods for achieving better estimates of heart surface potential distributions in terms of torso potentials through an inverse procedure. First, an adaptive meshing algorithm is described which minimizes the error in the forward problem due to spatial discretization. We have found that since the inverse problem relies directly on the accuracy of the forward solution, adaptive meshing produces a more accurate inverse transfer matrix. Secondly, we introduce a new local regularization procedure. This method works by breaking the global transfer matrix into sub-matrices and performing regularization only on those sub-matrices which have large condition numbers. Furthermore, the regularization parameters are specifically 'tuned' for each sub-matrix using an a priori scheme based on the L-curve method. This local regularization method provides substantial increases in accuracy when compared to global regularization schemes. Finally, we present specific examples of the implementation of these schemes using models derived from magnetic resonance imaging data from a human subject.

Until recently, positron emission tomography (PET) has been acquired and displayed in a standard transaxial image format. The development of whole body PET has allowed biochemical and physiologic imaging of the entire body, expanding the limited axial field of view of the conventional PET scanner. In this study, the application of whole body PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for tumor imaging was evaluated. Whole body PET studies were positive (presence of focal FDG uptake relative to surrounding tissue activity) in 61 of 70 patients (87%) with biopsy confirmed malignant tumors. PET images failed to reveal focal hypermetabolism in 9 of the 70 patients. Of the 17 patients with benign biopsies lesions, 13 patients had whole body PET studies without focal areas of FDG uptake. Because of the high glycolytic rate of malignant tissue, the whole body PET FDG technique has promise in the detection of a wide variety of both primary and metastatic malignancies. The presence of FDG uptake in benign inflammatory conditions may limit the specificity of the technique. The true positive rates for the characterization of known lesions was 87% in this series, and the PET FDG method is promising both in determining both the nature of a localized lesion, and in defining the systemic extent of malignant disease.

Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.

Medical blood gas analysis mainly incidental three parameters, the measurement of partial pressure of oxygen and carbon dioxide, the PO₂ and PCO₂ as well as measurement of the negative logarithm of hydrogen ion activity. Since there are several sophisticated blood gas analyzers commercially available the question arises whether there is still some reason to look for additional methods. Since it is known that optical sensors exist for measuring hydrogen ions and oxygen to blood gas analysis, we have particularly tested laser optical fiber sensor indicators that are more sensitive than absorption indicators. The value of blood samples determined by this meter and ABL-30 blood-gas analytic meter (Denmurk) were well correlated, shows slope/intercept values very close to 1 and correlation coefficients of greater than 0.97 for all three parameters.

The accuracy of intraarterial blood gas monitoring (IABGM) devices is challenging to assess under routine clinical conditions. When comparing discrete measurements by blood gas analyzer (BGA) to IABGM values, it is important that the BGA determinations (reference method) be as accurate as possible. In vitro decay of gas tensions caused by delay in BGA analysis is particularly problematic for specimens with high arterial oxygen tension (PaO₂) values. Clinical instability of blood gases in the acutely ill patient may cause disagreement between BGA and IABGM values because of IABGM response time lag, particularly in the measurement of arterial blood carbon dioxide tension (PaCO₂). We recommend that clinical assessments of IABGM accuracy by comparison with BGA use multiple bedside BGA instruments, and that blood sampling only occur during periods when IABGM values appear stable.

Studies have been made of the spectral properties of radiation scattered by the human skin in vivo and of the human blood preparation at different degrees of oxygenation. It has been found that the difference of the amplitudes of the characteristic local extrema present in both the reflection spectra of man in vivo and in the reflection spectrum of the blood preparation is considerably dependent on the degree of blood oxygenation. The results obtained have enabled us to develop a contactless noninvasive method of quantitative estimation of oxyhemoglobin concentrations in the human skin blood flow in vivo.

We report on the fluorescence spectroscopy of a multicellular tumor spheroid treated and non- treated with (beta) -all-trans retinoic acid. Following ten days of treatment with RA (10^-6M), reproducible fluorescent changes were measured using a Mediscience CD scanner. The most significant changes included an increase in emission at 520 nm in the RA treated spheroids when excited at 340 nm. When investigating fluorescence emission at 450 nm, a blue shift in the excitation profile was noted. Molecular alterations induced by RA and as measured by optical fluorescence spectroscopy may arise from qualitative and/or quantitative changes in a number of key molecules involved in cellular differentiation, proliferation and/or electron transfer, i.e. NADH at (450 nm emission), flavins (520 nm), or cytokeratins (520 nm). To further explore alterations of cytokeratins, immunohistochemical staining showed an increase in AE1 positive cells induced by RA which paralleled the increased 520 nm signal. Our results indicate that certain vitamin derivatives are capable of modulating the intrinsic fluorescence profile emitted by neoplastic mucosa. Tissue autofluorescence may represent a significant marker for the biologic effect of cancer preventing agents in clinical trials.

Fluorescence spectroscopy of the human thymus gland and surrounding mediastinal fat were measured to evaluate this approach in distinguishing between thymus and fat tissues during therapeutic surgery for myasthenia gravis disease.

Both 'in vivo' and 'ex vivo' spectrofluorometric studies of neoplastic and non-neoplastic mucosa of human colon have been carried out, in order to verify the potentials of tissue natural fluorescence as a possible parameter to distinguish normal from diseased tissues, Spectrofluorometric analysis performed at colonoscopy on patients affected by neoplasia, showed that adenocarcinoma, adenoma and non-neoplastic mucosa differ in the fluorescence emissions. The results have been interpreted according to the data obtained on cryostatic sections from biopsies by means of a microspectrofluorometric analysis carried out on each histological component.

The laser induced in-vivo autofluorescence in the visible spectral region of cells and tissues was studied using stationary and time-resolved fluorescence measurements as well as video- intensified- and confocal laser-scanning microscopy. Due to their excitation and emission spectra and their decay kinetics (ps- and ns-region) at least three intrinsic fluorophores were so far differentiated and attributed to the reduced pyridine coenzymes NADH/NADPH, free and bound flavin molecules and endogenous porphyrins. It was found, that defects in the mitochondrial respiratory chain as well as photodynamically or chemically induced cell destruction results in an increase of the fluorescence intensity in the blue/green spectral range.

The spatial detail of the EEG has been greatly improved by increasing the number of recording electrodes from the usual 19 to over 120, and by developing mathematical procedures which use realistic finite element models of the head and brain to correct blur distortion produced by conduction through the skull and other tissues. Registration of EEGs with 3-D models of the cortex derived from each subject's MRI has also been accomplished. The result of these procedures is an estimate of the EEG on the exposed brain surface from recording made at the scalp. Examples of deblurred sensory and cognitive evoked potentials are presented, including an initial validation by comparison with subdural grid recordings from epileptic patients.

The expectation maximization method for maximum likelihood image reconstruction (ML- EM) is one of the most popular algorithms used in SPECT and PET, because it is based on the realistic assumption that photon emission and counts follow a Poisson process. Moreover, this method retains two important theoretical and practical properties namely nonnegativity and self-normalization of the reconstructed image. This latter property means that the number of emitted photons is equal to the number of counts. However, the major disadvantage of this method is the large amount of computation that is required, due to its slow rate of convergence. In this paper, we demonstrate that the ML-EM algorithm is a special case of the modified Newton method and can thus be accelerated by multiplying at each iteration the changes to the image, as calculated by the standard algorithm, by an overrelaxation parameter. This accelerated ML-EM algorithm can further be optimally accelerated, and converges to a good maximum likelihood estimator.

The bulk of our work on imaging the spatial distribution of NIR absorption in biological tissue has employed various perturbation methods for the image reconstructions. In the last two years, members of our group, have also been actively investigating the use of neural net algorithms for this purpose. An important lesson of our first round of image reconstruction by this method is the importance of preprocessing operations, i.e., making use of information from sources other than the intensity- or flux-measurement data to restrict the set of possible solutions.

The main problem of endometriosis is the detection of microscopic and atypical lesions. The successful destruction of these endometriotic sites depends on their detection. This study aimed to develop a spectrofluorometric method to increase the sensitivity of detection of endometriosis. A surgical-induced endometriosis was performed in ten rabbits. Five weeks later, the fluorescence of these endometriotic lesions was studied after injection of tamoxifen and local application of eosin. This fluorescence was compared with that of healthy broad ligament and that obtained without tamoxifen and without eosin. A spectral analysis showed a specific fluorescence of eosin-tamoxifen association, more intense than autofluorescence and selectively observed within endometriosis.

Reflectance oximetry can offer an advantage of being applicable to any portion of the body. However, the major problem of reflectance oximetry is low pulsatile signal level which prevents prolonged clinical application during extreme situations, such as hypothermia and vasoconstriction. In order to improve the pulsatile signal level of reflectance pulse oximeter and thus its accuracy, three different sensors, with the separation distances (SPD) between light emitting diode (LED) and photodiode being 3, 5, and 7 mm respectively, were studied on nine healthy volunteers. With the increase of the SPD, it was found that both the red (660 nm) and near-infrared (830 nm) pulsatile to average signal ratio (AC/DC) increased, and the standard deviations of (AC/DC)_red/(AC/DC)_infrared ratio decreased, in spite of the decrease of the absolute signal level. Further clinical studies of 3 mm and 7 mm SPD sensors on seven patients also showed that the (AC/DC)_red/(AC/DC)_infrared ratio measured by the 7 mm sensor were less disturbed than the 3 mm sensor during the surgery. A theoretical study based on the three-dimensional photon diffusion theory supports the experimental and clinical results. As a conclusion, the 7 mm sensor has the highest signal-to- noise ratio among three different sensors. A new 7 mm SPD reflectance sensor, with the increased number of LEDs around the photodiode, was designed to increase the AC/DC ratio, as well as to increase the absolute signal level.

We consider certain models that have been used recently to describe photon migration in a random media with the purpose of imaging this unknown media on the basis of boundary measurements. We discuss the performance of numerical algorithms to tackle the reconstruction problem associated to such models. Some of these algorithms are of nonlinear optimization type, while others proceed in a finite number of steps and do not require iteration. We study also the effect of noise in the performance of these algorithms as well as the deterioration of their performance as the amount of data is reduced.

Diagnosis and treatment of some disease states of the heart can be facilitated with knowledge of the electrical activity and resistivity properties within the heart muscle. A method of obtaining such information is through the use of electrical impedance tomography. Impedance imaging systems apply current patterns to the exterior of an object, measure the resulting voltages, and from these measurements construct an approximation to the spatially varying resistivity of the interior. By placing electrodes on the exterior of the heart or thorax as well as inside one of the heart chambers, using a catheter or by other means, it may be possible to construct images which reflect the resistivity distribution of the heart wall. In this work, we consider a simple model of the heart and thorax where electrodes are situated on both the interior and exterior boundaries of an annulus. The optimal current patterns to be applied are determined for the case of a homogeneous resistivity distribution and for the case of a single inhomogeneous layer. The question of the measurement precision required to distinguish between a homogeneous resistivity distribution and an inhomogeneous resistivity distribution is also discussed.

Completely non-invasive, real time (at a frame resolution of a second or less) tomographic movies of dynamic human visual system and motor system activity are demonstrated. These images are based on single shot functional magnetic resonance imaging (MRI) techniques sensitive to changes in either cerebral blood flow (CBF) or blood oxygenation. Given the close correspondence in both space and time between cerebral hemodynamic changes and neuronal activation, these data provide the highest spatial and temporal resolution tomographic maps of human brain activity reported to date.

Magnetic Resonance Spectroscopic Imaging (MRSI) methods combine the analytic capabilities of NMR with spatial discrimination methods of MR imaging, and provides a unique method for evaluation of metabolism in vivo. The low sensitivity of the MR resonances typically observed for MRSI studies requires lengthy spatial encoding methods and signal averaging, which lead to long acquisition times. Simple modifications of the spatial encoding techniques used for MRI are described which optimize spatial resolution and data acquisition times for in vivo applications of MRSI.

In order to determine in vivo resistivity of tissues in the thorax, the possibility of combining electrical impedance imaging (EII) techniques with (1) anatomical data extracted from high resolution images, (2) a prior knowledge of tissue resistivities, and (3) a priori noise information was assessed in this study. A Least Square Error Estimator (LSEE) and a statistically constrained Minimum Mean Square Error Estimator (MiMSEE) were implemented to estimate regional electrical resistivities from potential measurements made on the body surface. A two dimensional boundary element model of the human thorax, which consists of four different conductivity regions (the skeletal muscle, the heart, the right lung, and the left lung) was adopted to simulate the measured EII torso potentials. The calculated potentials were then perturbed by simulated instrumentation noise. The signal information used to form the statistical constraint for the MiMSEE was obtained from a prior knowledge of the physiological range of tissue resistivities. The noise constraint was determined from a priori knowledge of errors due to linearization of the forward problem and to the instrumentation noise.

Methods to localize the sources of Brain Evoked Potential Maps based on modeling of the sources as point dipoles have been widely used for more than twenty years. Such methods still lack a basic theory which can answer questions regarding the resolution and uniqueness of the results in the context of a realistic head model, with no a prior restrictions on the sources. In the first part of the paper we present simple physical models for the origin of far-field potentials associated with the auditory and somatosensory systems. An action potential travels along a straight axon can only produce a quadrupole field at far distances. We show that the far field potentials must originate when the action potential passes through a bent axon or through changes in the conductivities or in the external boundaries of the volume conductor surrounding the axon. We discuss the question of uniqueness of the solution for the 'inverse problem' of evoked potentials. This problem involved the reconstruction of the location and pattern of activity of the neuronal generators in the brain, given the map of the scalp electric potentials. We show that in a head shape with a realistic geometry spatially distinct points, line or open surface generators cannot create the same scalp potential map. The same applies to two non-overlapping generators occupying finite volumes.

A series of supersensitive apparatuses constructed in the laboratory of this author for the steady-state, time-resolved and combined time-resolved-spectral measurements of infrared luminescence of singlet molecular oxygen has been described. All apparatuses were based on the use of cooled S-1 photomultipliers. Steady-state measurements were carried out using mechanical phosphoroscopes or the mode of a conventional fluorimeter. Time-resolved measurements were performed using pulsed lasers and averaging photon counting electronics based on the use of multichannel analyzers. This technique allowed pioneering measurements of photosensitized singlet oxygen luminescence in organic and aqueous media and systematic investigation of generation and quenching of singlet oxygen by numerous biologically important compounds. The data suggest that the development of the PMT-based technique for detection of singlet oxygen luminescence is highly promising for various biomedical applications and might be useful for imaging photodynamically active sites of living tissues.