[A software tool for analysis and quantification of regional pulmonary ventilation using dynamic hyperpolarised-(3)He-MRI]. / Ein Auswerteprogramm zur quantitativen Untersuchung der Lungenventilation mittels dynamischer MRT von hochpolarisiertem.

PURPOSE: (3)He-MRI is able to visualize the regional distribution of lung ventilation with a temporal and spatial resolution so far unmatched by any other technique. The aim of the study was the development of a new software tool for quantification of dynamic ventilation parameters in absolute physical units. MATERIALS AND METHODS: During continuous breathing, a bolus of hyperpolarized (3)He (300 ml) was applied at inspiration and a series of 168 coronal projection images simultaneously acquired using a 2D FLASH-sequence. Postprocessing software was developed to analyze the (3)He distribution in the lung. After correction for lung motion, several ventilation parameters (rise time, delay time, (3)He amount and (3)He peak flow) were calculated. Due to normalization of signal intensities, these parameters are presented in absolute physical units. The data sets were analyzed on a ROI basis as well as on a pixel-by-pixel basis. RESULTS: Using the developed software, the measurements were analyzed in 6 lung-healthy volunteers, in one patient after lung transplantation, and in one patient with lung emphysema. The volunteers' parameter maps of the pixel-based analysis showed an almost homogeneous distribution of the ventilation parameters within the lung. In the parameter maps of both patients, regions with poor ventilation were observed. CONCLUSION: The developed software permits an objective and quantitative analysis of regional lung ventilation in absolute physical units. The clinical significance of the parameters, however, has to be determined in larger clinical studies. The software may become valuable in grading and following pulmonary function as well as in monitoring any therapy.

[Remote controlled drug release in the alimentary tract by local power deposition in alternating magnetic fields]. / Remote controlled drug release in the alimentary tract by local power deposition in alternating magnetic fields.

Remote controlled release of agents in the alimentary tract is an important task of gastroenterology and pharmacy. We investigated two different methods of drug release by heating locally restricted parts in medical capsules: hysteresis losses of magnetite powder and eddy current losses of metals in alternating magnetic fields. The comparison of our experimental results with theoretically derived expectations show that both methods are suitable techniques if special technical conditions are met. In order to demonstrate the feasibility of simple constructions, we used a gelatin capsule, consisting of two parts which were kept together by a belt of wax and a small copper coil. This capsule was placed in water and the belt was heated in an alternating magnetic field until melting and releasing a test fluid after about 60 s.

[Quantitative evaluation of cavitation bubble fields induced by lithotripter shock waves]. / Quantitative evaluation of cavitation bubble fields induced by lithotripter shock waves.

Extracorporeal shock wave lithotripsy is the world-wide standard therapy for renal stones. The rare-faction phase of the shock wave can induce cavitation within the body. Cavitation contributes to stone disintegration but also to medical side effects. The aim of this study was to evaluate the spatial and size distribution of the cavitation bubble fields. To this end, the bubble fields were photographed digitally and evaluated automatically by image processing. The influence of various medium (water) and shock wave parameters was investigated. Water purity, i.e. the number of cavitation nuclei, was the most critical medium parameter which has to be controlled. At oxygen levels higher than 4 mg/l, cavitation increased rapidly when high shock wave frequencies of 2 Hz were used.

[Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study]. / Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study.

Transmission measurements are performed in SPECT to correct for attenuation of the gamma quanta in the body. In this study, we measured the additional radiation dose caused by transmission scans using a field of collimated 153Gd rod sources. Two measurement series were performed with an anthropomorphic phantom and thermoluminescence dosimeters. For a typical SPECT study, we found a mean dose rate of 2.2 +/- 0.8 micro Sievert per hour (range: 1.2-3.9 micro Sievert per hour). For a measurement time of 20 min, this corresponds to a mean equivalent patient radiation dose of 0.73 micro Sievert. Thus, the radiation exposure caused by transmission scans can be neglected compared to the radiopharmaceutical dose and may not be considered as a limiting factor for the clinical application of attenuation correction in SPECT.

[A 3D FEM model for calculation of electromagnetic fields in transmagnetic stimulation]. / A 3D FEM model for calculation of electromagnetic fields in transcranial magnetic stimulation.

We developed a realistic finite elements method (FEM) model of the brain for the calculation of electromagnetic fields in transcranial magnetic stimulation (TMS). A focal butterfly stimulation coil was X-rayed, parameterized, and modeled. The magnetic field components of the TMS coil were calculated and compared for validation to pointwise measurements of the magnetic fields with a Hall sensor. We found a mean deviation of 7.4% at an axial distance of 20 mm to the coil. A 3D brain model with the biological tissues of white and gray matter, bone, and cerebrospinal fluid was developed. At a current sweep of 1000 A in 120 microseconds, the maximum induced current density in gray matter was 177 mA/m2 and the strongest electric field gradient covered an area of 40 mm x 53 mm.

DTI measurements of isotropic and anisotropic media.

The ability to measure different rates of diffusion along different directions is one of the features that distinguish DTI from other imaging methods. It allows to extract and visualize information on tissue microstructure and microdynamics. However, to correctly determine the full diffusion tensor, the so-called b-matrix has to be calculated by taking into account the non-negligible influences of image gradients and cross-terms between imaging and diffusion gradients. In this work validation of this b-matrix correction was investigated by determining self-diffusion coefficients of several isotropic media on a 1.5 T clinical whole-body scanner. To investigate these influences on the measurements of anisotropic media the same experiments were performed with a carrot.

[Quantification and visualization of oxygen partial pressure in vivo by 19F NMR imaging of perfluorocarbons]. / Quantification and visualization of oxygen partial pressure in vivo by 19F NMR imaging of perfluorocarbons.

Due to the high solubility of molecular oxygen in perfluorocabons (PFC), this class of fluorinated compounds has gained wide-spread interest for its biomedical application as temporary blood substitutes and as radiosensitizers. Since the observation that the NMR spin-lattice relaxation times (T1) of some 19F PFC resonances are sensitive to oxygen tension (pO2), this paramagnetic effect has been used to non-invasively probe pO2 in vivo. In this study, combined 19F/1H NMR image data of Copenhagen rats after PFC application were evaluated with the software package MATLAB. The analysis of the 19F NMR data resulted in image matrices with calculated T1 values in each pixel. By using a calibration curve, the corresponding pO2 values were computed. Color overlays of pO2 contour lines on T1-weighted 1H images show a good anatomical-functional correspondence.

[Implementation of a measurement protocol to evaluate system parameters in positron emission tomography]. / Implementation of a measurement protocol to evaluate system parameters in positron emission tomography.

To evaluate system parameters in PET measurements, several different activity ratios of the investigated phantom must be analyzed. The aim of this study was to develop a measurement protocol which requires just one filling of the phantom to measure adequate image contrasts and count ranges. We used 11C for the hollow spheres and 18F for the background of the whole-body PET phantom. Because of the different half-lives of the radionuclides, the dynamic acquisition of the frames (duration compensated for 18F decay) realizes various activity ratios between the spheres and the constant background. By summing up different frames, the counts in the background can also be varied. The presented method reduces the radiation exposure of the staff and economizes the use of the tomograph.

[Assessment of image reconstruction parameters in PET using physical and statistical figures of merit]. / Assessment of image reconstruction parameters in PET using physical and statistical figures of merit.

The aim of this study was to analyze the recommended OSEM image reconstruction parameters in positron emission tomography (PET). Spatial resolution, signal-to-noise ratio, and contrast were used as physical figures of merit (FOM). For statistical FOMs, the t-value and the area under the receiver operating characteristic (ROC) were employed. The spatial resolution was measured with 21 point sources. The signal-to-noise ratio, the contrast, and the t-value were investigated with a whole-body phantom with hollow spheres inserted. A phantom containing line sources was used for ROC analysis. As result, the reconstruction parameters recommended for visual evaluation lead to images with an adequate lesion detectability. The quantitative reconstruction, however, needs improvement.

[Development of a laser-optical tomograph for demonstration of CT imaging without ionizing radiation]. / Development of a laser-optical tomograph for demonstration of CT imaging without ionizing radiation.

Computed X-ray tomography (CT) is one of the most powerful diagnostic procedures in medicine. In this study, we developed a laser-optical CT scanner for the use by students as part of their curriculum in biomedical engineering. Our CT set-up employs a linear-scan technique where the measurement objects (light absorbing phantoms embedded in immersion oil), the light emitter (modulated laserdiode), and the detector (photodiode) are moved by linear-step motors. The spatial resolution is limited by the width of the laser beam (2 mm) and the smallest achievable raster step size (0.02 mm). Optical tomographic images of various objects can be measured within a few minutes and allow the demonstration of imaging principles like extinction, scanning, projection, and reconstruction techniques.

[Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study]. / Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study.

Transmission measurements are performed in SPECT to correct for attenuation of the gamma quanta in the body. In this study, we measured the additional radiation dose caused by transmission scans using a field of collimated 153Gd rod sources. Two measurement series were performed with a anthropomorphic phantom and thermoluminescence dosimeters. For a typical SPECT study, we found a mean dose rate of 2.2 +/- 0.8 micro Sievert per hour (range: 1.2-3.9 micro Sievert per hour). For a measurement time of 20 min, this corresponds to a mean equivalent patient radiation dose of 0.73 micro Sievert. Thus, the radiation exposure caused by transmission scans can be neglected compared to the radiopharmaceutical dose and may not be considered as a limiting factor for the clinical application of attenuation correction in SPECT.

[Recovery coefficients for the quantification of the arterial input functions from dynamic PET measurements: experimental and theoretical determination]. / Recovery-Koeffizienten zur Quantifizierung der arteriellen Inputfunktion aus dynamischen PET-Messungen: experimentelle und theoretische Bestimmung.

AIM: For kinetic modelling of dynamic PET data, the arterial input function can be determined directly from the PET scans if a large artery is visualized on the images. It was the purpose of this study to experimentally and theoretically determine recovery coefficients for cylinders as a function of the diameter and level of background activity. METHODS: The measurements were performed using a phantom with seven cylinder inserts (Ø = 5-46 mm). The cylinders were filled with an aqueous 68Ga solution while the main chamber was filled with a 18F solution in order to obtain a varying concentration ratio between the cylinders and the background due to the different isotope half lives. After iterative image reconstruction, the activity concentrations were measured in the center of the cylinders and the recovery coefficients were calculated as a function of the diameter and the background activity. Based on the imaging properties of the PET system, we also developed a model for the quantitative assessment of recovery coefficients. RESULTS: The functional dependence of the measured recovery data from the cylinder diameter and the concentration ratio is well described by our model. For dynamic PET measurements, the recovery correction must take into account the decreasing concentration ratio between the blood vessel and the surrounding tissue. Under the realized measurement and data analysis conditions, a recovery correction is required for vessels with a diameter of up to 25 mm. CONCLUSIONS: Based on the experimentally verified model, the activity concentration in large arteries can be calculated from the measured activity concentration in the blood vessel and the background activity. The presented approach offers the possibility to determine the arterial input function for pharmacokinetic PET studies non-invasively from large arteries (especially the aorta).

[Development of a nonmagnetic angle encoder for active shielding during biomagnetic measurements]. / Entwicklung eines nichtmagnetischen Winkel-Encoders zur aktiven Abschirmung bei biomagnetischen Messungen.

Biomagnetic fields--in particular in the low-frequency range--are subject to environmental interference, which cannot be adequately reduced by most passive shielding methods. However, the signal-to-noise ratio can be increased by active compensation. For this purpose, the interference is detected by reference sensors and fed back through integrated compensation coils. To establish deviation of normal directions between reference sensors and compensation coils, an angle encoder was developed. The rotation of the reference sensors about two axes at right angles to each other, is converted into voltage pulses by means of codewheels and photoelectric beams. The pulses are counted by incremental encoders, and represent a measure of the angles. A cardanic suspension and a plumb-line act as a reference system. The pulses counted are converted into binary angle values, which are used for coordinate transformation of the interfering fields. The angle encoder can determine the tilt of the reference sensors with an accuracy of 1 degree within a range between -45 and +45 degrees. The noise level of the system remains unaffected during a biomagnetic measurement. Magnetic signals of up to 5 pT arising during the oscillation of the plumb-line can be neglected because of the static nature of the angular measurement.

[Quantitative measurement of induced skin reddening using optical reflection spectroscopy--methodology and clinical application]. / Quantitative Messung induzierter Hautrötungen durch optische Reflexionsspektroskopie--Methodik und klinische Anwendung.

Optical reflection spectroscopy is a simple and quick method for the quantification of colour intensity, and is thus suitable for the determination of changes in skin reddening (erythema) due to local vasodilatation. To quantify the time course of this erythema, the oxyhaemoglobin absorption double peak with maxima at 542 and 577 nm is an appropriate parameter. A compact handheld optical spectrometer makes the technique applicable to clinical use, an example being the niacin patch test described herein. This noninvasive test provides information about the cell membrane metabolism via the skin flush induced by niacin (vitamin B3) and mediated by prostaglandin. The aim of this study was to adapt optical reflection spectroscopy to the requirements of the clinical niacin patch test. To that end, we investigated 60 healthy volunteers. Analysis of the spectroscopic data with regard to physiological covariables of niacin sensitivity revealed faster and more intense erythema in females--a gender effect that to our knowledge has not previously been reported. In the light of these results, the findings of other researchers based on semi-quantitative test methods should be reassessed, with consideration given to the gender effect.

Parametric display of myocardial function.

Quantitative assessment of regional heart motion has significant potential to provide more specific diagnosis of cardiac disease and cardiac malfunction than currently possible. Local heart motion may be captured from various medical imaging scanners. In this study, 3-D reconstructions of pre-infarct and post-infarct hearts were obtained from the Dynamic Spatial Reconstructor (DSR)[Ritman EL, Robb RA, Harris LD. Imaging physiological functions: experience with DSR. Philadelphia: Praeger, 1985; Robb RA, Lent AH, Gilbert BK, Chu A. The dynamic spatial reconstructor: a computed tomography system for high-speed simultaneous scanning of multiple cross sections of the heart. J Med Syst 1980;4(2):253-88; Jorgensen SM, Whitlock SV, Thomas PJ, Roessler RW, Ritman EL. The dynamic spatial reconstructor: a high speed, stop action, 3-D, digital radiographic imager of moving internal organs and blood. Proceedings of SPIE, Ultrahigh- and High-speed Photography, Videography, Photonics, and Velocimetry 1990;1346:180-91.] (DSR). Using functional parametric mapping of disturbances in regional contractility and relaxation, regional myocardial motion during a cardiac cycle is color mapped onto a deformable heart model to facilitate appreciation of the structure-to-function relationships in the myocardium, such as occurs in regional patterns of akinesis or dyskinesis associated with myocardial ischemia or infarction resulting from coronary artery occlusion.

Quantification of [(18)F]FDG uptake in the normal liver using dynamic PET: impact and modeling of the dual hepatic blood supply.

UNLABELLED: For quantification of hepatic [(18)F]FDG uptake, the dual blood supply to the liver must be considered. In contrast to the arterial input, however, the portal venous blood supply to the liver cannot be monitored directly by PET because of the inaccessibility of the portal vein on PET scans. In this study, we investigated whether the dual hepatic input can be predicted from the measurable arterial input. Moreover, we assessed the effect of different input models on the rate constants of the standard 3-compartment model describing regional uptake of FDG. METHODS: Dynamic FDG PET scanning was performed on 5 foxhounds. Activity concentrations in blood from the aorta and the portal vein were measured simultaneously using external circuits. After image reconstruction, time--activity courses were determined from the aorta and the liver. The venous input was approximated by convolving the arterial input with a notional system function describing the dispersion of the arterial input on its way through the gastrointestinal tract. On the basis of these data, 5 different hepatic input models, which pertain to a single-input as well as a dual-input scenario, were statistically compared with regard to the adequacy of the model fits to liver data and to differences in the estimated rate constants. RESULTS: Portal venous input to the liver could be approximated by convolving the arterial input function with a system function. From this function, a mean transit time of 25 s was computed for FDG to pass through the gastrointestinal tract. According to the statistical analysis, dual-input models were superior to their single-input counterparts. However, differences in the rate constants estimated for the 5 input models were in the same order as interindividual variations within the different model groups. For the dephosphorylation rate constant, a consistent value of 0.05 +/- 0.01 min(-1) was found. CONCLUSION: Dual-input models proved to be superior to single-input models with respect to the adequacy of FDG model fits to normal liver data. However, the hepatic blood supply may be approximated by the arterial input function as well, especially for the evaluation of liver lesions mainly fed by the hepatic artery.

Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine.

Apoptosis has been described as an energy-consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynamic positron emission tomography (PET) measurements of fluorine-18 fluorodeoxyglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to and after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measurements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determined using the TUNEL reaction. In vivo an increase in FDG transport and phosphorylation occurred early after gemcitabine treatment, although TdR incorporation into the DNA of the tumours declined. In vitro, an enhanced glucose transport, an increase in TdR uptake in the cytoplasm and a decrease in TdR incorporation in the nucleic acid fraction early after treatment occurred. Inhibition of glucose transport caused an increase in the amount of apoptotic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytotoxic drugs like gemcitabine.

A novel method for real-time magnetic marker monitoring in the gastrointestinal tract.

In internal medicine, a simple method for the functional examination of the gastrointestinal tract without the risk of radiation exposure is required. We describe a novel principle based on the monitoring of magnetic markers which meets these demands. Our method employs a special permanent magnet which is repeatedly aligned by a vertically oriented pulsed magnetic field. Due to this alignment, the marker position can be derived from the stray field components measured by commercial field sensors. Our method was evaluated by means of a 3D intestinal phantom. The monitoring procedure yielded the time course of the marker position as a 3D plot either in real-time or as a time-lapse movie. The spatial resolution, expressed by the mean square deviation, was better than 10 mm and is thus sufficiently high to distinguish between adjacent loops of the gut. The temporal resolution, i.e. the minimum time between two successive measurements, was about 1 s. The presented method has very moderate technical demands and allows us to monitor magnetic markers in real-time. The technique may be useful with respect to functional examination of the gastrointestinal tract. In pharmaceutical research, our method offers the opportunity for remote drug release at any position of the gut.

Biochemical modulation of the catabolism and tissue uptake of the anticancer drug 5-fluorouracil by 5-bromovinyluracil: assessment with metabolic (19)F MR imaging.

Using chemical shift-selective (19)F magnetic resonance (MR) imaging, we investigated the biomodulating action of 5-bromovinyluracil (BVU) on the degradation of the anticancer drug 5-fluorouracil (5-FU) to its major catabolite alpha-fluoro-beta-alanine (FBAL) and the tissue uptake of 5-FU in ACI rats with transplanted Morris hepatoma. Rats in the control group (n = 7) received 200 mg/kg body weight of 5-FU intravenously, whereas the rats in the BVU group (n = 7) additionally received 30 mg/kg body weight of BVU intraperitoneally about 45 min before 5-FU injection. In each animal examination, three selective (19)F MR images were acquired sequentially after 5-FU administration with an acquisition time of 32 min each: an early 5-FU image (dominant Fourier line, 8 min p.i.) that characterized the early uptake of the drug into the various tissues, an FBAL image (dominant Fourier line, 56 min p.i.) that reflected the catabolism of the drug, and a late 5-FU image (dominant Fourier line, 78 min p.i.) that assessed the retention ("trapping") of unmetabolized 5-FU and its MR-visible anabolites. Pretreatment with BVU resulted in a highly statistical significant decrease (P < 0.001) of the FBAL signal in the liver. The marked effect of BVU on 5-FU degradation, however, improved neither the early uptake nor the retention of 5-FU in skeletal muscle and tumor tissue (P > 0.7). Moreover, our results indicate that 5-FU tumor uptake is not only dependent on the plasma concentration of unmetabolized 5-FU but is also determined by tumor-specific factors, these showing considerable variations between individual neoplasms. Magn Reson Med 42:936-943, 1999.

Subsets and overrelaxation in iterative image reconstruction.

A number of iterative image reconstruction algorithms were integrated into one formula characterizing each algorithm by only two parameters: overrelaxation and number of subsets. From the formula it follows that the ordered-subsets iteration (OS-EM) is equivalent to iteration with overrelaxation, where the OS level corresponds to the overrelaxation parameter. Algorithms represented by the formula were studied with respect to speed of convergence and image characteristics. In particular, OS-EM was compared with a single-projection iteration procedure using an optimized sequence of overrelaxation parameters (HOSP) which combines rapid convergence with reduced storage requirements. As a result, OS-EM with a constant number of subsets either needed more iteration steps than HOSP or provoked additional noise, depending on the number of subsets used during iteration. OS-EM can be improved by using decreasing OS levels, imitating the decreasing overrelaxation parameters used for HOSP. The resulting OS-EM may be slightly more rapid than HOSP, due to the increasing number of projections used simultaneously.