Raymond R. Raylman

Acute effects of dobutamine on myocardial oxygen consumption and cardiac efficiency measured using carbon-11 acetate kinetics in patients with dilated cardiomyopathy☆

OBJECTIVES The aim of this study was to use positron emission tomography (PET)-derived carbon (C)-11 acetate kinetics to determine the effects of dobutamine on oxidative metabolism and its effects on myocardial efficiency in a group of patients with dilated cardiomyopathy. BACKGROUND Dobutamine is known to improve myocardial function but may do so at the expense of myocardial oxygen consumption, which could be a potential deleterious effect. Carbon-11 acetate kinetics correlate with myocardial oxygen consumption as shown in animal models. Combining these scintigraphic measurements of oxygen consumption with estimates of cardiac work results in a work-metabolic index, which reflects cardiac efficiency. METHODS Eight patients with nonischemic dilated cardiomyopathy underwent dynamic PET imaging, echocardiography and hemodynamic measurements. Seven of these patients were also studied while receiving dobutamine. Direct measurements of myocardial oxygen consumption using coronary sinus catheterization were obtained with eight of the PET studies to validate C-11 acetate in patients with cardiomyopathy. RESULTS The mean (+/- SD) C-11 clearance rate significantly increased with dobutamine from 0.105 +/- 0.027 to 0.155 +/- 0.023 min-1 (p = 0.001). Directly measured myocardial oxygen consumption had a linear relation to the mean C-11 clearance rate (r = 0.8, p = 0.018). Dobutamine was noted to significantly reduce systemic vascular resistance as well as the severity of mitral regurgitation. The work-metabolic index determined using hemodynamic variables and PET data increased from 2 +/- 0.7 x 10(4) to 2.6 +/- 0.6 x 10(4) (p = 0.04). Efficiency, estimated by employing the oxygen consumption to k2 relation, also increased from 13 +/- 4.5% to 16.9 +/- 6.4% (p = 0.04). CONCLUSIONS Despite an increase in myocardial oxygen consumption, dobutamine led to an increase in work-metabolic index in patients with dilated nonischemic cardiomyopathy. Dobutamine reduced systemic vascular resistance and mitral regurgitation, suggesting that in this group of patients, it had important vasodilatory action in addition to its inotropic effects. The use of the C-11 acetate PET for determining myocardial oxygen consumption and estimating efficiency could potentially complement existing clinical measures of ventricular performance and may allow improved and objective evaluation of therapy in patients with heart failure.

The positron emission mammography/tomography breast imaging and biopsy system (PEM/PET): design, construction and phantom-based measurements

Tomographic breast imaging techniques can potentially improve detection and diagnosis of cancer in women with radiodense and/or fibrocystic breasts. We have developed a high-resolution positron emission mammography/tomography imaging and biopsy device (called PEM/PET) to detect and guide the biopsy of suspicious breast lesions. PET images are acquired to detect suspicious focal uptake of the radiotracer and guide biopsy of the area. Limited-angle PEM images could then be used to verify the biopsy needle position prior to tissue sampling. The PEM/PET scanner consists of two sets of rotating planar detector heads. Each detector consists of a 4 x 3 array of Hamamatsu H8500 flat panel position sensitive photomultipliers (PSPMTs) coupled to a 96 x 72 array of 2 x 2 x 15 mm(3) LYSO detector elements (pitch = 2.1 mm). Image reconstruction is performed with a three-dimensional, ordered set expectation maximization (OSEM) algorithm parallelized to run on a multi-processor computer system. The reconstructed field of view (FOV) is 15 x 15 x 15 cm(3). Initial phantom-based testing of the device is focusing upon its PET imaging capabilities. Specifically, spatial resolution and detection sensitivity were assessed. The results from these measurements yielded a spatial resolution at the center of the FOV of 2.01 +/- 0.09 mm (radial), 2.04 +/- 0.08 mm (tangential) and 1.84 +/- 0.07 mm (axial). At a radius of 7 cm from the center of the scanner, the results were 2.11 +/- 0.08 mm (radial), 2.16 +/- 0.07 mm (tangential) and 1.87 +/- 0.08 mm (axial). Maximum system detection sensitivity of the scanner is 488.9 kcps microCi(-1) ml(-1) (6.88%). These promising findings indicate that PEM/PET may be an effective system for the detection and diagnosis of breast cancer.

Exposure to Strong Static Magnetic Field Slows the Growth of Human Cancer Cells In Vitro

Proposals to enhance the amount of radiation dose delivered to small tumors with radioimmunotherapy by constraining emitted electrons with very strong homogeneous static magnetic fields has renewed interest in the cellular effects of prolonged exposures to such fields. Past investigations have not studied the effects on tumor cell growth of lengthy exposures to very high magnetic fields. Three malignant human cell lines, HTB 63 (melanoma), HTB 77 IP3 (ovarian carcinoma), and CCL 86 (lymphoma: Raji cells), were exposed to a 7 Tesla uniform static magnetic field for 64 hours. Following exposure, the number of viable cells in each group was determined. In addition, multicycle flow cytometry was performed on all cell lines, and pulsed-field electrophoresis was performed solely on Raji cells to investigate changes in cell cycle patterns and the possibility of DNA fragmentation induced by the magnetic field. A 64 h exposure to the magnetic field produced a reduction in viable cell number in each of the three cell lines. Reductions of 19.04 +/- 7.32%, 22.06 +/- 6.19%, and 40.68 +/- 8.31% were measured for the melanoma, ovarian carcinoma, and lymphoma cell lines, respectively, vs. control groups not exposed to the magnetic field. Multicycle flow cytometry revealed that the cell cycle was largely unaltered. Pulsed-field electrophoresis analysis revealed no increase in DNA breaks related to magnetic field exposure. In conclusion, prolonged exposure to a very strong magnetic field appeared to inhibit the growth of three human tumor cell lines in vitro. The mechanism underlying this effect has not, as yet, been identified, although alteration of cell growth cycle and gross fragmentation of DNA have been excluded as possible contributory factors. Future investigations of this phenomenon may have a significant impact on the future understanding and treatment of cancer.

Simultaneous MRI and PET imaging of a rat brain.

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Combined MRI-PET scanner: a Monte Carlo evaluation of the improvements in PET resolution due to the effects of a static homogeneous magnetic field

Positron emission tomography (PET) relies upon the detection of photons resulting from the annihilation of positrons emitted by a radiopharmaceutical. The combination of images obtained with PET and magnetic resonance imaging (MRI) have begun to greatly enhance the study of many physiological processes. A combined MRI-PET scanner could alleviate much of the spatial and temporal coregistration difficulties currently encountered in utilizing images from these complementary imaging modalities. In addition, the resolution of the PET scanner could be improved by the effects of the magnetic field. In this computer study, the utilization of a strong static homogeneous magnetic field to increase PET resolution by reducing the effects of positron range and photon noncollinearity was investigated, The results reveal that significant enhancement of resolution can be attained, For example, an approximately 27% increase in resolution is predicted for a PET scanner incorporating a 10-Tesla magnetic field. Most of this gain in resolution is due to magnetic confinement of the emitted positrons. Although the magnetic field does mix some positronium states resulting in slightly less photon noncollinearity, this reduction does not significantly affect resolution. Photon noncollinearity remains as the fundamental limiting factor of large PET scanner resolution.

Positron emission mammography with tomographic acquisition using dual planar detectors: initial evaluations

Positron emission mammography (PEM) with tomographic acquisition using dual planar detectors rotating about the breast can obtain complete angular sampling and has the potential to improve activity estimation compared with PEM using stationary detectors. PEM tomography (PEMT) was compared with stationary PEM for point source and compressed breast phantom studies performed with a compact dual detector system. The acquisition geometries were appropriate for the target application of PEM guidance of stereotactic core biopsy. Images were reconstructed with a three-dimensional iterative maximum likelihood expectation maximization algorithm. PEMT eliminated blurring normal to the detectors seen with stationary PEM. Depth of interaction effects distorted the shape of the point spread functions for PEMT as the angular range from normal incidence of lines of response used in image reconstruction increased. Streak artefacts in PEMT for large detector rotation increments led to the development of an expression for the maximum rotation increment that maintains complete angular sampling. Studies with a compressed breast phantom were used to investigate contrast and signal-to-noise ratio (SNR) trade-offs for different sized spherical tumour models. PEMT and PEM both had advantages depending on lesion size and detector separation. The most appropriate acquisition method for specific detection or quantitation tasks requires additional investigation.

Investigation of muscle lipid metabolism by localized one- and two-dimensional MRS techniques using a clinical 3T MRI/MRS scanner

To demonstrate the feasibility of estimating the relative intra‐ and extramyocellular lipid (IMCL and EMCL) pool magnitudes and calculating the degree of lipid unsaturation within soleus muscle using single‐voxel localized one‐ and two‐dimensional (1D and 2D) MR spectroscopy (MRS).

Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans

The link between body weight, lipid metabolism, and health risks is poorly understood and difficult to study. Magnetic resonance spectroscopy (MRS) permits noninvasive investigation of lipid metabolism. We extended existing two-dimensional MRS techniques to permit quantification of intra- and extramyocellular lipid (IMCL and EMCL, respectively) compartments and their degree of unsaturation in human subjects and correlated these results with body mass index (BMI). Using muscle creatine for normalization, we observed a statistically significant (P < 0.01) increase in the IMCL-to-creatine ratio with BMI (n = 8 subjects per group): 5.9 +/- 1.7 at BMI < 25, 10.9 +/- 1.82 at 25 < BMI < 30, and 13.1 +/- 0.87 at BMI > 30. Similarly, the degree of IMCL unsaturation decreased significantly (P < 0.01) with BMI: 1.51 +/- 0.08 at BMI < 25, 1.30 +/- 0.11 at 25 < BMI < 30, and 0.90 +/- 0.14 at BMI > 30. We conclude that important aspects of lipid metabolism can be evaluated by two-dimensional MRS and propose that degree of unsaturation measured noninvasively may serve as a biomarker for lipid metabolic defects associated with obesity.

Evaluation of ion‐implanted‐silicon detectors for use in intraoperative positron‐sensitive probes

The continuing development of probes for use with beta (positron and electron) emitting radionuclides may result in more complete excision of tracer-avid tumors. Perhaps one of the most promising radiopharmaceuticals for this task is 18F-labeled-Fluoro-2-Deoxy-D-Glucose (FDG). This positron-emitting agent has been demonstrated to be avidly and rapidly absorbed by many human cancers. We have investigated the use of ion-implanted-silicon detectors in intraoperative positron-sensitive surgical probes for use with FDG. These detectors possess very high positron detection efficiency, while the efficiency for 511 keV photon detection is low. The spatial resolution, as well as positron and annihilation photon detection sensitivity, of an ion-implanted-silicon detector used with 18F was measured at several energy thresholds. In addition, the ability of the device to detect the presence of relatively small amounts of FDG during surgery was evaluated by simulating a surgical field in which some tumor was left intact following lesion excision. The performance of the ion-implanted-silicon detector was compared to the operating characteristics of a positron-sensitive surgical probe which utilizes plastic scintillator. In all areas of performance the ion-implanted-silicon detector proved superior to the plastic scintillator-based probe. At an energy threshold of 14 keV positron sensitivity measured for the ion-implanted-silicon detector was 101.3 cps/kBq, photon sensitivity was 7.4 cps/kBq. In addition, spatial resolution was found to be relatively unaffected by the presence of distant sources of annihilation photon flux. Finally, the detector was demonstrated to be able to localize small amounts of FDG in a simulated tumor bed; indicating that this device has promise as a probe to aid in FDG-guided surgery.

Investigation of breast cancer using two-dimensional MRS

Proton (1H) MRS enables non‐invasive biochemical assay with the potential to characterize malignant, benign and healthy breast tissues. In vitro studies using perchloric acid extracts and ex vivo magic angle spinning spectroscopy of intact biopsy tissues have been used to identify detectable metabolic alterations in breast cancer. The challenges of 1H MRS in vivo include low sensitivity and significant overlap of resonances due to limited chemical shift dispersion and significant inhomogeneous broadening at most clinical magnetic field strengths. Improvement in spectral resolution can be achieved in vivo and in vitro by recording the MR spectra spread over more than one dimension, thus facilitating unambiguous assignment of metabolite and lipid resonances in breast cancer. This article reviews the recent progress with two‐dimensional MRS of breast cancer in vitro, ex vivo and in vivo. The discussion includes unambiguous detection of saturated and unsaturated fatty acids, as well as choline‐containing groups such as free choline, phosphocholine, glycerophosphocholine and ethanolamines using two‐dimensional MRS. In addition, characterization of invasive ductal carcinomas and healthy fatty/glandular breast tissues non‐invasively using the classification and regression tree (CART) analysis of two‐dimensional MRS data is reviewed. Copyright