Subchondral fluid dynamics in a model of osteoarthritis: use of dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: The hypothesis of this study is that changes in fluid dynamics in subchondral bone bear a functional relationship to bone remodeling and cartilage breakdown in osteoarthritis (OA). We have utilized dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to extract kinetic parameters of bone perfusion at various stages in the development of OA in the Dunkin-Hartley guinea pig. DESIGN: Animals of four different ages (6, 9, 12 and 15 months), representing various stages in the development of OA, were studied. All animals underwent DCE MRI and perfusion data were analyzed based on the Brix two-compartment pharmacokinetic model. Regions of interest were studied at the medial and lateral tibial plateaus and compared to histological-histochemical scores of articular cartilage and subchondral bone plate thickness. RESULTS: A decrease in perfusion as well as outflow obstruction was observed in animals between 6 and 9 months of age, only in the medial tibial plateau subchondral bone. The eventual cartilage and bone lesions of OA occurred also in the medial tibia. Changes in perfusion occurred in the lateral tibia but not until OA lesions were established. Kinetic parameters of inflow were unchanged in both the medial and lateral plateaus. CONCLUSIONS: DCE MRI can be used to extract kinetic information on bone perfusion in an animal model of OA. The signal enhancement in subchondral bone temporally precedes and spatially localizes at the same site of the eventual bone and cartilage lesions. Time-intensity curves suggest outflow obstruction as an underlying mechanism.

Assessing disease severity in late infantile neuronal ceroid lipofuscinosis using quantitative MR diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity. MATERIALS AND METHODS: This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL. RESULTS: ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R2=0.71) and disease duration (R2=0.68), whereas the correlation with the central nervous system disability scale (R2=0.27) was much weaker. CONCLUSION: This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.

Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors.

Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.

In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation.

Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

Changes in radiation sensitization induced by Fluosol-DA as measured by 31P nuclear magnetic resonance spectroscopy.

Numerous agents have been studied in attempts to sensitize radioresistant hypoxic tumor cells. We have investigated the effect of Fluosol-DA plus carbogen (95% oxygen and 5% CO2) on the sensitivity of a radioresistant mammary carcinoma in C3H/He mice and also on tumor metabolism by 31P nuclear magnetic resonance spectroscopy. Statistically significant increases in phosphocreatine/Pi were noted for small- (150-350 mm3) and medium- (351-650 mm3) sized tumors treated with Fluosol-DA plus carbogen. Small tumors were shown to undergo significant radiosensitization in the presence of Fluosol-DA plus carbogen and medium-sized tumors showed a lesser degree of radiosensitization. Large tumors (greater than 900 mm3) showed no effect. Fluosol-DA or carbogen alone had no effects on animals with any tumor volume, as monitored by significant changes in radiosensitivity or nuclear magnetic resonance parameters. An approximately linear relationship was found between the decrease in the values for radiation dose which yields 50% tumor control and the increase in phosphocreatine/Pi, with a correlation of r = -0.93. 31P nuclear magnetic resonance spectroscopy may be useful for monitoring changes in radiosensitivity induced by agents which alter tumor oxygenation and subsequent metabolic status.

Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo.

The feasibility of noninvasive imaging of adenoviral-mediated herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression was assessed in a well-studied animal model of metastatic colon carcinoma of the liver. Tumors were produced in syngeneic BALB/c mice by intrahepatic injection of colon carcinoma cells (MCA-26). Seven days later, three different doses (3 x 10(8), 1 x 10(8), and 3 x 10(7) plaque-forming units (pfu) of the recombinant adenoviral vector ADV. Rous sarcoma virus (RSV)-tk bearing the HSV1-tk gene were administered by intratumoral injection in separate groups of mice. Two control groups of tumor-bearing mice received intratumoral injections of the control adenoviral vector dl-312 or buffer alone, respectively. T2-weighted magnetic resonance (MR) images of mice were obtained before administering the virus and provided an anatomical reference of hepatic tumor localization. Eighteen h after the virus injection, one group of animals was given i.v. injections of 300 microCi of no-carrier-added 5-[131I]-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera. In some animals, the tumors were sampled and processed for histology and quantitative autoradiography (QAR). The gamma camera images demonstrated highly specific localization of [131I]FIAU-derived radioactivity to the area of ADV.RSV-tk-injected tumors in the liver, which was confirmed by coregistering the gamma camera and T2-weighted MR images. There was no accumulation of [131I]FIAU-derived radioactivity in tumors that were injected with the control vector or injection solution alone. A more precise distribution of radioactivity in the area of transfected tumor was obtained by histological and QAR comparisons. A heterogeneous pattern of radioactivity distribution in transfected tumors was observed. A punctate pattern of radioactivity distribution was observed in peritumoral liver tissue in animals given injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals given injections of 3 x 10(7) pfu nor in control animals. A QAR-microscopic comparison showed that the punctate areas of radioactivity colocalized with cholangial ducts. The level of [131I]FIAU-derived radioactivity accumulation (HSV1-tk expression) in the transfected tumors was viral dose-dependent. The viral dose-dependency of radioactivity accumulation was more pronounced in peritumoral liver, which was confirmed by reverse transcription-PCR analysis. A separate group of tumor-bearing animals received different doses of ADV.RSV-tk vector followed by treatment with ganciclovir (GCV), 10 mg/kg i.p. b.i.d. for 6 days. The ADV.RSV-tk transfected tumors significantly regressed with GCV treatment; the control tumors continued to grow. During the GCV treatment, the levels of liver transaminases (ALT and AST) were significantly increased in animals that received injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals that received injections of 3 x 10(7) pfu and in control animals. The observed liver toxicity confirms the results of gamma camera and QAR imaging, which demonstrated an unwanted spread of ADV.RSV-tk vector and HSV1-tk expression in peritumoral and remote liver tissue at higher doses. These and our previous results indicate that noninvasive imaging of adenoviral-mediated HSV1-tk gene expression is feasible for monitoring cancer gene therapy in patients.

Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

BACKGROUND AND PURPOSE: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation. MATERIALS AND METHODS: Coronal MR imaging was performed on mice treated with mannitol (n = 6) for disruption of the BBB and controls treated with saline (n = 5). Permeability surface-area product was determined by ROI placement and was compared between saline- and mannitol-treated mice. Correlation was made with contrast-enhancement measurements and immunohistologic-stained sections of tripeptidyl peptidase-1 distribution in mice treated with mannitol and saline followed by injection of a viral vector containing the CLN2 gene, which directs production of tripeptidyl peptidase-1. RESULTS: Significantly increased permeability surface-area product was seen in mannitol- compared with saline-treated mice in the whole brain (P = .008), MCA territory (P = .014), and mixed vascular territories (P = .008). These findings were compared with contrast-enhancement measurements of BBB permeability and were correlated with immunohistologic-stained sections demonstrating BBB permeability to a large vector. CONCLUSIONS: Permeability surface-area product is increased in situations with known disruptions of the BBB, as evidenced by immunologic staining of large-vector passage through the BBB and concordance with contrast-enhancement measurements in a murine model. Quantitative permeability surface-area product has potential as an imaging marker of BBB permeability.

Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease).

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.

The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow.

Pretreatment of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1 enhances the cytotoxicity of most chemotherapeutic agents. However, in the case of paclitaxel, this effect has been shown in vitro to be best achieved when bryostatin-1 follows (rather than precedes) paclitaxel treatment. With combination trials of bryostatin-1 and paclitaxel planned for clinical trials and with only in vitro data available regarding drug sequence, we elected to undertake an in vivo study evaluating the effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing mouse model and to correlate this effect to cell cycle events, tumor metabolism, and tumor blood flow. At the maximum tolerated i.p. dose, bryostatin-1 at 80 microg/kg resulted in a small but significant increase in tumor doubling time (4.2 +/- 0.3 days) compared with control tumors (3.0 +/- 0.3 days; P < 0.01). Mice treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every 12 h for three doses, weekly for 3 weeks, had a tumor doubling time of 23.4 +/- 1.7 days. Mice pretreated with i.p. bryostatin-1 (80 microg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg every 12h for three doses) weekly for 3 weeks had a tumor doubling time of 9.7 +/- 1.1 days. This was significantly less (P < .001) than paclitaxel alone, which indicated an inhibitory effect by bryostatin-1 on paclitaxel therapy. In comparison, tumor-bearing mice that were treated with the same dose but with the sequence of paclitaxel followed by bryostatin-1 had a tumor doubling time of 29.6 +/- 0.6 days. This was significantly greater than the tumor doubling times for any condition tested (P < 0.01), demonstrating the sequence dependence of this combination. The efficacy of paclitaxel is dependent on mitotic entry, a step that requires activation of p34cdc2 kinase activity. Treatment with paclitaxel in vivo increased p34 cdc2 kinase activity in the mouse mammary tumors, whereas administration of bryostatin-1 before paclitaxel prevented the p34cdc2 kinase activation by paclitaxel. This was further evaluated in vitro by flow cytometry in MKN-74 human gastric cancer cells. As determined by MPM-2 labeling, which identifies cells in mitosis, pretreatment with bryostatin-1 prevented paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been reported to induce changes in muscle metabolism and to decrease muscle blood flow. These events could impact on the interaction of bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy in vivo, bryostatin-1 at 80 micro1g/kg induced a decrease in both intratumoral pH and high-energy phosphates. In vivo perfusion studies, using dynamic enhanced NMR imaging with gadolinium diethylenetriamine pentaacetic acid, also demonstrated decreased tumor blood flow. These studies suggest that the inhibition of tumor response to paclitaxel by bryostatin-1 is multifactorial and includes such diverse factors as inhibition of cell entry into mitosis, a decrease in pH and energy metabolism, and a decrease in tumor blood flow. These results indicate that, as this combination enters Phase I clinical trials, the sequence of paclitaxel followed by bryostatin-1 will be critical in the clinical trial design.

Developments in nuclear magnetic resonance imaging and spectroscopy: application to radiation oncology.

Nuclear magnetic resonance techniques have advanced to the point where functional, physiologic, and biochemical information may be obtained from patients. Magnetic resonance imaging of tissue water can be used to measure perfusion and diffusion with submillimeter resolution. Magnetic resonance spectroscopy may be applied to the assessment of tissue metabolites that contain protons, phosphorus, fluorine, or other nuclei. The combination of imaging and spectroscopy technologies has lead to spectroscopic imaging techniques that are capable of mapping proton metabolites at resolutions as small as 0.25 cm(3) within the time constraints of a clinical imaging study. This article provides a brief review of magnetic resonance techniques for imaging of tissue physiological function and addresses possible applications in the realm of radiation oncology.

Iododeoxyuridine uptake and retention as a measure of tumor growth.

Iodine-131-iododeoxyuridine (IUdR) uptake and retention was measured in two C6 glioma cell lines (C6m and C6a) with different growth characteristics. Animals with intracerebral (i.c.) C6a tumors had a mean survival of 16 days, whereas only 1 of 20 animals with i.c. C6m tumors died during an 8-wk period of observation. The growth of i.c. C6m tumors could be described by the Gompertz equation; tumor doubling time increased from 1.9 to 5.2 days between Days 8 and 16 after tumor inoculation. Corresponding measurements of 131I-IUdR uptake and retention (24 hr after IUdR administration) by i.c. C6m tumors were also time-dependent and decreased from 0.075 to 0.027 to 0.011 %dose/g in 8-, 10- and 16-day-old tumors, respectively. Iodine-131-IUdR uptake in "rapidly growing" i.c. C6a tumors was substantially higher (0.30 %dose/g at 24 hr) than that in "slowly growing" i.c. C6m tumors and corresponded with differences in the survival data. Subcutaneous C6a tumors had comparable high uptake values (0.49 %dose/g at 24 hr), and 93% of total tumor radioactivity was recovered in DNA 24 hr after IUdR administration. Clearance of radioactivity was rapid in nonproliferative tissues; more than 80% of plasma radioactivity was cleared in 24 hr. Tumor-to-cortex radioactivity ratios ranged from 100/1 to 120/1 and 150/1 between 24, 48 and 96 hr after IUdR injection respectively. A "washout strategy," which reduces tissue background activity and increases specificity for PET and SPECT imaging of IUdR-DNA incorporation, is possible with longer-lived radioisotopes of iodine.

Monte Carlo simulation of a cobalt-60 beam.

We have used the Stanford Electron Gamma Shower (EGS) Monte Carlo code to compute photon spectra from an AECL Theratron 780 cobalt-60 unit. Particular attention has been paid to the careful modeling of the geometry and material construction of the cobalt-60 source capsule, source housing, and collimator assembly. From our simulation, we conclude that the observed increase in output of the machine with increasing field size is caused by scattered photons from the primary definer and the adjustable collimator. We have also used the generated photon spectra as input to a pencil beam model to calculate the tissue-air ratios in water and compared it to a model which uses a monochromatic photon energy of 1.25 MeV.

The effect of angular spread on the intensity distribution of arbitrarily shaped electron beams.

Knowledge of the relative intensity distribution at the patient's surface is essential for pencil beam calculations of three-dimensional dose distributions for arbitrarily shaped electron beams. To calculate the relative intensity distribution, the spatial spread resulting from angular spread is convolved with a two-dimensional step function whose shape corresponds to the applicator aperture. Two different approaches to obtain angular spread or the equivalent spatial spread are investigated. In the first method, the pencil beam angular spread is assumed to be Gaussian in shape. The angular spread constants (sigma theta) are then obtained from the slopes of measured intensity profiles. In the second method, the angular spread, in the form of an array of numerical values, is obtained by the deconvolution of measured intensity profiles. After obtaining the angular spread, the calculation for convolution is done in a number of parallel planes normal to the central axis at various distances from the electron collimator. Intensity at any arbitrary point in space is computed by interpolating between intensity distributions in adjacent planes on either side of the point. The effects of variations in angular spread as a function of field size for two treatment machines, one with a scanned electron beam and the other with a scattering foil, have been studied. The consequences of assuming angular spread to be of Gaussian shape are also examined. The electron intensity calculation techniques described in this paper apply primarily to methods of dose calculations that employ pencil beams generated using Monte Carlo simulations.

Spatial mapping of the percentage cellularity in human bone marrow using magnetic resonance imaging.

A noninvasive assay for the spatial distribution of the percentage cellularity in human bone marrow is presented. Twelve individuals were studied using two magnetic resonance imaging techniques: (1) fast spin echo imaging with frequency selective presaturation, and (2) three-point chemical shift imaging. The data were compared to results obtained using a previously validated stimulated echo spectroscopic method. The results of this study demonstrate that a measure of the percentage cellularity in bone marrow is possible using magnetic resonance imaging techniques provided that high-quality water or lipid suppression is achieved across the region of interest. Since the method is applicable to bone marrow at any anatomic location, it may prove useful in dosimetric calculations during and after a course of internal or external beam radiotherapy.

An automated iterative algorithm for water and fat decomposition in three-point Dixon magnetic resonance imaging.

An iterative, outlier exclusion, second-order surface fitting algorithm has been developed to solve the well-known phase wraparound problem associated with in vivo applications of the three-point Dixon magnetic resonance imaging method. The technique was optimized for speed by reducing the problem to a pair of planar fits. The spatial misalignment between water and fat components due to the chemical shift was handled on a subpixel level by invoking the shift theorem of Fourier transformation. From the chemical shift corrected water and fat images, high quality recombined MR images were generated. The algorithm was validated in both phantom and patient studies. In vivo breast images and pelvic images are provided as a demonstration of the method.

A stereotactic method for the three-dimensional registration of multi-modality biologic images in animals: NMR, PET, histology, and autoradiography.

The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.

Nuclear magnetic resonance: principles and applications to pathology.

Nuclear magnetic resonance is a valuable tool in the analytical chemistry laboratory. Recent technological advances have increased its sensitivity so that it can be used to detect millimolar and submillimolar quantities. It can be used to analyze body fluids for different metabolites and drugs. The technique is not destructive; therefore, it can be used as an initial screening tool, which can guide the subsequent selection of more sensitive analytical techniques for more definitive quantitation.

An analysis of the intrinsic resonance offset dependence of magnetization generated by stimulated echo pulse sequences for noncoupled spins.

It is demonstrated that the basic radiofrequency pulse train used to generate stimulated echoes (90x-tau TE-90x-tau TM-90x-tau TE-Acq.) is in general characterized by strong amplitude and phase modulations of the transverse magnetization as a function of the resonance offset. Two dephasing techniques which eliminate the modulations are investigated both theoretically and experimentally, and a simple formula is derived for calculating the relative modulation across a spectrum as a function of gradient strength and duration, echo delay, and spectral linewidth.

Doubly tuned solenoidal resonators for small animal imaging and spectroscopy at 1.5 Tesla.

The design and construction of solenoidal resonators for use with small animals in a 1.5-Tesla clinical imaging system are described. The coils have been designed to exploit the B1 distributions of two resonant modes of a four-turn solenoid whose windings are in parallel. Both singly and doubly tuned versions have been constructed. 1H images of normal and pathologic anatomy in mice and rats as well as a 31P spectrum of a Walker 256 rat sarcoma are presented. A primary advantage of this design is that the coils are easy to build and implement while providing the necessary sensitivity to allow high quality images to be obtained with no changes to the hardware or software of the clinical unit.

A birdcage resonator for intracavitary MR imaging.

An intracavitary probe for magnetic resonance imaging of the pelvis has been developed that takes advantage of the "inside-out" spatial characteristics of a birdcage resonator. The probe consists of an eight-leg, birdcage resonator in a low-pass configuration operating in receive-only mode. The resonator circuit is mounted on a solid rod, is encased in Teflon, and has been used to obtain detailed images of pelvic anatomy in a male canine. The approximate cylindrical symmetry of the external sensitivity profile of this type of circuit, employed in an intracavitary application, demonstrates the potential superiority of this type of probe design over single-loop intracavitary coils. Axial, coronal, and sagittal MR images, obtained with 8 and 16 cm fields of view, are presented to illustrate the advantages of this type of intracavitary probe compared with conventional body-coil images. The prototype described in this report has been designed for clinical use in human subjects and is currently undergoing testing to determine its efficacy in the evaluation of rectal, prostate, and gynecologic pathology.