Correlation of cocarcinogenic activity among n-alkanes with their physical effects on phospholipid micelles.

N-alkanes from C12 to C28 were tested for their cocarcinogenic or promoting activities to evaluate a correlation of their biologic activity with their effects on transport properties of phospholipid micelles. On this basis, we had predicted that the C18 and C20 homologues would be more active than the better known dodecane. The C12, C16, C18, and C20 n-alkanes, at various dilutions from 6 to 40% by volume in decahydronaphthalene (Decalin), were tested for their relative activity in a cocarcinogenic relationship to benzo[a]pyrene. At a 20% alkane concentration level, the solutions containing octadecane and eicosane induced tumors most rapidly. A 40% dodecane concentration was required to produce this level of cocarcinogenic activity. The activity of octadecane paralleled its physical effects on transport kinetics closely in the 6-40% (by volume) concentration. The C18, C20, and C28 n-alkanes and the C30 olefin squalene at dilutions from 10 to 40% in Decalin (by volume) were tested for their relative promoting activity after a single application of 7,12-dimethylbenz[a]anthracene in benzene. At comparable mole fractions in Decalin, the three n-alkanes had essentially the same promoting activity; squalene, at 20%, showed only borderline activity. Thus the high biologic activity of the C18, C20, and C28 n-alkanes correlated well with their physical effects on the structure of phospholipid micelles (chain-chain interactions of the alkanes with the acyl chains of the lipid). This correlation was interpreted as a strong indication that the liquid crystalline region of the phospholipid assembly (adjacent to the aqueous interface) in the membranes of latent (initiated) cancer cells was the site of action of hydrocarbon cocarcinogens. Application of a modified physical model to pristane, a branched-chain C19 alkane from coal and Colorado shale, indicated higher cocarcinogenic activity than that of n-C18H38. Applied to purified samples of docosane and tetracosane, activity comparable to that of octadecane was indicated.

Regional myocardial stress distribution from magnetic resonance image-based mathematical models.

The instantaneous regional stress distribution within the myocardium, which cannot be directly measured, has been estimated using improved numerical methods and nonaxisymmetric biventricular geometry. To do this, we have employed computer-aided solid mathematical modeling to generate a three-dimensional representation for an ex vivo canine biventricular unit using magnetic resonance imaging. A two-dimensional transverse section was isolated from the solid mathematical model for regional stress analysis using p-version finite element analysis. Loading conditions and material property descriptions were taken from published reports. Analyses showed the maximum principal stresses to range from -1.76 X 10(5) to 8.52 X 10(5) dynes/cm2 during systolic loading, and from -3.85 X 10(4) to 1.13 X 10(5) dynes/cm2 during diastolic loading. This study demonstrates that magnetic resonance image-based solid mathematical biventricular models are suitable for regional stress analysis using p-version finite element analysis. p-Version finite element analysis using magnetic resonance image-based cardiac representations facilitates in vivo stress-strain analyses and may allow the clinical estimation of regional myocardial stress.

In vivo NMR imaging of tissue sodium in the intact cat before and after acute cerebral stroke.

The first in vivo nuclear magnetic resonance (NMR) images of tissue sodium in the intact animal are presented. The distribution of sodium in the normal cat's head is described. An experimental stroke was surgically induced. Sodium NMR imaging showed a pronounced focal increase in cerebral sodium concentration 9 hr after ligation of the middle cerebral artery. The method appears to be very sensitive for early detection of infarction. The measured increase in the regional sodium NMR signal probably reflects both a true increase in concentration of brain sodium and an increased NMR visibility of the sodium nucleus in the region of the infarction.

Evaluation of a prototype dual-energy computed tomographic apparatus. I. Phantom studies.

We report the evaluation of a prototype dual-energy implementation using rapid kVp switching on a clinical computed tomographic scanner. The method employs prereconstruction basis material decomposition of the dual-energy projection data. Each dual-energy scan can be processed into conventional single-kVp images, basis material density images, and monoenergetic images. Phantom studies were carried out to qualitatively and quantitatively evaluate and validate the approach.

Improved detectability in low signal-to-noise ratio magnetic resonance images by means of a phase-corrected real reconstruction.

We show that for magnetic resonance (MR) images with signal-to-noise ratio (SNR) less than 2 it is advantageous to use a phase-corrected real reconstruction, rather than the more usual magnitude reconstruction. We discuss the results of the phase correction algorithm used to experimentally verify the result. We supplement the existing literature by presenting closed form expressions (in an MR context) for the probability distribution and first moments of the signal resulting from a magnitude reconstruction.

Oblique magnetic resonance imaging of the bronchi.

The trachea and main bronchi of a supine patient in a magnetic resonance (MR) scanner are not contained in a single standard coronal plane, but instead intersect this coronal plane at some angle, usually 20 degrees - 35 degrees. We have developed a new MR imaging protocol to determine the oblique imaging plane which best contains the trachea and main bronchi. The resulting oblique images simplify anatomical identification, and allow the user to select additional oblique planes which cut any desired portion of main bronchus in true cross section. Accurate lumen shapes and areas may then be extracted from these cross-sectional images. The method does not require the patient to be moved or rotated, and does not require hardware modification. We demonstrate the clinical application of the protocol with both a normal volunteer and a patient with an endobronchial tumor. The use of gradient echo pulse sequences together with this protocol to distinguish between vessels and bronchi is presented. We provide phantom verification to demonstrate the quantitative accuracy of the method to provide lumen areas.

Pulse sequence generated oblique magnetic resonance imaging: applications to cardiac imaging.

A pulse sequence procedure for producing oblique magnetic resonance images is described. Using this procedure we present a new, accurate method to obtain true short-axis views and true long-axis views (both parallel and perpendicular to the septal plane) of the heart. The method is accurate regardless of the orientation of patient's heart. The method does not require the patient to be rotated, nor otherwise moved, and does not require any additional hardware. The method is experimentally verified with both human and phantom studies. The phantom study indicates accuracy of approximately 1 degree with a commercial scanner that reports angular measurements to a precision of 1 degree. Application of the short-axis views to measurement of left ventricular volume, and possible advantages of Gauss-Legendre integration for this measurement are discussed. Finally, multiphase oblique cardiac images are presented.

Evaluation of a prototype dual-energy computed tomographic apparatus. II. Determination of vertebral bone mineral content.

A prototype dual-energy computed tomographic (CT) scanner (Siemens Somatom DR3) with rapid kVp switching and prereconstruction processing has been used to measure vertebral bone mineral density. With this approach misregistration and beam hardening inaccuracies can be reduced considerably. Basis material images of aluminum- and Lucite-equivalent density enable measurements of bone mineral density that are nearly independent of the amount of marrow fat. To simulate variable marrow fat, alcohol-water mixtures were used as media in calibration standards. A section of dried trabecular bone was also scanned immersed in varying alcohol-water mixtures. In both simulations it was shown that the dual-energy measurement is nearly independent of marrow composition whereas the single-energy measurement would be strongly influenced by marrow fat. Dual-energy CT was compared to dual-photon absorptiometry (153Gd) for the measurement of bone mineral mass of ten excised human vertebrae. There was a high degree of correlation between the two measurements (r = 0.97). Dual-energy and single-energy CT measurements on 17 patients with suspected metabolic bone disease strongly support the conclusion that the influence of fat can lead to significant errors in single-energy determinations of the mineral density of trabecular bone.

Clinical and experimental sodium magnetic resonance imaging.

In conclusion, sodium MR imaging has potential for providing physiologic information relevant to cell mitosis, cell energy state, rCBV, and seizures. Considerable technical and experimental development is necessary, however, before sodium MRI becomes a routine examination in the clinical setting.

Magnetic resonance imaging of gadolinium-labeled monoclonal antibody polymers directed at human T lymphocytes implanted in canine brain.

Two different murine monoclonal anti-human T cell antibodies, that were coupled to gadolinium (Gd), bind specifically to human T lymphocyte cells implanted in canine brain. This binding was at a concentration of Gd sufficient to detect the implanted cells and to distinguish them from the surrounding brain tissue with magnetic resonance imaging (MRI) at a field strength of 1.5 Tesla. These Gd-labeled immunoglobulin preparations did not bind bovine T cells at a concentration sufficient to be detected on MRI. A protein solution containing the immunoglobulins (100 micrograms), gelatin (2 mg), and bovine serum albumin (2.5 mg) was reacted with the dianhydride of diethylenetriaminepentaacetic acid (DTPA); the DTPA serves as a metal chelator and as a protein crosslinking agent. The DTPA-protein complex was reacted with Gd chloride. There were approximately 10 DTPA residues per protein molecule in the modified protein mixture. Isolated human or bovine monocytes (approximately 12 million cells) were implanted in the brains of anesthetized dogs in a volume of 40 microliters. The blood-brain barrier was then disrupted by the intra-arterial injection of hyperosmotic mannitol, and the Gd-labeled antibodies were injected through a catheter placed at the branch of the internal and external carotid arteries. The brains were imaged 48 to 72 hours later. The MRI scans revealed a markedly decreased T1 relaxation time with a high signal intensity (TE = 25 msec, TR = 200 msec) related to the human T cell implants. There was no evidence of decreased T1 at the site of the bovine T cells. Neither control murine gamma globulin coupled to Gd-DTPA nor anti-human T cell antibodies uncoupled to Gd modified the MRI contrast of the human T cells in the brain.

Mathematical modeling of the heart using magnetic resonance imaging.

A hybrid three-dimensional solid mathematical model of cardiac ventricular geometry developed using magnetic resonance (MR) images of an in vivo canine heart is discussed. The modeling techniques were validated using MR images of an ex vivo heart and direct measurements of cardiac geometry and mass properties. A spin-echo MR sequence with in-plane resolution of 1.0 mm was used to image the canine heart in eleven short-axis planes at contiguous 5-mm intervals. Contour points on the epicardial, left ventricle (LV), and right ventricle (RV) boundaries were selected manually at each slice level. A boundary representation geometric model was constructed by fitting third-order nonuniform rational B-spline surfaces through each set of surface points. Compared to the anatomic specimen (AS), volume errors of the ex vivo model were 0.3, 1.5, and 5.8% for the LV cavity, RV cavity, and total enclosed volumes, respectively. Comparison of cross-sectional areas of the AS and the model at ten levels demonstrated mean model errors of 4.1, 2.5, and 2.9% for the LV, RV, and epicardial boundaries, respectively.

Separation of spin populations with gradient echoes as an aid in pulse sequence tuning.

Tuning of nuclear magnetic resonance pulse sequences with pulsed "crusher" gradients or phase cycling serves to remove unwanted spin populations from the data acquisition window. Verification that unwanted spin population are not detected is often determined by the absence of obvious artifacts in an image. This approach is unsatisfactory in some instances because signal contamination with unwanted spin populations may not be obvious. This is a particular concern with multiple-spin echo, volume-selective, and other multiple-pulse sequences. A solution to this problem is the separation of spin populations using gradient echoes, allowing the existence of unwanted populations to be easily observed separately. Tuning of a pulse sequence is straightforward when spin populations can be independently observed.

A half-Fourier gradient echo technique for dynamic MR imaging.

Recently we developed the simultaneous dual FLASH (SDFLASH) pulse sequence that simultaneously obtains sequential images from the brain and the internal-carotid arteries in the neck with 1-sec temporal resolution using a standard MR scanner. The high temporal resolution (1 sec) of the SDFLASH technique was achieved partly by using a low number of phase-encoding views which thereby limited our in-plane spatial resolution to 6.25 x 3.12 mm pixels. To overcome this limitation we have developed a calibration technique which corrects distortions in signal intensity and object shape when using gradient echo half-Fourier spin warp imaging. Using this calibration technique, the operator can use the 41% decrease in scan time to either double the spatial or temporal resolution. We have successfully used this technique to acquire SDFLASH images of the head and neck with 1.0 sec temporal resolution and 3.12 x 1.6 mm spatial resolution.

Large angle spin-echo imaging.

A study was undertaken to assess the use of excitation flip angles greater than 90 degrees for T1 weighted spin-echo (SE) imaging with a single 180 degrees refocusing pulse and short TR values. Theoretical predictions of signal intensity for SE images with excitation pulse angles of 90-180 degrees were calculated based on the Bloch equations and then measured experimentally from MR images of MnCl2 phantoms of various concentrations. Liver signal-to-noise ratios (SNR) and liver-spleen contrast-to-noise ratios (CNR) were measured from breathhold MR images of the upper abdomen in 16 patients using 90 and 110 degrees excitation flip angles. The theoretical predictions showed significant improvements in SNR with excitation flip angles > 90 degrees, which were more pronounced at small TR values. The phantom studies showed reasonably good agreement with the theoretical predictions in correlating the excitation pulse angle with signal intensity. In the human imaging studies, the 110 degrees excitation pulse angle resulted in a 7.4% (p < .01) increase in liver SNR and an 8.2% (p = .2) increase in liver-spleen CNR compared to the 90 degrees pulse angle at TR = 275 ms. Increased signal intensity resulting from the use of large flip angle excitation pulses with a single echo SE pulse sequence was predicted and confirmed experimentally in phantoms and humans.

A fast 3D-imaging technique for performing dynamic Gd-enhanced MRI of breast lesions.

The characterization of breast lesions by their Gd-enhancement profiles has been proposed as a method for differentiating benign from malignant breast lesions. The limitations of dynamic contrast enhanced 2D imaging of the breast are the low number of slices that can be acquired, and the need to know the location of the lesion a priori to correctly select the noncontiguous 2D slice locations. These problems are exacerbated when multi-focal disease is present but not anticipated. Standard fast 3D gradient-echo imaging has a variable delay between successive acquisitions. We have developed a fast 3D gradient-echo imaging technique for dynamic Gd-DTPA enhanced breast imaging which obtains multiple 3D image sets of 32 contiguous images at 44 s intervals without an interscan delay time. This rapid 3D imaging technique achieves good temporal resolution and reduces patient motion between pre- and postcontrast images while covering a much larger portion of the breast and eliminating the need for a priori knowledge concerning the location of the lesion(s) when performing Gd-enhanced dynamic MR imaging.

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times.

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.

Dynamic sequential 3D gadolinium-enhanced MRI of the whole breast.

Dynamic contrast-enhanced 2D MR imaging of the breast has shown high sensitivity and specificity for the detection and characterization of breast lesions. We investigated the ability of a dynamic fast 3D MR imaging technique that repeatedly scans the whole breast in 44-s intervals without an interscan delay time to obtain similar sensitivity and specificity as 2D imaging. Fifty-six patients scheduled for breast biopsy were entered into the study, and 83 lesions detected by 3D dynamic scanning were biopsied. Dynamic 3D contrast-enhanced breast imaging with subtraction detected and correctly classified all 23 cancers, and 44 of the 60 benign lesions yielding a sensitivity of 100%, a specificity of 73%, and a 100% predictive negative value. The enhancement profiles of metastatic lymph nodes were similar to those of primary cancer. This technique allowed detection of multifocal and multicentric lesions and did not require a prior knowledge of lesion location. These results indicate that dynamic contrast-enhanced 3D MRI of the whole breast is a useful and economically feasible method for staging breast cancer, providing a comprehensive noninvasive method for total evaluation of the breast and axilla in patients considering breast conservation surgery or lumpectomy.

Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings.

A 55 year old female receiving gemcitabine for stage IV non-small cell carcinoma of the lung developed the clinical-radiologic syndrome of posterior reversible encephalopathy syndrome (PRES). She had clinical manifestations of headaches, increasing somnolence and tonic-clonic seizures. The fluid-attentuated inversion recovery (FLAIR) MR imaging sequence conspicuously showed bihemispheric, symmetrical cortical and subcortical white matter hyperintensities that preponderantly involved the parietal and occipital lobes. Diffusion-weighted imaging (DWI) sequence reflected the preponderant existence of vasogenic edema in the involved areas. MR spectroscopy showed no significant N-acetyl aspartate (NAA) depletion or lactate elevation prospectively, indicating the absence of significant neuronal loss and reversibility of the brain parenchymal changes. The clinical and radiologic manifestations essentially resolved completely with discontinuation of the drug.

Contrast manipulation in NMR imaging.

The past few years have shown rapid growth of NMR imaging in both image quality and diagnostic usefulness. It has become apparent, as the images have been published, that both inter- and intra-group imaging of the same underlying pathology produces images which can have vastly differing appearance. This effect is mainly due to imaging techniques which use different pulse sequence types and timings thus varying the relative contribution of the protpn density, T1, and T2 properties of the tissues. In this paper we investigate the contrast manipulation effects and methods for SNR optimization for the saturation recovery, inversion recovery, spin echo, and inversion recovery spin echo pulse sequences when applied to three clinically relevant imaging tasks.

Evaluation of two new gadolinium chelates as contrast agents for MRI.

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.