Magnetic resonance microscopy in basic studies of brain structure and function.
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Animals↗
Biomedical subjects
G A Johnson
Publications and source records attributed to G A Johnson.
Dynamics of magnetization in hyperpolarized gas MRI of the lung.
The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized 3He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution < 4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.
Animals↗
MR microimaging of the lung using volume projection encoding.
Radial acquisition (RA) techniques have been extended to produce isotropic, three-dimensional images of lung in live laboratory animals at spatial resolution down to 0.013 mm3 with a signal-to-noise ratio of 30:1. The pulse sequence and reconstruction algorithm have been adapted to allow acquisition of image matrices of up to 256(3) in less than 15 min. Scan-synchronous ventilation has been incorporated to limit breathing motion artifacts. The imaging sequence permits randomizing and/or discarding selected views to minimize the consequences of breathing motion. The signal in lung parenchyma was measured as a function of flip angle (alpha) for different repetition times and found to follow the predictions for which there is an optimum excitation (Ernst) angle. A single T1 relaxation value of 780 +/- 54 ms fits all data from six guinea pigs at 2.0 T. This T1 value parameterizes the signal and allows for a priori optimization, such as calculation of the Ernst angle appropriate for lung imaging.
Animals↗
Tumor cell endocytosis imaging facilitates delineation of the glioma-brain interface.
We describe a method for measuring tumor cell endocytosis in vivo and provide the anatomic correlate of this tumor cell function using a superparamagnetic and histologically detectable marker for cell uptake (MION). Rats (n = 22) were intrahemispherically implanted with a thymidine kinase (TK)-positive 9L gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and underwent MR imaging ex vivo at near-microscopic resolution (isotropic voxel size of 86 microm, 9.4 T) prior to histologic processing. The imaging probe accumulated within tumor cells adjacent to the hyperpermeable tumor-brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has potential research and clinical implications for delineating the tumor-brain interface prior to therapy and/or for providing a rational basis for imaging nanocolloid drug delivery to solid tumors.
Animals↗
Epidermal growth factor receptor in vulvar malignancies and its relationship to metastasis and patient survival.
OBJECTIVE: To evaluate the level of epidermal growth factor receptor (EGF-R) expression in vulvar malignancies and to determine if a correlation exists between EGF-R levels and metastasis or patient survival. METHODS: All patients with a diagnosis of invasive squamous cell carcinoma of the vulva who were treated at our institution with a primary radical vulvectomy and inguinal lymph node dissection from 1983 to 1993 were eligible for the study. Sixty-one patients with available tissue blocks of benign vulvar epithelium, the primary malignant vulvar lesion, and groin node metastasis (when positive) were included in the study. Semiquantitative EGF-R expression was determined in a blinded fashion utilizing immunohistochemical staining of appropriate tissue samples. Survival was calculated utilizing Kaplan-Meier life table analysis based upon disease-free survival. RESULTS: A significant increase (P < 0.001) in mean EGF-R levels was demonstrated in the primary tumor (67%) versus benign vulvar epithelium (31%). In the 14 patients with lymph node metastasis, the mean EGF-R level in the primary tumor was 65% versus 88% in the metastatic lesion (P < 0.001). The likelihood of lymph node metastasis was elevated in those patients with a benign tissue EGF-R level > or =40% (P < 0.03) and in those patients with a primary tumor EGF-R level > or =90% (P < 0.025). Life table analysis revealed a cumulative disease-free survival of 45% for all patients. Disease-free survival in those patients with EGF-R levels > or =90% in the primary tumor was 25%, contrasting with a disease-free survival of 54% in those patients with EGF-R levels <90% (P < 0.05). CONCLUSIONS: There is a progressive increase in EGF-R expression from benign vulvar epithelium to primary malignant tissue to metastatic lesions within the same patient. Increased expression of EGF-R in the primary vulvar malignancy is significantly associated with lymph node metastasis and decreased patient survival. Increased expression of EGF-R in histologically benign vulvar epithelium has a significant association with lymph node metastasis and may predict decreased patient survival.
Carcinoma, Squamous Cell↗
Feasibility of an immunoassay for mevalonolactone.
Mevalonic acid is a key intermediate in a broad spectrum of cellular biological processes and their regulation. Availability of a rapid, sensitive and accurate method for its assay would be highly useful. Therefore, the feasibility of developing an immunoassay for mevalonic acid in biological samples was explored. The strategy employed was to synthesize several racemic haptens structurally resembling R-mevalonolactone, the cyclic form of mevalonic acid present at lower pH and presumed to be more antigenic. Two of these haptens were coupled to keyhole limpet hemocyanin, and the resulting conjugates were used successfully to generate antibodies in rabbits. The first antiserum bound to R,S-mevalonolactone much more effectively at pH 4.0 than at pH 6.0, consistent with the structural resemblance of the haptens to the lactone form. This antiserum also bound the free hapten from which it was generated and two others of different structure with comparable effectiveness; and slightly better than it bound R,S-mevalonolactone at pH 4.0. Similar results were obtained with the antiserum to the second hapten. The binding of either antiserum to the natural enantiomer, R-mevalonolactone, was 20 times weaker than to R,S-mevalonolactone, suggesting that the nonbiological enantiomer was more antigenic. Nevertheless, the results demonstrate that an immunochemical approach to accurate quantitation of mevalonic acid in biological samples is feasible.
Animals↗
Automated feedback control of body temperature for small animal studies with MR microscopy.
A temperature control system consisting of a thermistor, signal processor, and computer algorithm was developed for magnetic resonance (MR) microscopy of small live animals. With control of body temperature within +/- 0.2 degree C of the set point, heart rate is stabilized and, in turn, repetition time (TR) during cardiac-gated studies is less variable. Thus, image quality and resolution are improved.
Animals↗
Quality control phantom for digital chest radiography.
PURPOSE: To develop and test a chest phantom for routine quality control testing of digital radiography systems. MATERIALS AND METHODS: The phantom was constructed from sheets of copper, aluminum, and acrylic, which were cut and arranged to yield a radiographic projection resembling that of a human thorax. Regional test objects allowed quantitative assessment of optical density, contrast detail, and spatial resolution. Validation tests were performed to assess image stability in a stable imaging environment and sensitivity to changes in image quality when they occur. RESULTS: The phantom yielded consistent pseudoclinical images when used in a routine quality control program and facilitated detection of simulated problems that were induced in imaging system performance. CONCLUSION: The chest phantom enables quantitative, full-system testing of digital radiography system as they are used clinically for chest radiography.
Humans↗
Transient ubiquitin cross-reactive protein gene expression in the bovine endometrium.
Bovine ubiquitin cross-reactive protein (boUCRP) is secreted by the endometrium from days 15 to 26 of pregnancy in response to conceptus-derived interferon-tau (IFN-tau). We hypothesized that the gene encoding boUCRP was under transcriptional control by the conceptus and IFN-tau. Northern blots using radiolabeled UCRP cDNA revealed a single UCRP transcript of approximately 700 b that was present (P < 0.05) in endometrial cells cultured with 25 nM rboIFN-tau. The UCRP mRNA was not detected in endometrium on days 15, 17, 18 or 19 of the estrous cycle (n = 4 cows on each day) or in spleen, kidney, liver, corpus luteum or muscle. Bovine UCRP mRNA was detectable (P < 0.05) in endometrium from pregnant cows by day 15, reached highest levels by day 17, remained elevated on days 18, 19 and 21, and then declined to amounts on day 26 that were not detectable. Northern blot using radiolabeled ubiquitin cDNA revealed presence of the two major ubiquitin transcripts UbB (1.2 Kb) and UbC (2.6 Kb) in all tissues examined. The bovine UCRP cDNA did not cross-hybridize with these ubiquitin transcripts. We conclude that transcription of the UCRP gene is transient during early pregnancy and regulated by IFN-tau.
Animals↗
Digital image-intensifier radiography at a level I trauma center.
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Humans↗
Bovine granulocyte chemotactic protein-2 is secreted by the endometrium in response to interferon-tau (IFN-tau).
Interferon-tau (IFN-tau) is secreted by the bovine conceptus and may regulate synthesis of uterine endometrial cytokines to provide an environment that is conductive to embryo development and implantation. Interferon-tau stimulates secretion of an 8-kDa uterine protein (P8) in the cow. P8 was purified, digested to yield internal peptides, and partially sequenced to determine identity. Two internal peptides had 100% (13-mer) and 92% (12-mer) amino acid sequence identity with bovine granulocyte chemotactic protein-2 (bGCP-2). Bovine GCP-2 is an alpha-chemokine that acts primarily as a potent chemoattractant for granulocyte cells of the immune system. A peptide was synthesized based on a region of bGCP-2 that overlapped with a P8 peptide amino acid sequence, coupled to keyhole limpet hemocyanin, and used to generate high titer polyclonal antiserum in sheep. Western blots revealed that bGCP-2 was not released by endometrium from day 14 nonpregnant cows, but was released in response to 25 nM IFN-tau (p<0.05). Uterine GCP-2 exhibited high affinity to heparin agarose, a characteristic shared by all alpha chemokines. This is the first report describing presence of GCP-2 in the uterine endometrium and regulation by IFN-tau. The regulation of bGCP-2 by IFN-tau may have important implications for cytokine networking in the uterus during pregnancy. Also, the regulation of inflammation and angiogenesis by bGCP-2 working together with other cytokines may be integral to establishing early pregnancy and implantation in the cow.
Amino Acid Sequence↗
T1 rho relaxation and its application to MR histology.
The application of T1 rho an an alternative contrast parameter in high-field magnetic resonance histology (MRH) has been investigated. Spectroscopic measurements of T1 rho were performed on 5.75% agar and 1.0 mM MnCI2 phantoms at 9.4 T to validate the accuracy of the imaging measurements. Image studies were performed at 2.0 and 9.4 T on perfusion-fixed 17.5-day-old mouse embryos. T1, T2, and T1 rho relaxation times were calculated for the phantoms and muscle, diencephalon, and liver tissues. The 5.75% agar phantom and all tissues showed T1 rho dispersion with B1L, whereas the 1.0 mM MnCI2 phantom showed no significant B1L dependence. T1 rho dispersion with B(O) was observed arising from the effects of diffusion through susceptibility-induced gradients. T1 rho shows promise as a contrast parameter in high-field MRH because it is capable of producing T2-like contrast without the susceptibility artifacts associated with T2-weighted images.
Animals↗
Hepatic venoocclusive disease as a complication of whole abdominopelvic irradiation and treatment with the transjuglar intrahepatic portosystemic shunt: case report and literature review.
We report the novel use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure for the treatment of intractable ascites due to hepatic venooclusive disease as a result of whole abdominopelvic radiotherapy. A patient with Stage III endometrioid carcinoma of the endometrium treated with postoperative whole abdominopelvic irradiation developed intractable ascites. Multiple paracenteses and computerized tomography were negative for recurrent carcinoma. Liver biopsy demonstrated hepatic venoocclusive disease, a rare complication of therapeutic radiation involving the liver. Successful relief of ascites and its adverse symptomology were achieved with the transjugular intrahepatic portosystemic shunt. Relevant literature regarding the pathogenesis, prognosis, and treatment of radiotherapy-related hepatic venoocclusive disease are reviewed.
Abdomen↗
A new in vivo method for quantitative analysis of stroke lesions using diffusion-weighted magnetic resonance microscopy.
Using three-dimensional diffusion-weighted MR microscopy and a rat model of focal cerebral ischemia, we evaluated the statistical characteristics of two parameters: absolute stroke volumes and change in stroke volumes over 6 h of middle cerebral artery (MCA) occlusion. In all rats, the absolute stroke volumes increased linearly over the 6-h MCA occlusion time period. On average, stroke volume growth rate was 2.1 +/- 0.5%/h. Sample size power analysis of our data demonstrated that to demonstrate a 10% reduction of the 6-h volumes, sample size per group would require 29 animals (these calculations are based on alpha = 0.05, beta = 0.20 using normal approximation). A similar 30% reduction of stroke volume at 6 h poststroke (from approximately equal to 200 to 140 mm3) would, in our "slope model," translate into a reduction of stroke growth rate from the normal + 11.25 mm3/h (150 to 200 mm3 over 4 h) to 7 mm3/h (150 to 178 mm3 over 4 h); power analysis in this case demonstrated that sample size is reduced to 15 animals per group (these calculations are based on alpha = 0.05, beta = 0.20 using normal approximation). We conclude that from a statistical standpoint our study demonstrates that stroke growth rate might be a more suitable parameter for evaluating the effect of treatment in both clinical and experimental stroke trials.
Animals↗
A single integral finite strain viscoelastic model of ligaments and tendons.
A general continuum model for the nonlinear viscoelastic behavior of soft biological tissues was formulated. This single integral finite strain (SIFS) model describes finite deformation of a nonlinearly viscoelastic material within the context of a three-dimensional model. The specific form describing uniaxial extension was obtained, and the idea of conversion from one material to another (at a microscopic level) was then introduced to model the nonlinear behavior of ligaments and tendons. Conversion allowed different constitutive equations to be used for describing a single ligament or tendon at different strain levels. The model was applied to data from uniaxial extension of younger and older human patellar tendons and canine medial collateral ligaments. Model parameters were determined from curve-fitting stress-strain and stress-relaxation data and used to predict the time-dependent stress generated by cyclic extensions.
Adult↗
In vivo He-3 MR images of guinea pig lungs.
The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.
Animals↗
Human lung air spaces: potential for MR imaging with hyperpolarized He-3.
Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.
Adult↗