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Biomedical subjects

C A Cuenod

Publications and source records attributed to C A Cuenod.

At least 19 recordsLinked to original sources

Confocal image characterization of human papillomavirus DNA sequences revealed with Eu in HeLa cell nuclei stained with Hoechst 33342.

OBJECTIVE: To visualize and localize specific viral DNA sequences revealed with Eu by fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM) and factor analysis of biomedical image sequences (FAMIS). STUDY DESIGN: Human papillomavirus DNA (HPV-DNA) was identified in HeLa cells with biotinylated DNA probes recognizing HPV-DNA types 16/18. DNA-DNA hybrids were revealed by a three-step immunohistochemical amplification procedure involving an antibiotin mouse monoclonal antibody, a biotinylated goat antimouse polyclonal antibody and streptavidin-Eu. Cell nuclei were counterstained with Hoechst 33342. Image sequences were obtained using a CLSM that made possible ultraviolet excitation. The location of fluorescent signals inside cellular preparations was determined by FAMIS and selection of filters at emission. Image sequences were summarized into a reduced number of images, or factor images, and curves, or factors. Factors estimate spectral or temporal patterns and depth emission profiles. Factor images correspond to spatial distributions of the different factors. RESULTS: We distinguished between Eu corresponding to HPV-DNA hybridization signals and nuclear staining by taking into account differences in their spectral and temporal patterns and (using their decay rates). CONCLUSION: FAMIS, together with CLSM and Eu, made possible the detection and characterization of viral papillomavirus DNA sequences in HeLa cells.

Base Sequence↗

Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vascularization of diethylnitrosamine-induced hepatocarcinomas using a computerized tomography scanner approach. The efficacy of gene transfer was then evaluated by three routes of administration: intraportal, selective injection through the hepatic artery and direct injection into the tumor. Diethylnitrosamine-induced hepatocarcinomas had predominantly an arterial blood supply, 67% of the total liver blood supply. Compared with intraportal administration, arterial injection improved gene transfer into tumors whereas that to the non-tumor areas was diminished. In addition, this route of injection allowed the efficient transduction of dysplastic nodules. Diethylnitrosamine-induced hepatocarcinoma in rats is a relevant model for the study of human hepatocarcinoma due to its vascularization. Arterial infusion improved the ratio of transduced tumorous to nontumorous cells and allowed targeting of gene transfer to dysplastic nodules. This will be useful in the design of gene therapy for hepatocarcinoma.

Adenoviridae↗

Symptomatic hepatic cysts: treatment with single-shot injection of minocycline hydrochloride.

PURPOSE: To assess the efficacy of percutaneous minocycline hydrochloride sclerotherapy in symptomatic hepatic cysts. MATERIALS AND METHODS: From November 1992 to June 1994, seven of eight consecutive adults with large symptomatic hepatic cysts (diameter, 55-130 mm) were treated with a single intracystic injection of minocycline hydrochloride in an ambulatory procedure. Five patients had a solitary cyst, and two had polycystic liver disease. The target cyst was punctured under ultrasound guidance and local anesthesia with a 22-gauge Chiba needle. Half of the cyst content was aspirated before injection of 100-500 mg of minocycline hydrochloride diluted in 5-25 mL of saline. The minocycline hydrochloride was left in the cyst at the end of the procedure. RESULTS: After a mean follow-up of 28 months (range, 24-42 months), all five patients with solitary cysts were asymptomatic and four had documented complete cyst regression; the two patients with multiple hepatic cysts showed only transient clinical improvement. CONCLUSION: Single-shot injection of minocycline hydrochloride is an effective treatment for symptomatic solitary hepatic cysts but is less effective in polycystic liver disease.

Anti-Bacterial Agents↗

[What is bright on T1 MRI scans?].

The list of entities associated with a high signal intensity on T1-weighted images is extensive and classically includes fat, proteins, hemorrhage, melanin and gadolinium. However, additional entities may be responsible for abnormally high signal intensity on T1-weighted images. These include ion deposition in metabolic disorders, free radicals, increased proton density, flow phenomena, some artifacts, and new contrast agents. The aim of this article is to display both the common and uncommon causes for a high T1 signal intensity and to discuss the underlying mechanisms or attributable pathophysiology for this phenomenon.

Artifacts↗

Measurement of liver blood volume using a macromolecular MRI contrast agent at equilibrium.

Liver regional blood volume (LRBV) is altered by several disease states and various drugs. Preliminary studies in the rat, using research MR imaging instruments at 2T and vascular contrast agents, have suggested that MRI may be used to measure LRBV. Our goal was to develop a technique for measuring LRBV using a clinical machine at 1.5 T. This study was performed in the rabbit, using CarboxyMethylDextran Gd-DTPA, a macromolecular contrast agent with a molecular weight of 158 kDa. MRI was performed at 1.5 T, in the plane of the inferior vena cava, with and without flow compensation, before contrast injection and in the steady state after injection. Accuracy and stability of LRBV measurement, over 2 h and with various doses (0.01-0.05 mmol/kg), was tested against a standard Evan's Blue dye-indicator technique. LRBV was 28 +/- 2 mL/100 g when measured by MRI with flow compensation, which is in good agreement with the literature and with the 26 +/- 6 mL/100 g, measured by the Evan's Blue dilution technique. Measurements varied less than 7% over time and less than 9% over the range of doses. LRBV was overestimated using a sequence without flow compensation especially when large doses of contrast agent were injected. This noninvasive MRI technique provides a simple method for measuring liver LRBV and offers new prospects for future physiological and pathological studies.

Animals↗

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

BACKGROUND: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy. METHODS: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. RESULTS: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. CONCLUSIONS: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Adolescent↗

Proton transverse nuclear magnetic relaxation in oxidized blood: a numerical approach.

When red blood cells are deoxygenated, hemoglobin, which is then transformed into deoxyhemoglobin or methemoglobin, becomes paramagnetic. The transverse nuclear magnetic relaxation rate of water protons is considerably enhanced by this chemical transformation. A general agreement exists about the origin of the phenomenon--local field inhomogeneities induced by paramagnetic centers randomly distributed within the cell--but the localization of the region that dominates the relaxation is unclear. We addressed this problem with a computer simulation devoted to the determination of transverse magnetic relaxation of water protons in the presence of superparamagnetic MRI contrast agent candidates. The simulation confirms an earlier experimental result that shares equitably the responsibility for the observed relaxation between intracellular and extracellular water.

Blood↗

Anomalous transverse relaxation in 1H spectroscopy in human brain at 4 Tesla.

Longitudinal (T1) and apparent transverse relaxation times (T2) of choline-containing compounds (Cho), creatine/phosphocreatine (Cr/PCr), and N-acetyl aspartate (NAA) were measured in vivo in human brain at 4 Tesla. Measurements were performed using a water suppressed stimulated echo pulse sequence with complete outside volume presaturation to improve volume localization at short echo times. T1-values of Cho (1.2 +/- 0.1 s), Cr (1.6 +/- 0.3 s), and NAA (1.6 +/- 0.2 s) at 4 Tesla in occipital brain were only slightly larger than those reported in the literature at 1.5 Tesla. Thus, TR will not adversely affect the expected enhancement of signal-to-noise at 4 Tesla. Surprisingly, apparent T2-values of Cho (142 +/- 34 ms), Cr (140 +/- 13 ms), and NAA (185 +/- 24 ms) at 4 Tesla were significantly smaller than those at 1.5 Tesla and further decreased when increasing the mixing interval TM. Potential contributing factors, such as diffusion in local susceptibility related gradients, dipolar relaxation due to intracellular paramagnetic substances and motion effects are discussed. The results suggest that short echo time spectroscopy is advantageous to maintain signal to noise at 4 Tesla.

Artifacts↗

Functional MRI during word generation, using conventional equipment: a potential tool for language localization in the clinical environment.

OBJECTIVE: To test the accuracy of bilateral language mapping using a standard clinical magnetic resonance (MR) imaging device during word generation. DESIGN: A study of normal volunteers. SETTING: Volunteers from the Washington, DC, area. PARTICIPANTS: Nine normal, right-handed, native English speakers (four women, five men, mean age 31 years). INTERVENTIONS: During four MR acquisition periods, subjects would alternately rest and silently generate words. Sagittal MR images covered the middle and inferior frontal gyri, insulae, and part of the temporal and parietal lobes bilaterally. MAIN OUTCOME MEASURES: (1) Anatomic maps of task-related signal changes obtained by comparing, in each voxel, the signal during word generation and rest periods, and (2) analysis of the time course of the signal. RESULTS: Maximum responses were in the left hemisphere, mainly in the frontal lobe (Broca's area, premotor cortex, and dorsolateral prefrontal cortex) but also in posterior regions such as Wernicke's area. In agreement with previous studies, some degree of task-related changes was present in a subset of the corresponding regions in the right hemisphere. CONCLUSION: Despite certain limitations, it is possible, using widely available MR equipment, to obtain results consistent with previous studies. The technique may have important implications for assessment of cognitive functions in patients with neurologic disorders in a clinical environment.

Adult↗

Simultaneous temperature and regional blood volume measurements in human muscle using an MRI fast diffusion technique.

The thermal dependence of the translational diffusion coefficient and of the regional blood volume was investigated in vivo by using a special MR pulsed gradient technique with reduced sensitivity to bulk tissue motion. Measurements were done at 0.5 T, using a small gradient insert. The diffusion coefficient of muscle water was calibrated against thermocouple-measured temperature in vitro, both with the muscle fibers parallel and perpendicular to the diffusion gradient. The maximum muscle temperature variation obtained by percutaneous conduction was -8.8 +/- 1.6 degrees C under cooling and +3.7 +/- 1.6 degrees C under heating, from basal state. Simultaneously the fractional regional blood volume decreased by a factor of 3.5 under cooling and increased by a factor of 2.7 under heating. Due to the interdependence of microcirculation and tissue temperature, this technique may be used to follow heat production or deposition in living tissue (muscle exercise, electromagnetic irradiation, etc.).

Artifacts↗

Human brain: proton diffusion MR spectroscopy.

Diffusion of brain metabolites was measured in 10 healthy volunteers by using localized proton diffusion magnetic resonance (MR) spectroscopy. Measurements were conducted with a clinical MR imager by using a stimulated-echo pulse sequence (3,000/60 [repetition time msec/echo time msec], 200-msec mixing time) with additional outside-volume suppression. Motion artifacts due to macroscopic brain movements were compensated by means of peripheral cardiac gating and separate collection of individual spectroscopic acquisitions into a two-dimensional data matrix. Phase errors due to macroscopic motion were subsequently corrected in individual data traces prior to spectral averaging. Mean (+/- 1 standard deviation) apparent diffusion coefficients of choline-containing compounds ([0.13 +/- 0.03] x 10(-3) mm2/sec), creatine and phosphocreatine ([0.15 +/- 0.03] x 10(-3) mm2/sec), and N-acetyl aspartate ([0.18 +/- 0.02] x 10(-3) mm2/sec) were substantially smaller than that of water and were consistent with recently published data obtained in anesthetized and paralyzed animals. Adequate diffusion sensitivity for metabolites in the human brain can be obtained with clinical whole-body imagers despite macroscopic head and brain movements.

Adult↗