Nuclear Magnetic Resonance Imaging Studies Research Articles

Anatomical and mesoscopic characterization of the dystrophic diaphragm: An in vivo nuclear magnetic resonance imaging study in the Golden retriever muscular dystrophy dog

Because respiratory failure remains a major issue in Duchenne Muscular Dystrophy patients, respiratory muscles are a key target of systemic therapies. In the Golden Retriever Muscular Dystrophy (GRMD) dogs, the disease shows strong clinical and histological similarities with the human pathology, making it a valuable model for preclinical therapeutic trials. We report here the first nuclear magnetic resonance (NMR) imaging anatomical study of the diaphragm in GRMD dogs and healthy controls. Both T1- and T2-weighted images of the diaphragm of seven healthy and thirteen GRMD dogs, from 3 to 36 months of age, were acquired on a 3 tesla NMR scanner. Abnormalities of texture and shape were revealed and consisted of increases in signal intensity on T2-weighted images and in signal heterogeneity on both T1- and T2-weighted images of the dystrophic diaphragm. These abnormalities were associated with a significant thickening of the muscle and we identified a clear 8-mm-threshold distinguishing clinically preserved GRMD dogs from those more severely affected. In this study, we demonstrated the feasibility of NMR imaging of the diaphragm and depicted several anatomical and mesoscopic anomalies in the dystrophic diaphragm. NMR imaging of the diaphragm shows a promise as an outcome measure in preclinical trials using GRMD dogs.

Bilateral Abducens Palsies and Facial Weakness as Initial Manifestations of a Chiari 1 Malformation

Chiari I malformations are rare, congenital anomalies involving the caudal herniation of the cerebellar tonsils into the upper cervical spinal canal. Osseous abnormalities of the skull permit the extension of the hindbrain below the foramen magnum and engender syringohydromyelia formation. Neuroophthalmic manifestations are not uncommon; nevertheless, this is the first report of concomitant bilateral abducens palsies and facial nerve impairment as presenting manifestations of a Chiari I malformation. A 30-year-old black female presented with a recent history of blurred vision and binocular diplopia in both left and right gazes. Headaches, dizziness, and orofacial sensorimotor impairments were noted in conjunction with the onset of her diplopia. No history of surgery, trauma, or systemic illness was elicited. Extraocular motility testing confirmed a complete bilateral abduction deficit. Additional cranial nerve testing revealed bilateral facial nerve weakness and tactile hypesthesia in the perioral region. No taste disturbances were reported. Nuclear magnetic resonance imaging studies revealed a Chiari I malformation with a syringohydromyelia formation in the vicinity of the patient's sixth cervical vertebrae. Foramen magnum decompression surgery was performed. Two months after surgery, abduction capacity was restored along with resolution of symptoms of perioral numbness and signs of facial weakness. Bilateral sixth nerve palsies are rare clinical commodities especially when they do not occur in isolation. Intracranial neoplams, trauma, subarachnoid hemorrhaging, demyelinating disease, and meningeal infarcts have all been shown to induce mixed cranial neuropathies. The concomitant bilateral abducens palsy and concomitant facial nerve weakness reported in this case represents an atypical and previously unreported presentation of a Chiari I malformation.

NMR Imaging Study of Hydrates in Sediments

Abstract: In this study, hydrates were generated in synthetic sediments in a laboratory cell. After hydrate formation took place and the sediment solidified, the samples were investigated both visually and by the use of nuclear magnetic resonance (NMR) imaging. The hydrates in this initial study were formed from model systems at low pressure. The results show hydrates distribution effects. Scans in the NMR apparatus were also made of the unfrozen samples to serve as a basis for comparison. NMR here maps the mobility of hydrogen atoms and their distribution in a sample. The relevant factor is the density of mobile H‐atoms, and this is shown to be about five times smaller for a volume of (for example) tetrahydrofuran (THF, C4H8O) hydrate than for the fluids of water and/or THF. This correlates very well with an observed signal decrease by a factor of six in an NMR‐studied sample after hydrate formation had taken place.

Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations. In short-term studies, histological examination revealed a significant decrease in tumor volume in GCV-treated animals from day 1 or from day 10 after cell inoculation. We observed that late GCV delivery is as efficient as early delivery, probably because GCV can reach tumor cells more easily when neoangiogenesis occurs. In long-term experiments, the survival of treated rats bearing 15-day tumors was improved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imaging demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tumors, in contrast with the microscopic tumor formations previously reported.

NMRI study: asial migration of radially segregated core of granular mixtures in a horizontal rotating cylinder

In this study, we use NMRI (nuclear magnetic resonance imaging) to non-invasively study the three-dimensional evolution of a segregation phenomenon which occurs in a simple geometry, a long horizontal cylindrical drum or a kiln. We show, for the first time, in a binary size mixture of spheres, the development of a radial core of small particles along the axis of the cylinder which evolves to axially segregated bands.

A comparative structural characterization of two cellobiohydrolases from Trichoderma reesei: a high resolution electron microscopy study

The molecular structure of two homogeneously purified cellobiohydrolases from Trichoderma reesei has been studied employing high resolution transmission electron microscopy (TEM) and digital image processing. By combining low dose TEM, a 3% (w/v) solution of methylamine tungstate as the negative staining agent, and digital image processing, it has been possible to view intact molecular architectures of cellobiohydrolases from Trichoderma reesei. Cellobiohydrolase I (CBH I) and Cellobiohydrolase II (CBH II) have ellipsoidal heads and long, extended helical tails. CBH I is composed of a head with an average diameter of 4.5 ± 0.5 nm. The average length of CBH I is 15.1 ±1.3 nm. CBH II's head has an average diameter of 4.4 ± 0.3 nm. The average length of CBH I is 13.4 ± 2.6 nm. Overall, the structure of the digitally enhanced TEM images of these two glycosyl hydrolases correlated reasonably well with the reported models based on small angle X-ray scattering (SAXS), X-ray crystallography, and nuclear magnetic resonance imaging studies, thereby establishing the reliability of high resolution TEM studies in a novel way. The linker regions (LRs) of the two CBHs have been visualized. The LRs of both enzymes are probably helical in nature, suggesting an extended peptide sequence that lacks secondary structure due to the absence of amino acid/amino acid interactions in this region. A possible structural and functional role of O-glycosylation affiliated with these linker regions is discussed on the basis of combining the TEM observations with known biochemical data.

A nuclear magnetic resonance imaging study of the effect of incorporating a macromolecular drug in poly (glycolic acid-co- dl-lactic acid)

Biodegradable polymers based on poly(glycolide-co-lactide) (PGLA) are becoming increasingly popular as drug delivery systems, particularly for the delivery of high molecular weight drugs. The purpose of this study has been to examine the effect of incorporating a high molecular weight peptide in 50:50 poly(glycolide-co- dl-lactide). Using nuclear magnetic resonance (NMR) imaging it was possible to qualitatively and quantitatively probe the effect of the presence of drug on the buffer uptake kinetics, the polymer morphology, the physicochemical environment of the liquid in the polymer, and the drug distribution within the polymer. Rapid Super-Case II buffer diffusion was observed in the drug-free polymer, while much slower diffusion was observed in the drug-loaded material, approaching Fickian and Case II limits in different regions of the polymer. A strong drug-polymer interaction was observed which affected the polymer chain configuration and mobility, and therefore the transport of buffer molecules in the polymer.

Lysing patterns of blood clots: a nuclear magnetic resonance imaging study in vitro and mathematical modelling of the lysing pattern kinetics

Blood clot lysing patterns have been modelled with a pedestrian random walk model. The resulting patterns are in close agreement with the experimental results.

First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease

Nuclear magnetic resonance (NMR) imaging has been shown to accurately portray cardiac anatomy and function. To investigate the potential of NMR imaging for the assessment of coronary stenosis in patients with chest pain, ultrafast NMR imaging in conjunction with a T1(longitudinal relaxation time) contrast agent was performed in 17 patients with chest pain who had undergone cardiac catheterization. These included 12 patients with significant coronary artery stenoses and 4 who underwent repeat NMR study after myocardial revascularization. Cardiac images at rest were obtained during rapid intravenous injection of gadolinium-DTPA (0.04 mM/kg). Electrocardiographic-gated images were acquired over 380 ms, with repetitive images obtained every 3 to 4 s.After contrast injection, there was pronounced signal enhancement in the right ventricular cavity, followed by enhancement in the left ventricular cavity and myocardium. Regional myocardium perfused by a diseased vessel demonstrated a lower peak signal intensity (p = 0.001) and lower rate of signal increase (p = 0.001) than did myocardium perfused by coronary arteries without stenosis. Repeat NMR study after revascularization showed an increase in peak signal intensity (p < 0.002).These results demonstrate the clinical potential of dynamic gadolinium-DTPA-enhanced NMR imaging for the assessment of coronary artery disease in patients with chest pain. In combination with anatomic and functional NMR imaging, this technique has the potential to provide a comprehensive noninvasive cardiac evaluation of patients with suspected coronary artery disease.

Sodium-23 and proton nuclear magnetic resonance imaging studies of carbon tetrachloride-induced liver damage in the rat

Magnetic resonance imaging techniques were used to investigate the response of the liver of the rat in situ to a toxicological challenge by carbon tetrachloride. Proton images were taken as transverse slices through the rat before and after intraperitoneal administration of the hepatotoxin. Two to three hours after carbon tetrachloride was given, a region of high proton signal intensity was observed where the portal vein enters the liver. Sodium-23 images were also taken, and a region of high sodium intensity was observed in the same location within the liver as the increased proton intensity. The results suggest that acute administration of carbon tetrachloride induces localized liver damage in the region where the hepatotoxin first enters the liver. This liver damage is manifest as edema with a buildup of sodium ion and water, which can be readily detected by sodium-23 and proton NMR imaging techniques, respectively.

Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology.

The spatial correlation of nuclear magnetic resonance imaging (NMRI) and cerebral blood flow (CBF) may improve our ability to identify ischemic brain lesions and may provide further insight into the pathophysiology of early cerebral ischemia. Eleven pentobarbital-anesthetized adult cats underwent exposure of the common carotid arteries bilaterally and the right middle cerebral artery through a transorbital approach. Baseline NMRI images were obtained with a single spin-echo, multislice technique using a 0.6-T field, 0.4-cm slice thickness, and a surface coil. Focal ischemia was produced with right middle cerebral artery occlusion and potentiated with bilateral common carotid artery ligation. Sequential NMRI studies were then performed at 1, 2, 4, 6, and 12 hours or until CBF was determined in the same cats using [14C]iodoantipyrine at either 2 (n = 2), 4 (n = 2), 6 (n = 2), or 12 (n = 1) hours after the time of occlusion. This protocol allowed temporal and spatial correlation of NMRI and CBF. Alternate 5-mm brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride (TTC) for 45 minutes at 37-41 degrees C and frozen in liquid Freon for later autoradiographic CBF determination. Four cats were studied only with NMRI and TTC (not CBF). The correlation between areas of increased NMRI signal intensity observed in T2-weighted images (repetition time 2,000 msec, echo time 120 msec), vital staining with TTC, low CBF, and routine histology was evaluated. During the early phase (less than 6 hours), T2-weighted NMRI changes were localized to the central ischemic gray matter areas, as defined in the later CBF images, with no involvement of the white matter. By the twelfth hour the NMRI changes involved the entire ischemic area including gray and white matter. The initial visible changes seen on T2-weighted NMRI are suggestive of cellular edema, and the later changes are characteristic of vasogenic edema. The spread of NMRI changes compared with the ischemic area determined from autoradiographic CBF is consistent with the previously described biphasic evolution of ischemic injury. These data suggest that T2-weighted NMRI could be used clinically to delineate areas of acute ischemic stroke.

Nuclear magnetic resonance spectroscopy and imaging in the study of experimental liver diseases.

We are investigating potential noninvasive new strategies for the assessment of liver injury, steatosis, and hepatic tumor development. These techniques employ nuclear magnetic resonance (NMR) imaging and spectroscopy. Accordingly, several experimental animal models of liver injury and steatosis produced in rats by ethanol, azaserine, L-ethionine, carbon tetrachloride, and D-galactosamine. Ethanol and L-ethionine induce acute steatosis without necrosis, whereas azaserine, carbon tetrachloride, and D-galactosamine are known to produce steatosis with varying degrees of hepatic necrosis. Triglyceride content and protein spin relaxation times were measured. T1 values were analyzed by using an inversion recovery technique at eight different tau values (20 msec to 2.50 sec) and T2 by Carr-Purcell-Meibloom-Gill pulse sequences with 10 spin echoes (4-40 msec). We also performed NMR imaging studies on controls and ethanol-induced steatosis using a 60-MHz Technicare 8-cm bore superconducting system. Results of these experiments indicate that varying degrees of steatosis produce striking changes in T2 without inducing changes in T1, whereas necrosis superimposed on steatosis produces T1 changes as well. Thus, these NMR spectroscopy and imaging studies demonstrated that steatosis may be clearly defined in vitro and in vivo.

Silent brain lesions in patients with isolated idiopathic optic neuritis. A clinical and nuclear magnetic resonance imaging study.

Eight of 16 patients with isolated idiopathic optic neuritis were found to have one to several brain lesions by nuclear magnetic resonance scanning. The brain lesions were predominantly located in the periventricular white matter; their appearances, locations, and extents were similar to those seen in recent nuclear magnetic resonance studies of patients with definite multiple sclerosis. All of these brain lesions were clinically silent and were missed by computerized tomography. Idiopathic optic neuritis may be the only manifestation of a multicentric disease process that is disseminated in the central nervous system in the majority of cases.