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Biomedical subjects

A C Price

Publications and source records attributed to A C Price.

At least 19 recordsLinked to original sources

Phase III multicenter trial of high-dose gadoteridol in MR evaluation of brain metastases.

PURPOSE: To assess the efficacy and safety profile of high-dose (0.3 mmol/kg cumulative dose) gadoteridol in patients with suspected central nervous system metastatic disease. METHODS: We studied 67 patients using an incremental-dose technique. Patient monitoring included a medical history, physical examination, vital signs, and extensive laboratory tests within 24 hours before and after the MR examination. Precontrast T1- and T2-weighted spin-echo studies were performed, followed by intravenous injection of 0.1 mmol/kg of gadoteridol. T1-weighted images were acquired immediately after and at 10 and 20 minutes after injection. At 30 minutes an additional 0.2 mmol/kg of gadoteridol was administered (0.3-mmol/kg cumulative dose), and T1-weighted images were acquired. Cases demonstrating abnormal MR findings were assessed for efficacy by unblinded and blinded reviewers and were analyzed quantitatively. RESULTS: Three adverse effects in two patients were considered to be related to gadoteridol administration. No adverse effects were serious; all self-resolved. Forty-nine cases showed abnormal MR findings and were included in the efficacy analysis. A significantly greater number of lesions was seen on the high-dose as opposed to the standard-dose images. Blinded and unblinded readers identified 5 and 8 patients, respectively, with solitary lesions on standard-dose examination and multiple lesions on high-dose examination. Two patients who had normal standard-dose findings had lesions identified on high-dose studies. Quantitative analysis of 133 lesions in 45 patients demonstrated significant increases in lesion signal intensity on high-dose studies when compared with standard-dose studies. CONCLUSION: Gadoteridol can be safely administered up to a cumulative dose of 0.3 mmol/kg. High-dose contrast studies provide improved lesion detectability and additional diagnostic information over studies performed in the same patients with a 0.1-mmol/kg dose and aid in patient diagnosis and treatment. High-dose gadoteridol study may facilitate the care of patients with suspected central nervous system metastasis.

Adolescent

The prospective evaluation of Gd-DTPA in 225 consecutive cranial cases: adverse reactions and diagnostic value.

This prospective study evaluates two facets of gadopentetate dimeglumine (Gd-DTPA) enhanced MR imaging in 225 consecutive cranial cases in patients greater than 18 years of age: (i) patient and physician perception of adverse reactions, (ii) diagnostic value of the Gd-DTPA enhanced exam. The 225 cases included 173 head cases, 27 IAC cases, and 25 sella cases. Forty-six percent of the cases were abnormal excluding cases of mild atrophy and ischemic white matter disease judged to be related to aging and not pertinent to the patient's presenting complaint. Concerning adverse reactions, 83% of patients had no complaints. Five percent of the patients had reactions that were judged by the physician to be related to Gd-DTPA. All reactions were minor and required no therapy. In a subset of exams (115) that were blindly and independently interpreted by two board-certified, fellowship-trained radiologists, the Gd-DTPA-enhanced exam resulted in a change in diagnosis in 5%-8% of cases. Additionally, a major benefit of Gd-DTPA administration was the increased diagnostic confidence afforded by the addition of a contrast enhanced exam due to improved lesion characterization and exclusion of additional significant intracranial pathology. In 52%-69% of the abnormal cases, Gd-DTPA provided additional diagnostic information and in 26%-39% the absence of enhancement aided in interpretation. The Gd-DTPA-enhanced exam aids in the diagnosis and characterization of neoplastic disease, acoustic neuroma, subacute infarction, inflammatory disease (meningeal and parenchymal), and certain vascular abnormalities.

Brain Diseases

Remyelination in the human central nervous system.

Remyelination, albeit incomplete, has been demonstrated in human central nervous system (CNS). However, information about the initial stage and the final extent of such remyelination is not available. We describe the morphologic findings of a demyelinating lesion with evidence of early remyelination in a biopsy obtained from a 15-year-old boy about two weeks after the onset of neurologic symptoms. The demyelinated area appeared hypercellular with a relatively large number of oligodendrocytes frequently seen in the process of new myelin formation. In addition to the usual reactive changes, the astrocytes were often seen to contain otherwise normal-looking oligodendrocytes within their cytoplasm. In the ensuing months, the patient made apparently total functional recovery accompanied by nearly complete resolution of the white matter lesions demonstrated by the subsequent magnetic resonance studies. These observations suggested that the initial remyelination seen in the biopsy eventually succeeded in producing extensive remyelination in the lesion. Although the exact nature of the demyelinating disorder in our patient remains undetermined, this study indicates that clinically significant remyelination is possible in human CNS. Also, our findings appeared strikingly similar to those described in certain experimental animal models in which widespread remyelination is known to occur.

Adolescent

Gd DTPA. Clinical efficacy.

Both the diagnostic accuracy and sensitivity of the MRI diagnosis of central nervous system neoplasms appear to be improved by the administration of a paramagnetic contrast agent, Gd DTPA.

Brain Neoplasms

Primary glioma: diagnosis with magnetic resonance imaging.

Seventeen patients with surgically documented primary glial-origin brain tumors were evaluated by magnetic resonance imaging and high-resolution computed tomography. The exclusion of CT ring-enhancing lesions directed the focus of this study toward lower grade tumors that were more difficult to diagnose. The computed tomography abnormalities were often subtle and included areas of low attenuation, mass effect, and focal enhancement. Spin-echo sequences with both heavy T1 and T2 weighting were utilized. Prolonged T1 and T2 values were observed in all tumors. The T2-weighted spin-echo 1000/120 sequence was the most sensitive in tumor detection and was positive in all cases. Magnetic resonance imaging was superior to computed tomography in tumor detection, tumor localization, assessment of tumor extent, and determination of associated changes, ie, brain stem encroachment. All the magnetic resonance sequences used showed an increase in severity of imaging changes with increasing tumor grade. The T2-weighted sequence showed progressive margin irregularity, whereas the T1-weighted (inversion recovery) sequence showed increasing severity of internal tissue changes. The superior resolution of these changes by magnetic resonance imaging may have implications for better assessment of tumor grade in the future than is currently possible with computed tomography.

Adolescent

Early changes in experimental hydrocephalus.

In acute obstruction of the cerebral spinal fluid (CSF) absorption pathways, fluid is produced more rapidly than it is absorbed, and the ventricles enlarge proximal to the obstructions. Communicating hydrocephalus results from a difference between the rates of production and absorption of cerebrospinal fluid. In animals with chronic communicating hydrocephalus, the initial pathologic changes appear to involve the periventricular tissue near the angles of the lateral ventricles. The present investigation was designed to identify the various changes associated with the production of communicating hydrocephalus in acutely hydrocephalic preparations and to relate these findings to those found in experimental animals with chronic communicating hydrocephalus. The results of this study seem to confirm that the changes noted in the chronically hydrocephalic animals occur as early as 12 hours after the restriction of the normal flow of CSF.

Animals

Magnetic resonance imaging and other techniques in the diagnosis of multiple sclerosis.

We evaluated 35 patients with multiple sclerosis (MS) by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, evoked potential testing, and computed tomographic (CT) scanning. As classified by the McAlpine et al and McDonald and Halliday criteria, 27 patients had definite MS, three had probable MS, and five had possible MS. All of the patients had multiple white matter lesions detectable by MRI that were evident predominantly in the periventricular areas but also in the cerebral or cerebellar white matter. The severity of the MRI abnormality, as judged by the number and size of the lesions, correlated with the likelihood of a positive CT scan but not with the duration of disease, the degree of disability, or positive CSF oligoclonal banding. Magnetic resonance imaging successfully demonstrated brain-stem lesions in 15 patients (none were seen on CT scans). Magnetic resonance imaging seems to be a sensitive indicator of MS lesions, but clinical assessment will continue to be crucial to the diagnosis of MS.

Adult

The use of Gd DTPA as a perfusion agent and marker of blood-brain barrier disruption.

To provide contrast enhancement in magnetic resonance imaging, a new class of compounds has been developed, the paramagnetic metal ion chelates. Gadolinium (Gd) DTPA, a prototype of this class, shows a sufficiently high in vivo stability and low toxicity for use in initial clinical trials. This type of agent, designed for rapid clearance by glomerular filtration, allows the assessment on MRI of renal function, alterations in tissue perfusion, myocardial ischemia, and perhaps most significantly disruption of the blood-brain barrier (BBB). Research at Vanderbilt has demonstrated these applications, with particular emphasis in three areas. Tissue perfusion changes, such as those produced by ligation of the arterial blood supply to portions of the spleen and kidney, cannot easily be detected on unenhanced MRI. These acute tissue infarcts can be readily identified following the administration of Gd DTPA. The question of field strength dependence of Gd DTPA has been addressed by experimentation at 0.15, 0.5, and 1.5 tesla. Furthermore, the ability to detect an alteration of the BBB, when present without associated edema, has been demonstrated with the application of control enhancement. The use of contrast agents in MRI will enhance both the sensitivity and specificity of magnetic resonance imaging.

Animals

Contrast enhanced MRI. Evaluation of a canine model of osmotic blood-brain barrier disruption.

An osmotic model of blood-brain barrier (BBB) disruption was studied by magnetic resonance (MR) imaging (0.5 T) in 17 canines. The animals were killed after imaging and the lesions confirmed on gross pathology by the presence of Evans blue dye. No accompanying cerebral edema was demonstrated on histologic examination. The disrupted BBB could be identified in only one of five control animals on unenhanced MRI, despite the use of calculated T1 and T2 images. In a second group of five animals, the area of abnormal vascular permeability was consistently demonstrated after IV injection of 0.25 mmol/kg Gd DTPA. The time course of enhancement was evaluated in four additional animals. The brain tissue concentration of the gadolinium ion responsible for the observed enhancement was determined by ion coupled plasma analysis in the last three canines. In a study of pulse techniques, spin echo sequences with both short TRs and TEs (ie, SE 500/30) and inversion recovery techniques proved to be most efficacious for the detection of contrast enhancement. However, contrast could be demonstrated on more T2 weighted sequences.

Animals

Intravascular contrast agents suitable for magnetic resonance imaging.

Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging (MR) using a 0.5-T superconducting scanner. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.

Animals

Magnetic resonance imaging of multiple sclerosis: a study of pulse-technique efficacy.

Forty-two patients with the clinical diagnosis of multiple sclerosis were examined by proton magnetic resonance imaging (MRI) at 0.5 T. An extensive protocol was used to facilitate a comparison of the efficacy of different pulse techniques. Results were also compared in 39 cases with high-resolution x-ray computed tomography (CT). MRI revealed characteristic abnormalities in each case, whereas CT was positive in only 15 of 33 patients. Milder grades 1 and 2 disease were usually undetected by CT, and in all cases, the abnormalities noted on MRI were much more extensive than on CT. Cerebral abnormalities were best shown with the T2-weighted spin-echo sequence (TE/TR = 120/1000); brainstem lesions were best defined on the inversion-recovery sequence (TE/TI/TR = 30/400/1250). Increasing TE to 120 msec and TR to 2000 msec heightened the contrast between normal and abnormal white matter. However, the signal intensity of cerebrospinal fluid with this pulse technique obscured some abnormalities.

Adult

Paramagnetic contrast agents in magnetic resonance imaging: research at Vanderbilt University.

Experimental studies in animals have demonstrated the application of particulate and chelated paramagnetic oral contrast agents in magnetic resonance imaging (at 0.5 tesla). The ability of a soluble paramagnetic species, ferrous gluconate, to improve imaging studies of the pancreas presently is being evaluated in clinical trials. Two paramagnetic metal ion chelates, Cr EDTA and Gd DTPA, have been evaluated extensively as potential intravascular contrast agents. Renal function, tissue vascularity, abnormalities of the blood-brain barrier, and infarction of myocardial tissue may all be assessed with IV contrast enhanced magnetic resonance imaging. The contrast materials tested all represent first generation compounds. Improved relaxation characteristics, toxicity, distribution, and flexibility will result from development of second generation agents, primarily within the particulate and chelate classes.

Animals

Intervertebral disk-space infection: CT changes. Work in progress.

Seven patients who had spinal interspace infections underwent clinical, laboratory, and radiographic examinations, and findings are reported. Lytic fragmentation of adjacent vertebral bodies is a characteristic appearance on CT scans. Sagittal-coronal reformations confirm the end-plate irregularity and establish the diagnosis. Since the changes of diskitis are delayed and often obscured by accompanying degenerative disease on plain radiographs, CT appears to offer a diagnostic modality that shortens the usual delay from onset of symptoms to diagnosis.

Adult

Therapeutic embolization of juvenile angiofibroma.

Therapeutic embolization of juvenile angiofibromas was performed in 15 boys, aged 12--18 years, 11 of whom subsequently underwent surgery. Intraoperative blood loss was reduced from an average of 2,400 ml in nonembolized patients to 800 ml after embolization. Angiography is of value to confirm the diagnosis prior to excision and to delineate the extent of the tumor. Embolization may be performed at the same sitting as a presurgical adjunct or possibly as a definitive or palliative therapeutic method. The embolization procedure is discussed in detail, emphasizing techniques and potential hazards of such procedures.

Adolescent