PubMed Health⌕ Search

Biomedical subjects

M G Pomper

Publications and source records attributed to M G Pomper.

At least 19 recordsLinked to original sources
PubMed2005

Spectroscopic evidence of cerebral axonopathy in patients with "pure" adrenomyeloneuropathy.

BACKGROUND: Adrenomyeloneuropathy (AMN) is the adult variant of X-linked adrenoleukodystrophy. The disease pathology is usually limited to spinal cord and peripheral nerves, and when this is the case, it is referred to as "pure" AMN. Histopathology shows cerebral involvement even in pure AMN; however, not much is known about the nature, extent, and clinical relevance of these findings. OBJECTIVE: To investigate brain involvement in AMN patients with normal MRI, employing multislice MR spectroscopic imaging. METHODS: Twelve men with pure AMN were compared with 19 age-matched healthy volunteers. Metabolite ratios (N-acetylaspartate [NAA]/choline [Cho], NAA/creatine [Cr], and Cho/Cr) were measured from seven brain regions. Global metabolite ratios were generated as an average of these seven regional ratios. The Expanded Disability Status Scale (EDSS) was used for neurologic evaluation. RESULTS: The patients with AMN showed reduced global NAA/Cho (AMN 1.40 +/- 0.16 vs controls 1.75 +/- 0.34; p = 0.003)) and global NAA/Cr (AMN 2.32 +/- 0.13 vs controls 2.62 +/- 0.43; p = 0.03). Regionally, NAA/Cho was lowered in the internal capsule (AMN 1.30 +/- 0.20 vs controls 1.69 +/- 0.37; p = 0.002) and in parieto-occipital white matter (AMN 1.45 +/- 0.19 vs controls 1.78 +/- 0.55; p = 0.04). NAA/Cr was lowered in parieto-occipital white matter (AMN 2.34 +/- 0.31 vs controls 2.83 +/- 0.71; p = 0.04). EDSS demonstrated an inverse association with global NAA/Cr (r = -0.65, p = 0.02) and NAA/Cr in centrum semiovale (r = -0.73, p = 0.006) and in parieto-occipital white matter (r = -0.64, p = 0.02). Cho/Cr was not significantly elevated. CONCLUSIONS: (1)H-MR spectroscopic imaging is able to detect biochemical abnormalities suggestive of axonal damage even in the brains of patients with pure adrenomyeloneuropathy. The axonopathy is most prominent in internal capsule and parieto-occipital white matter and may contribute to clinical disability.

Adrenoleukodystrophy↗
PubMed2001

Positron emission tomography in the detection and management of sarcomatous transformation in neurofibromatosis.

Benign neurofibromas undergo sarcomatous transformation in approximately 5% of patients with neurofibromatosis type I. The clinical and radiologic diagnosis of sarcomatous change remains difficult. Positron emission tomography with F-18 fluorodeoxyglucose is a method to assess increased glucose metabolism in malignant tissue such as sarcomas. In this case report, positron emission tomography accurately distinguished malignant from benign neurofibromas. The technique may be useful as a noninvasive screening tool for malignant transformation of neurofibromas.

Adult↗
PubMed2001

Reliability of normal findings on MR imaging for excluding the diagnosis of vasculitis of the central nervous system.

OBJECTIVE: We attempt to determine whether angiography is indicated in patients with suspected central nervous system (CNS) vasculitis who present with negative findings on MR imaging studies. CONCLUSION: MR imaging findings may be negative in the setting of CNS vasculitis confirmed on angiography, indicating that advanced imaging techniques tailored to detect infarction (i.e., fluid-attenuated inversion recovery, diffusion-weighted, and perfusion imaging) may be necessary to enhance the sensitivity of an MR study and that despite the high sensitivity of MR imaging for CNS vasculitis, angiography may still be required to render an accurate diagnosis.

Cerebral Angiography↗
PubMed2001

Chordoid glioma: a neoplasm unique to the hypothalamus and anterior third ventricle.

BACKGROUND AND PURPOSE: Chordoid glioma is a new clinicopathologic entity that occurs in the region of the hypothalamus/anterior third ventricle. The aims of this study were to describe the characteristic radiographic features of chordoid glioma, identify specific imaging features that may enable differentiation of chordoid glioma from other suprasellar tumors, and increase neuroradiologists' awareness of this newly described tumor, facilitating prospective diagnosis. METHODS: CT scans and/or MR images of six patients with chordoid glioma were reviewed retrospectively to determine whether any characteristic radiographic features would emerge. Reports of the clinical presentation, pathologic findings, and radiographic findings of another six patients were reviewed and included, for a total patient population of 12 (mean age +/- SD, 46 +/- 13 years). RESULTS: Imaging features were strikingly similar for all tumors. In each case, the mass was ovoid, was well circumscribed, was located in the region of the hypothalamus/anterior third ventricle, and enhanced uniformly and intensely. Tumors were hyperdense to gray matter on CT scans and were isointense on T1-weighted MR images and slightly hyperintense on long-TR MR images. In two patients, vasogenic edema extended into the optic tracts, and in three, there was hydrocephalus. CONCLUSION: Chordoid glioma is a recently described unique histopathologic entity that has been added to the World Health Organization glioma classification scheme and must be included in the differential diagnosis of a suprasellar mass. Distinctive imaging features are its location, ovoid shape, hyperdensity on CT scans, and uniform intense contrast enhancement.

Adult↗
PubMed2000

Human skeletal muscle: sodium MR imaging and quantification-potential applications in exercise and disease.

PURPOSE: To use sodium 23 magnetic resonance (MR) imaging to quantify noninvasively total sodium in human muscle and to apply the technique in exercise and musculoskeletal disease. MATERIALS AND METHODS: Total [Na] sodium was determined from the ratio of the relaxation-corrected (23)Na signal intensities measured from short echo-time (0.4 msec) (23)Na images to those from an external saline solution reference. The method was validated with the blinded use of saline solutions of varying sodium concentrations. [Na] was measured in the calf muscles in 10 healthy volunteers. (23)Na MR imaging also was performed in two healthy subjects after exercise, two patients with myotonic dystrophy, and two patients with osteoarthritis. RESULTS: (23)Na MR imaging yielded a total [Na] value of 28.4 mmol/kg of wet weight +/- 3.6 (SD) in normal muscle, consistent with prior biopsy data. Spatial resolution was 0.22 mL, with signal-to-noise ratio of 10-15. Mean signal intensity elevations were 16% and 22% after exercise and 47% and 70% in dystrophic muscles compared with those at normal resting levels. In osteoarthritis, mean signal intensity reductions were 36% and 15% compared with those in unaffected knee joints. CONCLUSION: (23)Na MR imaging can be used to quantify total [Na] in human muscle. The technique may facilitate understanding of the role of the sodium-potassium pump and perfusion in normal and diseased muscle.

Adult↗
PubMed2000

Radiolabeled neuronal nitric oxide synthase inhibitors: synthesis, in vivo evaluation, and primate PET studies.

UNLABELLED: The objectives of this study were to synthesize neuronal nitric oxide synthase (NOS-I)-selective imaging agents based on the 2 potent, selective inhibitors AR-R 17443 [N-(4-((2-((phenylmethyl) (methyl)-amino)ethyl)phenyl)-2-thiophenecarboximidamide)] and AR-R 18512 [(N(2-methyl-1,2,3,4-tetrahydroisoquinoline-7-yl)-2-thiophenecarboxim idamide)] in positron-emitting form and to evaluate regional brain uptake in rodents and primates. METHODS: [11C]AR-R 17443 and [11C]AR-R 18512 were produced by N-alkylation of the corresponding desmethyl precursors using [11C]iodomethane. Regional brain uptake of [11C]AR-R 17443 and [11C]AR-R 18512 was assayed in rats and NOS-I knockout mice, and PET was performed in baboons. Tracer kinetic modeling used a 2-compartment plasma and brain tissue model. RESULTS: Yields of [11C]AR-R 17443 and [11C]AR-R 18512 ranged from 8% to 16% at the end of synthesis, with specific activities of 50-178 GBq/micromol (1,350-4,800 Ci/mmol) at the end of synthesis. In rat cerebellum and cortex at 30 min after injection, [11C]AR-R 17443 showed 1.01 +/- 0.01 and 1.63 +/- 0.12 percentage injected dose per gram (%ID/g) uptake, respectively, whereas [11C]AR-R 18512 showed 0.88 +/- 0.01 and 1.30 +/- 0.07 %ID/g uptake, respectively. Attempts to block tracer uptake by pretreatment with the NOS-I-selective inhibitor 7-nitroindazole or the corresponding unlabeled inhibitor (or desmethyl precursor to AR-R 17443 of similar potency) were unsuccessful. A small but significant (20%) decrease in cerebellar uptake of [11C]AR-R 18512 was present in NOS-I knockout mice compared with control mice. PET of [11C]AR-R 18512 in baboons with concurrent regional cerebral blood flow (rCBF) determination before and after administration of blocker showed dose-related decreases in cerebellar uptake that were greater than or equal to decreases in rCBF. Plasma metabolites accounted for 27% of total activity at 30 min after injection. Kinetic modeling of binding potentials revealed a distribution volume of 334 in cerebral blood that dropped 51% after blocker administration. CONCLUSION: Rodent studies for [11C]AR-R 17443 and [11C]AR-R 18512 showed little evidence of specific NOS-I binding. In baboons, we detected a higher uptake of [11C]AR-R 18512 in the cerebellum than in the cortex (approximately 5%, accounting for decreased rCBF because of blockade), indicating minimal specific binding. Analogs of higher affinity are likely required if this class of agents is to prove viable for PET.

Animals↗
PubMed2000

New techniques in MR imaging of brain tumors.

The past decade has seen many new MR imaging techniques that have been applied to brain tumor imaging. As MR imaging is applied further to cellular and molecular imaging (e.g., imaging of gene transfer and expression), more possibilities for brain tumor diagnosis and treatment will become evident. The superior contrast, resolution, and lack of need for image coregistration suggest that MR imaging techniques may displace PET as the preeminent modality for studying brain and tumor physiology and chemistry for indications other than receptor-based imaging. Nevertheless, the new MR imaging techniques require further histologic, physiologic, and intraoperative validation in suitable animal models and in clinical studies, and should be used to complement PET. Application of echo-planar imaging and other fast imaging sequences can permit the merger of several MR imaging studies (e.g., perfusion imaging, DWI, and MRS(I) into a typical (1-hour) clinical time slot). Synergistic information provided by these new techniques might soon enable physicians to reach the ultimate goals of noninvasive tumor grading and avoidance of having to obtain a biopsy.

Adult↗
PubMed1999

CNS vasculitis in autoimmune disease: MR imaging findings and correlation with angiography.

BACKGROUND AND PURPOSE: MR findings in CNS vasculitis and their correlation with angiography have not been clearly defined. We therefore explored three hypotheses regarding CNS vasculitis associated with autoimmune disease: 1) MR imaging is highly sensitive; 2) a typical MR appearance exists; and, 3) MR and angiographic findings correlate well. METHODS: We studied 18 patients with CNS vasculitis associated with autoimmune disease, characterized the MR lesions by type, size, number, and location, and correlated the MR findings with those of angiography. RESULTS: All patients with CNS vasculitis had abnormalities on MR studies. On average, four +/- two lesions per patient were detected on MR images. The lesions were located in the subcortical white matter (n = 20), cortical gray matter (n = 16), deep gray matter (n = 16), deep white matter (n = 9), and cerebellum (n = 9). Only 65% of MR lesions were evident on angiograms; 44% of the lesions revealed on angiograms were detected by MR. CONCLUSION: MR imaging is sensitive for CNS vasculitis. Lesions attributable to CNS vasculitis in autoimmune disease are distributed nearly equally among cortical, subcortical, and deep gray matter structures. The modest correlation between MR imaging and angiography suggests that the two techniques provide different information about CNS vasculitis and that both types of studies are needed for the complete assessment of damage caused by vascular abnormalities.

Adolescent↗
PubMed1998

Histoplasmosis mimicking vasculitis of the central nervous system.

We describe a case of disseminated histoplasmosis that was erroneously diagnosed as central nervous system vasculitis and treated with immunosuppressive therapy. Our case emphasizes the importance of excluding infections before initiating treatment for presumed central nervous system vasculitis. Clinical clues to underlying Histoplasma infections are also discussed.

Brain Diseases↗
PubMed1994

Sensitivities of noninvasive tests for central nervous system vasculitis: a comparison of lumbar puncture, computed tomography, and magnetic resonance imaging.

OBJECTIVE: To determine the sensitivities of lumbar puncture (LP), computed tomography (CT), and magnetic resonance imaging (MRI) for central nervous system (CNS) vasculitis. METHODS: We reviewed the charts and radiologic studies of 20 patients with angiogram positive CNS vasculitis. RESULTS: The patients ranged in age from 7-72 years, with a mean of 43.7 +/- 15.5 years. Twelve patients (60%) were women; 8 (40%) were men. Seven had primary angiitis of the CNS (PACNS), 8 had rheumatological illnesses (4 had systemic lupus erythematosus), and 5 had vasculitis due to other diverse etiologies, including 2 who had CNS infections. LP was positive in 8/15 angiographically proven cases, for a sensitivity of 53% [95% confidence interval (CI): 27-79]. The sensitivity of CT was 65% (11/17) (95% CI: 38-86), and that of MRI 75% (12/16) (CI: 48-93). The use of LP plus either CT or MRI was more sensitive than LP alone: for LP and CT, the sensitivity was 92% (11/12) (CI: 62-100), and for LP and MRI, 100% (12/12) (CI: 74-100). The combination of CT and MRI was not more sensitive than either test alone. CONCLUSION: The sensitivities of LP, CT, and MRI for angiogram positive vasculitis are only modest. CT and MRI may be completely normal in cases of CNS vasculitis when the angiogram is positive. LP and either CT or MRI are of additive benefit in the diagnosis of CNS vasculitis, and should be done before angiography; and, in a patient with both a normal LP and a normal CT or MRI, a CNS angiogram is unlikely to be positive for vasculitis.

Adolescent↗
PubMed1992

Preparation and evaluation of 17-ethynyl-substituted 16 alpha-[18F]fluoroestradiols: selective receptor-based PET imaging agents.

We have prepared and studied six new analogs of 16 alpha-fluoroestradiol (FES): 17 alpha- and 17 beta-ethynyl-FES (7 [FEES] and 7a), and the 11 beta-ethyl (8 and 8a) and 11 beta-methoxy (9 and 9a) derivatives, novel estrogen receptor-based PET imaging agents. The relative binding affinity (RBA) for the estrogen receptor (ER) versus FES is increased for 7, 9 and 9a but decreased for 7a, 8 and 8a. All six analogs have been labeled in the 16 alpha position with 18F by the nucleophilic displacement of the corresponding 16 beta-trifluoromethanesulfonate with nBu4N18F. Subsequent ethynylation with lithium trimethylsilylacetylide yielded the FEES analogs (total synthesis time: 120 min; effective specific activity: 200-2400 Ci/mmol). Selective uptake in the uterus was high for [18F]7, [18F]8, [18F]9 and [18F]9a (% ID/g values at 1 h: 11.2, 12.9, 9.9 and 8.3, respectively), while uptake was effectively blocked by coinjection of an excess of unlabeled estradiol. The FEES analogs, [18F]7, [18F]8 and [18F]9, exhibited the highest selectivity, in terms of target (uterus)-to-blood ratios, ever seen amongst estrogen radiopharmaceuticals, 154, 145 and 169, respectively. The analogs [18F]7a and [18F]8a displayed no uptake in the uterus, consistent with their low RBAs. Metabolism studies revealed that most of the uterine activity is unmetabolized while the blood exhibits a rapid and subsequently sustained mixture of metabolites. The muscle shows a metabolic profile intermediate to the uterus and blood. These analogs provide an array of desirable characteristics for the optimal PET imaging of ER-rich target tissues.

Animals↗
PubMed1992

Fluorine-substituted corticosteroids: synthesis and evaluation as potential receptor-based imaging agents for positron emission tomography of the brain.

We have prepared eight fluorine-substituted corticosteroids representing ligands selective for Type I and Type II corticosteroid receptor subtypes as potential imaging agents for corticosteroid receptor-containing regions of the brain. Receptor binding affinity assays show that fluorine substitution for hydroxyl or hydrogen in these steroids generally results in some reduction in affinity, with the result that the absolute affinity of these fluorine-substituted ligands for receptor is less than that typical for steroid hormones that show receptor-based, target selective uptake in vivo. Five of these compounds were prepared in fluorine-18 labeled form by a simple sulfonate ester displacement reaction, and their tissue distribution was studied in the adrenalectomized rat. There is no selective accumulation nor selective retention of the Type I selective corticosteroids (18F-RU 26752, 21-[18F]fluoroprogesterone, 21-[18F]fluoro-11 beta-hydroxyprogesterone) in either the brain, or other target tissues (pituitary, kidney, liver). The Type II selective corticosteroids (18F-RU 28362, 18F-triamcinolone acetonide) show uptake into the hippocampus which can be partially blocked by a competing ligand; in target tissues outside the brain, the blocking is more complete. All of the 18F-labeled compounds show considerable defluorination, evident as high bone activity levels. These results, coupled with earlier findings in the literature, suggest that radiolabeled corticosteroid receptor ligands with both greater metabolic stability and higher receptor binding affinity and selectivity are needed for imaging corticosteroid receptors in the hippocampus.

Adrenal Cortex Hormones↗
PubMed1991

Assessment of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone as a positron-emitting radiopharmaceutical for the detection of progestin receptors in human breast carcinomas.

We have used 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP) for imaging progestin receptors by PET in patients with primary carcinoma of the breast. In vitro binding and in vivo tissue distribution studies in rats have shown that FENP has high specific activity, high affinity for progestin receptors, and receptor-mediated uptake in target tissues. Eight patients with primary breast carcinoma were studied. Breast carcinoma was identified correctly in 50% of the patients with progestin-receptor-positive tumors; however, the FENP uptake was not correlated with progestin-receptor levels. We noted a low target-to-background ratio in humans, with high relative activity in the spine, blood pool, and normal breast tissue. Our findings indicate that FENP is not a suitable agent for imaging progestin receptors in humans.

Breast Neoplasms↗
PubMed1990

Target tissue uptake selectivity of three fluorine-substituted progestins: potential imaging agents for receptor-positive breast tumors.

We have studied three new fluorine-substituted progestins (1-3) as potential imaging agents for progesterone receptor (PgR)-positive human breast tumors. Two of these are fluorine-substituted analogs of the potent progestin R5020 (promegestone), derived from (21S)-hydroxy R 5020 (RU 27987) and (21R)-hydroxy R 5020 (RU 27988), known metabolites of R 5020, which have affinities for PgR that are 116 and 4%, respectively (relative to R 5020 = 100%). These precursors were protected as their 3,3-dioxolane derivatives and converted to the 21-trifluoromethanesulfonate derivatives. Fluoride ion displacement, followed by acid-catalyzed deprotection, furnished in good yield the epimeric fluoroanalogs, (21S)- and (21R)-fluro R 5020 (1 and 2, affinities for PgR, 11 and 45%, respectively). These compounds were also prepared in 18F labeled form by the same route, in 14-32% overall radiochemical yield (decay corrected; synthesis time 90 min; sp. act. 370-1060 Ci/mmol). In tissue distribution studies in estrogen-primed immature rats, uterus-to-muscle ratios were 4.3 at 1 h for the 21S-epimer and 1.1 for the 21R-epimer, paralleling their relative binding affinities. Considerable metabolic defluorination was observed. The third fluorine-substituted progestin, DU 41165, has a novel retroprogesterone (9 beta, 10 alpha) structure, substituted with fluorine at C-6; its binding affinity is 145% relative to R 5020, and it was prepared in tritium-labeled form by acetylation of DU 41231, the 17 alpha-hydroxy precursor, with [3H]acetic anhydride. In estrogen-primed immature rats, this compound shows uterus-to-muscle ratios of 15 at 1 h, and 18-71 between 2 and 6 h, suggesting that compounds in this retroprogesterone series may be very promising candidates for selective imaging of PgR-positive tissues and tumors.

Animals↗
PubMed1990

11 beta-methoxy-, 11 beta-ethyl- and 17 alpha-ethynyl-substituted 16 alpha-fluoroestradiols: receptor-based imaging agents with enhanced uptake efficiency and selectivity.

We have prepared three analogues of 16 alpha-fluoroestradiol (FES) substituted either with an 11 beta-methoxy group (1, 11 beta-MeO-FES), an 11 beta-ethyl group (2, 11 beta-Et-FES), or a 17 alpha-ethynyl group (3, 17 alpha-ethynyl-FES). These substituents all lower the binding of FES to the serum proteins alphafetoprotein and sex steroid binding protein, but their effect on estrogen receptor binding varies: Receptor binding is increased by the 11 beta-ethyl and 17 alpha-ethynyl groups, but decreased by the 11 beta-methoxy group. These substituents also have a parallel effect on the lipophilicity, and hence the nonspecific binding estimated for these compounds. All three compounds were prepared in fluorine-18 labeled form, at effective specific activities of 90-1600 Ci/mmol, by fluoride ion displacement reactions as done previously with FES. Tissue distribution studies in immature rats show high uptake selectivity by target tissue (uterus) and effective competition by an excess of unlabeled estradiol. Percent injected dose per gram values (% ID/g) at 1 h are 6% for 11 beta-MeO-FES and 11-13% for 11 beta-Et-FES and 17 alpha-ethynyl-FES (FES itself has a % ID/g of 9%). Uptake selectivity in terms of uterus to blood or muscle ratios at 1 h is highest for 11 beta-MeO-FES and 17 alpha-ethynyl-FES (43-149). Metabolic consumption studies show that most activity in uterus is unmetabolized and in blood is rapidly and nearly completely metabolized. In muscle, FES and the substituted estrogens show intermediate levels of metabolic consumption; in some cases activity in muscle extracts is nearly unmetabolized. Thus, the substituents on FES cause major alterations in receptor and nonreceptor binding affinity, uptake efficiency and selectivity, and extent of metabolism. It is not readily clear, however, whether the alterations in uptake efficiency and selectivity are the result of differences in receptor or nonreceptor binding or lipophilicity, or altered patterns of metabolism. Nevertheless, these compounds should be useful in providing a spectrum of uptake properties that could be used for imaging different estrogen-receptor-containing structures.

Animals↗
PubMed1988

Uptake of three [3H]progestins by target tissues in vivo: implications for the design of diagnostic imaging agents.

We have investigated the tissue distribution of radioactivity for 0.5-4 h following the i.v. injection of three tritium-labeled progestins in estrogen-primed, immature rats. Whereas [3H]progesterone shows minimal uterine uptake (less than 0.7% injected dose per gram; %ID/g), the two higher affinity, synthetic progestins [3H]R 5020 (promegestrone) and [3H]ORG 2058 show highly selective uptake that reaches 4-5% ID/g by 1-3 h. The uterus to non-target tissue activity ratio at 2-4 h is approximately 12-20 for R 5020 and ORG 2058, but less than 2 for progesterone; the uterus to blood activity ratio for R 5020 is also high (approximately 15), but is lower for ORG 2058, possibly due to the accumulation of radiolabeled metabolites in the blood. The uterine uptake is selectively blocked by simultaneous injection of a large dose of unlabeled steroid, indicating that the uptake is mediated by a high affinity, low capacity binding system, presumably the progesterone receptor. Pronounced uptake is also observed by the liver and into fat, but is not receptor-mediated. The highly selective target tissue uptake by the two synthetic steroids, but not by progesterone, indicates that one must have ligands with sufficiently high affinity for the target tissue receptor, as well as low affinity for certain non-receptor binding proteins, in order to obtain adequate contrast between target and non-target tissues in dynamic uptake studies. These guidelines will be important in the development of suitable in vivo imaging agents based on the progesterone receptor.

Animals↗