Search PubMed⌕ Search

Biomedical subjects

C C Meltzer

Publications and source records attributed to C C Meltzer.

71 records · Page 4Linked to original sources

Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness.

In a previous study of 10 drug-naive schizophrenic patients, the density of D2 dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N-[11C]methyl-spiperone ([11C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D2-like dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging? Are D2-like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. D2-like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D2 dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects.

Adult↗

Mirror-image optic nerve dysplasia with associated anisometropia in identical twins.

BACKGROUND: Monozygotic (MZ) or "identical" twins arise from a single fertilized egg, which divides into two embryos at an early stage of development. As a result, MZ twins have identical genomes and are always of the same sex. METHODS: A case of optic nerve hypoplasia and anisometropia, in association with mirror-image presentation in a set of 12-year-old identical twins, is reported. The monozygotic twinning event responsible for identical twins--as well as the rare phenomenon of mirror imaging--is described. RESULTS: The combined occurrence of anisometropia and optic nerve hypoplasia in mirror-image presentation in a set of monozygotic twins provides a unique opportunity to study the genetic versus environmental influences on the development of optic nerve hypoplasia. CONCLUSIONS: Although the cause of optic nerve hypoplasia remains unclear, its associated mirror-image presentation in this case suggests a possible genetic predisposition.

Anisometropia↗

MR-based correction of brain PET measurements for heterogeneous gray matter radioactivity distribution.

Partial volume and mixed tissue sampling errors can cause significant inaccuracy in quantitative positron emission tomographic (PET) measurements. We previously described a method of correcting PET data for the effects of partial volume averaging on gray matter (GM) quantitation; however, this method may incompletely correct GM structures when local tissue concentrations are highly heterogeneous. We have extended this three-compartment algorithm to include a fourth compartment: a GM volume of interest (VOI) that can be delineated on magnetic resonance (MR) imaging. Computer simulations of PET images created from human MR data demonstrated errors of up to 120% in assigned activity values in small brain structures in uncorrected data. Four-compartment correction achieved full recovery of a wide range of coded activity in GM VOIs such as the amygdala, caudate, and thalamus. Further validation was performed in an agarose brain phantom in actual PET acquisitions. Implementation of this partial volume correction approach in [18F]fluorodeoxyglucose and [11C]-carfentanil PET data acquired in a healthy elderly human subject was also performed. This newly developed MR-based partial volume correction algorithm permits the accurate determination of the true radioactivity concentration in specific structures that can be defined by MR by accounting for the influence of heterogeneity of GM radioactivity.

Aged↗

MR imaging of the meninges. Part I. Normal anatomic features and nonneoplastic disease.

The structural organization of the dura and leptomeninges is reflected in its magnetic resonance (MR) imaging appearance in normal and disease states. Two distinct enhancement patterns are characterized: dura-arachnoid enhancement and pia-subarachnoid space enhancement. The dura-arachnoid pattern consists of curvilinear enhancement overlying the brain and immediately deep to the inner table of the calvaria, as well as along the falx and tentorium. Pial enhancement closely follows the brain surface into sulci and outlines the basal cisterns. Recognition of these enhancement patterns and other MR imaging characteristics may enhance the role of MR imaging in the detection, diagnosis, and follow-up of neoplastic and nonneoplastic disorders affecting the meninges. The focus of this article (Part I) is the MR appearance of the normal meninges and nonneoplastic causes of meningeal disease. Part II of this series will discuss neoplastic conditions affecting the coverings of the brain and spinal cord with an emphasis on pathways of disease spread.

Cerebrovascular Disorders↗

Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging.

Measurements of cerebral metabolism in patients with Alzheimer's disease (AD) using PET are artifactually depressed due to partial volume averaging of brain tissue activity with enlarged CSF spaces. To investigate the effects of correction for the expansion of CSF spaces on regional metabolic measures, as well as the correlations between neuropsychological test results and resting cerebral metabolism before and after partial volume correction, we applied an MRI-based method of partial volume correction to 18F-fluorodeoxyglucose (FDG)-PET data from eight patients diagnosed with probable AD and ten healthy elderly individuals. Before correction, the AD group had significantly lower cortex-to-cerebellum ratios in the posterior temporal, parietal, and frontal lobes in comparison to the control subjects. Partial volume correction of PET data resulted in 19 to 49% increases in regional activity in the AD group and 16 to 38% increases in the control group. The patients' persistence of significant hypometabolism in the frontal, posterior temporal, and parietal regions after partial volume correction suggests that a true reduction in regional cerebral glucose metabolism occurs in AD, even though its magnitude is a result of both metabolic reductions and the effects of atrophy. Partial volume correction of PET data in the AD group had a significant impact on the correlations between regional glucose metabolism and neuropsychological performance. These findings suggest that accounting for differential extent and distribution of cerebral atrophy in patients with AD and in healthy individuals may potentially improve our ability to interpret specific cognitive dysfunction in the context of the functional imaging data.

Aged↗

The striated cerebellum: an MR imaging sign in Lhermitte-Duclos disease (dysplastic gangliocytoma).

PURPOSE: To correlate the magnetic resonance (MR) imaging features of and histologic findings in Lhermitte-Duclos disease (LDD) (dysplastic gangliocytoma). MATERIALS AND METHODS: MR imaging and histologic data from eight patients with the diagnosis of LDD were retrospectively reviewed. Gross pathologic specimens were also available in one case. Contrast material-enhanced MR images were obtained in seven of the eight patients. RESULTS: At MR imaging, a non-enhancing mass in the cerebellar hemisphere was characterized by a striated pattern of hyperintensity on T2-weighted images and corresponding hypointensity on T1-weighted images, which represented the abnormally thickened folia. None of the masses demonstrated enhancement. CONCLUSION: Most other cerebellar masses destroy the folial pattern and show enhancement. The nonenhancing striated MR appearance of thickened folia in patients with LDD is distinctive and should suggest this diagnosis.

Adult↗

Computed tomography appearance of bone metastases of leiomyosarcoma.

Bone lesions in leiomyosarcoma are uncommon. When encountered, they are usually a late manifestation of disease seen in the setting of widespread systemic metastases. We present five cases of metastatic leiomyosarcoma, including one in which a bone lesion predated detection of a primary gastric leiomyosarcoma and one in which bone metastases signaled disease recurrence. Computed tomography in 14 of 16 osseous leiomyosarcomas demonstrated a lytic, non-expansile pattern.

Adult↗

Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

Amygdala↗

Case report 698: Osteoma of the clavicle.

We have presented a case of an osteoma of the clavicle in a 41-year-old man. The possibility of alternate diagnoses--in particular, ancient osteochondroma, posttraumatic hyperostosis, and parosteal osteosarcoma--was addressed. However, the pathological examination was most consistent with the diagnosis of osteoma. This benign bone lesion is most often found in the calvarium, jaw, and face. Osteomas of long bones remain extremely rare, except in the setting of Gardner's syndrome.

Adult↗

Tumoral calcinosis causing bone erosion in a renal dialysis patient.

Tumoral calcinosis is a rare disorder manifest by large calcific periarticular masses. Associated bone destruction has been described previously only once. The radiographic and computed tomographic (CT) findings of bone erosion in a case of tumoral calcinosis in a renal dialysis patient are presented. Although the presence of bone destruction may suggest a neoplasm, it does not exclude the diagnosis of tumoral calcinosis.

Aged↗

A positron emission tomography (PET) study of autobiographical memory retrieval.

Memory for the experiences of one's life, autobiographical memory (AM), is one of the most human types of memory, yet comparatively little is known of its neurobiology. A positron emission tomography (PET) study of AM retrieval revealed that the left frontal cortex was significantly active during retrieval (compared to memory control tasks), together with activation in the inferior temporal and occipital lobes in the left hemisphere. We propose that this left frontal lobe activation reflects the operation of control processes that modulate the construction of AMs in posterior neocortical networks.

Adult↗

Anatomical localization for PET using MR imaging.

Accurate localization of an imaging plane of interest is often needed prior to a positron emission tomographic (PET) study. We have developed a simple method for accurate and reproducible selection of an imaging plane for PET using magnetic resonance (MR) imaging. This method is useful when optimal sampling of specific brain structures, such as small subcortical nuclei, or when a specific imaging angle is required for the PET study. An external localizing device, consisting of a series of tubes visible on MR, is affixed to an individually fitted thermoplastic mask. This mask system is worn by the patient during both the MR and PET studies. A plane of interest is planned from the sagittal MR image and defined by its relation to the localizing device and to the MR scanner's "landmark" or reference position. This plane is transferred to the mask by means of a calibrated alignment laser. The coplanar acquisition of MR and PET images allows individualized analysis of brain structure-function relationships. Phantom studies demonstrated the accuracy and reproducibility of imaging plane selection by this method to be within 1 mm and 1 degree. Application of the localization protocol in a human subject is also presented.

Adult↗

Correction of PET data for partial volume effects in human cerebral cortex by MR imaging.

Due to the limited spatial resolution of positron emission tomography (PET), the accuracy of quantitative measurements of regional metabolism or neuroreceptor concentration is influenced by partial volume averaging of brain with CSF, bone, and scalp. This effect is increased in the presence of cortical atrophy, as in patients with Alzheimer disease (AD). Correction for this underestimation in PET measurements is necessary for the comparison of AD patients and normal controls. We have developed a method for three-dimensional correction of human PET data using magnetic resonance (MR) imaging. A composite brain tissue image is created by summing the binary representation of nine MR images, weighted to the PET z-axis line-spread function. This composite tissue image is convolved to the resolution of the PET image. The original PET image is divided by the convolved tissue image on a pixel-by-pixel basis, resulting in an atrophy-corrected PET image in which count density represents activity per volume of brain tissue rather than spatial volume. This has been performed in [11C]carfentanil mu-opiate receptor PET studies of the temporal cortex in two AD patients and one normal volunteer. After correction, average regional increases in count density were 11% (range = 4-21%) in the normal and 46% (range = 28-99%) and 48% (range = 14-109%) in the patient studies. The accuracy of this method of partial volume correction was estimated using a spherical phantom.

Aged↗

Influence of spatially heterogeneous background activity on "hot object" quantitation in brain emission computed tomography.

PURPOSE: Our goal was to evaluate the influence of spatially heterogeneous background activity on "hot object" quantitation in brain emission CT. METHOD: We studied the effects of spatially heterogeneous background activity on hot object quantitative recovery in simulations of both spheres and realistic brain distributions (utilizing human MRI data). RESULTS: Significant underestimation of object activity concentration was seen for both cortical and subcortical hot objects, with increasing underestimation for increasing hot object/surrounding gray matter contrast. Significant "spill-in" of counts from surrounding activity was present. CONCLUSION: Hot objects are significantly influenced by both "spill-out" and "spill-in." Qualitative and quantitative analyses of such objects must explicitly consider both spill-out and spill-in; this implies a correction scheme that goes beyond simple division of the observed value by a conventional recovery coefficient.

Brain↗

[Neuropharmacology and receptor studies in the elderly].

Functional brain imaging has provided unique and exciting opportunities to strengthen our knowledge of the biological substrate of the aging brain and neuropsychiatric disorders. Positron emission tomography (PET) is a particularly powerful tool for quantifying the neurobiological correlates of cognition, mood and behavior. Initial PET studies of aging, psychiatric disorders and neurodegenerative disease focused primarily on generalized physiological parameters such as cerebral blood flow and metabolism, and early neuroreceptor imaging studies relied on relatively non selective markers. New, selective receptor radioligands now offer a previously inaccessible means to investigate the dynamic relationships among neurochemistry, aging and psychopathology in vivo. This approach has substantial advantages over peripheral (platelet and cerebrospinal fluid) markers, neuroendocrine challenge studies, animal models, and postmortem receptor binding assays. Advances in tracer kinetic modeling, magnetic resonance imaging (MRI) to PET registration, radiochemistry techniques, instrumentation and image processing have helped pave the way for increased emphasis on functional imaging studies of neuropsychiatric disorders of the elderly. The capability to correct PET image data for the confounding effect of cerebral atrophy permits relationships among age related brain changes and neurobiological disease mechanisms to be more accurately examined in the course of normal aging and in elderly patient populations.

Aging↗

[Imaging of mild cognitive impairment].

The refinement of in vivo imaging approaches to investigating the structure and function of the aging brain has provided the opportunity to strengthen our knowledge of the biological substrate of normal aging and late life neurological and psychiatric disorders. While postmortem studies are biased toward the end stages of disease, functional and structural imaging have permitted us to characterize the brain changes accompanying early Alzheimer s disease (AD). As more effective therapeutic approaches to slowing (and potentially reversing) disease progression are developed, the role of imaging in determining pre AD or high risk conditions becomes increasingly important. The goal of applying non invasive means to identify the transition state of mild cognitive impairment (MCI) is of considerable public health importance. Further, emerging imaging strategies may be used to monitor the efficacy of therapeutic regimens.

Aged↗