International workshop on standardization in clinical MRS measurements: proceedings and recommendations.
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Biomedical subjects
Publications and source records attributed to S J Nelson.
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The Metathesaurus is a machine-created, human edited and enhanced synthesis of authoritative biomedical terminologies. Its formal properties permit it to be a) exploited by computers, and b) modified and enhanced without compromising that usage. If further constraints were imposed on the existence and identity of Metathesaurus relationships, i.e., if every Metathesaurus concept had a "genus" and a "differentia," then the Metathesaurus could be converted into an "Aristotelian Hierarchy." In this sense, a genus is a concept that classifies another concept, and a differentia is a concept that distinguishes the classified concept from all other concepts in the same class. Since, in principle, these constraints would make the Metathesaurus easier to leverage and maintain computationally, it is interesting to ask to what degree the maintenance and enhancement procedures now in place are producing a Metathesaurus that is also an "Aristotelian Hierarchy." Given a liberal interpretation of the current Metathesaurus schema, the proportion of the Metathesaurus that is "Aristotelian" in each annual version is increasing in spite of dramatic concurrent increases in the number of Metathesaurus concepts. Without formality there is no modifiability nor scalability. [1] We need formal methods and computer-based tools that can help us with the task [of controlled medical vocabulary construction]. We need research in which controlled vocabulary development is the focus rather than a stepping stone for work on other theories and applications. [2]
Children with AIDS frequently have neurological manifestations due to complications of immunodeficiency or intrinsic effects of human immunodeficiency virus type 1 (HIV-1) on the central nervous system (CNS). The most common neurological disorders not directly related to HIV-1 infection include cerebrovascular disease and lymphoma. Global anoxic-ischemic and necrotizing encephalopathies are frequent, while CNS hemorrhages and arteriopathies are less frequent. Opportunistic CNS infections are uncommon, limited predominantly to monilial and cytomegaloviral encephalitides. Only a few cases of CNS toxoplasmosis have been reported in children. CNS lymphomas often occur in the setting of systemic polymorphous, polyclonal B-cell proliferations that have been associated with Epstein-Barr virus infection. Intrinsic effects of HIV-1 on the CNS include microcephaly, diffuse gliosis, basal ganglia mineralization, HIV encephalitis, and corticospinal tract degeneration. Although viral antigens can be detected in microglia and multinucleated cells in HIV encephalitis, most of the CNS effects of HIV-1 infection cannot be attributed to detectable levels of viral antigen, suggesting that the pediatric CNS is unusually susceptible to low-level HIV-1 infection or to systemic effects of HIV-1 infection, possibly mediated by soluble factors, including the inflammatory cytokines, interleukin-1 beta, and tumor necrosis factor-alpha, which have been shown to be increased in serum and cerebrospinal fluid of children with AIDS.
T1 relaxation times of PCr and beta-ATP in human cardiac and skeletal muscle were evaluated using a variable nutation method. This allows T1 measurements with a constant TR and a significant reduction in acquisition time compared with the partial saturation method. Four 1D CSI datasets were obtained using 30 degrees, 45 degrees, 60 degrees, and 90 degrees BIR-4 adiabatic RF pulses within 40 min. The T1 of the phosphate phantom obtained with this method agreed with values obtained with the partial saturation method. The T1s of PCr and beta-ATP in heart are 3.98 +/- 0.18 s and 1.86 +/- 0.16 s (mean +/- SE). Our results demonstrated that T1 values in heart and skeletal muscle are not significantly different.
Left ventricular (LV) volumes and mass were evaluated in 10 healthy volunteers with breath-hold cine magnetic resonance (MR) imaging. The results were compared with those obtained with conventional cine MR imaging. The breath-hold studies showed no ghosting artifact, and cardiac edges were clearly identified because of the reduced blurring. Measurements of LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV mass obtained with breath-hold cine MR imaging showed close correlation with those obtained with conventional cine MR imaging (r = .98, .97, and .99, respectively). The interobserver variabilities for LVEDV, LVESV, and LV mass determined with breath-hold cine MR imaging (4.0%, 8.0%, and 3.7%, respectively) were equal to or less than those determined with conventional cine MR imaging (4.0%, 8.6%, and 5.0%, respectively). The authors conclude that breath-hold cine MR imaging is highly useful because an accurate assessment of cardiac function is obtained in less than 5 minutes.
PURPOSE: Image-guided, single-voxel, localized proton magnetic resonance (MR) spectroscopy was performed to assess white matter in childhood adrenoleukodystrophy (ALD). MATERIALS AND METHODS: Eleven X-linked ALD subjects, seven with neurologic symptoms or white matter lesions at MR imaging and four asymptomatic patients, were compared with nine aged-matched, healthy volunteers. RESULTS: Compared with those from normal white matter, MR spectra from white matter lesions (n = 6) showed 65% reduction in the ratio of N-acetyl aspartate (NAA) to total creatine (tCr) (P < .01); 55% increase in the ratio of choline-containing compounds (Cho) to tCr (P < .02); substantial levels of tCr; 94% increase in the ratio of glutamate, glutamine, or inositol to tCr (P < .02); and lactate accumulation in four patients. Patients without brain lesions (n = 4) exhibited a 51% increase in Cho-to-tCr ratio (P < .01) and 11% nonsignificant increase in NAA-to-tCr ratio. CONCLUSION: Proton MR spectroscopy may prove a valuable technique for noninvasive diagnostic and prognostic assessment of ALD.
Can new medical knowledge be recognized computationally? We know knowledge is changing, and our knowledge-based systems will need to accommodate that change in knowledge on a regular basis if they are to stay successful. Computational recognition of these changes seems desirable. It is unlikely that low level objects in the computational universe, bits and characters, will change much over time, higher level objects of language, where meaning begins to emerge, may show change. An analysis of ten arbitrarily selected paragraphs from the Medical Knowledge Self-Assessment Program of the American College of Physicians was used as a test bed for nominal phrase recognition. While there were words not known to Meta-1.2, only 8 of the 32 concepts new to the primary author were pointed to by new words. Use of a barrier word method was successful in identifying 23 of the 32 new concepts. Use of co-occurrence (in sentences) of putative nominal phrases may reduce the amount of human effort involved in recognizing the emergence of new relationships.
Most care-giver "knowledge" needs arise at the point of care and are "patient-centered." Many of these knowledge needs can be met using existing on-line knowledge sources, but the process is too time-consuming, currently, for even the computer-proficient. We are developing a set of public domain standards aimed at bringing potentially relevant knowledge to the point of care in a straight-forward and timely fashion. The standards will a) make use of selected items from a Computer-based Patient Record (CPR), e.g., a diagnosis and measure of severity, b) anticipate certain care-giver knowledge needs, e.g., "therapy," "protocols," "complications," and c) try to satisfy those needs from available knowledge sources, e.g., knowledge-bases, citation databases, practice guidelines, and on-line textbooks. The standards will use templates, i.e., fill-in-the-blank structures, to anticipate knowledge needs and UMLS Metathesaurus enhancements to represent the content of knowledge sources. Together, the standards will form the specification for a "Knowledge-Server" (KS) designed to be accessed from any CPR system. Plans are in place to test an interim version of this specification in the context of medical oncology. We are accumulating anecdotal evidence that a KS operating in conjunction with a CPR is much more compelling to users than either a CPR or a KS operating alone.
The application of spectroscopy techniques to the study of normal and pathological tissue is currently limited by the difficulties of acquiring precisely localized spectra and analyzing the resulting, relatively low signal-to-noise data. Interpretation of multivoxel spectroscopy data is greatly facilitated by estimating peak parameters and representing their spatial distribution as metabolite images. We present here the new algorithm MIMSTATS, which performs an analysis of these images and determines whether the variations in the images are statistically significant. The algorithm has been developed and tested by application to 31P CSI data from the human forearm and brain. Our results demonstrate that MIMSTATS can detect signal at a very low signal-to-noise ratio in a reliable and reproducible fashion and provides a sound basis for testing hypotheses concerning differences in distribution of metabolites.
Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.
Disseminated histoplasmosis (DH) and progressive multifocal leukoencephalopathy occur in acquired immunodeficiency syndrome (AIDS). At autopsy, DH patients with central nervous system involvement almost always show extensive involvement of the lungs and reticuloendothelial system in addition to the brain, and progressive multifocal leukoencephalopathy is manifest as multiple demyelinating lesions in several locations in the brain. We describe an AIDS patient with a long history of aggressively treated DH who died with DH in the brain only; fungus was not found elsewhere at autopsy. In addition, there was a papovavirus infection restricted to the cerebellum with predominant involvement of the internal granular cell layer; again, demyelinating lesions were not found elsewhere in the brain. Each of these patterns of brain involvement is rare. As the incidence of AIDS increases and patients are treated aggressively, the frequency of unusual neuropathologic patterns of opportunistic infections may be expected to increase.
OBJECTIVE: The presence of HIV-1 in postmortem brain tissue from 31 patients with AIDS and 12 HIV-1-negative controls was investigated. DESIGN: Most laboratories have access to the methods used. We readily applied in situ hybridization and immunohistochemistry to archival formalin-fixed paraffin-embedded (FFPE) brain specimens. METHODS: The techniques used to detect HIV-1 were explant culture, in situ hybridization with 35S-labeled polymerase (pol) gene riboprobes and immunohistochemistry with monoclonal antibody to gp41. RESULTS: HIV-1 was isolated from explant cultures in 13 out of 20 (65%) patients, whereas HIV-1-infected cells were detected in FFPE brain tissue from nine out of 26 (35%) patients examined by in situ hybridization and in seven out of 26 (27%) patients examined by immunohistochemistry. CONCLUSIONS: Although the isolation technique was the most sensitive of the three techniques tested, infected cells may be identified with in situ hybridization in conjunction with immunohistochemistry.
Two-dimensional phosphorus chemical shift imaging (2D-31P-CSI) was used to investigate macroscopic heterogeneity within the flexor digitorum profundus (FDP) muscle of the human forearm during exercise. Subjects performed low-frequency steady-state finger flexion exercise at submaximal work levels using a bulb ergometer. The number of fingers actively involved in finger flexion exercise was varied in a total of 12 experiments. Active muscles could be determined by the increase of Pi and decrease of phosphocreatine observed in the localized spectra. Within the FDP, regions of active and inactive fibers were significantly different in levels of Pi and phosphocreatine (P less than 0.01) during flexion of individual fingers. Individual flexion of the index finger was found to involve only fibers in the deep region of the FDP. Fibers in the central region were found to be involved in flexion of the middle finger, and fibers in the superficial region were involved in flexion of the ring and little fingers. The results of this study demonstrate the potential of 2D-31P-CSI for in vivo investigation of intramuscular heterogeneity in human skeletal muscle.
Dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 produced by UC 11065 were evaluated as anthelmintics. Assays used to examine these compounds included effects on the free-living nematode Caenorhabditis elegans, ability to clear target nematodes (Haemonchus contortus and Trichostrongylus colubriformis) from jirds, and clearance of Haemonchus contortus from lambs. A crude extract of UC 11065 containing dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 was active against C. elegans and against H. contortus in the jird. Purified and/or synthetic samples of dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 were tested in the jird model; only dioxapyrrolomycin exhibited appreciable activity against H. contortus (greater than or equal to 90.9% clearance at 0.33 mg/jird), while none of the compounds showed appreciable activity against T. colubriformis. Dioxapyrrolomycin cleared 99.9% of H. contortus from lambs at 12.5 mg/kg. An in vitro migration study using susceptible and closantel-resistant H. contortus showed there is cross-resistance between dioxapyrrolomycin and closantel. Dioxapyrrolomycin appears to be a narrow-spectrum anthelmintic which works through a closantel-like mode-of-action.
The third version of the UMLS Metathesaurus, Meta-1.2, to be released in October 1992, will have a simpler schema and simpler distribution formats than the first two versions, Meta-1.0 and Meta-1.1 released in October 1990 and 1991, respectively. For one thing, it will have only a single kind of entry (Concept), rather than three (Concept, Related, and Synonym). Further, the Relational Format, will consist of four logical relations, or tables, instead of the nearly three score different tables used to represent the same kind of information in Meta-1.1. These four tables will contain, respectively, (1) the names of each concept, (2) the relationships between concepts, (3) attributes of the concepts, and (4) a word-based index into the concept names. We argue that the new schema and formats provide a better conceptual model of the Metathesaurus, and represent the information contained there more uniformly. Even though these changes are incremental and evolutionary, both users and software developers should find the Meta-1.2 significantly easier to understand, and the information contained in it significantly easier to use.
Meta-1.1, the UMLS metathesaurus, represents medical knowledge in the forms of names of concepts and links between those concepts. The representations of the semantic neighborhood of a concept can be thought of as dimensions of the property of semantic locality and include term information (broader, narrower, or otherwise related), the contextual information (parent-child, siblings in a hierarchy), the semantic types, and the co-occurrence data (links discovered empirically from concepts used to index the medical literature.) The degree of redundancy of each of these dimensions was investigated by reviewing the extent of multiple presentations of concepts which appear as related to a given concept. The degree of overlap was surprisingly small. While the co-occurrence data finds some of the links represented by other dimensions, those links are but minute fractions of the vast amount of co-occurrence derived links. Because parent-child relationships are often subsumptive (or categorical) in nature, it might be expected that siblings usually share the same semantic types. While true in the aggregate, the wide variance in percent of types shared may reflect the intended usages of the source vocabularies. Noun phrases were extracted from the definitions of 40 concepts in Meta-1 in order to assess systematically the coverage of important concepts by Meta-1, and to assess whether the links between these definitional concepts, which may have special value, and the concept being defined were indeed present. Out of 161 of these definitional concepts, 29 were not represented in Meta-1, and 37 of those represented in Meta-1 had no direct link to the concept they were defining.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain.