Diffusion tensor MR imaging of the human brain

PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.     

The anatomical basis of anal endosonography. A study in postmortem specimens

PURPOSE: Anal endosonography is an imaging modality new to the diagnostic workup of incontinence. Interpretations even of normal endosonomorphologic findings now vary considerably. The conjoined longitudinal muscle (LM), a widely ignored structure, has until recently not been fully recognized by anal endosonography. The aim of this study, therefore, was to accurately determine the normal anatomy of the anal canal and correlate it with the findings obtained by anal endosonography. METHODS: Eight postmortem specimens of the anal canal were examined by endosonography. The findings were correlated with macroscopical dissection and gross sectional histology of the same specimens. RESULTS: The external echogenic ring is composed of two anatomical structures: the LM and the external anal sphincter (EAS). However, during anal endosonography the LM cannot always be differentiated from the EAS. Histologically, the relation of the diameters of the LM and the EAS ranged from 0.45:1 to 1.25:1. The narrow hyperechogenic ring between the inner hypoechoic layer and the external hyperechoic ring is an artificial finding that cannot be related to a distinct anatomical structure and most likely represents a sonographic interface. CONCLUSIONS: This study exactly outlines the relation of diameters of the conjoined longitudinal muscle and external anal sphincter for the first time. Until now, the LM has been underestimated in its dimensions. The role of such a thick muscular structure should be included in the conception of anal continence in the future. Especially in view of the fact that anal endosonography is increasingly used in the diagnostic workup of incontinence and fistula in ano, it is essential to understand the anatomical basis of endosonography. This study accurately delineates the sonomorphology of the anal muscles. When viewed in light findings reported here, endosonographic findings in diseases of the anal canal are nor based on a correct idea of the correlation between endosonomorphology and anal anatomy.     

MR imaging of symptomatic osteochondromas with pathological correlation

Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules depends on translocation of cytosolic peptides into the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP). Peptide transport by TAP is thought to include at least two steps: initial binding of peptide to TAP, and its subsequent translocation requiring ATP hydrolysis. These events can be monitored in peptide binding and transport assays. Previous studies have shown that the efficiency of peptide transport by human, mouse and rat transporters varies according to the C-terminals of peptide substrates in an allele and species-specific manner. However, it has not been clear during which step of peptide interaction with TAP selection occurs. We used an assay monitoring the peptide binding step to study the binding affinity of a library of 199 peptides for human TAP and the two major allelic rat TAP complexes. We observed a dominant influence of the C-terminus on peptide binding affinity for all transporters, and highly restrictive selection of peptides with aliphatic and aromatic C-terminals by rat TAP1/TAP2u complexes. The selectivity of peptide binding to rat TAP complexes is in full accordance with published data on selective peptide transport and on control of antigen presentation by rat TAP. These results strongly suggest that (i) peptide selection by TAP occurs exclusively in the initial binding step; (ii) all factors involved in peptide selection by TAP are present in insect cells.     

Hepatic lesion detection at MR imaging: a comparative study with four sequences

PURPOSE: To compare results with the following magnetic resonance (MR) imaging sequences in the detection of focal hepatic lesions: fast spin-echo (SE) before and after administration of superparamagnetic iron oxide (SPIO) particles, fat-suppressed T2-weighted SE, and dynamic gadolinium-enhanced fast low-angle shot (FLASH). MATERIALS AND METHODS: In 26 patients with known malignancy and documented focal liver lesions, 1.0-T MR imaging was performed prior to hepatic resection. All images were reviewed independently by four blinded observers. Sensitivity was calculated for each sequence and for each observer by means of alternative-free-response receiver operating characteristic (ROC) methods. RESULTS: The mean area under the alternative-free-response ROC curve with SPIO-enhanced fast SE (0.85) was significantly greater (P < .02) than that with all other sequences. Detection was significantly improved with SPIO-enhanced fast SE compared with dynamic gadolinium-enhanced FLASH (which was the best of the other three sequences) for all lesions (P < .002) and for malignant lesions (P < .0002). CONCLUSION: Findings with the SPIO-enhanced fast SE sequence improved detection of focal liver lesions and had the highest diagnostic accuracy.     

Diltiazem and pentoxifylline determination in postmortem specimens

A 78-year-old woman was found dead in her basement. Qualitative screening of available postmortem specimens detected the presence of diltiazem and pentoxifylline. Quantitations were carried out by gas chromatography using nitrogen-phosphorus detection and confirmed by gas chromatography-mass spectrometry with the following results: blood, 0.59 mg/dL diltiazem and 0.63 mg/dL pentoxifylline; urine, 1.17 mg/dL diltiazem and 0.08 mg/dL pentoxifylline; bile, 0.40 mg/dL diltiazem and 0.22 mg/dL pentoxifylline; gastric contents, 0.28 mg/dL diltiazem and 0.02 mg/dL pentoxifylline. Both drugs were found qualitatively in formaline-fixed tissues.     

Effects of cocaine on dopamine receptor gene expression: a study in the postmortem human brain

The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human.     

Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat

This study characterized agent differential permeability, three-dimensional tumor volume, and survival in an LX-1 human small cell lung carcinoma intracerebral xenograft model in the nude rat. The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor. Magnetic resonance imaging and histology were used to quantitate intracerebral tumor volume (mm3). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, and subcutaneous tumor decreased with increasing molecular weight of the agent, regardless of the number of days after inoculation. Accessible tissue space in intracranial tumor increased between 8 and 16 days for all agents except dextran 70. There was little change in the subcutaneous tumor or other tissues with time. Tumor volume calculations from imaging studies correlated with volumetric measurements from histological sections (r2 = 98.5%) and illustrated natural tumor progression (9 to 225 mm3). These results provide a basis for therapeutic design based on differential permeability of specific agents and the ability to quantitatively measure brain tumor volume for accessing tumor response.     

Multivoxel proton MR spectroscopy and hemodynamic MR imaging of childhood brain tumors: preliminary observations

PURPOSE: To assess multivoxel proton MR spectroscopy combined with MR imaging and hemodynamic MR imaging in the evaluation of brain tumors in children and young adults. METHODS: Fifteen patients with brain tumors and 10 healthy children underwent MR imaging and MR spectroscopy on a 1.5-T system. Ten patients with tumors had both MR spectroscopy and hemodynamic MR imaging. MR spectroscopy data sets with 1 cm3 to 3.4 cm3 resolution were acquired within 8.5 minutes by using a point-resolved spectroscopic, chemical-shift imaging technique in two dimensions with volume preselection. MR imaging was performed using fast spin-echo techniques. Hemodynamic MR imaging data were acquired every 2.5 seconds at one anatomic level using a spoiled gradient-echo sequence during intravenous bolus administration of contrast material. RESULTS: Assessment with multivoxel MR spectroscopy and hemodynamic MR imaging added about 30 minutes to the total MR examination time. Normal tissue exhibited spectral peaks from biologically significant compounds such as N-acetylaspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Twelve biopsy-proved tumors exhibited prominent Cho, reduced NAA, variable tCr, and/or lactate or lipids, and two showed increased hemodynamic parameters. Three of the tumors treated with radiation did not reveal prominent levels of Cho. Tissue necrosis had no Cho, NAA, or tCr, and reduced hemodynamics. CONCLUSIONS: Preliminary findings by MR spectroscopy combined with MR imaging and hemodynamic MR imaging suggest that regions of active tumor may be differentiated from areas of normal tissue and areas of necrosis. These findings may enable metabolic and hemodynamic characterization of childhood brain tumors as well as suggest their response to therapy.     

Efficacy of gadolinium in MR brain imaging of HIV-infected patients

PURPOSE: To determine the value of gadolinium in routine head MR imaging of HIV-infected patients. METHODS: One hundred and three consecutive human immunodeficiency virus-infected patients referred for head MR imaging were scanned without and with intravenous gadopentetate dimeglumine (Gd-DTPA) contrast. RESULTS: The precontrast scans of 82 patients were either normal, or had atrophy or diffuse white matter changes only. Sixteen of these 82 demonstrated enhancing abnormalities: eight meningeal/ependymal enhancement and eight focal enhancing lesions. Twenty-one of the 103 scans had focal or mass lesions on the precontrast images; in eight of these scans, new information was obtained with Gd-DTPA. Of the 24 patients in both groups where new information was obtained with Gd-DTPA, the information contributed to a change in the clinical care of nine patients. CONCLUSION: Gadolinium-enhanced MR is useful in the management of selected patients with human immunodeficiency virus infection, for example those with symptoms suggesting meningeal involvement, focal brain lesions, or if the unenhanced MR does not explain all the patient's symptoms.     

MR imaging of perinatal brain damage: comparison of clinical outcome with initial and follow-up MR findings

BACKGROUND AND PURPOSE: The purpose of our study was to determine whether MR studies in the neonatal period are predictive of the neuroradiologic sequelae and clinical outcome in premature and term infants with perinatal brain injury. METHODS: Thirty subjects (15 premature and 15 term infants) with abnormalities revealed by initial MR studies were reexamined approximately 1 year after birth with both MR imaging and a neurologic assessment. All initial MR studies were performed between 35 and 45 weeks corrected age in premature infants and within 28 days of life in term infants. The initial MR studies were evaluated for deep gray matter involvement, hemispheric parenchymal change, intracranial hemorrhage, and periventricular signal and/or morphologic changes. These MR findings were compared with the follow-up MR findings and with the neurologic outcome. RESULTS: The development of cerebral palsy in premature infants was related to the following initial MR findings: subependymal hemorrhage associated with parenchymal destruction, periventricular signal alteration with irregularity of the ventricular wall, and widespread cerebral infarction. These MR findings were predictive of the subtypes of cerebral palsy. In term asphyxiated infants, T2 signal alterations of the deep gray matter rather than T1 shortening and diffuse involvement of the hemispheres were predictive of an unfavorable outcome. Both in term and premature infants, focal hemispheric parenchymal lesions alone (including infarction and intracerebral, subdural, intraventricular, and subarachnoid hemorrhage) did not produce poor outcomes. CONCLUSION: MR studies performed at or near term in either premature or term infants with perinatal brain damage are effective in predicting both late neuroradiologic and clinical outcome.     

Detection of brain metastasis: comparison of Turbo-FLAIR imaging, T2-weighted imaging and double-dose gadolinium-enhanced MR imaging

Methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized cause of hospital-acquired sepsis. We reviewed the clinical features of a new variant of community-acquired MRSA originally described from the Kimberley region of northern Western Australia (WA MRSA). This strain has become an increasing cause of community- and hospital-acquired sepsis at Royal Darwin Hospital (RDH) in the Northern Territory, especially in Aboriginal Australians from remote communities. Fifty percent of WA MRSA was community-acquired, with 76% in Aboriginals. Like the MRSA from eastern Australia (EA MRSA), WA MRSA commonly caused skin sepsis but was less likely to cause respiratory or urinary infections compared with EA MRSA. Twelve out of 125 (9.6%) WA MRSA and 7/93 (7.5%) EA MRSA infections were septicaemias. Septicaemia due to WA MRSA occurred in adult medical patients, especially those with temporary haemodialysis catheters, while EA MRSA septicaemia occurred throughout the hospital. Aboriginal people were more likely to develop both community- and hospital-acquired WA MRSA septicaemia [overall relative risk (RR) 12.3 (95% CI 3.7-40.7)]. Control of WA MRSA requires policies to reduce transmission in both hospitals and communities. Community-based control programmes need support for individual patient management, improved housing and hygiene, control of skin sepsis and appropriate use of antibiotics, especially in rural Aboriginal communities in northern Australia.     

Addiction and imaging of the living human brain

The CYP1A1, CYP2D6 and GSTM1 genes encode biotransforming enzymes involved in activation and detoxification of xenobiotics. Metabolically activated chemical compounds may interact with DNA and form adducts. In this study, the effect of the GSTM1, CYP1A1 exon 7 and CYP2D6 polymorphisms on DNA adduct levels was studied in 170 healthy volunteers. DNA adducts levels were measured by 32P-postlabelling in mononuclear white blood cells (WBC, lymphocytes and monocytes) and granulocytes collected in summer and winter. The influence of the genotype on the level of DNA adducts in both types of WBCs was observed only in summer samples. Individuals with GSTM1 deficient (null) genotype had significantly elevated level of adducts in mononuclear WBCs (p = 0.045) and granulocytes (p = 0.031) compared to GSTM1 positives. Higher adduct levels in carriers of combined GSTM1(null)/CYP1A1-Ile/Val genotype were found in both types of WBCs when compared to GSTM1(+)/CYP1A1-Ile/Ile genotype carriers (p = 0.046 in granulocytes, p = 0.092 in mononuclear WBCs). CYP2D6 wild-type homozygotes (EMs) and heterozygotes (HEMs) were shown to have significantly higher mononuclear WBC DNA adduct levels than mutant homozygotes (PMs) (p = 0.037 and p = 0.014). When confounding factors associated with PAH exposure were taken into account a statistically significant effect of CYP1A1 exon 7 polymorphism on DNA adduct levels was found (p = 0.012 in mononuclear WBCs, p = 0.043 in granulocytes). In a subgroup of current smokers (n = 95) high DNA adduct levels in granulocytes were associated with GSTM1(null) genotype, and increased adduct levels in mononuclear WBCs correlated with CYP2D6 EM and HEM genotypes. In winter samples the association between the genotype and DNA adduct levels was not observed.     

MR imaging of the brain: comparison of gradient-echo and spin-echo pulse sequences

OBJECTIVE: Gradient-echo pulse sequences can reduce imaging time and decrease motion artifacts. If gradient-echo pulse sequences are shown to be comparable to spin-echo sequences in MR imaging of the brain, then gradient-echo imaging can be valuable for examining critically ill, anxious, or uncooperative patients and can increase patient throughput. The purpose of this study was to prospectively compare one fast multiplanar spoiled gradient-recalled acquisition in the steady state (GRASS) (FMPSPGR) sequence with one conventional T1-weighted spin-echo sequence to determine the reliability of the FMPSPGR sequence for detecting cerebral lesions. SUBJECTS AND METHODS: Fifty-one patients with 142 cranial lesions, including brain tumors, infarction, infection, and noninflammatory lesions, were examined. Forty-two unenhanced and 39 contrast-enhanced FMPSPGR (113-240/2.6-3.6/90 degrees/4 [TR/TE/flip angle/acquisitions]) and spin-echo T1-weighted (400-579/11-12/90 degrees/2) MR images of the head were obtained with a 1.5-T system. The visibility, margination, and extent of the lesions; image quality; contrast; and artifacts were qualitatively and quantitatively compared. RESULTS: Supratentorial lesions were more conspicuous on the unenhanced FMPSPGR images because of the higher signal-to-noise ratio of the normal brain resulting in higher lesion contrast. The higher contrast-to-noise ratio of neoplasms on the contrast-enhanced spin-echo images was not found to be significant in the independent qualitative analysis. The conspicuity and extent of other lesions evaluated with the two pulse sequences were not significantly different for either the unenhanced or the contrast-enhanced studies. Vascular pulsation artifacts were significantly reduced on the contrast-enhanced FMPSPGR images. Susceptibility and chemical-shift phase-cancellation artifacts were more pronounced on the FMPSPGR images. CONCLUSION: The FMPSPGR sequence provides high-quality images with fewer vascular pulsation artifacts three to four times faster than the spin-echo sequence. The FMPSPGR sequence can reliably show intracranial lesions and can substitute for the T1-weighted spin-echo sequence in routine brain imaging.     

Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain

The peptide somatostatin (SS) is widely distributed in the mammalian brain where it modulates neuronal activity through interactions with specific membrane-bound receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5) and their selective agonists were developed on the basis of their binding specificity. SS and ssts are transiently expressed in the developing brain, suggesting a functional role of somatostatinergic systems in neuronal maturation. In the present study, we investigated the effects of chronic exposure to either the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual cortex of the rat. SS-ir maturation was investigated both by an evaluation of the number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the levels of SS in the postnatal visual cortex. In the visual cortex of normal rats, the number of SS-positive cells markedly increased during the second postnatal week and then significantly decreased until the adult value was reached at the third week. Early and repeated intracerebroventricular (i.c.v.) injections of either SS-14 or octreotide prevented the increase in the number of SS-positive cells, with adult values reached at the end of the first postnatal week. Similarly, administration of either SS-14 or octreotide significantly decreased the SS content of the visual cortex, measured at the end of the second postnatal week. These results show that high local concentrations of either SS-14 or octreotide interfere with SS expression in developing cortical neurons in a restricted postnatal period.     

Measurement of brain activity with bolus administration of contrast agent and gradient-echo MR imaging

This study was performed to measure changes in cerebral blood volume (CBV) associated with visual activation by use of bolus administration of contrast agent and conventional, clinically configured magnetic resonance (MR) hardware and software. Fast gradient-recalled acquisition in the steady state technique was used to study five healthy subjects during visual activation and a control dark state. MR images were obtained every 2.048 seconds for 2 minutes. A bolus of gadopentetate dimeglumine was injected during visual stimulation and darkness. Cine images produced from the series of rapid images clearly depicted arterial, capillary, and venous phases. Analysis of serial concentration maps derived from the rapid images revealed expected differences between the relative CBV of gray matter and that of white matter, as well as significantly increased relative CBV in calcarine cortex during visual activation versus the control state (mean increase, 15.24%; range, 6.41%-27.78%; P < .05). These results confirm those reported in echo-planar imaging studies and demonstrate that brain function can be assessed with the bolus method by means of MR imaging hardware and software with conventional clinical configurations.     

Synaptic organization of the human striatum: a postmortem ultrastructural study

Converging with psycho-social research findings, animal and human laboratory studies indicate that behavioral alternatives are important determinants of drug-taking. To investigate associations between how early adolescents spend their time, i.e. their behavioral repertoire and drug use (use of marijuana, crack/cocaine or inhalants), we analyzed data from an epidemiological sample of 1516 urban middle-school students who had completed private interviews in spring 1993. The interview included a 36-item questionnaire to assess how frequently the youth engaged in different activities; history of drug-taking was assessed separately. Multiple logistic regression was used to estimate associations between drug use and each of seven behavioral domains as well as sex, age and racial-ethnic status. Youths spending a great deal of time working for pay and assuming other adult-like roles were more likely to have initiated drug use (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in religious activities were less likely (OR = 0.2, p <0.001). An exploratory search for interactions disclosed other associations that merit attention in future research. These results corroborate evidence on the potential etiological significance of behavioral repertoire in relation to risk of drug use.     

3H]Neurotensin receptor densities in human postmortem brain tissue obtained from normal and schizophrenic persons. An autoradiographic study

[3H]Neurotensin binding and autoradiographic techniques were used to determine the distribution and density of neurotensin receptors in normal and schizophrenic postmortem brain tissue. Coronal hemi-brain blocks of tissue were cut at the level of the caudate and hippocampus from frozen brain tissue obtained from normal individuals with no known psychiatric or neurologic illnesses and from schizophrenic subjects off- or on-antipsychotic drugs at the time of death. Each hemi-block was further divided, sectioned, thaw mounted on to slides, incubated with [3H]neurotensin and apposed to film. Digitized images were analyzed for binding densities. Areas of intense binding include the substantia nigra, the entorhinal cortex, superficial layers of the cingulate, middle frontal, and insular cortices; and with moderate binding in nucleus accumbens, and caudate. Schizophrenic patients off- (3 months or more) or on-antipsychotic drugs at the time of death were tested; all patients showed a reduced level of neurotensin receptors in the caudate (68% of normals), cingulate (34%) and prefrontal cortices (25%).