Probing human sperm metabolism using 13C-magnetic resonance spectroscopy.

STUDY QUESTION: Can 13C-Magnetic Resonance Spectroscopy (MRS) of selected metabolites provide useful information about human sperm metabolism and how glycolysis or oxidative phosphorylation are used by different sperm populations? SUMMARY ANSWER: Sperm populations, prepared by density gradient centrifugation (DGC) and incubated with either 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate, showed consistent evidence of metabolism generating principally lactate and more intermittently bicarbonate, and significantly more lactate was produced from 13Cu-glucose by vital or motile sperm recovered from the 40/80% interface compared to those from the pellet, which could not be accounted for by differences in the non-sperm cells present. WHAT IS KNOWN ALREADY: Previous studies have focused on CO2 or other specific metabolite production by human sperm and there remains considerable debate about whether glycolysis and/or oxidative phosphorylation is the more important pathway for ATP production in sperm. STUDY DESIGN, SIZE, DURATION: Sperm populations were prepared by DGC and subjected to 13C-MRS to answer the following questions. (i) Is it possible to detect human sperm metabolism of 13C substrates implicated in energy generation? (ii) What are the kinetics of such reactions? (iii) Do different sperm populations (e.g. '80%' pellet sperm and '40%' interface sperm) utilise substrates in the same way? Semen samples from 97 men were used in these experiments; 52 were used in parallel for aims (i) and (ii) and 45 were used for aim (iii). PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm populations were prepared from ejaculates of healthy men using a Percoll/Phosphate Buffered Saline (PBS) DGC and then incubated with a range of 13C-labelled substrates (13Cu-glucose, 13Cu-fructose, 13C1-pyruvate, 13C1-butyrate, 13C3-lactate, 13C2,4-D-3-hydroxybutyrate, 13C5-l-glutamate, 13C1,2-glycine or 13Cu-galactose) along with penicillin/streptomycin antibiotic at 37°C for 4 h, 24 h or over 48 h for an estimated rate constant. Sperm concentration, vitality and motility were measured and, for a subset of experiments, non-sperm cell concentration was determined. A 9.4 T magnetic resonance spectrometer was used to acquire 1D 13C, inverse gated 1H decoupled, MRS spectra. Spectrum processing was carried out using spectrometer software and Matlab scripts to determine peak integrals for each spectrum. MAIN RESULTS AND THE ROLE OF CHANCE: 13Cu-glucose, 13Cu-fructose and 13C1-pyruvate were consistently converted into lactate and, to a lesser extent, bicarbonate. There was a significant correlation between sperm concentration and lactate peak size for 13Cu-glucose and 13Cu-fructose, which was not observed for 13C1-pyruvate. The lactate peak did not correlate with the non-sperm cell concentration up to 6.9 × 106/ml. The concentration of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate (1.8, 3.6, 7.2 or 14.4 mM) had no influence on the size of the observed lactate peak over a 4 h incubation. The rate of conversion of 13C1-pyruvate to lactate was approximately three times faster than for 13Cu-glucose or 13Cu-fructose which were not significantly different from each other. After incubating for 4 h, the utilisation of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate by sperm from the '40%' interface of the DGC was no different from those from the pellet when normalised to total sperm concentration. However, after normalising by either the vital or motile sperm concentration, there was a significant increase in conversion of 13Cu-glucose to lactate by '40%' interface sperm compared to pellet sperm (Vital = 3.3 ± 0.30 × 106 vs 2.0 ± 0.21 × 106; P = 0.0049; Motile = 7.0 ± 0.75 × 106 vs 4.8 ± 0.13 × 106; P = 0.0032. Mann-Whitney test P < 0.0055 taken as statistically significant). No significant differences were observed for 13Cu-fructose or 13C1-pyruvate. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Only 13C labelled metabolites that accumulate to a sufficiently high concentration can be observed by 13C MRS. For this reason, intermediary molecules in the metabolic chain are difficult to observe without trapping the molecule at a particular step using inhibitors. Non-sperm cell concentration was typical of the general population and no link was found between these cells and the magnitude of the 13C-lactate peak. However, it is possible that higher concentrations than the maximum observed (6.9 × 106/ml) may contribute to exogenous substrate metabolism in other experiments. WIDER IMPLICATIONS OF THE FINDINGS: 13C-MRS can provide information on the underlying metabolism of multiple pathways in live sperm. Dysfunction in sperm metabolism, as a result of either impaired enzymes of lack of metabolisable substrate, could be detected in sperm by a non-destructive assay, potentially offering new treatment options to improve overall sperm quality and outcomes for reproduction. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.

1H Magnetic Resonance Spectroscopy of live human sperm.

STUDY QUESTION: Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa? SUMMARY ANSWER: Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface. WHAT IS KNOWN ALREADY: Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm. MAIN RESULTS AND THE ROLE OF CHANCE: DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n = 20). ROC curve analysis of these region showed significant ability to distinguish between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid ROC AUC = 0.86-0.87. LIMITATIONS, REASONS FOR CAUTION: Only 3-4 semen samples were used to assess the efficacy of each sperm washing protocol that were examined. The estimated minimum sperm concentration required for MRS is specific to the hardware used in our study and may be different in other spectrometers. Spectrum binning is a low resolution analysis method that sums MRS peaks within a chemical shift range. This can obscure the identity of which metabolite(s) are responsible for differences between sperm populations. Further work is required to determine the relative contribution of somatic cells to the MRS spectrum from the '40%' and '80%' sperm. WIDER IMPLICATIONS OF THE FINDINGS: 1H MRS can provide information about the molecules present in live human sperm and may therefore permit the study of the underlying functional biology or metabolomics of live sperm. Given the relatively low concentration of sperm required to obtain a suitable MRS signal (~3 × 106/ml), this could be carried out on sperm from men with oligo-, astheno- or teratozoospermia. This may lead to the development of new diagnostic tests or ultimately novel treatments for male factor infertility. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.

Diffusion-weighted imaging and magnetic resonance proton spectroscopy following preterm birth.

AIM: To study the associations between magnetic resonance proton spectroscopy (MRS) data and apparent diffusion coefficients (ADC) from the preterm brain with developmental outcome at 18 months corrected age and clinical variables. MATERIALS AND METHODS: A prospective observational cohort study of 67 infants born before 35 weeks gestational age who received both magnetic resonance imaging of the brain between 37 and 44 weeks corrected gestational age and developmental assessment around 18 months corrected age. RESULTS: No relationships were found between ADC values and MRS results or outcome. MRS ratios involving N-acetyl aspartate (NAA) from the posterior white matter were associated with "severe" and "moderate to severe" difficulties, and fine motor scores were significantly lower in participants with a visible lactate doublet in the posterior white matter. The presence of a patent ductus arteriosus (PDA) was the only clinical factor related to NAA ratios. CONCLUSION: Altered NAA levels in the posterior white matter may reflect subtle white matter injury associated with neuro-developmental difficulties, which may be related to a PDA. Further work is needed to assess the longer-term neuro-developmental implications of these findings, and to study the effect of PDAs on developmental outcome in later childhood/adolescence.

Kinetic modeling of hyperpolarized (13)C pyruvate metabolism in tumors using a measured arterial input function.

Mathematical models are required to estimate kinetic parameters of [1-(13)C] pyruvate-lactate interconversion from magnetic resonance spectroscopy data. One- or two-way exchange models utilizing a hypothetical approximation to the true arterial input function (AIF), (e.g. an ideal 'box-car' function) have been used previously. We present a method for direct measurement of the AIF in the rat. The hyperpolarized [1-(13)C] pyruvate signal was measured in arterial blood as it was continuously withdrawn through a small chamber. The measured signal was corrected for T1 relaxation of pyruvate, RF pulses and dispersion of blood in the chamber to allow for the estimation of the direct AIF. Using direct AIF, rather than the commonly used box-car AIF, provided realistic estimates of the rate constant of conversion of pyruvate to lactate, kpl, the rate constant of conversion of lactate to pyruvate klp, the clearance rate constant of pyruvate from blood to tissue, Kip, and the relaxation rate of lactate T1la. Since no lactate signal was present in blood, it was possible to use a simple precursor-product relationship, with the tumor tissue pyruvate time-course as the input for the lactate time-course. This provided a robust estimate of kpl, similar to that obtained using a directly measured AIF.

Investigation of protein induction in tumour vascular targeted strategies by MALDI MSI.

Characterising the protein signatures in tumours following vascular-targeted therapy will help determine both treatment response and resistance mechanisms. Here, mass spectrometry imaging and MS/MS with and without ion mobility separation have been used for this purpose in a mouse fibrosarcoma model following treatment with the tubulin-binding tumour vascular disrupting agent, combretastatin A-4-phosphate (CA-4-P). Characterisation of peptides after in situ tissue tryptic digestion was carried out using Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) and Matrix-Assisted Laser Desorption/Ionisation-Ion Mobility Separation-Mass Spectrometry Imaging (MALDI IMS-MSI) to observe the spatial distribution of peptides. Matrix-Assisted Laser Desorption/Ionisation-Ion Mobility Separation-Tandem Mass Spectrometry (MALDI-IMS-MS/MS) of peaks was performed to elucidate any pharmacological responses and potential biomarkers. By taking tumour samples at a number of time points after treatment gross changes in the tissue were indicated by changes in the signal levels of certain peptides. These were identified as arising from haemoglobin and indicated the disruption of the tumour vasculature. It was hoped that the use of PCA-DA would reveal more subtle changes taking place in the tumour samples however these are masked by the dominance of the changes in the haemoglobin signals.

Observer accuracy in the detection of pulmonary nodules on CT: effect of cine frame rate.

AIM: To assess the effect of cine frame rate on the accuracy of the detection of pulmonary nodules at computed tomography (CT). MATERIALS AND METHODS: CT images of 15 consecutive patients with (n = 13) or without (n = 2) pulmonary metastases were identified. Initial assessment by two thoracic radiologists provided the "actual" or reference reading. Subsequently, 10 radiologists [board certified radiologists (n = 4) or radiology residents (n = 6)] used different fixed cine frame rates for nodule detection. Within-subjects analysis of variance (ANOVA) was used to evaluate the data. RESULTS: Eighty-nine nodules were identified by the thoracic radiologists (median 8, range 0-29 per patient; median diameter 9 mm, range 4-40 mm). There was a non-statistically significant trend to reduced accuracy at higher frame rates (p=0.113) with no statistically significant difference between experienced observers and residents (p = 0.79). CONCLUSION: The accuracy of pulmonary nodule detection at higher cine frame rates is reduced, unrelated to observer experience.

The impact of COVID-19 on African American communities in the United States.

IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.

Post-mortem MRI as an adjunct to fetal or neonatal autopsy.

CONTEXT: Understanding what was wrong with a dead fetus or why a newborn child died can help the parents to grieve, while any findings can be used to inform the parents if there is a risk to future pregnancies and the level of risk. This information is mainly obtained from autopsies, but the number of parents agreeing to autopsy has dropped, which has prompted the search for adjuncts to autopsy. STARTING POINT: The UK's Chief Medical Officer outlined the rationale for exploring alternatives to autopsy in 2000 and 2001. After wide consultation, MRI was deemed to offer the most realistic chance of making a contribution. Results so far are promising, but of insufficient depth and quality to make firm recommendations about providing a service in the future. In 2004, the UK Department of Health therefore tendered for this research to be done in fetal and neonatal (and adult) cases, and this work is due to start in 2005. WHERE NEXT? High-quality anatomical information about the brain and spine of fetuses and neonates can be easily obtained with standard MRI scanners. Most developmental and acquired abnormalities can be seen on post-mortem MRI. More work needs to be done on organs not in the central nervous system, and heart malformations, in particular, might present diagnostic problems. A possible outcome could be whole-body MRI plus targeted biopsies of abnormalities taken under image guidance as an adjunct to formal autopsy.

Combined simulated annealing and Shinnar-Le Roux pulse design of slice-multiplexed RF pulses for multi-slice imaging.

Slice-multiplexed RF pulses have recently been introduced for simultaneous multi-slice imaging. Their novel aspect is that each slice is given a different linear phase profile, and hence a different slice-rephasing requirement, by the pulse. During readout, extra slice gradients are applied such that when one slice is rephased, the others are dephased to prevent aliasing. In this paper, an improved method of designing slice-multiplexed RF pulses is presented: component pulses which are optimized with simulated annealing for a specific rephasing are combined using Shinnar-Le Roux methods. In this way, non-linearities at higher flip angles are taken into account and more slices can be excited. Bloch simulations show the phase and amplitude profile of component pulses are faithfully preserved in the multiplexed pulse. Three- and four-slice multiplex pulses are demonstrated in gradient- and spin-echo in-vivo imaging.

Normal fetal lumbar spine on postmortem MR imaging.

BACKGROUND AND PURPOSE: There is an increasing interest in use of postmortem MR imaging as an adjunct or alternative to autopsy. Before evaluating spinal pathology on postmortem MR imaging, it is important to have knowledge of the normal appearance of the fetal spine at different gestational ages. The aim of this study is to describe the MR imaging appearances of normal development of the fetal spine at different gestational ages. METHODS: Postmortem MR imaging was performed on 30 fetuses ranging from 14 to 41 gestational weeks. There was no structural abnormality of the spine in these fetuses on MR imaging or at autopsy. Fast spin-echo T2-weighted MR imaging of the lumbar spine was performed in the coronal plane in all cases and supplemented by sagittal and/or axial imaging. The following parameters were measured: height of the L1/2 disk and L2 vertebral body and area of ossification center in L2 vertebral body as well as area of vertebral body. The signal intensity of the disk space and the vertebral level of conus termination were also assessed. RESULTS: The height and area of the vertebral body increased linearly with gestational age (P <.01). The increase in disk space was proportionally greater than the increase in vertebral body height as gestational age increased (P <.01). The disk space appeared as a linear low-signal-intensity area in fetuses < or = 21 weeks gestation but increasingly developed high signal intensity in the disk after 21 weeks. The size of the ossification center increased with gestational age (P <.01), and the ratio of ossification center to the overall size of the vertebral body also increased with gestational age (P <.01). In fetuses less than 35 weeks of age, the conus lay between L2 and L5 level, whereas in fetuses more than 35 weeks of age, the conus lay between L1/2 and L2/3 level. CONCLUSION: Understanding the normal growth and signal-intensity characteristics of the fetal spine on postmortem MR imaging is essential before studying abnormal fetal spine.

Post-mortem fetal MRI: what do we learn from it?

Post-mortem magnetic resonance (MR) imaging is of increasing interest not only as an alternative to autopsy but as a research tool to aid the interpretation and diagnosis of in utero MR images. The information from the post-mortem MR has allowed the development of imaging sequences applicable to in utero imaging and neonatal imaging. It has established brain development during gestation and has provided data on this to which in utero MR can be compared. The detail available from the post-mortem images is such that brain development can be studied in a non-invasive manner, a permanent record on the normal and abnormal areas is available and a greater understanding of developmental abnormalities is possible.

Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors.

BACKGROUND: Subdural haematomas are thought to be uncommon in babies born at term. This view is mainly based on findings in symptomatic neonates and babies in whom subdural haemorrhages are detected fortuitously. We aimed to establish the frequency of subdural haemorrhages in asymptomatic term neonates; to study the natural history of such subdural haematomas; and to ascertain which obstetric factors, if any, are associated with presence of subdural haematoma. METHODS: We did a prospective study in babies who were born in the Jessop wing of the Central Sheffield University Hospitals between March, 2001, and November, 2002. We scanned neonates with a 0.2 T magnetic resonance machine. FINDINGS: 111 babies underwent MRI in this study. 49 were born by normal vertex delivery without instrumentation, 25 by caesarean section, four with forceps, 13 ventouse, 18 failed ventouse leading to forceps, one failed ventouse leading to caesarean section, and one failed forceps leading to caesarean section. Nine babies had subdural haemorrhages: three were normal vaginal deliveries (risk 6.1%), five were delivered by forceps after an attempted ventouse delivery (27.8%), and one had a traumatic ventouse delivery (7.7%). All babies with subdural haemorrhage were assessed clinically but no intervention was needed. All were rescanned at 4 weeks and haematomas had completely resolved. INTERPRETATION: Presence of unilateral and bilateral subdural haemorrhage is not necessarily indicative of excessive birth trauma.

Total mandibular reconstruction for massive osteolysis of the mandible (Gorham-Stout syndrome).

Massive osteolysis (Gorham-Stout syndrome) is a rare condition of unknown aetiology that is thought to result from a localised endothelial proliferation of lymphatic vessels resulting in destruction and absorption of bone. The diagnosis of Gorham-Stout syndrome can be made only after first excluding osteolysis from infection, inflammation, endocrine disease, and cancer. The syndrome is rarely seen in the facial skeleton and has a variable prognosis. Many treatments have been advocated but only surgery and radiotherapy have had some success. We present a case of massive osteolysis of the entire mandible, which was reconstructed with a free vascularised fibular graft and bilateral prosthetic replacements of the temporomandibular (TMJ) joints. Four years later the fibular graft had been absorbed requiring further reconstruction with another fibula graft.

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. DESIGN: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS.

Human immunodeficiency virus (HIV) infection as seen in Europe and the United States has predominantly been contracted through male homosexual sex or intravenous drug abuse. In infected subjects, the brain is frequently affected both clinically and neuropathologically. The aim of this multicenter study has been to evaluate the value of single-voxel proton magnetic resonance spectroscopy (MRS) in the assessment of the neurological complications of acquired immunodeficiency syndrome (AIDS). MRS (voxel size = 8 ml, TR/TE = 1600/135 msec) was performed in 137 HIV-1-seropositive patients and 64 healthy controls without risk factors at three clinical MR sites operating at 1.5 T. The first result of this multicenter trial is that good reproducibility of results among participating sites was found. This demonstrates the reliability and robustness of MRS in the study of in vivo brain metabolism. In HIV patients, there was no significant correlation between metabolite ratios of brain detected by MRS and CDC grouping of patients or CD4 count. In contrast, the variations of brain metabolite ratios (NA/Cr, NA/Cho, and Cho/Cr) were related to the occurrence of encephalopathy, brain atrophy, or diffuse white matter lesions. There was no significant difference in brain metabolites between male homosexual AIDS patients and male intravenous drug user AIDS patients, whatever their neurological status (neurosymptomatic or neuroasymptomatic). Thus, the mode of transmission of HIV infection does not appear to affect the cerebral changes observed in the proton spectra from AIDS patients. Because of its ease of implementation and high information content, single-voxel proton MRS is likely to play a significant role in the evaluation of HIV-related encephalopathies.

Pseudo-random procedures for rapid presentation rates using optical imaging and spectroscopy.

Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cortical architecture. We describe an event-related procedure (ERP) for optical imaging based on selective signal averaging as reported by Burock et al., using an anti-correlative pseudo-random event sequence. The sequence used 1 s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid presentation rate allows for greater statistical power per unit time, and allows for direct comparison of event-related studies with other imaging modalities. The spatio-temporal characteristics of single wavelength and spectrographic results were found to be comparable with those obtained by standard techniques, although a general lessening of haemodynamic response function (HRF) was noted. We also describe a method of locating barrel activity by spectral analysis of summed event data. Using this technique, the power spectrum of remitted light from the barrel region was found to peak within +/- 0.12 Hz of the inter-event interval frequency.

Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread.

BACKGROUND: Thymoma and thymic carcinoma with pleural spread have a high rate of locoregional recurrence and poor prognosis. Maximal debulking coupled with aggressive local treatment could offer a chance for cure. This study evaluates the early and midterm results of operation and hyperthermic pleural perfusion with cisplatinum for thymic malignancies. METHODS: Fifteen patients (11 men), 20 to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst) underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All had pleural spread proven before or intraoperatively. Six of the thymoma cases were recurrent. Current operation included resection without pleurectomy (9 patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1 patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural temperature reached 40.3 degrees C to 43 degrees C. The total dose of cisplatinum was 150 mg or more in 14 patients. RESULTS: Complete resection (R0) was achieved in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative mortality, no hemodynamic or respiratory disturbances during perfusion, and no hematologic, neurologic, or renal complications. Complications consisted of significant bleeding (2 patients), fever (2), and air leak (1 patient). Two patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with no evidence of disease at 54 months. Two patients with thymoma died after 7 and 36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive without local recurrence more than 60 months after operation and hyperthermic pleural perfusion. CONCLUSIONS: Operation and thermochemotherpy is feasible and safe in patients with thymic tumors. This method seems to offer excellent local control for patients with stage IV-a thymic malignancies. Midterm results suggest that operation plus hyperthermic pleural perfusion may lengthen survival in stage IV-a thymoma.

Exostosis of a rib causing laceration of the diaphragm: diagnosis and management.

A 17-year-old boy presented with spontaneous hemothorax due to a puncture wound of the diaphragm by an inward facing exostosis of the rib. Diagnosis was made by computed tomographic scan, and the patient underwent a video-assisted thoracoscopic procedure to remove the exostosis. This is only the eighth reported case of an exostosis causing hemothorax.

Psammomatous melanotic schwannoma: presentation of a rare primary lung tumor.

A 30-year-old nonsmoking man underwent a left lower lobectomy with bronchoplasty for an obstructing lesion of the left lower lobe. Pathology results demonstrated a psammomatous melanotic schwannoma, a rare pigmented neural tumor of which only 25 cases have been reported as originating in the respiratory tract.

Localized cerebral proton MR spectroscopy in HIV infection and AIDS.

PURPOSE: To document differences in the cerebral proton MR spectra of patients with early and late stages of human immunodeficiency virus (HIV) infection. METHOD: We studied the relative N-acetyl-aspartate (NAA) levels by localized proton spectroscopy of the parietooccipital region of the brain in 43 HIV-seropositive patients, including 26 with an acquired immunodeficiency syndrome (AIDS)-defining diagnosis, and in eight control subjects. RESULTS: Reduced relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1-associated cognitive/motor complex against neurologically healthy patients (P < .007); 3) with encephalopathic changes on MR against those with normal imaging (P < .001); and 4) on follow-up against their results on initial study (P < .03). CONCLUSIONS: By clinical (Centers for Disease Control classification) and radiologic (MR evidence of white-matter disease) criteria indicating late-stage HIV infection, reduced relative levels of NAA have been demonstrated. Spectroscopic abnormalities can be quantitatively tracked with time. This paper demonstrates the clinical use of detecting NAA as a putative in vivo measure of the neuronal loss that has been demonstrated in postmortem studies of patients with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated cognitive/motor complex, is thought to be attributable directly or indirectly to the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative noninvasive indicator of this aspect of cerebral involvement in HIV disease.