T. P. Roberts

Identification of "premyelination" by diffusion-weighted MRI.

Objective The purpose of this study was to compare white matter maturation as demonstrated with diffusion-weighted MRI and with myelin-sensitive histological staining. Materials and Methods The diffusion-, T1-, and T2-weighted SE MRI at 4.7 T was performed weekly in a total of 16 rat pups, aged from 5 days to 8 weeks, 2 animals evaluated per week. Heavily diffusion-weighted sequences were obtained with the diffusion-sensitizing gradient switched alternately in two orthogonal directions. To enhance signal intensity of anisotropic structures, a synthesized image (referred to as the “anisotropy index map”) was constructed from the ratio of pairs of images acquired with diffusion sensitization of identical magnitude but orthogonal direction sensitivity. The anisotropy index maps were used for comparison with T1-weighted and heavily T2-weighted SE sequences and histological sections, respectively. Results The first evidence of diffusion anisotropy on anisotropy index maps preceded initial myelin as well as neurofibril staining by 5–12 days and T2 shortening by 2 weeks. The T1-weighted sequences did not yield visible changes and were not helpful for the assessment of ongoing white matter maturation in this model. Conclusion Magnetic resonance imaging signal intensity changes based on anisotropic water diffusion were demonstrated in regions of unmyelinated cerebral white matter tracts of albino rat pups before the onset of histologically detectable myelin. The ability of in vivo mapping of premyelinating white matter maturation indicates a new diagnostic use of MRI in evaluating cerebral white matter maturation.

Somatotopic Organization of Cortical Fields in the Lateral Sulcus of Homo sapiens: Evidence for SII and PV

The human somatosensory cortex in the Sylvian fissure was examined using functional magnetic resonance imaging to describe the number and internal organization of cortical fields present. Somatic stimuli were applied to the lips, face, hand, trunk, and foot of 18 human subjects. Activity patterns were transposed onto three‐dimensional magnetic resonance images of the brain so that the location of activity associated with the different stimuli could be related to specific regions of the cortex. There were several consistent findings. First, there were three regions of activity in the lateral sulcus associated with stimulation of the contralateral body. The most consistent locus of activation was on the upper bank of the lateral sulcus, continuing onto the operculum. The other two areas, one rostral and one caudal to this large central area, were smaller and were activated less consistently. Second, when activity patterns in the large central area resulting from stimulation of all body parts were considered, this region appeared to contain two fields that corresponded in location and somatotopic organization to the second somatosensory area (SII) and the parietal ventral area (PV). Finally, patterns of activation within SII and PV were somewhat variable across subjects. Repeated within‐subject stimulus presentation indicated that differences across subjects were not due to inconsistent stimulus presentation. Comparisons with other mammals suggest that some features of organization are found only in primates. It is hypothesized that these features may be associated with manual dexterity and coordination of the hands, a characteristic generally restricted to the primate lineage. J. Comp. Neurol. 418:1–21, 2000.

The ultraluminous state

We revisit the question of the nature of ultraluminous X-ray sources (ULXs) through a detailed investigation of their spectral shape, using the h ighest quality X-ray data available in the XMM-Newton public archives ( � 10, 000 counts in their EPIC spectrum). We confirm that simple spectral models commonly used for the analys is and interpretation of ULXs (power-law continuum and multi-colour disc blackbody models) are inadequate in the face of such high quality data. Instead we find two near ubiquitous features in the spectrum: a soft excess and a roll-over in the spectrum at energies above 3 keV. We investigate a range of more physical models to describe these data. Slim discs which include radiation trapping (approximated by a p-free disc model) do not adequately fit the data, and several o bjects give unphysically high disc temperatures (kTin > 3 keV). Instead, disc plus Comptonised corona models fit the data well, but the derived corona is cool, and op tically thick (� � 5 30). This is unlike the � � 1 coronae seen in Galactic binaries, ruling out models where ULXs are powered by sub-Eddington accretion onto an intermediate mass black hole despite many objects having apparently cool disc temperatures. We argue that these observed disc temperatures are not a good indicator of the black hole mass as the powerful, optically thick corona drains energy from the inner disc, and obscures it. We estimate the intrinsic (corona-less) disc temperature, and demonstrate that in most cases it lies in th e regime of stellar mass black holes. These objects have spectra which range from those similar to the highest mass accretion rate states in Galactic binaries (a single peak at 2‐3 ke V), to those which clearly have two peaks, one at energies below 1 keV (from the outer, unComptonised disc) and one above 3 keV (from the Comptonised, inner disc). However, a few ULXs have a significantly cooler corrected disc temperature; we suggest that these are the most extreme stellar mass black hole accretors, in which a massive wind completely envelopes the inner disc regions, creating a cool photosphere. We conclude that ULXs provide us with an observational template for the transition between Eddington and super-Eddington accretion flows, with the latter occupying a new ultraluminousaccretion state.

XMM–Newton observations of the brightest ultraluminous X-ray sources

We present an analysis of 13 of the best quality ultraluminous X-ray source (ULX) data sets available from XMM‐Newton European Photon Imaging Camera (EPIC) observations. We utilize the high signal-to-noise in these ULX spectra to investigate the best descriptions of their spectral shape in the 0.3‐10 keV range. Simple models of an absorbed power law or multicolour disc blackbody prove inadequate at describing the spectra. Better fits are found using a combination of these two components, with both variants of this model ‐ a cool (∼0.2 keV) disc blackbody plus hard power-law continuum, and a soft power-law continuum, dominant at low energies, plus a warm (∼1.7 keV) disc blackbody ‐ providing good fits to 8/13 ULX spectra. However, by examining the data above 2 keV, we find evidence for curvature in the majority of data sets (8/13 with at least marginal detections), inconsistent with the dominance of a power law in this regime. In fact, the most successful empirical description of the spectra proved to be a combination of a cool (∼0.2 keV) classic blackbody spectrum, plus a warm disc blackbody that fits acceptably to 10/13 ULXs. The best overall fits are provided by a physically self-consistent accretion disc plus Comptonized corona model (DISKPN + EQPAIR), which fits acceptably to 11/13 ULXs. This model provides a physical explanation for the spectral curvature, namely that it originates in an optically thick corona, though the accretion disc photons seeding this corona still originate in an apparently cool disc. We note similarities between this fit and models of Galactic black hole binaries at high accretion rates, most notably the model of Done & Kubota. In this scenario the inner disc and corona become energetically coupled at high accretion rates, resulting in a cooled accretion disc and optically thick corona. We conclude that this analysis of the best spectral data for ULXs shows it to be plausible that the majority of the population are high accretion rate stellar-mass (perhaps up to 80 M� ) black holes, though we cannot categorically rule out the presence of larger,

A Chandra Perspective on Galaxy-wide X-ray Binary Emission and its Correlation with Star Formation Rate and Stellar Mass: New Results from Luminous Infrared Galaxies

We present newChandra observations that complete a sample of seventeen (17) luminous infrared galaxies (LIRGs) with D< 60 Mpc and low Galactic column densities of NH 5 × 10 20 cm −2 . The LIRGs in our sample have total infrared (8–1000 μm) luminosities in the range of LIR ≈ (1–8) × 10 11 L� . The high-resolution imaging and X-ray spectral information from our Chandra observations allow us to measure separately X-ray contributions from active galactic nuclei and normal galaxy processes (e.g., X-ray binaries and hot gas). We utilized total infrared plus UV luminosities to estimate star formation rates (SFRs) and K-band luminosities and optical colors to estimate stellar masses (M� ) for the sample. Under the assumption that the galaxy-wide 2–10 keV luminosity (L gal ) traces the combined emission from high-mass X-ray binaries (HMXBs) and low-mass X-ray binaries, and that the power output from these components is linearly correlated with SFR and M� , respectively, we constrain the relation L gal = αM� + βSFR. To achieve this, we construct a Chandra-based data set composed of our new LIRG sample combined with additional samples of less actively star-forming normal galaxies and more powerful LIRGs and ultraluminous infrared galaxies (ULIRGs) from the literature. Using these data, we measure best-fit values of α = (9.05 ± 0.37) × 10 28 erg s −1 M −1 ...

Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma

BACKGROUND We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkins lymphoma. METHODS Patients with newly diagnosed advanced classic Hodgkins lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkins lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Latency of the auditory evoked neuromagnetic field components: stimulus dependence and insights toward perception.

This review will focus on investigations of the auditory evoked neuromagnetic field component, the M100, detectable in the magnetoencephalogram recorded during presentation of auditory stimuli, approximately 100 milliseconds after stimulus onset. In particular, the dependence of M100 latency on attributes of the stimulus, such as intensity, pitch and timbre will be discussed, along with evidence relating M100 latency observations to perceptual features of the stimuli. Comparison with investigation of the analogous electrical potential component, the N1, will be made. Parametric development of stimuli from pure tones through complex tones to speech elements will be made, allowing the influence of spectral pitch, virtual pitch and perceptual categorization to be delineated and suggesting implications for the role of such latency observations in the study of speech processing. The final section will deal with potential clinical applications offered by M100 latency measurements, as objective indices of normal and abnormal cortical processing.

Task-induced asymmetry of the auditory evoked M100 neuromagnetic field elicited by speech sounds

The auditory evoked neuromagnetic fields elicited by synthesized speech sounds (consonant-vowel syllables) were recorded in six subjects over the left and right temporal cortices using a 37-channel SQUID-based magnetometer. The latencies and amplitudes of the peaks of the M100 evoked responses were bilaterally symmetric for passively presented stimuli. In contrast, when subjects were asked to discriminate among the same syllabic stimuli, the amplitude of the M100 increased in the left and decreased in the right temporal cortices. Single equivalent current dipole modeling of the activity elicited by all stimulus-types localized to a well-circumscribed area in supratemporal auditory cortex. The results suggest that attentional modulation affects the two supratemporal cortices in a differential manner. Task-conditioned attention to speech sounds is reflected in lateralized supratemporal cortical responses possibly concordant with hemispheric language dominance.

Evolution of Brain Injury After Transient Middle Cerebral Artery Occlusion in Neonatal Rats

BACKGROUND AND PURPOSE Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. RESULTS On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. CONCLUSIONS In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

THE ORBITAL PERIOD OF THE WOLF-RAYET BINARY IC 10 X-1: DYNAMIC EVIDENCE THAT THE COMPACT OBJECT IS A BLACK HOLE

IC 10 X-1 is a bright (LX = 1038 ergs s-1) variable X-ray source in the Local Group starburst galaxy IC 10. The most plausible optical counterpart is a luminous Wolf-Rayet star, making IC 10 X-1 a rare example of a Wolf-Rayet X-ray binary. In this Letter, we report on the detection of an X-ray orbital period for IC 10 X-1 of 34.4 hr. This result, combined with a reexamination of optical spectra, allows us to determine a mass function for the system of f(M) = 7.8 M☉ and a probable mass for the compact object of 24-33 M☉. If this analysis is correct, the compact object is the most massive stellar-mass black hole known. We further show that the observed period is inconsistent with Roche lobe overflow, suggesting that the binary is detached and that the black hole is accreting the wind of the Wolf-Rayet star. The observed mass-loss rate of [MAC92] 17A is sufficient to power the X-ray luminosity of IC 10 X-1.