bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunocytochemical and autoradiographic studies on the process of keratinization in avian epidermis suggests absence of keratohyalin
Authors: Alibardi Lorenzo
Published: January 2004

The process of keratinization in apteric avian epidermis and in scutate scales of some avian species has been studied by autoradiography for histidine and immunohistochemistry for keratins and other epidermal proteins. Acidic or basic alpha‐keratins are present in basal, spinosus, and transitional layers, but are not seen in the corneous layer. Keratinization‐specific alpha‐keratins (AE2‐positive) are observed in the corneous layer of apteric epidermis but not in that of scutate scales, which contain mainly beta‐keratin. Alpha‐keratin bundles accumulate along the plasma membrane of transitional cells of apteric epidermis. In contrast to the situation in scutate scales, in the transitional layer and in the lowermost part of the corneous layer of apteric epidermis, filaggrin‐like, loricrin‐like, and transglutaminase immunoreactivities are present. The lack of isopeptide bond immunoreactivity suggests that undetectable isopeptide bonds are present in avian keratinocytes. Using immunogold ultrastructural immunocytochemistry a low but localized loricrin‐like and, less, filaggrin‐like labeling is seen over round‐oval granules or vesicles among keratin bundles of upper spinosus and transitional keratinocytes of apteric epidermis. Filaggrin‐and loricrin‐labeling are absent in alpha‐keratin bundles localized along the plasma membrane and in the corneous layer, formerly considered keratohyalin. Using ultrastructural autoradiography for tritiated histidine, occasional trace grains are seen among these alpha‐keratin bundles. A different mechanism of redistribution of matrix and corneous cell envelope proteins probably operates in avian keratinocytes as compared to that of mammals. Keratin bundles are compacted around the lipid‐core of apteric epidermis keratinocytes, which do not form complex chemico/mechanical‐resistant corneous cell envelopes as in mammalian keratinocytes. These observations suggest that low amounts of matrix proteins are present among keratin bundles of avian keratinocytes and that keratohyalin granules are absent. J. Morphol. 259:238–253, 2004. © 2003 Wiley‐Liss, Inc.
Comparison of Fourier and wavelet resampling methods
Authors: Laird Angela R. , Rogers Baxter P. , Meyerand M. Elizabeth
Published: January 2004

Resampling can be used to compute the null distribution of any test statistic for the purpose of measuring the significance of the measured value. This study investigated how well the spatial and temporal correlations of simulated and experimentally observed fMRI time series were preserved under Fourier and wavelet resampling methods. The null distributions of a test statistic estimated by each resampling method were compared. In addition, both resampling methods were applied to locate activated voxels in an fMRI dataset and ROC analysis showed that wavelet resampling performed more accurately than Fourier resampling. Magn Reson Med 51:418–422, 2004. © 2004 Wiley‐Liss, Inc.
Biexponential diffusion tensor analysis of human brain diffusion data
Authors: Maier Stephan E. , Vajapeyam Sridhar , Mamata Hatsuho , Westin Carl‐Fredrik , Jolesz Ferenc A. , Mulkern Robert V.
Published: January 2004

Several studies have shown that in tissues over an extended range of b‐factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b‐factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b‐factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast‐diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow‐diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas. Magn Reson Med 51:321–330, 2004. © 2004 Wiley‐Liss, Inc.
Fat and water separation in balanced steady‐state free precession using the Dixon method
Authors: Huang Teng‐Yi , Chung Hsiao‐Wen , Wang Fu‐Nien , Ko Cheng‐Wen , Chen Cheng‐Yu
Published: January 2004

In this work the feasibility of separating fat and water signals using the balanced steady‐state free precession (SSFP) technique is demonstrated. The technique is based on the observation (Scheffler and Hennig, Magnetic Resonance in Medicine 2003;49:395–397) that at the nominal values of TE = TR/2 in SSFP imaging, phase coherence can be achieved at essentially only two orientations (0° and 180°) relative to the RF pulses in the rotating frame, under the assumption of TR << T2, and independently of the SSFP angle. This property allows in‐phase and out‐of‐phase SSFP images to be obtained by proper choices of the center frequency offset, and thus allows the Dixon subtraction method to be utilized for effective fat–water separation. The TR and frequency offset for optimal fat–water separation are derived from theories. Experimental results from healthy subjects, using a 3.0 Tesla system, show that nearly complete fat suppression can be accomplished. Magn Reson Med 51:243–247, 2004. © 2004 Wiley‐Liss, Inc.
Longitudinal MRI tracking of the angiogenic response to hind limb ischemic injury in the mouse
Authors: Ziv Keren , Nevo Nava , Dafni Hagit , Israely Tomer , Granot Dorit , Brenner Ori , Neeman Michal
Published: January 2004

Ischemic injury and revascularization are frequently associated with hyperpermeability. Although extravasation of plasma proteins may promote tissue recovery through the generation of the provisional matrix that supports angiogenesis, edema may also result in progressive damage to the muscle. The aim of this research was to determine the time course of hyperpermeability associated with the angiogenic response induced by ligation of the femoral artery at the right posterior limb in mice. Hyperpermeability was followed noninvasively by MRI using an in‐house‐built permanent polyethylene catheter that enabled daily intravenous administration of biotin‐BSA‐Gd‐DTPA. The mice were scanned once prior to ligation and five times during the week post‐ligation. The MRI data, along with histopathology, indicated that the early hemodynamic compensation over loss of arterial blood supply occurred by angiogenesis and dilation of vessels in the skin and subcutaneous fat, and was accompanied by vascular hyperpermeability around the site of ligation. Functional recovery of the ischemic limb (i.e., regaining the ability to step on the limb), and the color and shape of the toes correlated with regeneration as shown by histopathology and MRI analysis. Thus, MRI provided valuable information on the transient hyperpermeability induced during the early stages of angiogenesis, and its subsequent resolution along with functional recovery from acute hind limb ischemia in mice. Magn Reson Med 51:304–311, 2004. © 2004 Wiley‐Liss, Inc.
Spiral MR myocardial tagging
Authors: Ryf Salome , Kissinger Kraig V. , Spiegel Marcus A. , Börnert Peter , Manning Warren J. , Boesiger Peter , Stuber Matthias
Published: January 2004

In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid‐tagged images with a tagline distance as low as 4 mm in a single breath‐hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8‐mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high‐quality images can be obtained and the tags persist throughout the entire cardiac cycle. Magn Reson Med 51:237–242, 2004. © 2004 Wiley‐Liss, Inc.
Artifact suppression in imaging of myocardial infarction using B1‐weighted phased‐array combined phase‐sensitive inversion recovery†
Authors: Kellman Peter , Dyke Christopher K. , Aletras Anthony H. , McVeigh Elliot R. , Arai Andrew E.
Published: January 2004

Regions of the body with long T1, such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium‐hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T1 may cause ghosts, with the number of ghosts being equal to the number of segments. B1‐weighted phased‐array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B1‐weighted phased‐array combining of multiple receiver coils. Magn Reson Med 51:408–412, 2004. Published 2004 Wiley‐Liss, Inc.
Comparison of FAIR perfusion kinetics with DSC‐MRI and functional histology in a model of transient ischemia
Authors: Schepers Janneke , Veldhuis Wouter B. , Pauw Robert‐Jan , de Groot Jan‐Willem , van Osch Matthias J.P. , Nicolay Klaas , van der Sanden Boudewijn P.J.
Published: January 2004

Flow‐sensitive alternating inversion recovery (FAIR) is a noninvasive method for perfusion imaging. It has been shown that the FAIR signal may depend on hemodynamic parameters other than perfusion, the most important one being transit delays of labeled spins to the observed tissue. These parameters are expected to change with ischemia. The goal of this study was to assess the effect of these changes on the interpretation of FAIR results in the case of altered perfusion. This was investigated in a rat model of transient cerebral ischemia. It was shown that the ratio of FAIR signal in the infarct compared to the contralateral side was lower at short inflow times, which suggests that transit times affected the effective FAIR signal. The FAIR results were compared with those from functional histology and dynamic susceptibility contrast MRI, and the findings indicated that the altered kinetics of the FAIR signal were related to reduced and delayed inflow in the infarct region—not to a decrease in the number of functional vessels. Magn Reson Med 51:312–320, 2004. © 2004 Wiley‐Liss, Inc.
Noquist: Reduced field‐of‐view imaging by direct Fourier inversion
Authors: Brummer Marijn E. , Moratal‐Pérez David , Hong Chung‐Yi , Pettigrew Roderic I. , Millet‐Roig José , Dixon W. Thomas
Published: January 2004

A novel technique called “Noquist” is introduced for the acceleration of dynamic cardiac magnetic resonance imaging (CMRI). With the use of this technique, a more sparsely sampled dynamic image sequence is reconstructed correctly, without Nyquist foldover artifact. Unlike most other reduced field‐of‐view (rFOV) methods, Noquist does not rely on data substitution or temporal interpolation to reconstruct the dynamic image sequence. The proposed method reduces acquisition time in dynamic MRI scans by eliminating the data redundancy associated with static regions in the dynamic scene. A reduction of imaging time is achieved by a fraction asymptotically equal to the static fraction of the FOV, by omitting acquisition of an appropriate subset of phase‐encoding views from a conventional equidistant Cartesian acquisition grid. The theory behind this method is presented along with sample reconstructions from real and simulated data. Noquist is compared with conventional cine imaging by retrospective selection of a reduced data set from a full‐grid conventional image sequence. In addition, a comparison is presented, using real and simulated data, of our technique with an existing rFOV technique that uses temporal interpolation. The experimental results confirm the theory, and demonstrate that Noquist reduces scan time for cine MRI while fully preserving both spatial and temporal resolution, but at the cost of a reduced signal‐to‐noise ratio (SNR). Magn Reson Med 51:331–342, 2004. © 2004 Wiley‐Liss, Inc.
Strategy for the spectral filtering of myo‐inositol and other strongly coupled spins
Authors: Kim Hyeonjin , Wild James M. , Allen Peter S.
Published: January 2004

A multiple quantum filter strategy is presented for spectrally discriminating metabolites with strongly coupled spins from those whose spins are either uncoupled or weakly coupled. The strategy also includes a means for selectively suppressing the background multiplets of metabolites that also have strongly coupled spins. As a demonstration of its efficacy at 3.0 T, the strategy is shown to enhance by a factor of ∼5 the signal‐to‐background ratio of the myo‐inositol band at 3.6 ppm relative to that in response to a PRESS sequence with the same sequence timings. This is done by eliminating the uncoupled resonance of glycine and the weakly coupled multiplets of glutamate and glutamine, and by selectively suppressing the strongly coupled taurine multiplet 3‐fold. The macromolecular background was effectively removed through its transverse decay over 105 ms. The associated cost of gaining the signal to background enhancement is a drop in signal yield by a factor of 0.75 relative to PRESS at the same timings. The myo‐inositol signal to noise ratio was nevertheless maintained by the filter at ∼12. Magn Reson Med 51:263–272, 2004. © 2004 Wiley‐Liss, Inc.
Detection of simulated pulmonary embolism in a porcine model using hyperpolarized 3He MRI
Authors: Jalali Aman , Ishii Masaru , Edvinsson Johan M. , Guan Liang , Itkin Maxim , Lipson David A. , Baumgardner James E. , Rizi Rahim R.
Published: January 2004

Several radiological imaging modalities are available to assist with the clinical diagnosis of pulmonary embolism (PE). The most frequently used techniques—nuclear medicine ventilation‐perfusion (VP) scan, computed tomography (CT), magnetic resonance angiography (MRA), and pulmonary angiography (PA)—all have literature‐supported, substantial limitations with respect to timeliness and patient safety. Hyperpolarized 3He magnetic resonance gas distribution imaging (HP 3He MRI) recently has shown potential as a safer and faster alternative. In this study, we performed HP 3He MRI on a porcine model (N = 6) of simulated PE using selective occlusion balloon catheterization (N = 4) and nonselective aged autologous clot injection (N = 1). The technique was also performed on a normal pig and again after the animal was killed. Temporal depletion of regional HP 3He MRI signal intensity provided for a qualitative assessment of simulated PE (N = 4), and regional PAO2 (alveolar partial pressure of oxygen) was calculated in affected airspaces for a quantitative assessment of simulated PE (N = 1). The preliminary results suggest that HP 3He MRI shows promise as a means of assessing regional pulmonary perfusion abnormalities in the porcine models of simulated PE that were used in this study. Magn Reson Med 51:291–298, 2004. © 2004 Wiley‐Liss, Inc.
Regional variations in normal brain shown by quantitative magnetization transfer imaging
Authors: Sled J.G. , Levesque I. , Santos A.C. , Francis S.J. , Narayanan S. , Brass S.D. , Arnold D.L. , Pike G.B.
Published: January 2004

A quantitative magnetization transfer imaging (qMTI) study, based on a two‐pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high‐resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white‐matter regions and gray‐matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10–50‐ms T2 component described as myelin water. Magn Reson Med 51:299–303, 2004. © 2004 Wiley‐Liss, Inc.
The existence of biexponential signal decay in magnetic resonance diffusion‐weighted imaging appears to be independent of compartmentalization
Authors: Schwarcz Attila , Bogner Peter , Meric Philippe , Correze Jean‐Loup , Berente Zoltan , Pál József , Gallyas Ferenc , Doczi Tamas , Gillet Brigitte , Beloeil Jean‐Claude
Published: January 2004

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion‐weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b‐values (up to 10000 mm–2 s) under intact, global ischemic, and cold‐injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron‐microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments. Magn Reson Med 51:278–285, 2004. © 2004 Wiley‐Liss, Inc.
Floating navigator echo (FNAV) for in‐plane 2D translational motion estimation
Authors: Kadah Yasser M. , Abaza Ayman A. , Fahmy Ahmed S. , Youssef Abou‐Bakr M. , Heberlein Keith , Hu Xiaoping P.
Published: January 2004

A modification of the classical navigator echo (NAV) technique is presented whereby both 2D translational motion components are computed from a single navigator line. Instead of acquiring the NAV at the center of thek‐space, akxline is acquired off‐center in the phase‐encoding (ky) direction as a floating NAV (FNAV). It is shown that the translational motion in both the readout and phase‐encoding directions can be computed from this line. The algorithm used is described in detail and verified experimentally. The new technique can be readily implemented to replace classic NAV in MRI sequences, with little to no additional cost or complexity. The new method can help suppress 2D translational motion and provide more accurate motion estimates for other motion‐suppression techniques, such as the diminishing variance algorithm. Magn Reson Med 51:403–407, 2004. © 2004 Wiley‐Liss, Inc.
Pulse sequence for multislice T1ρ‐weighted MRI
Authors: Wheaton Andrew J. , Borthakur Arijitt , Charagundla Sridhar R. , Reddy Ravinder
Published: January 2004

A 2D multislice spin‐lock (MS‐SL) MR pulse sequence is presented for rapid volumetric T1ρ‐weighted imaging. Image quality is compared with T1ρ‐weighted data collected using a single‐slice (SS) SL sequence and T2‐weighted data from a standard MS spin‐echo (SE) sequence. Saturation of longitudinal magnetization by the application of nonselective SL pulses is experimentally measured and theoretically modeled as T2ρ decay. The saturation data is used to correct the image data as a function of the SL pulse duration to make quantitative measurements of T1ρ. Measurements of T1ρ using the saturation‐corrected MS‐SL data are nearly identical to those measured using an SS‐SL sequence. The MS‐SL sequence produces quantitative T1ρ maps of an entire sample volume with the high‐SNR advantages conferred by SE‐based sequences. Magn Reson Med 51:362–369, 2004. © 2004 Wiley‐Liss, Inc.
Event‐related fMRI technique for auditory processing with hemodynamics unrelated to acoustic gradient noise
Authors: Schmithorst Vincent J. , Holland Scott K.
Published: January 2004

Acoustic noise from the imaging gradients presents a major difficulty in functional MRI (fMRI) studies of auditory cortical function. For studies involving hearing‐impaired pediatric subjects, the auditory stimuli should be presented during completely silent gradient intervals. In addition, the scan time is limited by constraints involving subject motion and subject compliance. A novel event‐related method for conducting fMRI studies of auditory function is proposed. Auditory stimuli are presented during completely silent gradient intervals, but using a variable TR. A general nonlinear model (GNLM) is proposed as a postprocessing methodology for the data. The technique increases the flexibility of the experimental design, with minimal loss of sensitivity compared to standard fMRI acquisition techniques, and may therefore be useful for fMRI studies of auditory function in hearing‐impaired pediatric subjects. Magn Reson Med 51:399–402, 2004. © 2004 Wiley‐Liss, Inc.
SENSE‐DTI at 3 T
Authors: Jaermann T. , Crelier G. , Pruessmann K.P. , Golay X. , Netsch T. , van Muiswinkel A.M.C , Mori S. , van Zijl P.C.M. , Valavanis A. , Kollias S. , Boesiger P.
Published: January 2004

While holding vast potential, diffusion tensor imaging (DTI) with single‐excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal‐to‐noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in‐plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high‐resolution tensor mapping is demonstrated. Magn Reson Med 51:230–236, 2004. © 2004 Wiley‐Liss, Inc.
Quantitative diffusion imaging with steady‐state free precession
Authors: Deoni Sean C.L. , Peters Terry M. , Rutt Brian K.
Published: January 2004

The addition of a single, unbalanced diffusion gradient to the steady‐state free precession (SSFP) imaging sequence sensitizes the resulting signal to free diffusion. Unfortunately, the confounding influence of both longitudinal (T1) and transverse (T2) relaxation on the diffusion‐weighted SSFP (dwSSFP) signal has made it difficult to quantitatively determine the apparent diffusion coefficient (ADC). Here, a multistep method in which the T1, T2, and spin density (Mo) constants are first determined using a rapid mapping technique described previously is presented. Quantitative ADC can then be determined through a novel inversion of the appropriate signal model. The accuracy and precision of our proposed method (which we term DESPOD) was determined by comparing resulting ADC values from phantoms to those calculated from traditional diffusion‐weighted echo planar imaging (dwEPI) images. Error within the DESPOD‐derived ADC maps was found to be less than 3%, with good precision over a biologically relevant range of ADC values. Magn Reson Med 51:428–433, 2004. © 2004 Wiley‐Liss, Inc.
FAIR true‐FISP perfusion imaging of the kidneys
Authors: Martirosian Petros , Klose Uwe , Mader Irina , Schick Fritz
Published: January 2004

Most arterial spin labeling (ASL) techniques apply echoplanar imaging (EPI) because this strategy provides relatively high SNR in short measuring times. Unfortunately, those techniques are very susceptible to static magnetic field inhomogeneities and perfusion signals from organs with fast transverse relaxation might decrease due to the exchange of water molecules in capillaries and organ tissue combined with relatively long echo times of EPI sequences. To overcome these problems a novel imaging technique, FAIR True‐FISP, was developed. It combines a FAIR (flow‐sensitive alternating inversion recovery) perfusion preparation and a true fast imaging with steady precession (True‐FISP) data acquisition strategy. True‐FISP was chosen since this sequence type does not show the mentioned disadvantages of EPI, but provides a similar SNR per measuring time. An important problem of this approach is that True‐FISP sequences usually work in a steady state which is independent of a previous preparation of magnetization. For this reason a sequence structure had to be developed which keeps the advantages of True‐FISP and makes the signal intensity sensitive to the FAIR preparation. Breathhold and nonbreathhold examinations of kidneys are presented and possible strategies to quantitative flow measurements are reported. It is shown that correction of spatially inhomogeneous receiver coil characteristics is easily feasible and leads to clinically valuable perfusion examinations of kidneys without application of potentially nephrotoxic contrast media. Magn Reson Med 51:353–361, 2004. © 2004 Wiley‐Liss, Inc.
dGEMRIC (delayed gadolinium‐enhanced MRI of cartilage) indicates adaptive capacity of human knee cartilage
Authors: Tiderius Carl Johan , Svensson Jonas , Leander Peter , Ola Thorsson , Dahlberg Leif
Published: January 2004

Delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) is a new imaging technique to estimate joint cartilage glycosaminoglycan content byT1‐relaxation time measurements after penetration of the hydrophilic contrast agent Gd‐DTPA2‐. This study compares dGEMRIC in age‐matched healthy volunteers with different levels of physical activity: Group 1 (n = 12): nonexercising individuals; Group 2 (n = 16): individuals with physical exercise averaging twice weekly; Group 3 (n = 9): male elite runners. dGEMRIC was performed 2 hr after an intravenous injection of Gd‐DTPA2‐at 0.3 mmol/kg body weight.T1differed significantly between the three different levels of physical exercise.T1values (mean of medial and lateral femoral cartilage) for Groups 1, 2, and 3 were: 382 ± 33, 424 ± 22 and 476 ± 36, respectively (ms, mean ± SD) (P= 0.0004, 1 vs. 2 and 0.0002, 2 vs. 3). Irrespective of the exercise level,T1was longer in lateral compared to medial femoral cartilage (P= 0.00005; n = 37). In conclusion, this cross‐sectional study indicates that human knee cartilage adapts to exercise by increasing the glycosaminoglycan content. Furthermore, results suggest a compartmental difference within the knee with a higher glycosaminoglycan content in lateral compared to medial femoral cartilage. A higher proportion of extracellular water, i.e., larger distribution volume, may to some extent explain the highT1in the elite runners. Magn Reson Med 51:286–290, 2004. © 2004 Wiley‐Liss, Inc.
1H NMR detection of vitamin C in human brain in vivo
Authors: Terpstra Melissa , Gruetter Rolf
Published: January 2004

Vitamin C (ascorbate) is well established as an essential nutrient that functions as an antioxidant. Since it is present in the human brain at detectable concentrations, this study was designed to detect and quantify ascorbate in the human brain in vivo using 1H NMR spectroscopy (MRS). Ascorbate was consistently detected in all five study subjects, and was measured using MEGA‐PRESS difference editing. The in vivo resonance pattern was consistent with that of ascorbate based on position, line width, peak pattern, and relative intensity. Metabolites with a potential for coediting were assessed using phantom solutions. The putative resonances of myo‐inositol, lactate, glycerophosphocholine, phosphocholine, and phosphoethanolamine were detected at positions distinct from those of ascorbate. This study represents the first in vivo detection of vitamin C in the human brain using 1H MRS. A concentration of 1.3 ± 0.3 μmol/g (mean ± SD, N = 4) was estimated. Magn Reson Med 51:225–229, 2004. © 2004 Wiley‐Liss, Inc.
Distribution of intramyocellular lipids in human calf muscles as determined by MR spectroscopic imaging
Authors: Vermathen Peter , Kreis Roland , Boesch Chris
Published: January 2004

In this study the distribution of intramyocellular lipids (IMCL) in human calf muscles was determined by 1H‐MR spectroscopic imaging (MRSI) measurements. An obstacle for MRSI measurements in the calf, including different muscles, is the inevitable inclusion of regions with high concentrations of extramyocellular lipids (EMCL). This can lead to signal bleeding and consequently to unpredictable overlaps of IMCL resonances with EMCL in voxels of interest. The results of this study show that signal bleeding from EMCL can be substantially reduced in voxels from calf muscles by the application of a lipid extrapolation (LE) procedure (Haupt et al., Magn Reson Med 1996;35:678). The spectra of all voxels located within muscle tissue were fitted, and the metabolite values were assigned to one of 10 different muscles based on image segmentation. Significant IMCL differences between some muscles were obtained, with high values in m. soleus and two to three times lower values in the tibialis anterior, tibialis posterior, and gastrocnemius muscles. In addition to gross differences between muscles, significant intersubject differences were observed in both IMCL content and distribution over different muscles. A significant correlation between fiber orientation (obtained from orientation‐dependent dipolar coupling of creatine and taurine resonances) and IMCL content was found, indicating that IMCL content is directly correlated to biomechanical properties. Magn Reson Med 51:253–262, 2004. © 2004 Wiley‐Liss, Inc.
Quantification of multicontrast vascular MR images with NLSnake, an active contour model: In vitro validation and in vivo evaluation
Authors: Desbleds Mansard Catherine , Canet Soulas Emmanuelle P. , Anwander Alfred , Chaabane Linda , Neyran Bruno , Serfaty Jean‐Michel , Magnin Isabelle E. , Douek Philippe C. , Orkisz Maciej
Published: January 2004

Vessel‐wall measurements from multicontrast MRI provide information on plaque structure and evolution. This requires the extraction of numerous contours. In this work a contour‐extraction method is proposed that uses an active contour model (NLSnake) adapted for a wide range of MR vascular images. This new method employs length normalization for the purpose of deformation computation and offers the advantages of simplified parameter tuning, fast convergence, and minimal user interaction. The model can be initialized far from the boundaries of the region to be segmented, even by only one pixel. The accuracy and reproducibility of NLSnake endoluminal contours were assessed on vascular phantom MR angiography (MRA) and high‐resolution in vitro MR images of rabbit aorta. An in vivo evaluation was performed on rabbit and clinical data for both internal and external vessel‐wall contours. In phantoms with 95% stenoses, NLSnake measured 94.3% ± 3.8%, and the accuracy was even better for milder stenoses. In the images of rabbit aorta, variability between NLSnake and experts was less than interobserver variability, while the maximum intravariability of NLSnake was equal to 1.25%. In conclusion, the NLSnake technique successfully quantified the vessel lumen in multicontrast MR images using constant parameters. Magn Reson Med 51:370–379, 2004. © 2004 Wiley‐Liss, Inc.
MRI detection of early endothelial activation in brain inflammation
Authors: Sibson Nicola R. , Blamire Andrew M. , Bernades‐Silva Martine , Laurent Sophie , Boutry Sébastien , Muller Robert N. , Styles Peter , Anthony Daniel C.
Published: January 2004

MRI is an increasingly important clinical tool, but it is clear that conventional imaging fails to identify the full extent of lesion load in certain conditions, such as multiple sclerosis. The aim of this study was to determine whether a novel contrast agent (Gd‐DTPA‐B(sLeX)A, which contains an sLeX mimetic moiety that enables it to bind to the adhesion molecule E‐selectin) can be used to identify endothelial activation in the brain. Microinjection of the proinflammatory cytokines IL‐1β or TNF‐α into the striatum of Wistar rats rapidly induces focal adhesion molecule expression on the endothelium in the absence of MRI‐visible changes. This phenomenon was used to investigate the potential of Gd‐DTPA‐B(sLeX)A to reveal MRI‐invisible brain pathology. T1‐weighted serial images were acquired in anesthetized animals before and after administration of Gd‐DTPA‐B(sLeX)A, 3–4 hr after cytokine was injected intracerebrally. Both TNF‐α and IL‐1β up‐regulated E‐selectin on the brain endothelium, which correlated with increased signal intensity observed after administration of the novel contrast agent. No enhancement was visible with the nonselective contrast agent Gd‐DTPA‐BMA, indicating that there was no leakage of the agent across the blood–brain barrier (BBB) or nonselective binding to the endothelium. These data demonstrate the potential of such contrast agents for the early detection of brain injury and inflammation. Magn Reson Med 51:248–252, 2004. © 2004 Wiley‐Liss, Inc.
Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin
Authors: Kısmet Erol , Varan Ali , Ayabakan Canan , Alehan Dursun , Portakal Oytun , Büyükpamukçu Münevver
Published: January 2004

Objective

We investigated the usefulness of serum cardiac Troponin T (cTnT) to detect doxorubicin related cardiotoxicity as a non‐invasive and reliable method.

Patients and Methods

Twenty‐four patients who received doxorubicin for their solid tumors at cumulative doses of 400 mg/m2 or higher, between June 1982 and August 2000, were included in this study. None of them had clinical signs or symptoms of cardiotoxicity. The age range was 3–31 years (median 14), and male to female ratio was 14/10. The systolic and diastolic cardiac functions were evaluated by two‐dimensional, M‐mode, and Doppler echocardiography. Serum cTnT levels were measured by a third generation immunoassay method and the lowest detectable level was 0.010 ng/ml.

Results

The cumulative doxorubicin doses were at the range of 400 and 840 mg/m2 (median 480). The time past from the last doxorubicin dose was 1–168 months (median 12). All of the patients had normal chest X‐rays, electrocardiograms, and nine patients (37.5%) had abnormal systolic or diastolic cardiac function parameters. The median cumulative doxorubicin doses of the patients with normal and abnormal echocardiographic parameters were 480 and 440 mg/m2, respectively. Serum cTnT values of 21 patients were below the detection limit (< 0.010 ng/ml). There was no statistical difference between serum cTnT levels of the patients with normal and abnormal echocardiographic findings (P = 0.376).

Conclusions

No correlation was found between serum cTnT values, cumulative doxorubicin doses, and systolic or diastolic cardiac functions. We can conclude that echocardiographic follow‐up is more reliable than serum cTnT levels for detecting subclinical cardiac toxicity. © 2003 Wiley‐Liss, Inc.
High‐dose chemotherapy with autologous stem‐cell rescue in the treatment of patients with recurrent non‐cerebellar primitive neuroectodermal tumors
Authors: Broniscer Alberto , Nicolaides Theodore P. , Dunkel Ira J. , Gardner Sharon L. , Johnson James , Allen Jeffrey C. , Sposto Richard , Finlay Jonathan L.
Published: January 2004

Background

Recurrent non‐cerebellar primitive neuroectodermal tumors (PNETs) carry a dismal prognosis when treated with conventional chemotherapy alone. XSWe tested the efficacy of high‐dose chemotherapy (HDC) followed by autologous stem‐cell rescue (ASCR) in this setting.

Procedure

Eligibility mandated either minimal residual disease or evidence of chemosensitivity before HDC. Conditioning consisted of carboplatin (CBDCA) (500 mg/m2 or AUC = 7 mg/ml min using the Calvert formula) on days −8 to −6, thiotepa (300 mg/m2), and etoposide (250 mg/m2) on days −5 to −3. Irradiation was given post HDC selectively.

Results

Among 17 patients treated in this study, there were eight pineoblastoma(s) (pineo), seven cortical PNETs, and two arising elsewhere. Relapse was either local (nine) or metastatic to the brain (four) or spine (four). Two patients received HDC as the sole therapy for recurrence; additionally, eight underwent surgical debulking before HDC, and nine received irradiation, including six after HDC. Median age at ASCR was 3.9 years. Two patients died of toxicity (11%) and ten experienced tumor relapse (range: 23–361 days post ASCR). Five patients with cortical PNETs remain alive disease‐free (median follow‐up: 8.3 years); four of them received irradiation post HDC. The difference in 5‐year event‐free survival (EFS) between patients with pineo and other supratentorial PNETs was significant (0 vs. 62.5 ± 17%, P = 0.0065). Both surgery at relapse and irradiation post HDC were favorable prognostic factors (P = 0.006 and 0.01, respectively).

Conclusions

Patients with recurrent cortical PNETs can be cured with this strategy. Surgical debulking before, and irradiation after HDC play an important role in treatment success. © 2003 Wiley‐Liss, Inc.
Clonal proliferation of T‐Cell large granular lymphocytes
Authors: Boeckx Nancy , Uyttebroeck Anne , Langerak Anton W. , Brusselmans Caroline , Goossens Willy , Bossuyt Xavier
Published: January 2004

Background

T‐cell large granular lymphocyte (T‐LGL) leukemia is a disorder only rarely reported in children. We diagnosed a new case of a clonal T‐LGL proliferation in a 6‐year‐old girl presenting with severe neutropenia and pure red blood cell aplasia (PRCA).

Procedure

Flow cytometric analysis including TCR‐Vβ repertoire analysis and molecular studies using reverse transcriptase polymerase chain reaction (RT‐PCR), PCR heteroduplex analysis and GeneScan analysis were performed to investigate the clonal nature of the T‐LGL.

Results

Flow cytometric analysis revealed a Vβ3 clonal nature. Molecular studies identified a clonal Vβ3‐Cβ RT‐PCR product. Both PCR heteroduplex analysis and GeneScan analysis found clonal TCRB and TCRG gene rearrangements.

Conclusions

An underlying T‐LGL leukemia should be investigated in the diagnostic evaluation of acquired PRCA and neutropenia in young children. Both flow cytometric and molecular analyses can be used to establish the clonal nature of T‐LGL. © 2003 Wiley‐Liss, Inc.
Starting an adolescent cancer unit: Why does it take so long?
Authors: Windebank Kevin , Morgan Sue
Published: January 2004

A pragmatic approach is discussed based on the authors' differing experiences while designing new units specifically for adolescents with cancer in Leeds and Newcastle upon Tyne. Planning and implementation are complex and very time consuming. Areas to be considered include: formally identifying needs and adapting to existing local circumstances, convening a working group and involving potential stakeholders at an early stage, designing a suitable physical space, recruiting and integrating staff to create a supportive environment, obtaining financial support, and developing operational policies. For successful running of an adolescent unit, old prejudices must be disavowed and new models of medical care considered. © 2003 Wiley‐Liss, Inc.
Treatment of CNS malignant rhabdoid tumors
Authors: Ronghe M.D. , Moss T.H. , Lowis S.P.
Published: January 2004

Background

Central Nervous System (CNS) rhabdoid tumours are a highly malignant group of neoplasms usually occurring in children under 2 years of age with characteristic histopathologic findings but unclear histiogenesis and almost uniformly fatal outcome. There is still no proven curative therapy available.

Procedure

The clinical course and the successful outcome of therapy in two children with primary CNS rhabdoid tumour are described in this context. Both children had subtotal excision of the primary tumour and received chemotherapy based on the SIOP Malignant Mesenchymal Tumour (MMT‐95) protocol with addition of triple intrathecal chemotherapy. Following this, one of the patients received high dose therapy (busulphan and thiotepa), whereas the other had craniospinal radiotherapy with a boost to the primary site.

Results

The treatment was reasonably well tolerated and both patients are alive with no evidence of disease 52 months and 65 months after the primary diagnosis. Their favourable outcomes are compared with those of 49 others reported in the literature.

Conclusions

Intensified therapy (with autologous bone marrow transplantation and intrathecal chemotherapy) may improve the prognosis of patients with malignant rhabdoid tumour. © 2003 Wiley‐Liss, Inc.
Decreasing the number of MOPP courses reduces gonadal damage in survivors of childhood hodgkin disease
Authors: van den Berg H. , Furstner F. , van den Bos C. , Behrendt H.
Published: January 2004

Background

Children treated for Hodgkin disease are at risk for gonadal damage. Since most children were treated with radiotherapy (RT) in combination with chemotherapy, the presumed detrimental effect of MOPP (mustine, vincristine, procarbazine, and prednisone) (in contrast to schemes with less or without alkylating agents) could not be discerned completely from the effects of RT.

Procedures

Children with Hodgkins disease treated without RT were included in sequential protocols containing six courses of MOPP (n = 24), six courses of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (n = 17), or three courses of MOPP/ABVD (n = 35). Of these 76 patients, 48, who had completed treatment and had reached puberty, were investigated for gonadal damage.

Results

Of the male patients, 81% of MOPP treated patients had increased follicular stimulating hormone (FSH) values, in 23% luteinizing hormone (LH) values were abnormal. In ABVD treated patients, no elevated levels of FSH or LH were noted. In 30% of patients treated with MOPP/ABVD, FSH values were abnormal, but no abnormal LH values were found. Median testicular volume per group decreased in relation to a higher number of MOPP courses. Sperm analysis revealed azoospermia in nearly all MOPP treated patients. In ABVD and MOPP/ABVD treated patients both oligospermia and azoospermia were noted. The number of sperm samples were too less to make any sound conclusions. Menarche occurred in all females, however in some at a relatively later age. One female patient treated with MOPP/ABVD had a normal pregnancy.

Conclusions

Limitation of MOPP therapy to three courses, in children treated without any RT, results in less gonadal damage as compared with six MOPP courses. From our data, MOPP damages Sertoli cells and may also damage Leydig cells as suggested by the higher LH values in conjunction with normal testosterone levels. © 2003 Wiley‐Liss, Inc.
Osteochondroma after total body irradiation: An age‐related complication
Authors: Taitz Jonathan , Cohn Richard J. , White Les , Russell Susan J. , Vowels Marcus R.
Published: January 2004

Background

The discovery of a mass lesion in a long‐term cancer survivor causes significant anxiety. The causes of such a mass include benign osteochondroma, which has been reported following focal irradiation and total body irradiation (TBI).

Procedure

To establish the incidence of osteochondromas following TBI, the medical records of all children treated at the Sydney Children's Hospital who received TBI as part of the conditioning prior to bone‐marrow transplantation between 1978 and 1997 were reviewed.

Results

Five of 58 children who received TBI as part of the conditioning therapy for bone‐marrow transplantation and who have been followed for at least 30 months post‐irradiation, developed osteochondromas. All five of the patients had been under 5 years of age when they received TBI (mean 2.4 years), giving an incidence of osteochondroma of 24% in those who received TBI in the first 5 years of life. No osteochondromas have been diagnosed among the 37 patients who were aged between 5 years and 15 years at the time of receiving TBI. The mean latent time to diagnosis of osteochondroma was 4.6 years (range 2.5–9 years). Two patients developed multiple osteochondromas. Two patients required resection of their osteochondromas because of symptoms. Neither showed malignant degeneration.

Conclusions

Younger patients are at increased risk of osteochondroma following TBI. Review of the available literature suggests a low malignant potential of radiation‐induced osteochondromas. Knowledge about the behaviour of post‐irradiation osteochondromas will help clinicians manage patients appropriately. © 2003 Wiley‐Liss, Inc.
Self‐concept in adult survivors of childhood acute lymphoblastic leukemia: A Cooperative Children's Cancer Group and National Institutes of Health Study
Authors: Seitzman Robin L. , Glover Dorie A. , Meadows Anna T. , Mills James L. , Nicholson H. Stacy , Robison Leslie L. , Byrne Julianne , Zeltzer Lonnie K.
Published: January 2004

Background

Self‐concept was compared between adult survivors of childhood acute lymphoblastic leukemia (ALL) and sibling controls. Adult survivor subgroups at greatest risk for negative self‐concept were identified.

Procedure

Survivors (n = 578) aged ≥18 years, treated before age 20 years on Children's Cancer Group (CCG) ALL protocols, and 396 sibling controls completed a telephone interview and the Harter Adult Self‐Perception Profile (ASPP).

Results

Survivors global self‐worth scores were significantly lower than sibling controls (mean 3.09 vs. 3.18; P = 0.022). Unemployed survivors reported lower global self‐worth scores than employed (mean 2.77 vs. 3.12; P = 0.0001), whereas employment status was not associated with self‐worth in controls. Among survivors, predictors of negative self‐concept included unemployment (odds ratio (OR) = 2.87; 95% CI: 1.50–5.50), and believing that cancer treatment limited employability (OR = 3.17; 95% CI: 1.79–5.62). Unemployment increased the odds for negative self‐concept among survivors who received combinations of central nervous system (CNS) irradiation (CRT) and intrathecal methotrexate (IT‐MTX), except high CRT with no or low dose IT‐MTX. Employed survivors who perceived that treatment limited their employability showed increased odds of negative self‐concept for all treatment groups compared to those who did not. Minority ethnic group membership was a borderline significant predictor of negative self‐concept (OR = 1.79; 95% CI: 0.94–3.33).

Conclusions

Global self‐worth was significantly lower in ALL survivors than sibling controls, however, 81% of survivors had positive self‐concept. Survivor subgroups most vulnerable to negative self‐concept were the unemployed survivors, believing that cancer treatment affected employability, and ethnic minority group members. Targeted intervention may have greater clinical relevance for these subgroups. © 2003 Wiley‐Liss, Inc.