bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of [14C]ABT‐770, matrix metalloproteinase inhibitor (MMPI), labelled in the phenoxy ring
Authors: Raja Shirish N.
Published: August 2003

The MMPI [14C]ABT‐770 (1), N‐[(1S)‐1‐[(4,4‐Dimethyl‐2,5‐dioxo‐1‐imi‐dazolidinyl)methyl]]‐2‐[[4′‐(trifluoromethoxy)[1,1′‐biphenyl]‐4‐yl]oxy]ethyl]‐N‐hydroxyformamide was synthesized in 8 steps using 4‐bromophenol‐UL‐14C (10) as a starting material. The Carbon‐14 label was introduced in one of the metabolically stable biphenyl rings. The key sequence of the synthesis was a three‐step one‐pot reaction in which the hydantoin moiety was introduced, the imine oxidized and further hydrolyzed to get the penultimate precursor to [14C]ABT‐770 (1) in 56% yield. Copyright © 2003 John Wiley & Sons, Ltd.
Sub‐acute changes in lesion conspicuity and geometry following MR‐guided radiofrequency ablation
Authors: Lazebnik Roee S. , Weinberg Brent D. , Breen Michael S. , Lewin Jonathan S. , Wilson David L.
Published: August 2003

Purpose

To evaluate MR signal and lesion zone volume evolution through the sub‐acute phase following image‐guided radiofrequency (RF) thermal ablation.

Materials and Methods

For many tissues, including muscle and liver, thermal lesions that result from RF heating have a characteristic two‐boundary appearance featuring an inner core (zone I) surrounded by a hyper‐intense margin (zone II) and normal tissue (zone III), found in both T2 and contrast enhanced (CE) T1‐weighted MR images, both immediately post‐ablation and four days later. First, we compared corresponding points between manually segmented zone boundaries apparent in T2‐ and CE T1‐weighted images. Second, we examined the contrast‐to‐noise ratio (CNR) between all zone combinations. Third, we quantified the volume of zone I, zone II, and the entire lesion using a three‐dimensional lesion geometry model fitted to segmented images.

Results

On a slice‐by‐slice basis, no statistically significant differences were found between zone boundaries apparent in T2 and CE T1‐weighted images. The contrast to noise ratio (CNR) of zone I vs. zone II, zone I vs. background muscle, and zone II vs. background muscle was always equal or greater for T2‐weighted images than for CE T1‐weighted images. In addition, by day four, zone II significantly increased in intensity compared to background muscle. The median Zone I volume increase was 44.2% (42.6%) using T2 weighted images and 55.5% (68.7% interquartile range) using CE T1‐ weighted images. This expansion likely corresponds to an enlargement of the ablated, coagulative necrosis, region. The median Zone II volume increase was 15.0% (42.6%) using T2‐ weighted images 1.5% (38.8%) using CE T1‐weighted images.

Conclusions

1) There are no significant differences between the apparent zone boundaries in T2‐ and CE T1‐weighted images; 2) CNR is equal or greater for T2‐weighted images as compared to CE T1‐images; and 3) both the inner and outer lesion zone volumes typically increase several days post‐ablation. J. Magn. Reson. Imaging 2003;18:353–359. © 2003 Wiley‐Liss, Inc.
Single breath‐hold diffusion‐weighted imaging of the abdomen
Authors: Chow Lawrence C. , Bammer Roland , Moseley Michael E. , Sommer F. Graham
Published: August 2003

Purpose

To generate high quality diffusion‐weighted images (DWI) and corresponding isotropic ADC maps of the abdomen with full organ (kidneys) coverage in a single breath‐hold.

Materials and Methods

DWI was performed in 12 healthy subjects with an asymmetric, spin‐echo, single‐shot EPI readout on a system with high performance gradients (40 mT/minute). The isotropic diffusion coefficient 〈D〉 was measured from 〈D〉 maps and SNR was determined for both diffusion‐weighted and reference images in the liver, spleen, pancreas, and kidneys. In six patients, single‐axis diffusion encoding along three orthogonal axes (12 NEX) was employed to assess anisotropic diffusion in kidneys.

Results

This technique yielded images of quality and resolution which compares favorably to that of prior work. SNR ranged from 27.0 in liver to 44.1 in kidneys for the diffusion‐weighted images, and from 19.6 in liver to 39.0 in kidneys in reference images. ADCs obtained in the renal medulla, renal cortex, liver, spleen, and pancreas were (2091 ± 55) × 10−6, (2580 ± 53) × 10−6, (1697 ± 52) × 10−6, (1047 ± 82) × 10−6, and (2605 ± 168) × 10−6 mm2/second, respectively (mean ± SE). Apparent diffusion coefficient (ADC) in the renal medulla and cortex were significantly different by paired t‐test (P = 4.22 × 10−10). Renal medulla and cortex yielded anisotropy indices (AI) of 0.129 and 0.067, respectively.

Conclusions

1) Single‐shot SE EPI DWI in the abdomen with this technique provides high quality images and 〈D〉 maps with full organ coverage in a single breath‐hold; 2) ADCs obtained in the renal medulla and cortex are significantly different; and 3) diffusion within the renal medulla is moderately anisotropic. J. Magn. Reson. Imaging 2003;18:377–382. © 2003 Wiley‐Liss, Inc.
Application of a B‐spline active surface technique to the measurement of cervical cord volume in multiple sclerosis from three‐dimensional MR images
Authors: Hickman Simon J. , Coulon Olivier , Parker Geoffrey J.M. , Barker Gareth J. , Stevenson Valerie L. , Chard Declan T. , Arridge Simon R. , Thompson Alan J. , Miller David H.
Published: August 2003

Purpose

To evaluate the ability of a B‐spline active surface technique to detect cervical spinal cord atrophy due to multiple sclerosis (MS) compared with intensity‐based contouring.

Materials and Methods

In a previously reported study, the cervical spinal cords of 28 MS patients and 13 age‐matched controls were imaged with a volume‐acquired inversion‐prepared fast spoiled gradient echo sequence at baseline and after one year. The images were reanalyzed using the B‐spline technique and the results compared with the results obtained in the original report using intensity‐based contouring.

Results

The mean cervical spinal cord volume determined by the active surface programme was 6487 mm3 in 28 patients compared with 7117 mm3 in controls (P = 0.002, corrected for age and gender). The patients' cervical spinal cord volumes were associated with expanded disability status scale scores (parameter estimate = −1.21 × 10−3, r2 = 0.39, P = 0.001). The patients' cervical spinal cord volumes did not decrease significantly over one year, unlike the mean cervical spinal cord areas at C2/3 calculated using intensity‐based contouring.

Conclusion

The active surface technique can detect cervical spinal cord atrophy due to MS, which has functional significance. However, this methodology is less sensitive at detecting small serial changes compared with the previously reported method. J. Magn. Reson. Imaging 2003;18:368–371. © 2003 Wiley‐Liss, Inc.
Single‐shot spiral image acquisition with embedded z‐shimming for susceptibility signal recovery
Authors: Guo Hua , Song Allen W.
Published: August 2003

Purpose

To efficiently and effectively recover the susceptibility‐induced signal losses for functional MRI (fMRI) experiments.

Materials and Methods

The signal losses near air/tissue interfaces at the ventral brain regions introduce difficulties in the neuroimaging studies concerned with brain functions such as memory, emotion, and olfaction processes. The z‐shimming technique has been introduced in fMRI image acquisition to recover such losses. One significant drawback of such an approach is its time consuming nature. In this report, a single‐shot spiral imaging method, which combines spiral‐in and spiral‐out acquisitions along with embedded z‐shimming gradient, was proposed and implemented to achieve signal recovery without sacrificing temporal resolution.

Results

Using the proposed method, final images were shown in the ventral brain regions. The images were acquired with a throughput of 16 slices/second and demonstrated effectiveness and efficiency in signal recovery near air/tissue interfaces.

Conclusion

Uniform recovery can be achieved efficiently near air/tissue interfaces where susceptibility‐induced spatial gradients are pronounced. We anticipate that our method would be well suited for fMRI studies involving the ventral brain areas. J. Magn. Reson. Imaging 2003;18:389–395. © 2003 Wiley‐Liss, Inc.
The interrupted rim sign in acute cholecystitis: A method to identify the gangrenous form with MRI
Authors: Pedrosa Ivan , Guarise Alessandro , Goldsmith Jeffrey , Procacci Carlo , Rofsky Neil M.
Published: August 2003

We present the imaging findings on MR of a patient with acute gangrenous cholecystitis that demonstrated patchy enhancement of the gallbladder mucosa on gadolinium‐enhanced fat‐saturated T1‐weighted gradient echo images. This interrupted rim of mucosal enhancement correlated with patchy areas of necrosis and inflammation of the gallbladder mucosa on the histopathological examination. J. Magn. Reson. Imaging 2003;18:360–363. © 2003 Wiley‐Liss, Inc.
Assessment of normal, inflammatory, and tumor‐bearing lymph nodes with contrast‐enhanced interstitial magnetic resonance lymphography: Preliminary results in rabbits
Authors: Herborn Christoph U. , Vogt Florian M. , Lauenstein Thomas C. , Goyen Mathias , Dirsch Olaf , Corot Claire , Debatin Jörg F. , Ruehm Stefan G.
Published: August 2003

Purpose

To assess different gadolinium (Gd)‐based contrast agents for interstitial magnetic resonance (MR) lymphography in normal, inflammatory, and tumor‐bearing lymph nodes in rabbits.

Materials and Methods

Three paramagnetic contrast agents were assessed: a standard extracellular 0.5 M Gd‐chelate, gadoterate meglumine (Gd‐DOTA), and two macromolecular agents, P792 and P760 (all Guerbet, Aulnay‐sous‐Bois, France). A volume of 0.5 mL of each agent were injected subcutaneously into the dorsal footpads of six rabbits (three groups, 18 rabbits). Imaging was performed prior to as well as two weeks following induction of either reactive (complete Freund adjuvant) or tumorous (VX2 tumor) lymph nodes. T1‐weighted three‐dimensional gradient‐echo and maximum intensity projection (MIP) images were obtained up to 120 minutes as well as 24 hours after administration of the different compounds. Signal‐to‐noise ratios (SNRs) of enhancing lymph nodes were calculated. The different compounds were compared regarding nodal enhancement over time, depiction of regional nodes, and lymphatic vessels. Furthermore, enhancement patterns were compared between normal, inflammatory, and metastasized nodes.

Results

Inguinal and iliac lymph nodes and lymph vessels revealed enhancement following interstitial injection of all evaluated compounds. For all agents, inflammatory lymph nodes revealed no significantly different SNRs compared to normal nodes (P > 0.2), whereas tumorous nodes showed signal voids and significantly lower SNRs (P < 0.05). Compared to P760 and P792, depiction of tumor‐bearing nodes with Gd‐DOTA was less reliable.

Conclusion

Interstitial MR lymphography with P760 and P792 allows differentiation of tumor‐bearing lymph nodes from reactive inflammatory and normal nodes based on a contrast uptake pattern assessed qualitatively as well as quantitatively.J. Magn. Reson. Imaging 2003;18:328–335. © 2003 Wiley‐Liss, Inc.
T1ρ‐relaxation mapping of human femoral‐tibial cartilage in vivo
Authors: Regatte Ravinder Reddy , Akella Sarma V.S. , Wheaton Andrew J. , Borthakur Arijitt , Kneeland J. Bruce , Reddy Ravinder
Published: August 2003

Purpose

To demonstrate the in vivo feasibility of measuring spin‐lattice relaxation time in the rotating frame (T1ρ); and T1ρ‐dispersion in human femoral cartilage. Furthermore, we aimed to compute the baseline T1ρ‐relaxation times and spin‐lock contrast (SLC) maps on healthy volunteers, and compare relaxation times and signal‐to‐noise ratio (SNR) with corresponding T2‐weighted images.

Materials and Methods

All MR imaging experiments were performed on a 1.5 T GE Signa scanner (GEMS, Milwaukee, WI) using a custom built 15‐cm transmit‐receive quadrature birdcage radio‐frequency (RF) coil. The T1ρ‐prepared magnetization was imaged with a single‐slice two‐dimensional fast spin‐echo (FSE) pulse sequence preencoded with a three‐pulse cluster consisting of two hard 90° pulses and a low power spin‐lock pulse. T1ρ‐dispersion imaging was performed by varying the spin‐lock frequency from 100 to 500 Hz in five steps in addition to varying the length of the spin‐lock pulse.

Results

The average T1ρ‐relaxation times in the weight‐bearing (WB) and nonweight‐bearing (NWB) regions of the femoral condyle were 42.2 ± 3.6 msec and 55.7 ± 2.3 msec (mean ± SD, N = 5, P < 0.0001), respectively. In the same regions, the corresponding T2‐relaxation times were 31.8 ± 1.5 msec and 37.6 ± 3.6 msec (mean ± SD, N = 5, P < 0.0099). T1ρ‐weighted images have ∼20%–30% higher SNR than the corresponding T2‐weighted images for similar echo time. The average SLC in the WB region of femoral cartilage was 30 ±4.0%. Furthermore, SLC maps provide better contrast between fluid and articular surface of femoral‐tibial joint than T1ρ‐maps. The T1ρ‐relaxation times varied from 32 msec to 42 msec (∼31%) in the WB and 37 msec to 56 msec (∼51%) in NWB regions of femoral condyle, respectively, in the frequency range 0–500 Hz (T1ρ‐dispersion).

Conclusion

The feasibility of performing in vivo T1ρ relaxation mapping in femoral cartilage at 1.5T clinical scanner without exceeding Food and Drug Administration (FDA) limits on specific absorption rate (SAR) of RF energy was demonstrated. J. Magn. Reson. Imaging 2003;18:336–341. © 2003 Wiley‐Liss, Inc.
Spatial resolution of numerical models of man and calculated specific absorption rate using the FDTD method: A study at 64 MHz in a magnetic resonance imaging coil
Authors: Collins Christopher M. , Smith Michael B.
Published: August 2003

Purpose

To examine how fine a model resolution is necessary for calculation of specific energy absorption rate (SAR) for the human head in regions as small as 1 g.

Materials and Methods

Here we perform a simple study comparing the maximum SAR averaged over any 1 cm3 and SAR averaged over the entire head for several models of the same human head within the same radiofrequency coil, but with spatial resolutions varying from 8–100 Yee cells per cm3.

Results

Over the range of model resolutions from 8–100 Yee cells per cm3, there is only a 16% variation in maximum SAR in any 1 cm3 of tissue in the head, and only a 7% variation in SAR averaged over the entire head.

Conclusion

While it is always desirable to perform SAR calculations with the greatest possible accuracy, in calculations of the maximum SAR levels in any 1 cm3 of tissue, spatial resolutions greater than 5 mm may not yield notably different results than those with a spatial resolution of 5 mm. J. Magn. Reson. Imaging 2003;18:383–388. © 2003 Wiley‐Liss, Inc.
Quantitative T2 in the occipital lobe: The role of the CPMG refocusing rate
Authors: Stefanovic Bojana , Sled John G. , Pike G. Bruce
Published: August 2003

Purpose

To investigate the dependence of occipital gray and white matter T2 on the Carr‐Purcell‐Meiboom‐Gill (CPMG) refocusing interval, thereby testing the basis of a novel functional magnetic resonance imaging (fMRI) method for blood volume quantification, and addressing recent questions surrounding T2 contrast in the occipital lobe.

Materials and Methods

A CPMG sequence with 1 × 1 × 5 mm3 resolution was used to quantify T2 in a single axial slice at the midlevel of the occipital lobe in 23 healthy adult volunteers. Refocusing intervals of 8, 11, and 22 msec were compared. A Bayesian classifier was used to classify a 1 × 1 × 1 mm3 T1‐weighted three‐dimensional data set into gray matter, white matter, and cerebrospinal fluid, with an average 95% a posteriori probability used as the threshold for inclusion into a tissue‐specific region of interest (ROI).

Results

The usual T2 contrast between the gray and white matter (i.e., T2GM > T2WM) was observed, with a highly significant effect of tissue type on the estimated T2 (P < 10−5). The observed T2 gradually decreased with increasing refocusing interval, for a decrease of 3.3 ± 1.5 msec in gray matter and 3.0 ± 1.5 msec in white matter between the 8 and 22 msec refocusing interval acquisitions.

Conclusion

The observed T2 shortening is consistent with the effect of the dramatic decrease in T2 of partly deoxygenated blood on this range of refocusing rates. J. Magn. Reson. Imaging 2003;18:302–309. © 2003 Wiley‐Liss, Inc.
Dynamic contrast enhanced perfusion MRI in mycosis fungoides
Authors: Law Meng , Teicher Noah , Zagzag David , Knopp Edmond A.
Published: August 2003

Mycosis fungoides is a malignant, cutaneous lymphoma of T‐helper (TH or CD4+) cells. At presentation, the disease is usually limited to the skin, with lesions that resemble eczema or psoriasis. Neurologic involvement is uncommon. This case demonstrates the conventional MRI and dynamic contrast enhanced perfusion MRI findings in intracerebral mycosis fungoides. T1‐weighted spin echo imaging demonstrated a lesion with slightly decreased signal within the body of the corpus callosum. The lesion was isointense with grey matter on axial T2‐weighted imaging. Following administration of contrast, there was patchy heterogeneous enhancement. Multiple relative cerebral blood volume (rCBV) measurements were made and the minimum rCBV was 0.30 with the maximum rCBV being 1.61. The mean rCBV was 0.81 ± 0.49 (average of 10 measurements and standard deviation). J. Magn. Reson. Imaging 2003;18:364–367. © 2003 Wiley‐Liss, Inc.
Enhanced gray and white matter contrast of phase susceptibility‐weighted images in ultra‐high‐field magnetic resonance imaging
Authors: Abduljalil Amir M. , Schmalbrock Petra , Novak Vera , Chakeres Donald W.
Published: August 2003

Purpose

To evaluate if magnetic susceptibility sensitive phase postprocessed images can be used to enhance the inherent brain/gray white matter contrast in gradient echo (GE) images at 8‐Tesla (T) magnetic resonance (MR).

Materials and Methods

Phase and magnitude images of high‐resolution GE MR 8‐T images were created. Comparisons were made between the magnitude, the product of the magnitude and phase, and pure phase images.

Results

The pure phase images significantly improved the contrast between the gray and white matter structures. In general, the higher the iron content or subvoxel field inhomogeneities, the higher was the contrast, and the greater were the resultant phase shifts. The phase images best demonstrated anatomy that was not apparent on the standard magnitude images.

Conclusion

Phase imaging can significantly improve the demonstration of the internal anatomical brain structures over standard magnitude GE imaging techniques at high field. J. Magn. Reson. Imaging 2003;18:284–290. © 2003 Wiley‐Liss, Inc.
Inflow effect in first‐pass cardiac and renal MRI
Authors: Ivancevic Marko K. , Zimine Ivan , Foxall David , Lecoq Guillaume , Righetti Alberto , Didier Dominique , Vallée Jean‐Paul
Published: August 2003

Purpose

To estimate the effect of the inflow effect on the arterial input function in vivo in cardiac and renal MR perfusion imaging using fast gradient echo (GRE) sequences and contrast media.

Materials and Methods

The MR exam protocol was designed to acquire images at different phases of the cardiac cycle. The arterial input was thus influenced by various blood flow velocities.

Results

It was found that the inflow effect was negligible in the left ventricle of the heart, while it was significantly higher in the aorta for the kidney perfusion measurement. This was principally due to the higher through‐the‐plane component of the blood flow velocity in the aorta than in the left ventricle.

Conclusion

The inflow effect can be neglected in the heart cavity, but should be taken into account in renal perfusion. J. Magn. Reson. Imaging 2003;18:372–376. © 2003 Wiley‐Liss, Inc.
Fat suppression strategies in enhanced MR imaging of the breast: Comparison of SPIR and water excitation sequences
Authors: Niitsu Mamoru , Tohno Eriko , Itai Yuji
Published: August 2003

Purpose

To compare two fat suppression techniques of spectrally‐selective inversion pulse (spectral presaturation with inversion recovery—SPIR) and spectral‐spatial excitation pulse of water excitation (WE) for contrast‐enhanced MR imaging of the breast.

Materials and Methods

Forty women with histologically‐proven breast cancer were examined. Both pulse types were applied to postcontrast, axial, three‐dimensional field echo sequence. Contrast noise ratios (CNR) of lesion‐to‐breast parenchyma, lesion‐to‐fat, and parenchyma‐to‐fat were determined. Qualitative image analysis using a four‐point scale was also performed by two observers.

Results

All the CNR values of obtained with WE techniques were significantly higher than those with SPIR. Qualitative analysis indicated that the WE images were statistically superior for the lesion‐to‐breast parenchyma contrast while being slightly inferior to the SPIR images for fat suppression homogeneity without statistical significance.

Conclusion

Compared to SPIR, the WE technique suppressed the subcutaneous fat signal more potently and improved the contrast of the enhanced breast lesion against the parenchyma and the subcutaneous fat. WE will be a powerful fat suppression strategy for enhanced MR imaging of the breast. J. Magn. Reson. Imaging 2003;18:310–314. © 2003 Wiley‐Liss, Inc.
Three‐dimensional analysis of the geometry of individual multiple sclerosis lesions: Detection of shape changes over time using spherical harmonics
Authors: Goldberg‐Zimring Daniel , Achiron Anat , Guttmann Charles R.G. , Azhari Haim
Published: August 2003

Purpose

To suggest a quantitative method for assessing the temporal changes in the geometry of individual multiple sclerosis (MS) lesions in follow‐up studies of MS patients.

Materials and Methods

Computer simulated and in vivo magnetic resonance (MR) imaged MS lesions were studied. Ten in vivo MS lesions were identified from sets of axial MR images acquired from a patient scanned consecutively for 24 times during a one‐year period. Each of the lesions was segmented and its three‐dimensional surface approximated using spherical harmonics (SH). From the obtained SH polynomial coefficients, indices of shape were defined, and analysis of the temporal changes in each lesion's geometry throughout the year was performed by determining the mean discrete total variation of the shape indices.

Results

The results demonstrate that most of the studied lesions undergo notable geometrical changes with time. These changes are not necessarily associated with similar changes in size/volume. Furthermore, it was found that indices corresponding to changes in lesion shape could be 1.4 to 8.0 times higher than those corresponding to changes in the lesion size/volume.

Conclusion

Quantitative three‐dimensional shape analysis can serve as a new tool for monitoring MS lesion activity and study patterns of MS lesion evolution over time. J. Magn. Reson. Imaging 2003;18:291–301. © 2003 Wiley‐Liss, Inc.
Randomized comparison of cognitive function in humans at 0 and 8 Tesla
Authors: Chakeres Donald W. , Bornstein Robert , Kangarlu Allahyar
Published: August 2003

Purpose

To discover whether there was a measurable alteration in cognitive performance in humans when exposed to a static magnetic field of 8 Tesla (T).

Materials and Methods

Twenty‐five normal human subjects were evaluated at both 0.05 and 8 T in a randomized order. Six standardized neuropsychological tests were administered and auditory reaction times were assessed. The cognitive assessment included measures of learning and retention, verbal fluency (spontaneous word generation), auditory attention, and auditory working memory. Alternate test forms were utilized to reduce practice effects. The sequential order of testing, 0.05 T first vs. 8 T first exposure, was randomized. The data was analyzed using univariate comparisons for correlated means to assess potential differences under the two conditions.

Results

There were no clinically significant differences in any of the measures. On a measure of recognition memory the subjects performed significantly better in the 0.05T condition, but the difference was extremely small, not clinically meaningful, and likely due to statistical artifact.

Conclusion

This study shows that exposure of the brain to high magnetic fields of up to 8 T does not appear to alter human cognitive performance. J. Magn. Reson. Imaging 2003;18:342–345. © 2003 Wiley‐Liss, Inc.
Effect of static magnetic field exposure of up to 8 Tesla on sequential human vital sign measurements
Authors: Chakeres Donald W. , Kangarlu Alayar , Boudoulas Harisios , Young Donn C.
Published: August 2003

Purpose

To determine if increasing static magnetic field strength exposures up to 8 Tesla (T) affect vital signs or electrocardiograms (ECGs) in normal human volunteers.

Materials and Methods

We studied 25 normal subjects, consisting of 19 men and six women, ages 24–53 years. The vital signs and ECGs of the subjects were measured 14 times inside and outside the magnetic field. This included the heart rate, respiratory rate, systolic and diastolic blood pressures, finger pulse oxygenation levels, core body temperature via the external auditory canal temperature, and fiber optic core body sublingual temperatures. Inside the magnetic field the vital signs were measured sequentially at field strengths of 8, 6, 4.5, 3, and 1.5 T.

Results

The only statistically significant effect of magnetic field strength was observed with systolic blood pressure. An average increase of 3.6 mm Hg in systolic blood pressure was seen with 8 T exposure. ECG rhythm strip analysis demonstrated no significant changes post‐exposure.

Conclusions

Normal subjects exposed to varying magnetic field strengths of up to 8 T demonstrated no clinically significant changes in vital signs. Transient ECG artifacts were noted to increase with the field strength. J. Magn. Reson. Imaging 2003;18:346–352. © 2003 Wiley‐Liss, Inc.
Pain dynamics observed by functional magnetic resonance imaging: Differential regression analysis technique
Authors: Cho Zang‐Hee , Son Young‐Don , Kang Chang‐Ki , Han Jae‐Yong , Wong Edward K. , Bai Sun‐Joon
Published: August 2003

Purpose

To observe the dynamic responses of the cortical areas related to the pain processing by using the differential regression analysis (DRA) technique in functional magnetic resonance imaging (fMRI) and investigation of pain mechanisms.

Materials and Methods

For pain studies, thermal stimulation was applied by immersing the index finger into a hot bath of water with a temperature of 50–52°C. Motor (finger tapping) and visual (flickering light) stimulation experiments were conducted to elucidate the physiological differences between the simple sensory tasks and pain tasks. To obtain dynamic responses, T values (regression analysis) were sequentially estimated by using a series of shifted differential window functions (narrow width).

Results

By using the DRA technique, well‐defined prompt responses were observed for both motor and visual stimuli. On the other hand, in the pain experiment, a set of sequentially varying responses was observed for the thalamus (Thal), the dorsal anterior cingulate cortex (dACC), the caudal ACC (cACC), and the rostral ACC (rACC). This time‐dependent response suggests the dynamics of pain signal processing in cortical areas.

Conclusion

The results support the hypothesis that the activated areas are similar to the previously reported pain processing areas; however, new sequential responses were observed, suggesting that the technique may reveal dynamics of pain perception and their pathway, important elements in understanding the mechanism of pain. The DRA technique can provide a new opportunity for many spatiotemporal analyses, for example, the physiologically complex and little‐studied physiological phenomena, such as pain dynamics. J. Magn. Reson. Imaging 2003;18:273–283. © 2003 Wiley‐Liss, Inc.
Method for quantitation of dynamic MRI contrast agent uptake in colorectal liver metastases
Authors: van Laarhoven Hanneke W.M. , Rijpkema Mark , Punt Cornelis J.A. , Ruers Theo J. , Hendriks Jan C.M. , Barentsz Jelle O. , Heerschap Arend
Published: August 2003

Purpose

To investigate the reproducibility of dynamic contrast‐enhanced MRI (DCE‐MRI) in colorectal liver metastases using a vascular normalization function (VNF) from pixels in the spleen and to compare this with a technique using an arterial input function (AIF) from pixels in the aorta.

Materials and Methods

DCE‐MRI with gadolinium‐DTPA (Gd‐DTPA) was performed in patients with colorectal liver metastases. The VNF and AIF were determined using an automated algorithm. The average Gd‐DTPA uptake rate (kep) was calculated for the metastases using a physiological pharmacokinetic model. The protocol was repeated on a second day to calculate the repeatability coefficient of the measurements of kep.

Results

Using the VNF from the spleen the overall mean kep of the two sessions for 11 patients was 0.033 per second and the repeatability coefficient was 0.009 per second. Using the AIF from the aorta these values were 0.031 per second and 0.028 per second, respectively.

Conclusion

The mean Gd‐DTPA uptake rate using a VNF taken from the spleen can be determined with adequate reproducibility in colorectal liver metastases. The use of a VNF from pixels in the spleen is better than an AIF from pixels in the aorta in terms of reproducibility, and is recommended when this DCE‐MRI technique is used for prediction and monitoring of therapy outcome in colorectal liver metastases. J. Magn. Reson. Imaging 2003;18:315–320. © 2003 Wiley‐Liss, Inc.
Magnetization transfer contrast imaging in Niemann pick type C mouse liver
Authors: Guo Jingyu , Erickson Robert , Trouard Theodore , Galons Jean‐Philippe , Gillies Robert
Published: August 2003

Purpose

To investigate livers of mice afflicted with Niemann Pick type C (NP‐C) disease using magnetization transfer contrast (MTC) imaging and to test the hypothesis that the MT ratio reproducibly changes during disease progression.

Background

NP‐C is a heritable defect of lipid metabolism that results in the accumulation of unesterified cholesterol and gangliosides in virtually all cells. Symptoms predominate in brain and liver, which have high endogenous rates of lipid turnover. It is fatal to children, usually early in the second decade of life. Previous work has shown that the efficiency of magnetization transfer (MT) can be affected by cholesterol and collagen in tissues. The MT ratio (MTR) was calculated and compared during growth and therapy of diseased and control mice.

Results

Significant differences in the MTR were observed between livers of diseased and control mice. These ratios were consistent with collagen deposition associated with fibrosis, and not the accumulation of unesterified cholesterol in this organ.

Conclusion

These results indicate that MTC imaging may have clinical potential for monitoring progression and therapy in NP‐C disease. J. Magn. Reson. Imaging 2003;18:321–327. © 2003 Wiley‐Liss, Inc.
Probing of arginine residues in peptides and proteins using selective tagging and electrospray ionization mass spectrometry
Authors: Leitner Alexander , Lindner Wolfgang
Published: August 2003

A general labelling method is presented which allows the determination of the number of guanidine groups (related to arginine and homoarginine in peptides and proteins) by means of mass spectrometry. It implies a guanidine‐selective derivatization step with 2,3‐butanedione and an arylboronic acid under aqueous, alkaline conditions (pH 8–10). The reaction mixture is then directly analysed by electrospray ionization mass spectrometry without further sample pretreatment. Other amino acids are not affected by this reaction although it is demonstrated that lysine side‐chains may be unambiguously identified when they are converted to homoarginine prior to derivatization. Guanidine functionalities, as e.g. in the amino acid arginine, are easily identified by the characteristic mass shift between underivatized and derivatized analyte. The tagging procedure is straightforward and selective for guanidine groups. The influence of several experimental parameters, especially the pH of the solution and the choice of reagents, is examined and the method is applied to various arginine‐containing peptides and to lysozyme as a representative protein. Possible applications of this technique and its limitations are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Sensitive liquid chromatographic/tandem mass spectrometric method for the determination of beclomethasone dipropionate and its metabolites in equine plasma and urine
Authors: Guan Fuyu , Uboh Cornelius , Soma Lawrence , Hess Anne , Luo Yi , Tsang Deborah S.
Published: August 2003

Beclomethasone dipropionate (BDP) is a potent pro‐drug to beclomethasone (BOH) and is used in the treatment of chronic and acute respiratory disorders in the horse. The therapeutic dose of BDP (325 µg per horse) by inhalation results in very low plasma and urinary concentrations of BDP and its metabolites that pose a challenge to detection and confirmation by equine forensic laboratories. To solve this problem, a method involving the use of a liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed for the detection, confirmation and quantification of the analytes in equine samples. Ammonium formate or acetate buffer added to LC mobile phase favored the formation of [M + H]+ions from BDP and its metabolites, whereas formic acid led to the formation of sodium and potassium adduct ions ([M + Na]+, [M + K]+) together with [M + H]+ions. Acetonitrile, on the other hand, favored the formation of abundant solvent adduct ions [M + H + CH3CN]+with the analytes under electrospray ionization (ESI) and atmospheric pressure chemical ionization conditions. In contrast, methanol formed much less solvent adduct ions than acetonitrile. The solvent adduct ions were thermally stable and could not be completely desolvated under the experimental conditions, but they were very fragile to collision‐induced dissociation (CID). Interestingly, these solvent adduct ions were observed on a triple‐quadrupole mass spectrometry but not on an ion trap instrument where helium used as a damping gas in the ion trap might cause the solvent adduct ions desolvated by collision. By CID studies on the [M + H]+ions of BDP and its metabolites, their fragmentation paths were proposed. In equine plasma at ambient temperature over 2 h, BDP and B21P were hydrolyzed in part to B17P and BOH, respectively, but B17P was not hydrolyzed. Sodium fluoride added to equine plasma inhibited the hydrolysis of BDP and B21P. The matrix effect in ESI was evaluated in equine plasma and urine samples. The method involved the extraction of BDP and its metabolites from equine plasma and urine samples by methyltert‐butyl ether, resolution on a C8column with a mobile phase gradient consisting of methanol and ammonium formate (2 mmol l−1, pH 3.4) and multiple reaction monitoring for the analytes on a triple‐quadrupole mass spectrometer. The detection limit was 13 pg ml−1for BDP and B17P, 25 pg ml−1for BOH and 50 pg ml−1for B21P in plasma and 25 pg ml−1for BOH in urine. The method was successfully applied to the analysis of equine plasma and urine samples for the analytes following administration of BDP to horses by inhalation. B17P, the major and active metabolite of BDP, was detected and quantified in equine plasma up to 4 h post‐administration by inhalation of a very low therapeutic dose (325 µg per horse) of BDP. Copyright © 2003 John Wiley & Sons, Ltd.
Study of the fragmentation mechanism of novel functionalized macrocycles by Fourier transform ion cyclotron resonance mass spectrometry
Authors: Chen Hui , Du Da‐Ming , Hua Wen‐Ting , He Meiyu , Xin Bin
Published: August 2003

Liquid secondary ion mass spectrometry (L‐SIMS) of six new functionalized macrocycles was investigated. All six compounds yielded abundant fragment ions and protonation molecular ions [M + H]+ under L‐SIMS conditions. The proposed fragmentation mechanisms were supported by high‐resolution accurate mass data from Fourier transform ion cyclotron resonance mass spectrometric and MSn experiments on using sustained off‐resonance irradiation collision‐induced dissociation. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison of electrospray ionization and atmospheric pressure chemical ionization techniques in the analysis of the main constituents from Rhodiola rosea extracts by liquid chromatography/mass spectrometry
Authors: Tolonen Ari , Hohtola Anja , Jalonen Jorma
Published: August 2003

Rhodiola rosea L. (Golden Root) has been used for a long time as an adaptogen in Chinese traditional medicine and is reported to have many pharmacological properties. A liquid chromatographic (LC) method with mass spectrometric (MS) detection based on selected ion monitoring (SIM) was developed for determining salidroside, sachaliside 1, rosin, 4‐methoxycinnamyl‐O‐β‐glucopyranoside, rosarin, rosavin, cinnamyl‐(6′‐O‐β‐xylopyranosyl)‐O‐β‐glucopyranoside, 4‐methoxy‐cinnamyl‐(6′‐O‐α‐arabinopyranosyl)‐O‐β‐glucopyranoside, rosiridin and benzyl‐O‐β‐glucopyranoside from the callus and plant extracts in one chromatographic run. Good linearity over the range 0.5–500 ng ml−1 for salidroside, 2–2000 ng ml−1 for rosavin and 2–500 ng ml−1 for benzyl‐O‐β‐glucopyranoside was observed. The intra‐assay accuracy and precision within quantitation ranges varied between −10.0 and +13.2% and between 0.7 and 9.0%, respectively. Optimization of the ionization process was performed with electrospray and atmospheric pressure chemical ionization techniques using four different additive compositions for eluents in the LC/MS scan mode, using both positive and negative ion modes. The best ionization sensitivity for the compounds studied was obtained with electrospray ionization when using pure water without any additives as the aqueous phase. Copyright © 2003 John Wiley & Sons, Ltd.
Gas‐phase hydrogen/deuterium exchange of adenine nucleotides
Authors: Crestoni Maria Elisa , Fornarini Simonetta
Published: August 2003

Gas‐phase hydrogen/deuterium exchange reactions of (de)protonated (sodiated) adenosine‐5′‐mono‐, di‐ and triphosphate ions with CD3OD, CD3CO2D and ND3 were achieved using a combination of electrospray ionization and Fourier transform ion cyclotron resonance mass spectrometry. The reaction kinetics are dependent on factors such as the charge state, the phosphate chain length, the properties of the exchange reactants and the sodium content. The results indicate that the overall H/D exchange may involve specific sites even if endowed with high energetic barriers. The enhanced reactivity exhibited by adenosine polyphosphate ions compared with adenosine‐5′‐monophosphate suggests a critical role of the polyphosphate chain in rendering conformationally accessible remote H‐donor sites. Low‐energy collision‐induced dissociation of (sodiated) adenine nucleotides anions supports the aptitude of the (poly)phosphate chain in probing distant sites via the intermediacy of a cyclic structure. Copyright © 2003 John Wiley & Sons, Ltd.
Band composition analysis: a new procedure for deconvolution of the mass spectra of organometallic compounds
Authors: Szymura Jacek A. , Lamkiewicz Jan
Published: August 2003

A new chemometric procedure called band composition analysis (BCA) designed for the deconvolution of mass spectra of organometallics is proposed. BCA generates theoretical bands Ti, then combines them to obtain a model band M, which is finally compared with the experimental band E. All of these steps are realized with computer assistance. This modeling yields four parameters characterizing the experimental band: theoretical and model variances s2theor and s2model, a fit factor α and a contribution xi from the theoretical band. If s2theor > 20 the band is deemed complex and needs modeling. The values α > 90 indicate that there is good agreement between the experimental and model bands. BCA is particularly effective for the modeling of complex isotopic bands often present in organometallics. Two illustrations of BCA for tetrabutyltin, C16H36Sn, and 1,1′,2,2′,3,3′‐hexachloroferrocene, C10H4Cl6Fe, are shown. Copyright © 2003 John Wiley & Sons, Ltd.
Stable isotope labeling for matrix‐assisted laser desorption/ionization mass spectrometry and post‐source decay analysis of ribonucleic acids
Authors: Berhane Beniam T. , Limbach Patrick A.
Published: August 2003

Matrix‐assisted laser desorption/ionization mass spectrometry is a powerful analytical tool for the structural characterization of oligonucleotides and nucleic acids. Here we report the application of stable isotope labeling for the simplified characterization of ribonucleic acids (RNAs). An 18O label is incorporated at the 3′‐phosphate of oligoribonucleotides during the enzymatic processing of intact RNAs. As implemented, a buffer solution containing a 50 : 50 mixture of H2O and 18O‐labeled H2O is used during endonuclease digestion. Upon digestion, characteristic doublets representative of the isotopic distribution of oxygen are noted for those products that contain 3′‐phosphate groups. This approach is used to distinguish readily endonuclease digestion products from incomplete digestion products and non‐specific cleavage products. In addition, RNase digestion products containing the characteristic isotopic doublet can be selected for further characterization by post‐source decay (PSD) analysis. PSD products carrying the 3′‐phosphate group will appear as a doublet, thereby simplifying fragment ion assignment. Copyright © 2003 John Wiley & Sons, Ltd.
Strategy for structural elucidation of drugs and drug metabolites using (MS)n fragmentation in an electrospray ion trap
Authors: Tozuka Zenzaburo , Kaneko Hayato , Shiraga Toshifumi , Mitani Yasuyuki , Beppu Manabu , Terashita Shigeyuki , Kawamura Akio , Kagayama Akira
Published: August 2003

Triple‐stage quadrupole (TSQ) electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and ion trap ESI‐MS/MS can be used to cleave protonated molecules to produce carbocations and neutral molecules in the positive ion mode. Dissociation products which correspond to protonated forms of neutral fragment molecules can also be trapped and detected. These protonated molecules in turn can cleave via carbocation cleavage, ipso cleavage, onium cleavage or McLafferty or related rearrangements. One can elucidate the structures of metabolites from the differences in m/z ratios of the fragments arising from the original drug compound and its metabolite. This strategy for structural elucidation is further facilitated by estimates of the reactivity of drugs with oxygen diradicals involved in cytochrome P‐450 cycles. Copyright © 2003 John Wiley & Sons, Ltd.
Deletions in env gene of HIV‐1 in AIDS patients treated with highly active antiretroviral therapy (HAART)
Authors: Saurya Shreesh , Lichtenstein Zelman , Karpas Abraham
Published: August 2003

Many AIDS patients retain high CD4+ T‐cell counts despite a significant increase in PCR viral load after varied periods of treatment on drug combination with Highly Active Antiretroviral Therapy (HAART). In order to investigate this contradictory phenomenon, we assayed for infectious HIV‐1 from the plasma of such patients. Since the biological assays failed to reveal any infectious virus, we undertook molecular characterization of the plasma HIV‐1 genes. These studies revealed large deletions in the env gene of the free virus, while there were no deletions in the proviral DNA obtained from the infected cells of the patients' blood. This suggests that the viral particles produced and released by the infected cells during the HAART treatment have deletions in the env gene. The deletions were large enough to produce an envelop‐deficient virus, which can readily explain why it is not infectious. Such a defective virus is the most likely explanation for its failure to infect the T‐cells, which in turn lead to the discordance between the high PCR viral load and stable CD4+ T cell counts. J. Med. Virol. 71:167–172, 2003. © 2003 Wiley‐Liss, Inc.
HIV‐2 derived lentiviral vectors: Gene transfer in Parkinson's and Fabry disease models in vitro
Authors: D'Costa Jenice , Harvey‐White Judith , Qasba Pankaj , Limaye Advait , Kaneski Christine R. , Davis‐Warren Alberta , Brady Roscoe O. , Bankiewicz Krys S. , Major Eugene O. , Arya Suresh K.
Published: August 2003

Lentiviral vectors are prime candidate vectors for gene transfer into dividing and non‐dividing cells, including neuronal cells and stem cells. For safety, HIV‐2 lentiviral vectors may be better suited for gene transfer in humans than HIV‐1 lentiviral vectors. HIV‐2 vectors cross‐packaged in HIV‐1 cores may be even safer. Demonstration of the efficacy of these vectors in disease models will validate their usefulness. Parkinson's disease and Fabry disease provide excellent models for validation. Parkinson's disease is a focal degeneration of dopaminergic neurons in the brain with progressive loss of ability to produce the neurotransmitter dopamine. Current treatment entails administration of increasing doses of L‐dopa, with attendant toxicity. We explore here the hypothesis that gene transfer of aromatic acid decarboxylase (AADC), a key enzyme in the pathway, will make neuronal cells more efficiently convert L‐dopa into dopamine. Fabry disease on the other hand is a monogenic inherited disease, characterized by α‐galactosidase A (AGA) deficiency, resulting in glycolipid accumulation in several cell types, including fibroblasts. Animal models for preclinical investigations of both of these diseases are available. We have designed monocistronic HIV‐1 and HIV‐2 vectors with the AADC transgene and monocistronic and bicistronic HIV‐2 vectors with the AGA and puromycin resistance transgenes. They were packaged with either HIV‐2 cores or HIV‐1 cores (hybrid vectors). Gene transfer of AADC gene in neuronal cells imparted the ability on the transduced cells to efficiently convert L‐dopa into dopamine. Similarly, the AGA vectors induced Fabry fibroblasts to produce high levels of AGA enzyme and caused rapid clearance of the glycolipids from the cells. Both monocistronic and bicistronic vectors were effective. Thus, the insertion of a second gene downstream in the bicistronic vector was not deleterious. In addition, both the self‐packaged vectors and the cross‐packaged hybrid vectors were effective in gene transfer. J. Med. Virol. 71:173–182, 2003. © 2003 Wiley‐Liss, Inc.
Determination of HBsAg subtypes in Western Siberian part of Russia
Authors: Netesova I.G. , Swenson P.D. , Osipova L.P. , Gubina M.A. , Posukh O.L. , Netesov S.V.
Published: August 2003

A set of monoclonal antibodies with specificity for hepatitis B surface antigen (HBsAg) was used for subtyping this antigen in sera from indigenous natives, blood donors, and drug users in Western Siberia with a modified commercial enzyme immunoassay kit for HBsAg detection. Three subtypes of HBsAg in a ratio of 36 (78%) ayw2:8 ayw3varB (18%):2 (4%) adw2 were found in 46 (100%) HBsAg‐positive sera of different aboriginal populations of Western Siberia: the Tundra Nenets, Northern Khanty, Southern Altaians, and Kazakhs. Four subtypes of HBsAg in a ratio of 81 (57%) ayw2:58 (15 ayw3varA and 43 ayw3varB; 44%):2 (1%) adw2 were detected in 141 (100%) samples of blood donors from ten cities of Western Siberia. Three subtypes of HBsAg in a ratio of 34 ayw3:(both variants, 33 ayw3varA and 1 ayw3varB; 97.1%):1 (2.9%) ayw2 were found in blood of 35 injection drug users in Novosibirsk. J. Med. Virol. 71:183–187, 2003. © 2003 Wiley‐Liss, Inc.