Faculty Bibliography

At high and ultra-high magnetic field strengths, understanding interactions between tissues and the electromagnetic fields generated by radiofrequency coils becomes crucial for safe and effective coil design as well as for insight into limits of performance. In this work, we present a rigorous electrodynamic modeling framework, using dyadic Green's functions, to derive the electromagnetic field in homogeneous spherical and cylindrical samples resulting from arbitrary surface currents in the presence or absence of a surrounding radiofrequency shield. We show how to calculate ideal current patterns that result in the highest possible signal-to-noise ratio (ultimate intrinsic signal-to-noise ratio) or the lowest possible radiofrequency power deposition (ultimate intrinsic specific absorption rate) compatible with electrodynamic principles. We identify familiar coil designs within optimal current patterns at low to moderate field strength, thereby establishing and explaining graphically the near-optimality of traditional surface and volume quadrature designs. We also document the emergence of less familiar patterns, e.g., involving substantial electric- as well as magnetic-dipole contributions, at high field strength. Performance comparisons with particular coil array configurations demonstrate that optimal performance may be approached with finite arrays if ideal current patterns are used as a guide for coil design. Magn Reson Med, 2011. (c) 2011 Wiley Periodicals, Inc

We present high-resolution anatomical imaging of the cervical spinal cord in healthy volunteers at the ultrahigh field of 7 T with a prototype four-channel radiofrequency coil array, in comparison with 3-T imaging of the same subjects. Signal-to-noise ratios at both field strengths were estimated using the rigorous Kellman method. Spinal cord cross-sectional area measurements were performed, including whole-cord measurements at both fields and gray matter segmentation at 7 T. The 7-T array coil showed reduced sagittal coverage, comparable axial coverage and the expected significantly higher signal-to-noise ratio compared with equivalent 3-T protocols. In the cervical spinal cord, the signal-to-noise ratio was found by the Kellman method to be higher by a factor of 3.5 with the 7-T coil than with standard 3-T coils. Cervical spine imaging in healthy volunteers at 7 T revealed not only detailed white/gray matter differentiation, but also structures not visualized at lower fields, such as denticulate ligaments, nerve roots and rostral-caudal blood vessels. Whole-cord cross-sectional area measurements showed good agreement at both field strengths. The measurable gray/white matter cross-sectional areas at 7 T were found to be comparable with reports from histology. These pilot data demonstrate the use of higher signal-to-noise ratios at the ultrahigh field of 7 T for significant improvement in anatomical resolution of the cervical spinal cord, allowing the visualization of structures not seen at lower field strength, particularly for axial imaging

Kidney stones composed predominantly (50% or more) of calcium phosphate constitute up to 10% of all stones and 15%-20% of calcium stones, 80% of which are composed of calcium oxalate. Calcium phosphate is a minor component of up to 30% of calcium oxalate stones as well. The cause of calcium phosphate stones is often obscure but most often related to a high urine pH. Some patients with calcium phosphate stones may have incomplete renal tubular acidosis. Others have distal renal tubular acidosis characterized by hyperchloremic acidosis, hypocitraturia, and high urine pH. The use of carbonic anhydrase inhibitors such as acetazolamide, topiramate, and zonisamide leads to a similar picture. Treatment options to specifically prevent calcium phosphate stone recurrence have not been tested in clinical trials. Increases in urine volume and restriction of sodium intake to limit calcium excretion are important. Citrate supplementation is probably effective, although the concomitant increase in urine pH may increase calcium phosphate supersaturation and partially offset the inhibition of crystallization resulting from the increased urine citrate excretion and the alkali-associated reduction in urine calcium excretion. Thiazides lower urine calcium excretion and may help ensure the safety of citrate supplementation.

Tubulocystic renal cell carcinoma (TC-RCC) is a rare, typically unilateral renal tumor. We report the first case of bilateral multifocal TC-RCC associated with end-stage renal disease with cytogenetic, immunohistochemical, and ultrastructural studies. A 62-year-old man with type 2 diabetes, hypertension, and end-stage renal disease on hemodialysis had bilateral complex renal masses smaller than 3.0 cm in greatest dimension found incidentally. Follow-up imaging studies demonstrated slowly enlarging masses. The patient underwent bilateral laparoscopic radical nephrectomy. Grossly, both kidneys had multifocal, unencapsulated, sharply demarcated, gray, spongy cystic lesions (0.3-2.5 cm) in cortex and medulla. The lesions contained clear serous fluid. Microscopically, the background kidneys showed end-stage changes with glomerulosclerosis and atrophic tubules. The well-delineated cystic lesions are composed of tightly packed tubules and cysts, separated by bland fibrous stroma. The lining cells are single-layer, flattened, cuboidal to columnar, with abundant eosinophilic cytoplasm, large round to oval nuclei, and prominent nucleoli. Hobnail cells are common. No desmoplastic reaction or cellular ovarian-like stroma is present. No solid growth or papilla is seen in either kidney. Immunohistochemically, the tumor cells showed diffuse and strong positivity for AMACR, AE1/AE3, CK8/18, CD10, and PAX2; focally strong positivity for CK7, EMA, vimentin, and 34BE12; and negativity for p63 and CK20. TC-RCC was diagnosed. Fuhrman nuclear grade was 2 to 3. Pathologic stage was pT1 on both kidneys. Fluorescence in situ hybridization shows gain of chromosome 7 and chromosome 17. Transmission electronic microscopy showed 2 types of epithelial cells: type I cells reminiscent of proximal tubular cells and lining the tubules and type II cells reminiscent of distal tubular cells lining the cysts. The patient was disease-free 3 years after radiologic detection and 12 months after bilateral nephrectomy. Our studies suggest TC-RCC is closely related to papillary RCC. This tumor appears to be low-grade with no metastasis

RATIONALE: Although high anxiety is commonly associated with drug addiction, its causal role in this disorder is unclear. OBJECTIVES: In light of strong evidence for dissociable neural mechanisms underlying heroin and cocaine addiction, the present study investigated whether high anxiety predicts the propensity of rats to lose control over intravenous cocaine or heroin self-administration. METHODS: Sixty-four rats were assessed for anxiety in the elevated plus-maze, prior to extended access to intravenous cocaine or heroin self-administration. RESULTS: High-anxious rats, identified in the lower quartile of the population, showed a greater escalation of cocaine, but not heroin, self-administration compared with low-anxious rats selected in the upper quartile of the population. Anxiety scores were also positively correlated with the extent of escalation of cocaine self-administration. CONCLUSIONS: The present data suggest that high anxiety predisposes rats to lose control over cocaine-but not heroin-intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.

Sesterterpenoids account for many bioactive natural products, often with unusual and complex structural features, which makes them attractive targets for synthetic chemists. This review surveys efforts undertaken toward the synthesis of sesterterpenoids, focusing on completed total syntheses and covering ca. 50 natural products in total.

Better late than never! Two herbicidins, members of an important family of nucleoside antibiotics, have been synthesized for the first time. The route integrates a stereoselective C-glycosylation with several reagent-controlled stereoselective transformations and a surprisingly facile and highly diastereoselective late-stage N-glycosylation.

Pyramidal cells of the cerebral cortex are born in the ventricular zone and migrate through the intermediate zone to enter into the cortical plate. In the intermediate zone, these migrating precursors move tangentially and initiate the extension of their axons by transiently adopting a characteristic multipolar morphology. We observe that expression of the forkhead transcription factor FoxG1 is dynamically regulated during this transitional period. By utilizing conditional genetic strategies, we show that the downregulation of FoxG1 at the beginning of the multipolar cell phase induces Unc5D expression, the timing of which ultimately determines the laminar identity of pyramidal neurons. In addition, we demonstrate that the re-expression of FoxG1 is required for cells to transit out of the multipolar cell phase and to enter into the cortical plate. Thus, the dynamic expression of FoxG1 during migration within the intermediate zone is essential for the proper assembly of the cerebral cortex.

To explore the relative development of the dorsal and ventral extrastriate processing streams, we studied the development of sensitivity to form and motion in macaque monkeys (Macaca nemestrina). We used Glass patterns and random dot kinematograms (RDK) to assay ventral and dorsal stream function, respectively. We tested 24 animals, longitudinally or cross-sectionally, between the ages of 5 weeks and 3 years. Each animal was tested with Glass patterns and RDK stimuli with each of two pattern types--circular and linear--at each age using a two alternative forced-choice task. We measured coherence threshold for discrimination of the global form or motion pattern from an incoherent control stimulus. Sensitivity to global motion appeared earlier than to global form and was higher at all ages, but performance approached adult levels at similar ages. Infants were most sensitive to large spatial scale (Deltax) and fast speeds; sensitivity to fine scale and slow speeds developed more slowly independently of pattern type. Within the motion domain, pattern type had little effect on overall performance. However, within the form domain, sensitivity for linear Glass patterns was substantially poorer than that for concentric patterns. Our data show comparatively early onset for global motion integration ability, perhaps reflecting early development of the dorsal stream. However, both pathways mature over long time courses reaching adult levels between 2 and 3 years after birth.