A thiocyanopalladation/carbocyclization transformation identified through enzymatic screening: stereocontrolled tandem C-SCN and C-C bond formation.

Herein we describe a formal thiocyanopalladation/carbocyclization transformation and its parametrization and optimization using a new elevated temperature plate-based version of our visual colorimetric enzymatic screening method for reaction discovery. The carbocyclization step leads to C-SCN bond formation in tandem with C-C bond construction and is highly stereoselective, showing nearly absolute 1,2-anti-stereoinduction (5 examples) for substrates bearing allylic substitution, and nearly absolute 1,3-syn-stereoinduction (16 examples) for substrates bearing propargylic substitution. Based upon these high levels of stereoinduction, the dependence of the 1,2-stereoinduction upon cyclization substrate geometry, and the generally high preference for the transoid vinyl thiocyanate alkene geometry, a mechanistic model is proposed, involving (i) Pd(ii)-enyne coordination, (ii) thiocyanopalladation, (iii) migratory insertion and (iv) ß-elimination. Examples of transition metal-mediated C-SCN bond formation that proceed smoothly on unactivated substrates and allow for preservation of the SCN moiety are lacking. Yet, the thiocyanate functionality is of great value for biophysical chemistry (vibrational Stark effect) and medicinal chemistry (S,N-heterocycle construction). The title transformation accommodates C-, O-, N- and S-bridged substrates (6 examples), thereby providing the corresponding carbocyclic or heterocyclic scaffolds. The reaction is also shown to be compatible with a significant range of substituents, varying in steric and electronic demand, including a wide range of substituted aromatics, fused bicyclic and heterocyclic systems, and even biaryl systems. Combination of this new transformation with asymmetric allylation and Grubbs ring-closing metathesis provides for a streamlined enantio- and diastereoselective entry into the oxabicyclo[3.2.1]octyl core of the natural products massarilactone and annuionone A, as also evidenced by low temperature X-ray crystal structure determination. Utilizing this bicyclic scaffold, we demonstrate the versatility of the thiocyanate moiety for structural diversification post-cyclization. Thus, the bridging vinyl thiocyanate moiety is smoothly elaborated into a range of derivative functionalities utilizing transformations that cleave the S-CN bond, add the elements of RS-CN across a π-system and exploit the SCN moiety as a cycloaddition partner (7 diverse examples). Among the new functionalities thereby generated are thiotetrazole and sulfonyl tetrazole heterocycles that serve as carboxylate and phosphate surrogates, respectively, highlighting the potential of this approach for future applications in medicinal chemistry or chemical biology.

Intracranial ependymomas: a review.

Ependymomas are rare neuroectodermal tumors arising from ependymal cells of the ventricular system, choroid plexus, filum terminale, and central canal of the spinal cord (1,2). This review focuses on intracranial ependymomas with special emphasis on pathology, etiology, cytogenetic characteristics, and adjuvant radiation therapy. Recent advances in neurosurgical technique, radiation therapy, and molecular biology have affected management of these tumors and have the potential to increase long-term cure rates. The role of highly advanced radiation therapy techniques such as stereotactic radiosurgery will need to be better defined.

Outpatient total body irradiation prior to bone marrow transplantation in pediatric patients: a feasibility analysis.

Outpatient total body irradiation (TBI) prior to bone marrow transplantation has been accomplished in a total of 68 pediatric patients. The TBI regimen was fractionated with a total dose of 12 Gy in eight fractions twice daily. Antiemetic therapy consisted of oral ondansetron three times daily throughout the TBI course. Eight patients experienced mild nausea without vomiting, and four patients experienced mild nausea and vomiting. One patient required intravenous hydration after severe nausea and vomiting. Another patient experienced intractable diarrhea and dehydration which required inpatient management. Outpatient TBI prior to bone marrow transplantation is feasible in pediatric patients.

Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).

Fast three-dimensional time-of-flight MR angiography of the intra-cranial vasculature.

Magnetic resonance angiography is most commonly performed with the three-dimensional (3D) time-of-flight (TOF) technique. As currently practiced, this requires long image acquisition times (5-10 minutes). The authors show that the acquisition time of 3D TOF images can be reduced to less than 1 minute by using a very short TR (< 10 msec). Under normal flow conditions, the major vessels of the circle of Willis were consistently well demonstrated on these fast 3D TOF images. Signal saturation was observed in studies of patients with abnormal blood flow. In those cases, it was demonstrated that serial acquisition of fast 3D TOF data during and after contrast agent administration could be used to overcome the saturation effects. Time-resolved fast 3D TOF imaging during and after contrast agent administration can also provide qualitative assessment of flow and may depict other features that cannot be observed in TOF studies with long imaging times.

Evaluation of the renal arteries in kidney donors: value of three-dimensional phase-contrast MR angiography with maximum-intensity-projection or surface rendering.

OBJECTIVE: Donors routinely undergo preoperative conventional arteriography to evaluate the renal arteries before nephrectomy. The purpose of this study was to assess the capability of three-dimensional phase-contrast MR angiograms postprocessed with maximum-intensity-projection and surface-rendering techniques to show the renal arteries of potential donors. MATERIALS AND METHODS: Postprocessed three-dimensional phase-contrast MR angiograms of 17 patients were retrospectively reviewed by two experienced radiologists for the number and length of renal arteries visualized. Conventional arteriograms were used as the reference standard. Coronal maximum-intensity-projection and surface-rendered MR angiograms were also compared with each other with regard to the delineation of renal arteries from overlapping vessels. RESULTS: MR angiograms showed all 34 single or dominant renal arteries but only eight of 10 accessory arteries seen on conventional arteriograms. One of the nonvisualized accessory arteries was located within the imaged volume, and the other one arose from the distal aorta beyond the imaged regions. Five of six arterial branches arising from the proximal 30-mm portions of the renal arteries were seen on MR angiograms. Postprocessing with either maximum-intensity projection or surface-rendering showed the same number of renal arteries, although surface rendering separated overlapping veins from the renal arteries better than the maximum-intensity-projection technique. CONCLUSION: These results suggest that three-dimensional MR angiography is a reliable method of imaging single or dominant renal arteries, but not for showing all accessory renal arteries and small arterial branches. Surface rendering may provide specific advantages over maximum-intensity-projection in delineating renal arteries from overlapping vessels.

The MR appearance of cruciate ganglion cysts: a report of 16 cases.

Intra-articular ganglion cysts arising from the cruciate ligaments are unusual lesions, there being only nine previously reported cases. We report 16 cases and describe their MR appearance. Nine ganglia originated from the posterior cruciate ligament, most often appearing as well-defined multilocular lesions. The seven ganglia arising from the anterior cruciate ligament most often appeared as fusiform cystic lesions extending along and interspersed within the fibers of the ligament. Although uncommon, intra-articular ganglion cysts arising from the knee appear to have a distinctive MR appearance which should allow their correct diagnosis.

MR diagnosis of recurrent tears in the knee: value of intraarticular contrast material.

OBJECTIVE: After surgical resection or repair of a torn meniscus, the healed area may have areas of abnormal signal intensity on MR images. Consequently, routine MR imaging is not reliable for detecting recurrent meniscal tears. As a result, we studied the efficacy of MR imaging with intraarticular contrast material (MR arthrography) for detecting recurrent tears of the meniscus. SUBJECTS AND METHODS: Thirty-seven patients who previously had a meniscal tear treated by either meniscal resection or repair had conventional MR imaging and MR arthrography with 40-50 ml of a 1:100 solution of gadopentetate dimeglumine in saline. All patients had arthroscopy shortly after the MR studies. Follow-up arthroscopic surgery was performed within an average of 6.6 weeks after the MR arthrograms. The routine MR images and MR arthrograms were reviewed separately and randomly, and these results were compared with the arthroscopic findings. Meniscal morphology, signal intensity, and the presence of joint fluid tracking into recurrent tears were evaluated. RESULTS: The overall accuracy in diagnosing recurrent meniscal tears in the post-operative meniscus was 66% when conventional MR imaging was used and 88% when MR arthrography was used. In patients who had only minimal meniscal resection, both methods had an accuracy of 89%. In patients who had more extensive meniscal resection, accuracy was 65% with conventional MR imaging and 87% with MR arthrography. In four patients who had only a small meniscal remnant, the accuracy was 50% with routine MR imaging and 100% with MR arthrography. On conventional MR images, the presence of an effusion tracking into a meniscal tear had a sensitivity and positive predictive value of 90% for detection of recurrent meniscal tears; however, the sensitivity was only 41%. CONCLUSION: Our results show that the sensitivity of MR imaging in detecting meniscal tears after surgery varies with the extent of the resection. Sensitivity was considerably improved when intraarticular contrast material was used. MR arthrography should be considered as an alternative to arthroscopy in patients who have had resection or repair of the meniscus.

Magnetic resonance arthrography of the shoulder.

Recently, there have been attempts to improve the accuracy of MR imaging by distending the glenohumeral joint with fluid prior to imaging. This article reviews the techniques employed in performing MR arthrography, imaging characteristics of MR arthrography, and diagnostic use of the procedure.

Imaging of the saphenous vein graft bypass of the cavernous carotid artery.

PURPOSE: To describe the radiographic appearance of the interpositional carotid saphenous vein graft and to compare the efficacy of MR angiography with conventional angiography in determining graft patency and identifying graft irregularities. METHODS: The authors examined saphenous vein graft bypasses of the cavernous carotid artery in 14 patients using CT, MR, and conventional and MR angiography. RESULTS: The course of the graft was typically more inferior, lateral, and anterior than the course of the native vessel. Mild irregularities were found in four of the grafts, but all four "filled out" in a period of months. Time-of-flight angiography was comparable to conventional angiography in four of five patients. Phase-contrast angiography was comparable to conventional angiography in nine of nine cases. CONCLUSIONS: MR angiography is a useful screening modality in the postoperative evaluation of vascular grafts.

Blood flow in the portal vein: velocity quantitation with phase-contrast MR angiography.

Quantitative phase-contrast magnetic resonance (MR) angiography of the portal vein was prospectively evaluated in 79 fasting patients and 23 healthy volunteers. Images were obtained during a 12-second breath-hold acquisition in the coronal (n = 102) and axial (n = 11) planes. Pathologic correlation was available in 55 of 79 patients and included findings of cholangiocarcinoma, cirrhosis, hepatocellular carcinoma, hepatitis, and metastatic disease. Forty-one patients had correlative Doppler ultrasound (US) findings. MR and US findings correlated as to flow direction in all cases. In nine patients, Doppler US velocity measurements were available and closely correlated with MR findings. A comparison of axial and coronal portal venous phase-contrast measurements in 11 patients revealed no substantial difference with regard to the plane used. Quantitative phase-contrast MR angiography is a simple and rapid technique for the assessment of portal venous patency, flow direction, and flow velocity and, combined with high-resolution conventional MR imaging, may obviate the current use of both computed tomographic and US examinations.

MR angiography of the head and neck: value of two-dimensional phase-contrast projection technique.

MR angiography is commonly performed by using two- and three-dimensional time-of-flight and three-dimensional phase-contrast techniques. These procedures require long examination times and processing of imaging data by computing maximum intensity projections. Two-dimensional phase-contrast projection angiography has neither of these disadvantages. We analyzed the value of this technique for head and neck MR angiography in 84 patients and 15 control subjects. Patients were examined to resolve specific clinical questions such as the presence of arteriovenous malformations (20 cases), patency of carotid and vertebral arteries (35 cases), patency of the superior sagittal sinus (14 cases), patency of saphenous vein bypass grafts (11 cases), and vascularity of masses (four cases). Conventional angiograms were available for correlation in 22 patients. Two-dimensional phase-contrast projection angiograms were generated by using a gradient-recalled-echo sequence sensitized to flow with the use of flow-encoding gradients. Projection MR angiograms were obtained in approximately 3.5 min by combining images obtained with flow-encoding gradients applied along the axes defining the image plane. MR angiograms were subjectively evaluated by three observers without reference to routine MR images or conventional angiograms. High-quality studies were obtained in 93% of control subjects and 90% of patients examined. The findings based on phase-contrast angiography were confirmed with conventional angiography in 21 of 22 patients for whom conventional angiograms were available. Evaluation of vascular grafts and of the patency of major cranial vessels was easily done with two-dimensional phase-contrast angiography and was useful in postoperative follow-up examinations. We also advocate its use for superior sagittal sinus thrombosis and follow-up examinations in patients with arteriovenous malformations.

Variability in the enhancement of the normal central skull base in children.

We studied the signal and enhancement characteristics of the central skull base prospectively in 40 children aged 13 days to 8 years, on a 1.5 T MRI system. Identical standard short TR/TE spin echo sequences in the sagittal plane were performed before and after intravenous gadolinium-DTPA. The sequences used for comparison were filmed at identical window and level settings. Three independent observers assessed (1) the intensity of contrast enhancement of the basisphenoid, basiocciput and presphenoid, (2) the signal intensity of the spheno-occipital synchondrosis, (3) the degree of pneumatization of the sphenoid sinus and (4) the uniformity of signal intensity reflecting fatty replacement of the marrow of the basisphenoid, basiocciput and presphenoid. In 16% and 28% respectively of cases there was no enhancement of the basisphenoid and basiocciput after gadolinium administration; in 42% and 44% there was mild enhancement, and moderate or intense enhancement was observed in 42% and 28% of cases. Even when there was irregular fatty replacement, residual hemopoietic clements could enhance intensely. When skull base neoplasms are being investigated, the normal signal irregularity and enhancement of the central skull base in children must not be confused with pathologic invasion of the marrow.

Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5 T vs biopsy.

Quantification of hepatic fat content by application of MR phase-contrast imaging (Dixon method) at 1.5 T was compared with results of biopsy in 16 patients with a variety of liver abnormalities. Motion artifact was suppressed by employing six or eight averages of short TR in-phase (echo offset, 0 msec), out-of-phase (echo offset, 1.1 msec), and in-phase (echo offset, 2.2 msec) spin-echo pulse sequences. The 360 degree out-of-phase sequence was used to assess the impact of T2* decay on this method of estimating fat fraction. A standard two-echo long TR sequence also was obtained in all patients. Histologic preparations from the biopsy specimens were examined by a pathologist who had no knowledge of the MR results and were graded according to overall visual assessment as belonging to one of four categories of fat fraction. Results of the MR-calculated apparent fat fraction were compared directly with biopsy category and were also placed in MR fat fraction categories, allowing estimation of the statistical correlation between the biopsy and MR grading systems. Eight of eight patients with biopsy categories indicating a fat fraction of less than 0.25 were computed by MR to have a fat fraction of less than 0.1. Seven of eight patients with biopsy categories indicating a fat fraction of greater than 0.25 were computed by MR to have a fat fraction of at least 0.24. The MR-calculated apparent fat fraction category correlated significantly with the histologic biopsy category (r = .86, p less than .01). When compared with the in-phase image, decreased signal from liver was visually apparent on the 180 degree out-of-phase images in all cases in which the fat fraction was at least 0.24, but there was no indication of fatty liver on the standard T1- or T2-weighted images. Calculated T2 also showed no correlation with degree of fatty deposition. Correction for T2* decay by using the 360 degree out-of-phase acquisition in addition to the standard 0 degree and 180 degree out-of-phase images had little effect on fat fraction computation. Phase-contrast MR is a promising noninvasive method for quantitative assessment of fatty deposition in the liver.

Pyomyositis: early detection utilizing multiple imaging modalities.

Pyomyositis represents 3% to 4% of surgical admissions in East Africa, however, there were no reported cases in the United States prior to 1971. Since, there have been numerous reports of this entity. Four recent cases are presented utilizing multiple imaging modalities including magnetic resonance. MR was very sensitive to early soft tissue inflammatory processes and demonstrated these focal abscesses with superior anatomic localization. MR is advocated in the initial evaluation of a focal process. In a systemic, nonfocal process, nuclear medicine WBC or Gallium Scans to localize areas for further MR scanning is recommended.