Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study.

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.     

Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells

Two FDA-approved agents, ferumoxides (Feridex), a suspension of superparamagnetic iron oxide (SPIO) nanoparticles and protamine sulfate, a drug used to reverse heparin anticoagulation, can be complexed and used to label cells magnetically ex vivo. Labeling stem cells with ferumoxides-protamine sulfate (FePro) complexes allows for non-invasive monitoring by MRI. However, in order for stem cell trials or therapies to be effective, this labeling technique must not inhibit the ability of cells to differentiate. In this study, we examined the effect of FePro labeling on stem cell differentiation. Viability, phenotypic expression and differential capacity of FePro labeled CD34 + hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) were compared with unlabeled control cells. Colony-forming unit (CFU) assays showed that the capacity to differentiate was equivalent for labeled and unlabeled HSC. Furthermore, labeling did not alter expression of surface phenotypic markers (CD34, CD31, CXCR4, CD20, CD3 and CD14) on HSC, as measured by flow cytometry. SDF-1-induced HSC migration and HSC differentiation to dendritic cells were also unaffected by FePro labeling. Both FePro-labeled and unlabeled MSC were cultured in chondrogenesis-inducing conditions. Alcian blue staining for proteoglycans revealed similar chondrogenic differentiation for both FePro-labeled and unlabeled cells. Furthermore, collagen X proteins, indicators of cartilage formation, were detected at similar levels in both labeled and unlabeled cell pellets. Prussian blue staining confirmed that cells in labeled pellets contained iron oxide, whereas cells in unlabeled pellets did not. It is concluded that FePro labeling does not alter the function or differentiation capacity of HSC and MSC. These data increase confidence that MRI studies of FePro-labeled HSC or MSC will provide an accurate representation of in vivo trafficking of unlabeled cells.     

Dynamic 99Tcm-ECD SPET correlates well with 201Tl indices in brain tumours

The dynamic 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) single photon emission tomographic (SPET) characteristics of brain tumours were investigated and compared with 201Tl-chloride SPET indices. Thirty-five patients with histologically confirmed benign and malignant tumours were evaluated using dynamic and standard 99Tcm-ECD. Twenty-eight patients were also examined using standard 201Tl SPET. The following 201Tl indices were calculated: early uptake ratio, delayed uptake ratio, washout rate and retention index. The relationship between uptake of 99Tcm-ECD on dynamic SPET and 201Tl indices was analysed. Nine patients showed positive uptake on dynamic 99Tcm-ECD SPET, all of whom had benign tumours, including five meningothelial meningiomas, three pituitary adenomas of the chromophobe type and one chemodectoma without malignancy. The mean early uptake ratio of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (17.1 +/- 5.5 vs 9.0 +/- 5.7, P = 0.004). The mean washout rate of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (61.0 +/- 27.7 vs 0.35 +/- 30.9, P = 0.0004). The mean retention index of the tumours with positive uptake was significantly lower than that of the tumours with negative uptake (0.27 +/- 0.12 vs 0.88 +/- 0.48, P = 0.000006). Only benign tumours showed positive uptake on dynamic 99Tcm-ECD SPET. The 201Tl indices correlated well with the uptake of 99Tcm-ECD on dynamic SPET. The results suggest that dynamic 99Tcm-ECD SPET can identify the benign character of tumours of the brain.     

Simultaneous display of MRA and MPR in detecting vascular compression for trigeminal neuralgia or hemifacial spasm: comparison with oblique sagittal views of MRI

A new technique, simultaneous display of magnetic resonance angiography (MRA) and multiplanar reconstruction (MPR), was performed by a workstation to identify the involved vessels in patients with trigeminal neuralgia (TN) or hemifacial spasm (HFS), and the results were compared with those of oblique sagittal MRI technique. Twelve patients with either HFS or TN were prospectively assessed by simultaneous display of MRA and MPR, and oblique sagittal techniques, to point out the neurovascular compression and to identify the involved vessels. Three-dimensional (3D) time-of-flight (TOF) spoiled gradient-echo (SPGR) images were acquired to create MRA and MPR. Oblique sagittal views were also created and displayed on films. A total of 15 vessels in 12 patients were identified as compressing vessels during surgery. Simultaneous display of MRA and MPR technique pointed out the presence of vessels at and/or around root entry/exit zone (REZ) in all 12 patients, but proper identification by the name of the individual vessel was correct in 13 of 15 cases. However, oblique sagittal technique indicated the presence of vessels at and/or around REZ in 11 patients, but only 8 of 14 vessels were correctly identified. Our new method, simultaneous display of MRA-MPR, facilitated correct identification of the involved vessels compared with the oblique sagittal view method. Received: 30 June 1999; Revised: 9 September 1999; Accepted: 23 November 1999     

Practical approaches to labelling terminal alkynes with deuterium

Base catalysed exchange with sodium hydroxide, calcium oxide or N,N,N,N-tetramethylguanidine in deuterium oxide is a viable procedure for the preparation of terminally deuterated alkynes for those alkynes stable to strong base. The use of silver perchlorate as a catalyst is an alternative practical option when labelling alkynes which are sensitive to base or contain functionalities which would lead to labelling elsewhere in the molecule. Labelling with this catalyst takes place smoothly at ambient temperature in a mixture of N,N-dimethylformamide and deuterium oxide.     

Talus verticalis

Congenital vertical talus is a rare condition which presents as an isolated deformity or in association with neuromuscular and/or genetic disorders. Pathoanatomically the deformity shows a dislocated talonavicular and subtalar joint. The etiology and pathogenesis are still not finally determined although in some cases a genetic basis has been identified. The clinical picture is that of a flat, convex longitudinal arch with abduction and dorsiflexion of the forefoot and an elevated heel. Clinical diagnosis is confirmed by plain radiographic imaging. Congenital vertical talus should not be confused with other deformities of the foot, such as congenital oblique talus, flexible flat feet or pes calcaneus. The object of treatment of congenital vertical talus is to restore a normal anatomical relationship between the talus, navicular and calcaneus to obtain a pain-free foot. Major reconstructive surgery has been reported to be effective but is associated with substantial complications. Good early results of a modified non-operative treatment using serial manipulation, cast treatment and minimally invasive surgery may change therapeutic concepts.     

Treatment strategies for severe C1C2 luxation due to congenital os odontoideum causing tetraplegia

Purpose

High-grade C1C2 luxation is a rare pathology. There is no clear evidence as to how to treat this deformity. There is only limited evidence about the different surgical techniques and possible approaches including advantages, disadvantages, and complications.

Methods

This is an uncommon case of a 13-year-old child with progressive, tetraplegia due to congenital os odontoideum with translational instability between C1 and C2, and progressive luxation of C2. An irreducible dislocation of the C0/C1 complex caused significant compression at the cervicomedullary junction and neurologic deficit. In this paper we highlight the different types of os odontoideum, a review of existing evidence of surgical correction. We will discuss the different treatment strategies which could be applied and the current solution will be described.

Results

Continuous skeletal traction and translational reduction was achieved by a specially designed halo traction system including continuous skeletal traction in a wheelchair for 6 weeks. The surgical treatment consisted of a posterior only release, translational reduction and posterior instrumentation from C0 to C4 with a Y plate and homologous bone graft. Neurological deficits started to improve during halo traction. After surgery the patient was ambulatory without any assistance and reached a Frankel stage E. Postoperative X-rays and CT scan revealed complete reduction at the C1/C2 level and a decompressed cervicomedullary junction.

Conclusion

Treatment of severe C1C2 luxation is difficult with limited evidence in the literature. The current case shows a successful treatment strategy to reduce the deformity and lists alternative approaches.      

Assessment of oxidative metabolism in adults with hepatocellular carcinoma in the Sudan.

The hypothesis that an increased rate of oxidative metabolism may be an initiator or promoter of hepatocellular carcinoma was tested in vivo. Elimination of antipyrine (phenazone) was used as an index of the activity of microsomal mixed function oxidative enzymes. Plasma antipyrine kinetics were examined in 10 patients with hepatocellular carcinoma and in 10 normal Sudanese adults. The half life, volume of distribution and clearance of antipyrine in patients were 18.8 +/- 7.9 hours (mean +/- SD), 33.8 +/- 7.7 litres and 23.7 +/- 10.1 ml/min, respectively; and in normal adults were 20.3 +/- 8.8 hours, 40.1 +/- 10.4 litres and 25.7 +/- 12.0 ml/min, respectively. These differences were not significant. Antipyrine plasma clearance when corrected for weight was similar in the two groups. This study suggests that in a population at risk for hepatocellular carcinoma, the overall activity of mixed function oxidative enzymes is not an important determinant in selectively increasing this risk.     

Brain perfusion measured by flow-sensitive alternating inversion recovery (FAIR) and dynamic susceptibility contrast-enhanced magnetic resonance imaging: comparison with nuclear medicine technique

The aim of this study was to compare cerebral perfusion images and regional cerebral blood flow (rCBF) of SPECT study with the images and regional intensity of relative cerebral blood flow (CBF) images acquired by contrast-enhanced perfusion MR imaging (pMRI) and flow-sensitive alternating inversion recovery (FAIR). Twelve patients with various cerebral diseases were underwent I-123-IMP SPECT, pMRI, and FAIR studies to measure rCBF. A total of 12 regions of interest (ROI) were created over cerebrum and cerebellum to acquire the corresponding rCBF from I-123-IMP study and regional average signal intensity from CBF images of pMRI and FAIR studies. Left-to-right (L/R) and cerebral-to-cerebellar (CCR) ratios were created from the rCBF of I-123-IMP and signal intensity of CBF images of pMRI and FAIR. Image quality of FAIR was the poorest among all; however, CBF images of pMRI and FAIR images show comparatively decreased intensity at the corresponding site of decreased perfusion on I-123-IMP images. Both FAIR and pMRI images showed high intensity along the sinuses, choroid plexus, and large vessels in sulci. No significant correlation was found among all imaging modalities. But L/R ratio of I-123-IMP showed significant correlation with those of pMRI and FAIR, but for CCR, significant correlation was observed only between I-123-IMP and FAIR. Perfusion images of both pMRI and FAIR may produce images comparable to SPECT study. But to calculate absolute CBF more easy-to-apply and accurate algorithms are needed to overcome the artifacts from large vessels. Received: 25 January 2000 Revised: 7 June 2000 Accepted: 8 June 2000