Monitoring rate and predictability of intraoperative monitoring in patients with intradural extramedullary and epidural metastatic spinal tumors.

STUDY DESIGN: Single-center retrospective study. OBJECTIVES: To evaluate the monitoring rate, sensitivity and specificity of intraoperative monitoring (IOM) during removal of intradural extramedullary (IDEM) or epidural metastatic spinal tumors. Also, to assess the efficacy of monitoring somatosensory-evoked potentials (SSEP) when motor-evoked potentials (MEP) are not measurable. SETTING: The Neuro-Oncology Clinic, National Cancer Center, Korea. METHODS: Patients (n=101) with IDEM or epidural metastatic spinal tumors at the cord level underwent surgeries monitored with SSEP and/or MEP. The monitoring rate was defined as negative when MEP or SSEP could not be measured after reversal of the neuromuscular block under general anesthesia. Positive IOM changes included more than a 50% change in the MEP or SSEP amplitude and more than a 10% delay in SSEP latency. RESULTS: MEP was measurable in 73% of patients. The MEP monitoring rate in patients with motor power grades of 3 or less was 39%, which was lower than that of SSEP (83%). The sensitivity, specificity and predictability of MEP for motor changes were 93, 90 and 91%, respectively. Conversely, the sensitivity, specificity and predictability of SSEP were 62, 97 and 89%, respectively. In patients in whom MEP was not measurable (n=24), SSEP was monitored with a predictability of 83%. CONCLUSION: In cases of extramedullary spinal tumors, MEP shows a higher sensitivity than SSEP does. However, the monitoring rate of MEP in non-ambulatory patients was lower than that of SSEP. In those cases, SSEP can be useful to monitor for postoperative neurological deficits.

Rapid genotyping of Plasmodium vivax Pvs25 and Pv38 genes by using mismatch specific endonuclease.

Mismatch specific endonuclease (MSE) method was used to detect natural polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes were amplified by polymerase chain reaction (PCR), and the PCR amplicons were mixed with reference DNA sequences. Following the denaturation and gradual annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were readily detected by gel electrophoresis, where extra bands with shorter sizes would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25 mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp products presented two genotypes in ROK isolates. After the MSE cleavage, the mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results were in complete agreement with the MSE analyses. In conclusion, genotyping of Pvs25 and Pv38 with MSE cleavage could be a potential method for the high-throughput screening of the large field samples.

Rapid genotyping of Plasmodium vivax Pvs25 and Pv38 genes by using mismatch specific endonuclease

Mismatch specific endonuclease (MSE) method was used to detect natural polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes were amplified by polymerase chain reaction (PCR), and the PCR amplicons were mixed with reference DNA sequences. Following the denaturation and gradual annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were readily detected by gel electrophoresis, where extra bands with shorter sizes would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25 mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp products presented two genotypes in ROK isolates. After the MSE cleavage, the mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results were in complete agreement with the MSE analyses. In conclusion, genotyping of Pvs25 and Pv38 with MSE cleavage could be a potential method for the high-throughput screening of the large field samples.

Impact of multileaf collimator leaf positioning accuracy on intensity modulation radiation therapy quality assurance ion chamber measurements.

Quality assurance (QA) procedures for intensity modulation radiation therapy (IMRT) usually involve an ion chamber measurement in a phantom using the beam configuration of the actual treatment plan. In our QA procedures it was observed that the degree of agreement between the measurement and the calculation could vary from plan to plan, from linac to linac, as well as over time, with a discrepancy up to 8%. In this paper we examine one aspect of the process which can contribute to such poor reproducibility, namely, the leaf end position accuracy. A series of measurements was designed to irradiate an ion chamber using small beam segments where one multileaf collimator (MLC) edge covers half of the chamber. It was shown that the reproducibility varied up to 13%, which provides a possible explanation for the observed discrepancies above. A useful tool was also developed to measure ionization signals from individual segments of an IMRT sequence. In addition, an understanding of the leaf end position variations offers some insight into the overall quality of an IMRT dose distribution.

An automated procedure for the quality assurance of electron beam output and energy.

In this article, we report on the development of a simple and accurate method for quality assurance of electron beam output and energy. Aluminum disks of thicknesses d(max) or d50 of the particular electron energy are positioned sequentially over a parallel-plate ion chamber and the ratio of the two signals is compared to the standard. The positioning of the aluminum disks is carried out remotely and automatically to eliminate the necessity of multiple setups. One method utilizes the remote control feature of the treatment couch and another employs a motor-driven carousel. The superior sensitivity over a commercially available energy monitor is illustrated.

Automatic verification of step-and-shoot IMRT field segments using portal imaging.

In step-and-shoot IMRT, many individual beam segments are delivered. These segments are generated by the IMRT treatment planning system and subsequently transmitted electronically through computer hardware and software modules before they are finally delivered. Hence, an independent system that monitors the actual field shape during treatment delivery is an added level of quality assurance in this complicated process. In this paper we describe the development and testing of such a system. The system verifies the field shape by comparing the radiation field detected by the built-in portal imaging system on the linac to the actual field shape planned on the treatment planning system. The comparison is based on a software algorithm that detects the leaf edge positions of the radiation field on the portal image and compares that to the calculated positions. The process is fully automated and requires minimal intervention of the radiation therapists. The system has been tested with actual clinical plan sequences and was able to alert the operator of incorrect settings in real time.

A personal-computer-based method to obtain "star-shots" of mechanical and optical isocenters for gantry rotation of linear accelerators.

This work describes a method to obtain "star-shots" of the mechanical and optical isocenters of linear accelerators, similar to the star-shots of radiation isocenters normally obtained using films. In this method a digital camera is connected to a personal computer so that multiply exposed images can be taken at a fixed camera position. A mechanical pointer or a wire aligned along the optical axis can then be imaged by the camera. Multiple exposures at varying gantry angles are then superimposed on a digital image which can be analyzed by the computer to give a high-resolution star-shot. The method provides a convenient way for a linear accelerator quality assurance procedure.

An optical edge detector for the accurate delineation of the light field in radiotherapy machines.

A hand-held detector was developed which allows for the unambiguous and consistent determination of the edge of the light (optical) field on treatment machines conveniently and practically. The design incorporates an electronic circuit using three miniature photodiodes. The complete module is housed conveniently in a hand-held box measuring 6 cm x 10 cm x 1.5 cm. The device eliminates any observer subjectivity on the position of the edge of the light field and hence facilitates greatly any commissioning and quality assurance procedures requiring light-radiation field coincidence. Other applications are possible, including alignment of the light field on patients.

The lens membrane skeleton contains structures preferentially enriched in spectrin-actin or tropomodulin-actin complexes.

The spectrin-based membrane skeleton plays an important role in determining the distributions and densities of receptors, ion channels, and pumps, thus influencing cell shape and deformability, cell polarity, and adhesion. In the paradigmatic human erythrocyte, short tropomodulin-capped actin filaments are cross-linked by spectrin into a hexagonal network, yet the extent to which this type of actin filament organization is utilized in the membrane skeletons of nonerythroid cells is not known. Here, we show that associations of tropomodulin and spectrin with actin in bovine lens fiber cells are distinct from that of the erythrocyte and imply a very different molecular organization. Mechanical disruption of the lens fiber cell membrane skeleton releases tropomodulin and actin-containing oligomeric complexes that can be isolated by gel filtration column chromatography, sucrose gradient centrifugation and immunoadsorption. These tropomodulin-actin complexes do not contain spectrin. Instead, spectrin is associated with actin in different complexes that do not contain tropomodulin. Immunofluorescence staining of isolated fiber cells further demonstrates that tropomodulin does not precisely colocalize with spectrin along the lateral membranes of lens fiber cells. Taken together, our data suggest that tropomodulin-capped actin filaments and spectrin-cross-linked actin filaments are assembled in distinct structures in the lens fiber cell membrane skeleton, indicating that it is organized quite differently from that of the erythrocyte membrane skeleton.

The regional Monte Carlo method: a dose calculation method based on accuracy requirement.

In this work we propose the regional Monte Carlo (RMC) method of dose calculation. This method combines the Monte Carlo (MC) algorithm and a non-MC algorithm (such as the convolution method) for optimal speed and accuracy in dose calculation for both photon and electron beams and for various irradiation and patient geometries. For specific regions in the geometry where high accuracy is required but difficult to obtain with analytical or empirical calculations, such as critical organs surrounded by complicated inhomogeneities, the MC algorithm is used. For regions with simple geometries, or where a high degree of dose accuracy is not critical, the non-MC algorithm is used to increase speed. There are two aspects of the RMC method. The first one involves determining critical regions and boundaries, and the other involves the actual implementation and mixing of the two computational algorithms. Two examples of different geometries are used to illustrate the different ways to apply the RMC method. The possibility to extend the method to more complicated geometries and inhomogeneities, as well as the ability of the method to incorporate different calculation algorithms, are also discussed.

Radiation protection design philosophy for a door interlock system for shared room remote afterloading brachytherapy.

A single remote afterloading system can sometimes be used for the radiation treatment of two or more patients in separate rooms simultaneously. This configuration poses certain radiation protection problems, especially in a busy clinic where some of the treatment rooms have to be used for other non-radiation related patients even though not all radiation treatments have been completed. In this report we describe a door interlock system that has been designed to allow for radiation protection purposes during radiation treatment but is disabled when the radiation treatment is completed--with enough safeguard built in to prevent accidental bypass of the interlock. In addition, the quality control procedures of the radiation monitor devices for these treatment rooms are described. These radiation protection procedures could be generalized to other remote afterloading systems.

A displacement model for thermoluminescent dosimetry in radioimmunotherapy.

A model is developed to enable dose determination for thermoluminescent dosimeters immersed in a radioactive solution such as used in radioimmunotherapy. For low energy beta emitters used in such therapy the size of the dosimeter results in a much lower light output than when irradiated with an external Cobalt-60 (60Co) beam to the same dose as delivered to the medium. The model takes the size of the dosimeter into account and hence allows calculation of the dose in the actual medium. The application to different dosimeter sizes as well as different radionuclide energies is also illustrated. Finally, the model can be extended to dose calculation in a mixed gamma and beta irradiation geometry.

Software control procedures for treatment planning systems.

In radiotherapy treatment planning systems, the software programs as well as the beam data have to be updated frequently, when new software versions are released or as beam data change. This update procedure has to be carried out carefully, to ensure the integrity of the system software and data. Moreover, the version of software used for a particular patient treatment plan is important, not only as a record to be retrieved when necessary, but also when there are multiple terminals connected to the same computer. This process of version control is not always carried out in a systematic and standardized fashion. Most clinics often have their own systems to implement this procedure, but while some systems are comprehensive, others may not necessarily incorporate enough safeguards for errors. In addition, treatment planning system manufacturers often do not offer well-designed and fail-safe facilities for this important issue. This report describes the software update control procedures we have implemented on our treatment planning system as well as suggests some general principles that could be applied to other planning systems.

Identification and characterization of tropomodulin and tropomyosin in the adult rat lens.

The lens fiber cells express all the major components of the erythrocyte membrane skeleton including spectrin, protein 4.1 and ankyrin. We have used immunoblot and immunoprecipitation analyses, as well as immunofluorescence localization to identify and characterize two additional components of the membrane skeleton in the rat lens: tropomyosin and the tropomyosin-binding protein tropomodulin. In the erythrocyte, tropomyosin and tropomodulin are proposed to stabilize and limit the lengths of the short actin filaments of the spectrin-actin network, thus influencing the organization and mechanical properties of the erythrocyte membrane skeleton. Antibodies directed against erythrocyte tropomodulin specifically recognize a M(r) 43,000 polypeptide from rat lens that comigrates with erythrocyte tropomodulin on SDS-gels. A non-muscle isoform of tropomyosin is also present in the lens. This tropomyosin isoform migrates on SDS-gels with a M(r) of approximately 28,000 and is distinct from the two erythrocyte isoforms of tropomyosin (M(r) 27,000 and 29,000). Indirect immunofluorescence staining of 5 microns cryosections of adult rat lens reveals that both tropomodulin and tropomyosin colocalize with rhodamine phalloidin staining for actin filaments on fiber cell plasma membranes. Lens tropomodulin exhibits many characteristics that are similar to its erythrocyte counterpart. For example, lens tropomodulin binds tropomyosin in a solid-phase blot binding assay, and extraction experiments with Triton X-100, urea and NaOH show that the membrane-bound tropomodulin in the lens is a tightly associated peripheral membrane protein that is a component of the Triton-insoluble cytoskeleton. However, unlike the erythrocyte, there are approximately 2000 actin monomers per tropomodulin in the lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of photon beam exit dose using photon point kernels.

The Monte Carlo method is used to analyse the dose fall-off at the exit surface of a megavoltage photon beam. The convolution/superposition method of dose calculation using Monte-Carlo-generated homogeneous photon kernels is shown to be in error for exit dose calculation. Instead, photon kernels that incorporate modelling of the exit surface were generated, also using Monte Carlo, to analyse the problem, and the calculated dose fall-off using these kernels agrees well with measured data. In addition, the physics underlying the characteristics of the dose fall-off is analysed based on complete Monte Carlo modelling. Practical improvements to the convolution/superposition method are suggested.

Solid-phase binding analysis of N-CAM interactions with brain fodrin.

The large cytoplasmic domain form of the neural cell adhesion molecule N-CAM has been reported to interact specifically with fodrin, a submembranous cytoskeletal protein. We tested the abilities of fodrins from bovine brain and embryonic chicken brain to bind to N-CAM that had been isolated from differentiated or undifferentiated mouse N2A neuroblastoma cells or from the brains of embryonic day 11 or day 14 chickens. Labeled fodrin samples bound with immobilized fodrin at a minimum soluble fodrin concentration of 2.5 x 10(-8) M, but the labeled fodrin did not bind to the immobilized N-CAM when incubated at 20-fold higher fodrin concentrations.

A phantom for beam positioning and visualization.

PURPOSE: A system was developed which uses the light field on the simulator to allow easy visualization of the treatment field in the sagittal plane of a phantom for complex treatment geometries. METHODS AND MATERIALS: The phantom consists of a plastic shell with a vertical metallic plate in the sagittal plane. Magnetic strips attach to the plate to mark the lateral field while the anterior field is marked by a special pointer. CONCLUSION: This method is useful for teaching and technique development by showing how the field is distorted after gantry, collimator, and couch rotations, as well as any overlap or gap in field matching for certain treatment techniques. It could be modified for actual patient setup.

The large cytoplasmic domain is not required for concentration of N-CAM at cell-cell contacts in transfected mouse neuroblastoma cells.

We examined the localization of the 140- and 180-kDa transmembrane isoforms of chicken N-CAM following transfection into mouse N2A neuroblastoma cells. Both isoforms were expressed at the cell surface and became partially or completely localized at areas of cell-cell contact after several days of culture or of in vitro differentiation. These results indicate that the presence of the large cytoplasmic domain of the 180-kDa N-CAM isoform is not necessary to bring about the localization of N-CAM to points of cell-cell contact.

Measurement of cell-monolayer adhesion in cells transfected with N-CAM cDNAs.

To measure the adhesion of cells expressing the neural cell adhesion molecule N-CAM, mouse Lmtk- fibroblast cells were transfected by a calcium phosphate precipitation technique with eucaryotic expression vectors encoding N-CAM polypeptides. We obtained cell lines expressing the 140-kDa transmembrane isoform of N-CAM at high levels by several rounds of selection by fluorescence-activated cell sorting and compared the adhesion of these cells to that of untransfected cells using a centrifugal removal assay that measures the centrifugal force required to remove radiolabeled probe cells from a cell monolayer. The adhesion of cells prepared from embryonic chicken neural retinas also was examined. Retinal probe cells remained associated with a retinal cell monolayer with an adhesive force of approximately 5 x 10(-6) dyn/cell, and this force was not reduced by treatment with specific anti-N-CAM antibody fragments. Transfected and untransfected mouse L cells each were dislodged from transfected cell monolayers with a removal force of 5 x 10(-5) dyn/cell and thus did not differ in their adhesion. These results support the hypothesis that N-CAM-mediated homophilic adhesion in retinal cells and transfected fibroblasts is relatively weak and that the major adhesive interaction involved in N-CAM-mediated cell-cell adhesion is heterophilic.

Treatment planning for asymmetric jaws on a commercial TP system.

In this work, the accuracy of the asymmetric jaws planning feature in a commercial treatment planning (TP) system is assessed. In the latest version of this software, the off-axis beam quality variation is handled by a function g(d,r), which is derived from measured horizontal beam profiles at four different depths. The calculated and measured isodoses for a 6-MV linear accelerator with asymmetric jaws agree to +/- 0.5% along the central axis and to within 2 mm at the beam edge. Formulas for treatment time calculations using the output data reported by the computer program are described, as well as formulas for manual calculations based on pregenerated data tables. Doses calculated based on these formulas are compared to measurement and the accuracy is +/- 1% and +/- 2% for the computer and manual calculations, respectively. It is concluded that this version of the treatment planning system as well as the treatment time calculation formulas can be used adequately for asymmetric jaw computerized and manual treatment planning.