TOPAS: an innovative proton Monte Carlo platform for research and clinical applications.

PURPOSE: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. METHODS: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. RESULTS: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. CONCLUSIONS: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community.

TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation.

The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology.

The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Monte Carlo simulation of chemistry following radiolysis with TOPAS-nBio.

Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields Gx (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05-230 keV µm-1. The calculated Gx values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for [Formula: see text] agreed with simulated results within 7% ± 8% over the entire time range; for [Formula: see text] over the full time range within 3% ± 4%; for H2O2 from 49% ± 7% at earliest stages and 3% ± 12% at saturation. For the LET-dependent Gx, the mean ratios to the experimental data were 1.11 ± 0.98, 1.21 ± 1.11, 1.05 ± 0.52, 1.23 ± 0.59 and 1.49 ± 0.63 (1 standard deviation) for [Formula: see text], [Formula: see text], H2, H2O2 and [Formula: see text], respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data.

Improved efficiency in Monte Carlo simulation for passive-scattering proton therapy.

The aim of this work was to improve the computational efficiency of Monte Carlo simulations when tracking protons through a proton therapy treatment head. Two proton therapy facilities were considered, the Francis H Burr Proton Therapy Center (FHBPTC) at the Massachusetts General Hospital and the Crocker Lab eye treatment facility used by University of California at San Francisco (UCSFETF). The computational efficiency was evaluated for phase space files scored at the exit of the treatment head to determine optimal parameters to improve efficiency while maintaining accuracy in the dose calculation. For FHBPTC, particles were split by a factor of 8 upstream of the second scatterer and upstream of the aperture. The radius of the region for Russian roulette was set to 2.5 or 1.5 times the radius of the aperture and a secondary particle production cut (PC) of 50 mm was applied. For UCSFETF, particles were split a factor of 16 upstream of a water absorber column and upstream of the aperture. Here, the radius of the region for Russian roulette was set to 4 times the radius of the aperture and a PC of 0.05 mm was applied. In both setups, the cylindrical symmetry of the proton beam was exploited to position the split particles randomly spaced around the beam axis. When simulating a phase space for subsequent water phantom simulations, efficiency gains between a factor of 19.9 ± 0.1 and 52.21 ± 0.04 for the FHTPC setups and 57.3 ± 0.5 for the UCSFETF setups were obtained. For a phase space used as input for simulations in a patient geometry, the gain was a factor of 78.6 ± 7.5. Lateral-dose curves in water were within the accepted clinical tolerance of 2%, with statistical uncertainties of 0.5% for the two facilities. For the patient geometry and by considering the 2% and 2mm criteria, 98.4% of the voxels showed a gamma index lower than unity. An analysis of the dose distribution resulted in systematic deviations below of 0.88% for 20% of the voxels with dose of 20% of the maximum or more.

A framework for implementation of organ effect models in TOPAS with benchmarks extended to proton therapy.

The aim of this work was to develop a framework for modeling organ effects within TOPAS (TOol for PArticle Simulation), a wrapper of the Geant4 Monte Carlo toolkit that facilitates particle therapy simulation. The DICOM interface for TOPAS was extended to permit contour input, used to assign voxels to organs. The following dose response models were implemented: The Lyman-Kutcher-Burman model, the critical element model, the population based critical volume model, the parallel-serial model, a sigmoid-based model of Niemierko for normal tissue complication probability and tumor control probability (TCP), and a Poisson-based model for TCP. The framework allows easy manipulation of the parameters of these models and the implementation of other models. As part of the verification, results for the parallel-serial and Poisson model for x-ray irradiation of a water phantom were compared to data from the AAPM Task Group 166. When using the task group dose-volume histograms (DVHs), results were found to be sensitive to the number of points in the DVH, with differences up to 2.4%, some of which are attributable to differences between the implemented models. New results are given with the point spacing specified. When using Monte Carlo calculations with TOPAS, despite the relatively good match to the published DVH's, differences up to 9% were found for the parallel-serial model (for a maximum DVH difference of 2%) and up to 0.5% for the Poisson model (for a maximum DVH difference of 0.5%). However, differences of 74.5% (in Rectangle1), 34.8% (in PTV) and 52.1% (in Triangle) for the critical element, critical volume and the sigmoid-based models were found respectively. We propose a new benchmark for verification of organ effect models in proton therapy. The benchmark consists of customized structures in the spread out Bragg peak plateau, normal tissue, tumor, penumbra and in the distal region. The DVH's, DVH point spacing, and results of the organ effect models are provided. The models were used to calculate dose response for a Head and Neck patient to demonstrate functionality of the new framework and indicate the degree of variability between the models in proton therapy.

Intra-arterial thrombolysis for perioperative stroke after open heart surgery.

Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.

Reduced transverse spinal area secondary to burst fractures: is there a relationship to neurologic injury?

A retrospective case-control study was undertaken to determine the best technique to measure neural canal encroachment at each lumbar level following burst fracture and its relationship to the presence of neurologic deficit. Only patients with postinjury CT scans demonstrating a disrupted posterior body with a retropulsed bone fragment were included. Patients were divided into groups based on the level of bony injury (T12-L5) and neurologic status. Neurologic injury was classified as follows: normal (N), root (R), or cauda equina/conus/paraplegic/paraparetic (C/P). The mean transverse spinal area (TSA, cm2), spinal canal percentage patency (PP), and midsagittal diameter (MSD) were determined for each neurologic group and lumbar level. A "calculated" TSA, based on midsagittal and anterior-posterior diameters, was also derived for each patient. The data were compared level by level and correlated with the patient's neurologic status. At L1, the critical TSA was 1.0 cm2. All patients with TSAs less than this were paraplegic. At both T12 and L1, TSAs in the range of 1.0-1.25 cm2 were observed in both normal and neurologically impaired patients. A critically significant TSA was not established for levels T12, L2, L3, L4, or L5; however, the data indicated that a smaller TSA can be tolerated at successively caudal levels without neurologic deficit. No meaningful correlation between root injury and TSA was observed. The data also indicated that measurement of TSA is a more accurate method for evaluating neural canal encroachment than PP or MSD. The "calculated" TSA is a simple, objective method for obtaining this information without the aid of a computer. This study suggests that absolute TSA should be utilized in future studies evaluating decompressive treatment of thoracolumbar pathology.

Central nervous system complications after lung transplantation.

PURPOSE: This study describes the central nervous system (CNS) events after lung transplantation. METHODS: A chart review of all lung transplant recipients (LTR) to collect the clinical and neuroimaging data for CNS events defined as seizures, severe headaches, confusion, or stroke. RESULTS: Twenty-six patients of 100 LTRs from 1990 through 1995 had a CNS event; more than one event occurred in 5 patients for a total of 32 events. Severe headache was most common, occurring in 14 patients, followed by seizures in 10, stroke in 5, and confusion in 3. The CNS event was related to infection in three of the 26 patients. Of all evaluations performed, magnetic resonance imaging (MRI) identified the most abnormalities, the most common being white matter changes consistent with cyclosporine toxicity. Cyclosporine levels were elevated in slightly more than half of the patients. Hypomagnesemia was present in three of 10 patients with seizures. Prognosis for recovery from these complications was good, with only five patients having ongoing problems with headaches, one requiring long term anticonvulsant therapy, three having minor or no limitations from stroke and no long-term problems with confusion. One patient with seizures resulting from an aspergilloma died. CONCLUSION: CNS events occur commonly in LTRs, mostly related to cyclosporine toxicity or infection. MRI identifies more abnormalities than computed tomography. These events were not consistently associated with documented high cyclosporine levels and hypomagnesemia. In spite of significantly abnormal MRIs, the functional outcome is favorable.

Naloxone has no effect on ethanol-induced impairment of psychomotor performance in man.

In a study designed to investigate the effect of naloxone on ethanol-induced performance deficits in man, ethanol (0.75 g/kg) and naloxone (0.4 mg) or saline were administered to 39 volunteers in a double-blind fashion. Psychomotor performance was assessed on a battery of tests (standing steadiness, pursuit rotor, simple and complex reaction times, a speeded number test and the Vienna Determination Apparatus) and blood and breath ethanol concentrations were monitored. Two experiments were performed: in Experiment 1 ethanol was given before naloxone and in Experiment 2 naloxone was administered before ethanol. There were no significant differences in either blood or breath ethanol concentrations at any time between the ethanol + naloxone and ethanol + saline groups in either Experiment 1 or 2. Although ethanol produced a significant decrement on most of the performance measures, naloxone was without effect. There was no suggestion of ethanol impairment being moderated by naloxone, whether it was given before or after ethanol.

Cerebral embolism associated with left ventricular assist device support and successful therapy with intraarterial urokinase.

A patient with a bioprosthetic aortic valve sustained a cerebral embolism during support with an implantable left ventricular assist device. This was lysed with intraarterial urokinase with complete resolution of the neurological deficit. Subsequently the patient underwent heart transplantation and remains neurologically intact. This case report is the first successful use of thrombolysis for cerebral embolism associated with a mechanical assist device.

Serum S-100beta as a possible marker of blood-brain barrier disruption.

Two brain-specific proteins, S-100beta and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100beta levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100beta is a marker of blood-brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100beta increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100beta is an early marker of BBB opening that is not necessarily related to neuronal damage.

Detachable balloon embolization: concomitant use of a second safety balloon.

We describe a relatively unusual case of carotid cavernous fistula in association with a persistent trigeminal artery, presumably related to aneurysm rupture near the carotid origin of the vessel. We emphasize the use of a second, nondetachable balloon solely for the purpose of stabilizing placement of the first device at the time of detachment.

Endovascular occlusion of the carotid or vertebral artery with temporary proximal flow arrest and microcoils: clinical results.

PURPOSE: To determine the clinical effectiveness of parent artery occlusion of the carotid or vertebral artery by means of temporary proximal flow arrest and microcoils. METHODS: Nineteen parent artery occlusions (15 carotid, four vertebral) were performed in 19 patients who successfully passed a balloon test occlusion. In these patients, endovascular occlusion of the carotid or vertebral artery was accomplished with the use of temporary proximal flow arrest and microcoils. RESULTS: All 19 parent arteries were occluded. Eighteen patients (95%) had good outcomes and one (5%) had a poor outcome. Fourteen patients (74%) had no complications and five (26%) had complications, of whom only one was left with a permanent neurologic deficit. Three (60%) of the complications were the result of delayed ischemic events after parent artery occlusion and were not predicted by balloon test occlusion. CONCLUSION: Endovascular occlusion with temporary proximal flow arrest and microcoils can be done effectively and successfully. The predictive value of the balloon test occlusion is the major complicating factor, as it is with balloon occlusion. This technique offers an additional tool that can be used for endovascular occlusion of the carotid or vertebral artery and seems to be less difficult technically. It is our primary technique for parent artery occlusion.

Basilar artery rethrombosis: successful treatment with platelet glycoprotein IIB/IIIA receptor inhibitor.

We describe the use of abciximab to prevent rethrombosis of the basilar artery after transluminal angioplasty. A 60-year-old patient with vertebral basilar insufficiency and acute occlusion of the basilar artery underwent revascularization with urokinase and angioplasty. Despite the repeated use of urokinase and angioplasty under anticoagulation with heparin, the basilar artery immediately rethrombosed. In a final attempt to prevent rethrombosis, abciximab was administered before the final angioplasty, resulting in a widely patent basilar artery and no rethrombosis.

Hemorrhage detected using MR imaging in the setting of acute stroke: an in vivo model.

BACKGROUND AND PURPOSE: The treatment algorithm for acute cerebrovascular accidents has traditionally sorted these accidents as either hemorrhagic or nonhemorrhagic, and MR imaging, with its ability to allow expeditious assessment of vascular substrates and regional blood volume, is well suited for this purpose. Our purpose was to delineate the accuracy of MR imaging in acute, hemorrhagic forms of stroke during the time frame considered beneficial for intervention in an animal model. METHODS: Eighteen dogs with small, iatrogenic parenchymal, subarachnoid hemorrhage (SAH), or both were serially scanned over the initial 6-hour postictal period. Confirmatory pathologic specimens and 3-hour postictal CT scans were obtained in all animals. The MR and CT studies were then interpreted in a blinded fashion by two neuroradiologists for the presence of hemorrhage. The results were subjected to receiver operating characteristic analysis. RESULTS: MR imaging depicted acute parenchymal hemorrhage and SAH with a high degree of accuracy at 1.5 T. This finding was independent of each of the time points studied during the 6-hour window. For SAH, the MR accuracy for reader 1 was 0.86 (95% CI, 0.76-0.97); for reader 2, accuracy was 0.85 (95% CI, 0.71-0.99). The CT accuracy for the two readers was 0.42 (95% CI, 0.26-0.58) and 0.66 95% CI, 0.43-0.89), respectively. Fluid-attenuated inversion-recovery images improved the conspicuity of SAH on MR images and, along with spin-density-weighted spin-echo sequences, helped to establish the hemorrhagic nature. For parenchymal hemorrhage, the MR accuracy for reader 1 was 0.90 (95% CI, 0.81-0.99); for reader 2, accuracy was 0.93 (95% CI, 0.84-1.00). With CT, the accuracy of reader 1 was 0.91 (95% CI, 0.85-0.97) whereas for reader 2 accuracy was 0.76 (95% CI, 0.69-.83). Parenchymal hemorrhage detection and diagnosis was best with T2*-weighted gradient-echo images. CONCLUSION: MR imaging with appropriately selected sequences appears able to provide information regarding the presence (or absence) of hemorrhage in an acute stroke model requisite to the initiation of treatment.

Early treatment of ruptured aneurysms with Guglielmi detachable coils: effect on subsequent bleeding.

The major causes of mortality and morbidity in patients surviving the rupture of a saccular aneurysm are subsequent bleeding and vasospasm. The purpose of this study was to evaluate the influence of early treatment of ruptured aneurysms with Guglielmi detachable coils on the incidence of subsequent bleeding. Thirteen patients were treated within 72 hours of initial aneurysm rupture with Guglielmi detachable coils. Excluding three patients who died 2, 4, and 12 weeks after initial hemorrhage, all others have been followed up for intervals between 6 and 36 months (mean, 16 mo). None of these have had either clinical or radiographic evidence of subsequent bleeding. Assuming that there is a 30% incidence of subsequent bleeding in conservatively (nonsurgically) treated patients, the 0% subsequent bleed rate observed in this subgroup was significant at a P value of 0.01. Only one procedure-related complication occurred in this series, and 9 of 13 (69%) aneurysms were 100% occluded at the time of initial treatment. All aneurysms were at least 90% occluded at the end of initial treatment. In addition to reducing the risk of subsequent bleeding, early treatment facilitated the institution of an aggressive approach for management of both vasospasm and increased intracranial pressure. Patient outcome, as measured by the Glasgow Outcome Scale, was good in 9 of 13 (69%), poor in 1 of 13 (8%), and death in 3 of 13 (23%) patients. The results of this study suggest that early Guglielmi detachable coil treatment of ruptured aneurysms may be effective in reducing the incidence of subsequent bleeding and can be performed with a low incidence of complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging.

There remains uncertainty as to the effect of radioactive iodine (131I) therapy on the associated ophthalmopathy (GO). Twenty newly diagnosed patients with Graves' hyperthyroidism treated with 131I (median dose, 15.5 mCi) were followed with ophthalmologic evaluations (OE) and magnetic resonance imaging (MRI) at baseline, 2, and 6 months, and with OE alone at 3 years. For MRI, the superior, inferior, and medial rectus muscle volumes and total muscle volumes (TMV) were measured. Replacement levothyroxine was initiated as low thyroxine (T4) levels were noted. At baseline, 10 patients (50%) showed evidence of mild GO by OE and/or MRI. There was a significant difference in TMV between the 20 patients with Graves' hyperthyroidism and 10 controls (mean +/- standard error [SE]; 2,652 +/- 118 vs. 2,046 +/- 96 mm3; P = 0.002) and between the 10 patients with and 10 without GO (3,006 +/- 96 vs. 2,298 +/- 61 mm3; P = 0.001). TMV correlated with the Hertel score (r = 0.56, P = 0.01). TMV showed no significant change at 2 or 6 months posttreatment. The inferior rectus volume increased slightly at 2 months posttreatment (P = 0.03) but remained stable at 6 months. Furthermore, no significant changes occurred in Hertel scores or in clinical assessments up to 3 years posttreatment and none showed worsening or new development of GO. In conclusion, our results show no significant risk for radioiodine-induced initiation or progression of mild GO.

Stent-assisted angioplasty of intracranial vertebrobasilar atherosclerosis: an initial experience.

OBJECT: Patients with intracranial vertebrobasilar artery (VBA) atherosclerotic occlusive disease have few therapeutic options. Unfortunately, VBA transient ischemic attacks (TIAs) herald a lethal or devastating event within 5 years in 25 to 30% of patients. The authors report their initial experience with eight patients in whom medically refractory TIAs secondary to intracranial posterior circulation atherosclerotic occlusive lesions were treated with stent-assisted angioplasty. METHODS: Eight patients (six men), ranging in age from 43 to 77 years, experienced signs and symptoms of VBA insufficiency despite combination therapy with warfarin and antiplatelet agents. Angiographic studies revealed severe distal vertebral (four patients), proximal basilar (one patient), or proximal and midbasilar stenoses (three patients). Aspirin and clopidogrel were administered for 3 days before primary angioplasty and stent placement, and this regimen was maintained by the patients on discharge. Patients underwent heparinization during the procedure and were given a bolus and 12-hour infusion of abciximab. A neurologist specializing in stroke evaluated all patients before and after the procedure. The VBAs in all patients were successfully revascularized with 7 to 28% residual stenosis. Six patients experienced no neurological complications. One patient died the evening of the procedure due to a massive subarachnoid hemorrhage. Two patients had groin hematomas, one developed congestive heart failure, and one had transient encephalopathy. All surviving patients are asymptomatic up to 8 months postoperatively. CONCLUSIONS: Although primary intracranial VBA angioplasty with stent insertion is technically feasible, complications associated with the procedure can be life threatening. As experience is gained with this procedure, it may be offered routinely as an alternative therapy to patients with medically refractory posterior circulation occlusive disease that may develop into catastrophic VBA insufficiency.