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Russell R. Lonser, John A. Butman, Ruwan Kiringoda, Debbie Song and Edward H. Oldfield

obtained. Imaging Evaluation Patients underwent serial enhanced and unenhanced MR imaging studies (including T1-and T2-weighted and FLAIR sequences) at 6-month clinical visits. Tumor location and size (volume = largest anteroposterior dimension × largest mediolateral dimension × largest dorsoventral dimension/2) were determined and recorded based on enhanced T1-weighted MR images. Results General Patient Characteristics A total of 250 patients with VHL disease were included in the study protocol (120 male and 130 female patients). Twenty-seven (11%) of

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Jay Jagannathan, Stuart Walbridge, John A. Butman, Edward H. Oldfield and Russell R. Lonser

then secured to the skull with methylmethacrylate. After the inner cannula (outer diameter 0.014 in, inner diameter 0.006 in) was connected to the infusion apparatus, it was placed through the outer guide cannula to the target. To distribute infusate into the brain using convection, we used a previously described noncompliant system that is gas-tight with no dead volume. 9 A PHD 2000 syringe pump (Harvard Apparatus) was used to generate continuous pressure throughout the infusion procedure. During infusion, pressure was transmitted from the pump to an infusate

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Joshua M. Ammerman, Russell R. Lonser, James Dambrosia, John A. Butman and Edward H. Oldfield

tumor locations (cerebellum, brainstem, and spinal cord). The time period of tumor observation up to the point of intervention (prompted by symptom formation) was evaluated using a Cox proportional hazards model, with tumor location, tumor volume at initial examination, categorized at three levels with respect to location, and annual growth rate as covariates. Because of differences associated with spatial constraints imposed by the anatomy, categorization of tumor volume was accomplished by terciles of volume separately for each location. Growth rates were computed

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Ryszard M. Pluta, John A. Butman, Bawarjan Schatlo, Dennis L. Johnson and Edward H. Oldfield

related to the risk of vasospasm and clinical outcome. 12 , 24 The risk of vasospasm development, which is zero during the first 2 days after SAH, 46 gradually increases by almost 11% a day through Day 7 and then decreases through the next week. 40 , 46 The dissolution of the clot in the subarachnoid space has a half-life of 5.4 days and is independent of initial clot volume. 30 Because resolution of vasospasm is related to diminishing clot volume, 40 , 47 many investigators attempt to accelerate clot resolution using intrathecal or intraventricular thrombolysis

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Gregory J. A. Murad, Stuart Walbridge, Paul F. Morrison, Nicholas Szerlip, John A. Butman, Edward H. Oldfield and Russell R. Lonser

convection, we used a previously described noncompliant delivery system that is gastight with no dead volume. 16 A syringe pump (PHD 2000, Harvard Apparatus, Inc.) was used to generate continuous pressure throughout the infusion procedure. During infusion, the pressure was transmitted from the pump to an infusate-filled, gastight, glass Hamilton syringe (total volume 250 μl), which was connected to thick-walled polyethylene tubing (OD 0.050 in, ID 0.023 in; Plastics One). The tubing was connected to the inner infusion cannula, the tip of which was placed directly into the

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Russell R. Lonser, Scott D. Wait, John A. Butman, Alexander O. Vortmeyer, McClellan M. Walther, Lance S. Governale and Edward H. Oldfield

examinations were conducted at initial screening, immediately before and after an operation, and at approximately 6-month intervals after surgery. Data derived from inpatient charts, clinic notes, and operative reports were recorded. Neuroimaging Evaluation All patients underwent pre- and postoperative serial T 1 -weighted pre- and postcontrast MR imaging in a 1.5-tesla MR imager (General Electric, Milwaukee, WI). Tumor volumes were calculated by determining the largest diameter in all three coordinate planes and then computing the volume according to the following

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David Croteau, Stuart Walbridge, Paul F. Morrison, John A. Butman, Alexander O. Vortmeyer, Dennis Johnson, Edward H. Oldfield and Russell R. Lonser

matched tracer can be used to assess the precise anatomical location and volume of drug distribution. This will be an important feature in determining the efficacy of new treatment approaches using CED. Nguyen, et al., 18 previously demonstrated the successful use of iopanoic acid—labeled albumin as a surrogate tracer for CT scanning of HMW compounds; however, HMW tracers may not reliably reflect the distribution of smaller therapeutic agents. Because of the advantages associated with the development of an imaging tracer to be used in combination with CED of various

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Russell R. Lonser, Stuart Walbridge, Kayhan Garmestani, John A. Butman, Hugh A. Walters, Alexander O. Vortmeyer, Paul F. Morrison, Martin W. Brechbiel and Edward H. Oldfield

bicarbonate and 0.15 M NaCl at pH 8.5. To this solution, 45 mg of 1B4M-DTPA dissolved in 1 ml H 2 O (initial ratio of ligand/HSA, 30) was then added. The reaction mixture was rotated at room temperature overnight. The unreacted or free ligand was then separated from the HSA conjugate by centrifugation. The final ligand/HSA ratio was then determined spectrophotometrically. 16 The final volume of the purified HSA—1B4M-DTPA was adjusted to deliver a concentration of approximately 10 mg/ml HSA. The Gd (III) was then reacted with the HSA—1B4M-DTPA at an initial 2:1 molar

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Kristin Huntoon, Tianxia Wu, J. Bradley Elder, John A. Butman, Emily Y. Chew, W. Marston Linehan, Edward H. Oldfield and Russell R. Lonser

best assess cyst biology and clinical features, patients and peritumoral cysts with less than a 2-year follow-up were excluded. 11 To avoid confounding information, imaging data analysis was terminated in patients and cysts at the initiation of systemic chemotherapy, stereotactic radiosurgery, or craniospinal radiation. 2 , 24 MRI was used to calculate hemangioblastoma (T1-weighted, after contrast addition) and associated cyst (T2-weighted) volume by a modified ellipsoid formula at each visit. 15 Cyst growth patterns were classified as saltatory (growth and

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Russell R. Lonser, John A. Butman, Kristin Huntoon, Ashok R. Asthagiri, Tianxia Wu, Kamran D. Bakhtian, Emily Y. Chew, Zhengping Zhuang, W. Marston Linehan and Edward H. Oldfield

enhancing tumor) postcontrast MRI. Volume assessment values were initially assessed serially by a single observer and confirmed by at least one other observer. Patterns of tumor growth were classified as saltatory (exhibiting periods of growth and growth quiescence), linear, or exponential. Tumors that did not progress in size were classified as stable. Statistical Analysis Descriptive statistics were used to summarize patient characteristics and hemangioblastoma features. To examine the effect of factors, such as age and sex, on tumor growth rate, a linear mixed