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Prashant Chittiboina, John D. Heiss, Katherine E. Warren and Russell R. Lonser

. The application of coinfused MRI surrogate tracers now provides an opportunity to gain direct and potent insights into the clinical use of convective drug distribution in real time in a noninvasive manner. Preclinical data indicate that Gd-DTPA can be used in MRI to accurately monitor convective drug delivery over a wide range of clinical applications and putative therapeutic compounds. Specifically, autoradiographic analysis demonstrates that Gd-DTPA can accurately track large-molecular-weight compounds, including proteins, over the volume of infusion (Vi

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Paul F. Morrison, Russell R. Lonser and Edward H. Oldfield

-enhanced delivery permits a pressure-driven distribution of molecules directly within brain parenchyma via a cannula or catheter and can be used to target selected regions of the central nervous system (for example, deep brain nuclei) in a manner that bypasses the blood–brain barrier. Data from previous studies have also shown that CED can be used to distribute small and large molecules within the brain, brainstem, and spinal cord reliably, safely, and homogeneously over a wide range of volumes. 7 , 19 , 21–23 For macromolecules, the perfused tissue volume is related to the

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John D. Heiss, Stuart Walbridge, Ashok R. Asthagiri and Russell R. Lonser

, dead-volume-free, gastight delivery system. 12 A Harvard syringe pump (PHD 2000, Harvard Apparatus, Inc.) was used to create a small amount of hydrostatic pressure during the infusion. The pressure was transmitted to an infusate-filled syringe (250 μl total volume) that was connected to polyethylene tubing (outer diameter 1.270 mm, inner diameter 0.584 mm) (Plastics One). The inner infusion cannula was connected to the polyethylene tubing. Infusions were performed at 0.1–0.5 μl/minute. On completion of the infusions, animals were killed by an overdose of anesthesia

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Ashok R. Asthagiri, Stuart Walbridge, John D. Heiss and Russell R. Lonser

trajectory and secured with methylmethacrylate. Inner cannulae (outer diameter 0.014 in, inner diameter 0.006 in) were then placed through outer guide cannulae to the striatal targets. Once inner cannulae were on target, infusate was delivered by convection (rate of 1 μl/minute) using a previously described system. 14 Briefly, a PHD 2000 Harvard syringe pump (Harvard Apparatus, Inc.) was used to generate continuous hydrostatic pressure that was transmitted directly to an infusate-filled, gas-tight glass Hamilton syringe (250 μl total volume, Hamilton Company) connected

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Edjah K. Nduom, Stuart Walbridge and Russell R. Lonser

. The volume of infusate lost to leakback was not distributed to interstitial spaces where it would distribute over approximately 5-fold greater tissue area (that is, a Vd:Vi ratio of 5). Because infusions into either gray or white matter were greater than 1 cm into the brain parenchyma, it would be unlikely that the depth of infusion cannula would account for any differences in leakback (that is, more superficial infusions may be associated with more leakback) between gray and white matter. Nevertheless, it is possible that leakback would be significant with very

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Donald Y. Ye, Kamran D. Bakhtian, Ashok R. Asthagiri and Russell R. Lonser

including age, ethnicity, height, weight, presence of other VHL disease–related neoplasms, number of hemangioblastomas, number of hemangioblastomas treated, and time to treatment (if needed) after pregnancy. Hemangioblastomas were characterized by their anatomical location, number of pregnancies exposed, maximum volume, associated peritumoral cyst(s), and need for resection. Annualized tumor growth rates were calculated from the logarithmic difference in tumor volume and the time interval between evaluations to account for exponential growth in absolute tumor volume

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Mark M. Souweidane

Gd-DTPA. This work is profound in that it offers more than anecdotal evidence that Gd-DTPA, coadministered via local delivery, can be used to detect distribution using an in vivo methodology in humans. Additionally, the reported volumes and patterns of distribution provide further clarity of infusion parameters (volume of distribution/volume of infusion [Vd/Vi] ratio and infusion rate) that should be employed when using CED in the brainstem of children with DIPG. The paper also provides convincing information that the concentration of Gd-DPTA is important for a

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Russell R. Lonser, Malisa Sarntinoranont, Paul F. Morrison and Edward H. Oldfield

developed that account for water uptake in tissue 70 and tissue swelling with pressurization. 5 , 17 , 85 , 103 Tissue transport of the infused species is described by a differential mass balance relation governing tissue concentration as a function of space and time, which is formulated to account for convection, diffusion, metabolism, binding, and net transport across the microvasculature: ∂ C/∂ t = D∇ 2 C − ∇(vC/ f ) − k m C/ f − Ρ × s(C/ f − C p ), where k m is the first-order metabolic rate constant in tissue (the rate of degradation), f is the fluid volume

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John E. Wanebo, Russell R. Lonser, Gladys M. Glenn and Edward H. Oldfield

lesion thus had to be at least 0.3 cm wide to be included in this analysis. Maximum lesion diameters were measured in three planes and lesion volumes were approximated using the following formula: volume = (length × width × height) × 0.5. 23 Patients' charts were evaluated for documentation of their neurological condition at each follow-up examination and the neurological status of each patient was correlated with findings on MR images of the head and spine that were obtained at that visit. Tumor and cyst sizes were recorded when patients were asymptomatic

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Russell R. Lonser, John D. Heiss and Edward H. Oldfield

devascularization in four patients with central nervous system neoplasms Case No. Preop Embolization Tumor Location Tumor Type Total Volume of ETOH (ml) 1 partial thoracic spine renal cell carcinoma 1 2 no thoracic spine renal cell carcinoma 3 3 no thoracic spine rhabdomyosarcoma 2 4 no cerebellum hemangioblastoma 3 Technique A 1-ml tuberculin syringe filled with dehydrated absolute ETOH (Abbott Laboratories, Chicago, IL) was used for injection. Leakage of ETOH from the