Convection-Enhanced Delivery: Neurosurgical Issues

Wa, Hall

doi:10.2174/138945009787354575

Cited by 17 publications

(10 citation statements)

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“…This could be circumvented by directly administering them i.c. by means of CED, if the delivery parameters can be optimized [19]. Readers interested in more detailed information relating to CED of liposomes for the treatment of brain tumors are referred to a recent review on this topic [20].…”

Section: Introductionmentioning

confidence: 99%

Preparation, Biodistribution and Neurotoxicity of Liposomal Cisplatin following Convection Enhanced Delivery in Normal and F98 Glioma Bearing Rats

et al. 2012

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The purpose of this study was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment of the F98 rat glioma. The first was a commercially produced agent, Lipoplatin™, which currently is in a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC). The second, produced in our laboratory, was based on the ability of cisplatin to form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS). The in vitro tumoricidal activity of the former previously has been described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency of 25% and showed more potent in vitro cytotoxicity against F98 glioma cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention at 24 h after intracerebral (i.c.) convection enhanced delivery (CED) to F98 glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor bearing Fischer rats following i.c. CED of Lipoplatin™ or CHEMS liposomes or their “hollow” counterparts. Unexpectedly, Lipoplatin™ was highly neurotoxic when given i.c. by CED and resulted in death immediately following or within a few days after administration. Similarly “hollow” Lipoplatin™ liposomes showed similar neurotoxicity indicating that this was due to the liposomes themselves rather than the cisplatin. This was particularly surprising since Lipoplatin™ has been well tolerated when administered intravenously. In contrast, CHEMS liposomes and their “hollow” counterparts were clinically well tolerated. However, a variety of dose dependent neuropathologic changes from none to severe were seen at either 10 or 14 d following their administration. These findings suggest that further refinements in the design and formulation of cisplatin containing liposomes will be required before they can be administered i.c. by CED for the treatment of brain tumors and that a formulation that may be safe when given systemically may be highly neurotoxic when administered directly into the brain.

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Section: Introductionmentioning

confidence: 99%

Preparation, Biodistribution and Neurotoxicity of Liposomal Cisplatin following Convection Enhanced Delivery in Normal and F98 Glioma Bearing Rats

et al. 2012

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“…There were low shifts of the deep tumor margin in 34 % of cases, moderate shifts in 42 %, and high shifts in 24 %." Others have also shown similar iMR studies [38,41] and within other brain surgery applications (e.g., deep brain stimulation [42], and convection-enhanced chemotherapy [43]). What is clear is that in one of the most confined soft-tissue domains within the human body, moderate-to-high softtissue shifts of the brain surface, and deep tumor margins was suggested to occur in approximately 75+ % of cases.…”

Section: Organ Deformationmentioning

confidence: 62%

Organ Deformation and Navigation

Gallowayjr

Miga

2015

Imaging and Visualization in the Modern Operating Room

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As image-guided surgery (IGS) expands beyond intracranial neurosurgery, it takes on additional challenges. Organs other than the brain lack the encompassing bone of the skull which allows them to move and deform as a result of operative pose, respiratory and cardiac motion, and tractions placed on the tissue during the interventional process. Additionally, the skull was easily accessible via a minor incision into the skin. That allowed for the implantation of rigid reference points, or fiducial markers, which allowed for easy registration of tomographic spaces and physical space [1][2][3]. In other organs that rigid platform was not available. So both additional ways of using image information to guide procedures and techniques to account for deformation had to be developed.Image-guided procedures require a methodology of matching imaging data with physiological position and tool orientation. This requires either a registration or a calibration. The difference is in the application. In a calibration, a device is created which can reach any point within a tomographic scanner (computed tomography, CT; magnetic resonance imaging, MRI; positron emission tomography, PET; or single-photon emission computed tomography, SPECT). A phantom object containing easy-to-locate and well-described points is first volumetrically scanned and then located by the device. This allows the determination of the mathematical relationship between localizer position and orientation to locations within the scanner. Then, when a patient is scanned, the image information is used to find targets of interest in the images and thus scanner space [4]. The localization device is then used to reach the point in scanner space. If desired, a second scan can be performed to confirm the accuracy.Using ultrasound as a guidance method can also be considered a calibration. Here, a tracking system is attached to an ultrasound system and the mathematical relationship between the tracked ultrasound and its image slice is determined by a phantom process [5,6]. That allows the location of objects seen in the ultrasound to be determined in tracking system space. Then a tracked surgical instrument (also localized in tracking system space) can move to the location determined in the ultrasound (see Fig. 9.1).The strength of a calibration technique is that it requires no processing of the images and the time between obtaining the scan and the interventional procedure is minimized [7]. However, the most important issue to be addressed in a tomographic calibration technique is that no motion or deformation has occurred between the acquisition and Y. Fong et al. (eds.), Imaging and Visualization in The Modern Operating Room,

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“…The use of a head frame-based introducer is necessary to minimise unwanted movements that can open up pericatheter spaces and increase the risk of reflux. 10 In intraputaminal CED, the distance from the ''step'' to the corpus callosum is a major determinant of leakage into the low resistance white matter pathway. 11,12 Monitoring catheter placement and Vd during surgery with, for example intra-operative MRI, may be advantageous.…”

Section: Catheter Placementmentioning

confidence: 99%