Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a Phase I/II clinical study

2004 ◽  
Vol 100 (3) ◽  
pp. 472-479 ◽  
Author(s):  
Zvi Lidar ◽  
Yael Mardor ◽  
Tali Jonas ◽  
Raphael Pfeffer ◽  
Meir Faibel ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tumor Response ◽  
Response Rate ◽  
Malignant Gliomas ◽  
Tumor Resection ◽  
Mr Images ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Diffusion Weighted ◽  
Fine Print

Object. A minority of patients with recurrent glioblastomas multiforme (GBMs) responds to systemic chemotherapy. The authors investigated the safety and efficacy of intratumoral convection-enhanced delivery (CED) of paclitaxel in patients harboring histologically confirmed recurrent GBMs and anaplastic astrocytomas. Methods. Fifteen patients received a total of 20 cycles of intratumoral CED of paclitaxel. The patients were observed daily by performing diffusion-weighted (DW) magnetic resonance (MR) imaging to assess the convective process and routine diagnostic MR imaging to identify the tumor response. Effective convection was determined by the progression of the hyperintense signal within the tumor on DW MR images, which corresponded to a subsequent lytic tumor response displayed on conventional MR images. Of the 15 patients, five complete responses and six partial responses were observed, giving a response rate of 73%. The antitumor effect was confirmed by one biopsy and three en bloc resections of tumors, which showed a complete response, and by one tumor resection, which demonstrated a partial response. Lack of convection and a poor tumor response was associated with leakage of the convected drug into the subarachnoid space, ventricles, and cavities formed by previous resections, and was seen in tumors containing widespread necrosis. Complications included transient chemical meningitis in six patients, infectious complications in three patients, and transient neurological deterioration in four patients (presumably due to increased peritumoral edema). Conclusions. On the basis of our data we suggest that CED of paclitaxel in patients with recurrent malignant gliomas is associated with a high antitumor response rate, although it is associated with a significant incidence of treatment-associated complications. Diffusion-weighted MR images may be used to predict a response by demonstrating the extent of convection during treatment. Optimization of this therapeutic approach to enhance its efficacy and reduce its toxicity should be explored further.

Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13—PE38QQR for recurrent malignant glioma

2005 ◽  
Vol 102 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Ian F. Parney ◽  
Sandeep Kunwar ◽  
Michael McDermott ◽  
Mitchel Berger ◽  
Michael Prados ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Malignant Glioma ◽  
Tumor Resection ◽  
Therapeutic Agents ◽  
Grading System ◽  
Recurrent Malignant Glioma ◽  
Mr Images ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Fine Print

Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13—PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13—PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13—PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

Fluorescence-guided resection of glioblastoma multiforme utilizing 5-ALA-induced porphyrins: a prospective study in 52 consecutive patients

2000 ◽  
Vol 93 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Walter Stummer ◽  
Alexander Novotny ◽  
Herbert Stepp ◽  
Claudia Goetz ◽  
Karl Bise ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Aminolevulinic Acid ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Mr Images ◽  
Content Type ◽  
Tissue Fluorescence ◽  
Solid Fluorescence ◽  
Fine Print

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

Accelerated spondylotic changes adjacent to the fused segment following central cervical corpectomy: magnetic resonance imaging study evidence

2004 ◽  
Vol 100 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Vaijayantee Kulkarni ◽  
Vedantam Rajshekhar ◽  
Lakshminarayan Raghuram
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Imaging Study ◽  
Degenerative Changes ◽  
Adjacent Segment ◽  
Mr Images ◽  
Short Term ◽  
Content Type ◽  
Fine Print

Object. The authors studied whether cervical spine motion segments adjacent to a fused segment exhibit accelerated degenerative changes on short-term follow-up magnetic resonance (MR) imaging. Methods. Preoperative and short-term follow-up (mean duration 17.5 months, range 10–48 months) cervical MR images obtained in 44 patients who had undergone one- or two-level corpectomy for cervical spondylotic myelopathy were evaluated qualitatively and quantitatively. The motion segment adjacent to the fused segment and a segment remote from the fused segment were evaluated for indentation of the thecal sac, disc height, and sagittal functional diameter of the spinal canal on midsagittal T2-weighted MR images. Thecal sac indentations were classifed as mild, moderate, and severe. New indentations of the thecal sac of varying severity (mild in 17 patients [38.6%], moderate in 10 [22.7%], and severe in six [13.6%]) had developed at the adjacent segments in 33 (75%) of 44 patients. The degenerative changes were seen at the superior level in 11 patients, inferior level in 10 patients, and at both levels in 12 patients and resulted from both anterior and posterior element degeneration in the majority (23 [69.6%]) of patients. The remote segments showed mild thecal sac indentations in seven patients and moderate indentations in two patients (nine [20.5%] of 44). Compared with the changes at the remote segment, the canal size was significantly decreased at the superior adjacent segment by 0.9 mm (p = 0.007). No patient sustained a new neurological deficit due to adjacent-segment changes. Conclusions. On short-term follow-up MR imaging, levels adjacent to the fused segment exhibited more pronounced degenerative changes (compared with remote levels) in 75% of patients who had undergone one- or two-level central corpectomy.

Lack of agreement between direct magnetic resonance imaging and statistical determination of a subthalamic target: the role of electrophysiological guidance

2002 ◽  
Vol 97 (3) ◽  
pp. 591-597 ◽  
Author(s):  
Emmanuel Cuny ◽  
Dominique Guehl ◽  
Pierre Burbaud ◽  
Christian Gross ◽  
Vincent Dousset ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Functional Response ◽  
Anterior Commissure ◽  
Surgical Techniques ◽  
High Frequency Stimulation ◽  
Mr Images ◽  
Posterior Commissure ◽  
Content Type ◽  
Fine Print

Object. The goal of this study was to determine the most suitable procedure(s) to localize the optimal site for high-frequency stimulation of the subthalamic nucleus (STN) for the treatment of advanced Parkinson disease. Methods. Stereotactic coordinates of the STN were determined in 14 patients by using three different methods: direct identification of the STN on coronal and axial T2-weighted magnetic resonance (MR) images and indirect targeting in which the STN coordinates are referred to the anterior commissure—posterior commissure (AC—PC) line, which, itself, is determined either by using stereotactic ventriculography or reconstruction from three-dimensional (3D) MR images. During the surgical procedure, electrode implantation was guided by single-unit microrecordings on multiple parallel trajectories and by clinical assessment of stimulations. The site where the optimal functional response was obtained was considered to be the best target. Computerized tomography scanning was performed 3 days later and the scans were combined with preoperative 3D MR images to transfer the position of the best target to the same system of stereotactic coordinates. An algorithm was designed to convert individual stereotactic coordinates into an all-purpose PC-referenced system for comparing the respective accuracy of each method of targeting, according to the position of the best target. Conclusions. The target that is directly identified by MR imaging is more remote (mainly in the lateral axis) from the site of the optimal functional response than targets obtained using other procedures, and the variability of this method in the lateral and superoinferior axes is greater. In contrast, the target defined by 3D MR imaging is closest to the target of optimal functional response and the variability of this method is the least great. Thus, 3D reconstruction adjusted to the AC—PC line is the most accurate technique for STN targeting, whereas direct visualization of the STN on MR images is the least effective. Electrophysiological guidance makes it possible to correct the inherent inaccuracy of the imaging and surgical techniques and is not designed to modify the initial targeting.

Vertical atlantoaxial distraction injuries: radiological criteria and clinical implications

2004 ◽  
Vol 1 (3) ◽  
pp. 273-280 ◽  
Author(s):  
L. Fernando Gonzalez ◽  
David Fiorella ◽  
Neil R. Crawford ◽  
Robert C. Wallace ◽  
Iman Feiz-Erfan ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Control Group ◽  
Lateral Mass ◽  
Healthy Individuals ◽  
Mr Images ◽  
Content Type ◽  
Radiological Criteria ◽  
Surgical Fusion ◽  
Imaging Results ◽  
Fine Print

Object. The authors sought to establish radiological criteria for the diagnosis of C1–2 vertical distraction injuries. Methods. Conventional radiography, computerized tomography (CT), and magnetic resonance (MR) imaging findings in five patients with a C1–2 vertical distraction injury were correlated with their clinical history, operative findings, and autopsy findings. The basion—dens interval (BDI) and the C-1 and C-2 lateral mass interval (LMI) were measured in 93 control patients who underwent CT angiography; these measurements were used to define the normal BDI and LMI. The MR imaging results obtained in 30 healthy individuals were used to characterize the normal signal intensity of the C1–2 joint. The MR imaging results were compared with MR images obtained in five patients with distraction injuries. In the 93 patients, the BDI averaged 4.7 mm (standard deviation [SD] 1.7 mm, range 0.6–9 mm) and the LMI averaged 1.7 mm (SD 0.48 mm, range 0.7–3.3 mm). Based on CT scanning in the five patients with distraction injuries, the BDIs (mean 11.9 mm, SD 3.2 mm; p < 0.001) and LMIs (mean 5.5 mm, SD 2 mm; p < 0.0001) were significantly greater than in the control group. Fast—spin echo inversion-recovery MR images obtained in these five patients revealed markedly increased signal distributed throughout the C1–2 lateral mass articulations bilaterally. Conclusions. In 95% of healthy individuals, the LMI ranged between 0.7 and 2.6 mm. An LMI greater than 2.6 mm indicates the possibility of a distraction injury, which can be confirmed using MR imaging. Patients with a suspected C1–2 distraction injury may be candidates for surgical fusion of C1–2.

Intraoperative magnetic resonance imaging during transsphenoidal surgery

2001 ◽  
Vol 95 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Rudolf Fahlbusch ◽  
Oliver Ganslandt ◽  
Michael Buchfelder ◽  
Werner Schott ◽  
Christopher Nimsky
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Early Stage ◽  
Intraoperative Imaging ◽  
Tumor Resection ◽  
Tumor Removal ◽  
Content Type ◽  
Early Evaluation ◽  
Flexible Coil ◽  
Fine Print

Object. The aim of this study was to evaluate whether intraoperative magnetic resonance (MR) imaging can increase the efficacy of transsphenoidal microsurgery, primarily in non—hormone-secreting intra- and suprasellar pituitary macroadenomas. Methods. Intraoperative imaging was performed using a 0.2-tesla MR imager, which was located in a specially designed operating room. The patient was placed supine on the sliding table of the MR imager, with the head placed near the 5-gauss line. A standard flexible coil was placed around the patient's forehead. Microsurgery was performed using MR-compatible instruments. Image acquisition was started after the sliding table had been moved into the center of the magnet. Coronal and sagittal T1-weighted images each required over 8 minutes to acquire, and T2-weighted images were obtained optionally. To assess the reliability of intraoperative evaluation of tumor resection, the intraoperative findings were compared with those on conventional postoperative 1.5-tesla MR images, which were obtained 2 to 3 months after surgery. Among 44 patients with large intra- and suprasellar pituitary adenomas that were mainly hormonally inactive, intraoperative MR imaging allowed an ultra-early evaluation of tumor resection in 73% of cases; such an evaluation is normally only possible 2 to 3 months after surgery. A second intraoperative examination of 24 patients for suspected tumor remnants led to additional resection in 15 patients (34%). Conclusions. Intraoperative MR imaging undoubtedly offers the option of a second look within the same surgical procedure, if incomplete tumor resection is suspected. Thus, the rate of procedures during which complete tumor removal is achieved can be improved. Furthermore, additional treatments for those patients in whom tumor removal was incomplete can be planned at an early stage, namely just after surgery.

In vivo magnetic resonance imaging of fetal cat neural tissue transplants in the adult cat spinal cord

1992 ◽  
Vol 76 (2) ◽  
pp. 261-274 ◽  
Author(s):  
Edward D. Wirth ◽  
Daniel P. Theele ◽  
Thomas H. Mareci ◽  
Douglas K. Anderson ◽  
Stacey A. Brown ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Neural Tissue ◽  
Injured Spinal Cord ◽  
Mr Images ◽  
Compression Injury ◽  
Content Type ◽  
Graft Tissue ◽  
Fine Print

✓ Magnetic resonance (MR) imaging was evaluated for its possible diagnostic application in determining the survival of fetal central nervous system tissue grafts in the injured spinal cord. Hemisection cavities were made at the T11—L1 level of eight adult female cats. Immediately thereafter, several pieces of tissue, either obtained from the fetal cat brain stem on embryonic Day 37 (E-37), from the fetal neocortex on E-37, or from the fetal spinal cord on E-23, were implanted into the cavities made in seven cats. The eighth cat served as a control for the effect of the lesion only. In another group of four animals, a static-load compression injury was made at the L-2 level. Seven weeks later, the lesion was resected in three cases and fragments of either fetal brainstem or spinal cord tissue were introduced. A small cyst was observed in a fourth cat in the compression injury group and a suspension of dissociated E-23 brain-stem cells was injected into this region of cavitation without disturbing the surrounding leptomeninges. Five months to 2 years posttransplantation, MR imaging was performed with a 2.0-tesla VIS imaging spectrometer by acquiring multislice spin-echo images (TR 1000 msec, TE 30 msec) in both the transverse and sagittal planes. Collectively, these intermediate-weighted images revealed homogeneous, slightly hyperintense signals at the graft site relative to the neighboring host tissue in seven of the 11 graft recipients. Two of the remaining four cats exhibited signals from the graft site that were approximately isointense with the adjacent host spinal cord, and the final two cats and the lesion-only control presented with very hypointense transplant/resection regions. The hyperintense and isointense images were tentatively interpreted as representing viable graft tissue, whereas the hypointense transplant/resection sites were considered to be indicative of a lack of transplant survival or the absence of tissue in the lesion-only control animal. Postmortem gross inspection of fixed specimens and light microscopy verified the MR findings in the control animal in 10 of the 11 graft recipients by showing either transplants and/or cysts corresponding to the MR images obtained. In one cat in the hemisection group, histological analysis revealed a very small piece of graft tissue that was not detected on the MR images. Therefore, it is suggested that within certain spatial- and contrast-resolution limits, MR imaging can reliably detect the presence of transplanted neural tissue in both the hemisected and compression-injured spinal cord of living animals. Thus, MR imaging can serve as an important adjunct to histological, electrophysiological, and long-term behavioral analyses of graft-mediated anatomical and functional repair of the injured spinal cord. It is further suggested that this noninvasive diagnostic approach offers many advantages in terms of the judicious and optimum use of valuable animal models, and that these findings address an important prerequisite (in situ verification of transplant survival) for any future clinical trials involving these or equivalent neural tissue grafting approaches, when such are warranted.

Extracerebral fluid collections in infancy: role of magnetic resonance imaging in differentiation between subdural effusion and subarachnoid space enlargement

1994 ◽  
Vol 81 (1) ◽  
pp. 20-23 ◽  
Author(s):  
Nobuhiko Aoki
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Subdural Effusion ◽  
Mr Images ◽  
Content Type ◽  
Vascular Flow ◽  
Flow Void ◽  
Subarachnoid Spaces ◽  
Fluid Collections ◽  
Fine Print

✓ The pathological process of extracerebral fluid collections in infancy includes subdural effusion and enlargement of the subarachnoid spaces. Both conditions have traditionally been investigated as a single clinical entity, because of difficulty in differentiating between them. The prognosis of subdural effusion is not as benign as that of enlargement of subarachnoid spaces, requiring differential diagnosis between these disorders. The present study was conducted to elucidate whether this differentiation could be made on magnetic resonance (MR) images. The series consisted of 16 infants aged 10 months or younger, including eight with verified subdural effusion and eight in whom a diagnosis of enlargement of the subarachnoid spaces was achieved by neuroimaging studies other than MR imaging. In all eight patients with subdural effusion, the intensity of the fluid was greater than that of cerebrospinal fluid (CSF) in at least one of the sequences using T1-weighted, proton-density, and T2-weighted MR images. The flow-void sign, indicating vessels in the fluid spaces, was not seen in any of these eight patients. On the other hand, in all eight patients with enlargement of the subarachnoid spaces, the fluid was isointense in relation to CSF, and vascular flow-void areas were seen in at least one of the MR imaging sequences. Based on these observations, it is concluded that differentiation between subdural effusion and enlargement of the subarachnoid spaces can be established by focusing on two aspects of MR imaging findings: 1) the intensity of the fluid, which is either iso- or hyperintense relative to CSF, and 2) the presence or absence of vascular flow-void areas in the fluid spaces.

Perfusion- and diffusion-weighted magnetic resonance imaging for monitoring decompressive craniectomy in animals with experimental hemispheric stroke

2002 ◽  
Vol 96 (5) ◽  
pp. 933-940 ◽  
Author(s):  
Arnd Doerfler ◽  
Tobias Engelhorn ◽  
Sabine Heiland ◽  
Thomas Benner ◽  
Michael Forsting
Keyword(s):  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Decompressive Craniectomy ◽  
Mr Images ◽  
Content Type ◽  
Hemispheric Stroke ◽  
Diffusion Weighted ◽  
And Diffusion ◽  
Cortical Perfusion ◽  
Fine Print

Object. The aim of this study was to use two types of serial magnetic resonance (MR) imaging—perfusionweighted (PW) and diffusion-weighted (DW)—to monitor craniectomy in rats with hemispheric stroke. Methods. Focal cerebral ischemia was induced in 36 rats by using an endovascular method of occlusion of the middle cerebral artery (MCAO). Craniectomy was performed 4 or 24 hours later in 12 animals each. Twelve control animals underwent occlusion but did not receive treatment. Perfusion-weighted, DW, and T2-weighted MR images were obtained at 4, 24, 48, 72, and 168 hours postocclusion in all animals. Relative regional cerebral blood volumes and apparent diffusion coefficients (ADCs) were calculated for the cortex and basal ganglia. Hemispheric lesion volumes (expressed as percentages of total brain volumes; %HLV) as they appeared on DW and T2-weighted MR images and on histological slices stained with 2,3,5-triphenyltetrazolium chloride were compared. Neurological performances and infarct volumes measured 7 days postocclusion were used as study end points. Both PW and DW images demonstrated ischemic tissue 4 hours after MCAO in all animals. Early treatment by performing craniectomy significantly improved cortical perfusion (p < 0.01), whereas the same procedure conveyed no benefit to the basal ganglia. Compared with findings in control animals, the DW image—derived %HLV was significantly reduced (p < 0.01) and the cortical ADCs at 4 and 24 hours postocclusion were significantly higher in animals treated early (p < 0.05). Late treatment with craniectomy did not significantly affect cerebral perfusion. The correlation between the DW imaging—derived %HLV and the histologically derived %HLV at 4 to 72 hours postocclusion was good (r = 0.74), whereas at Day 7 postocclusion the %HLV was underestimated up to 41% on DW imaging. At 4 hours postocclusion T2-weighted imaging failed to demonstrate the ischemic lesion, whereas from 24 to 72 hours postocclusion the correlation between the T2-weighted imaging—derived %HLV and the histologically derived %HLV was good (r > 0.81). Neurological performance was significantly improved in animals treated using craniectomy. Conclusions. Early craniectomy significantly improves cortical perfusion through leptomeningeal collateral vessels, significantly reduces infarct size, and improves neurological performance in animals with experimental acute hemispheric infarction. Both PW and DW imaging are suitable for noninvasive monitoring of the effects of decompressive craniectomy.

A realistic brain tissue phantom for intraparenchymal infusion studies

2004 ◽  
Vol 101 (2) ◽  
pp. 314-322 ◽  
Author(s):  
Zhi-Jian Chen ◽  
George T. Gillies ◽  
William C. Broaddus ◽  
Sujit S. Prabhu ◽  
Helen Fillmore ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Bromophenol Blue ◽  
Agarose Gel ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Force Profile ◽  
The Brain ◽  
Fine Print

Object. The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery. Methods. Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 µl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] ∼690) and gadodiamide (MW ∼573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10–20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution. Conclusions. Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

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