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

✓ Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection.

Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.

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

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Prashant Chittiboina, John D. Heiss and Russell R. Lonser

An intraoperative MRI (iMRI)–compatible system has been developed for direct placement of convection-enhanced delivery (CED) cannulae using real-time imaging. To establish the precision and feasibility of this technology, the authors analyzed findings in patients who underwent direct iMRI CED cannula placement.

Three consecutive patients underwent iMRI-guided placement of CED infusion cannulae (6 cannulae) for treatment of diffuse intrinsic brainstem glioma (2 patients) or Parkinson's disease (1 patient). Convective infusion cannulae were guided to the target using the ClearPoint iMRI-based navigation platform (MRI Interventions, Inc.). Placement accuracy was analyzed.

Real-time iMRI during infusion cannula insertion allowed for monitoring of trajectory accuracy during placement. During cannula insertion, no reinsertions or changes due to errors in targeting were necessary. The mean radial error was 1.0 ± 0.5 mm (± SD). There was no correlation between the total length of the planned trajectory and the radial error (Pearson's coefficient: −0.40; p = 0.5). The mean anteroposterior and lateral errors were 0.9 ± 0.5 and 0.3 ± 0.2 mm, respectively. The mean in-plane distance error was 1.0 ± 0.4 mm. The mean tip error (scalar distance between the planned target and actual tip) was 1.9 ± 0.9 mm. There was no correlation between the length of the planned trajectory and any of the measured errors. No complications were associated with cannula placement.

Real-time iMRI-based targeting and monitoring of infusion cannula placement is a safe, effective, and accurate technique that should enable more selective perfusion of brain regions.

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Editorial

Chiari malformation Type I

Mark M. Souweidane

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Han Soo Chang, Tsukasa Tsuchiya and Toru Matsui

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

Object

Accurate real-time imaging of coinfused surrogate tracers can be used to determine the convective distribution of therapeutic agents. To assess the effect that a concentration of a Gd-based surrogate tracer has on the accuracy of determining the convective distribution, the authors infused different concentrations of Gd-diethylenetriamine pentaacetic acid (DTPA) in primates during MR imaging.

Methods

Five nonhuman primates underwent convective infusion (1 or 5 mM, 21–65 μl) of Gd-DTPA alone, Gd-DTPA and 14C-sucrose, or Gd-DTPA and 14C-dextran into the bilateral striata. Animals underwent real-time MR imaging during infusion (5 animals) and autoradiographic analysis (2 animals).

Results

Gadolinium-DTPA could be seen filling the striata at either concentration (1 or 5 mM) on real-time MR imaging. While the volume of distribution (Vd) increased linearly with the volume of infusion (Vi) for both concentrations of tracer (1 mM: R2 = 0.83; 5 mM: R2 = 0.96), the Vd/Vi ratio was significantly (p < 0.0001) less for the 1-mM (2.3 ± 1.0) as compared with the 5-mM (7.4 ± 1.9) concentration. Autoradiographic and MR volumetric analysis revealed that the 5-mM concentration most accurately estimated the Vd for both small (sucrose [359 D], 12% difference between imaging and autoradiographic distribution) and large (dextran [70 kD], 0.2% difference) molecules compared with the 1-mM concentration (sucrose, 65% difference; dextran, 68% difference).

Conclusions

The concentration of infused Gd-DTPA plays a critical role in accurately assessing the distribution of molecules delivered by CED. A 5-mM concentration of Gd-DTPA most accurately estimated the Vd over a wide range of molecular sizes.

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Nicholas M. Wetjen, John D. Heiss and Edward H. Oldfield

Object

To better understand syrinx pathophysiology, the authors performed a prospective study in which they used findings from serial clinical and magnetic resonance (MR) imaging examinations performed before and after craniocervical decompression to establish the time course of syrinx narrowing.

Methods

Serial clinical examinations and cervical MR imaging were performed in 29 consecutive patients with Chiari malformation Type I (CM-I) and syringomyelia before surgery, 1 week, and 3–6 months after surgery, and then annually. Time to narrowing of the syrinx (> 50% decrease in maximal anteroposterior diameter) following surgery was calculated using the Kaplan–Meier method.

Results

All syringes decreased in diameter and length (number of segments) on MR images at 3–6 months, 1 year, and 2 years or later. The syrinx diameter decreased from 6.9 ± 2.1 mm (mean ± standard deviation) preoperatively to < 1.5 mm at last evaluation (p < 0.0001). The median time to syrinx narrowing was 3.6 months following CM-I decompression (95% confidence interval 3.0–6.5 months). After surgery 94% of patients had improved symptoms, but symptoms resolved incompletely in 68% of patients; 52 and 59% of patients had residual dysesthesias and sensory loss, respectively. Clinical improvement occurred before partial or complete disappearance of the syrinx on MR images. Patient age, duration of symptoms, sex, preoperative syrinx diameter, and length of syrinx were unrelated to time to syrinx narrowing.

Conclusions

Most patients improve after decompression for CM-I, but many have residual symptoms. Syringes may continue to diminish for months to years after surgical decompression. A collapsed syrinx (absence of distention of the spinal cord) indicates that the pathophysiology has been reversed by treatment regardless of the completeness of elimination of the cavity on MR images.

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

Object

Muscimol is a potent γ-aminobutyric acid-A receptor agonist that temporarily and selectively suppresses neurons. Targeted muscimol suppression of neuronal structures could provide insight into the pathophysiological processes and treatment of a variety of neurological disorders. To determine if muscimol delivered to the brain by convection-enhanced delivery could be monitored using a coinfused surrogate MR imaging tracer, the authors perfused the striata of primates with tritiated muscimol and Gd–diethylenetriamine pentaacetic acid (DTPA).

Methods

Three primates underwent convective coinfusion of 3H-muscimol (0.8 μM) and Gd-DTPA (5 mM) into the bilateral striata. Primates underwent serial MR imaging during infusion, and the animals were killed immediately after infusion. Postmortem quantitative autoradiography and histological analysis was performed.

Results

Real-time MR imaging revealed that infusate (tritiated muscimol and Gd-DTPA) distribution was clearly discernible from the noninfused parenchyma. Real-time MR imaging of the infusion revealed the precise region of anatomical perfusion in each animal. Imaging analysis during infusion revealed that the distribution volume (Vd) of infusate linearly increased (R = 0.92) with volume of infusion (Vi). Overall, the mean (± SD) Vd/Vi ratio was 8.2 ± 1.3. Autoradiographic analysis revealed that MR imaging of Gd-DTPA closely correlated with the distribution of 3H-muscimol, and precisely estimated its Vd (mean difference in Vd, 7.4%). Quantitative autoradiograms revealed that muscimol was homogeneously distributed over the perfused region in a square-shaped concentration profile.

Conclusions

Muscimol can be effectively delivered to clinically relevant volumes of the primate brain. Moreover, the distribution of muscimol can be tracked using coinfusion of Gd-DTPA and MR imaging. The ability to perform accurate monitoring and to control the anatomical extent of muscimol distribution during its convection-enhanced delivery will enhance safety, permit correlations of muscimol distribution with clinical effect, and should lead to an improved understanding of the pathophysiological processes underlying a variety of neurological disorders.