Frame-Based Stereotactic Biopsy of Canine Brain Masses: Technique and Clinical Results in 26 Cases.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

Fiberoptic microneedle device facilitates volumetric infusate dispersion during convection-enhanced delivery in the brain.

BACKGROUND AND OBJECTIVES: A fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064 nm laser energy in an in vivo rodent model. MATERIALS AND METHODS: FMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5 mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 µl/min for 1 hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses. RESULTS: Analysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.8 ± 0.6 mm(3) for 100 mW compared to 10.0 ± 0.4 mm(3) for its fluid only control and 18.0 ± 0.3 mm(3) for 200 mW compared to 10.3 ± 0.7 mm(3) for its fluid only control. Brains treated with 200 mW co-delivery exhibited thermal lesions, while 100 mW co-deliveries were associated with preservation of brain cytoarchitecture. CONCLUSION: Both lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures.

Intracranial hyperthermia through local photothermal heating with a fiberoptic microneedle device.

BACKGROUND AND OBJECTIVES: The fiberoptic microneedle device (FMD) seeks to leverage advantages of both laser-induced thermal therapy (LITT) and convection-enhanced delivery (CED) to increase volumetric dispersal of locally infused chemotherapeutics through sub-lethal photothermal heat generation. This study focused on determination of photothermal damage thresholds with 1,064 nm light delivered through the FMD into in vivo rat models. MATERIALS AND METHODS: FMDs capable of co-delivering laser energy and fluid agents were fabricated through a novel off-center splicing technique involving fusion of a multimode fiberoptic to light-guiding capillary tubing. FMDs were positioned at a depth of 2.5 mm within the cerebrum of male rats with fluoroptic temperature probes placed within 1 mm of the FMD tip. Irradiation (without fluid infusion) was conducted at laser powers of 0 (sham), 100, 200, 500, or 750 mW. Evans blue-serum albumin conjugated complex solution (EBA) and laser energy co-delivery were performed in a second set of preliminary experiments. RESULTS: Maximum, steady-state temperatures of 38.7 ± 1.6 and 42.0 ± 0.9 °C were measured for the 100 and 200 mW experimental groups, respectively. Histological investigation demonstrated needle insertion damage alone for sham and 100 mW irradiations. Photothermal damage was detected at 200 mW, although observable thermal damage was limited to a small penumbra of cerebral cortical microcavitation and necrosis that immediately surrounded the region of FMD insertion. Co-delivery of EBA and laser energy presented increased volumetric dispersal relative to infusion-only controls. CONCLUSION: Fluoroptic temperature sensing and histopathological assessments demonstrated that a laser power of 100 mW results in sub-lethal brain hyperthermia, and the optimum, sub-lethal target energy range is likely 100-200 mW. The preliminary FMD-CED experiments confirmed the feasibility of augmenting fluid dispersal using slight photothermal heat generation, demonstrating the FMD's potential as a way to increase the efficacy of CED in treating MG.