title: Fiberoptic microneedle device facilitates volumetric infusate dispersion during convection-enhanced delivery in the brain.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, 24061.
authors.forename: R Lyle
authors.initials: RL
authors.lastname: Hood
authors.forename: Rudy T
authors.initials: RT
authors.lastname: Andriani
authors.forename: Samantha
authors.initials: S
authors.lastname: Emch
authors.forename: John L
authors.initials: JL
authors.lastname: Robertson
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Rylander
authors.forename: John H
authors.initials: JH
authors.lastname: Rossmeisl
mesh_terms: D000818:Animals; D054022:Cerebrum; D004396:Coloring Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018481:Convection; D003399:Craniotomy; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D005070:Evans Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics; D006979:Hyperthermia, Induced / Q000295:instrumentation / Q000379:methods*; D057967:Infusions, Intraventricular; D007834:Lasers; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D008297:Male; D009339:Needles; D055100:Optical Fibers; D051381:Rats; D011916:Rats, Inbred F344; D012235:Rhodamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D004396:Coloring Agents; D008081:Liposomes; D012235:Rhodamines; D012709:Serum Albumin; D005070:Evans Blue; D005682:Gadolinium
keywords: Evans blue; intracranial; liposomal rhodamine; malignant glioma; photothermal; rat study; simultaneous co-delivery