The Use of ALZET® Osmotic Pumps during Magnetic Resonance Imaging or Nuclear Magnetic Resonance Studies

Magnetic resonance imaging (MRI) is a noninvasive imaging technique used to obtain information on tissue characterization. This procedure provides high-resolution images of internal structures useful in the detection, localization, and assessment of disease and tissue damage. Magnetic resonance images are obtained by placing the area of interest within a powerful, highly uniform, static magnetic field. For this reason, MRI requires that no ferromagnetic materials be present during the procedure, as metallic objects can cause poor image resolution and can be attracted to the magnetic source. This presents a matter of concern to investigators planning to use ALZET osmotic pumps during MRI studies, since the flow moderator of the pumps is made of stainless steel. However, ALZET pumps can still be used during MRI procedures by replacing the stainless steel flow moderator with tubing of the same length and outer diameter as the original flow moderator. One such material is PEEK (polyetheretherketone) medical microtubing which has an outer diameter of 0.032 inches and an inner diameter of 0.018 inches and may be purchased from DURECT Corporation.

DURECT Catalog Numbers:

ALZET Pump Model 1003D, 1007D, 1002, 1004 2001D, 2001, 2002, 2004, 2006 2ML1, 2ML2, 2ML4
PEEK Catalog Numbers 0002612 0002496 0002511

In addition, researchers may be interested in obtaining magnetic resonance images of the brain while infusing agents through a brain infusion cannula. When such an experimental procedure is required, a non-metallic brain infusion cannula must be used. Cannula systems compatible with ALZET osmotic pumps and made with non-metallic components, such as plastic, teflon, and fused silica, may be purchased from Plastics One, Inc.

The following publication includes information on the use of ALZET osmotic pumps during MRI procedures:

Carpenter, T.A., Hall, L.D., and Hogan, P.G. Magnetic resonance imaging of the delivery of a paramagnetic contrast agent by an osmotic pump. Drug Design Delivery;1988;3:263-266.

 

Procedure for Replacing the Stainless Steel Flow Moderator with PEEK Tubing for MRI Studies

To effectively use ALZET Osmotic Pumps in conjunction with MRI, the stainless steel flow moderators should be replaced with non-metallic flow moderators. A suitable replacement for the stainless steel flow moderator is PEEK (polyetheretherketone) tubing. PEEK tubing has excellent chemical compatibility and is used for a wide variety of medical applications. PEEK can be sterilized by autoclave, gamma irradiation or ethylene oxide (gas sterilization).

For more information on PEEK tubing, call DURECT Corporation at 800-692-2990. DURECT Corporation provides sterile PEEK tubing, cut and packaged (10 per bag), as replacement Flow Moderators for every available pump model.

 

Cutting PEEK Tubing

Cut a piece of PEEK tubing to the appropriate length for the pump being used. The table below lists the appropriate tubing length corresponding to each pump model. (NOTE: This step can be avoided if the tubing is purchased from DURECT Corporation.) The PEEK flow moderator can be connected to catheter tubing to achieve targeted delivery, or it can be glued into the polyethylene cap of the original flow moderator for systemic administration.

    ALZET Pump Model 1003D, 1007D, 1002, 1004 2001D, 2001, 2002, 2004, 2006 2ML1, 2ML2, 2ML4
    Tubing length 13 mm (1.3 cm) 22 mm (2.2 cm) 43 mm (4.3 cm)

Flow Moderator Modification for Systemic Administration

The polyethylene flow moderator caps are provided sterile and cannot be autoclaved. It is important to use sterile technique once the cap is being handled. If irradiation, or gas sterilization is available, sterile technique can be avoided and the entire assembly can be sterilized once the modification is complete.

200 µl and 2 ml Models

  1. If gas or irradiation sterilization methods are not available, autoclave the cut pieces of PEEK tubing and use sterile technique for the following procedure.
  2. Remove the plastic polyethylene cap from the original stainless steel flow moderator and set aside for further use. ( Fig. A )
  3. Insert the pre-cut, PEEK tubing into the polyethylene cap just far enough to plug the hole.
  4. Apply a small amount of cyanoacrylate glue to the underside of the polyethylene cap and around the PEEK tubing. ( Fig. B )
  5. Once the glue is applied, insert the PEEK tubing the rest of the way, so the distal end of the PEEK tubing is flush with the distal end of the polyethylene cap. Allow at least two hours for drying time. Leaving the glued assembly to dry overnight will elicit the best results.
  6. To ensure that the glue has not obstructed the exit port and to verify patency, inject sterile saline through the PEEK tubing to ensure it exits the distal end.
  7. The PEEK flow moderator is now ready to be used. This figure shows the PEEK flow moderator being inserted into the filled ALZET pump. ( Fig. C )  

100 µl pump

  1. Remove the white flange from the original stainless steel flow moderator and set aside. Tip : To remove the flange, hold the flow moderator vertically by the flange with the steel tube pointing down. Place it over a firm sterile surface and press down until the flange dislodges from the metal. ( Fig. E )
  2. Insert the PEEK tubing all the way into the flange, so the distal end of the PEEK is flush with the distal end of the flange. ( Fig. F )
  3. Apply a small amount of cyanoacrylate glue to the underside of the flange and around the PEEK tubing. ( Fig. G )
  4. Allow at least two hours for drying time. Leaving the glued assembly to dry overnight will elicit the best results.
  5. To ensure that the glue has not obstructed the exit port and to verify patency, inject sterile saline through the PEEK tubing.
  6. The PEEK flow moderator is now ready to be used. This figure shows the PEEK flow moderator being inserted into the filled ALZET pump. ( Fig. H )

Flow Moderator Modification When Using a Catheter

Polyethylene tubing can be sterilized by gamma irradiation or ethylene oxide (gas sterilization). Vinyl tubing can be irradiated, gas sterilized, or autoclaved.

Vinyl Tubing

When using vinyl tubing, it is not necessary to use sterile technique for the steps below. The completed assembly can be autoclaved, irradiated or gas sterilized together when complete.

  1. Place a cut length of vinyl tubing (V/3A, V/3 or V/4) over one end of the cut PEEK tubing (sterile V/3A is available from DURECT Corporation).
  2. Place the vinyl catheter tubing far enough over the PEEK tubing to grip tightly. Use the table below to determine how far the vinyl tubing will need to be placed over the PEEK tubing.

    1003D, 1007D, 1002, 1004 2001D, 2001, 2002, 2004, 2006 2ML1, 2ML2, 2ML4
    3 mm 3 mm 4 mm
  1. Autoclave, irradiate, or gas sterilize the entire glued assembly.
  2. The PEEK and vinyl catheter assembly is now ready to use. When inserting it into the filled pump, push the PEEK tubing in until the vinyl tubing contacts the ALZET pump. This will act as a stop to ensure the PEEK tubing does not go all the way into the pump. ( Fig. D )
  3. The filled pump and catheter assembly can now be primed.

Polyethylene Tubing

  1. Autoclave the cut pieces of PEEK tubing and follow the rest of the procedure using sterile technique. (If gamma irradiation or ethylene oxide sterilization is available, sterile technique can be avoided and the entire assembly can be sterilized together once completed.)
  2. Place a cut length of polyethylene tubing (PE-50 or PE-60) over the end of the PEEK tubing. (Sterile PE-60 is available from DURECT Corporation.)
  3. Place the polyethylene catheter tubing far enough over the PEEK tubing to grip tightly. Use the table below to determine how far the polyethylene tubing will need to be placed over the PEEK tubing.

    1003D, 1007D, 1002, 1004 2001D, 2001, 2002, 2004, 2006 2ML1, 2ML2, 2ML4
    3 mm 3 mm 4 mm
  1. If sterile technique was not used, irradiate or gas sterilize the entire glued assembly.
  2. The PEEK and polyethylene catheter assembly is now ready to use. When inserting it into the filled pump, push the PEEK tubing in until the polyethylene tubing contacts the ALZET pump. This will act as a stop to ensure the PEEK tubing does not go all the way into the pump. ( Fig. D )

Pump Advantages

  • Ensure around-the-clock exposure to test agents at predictable levels
  • Permit continuous administration of short half-life proteins and peptides
  • Provide a convenient method for the chronic dosing of laboratory animals
  • Minimize unwanted experimental variables and ensure reproducible, consistent results
  • Eliminate the need for nighttime or weekend dosing
  • Reduce handling and stress to laboratory animals
  • Small enough for use in mice or very young rats
  • Allow for targeted delivery of agents to virtually any tissue
  • Cost-effective research tool

 

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Researchers are saying...

“We found recently that 21 d of treatment of rats with SSRIs, at clinically relevant and stable serum concentrations (achieved by the use of osmotic minipumps), caused robust downregulation of the SERT.”... “Studies on the effects of chronic antidepressants on the SERT have resulted in inconsistent reports (Owens and Nemeroff, 1998). Among the factors that may contribute to such inconsistency is the route of drug administration. In most studies of chronic administration of Ads to rats, the drugs are given intraperitoneally or subcutaneously, either once or twice daily. As rats metabolize these drugs more rapidly than humans, such dosage schedules can result in appreciable fluctuations in the serum concentration of drug throughout the day. For certain pharmacologic effects, sustained drug action may be needed” Benmansour et al. The Journal of Neuroscience 2002; 22(15):6766-6772.