Usefulness of Imaging for Intrathecal Drug Delivery Systems: An update

Main Article Content

Denis Dupoiron Thomas Douillard, Dr Garbriel Carvajal, Dr

Abstract

Intrathecal Drug Delivery Systems are invasive pain treatment techniques that require bypassing the blood-brain barrier in order to implant a catheter inside the CSF. Imaging is a key element before and during implantation as well as in the diagnosis of complications.


The understanding of delivery mechanisms has been greatly improved using MRI. Drug diffusion can now be modeled according to infusion level and flow rate for each individual patient. MRI and CT are useful in diagnosing the patient, targeting spinal level, and accurately evaluating implantation concerns or contraindications. 


Imaging is a key tool during the implantation of the device. Catheter positioning is essential as the treatment diffusion is limited, and the tip of the catheter must be set behind the spinal cord. Currently, fluoroscopy is the gold standard for catheter placement. Biplane Interventional Imaging and surgical CT scan will soon be able to help with more accurate positioning. An ultrasound-guided technique is helpful to localize a recessed septum in challenging pump refill procedures where pumps are deeply situated.


Imaging is also essential for device malfunction diagnosis. Plain radiology is currently limited as new catheters have a poor opacity, but it remains useful for confirming motor stall of the peristaltic pump and is appropriate for the diagnosis of pump rotation. High-resolution three-dimensional Computer Tomography   reconstruction allows accurate control of catheter positioning and the diagnosis of dislodgment, kinking, and breaking.   MRI is the most accurate imagery to diagnose spinal cord injuries following implantation or as an adverse effect of IT treatment such as granuloma.   Diffusion control requires dynamic imaging which can be performed by TC99 scintigraphy. This allows for the visualization of drug diffusion and velocity. In the near future, novel techniques such as PET- CT scan could be useful for testing the distribution of intrathecal drugs

Keywords: Cancer pain, Chronic Pain, therapy management, Infusions, Spinal, Infusion Pumps, Implantable

Article Details

How to Cite
DUPOIRON, Denis; DOUILLARD, Thomas; CARVAJAL, Garbriel. Usefulness of Imaging for Intrathecal Drug Delivery Systems: An update. Medical Research Archives, [S.l.], v. 8, n. 7, july 2020. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2175>. Date accessed: 24 apr. 2024. doi: https://doi.org/10.18103/mra.v8i7.2175.
Section
Research Articles

References

Atweh SF, Kuhar MJ. Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res. 1977;124(1):53-67.
2. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267-84.
3. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979;50(2):149-51.
4. Onofrio BM, Yaksh TL, Arnold PG. Continuous low-dose intrathecal morphine administration in the treatment of chronic pain of malignant origin. Mayo Clin Proc. 1981;56(8):516-20.
5. Liu HJ, Li WY, Chen HF, Cheng ZQ, Jin Y. Long-Term Intrathecal Analgesia With a Wireless Analgesia Pump System in the Home Care of Patients With Advanced Cancer. Am J Hosp Palliat Care. 2017;34(2):148-53.
6. Pilon RN, Narang S, Desai SP. A report on the consequences of the first implanted device for long-term analgesia in refractory cancer pain. J Clin Anesth. 2016;32:289-93.
7. Deer TR, Pope JE, Hayek SM, Bux A, Buchser E, Eldabe S, et al. The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines. Neuromodulation. 2017;20(2):96-132.
8. Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl 4):iv166-iv91.
9. Carvajal G, Dupoiron D, Seegers V, Lebrec N, Bore F, Dubois PY, et al. Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center. Anesth Analg. 2018;126(6):2038-46.
10. Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):4040-9.
11. Stearns LM, Abd-Elsayed A, Perruchoud C, Spencer R, Hammond K, Stromberg K, et al. Intrathecal Drug Delivery Systems for Cancer Pain: An Analysis of a Prospective, Multicenter Product Surveillance Registry. Anesth Analg. 2020;130(2):289-97.
12. Bernards CM. Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Pract Res Clin Anaesthesiol. 2002;16(4):489-505.
13. Hsu Y, Hettiarachchi HD, Zhu DC, Linninger AA. The frequency and magnitude of cerebrospinal fluid pulsations influence intrathecal drug distribution: key factors for interpatient variability. Anesth Analg. 2012;115(2):386-94.
14. Khani M, Lawrence BJ, Sass LR, Gibbs CP, Pluid JJ, Oshinski JN, et al. Characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging. PLoS One. 2019;14(2):e0212239.
15. Stockman HW. Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space. J Biomech Eng. 2006;128(1):106-14.
16. Tangen KM, Leval R, Mehta AI, Linninger AA. Computational and In Vitro Experimental Investigation of Intrathecal Drug Distribution: Parametric Study of the Effect of Injection Volume, Cerebrospinal Fluid Pulsatility, and Drug Uptake. Anesth Analg. 2017;124(5):1686-96.
17. Hettiarachchi HD, Hsu Y, Harris TJ, Jr., Penn R, Linninger AA. The effect of pulsatile flow on intrathecal drug delivery in the spinal canal. Ann Biomed Eng. 2011;39(10):2592-602.
18. Glud AN, Jakobsen S, Landau AM, Olsen Alstrup AK, Hedemann Sorensen JC. Visualization of intrathecal delivery by PET-imaging. J Neurosci Methods. 2019;317:45-8.
19. Wolf DA, Hesterman JY, Sullivan JM, Orcutt KD, Silva MD, Lobo M, et al. Dynamic dual-isotope molecular imaging elucidates principles for optimizing intrathecal drug delivery. JCI Insight. 2016;1(2):e85311.
20. Brogan SE, Winter NB, Okifuji A. Prospective Observational Study of Patient-Controlled Intrathecal Analgesia: Impact on Cancer-Associated Symptoms, Breakthrough Pain Control, and Patient Satisfaction. Reg Anesth Pain Med. 2015;40(4):369-75.
21. Dupoiron D. Intrathecal therapy for pain in cancer patients. Curr Opin Support Palliat Care. 2019;13(2):75-80.
22. Chai T, Bruel BM, Nouri KH, Driver L. Complications after intrathecal drug delivery due to the underlying malignancy in two patients with intractable cancer pain. Pain Physician. 2013;16(2):E107-11.
23. Flack SH, Anderson CM, Bernards C. Morphine distribution in the spinal cord after chronic infusion in pigs. Anesth Analg. 2011;112(2):460-4.
24. Wallace M, Yaksh TL. Characteristics of distribution of morphine and metabolites in cerebrospinal fluid and plasma with chronic intrathecal morphine infusion in humans. Anesth Analg. 2012;115(4):797-804.
25. Jose de A, Luciano P, Vicente V, Juan Marcos AS, Gustavo FC. Role of Catheter's Position for Final Results in Intrathecal Drug Delivery. Analysis Based on CSF Dynamics and Specific Drugs Profiles. Korean J Pain. 2013;26(4):336-46.
26. Hayek SM, Sweet JA, Miller JP, Sayegh RR. Successful Management of Corneal Neuropathic Pain with Intrathecal Targeted Drug Delivery. Pain Med. 2016;17(7):1302-7.
27. Qureshi AI, Khan AA, Malik AA, Afzal MR, Herial NA, Qureshi MH, et al. Lumbar Catheter Placement Using Paramedian Approach Under Fluoroscopic Guidance. J Vasc Interv Neurol. 2016;8(5):55-62.
28. Robinson S, Robertson FC, Dasenbrock HH, O'Brien CP, Berde C, Padua H. Image-guided intrathecal baclofen pump catheter implantation: a technical note and case series. J Neurosurg Spine. 2017;26(5):621-7.
29. Servello D, Zekaj E, Saleh C, Pacchetti C, Porta M. The pros and cons of intraoperative CT scan in evaluation of deep brain stimulation lead implantation: A retrospective study. Surg Neurol Int. 2016;7(Suppl 19):S551-6.
30. Fluckiger B, Knecht H, Grossmann S, Felleiter P. Device-related complications of long-term intrathecal drug therapy via implanted pumps. Spinal Cord. 2008;46(9):639-43.
31. Carr BN, Sernas T, Mazzola CA. X-ray Imaging Analysis of Intrathecal Baclofen Pumps for Pediatric Emergency Medicine. Pediatr Emerg Care. 2018;34(5):e85-e6.
32. Delhaas EM, Harhangi BS, Frankema SPG, Huygen F, van der Lugt A. Plain radiography in patients treated with intrathecal drug delivery using an implantable pump device. Insights Imaging. 2017;8(5):499-511.
33. Miracle AC, Fox MA, Ayyangar RN, Vyas A, Mukherji SK, Quint DJ. Imaging evaluation of intrathecal baclofen pump-catheter systems. AJNR Am J Neuroradiol. 2011;32(7):1158-64.
34. Dupoiron D, Carvajal G. High-Resolution Three-Dimensional Computed Tomography Reconstruction as First-Line Imaging Modality to Detect Intrathecal Catheter Malfunction. Neuromodulation. 2018;21(7):717-20.
35. Ellis JA, Leung R, Winfree CJ. Spinal infusion pump-catheter leak detected by high-resolution 3D computed tomography. J Neurosurg Spine. 2011;15(5):555-7.
36. Morgalla M, Fortunato M, Azam A, Tatagiba M, Lepski G. High-Resolution Three-Dimensional Computed Tomography for Assessing Complications Related to Intrathecal Drug Delivery. Pain Physician. 2016;19(5):E775-80.
37. Delhaas EM, van der Lugt A. Low-Dose Computed Tomography With Two- and Three-Dimensional Postprocessing as an Alternative to Plain Radiography for Intrathecal Catheter Visualization: A Phantom Pilot Study. Neuromodulation. 2019;22(7):818-22.
38. Delhaas EM, Harhangi BS, Frankema SPG, Huygen F, van der Lugt A. Catheter Access Port (Computed Tomography) Myelography in Intrathecal Drug Delivery Troubleshooting: A Case Series of 70 Procedures. Neuromodulation. 2020.
39. Teodorczyk J, Szmuda T, Sieminski M, Lass P, Sloniewski P. Evaluation of usefulness of scintigraphic imaging in diagnosis of intrathecal drug delivery system malfunction - a preliminary report. Pol J Radiol. 2013;78(3):21-7.
40. Crawley MT, Murphy P, Jamous A, Bodley R. A low-dose radioisotope procedure for assessment of subcutaneous drug delivery systems used for slow intrathecal infusion of antispasmodic agents. Spinal Cord. 2004;42(10):581-4.
41. De Andres J, Villanueva V, Palmisani S, Cerda-Olmedo G, Lopez-Alarcon MD, Monsalve V, et al. The safety of magnetic resonance imaging in patients with programmable implanted intrathecal drug delivery systems: a 3-year prospective study. Anesth Analg. 2011;112(5):1124-9.
42. Zimmerman A, Rauck RL. The delayed appearance of neurological signs in intrathecal granuloma warrants imaging surveillance: a case series and review of the literature. Pain Pract. 2012;12(7):561-9.
43. Ko WM, Ferrante FM. New onset lumbar radicular pain after implantation of an intrathecal drug delivery system: imaging catheter migration. Reg Anesth Pain Med. 2006;31(4):363-7.
44. Deer TR, Raso LJ, Coffey RJ, Allen JW. Intrathecal baclofen and catheter tip inflammatory mass lesions (granulomas): a reevaluation of case reports and imaging findings in light of experimental, clinicopathological, and radiological evidence. Pain Med. 2008;9(4):391-5.
45. Miele VJ, Price KO, Bloomfield S, Hogg J, Bailes JE. A review of intrathecal morphine therapy related granulomas. Eur J Pain. 2006;10(3):251-61.
46. Peccora CD, Ross EL, Hanna GM. Aberrant intrathecal pump refill: ultrasound-guided aspiration of a substantial quantity of subcutaneous hydromorphone. Reg Anesth Pain Med. 2013;38(6):544-6.
47. Gofeld M, McQueen CK. Ultrasound-guided intrathecal pump access and prevention of the pocket fill. Pain Med. 2011;12(4):607-11.
48. Matthys C, Jacobs M, Rossat J, Perruchoud C. Accuracy of Template Versus Ultrasound Identification of the Reservoir Access Port of Intrathecal Drug Delivery System. Neuromodulation. 2019.
49. Maino P, van Kuijk SMJ, Perez R, Koetsier E. Ease of Fill Port Access During the Ultrasound-Guided vs. the Blind Refill Technique of Intrathecal Drug Delivery Systems With a Raised Septum, a Prospective Comparison Study. Neuromodulation. 2018;21(7):641-7.
50. Singa RM, Buvanendran A, McCarthy RJ. A Comparison of Refill Procedures and Patient Outcomes Following Ultrasound-Guided and Template-Guided Intrathecal Drug Delivery Systems With Recessed Ports. Neuromodulation. 2019.
51. Narouze SN, Yonan S, Kapural L, Malak O. Erosion of the inferior epigastric artery: a rare complication of intrathecal drug delivery systems. Pain Med. 2007;8(5):468-70.