Skip to main content

Scintigraphy of Human CSF Flow in Patients with Leptomeningeal Metastasis

  • Chapter
  • First Online:
Radiopharmaceuticals in the Management of Leptomeningeal Metastasis

Abstract

Radiopharmaceuticals have the unique advantage of requiring minute physical amounts (<microgram) which are not likely to cause chemical toxicity nor pharmaceutical perturbation of physiology. Intrathecal radiopharmaceuticals allow imaging of physiologic, biochemical, and pathologic processes inside the CSF space which are largely unexplored.

The relevant physiology of human cerebrospinal fluid (CSF) flow is outlined. A survey of radiopharmaceuticals used in studying human CSF flow is conducted. Technical details for CSF scintigraphy are briefly discussed. The significance of CSF flow abnormality in patients with leptomeningeal metastasis (LM) and the ability of In-111 DTPA to predict intrathecal pharmacokinetics are reviewed. Whole-body scan schemes provide simplified procedures of CSF scintigraphy, while geometric-mean images allow semi-quantification and derivation of effective half-life (Te) for CSF. These technical advances have been integrated into patient care. Selected results from a retrospective review of CSF flow scintigraphy of patients afflicted with LM are presented with commonly encountered clinical scenarios including CSF block, along with additional studies of Ommaya reservoir malfunction, VP shunt block, and CSF leakage.

Radiopharmaceuticals to study LM and to treat LM patients will continue to be important research tools and likely become a mainstay. With advances in nuclear imaging techniques and radiation dosimetry, it may even be feasible to predict potential efficacy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bering EA Jr. Circulation of the cerebrospinal fluid. Demonstration of the choroid plexuses as the generator of the force for flow of fluid and ventricular enlargement. J Neurosurg. 1962;19:405–13.

    Article  PubMed  Google Scholar 

  2. Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128(6):309–16.

    Article  CAS  PubMed  Google Scholar 

  3. Dreha-Kulaczewski S, et al. Respiration and the watershed of spinal CSF flow in humans. Sci Rep. 2018;8(1):5594.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Enzmann DR, Pelc NJ. Normal flow patterns of intracranial and spinal cerebrospinal fluid defined with phase-contrast cine MR imaging. Radiology. 1991;178(2):467–74.

    Article  CAS  PubMed  Google Scholar 

  5. Levy LM, Di Chiro G. MR phase imaging and cerebrospinal fluid flow in the head and spine. Neuroradiology. 1990;32(5):399–406.

    Article  CAS  PubMed  Google Scholar 

  6. Price RA, Johnson WW. The central nervous system in childhood leukemia. I. The arachnoid. Cancer. 1973;31(3):520–33.

    Article  CAS  PubMed  Google Scholar 

  7. Gilbert MR. Neoplastic meningitis: a unique disease process or a ‘test tube’ for evaluating cancer treatments? Curr Oncol Rep. 2003;5(1):11–4.

    Article  PubMed  Google Scholar 

  8. Hartmann K, et al. First in vivo visualization of the human subarachnoid space and brain cortex via optical coherence tomography. Ther Adv Neurol Disord. 2019;12:1756286419843040.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Doge H, Hliscs R. Intrathecal therapy with 198Au-colloid for meningosis prophylaxis. Eur J Nucl Med. 1984;9(3):125–8.

    Article  CAS  PubMed  Google Scholar 

  10. Morin RL, Brookeman VA. 169Yb-DTPA distribution and dosimetry in cisternography. J Nucl Med. 1974;15(9):786–96.

    CAS  PubMed  Google Scholar 

  11. Enzmann DR, et al. Metrizamide and radionuclide cisternography in communicating hydrocephalus. Radiology. 1979;130(3):681–6.

    Article  CAS  PubMed  Google Scholar 

  12. Li H, et al. Value of (18)F-FDG hybrid PET/MR in differentiated thyroid cancer patients with negative (131)I whole-body scan and elevated thyroglobulin levels. Cancer Manag Res. 2021;13:2869–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wu Y, et al. Whole-body parametric imaging of FDG PET using uEXPLORER with reduced scan time. J Nucl Med. 2022;63(4):622–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Burns R, et al. Optimization of whole-body 2-[(18)F]FDG-PET/MRI imaging protocol for the initial staging of patients with myeloma. Eur Radiol. 2022;32(5):3085–96.

    Article  CAS  PubMed  Google Scholar 

  15. Green MA, et al. In vivo quantitative whole-body perfusion imaging using radiolabeled copper(II) bis(thiosemicarbazone) complexes and positron emission tomography (PET). Methods Mol Biol. 2022;2393:751–71.

    Article  PubMed  Google Scholar 

  16. Lehnert W, et al. Whole-body biodistribution and radiation dosimetry of [(18)F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders. EJNMMI Res. 2022;12(1):1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rashidi A, et al. Diagnostic accuracy of 2-[(18)F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults. Eur Radiol. 2022;32(7):4967–79.

    Article  CAS  PubMed  Google Scholar 

  18. Toyonaga T, et al. Deep learning-based attenuation correction for whole-body PET—a multi-tracer study with (18)F-FDG, (68) Ga-DOTATATE, and (18)F-fluciclovine. Eur J Nucl Med Mol Imaging. 2022;49(9):3086–97.

    Article  CAS  PubMed  Google Scholar 

  19. Grossman SA, et al. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111indium-DTPA ventriculography. Am J Med. 1982;73(5):641–7.

    Article  CAS  PubMed  Google Scholar 

  20. Goodwin DA, et al. Preparation, physiology, and dosimetry of 111 In-labeled radiopharmaceuticals for cisternography. Radiology. 1973;108(1):91–8.

    Article  CAS  PubMed  Google Scholar 

  21. Wagner HN Jr, et al. A new radiopharmaceutical for cisternography: chelated ytterbium 169. Radiology. 1970;95(1):121–5.

    Article  PubMed  Google Scholar 

  22. Dichiro G, Reames PM, Matthews WB Jr. Risa-ventriculography and risa-cisternography. Neurology. 1964;14:185–91.

    Article  CAS  PubMed  Google Scholar 

  23. Di Chiro G, et al. Descent of cerevrospinal fluid to spinal subarachnoid space. Acta Radiol Diagn (Stockh). 1973;14(4):379–84.

    Article  Google Scholar 

  24. Hosain F, Reba RC, Wagner HN Jr. Ytterbium-169 diethylenetriaminepentaacetic acid complex. A new radiopharmaceutical for brain scanning. Radiology. 1968;91(6):1294. passim.

    Article  PubMed  Google Scholar 

  25. Lette J, et al. A reproducible radionuclide procedure for measurement of cerebrospinal fluid shunt flow. Eur J Nucl Med. 1986;12(5–6):240–3.

    Article  CAS  PubMed  Google Scholar 

  26. de Rougemont J, et al. [Outflow in ventricular peritoneal derivations. Its determination with Na 131-I]. Neurochirurgie. 1970;16(4):307–18.

    Google Scholar 

  27. Wong FC, Groves M, Papadopulos N, Conrad C, Meyers C, Kim S, Puduvali V, Hsu S, Kim EE. Toxicity and efficacy profiles of intrathecal injection of I-131 NaI via intraventricular (IVent) or intralumbar (Ilumb) route for leptomeningeal metastases (LM) therapy. J Clin Oncol. 2006;24(18S):70s.

    Google Scholar 

  28. Rebischung C, et al. First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX plus (125)IUdR. Int J Radiat Biol. 2008;84(12):1123–9.

    Article  CAS  PubMed  Google Scholar 

  29. Bergstrand G, et al. Positron emission tomography with 68Ga-EDTA in the diagnosis and localization of CSF fistulas. J Comput Assist Tomogr. 1982;6(2):320–4.

    Article  CAS  PubMed  Google Scholar 

  30. Maziere B, et al. [55Co]- and [64Cu]DTPA: new radiopharmaceuticals for quantitative tomocisternography. Int J Appl Radiat Isot. 1983;34(3):595–601.

    Article  CAS  PubMed  Google Scholar 

  31. Freesmeyer M, et al. High-resolution PET cisternography with 64Cu-DOTA for CSF leak detection. Clin Nucl Med. 2019;44(9):735–7.

    Article  PubMed  Google Scholar 

  32. Muriel FS, et al. Remission maintenance therapy for meningeal leukaemia: intrathecal methotrexate and dexamethasone versus intrathecal craniospinal irradiation with a radiocolloid. Br J Haematol. 1976;34(1):119–27.

    Article  CAS  PubMed  Google Scholar 

  33. Moseley RP, et al. Carcinomatous meningitis: antibody-guided therapy with I-131 HMFG1. J Neurol Neurosurg Psychiatry. 1991;54(3):260–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lashford LS, et al. A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. Cancer. 1988;61(5):857–68.

    Article  CAS  PubMed  Google Scholar 

  35. Moseley RP, Benjamin JC, Ashpole RD. Carcinomatous meningitis: antibody-guided therapy with I-131 HMFG1. J Neurol Neurosurg Psychiatry. 1991;54(3):260–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pandit-Taskar N, et al. Biodistribution and dosimetry of intraventricularly administered (124)I-omburtamab in patients with metastatic leptomeningeal tumors. J Nucl Med. 2019;60(12):1794–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Moseley RP, et al. Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis. Br J Cancer. 1990;62(4):637–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Iacoangeli M, et al. Intrathecal chemotherapy for treatment of overt meningeal leukemia: comparison between intraventricular and traditional intralumbar route. Ann Oncol. 1995;6(4):377–82.

    Article  CAS  PubMed  Google Scholar 

  39. Ommaya AK. Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet. 1963;2(7315):983–4.

    Article  CAS  PubMed  Google Scholar 

  40. Partain CL, et al. A multiregional kinetics model for cerebrospinal fluid. Radiology. 1978;127(3):705–11.

    Article  CAS  PubMed  Google Scholar 

  41. Chamberlain MC, Corey-Bloom J. Leptomeningeal metastases: 111indium-DTPA CSF flow studies. Neurology. 1991;41(11):1765–9.

    Article  CAS  PubMed  Google Scholar 

  42. Chamberlain MC, Kormanik P, Jaeckle KA. 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1999;52(1):216–7.

    Article  CAS  PubMed  Google Scholar 

  43. James AE Jr, et al. Normal-pressure hydrocephalus. Role of cisternography in diagnosis. JAMA. 1970;213(10):1615–22.

    Article  PubMed  Google Scholar 

  44. Galli G, Troncone L, De Rossi G. 131-I-HSA cisternography and 131-I-HSA transfer from CSF to blood in normal pressure hydrocephalus. J Nucl Biol Med. 1973;17(2):64–70.

    CAS  PubMed  Google Scholar 

  45. Larsson A, et al. Predictive value of quantitative cisternography in normal pressure hydrocephalus. Acta Neurol Scand. 1990;81(4):327–32.

    Article  CAS  PubMed  Google Scholar 

  46. Patten DH, Benson DF. Diagnosis of normal-pressure hydrocephalus by RISA cisternography. J Nucl Med. 1968;9(8):457–61.

    CAS  PubMed  Google Scholar 

  47. Khan SH, Rather TA, Sinha S. Cerebral spinal fluid cisternography in normal pressure hydrocephalus of the elderly. Indian J Nucl Med. 2017;32(3):250–1.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Algin O, et al. MR cisternography: is it useful in the diagnosis of normal-pressure hydrocephalus and the selection of “good shunt responders”? Diagn Interv Radiol. 2011;17(2):105–11.

    PubMed  Google Scholar 

  49. Andersson J, et al. Challenges in diagnosing normal pressure hydrocephalus: evaluation of the diagnostic guidelines. eNeurologicalSci. 2017;7:27–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Keong NC, et al. Imaging normal pressure hydrocephalus: theories, techniques, and challenges. Neurosurg Focus. 2016;41(3):E11.

    Article  PubMed  Google Scholar 

  51. Aunan-Diop JS, et al. Magnetic resonance elastography in normal pressure hydrocephalus-a scoping review. Neurosurg Rev. 2021;45(2):1157–69.

    Article  PubMed  Google Scholar 

  52. Oliveira LM, Nitrini R, Roman GC. Normal-pressure hydrocephalus: a critical review. Dement Neuropsychol. 2019;13(2):133–43.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Scully AE, et al. A systematic review of the diagnostic utility of simple tests of change after trial removal of cerebrospinal fluid in adults with normal pressure hydrocephalus. Clin Rehabil. 2018;32(7):942–53.

    Article  PubMed  Google Scholar 

  54. Hentschel SJ, et al. Subarachnoid-pleural fistula after resection of thoracic tumors. J Neurosurg. 2004;100(4 Suppl Spine):332–6.

    PubMed  Google Scholar 

  55. Slart RH, et al. Persistent aseptic meningitis due to post-surgical spinal CSF leakage: value of fused (111m)In-DTPA SPECT-CT cisternography. Eur J Nucl Med Mol Imaging. 2006;33(7):856.

    Article  PubMed  Google Scholar 

  56. Jeffery PJ, et al. Bowel visualization during indium-111-labelled diethylene triamine penta-acetic acid cisternography due to massive cerebrospinal fluid leak. Case report and review of the literature. Eur J Nucl Med. 1990;17(6–8):365–8.

    Article  CAS  PubMed  Google Scholar 

  57. Kosuda S, et al. [Reassessment of a combination of cerebrospinal fluid scintigraphy and nasal pledget counts in patients with suspected rhinorrhea]. Kaku Igaku. 1998;35(6):435–41.

    Google Scholar 

  58. McKusick KA, et al. Radionuclide cisternography: normal values for nasal secretion of intrathecally injected 111In-DTPA. J Nucl Med. 1973;14(12):933–4.

    CAS  PubMed  Google Scholar 

  59. Schicha H, Voth E, Emrich D. Detection of occult and intermittent rhinorrhea using 111In-DTPA. Eur J Nucl Med. 1985;11(2–3):76–9.

    CAS  PubMed  Google Scholar 

  60. Wong F, McCutcheon I, Groves M, Kim E. Evaluation of CSF flow by whole-body scintigraphy. J Nucl Med. 2010;51:1789.

    Google Scholar 

  61. Glantz MJ, et al. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995;75(12):2919–31.

    Article  CAS  PubMed  Google Scholar 

  62. Chamberlain MC, Kormanik PA. Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology. 1996;46(6):1674–7.

    Article  CAS  PubMed  Google Scholar 

  63. Korkmaz M, et al. In-111 DTPA Ommayagrams in leptomeningeal carcinomatosis. Clin Nucl Med. 1995;20(7):610–2.

    Article  CAS  PubMed  Google Scholar 

  64. Eltobgy M, et al. Impact of cerebrospinal fluid flow study in patients undergoing intrathecal chemotherapy via ventricular catheter reservoir. J Neurooncol. 2021;153(1):161–7.

    Article  CAS  PubMed  Google Scholar 

  65. Hayden PW, Rudd TG, Shurtleff DB. Combined pressure-radionuclide evaluation of suspected cerebrospinal fluid shunt malfunction: a seven-year clinical experience. Pediatrics. 1980;66(5):679–84.

    Article  CAS  PubMed  Google Scholar 

  66. Gok B, et al. Radionuclide shunt patency study for suspected ventriculoatrial shunt malfunction. Clin Nucl Med. 2013;38(7):527–33.

    Article  PubMed  Google Scholar 

  67. Miller KT, Wilkinson DS. Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics. Ther Drug Monit. 1989;11(3):231–7.

    Article  CAS  PubMed  Google Scholar 

  68. Mason WP, Yeh SD, DeAngelis LM. 111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1998;50(2):438–44.

    Article  CAS  PubMed  Google Scholar 

  69. Chamberlain MC, et al. 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1999;52(1):216–7.

    Article  CAS  PubMed  Google Scholar 

  70. Wong F. Effective half-life of in-111 DTPA in the CSF from whole-body Ommayogram/Cisternogram correlates with CSF leakage and blockade. J Nucl Med Mol Imaging. 2022;63 (Suppl 2):2917.

    Google Scholar 

  71. Wong F, Kim E, Groves M, McCutcheon E, Podoloff D. The clearance rates of In-111 DTPA from CSF vary with different types of CSF blockade. J Nucl Med. 2002;29(8):286.

    Google Scholar 

Download references

Acknowledgments

The authors are grateful to E. Edmund Kim MD, Professor of Radiology in the University of California at Irvine for his participating in reading scintigraphic scans of CSF flows of protocol DR10-0344.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Franklin C. L. Wong .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wong, F.C.L., McCutcheon, I.E. (2022). Scintigraphy of Human CSF Flow in Patients with Leptomeningeal Metastasis. In: Wong, F.C. (eds) Radiopharmaceuticals in the Management of Leptomeningeal Metastasis. Springer, Cham. https://doi.org/10.1007/978-3-031-14291-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-14291-8_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-14290-1

  • Online ISBN: 978-3-031-14291-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics