Top

Published in:

01-12-2020 | Magnetic Resonance Imaging | Original research

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by ¹⁸F-positron emitting tomography and fluorescence

Authors: Hua Guo, Harikrishna Kommidi, Carl C. Lekaye, Jason Koutcher, Martin S. Judenhofer, Simon R. Cherry, Amy P. Wu, Oguz Akin, Mark M. Souweidane, Omer Aras, Zhaohui Zhu, Richard Ting

Published in: EJNMMI Research | Issue 1/2020

Abstract

Purpose

Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS).

Methods

We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [¹⁸F]-IR783-AMBF₃. [¹⁸F]-IR783-AMBF₃ was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes.

Results

IR783-AMBF₃ was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF₃ (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF₃ was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF₃ was safe under the tested dosage both in vitro and in vivo.

Conclusion

The superior imaging properties of IR783-AMBF₃ could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

Available only for authorised users

Tsien RY. Imagining imaging’s future. Nat Rev Mol Cell Biol. 2003;Suppl:SS16-21.

An FF, Chan M, Kommidi H, Ting R. Dual PET and near-infrared fluorescence imaging probes as tools for imaging in oncology. AJR Am J Roentgenol. 2016;207:266–73. https://doi.org/10.2214/AJR.16.16181.CrossRefPubMedPubMedCentral

Disselhorst JA, Brom M, Laverman P, Slump CH, Boerman OC, Oyen WJ, et al. Image-quality assessment for several positron emitters using the NEMA NU 4-2008 standards in the Siemens Inveon small-animal PET scanner. J Nucl Med. 2010;51:610–7. https://doi.org/10.2967/jnumed.109.068858.CrossRefPubMed

Nguyen QT, Tsien RY. Fluorescence-guided surgery with live molecular navigation--a new cutting edge. Nat Rev Cancer. 2013;13:653–62. https://doi.org/10.1038/nrc3566.CrossRefPubMedPubMedCentral

Paulus A, Desai P, Carney B, Carlucci G, Reiner T, Brand C, et al. Development of a clickable bimodal fluorescent/PET probe for in vivo imaging. EJNMMI Res. 2015;5:120. https://doi.org/10.1186/s13550-015-0120-4.CrossRefPubMed

Rosenthal EL, Warram JM, De Boer E, Chung TK, Korb ML, Brandwein-Gensler M, et al. Safety and tumor specificity of cetuximab-IRDye800 for surgical navigation in head and neck cancer. Clin Cancer Res. 2015;21:3658–66.CrossRef

Cheng L, Kamkaew A, Sun H, Jiang D, Valdovinos HF, Gong H, et al. Dual-modality positron emission tomography/optical image-guided photodynamic cancer therapy with chlorin e6-containing nanomicelles. ACS Nano. 2016;10:7721–30.CrossRef

Guo H, Harikrishna K, Vedvyas Y, McCloskey JE, Zhang W, Chen N, et al. A fluorescent,[18F]-positron-emitting agent for imaging PMSA allows genetic reporting in adoptively-transferred, genetically-modified cells. ACS Chem Biol. 2019.

Carlucci G, Carney B, Brand C, Kossatz S, Irwin CP, Carlin SD, et al. Dual-modality optical/PET imaging of PARP1 in glioblastoma. Mol Imaging Biol. 2015;17:848–55. https://doi.org/10.1007/s11307-015-0858-0.CrossRefPubMedPubMedCentral

10.

Khazim R, Dannawi Z, Spacey K, Khazim M, Lennon S, Reda A, et al. Incidence and treatment of delayed symptoms of CSF leak following lumbar spinal surgery. Eur Spine J. 2015;24:2069–76.CrossRef

11.

Schievink WI, Maya MM, Chu RM, Moser FG. False localizing sign of cervico-thoracic CSF leak in spontaneous intracranial hypotension. Neurology. 2015;84:2445–8.CrossRef

12.

Jiang D, Dalong N, Li S, Ehlerding E, Sun T, Cao T, et al. Framework DNA nanocages alleviate ischemic stroke via intrathecal injection. J Nucl Med. 2019;60:335.CrossRef

13.

Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest. 2013;123:1299–309. https://doi.org/10.1172/JCI67677.CrossRefPubMedPubMedCentral

14.

Kwon S, Janssen CF, Velasquez FC, Sevick-Muraca EM. Fluorescence imaging of lymphatic outflow of cerebrospinal fluid in mice. J Immunol Methods. 2017;449:37–43.CrossRef

15.

Strazielle N, Ghersi-Egea JF. Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm. 2013;10:1473–91. https://doi.org/10.1021/mp300518e.CrossRefPubMed

16.

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.

17.

George N, Gean EG, Nandi A, Frolov B, Zaidi E, Lee H, et al. Advances in CNS imaging agents: focus on PET and SPECT tracers in experimental and clinical use. CNS Drugs. 2015;29:313–30.CrossRef

18.

Sese D, Blaha T, Khurana R, Wachsman A, Al-ali F, Murray T, et al. A leaky situation: gadolinium contrast induced neurotoxicity from intrathecal contrast. D45 CRITICAL CARE CASE REPORTS: I (DON'T) WANT TO BE SEDATED-NEUROCRITICAL CARE, SEDATION, AND DELIRIUM: American Thoracic Society; 2018. p. A6888-A.

19.

Starke RM, Dumont AS. Intraoperative imaging and assessment of cerebral blood flow in cerebrovascular surgery: hybrid operating rooms, intraoperative angiography and magnetic resonance imaging, Doppler ultrasound, cerebral blood flow probes, endoscopic assistance, indocyanine green videography, and laser speckle contrast imaging. World Neurosurg. 2014;82:e693–6. https://doi.org/10.1016/j.wneu.2013.10.045.CrossRefPubMed

20.

Kommidi H, Guo H, Chen N, Kim D, He B, Wu AP, et al. An [18F]-positron-emitting, fluorescent, cerebrospinal fluid probe for imaging damage to the brain and spine. Theranostics. 2017;7:2377–91. https://doi.org/10.7150/thno.19408.CrossRefPubMedPubMedCentral

21.

Guo H, Kommidi H, Maachani UB, Voronina JC, Zhang W, Magge RS, et al. An [(18)F]-positron emitting fluorophore allows safe evaluation of small molecule distribution in the CSF, CSF fistulas, and CNS device placement. Mol Pharm. 2019;16:3636–46. https://doi.org/10.1021/acs.molpharmaceut.9b00485.CrossRefPubMed

22.

Sajedi S, Sabet H, Choi HS. Intraoperative biophotonic imaging systems for image-guided interventions. Nanophotonics. 2018;8:99–116.CrossRef

23.

Wang Y, An F-F, Chan M, Friedman B, Rodriguez EA, Tsien RY, et al. 18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model. J Cereb Blood Flow Metab. 2017:0271678X16682510. doi:10.1177/0271678X16682510.

24.

Catana C, Wu Y, Judenhofer MS, Qi J, Pichler BJ, Cherry SR. Simultaneous acquisition of multislice PET and MR images: initial results with a MR-compatible PET scanner. J Nucl Med. 2006;47:1968–76.PubMed

25.

Wu Y, Catana C, Farrell R, Dokhale PA, Shah KS, Qi J, et al. PET performance evaluation of an MR-compatible PET insert. IEEE Trans Nucl Sci. 2009;56:574–80. https://doi.org/10.1109/TNS.2009.2015448.CrossRefPubMedPubMedCentral

26.

Liu Z, Lin KS, Benard F, Pourghiasian M, Kiesewetter DO, Perrin DM, et al. One-step (18)F labeling of biomolecules using organotrifluoroborates. Nat Protoc. 2015;10:1423–32. https://doi.org/10.1038/nprot.2015.090.CrossRefPubMedPubMedCentral

27.

Liu Z, Pourghiasian M, Radtke MA, Lau J, Pan J, Dias GM, et al. An organotrifluoroborate for broadly applicable one-step F-labeling. Angew Chem Int Ed Eng. 2014. https://doi.org/10.1002/anie.201406258.

28.

Liu Z, Li Y, Lozada J, Wong MQ, Greene J, Lin K-S, et al. Kit-like 18F-labeling of RGD-19F-Arytrifluroborate in high yield and at extraordinarily high specific activity with preliminary in vivo tumor imaging. Nucl Med Biol. 2013;40:841–9. https://doi.org/10.1016/j.nucmedbio.2013.05.002.CrossRef

29.

Seth R, Rajasekaran K, Benninger MS, Batra PS. The utility of intrathecal fluorescein in cerebrospinal fluid leak repair. Otolaryngol Head Neck Surg. 2010;143:626–32. https://doi.org/10.1016/j.otohns.2010.07.011.CrossRefPubMed

30.

Banu MA, Kim J-H, Shin BJ, Woodworth GF, Anand VK, Schwartz TH. Low-dose intrathecal fluorescein and etiology-based graft choice in endoscopic endonasal closure of CSF leaks. Clin Neurol Neurosurg. 2014;116:28–34.CrossRef

31.

Bernard-Gauthier V, Bailey JJ, Liu Z, Wangler B, Wangler C, Jurkschat K, et al. From unorthodox to established: the current status of (18)F-trifluoroborate- and (18)F-SiFA-based radiopharmaceuticals in PET nuclear imaging. Bioconjug Chem. 2016;27:267–79. https://doi.org/10.1021/acs.bioconjchem.5b00560.CrossRefPubMed

32.

Perrin DM. [18F]-organotrifluoroborates as radioprosthetic groups for PET Imaging: from design principles to preclinical applications. Acc Chem Res. 2016. https://doi.org/10.1021/acs.accounts.5b00398.

33.

Schirrmacher E, Wängler B, Cypryk M, Bradtmöller G, Schäfer M, Eisenhut M, et al. Synthesis of p-(di-tert-butyl [18F] fluorosilyl) benzaldehyde ([18F] SiFA-A) with high specific activity by isotopic exchange: a convenient labeling synthon for the 18F-labeling of N-amino-oxy derivatized peptides. Bioconjug Chem. 2007;18:2085–9.CrossRef

34.

Yadav YR, Parihar V, Sinha M. Lumbar peritoneal shunt. Neurol India. 2010;58:179–84. https://doi.org/10.4103/0028-3886.63778.CrossRefPubMed

35.

Kranz PG, Luetmer PH, Diehn FE, Amrhein TJ, Tanpitukpongse TP, Gray L. Myelographic techniques for the detection of spinal CSF leaks in spontaneous intracranial hypotension. Am J Roentgenol. 2016;206:8–19.CrossRef

36.

Kranz P, Gray L, Taylor J. CT-guided epidural blood patching of directly observed or potential leak sites for the targeted treatment of spontaneous intracranial hypotension. Am J Neuroradiol. 2011;32:832–8.CrossRef

37.

Melamed J, Stone B, Beaucher WN. Spontaneous cerebrospinal fluid rhinorrhea with associated sinusitis and allergic rhinitis. Allergy Proc. 1994;15:197–200.CrossRef

38.

Park K-W, Im S-B, Kim B-T, Hwang S-C, Park J-S, Shin W-H. Neurotoxic manifestations of an overdose intrathecal injection of gadopentetate dimeglumine. J Korean Med Sci. 2010;25:505–8.CrossRef

39.

Feng X, Xia Q, Yuan L, Yang X, Wang K. Impaired mitochondrial function and oxidative stress in rat cortical neurons: implications for gadolinium-induced neurotoxicity. Neurotoxicology. 2010;31:391–8.CrossRef

40.

Mokri B. Radioisotope cisternography in spontaneous CSF leaks: interpretations and misinterpretations. Headache: The Journal of Head and Face Pain. 2014;54:1358–68.CrossRef

41.

Howard BA, Gray L, Isaacs RE, Borges-Neto S. Definitive diagnosis of cerebrospinal fluid leak into the pleural space using 111In-DTPA cisternography. Clin Nucl Med. 2015;40:220–3.CrossRef

42.

Rahmim A, Zaidi H. PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun. 2008;29:193–207. https://doi.org/10.1097/MNM.0b013e3282f3a515.CrossRefPubMed

Title: A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by 18F-positron emitting tomography and fluorescence
Authors: Hua Guo
Harikrishna Kommidi
Carl C. Lekaye
Jason Koutcher
Martin S. Judenhofer
Simon R. Cherry
Amy P. Wu
Oguz Akin
Mark M. Souweidane
Omer Aras
Zhaohui Zhu
Richard Ting
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Computed Tomography
Computed Tomography
Positron Emission Tomography
Published in: EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-020-0609-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by ¹⁸F-positron emitting tomography and fluorescence

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2020

Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model

The value of 18F-PSMA-1007 PET/CT in identifying non-metastatic high-risk prostate cancer

FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients

Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity

Correction to: Neurologically asymptomatic cerebral oligometastatic prostate carcinoma metastasis identified on [Ga]Ga-THP-PSMA PET/CT

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study