NEURORADIOLOGY / ORIGINAL PAPER
Assessing glymphatic dysfunction using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index in gliomas and metastases
1
St. John’s Medical College Hospital, Bangladore, Karnataka, India
2
Aster Group of Hospitals, Bangladore, Karnataka, India
These authors had equal contribution to this work
Submission date: 2025-06-23
Acceptance date: 2025-08-21
Publication date: 2025-12-15
Corresponding author
Shreyas Reddy K
St. John’s Medical College Hospital, Sarjapur Road, Bangalore 560034, Karnataka, India
St. John’s Medical College Hospital, Sarjapur Road, Bangalore 560034, Karnataka, India
Pol J Radiol, 2025; 90: 611-620
KEYWORDS
TOPICS
ABSTRACT
Purpose:
To evaluate glymphatic dysfunction using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index in patients with low-grade gliomas (LGGs), high-grade gliomas (HGGs), and metastases, assess its feasibility as a non-invasive biomarker for tumour differentiation, and examine its relationship with tumour-specific characteristics.
Material and methods:
This single-centre retrospective study examined patients with LGGs (n = 30), HGGs (n = 30), and metastases (n = 20), calculating the DTI-ALPS index. Tumour volume, peritumoral oedema, tumour volumeto-total brain volume ratio (TV/TBV), and peritumoral oedema-to-total brain volume ratio (PTE/TBV) were obtained using 3D segmentation. The DTI-ALPS index was compared across the 3 tumour groups, and its relationships with tumour-associated oedema, peritumoral oedema, TV/TBV, and PTE/TBV were analysed within and between the groups. Additionally, the DTI-ALPS index was compared between isocitrate dehydrogenase-1 (IDH1) mutant and IDH1 wild-type gliomas.
Results:
There was a significant difference in the DTI-ALPS index between the 3 groups (p < 0.001), with HGGs having the lowest DTI-ALPS index values, followed by metastases and LGGs. Receiver operating characteristic (ROC)analysis showed that the DTI-ALPS index had excellent sensitivity and specificity for LGGs (> 1.3838) and HGGs (< 1.317). No significant correlation was found between the DTI-ALPS index and tumour volume, TV/TBV, PTE/TBV, or peritumoral oedema. Furthermore, the mean DTI-ALPS index in IDH1 wild-type gliomas (1.23 ± 0.08) was significantly lower than that observed in IDH1 mutant tumours (1.42 ± 0.10; p < 0.001).
Conclusions:
The DTI-ALPS index provides valuable insights into glymphatic dysfunction in brain tumours. This study underscores its potential as a non-invasive biomarker in differentiating these tumour groups.
To evaluate glymphatic dysfunction using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index in patients with low-grade gliomas (LGGs), high-grade gliomas (HGGs), and metastases, assess its feasibility as a non-invasive biomarker for tumour differentiation, and examine its relationship with tumour-specific characteristics.
Material and methods:
This single-centre retrospective study examined patients with LGGs (n = 30), HGGs (n = 30), and metastases (n = 20), calculating the DTI-ALPS index. Tumour volume, peritumoral oedema, tumour volumeto-total brain volume ratio (TV/TBV), and peritumoral oedema-to-total brain volume ratio (PTE/TBV) were obtained using 3D segmentation. The DTI-ALPS index was compared across the 3 tumour groups, and its relationships with tumour-associated oedema, peritumoral oedema, TV/TBV, and PTE/TBV were analysed within and between the groups. Additionally, the DTI-ALPS index was compared between isocitrate dehydrogenase-1 (IDH1) mutant and IDH1 wild-type gliomas.
Results:
There was a significant difference in the DTI-ALPS index between the 3 groups (p < 0.001), with HGGs having the lowest DTI-ALPS index values, followed by metastases and LGGs. Receiver operating characteristic (ROC)analysis showed that the DTI-ALPS index had excellent sensitivity and specificity for LGGs (> 1.3838) and HGGs (< 1.317). No significant correlation was found between the DTI-ALPS index and tumour volume, TV/TBV, PTE/TBV, or peritumoral oedema. Furthermore, the mean DTI-ALPS index in IDH1 wild-type gliomas (1.23 ± 0.08) was significantly lower than that observed in IDH1 mutant tumours (1.42 ± 0.10; p < 0.001).
Conclusions:
The DTI-ALPS index provides valuable insights into glymphatic dysfunction in brain tumours. This study underscores its potential as a non-invasive biomarker in differentiating these tumour groups.
REFERENCES (42)
1.
Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS. Epidemiology of gliomas. Cancer Treat Res 2015; 163: 1-14.
2.
Lapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet 2018; 392: 432-446.
3.
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012; 4: 147ra111. DOI: 10.1126/scitranslmed. 3003748.
4.
Hablitz LM, Nedergaard M. The glymphatic system: a novel component of fundamental neurobiology. J Neurosci 2021; 41: 7698-7711.
5.
Iliff JJ, Nedergaard M. Is there a cerebral lymphatic system? Stroke 2013; 44: S93-S95.
6.
Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Jpn J Radiol 2017; 35: 172-178.
7.
Chang HI, Huang CW, Hsu SW, Huang SH, Lin KJ, Ho TY, et al. Gray matter reserve determines glymphatic system function in young-onset Alzheimer’s disease: Evidenced by DTI-ALPS and compared with age-matched controls. Psychiatry Clin Neurosci 2023; 77: 401-409.
8.
Silva I, Silva J, Ferreira R, Trigo D. Glymphatic system, AQP4, and their implications in Alzheimer’s disease. Neurol Res Pract 2021. 3: 5. DOI: 10.1186/s42466-021-00102-7.
9.
Hsu J, Wei Y, Toh CH, Hsiao I, Lin K, Yen T, et al. Magnetic resonance images implicate that glymphatic alterations mediate cognitive dysfunction in Alzheimer disease. Ann Neurol 2023; 93: 164-174.
10.
Yokota H, Vijayasarathi A, Cekic M, Hirata Y, Linetsky M, Ho M, et al. Diagnostic performance of glymphatic system evaluation using diffusion tensor imaging in idiopathic normal pressure hydrocephalus and mimickers. Curr Gerontol Geriatr Res 2019; 2019: 5675014. DOI: 10.1155/2019/5675014.
11.
Georgiopoulos C, Tisell A, Holmgren RT, Eleftheriou A, Rydja J, Lundin F, et al. Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging. J Neurosurg 2024; 140: 612-620.
12.
Eide PK, Pripp AH, Ringstad G, Valnes LM. Impaired glymphatic function in idiopathic intracranial hypertension. Brain Commun 2021; 3: fcab043. DOI: 10.1093/braincomms/fcab043.
13.
Liu W, Jia L, Xu L, Yang F, Cheng H, Li H, et al. Idiopathic intracranial hypertension in patients with cerebral small vessel disease: a case report. Medicine 2023; 102: e32639. DOI: 10.1097/MD. 0000000000032639.
14.
Jones O, Cutsforth-Gregory J, Chen J, Bhatti MT, Huston J, Brinjikji W. Idiopathic intracranial hypertension is associated with a higher burden of visible cerebral perivascular spaces: the glymphatic connection. AJNR Am J Neuroradiol 2021; 42: 2160-2164.
15.
Toh CH, Siow TY. Glymphatic dysfunction in patients with ischemic stroke. Front Aging Neurosci 2021; 13: 756249. DOI: 10.3389/fnagi.2021.756249.
16.
Zhang C, Sha J, Cai L, Xia Y, Li D, Zhao H, et al. Evaluation of the glymphatic system using the DTI-ALPS index in patients with spontaneous intracerebral haemorrhage. Oxid Med Cell Longev 2022; 2022: 2694316. DOI: 10.1155/2022/2694316.
17.
Gaberel T, Gakuba C, Goulay R, De Lizarrondo SM, Hanouz JL, Emery E, et al. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis? Stroke 2014; 45: 3092-3096.
18.
Piantino J, Schwartz DL, Luther M, Newgard C, Silbert L, Raskind M, et al. Link between mild traumatic brain injury, poor sleep, and magnetic resonance imaging: visible perivascular spaces in veterans. J Neurotrauma 2021; 38: 2391-2399.
19.
Chen HL, Chen PC, Lu CH, Tsai NW, Yu CC, Chou KH, et al. Associations among cognitive functions, plasma DNA, and diffusion tensor image along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease. Oxid Med Cell Longev 2021; 2021: 4034509. DOI: 10.1155/2021/4034509.
20.
Yang DX, Sun Z, Yu MM, Zou QQ, Li PY, Zhang JK. Associations of MRI-derived glymphatic system impairment with global white matter damage and cognitive impairment in mild traumatic brain injury: a DTI-ALPS study. J Magn Reson Imaging 2024; 59: 639-647.
21.
Toh CH, Siow TY, Castillo M. Peritumoral brain edema in metastases may be related to glymphatic dysfunction. Front Oncol 2021; 11: 725354. DOI: 10.3389/fonc.2021.725354.
22.
Toh CH, Siow TY, Castillo M. Peritumoral Brain Edema in Meningiomas May Be Related to Glymphatic Dysfunction. Front Neurosci 2021; 15: 674898. DOI: 10.3389/fnins.2021.674898.
23.
Toh CH, Siow TY. Factors associated with dysfunction of glymphatic system in patients with glioma. Front Oncol 2021; 11: 744318. DOI: 10.3389/fonc.2021.744318.
24.
Zeng S, Huang Z, Zhou W, Ma H, Wu J, Zhao C, et al. Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space. J Neurosurg 2024; 142: 187-196.
25.
Sinnaeve D. The Stejskal – tanner equation generalized for any gradient shape – an overview of most pulse sequences measuring free diffusion. Concepts Magn Reson 2012; 40A: 39-65.
26.
Bouget D, Alsinan D, Gaitan V, Helland RH, Pedersen A, Solheim O, et al. Raidionics: an open software for pre- and postoperative central nervous system tumor segmentation and standardized reporting. Sci Rep 2023; 13: 15570. DOI: 10.1038/s41598-023-42048-7.
27.
Jamovi – open statistical software for the desktop and cloud. Available from: https://www.jamovi.org/ (Assessed: 16.01.2025).
28.
Lan Y, Wang H, Chen A, Zhang J. Update on the current knowledge of lymphatic drainage system and its emerging roles in glioma management. Immunology 2023; 168: 233-247.
29.
Xu D, Zhou J, Mei H, Li H, Sun W, Xu H. Impediment of cerebrospinal fluid drainage through glymphatic system in glioma. Front Oncol 2022; 11: 790821. DOI: 10.3389/fonc.2021.790821.
30.
Kaur J, Ding G, Zhang L, Lu Y, Luo H, Li L, et al. Imaging glymphatic response to glioblastoma. Cancer Imaging 2023; 23: 107. DOI: 10.1186/s40644-023-00628-w.
31.
Scalia G, Ferini G, Silven MP, Noto M, Costanzo R, Maugeri R, et al. Alterations of the glymphatic system in glioblastomas: a systematic review. Anticancer Res 2024; 44: 3223-3230.
32.
Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol 2007; 22: 778-784.
33.
Trillo-Contreras JL, Toledo-Aral JJ, Echevarría M, Villadiego J. AQP1 and AQP4 contribution to cerebrospinal fluid homeostasis. Cells 2019; 8: 197. DOI: 10.3390/cells8020197.
34.
Wrobel JK, Toborek M. Blood-brain barrier remodeling during brain metastasis formation. Mol Med 2016; 22: 32-40.
35.
Hu X, Deng Q, Ma L, Li Q, Chen Y, Liao Y, et al. Meningeal lymphatic vessels regulate brain tumor drainage and immunity. Cell Res 2020; 30: 229-243.
36.
Guan Z, Lan H, Cai X, Zhang Y, Liang A, Li J. Blood-brain barrier, cell junctions, and tumor microenvironment in brain metastases, the biological prospects and dilemma in therapies. Front Cell Dev Biol 2021; 9: 722917. DOI: 10.3389/fcell.2021.722917.
37.
Jin P, Munson JM. Fluids and flows in brain cancer and neurological disorders. WIREs Mech Dis 2023; 15: e1582. DOI: 10.1002/wsbm.1582.
38.
Ma Q, Schlegel F, Bachmann SB, Schneider H, Decker Y, Rudin M, et al. Lymphatic outflow of cerebrospinal fluid is reduced in glioma. Sci Rep 2019; 9: 14815. DOI: 10.1038/s41598-019-51373-9.
39.
Zhu H, Xie Y, Li L, Liu Y, Li S, Shen N, et al. Diffusion along the perivascular space as a potential biomarker for glioma grading and isocitrate dehydrogenase 1 mutation status prediction. Quant Imaging Med Surg 2023; 13: 8259273-8258273.
40.
Gao M, Liu Z, Zang H, Wu X, Yan Y, Lin H, et al. A histopathologic correlation study evaluating glymphatic function in brain tumors by multiparametric MRI. Clin Cancer Res 2024; 30: 4876-4886.
41.
Dubois LG, Campanati L, Righy C, D’Andrea-Meira I, de Sampaio E Spohr TCL, Porto-Carreiro I, et al. Gliomas and the vascular fragility of the blood brain barrier. Front Cell Neurosci 2014; 8: 418. DOI: 10.3389/fncel.2014.00418.
42.
Ohmura K, Tomita H, Hara A. Peritumoral edema in gliomas: a review of mechanisms and management. Biomedicines 2023; 11: 2731. DOI: 10.3390/biomedicines11102731.
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