Skip to main content

Advertisement

Log in

Neuroimaging of central diabetes insipidus—when, how and findings

  • Review
  • Published:
Neuroradiology Aims and scope Submit manuscript

Abstract

Central or neurogenic diabetes insipidus (CDI) is due to deficient synthesis or secretion of antidiuretic hormone (ADH), also known as arginine vasopressin peptide (AVP). It is clinically characterised by polydipsia and polyuria (urine output > 30 mL/kg/day) of dilute urine (< 250 mOsm/L). It is the result of a defect in one of more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei of the hypothalamus, median eminence of the hypothalamus, infundibulum or the posterior pituitary gland. A focused MRI pituitary gland or sella protocol is essential. There are several neuroimaging correlates and causes of CDI, illustrated in this review. The most common causes are benign or malignant neoplasms of the hypothalamic-pituitary axis (25%), surgery (20%), head trauma (16%) or familial causes (10%). No cause is identified in up to 30% of cases. Knowledge of the anatomy and physiology of the hypothalamo-neurohypophyseal axis is crucial when evaluating a patient with CDI. Establishing the aetiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. The aim of the pictorial review is to illustrate the wide variety of causes of CDI on neuroimaging, highlight the optimal MRI protocol and to revise the detailed neuroanatomy and neurophysiology required to interpret these studies.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20

Similar content being viewed by others

Abbreviations

CDI:

Central diabetes insipidus

HPA:

Hypothalamic pituitary axis

PPBS:

Posterior pituitary bright spot

ADH:

Antidiuretic hormone

AVP:

Arginine vasopressin peptide

References

  1. Tien R, Kucharczyk J, Kucharczyk W (1991) MR imaging of the brain in patients with diabetes insipidus. AJNR Am J Neuroradiol 12:533–542

    CAS  PubMed  Google Scholar 

  2. Di Iorgi N, Napoli F, Allegri AEM et al (2012) Diabetes insipidus—diagnosis and management. Horm Res Paediatr 77:69–84. https://doi.org/10.1159/000336333

    Article  CAS  PubMed  Google Scholar 

  3. Juul KV, Schroeder M, Rittig S, Nørgaard JP (2014) National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients. J Clin Endocrinol Metab 99:2181–2187. https://doi.org/10.1210/jc.2013-4411

    Article  CAS  PubMed  Google Scholar 

  4. Phulwani N, Pandey T, Khatri J, et al (2011) Imaging manifestations and techniques in diabetes insipidus. In: Kamoi K (ed) Diabetes insipidus. InTech

  5. Fenske W, Allolio B (2012) Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review. J Clin Endocrinol Metab 97:3426–3437. https://doi.org/10.1210/jc.2012-1981

    Article  CAS  PubMed  Google Scholar 

  6. Heinbecker P, White HL (1939) The role of the pituitary gland in water balance. Ann Surg 110:1037–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Leroy C, Karrouz W, Douillard C, Do Cao C, Cortet C, Wémeau JL, Vantyghem MC (2013) Diabetes insipidus. Ann Endocrinol 74:496–507. https://doi.org/10.1016/j.ando.2013.10.002

    Article  Google Scholar 

  8. Maghnie M, Cosi G, Genovese E, Manca-Bitti ML, Cohen A, Zecca S, Tinelli C, Gallucci M, Bernasconi S, Boscherini B, Severi F, Aricò M (2000) Central diabetes insipidus in children and young adults. N Engl J Med 343:998–1007. https://doi.org/10.1056/NEJM200010053431403

    Article  CAS  PubMed  Google Scholar 

  9. Capatina C, Paluzzi A, Mitchell R, Karavitaki N (2015) Diabetes insipidus after traumatic brain injury. J Clin Med 4:1448–1462. https://doi.org/10.3390/jcm4071448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Khardori R, Ullal J, Cooperman M, Griffing GT. Diabetes insipidus In: Emedicine 2018 https://emedicine.medscape.com/article/117648-overview#a7 Accessed 28 Feb 2018

  11. Dorton AM (2000) The pituitary gland: embryology, physiology, and pathophysiology. Neonatal Network: J Neonatal Nurs 19:9–17. https://doi.org/10.1891/0730-0832.19.2.9

    Article  CAS  Google Scholar 

  12. Bladowska J, Sokolska V, Czapiga E, Badowski R, Koźmińska U, Moroń K (2004) Advances in diagnostics imaging of the pituitary and the parasellar region. Adv Clin Exp Med 13(2004):709–717

    Google Scholar 

  13. Shin JH, Lee HK, Choi CG, Suh DC, Kim CJ, Hong SK, Na DG (2001) MR imaging of central diabetes insipidus: a pictorial essay. Korean J Radiol 2:222–230. https://doi.org/10.3348/kjr.2001.2.4.222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Elster AD (1993) Modern imaging of the pituitary. Radiology 187:1–14. https://doi.org/10.1148/radiology.187.1.8451394

    Article  CAS  PubMed  Google Scholar 

  15. Elster AD, Sanders TG, Vines FS, Chen MY (1991) Size and shape of the pituitary gland during pregnancy and post partum: measurement with MR imaging. Radiology 181:531–535. https://doi.org/10.1148/radiology.181.2.1924800

    Article  CAS  PubMed  Google Scholar 

  16. Elster AD (1993) Imaging of the sella: anatomy and pathology. Seminars in Ultrasound, CT and MRI 14:182–194. https://doi.org/10.1016/S0887-2171(05)80079-4

    Article  CAS  PubMed  Google Scholar 

  17. Chaudhary V, Bano S (2011) Imaging of the pituitary: recent advances. Indian J Endocrinol Metab 15:216. https://doi.org/10.4103/2230-8210.84871

    Article  Google Scholar 

  18. Maghnie M (1998) Lymphocytic hypophysitis and central diabetes insipidus during adolescence: what are the criteria for diagnosis? Eur J Pediatr 157:A693–A693. https://doi.org/10.1007/PL00008292

    Article  Google Scholar 

  19. Ma L, Gao Y, Cai Y, Li T, Liang Y (1996) MR evaluation of the brain in central diabetes insipidus. Chin Med J 109:724–729

    CAS  PubMed  Google Scholar 

  20. Brooks BS, el Gammal T, Allison JD, Hoffman WH (1989) Frequency and variation of the posterior pituitary bright signal on MR images. AJNR Am J Neuroradiol 10:943–948

    CAS  PubMed  Google Scholar 

  21. Bonneville J-F, Bonneville F, Cattin F (2005) Magnetic resonance imaging of pituitary adenomas. Eur Radiol 15:543–548. https://doi.org/10.1007/s00330-004-2531-x

    Article  PubMed  Google Scholar 

  22. Werny D, Elfers C, Perez FA, Pihoker C, Roth CL (2015) Pediatric central diabetes insipidus: brain malformations are common and few patients have idiopathic disease. J Clin Endocrinol Metab 100:3074–3080. https://doi.org/10.1210/jc.2015-1287

    Article  CAS  PubMed  Google Scholar 

  23. Maghnie M, Aricò M, Villa A, Genovese E, Beluffi G, Severi F (1992) MR of the hypothalamic-pituitary axis in Langerhans cell histiocytosis. AJNR Am J Neuroradiol 13:1365–1371

    CAS  PubMed  Google Scholar 

  24. Erşahin Y, Ozdamar N, Demirtaş E, Mutluer S (1995) A case of Rathke’s cleft cyst presenting with diabetes insipidus. Clin Neurol Neurosurg 97:317–320

    Article  PubMed  Google Scholar 

  25. Kumar M, Dutta D, Jain R, Sen A, Biswas D, Mukhopadhyay M, Ghosh S, Mukhopadhyay S, Chowdhury S, Shivaprasad KS (2013) Diabetes insipidus as a presenting manifestation of Rathke′s cleft cyst. Indian J Endocrinol Metab 17:127. https://doi.org/10.4103/2230-8210.119529

    Article  Google Scholar 

  26. Rao VJ, James RA, Mitra D (2008) Imaging characteristics of common suprasellar lesions with emphasis on MRI findings. Clin Radiol 63:939–947. https://doi.org/10.1016/j.crad.2007.10.003

    Article  CAS  PubMed  Google Scholar 

  27. Ghirardello S, Hopper N, Albanese A, Maghnie M (2006) Diabetes insipidus in craniopharyngioma: postoperative management of water and electrolyte disorders. J Pediatr Endocrinol Metab 19(Suppl 1):413–421

    PubMed  Google Scholar 

  28. Edate S, Albanese A (2015) Management of electrolyte and fluid disorders after brain surgery for pituitary/suprasellar tumours. Horm Res Paediatr 83:293–301. https://doi.org/10.1159/000370065

    Article  CAS  PubMed  Google Scholar 

  29. Saleem SN, Said A-HM, Lee DH (2007) Lesions of the hypothalamus: MR imaging diagnostic features. RadioGraphics 27:1087–1108. https://doi.org/10.1148/rg.274065123

    Article  PubMed  Google Scholar 

  30. Ghanta R, Kongara S, Koti K, Meher G (2011) Surgical excision of hypothalamic hamartoma in a twenty months old boy with precocious puberty. Indian J Endocrinol Metab 15:255. https://doi.org/10.4103/2230-8210.84880

    Article  Google Scholar 

  31. Gan H-W, Bulwer C, Spoudeas H (2000) Pituitary and hypothalamic tumor syndromes in childhood. In: De Groot LJ, Chrousos G, Dungan K et al (eds) Endotext. MDText.com, Inc., South Dartmouth (MA)

    Google Scholar 

  32. Saeki N, Uchida D, Tatsuno I et al (1999) MRI detection of suprasellar germinoma causing central diabetes insipidus. Endocr J 46:263–267

    Article  CAS  PubMed  Google Scholar 

  33. Vyas S, Prabhakar N, Tewari MK, Radotra BD, Khandelwal N (2013) Hypothalamic glioma masquerading as craniopharyngioma. J Neurosci Rural Pract 4:323–325. https://doi.org/10.4103/0976-3147.118790

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lu Z-F, Cheng X-B, Zhao Y-G, Shi B-Z (2013) Twenty-nine cases of resection of suprasellar meningioma through small bone window: an interhemispheric approach. Contemp Oncol (Pozn) 17:525–529. https://doi.org/10.5114/wo.2013.38913

    Article  Google Scholar 

  35. Layden BT, Dubner S, Toft DJ, Kopp P, Grimm S, Molitch ME (2011) Primary CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus. Pituitary 14:194–197. https://doi.org/10.1007/s11102-008-0166-7

    Article  PubMed  PubMed Central  Google Scholar 

  36. Masse SR, Wolk RW, Conklin RH (1973) Peripituitary gland involvement in acute leukemia in adults. Arch Pathol 96:141–142

    CAS  PubMed  Google Scholar 

  37. Ra’anani P, Shpilberg O, Berezin M, Ben-Bassat I (1994) Acute leukemia relapse presenting as central diabetes insipidus. Cancer 73:2312–2316

    Article  PubMed  Google Scholar 

  38. Guermazi A, Feger C, Rousselot P, Merad M, Benchaib N, Bourrier P, Mariette X, Frija J, Kerviler E (2002) Granulocytic sarcoma (chloroma): imaging findings in adults and children. AJR Am J Roentgenol 178:319–325. https://doi.org/10.2214/ajr.178.2.1780319

    Article  CAS  PubMed  Google Scholar 

  39. Chiloiro S, Giampietro A, Bianchi A, De Marinis L (2016) Clinical management of teratoma, a rare hypothalamic-pituitary neoplasia. Endocrine 53:636–642. https://doi.org/10.1007/s12020-015-0814-4

    Article  CAS  PubMed  Google Scholar 

  40. Kim YS, Kang SG, Kim YO (2010) Pituitary teratoma presenting as central diabetes insipidus with a normal MRI finding. Yonsei Med J 51:293–294. https://doi.org/10.3349/ymj.2010.51.2.293

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bladowska J, Ssiadek M (2012) Diagnostic imaging of the pituitary and parasellar region. In: Rahimi-Movaghar V (ed) Pituitary adenomas. InTech

  42. Wu X, Mao J, Nie M, Zhang JL, Lu SH (2011) Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: clinical presentations, diagnosis, and management. J Postgrad Med 57:302. https://doi.org/10.4103/0022-3859.90080

    Article  PubMed  Google Scholar 

  43. Szuwart U, König HJ, Bennefeld H, Weritz C, Kleinhans G (1988) Clinical aspects of hypophyseal metastases. Onkologie 11:66–69. https://doi.org/10.1159/000216489

    Article  CAS  PubMed  Google Scholar 

  44. Huinink DT, Veltman GA, Huizinga TW et al (2000) Diabetes insipidus in metastatic cancer: two case reports with review of the literature. Ann Oncol 11:891–895

    Article  CAS  PubMed  Google Scholar 

  45. Schreckinger M, Szerlip N, Mittal S (2013) Diabetes insipidus following resection of pituitary tumors. Clin Neurol Neurosurg 115:121–126. https://doi.org/10.1016/j.clineuro.2012.08.009

    Article  PubMed  Google Scholar 

  46. Hensen J, Henig A, Fahlbusch R, Meyer M, Boehnert M, Buchfelder M (1999) Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol 50:431–439

    Article  CAS  Google Scholar 

  47. Lipsett MB, Maclean JP, West CD et al (1956) An analysis of the polyuria induced by hypophysectomy in man. J Clin Endocrinol Metab 16:183–195. https://doi.org/10.1210/jcem-16-2-183

    Article  CAS  PubMed  Google Scholar 

  48. Shah S, Har-El G (2001) Diabetes insipidus after pituitary surgery: incidence after traditional versus endoscopic transsphenoidal approaches. Am J Rhinol 15:377–379

    Article  CAS  PubMed  Google Scholar 

  49. Sigounas DG, Sharpless JL, Cheng DML, Johnson TG, Senior BA, Ewend MG (2008) Predictors and incidence of central diabetes insipidus after endoscopic pituitary surgery. Neurosurgery 62:71–78; discussion 78-79. https://doi.org/10.1227/01.NEU.0000311063.10745.D8

    Article  PubMed  Google Scholar 

  50. Nemergut EC, Zuo Z, Jane JA, Laws ER (2005) Predictors of diabetes insipidus after transsphenoidal surgery: a review of 881 patients. J Neurosurg 103:448–454. https://doi.org/10.3171/jns.2005.103.3.0448

    Article  PubMed  Google Scholar 

  51. Boughey JC, Yost MJ, Bynoe RP (2004) Diabetes insipidus in the head-injured patient. Am Surg 70:500–503

    PubMed  Google Scholar 

  52. Maiya B, Newcombe V, Nortje J, Bradley P, Bernard F, Chatfield D, Outtrim J, Hutchinson P, Matta B, Antoun N, Menon D (2008) Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury. Intensive Care Med 34:468–475. https://doi.org/10.1007/s00134-007-0902-x

    Article  PubMed  Google Scholar 

  53. Wake DJ, Jadhav V, Whittome LR, Campbell IW (2005) Wolfram syndrome: DIDMOAD. Br J Diabetes Vasc Dis 5:236–237. https://doi.org/10.1177/14746514050050040901

    Article  Google Scholar 

  54. Johnston PC, Chew LS, Hamrahian AH, Kennedy L (2015) Lymphocytic infundibulo-neurohypophysitis: a clinical overview. Endocrine 50:531–536. https://doi.org/10.1007/s12020-015-0707-6

    Article  CAS  PubMed  Google Scholar 

  55. Koshiyama H, Sato H, Yorita S et al (1994) Lymphocytic hypophysitis presenting with diabetes insipidus: case report and literature review. Endocr J 41:93–97

    Article  CAS  PubMed  Google Scholar 

  56. Angelousi A, Chatzellis E, Kaltsas G (2018) New molecular, biological, and immunological agents inducing hypophysitis. Neuroendocrinology 106:89–100. https://doi.org/10.1159/000480086

    Article  CAS  PubMed  Google Scholar 

  57. Caturegli P, Di Dalmazi G, Lombardi M et al (2016) Hypophysitis secondary to cytotoxic T-lymphocyte-associated protein 4 blockade: insights into pathogenesis from an autopsy series. Am J Pathol 186:3225–3235. https://doi.org/10.1016/j.ajpath.2016.08.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Carpenter KJ, Murtagh RD, Lilienfeld H, Weber J, Murtagh FR (2009) Ipilimumab-induced hypophysitis: MR imaging findings. Am J Neuroradiol 30:1751–1753. https://doi.org/10.3174/ajnr.A1623

    Article  CAS  PubMed  Google Scholar 

  59. Stern BJ, Krumholz A, Johns C, Scott P, Nissim J (1985) Sarcoidosis and its neurological manifestations. Arch Neurol 42:909–917

    Article  CAS  PubMed  Google Scholar 

  60. Smith JK, Matheus MG, Castillo M (2004) Imaging manifestations of neurosarcoidosis. Am J Roentgenol 182:289–295. https://doi.org/10.2214/ajr.182.2.1820289

    Article  Google Scholar 

  61. Urbach H, Kristof R, Zentner J, Brechtelsbauer D, Solymosi L, Wolf HK (1997) Sarcoidosis presenting as an intra- or extra-axial cranial mass: report of two cases. Neuroradiology 39:516–519

    Article  CAS  PubMed  Google Scholar 

  62. Ginat DT, Dhillon G, Almast J (2011) Magnetic resonance imaging of neurosarcoidosis. J Clin Imaging Sci 1:15. https://doi.org/10.4103/2156-7514.76693

    Article  PubMed  PubMed Central  Google Scholar 

  63. Cunnington JR, Jois R, Zammit I, Scott D, Isaacs J (2009) Diabetes insipidus as a complication of Wegener’s granulomatosis and its treatment with biologic agents. Int J Rheumatol 2009:1–4. https://doi.org/10.1155/2009/346136

    Article  Google Scholar 

  64. Ghirardello S, Garrè M-L, Rossi A, Maghnie M (2007) The diagnosis of children with central diabetes insipidus. J Pediatr Endocrinol Metab 20:359–375

    Article  PubMed  Google Scholar 

  65. Marchand I, Barkaoui MA, Garel C, Polak M, Donadieu J, for the Writing Committee (2011) Central diabetes insipidus as the inaugural manifestation of Langerhans cell histiocytosis: natural history and medical evaluation of 26 children and adolescents. J Clin Endocrinol Metab 96:E1352–E1360 . doi: https://doi.org/10.1210/jc.2011-0513

    Article  CAS  Google Scholar 

  66. Patel R, Mustafa W, Sheaff MT, Khan S (2016) IgG4-related hypophysitis presenting as diabetes insipidus with tubulo-interstital nephritis and mediastinal lymphadenopathy. Endocrinol Diabetes Metabol Case Reports. https://doi.org/10.1530/EDM-16-0024

  67. Harano Y, Honda K, Akiyama Y, Kotajima L, Arioka H (2015) A case of IgG4-related hypophysitis presented with hypopituitarism and diabetes insipidus. Clin Med Insights Case Rep 8:23–26. https://doi.org/10.4137/CCRep.S15352

    Article  PubMed  PubMed Central  Google Scholar 

  68. Franco-Paredes C (2001) Diabetes insipidus due to Streptococcus pneumoniae meningitis. Arch Intern Med 161:1114–1115. https://doi.org/10.1001/archinte.161.8.1114

    Article  CAS  PubMed  Google Scholar 

  69. Greger NG, Kirkland RT, Clayton GW, Kirkland JL (1986) Central diabetes insipidus. 22 years’ experience. Am J Dis Child 140:551–554

    Article  CAS  PubMed  Google Scholar 

  70. Domiciano DS, de Carvalho JF, Macedo AR, Laurindo IMM (2010) Central diabetes insipidus induced by tuberculosis in a rheumatoid arthritis patient. Acta Reumatol Port 35:232–235

    PubMed  Google Scholar 

  71. Lee YJ, Huang FY, Shen EY et al (1996) Neurogenic diabetes insipidus in children with hypoxic encephalopathy: six new cases and a review of the literature. Eur J Pediatr 155:245–248

    Article  CAS  PubMed  Google Scholar 

  72. White ML, Zhang Y, Helvey JT, Omojola MF (2013) Anatomical patterns and correlated MRI findings of non-perinatal hypoxic–ischaemic encephalopathy. Br J Radiol 86:20120464–20120464. https://doi.org/10.1259/bjr.20120464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Masri-Iraqi H, Hirsch D, Herzberg D, Lifshitz A, Tsvetov G, Benbassat C, Shimon I (2017) Central diabetes insipidus: clinical characteristics and long-term course in a large cohort of adults. Endocr Pract 23:600–604. https://doi.org/10.4158/EP161555.OR

    Article  PubMed  Google Scholar 

  74. Di Iorgi N, Allegri AEM, Napoli F et al (2014) Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab 99:1264–1272. https://doi.org/10.1210/jc.2013-3724

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. C. Adams.

Ethics declarations

Funding

No funding was received for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Additional information

Key points

• Central or neurogenic diabetes insipidus (CDI) occurs when there is a defect in one of more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei of the hypothalamus, median eminence of the hypothalamus, infundibulum or the posterior pituitary gland resulting in deficient synthesis or secretion of antidiuretic hormone (ADH).

• A focussed pituitary MRI pituitary gland and sella protocol is essential in all patients without a clear aetiology.

• Common causes found on MRI include neurosurgery, head trauma, craniopharyngioma, germinoma, langerhans cell histiocytosis and congenital structural abnormalities.

• In patients over 50 years with acute onset of CDI, pituitary metastases should be considered and appropriate investigations including chest radiograph should be performed.

• There are several neuroimaging correlates and causes of CDI, illustrated in this review.

• A cause for CDI cannot be established in 12.2% of paediatric and 30% of adult cases despite biochemical and radiological evaluation

• When initial imaging is normal, serial follow-up imaging should be performed before a diagnosis of idiopathic CDI can be made. Current literature suggests at least a follow-up MRI after 6 months and a duration of follow-up of 3 years. Larger studies are required to inform evidence-based guidelines for follow-up of CDI.

• The aim of the pictorial review is to illustrate the wide variety of causes of CDI on neuroimaging, highlight the optimal MRI protocol and to revise the detailed neuroanatomy and neurophysiology required to interpret these studies.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adams, N.C., Farrell, T.P., O’Shea, A. et al. Neuroimaging of central diabetes insipidus—when, how and findings. Neuroradiology 60, 995–1012 (2018). https://doi.org/10.1007/s00234-018-2072-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00234-018-2072-7

Keywords

Navigation