Description of technique and lower reference limit for magnetic resonance imaging of hippocampal volumetry in dogs

Marjorie E. Milne Department of Radiology, University of Melbourne, Werribee, VIC 3030, Australia.

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Garry A. Anderson University of Melbourne Veterinary Hospital, Faculty of Veterinary Science, University of Melbourne, Werribee, VIC 3030, Australia.

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Kathleen E. Chow Department of Radiology, University of Melbourne, Werribee, VIC 3030, Australia.

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Terrence J. O'Brien Department of Medicine, The Royal Melbourne Hospital, Faculty of Medicine, University of Melbourne, Parkville, VIC 3050, Australia.

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Bradford A. Moffat Department of Radiology, The Royal Melbourne Hospital, Faculty of Medicine, University of Melbourne, Parkville, VIC 3050, Australia.

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Sam N. Long Department of Neurology and Neurosurgery, University of Melbourne, Werribee, VIC 3030, Australia.

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Abstract

Objective—To evaluate the use of high-resolution MRI for hippocampal volumetry in dogs and to define a lower reference limit for hippocampal formation (HF) volume.

Animals—20 dogs (with no history of seizures and no underlying structural brain disease) that underwent MRI of the brain.

Procedures—The MRI protocol included a high-resolution T1-weighted 3-D ultrafast gradient-echo sequence aligned in a dorsal plane perpendicular to the long axis of the HF. Images obtained with MRI were retrospectively analyzed by 2 observers (A and B). Intraobserver and interobserver agreement were calculated with the Lin concordance correlation coefficient. Volume measurements of the HF were adjusted for intracranial volume, and a lower 95% reference limit for adjusted HF volume was calculated.

Results—There was substantial intraobserver agreement (Lin concordance correlation coefficient, 0.97 [95% confidence interval {CI}, 0.94 to 0.99]) but poor interobserver agreement (Lin concordance correlation coefficient, 0.63 [95% CI, 0.37 to 0.79]). The lower 95% reference limit for adjusted HF volume was 0.56 cm3 (90% CI, 0.52 to 0.60 cm3) for the right HF and 0.55 cm3 (90% CI, 0.52 to 0.58 cm3) for the left HF.

Conclusions and Clinical Relevance—HF volumes should be adjusted for intracranial volume to account for the large variation in canine skull size. The amount of time required to perform HF volumetry and low interobserver agreement may restrict this technique to research applications, such as the investigation of epileptic patients for hippocampal sclerosis or other cognitive disorders.

Abstract

Objective—To evaluate the use of high-resolution MRI for hippocampal volumetry in dogs and to define a lower reference limit for hippocampal formation (HF) volume.

Animals—20 dogs (with no history of seizures and no underlying structural brain disease) that underwent MRI of the brain.

Procedures—The MRI protocol included a high-resolution T1-weighted 3-D ultrafast gradient-echo sequence aligned in a dorsal plane perpendicular to the long axis of the HF. Images obtained with MRI were retrospectively analyzed by 2 observers (A and B). Intraobserver and interobserver agreement were calculated with the Lin concordance correlation coefficient. Volume measurements of the HF were adjusted for intracranial volume, and a lower 95% reference limit for adjusted HF volume was calculated.

Results—There was substantial intraobserver agreement (Lin concordance correlation coefficient, 0.97 [95% confidence interval {CI}, 0.94 to 0.99]) but poor interobserver agreement (Lin concordance correlation coefficient, 0.63 [95% CI, 0.37 to 0.79]). The lower 95% reference limit for adjusted HF volume was 0.56 cm3 (90% CI, 0.52 to 0.60 cm3) for the right HF and 0.55 cm3 (90% CI, 0.52 to 0.58 cm3) for the left HF.

Conclusions and Clinical Relevance—HF volumes should be adjusted for intracranial volume to account for the large variation in canine skull size. The amount of time required to perform HF volumetry and low interobserver agreement may restrict this technique to research applications, such as the investigation of epileptic patients for hippocampal sclerosis or other cognitive disorders.

Contributor Notes

Presented at the 2012 American College of Veterinary Internal Medicine Forum, New Orleans, June 2012.

Address correspondence to Dr. Milne (mmil@unimelb.edu.au).
  • 1. Van Hoesen GW. Anatomy of the medial temporal lobe. Magn Reson Imaging 1995; 13: 10471055.

  • 2. Apostolova LG, Hwang KS, Medina LD, et al. Cortical and hippocampal atrophy in patients with autosomal dominant familial Alzheimer's disease. Dement Geriatr Cogn Disord 2011; 32: 118125.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Dawe RJ, Bennett DA, Schneider JA, et al. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. PLoS One 2011; 6:e26286.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Radonic E, Rados M, Kalember P, et al. Comparison of hippocampal volumes in schizophrenia, schizoaffective and bipolar disorder. Coll Antropol 2011; 35 (suppl 1), 249252.

    • Search Google Scholar
    • Export Citation
  • 5. Cole J, Costafreda SG, McGuffin P, et al. Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord 2011; 134: 483487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Anderson VM, Fisniku LK, Khaleeli Z, et al. Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler 2010; 16: 10831090.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Margerison JH, Corsellis JA. Epilepsy and the temporal lobes. A clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain 1966; 89: 499530.

    • Search Google Scholar
    • Export Citation
  • 8. Ashtari M, Barr WB, Schaul N, et al. Three-dimensional fast low-angle shot imaging and computerized volume measurement of the hippocampus in patients with chronic epilepsy of the temporal lobe. AJNR Am J Neuroradiol 1991; 12: 941947.

    • Search Google Scholar
    • Export Citation
  • 9. Blumcke I, Pauli E, Clusmann H, et al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 2007; 113: 235244.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Blumcke I, Thom M, Wiestler OD. Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 2002; 12: 199211.

    • Search Google Scholar
    • Export Citation
  • 11. Blumcke I. Neuropathology of focal epilepsies: a critical review. Epilepsy Behav 2009; 15: 3439.

  • 12. Lee DH, Gao FQ, Rogers JM, et al. MR in temporal lobe epilepsy: analysis with pathologic confirmation. AJNR Am J Neuroradiol 1998; 19: 1927.

    • Search Google Scholar
    • Export Citation
  • 13. Jack CR Jr, Theodore WH, Cook M, et al. MRI-based hippocampal volumetrics: data acquisition, normal ranges, and optimal protocol. Magn Reson Imaging 1995; 13: 10571064.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Jackson GD. The diagnosis of hippocampal sclerosis: other techniques. Magn Reson Imaging 1995; 13: 10811093.

  • 15. Cascino GD. Clinical correlations with hippocampal atrophy. Magn Reson Imaging 1995; 13: 11331136.

  • 16. Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001; 345: 311318.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Zimmermann R, Hulsmeyer VI, Sauter-Louis C, et al. Status epilepticus and epileptic seizures in dogs. J Vet Intern Med 2009; 23: 970976.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Pakozdy A, Leschnik M, Tichy AG, et al. Retrospective clinical comparison of idiopathic versus symptomatic epilepsy in 240 dogs with seizures. Acta Vet Hung 2008; 56: 471483.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Podell M, Fenner WR, Powers JD. Seizure classification in dogs from a nonreferral-based population. J Am Vet Med Assoc 1995; 206: 17211728.

    • Search Google Scholar
    • Export Citation
  • 20. Thomas WB. Idiopathic epilepsy in dogs and cats. Vet Clin North Am Small Anim Pract 2010; 40: 161179.

  • 21. Schwartz-Porsche D, Loscher W, Frey HH. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J Vet Pharmacol Ther 1985; 8: 113119.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Podell M, Fenner WR. Bromide therapy in refractory canine idiopathic epilepsy. J Vet Intern Med 1993; 7: 318327.

  • 23. Montgomery DL, Lee AC. Brain damage in the epileptic Beagle dog. Vet Pathol 1983; 20: 160169.

  • 24. Morita T, Shimada A, Ohama E, et al. Oligodendroglial vacuolar degeneration in the bilateral motor cortices and astrocytosis in epileptic Beagle dogs. J Vet Med Sci 1999; 61: 107111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Breitschwerdt EB, Breazile JE, Broadhurst JJ. Clinical and electroencephalographic findings associated with ten cases of suspected limbic epilepsy in the dog. J Am Anim Hosp Assoc 1979; 15: 3750.

    • Search Google Scholar
    • Export Citation
  • 26. Yamasaki H, Furuoka H, Takechi M, et al. Neuronal loss and gliosis in limbic system in an epileptic dog. Vet Pathol 1991; 28: 540542.

  • 27. Buckmaster PS, Smith MO, Buckmaster CL, et al. Absence of temporal lobe epilepsy pathology in dogs with medically intractable epilepsy. J Vet Intern Med 2002; 16: 9599.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Kuwabara T, Hasegawa D, Kobayashi M, et al. Clinical magnetic resonance volumetry of the hippocampus in 58 epileptic dogs. Vet Radiol Ultrasound 2010; 51: 485490.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Vullo T, Deo-Narine V, Stallmeyer MJ, et al. Quantitation of normal canine hippocampus formation volume: correlation of MRI with gross histology. Magn Reson Imaging 1996; 14: 657662.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Jung MA, Nahm SS, Lee MS, et al. Canine hippocampal formation composited into three-dimensional structure using MPRAGE. J Vet Med Sci 2010; 72: 853860.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Jeukens CR, Vlooswijk MC, Majoie HJ, et al. Hippocampal MRI volumetry at 3 Tesla: reliability and practical guidance. Invest Radiol 2009; 44: 509517.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Malykhin NV, Bouchard TP, Ogilvie CJ, et al. Three-dimensional volumetric analysis and reconstruction of amygdala and hippocampal head, body and tail. Psychiatry Res 2007; 155: 155165.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Beitz AJ, Fletcher TF. Chapter 18—the brain. In: Evans H, ed. Miller's anatomy of the dog. Philadelphia: Saunders, 1993;894952.

    • Search Google Scholar
    • Export Citation
  • 34. Adrianov OS, Domino KE, Domino EF, eds. Atlas of the canine brain. Arlington, Mass: NPP Books, 2010.

  • 35. Welker W, Johnson JI, Noe A. Comparative mammalian brain collections. 1999. Available at: www.brainmuseum.org/Specimens/carnivora/basenji/sections/cellthumbnail.html. Accessed Jun 1, 2011.

    • Search Google Scholar
    • Export Citation
  • 36. Fletcher TF. Canine brain transections (twenty transverse sections). Available at: vanat.cvm.umn.edu/brainsect/. Accessed Jun 1, 2011.

    • Search Google Scholar
    • Export Citation
  • 37. Jack CR Jr, Twomey CK, Zinsmeister AR, et al. Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology 1989; 172: 549554.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989; 45: 255268.

  • 39. Lin LI. A note on the concordance correlation coefficient. Biometrics 2000; 56: 324325.

  • 40. McBride GB. A proposal for strength-of-agreement criteria for Lin's concordance correlation coefficient. Hamilton, New Zealand: National Institute of Water & Atmospheric Research, 2005.

    • Search Google Scholar
    • Export Citation
  • 41. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 327: 307310.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Horowitz GL, Altaie S, Boyd JC, et al. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline. Clinical Laboratory Standards Institute document C28-A3. 3rd ed. Wayne, Pa: Clinical and Laboratory Standards Institute, 2008.

    • Search Google Scholar
    • Export Citation
  • 43. Cheon JE, Chang KH, Kim HD, et al. MR of hippocampal sclerosis: comparison of qualitative and quantitative assessments. AJNR Am J Neuroradiol 1998; 19: 465468.

    • Search Google Scholar
    • Export Citation
  • 44. Free SL, Bergin PS, Fish DR, et al. Methods for normalization of hippocampal volumes measured with MR. AJNR Am J Neuroradiol 1995; 16: 637643.

    • Search Google Scholar
    • Export Citation
  • 45. Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed. Mol Psychiatry 2005; 10: 147159.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46. Hammers A, Heckemann R, Koepp MJ, et al. Automatic detection and quantification of hippocampal atrophy on MRI in temporal lobe epilepsy: a proof-of-principle study. Neuroimage 2007; 36: 3847.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47. Hogan RE, Mark KE, Wang L, et al. Mesial temporal sclerosis and temporal lobe epilepsy: MR imaging deformation-based segmentation of the hippocampus in five patients. Radiology 2000; 216: 291297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48. Jack CR Jr, Bentley MD, Twomey CK, et al. MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe: validation studies. Radiology 1990; 176: 205209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49. Scorzin JE, Kaaden S, Quesada CM, et al. Volume determination of amygdala and hippocampus at 1.5 and 3.0T MRI in temporal lobe epilepsy. Epilepsy Res 2008; 82: 2937.

    • Crossref
    • Search Google Scholar
    • Export Citation

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