title: Histology-derived volumetric annotation of the human hippocampal subfields in postmortem MRI.
abstract: Recently, there has been a growing effort to analyze the morphometry of hippocampal subfields using both in vivo and postmortem magnetic resonance imaging (MRI). However, given that boundaries between subregions of the hippocampal formation (HF) are conventionally defined on the basis of microscopic features that often lack discernible signature in MRI, subfield delineation in MRI literature has largely relied on heuristic geometric rules, the validity of which with respect to the underlying anatomy is largely unknown. The development and evaluation of such rules are challenged by the limited availability of data linking MRI appearance to microscopic hippocampal anatomy, particularly in three dimensions (3D). The present paper, for the first time, demonstrates the feasibility of labeling hippocampal subfields in a high resolution volumetric MRI dataset based directly on microscopic features extracted from histology. It uses a combination of computational techniques and manual post-processing to map subfield boundaries from a stack of histology images (obtained with 200μm spacing and 5μm slice thickness; stained using the Kluver-Barrera method) onto a postmortem 9.4Tesla MRI scan of the intact, whole hippocampal formation acquired with 160μm isotropic resolution. The histology reconstruction procedure consists of sequential application of a graph-theoretic slice stacking algorithm that mitigates the effects of distorted slices, followed by iterative affine and diffeomorphic co-registration to postmortem MRI scans of approximately 1cm-thick tissue sub-blocks acquired with 200μm isotropic resolution. These 1cm blocks are subsequently co-registered to the MRI of the whole HF. Reconstruction accuracy is evaluated as the average displacement error between boundaries manually delineated in both the histology and MRI following the sequential stages of reconstruction. The methods presented and evaluated in this single-subject study can potentially be applied to multiple hippocampal tissue samples in order to construct a histologically informed MRI atlas of the hippocampal formation.
authors.affiliation: Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, 3600 Market Street, Suite 370, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, USA. Electronic address: danadler@seas.upenn.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Adler
authors.forename: John
authors.initials: J
authors.lastname: Pluta
authors.forename: Salmon
authors.initials: S
authors.lastname: Kadivar
authors.forename: Caryne
authors.initials: C
authors.lastname: Craige
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.forename: Brian B
authors.initials: BB
authors.lastname: Avants
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yushkevich
mesh_terms: D000369:Aged, 80 and over; D000465:Algorithms; D001344:Autopsy / Q000379:methods*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011180:Postmortem Changes; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: Hippocampus; Histology; MRI; Postmortem; Reconstruction; Subfields
references.citation: AJNR Am J Neuroradiol. 2002 Sep;23(8):1313-21
references.pmid: 12223371
references.citation: Inf Process Med Imaging. 2009;21:350-61
references.pmid: 19694276
references.citation: J Neurosurg. 2009 Feb;110(2):208-19
references.pmid: 18976051
references.citation: Neuroimage. 2004 Apr;21(4):1585-95
references.pmid: 15050582
references.citation: J Comp Neurol. 1997 Mar 24;379(4):482-94
references.pmid: 9067838
references.citation: Front Hum Neurosci. 2010 May 28;4:43
references.pmid: 20577633
references.citation: IEEE Trans Inf Technol Biomed. 2003 Dec;7(4):394-403
references.pmid: 15000365
references.citation: Nat Rev Neurosci. 2008 Mar;9(3):182-94
references.pmid: 18270514
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4034-9
references.pmid: 10097158
references.citation: Neuroimage. 2012 Sep;62(3):2065-82
references.pmid: 22677150
references.citation: Neuroimage. 2003 Oct;20(2):667-82
references.pmid: 14568443
references.citation: Front Hum Neurosci. 2012 Oct 18;6:290
references.pmid: 23087638
references.citation: J Biomech. 2010 Aug 10;43(11):2087-92
references.pmid: 20444453
references.citation: Neuroinformatics. 2011 Dec;9(4):381-400
references.pmid: 21373993
references.citation: Magn Reson Med. 2005 Aug;54(2):324-32
references.pmid: 16032673
references.citation: J Comp Neurol. 1990 Jun 1;296(1):1-22
references.pmid: 2358525
references.citation: Nat Rev Neurosci. 2011 Sep 07;12(10):585-601
references.pmid: 21897434
references.citation: Magn Reson Imaging. 2011 Jun;29(5):683-92
references.pmid: 21546191
references.citation: Neuroimage. 2007 Jan 15;34(2):618-38
references.pmid: 17110133
references.citation: Hippocampus. 2009 Jun;19(6):558-64
references.pmid: 19405132
references.citation: Acta Neuropathol. 1991;82(4):239-59
references.pmid: 1759558
references.citation: J Neurosci Methods. 2008 May 30;170(2):332-44
references.pmid: 18321589
references.citation: Mol Psychiatry. 2005 Feb;10(2):160-84
references.pmid: 15356639
references.citation: Nature. 2007 Jan 11;445(7124):168-76
references.pmid: 17151600
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: J Magn Reson Imaging. 2008 Nov;28(5):1266-72
references.pmid: 18972336
references.citation: Mol Imaging. 2006 Jan-Mar;5(1):16-23
references.pmid: 16779966
references.citation: Med Image Anal. 1997 Sep;1(4):379-98
references.pmid: 9873917
references.citation: Neuroimage. 2012 Jul 16;61(4):1043-9
references.pmid: 22440643
references.citation: Anat Embryol (Berl). 2005 Dec;210(5-6):343-52
references.pmid: 16208455
references.citation: Neuroimage. 2010 Jul 1;51(3):1037-46
references.pmid: 20226256
references.citation: Nat Rev Neurosci. 2011 Dec 20;13(1):70
references.pmid: 22183437
references.citation: J Neurosci. 2009 Aug 26;29(34):10512-9
references.pmid: 19710304
references.citation: Neuroimage. 1999 Nov;10(5):489-99
references.pmid: 10547327
references.citation: Neuroimage. 2007 Aug 15;37(2):530-8
references.pmid: 17604650
references.citation: Annu Rev Neurosci. 1993;16:547-63
references.pmid: 8460903
references.citation: Neuroimage. 2009 Aug 1;47(1):8-17
references.pmid: 19376238
references.citation: J Neurosci Methods. 1998 Oct 1;84(1-2):77-86
references.pmid: 9821637
references.citation: J Neurosci Methods. 2007 Aug 15;164(1):191-204
references.pmid: 17560659
references.citation: AJNR Am J Neuroradiol. 2011 Oct;32(9):1658-61
references.pmid: 21835940
references.citation: Brain Res Rev. 2009 Dec 11;62(1):1-18
references.pmid: 19744521
references.citation: Alzheimers Dement. 2011 Jul;7(4):474-485.e4
references.pmid: 21784356
references.citation: Arch Neurol. 2001 Sep;58(9):1395-402
references.pmid: 11559310
references.citation: Neuroimage. 2004 Sep;23(1):111-27
references.pmid: 15325358
references.citation: Neuron. 2002 Aug 15;35(4):625-41
references.pmid: 12194864
references.citation: Neuroimage. 2010 Feb 1;49(3):2053-62
references.pmid: 19853042
references.citation: Neuroimage. 2009 Aug 1;47(1):42-9
references.pmid: 19303448
references.citation: Clin Anat. 2005 Mar;18(2):88-91
references.pmid: 15696533
references.citation: Brain Res Rev. 2009 May;60(2):349-67
references.pmid: 19248810
references.citation: Neuroimage. 2006 Apr 1;30(2):359-76
references.pmid: 16406816
references.citation: Phys Med Biol. 2009 Dec 21;54(24):7315-27
references.pmid: 19926915
references.citation: J Neurosci Methods. 2006 Sep 30;156(1-2):84-100
references.pmid: 16580732
references.citation: Acta Neuropathol. 2006 Oct;112(4):389-404
references.pmid: 16906426
references.citation: Brain Res. 1998 Sep 14;805(1-2):267-9
references.pmid: 9733982
references.citation: Front Aging Neurosci. 2011 Feb 04;3:2
references.pmid: 21331174
references.citation: Neurobiol Aging. 2009 Nov;30(11):1711-23
references.pmid: 18346820
references.citation: J Alzheimers Dis. 2012;31(1):85-99
references.pmid: 22504319
references.citation: Hippocampus. 2001;11(5):551-68
references.pmid: 11732708
references.citation: AJNR Am J Neuroradiol. 2007 May;28(5):958-64
references.pmid: 17494678
references.citation: Med Image Anal. 2006 Jun;10(3):465-83
references.pmid: 15963755
references.citation: Ann Biomed Eng. 2005 Aug;33(8):1100-12
references.pmid: 16133918
references.citation: Comput Med Imaging Graph. 2005 Sep;29(6):405-17
references.pmid: 16006097
references.citation: IEEE Trans Med Imaging. 2003 Nov;22(11):1480-9
references.pmid: 14606681
references.citation: Magn Reson Med. 2009 Apr;61(4):810-8
references.pmid: 19189294
references.citation: Neuroimage. 2010 Dec;53(4):1208-24
references.pmid: 20600984
references.citation: Neuroimage. 2011 Oct 15;58(4):1121-30
references.pmid: 21763431
references.citation: Philos Trans R Soc Lond B Biol Sci. 1997 Oct 29;352(1360):1469-74
references.pmid: 9368935
references.citation: Neuron. 2011 Dec 22;72(6):931-7
references.pmid: 22196329
references.citation: Science. 2013 Jun 21;340(6139):1472-5
references.pmid: 23788795
references.citation: Neuroimage. 2010 Jul 1;51(3):1242-52
references.pmid: 20338246
references.citation: Neuroimage. 2013 Jul 1;74:254-65
references.pmid: 23415948
references.citation: J Neurosci. 1996 Jul 15;16(14):4491-500
references.pmid: 8699259
references.citation: Magn Reson Imaging. 2009 Apr;27(3):401-16
references.pmid: 18786794
references.citation: Med Image Anal. 2008 Feb;12(1):26-41
references.pmid: 17659998
references.citation: J Anat. 2004 Feb;204(2):93-102
references.pmid: 15032916
references.citation: Neurobiol Aging. 2007 May;28(5):719-26
references.pmid: 16713659
references.citation: Neuroimage. 2010 Jan 15;49(2):1224-30
references.pmid: 19786104
references.citation: J Anat. 1999 Jul;195 ( Pt 1):131-5
references.pmid: 10473300
references.citation: Cereb Cortex. 1998 Dec;8(8):710-8
references.pmid: 9863698
references.citation: Brain. 2006 Nov;129(Pt 11):2867-73
references.pmid: 17018552
references.citation: Lancet. 1994 Sep 17;344(8925):769-72
references.pmid: 7916070
references.citation: Hippocampus. 2009 Jun;19(6):549-57
references.pmid: 19405131
references.citation: Neuroimage. 2009 Jan 15;44(2):385-98
references.pmid: 18840532
references.citation: Phys Med Biol. 2010 Oct 21;55(20):6215-42
references.pmid: 20885021
references.citation: Neuroimage. 2009 Mar 1;45(1):52-9
references.pmid: 19059346
references.citation: Brain Res Bull. 1997;43(2):141-8
references.pmid: 9222526
references.citation: Alzheimers Dement. 2011 Mar;7(2):171-4
references.pmid: 21414554
references.citation: Comput Med Imaging Graph. 2011 Oct-Dec;35(7-8):568-78
references.pmid: 21255974
references.citation: Comput Med Imaging Graph. 1997 Mar-Apr;21(2):131-41
references.pmid: 9152579
references.citation: Neuroimage. 2006 Jul 1;31(3):1116-28
references.pmid: 16545965
references.citation: IEEE Trans Med Imaging. 1995;14(1):25-35
references.pmid: 18215807
references.citation: Med Image Comput Comput Assist Interv. 2011;14(Pt 2):582-9
references.pmid: 21995076
references.citation: Radiology. 2011 Oct;261(1):199-209
references.pmid: 21746814
references.citation: Nat Neurosci. 2001 Apr;4(4):442-9
references.pmid: 11276237
references.citation: Acad Radiol. 2008 Aug;15(8):1027-39
references.pmid: 18620123
references.citation: Front Hum Neurosci. 2010 May 28;4:42
references.pmid: 20577631
references.citation: Annu Rev Neurosci. 2004;27:279-306
references.pmid: 15217334
references.citation: J Neurosci Methods. 2003 Mar 30;124(1):93-102
references.pmid: 12648768
references.citation: Science. 2007 Feb 16;315(5814):961-6
references.pmid: 17303747
references.citation: AJNR Am J Neuroradiol. 2009 Jun;30(6):1134-41
references.pmid: 19357387
references.citation: J Alzheimers Dis. 2011;26 Suppl 3:61-75
references.pmid: 21971451
references.citation: Science. 2008 Mar 21;319(5870):1640-2
references.pmid: 18356518
references.citation: Hum Brain Mapp. 2007 Oct;28(10):959-66
references.pmid: 17133381
references.citation: Neuroimage. 2000 Jun;11(6 Pt 1):668-83
references.pmid: 10860795
references.citation: Acta Radiol. 1999 Nov;40(6):593-7
references.pmid: 10598845
references.citation: Brain. 1999 Jan;122 ( Pt 1):47-59
references.pmid: 10050894
references.citation: J Neuropathol Exp Neurol. 1953 Oct;12(4):400-3
references.pmid: 13097193
references.citation: Neuroimage. 2010 Nov 1;53(2):506-14
references.pmid: 20600996