In Vivo Morphological Features of Human Lumbar Discs
`
`Weiye Zhong, MD, Sean J. Driscoll, MEng, Minfei Wu, MD, Shaobai Wang, PhD, Zhan Liu,
`PhD, Thomas D. Cha, MD, MBA, Kirkham B. Wood, MD, and Guoan Li, PhD
`
`Abstract: Recent biomechanics studies have revealed distinct kin-
`ematic behavior of different lumbar segments. The mechanisms behind
`these segment-specific biomechanical features are unknown. This study
`investigated the in vivo geometric characteristics of human lumbar
`intervertebral discs.
`Magnetic resonance images of the lumbar spine of 41 young Chinese
`individuals were acquired. Disc geometry in the sagittal plane was
`measured for each subject, including the dimensions of the discs, nucleus
`pulposus (NP), and annulus fibrosus (AF). Segmental lordosis was also
`measured using the Cobb method.
`In general, the disc length increased from upper to lower lumbar
`levels, except that the L4/5 and L5/S1 discs had similar lengths. The L4/5
`NP had a height of 8.6 1.3 mm, which was significantly higher than all
`other levels (P < 0.05). The L5/S1 NP had a length of 21.6 3.1 mm,
`which was significantly longer than all other levels (P < 0.05). At L4/5,
`the NP occupied 64.0% of the disc length, which was significantly less
`than the NP of the L5/S1 segment (72.4%) (P < 0.05). The anterior AF
`occupied 20.5% of the L4/5 disc length, which was significantly greater
`than that of the posterior AF (15.6%) (P < 0.05). At the L5/S1 segment,
`the anterior and posterior AFs were similar in length (14.1% and 13.6% of
`the disc, respectively). The height to length (H/L) ratio of the L4/5 NP
`was 0.45 0.06, which was significantly greater than all other segments
`(P < 0.05). There was no correlation between the NP H/L ratio and
`lordosis.
`Although the lengths of the lower lumbar discs were similar, the
`geometry of the AF and NP showed segment-dependent properties. These
`data may provide insight into the understanding of segment-specific
`biomechanics in the lower lumbar spine. The data could also provide
`baseline knowledge for the development of segment-specific surgical
`treatments of lumbar diseases.
`
`(Medicine 93(28):e333)
`
`Abbreviations: AF = annulus fibrosus, DDD = degenerative disc
`disease, H/L = height to length, IVD = intervertebral disc, MR =
`magnetic resonance, NP = nucleus pulposus.
`
`revised: October 29, 2014; accepted:
`
`Editor: Zelena Dora.
`Received: September 5, 2014;
`November 4, 2014.
`From the Bioengineering Laboratory (WZ, SJD, MW, SW, ZL, TDC,
`KBW, GL), Department of Orthopedic Surgery, Harvard Medical School/
`Massachusetts General Hospital, Boston, MA; Department of Spinal
`Surgery (WZ), Second Xiangya Hospital and Central South University,
`Changsha, Hunan; and Department of Orthopedics (MW), China-Japan
`Union Hospital of Jilin University, Jilin, P.R. China.
`Correspondence: Guoan Li, Orthopedic Bioengineering Laboratory,
`Harvard Medical School/Massachusetts General Hospital, 55 Fruit
`Street—GRJ 1215, Boston, MA 02114 (e-mail: gli1@partners.org).
`The authors would like to gratefully acknowledge the financial support from
`the National Institute of Health (R21AR057989), Synthes, Inc, Depart-
`ment of Orthopedic Surgery of Massachusetts General Hospital, and
`China Scholarship Council (201306370122).
`The authors have no conflicts of interest to disclose.
`Copyright # 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
`This is an open access article distributed under the Creative Commons
`Attribution License 4.0, which permits unrestricted use, distribution, and
`reproduction in any medium, provided the original work is properly cited.
`ISSN: 0025-7974
`DOI: 10.1097/MD.0000000000000333
`
`INTRODUCTION
`
`L umbar degenerative disc diseases (DDDs) are often found at
`
`the lower lumbar levels.1– 3 Epidemiology studies have
`suggested a segment-dependent discrepancy in the development
`of certain pathologies. For example, lumbar disc herniation is
`found most often at the L5/S1 segment,1 –6 whereas lumbar
`degenerative spondylolisthesis is found most often at L4/5.7–10
`Further, segment-dependent clinical outcomes following surgi-
`cal
`treatment of L4/5 or L5/S1 have also been reported.
`Microdiscectomy of L5/S1 has shown superior clinical out-
`comes compared with the L4/5,11 whereas total lumbar disc
`replacement at L4/5 has shown superior clinical outcomes
`compared with the L5/S1.12 However, knowledge on seg-
`ment-specific physiology and clinical outcomes is limited.
`There are various potential factors that could influence
`segment-dependent physiological function of the lumbar spine,
`including the surrounding muscles, ligaments, and vertebral
`geometries.13,14 However, most biomechanics studies of the
`lumbar spine make no distinction between different segmental
`levels. For example, previous reports on pressure measurement
`and kinematics of the nucleus pulposus (NP) did not provide
`level-specific analysis.15– 17 Recent kinematic studies revealed
`distinct motion characteristics between the L4/5 and L5/S1
`segments.18–20 Knowledge on the mechanisms behind these
`segment-dependent pathologies and motion characters could be
`instrumental
`for
`the development of
`segment-dependent
`surgeries to treat lumbar diseases.
`Therefore, the objective of this study was to investigate the
`in vivo morphology of lumbar intervertebral discs (IVDs) at
`different segment levels using sagittal plane magnetic reson-
`ance (MR) images. Specifically, the dimensions of the NP and
`anterior/posterior annulus fibrosus (AF) were compared. The
`height to length (H/L) ratio of the NP was also calculated to
`investigate NP shapes. We hypothesize that the IVD has distinct
`geometric features at different levels of the lumbar spine.
`
`MATERIALS AND METHODS
`MR images of the lumbar spine were obtained from
`41 young Chinese subjects (18 men and 23 women, aged
`20–35 years) with institutional review board approval of the
`authors’ institution. Each subject was scanned using a 3.0 Tesla
`scanner (Achieva X-series; Philips, Eindhoven, The Nether-
`lands) in a nonweight-bearing supine position with a spine
`surface coil and a T2-weighted fat-suppressed 3D SPGR
`sequence (TE¼ 120 ms, TR¼ 3100 ms, FOV¼ 300 mm). Paral-
`lel sagittal images with a thickness of 4.0 mm, gap of 1.0 mm,
`and resolution of 256 256 pixels were obtained. The lumbar
`discs were examined using Pfirrmann classification.21 Any of
`the lumbar discs of Pfirrmann grade III–V was used for
`exclusion of the subject from the study.
`Geometric measurements for each subject were taken from
`the T2-weighted midsagittal images using a commercial soft-
`ware program (Rhinoceros; Robert McNeel & Associates,
`Seattle, WA) (Figure 1). The length of the NP was defined
`as a midline drawn in the anterior–posterior direction between
`
`Medicine  Volume 93, Number 28, December 2014
`
`www.md-journal.com | 1
`
`NUVASIVE - EXHIBIT 2040
`Alphatec Holdings Inc. et al. v. NuVasive, Inc. - IPR2019-00362
`
`

`

`Zhong et al
`
`Medicine  Volume 93, Number 28, December 2014
`
`B
`
`A
`
`FIGURE 1. (A) Segmental lordosis (a) and L1-S1 lordosis (b) measurements were made using the Cobb method. Segmental lordosis was
`defined as the angle subtended by the superior endplate line of the superior vertebrae and the inferior endplate line of the inferior
`vertebrae. L1-S1 lordosis was defined as the angle subtended by the superior endplate line of L1 and inferior endplate line of S1. (B) Disc
`geometry was measured from the sagittal plane. AB¼ anterior AF, AD¼ disc length, BC¼ NP length, CD¼ posterior AF, EF¼ NP height,
`O¼ midpoint of BC. AF¼ annulus fibrosus, NP¼ nucleus pulposus.
`
`Disc length
`Anterior AF length
`
`Posterior AF length
`
`NP
`Anterior AF
`Posterior AF
`
`Disc and AF length
`
`L1/2
`
`L2/3
`
`L3/4
`
`L4/5
`
`L5/S1
`
`NP and AF length ratio
`
`L1/2
`
`L2/3
`
`L3/4
`
`L4/5
`
`L5/S1
`
`40.0
`35.0
`30.0
`25.0
`20.0
`15.0
`10.0
`5.0
`0.0
`
`1
`0.9
`0.8
`0.7
`0.6
`0.5
`0.4
`0.3
`0.2
`0.1
`0
`
`Lenght (mm)
`
`A
`
`Ratio
`
`B
`
`FIGURE 2. (A) Disc, anterior AF, and posterior AF lengths. Disc
`length increased from L1/2 to L4/5, with L4/5 and L5/S1 having
`similar lengths. Anterior AF was significantly longer than posterior
`AF at all levels except L5/S1. (B) NP, anterior AF, and posterior AF
`lengths to disc length ratios. NP length ratio significantly
`decreased from L2/3 to L4/5, before statistically increasing at
`L5/S1. Anterior AF represented a significantly greater percentage
`of disc length than posterior AF at all
`levels except L5/S1.
`AF¼ annulus fibrosus, NP¼ nucleus pulposus.
`
`the margins of the NP. The height of the NP was defined by a
`perpendicular line through the midpoint of the length, between
`the inferior and superior margins of the NP. These measure-
`ments also allowed for the H/L ratio of the NP to be calculated.
`The line that defined the NP length was then extended to the
`anterior and posterior margins of the IVD. The distance of
`anterior extension was defined as the anterior AF length. The
`distance of posterior extension was defined as the posterior AF
`length. The total length of the extended line was defined as the
`disc length. Finally, segmental lordosis and L1-S1 lordosis were
`measured using the Cobb method.22
`A repeated measure of 2-way analysis of variance was used
`to compare the disc length, NP length, AF length, NP height,
`H/L ratio, and segmental Cobb angle across lumbar levels. A
`statistical difference was achieved when P < 0.05. A Newman–
`Keuls post hoc test was performed when a statistically signifi-
`cant difference was detected. NP H/L ratio and lordosis were
`also correlated using Pearson tests. The statistical analysis was
`done using the STATISTICA software version 12 (Statsoft Inc,
`Tulsa, OK).
`
`RESULTS
`The length of the discs gradually increased from upper to
`lower levels (Figure 2a). However, the L4/5 and L5/S1 levels
`had similar lengths (30.4 4.5 mm and 30.0 4.4 mm, respect-
`ively). The NP length of the L5/S1 segment (21.6 3.1 mm)
`was significantly longer than all other levels (P < 0.05). L4/5
`had the shortest NP length (19.3 2.9 mm) (Figure 3a). The
`anterior AF occupied 20.5% of the L4/5 disc length, which was
`significantly greater than that of the posterior AF (15.6%)
`(P < 0.05) (Figure 2b). At the L5/S1 segment, the anterior
`and posterior AFs were similar in length (4.3 1.6 mm and
`4.1 2.3 mm, respectively), representing 14.1% and 13.6% of
`
`2 | www.md-journal.com
`
`# 2014 Lippincott Williams & Wilkins
`
`

`

`Medicine  Volume 93, Number 28, December 2014
`
`Morphological Features of Lumbar Discs
`
`lower lumbar level (Table 1). The L5/S1 segment had a seg-
`mental lordosis of 37.5 5.78, which was significantly greater
`than all other levels (P < 0.05). There was no correlation
`between the NP H/L ratio and segmental lordosis (R2 < 0.26).
`
`DISCUSSION
`This study investigated the in vivo morphology of lumbar
`IVDs using MR images of 41 healthy human subjects. The data
`showed segment-dependent geometric features of the lumbar
`IVD. Notably, NP height was the greatest at the L4/5 segment
`and NP length was the greatest at the L5/S1 segment. Addition-
`ally, the anterior AF was longer than the posterior AF at all
`lumbar segments except L5/S1, where both the lengths were
`similar. The data proved our hypothesis that the IVD has distinct
`geometric features at different levels of the lumbar spine.
`Numerous studies have investigated the biomechanics
`of the lumbar IVD using in vitro or in vivo experimental
`setups.23– 29 In vitro cadaveric tests have used various segments
`to examine the biomechanical responses of the disc to external
`loads.23– 26 Finite element studies have also simulated loading
`of the lumbar spine at multiple levels.23,28,29 Although these
`studies have greatly improved our understanding of disc load-
`ing, few studies have specifically compared the biomechanics
`of different levels.
`Ranu15 investigated the pressure–volume relation within
`the NP of intact human cadaveric lumbar discs using a miniature
`strain gauge. NP pressure was found to rise rapidly with
`continuous saline infusion. Krag24 and Seroussi25 examined
`NP displacement by implanting metal beads into cadaveric
`IVDs and found that the NP displaced anteriorly in extension
`and posteriorly in flexion. Schnebel et al30 used discography to
`study the in vivo movement of the lumbar NP in response to
`flexion and extension. They found movement in the anterior and
`posterior portions of the disc to be the highest in the L4/5 and
`L5/S1 NPs, respectively. Subsequent in vivo kinematic studies
`of the NP during flexion and extension using magnetic reson-
`ance imaging (MRI) techniques demonstrated that the upper
`lumbar levels had more movement than the lower levels in the
`anterior portion of the disc, whereas the lower levels had more
`movement than the upper levels in the posterior portion of the
`disc.16,17,31– 33 Recently, Alexander34 and Nazari35 used an
`open-MRI technique to investigate functional weight-bearing
`positions of the body (sitting and standing), and found that
`the in vivo deformation and migration of the lower lumbar NPs
`(L4/5 and L5/S1 levels) were more affected by position than the
`upper lumbar NPs. Most of these studies consider the NP to be a
`hydraulic cushion within the IVD, acting only to distribute
`stress evenly between vertebrae.36 Few reports have discussed
`segment-dependent geometrical features of the IVD.
`Degenerative pathologies of the lumbar spine are often
`found at the lower levels of L4/5 and L5/S1.1–3 Numerous
`studies have attempted to elucidate factors for DDD such as age,
`
`25.0
`
`20.0
`
`15.0
`
`10.0
`
`5.0
`
`0.0
`
`0.60
`
`0.50
`
`0.40
`
`0.30
`
`0.20
`
`0.10
`
`0.00
`
`NP length and height
`
`L1/2
`
`L2/3
`
`L3/4
`
`L4/5
`
`L5/S1
`
`NP H/L ratio
`
`NP length
`
`NP Height
`
`NP H/L ratio
`
`L1/2
`
`L2/3
`
`L3/4
`
`L4/5
`
`L5/S1
`
`NP height and length (mm)
`
`A
`
`NP H/L ratio
`
`B F
`
`IGURE 3. (A) NP length and height. NP length significantly
`decreased from L2/3 to L4/5, before significantly increasing at
`L5/S1. NP height significantly increased at each level from L1/2 to
`L4/5, before significantly decreasing at L5/S1. NP height was the
`greatest at the L4/5 segment, whereas NP length was greatest at
`L5/S1. (B) NP H/L ratio. The NP H/L ratio significantly increased
`from L1/2 to L4/5, before significantly decreasing at L5/S1.
`The L4/5 NP H/L ratio was significantly greater than all other
`segments. H/L¼ height to length, NP¼ nucleus pulposus.
`
`the disc, respectively. In all levels, the NP length was signifi-
`cantly longer than both anterior and posterior AF lengths
`(P < 0.05) (Figures 2a and 3a).
`The NP height
`gradually
`increased
`from L1/2
`(5.5 1.1 mm) to L4/5 (8.6 1.3 mm), and then decreased at
`L5/S1 (7.3 1.3 mm) (Figure 3a). The L4/5 NP height was
`significantly greater than all other NPs (P < 0.05). The NP H/L
`ratio showed a similar trend to NP height, gradually increasing
`from L1/2 (0.27 0.06) to L4/5 (0.45 0.06) before decreasing
`at L5/S1 (0.34 0.05) (Figure 3b). The NP H/L ratio at L4/5
`was significantly greater than all other lumbar segments
`(P < 0.05).
`The overall lordosis of L1-S1 was 55.6 9.08. Segmental
`lordosis was similar at L1/2 and L2/3 (4.9 3.28 and 4.2 3.18,
`respectively) before significantly increasing at each subsequent
`
`TABLE 1. Segmental and L1-S1 Lordosis
`Level
`L1/2
`4.9 3.28
`
`Cobb angle
`
`L1/3
`4.2 3.18
`
`L1/4
`9.2 4.08
`
`L1/5
`21.6 5.08
`
`L5/S1
`37.5 5.78
`
`L1/S1
`55.6 9.08
`
`Values are represented as mean standard deviation. Segmental lordosis significantly increased from L2/3 to L5/S1.
`
`# 2014 Lippincott Williams & Wilkins
`
`www.md-journal.com | 3
`
`

`

`Zhong et al
`
`Medicine  Volume 93, Number 28, December 2014
`
`job activities, and vertebral motion
`body weight, physical
`features.2,18 Although lumbar disc herniation has been reported
`more often at L5/S11– 6 and lumbar degenerative spondylolisth-
`esis more often at L4/5,7– 10 surgical treatments of L4/5 or L5/S1
`have also reported segment-dependent clinical outcomes.11,12
`Recent in vivo kinematic studies have revealed distinct motion
`characteristics at the L4/5 and L5/S1 segments.18–20 However,
`few data has been reported on the segment-specific morphology
`of lumbar IVDs and its potential relationship to these segment-
`dependent features.
`In our study, the L4/5 NP was found to have the greatest
`height and smallest length among all segments. Additionally,
`the anterior AF was significantly thicker than the posterior AF
`at the L4/5 level. The L5/S1 NP was significantly longer than all
`other levels, with its anterior and posterior AFs being similar in
`thickness. Our data also demonstrated segment-dependent NP
`shapes. The NP H/L ratio gradually increased from L1/2 to L4/5
`and then decreased at L5/S1. The L4/5 NP showed the largest
`H/L ratio and was significantly greater than all other levels.
`There was no correlation between the NP H/L ratio and seg-
`mental lordosis in this group of subjects. Further study is
`warranted to examine how these geometric features may cor-
`relate with the distinct kinematic features of the lumbar spine.
`Several limitations of this study should be considered.
`First, it was limited to investigation of IVD morphology in the
`sagittal plane. Three-dimensional analysis would potentially
`provide an even better understanding of IVD geometry. Another
`limitation of this study is the relatively narrow age range of
`subjects. Future studies should consider age, sex, ethnicity,
`and body height/weight as study variables. Finally, IVD
`morphology was studied in a supine position under non-
`weight-bearing conditions. Future studies should investigate
`lumbar IVD geometry under various physiological loading
`conditions. Despite the above limitations, this study represents
`the first
`in vivo measurement and analysis of segment-
`dependent lumbar IVD morphology.
`In conclusion, this study investigated human lumbar IVD
`geometry using sagittal plane MR images and found segment-
`dependent properties. Notably, the NP of the L4/5 segment had
`the greatest height, whereas the NP of L5/S1 had the greatest
`length. These baseline data may provide insight into the under-
`standing of segment-specific pathology and biomechanics in the
`lower lumbar spine. These data may also be instrumental for
`the development of segment-specific surgical treatments that
`are aimed to restore native spine function.
`
`REFERENCES
`
`1. Cheung KM, Karppinen J, Chan D, et al. Prevalence and pattern of
`lumbar magnetic resonance imaging changes in a population study
`of one thousand forty-three individuals. Spine. 2009;34:934–940.
`
`2. Kanayama M, Togawa D, Takahashi C, et al. Cross-sectional
`magnetic resonance imaging study of lumbar disc degeneration in
`200 healthy individuals. J Neurosurg Spine. 2009;11:501–507.
`
`3. Biluts H, Munie T, Abebe M. Review of lumbar disc diseases at
`Tikur Anbessa Hospital. Ethiop Med J. 2012;50:57–65.
`
`4. Evans W, Jobe W, Seibert C. A cross-sectional prevalence study of
`lumbar disc degeneration in a working population. Spine.
`1989;14:60–64.
`
`5. Takatalo J, Karppinen J, Niinimaki J, et al. Prevalence of degen-
`erative imaging findings in lumbar magnetic resonance imaging
`among young adults. Spine. 2009;34:1716–1721.
`
`6. Gilbert JW, Martin JC, Wheeler GR, et al. Lumbar disk protrusion
`rates of symptomatic patients using magnetic resonance imaging. J
`Manipulative Physiol Ther. 2010;33:626–629.
`
`7. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus
`nonsurgical treatment for lumbar degenerative spondylolisthesis. N
`Engl J Med. 2007;356:2257–2270.
`
`8. Sengupta DK, Herkowitz HN. Degenerative spondylolisthesis:
`review of current trends and controversies. Spine. 2005;30 (6
`suppl):S71–S81.
`
`9. Jacobsen S, Sonne-Holm S, Rovsing H, et al. Degenerative lumbar
`spondylolisthesis: an epidemiological perspective: the Copenhagen
`Osteoarthritis Study. Spine. 2007;32:120–125.
`
`10. Iguchi T, Wakami T, Kurihara A, et al. Lumbar multilevel
`degenerative spondylolisthesis: radiological evaluation and factors
`related to anterolisthesis and retrolisthesis. J Spinal Disord Tech.
`2002;15:93–99.
`
`11. Dewing CB, Provencher MT, Riffenburgh RH, et al. The outcomes
`of lumbar microdiscectomy in a young, active population: correlation
`by herniation type and level. Spine. 2008;33:33–38.
`
`12. Siepe CJ, Mayer HM, Heinz-Leisenheimer M, et al. Total lumbar
`disc replacement: different results for different levels. Spine.
`2007;32:782–790.
`
`13. Keller TS, Colloca CJ, Harrison DE, et al. Influence of spine
`morphology on intervertebral disc loads and stresses in asymptomatic
`adults: implications for the ideal spine. Spine J. 2005;5:297–309.
`
`14. Kong MH, Morishita Y, He W, et al. Lumbar segmental mobility
`according to the grade of the disc, the facet joint, the muscle, and
`the ligament pathology by using kinetic magnetic resonance imaging.
`Spine. 2009;34:2537–2544.
`
`15. Ranu HS. Multipoint determination of pressure–volume curves in
`human intervertebral discs. Ann Rheum Dis. 1993;52:142–146.
`
`16. Edmondston SJ, Song S, Bricknell RV, et al. MRI evaluation of
`lumbar spine flexion and extension in asymptomatic individuals.
`Man Ther. 2000;5:158–164.
`
`17. Fazey PJ, Song S, Price RI, et al. Nucleus pulposus deformation in
`response to rotation at L1-2 and L4-5. Clin Biomech (Bristol, Avon).
`2013;28:586–589.
`
`18. Wu M, Wang S, Driscoll SJ, et al. Dynamic motion characteristics
`of the lower lumbar spine: implication to lumbar pathology and
`surgical treatment. Eur Spine J. 2014;23:2350–2358.
`
`19. Passias PG, Wang S, Kozanek M, et al. Segmental lumbar rotation
`in patients with discogenic low back pain during functional weight-
`bearing activities. J Bone Joint Surg Am. 2011;93:29–37.
`
`20. Fredericson M, Lee SU, Welsh J, et al. Changes in posterior disc
`bulging and intervertebral foraminal size associated with flexion-
`extension movement: a comparison between L4-5 and L5-S1 levels
`in normal subjects. Spine J. 2001;1:10–17.
`
`21. Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance
`classification of lumbar intervertebral disc degeneration. Spine.
`2001;26:1873–1878.
`
`22. Kim SB, Jeon TS, Heo YM, et al. Radiographic results of single
`level transforaminal lumbar interbody fusion in degenerative lumbar
`spine disease: focusing on changes of segmental lordosis in fusion
`segment. Clin Orthop Surg. 2009;1:207–213.
`
`23. Lipscomb KE, Sarigul-Klijn N, Klineberg E, et al. Biomechanical
`effects of human lumbar discography: in-vitro experiments and their
`finite element validation. J Spinal Disord Tech. 2014 Feb 6. DOI:
`10.1097/BSD.0000000000000077. [Epub ahead of print].
`
`24. Krag MH, Seroussi RE, Wilder DG, et al. Internal displacement
`distribution from in vitro loading of human thoracic and lumbar
`spinal motion segments: experimental results and theoretical predic-
`tions. Spine. 1987;12:1001–1007.
`
`4 | www.md-journal.com
`
`# 2014 Lippincott Williams & Wilkins
`
`

`

`Medicine  Volume 93, Number 28, December 2014
`
`Morphological Features of Lumbar Discs
`
`25. Seroussi RE, Krag MH, Muller DL, et al. Internal deformations of
`intact and denucleated human lumbar discs subjected to compres-
`sion, flexion, and extension loads. J Orthop Res. 1989;7:122–131.
`
`31. Beattie PF, Brooks WM, Rothstein JM, et al. Effect of lordosis on
`the position of the nucleus pulposus in supine subjects. A study
`using magnetic resonance imaging. Spine. 1994;19:2096–2102.
`
`26. Tsantrizos A, Ito K, Aebi M, et al. Internal strains in healthy and
`degenerated lumbar intervertebral discs. Spine. 2005;30:2129–2137.
`
`27. Wang S, Xia Q, Passias P, et al. Measurement of geometric
`deformation of lumbar intervertebral discs under in-vivo weightbear-
`ing condition. J Biomech. 2009;42:705–711.
`
`28. Schmidt H, Shirazi-Adl A, Galbusera F, et al. Response analysis of
`the lumbar spine during regular daily activities—a finite element
`analysis. J Biomech. 2010;43:1849–1856.
`
`29. Dreischarf M, Rohlmann A, Zhu R, et al. Is it possible to estimate
`the compressive force in the lumbar spine from intradiscal pressure
`measurements? A finite element evaluation. Med Eng Phys.
`2013;35:1385–1390.
`
`30. Schnebel BE, Simmons JW, Chowning J, et al. A digitizing
`technique for the study of movement of intradiscal dye in response
`to flexion and extension of the lumbar spine. Spine. 1988;13:309–
`312.
`
`the nucleus
`32. Fennell AJ, Jones AP, Hukins DW. Migration of
`pulposus within the intervertebral disc during flexion and extension
`of the spine. Spine. 1996;21:2753–2757.
`
`33. Brault JS, Driscoll DM, Laakso LL, et al. Quantification of lumbar
`intradiscal deformation during flexion and extension, by mathema-
`tical analysis of magnetic resonance imaging pixel intensity profiles.
`Spine. 1997;22:2066–2072.
`
`34. Alexander LA, Hancock E, Agouris I, et al. The response of the
`nucleus pulposus of the lumbar intervertebral discs to functionally
`loaded positions. Spine. 2007;32:1508–1512.
`
`35. Nazari J, Pope MH, Graveling RA. Reality about migration of the
`nucleus pulposus within the intervertebral disc with changing
`postures. Clin Biomech. 2012;27:213–217.
`
`36. Adams MA, Freeman BJ, Morrison HP, et al. Mechanical initiation
`of intervertebral disc degeneration. Spine. 2000;25:1625–1636.
`
`# 2014 Lippincott Williams & Wilkins
`
`www.md-journal.com | 5
`
`