Diagnostic Tools andImaging Methods inIntervertebral DiskDegeneration

Sharmila Majumdar, PhDa,b,*, Thomas M. Link, MDa,Lynne S. Steinbach, MDa, Serena Hu, MDb,John Kurhanewicz, PhDa

KEYWORDS

� Spine � Imaging � Disk � Magnetic resonance� Spectroscopy � T1rho � T2

The incidence of back pain is ubiquitous in manysocieties; it has been reported as ranging from8% to 80%.1–3 Most people experiencing backpain have self-limited episodes; however, a smallproportion of this pain becomes chronic and de-bilitating (see the article by Karppinen andcolleagues elsewhere in this issue for furtherexploration of this topic). Disorders of the lowback have may compromise quality of life andpresent a tremendous financial impact on societythrough lost productivity, increased health care,and societal costs.4,5 In contrast to individualswith spinal degeneration resulting in spinalstenosis and disk herniation, those with diskdegeneration have much more variable presenta-tions and responses to treatment. Although agingof individuals inevitably leads to aging and degen-eration of the spine, it has been proposed thatphysiologic degeneration is a different clinicalentity from pathologic degeneration, with theimplication that chronic back pain is the exceptionrather than the rule and that those with pathologicdegeneration do not have appropriate repair orcompensatory mechanisms (see the article byChan and colleagues elsewhere in this issue forfurther exploration of this topic).

a Department of Radiology and Biomedical Imaging, UniQB3 Building, 2nd Floor, Suite 203, 1700 4th Street, Sanb Department of Orthopedic Surgery, University of CalifoCA 94158, USA* Corresponding author. Department of Radiology anFrancisco, Campus Box 2520, QB3 Building, 2nd Floor, SuE-mail address: Sharmila.Majumdar@ucsf.edu

Orthop Clin N Am 42 (2011) 501–511doi:10.1016/j.ocl.2011.07.0070030-5898/11/$ – see front matter � 2011 Elsevier Inc. All

Intervertebral disks provide stable support toadjacent vertebral bodies and allow movement tothe vertebral bodies, thereby affecting spinal flex-ibility. They absorb and distribute loads duringdaily activities. Intervertebral disks undergo age-related degeneration, increase in back pain, andstiffness. The connections between pain and diskdegeneration are not fully understood (see the arti-cles by Inoue and Espinoza Orias, and Karppinenand colleagues, elsewhere in this issue for furtherexploration of this topic).

The intervertebral disk is composed of thenucleus pulposus, the annulus fibrosus, and thecartilaginous end-plates (see the article by Grun-hagen and colleagues elsewhere in this issue forfurther exploration of this topic). The nucleuspulposus is a viscous, mucoprotein gel that isapproximately centrally located within the disk6

and is composed of glycosaminoglycans in a loosenetwork of type II collagen. The annulus fibrosusforms the outer boundary of the disk and ismade up of type-I collagen fibers arranged inlamellae. The proteoglycans of the nucleus osmot-ically exert a “swelling pressure” that enables it tosupport spinal compressive loads. The pressur-ized nucleus also creates tensile stress within the

versity of California San Francisco, Campus Box 2520,Francisco, CA 94158, USArnia San Francisco, 1500 Owens Street, San Francisco,

d Biomedical Imaging, University of California Sanite 203, 1700 4th Street, San Francisco, CA 94158.

rights reserved. orthopedic.th

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Majumdar et al502

collagen fibers of the annulus and ligamentousstructures surrounding the nucleus.Disk degeneration is characterized by a loss of

cellularity and degradation of the extracellularmatrix resulting in morphologic changes and alter-ations in biomechanical properties. Changes inproteoglycan content within the nucleus leads toreduced water content, depressurization, and flat-tening of the disk. Disruption of the collagennetwork in the annulus ultimately leads to diskrupture and herniation. Disk-height loss alsoresults in narrowing of the vertebral foramen withcompression of the nerve roots and may lead tothe development of spinal stenosis as well asforaminal narrowing. It has been proposed thatbiochemical degradation, upregulation of genesassociated with collagen matrix degradation, andthe cumulative effect of mechanical loading, allstimulate the degenerative disk process and,thus, contribute to functional impairment andpain (see the articles by Chan and colleagues,Kao and colleagues, and Inoue and EspinozaOrias elsewhere in this issue for further explorationof this topic). Thus, biomarkers that may be ob-jectively associated with pain and functionalimpairment and yet provide noninvasive diagnosisof disk degeneration and its accompanying bio-chemical and biomechanical changes, are clearlyrequired. It is in this context that MRI and spec-troscopy has potential. In the following sections,the authors review the current diagnostic toolsand recent developments for assessing diskdegeneration.

DIAGNOSTIC IMAGING OF INTERVERTEBRALDISK

Conventional radiographs have been used toassess degenerative disk disease for many yearsand are still the first imaging test in patients withsuspected disk disease. Radiographic findings,however, provide indirect signs and include disk-space narrowing and reactive end-plate changeswith spondylophytes and sclerosis. Associatedanterolisthesis and retrolisthesis may also bea sign of degenerative disk disease. Radiographsare limited for assessing early-stage disease andquantifying the amount of disk degeneration.Disk bulges and herniations are not seen onradiographs.CT scanning was the first line of investigation for

suspected lumbar prolapsed intervertebral diskdisease in the past, but has been overtaken byMRI. CT scanning exposes the patient to ionizingradiation and does not adequately demonstratethe disk in relation to the surrounding tissuescompared with MRI because of inferior soft tissue

contrast resolution. Nevertheless, it may be helpfulin visualizing posterior osteophytes, which may beimportant for surgical planning. Although painprovocation using discography or CT discog-raphy7 has been shown to improve the odds ofa positive surgical outcome, there a high incidenceof false positives has been reported8,9 and thereremains a significant number of severely degener-ated disks that have been found to be painless.10

In part because of the widespread occurrence ofabnormal radiographic findings, the use of provoc-ative discography is theorized to determine whichdisk is the pain generator. Because degenerateddisks can develop in-growth of nerve fibers thatare sensitive to pain,11 it is thought that thesefibers will be stimulated and irritated by injectingthe disk and pressurizing it. Reproduction of thepatient’s typical pain should signify that thepatient’s pain is occurring at that disk level. Thesurgeon may use this test to determine at whichlevels the patient should have surgery. However,the test is painful, subjective, and can be difficultto interpret, particularly in chronic-pain patients.12

In addition, although fine needles are used for theinjection into the disk (22 g and 25 g), thereappears to be a higher incidence in late symptom-atic degeneration in normal levels compared withthose that were not injected (35% after discog-raphy compared with 14% in nondiscogramdisks).13

It is in this context that nonionizing MRIs, whichreflect changes in disk height and morphology, arebeing used for diagnostic purposes. Using T1- andT2-weighted images, structural changes in the diskare visualized, as seen on representative images inFigs. 1 and 2. A decrease in T2-weighted signalintensity with increased lumbar disk degenerationis often seen, as shown in Fig. 2. Normal interver-tebral disks show a well-defined, oval, high-signalintensity from the nucleus pulposus (see Fig. 1)and there is low-signal intensity from the annulusfibrosus, whereas degenerated disks are charac-terized by a change in the signal from the nucleuspulposus to give an irregular outline and a reduc-tion in signal intensity on longer TE sequences,such as proton density and T2-weighting (seeFig. 2). In advanced cases, there is no cleardemarcation between annulus and nucleus.10 Asemiquantitative assessment of morphologicdegeneration in intervertebral disk degenerationcan be performed using Pfirrmann grading, whichis a 5-point scale system and is assessed fromT2-weighted MRIs. Fig. 314 shows representativedisks with the different Pfirrmann grades. MRI iscapable of assessing the disk degeneration interms of signal changes and demonstrates poste-rior disk bulges, protrusions, extrusions, and

Fig. 1. Sagittal (A) T1-weighted and (B) fat-saturated T2-weighted fast spin echo sequences of the lumbar spine,showing normal disk spaces with normal disk and adjacent bone marrow signal.

Fig. 2. Sagittal T1-weighted and fat-saturated (A) T2-weighted fast spin echo (B) sequences of the lumbar spinedemonstrate severe degenerative disk disease at L3/4 and L4/5 with disk height loss, disk desiccation, decreasedsignal, posterior disk bulges, and Modic type 1 reactive end-plate changes at L4/5 (arrows). Note substantial spinalcanal narrowing from L3-S1.

Diagnostic Tools and Imaging Methods 503

Fig. 3. Representative images showing disks with varying Pfirrmann grades. (Courtesy of Gabby Joseph, Depart-ment of Radiology and Biomedical Imaging, UCSF.)

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sequestrations, as well as their effect upon theadjacent spinal cord and nerve roots.Less common findings in MRIs include Modic

end-plate changes,15 which are thought to bea sign of abnormal stresses at the disk and theso-called high intensity zone. This region, usuallyin the posterior aspect of the disk, with highersignal on T2 images, may correlate with an annulartear of the disk fibers and the resultant inflamma-tory response. Studies that have attempted tocorrelate the presence of these findings16,17 withpositive provocative discography are encouragingbut not conclusive.Investigators have used the uptake of gadoli-

nium triethylene triamine pentaacetic acid enhanc-ement to assess the intervertebral disk. There hasbeen recent interest in the high-signal intensityzone in the posterior annulus seen in T2-weightedimages,18,19 in which a band-like contrast en-hancement of the disk has been correlated withvascularization (often seen as a consequence ofannular tears) and which corresponds to pain,even in the absence of stenosis.20 In follow-upstudies, however, these high intensity zones didnot correlate with symptoms.21

QUANTITATIVE MRIFor Biochemical Assessment

In an effort to improve the capability of MRI tech-niques to quantitatively assess spinal degenera-tion (in particular, disk degeneration) surrogateMRI measures of tissue hydration, such as relaxa-tion times (T1 and T2) and, more recently, T1r are

being studied. In vitro studies have shown thatthere are highly significant differences betweenthe nucleus and the annulus in both T1 and T2relaxation times. A moderate negative correlationbetween the reciprocal of T2 and water contentfor disk tissue samples suggests that a weakenedcollagen network could permit a greater degree ofswelling (ie, a higher water content in the disk).22

There are significant differences in T1 by region,the nucleus having a higher value than the annulusand in the loaded disk versus the unloaded disk. T2values also show a significant difference by region.The nucleus is greater than the annulus and T2decreases with increasing degeneration.23 T1 andwater content in the nucleus and annulus arecorrelated, but the change of relaxation time withwater content is significantly higher in the nucleuscompared with the annulus.24 In vivo, the T1 and T2relaxation times and the proton density of thenucleus pulposus was measured in 107 normaland 18 surgically proven degenerate intervertebraldisks,25 showing no age-related dependence ofproton density, a marker of hydration, but showinghighly significant difference between the T1 valuesof normal and degenerate disks. T2 showed highlysignificant differences in the younger age groups,but not in older age groups.Boos and colleagues26 observed statistically

significant (P 5 .001) mean differences betweennormal (n 5 100) and herniated (n 5 20) interverte-bral disks (difference in T1 between the groupswas 196 millisecond and in T2 was 15 millisecond).In a subsequent study27 it was demonstrated that,when matched by age, gender, and occupational

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risk factors, asymptomatic patients showed a highrate (76%) of disk herniations. This was significantlyless than the symptomatic group incidence of 96%.T1 and T2

28 in 22 patients with sciatica severeenough to require a discectomy was comparedwith T1 and T2 in asymptomatic volunteers (controls)who were matched according to age, gender, disklevel, and the extent of herniation (protrusion orextrusion). The symptomatic subjects exhibitedsignificantly shorter T1 and T2 relaxation times thanthe matched asymptomatic subjects did.

Recent attention has been focused on MRI T1rrelaxation time measurements that have thepotential for assessing changes in the extracellularmatrix (ECM), particularly proteoglycan loss in theintervertebral disk. In vivo, using different durationspin-locking pulses, T1r-weighted images (Fig. 4)were obtained. Fitting an exponential to the decayof signal with the time of spin-locking (TSL), a T1rmap was generated (see Fig. 4) and the reproduc-ibility of disk T1r was found to be 4.59%.29 Studieshave demonstrated quantitatively that T1r corre-lates with proteoglycan content and water loss inthe disk.30 T1r varies between the nucleus andthe annulus,31 with the median T1r value for thenucleus being 116.6 � 21.4 milliseconds and84.1 � 11.7 milliseconds for the annulus, andthese values between the nucleus and annuluswere found to be significantly different (P<.05).The correlations between age and T1r relaxationtime in the nucleus (r2 5 �0.82, P 5 .0001) andannulus (r2 5�0.37, P5 .04) were also significant.T1r relaxation times decreased with disk degener-ation (Fig. 5),30,31 demonstrating the changes withPfirrmann grade and T2 (Fig. 6) and showing thecorrelation to patient-reported physical activityand disability as assessed by clinical question-naires (short form health survey [SF 36] andOswestry Disability Index [ODI]).32

MRI DIFFUSION MEASUREMENTS

Diffusion of water protons in MRI is modified by thebiochemical environment and diffusion-related

Fig. 4. Images obtained at different spin-locking times (TSJoseph, Department of Radiology and Biomedical Imaging

signal loss signal and has been used to studydisk degeneration in vitro. Significant differencesare demonstrated in the diffusion coefficientbetween the nucleus and annulus, the nucleushaving a higher value than the annulus. Diffusiondecreased with increasing Thompson grade (orincreased degeneration), and with loading of thedisk.23 Diffusion in the nucleus decreases withglycosaminoglycan content, water content, andcollagen degradation, and shows regional depen-dence.33 Diffusion changes in the annulus werenot as evident with changes in matrix except indirectional diffusion in the anterior annulus.A representative diffusion-weighted image andcalculation of the apparent diffusion coefficient isshown in Fig. 7.

Kerttula and colleagues34 showed decreaseddiffusion in degenerated disks in vivo comparedwith healthy controls. Kealey and colleagues35 re-ported a 9% reduction in the apparent diffusioncoefficient in abnormal disks compared withnormal disk. The impact of the diurnal loadingcycle on the disk diffusion coefficient was investi-gated36 and it was found that apparent diffusioncoefficient significantly decreased in the annulus(�5.2%) and the intermediate regions (�2.2%)with no significant changes in the nucleus,contrary to the regional changes seen in T2 valuesthat show changes in the nucleus and annulus.The relationship between diffusion measures andvisual degenerative changes in lumbar interverte-bral disks as measured by the Pfirrmann gradeshowed decreases of 4% to 5% in degenerateddisks, but there was considerable overlapbetween normal and degenerated disks.37

DIFFUSION OF CONTRAST AGENTS

The diffusion of gadodiamide 24 hours after injec-tion was studied in 150 disks (96 normal and 54degenerate).38 The study measured the enhance-ment percentage, peak enhancement percentagefor different regions in the disk, and the time takento achieve peak enhancement percentage. The

L) are used to construct a T1r map. (Courtesy of Gabby, UCSF.)

Fig. 5. Representative T1r maps in healthy and degen-erated disks showing a decrease in T1r with degener-ation. Bar plot showing the relationship betweenPfirrmann grade and T1r. Groups that are significantlydifferent (P<.05) are categorized by different colors.(Courtesy of Gabby Joseph, Department of Radiologyand Biomedical Imaging, UCSF.)

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peak enhancement in the end-plate zone wassignificantly correlated to the diffusion of contrastagent into the nucleus in the total sample of disks,as well as in degenerated disks. This indicates thepossible role of end-plate permeability in disknutrition.A recent study39 investigated the influence of

a sustained mechanical load on diffusion of smallsolutes in and out of the normal disk using serialpostcontrast (gadoteridol) enhanced imaging atdifferent time points: precontrast and 1.5, 3, 4.5,6, and 7.5 hours postcontrast, injection. Onemonth later, the same volunteers were subjectedto sustained supine loading for 4.5 hours. MRIscans were performed precontrast (beforeloading) and postcontrast (after loading) at 1.5, 3,and 4.5 hours. Their spines were then unloadedand recovery scans performed at 6 and 7.5 hours

Fig. 6. T1r and T2 maps showing differences in the spatialand T2 values. (Courtesy of Gabby Joseph, Department of

postcontrast. This study revealed significantlylower signal intensity ratios in the central regionof the loaded disk compared with the unloadeddisks, This indicates reduction in transport ratesfor the loaded disks. The behavior of the loadedand unloaded disks were significantly differentover the longer time periods, suggesting that sus-tained supine creep loading (50% of body weight)for 4.5 hours retards transport of small solutes intothe center of human disk. Three hours of acceler-ated diffusion in recovery were required to returnto normal.

MRI FOR BIOMECHANICAL ASSESSMENT

Spine kinematics, which has been studied usingopen-MRI scanners and have revealed relation-ships between spinal segment motion and facetjoint osteoarthritis, will not be reviewed at lengthin this article. However, in the context of diskdegeneration, in a study measuring segmentalmotion in flexion, extension, and neutral positions,Kong and colleagues40,41 found that abnormalspinal motion resulted in disk degeneration, inaddition to facet joint degeneration, and thatincreased translational motion of the segmentswas associated with severe disk degeneration. Inthe link between the different components anddisk degeneration, biomechanical instabilityclearly is implicated in lower back pain, andwarrants thorough investigation (see the articleby Inoue and Espinoza Orias elsewhere in thisissue for further exploration of this topic).

NUCLEAR MAGNETIC RESONANCE AND MRISPECTROSCOPY IN INTERVERTEBRAL DISKHigh-Resolution Magic-Angle Spinningin Specimens

High-resolution magic angle spinning (HR-MAS)nuclear magnetic resonance (NMR) spectroscopyis a nondestructive technique that has been suc-cessfully used to characterize the composition ofvarious intact biologic tissues, such as cartilage(Fig. 8).42 By using high-field strength, one is

distribution of T1r and T2. The correlation between T1rRadiology and Biomedical Imaging, UCSF.)

Fig. 7. Diffusion-weighted images and apparentdiffusion coefficient map of intervertebral disks.(Courtesy of Dimitrios Karampinos, Department ofRadiology and Biomedical Imaging, UCSF.)

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able to resolve resonances to a degree that allowsidentification of chemical markers that may facili-tate subtle distinctions between normal and de-generated tissues. HR-MAS spectroscopy has

Fig. 8. Representative 1H HR-MAS Carr-Purcell-Mei-boom-Gill (CPMG) spectra from the nucleus of (A)non-painful (Pfirrmann 3) and (B) painful (Pfirrmann 5)degenerative intervertebral disks. Alanine (Ala), theN-acetyl peak (Acetyl) of proteoglycans, phosphocho-line (PC), glycerophosphocholine (GPC), choline (Cho),lactate (Lac), and glucose (Glu) could be resolved andquantified in disk spectra. The peak at �0.5 ppmspectra, is the electronic concentration standard(ERETIC).

been applied to intervertebral disks spanninga range of Thompson grades to identify theNMR-observable chemicals and to determine thedifference in the ratios of these chemicals betweendisks at different stages of degeneration.43 Usingdata generated from patient tissue samplesremoved from surgery, it has been demonstratedthat MRI spectroscopy at high fields (11) canquantify chemical features specific to painfuldisks.44 Specifically, it has been demonstratedthat measures of lactate, proteoglycan, choline,and collagen may provide a quantitative discrimi-nator between painful and non-painful disks.

In a repeat study, specimens from 24 patientswith discogenic pain, degenerated disk disease,5 patients with degenerated disk disease but nopain, and 3 deformity patients with scoliosisundergoing anterior and posterior spinal fusionwere obtained, and immediately (within minutesof surgery) placed on dry ice and stored at�80�C. In order to classify the tissue, patientsagittal, and axial T1-weighted and T2-weightedMRI images were acquired, analyzed, and classi-fied using the Pfirrmann grading scheme.14 Thedisk nucleus was pathologically separated fromthe annulus before the HR-MAS study. HR-MASdata were acquired at 1.0 � 0.5�C and a 2250Hz spin rate using a Varian INOVA spectrometeroperating at 11.75 T (500 MHz for 1H) and equip-ped with a 4 mm gHX nanoprobe. A long echotime (echo time5 144 milliseconds) rotor synchro-nized Carr-Purcell-Meiboom-Gill (CPMG)sequence was used in these studies to filter outshort T2 lipids and accurately quantify lactatedoublet at 1.33 ppm from lipids. Unfortunately,as seen in the painful disk spectrum (seeFig. 8B), residual lipid often remained, prohibitingthe accurate quantification of the lactate doubletin disk samples. However, the lactate quartetwas well resolved and of a sufficiently goodsignal-to-noise ratio to robustly quantify lactatein the CPMG spectra. Also established, is a wayto calibrate the spectrum using the ElectronicReference To access In vivo Concentrations(ERETIC) method (see Fig. 8).45 The absolutelevels of the individual disk chemicals (chemicalpeak area to ERETIC peak area) for the nucleusof degenerated painful and non-painful disks aregiven in Fig. 9. The focus was on the HR-MASspectra of the nucleus because, for in vivo protonspectra of degenerated disks, the selected regionof interest is centered on the nucleus.

Visually, both spectra (see Fig. 6) demonstratedchemical changes typical of disk degeneration,including an increase in resolution of the reso-nances in the carbohydrate region of the spec-trum, decreased N-acetyl, and increased lactate

Fig. 9. Aplotof the individual (x) andmean (–)disk chemical toERETIC ratios and lactate toN-acetyl rationormalizedto sample weights from the nucleus of painful (n5 30) and non-painful (n5 16) degenerative intervertebral disks.

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peaks.43,44,46 Quantitatively, there were not anysignificant differences between individual chemi-cals from degenerated painful and non-painfuldisk spectra (see Fig. 7). Important to the currentstudy, there was a twofold higher mean lactate inpainful versus non-painful disk tissue, but due tothe large variability of lactate measurements inthe patient cohorts, the difference in lactate levelswas not significant (4.14 � 4.72 vs 2.17 � 1.11,P 5 .19). Additionally the N-acetyl peak was notdifferent between the painful and non-painfulcohorts (23.65 � 27.05 vs 17.74 � 8.17, P 5 .49).However, this study confirmed prior publishedresults,45 demonstrating discrimination between

Fig. 10. A box plot of lactate to N-acetyl ratios fromthe nucleus of painful (n 5 30) and non-painful (n 5 16)degenerative intervertebral disks.

painful and non-painful disks (Fig. 10) using thelactate to N-acetyl ratio. The mean lactate toN-acetyl ratio was significantly different betweenpainful and non-painful degenerated disks (mean50.166 � 0.076 vs 0.123 � 0.044, P 5 .024); how-ever, there was still overlap of individual ratios.

In Vivo Magnetic Resonance Spectroscopy

Extension of these spectroscopic methods in vivois limited by the low signal-to-noise ratio, the pres-ence of water in the disk and adjoining tissue, thepresence of lipids in adjoining bone marrow, andthe broad line widths seen in vivo due to bonesusceptibility-induced line broadening. However,at higher field strengths, with spatially selectivepulses and improved localized shimming, a recentstudy using 1H- magnetic resonance spectros-copy (MRS) in bovine and human cadaver disks re-ported changes in metabolic concentration withincreasing grade of disk degeneration and a rela-tionship between metabolic concentration andproteoglycan content.47 Representative in vivospectra in human subjects are shown in Fig. 11.For spectroscopy scans, only the N-acetyl reso-nance (2.04 ppm) that is associated with proteo-glycan and the water resonance (4.7 ppm) canbe robustly quantified; the other metabolitescannot be accurately quantified because of thelimitation of the signal-to-noise ratio in in vivoscans. Furthermore, the lactate peak seen in HR-MAS cannot be separated from lipid or accurately

Fig. 11. Water to proteoglycan (PG) peak area ratio is elevated in the disk with positive discography. Although all disks are Pfirrmann grade 2, the disk with positivediscography has elevated water to proteoglycan peak area ratio. The amplitude of water was normalized to 1 to illustrate the differences in water to PG peak area ratiobetween disks. (Courtesy of Jin Zuo, Department of Radiology and Biomedical Imaging, UCSF.)

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quantified in vivo. Thus, in vivo, the water peak andthe N-acetyl peak related to proteoglycans wasquantified. It was demonstrated that the water toproteoglycan peak area ratio was significantlyelevated in patients (compared with controls) andin disks with positive discography (compared withnegative discography). The water to proteoglycanpeak area ratio, normalized water, normalizedproteoglycans, and Pfirrmann grade were signifi-cantly associated with patient self-assessment ofdisability and physical composite score, althoughdisk height was not. Additional assessments ofdisk T1r demonstrated that there was significantassociation between T1r, thewater to proteoglycanratio, and normalized proteoglycan content (r2 50.61, P<.05), but not between T1r and normalizedwater content (r2 5 0.24, P>.05).

SUMMARY

MRI methods provide information pertaining todisk morphology and grading schemes that canbe used for clinical assessment of disease status.Biochemical changes are reflected by measures ofrelaxation times and diffusion, whereas contrastagents may have the potential to be used for theassessment of end-plate permeability. HRMAStechniques provide biochemical signatures rele-vant to degeneration of the disk and, whereas in-vivo spectroscopy may be a challenge at thispoint, there is a clear need for investigation andstudy. In vivo spectroscopic markers that correlatewith measures of relaxation times, such as T1r,may provide a measure of the relative role ofproteoglycan and water in disk degeneration.The ability to combine these measures of diskmorphology and composition with morphologicmeasures, including facet joint status, makesMRI a potentially powerful tool for determiningthe causes of lower back pain, and monitoringdisease progression and therapy.

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