advanced magnetic resonance imaging

8/14/2019 Advanced Magnetic Resonance Imaging

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Advanced Magnetic Resonance Imaging

of Articular Cartilage

Garry E. Gold, MD*, Brian A. Hargreaves, PhD,Kathryn J. Stevens, MD, Christopher F. Beaulieu, MD, PhD

Department of Radiology, Stanford University, 300 Pasteur Drive S0-56, Stanford, CA 94305-9510, USA

Articular cartilage pathology may be the result

of degeneration or acute injury. Osteoarthritis is

an important cause of disability in society [15]

and is primarily a disease of articular cartilage

[68]. Acute injury to cartilage may be character-

ized using MRI [9]. Whether the result of degener-

ation or injury, MRI offers a noninvasive means

of assessing the degree of damage to cartilage

and adjacent bone and measuring the effectiveness

of treatment.

Many imaging methods are available to assess

articular cartilage. Conventional radiography canbe used to detect gross loss of cartilage, evident as

narrowing of the distance between the bony

components of the joint [10], but it does not image

cartilage directly. Secondary changes, such as os-

teophyte formation, can be seen, but conventional

radiography is insensitive to early chondral dam-

age. Arthrography, alone or combined with con-

ventional radiography or CT, is mildly invasive

and provides information limited to the contour

of the cartilage surface [11].

MRI, with its excellent soft tissue contrast, is

the best technique currently available for assess-

ment of articular cartilage [1216]. Imaging of re-

gions of cartilage damage has the potential to

provide morphologic information about the re-

gion, such as fissuring, and presence of partial-

thickness or full-thickness cartilage defects. The

many tissue parameters that can be measured by

MRI techniques have the potential to provide bio-

chemical and physiologic information about carti-

lage [13].

An ideal MRI study for cartilage should pro-

vide accurate assessment of cartilage thickness

and volume, show morphologic changes of the

cartilage surface, show internal cartilage signal

changes, and allow evaluation of the subchondral

bone for signal abnormalities. Also desirable

would be an evaluation of the underlying cartilage

physiology, including the status of the proteogly-

can and collagen matrices. Conventional MRIsequences in current clinical use do not provide

a comprehensive assessment of cartilagedlacking

in spatial resolution [17] or specific information

about cartilage physiology or requiring impracti-

cally long scan times for such assessments.

Conventional magnetic resonance imaging

methods

MRI has emerged as the leading method of

imaging soft tissue structures around joints [18].

A major advantage of MRI is the ability to ma-

nipulate contrast to highlight tissue types. The

common contrast mechanisms used in MRI are

two-dimensional or multislice T1-weighted, pro-

ton density, and T2-weighted imaging, with or

without fat suppression. Imaging hardware and

software have changed considerably over time,

including improved gradients and radiofrequency

coils, fast or turbo spin echo imaging, and tech-

niques such as water-only excitation.

Although the tissue relaxation times and

imaging parameters are the major determinantsof contrast between cartilage and fluid, lipid

This article was supported by NIH grants

EB002524 and EB005790 and the Whitaker

Foundation.

* Corresponding author.E-mail address: [email protected] (G.E. Gold).

0030-5898/06/$ - see front matter 2006 Elsevier Inc. All rights reserved.

doi:10.1016/j.ocl.2006.04.006 orthopedic.theclinics.com

Orthop Clin N Am 37 (2006) 331347
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suppression increases contrast between non

lipid-containing and lipid-containing tissues andaffects how the MRI scanner sets the overall

dynamic range of the image. The most common

type of lipid suppression is fat saturation, in

which fat spins are excited then dephased before

imaging. Another option is spectral-spatial exci-

tation, in which only water spins in a slice are

excited [19]. Finally, in areas of magnetic field

inhomogeneity, inversion recovery provides

a way to suppress lipids at the expense of signal-

to-noise ratio (SNR) and contrast-to-noise ratio.

The type of contrast material used in cartilage

imaging is crucial to the visibility of lesions andthe SNR of the cartilage itself. Although T2-

weighted imaging creates contrast between

cartilage and synovial fluid, it does so at the

expense of cartilage signal. The high signal fromfluid is useful to highlight surface defects, such as

fibrillation or fissuring, but variation in internal

cartilage signal is poorly depicted. These scans

also are often two-dimensional in nature, leaving

a small gap between slices, which may miss small

areas of cartilage damage.

Three-dimensional spoiled gradient recalled

echo imaging with fat suppression (SPGR) pro-

duces high cartilage signal, but low signal from

adjacent joint fluid. Currently, this technique is the

standard for quantitative morphologic imaging of

cartilage [2022]. Three-dimensional SPGR isuseful for cartilage volume and thickness measure-

ments, but does not highlight adequately surface

Fig. 1. Axial images showing degrees of patella cartilage damage. (A) Axial intermediate-weighted FSE image shows

superficial fibrillation and signal changes in the patellar cartilage ( arrow). (B) Axial T2-weighted FSE image shows mar-

row edema at the same location (arrow). (C) Axial intermediate-weighted FSE image shows fissuring involving approx-

imately 50% of the thickness of the cartilage (arrow). (D) Axial intermediate-weighted FSE image shows a full-thickness

cartilage fissure in the patella (arrow).

332 GOLD et al


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defects with fluid and does not allow thorough eval-

uation of other joint structures, such as ligaments

or menisci.

MRI of cartilage requires close attention toimaging spatial resolution. To see degenerating

cartilage, imaging with resolution on the order of

0.2 to 0.4 mm is required [17]. The ultimate reso-

lution achievable is governed by the SNR possible

within a given imaging time and with a given ra-

diofrequency coil. Ultimately, a high-resolution

imaging technique that combines morphologic

and physiologic information would be ideal in

the evaluation of osteoarthritis. Given current

techniques, it is likely that a combination of

a high-resolution morphologic imaging sequencewith a sequence for matrix evaluation would be

the most useful.

Two-dimensional fast spin echo imaging

Currently, imaging of the musculoskeletal

system with MRI is often limited to two-dimen-sional multislice acquisitions acquired in multiple

planes. This imaging is commonly done with turbo

or fast spin echo (FSE) methods. These methods

provide excellent SNR and contrast between

tissues of interest, but the inherently anisotropic

voxels in these two-dimensional acquisitions re-

quire that multiple planes of data be acquired to

minimize partial-volume artifacts. A typical sagit-

tal image may have 0.3 to 0.6 mm in plane

resolution, but a slice thickness of 3 to 5 mm.

FSE techniques show excellent results in detection

of cartilage lesions (Figs. 1 and 2) [23]. Thesemethods provide excellent depiction of structures

in the imaging plane, but evaluation of oblique

Fig. 2. FSE images of a cartilage fragment from the patella cartilage with full-thickness loss (arrows). (A) Axial inter-

mediate-weighted FSE image shows the cartilage fragment. (B) Sagittal intermediate-weighted image without fat sup-

pression. (C) Sagittal T2-weighted image with fat suppression shows edema in the patella and the fragment ( arrow).

333ADVANCED MRI OF ARTICULAR CARTILAGE


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or small structures across multiple slices can be

challenging. For these reasons, three-dimensional

acquisitions with thin sections are appealing.

Three dimensional gradient echo techniques

Traditional three-dimensional gradient echo

(GRE) methods have the potential to acquire

data with more isotropic voxel sizes, but have

a lack of contrast compared with spin echo

approaches. High accuracy for cartilage lesions

has been shown with three-dimensional SPGR

imaging [2426]. There are two main disadvan-

tages to this approach: (1) lack of reliable contrast

between cartilage and fluid that outlines surface

defects, and (2) long imaging times (approxi-

mately 8 minutes). In addition, SPGR uses gradi-

ent and radiofrequency spoiling to reduce artifacts

and achieve near T1 weighting; this reduces the

overall signal compared with steady-state tech-

niques. Despite these limitations, three-dimen-

sional SPGR is considered the standard for

morphologic imaging of cartilage [20,27].

SPGR and GRE techniques produce excellent

quality images with high resolution (0.3 0.6

1.5 mm) [28]. The SPGR method suppresses signal

from joint fluid, whereas the GRE method accen-

tuates it. Compared with balanced steady-state

free precession (bSSFP), which is described laterin greater detail, these methods are less SNR effi-

cient, but also less sensitive to magnetic field inho-

mogeneity. An ideal three-dimensional cartilage

imaging sequence that provides an optimal combi-

nation of resolution, SNR efficiency, and minimal

artifacts has yet to be established. As such, many

newer techniques have been established to im-

prove cartilage imaging.

New magnetic resonance imaging methods

Dual-echo steady-state imaging

Dual-echo steady-state imaging (DESS) has

proved useful for evaluation of cartilage morphol-

ogy [2932]. This technique acquires two gradient

echoes separated by a refocusing pulse, then com-

bines both echoes into the image. An image results

with higher T2 weighting, which has bright carti-

lage signal and bright synovial fluid.

Driven equilibrium Fourier transform imagingDriven equilibrium Fourier transform (DEFT)

has been used in the past as a method of signal

enhancement in spectroscopy [33]. The sequence

uses a 90-degree pulse to return magnetization

to the z-axis, increasing signal from tissue with

long T1 relaxation times, such as synovial fluid.

In contrast to conventional T1-weighted or T2-

weighted MRI, the contrast in DEFT dependson the ratio of the T1 to T2 of a given tissue.

For musculoskeletal imaging, DEFT produces

contrast by enhancing the signal from synovial

fluid, rather than attenuation of cartilage signal as

in T2-weighted sequences. Bright synovial fluid

results at short repetition times (TR). At short

TR, DEFT shows much greater cartilage-to-fluid

contrast than SPGR, proton density FSE, or T2-

weighted FSE [34].

DEFT imaging has been combined with

a three-dimensional echo-planar readout tomake it an efficient three-dimensional cartilage

imaging technique. In DEFT, there is no blurring

of high spatial frequencies such as in proton

density FSE [35]. In contrast to T2-weighted

FSE, cartilage signal is preserved because of the

short echo time (TE). A high-resolution three-

dimensional data set of the entire knee using

512 192 matrix, 14 cm field of view (FOV), and

3-mm slices can be acquired in about 6 minutes.

Initial studies of cartilage morphology have been

done using DEFT imaging [36,37], but this tech-

nique has not been conclusively proven superiorto two-dimensional approaches. A sequence simi-

lar to DEFT that has been used in musculoskele-

tal imaging is FSE with driven equilibrium pulses,

referred to as DRIVE [38].

Balanced steady-state free precession imaging

bSSFP MRI is an efficient, high signal method

for obtaining three-dimensional MRI images [39].

Depending on the manufacturer of the MRI scan-

ner, this method also has been called True-FISP(Siemens Medical Solutions, Malvern, PA),

FIESTA (General Electric Healthcare, Waukesha,

WI), or Balanced FFE imaging (Phillips Medical

Systems, Andover, MA) [40]. With advances in

MRI gradient hardware, it is now possible to use

bSSFP without the banding or off-resonance arti-

facts that were previously a problem with this

method. Banding artifacts resulting from off-

resonance are still an issue, however, as repetition

time increases, or at 3 Tesla (T). TR usually is

kept at less than 10 ms with these techniques, which

limits overall image resolution. Multiple acquisi-tion bSSFPcan be used to achieve higher resolution

[41,42] at the cost of additional scan time.

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Fat suppression in balanced steady-state free

precession imaging

Many methods have been proposed to provide

fat suppression with bSSFP imaging. If the repeti-

tion time is sufficiently short and the magnetic

field homogeneous, conventional fat suppression

or water excitation pulses can be used [43]. Linearcombinations of bSSFP [44] and fluctuating

equilibrium MRI (FEMR) [45] use the frequency

difference betweenfat and water and multiple acqui-

sitions to separate fat and water. Intermittent fat

suppression [46] uses transient suppression methods

to provide intermittent fat saturation pulses and

suppress lipid signal. Iterative decomposition of wa-

ter and fat with echo asymmetry and least-squares

estimation (IDEAL) uses multiple acquisitions to

separate fat and water, but does not depend on the

fat-water frequency difference to constrain the rep-etition time [47]. Rapid separation of water and

fat can be achieved with phase detection [48,49].

Fat and water separation also has been achieved

with phase detection and a radial acquisition

method using multiple echoes [50,51].

Fig. 3. Two sagittal images from the knee of a normal volunteer. (A) FEMR, scan time 2:43 minutes. (B) SPGR, scantime 8:56 minutes. Both scans were done at the same spatial resolution (512 256, 2-mm slice thickness) and have sim-

ilar SNR. The higher SNR efficiency of FEMR allows a similar morphologic scan to be acquired in a much shorter time.

(From Gold GE, Hargreaves BA, Vasanawala SS, et al. Articular cartilage of the knee: evaluation with fluctuating equi-

librium MR imagingdinitial experience in healthy volunteers. Radiology 2006;238:7128; with permission.)

Fig. 4. bSSFP images of the knee of a normal volunteer acquired using IDEAL bSSFP. (A) Water image. (B) Fat image.

Joint fluid is bright in A using this bSSFP technique. (From Gold GE, Reeder SB, Yu H, et al. Rapid 3D cartilage MR

imaging at 3.0 T with IDEAL-SSFP: initial experience. Radiology 2006;240: in press. DOI:10.1148/radiol.2402050288;

with permission.)



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Fluctuating equilibrium magnetic resonance

imaging

FEMR is a variant of bSSFP that may be

useful in imaging cartilage [45]. Similar to DEFT,

FEMR and other bSSFP-based sequences pro-

duce contrast based on the ratio of T1 to T2 in tis-

sues. With appropriate choice of flip angle, bright

fluid signal results, while preserving cartilage sig-

nal. In scanning the entire knee, FEMR can pro-

duce three-dimensional images with a 2-mm slice

thickness, 512 256 matrix over a 16 cm FOV

in about 2 minutes and 30 seconds [52]. The TR

was set at 6.6 ms at 1.5 T, which can be used forfat-water separation with careful shimming to

minimize artifacts. An example water image using

high-resolution FEMR is shown in Fig. 3 com-

pared with a three-dimensional SPGR imagethat took almost 9 minutes to acquire.

Linear combinations of balanced steady-state

free precession and fat-suppressed steady-state

free precession

Other bSSFP approaches may provide more

reliable fat suppression at high resolution than

FEMR. These methods include linear combina-

tion bSSFP [44], which uses multiple acquisitions

to create fat and water images, and fat-suppressed

bSSFP, which uses intermittent fat saturationpulses with preparation pulses that allow transi-

tions in and out of the steady state [53].

Fig. 5. Phase-sensitive bSSFP images from the knee of a normal volunteer. This is from a three-dimensional dataset ac-

quired with fat and water separation with 0.625 0.625 2 mm resolution in 90 seconds.

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Iterative decomposition of water and fat

with echo asymmetry and least-squares estimation

steady-state free precessionAnother approach to fat-water separation that

is relatively insensitive to field variations combines

IDEAL with bSSFP [54]. Example knee images

using this technique are shown in Fig. 4. Excellent

separation of fat and water are seen, with little off-

resonance artifact [55]. This method works at 1.5

T and 3 T.

Phase-sensitive balanced steady-state free

precession imaging

Phase-sensitive bSSFP employs an bSSFP se-quence with the TE restricted to be half of the TR.

The spectral response of the signal with respect to

resonance frequency is periodic. The periodicity

decreases with decreasing TR, resulting in less

field inhomogeneity sensitivity [48]. Voxels are as-signed to water or fat to form two separate im-

ages. This method is a rapid means of fat-water

separation using bSSFP, not requiring additional

acquisitions or saturation pulses [49]. One draw-

back to this approach is partial volume artifact,

as pixels are assigned as either fat or water, so

high resolution is required. Example images of

this method are shown in Fig. 5. These images

show a three-dimensional, fat-suppressed data

set of an entire knee that can be acquired with

0.625 0.625 2 mm resolution in about 90 sec-

onds. In a limited study, phase-sensitive bSSFPwas sensitive to marrow edema and meniscal tears

in a similar manner to FSE imaging [49].

Fig. 6. IDEAL SPGR and GRE images at 3 T. (A) IDEAL SPGR image. (B) IDEAL GRE image, flip angle 14. (C)

IDEAL GRE, flip angle 25. Increasing the flip angle increases contrast between synovial fluid and articular cartilage.



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Vastly interpolated projection reconstruction

imaging

Imaging of the knee with a combination of

a three-dimensional radial k-space acquisition and

bSSFP has several advantages. Three-dimensional

radial acquisitions are often undersampled in

sparse, high contrast imaging environments, suchas contrast-enhanced magnetic resonance angiog-

raphy, to decrease imaging time. Vastly interpo-

lated projection reconstruction (VIPR), first

developed for time-resolved contrast-enhanced

magnetic resonance angiography [50], was later

adapted for bSSFP imaging of the musculoskele-

tal system. Instead of using the radial trajectory

to undersample in musculoskeletal imaging, the

radial acquisition allows for a very efficient

k-space trajectory that collects two radial lines

each TR without wasting time on frequency de-phasing and rephasing gradients. One radial line

begins at the k-space origin, while the other is ac-

quired along a different return path to the origin,

allowing acquisition to occur during nearly the en-

tire TR. The optimal TR needed for the most effi-

cient implementation of linear combinations of

bSSFP at 1.5 T (2.4 ms) can be met while still

having time for adequate spatial encoding.

Application of VIPR to the knee provides

isotropic 0.5- to 0.7-mm three-dimensional imag-

ing that allows for reformations in arbitrary

planes. Because this method is based on bSSFP, joint fluid is bright, providing excellent contrast

for diagnosis of meniscal tears, ligament injuries,

and cartilage damage [56]. Contrast between the

cartilage and bone is generated by separating fat

and water with linear combinations of bSSFP,

as shown in Fig. 6. Scan time for the isotropic

acquisition was only 5 minutes. An alternative

single-pass method separates fat and water by

exploiting the different phase progression of fatand water spins between the two echoes acquired

each TR [51]. At 3 T, fat and water separation is

achieved by using an alternative fat stopband

with a TR of 3.6 ms. Here the multiple echo acqui-

sition allows for the removal of the unwanted

passband between the water and fat resonance

frequencies at the longer TR [57].

High field magnetic resonance imaging

High-field MRI may enable the acquisition ofmorphologic images at spatial resolutions that

cannot be achieved in a reasonable scan time at

1.5 T. Currently, 3 T MRI units are available that,

theoretically, have twice the SNR of 1.5 T

scanners. In addition, the increased chemical shift

allows for shorter fat suppression or water exci-

tation pulses, improving the speed of three-

dimensional SPGR and three-dimensional GRE

scans. IDEAL fat-water separation also is avail-

able at 3 T [58,59] with SPGR and GRE imaging,

as shown in Fig. 7. Also available are fat, water,

and combined images that are corrected for chem-ical shift [60]. This method could be used to mea-

sure subchondral bone thickness. Other fat

Fig. 7. VIPR bSSFP imaging of the knee at 1.5 T. This SSFP-based technique produces isotropic 0.7-mm resolutionacross the knee, allowing reformations in any imaging plane. Scan time was only 5 minutes. ( A) Coronal image with

cartilage defect (arrow). (B) Sagittal reformation with cartilage defect (arrow) and the meniscus (arrowhead). (Courtesy

of R. Kijowski and W. Block, University of Wisconsin, Madison.)

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suppression methods for bSSFP imaging, such as

FEMR and linear combination bSSFP, are less

applicable to high field because the shortest TR

during which the relative phase of fat and waterchanges by p is only 1.1 ms. This TR is too short

to create any meaningful spatial encoding, and the

radiofrequency power deposition would be high.

Physiologic magnetic resonance imaging

of cartilage

Articular cartilage composition

Articular cartilage is approximately 70% water

by weight. The remainder of the tissue consistspredominately of type II collagen fibers and

proteoglycans. The proteoglycans contain

negative charges; mobile ions such as sodium

(Na) or charged gadolinium MRI contrast

agents such as Gd-DTPA2 distribute in cartilage

in relation to the proteoglycan concentration. Thecollagen fibers have an ordered structure, making

the water associated with them exhibit magnetiza-

tion transfer and magic-angle effects. Physiologic

MRI of articular cartilage takes advantage of

these characteristics to explore the collagen and

proteoglycan matrices for pathology. Although

the methods described here can be performed at

1.5 T, all of them benefit from the additional

SNR available on 3 T systems.

T2 relaxation time mappingMRI is characterized by excitation of water

molecules and relaxation of the molecules back to

Fig. 8. Medial compartment cartilage T2 maps from a healthy volunteer. (A) Spin echo maps acquired with four echoes

and a scan time of 11:30 minutes. (B) Spiral T2 map acquired in 7 minutes. T2 relaxation time in cartilage is sensitive to

collagen matrix damage of articular cartilage.



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an equilibrium state. The exponential time con-

stants describing this relaxation are referred to as

T1 and T2 relaxation times and are constant fora given tissue at a given MRI field strength.

Changes in these relaxation times can be due to

tissue pathology or introduction of a contrast

agent.

The T2 relaxation time of articular cartilage is

a function of the water content and collagen

ultrastructure of the tissue. Measurement of the

spatial distribution of the T2 relaxation time may

reveal areas of increased or decreased water

content, correlating with cartilage damage. To

measure the T2 relaxation time with a high degree

of accuracy, attention must be taken with theMRI technique [61]. Typically, a multiecho spin

echo technique is used, and signal levels are fitted

to one or more decaying exponentials, depending

on whether it is thought that there is more than

one distribution of T2 within the sample [62].For echo times used in conventional MRI, how-

ever, a single exponential fit is adequate. An image

of the T2 relaxation time is generated with either

a color or a gray-scale map representing the relax-

ation time as shown in Fig. 8.

Several investigators have measured the spatial

distribution of T2 relaxation times within articular

cartilage [63,64]. Aging seems to be associated with

an increase in T2 relaxationtimes in the transitional

zone [65]. Relaxation time measurements also have

been shown to be anisotropic with respect to orien-

tation in the main magnetic field [6668]. Focal in-creases in T2 relaxation times within cartilage have

been associated with matrix damage, particularly

Fig. 9. Inversion recovery bSSFP imaging to determine T1 and T2 relaxation times in knee cartilage, after arthroscopic

surgery. This method can be applied to monitor cartilage physiology. (A) bSSFP (T2/T1 weighting). (B) T1. (C) T2. (D)

Proton density maps of the articular cartilage are produced in the same 7-minute scan time.

340 GOLD et al


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loss of collagen integrity. Studies on T2 relaxation

times documenting the effects of age [69], gender

[70], and activity [71] have been published.

Contrast-enhanced imaging

The proteoglycan component of cartilage has

glycosaminoglycan (GAG) side chains with abun-

dant negatively charged carboxyl and sulfate

groups. If mobile ions are allowed time to

distribute in cartilage, they distribute in relation

to the negative fixed charge density of the carti-

lage, or effectively in relation to the GAG

concentration. One of the most common MRI

contrast agents, or Gd-DTPA2 (Magnevist; Ber-

lex, Richmond, CA) has a negative charge. After

intravenous injection of Gd-DTPA2, it pene-

trates into cartilage, and it distributes in higherconcentration in areas of cartilage in which the

GAG content is relatively low. Subsequent T1

imaging (which is reflective of Gd-DTPA2 con-

centration) yields an image depicting GAG

distribution. This technique is referred to as de-

layed gadolinium-enhanced MRI of cartilage

(dGEMRIC) (the delay referring to the time re-

quired to allow the Gd-DTPA2 to penetrate the

cartilage tissue) [72,73]. A T1 map of the cartilage

allows assessment of GAG content, with lower

values corresponding to areas of GAG depletion.In terms of clinical studies, numerous cross-

sectional studies on specified populations have

provided interesting observations. A study re-

ported that individuals who exercise on a regular

basis have higher dGEMRIC indices (denoting

Fig. 10. Color maps of T1p measurements as a functionof spin lock frequency (Hz) in a healthy volunteer. T1pimaging may be sensitive to proteoglycan depletion in

articular cartilage. These maps were acquired with a spi-

ral T1p technique.

Fig. 11. Twisted-projection imaging sodium images of the knee of a healthy volunteer done at 3 T. (A) Single-quantum

images. (B) Triple-quantum images. Sodium content in the patellofemoral cartilage is well seen in both cases. (Courtesy

of F. Boada, University of Pittsburgh.)



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higher GAG) than individuals who are sedentary

[74]. In a relatively large cross-sectional study of

patients with hip dysplasia, measures of the sever-

ity of dysplasia (the radiographically determined

lateral center edge angle) and of pain correlated

with the dGEMRIC index, but not with the stan-dard radiologic parameter of joint space narrow-

ing [75]. In another study, lesions in patients

with osteoarthritis were more apparent with the

dGEMRIC technique relative to standard MRI

scans [76]. There also have been studies looking

at the effects of gadolinium on measurement of

T2 relaxation times [77,78]. A study relevant to os-

teoarthritis showed that dGEMRIC correlated

with Kellgren/Lawrence radiographic grading of

osteoarthritis [79].

Physiologic methods such as dGEMRIC andT2 mapping can be time-consuming and difficult

to perform on a routine basis. bSSFP methods

show promise in improving the speed and SNR of

T1 and T2 relaxation time measurements [80,81].

Newbould and colleagues [82] developed an inver-

sion recovery method of acquiring proton density,

T1, and T2 maps using bSSFP in articular carti-

lage. This technique employs an inversion recov-

eryprepared three-dimensional bSSFP sequence,

where an adiabatic nonslice selective inversion

was used. Total scan time to acquire a 256

256 64 three-dimensional volume (FOV 16cm, 1 signal average, 2 mm slice thickness) with

in-plane resolution of 0.83 mm was 7:18 minutes.

Example images of this method are shown in

Fig. 9. Aside from generating quantitative T1,

T2, and proton density maps, bSSFP images

also are available for radiologic review. Quantita-

tive techniques such as this may elucidate physio-

logic changes better in musculoskeletal imaging.

T1p imaging

A promising technique for evaluating cartilage

is T1p imaging, or relaxation of spins under the in-

fluence of a radiofrequency field [83,84]. This tech-

nique may be sensitive to early proteoglycan

depletion [8587]. In typical T1p imaging, magne-

tization is tipped into the transverse plane and

spin-locked by a constant radiofrequency field.

An example of a T1p map from the patella of

a healthy volunteer is shown in Fig. 10.

Sodium magnetic resonance imaging

Atoms with an odd number of protons or

neutrons possess a nuclear spin momentum and

exhibit the MRI phenomenon. 23Na is an example

of a nucleus other than 1H that is useful in carti-

lage imaging. The Larmor frequency of 23Na is

11.262 MHz/T compared with 1H at 42.575

MHz/T. At 1.5 T, the resonant frequency of23Na is 16.9 MHz, whereas it is 63 MHz for 1H.

The concentration of 23Na in normal human car-tilage is about 320 mM, with T2 relaxation times

of 2 to 10 m s [88]. The combination of lower

Fig. 12. Three-dimensional SSFP DWI. (A) Proton density images. (B) Heat scale maps of the diffusion coefficient. The

b-values correspond to the degree of diffusion weighting. DWI gives a sense of translational water mobility within the

articular cartilage. The diffusion coefficients measured in normal cartilage are about 0.00145 mm2/s, which correspond to

similar values in the literature. (From Miller KL, Hargreaves BA, Gold GE, et al. Steady-state diffusion-weighted imag-

ing of in vivo knee cartilage. Magn Reson Med 2004;51:3948; with permission.)

342 GOLD et al


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resonant frequency, lower concentration, and

shorter T2 relaxation times than 1H make in

vivo imaging of 23Na challenging. Sodium imag-

ing requires the use of special transmit and receive

coils and relatively long imaging times to achieve

adequate SNR.Sodium MRI has shown some promising re-

sults in the imaging of articular cartilage; this is

based on the ability of sodium imaging to depict

regions of proteoglycan depletion [89]. 23Na atoms

are associated with the high fixed-charge density

present in proteoglycan sulfate and carboxylate

groups. Some spatial variation in 23Na concentra-

tion is present within normal cartilage [88]. Fig. 11

shows an example of a sodium image through the

patellar cartilage of a healthy volunteer done with

a twisted-projection technique at 3 T [90]. High so-dium concentration is seen throughout the normal

cartilage. In cartilage samples, sodium imaging has

been shown to be sensitive to small changes in pro-

teoglycan concentration [91,92]. This method

shows promise to be sensitive to early decreases

in proteoglycan concentration in osteoarthritis. It

also is possible to do triple-quantumfiltered imag-

ing of sodium in cartilage, which may be even

more sensitive to early changes [93].

Diffusion-weighted imagingImaging the diffusion of water through artic-

ular cartilage also is possible with MRI. Diffu-

sion-weighted imaging (DWI) of cartilage has

been shown in vitro to be sensitive to early

cartilage degradation [94,95]. The apparent diffu-

sion coefficient decreases at long diffusion times,

indicative of the water molecules being restricted

by cartilage components. At the diffusion times

typically used, this restriction is related to the col-

lagen network in cartilage [96].

In vivo DWI of cartilage poses several chal-lenges. The T2 relaxation time of cartilage varies

from 10 to 50 ms, so the TE must be short to

maximize cartilage signal. Diffusion-sensitizing

gradients increase the TE and render the sequence

sensitive to motion. Single-shot techniques have

been used for DWI, but these have relatively low

SNR and spatial resolution. Multiple acquisitions

improve the SNR and resolution, but motion

correction is required for accurate reconstruction

[97].

Articular cartilage measurements done in vivo

in healthy volunteers show that apparent diffusioncoefficient ranges from 1.5 to 2 103 mm2/s.

These values compare well with reported results

obtained on cartilage/bone plug specimens [95].

Fig. 12 shows in vivo DWI results in a normal vol-

unteer using a navigated DWI technique based on

SSFP [98]. This technique produces diffusion-

weighted images of cartilage with a resolution of

0.5 0.7 3 mm resolution, taking approxi-mately 4:40 minutes per b-value. Navigation with

DWI techniques is essential in this application to

prevent motion artifacts and allow for multiple ac-

quisitions, which improves resolution and SNR.

Discussion

MRI provides a powerful tool for the imaging

and understanding of cartilage. Improvements

have been made in morphologic imaging of carti-

lage, in terms of contrast, resolution, and acquisi-tion time. This improved imaging allows detailed

maps of the cartilage surface to be developed,

quantifying thickness and volume. Much progress

has been made in the understanding of cartilage

physiology and the ability to detect changes in

proteoglycan content and collagen ultrastructure.

The choice of a particular protocol for imaging

articular cartilage depends greatly on patient

factors. For many patients with internal derange-

ment, imaging with standard FSE or three-

dimensional SPGR sequences may suffice. For

patients being considered for surgical or pharma-cologic therapy, a more detailed evaluation may

be required. Fast morphologic imaging along with

evaluation of cartilage physiology may allow for

noninvasive evaluation of cartilage implants at

different time points.

The fundamental tradeoff between image res-

olution and SNR still limits the ability to image

cartilage in vivo with high resolution in an

efficient manner. Patient motion ultimately may

limit the resolution achievable at 1.5 Tesla; so

higher field systems may be required. New tech-niques based on bSSFP may shorten imaging

time, allowing the application of other sequences

to explore important questions about cartilage

physiology and biochemistry. Ideally, the combi-

nation of these techniques would lead to an MRI

examination for cartilage that is brief and well

tolerated, but contains important morphologic

and physiologic data.

Summary

MRI, with its unique ability to image andcharacterize soft tissue noninvasively, has emerged

as one of the most accurate imaging methods



14/17

available to diagnose disorders of articular carti-

lage. Currently, most evaluation of cartilage pa-

thology is done with two-dimensional acquisition

techniques, such as FSE imaging. Traditional

three-dimensional imaging techniques, such as

SPGR imaging, have allowed noninvasive quanti-fication of cartilage morphology. Newer and sub-

stantially faster three-dimensional imaging

methods show great promise to improve MRI of

cartilage. These methods may allow acquisition of

fluid-sensitive isotropic data that can be reformat-

ted into arbitrary planes for improved detection

and visualization of pathology. Sensitivity to fluid

and fat suppression are important issues in these

techniques to improve delineation of cartilage

contours, detect bone marrow edema, and di-

agnose abnormalities in other joint structures.Finally, unique MRI contrast mechanisms allow

clinicians to probe cartilage biochemistry and

detect the early signs of changes in cartilage

macromolecules that accompany disease.

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