Aci

Autologous ChondrocyteAutologous Chondrocyte
Implantation (ACI)Implantation (ACI)
 MRIMRI
 superior tissue contrastsuperior tissue contrast
 sensitivity to tissue compositionsensitivity to tissue composition

MRIMRI
 tremendous potential in the study oftremendous potential in the study of cartilage repaircartilage repair
 help to estimate thehelp to estimate the size, nature, and locationsize, nature, and location of lesionsof lesions
preoperatively, in orderpreoperatively, in order to optimize surgical planningto optimize surgical planning
 help to evaluate thehelp to evaluate the quality and success of tissue repairquality and success of tissue repair
processesprocesses after surgicalafter surgical treatmenttreatment
 allow one toallow one to monitor degenerative changesmonitor degenerative changes in the jointin the joint
after cartilage repair, potentially in comparison to patientsafter cartilage repair, potentially in comparison to patients
who have not been treated forwho have not been treated for cartilage lesionscartilage lesions

MRIMRI
 MRIMRI
 less invasive methodless invasive method
 directly depictsdirectly depicts
 Cartilage interiorCartilage interior
 subchondral bone and bone marrowsubchondral bone and bone marrow
 ArthroscopyArthroscopy
 cartilage surface (minor surface abnormalities)cartilage surface (minor surface abnormalities)
 tissue biopsy for histologic assessmenttissue biopsy for histologic assessment of theof the
implantimplant

MRIMRI
 MRIMRI
 MR arthrographyMR arthrography
 outline cartilage defectsoutline cartilage defects
 improveimprove the conspicuity of lesionsthe conspicuity of lesions
 Direct: Intra-articular GdDirect: Intra-articular Gd
 Indirect: IV GdIndirect: IV Gd

MRIMRI
 Morphological assessment:Morphological assessment:
 SurfaceSurface
 ThicknessThickness
 VolumeVolume
 Subchondral boneSubchondral bone
 Biochemical statusBiochemical status
 Biomechanical statusBiomechanical status

Preoperative estimation of lesion size, nature,Preoperative estimation of lesion size, nature,
and location: morphologyand location: morphology
 MR technique and sequencesMR technique and sequences
 fat-suppressed three-dimensional gradient echo (3D-fat-suppressed three-dimensional gradient echo (3D-
GRE): T1GRE): T1
 exact depiction of the thickness and surface of cartilageexact depiction of the thickness and surface of cartilage
 Intermediate-weightedIntermediate-weighted fast spin echo (FSE)fast spin echo (FSE)
techniques with ortechniques with or without fat-suppression: T2without fat-suppression: T2
 normal and abnormal internal structure of hyalinenormal and abnormal internal structure of hyaline
cartilagecartilage

and location:and location: morphologymorphology
IM TSE IM TSE FS

3D GRE FS3D GRE FS
DESSDESS TRUEFISPTRUEFISP

 MR technique and sequencesMR technique and sequences
 voxel size under 300 μm is required to reveal frayingvoxel size under 300 μm is required to reveal fraying
of the articular surface of cartilageof the articular surface of cartilage
 high-resolution threedimensional (3D) isotropic cartilage-high-resolution threedimensional (3D) isotropic cartilage-
sensitive sequencessensitive sequences
 High-field MRI scanners and new coil technologies:High-field MRI scanners and new coil technologies:
mult-element design with parallel imagingmult-element design with parallel imaging
 scan times can be kept well below 10 minscan times can be kept well below 10 min
 signal-to-noise ratiosignal-to-noise ratio

 Scoring methodsScoring methods
 MRI classification system (Yulish et al)MRI classification system (Yulish et al)
 Grade 1: abnormal intrachondral signal with a normalGrade 1: abnormal intrachondral signal with a normal
chondral surfacechondral surface
 Grade 2: mild surface irregularity and/or focal loss of lessGrade 2: mild surface irregularity and/or focal loss of less
than 50% of the cartilage thicknessthan 50% of the cartilage thickness
 Grade 3: severe surface irregularity with focal loss of 50%Grade 3: severe surface irregularity with focal loss of 50%
to 100% of the cartilage thicknessto 100% of the cartilage thickness
 Grade 4: complete loss of articular cartilage, withGrade 4: complete loss of articular cartilage, with
exposure of subchondral boneexposure of subchondral bone

 AccuracyAccuracy
 sensitivity of 93% and a specificity of 99% insensitivity of 93% and a specificity of 99% in
detecting chondral lesions with MRI when axial anddetecting chondral lesions with MRI when axial and
coronal images were combined,and values of 94 andcoronal images were combined,and values of 94 and
99% when images in all three planes99% when images in all three planes were usedwere used
 accuracy was highest for severe cartilage lesions andaccuracy was highest for severe cartilage lesions and
lowest for smaller lesionslowest for smaller lesions
Bredella MA, Tirman PF, Peterfy CG et al (1999) Accuracy of T2-weighted fast spin-echo MR imaging with fat saturation inBredella MA, Tirman PF, Peterfy CG et al (1999) Accuracy of T2-weighted fast spin-echo MR imaging with fat saturation in
detecting cartilage defects in the knee: comparison with arthroscopy in 130 patients. AJR Am J Roentgenol 172:1073–1080detecting cartilage defects in the knee: comparison with arthroscopy in 130 patients. AJR Am J Roentgenol 172:1073–1080

Evaluation of the quality of tissue-repairEvaluation of the quality of tissue-repair
processesprocesses after surgical treatment: morphologyafter surgical treatment: morphology
 Important to know:Important to know:
 Type of cartilage repairType of cartilage repair
 Size and location within the jointSize and location within the joint
 Concomitant procedures (eg osteotomy or ligament repair)Concomitant procedures (eg osteotomy or ligament repair)
 The MR sequences commonly used for evaluatingThe MR sequences commonly used for evaluating
the morphology of cartilage repair are identical withthe morphology of cartilage repair are identical with
those used for evaluating cartilage lesionsthose used for evaluating cartilage lesions
 Specific grading systemsSpecific grading systems

Evaluation of the quality of tissue-repair processesEvaluation of the quality of tissue-repair processes
after surgical treatment: morphologyafter surgical treatment: morphology
 MOCART:MOCART:
 filling of the defectfilling of the defect
 integration of the border zone to the adjacent cartilageintegration of the border zone to the adjacent cartilage
 surface of the repair tissuesurface of the repair tissue
 structurestructure of the repair tissueof the repair tissue
 signal intensity of the repair tissuesignal intensity of the repair tissue
 intactness of the subchondral laminaintactness of the subchondral lamina
 intactness of the subchondral boneintactness of the subchondral bone
 adhesionsadhesions
 effusioneffusion

 3D MOCART3D MOCART
 Defect fillDefect fill
 Cartilage interfaceCartilage interface
 Bone interfaceBone interface
 SurfaceSurface
 StructureStructure
 Signal intensitySignal intensity
 Subchondral laminaSubchondral lamina
 Chondral osteophytesChondral osteophytes
 Bone marrow edemaBone marrow edema
 Subchondral boneSubchondral bone
 EffusionEffusion

 MOCARTMOCART
 Almost perfect agreement between readersAlmost perfect agreement between readers
 Comparing the MRI scores with clinical outcome (knee-Comparing the MRI scores with clinical outcome (knee-
related quality of life) 2 years after ACI: a statisticallyrelated quality of life) 2 years after ACI: a statistically
significant correlation was found forsignificant correlation was found for
 structure of the repair tissuestructure of the repair tissue
 changes in the subchondral bonechanges in the subchondral bone
 signal intensities of the repair issuesignal intensities of the repair issue

 volume of repair tissue generally decreases slightlyvolume of repair tissue generally decreases slightly
after the immediate postoperative periodafter the immediate postoperative period
 Stabilization repair tissue: approximately 3 monthsStabilization repair tissue: approximately 3 months
after AICafter AIC

 filling:filling:
 CompleteComplete
 Hypertrophy: thickness greater than that of theHypertrophy: thickness greater than that of the
native cartilagenative cartilage
 IncompleteIncomplete
 >50%>50%
 <50%<50%
 subchondral bone exposedsubchondral bone exposed

Complete Incomplete HypertrophyComplete Incomplete Hypertrophy

 Integration to border zoneIntegration to border zone
 Integration between repair tissue andIntegration between repair tissue and
subchondral bonesubchondral bone

 Signal Intensity of Repair TissueSignal Intensity of Repair Tissue
 3D spoiled GRE imaging3D spoiled GRE imaging
 low SI of healthy repair tissue immediately afterlow SI of healthy repair tissue immediately after
autologous chondrocyte implantationautologous chondrocyte implantation
 SI increases with time and, 6–9 months later, resemblesSI increases with time and, 6–9 months later, resembles
that of native cartilagethat of native cartilage
 9–12 months after ACI, the signal intensity of normal9–12 months after ACI, the signal intensity of normal
repair tissue reaches a plateaurepair tissue reaches a plateau

 Signal Intensity of Repair TissueSignal Intensity of Repair Tissue

 Surface of the repair tissueSurface of the repair tissue

 Change in subchondral laminaChange in subchondral lamina
 Change in subchondral boneChange in subchondral bone
 Edema-like signal intensity isEdema-like signal intensity is
common in the earlycommon in the early
postoperative periodpostoperative period
 Persistence or progression of mayPersistence or progression of may
indicate a failure of graftindicate a failure of graft
incorporationincorporation

after surgical treatmentafter surgical treatment:: biochemical structurebiochemical structure
 quantitative MRI techniques give the option ofquantitative MRI techniques give the option of
studying the composition of the cartilage matrixstudying the composition of the cartilage matrix
ultrastructure and can therefore be consideredultrastructure and can therefore be considered
molecular-imaging techniquesmolecular-imaging techniques
 particular interest for the study of cartilageparticular interest for the study of cartilage
repair: potential to evaluaterepair: potential to evaluate
 cartilage maturationcartilage maturation
 cartilage adaptation after surgery in vivocartilage adaptation after surgery in vivo

after surgical treatment: biochemical structureafter surgical treatment: biochemical structure
 most promising techniques:most promising techniques:
 the longitudinal relaxation time T1 in the presence ofthe longitudinal relaxation time T1 in the presence of
gadolinium:T1Gd =gadolinium:T1Gd = dGEMRICdGEMRIC indexindex
 transverse relaxation time T2:transverse relaxation time T2: T2 mappingT2 mapping
 DWIDWI: diffusion-weighted: diffusion-weighted imagingimaging
 validation research on native cartilage tissue,validation research on native cartilage tissue,
limited validation inlimited validation in cartilage repair tissuecartilage repair tissue

 dGEMRICdGEMRIC (delayed Gd enhanced MRI of cartilage):(delayed Gd enhanced MRI of cartilage):
detect proteoglycan depletion in articular cartilagedetect proteoglycan depletion in articular cartilage
 IV Gd-DTPA2-IV Gd-DTPA2-
 Diffuses in the cartilage layerDiffuses in the cartilage layer
 Equilibrates in inverse relation to the FCSEquilibrates in inverse relation to the FCS
(fixed charge density)(fixed charge density)
 Directly relates to the GAGDirectly relates to the GAG
(glucosaminoglycans) concentration(glucosaminoglycans) concentration

 dGEMRICdGEMRIC
 T1 mapping:T1 mapping:
 T1 values high in normal cartilageT1 values high in normal cartilage
 T1 values low in GAG-depleted degenerative cartilageT1 values low in GAG-depleted degenerative cartilage

 dGEMRICdGEMRIC
 Double dose Gd IVDouble dose Gd IV
 Moderate exercise (10-20 minutes joint movementModerate exercise (10-20 minutes joint movement
eg walking up and down stairs)eg walking up and down stairs)
 T1 imaging 90 minutes after injectionT1 imaging 90 minutes after injection

 dGEMRICdGEMRIC
 repair tissue: heterogeneous T1 values compared torepair tissue: heterogeneous T1 values compared to
normal cartilage prior to the administration of Gdnormal cartilage prior to the administration of Gd
 postcontrast T1 mapping does not correlate directlypostcontrast T1 mapping does not correlate directly
with GAG content, but the difference between pre-with GAG content, but the difference between pre-
and postcontrast imaging doesand postcontrast imaging does

 dGEMRICdGEMRIC
 In cartilage repair both pre- and postcontrastIn cartilage repair both pre- and postcontrast
measurements are currently considered necessary formeasurements are currently considered necessary for
a maximum sensitivity of the techniquea maximum sensitivity of the technique
 overall examination time of 2 h diminishes theoverall examination time of 2 h diminishes the
attractiveness for clinical useattractiveness for clinical use
 dGEMRIC can be considered to be the currentdGEMRIC can be considered to be the current
gold standard in cartilage ultrastructure MRIgold standard in cartilage ultrastructure MRI

 T2-mappingT2-mapping
 Quantitative T2 mapping correlates toQuantitative T2 mapping correlates to
 Collagen orientationCollagen orientation
 Collagen concentrationCollagen concentration
 Free waterFree water
 Native hyaline cartilage: depth wise variationNative hyaline cartilage: depth wise variation
 Radial zone: collagen highly ordered – shorter T2 valuesRadial zone: collagen highly ordered – shorter T2 values
 Transitional zone: less organization of the collagen –Transitional zone: less organization of the collagen –
longer T2 valueslonger T2 values

 T2-mappingT2-mapping
 assess the repair tissue organization and identify sites
of early-stage degeneration (early disruption of the
collagen matrix) in cartilage
 visualize tissue remodeling over time with
eventual success signaled by the emergence of a
collagen network that has a shape and overall and
zonal organization similar to those seen in normal
cartilage.

 DWIDWI: diffusion weighted imaging: diffusion weighted imaging
 molecular motion thatmolecular motion that is influenced byis influenced by
intra- and extracellular barriers: Brownianintra- and extracellular barriers: Brownian
motion of water molecules in tissuemotion of water molecules in tissue
 it is possible to estimate biochemicalit is possible to estimate biochemical
structure and architecture of the tissue bystructure and architecture of the tissue by
measuring molecular movementmeasuring molecular movement

 DWI: diffusion weighted imagingDWI: diffusion weighted imaging
 healthy cartilage: diffusion of water molecules restricted byhealthy cartilage: diffusion of water molecules restricted by
cartilage componentscartilage components
 disruption of the cartilage matrix results in enhanced waterdisruption of the cartilage matrix results in enhanced water
mobilitymobility

 DWI: diffusion weighted imagingDWI: diffusion weighted imaging
 In comparison with dGEMRICIn comparison with dGEMRIC
 no contrast medium is neededno contrast medium is needed
 the anatomical coverage is largerthe anatomical coverage is larger
 The spatial resolution higherThe spatial resolution higher
 the scan times are shorterthe scan times are shorter
 Diffusion:Diffusion:
 promising tool for compositional evaluation of cartilagepromising tool for compositional evaluation of cartilage
transplants in the futuretransplants in the future
 may be added to dGEMRIC and T2 mapping in a clinicalmay be added to dGEMRIC and T2 mapping in a clinical
setting for evaluation of cartilage repair outcomessetting for evaluation of cartilage repair outcomes

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