Assessment and multiparametric functional MRI evaluation of Arthritis

Transcription

1 Assessment and multiparametric functional MRI evaluation of Arthritis T. Martin Noguerol, MD 1 ; A. Luna, MD 1 M. Gomez Cabrera 3, MD; J Vilanova 2, MD, PhD; M. Romero Rivera MD 3 ; F Caro Mateo MD 4 ; J. Broncano 4 ; SPAIN (t.martin.f@htime.org)

2 Purpose / aim 1. Optimize MRI protocols in the assessment of joints, including classic morphological and new functional sequences such as Dixon sequence, DWI, DCE-MRI and T2 mapping and dgemric for cartilage evaluation. 2. Analyze the utility of these techniques for articular evaluation, including large and small joints, in several clinical scenarios. Background The introduction of MRI for articular assessment has allowed a comprehensive evaluation of articular disease increasing the overall accuracy for joint evaluation. In the era of functional imaging, new advanced MRI sequences are being imported from other anatomical areas and successfully applied for articular evaluation in several clinical scenarios. These sequences are allowing a better understanding of the physiopathological processes that underlie the different types of arthritis providing valuable information that can be use as potential biomarkers of articular disease course and treatment response.

3 Introduction Joint diseases have been classically evaluated through conventional plain radiography (PR) Bone scintigraphy (BS) has been used for joint assessment as a criteria of active disease. Ultrasound (US) has also demonstrated to play a complementary paper in the evaluation of soft tissue involvement using Doppler techniques Computed tomography (CT) plays actually a limited role for specific joints or doubtful cases. The introduction of MRI for the joint assessment has supposed an overcome of several limitations of conventional imaging techniques. PR BS US CT MRI Bone erosions Bone edema Synovitis PR US Synovial fluid Cartilage evaluation Functional information Radiation Exogenous contrast /- - +/- Accessibility Charcot s arthropathy CT Sacroiliitis Joint effusion

4 Use of 3T magnets Bone marrow edema evaluation Phase/out of phase DIXON Phase-array or surface coils for small joint assesssment Use of parallell imaging for DWI adquisition Fitted FOV with high SNR 4D-DCE-MRI sequences for high temporal and spatial resolution Technical adjustments that allow improve the functional MRI evaluation of articular disease Multiecho T2 and postcontrast T1-weighted sequence with adjusted inversion time for cartilage assessment Metal artifacts reduction sequences (MARS) 3D sequences with Isotropic voxel to improve MPR

5 Sequences available for MRI articular evaluation Morphological sequences Functional techniques T1, T2 and PD-weighted Fat suppression: Spectral / non-spectral Chemical shift and DIXON DWI DCE-MRI Cartilage Quantification A B C D Multiparametric evaluation of synovitis. 59 y-o female with knee pain. (A) Axial T2 TSE shows mild joint effusion (arrows) without clear evidence of synovitis. (B and C) Axial DWI b800 and ADC map demonstrate absence of restricted diffusion within the fluid, consistent with transudate. (D) DCE-MRI study (maximum relative enhancement and time intensity curve) shows progressive enhancement of synovial (arrows) consistent with inflammatory synovitis.

6 Fat suppression techniques In the assessment of joint disease, the detection of bone edema / osteitis is very important,, along with synovial involvement. The presence of bone edema has been demonstrated to correlate with the overall patient outcome, preceding the existence of bone erosions and joint deformity. MRI is considered the single modality able to assess properly the presence, location and extension of bone edema. Several MRI sequences based on fat suppression techniques have been classically used for bone marrow edema evaluation. New technical optimization of these sequences are being developed to improve bone edema detection and quantification, such as chemical shift and DIXON. MARS protocols have been developed allowing to reduce metal related artifacts. However, we have to remind that, the classical TSE T1-weighted sequence still plays a major role in the detection of bone marrow edema. Radiographics 2000; 20: A C Metal artifacts reduction sequences (MARS). 59 y-o female with left hip recent surgery refers pain and local heat. (A) Coronal STIR image is not evaluable due to severe magnetic susceptibility artifact. (B) Coronal T1 MARS and (C and D) axial STIR MARS images allow to rule out edema, fluid or other signs of infection thanks to the reduction of metal artifacts with proper hip MRI evaluation. B D

7 Fat suppression techniques Chemical shift (CS) Inversion CS + Inversion In phaseout of phase Fat-sat (CHESS) Water excitation DIXON STIR SPIR SPAIR Physical basis Change of TE Selective RF pulse that suppresses fat Selective RF pulse that excites water Different TEs, mathematic postprocessing Selective inversion of short T1 tissues Spectrally selective RF pulse that suppresses fat Spectrally adiabatic selective RF pulse that suppresses fat Advantages Fast High SNR High SNR Contrast enhanced studies Fast 3D acquisition Four in one acquisition Quantification Less prone to Less prone to B0 and B1 Pre- and post contrast studies Insensitive to B1 B0 and B1 Drawbacks Sensitivity to B0 Sensitivity to B0 and B1 at large FOV Sensitivity to B0 Acquisition time Suppress all short T1 structures Sensitivity to B0 Sensitivity to B0 Msk system application Detection of bone infiltration Bone edema evaluation in joints MRarthrography Cartilage evaluation All in one technique High SNR Less metal induced artifacts Large FOV (spine) Multiple interfaces (fingers, toes, metal) Postcontrast imaging of inflammatory or neoplastic conditions Large FOV and high SNR needed: thigh or MRneurography RadioGraphics 2014; 34:

8 w f Chemical shift and DIXON Is well known that fat and water resonate at different frequencies. Changing the TE we can substrate fat w w T=0 TE=2.24 msec TE=4.48 msec IP = W signal + F signal OP = W signal F signal ½ [IP+OP] = ½ [(W+F) + (W-F)] = ½ [2W] = W only ½ [IP-OP] = ½ [(W+F) - (W-F)] = ½ [2F] = F only f f signal from water signal and obtain, in a basic sequence an in-phase and opposed-phase gradient echo acquisition. Several advanced sequences have emerged as a technical optimization of chemical shift based on DIXON experiment. DIXON technique is able to acquire several TE at the same time and combine them to obtain, not only a in phase or opposed phase imaging, but also a fat only and water only maps. Dixon imaging goes beyond a simple fat suppression technique. This approach supposes an improvement in lesion detection, as in only one acquisition 4 sets of images are got. In addition, it gives a robust quantitative tool for measurement of signal intensity in the different acquired image sets allowing treatment monitoring.

9 Chemical shift and DIXON Normal red marrow Edema/infiltration of red bone marrow Normal yellow marrow Edema in yellow marrow FAT ONLY OUT OF PHASE IN PHASE WATER ONLY Chemical shift scheme. In normal red marrow (red box) a similar proportion of water and fat protons is identified within a voxel. Thus, signal intensity is cancelled in out of phase (OP) images (1 st click). If an increase of water component (e.g. due to edema or metastasis) occurs, the signal intensity of the voxel will remain unchange (2 nd click). Scarce studies have evaluated the behavior of yellow marrow (yellow box) with chemical shift. The presence of higher fat than water avoids the cancellation of the signal intensity at OP (3 rd click). However if a there is an increase in water content (due to edema) that equals the fat proportion, a loss of signal will be detected at OP (4 th click). 32 y-o female with knee pain and suspected rheumatoid arthritis. OP image shows large hypointense areas at both condyles (arrows), more conspicuous than in IP image, consistent with bone edema. Note the presence of bone erosions and synovitis (red arrow) better depicted on W-O imaging.

10 DIFFUSION WEIGHTED IMAGING DWI evaluates the movement of the free water within tissues. This property allows an indirect estimation of cellularity and cells membrane integrity being able to discriminate hypercelullar lesions from normal tissues. DWI provides quantative information using the apparent diffusion coeficient (ADC) that represents the exponential decay of a single component of diffusion signal, used for lesion characterization and treatment monitoring. DWI is a SS-EPI sequence prone to susceptibility and motion artifacts, that are usual in joint evaluation, specially in fingers and toes, due to air-bone-soft tissue interfaces. For bone evaluation, the addition of PROPELLER is helpful, due to its ability to reduce artifacts. A multi-channel coil or surface coils are usually needed to use parallel imaging and obtain adequate SNR. Parameter 1.5T 3T RF Diffusion Gradient TE Field echoes EPI-readout Sequence SSh-EPI SSh-EPI TR/TE 5054/78 ms 5657/155 ms b values 0, 700 0, 900 FOV 166 x x 180 Matrix 84 x 57 mm 120 x 119 Plane Axial Axial Time (min) 3:50 2:44

11 DIFFUSION WEIGHTED IMAGING DWI allows a qualitative and quantitative assessment of arthritis without need of exogenous contrast and in a relative short scan time. It is not uncommon that patients with joint disease show an underlying systemic disease with renal function impairment or are children with juvenile idiopathic arthritis with inherent drawbacks for intravenous puncture. In this scenario, DWI can be considered as an alternative to contrast-enhanced sequences DWI may be used for joint evaluation for 3 aims: Soft tissue assessment, particularly for synovial involvement Joint effusion characterization Bone marrow edema detection A B C D ADC: 1.1 x 10-3 mm 2 /s Septic synovitis. (A) Axial postcontrast SPIR T1-weighted image shows a large joint effusion with intense synovial enhancement and thickening. (B and C) DWI b800 and ADC map demonstrated areas of severe restricted diffusion of articular fluid at lateral patellar recess consistent with exudate (proven by arthrocentesis). (D) Fusion of STIR and DWI helps to better correlate morphological and functional findings and to target the arthrocentesis in order to avoid false negative results. European Journal of Radiology 55 (2005) European Journal of Radiology 76 (2010) Eur Radiol (2003) 13:

12 DWI and bone marrow Normal yellow marrow is composed by fat: Lipid-bound water protons have restricted mobility. Lipids themselves show also low diffusivity. Reactive bone edema: The amount of water protons, and its movement increase, with consequent raising of ADC values. Thus, a shine through T2 effect like is identified. In osteomyelitis, there is a severe increase in water, inflammatory cells, debris and vasculature, with restricted water movement and high signal on high b values and low ADC (but not as lower as normal bone marrow). DWI Signal Intensity ADC values Water and cellularity

13 DCE-MRI DCE is usually based on a 3D gradient echo sequence with high temporal resolution (applying a dynamic scan < 4 seconds per dynamic). The use of DCE-MRI with high temporal resolution shows several advantages over conventional multiphase DCE-MRI (temporal resolution between 12 to 20 seconds) allowing a better and accurate assessment of the dynamic enhancement process. New 4D acquisitions that combine high temporal and spatial resolution have demonstrated a great utility. In joint disease, our target structure on DCE-MRI is the synovial. DCE-MRI helps to understand the specific and complex physiopathological process that underlies each specific type of arthritis. Most of the differential diagnosis may be performed in basis of the enhancement characteristics of the synovial along bone edema pattern and distribution. Sometimes the clue is not only in the first phases of dynamic contrast uptake but also in the latter equilibrium phases. For this reason, is highly recommendable to acquire delayed sequences with fat suppression up to 10 minutes after gadolinium injection. Skeletal Radiol (2012) 41:51 59 DCE-MRI of septic synovitis. Relative enhancement map shows a fast synovial gadolinium uptake (marked red TIC initial slope) with mild posterior wash-out compared with muscle (green line).

14 Kep DCE-MRI MODELS Ve Vp Ktrans MONOCOMPARTMENTAL: considers only the movement of contrast from artery to vein. BICOMPARTMENTAL: considers an extravascular extracellular space with leakage and recirculation of contrast from capillaries Qualitative Easy to perform Widely used in clinical setting Sample ROI error Visual TIC evaluation Semi-quantitative Obtain TIC, parametric maps and non-physiological data: maximum enhancement, rate of enhancement, time to peak, area under the curve Depend on sequence design TR, flip angle (FA), amount of contrast Parametric analysis of signal intensity Quantitative Physiological process Complex to apply T1 maps Contrast agent concentration Arterial input fraction (AIF) Obtain TIC, parametric maps and nonphysiological and physiological data: Kep, Ktrans, Ve, Vp Pharmacokinetic model

15 DCE-MRI ANALYSIS The analysis of DCE-MRI studies has been classically performed in basis on a ROI settings. ROIs provide an average of data included on an usually freehand draw area. This method, although widely used, is prone to several source of potential sample errors. Other semi-automatic analysis methods have been purposed based on a pixel by pixel evaluation of signal intensity data recorded on DCE-MRI studies. A certain TIC or value is assigned to each voxel allowing a better assessment of heterogeneity of synovitis process. Advantages Drawbacks ROI -Fast approach -Available on almost work stations -Volume partial effects (false positive and false negative results) -Scarce reproducibility -Average TICs generated that usually are overlapped -Mostly qualitative Pixel by pixel -Computer aided -Reproducible -Assess lesion heterogeneity -Quantitative -Need of specific software -Lack of standardization European Journal of Radiology (2013) Reports in Medical Imaging 2013:

16 CARTILAGE IMAGING: T2 mapping T2-mapping is based in the indirect estimation of collagen fiber content and its organization in cartilage. A direct lineal correlation between T2 relaxation time values and water cartilage content has been demonstrated. A indirect exponential correlation between T2 relaxation time and collagen cartilage content has also been demonstrated. For this aim, a multi-echo SE sequence is applied. Radiology (2013) 267, T2 mapping reflects the T2 relaxation time of cartilage. The presence of areas of increase of T2 values (arrows) is related with increase in water content and loss of collagen fibers (proteoglycans). 1. Water bounded to collagen fibers shows limited T2 relaxation times. Only superficial layers have higher T2 relaxation time. 2. With collagen loss, there is a release of water molecules, which increase the T2 relaxation time of cartilage.

17 CARTILAGE IMAGING: dgemric dgemric is used to estimate the joint cartilage glycosaminoglycan (GAG) content by T1-Relaxation time data after cartilage penetration of the hydrophilic contrast agent (Gd-DPTA2-). The protocol includes intravenous injection of Gd with posterior soft exercise of the joint for over min. 1-2 hours after Gd injection a FSE IR T1 sequence is adquired with variation of TI delay from 50 ms to 1600 ms with a fixed TE/TR of 14/1800 ms. An inverse linear correlation between GAG concentration and dgemric values is obtained. Areas with short T1 relaxation time have reduced GAGs content. Areas with long T1 relaxation time have high GAGs content The presence of enhanced areas (arrow) within cartilage in dgemric images is related to loss of GAGs and penetration of Gd inside of cartilage. Osteoarthirtis and Cartilage (2006) suppl The presence of GAGs negatively charged in normal cartilage, repels Gd molecules in synovial fluid. 2. With GAG loss, there is a passive transfer of Gd molecules inside the cartilage, shortening its T1 relaxation time.

18 CARTILAGE IMAGING: DWI DWI is able to characterize cartilage composition in basis of evaluation of free water motion at different cartilage layers. Water molecules motion in normal cartilage is relatively hindered due to presence of glycosaminoglycan (GSG) with ADC values between x 10-3 mm2/s A GAGs loss supposes an increase in free water motion and thus, higher ADC values. The presence of areas (arrow) within increase of ADC value is consistent with loss of GAGs and increase of free water motion within cartilage. Osteoarthirtis and Cartilage (2006) suppl The presence of GAGs conditions a restriction in free movement of water molecules. 2. With GAG loss, there is an increase in free water molecules motion with rise in ADC values.

19 A CARTILAGE IMAGING Cartilage evaluation has to be one of the goals for MRI joints evaluation. The loose of physiologic cartilage proprieties precedes the development of bone damage and joint deformity. The objective is to detect this cartilage injury before it can be evident on conventional MRI sequences. As we have seen each techniques is able to assess a different biological characteristic of cartilage. A multiparametric assessment can provide clues about the nature of cartilage damage and personalize therapeutics options. B C Cartilage damage evaluation. (A) Axial fat-suppressed PD weighted image shows a subtle area with increased signal intensity (arrow). (B) d-gemric sequence doesn t evidence any Gd uptake at the suspicious area (arrow). (C) T2 mapping shows moderate increase of relaxation times at this area (arrow). Those findings are consistent with cartilage damage due to loss of collagen fibers but without involvement of GAGs structure.

20 CLINICAL SCENARIOS INFECTIOUS ARTHRITIS SACROILIITIS RHEUMATOID AND OTHERS ARTHRITIS OSTEOARTHRITIS TRAUMATIC ARTHRITIS TREATMENT MONITORING

21 INFECTIOUS ARTHRITIS The most frequent causes of septic arthritis are direct invasion through an skin defect/ulcer or hematogenous spread. In other cases, the infection is related with previous joint replacement surgery. Clinical and biochemical criteria are usually enough for an appropriate diagnosis. However, in most cases, imaging tests are needed in order to evaluate the extension of the infection, specially to rule out bone involvement. MRI has demonstrated the higher accuracy for septic arthritis assessment. The introduction of functional MRI sequences may allow to increase the specificity of our diagnosis, specially in the evaluation of physiologic characteristics of synovial, joint effusion and neighbor bone. The use of DWI may allow to avoid unnecessary arthrocentesis with the consequent decrease of derived complications (secondary pyogenic arthritis, fistulae ). Journal of magnetic resonance imaging (2007) 25: Pediatric Rheumatology 2012, 10:20

22 Synovitis and joint effusion DWI has demonstrated high accuracy in differentiation between synovial thickening and reactive joint effusion with high signal intensity on high b values due to hyper cellularity. Intermediate ADC values ( x 10-3 mm 2 /s) in may be found due to synovial great vascularization and perfusion related effect associated. DWI can be used as a powerful tool in the differential between reactive effusion (transudate) and purulent fluid (exudate) showing the latter lower ADC values due to presence of pus, debris and cellular components. In a similar manner complicated septic tenosynovitis can be assess using DWI. DCE-MRI is also able to discriminate between synovial thickening and effusion and allows to assess the soft tissues involvement and rule out the presence of necrotic areas en severe septic arthritis. Skeletal Radiol 2000;29(6): A B C * ADC: 2.8 x 10-3 mm 2 /s Patient with knee swelling. A, B and C. Axial SPIR T1-gad, DWI b 900 and ADC map of a patient with articular fluid and synovial enhancement. Large articular effusion is seen without significant restricted diffusion consistent with transudate due to rheumatoid arthritis confirmed by arthrocentesis. Note the presence of condral erosion near to patellar apex (asterisk). A B Synovitis DCE-MRI assessment. (A) Axial T2 TSE show small amount of apparent fluid at rotator interval (arrow) and at glenohumeral joint. (B) Relative enhancement map demonstrated intense enhancement (arrow) of anterior fluid collection (red TIC) compared with muscle, consistent with synovitis.

23 Bone involvement In cases of reactive bone involvement, an increase of signal intensity on high b value DWI will be depicted with higher ADC values (T2 shine-through) compared with normal bone due to increase of water content at subchondral bone. Postcontrast fat suppression T1-weighted sequences usually help in the detection of bone marrow involvement due to the presence of increased enhancement. Normal yellow marrow, will show no significant change in signal intensity regarding the baseline. An intense enhancement with slight progressive increase the enhancement slope of the time intensity curve (TIC) compared to baseline marrow (type II curve) with no clear evidence of washout phenomena is identified in bone structures of joints with septic arthritis. However, it has been reported a lesser perfusion of bone structures than expected on the initial phases of DCE-MRI at epiphysis of involved bone, probably due to an increase of hydrostatic pressure or even septic thrombosis of epiphyseal vessels, circumstance that may lead in an avascular necrosis. AJR (2012) 198:2, B A ADC map/values T2 FFE DWI b800 Multiparametric bone involvement in septic arthritis. (A) DCE- MRI study with relative enhancement map shows intense uptake of subchondral bone (red curve) compared with normal bone (blue line). (B) DWI allows to evaluate bone involvement better than conventional sequences showing higher SI on b 800 and higher ADC values (arrows) than normal marrow.

24 SACROILIITIS Fat suppression techniques have high accuracy but relative lack of specificity in discrimination early acute vs subacute disease. DWI has demonstrated to increase the conspicuity of bone subchondral edema (probably thanks to a better background noise suppression) and the specificity of these changes in patient with early SI. Higher ADC values ( x 10-3 mm 2 /s ) have been found in affected subchondral bone compared with control groups ( x 10-3 mm 2 /s ). For spine spondyloarthritis higher ADC values at vertebral endplates have also be found compared with classical degenerative Modic type 1 inflammatory changes. Some papers have also demonstrated a significant correlation between ADC values and biochemical markers of disease activity (CPR). A D B b 800 C Acute sacroiliitis. (A) Coronal STIR shows left sacral foci of subchondral bone edema, which appear hyperintense on (B) DWI with higher ADC values (C) than contralateral bone surface. (D) Fused DWI and STIR images allows a better depiction of bone edema. European Journal of Radiology 83 (2014) A B C b 800 In chronic SI, there is low signal intensity on DWI and a decrease in ADC values (C) due to fatty replacement and sclerosis (arrows in A, axial STIR and B, DWI)

25 SACROILIITIS Postcontrast fat suppression T1-weighted images as well as DCE-MRI have demonstrated it usefulness for SI detection with higher accuracy of the latter for detection of active disease even in the earliest phases. Perfusion of SI may be also assessed by means of IVIM model with the advantage of avoid the use of exogenous contrast agent in patients that will probably undergo repeated MRI contrast enhanced studies. A Acute sacroiliitis. (A) Axial STIR shows severe edema at left sacroiliac joint with soft tissue involvement. (B) DCE-MRI with maximum enhancement map demonstrated intense and progressive enhancement of left SI joint (red curve) compared with right one (blue curve) as well as subchondral bone and soft tissue enhancement (green and blue areas on parametric map. B A B C Early detection of SI. (A) No signal abnormalities are identified at axial STIR. (B) DCE-MRI with maximum relative enhancement map shows subtle asymmetric uptake at subchondral bone of left SI joint (arrow and red curve) compared with contralateral joint (green curve). (C) Follow-up MRI 6 months later, STIR demonstrates the presence of subchondral edema (arrow) consistent with SI. Eur Radiol (2015) 25:

26 RHEUMATOID ARTHRITIS Rheumatoid arthritis (RA) pathogenesis starts with an autoimmune inflammatory reaction against antigens located at the synovium that usually leads in a joint destruction. As in SI, MRI has demonstrated to be superior than conventional imaging for detection of RA even in early phases. Detection and characterization of synovitis and subchondral bone edema have to be the main focus as it has been already demonstrated that is the stronger predictor of early RA and bone erosions respectively. This item has been included in a MRI scoring system for RA evaluation (RAMRIS) as indicator of disease activity. The range of fat suppression techniques available has improved the ability of MRI for bone edema detection. Functional sequences like DWI or DCE-MRI have also contributed to increase the overall accuracy of MRI for RA assessment and provides several parameters that may be used as biomarkers of RA activity.

27 RHEUMATOID ARTHRITIS DWI has demonstrated a high accuracy for synovitis detection in wrist and hand (specially in metacarpophalangeal and proximal phalangeal joints) in patients with RA. The synovium infiltration by inflammatory cells may lead in a hindered molecular water mobility. Besides, the inherent background suppression of surrounding tissues, increases the sensitivity and specificity of DWI over other techniques for synovitis (and tenosynovitis) detection. However, the application in hands and feet of DWI sequences is prone to suffer form inhomogeneities of magnetic field and low SNR. Magnetic Resonance Imaging 32 (2014) A B Multiparametric rheumatoid arthritis evaluation. (A) Coronal STIR shows severe articular surface erosions with subchondral edema and synovial hypertrophy at 3 rd metatarso-phalangeal joint (arrow). (B) Axial DWI b800 demonstrated markedly restricted diffusion within this joint with good correlation on (C) fused image. (D) DCE-MRI relative enhancement map shows intense and progressive gadolinium uptake (red curve) compared with adjacent joint (green curve) C D

28 RHEUMATOID ARTHRITIS A Rheumatoid arthritis evaluation. (A) Coronal STIR shows severe fingers deformity identifying areas of subchondral edema and bone erosion at 3 rd (not shown) and 5 th metacarpo-phalangeal joints (arrow). (B) DCE-MRI with maximum enhancement map demonstrates intense enhancement (red curve) compared with 4 th (not affected) metacarpophalangeal joint (green curve). Arthritis Research & Therapy 2014, 16:452 Arthritis Rheum 2003;48: Rheumatology 2012;51:1240?1245 B DCE-MRI studies have become the spearhead in evaluation of RA specially for the assessment of synovitis demonstrating a high correlation with clinical, biochemical and histological markers of disease activity. The steepness of TIC, usually with a fast initial enhancement phase and posterior plateau or washout phase, correlates better with the physiopathological synovitis process than the single use of pre and post-gad T1 sequences. Semi-quantitative parameters such as maximum enhancement (ME) or rate of early enhancement (REE) may be used as potential biomarkers and allow to detect changes in synovium vasculature before changes in synovium volume or bone edema occur. Parameters derived form pharmacokinetic models such as K trans or K ep have also demonstrated to be elevated in patient with RA reflecting the increase in both perfusion, extravascular space and permeability in synovitis with special utility for treatment monitoring. These parameters also allow to discriminate by themselves between patients with active from inactive disease and healthy persons.

29 RHEUMATOID ARTHRITIS Synovitis of cranio-cervical joint has been also studied by DWI and DCE-MRI sequences demonstrating synovitis before morphological changes. This early detection may help to prevent neurological complications in this crossroads region. Besides clinical and biochemical criteria, DCE-MRI has demonstrated to be able to discriminate between RA and psoriasic arthritis (PA). A significant difference has been founded in relative enhancement rate (RER), not in the first phases, but at delayed acquisition 15 min after Gad injection, with greater RER in RA. These results are a reflection of histopathology of synovitis in RA which presents higher cellullarity and greater number of vessels compared with PA. European Journal of Radiology 81 (2012) AJR 194 (2010) A C Rheumatoid arthritis involvement of cranio-cervical joint. (A) Sagittal STIR and (B) axial T2 TSE show severe hypertrophy of synovial pannus and small amount of fluid with erosive changes at odontoid process (arrow). (C) Tractography DTI reconstruction demonstrated low FA values with compression of medulla (arrow). B

30 Other arthritis Tophaceus gout with classical involvement of feet, or more infrequent, of knee can be studied through functional techniques: Bone edema and erosion can be properly assessed by fat suppression techniques, even DWI. DCE-MRI show sprogressive and intense enhancement at joints with gout deposits. Juvenile idiopathic arthritis has also been successfully evaluated with functional imaging with promising results for knee, wrist or hip involvement with several advantages in young patients: Lack of ionizing radiation Assess of activity or subclinical synovitis in patients with difficult clinical examination Identify high risk patient and treatment monitoring Value of DWI in order to avoid use of exogenous contrast as an alternative to assess bone edema and synovitis Tophaceus gout. 1. Classical involvement of 1 st metatarso-phalangeal joint with subchondral edema, erosions and intense and progressive enhancement on DCE-MRI Relative enhancement map (red curve) compared with adjacent joints. 2. Atypical knee gout. Ill-defined lesion is identified at upper patellar pole with involvement of quadriceps tendon and moderate restriction of diffusion (arrows). 1 STIR 2 DP b800 ADC Pediatr Radiol (2010) 40:

31 OSTEOARTHRITIS The active erosive changes that occurs in the first phases of osteoarthritis (OA) may be studied by functional MRI sequences. If treatment is introduced in this phase, before reparative changes occurs, the course of the disease may be stopped avoiding joint deformities. Based on DCE-MRI, differences between RA and OA can be found that reflects the different physiopathology of RA (inflammatory) and OA (degenerative). OA shows higher semi-quantitative (REE or ME) and quantitative (Ktrans, Kep) values than control subjects but in a lesser level than RA, probably due to a lower angiogenic potential and permeability of synovium in OA. A B C D E Osteoarthritis. (A) Axial STIR shows subchondral edema at lateral aspect of femoral condyle and minimal amount of intra-articular fluid, without evidence in DWI (b800) or ADC (B, C) of restricted diffusion (arrows). (D) DCE-MRI Relative enhancement map demonstrated moderate synovitis with progressive TIC (red curve) compared with synovial at contralateral compartment. (E) Sagittal T1 SPIR 5 minutes after gadolinium injection still shows synovial and subchondral reactive enhancement.

32 Cartilage evaluation In RA, due to the inner nature of the disease, there is an activation of inflammatory intermediaries that lead in a cartilage destruction. Early detection of cartilage damage may allow to treat patients with potential better outcome than in advanced RA or OA stages. In OA, cartilage damage is usually present at high pressure points. However, cartilage lesion in RA and other inflammatory arthritis can be seen at any area of cartilage joint surface. Chondromalacia assessment is nowadays one of the most important application of cartilage evaluation techniques. A C Cartilage evaluation. (A) Axial T2 FFE shows a doubtful area of increase intensity at it lateral aspect (arrow). (B) T2 map demonstrated a severe increase of T2 relaxation time at this level (arrow, blue area). (C) DWI-cartilage sequence shows a good correlation with severe increase of ADC values at the same zone on (D) color coded ADC map consistent with loss of GAGs and increase of free water movement (arrow). B D

33 TRAUMATIC ARTHRITIS The utility of functional MRI sequences in traumatic arthritis is limited, mainly due to its origin is almost always known (traumatic precedent)m and it course depends on the location and complications associated to trauma. However, is important to remind these characteristics in order to simplify the differential diagnosis in cases of doubtful traumatic origin or in patients with superimposed history of RA, OA or other arthropathy. Sports lesions, specially when cartilage is involved, are the other potential application of functional techniques in traumatic arthritis helping in the scoring the severity of the injury, prognosis prediction and close treatment monitoring. A C B D DIXON sequence for traumatic knee evaluation. With one acquisition a (A) fat only, (B) water only, and (C) phase/ (D) out of phase images set can be performed. In this patient an area of subchondral edema is identified at lateral femoral condyle better depicted at water only image (arrow). This lesion is more conspicuous at out of phase than in phase image. Note also the presence of moderate articular fluid and subcutaneous edema due to previous trauma.

34 Therapy monitoring DCE-MRI has been compared to progression of bone erosion and a significant correlation has been founded between the REE and the presence of erosive changes in the next 2 years. The response to steroid and non-steroid anti-inflammatory drugs can be assessed by reduction of angiogenesis in DCEderived parameters. Besides, cartilage techniques may reflect improvement after cartilage repair surgery or chondrocytes graft not only in its thickness, but also, in the itself cartilage composition. Treatment monitoring. (A and B) Wide area of cartilage denudation is identified on PD at medial femoral condyle (arrow) with increase of T2 relaxation time, (red box). (B and C) 6 months follow up after cartilage repair surgery demonstrated a thicker cartilage on PD at the same area with decrease of T2 relaxation time, consistent with adequate response to treatment and recovering of cartilage structure. Rheumatology 2000;39: A C B D

35 SUMMARY Technical improvements of fat suppression sequences enable a faster and better detection of bone involvement. Advanced MRI techniques, specially DWI and DCE provide functional information of bone and soft tissue in joint disease evaluation. New MRI cartilage sequences can evaluate early cartilage damage before conventional sequences can detect it, providing quantitative information. Integration of these functional techniques within conventional protocols should be considered not only for diagnostic purposes but also for treatment monitoring.