- Email: [email protected]
T1ρ Mri Assessment of Cartilage in a Large Animal Model of Traumatic Joint Injury
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Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
ms. 5mm width of subchondral trabecular bone of the medial joint was extracted (figure), and divided into 4 subregions: anterior, center, posterior, and medial. Trabecular bone microstructure at each region was measured by the dedicated software (TRI/3D-BON, Ratoc System Engineering Co., Ltd., Tokyo). Results: BV/TV (bone volume fraction) at the anterior, center, posterior, and medial regions were 29.5, 29.6, 15.5, 34.2 % respectively. Tb.Th (trabecular thickness) were 285, 294, 245, 338 mm, Tb.N (trabecular number) were 0.64, 0.58, 0.65, 0.61 /mm, and Conn.D (connectivity density) were 2.33, 2.38, 1.15, 2.48. Conclusions: Subchondral bones were increased particularly at the medial region of the medial proximal tibia, composed of thickened and well-connected trabecular bones. Subchondral bone microstructure measured by HR-pQCT may become a new imaging marker for OA knees.
410 T1r MRI ASSESSMENT OF CARTILAGE IN A LARGE ANIMAL MODEL OF TRAUMATIC JOINT INJURY D.R. Thedens, D.J. Heckelsmiller, B.J. Laughlin, M. Saad Eldine, D.R. Pedersen, D.C. Fredericks, J.E. Goetz. Univ. of Iowa, Iowa City, IA, USA Purpose: Osteoarthritis (OA) is the second leading cause of morbidity and disability in the United States and results in a high economic burden. An important subset of patients develop OA from traumatic joint injury that initiates the disease process. Post-traumatic OA (PTOA) tends to afflict younger and more physically active subjects, amplifying the physical and economic effects as these patients may become debilitated during their working years of life and are more likely to require joint replacement at a relatively young age. While radiographic evidence remains the clinical gold standard for OA diagnoses, such evidence of the degradation and loss of cartilage associated with OA may appear many years after the cascade of irreversible degenerative processes has begun. The resolution and outstanding soft tissue contrast of MRI offers the opportunity for early characterization of cartilage in injured joints. Emerging contrast mechanisms such as T1r relaxation have the potential to detect early stages of OA, when interventions may be possible to slow or forestall these degenerative processes. The purpose of this work was to investigate the ability of T1r to detect early cartilage changes in a large animal model of PTOA. Methods: Following an IACUC-approved protocol, five skeletally mature, castrated male goats were anesthetized and underwent an operation to introduce traumatic joint injury to the left knee. The procedure consisted of a partial meniscectomy of the anterior horn of the medial meniscus followed by a blunt impact to the weight bearing region of the medial femoral condyle using a hand-held impaction device. The original impact was approximately 6 mm in diameter and the trauma energy was 1.2 Joules. Following surgery, the goats roamed freely at pasture for a period of 24 weeks. At this time point, animals were euthanized and the impacted left knee and corresponding uninjured right knee were imaged intact. Scans were performed on a 3T Siemens Tim Trio scanner (Siemens, Erlangen, Germany). T1r weighted images derived from a segmented 3D GRE-based pulse sequence with a conventional T1r preparation block (þ90 tip-down, spin lock durations of 10, 20, 40, and 60ms at 400Hz amplitude, 90 tip-
up and crusher gradient (see figure below) applied prior to acquisition of segments of 16 centrically ordered k-space lines. Additional imaging parameters were intrasegment TR/TE ¼ 9.4/4.7ms, intersegment repetition time ¼ 1000ms, FOV ¼ 16cm x 16cm with 256x128 matrix covering 20 slices, BW¼260 Hz/pixel for a total scan time of 2:10 per spin lock time (8:40 per complete set). Images were acquired in the sagittal plane, selected to correspond to a 2D T2-weighted fat saturated acquisition for correlated morphology. T1r relaxation times were calculated using a monoexponential nonlinear least squares fit. Mean T1r relaxation times were computed for contours defined at consistent locations along the lateral femoral condyle for both left (injured) and right (control) knees and compared for each animal.
Results: The images below show a sample pair of injured and control knees with cartilage T1r relaxation time overlaid onto T2-weighted morphologic images, where the increased T1r is evident in the injured limb suggestive of degenerative cartilage changes. Mean T1r times trended consistently higher in the injured knee compared to the control knee in all five specimens, with injured knees having increased T1r by an average of 9% over the five samples, though the the difference did not reach statistical significance in this small sample (see chart below).
Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
Conclusions: This work demonstrates the feasibility of generating T1r assessments of cartilage condition in a large animal model of PTOA. T1r continues to show promise as an imaging biomarker for early detection of cartilage changes in vivo, trending towards increased relaxation times in injured cartilage as compared to the contralateral control. Further application of T1r relaxometry in this model in larger and longitudinal studies may potentially better elucidate the time course and mechanisms of cartillage degeneration in PTOA. 411 ANALYSIS OF SUBCHONDRAL BONE MICROSTRUCTURE BY HR-PQCT: RELATIONSHIP WITH THE SEVERITY OF KNEE OSTEOARTHRITIS AND ALIGNMENTS OF LOWER EXTREMITIES N. Okazaki, K. Chiba, M. Motoi, M. Osaki. Nagasaki Univ. Graduate Sch. of BioMed. Sci., Nagasaki, Japan Purpose: Changes of subchondral bone microstructure may have an important role in onset and progression of osteoarthritis (OA). We analyzed subchondral bone microstructure by using High Resolution peripheral Quantitative CT (HR-pQCT), and evaluated the relationship with the severity of knee OA and alignments of lower extremities. Methods: Subjects were 9 patients (10 knees) with knee OA (mean age 63.7 ± 8.9, range 51e78 years, all female, Kellgren-Lawrence (KL) grades I: 1, II: 1, III: 4, and IV: 4). Two cm width of proximal tibia was scanned by HR-pQCT (XtremeCT II, Scanco Medical, Switzerland) at the voxel size of 61 mm and integration time of 100 ms. Subchondral bone microstructure was analyzed by the dedicated software (TRI/3D-BON, Ratoc System Engineering Co., Ltd., Tokyo). 5mm width of subchondral trabecular bone of the medial joint was extracted, divided into 4 subregions: anterior, center, posterior, and medial, and trabecular bone microstructure at each region was measured. The alignments of lower extremity were measured in anteroposterior radiographs of lower extremities in standing position: percentage of mechanical axis (%MA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and medial minimum joint space width (mJSW). Relationship between subchondral bone microstructure, and the severity of knee osteoarthritis or alignments of lower extremities was analyzed. Statistical significant was established at p < 0.01. Results: At the medial region, %MA had a significantly negative correlation with trabecular thickness (Tb.Th) (r ¼ 0.782, p ¼ 0.008), and mLDFA and JLCA had a significantly positive correlation with Tb.Th (r ¼ 0.813, r ¼ 0.004, and r ¼ 0.826, p ¼ 0.003, respectively). Conclusions: Patients with genu varus malalignment had thickened trabecular bone at the medial region of the medial proximal tibia. In vivo assessment of subchondral bone microstructure changes by using HR-pQCT might be useful for elucidating the pathology of knee OA. 412 A NOVEL METHOD FOR IDENTIFYING RADIOGRAPHIC BASELINE RISK OF OSTEOARTHRITIS USING AN ANISOTROPY-BASED TEXTURE ANALYSIS ALGORITHM: DATA FROM THE OSTEOARTHRITIS INITIATIVE R. Ljuhar y, T. Haftner z, D. Ljuhar x, B. Norman y, A. Fahrleitner-Pammer k, H.P. Dimai k, J. Hladuvka ¶, S. Nehrer z. y ImageBiopsy Lab, Vienna, Austria; z Danube Univ. Krems, Krems, Austria; x Braincon Technologies, Vienna, Austria; k Dept. of Internal Med., Div. of Endocrinology and Metabolism, Graz, Austria; ¶ VrVis Ctr. for Visual Computing, Vienna, Austria Purpose: The accepted method for assessing OA - Joint space width (JSW) and Joint Space Area (JSA) measurements - have limited capabilities with respect to early identification and reproducible follow-ups of the disease. The objective of this abstract is to evaluate trabecular bone structure as area for early identification of OA risk, applying texture anisotropy algorithms and subsequently comparing the results to standard JSW and JSA measurements. Methods: This study was performed using data from the Osteoarthritis Initiative. The image data set was restricted to female, caucasian, right knee exams of the same modality which had a KL grade of 0 at the baseline exam with a deteriorating KL grade 2 at 96 months follow up. 22 CASES fulfilled these criteria with matching 22 CONTROLS with no signs of OA at 96 months follow up. The selected region of interest (ROI) for the analysis of the radiographic texture encompassed four ROIs in the subchondral tibia and one additional ROI in each femur condyle - in total 6 ROIs. For each individual ROI, the degree of texture anisotropy was calculated and
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compared between case/controls. In addition, JSW/JSA were calculated in both groups using a software-based method (i3a Technologies). Results: Whereas the JSW and the JSA measurements did not yield any significant differences with respect to their mean values (Cohen's d ¼ 0.139 and 0.028) , the calculated texture parameters showed that differences in values between Cases and Controls can be found in ROI1 and 2 with Cohens' d values of 0.625 and 0.831. With respect to selected patient groups, the differences in anisotropy results were significant using these texture parameters. Conclusions: Our results indicate that using the selected radiographic texture parameters, an early identification of patients at risk for developing OA using conventional x-rays can be achieved. This may offer an additional method for quantifying the risk of baseline OA. This is supported by the Conhen's d values that are by definition relatively large (0.625 and 0.831). Ongoing research focuses on larger sample set validation and the use of such algorithms for additional applications, such as the early identification of patients at risk for fractures.
Imaging: Preclinical Models 413 A NEW DOTA-FOLATE CONJUGATE (CM09) FOR IMAGING OF FOLATE RECEPTOR EXPRESSING MACROPHAGES IN A RAT MODEL OF OSTEOARTHRITIS H.M. de Visser y, N.M. Korthagen y, C. Muller z, F.P. Lafeber y, F.J. Beekman x, G.C. Krijger y, R.M. Ramakers x, S.C. Mastbergen y, H. Weinans y, k. y UMC Utrecht, Utrecht, Netherlands; z Paul Scherrer Inst., Villigen, Switzerland; x MILabs bv., Utrecht, Netherlands; k Delft Univ. of Technology, Delft, Netherlands Purpose: Inflammation in OA animal models can be monitored using SPECT/CT with a DOTA-folate radioconjugate targeting the folate receptor that is specifically expressed on activated macrophages. However, the increase in folate receptor expression on macrophages in OA animal models is small and radioactivity accumulates mainly in the kidneys. A novel DOTA-folate conjugate (cm09) was recently developed with a lowmolecular weight albumin-binding entity that enhances the blood circulation time of this conjugate, thereby improving the distribution of folate radioconjugates in the target tissue. In particular for its application in OA, where macrophages may be low abundant in the affected joint, this new radiotracer has potential applications. Our aim is to evaluate the in-vivo characteristics of the new 111In-Folate-conjugate (111In-cm09) in two different OA animal models compared to a control folate conjugate compound (111In-EC0800) without albumin binding entity. Methods: In 16 weeks old wistar rats OA was induced by either an intraarticular injection of MIA (n¼12) or groove surgery to induce local cartilage damage (n¼10). Saline injections and sham surgery was performed in the contralateral leg as an internal control. Four weeks after MIA injections and 12 weeks after groove surgery, the folate conjugates were radiolabeled with 111InCl3 at a specific activity of 20MBq/nmol and administrated via the lateral tail vein (60MBq in 600 mL of saline) under sedation. In addition, the specificity of the technique was tested by blockade of the Folate Receptor-b (FRb) by injection of an 500-fold excess of folic acid (100mg) immediately before radiofolate administration in 2 animals with MIA induced OA. SPECT/CT imaging with a high resolution rat multi-pinhole collimator (VECTor4CT, MILabs, Utrecht, The Netherlands) was performed 24 hours after radiolabeled folate administration. In-vivo whole-body and focused knee SPECT/CT images were obtained in all rats. Joint degeneration was assessed by histology using the OARSI histopathology score specific for the rat. Results: Labeling of compound cm09 had a high efficiency and a radiochemical purity of more than 98%. An increase in joint degeneration was observed in the MIA injected knee joints compared to the saline injected control knee joints (10,2 ± 2,1 vs. 1,8 ± 1,1; p¼0.011) together with a slightly increased synovial membrane inflammation (1.3 ± 0.8 vs 0.3 ± 0.7; p¼0.07). Four weeks after MIA induction in-vivo imaging resulted in a higher uptake in the experimental knee joints compared to the contralateral knee joints (0,217 %ID/cm3 ± 0,049 vs. 0,208 %ID/cm3 ± 0,052; p¼0.051, Figure 1). In parallel, in the groove operated knee joints, a mild joint degeneration was observed after 12 weeks, compared to the sham operated contralateral control knee joints (3,8 ± 1,1 vs. 1,56 ± 1,3; p¼0.026) without synovial membrane inflammation (0.3 ± 0.5 vs 0.1 ± 0.3; p¼0.32). In this mild non-inflammatory model no increase in macrophage activity was observed after 12 weeks compared
Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
ms. 5mm width of subchondral trabecular bone of the medial joint was extracted (figure), and divided into 4 subregions: anterior, center, posterior, and medial. Trabecular bone microstructure at each region was measured by the dedicated software (TRI/3D-BON, Ratoc System Engineering Co., Ltd., Tokyo). Results: BV/TV (bone volume fraction) at the anterior, center, posterior, and medial regions were 29.5, 29.6, 15.5, 34.2 % respectively. Tb.Th (trabecular thickness) were 285, 294, 245, 338 mm, Tb.N (trabecular number) were 0.64, 0.58, 0.65, 0.61 /mm, and Conn.D (connectivity density) were 2.33, 2.38, 1.15, 2.48. Conclusions: Subchondral bones were increased particularly at the medial region of the medial proximal tibia, composed of thickened and well-connected trabecular bones. Subchondral bone microstructure measured by HR-pQCT may become a new imaging marker for OA knees.
410 T1r MRI ASSESSMENT OF CARTILAGE IN A LARGE ANIMAL MODEL OF TRAUMATIC JOINT INJURY D.R. Thedens, D.J. Heckelsmiller, B.J. Laughlin, M. Saad Eldine, D.R. Pedersen, D.C. Fredericks, J.E. Goetz. Univ. of Iowa, Iowa City, IA, USA Purpose: Osteoarthritis (OA) is the second leading cause of morbidity and disability in the United States and results in a high economic burden. An important subset of patients develop OA from traumatic joint injury that initiates the disease process. Post-traumatic OA (PTOA) tends to afflict younger and more physically active subjects, amplifying the physical and economic effects as these patients may become debilitated during their working years of life and are more likely to require joint replacement at a relatively young age. While radiographic evidence remains the clinical gold standard for OA diagnoses, such evidence of the degradation and loss of cartilage associated with OA may appear many years after the cascade of irreversible degenerative processes has begun. The resolution and outstanding soft tissue contrast of MRI offers the opportunity for early characterization of cartilage in injured joints. Emerging contrast mechanisms such as T1r relaxation have the potential to detect early stages of OA, when interventions may be possible to slow or forestall these degenerative processes. The purpose of this work was to investigate the ability of T1r to detect early cartilage changes in a large animal model of PTOA. Methods: Following an IACUC-approved protocol, five skeletally mature, castrated male goats were anesthetized and underwent an operation to introduce traumatic joint injury to the left knee. The procedure consisted of a partial meniscectomy of the anterior horn of the medial meniscus followed by a blunt impact to the weight bearing region of the medial femoral condyle using a hand-held impaction device. The original impact was approximately 6 mm in diameter and the trauma energy was 1.2 Joules. Following surgery, the goats roamed freely at pasture for a period of 24 weeks. At this time point, animals were euthanized and the impacted left knee and corresponding uninjured right knee were imaged intact. Scans were performed on a 3T Siemens Tim Trio scanner (Siemens, Erlangen, Germany). T1r weighted images derived from a segmented 3D GRE-based pulse sequence with a conventional T1r preparation block (þ90 tip-down, spin lock durations of 10, 20, 40, and 60ms at 400Hz amplitude, 90 tip-
up and crusher gradient (see figure below) applied prior to acquisition of segments of 16 centrically ordered k-space lines. Additional imaging parameters were intrasegment TR/TE ¼ 9.4/4.7ms, intersegment repetition time ¼ 1000ms, FOV ¼ 16cm x 16cm with 256x128 matrix covering 20 slices, BW¼260 Hz/pixel for a total scan time of 2:10 per spin lock time (8:40 per complete set). Images were acquired in the sagittal plane, selected to correspond to a 2D T2-weighted fat saturated acquisition for correlated morphology. T1r relaxation times were calculated using a monoexponential nonlinear least squares fit. Mean T1r relaxation times were computed for contours defined at consistent locations along the lateral femoral condyle for both left (injured) and right (control) knees and compared for each animal.
Results: The images below show a sample pair of injured and control knees with cartilage T1r relaxation time overlaid onto T2-weighted morphologic images, where the increased T1r is evident in the injured limb suggestive of degenerative cartilage changes. Mean T1r times trended consistently higher in the injured knee compared to the control knee in all five specimens, with injured knees having increased T1r by an average of 9% over the five samples, though the the difference did not reach statistical significance in this small sample (see chart below).
Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
Conclusions: This work demonstrates the feasibility of generating T1r assessments of cartilage condition in a large animal model of PTOA. T1r continues to show promise as an imaging biomarker for early detection of cartilage changes in vivo, trending towards increased relaxation times in injured cartilage as compared to the contralateral control. Further application of T1r relaxometry in this model in larger and longitudinal studies may potentially better elucidate the time course and mechanisms of cartillage degeneration in PTOA. 411 ANALYSIS OF SUBCHONDRAL BONE MICROSTRUCTURE BY HR-PQCT: RELATIONSHIP WITH THE SEVERITY OF KNEE OSTEOARTHRITIS AND ALIGNMENTS OF LOWER EXTREMITIES N. Okazaki, K. Chiba, M. Motoi, M. Osaki. Nagasaki Univ. Graduate Sch. of BioMed. Sci., Nagasaki, Japan Purpose: Changes of subchondral bone microstructure may have an important role in onset and progression of osteoarthritis (OA). We analyzed subchondral bone microstructure by using High Resolution peripheral Quantitative CT (HR-pQCT), and evaluated the relationship with the severity of knee OA and alignments of lower extremities. Methods: Subjects were 9 patients (10 knees) with knee OA (mean age 63.7 ± 8.9, range 51e78 years, all female, Kellgren-Lawrence (KL) grades I: 1, II: 1, III: 4, and IV: 4). Two cm width of proximal tibia was scanned by HR-pQCT (XtremeCT II, Scanco Medical, Switzerland) at the voxel size of 61 mm and integration time of 100 ms. Subchondral bone microstructure was analyzed by the dedicated software (TRI/3D-BON, Ratoc System Engineering Co., Ltd., Tokyo). 5mm width of subchondral trabecular bone of the medial joint was extracted, divided into 4 subregions: anterior, center, posterior, and medial, and trabecular bone microstructure at each region was measured. The alignments of lower extremity were measured in anteroposterior radiographs of lower extremities in standing position: percentage of mechanical axis (%MA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and medial minimum joint space width (mJSW). Relationship between subchondral bone microstructure, and the severity of knee osteoarthritis or alignments of lower extremities was analyzed. Statistical significant was established at p < 0.01. Results: At the medial region, %MA had a significantly negative correlation with trabecular thickness (Tb.Th) (r ¼ 0.782, p ¼ 0.008), and mLDFA and JLCA had a significantly positive correlation with Tb.Th (r ¼ 0.813, r ¼ 0.004, and r ¼ 0.826, p ¼ 0.003, respectively). Conclusions: Patients with genu varus malalignment had thickened trabecular bone at the medial region of the medial proximal tibia. In vivo assessment of subchondral bone microstructure changes by using HR-pQCT might be useful for elucidating the pathology of knee OA. 412 A NOVEL METHOD FOR IDENTIFYING RADIOGRAPHIC BASELINE RISK OF OSTEOARTHRITIS USING AN ANISOTROPY-BASED TEXTURE ANALYSIS ALGORITHM: DATA FROM THE OSTEOARTHRITIS INITIATIVE R. Ljuhar y, T. Haftner z, D. Ljuhar x, B. Norman y, A. Fahrleitner-Pammer k, H.P. Dimai k, J. Hladuvka ¶, S. Nehrer z. y ImageBiopsy Lab, Vienna, Austria; z Danube Univ. Krems, Krems, Austria; x Braincon Technologies, Vienna, Austria; k Dept. of Internal Med., Div. of Endocrinology and Metabolism, Graz, Austria; ¶ VrVis Ctr. for Visual Computing, Vienna, Austria Purpose: The accepted method for assessing OA - Joint space width (JSW) and Joint Space Area (JSA) measurements - have limited capabilities with respect to early identification and reproducible follow-ups of the disease. The objective of this abstract is to evaluate trabecular bone structure as area for early identification of OA risk, applying texture anisotropy algorithms and subsequently comparing the results to standard JSW and JSA measurements. Methods: This study was performed using data from the Osteoarthritis Initiative. The image data set was restricted to female, caucasian, right knee exams of the same modality which had a KL grade of 0 at the baseline exam with a deteriorating KL grade 2 at 96 months follow up. 22 CASES fulfilled these criteria with matching 22 CONTROLS with no signs of OA at 96 months follow up. The selected region of interest (ROI) for the analysis of the radiographic texture encompassed four ROIs in the subchondral tibia and one additional ROI in each femur condyle - in total 6 ROIs. For each individual ROI, the degree of texture anisotropy was calculated and
S263
compared between case/controls. In addition, JSW/JSA were calculated in both groups using a software-based method (i3a Technologies). Results: Whereas the JSW and the JSA measurements did not yield any significant differences with respect to their mean values (Cohen's d ¼ 0.139 and 0.028) , the calculated texture parameters showed that differences in values between Cases and Controls can be found in ROI1 and 2 with Cohens' d values of 0.625 and 0.831. With respect to selected patient groups, the differences in anisotropy results were significant using these texture parameters. Conclusions: Our results indicate that using the selected radiographic texture parameters, an early identification of patients at risk for developing OA using conventional x-rays can be achieved. This may offer an additional method for quantifying the risk of baseline OA. This is supported by the Conhen's d values that are by definition relatively large (0.625 and 0.831). Ongoing research focuses on larger sample set validation and the use of such algorithms for additional applications, such as the early identification of patients at risk for fractures.
Imaging: Preclinical Models 413 A NEW DOTA-FOLATE CONJUGATE (CM09) FOR IMAGING OF FOLATE RECEPTOR EXPRESSING MACROPHAGES IN A RAT MODEL OF OSTEOARTHRITIS H.M. de Visser y, N.M. Korthagen y, C. Muller z, F.P. Lafeber y, F.J. Beekman x, G.C. Krijger y, R.M. Ramakers x, S.C. Mastbergen y, H. Weinans y, k. y UMC Utrecht, Utrecht, Netherlands; z Paul Scherrer Inst., Villigen, Switzerland; x MILabs bv., Utrecht, Netherlands; k Delft Univ. of Technology, Delft, Netherlands Purpose: Inflammation in OA animal models can be monitored using SPECT/CT with a DOTA-folate radioconjugate targeting the folate receptor that is specifically expressed on activated macrophages. However, the increase in folate receptor expression on macrophages in OA animal models is small and radioactivity accumulates mainly in the kidneys. A novel DOTA-folate conjugate (cm09) was recently developed with a lowmolecular weight albumin-binding entity that enhances the blood circulation time of this conjugate, thereby improving the distribution of folate radioconjugates in the target tissue. In particular for its application in OA, where macrophages may be low abundant in the affected joint, this new radiotracer has potential applications. Our aim is to evaluate the in-vivo characteristics of the new 111In-Folate-conjugate (111In-cm09) in two different OA animal models compared to a control folate conjugate compound (111In-EC0800) without albumin binding entity. Methods: In 16 weeks old wistar rats OA was induced by either an intraarticular injection of MIA (n¼12) or groove surgery to induce local cartilage damage (n¼10). Saline injections and sham surgery was performed in the contralateral leg as an internal control. Four weeks after MIA injections and 12 weeks after groove surgery, the folate conjugates were radiolabeled with 111InCl3 at a specific activity of 20MBq/nmol and administrated via the lateral tail vein (60MBq in 600 mL of saline) under sedation. In addition, the specificity of the technique was tested by blockade of the Folate Receptor-b (FRb) by injection of an 500-fold excess of folic acid (100mg) immediately before radiofolate administration in 2 animals with MIA induced OA. SPECT/CT imaging with a high resolution rat multi-pinhole collimator (VECTor4CT, MILabs, Utrecht, The Netherlands) was performed 24 hours after radiolabeled folate administration. In-vivo whole-body and focused knee SPECT/CT images were obtained in all rats. Joint degeneration was assessed by histology using the OARSI histopathology score specific for the rat. Results: Labeling of compound cm09 had a high efficiency and a radiochemical purity of more than 98%. An increase in joint degeneration was observed in the MIA injected knee joints compared to the saline injected control knee joints (10,2 ± 2,1 vs. 1,8 ± 1,1; p¼0.011) together with a slightly increased synovial membrane inflammation (1.3 ± 0.8 vs 0.3 ± 0.7; p¼0.07). Four weeks after MIA induction in-vivo imaging resulted in a higher uptake in the experimental knee joints compared to the contralateral knee joints (0,217 %ID/cm3 ± 0,049 vs. 0,208 %ID/cm3 ± 0,052; p¼0.051, Figure 1). In parallel, in the groove operated knee joints, a mild joint degeneration was observed after 12 weeks, compared to the sham operated contralateral control knee joints (3,8 ± 1,1 vs. 1,56 ± 1,3; p¼0.026) without synovial membrane inflammation (0.3 ± 0.5 vs 0.1 ± 0.3; p¼0.32). In this mild non-inflammatory model no increase in macrophage activity was observed after 12 weeks compared