Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Deletion of the mRNA stability factor ELAVL1 (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, α-smooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell-cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of signaling molecules involved in stromal activation and extracellular matrix organization [i.e. platelet-derived growth factor AA (PDGFAA) and pentraxin 3]. Ribonucleoprotein immunoprecipitation analysis and transcription inhibition studies validated PDGFA mRNA as a novel HuR target. These data suggest that tumor-intrinsic HuR supports extrinsic activation of the stroma to produce collagen and desmoplasia through regulating signaling molecules (e.g. PDGFAA). HuR-deficient PDAC in vivo tumors with an altered tumor microenvironment are more sensitive to the standard of care gemcitabine, as compared to HuR-proficient tumors. Taken together, we identified a novel role of tumor-intrinsic HuR in its ability to modify the surrounding tumor microenvironment and regulate PDGFAA.

An Advanced Thermal Decomposition Method to Produce Magnetic Nanoparticles with Ultrahigh Heating Efficiency for Systemic Magnetic Hyperthermia.

Due to the limited heating efficiency of available magnetic nanoparticles, it is difficult to achieve therapeutic temperatures above 44 °C in relatively inaccessible tumors during magnetic hyperthermia following systemic administration of nanoparticles at clinical dosage (≤10 mg kg-1 ). To address this, a method for the preparation of magnetic nanoparticles with ultrahigh heating capacity in the presence of an alternating magnetic field (AMF) is presented. The low nitrogen flow rate of 10 mL min-1 during the thermal decomposition reaction results in cobalt-doped nanoparticles with a magnetite (Fe3 O4 ) core and a maghemite (γ-Fe2 O3 ) shell that exhibit the highest intrinsic loss power reported to date of 47.5 nH m2 kg-1 . The heating efficiency of these nanoparticles correlates positively with increasing shell thickness, which can be controlled by the flow rate of nitrogen. Intravenous injection of nanoparticles at a low dose of 4 mg kg-1 elevates intratumoral temperatures to 50 °C in mice-bearing subcutaneous and metastatic cancer grafts during exposure to AMF. This approach can also be applied to the synthesis of other metal-doped nanoparticles with core-shell structures. Consequently, this method can potentially be used for the development of novel nanoparticles with high heating performance, further advancing systemic magnetic hyperthermia for cancer treatment.

Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti-factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis. The human recombinant analog, AB023, is in clinical development. The role of FXI in mediation of inflammation during DVT resolution is unknown. OBJECTIVES: Investigate the effects of pharmacological targeting of FXI with 14E11 in an experimental model of venous thrombosis. METHODS: Adult wild-type CD1 mice were treated with subcutaneous anti-FXI antibody (14E11, 5 mg/kg) versus saline prior to undergoing surgical constriction of the inferior vena cava (IVC). Mice were evaluated at various time points to assess thrombus weight and volume, as well as histology analysis, ferumoxytol enhanced magnetic resonance imaging (Fe-MRI), and whole blood flow cytometry. RESULTS: 14E11-treated mice had reduced thrombus weights and volumes after IVC constriction on day 7 compared to saline-treated mice. 14E11 treatment reduced circulating monocytes by flow cytometry and macrophage content within thrombi as evaluated by histologic staining and Fe-MRI. Collagen deposition was increased at day 3 while CD31 and smooth muscle cell actin expression was increased at day 7 in the thrombi of 14E11-treated mice compared to saline-treated mice. CONCLUSION: Pharmacologic targeting of FXI enhances the early stages of experimental venous thrombus resolution in wild-type CD1 mice, and may be of interest for future clinical evaluation of the antibody in DVT and PTS.

Targeted Nanoparticles with High Heating Efficiency for the Treatment of Endometriosis with Systemically Delivered Magnetic Hyperthermia.

Endometriosis is a devastating disease in which endometrial-like tissue forms lesions outside the uterus. It causes infertility and severe pelvic pain in ≈176 million women worldwide, and there is currently no cure for this disease. Magnetic hyperthermia could potentially eliminate widespread endometriotic lesions but has not previously been considered for treatment because conventional magnetic nanoparticles have relatively low heating efficiency and can only provide ablation temperatures (>46 °C) following direct intralesional injection. This study is the first to describe nanoparticles that enable systemically delivered magnetic hyperthermia for endometriosis treatment. When subjected to an alternating magnetic field (AMF), these hexagonal iron-oxide nanoparticles exhibit extraordinary heating efficiency that is 6.4× greater than their spherical counterparts. Modifying nanoparticles with a peptide targeted to vascular endothelial growth factor receptor 2 (VEGFR-2) enhances their endometriosis specificity. Studies in mice bearing transplants of macaque endometriotic tissue reveal that, following intravenous injection at a low dose (3 mg per kg), these nanoparticles efficiently accumulate in endometriotic lesions, selectively elevate intralesional temperature above 50 °C upon exposure to external AMF, and completely eradicate them with a single treatment. These nanoparticles also demonstrate promising potential as magnetic resonance imaging (MRI) contrast agents for precise detection of endometriotic tissue before AMF application.

3D MR fingerprinting using Seiffert spirals.

PURPOSE: Seiffert spirals were recently explored as an efficient way to traverse 3D k-space compared to traditional 3D techniques. Several studies have shown the ability of 3D MR fingerprinting (MRF) techniques to acquire T1 and T2 relaxation maps in a short period of time. However, these sequences do not sample across a large region of 3D k-space every TR, especially in the way that Seiffert trajectories can. METHODS: A 3D MRF sequence was designed using 8 Seiffert spirals rotated in 3D k-space, with flip angle modulation for T1 and T2 sensitivity. The sequence was compared to an MRF sequence using a 2D spiral rotated in 3D k-space using the tiny golden angle acquisition with similar resolution/readout duration. Both sequences were evaluated using simulations, phantom validation, and in vivo imaging. RESULTS: In all experiments, the Seiffert spiral MRF sequence performed similar to if not better than the multi-axis 2D spiral MRF sequence. Strong intraclass correlation coefficients (> 0.9) were found between conventional and MRF sequences in phantoms, whereas the in vivo results showed slightly less aliasing artifact with the Seiffert trajectory. CONCLUSION: In this study, Seiffert spirals were used within the MRF framework to acquire high-resolution T1 and T2 relaxation time maps in less than 2.5 min. The reduced aliasing artifacts seen with the Seiffert sequence suggests that sampling over 3D k-space evenly each TR can improve quantification or shorten scan times.

T1ρ magnetic resonance fingerprinting.

T1ρ relaxation imaging is a quantitative imaging technique that has been used to assess cartilage integrity, liver fibrosis, tumors, cardiac infarction, and Alzheimer's disease. T1 , T2 , and T1ρ relaxation time constants have each demonstrated different degrees of sensitivity to several markers of fibrosis and inflammation, allowing for a potential multi-parametric approach to tissue quantification. Traditional magnetic resonance fingerprinting (MRF) has been shown to provide quick, quantitative mapping of T1 and T2 relaxation time constants. In this study, T1ρ relaxation is added to the MRF framework using spin lock preparations. An MRF sequence involving an RF-spoiled sequence with TR , flip angle, T1ρ , and T2 preparation variation is described. The sequence is then calibrated against conventional T1 , T2 , and T1ρ relaxation mapping techniques in agar phantoms and the abdomens of four healthy volunteers. Strong intraclass correlation coefficients (ICC > 0.9) were found between conventional and MRF sequences in phantoms and also in healthy volunteers (ICC > 0.8). The highest ICC correlation values were seen in T1 , followed by T1ρ and then T2 . In this study, T1ρ relaxation has been incorporated into the MRF framework by using spin lock preparations, while still fitting for T1 and T2 relaxation time constants. The acquisition of these parameters within a single breath hold in the abdomen alleviates the issues of movement between breath holds in conventional techniques.

Multi-parametric T2 * magnetic resonance fingerprinting using variable echo times.

The use of quantitative imaging biomarkers in the imaging of various disease states, including cancer and neurodegenerative disease, has increased in recent years. T1 , T2 , and T2 * relaxation time constants have been shown to be affected by tissue structure or contrast infusion. Acquiring these biomarkers simultaneously in a multi-parametric acquisition could provide more robust detection of tissue changes in various disease states including neurodegeneration and cancer. Traditional magnetic resonance fingerprinting (MRF) has been shown to provide quick, quantitative mapping of T1 and T2 relaxation time constants. In this study, T2 * relaxation is added to the MRF framework using variable echo times (TE). To demonstrate the feasibility of the method and compare incremental and golden angle spiral rotations, simulated phantom data was fit using the proposed method. Additionally, T1 /T2 /T2 */δf MRF as well as conventional T1 , T2 , and T2 * acquisitions were acquired in agar phantoms and the brains of three healthy volunteers. Golden angle spiral rotation was found to reduce inaccuracy resulting from off resonance effects. Strong correlations were found between conventional and MRF values in the T1 , T2 , and T2 * relaxation time constants of the agar phantoms and healthy volunteers. In this study, T2 * relaxation has been incorporated into the MRF framework by using variable echo times, while still fitting for T1 and T2 relaxation time constants. In addition to fitting these relaxation time constants, a novel method for fitting and correcting off resonance effects has been developed.

Sagittal plane walking patterns are related to MRI changes over 18-months in people with and without mild-moderate hip osteoarthritis.

The purpose was to evaluate the association of sagittal plane gait mechanics with MRI changes in the hip joint over 18-months. Subjects with and without radiographic hip OA (n = 57) underwent MRI at baseline and 18 months for grading of cartilage lesions, bone marrow lesions (BML), cysts, and labral tears. 3D gait analyses at baseline were used for sagittal plane hip kinematics and kinetics during the stance phase. Subjects were classified as progressors or non-progressors based on increase in any MRI OA parameter. Multivariate ANOVA were used for differences in sagittal gait parameters between progressors and non-progressors at baseline while adjusting for age. Logistic regression was used to estimate the probability of being classified as a progressor or non-progressor with increasing hip flexion while adjusting for age, BMI, sex, and presence of radiographic hip OA. Of the 57, 35 were classified as non-progressors and 22 were classified as progressors. At baseline, the progressors walked with 4.5° greater hip flexion during early stance (p = 0.021) and 3.5° lesser hip extension in late stance that was nearly significant (p = 0.059). Walking with greater hip flexion at baseline was associated with a greater risk of increase in MRI defined structural changes in the hip joint (Odds Ratio = 1.1, p = 0.038). Greater hip flexion during walking was associated with a risk of structural progression of hip OA. The results may guide future interventions to alter the walking patterns and slow structural hip OA progression.© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1472-1477, 2018.

Spatial variations in magnetic resonance-based diffusion of articular cartilage in knee osteoarthritis.

PURPOSE: To evaluate a pulse sequence combining stimulated echo diffusion preparation with a 3D segmented spoiled gradient echo (SPGR) acquisition for diffusion tensor imaging (DTI) of knee cartilage in healthy and osteoarthritis (OA) populations for early diagnosis and characterization of OA. METHODS: Diffusion-weighted images of 40 subjects (20 healthy, 20 OA) at baseline and 20 subjects (10 healthy, 10 OA) at one year were obtained. The subjects were classified according to Kellgren Lawrence (KL) and whole organ magnetic resonance imaging scoring (WORMS) method acquired at 3 T. Cartilage full thickness and laminar mean diffusivity (MD) and fractional anisotropy (FA) values were quantified. The reproducibility of MD and FA values was assessed in five healthy human subjects based on test-retest scans. RESULTS: In general, the full thickness MD values were higher in subjects with knee OA compared to healthy controls in both the baseline and follow up cohort. Laminar analysis MD and FA results were significantly different (p<0.05) between the bone-articular and articular layer with the articular layer having higher MD and lower FA value compared to the bone layer. The global reproducibility error was 6.5% for MD and 11.6% for FA. CONCLUSION: The diffusion-weighted stimulated echo-based sequence may be used as a valuable tool for early diagnosis and characterization of knee OA at 3 T in the future.

Cartilage T1ρ and T2 Relaxation Times in Patients With Mild-to-Moderate Radiographic Hip Osteoarthritis.

OBJECTIVE: To analyze region-specific T1ρ and T2 relaxation times of the hip joint cartilage in relation to presence or absence of radiographic hip osteoarthritis (OA) and presence or absence of magnetic resonance imaging (MRI)-detected cartilage defects. METHODS: Weight-bearing radiographs and 3T MRI studies of the hip were obtained from 84 volunteers. Based on Kellgren/Lawrence (K/L) scoring of the radiographs, 54 subjects were classified as healthy controls (K/L grade ≤1) and 30 were classified as having mild or moderate radiographic hip OA (K/L grades 2 or 3, respectively). Two-dimensional fat-suppressed fast spin-echo MRI sequences were used for semiquantitative clinical scoring of cartilage defects, and a T1ρ/T2 sequence was used to quantitatively assess the cartilage matrix. The femoral and acetabular cartilage was then segmented into 8 regions and the mean T1ρ/T2 values were calculated. Differences in T1ρ and T2 relaxation times were compared between subjects with and those without radiographic hip OA, and those with and those without femoral or acetabular cartilage defects. RESULTS: Higher T1ρ and T2 relaxation times in the anterior superior and central regions of the acetabular cartilage were seen in individuals with radiographic hip OA and those with acetabular cartilage defects compared to their respective controls (P < 0.05). In the femoral cartilage, the differences in T1ρ and T2 were not significant for any of the comparisons. Significant differences in the T1ρ and T2 values (each P < 0.05) were found in more subregions of the cartilage and across the whole cartilage when subjects were stratified based on the presence of MRI-detected cartilage defects than when they were stratified based on the presence of radiographic hip OA. CONCLUSION: T1ρ and T2 relaxation parameters are sensitive to the presence of cartilage degeneration. Both parameters may therefore support MRI evidence of cartilage defects of the hip.

Anatomic correlates of reduced hip extension during walking in individuals with mild-moderate radiographic hip osteoarthritis.

To identify radiographic and MR features of hip osteoarthritis (OA) related to reduced hip extension during walking. Sixty six subjects, were stratified into those with (n = 36, KL = 2, 3) and without (n = 30, KL = 0, 1) radiographic hip OA. Cartilage and labrum lesions were graded semi-quantitatively on hip MRI. Alpha angle and lateral center edge (LCE) angle were measured. Sagittal kinematics and kinetics were calculated during walking at speed of 1.35 m/s using 3-D motion capture. All subjects completed Hip disability and Osteoarthritis Outcome Score (HOOS), timed up and go, and 6 min walk tests. Variables were compared between the two groups using one-way ANOVA (adjusting for age). Correlations of radiographic and MR parameters with peak hip extension were calculated. The OA group was older, had greater pain, and limitation of function. They also had lower peak hip extension and higher peak hip flexion; and worse acetabular and femoral cartilage lesions. Peak hip extension and flexion correlated with KL grade, cartilage lesions in the inferior and posterior femur. Reduced hip extension and greater hip flexion during walking are present in high functioning (HOOS > 85%) individuals with mild-moderate hip OA, and are associated with cartilage lesions.

Improved differentiation between knees with cartilage lesions and controls using 7T relaxation time mapping.

BACKGROUND/OBJECTIVE: T1ρ and T2 relaxation mapping in knee cartilage have been used extensively at 3 Tesla (T) as markers for proteoglycan and collagen, respectively. The objective of this study was to evaluate the feasibility of T1ρ and T2 imaging of knee cartilage at 7T in comparison to 3T and to evaluate the ability of T1ρ and T2 to determine differences between normal and osteoarthritis (OA) patients. MATERIALS AND METHODS: Twenty patients, seven healthy patients (Kellgren-Lawrence = 0), and 13 patients with signs of radiographic OA (Kellgren-Lawrence > 0) were scanned at 3T and 7T. The knee cartilage was segmented into six compartments and the T1ρ and T2 values were fit using a two-parameter model. Additionally, patients were stratified by the presence of cartilage lesions using the modified Whole Organ Magnetic Resonance Imaging Score classification of the knee. One-way analysis of variance was used to compare the healthy and OA groups at 3T and 7T. The specific absorption ratio was kept under Food and Drug Administration limits during all scans. RESULTS: T1ρ and T2 values at 3T and 7T were significantly higher in the lateral femoral condyle and patella in patients with OA. However, more regions were significant or approached significance at 7T compared with 3T, with the differences between healthy and OA patients also larger at 7T. The signal to noise ratio across all cartilage and meniscus compartments was 60% higher on average at 7T compared to 3T. CONCLUSION: T1ρ imaging at 7T has been established as a viable imaging method for the differentiation of degenerated cartilage despite previous concerns over specific absorption rate and imaging time. The potential increased sensitivity of T1ρ and T2 imaging at 7T may be useful for future studies in the development of OA.

Validation of bone marrow fat quantification in the presence of trabecular bone using MRI.

BACKGROUND: To validate six-echo, chemical-shift based MRI with T2 * correction for the quantification of bone marrow fat content in the presence of trabecular bone. METHODS: Ten bone phantoms were made using trabecular bone cores extracted from the distal femur and proximal tibia of 20 human cadaveric knees. Bone marrow was removed from the cores and the marrow spaces were filled with water-fat gelatin to mimic bone marrow of known fat fractions. A chemical-shift based water-fat separation method with T2 * correction was used to generate fat fraction maps. The proton density fat fractions (PDFF) between marrow regions with and without bone were compared with the reference standard of known fat fraction using the squared Pearson correlation coefficient and unpaired t-test. RESULTS: Strong correlations were found between the known fat fraction and measured PDFF in marrow without trabecular bone (R(2) = 0.99; slope = 0.99, intercept = 0.94) as well as in marrow with trabecular bone (R(2) = 0.97; slope = 1.0, intercept = -3.58). Measured PDFF between regions with and without bone were not significantly different (P = 0.5). However, PDFF was systematically underestimated by -3.2% fat fraction in regions containing trabecular bone. CONCLUSION: Our implementation of a six-echo chemical-shift based MRI pulse sequence with T2 * correction provided an accurate means of determining fat content in bone marrow in the presence of trabecular bone.

Magnetic resonance analysis of loaded meniscus deformation: a novel technique comparing participants with and without radiographic knee osteoarthritis.

OBJECTIVE: To establish a novel method of quantifying meniscal deformation using loaded MRI. More specifically, the goals were to evaluate the (1) accuracy, (2) inter-rater reliability, (3) intra-rater reliability, and (4) scan-rescan reliability. The secondary purpose of this experiment was to evaluate group differences in meniscal deformation in participants with and without radiographic knee OA. MATERIALS AND METHODS: Weight-bearing 3-T MRIs of the knee in full extension and 30° of flexion were processed to create 3D models of meniscal deformation. Accuracy was assessed using a custom-designed phantom. Twenty-one participants either with or without signs of OA were evaluated, and another six participants (14 knees, one subject was scanned twice) underwent repeated imaging to assess scan-rescan reproducibility. Intraclass correlation coefficient (ICC), root-mean squared error (RMSE), and root-mean-square percent coefficient-of-variation (RMS%CV) analyses were performed. Exploratory comparisons were made between those with and without OA to evaluate potential group differences. RESULTS: All variables were found to be accurate with RMSE ranging from 0.08 to 0.35 mm and 5.99 to 14.63 mm(2). Reproducibility of peak anterior-posterior meniscal deformation was excellent (ICC > 0.821; p < 0.013) with RMS%CV for intra-rater ranging from 0.06 to 1.53 % and 0.17 to 1.97 %, inter-rater ranging from 0.10 to 7.20 % and 3.95 to 18.53 %, and scan-rescan reliability ranging from 1.531 to 7.890 % and 4.894 to 9.142 %, for distance and area metric, respectively. Participants with OA were found to have significantly greater anterior horn movement of both the medial (p = 0.039) and lateral meniscus (p = 0.015), and smaller flexed medial meniscus outer area (p = 0.048) when compared to controls. CONCLUSIONS: MRI-based variables of meniscus deformation were found to be valid in participants with and without OA. Significant differences were found between those with and without radiographic OA; further study is warranted.

Scoring hip osteoarthritis with MRI (SHOMRI): A whole joint osteoarthritis evaluation system.

BACKGROUND: To develop a semi-quantitative MR-based hip osteoarthritis (OA) evaluation system (Scoring hip osteoarthritis with MRI, SHOMRI), and to test its reproducibility and face validity. METHODS: The study involved 98 subjects with informed consent. Three-Tesla MR imaging of hip was performed in three planes with intermediate-weighted fat saturated FSE sequences. Two radiologists assessed cartilage loss, bone marrow edema pattern, subchondral cyst in 10 subregions, and assessed labrum in 4 subregions. In addition, presence or absence of ligamentum teres integrity, paralabral cysts, intra-articular body, and effusion in the hip joint were analyzed using the SHOMRI system. The reproducibility was assessed with intra-class correlation coefficient (ICC), Cohen's Kappa values and percent agreement. SHOMRI scores were correlated with radiographic Kellgren-Lawrence (KL) and OARSI atlas gradings, and clinical parameters, the hip osteoarthritis outcome score (HOOS) and hip range of motion (ROM), using Spearman's rank correlation and ordinal logistic regression. RESULTS: ICC values were in the excellent range, 0.91 to 0.97. Cohen's Kappa values and percent agreement ranged from 0.55 to 0.79 and 66 to 99%, respectively. SHOMRI demonstrated significant correlations with KL and OARSI gradings as well as with clinical parameters, HOOS and ROM (P < 0.05). Among the SHOMRI features, subchondral cyst and bone marrow edema pattern showed the highest correlation with HOOS and ROM. CONCLUSION: SHOMRI demonstrated moderate to excellent reproducibility and significant correlation with radiographic gradings and clinical parameters.

Simultaneous acquisition of T1ρ and T2 quantification in knee cartilage: repeatability and diurnal variation.

PURPOSE: To develop a robust sequence that combines T1ρ and T2 quantifications and to examine the in vivo repeatability and diurnal variation of T1ρ and T2 quantifications in knee cartilage. MATERIALS AND METHODS: Six healthy volunteers were scanned in the morning and afternoon on 2 days using a combined T1ρ and T2 quantification sequence developed in this study. Repeatability of T1ρ and T2 quantification was estimated using root-mean-square coefficients-of-variation (RMS-CV). T1ρ and T2 values from morning scans were compared to those from afternoon scans using paired t-tests. RESULTS: The overall RMS-CV of in vivo T1ρ and T2 quantification was 5.3% and 5.2%, respectively. The RMS-CV of am scans was 4.2% and 5.0% while the RMS-CV of pm scans was 6.0% and 6.3% for T1ρ and T2 , respectively. No significant difference was found between T1ρ or T2 values in the morning and in the afternoon. CONCLUSION: A sequence that combines T1ρ and T2 quantification with scan time less than 10 minutes and is robust to B0 and B1 inhomogeneity was developed with excellent repeatability. For a cohort with low-level daily activity, although no significant diurnal variation of cartilage MR relaxation times was observed, the afternoon scans had inferior repeatability compared to morning scans.