MRI-derived Articular Cartilage Strains Predict Patient-Reported Outcomes Six Months Post Anterior Cruciate Ligament Reconstruction.

Key terms: Multicontrast and Multiparametric, Magnetic Resonance Imaging, Osteoarthritis, Functional Biomechanical Imaging, Knee Joint Degeneration What is known about the subject: dualMRI has been used to quantify strains in a healthy human population in vivo and in cartilage explant models. Previously, OA severity, as determined by histology, has been positively correlated to increased shear and transverse strains in cartilage explants. What this study adds to existing knowledge: This is the first in vivo use of dualMRI in a participant demographic post-ACL reconstruction and at risk for developing osteoarthritis. This study shows that dualMRI-derived strains are more significantly correlated with patient-reported outcomes than any MRI relaxometry metric. Background: Anterior cruciate ligament (ACL) injuries lead to an increased risk of osteoarthritis, characterized by altered cartilage tissue structure and function. Displacements under applied loading by magnetic resonance imaging (dualMRI) is a novel MRI technique that can be used to quantify mechanical strain in cartilage while undergoing a physiological load. Purpose: To determine if strains derived by dualMRI and relaxometry measures correlate with patient-reported outcomes at six months post unilateral ACL reconstruction. Study Design: Cohort study. Methods: Quantitative MRI (T2, T2*, T1ρ) measurements and transverse, axial, and shear strains were quantified in the medial articular tibiofemoral cartilage of 35 participants at six-months post unilateral ACL reconstruction. The relationships between patient-reported outcomes (WOMAC, KOOS, MARS) and all qMRI relaxation times were quantified using general linear mixed-effects models. A combined best-fit multicontrast MRI model was then developed using backwards regression to determine the patient features and MRI metrics that are most predictive of patient-reported outcome scores. Results: Higher femoral strains were significantly correlated with worse patient-reported functional outcomes. Femoral shear and transverse strains were positively correlated with six-month KOOS and WOMAC scores, after controlling for covariates. No relaxometry measures were correlated with patient-reported outcome scores. We identified the best-fit model for predicting WOMAC score using multiple MRI measures and patient-specific information, including sex, age, graft type, femoral transverse strain, femoral axial strain, and femoral shear strain. The best-fit model significantly predicted WOMAC score (p<0.001) better than any one individual MRI metric alone. When we regressed the model-predicted WOMAC scores against the patient-reported WOMAC scores, we found that our model achieved a goodness of fit exceeding 0.52. Conclusions: This work presents the first use of dualMRI in vivo in a cohort of participants at risk for developing osteoarthritis. Our results indicate that both shear and transverse strains are highly correlated with patient-reported outcome severity could serve as novel imaging biomarkers to predict the development of osteoarthritis.

Factors associated with attitudes toward research MRI in older Asian Americans.

INTRODUCTION: South Asian (SA) and East Asian (EA) older adults represent the fastest-growing racial/ethnic groups of Americans at risk for dementia. While recruiting older SA adults into a brain health study, we encountered unexpected hesitancy toward structural brain magnetic resonance imaging (MRI) analysis and stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as personal MRI experience, perceived MRI safety, and concerns for personal risk for future dementia/stroke. METHODS: We developed a brief cross-sectional survey to assess older adults' MRI experiences and perceptions, desire to learn of six incidental findings of increasing impact on health, and attitudes related to dementia (including LoC) and research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey (offered in English, Chinese, Korean, and Spanish) and modeled the proportional odds (PO) for favorable attitudes toward research activities. RESULTS: Seventy-seven SA and 84 EA respondents were analyzed alongside 95 White, Black, or Hispanic adults. White (PO = 2.54, p = 0.013) and EA (PO = 2.14, p = 0.019) respondents were both more likely than SA respondents to endorse healthy volunteers' participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p = 0.006) but still shared SA respondents' lower wish (measured by proportion of total) to learn of incidental MRI findings. DISCUSSION: SA-and EA compared to SA-older adults had low desire to learn of incidental MRI findings but had different attitudes toward future dementia/stroke risks. A culturally appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research. Highlights: Older Asian Americans have limited interest in incidental findings on research MRISouth Asians are most likely to attribute dementia to people's own behaviorsSouth Asians' attitudes mediate lower support for healthy volunteers in researchSouth and East Asians differ in dementia worries and research-related attitudes.

Too much information? Asian Americans' preferences for incidental brain MRI findings.

INTRODUCTION: South Asian (SA) and East Asian (EA) older adults represent the fastest growing group of Americans at risk for dementia, but their participation in aging and dementia research has been limited. While recruiting healthy SA older adults into a brain health study, we encountered unexpected hesitancy towards structural brain MRI analysis along with some stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as one's own MRI experience, perceived MRI safety, and concerns for one's own risks for future dementia/stroke. METHODS: We developed a brief cross-sectional survey to assess older adults' MRI experiences and perceptions, desire to learn of six incidental findings of increasing health implications, and attitudes related to dementia as well as research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey, and modeled the proportional odds (P.O.) for pro-research attitudes. RESULTS: 77 SA and 84 EA respondents were analyzed with 95 non-Asian adults. White (P.O.=2.54, p=0.013) and EA (P.O.=2.14, p=0.019) respondents were both more likely than SA respondents to endorse healthy volunteers' participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p=0.006), but still shared SA respondents' low desire to learn of incidental MRI findings. DISCUSSION: SA and EA older adults had different attitudes towards future dementia/stroke risks, but shared a low desire to learn of incidental MRI findings. A culturally-appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research.

Multi-frame biomechanical and relaxometry analysis during in vivo loading of the human knee by spiral dualMRI and compressed sensing.

PURPOSE: Knee cartilage experiences repetitive loading during physical activities, which is altered during the pathogenesis of diseases like osteoarthritis. Analyzing the biomechanics during motion provides a clear understanding of the dynamics of cartilage deformation and may establish essential imaging biomarkers of early-stage disease. However, in vivo biomechanical analysis of cartilage during rapid motion is not well established. METHODS: We used spiral displacement encoding with stimulated echoes (DENSE) MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and used compressed sensing on the k-space data. The applied compressive load was set for each participant at 0.5 times body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1ρ , T2 ) and after (T1ρ ) varus load. RESULTS: Displacement and strain maps showed a gradual shift of displacement and strain in time. Compressive strain was observed in the medial condyle cartilage and shear strain was roughly half of the compressive strain. Male participants had more displacement in the loading direction compared to females, and T1ρ values did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25% to 40% when comparing the displacement maps and substantially lowered the noise levels. CONCLUSION: These results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies because of the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities and that could serve as biomarkers of early osteoarthritis.

High frame rate deformation analysis of knee cartilage by spiral dualMRI and relaxation mapping.

PURPOSE: Daily activities including walking impose high-frequency cyclic forces on cartilage and repetitive compressive deformation. Analyzing cartilage deformation during walking would provide spatial maps of displacement and strain and enable viscoelastic characterization, which may serve as imaging biomarkers for early cartilage degeneration when the damage is still reversible. However, the time-dependent biomechanics of cartilage is not well described, and how defects in the joint impact the viscoelastic response is unclear. METHODS: We used spiral acquisition with displacement-encoding MRI to quantify displacement and strain maps at a high frame rate (25 frames/s) in tibiofemoral joints. We also employed relaxometry methods (T1 , T1ρ , T2 , T2 *) on the cartilage. RESULTS: Normal and shear strains were concentrated on the bovine tibiofemoral contact area during loading, and the defected joint exhibited larger compressive strains. We also determined a positive correlation between the change of T1ρ in cartilage after cyclic loading and increased compressive strain on the defected joint. Viscoelastic behavior was quantified by the time-dependent displacement, where the damaged joint showed increased creep behavior compared to the intact joint. This technique was also successfully demonstrated on an in vivo human knee showing the gradual change of displacement during varus load. CONCLUSION: Our results indicate that spiral scanning with displacement encoding can quantitatively differentiate the damaged from intact joint using the strain and creep response. The viscoelastic response identified with this methodology could serve as biomarkers to detect defects in joints in vivo and facilitate the early diagnosis of joint diseases such as osteoarthritis.

Quantitative Classification of 3D Collagen Fiber Organization From Volumetric Images.

Collagen fibers in biological tissues have a complex 3D organization containing rich information linked to tissue mechanical properties and are affected by mutations that lead to diseases. Quantitative assessment of this 3D collagen fiber organization could help to develop reliable biomechanical models and understand tissue structure-function relationships, which impact diagnosis and treatment of diseases or injuries. While there are advanced techniques for imaging collagen fibers, published methods for quantifying 3D collagen fiber organization have been sparse and give limited structural information which cannot distinguish a wide range of 3D organizations. In this article, we demonstrate an algorithm for quantitative classification of 3D collagen fiber organization. The algorithm first simulates five groups, or classifications, of fiber organization: unidirectional, crimped, disordered, two-fiber family, and helical. These five groups are widespread in natural tissues and are known to affect the tissue's mechanical properties. We use quantitative metrics based on features such as preferred 3D fiber orientation and spherical variance to differentiate each classification in a repeatable manner. We validate our algorithm by applying it to second-harmonic generation images of collagen fibers in tendon and cervix tissue that has been sectioned in specified orientations, and we find strong agreement between classification from simulated data and the physical fiber organization. Our approach provides insight for interpreting 3D fiber organization directly from volumetric images. This algorithm could be applied to other fiber-like structures that are not necessarily made of collagen.

Quantitative analysis of the effect of environmental-scanning electron microscopy on collagenous tissues.

Environmental-scanning electron microscopy (ESEM) is routinely applied to various biological samples due to its ability to maintain a wet environment while imaging; moreover, the technique obviates the need for sample coating. However, there is limited research carried out on electron-beam (e-beam) induced tissue damage resulting from using the ESEM. In this paper, we use quantitative second-harmonic generation (SHG) microscopy to examine the effects of e-beam exposure from the ESEM on collagenous tissue samples prepared as either fixed, frozen, wet or dehydrated. Quantitative SHG analysis of tissues, before and after ESEM e-beam exposure in low-vacuum mode, reveals evidence of cross-linking of collagen fibers, however there are no structural differences observed in fixed tissue. Meanwhile wet-mode ESEM appears to radically alter the structure from a regular fibrous arrangement to a more random fiber orientation. We also confirm that ESEM images of collagenous tissues show higher spatial resolution compared to SHG microscopy, but the relative tradeoff with collagen specificity reduces its effectiveness in quantifying collagen fiber organization. Our work provides insight on both the limitations of the ESEM for tissue imaging, and the potential opportunity to use as a complementary technique when imaging fine features in the non-collagenous regions of tissue samples.

Application of quantitative second-harmonic generation microscopy to posterior cruciate ligament for crimp analysis studies.

We use second-harmonic generation (SHG) microscopy to quantitatively characterize collagen fiber crimping in the posterior cruciate ligament (PCL). The obtained SHG images are utilized to define three distinct categories of crimp organization in the PCL. Using our previously published spatial-frequency analysis, we develop a simple algorithm to quantitatively distinguish the various crimp patterns. In addition, SHG microscopy reveals both the three-dimensional structural variation in some PCL crimp patterns as well as an underlying helicity in these patterns that have mainly been observed using electron microscopy. Our work highlights how SHG microscopy could potentially be used to link the fibrous structural information in the PCL to its mechanical properties.

Third-harmonic generation imaging of breast tissue biopsies.

We demonstrate for the first time the imaging of unstained breast tissue biopsies using third-harmonic generation (THG) microscopy. As a label-free imaging technique, THG microscopy is compared to phase contrast and polarized light microscopy which are standard imaging methods for breast tissues. A simple feature detection algorithm is applied to detect tumour-associated lymphocyte rich regions in unstained breast biopsy tissue and compared with corresponding regions identified by a pathologist from bright-field images of hematoxylin and eosin stained breast tissue. Our results suggest that THG imaging holds potential as a complementary technique for analysing breast tissue biopsies.

Effects of freeze-thaw and micro-computed tomography irradiation on structure-property relations of porcine trabecular bone.

We study the effects of freeze-thaw and irradiation on structure-property relations of trabecular bone. We measure the porosity, apparent density, mineral content, trabecular orientation, trabecular thickness, fractal dimension, surface area, and connectivity of trabecular bone using micro-computed tomography (micro-CT) and relate them to Young's modulus and ultimate strength measured by uniaxial compression testing. The analysis is done on six-month porcine trabecular bone from femoral heads. The effects of freeze-thaw are studied by using bones from three different groups: fresh bone and bones frozen for one and five years. We find that the porosity and apparent density have most dominant influence on the elastic modulus and strength of fresh bone. Also, five years of freezing lowers both Young's modulus and ultimate strength of trabecular bone. Additionally, the effects of radiation are investigated by comparing Young's modulus before and after micro-CT exposure. We find that the micro-CT irradiation has a negligible effect on the Young's modulus of trabecular bone. These findings provide insights on the effects of tissue preservation and imaging on properties of trabecular bone.