Nucleus pulposus structure and function assessed in shear using magnetic resonance elastography, quantitative MRI, and rheometry.

Background: In vivo quantification of the structure-function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure-function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI. Method: MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3-4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters. Results: MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content. Conclusion: This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure-function relationship between composition and shear mechanical behaviors of NP tissue.

Modic changes in the lumbar vertebral column of chondrodystrophic and non-chondrodystrophic dogs with intervertebral disc disease.

Introduction: Modic changes (MC) are signs of vertebral pathology visible on magnetic resonance (MR) images that have been associated with low back pain (LBP) and disc degeneration in people. Multiple breeds of dogs also develop MCs and coincident back pain. However, the association between breed, MC, and spinal pathologies has yet to be fully elucidated. This study aimed to identify the prevalence of MC that occur spontaneously in the lumbar vertebral column of dogs diagnosed with intervertebral disc disease (IVDD) and examine their association with demographic criteria and the disc width index (DWI). Methods: Medical records and lumbar vertebral column MR images were examined from 104 dogs (831 intervertebral disc spaces and adjacent vertebrae), which were divided into three groups: chondrodystrophic dogs (CD; n =54) and non-chondrodystrophic dogs (NCD; n =30) with IVDD as the primary diagnosis, and control dogs (n =20) with other spinal diseases as their primary diagnosis. Results: Increasing age and a diagnosis of IVDD were significantly associated with MC in dogs (p < 0.001 and p = 0.0062, respectively). In CD dogs with IVDD, Type 2 MC were most prevalent, whereas, in NCD dogs, Type 3 MC were the most prevalent type. Type 2 MC were distributed nearly equally across the lumbar vertebral column, while Type 3 MC were primarily detected at the level of L7-S1. Discussion: This study demonstrated that MC developed spontaneously in dogs, are common in dogs diagnosed with IVDD, and the type observed varies by breed. Further research is needed to understand the pathogenesis of MC; however, the increased presence of Type 2 MC in CD dogs, similar to what is found in people with disc degeneration, suggests that CD dogs could serve as models for MC in people.

Modeling the effects of hydration on viscoelastic properties of nucleus pulposus tissue in shear using the fractional Zener model.

Nucleus pulposus (NP) tissue in the intervertebral disc (IVD) is a viscoelastic material exhibiting both solid- and fluid-like mechanical behaviors. Advances in viscoelastic models incorporating fractional calculus, such as the Fractional Zener (FZ) model, have potential to describe viscoelastic behaviors. The objectives of this study were to determine whether the FZ model can accurately describe the shear viscoelastic properties of NP tissue and determine if the fractional order (α) is related to tissue hydration. 30 caudal IVDs underwent equilibrium dialysis in 5% or 25% polyethylene glycol solutions to alter tissue hydration. Excised NP tissue underwent stress relaxation testing in shear and unconfined compression. Stress relaxation data was fitted to the FZ model to obtain viscoelastic properties. In both loading modes, the initial modulus was greater for the less hydrated 25% equilibrated samples compared to 5% with no change in the equilibrium modulus. Samples with lower water content (25% samples) had shorter relaxation times in shear and longer time constants in compression, highlighting the different interactions between the fluid and solid matrix in loading modes. Samples with lower water content had α values closer to 0, indicating that less hydrated samples behaved more solid-like on the viscoelastic spectrum. Tissue hydration correlated with α values for 25% samples in shear. This study demonstrates that the FZ model may be used to describe IVD tissue behavior under both loading modes; however, the greatest utility of the FZ model is in describing flow-independent shear behaviors, and α may inform tissue hydration in shear.

Magnetic Resonance Elastography of Intervertebral Discs: Spin-Echo Echo-Planar Imaging Sequence Validation.

BACKGROUND: Magnetic resonance elastography (MRE) is an imaging technique that can noninvasively assess the shear properties of the intervertebral disc (IVD). Unlike the standard gradient recalled echo (GRE) MRE technique, a spin-echo echo-planar imaging (SE-EPI) sequence has the potential to improve imaging efficiency and patient compliance. PURPOSE: To validate the use of an SE-EPI sequence for MRE of the IVD compared against the standard GRE sequence. STUDY TYPE: Cross-over. SUBJECTS: Twenty-eight healthy volunteers (15 males and 13 females, age range: 19-55). FIELD STRENGTH/SEQUENCE: 3 T; GRE, SE-EPI with breath holds (SE-EPI-BH) and SE-EPI with free breathing (SE-EPI-FB) MRE sequences. ASSESSMENT: MRE-derived shear stiffnesses were calculated via principal frequency analysis. SE-EPI derived shear stiffness and octahedral shear strain signal-to-noise ratios (OSS-SNR) were compared against those derived using the GRE sequence. The reproducibility and repeatability of SE-EPI stiffness measurements were determined. Shear stiffness was evaluated in the nucleus pulposus (NP) and annulus fibrosus (AF) regions of the disc. Scan times between sequences were compared. STATISTICAL TESTS: Linear mixed models, Bland-Altman plots, and Lin's concordance correlation coefficients (CCCs) were used with P < 0.05 considered statistically significant. RESULTS: Good correlation was observed between shear stiffnesses derived from the SE-EPI sequences with those derived from the GRE sequence with CCC values greater than 0.73 and 0.78 for the NP and AF regions, respectively. OSS-SNR was not significantly different between GRE and SE-EPI sequences (P > 0.05). SE-EPI sequences generated highly reproducible and repeatable stiffness measurements with CCC values greater than 0.97 in the NP and AF regions and reduced scan time by at least 51% compared to GRE. SE-EPI-BH and SE-EPI-FB stiffness measurements were similar with CCC values greater than 0.98 for both regions. DATA CONCLUSION: SE-EPI-based MRE-derived stiffnesses were highly reproducible and repeatable and correlated with current standard GRE MRE-derived stiffness estimates while reducing scan times. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Heterogeneous Integration of CMOS Sensors and Fluidic Networks Using Wafer-Level Molding.

Direct sensing in liquids using CMOS-integrated optical and electrical sensors is attractive for lab-on-chip applications, where close physical proximity between sample and sensor can obviate optical lenses, enhance electrical sensitivity, and decrease noise due to parasitics. However, controlled delivery of fluid samples to the chip surface presents an ongoing challenge for lab-on-CMOS development, where traditional wire-bond packaging prevents integration of planar microfluidics. In this paper, we present a method for scalable heterogeneous integration of microfluidic channels and silicon-integrated circuit substrates using a commercial fan-out wafer-level packaging approach. The planar surface supports multiple approaches for fluidic integration; we present both a stacked laser-cut fluidic assembly and the fabrication of monolithic SU-8 microchannels over the IC surface. As a proof-of-principle, both electrical and fluidic routing are provided to a custom 0.18-m CMOS optical sensor IC, and optical transmission and fluorescence measurement experiments are demonstrated.