Study of human cadaveric discs quantifying endplate permeability and porosity and correlating these with measures of disc quality: cell density, proteoglycan content, and overall degeneration. Permeability and porosity increased with age and were not correlated with cell density or overall degeneration, suggesting that endplate calcification may not accelerate disc degeneration.Study Design-Experimental quantification of relationships between vertebral endplate morphology, permeability, disc cell density, glycosaminoglycan content and degeneration in samples harvested from human cadaveric spines.Objective-To test the hypothesis that variation in endplate permeability and porosity contribute to changes in intervertebral disc cell density and overall degeneration.Summary of Background Data-Cells within the intervertebral disc are dependent on diffusive exchange with capillaries in the adjacent vertebral bone. Previous findings suggest that blocked routes of transport negatively affect disc quality, yet there are no quantitative relationships between human vertebral endplate permeability, porosity, cell density and disc degeneration. Such relationships would be valuable for clarifying degeneration risk factors, and patient features that may impede efforts at disc tissue engineering.Methods-Fifty-one motion segments were harvested from 13 frozen cadaveric human lumbar spines (32 to 85 years) and classified for degeneration using the MRI-based Pfirrmann scale. A cylindrical core was harvested from the center of each motion segment that included vertebral bony and cartilage endplates along with adjacent nucleus tissue. The endplate mobility, a type of permeability, was measured directly using a custom-made permeameter before and after the cartilage endplate was removed. Cell density within the nucleus tissue was estimated using the picogreen method while the nuclear GAG content was quantified using the DMMB technique. Specimens were imaged at 8 μm resolution using microCT, bony porosity was calculated. Analysis of variance, linear regression, and multiple comparison tests were used to analyze the data.Results-Nucleus cell density increased as the disc height decreased (R 2 =0.13; p=0.01) but was not related to subchondral bone porosity (p>0.5), total mobility (p>0.4) or age (p>0.2). When controlling for disc height however, a significant, negative effect of age on cell density was NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976). Author manuscript; available in PMC 2012 April 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript observed (p=0.03). In addition to this, GAG content decreased with age non-linearly (R 2 =0.83, p<0.0001) and a cell function measurement, GAGs/cell decreased with degeneration (R 2 =0.24; p<0.0001). Total mobility (R 2 =0.14; p<0.01) and porosity (R 2 =0.1, p<0.01) had a positive correlation with age.Conclusion-Although cell density increased with degeneration, cell function indicated that GAGs/cell decreased. Since permeability and porosity increase w...

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n=96, 14 subjects, L1–L5 level, ages 35–85 (64±16 yrs.), degeneration grade 1(n=4), grade 2(n=32), grade 3(n=44), grade 4(n=10), grade 5(n=6)] that included subchondral bone, cartilage endplate and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using μCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50 and 130% and trabecular thickness decreased by between 20 and 50% with advancing disc degeneration (p<0.05). We also observed that nucleus cell density increased (R2=0.33, p<0.05) and proteoglycan content decreased (R2=0.47, p<0.05) as the endplate became more porous. Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues.

Superior and inferior lumbar levels showed different kinematic behaviors under heavy load carrying conditions. These findings suggest a postural, lumbar flexion strategy aimed at centralizing a heavy posterior load over the base of support.

BackgroundMulticompartmental modeling outperforms conventional diffusion‐weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer.PurposeTo optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo.Study TypeRetrospective.SubjectsForty‐six patients who underwent MRI examination for suspected prostate cancer; 23 had prostate cancer and 23 had no detectable cancer.Field Strength/Sequence3T multishell diffusion‐weighted sequence.AssessmentMulticompartmental models with 2–5 tissue compartments were fit to DWI data from the prostate to determine optimal compartmental apparent diffusion coefficients (ADCs). These ADCs were used to compute signal contributions from the different compartments. The Bayesian Information Criterion (BIC) and model‐fitting residuals were calculated to quantify model complexity and goodness‐of‐fit. Tumor contrast‐to‐noise ratio (CNR) and tumor‐to‐background signal intensity ratio (SIR) were computed for conventional DWI and multicompartmental signal‐contribution maps.Statistical TestsAnalysis of variance (ANOVA) and two‐sample t‐tests (α = 0.05) were used to compare fitting residuals between prostate regions and between multicompartmental models. T‐tests (α = 0.05) were also used to assess differences in compartmental signal‐fraction between tissue types and CNR/SIR between conventional DWI and multicompartmental models.ResultsThe lowest BIC was observed from the 4‐compartment model, with optimal ADCs of 5.2e‐4, 1.9e‐3, 3.0e‐3, and >3.0e‐2 mm2/sec. Fitting residuals from multicompartmental models were significantly lower than from conventional ADC mapping (P < 0.05). Residuals were lowest in the peripheral zone and highest in tumors. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Tumors had a greater proportion of signal from compartment 1 than normal tissue (P < 0.05). Tumor CNR and SIR were greater on compartment‐1 signal maps than conventional DWI (P < 0.05) and increased with model order.Data ConclusionThe 4‐compartment signal model best described diffusion in the prostate. Compartmental signal contributions revealed by this model may improve assessment of prostate cancer.Level of Evidence 3Technical Efficacy Stage 3J. MAGN. RESON. IMAGING 2021;53:628–639.

Competing Interest Statement Dr. Dale reports that he was a Founder of and holds equity in CorTechs Labs, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. He receives funding through research grants from GE Healthcare to UCSD. Dr. Rakow-Penner is a consultant for Human Longevity, Inc. and receives funding through research grants from GE Healthcare. The terms of these arrangements have been reviewed by and approved by UCSD in accordance with its conflict of interest policies. Dr. Igor Vidić is employed as a consultant for Cortechs Labs, Inc. Dr. Seibert reports personal honoraria in the past three years from Varian Medical Systems, Multimodal Imaging Services Corporation, and WebMD.