Purpose-A direct correlation between T 1ρ , T 2 and quantified proteoglycan and collagen contents in human osteoarthritic cartilage has yet to be documented. We aimed to investigate the orientation effect on T 1ρ and T 2 values in human osteoarthritic cartilage; and to quantify the correlation between T 1ρ , T 2 , versus biochemical composition and histology in human osteoarthritic cartilage.Materials and Methods-Thirty-three cartilage specimens were collected from patients who underwent total knee arthroplasty due to severe osteoarthritis, and scanned with a 3T MR scanner for T 1ρ and T 2 quantification. Nine specimens were scanned at three different orientations with respect to the B 0 : 0°, 90°, and 54.7°. Core punches were taken after MRI. Collagen and proteoglycan contents were quantified using biochemical assays. Histology sections were graded using Mankin scores. The correlation between imaging parameters, biochemical contents and histological scores were studied.Results-Both mean T 1ρ and T 2 at 54.7° were significantly higher than those measured at 90°a nd 0°, with T 1ρ showing a less increase compared to T 2 . R 1ρ (1/T 1ρ ) values had a significant, but moderate correlation with proteoglycan contents (R = 0.45, P = 0.002), while R 2 (1/T 2 ) was not correlated with proteoglycan. No significant correlation was found between relaxation times (T 1ρ or T 2 ) and collagen contents. The T 1ρ values of specimen sections with high Mankin scores were significantly higher than those with low Mankin scores (P < 0.05) © 2010 Elsevier Inc. All rights reserved.Corresponding author: Xiaojuan Li, PhD, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry Street, Suite 350, San Francisco, CA 94107, xiaojuan.li@radiology.ucsf.edu,. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Competing InterestThe authors declare that they have no competing interests. Conclusions-Quantitative MRI has a great potential to provide non-invasive imaging biomarkers for cartilage degeneration in OA. NIH Public Access

Purpose:To quantitatively assess bone marrow edema-like lesion (BMEL) and the overlying cartilage in osteoarthritis (OA) or anterior cruciate ligament (ACL)-injured knees using magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI). Materials and Methods:Eight healthy controls and 30 patients with OA and other injuries who showed BMEL were scanned at 3.0T. A regression model was constructed to automatically calculate the volume of BMEL. Normalized T 1 z-scores were calculated within BMEL-overlying cartilage. Three-dimensional (3D) MRSI was acquired in the BMEL and surrounding bone marrow. Results:The mean T 1 z-score was significantly higher in BMEL-overlying cartilage than that in surrounding cartilage in the lateral tibia of patients with ACL tears (P Ͻ 0.001). Significantly elevated water and unsaturated lipids, and decreased saturated lipids were observed in BMEL. The volume of elevated water correlated with the volume of BMEL. Water content was significantly higher within BMEL than that outside BMEL. The unsaturation index outside BMEL was significantly higher in patients with ACL tears than that in OA.Conclusion: 3D MRSI and T 1 mapping provide tools to quantitatively evaluate BMEL in OA and knee injury. This may allow us to better understand pathophysiology and evolution of injuries and degenerative conditions of the knee.

Post‐traumatic stress disorder (PTSD), which can affect 1 in 11 adults during their lifetime, is often comorbid with chronic alcohol use problems and increases alcohol relapse risk. PTSD and alcohol‐use phenotypes are associated with variants in the FKBP propyl isomerase 5 (FKBP5) gene, which encodes FK506‐binding protein 5 (FKBP5), a chaperone modulator of glucocorticoid receptors (GR) that is functionally implicated in stress‐related psychiatric disorders and alcohol withdrawal severity. Data suggests that FKBP5 inhibition may decrease alcohol intake, but its role in the post‐traumatic recurrence of alcohol drinking is unknown. Here, we tested the hypotheses that amygdala Fkbp5 expression is increased in rats with a history of traumatic stress and is associated with greater reacquisition of ethanol self‐administration. Then, we tested the hypothesis that benztropine mesylate, an FDA‐approved drug that disrupts FKBP5‐GR binding, reduces reacquisition of ethanol self‐administration in rats with a history of traumatic stress. Separate cohorts (for mRNA vs. benztropine studies) of male (n = 43) and female (n = 20) Wistar rats received 3 sessions of light‐cued footshock stress (30 min session, 60 footshocks, 1‐s 0.4 mA) before acquiring operant ethanol (10% v/v) self‐administration (1‐h sessions, fixed ratio1‐3), followed by extinction (16 sessions), and then renewed alcohol access. Amygdala Fkbp5 expression correlated significantly with increased ethanol self‐administration (rs(23) = 0.463, p = 0.023) during renewal of ethanol access. Subchronic (3 days) benztropine pretreatment (‐2 h, i.p., 0, 5, and 10 mg/kg [n = 10, 14, and 14]) significantly reduced the reacquisition of ethanol self‐administration. On days 2 and 3 of reacquisition, self‐administration was significantly reduced in drug treated animals (Dose x Day: F(4,64)=2.83, p < 0.04), culminating in a 68% reduction in males (0.78±0.16 vs. 0.25±0.13 g/kg) and a 41% reduction in females (0.88±0.14 vs. 0.52±0.13 g/kg) at the 10 mg/kg dose. Overall, the results warrant further study of benztropine and its potential inhibition of FKBP5 to reduce post‐traumatic alcohol relapse risk.

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