Contrast-enhanced CT imaging as a non-destructive tool for ex vivo examination of the biochemical content and structure of the human meniscus.
The biochemical and histopathological techniques used to investigate meniscal content and structure are destructive and time-consuming. Therefore, this study evaluated whether contrast-enhanced computed tomography (CECT) attenuation and contrast agent flux using the iodinated contrast agents CA4+ and ioxaglate correlate with the glycosaminoglycan (GAG) content/distribution and water content in human menisci. The optimal ioxaglate and CA4+ contrast agent concentrations for mapping meniscal GAG distribution were qualitatively determined by comparison of CECT color maps with Safranin-O stained histological sections. The associations between CECT attenuation and GAG content, CECT attenuation and water content, and flux and water content at various time points were determined using both contrast agents. Depth-wise analyses were also performed through each of the native surfaces to examine differences in contrast agent diffusion kinetics and equilibrium partitioning. The optimal concentrations for GAG depiction for ioxaglate and CA4+ were ≥80 and 12 mgI/ml, respectively. Using these concentrations, weak to moderate associations were found between ioxaglate attenuation and GAG content at all diffusion time points (1-48 h), while strong and significant associations were observed between CA4+ attenuation and GAG content as early as 7 h (R2≥ 0.67), being strongest at the equilibrium time point (48 h, R2= 0.81). CECT attenuation for both agents did not significantly correlate with water content, but CA4+ flux correlated with water content (R2= 0.56-0.64). CECT is a promising, non-destructive imaging technique for ex vivo assessment of meniscal GAG concentration and water content compared to traditional biochemical and histopathological methods. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1018-1028, 2017.
Harvard-MIT Health Sciences and Technology Program, Harvard Medical School, Cambridge, Massachusetts.|Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.
Daniel J
DJ
Oh
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.|Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave, Boston, Massachusetts, 02215.
Benjamin A
BA
Lakin
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.|Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave, Boston, Massachusetts, 02215.
Rachel C
RC
Stewart
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.|Department of Orthopaedic and Trauma, Kantonsspital Winterthur, Winterthur, Switzerland.
Martin
M
Wiewiorski
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.|Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, Massachusetts.
Jonathan D
JD
Freedman
Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave, Boston, Massachusetts, 02215.|Department of Chemistry, Boston University, Boston, Massachusetts.
Mark W
MW
Grinstaff
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, RN 115, Boston, Massachusetts, 02215.|Children's Hospital, Boston, Massachusetts.
Brian D
BD
Snyder
D000328:Adult; D005029:Ethylenediamines; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007462:Iodobenzenes; D007485:Ioxaglic Acid; D008297:Male; D008592:Menisci, Tibial / Q000000981:diagnostic imaging*; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D055815:Young Adult
D005029:Ethylenediamines; D006025:Glycosaminoglycans; D007462:Iodobenzenes; D007485:Ioxaglic Acid
computed tomography; diffusion flux; glycosaminoglycan; osteoarthritis; water content