Research

Computed Tomography (CT)

Basic principles

Computed tomography (CT) is a medical imaging technique developed almost 40 years ago. Method uses digital geometry processing to generate a three-dimensional image from a large set of two-dimensional X-ray images taken around a single axis of rotation. The basic physics is similar to conventional X-ray imaging; different materials have different attenuation coefficients that are dependent on density of the material. In order to acquire good quality images, the sample has to have enough internal density variation. CT is used also in fields other than healthcare, for example nondestructive material testing.

Figure 1. CT cross-sections are calculated from multiple projection images around the object.

University of Eastern Finland Kuopio campus area provides a continuum of computed tomography devices, beginning from micrometer-scale pre-clinical scanner to in vivo CT and further to clinical cone beam CT (Verity), pQCT and total body instruments.

Micro-CT image stacks can be used as a basis of 3D-models. Meshes created from cross-sectional images can be used, for example, in acoustic and mechanical finite element modeling.

Figure 2. Finite element mesh of cancellous bone, created from a micro-CT scan.

Specific aims

In our group computed tomography is currently being used for bone and articular cartilage research and for material characterization. Bone mineral density and structural parameters are often used as a reference technique when developing new methods for bone quality assessment. In articular cartilage research we aim to quantify cartilage quality and proteoglycan (PG) content, and to detect cartilage injuries.

Bone research

X-ray techniques have been used to image skeletal system since the discovery of X-rays. Computed tomography is no exception; it can be used to measure, for example, bone thickness, area and mineral density. With high-resolution scanners, also cancellous bone and even individual trabeculae are easily quantified. Structural data acquired with computed tomography is often used as a reference technique for morphological analyses.

Bone mineral density, as measured with dual-energy X-ray absorptiometry (DXA) and structural properties determined with micro-CT have been used as reference parameters for bone ultrasound studies.

Cartilage research

X-ray images, especifically the narrowing of knee joint space, have long been used in diagnosis of osteoarthrosis (OA). This method only shows changes when the cartilage has been destroyed and the damage is already irreversible. Recently, however, CT method (contrast enhanced computed tomography, CECT) analogous to the dGEMRIC has been used to quantify proteoglycan distribution and cartilage quality in articular cartilage [1, 2, 3, 4]. These methods utilize ionic contrast agents and hypothesis that the negatively charged glycosaminoglycans (GAG) in proteoglycans cause a fixed charge density (FCD) variation in cartilage; ionic contrast agent is supposed to distribute relatively to the FCD. This method has potential for early diagnosis of OA, when the cartilage still looks visually healthy.

Figure 3. Light microscopy images demonstrated severe trypsin-induced PG loss. Gadopentetate (A) and ioxaglate (B) enhanced pQCT detected sensitively the PG loss [3].

We have showed that CECT can be used to detect mechanical cartilage damage in bovine cartilage [5] (Fig. 4). As the final step of the continuum the method was applied to clinical patients, giving much info on the contrast agent dilution in the knee joint and diffusion into the cartilage when not n laboratory environment [6].

Figure 4. Light microscopy images visualize the mechanical injury on the sample. Contrast enhanced CT detects the injuries using (A, C) iodide and ioxaglate (B, D) [5].

References

  1. Palmer AW, Guldberg RE, Levenston ME. Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. Proc Natl Acad Sci USA 103: 19255-60, 2006.
  2. Cockman MD, Blanton CA, Chmielewski PA, Dong L, Dufresne TE, Hookfin EB, Karb MJ, Liu S, Wehmeyer KR. Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT. Osteoarthritis Cartilage 14: 210-4, 2006.
  3. Kallioniemi AS, Jurvelin JS, Nieminen MT, Lammi MJ, Töyräs J. Contrast agent enhanced pQCT of articular cartilage. Phys Med Biol 52: 1209-19, 2007.
  4. Silvast TS, Jurvelin JS, Aula AS, Lammi MJ, Töyräs J. Contrast agent-enhanced computed tomography of articular cartilage: association with tissue composition and properties. Acta Radiol 50:78-85, 2009.
  5. Kokkonen HT, Jurvelin JS, Tiitu V, Toyras J. Detection of mechanical injury of articular cartilage using contrast enhanced computed tomography. Osteoarthritis Cartilage 2011;19:295-301.
  6. Kokkonen HT, Aula AS, Kröger H, Suomalainen J-S, Lammentausta E, Mervaala E, et al. Contrast Enhanced Computed Tomography of Human Knee Cartilage in vivo. Cartilage 2012.

PhD thesis of our researchers

Antti Aula née Kallioniemi:
Computed Tomography and Ultrasound Methods for Simultaneous Evaluation of Articular Cartilage and Subchodral Bone

Publications from our research group

  1. Honkanen JTJ, Turunen MJ, Freedman JD, Saarakkala S, Grinstaff MW, Ylarinne JH, Jurvelin JS and Toyras J. Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus. Ann Biomed Eng. 2016 Oct;44(10):2913-2921. doi: 10.1007/s10439-016-1629-z. Epub

  2. Honkanen JT, ORCID: 0000-0002-9150-9253, Turunen MJ, Tiitu V, Jurvelin JS and Toyras J. Transport of Iodine Is Different in Cartilage and Meniscus. Ann Biomed Eng. 2016 Jul;44(7):2114-22. doi: 10.1007/s10439-015-1513-2. Epub 2015

  3. Honkanen JT, Danso EK, Suomalainen JS, Tiitu V, Korhonen RK, Jurvelin JS and Toyras J. Contrast enhanced imaging of human meniscus using cone beam CT. Osteoarthritis Cartilage. 2015 Aug;23(8):1367-76. doi:

  4. Kokkonen HT, Suomalainen JS, Joukainen A, Kroger H, Sirola J, Jurvelin JS, Salo J and Toyras J. In vivo diagnostics of human knee cartilage lesions using delayed CBCT arthrography. J Orthop Res. 2014 Mar;32(3):403-12. doi: 10.1002/jor.22521. Epub 2013 Nov 19.

  5. Kulmala KA, Karjalainen HM, Kokkonen HT, Tiitu V, Kovanen V, Lammi MJ, Jurvelin JS, Korhonen RK and Toyras J. Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking--contribution of steric and electrostatic effects. Med Eng Phys. 2013 Oct;35(10):1415-20. doi: 10.1016/j.medengphy.2013.03.010. Epub

  6. Silvast TS, Jurvelin JS, Tiitu V, Quinn TM and Toyras J. Bath Concentration of Anionic Contrast Agents Does Not Affect Their Diffusion and Distribution in Articular Cartilage In Vitro. Cartilage. 2013 Jan;4(1):42-51. doi: 10.1177/1947603512451023.

  7. Kokkonen HT, Aula AS, Kroger H, Suomalainen JS, Lammentausta E, Mervaala E, Jurvelin JS and Toyras J. Delayed Computed Tomography Arthrography of Human Knee Cartilage In Vivo. Cartilage. 2012 Oct;3(4):334-41. doi: 10.1177/1947603512447300.

  8. Kulmala KA, Pulkkinen HJ, Rieppo L, Tiitu V, Kiviranta I, Brunott A, Brommer H, van Weeren R, Brama PA, Mikkola MT, Korhonen RK, Jurvelin JS and Toyras J. Contrast-Enhanced Micro-Computed Tomography in Evaluation of Spontaneous Repair of Equine Cartilage. Cartilage. 2012 Jul;3(3):235-44. doi: 10.1177/1947603511424173.

  9. Kokkonen HT, Makela J, Kulmala KA, Rieppo L, Jurvelin JS, Tiitu V, Karjalainen HM, Korhonen RK, Kovanen V and Toyras J. Computed tomography detects changes in contrast agent diffusion after collagen cross-linking typical to natural aging of articular cartilage. Osteoarthritis Cartilage. 2011 Oct;19(10):1190-8. doi:

  10. Kokkonen HT, Jurvelin JS, Tiitu V and Toyras J. Detection of mechanical injury of articular cartilage using contrast enhanced computed tomography. Osteoarthritis Cartilage. 2011 Mar;19(3):295-301. doi:

  11. Kulmala KA, Korhonen RK, Julkunen P, Jurvelin JS, Quinn TM, Kroger H and Toyras J. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents. Med Eng Phys. 2010 Oct;32(8):878-82. doi: 10.1016/j.medengphy.2010.06.002. Epub

  12. Silvast TS, Kokkonen HT, Jurvelin JS, Quinn TM, Nieminen MT and Toyras J. Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage. Phys Med Biol. 2009 Nov 21;54(22):6823-36. doi: 10.1088/0031-9155/54/22/005. Epub

  13. Aula AS, Jurvelin JS and Toyras J. Simultaneous computed tomography of articular cartilage and subchondral bone. Osteoarthritis Cartilage. 2009 Dec;17(12):1583-8. doi:

  14. Silvast TS, Jurvelin JS, Aula AS, Lammi MJ and Toyras J. Contrast agent-enhanced computed tomography of articular cartilage: association with tissue composition and properties. Acta Radiol. 2009 Jan;50(1):78-85. doi: 10.1080/02841850802572526.

  15. Silvast TS, Jurvelin JS, Lammi MJ and Toyras J. pQCT study on diffusion and equilibrium distribution of iodinated anionic contrast agent in human articular cartilage--associations to matrix composition and integrity. Osteoarthritis Cartilage. 2009 Jan;17(1):26-32. doi: 10.1016/j.joca.2008.05.012.

  16. Kallioniemi AS, Jurvelin JS, Nieminen MT, Lammi MJ and Toyras J. Contrast agent enhanced pQCT of articular cartilage. Phys Med Biol. 2007 Feb 21;52(4):1209-19. doi: 10.1088/0031-9155/52/4/024. Epub

  17. Kokkonen HT, Aula AS, Kröger H, Suomalainen J-S, Lammentausta E, Mervaala E, et al. Contrast Enhanced Computed Tomography of Human Knee Cartilage in vivo. Cartilage 2012.

  18. Kulmala K, Pulkkinen H, Rieppo L, Tiitu V, Kiviranta I, Brünott A, et al. Contrast-Enhanced Micro–Computed Tomography in Evaluation of Spontaneous Repair of Equine Cartilage. Cartilage 2012.
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