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286

M. Iorga and G. Dougherty

plots the tortuosity of the first quintile of its length (closest to the optic disk) with the tortuosity of the entire vessel, for the 46 vessels of the marked database shown in Fig. 12.7. The correlation coefficient is 0.5777, corresponding to p < 0.0001. This indicates that there is little significant change in tortuosity along the length of a vessel, and therefore the tortuosity of the entire vessel can be confidently used to characterize each vessel.

12.7 Summary and Future Work

It has been recognized that the local flow hemodynamics of a curved vessel may dispose it to the formation of an aneurysm. The geometry of intracranial arteries, for example, has been implicated in the formation of aneurysms [10]. The branching patterns of the vessel network may also be useful in diagnosing and evaluating the severity of a disease such as diabetic retinopathy [34, 42].

We have shown that tortuosity is related to microaneurysm count, and we suggest that tortuosity increases with severity of diabetic retinopathy. It is too early to say with this limited data whether tortuosity could be used as an alternate predictor of the severity of such retinopathy. Longitudinal data would help to resolve the matter. Local flow hemodynamics will be affected by the tortuosity of the vessels, and it will affect the number of microaneurysms formed. Precisely which is cause and which is effect is difficult to ascertain, but as diabetic retinopathy becomes more severe it is likely that both tortuosity and microaneurysm count will increase, and our results confirm this trend. Blood pressure and the diameter of the vessels are also likely implicated in the changes. It may be that tortuosity is related to an integral effect of blood pressure, while microaneurysm responds more to local maxima.

Tortuosity can be measured easily from the digitized tracings of vessels in retinal images, and these tracings can be obtained using a semiautomated program such as NeuronJ. Fully automated tracing is an enticing prospect, although current algorithms would seem to require customized preprocessing of the image, which would then render the process semiautomatic again.

Fractal dimension (or the fractal signature [63]) may be an alternative method of measuring the bending within a blood vessel. Initial studies demonstrated that the blood vessels of the optic fundus are fractal, and that the fractal dimension can be used to identify PDR [64, 65]. Preliminary analysis of the skeletonized vascular patterns in the normal and NPDR macula suggested that vascular morphology had already changed by this relatively early stage of retinal disease [66].

A disadvantage of fractal dimension is that it is constrained within very tight limits (1–2 for a vessel tracing), and this limits its sensitivity. Another limitation is that different algorithms can result in different values [67]. Perhaps, its greatest potential is that it can deliver a quantitative summary value for the geometric complexity of a network, rather than a single vessel, and could therefore summarize the complete retinal vascular branching pattern in an image. Recent computerized studies [68, 69] suggest that increased fractal dimension of the retinal vasculature,

12 Tortuosity as an Indicator of the Severity of Diabetic Retinopathy

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reflecting increased geometric complexity of the retinal vascular branching pattern, is associated with early diabetic retinopathy microvascular damage. Although the differences in fractal dimension were small [69], the average fractal dimension was higher in participants with retinopathy than in those without retinopathy (median 1.46798 [interquartile range 1.45861–1.47626] compared with 1.46068 [1.44835–1.47062], respectively; p < 0.001). After adjustments for age and sex, greater fractal dimension was significantly associated with increased odds of retinopathy (odds ratio [OR] 4.04 [95%CI 2.21–7.49] comparing highest to lowest quartile of fractal dimension; OR 1.33 for each 0.01 increase in fractal dimension). This association remained with additional adjustments for diabetes duration, blood sugar, blood pressure, body mass index (BMI), and total cholesterol levels. Further adjustment for retinal arteriolar or venular caliber had minimal impact on the association (OR 3.92 [95% CI 1.98–7.75]).

Acknowledgments We acknowledge with thanks the help and assistance of Dr. Eric Meijering, Dr. Michal Sofka, and Dr. Michael Cree on issues regarding their respective software. A database of retinal images, with the microaneurysms manually identified by experts, was kindly supplied by Dr. Jean-Claude Klein of the Center of Mathematical Morphology of MINES, Paris Tech. One of us (G.D.) acknowledges the award of a Fulbright Senior Scholarship, which provided the opportunity to expand work in this area and others.

References

1.Hoover, A., Kouznetsova, V., Goldbaum, M.: Locating blood vessels in retinal images by piecewise threshold probing of a matched filter response. IEEE Trans. Med. Imaging 19, 203–210 (2000)

2.Witt, N., Wong, T.Y., Hughes, A.D., et al.: Abnormalities of retinal vasculature structure and the risk of mortality from ischemic heart disease and stroke. Hypertension 47, 975–981 (2006)

3.Wong, T.Y., Shankar, A., Klein, R., et al.: Retinal arteriolar narrowing, hypertension and subsequent risk of diabetes mellitus. Medicine 165, 1060–1065 (2005)

4.Cheung, N., Wong, T.Y., Hodgson, L.: Retinal vascular changes as biomarkers of systemic cardiovascular diseases. In: Jelinek, H.F., Cree, M.J. (eds.) Automated Image Detection of Retinal Pathology, pp. 185–219, CRC Press, Boca Raton, FL (2010)

5.Wong, T.Y., Mohamed, Q., Klein, R., et al.: Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes? Br. J. Ophthalmol. 90, 301–303 (2006)

6.Fong, D.S., Aiello, L., Gardner, T.W., et al.: Diabetic retinopathy. Diabetes Care 26, 226–229 (2003)

7.Dobrin, P.B., Schwarz, T.H., Baker, W.H.: Mechanisms of arterial and aneurismal tortuosity. Surgery 104, 568–571 (1988)

8.Wenn, C.M., Newman, D.L.: Arterial tortuosity. Aust. Phys. Eng. Sci. Med. 13, 67–70 (1990)

9.Dougherty, G., Varro, J.: A quantitative index for the measurement of the tortuosity of blood vessels. Med. Eng. Phys. 222, 567–574 (2000)

10.Bor, A.S.E., Velthuis, B.K., Majoie, C.B., et al.: Configuration of intracranial arteries and development of aneurysms: a follow-up study. Neurology 70, 700–705 (2008)

11.Klein, R., Meuer, S.M., Moss, S.E., et al.: Retinal aneurysm counts and 10-year progression of diabetic retinopathy. Arch. Ophthalmol. 113, 1386–1391 (1995)

12.Kohner, E.M., Stratton, I.M., Aldington, S.J., et al.: Microaneurysms in the development of diabetic retinopathy (UKPDS 42). Diabetologia 42, 1107–1112 (1999)

288

M. Iorga and G. Dougherty

13.Hellstedt, T., Immonen I.: Disappearance and formation rates of microaneurysms in early diabetic retinopathy. Br. J. Ophthalmol. 80, 135–139 (1996)

14.Kohner, E.M., Dollery, C.T.: The rate of formation and disappearance of microaneurysms in diabetic retinopathy. Eur. J. Clin. Invest. 1, 167–171 (1970)

15.Goatman, K.A., Cree, M.J., Olson, J.A., et al.: Automated measurement of microaneurysm turnover. Invest. Ophthalmol. Vis. Sci. 44, 5335–5341 (2003)

16.Phillips, R.P., Spencer, T., Ross, P.G., et al.: Quantification of diabetic maculopathy by digital imaging of the fundus. Eye 5, 130–137 (1991)

17.Phillips, R., Forrester, J., Sharp, P.: Automated detection and quantification of retinal exudates. Graefe’s Arch. Clin. Exp. Ophthalmol. 231, 90–94 (1993)

18.Osareh, A., Shadgar, B., Markham, R.: A computational-intelligence-based approach for detection of exudates in diabetic retinopathy images. IEEE Trans. Inf. Tech Biomed. 13, 535–545 (2009)

19.Preece, S.J., Claridge E. Monte Carlo modeling of the spectral reflectance of the human eye. Phys. Med. Biol. 47, 2863–2877 (2002)

20.Cree, M.J., Gamble, E., Cornforth, D.J.: Colour normalisation to reduce inter-patient and intrapatient variability in microaneurysm detection in colour retinal images. In: APRS Workshop in Digital Imaging (WDIC2005), Brisbane, Australia, pp. 163–168 (2005)

21.Niemeijer, M., van Ginneken, B., Cree, M.J., et al.: Retinopathy online challenge: automatic detection of microaneurysms in digital color fundus photographs. IEEE Trans. Med. Imaging 29, 185–195 (2010)

22.Baudoin, C.E., Lay, B.J., Klein, J.C.: Automatic detection of microaneurysms in diabetic fluorescein angiographies. Revue D’Epid´emiologie et de Sante Publique 32, 254–261 (1984)

23.Spencer, T., Olson, J.A., McHardy, K.C., et al.: An image-processing strategy for the segmentation and quantification in fluorescein angiograms of the ocular fundus. Comput. Biomed. Res. 29, 284–302 (1996)

24.Cree, M.J., Olson, J.A., McHardy, K.C., et al.: A fully automated comparative microaneurysm digital detection system. Eye 11, 622–628 (1997)

25.Frame, A.J., Undrill, P.E., Cree, M.J., et al.: A comparison of computer based classification methods applied to the detection of microaneurysms in ophthalmic fluorescein angiograms. Comput. Biol. Med. 28, 225–238 (1998)

26.Streeter, L., Cree, M.J.: Microaneurysm detection in colour fundus images. In: Proceedings of the Image and Vision Computing New Zealand Conference (IVCNZ’03), Palmerston North, New Zealand, pp. 280–285 (2003)

27.Cree, M.J., Gamble, E., Cornforth, D.: Colour normalisation to reduce inter-patient and intrapatient variability in microaneurysm detection in colour retinal images. In: Proceedings of APRS Workshop on Digital Image Computing (WDIC2005), Brisbane, Australia, pp. 163–168 (2005)

28.Vincent, L.: Morphological grayscale reconstruction in image analysis: applications and efficient algorithms. IEEE Trans. Image Process. 2, 176–201 (1993)

29.Dupas, B., Walter, T., Erginay, A., et al.: Evaluation of automated fundus photograph analysis algorithms for detecting microaneurysms, haemorrhages and exudates, and of a computerassisted diagnostic system for grading diabetic retinopathy. Diabetes Metab. 36, 213–220 (2010)

30.Quellec, G., Lamard, M., Josselin, P.M., et al.: Optimal wavelet transform for the detection of microaneurysms in retina photographs. IEEE Trans. Med. Imaging 27, 1230–1241 (2008)

31.Niemeijer, M., Staal, J.S., van Ginneken, B., et al.: Comparative study of retinal vessel segmentation on a new publicly available database. Proc. SPIE 5370–5379 (2004)

32.Staal, J., Abramoff, M., Neimeijer, Mc, et al.: Ridge-based vessel segmentation in color images of the retina. IEEE Trans. Med. Imaging 23, 501–509 (2004)

33.Early Treatment Diabetic Retinopathy Study Research Group: Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. ETDRS report #10. Ophthalmology 98, 786–806 (1991)

12 Tortuosity as an Indicator of the Severity of Diabetic Retinopathy

289

34.Hart, W.E., Goldbaum, M., Cot´e, B., et al.: Measurement and classification of retinal vascular tortuosity. Int. J. Med. Inform. 53, 239–252 (1999)

35.Aslam, T., Fleck, B., Patton, N., et al.: Digital image analysis of plus disease in retinopathy of prematurity. Acta ophthalmol. 87, 368–377 (2009)

36.Capowski, J.J., Kylstra, J.A., Freedman, S.F.: A numeric index based on spatial frequency for the tortuosity of retinal vessels and its application to plus disease in retinopathy of prematurity. Retina 15, 490–500 (1995)

37.Wallace, D.K.: Computer-assisted quantification of vascular tortuosity in retinopathy of prematurity. Trans. Am. Ophthalmol. Soc. 105, 594–615 (2007)

38.Owen, C.G., Rudnicka, A.R., Mullen, R., et al.: Measuring retinal vessel tortuosity in 10- year-old children: validation of the computer-assisted image analysis of the retina (CAIAR) program. Invest. Ophthalmol. Vis. Sci. 50, 2004–2010 (2009)

39.Lotmar, W., Freiburghaus, A., Bracker, D.: Measurement of vessel tortuosity on fundus

photographs. Graefe’s Arch. Clin. Exp. Ophthalmol. 211, 49–57 (1979)

¨

40. Smedby, O., H¨ogman, N., Nilsson, U., et al.: Two-dimensional tortuosity of the superficial femoral artery in early atherosclerosis. J. Vasc. Res. 30, 181–191 (1993)

41. Saidl´ear, C.A.: Implementation of a Quantitative Index for 3-D Arterial Tortuosity. M.Sc. thesis, University of Dublin, 2002

42. Bullitt, E., Gerig, G., Pizer, S.M., et al.: Measuring tortuosity of the intracerebral vasculature from MRA images. IEEE Trans. Med. Imaging 22, 1163–1171 (2003)

43. Grisan, E., Foracchia, M., Ruggeri, A.: A novel method for the automatic evaluation of retinal vessel tortuosity. IEEE Trans. Med. Imaging 27, 310–319 (2008)

44. Johnson, M.J., Dougherty, G.: Robust measures of three-dimensional vascular tortuosity based on the minimum curvature of approximating polynomial spline fits to the vessel mid-line. Med. Eng. Phys. 29, 677–690 (2007)

45. Dougherty, G., Johnson, M.J.: Clinical validation of three-dimensional tortuosity metrics based on the minimum curvature of approximating polynomial splines. Med. Eng. Phys. 30, 190–198 (2008)

46. Dougherty, G., Johnson, M.J., Wiers, M.D.: Measurement of retinal vascular tortuosity and its application to retinal pathologies. Med. Biol. Eng. Comput. 48, 87–95 (2010)

47. Sonka, M., Hlavac, V., Boyle, R.: Image Processing, Analysis, and Machine Vision, 3rd edn. Cengage Learning, Florence, KY (2007)

48. Dougherty G.: Digital Image Processing for Medical Applications. Cambridge University Press, Cambridge (2009) (a) pp. 259–263; (b) pp. 157–159; (c) pp. 296–301; (d) pp. 140–144 49. Meijering, E., Jacob, M., Sarria, J.C.F., et al.: Design and validation of a tool for Neurite tracing

and analysis in fluorescence microscopy images. Cytometry A 58, 167–176 (2004)

50. Xiong, G., Zhou, X., Degterev, A., et al.: Automated neurite labeling and analysis in fluorescence microscopy images. Cytometry A 69, 494–505 (2006)

51. Zhang, Y., Zhou, X., Witt, R.M., et al.: Dendritic spine detection using curvilinear structure detector and LDA classifier. Neuroimage 36, 346–360 (2007)

52. Fan, J., Zhou, X., Dy, J.G., et al.: An automated pipeline for dendrite spine detection and tracking of 3D optical microscopy neuron images of in vivo mouse models. Neuroinformatics 7, 113–130 (2009)

53. Yuan, X., Trachtenberg, J.T., Potter, S.M., et al.: MDL constrained 3-D grayscale skeletonization algorithm for automated extraction of dendrites and spines from fluorescence confocal images. Neuroinformatics 7, 213–232 (2009)

54. Sofka, M., Stewart, C.V.: Retinal vessel centerline extraction using multiscale matched filters, confidence and edge measures. IEEE Trans. Med. Imaging 25, 1531–1546 (2006)

55. Sun, C., Vallotton, P.: Fast linear feature detection using multiple directional non-maximum suppression. J. Microsc. 234, 147–157 (2009)

56. Lindeberg, T.: Feature detection with automatic scale selection. Int. J. Comput. Vis. 30(2), 77–116 (1998)

57. Barrett, W.A., Mortensen, E.N.: Interactive live-wire boundary extraction. Med. Image Anal. 1, 331–341 (1996)

290

M. Iorga and G. Dougherty

58.Falc˜ao, A.X., Udupa, J.K., Samarasekera, S., et al.: User-steered image segmentation paradigms: live wire and live lane. Graph. Models Image Process. 60, 233–260 (1998)

59.Falc˜ao, A.X., Udupa, J.K., Miyazawa, F.K.: An ultra-fast user-steered image segmentation paradigm: LiveWire on the fly. IEEE Trans. Med. Imaging 19, 55–62 (2000)

60.Vallotton, P., Lagerstrom, R., Sun, C., et al.: Automated analysis of neurite branching in cultured cortical neurons using HCA-vision. Cytometry A 71, 889–895 (2007)

61.Conrad, C., Gerlich D.W.: Automated microscopy for high-content RNAi screening. J. Cell Biol. 188, 453–461 (2010)

62.Vallotton, P., Sun, C., Wang, D., et al.: Segmentation and tracking of individual Pseudomonas aeruginosa bacteria in dense populations of motile cells. In: Image and Vision Computing New Zealand, Wellington, New Zealand, 2009

63.Dougherty, G., Henebry, G.M.: Fractal signature and lacunarity in the measurement of the texture of trabecular bone in clinical CT images. Med. Eng. Phys. 23, 369–380 (2001)

64.Family, F., Masters, B.R., Platt, D.: Fractal pattern formation in human retinal vessels. Physica D 38, 98–103 (1989)

65.Daxer, A.: The fractal geometry of proliferative diabetic retinopathy: implications for the diagnosis and the process of retinal vasculogenesis. Curr. Eye Res. 12, 1103–1109 (1993)

66.Avakian, A., Kalina, R.E., Sage, E.H., et al.: Fractal analysis of region-based vascular change in the normal and non-proliferative diabetic retina. Curr. Eye Res. 24, 274–280 (2002)

67.Schepers, H.E., Van Beek, J.H.G.M., Bassingthwaighte, J.B.: Four methods to estimate the fractal dimension from self-affine signals. IEEE Eng. Med. Biol. 11, 57–64 (1992)

68.MacGillivray, T.J., Patton, N.: A reliability study of fractal analysis of the skeletonised vascular network using the “box-counting” technique. Conf. Proc. IEEE Eng. Med. Biol. Soc. 1, 4445–4448 (2006)

69.Cheung, N., Donaghue, K.C., Liew, G., et al.: Quantitative assessment of early diabetic retinopathy using fractal analysis. Diabetes Care 32, 106–110 (2009)

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