Histology, Ultrasound and Biomedical Models

University of St AndrewsSchool of Computer Science

Histology, Ultrasound and Biomedical Models

SICSA Medical Imaging and Sensing in Computing

Tom Kelsey

School of Computer Science

Overview

• Non-growing follicles– image analysis– normative model

• Ovarian Volume– image analysis– normative model

• Mean Follicle Density• Clinical relevance

18/02/2015Tom Kelsey - SICSA Medical Imaging

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• Equations• Imaging techniques• Statistics

– p-values– Correlation coefficients – Confidence intervals

• Derivation details


Non-Growing Follicles

• Ovarian reserve – Born with a population that declines until

menopause – NGFs are selected for maturation– Primary follicles, secondary follicles, ..., eggs– Many die off at each stage

• Impossible to measure in vivo – Using current technologies

• Populations are counted in vitro – Histological examination of stained tissue


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NGFs


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NGF Detection

• The gold standard is still counting by a human expert

• It would be useful to (semi-)automate the process– Threshold, segment, filter images to isolate and

enumerate NGFs

• We have promising initial results• These don’t yet work in arbitrary labs

– Stain, camera settings, slide preparation, etc.


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NGF Detection


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NGF Detection


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NGFs - Faddy & Gosden 1992


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NGFs – Hansen et al. 2008


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Our Methodology

• Data aggregation– Systematic search for data sources from the

literature• Tables, charts, descriptive statistics

– Our own data – if available

• Data selection – Exclusion & inclusion criteria (e.g. exclude

infertile)

• Homogeneous data set that approximates the healthy population for a wide range of ages


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Our Methodology

• Comparative analysis of biologically plausible models– Goodness of fit

• Accurate enough to capture important features

• But not too accurate– A fantastic fit to the known data– Not useful when predicting new data


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NGFs – Wallace & Kelsey 2010


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Ovarian Volume

• Useful indirect measure of ovarian reserve• Measured by ultrasound

– 2D: measure largest dimensions– 3D: draw and rotate, produce a solid

• Again, gold standard is still human expert• Again, semi-automation is a goal but there

are many image-analysis problems– Lab, user and US machine specific


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2D Measurement


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2D Measurement


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3D Measurement


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3D Measurement


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Ovarian Volume Model

• Same methodology as for NGFs• Combine our data with data from published

studies• Calculate a model that gives average

volumes for any age– and also variation at any age

• Useful when deciding if an ovary is abnormally small or large


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Validated model of log-adjusted ovarian volume throughout life.


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Mean Follicle Density


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• Histology studies often report the average number of NGFs per cubic millimeter of tissue

• We currently have no reference values for expected MFD at a given age

• And the only way to calculate MFDs is to remove ovarian tissue– clearly having a negative effect on fertility

• We have combined our two models to produce an estimate of age-related MFD– and compared with observed values– from two different labs


MFD Observations


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MFD Model


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Clinical Relevance

• Valuable for assessment of MFD in ovarian biopsies in a range of pathological and experimental situations

• Assessment of gonadotoxicity induced by radio- and chemotherapy– and the development of approaches to mitigate such

damage• Potential effects of environmental exposures

where only post-treatment/exposure sampling is possible


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References

• Faddy MJ, Gosden RG. A mathematical model of follicle dynamics in the human ovary. Hum Reprod. 1995;10(4):770-5.

• Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod. 2008;23(3):699-708.

• TW Kelsey, WHB Wallace. Ovarian volume correlates strongly with the number of nongrowing follicles in the human ovary. Obstetrics and Gynecology International. 2012


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References

• Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS ONE. 2010;5(1):e8772.

• Kelsey TW, Dodwell SK, Wilkinson AG, et al. Ovarian volume throughout life: a validated normative model. PLoS ONE. 2013;8(9):e71465.

• M McLaughlin, T W Kelsey, W H B Wallace, R A Anderson, E E Telfer. An externally validated age-related model of mean follicle density in the cortex of the human ovary. Journal of Assisted Reproduction and Genetics. 2015 (under review)


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Thank You

Any questions?


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Documents

Histology, Ultrasound and Biomedical Models