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
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• Equations• Imaging techniques• Statistics
– p-values– Correlation coefficients – Confidence intervals
• Derivation details
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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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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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NGFs - Faddy & Gosden 1992
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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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School of Computer Science
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
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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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School of Computer Science
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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