histology, ultrasound and biomedical models
TRANSCRIPT
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
2
• Equations• Imaging techniques• Statistics
– p-values– Correlation coefficients – Confidence intervals
• Derivation details
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
3
School of Computer Science
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.
18/02/2015Tom Kelsey - SICSA Medical Imaging
5
School of Computer Science
NGFs - Faddy & Gosden 1992
18/02/2015Tom Kelsey - SICSA Medical Imaging
8
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
10
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
11
School of Computer Science
NGFs – Wallace & Kelsey 2010
18/02/2015Tom Kelsey - SICSA Medical Imaging
12
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
13
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
18
Validated model of log-adjusted ovarian volume throughout life.
18/02/2015Tom Kelsey - SICSA Medical Imaging
19
School of Computer Science
Mean Follicle Density
18/02/2015Tom Kelsey - SICSA Medical Imaging
20
• 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
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
23
School of Computer Science
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
18/02/2015Tom Kelsey - SICSA Medical Imaging
24
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)
18/02/2015Tom Kelsey - SICSA Medical Imaging
25