BoneXpert Online - Instructions for Use

2021-05	Manufacturer: Visiana Fremtidsvej 1 2970 Hørsholm Denmark www.bonexpert.com support@BoneXpert.com

BoneXpert is a registered trademark

Version: 1.1

1. Introduction

These instructions are for BoneXpert Online, a browser-based application for bone age assessment. The application is intended for interactive use.

For clinical use, the application interprets images in DICOM format. The JPG, PNG, and BMP file formats are also supported for research purposes.

For clinics with PACS system, we also provide BoneXpert Server, a Windows Service, providing the same bone age calculations as BoneXpert Online. BoneXpert Server is designed to exchange images with the PACS system. The installation itself takes less than an hour

2. Intended use

The intended use of BoneXpert is to perform an autonomous determination of bone age (BA) and Bone Health Index (BHI).

The bone age determination can replace the conventional manual rating and the operation needs no supervision by an expert.

For clinical use, the hand radiograph must be provided as a DICOM file.

2.1. Intended user

The intended user of BoneXpert is a health-care professional, e.g. a radiologist, a radiographer, an endocrinologist or a nurse.

2.2. Intended conditions of use

The user must have the ability to obtain digital hand radiographs in the DICOM format recorded with sufficiently good quality as detailed in the section ''Requirements for the radiograph''

3. Range of applications

3.1. Bone age

Bone age assessment is a standard procedure in paediatrics, and BoneXpert can be used to determine bone age in the bone age range 0-19 years for boys and 0-18 for girls, and for the following range of indications:

3.2. Ethnicity range

Bone age assessment, as it is done manually, and as is done by BoneXpert, is based on the image and the gender alone, without taking any ethnicity information into account.

3.3. Range of disorders

BoneXpert can assess in both bone age in normal/healthy children and in the children diagnosed with the following disorders:

Children with short stature diagnoses: Turner Syndrome, Growth Hormone Deficiency (GHD), Silver-Russell Syndrome, children born small for gestational age (SGA), Noonan, and short stature homeobox-containing gene (SHOX)
Children with puberties praecox
Children with tall stature
Children with CAH (congenital adrenal hyperplasia)
Children with Klinefelter
Children with other known or suspected hormonal disturbances, which can affect growth and/or maturation
Children considered to undergo an orthopaedic or orthodontic treatment, which can benefit from being planned relative to the growth spurt or the amount of growth left

3.4. Bone Health Index

Whenever BoneXpert has determined the bone age, it also attempts to determine the Bone Health Index (BHI), which quantifies the amount of cortical bone in the three middle metacarpal shafts. This should not be the primary indication for use of BoneXpert and BHI should be considered supplementary information, mainly for research use.

3.5. Non-medical indications

BoneXpert can also be used to determine the bone age in children for

Sport activities
Legal purposes

3.6. Contraindications

BoneXpert might reject images of children with severe skeletal dysplasia, e.g. achondroplasia, or other disorders that alter the bone structure or hand pose to a large degree, such as cerebral palsy. In such cases of rejection, a radiologist should assess the image. Note however, that if BoneXpert gives a bone age value for an image, it can always be considered safe, so use in conditions with altered bone structure is an inefficiency, not a risk.

4. Performance data

Bone age	Bone age scales	Greulich-Pyle (GP), Tanner-Whitehouse 3 (TW3)
	Bone age precision, SD	0.00 years when rerating same image 0.16 years or less when taking a new X-ray of the same hand.
	Bone age accuracy, RMSE	0.63 years (GP bone age, relative to typical manual rater) 0.59 years (TW3 bone age, relative to an excellent rater)
	Bone age sensitivity to image quality	<0.20 years (95% confidence level)
Bone Health Index	BHI precision SD	1.4% at age 10 years
Bone Health Index	BHI sensitivity to image quality (accuracy)	<5.5% (95% confidence level)

Performance data pertaining to the determination of bone age and Bone Health Index.
Accuracy and precision are used according to ISO 5725-1.

If the image is inadequate for bone age assessment, the image is automatically rejected. As a result, the user can safely assume, that a bone age assigned by BoneXpert is valid, and in accordance with the performance numbers in the table.

When BoneXpert rejects an image, it can be due to the following causes

It is not child hand X-ray,
The radiographic quality is poor, e.g. the hand pose is wrong, or there are occluding objects,
A too strong post processing has been applied to the image,
The morphology of the bones is abnormal, e.g. in case of severe skeletal dysplasia,
No obvious reason – this category amounts to less than 0.2% of the total number of analyzed images.

5. The workflow

BoneXpert Online features a graphical user interface for viewing and validation of hand X-ray images and for automated determination of bone age. The workflow is outlined below.

Select Image: The first step involves uploading and viewing the image that is to be analysed.
Validation and Preview: The second step requires you to click ‘Next’ to validate the image. The anonymised image is forwarded to Visiana’s server for analysis. No sensitive data is transferred during this process.

Step 2 allows you to validate the quality of a hand X-ray for bone age assessment using BoneXpert at no cost.

3. Analysis and Payment: Once the anonymised image has been uploaded, it is analysed by the BoneXpert server. The validation outcome is then displayed on the screen (refer to the image on the right). If the analysis is successful and the bone outlines are displayed, the user is prompted to proceed with the payment to see the bone age results. These results include:

Greulich and Pyle bone age
Tanner-Whitehouse 3 bone age
Carpal bone age (for bone age <9.5y / F and <11.5y / M)
Bone Health Index (for DICOM images)
Metacarpal Index (for non-DICOM images)

4. Bone Age Assessment Result: The analysed image is displayed, and a link is provided to download the PDF report

If the file uploaded is in DICOM format, the metadata will temporarily be stored locally on the user's browser.

If the input file lacks the information on the patient's gender, the user will be asked to specify the correct gender to ensure the accuracy of the results.

5.1. PDF Report

Results can be printed as a PDF report. The PDF report will initially be prefilled with data from the original DICOM file to fill out the Patient name, ID, clinic name, birth date, and x-ray date.

Upon successful analysis, users have the option to modify the report data

Fields that are modified by the user will have an asterisk ( * ) and the note will be displayed beneath the results stating: *: This field had been changed relative to the information on the original DICOM file.

In the cases where the DICOM details are modified, an additional note is displayed: These results are not intended for clinical use.

The same note will be displayed on analysis reports generated from non-DICOM image format analysis.

6. Minimum system requirements

Internet connection
Internet Browser
- Firefox version 60+
- Chrome version 85+
- Microsoft Edge version 80+

7. Image format

BoneXpert analyses all conventional bone age radiographs in digital form, as long as a radiographer considers them to be of reasonably good quality.

For research purposes, additional image file formats are supported: JPG, PNG, and BNP files. They must be greyscale images, and in the case of JPG images, the degree of compression should be moderate, so that there are no visible artifacts on the image.

DICOM files must have a resolution of 100-720 dpi (dots per inch).

DICOM files have the advantage that they contain the gender, study date, and image resolution in the header. For the other image formats, the system requests the user to enter the gender when the image is loaded.

8. Requirements for the radiograph

There are in general no special requirements for the bone age hand radiographs to be analysed by BoneXpert, as long as they are taken following best practices over the last 60 years.

There should therefore be no surprises in the following list of specific requirements that should be followed to ensure that the image is adequate for bone age determination by BoneXpert.

The image must be a posterior-anterior radiograph including at least 3 cm of radius measured from the distal end of its epiphysis.
The distance between the detector and the X-ray tube (the so-called film-focus distance) should preferably be 1 meter, but any distance between 0.50 and 2 meters is acceptable.
The distance between the palm surface and the detector should be no larger than 2 cm to limit the magnification (bone age and the metacarpal index are insensitive to magnification, but the Bone Health Index is not).
Preferably, the focus should be at the head of the third metacarpal (i.e. the X-ray tube should be perpendicularly above this point).
The tube voltage should be between 45 and 60 kVp.
The hand should be pressed firmly towards the plane surface, and the fingers should be stretched. The fingers should not touch each other, and the angle of the thumb relative to the index finger should be at least 15 degrees; often 30 degrees is preferred. For infants and toddlers, a plastic plate covering the entire hand should be used for compression.
Metacarpals 2-5 should be totally contained in the image and not occluded by any material. It is tolerable that a few of the other bones are occluded to a smaller or larger extent, for instance, a ring on a finger usually does not prevent the program from analysing the bone.
The image must have a resolution of 100-720 dpi (dots per inch).
The image must not be subjected to too much postprocessing (edge enhancement, sharpening), because it can lead to skewed bone age values and even rejection of images. A minor degree of edge enhancement is acceptable - Visiana provides support with this issue.

9. Adult Height Prediction

The prediction of adult height is a common application of bone age.

It is recommended to do the adult height prediction (AHP) using the calculator on www.BoneXpert.com/ahp. The PDF report generated by BoneXpert contains an URL to this AHP; it contains bone age and information such as age taken from the original DICOM.

BoneXpert uses a new method, called the BoneXpert Adult Height Prediction method version 3.0, which is a modernisation and extension of the Bayley-Pinneau method from 1952. It uses the current height, age, bone age, and gender to predict adult height. Optionally, the user can enter the parents’ heights, which are then also used. Furthermore, for girls, the height at the time of the menarche can be entered.

The manual for the adult height predictor can be found at:
https://bonexpert.com/files/BoneXpert_AdultHeightPredictor_v3-005.pdf

10. License control

BoneXpert is licensed on a pay-per-analysis basis.

11. Warnings

	BoneXpert must not be used to analyse hand radiographs recorded on film
	For the BHI measurement to be correct, the radiograph must be taken with the hand directly on the “cassette”, so that the distance between the palm surface and the detector is at most 2 cm.
	The image must not be subjected to too much postprocessing (edge enhancement, sharpening), because it can lead to skewed bone age values and even rejection of images. A minor degree of edge enhancement is acceptable. Visiana provides support with this issue.

12. Risk

There are no known risks or side effects associated with the use of the BoneXpert program. Risk assessment has been conducted following ISO 14971:2012.

13. Description of symbols used in this manual

Symbol	Name	Description of symbols used in this manual
2021-05	Manufacturer	The device is produced by the manufacturer whose name and address are stated next to the symbol. It indicates the medical device manufacturer, as defined in EU Directives 93/42/EEC. Date of manufacture is listed below.
	Electronic instruction for use	Indicates that the user needs to consult the instructions for use. The instruction for use can be found in the BoneXpert Online, under the menu in the upper right corner.
	Warnings	Text marked with a warning symbol must be read before using the device. If the directions of the warnings are not followed it could lead to clinical misdiagnosis and/or loss of damage to patient-related data.
	CE mark	The device complies with Medical Device Directive 93/42/EEC.

14. Abbreviations

BA	Bone Age
BHI	Bone Health Index
MCI	Metacarpal Index
SD	Standard Deviation
RMSE	Root Mean Square Error
SDS	Standard Deviation Score
GP	Greulich-Pyle
TW	Tanner Whitehouse
AHP	Adult Height Prediction
PAH	Percent Adult Height
DICOM	Digital Imaging and Communication in Medicine
PACS	Picture Archiving and Communication System
GHD	Growth Hormone Deficiency
SGA	Small for Gestational Age
SHOX	Short Stature Homebox-Containing Gene
CAH	Congenital Adrenal Hyperplasia

Appendix A: List of errors and warnings

When loading a DICOM file, BoneXpert can report the following errors:

Long message	Reason
Invalid file type	Accepted file types: DICOM, JPG, BMP, PNG
Unknown DICOM error	An unknown error occured. Please make sure that the file is not corrupt, and that all DICOM tags are valid.
Invalid file size. Maximum file size exceeded	The file size cannot be greater than 20.4 MB
DICOM no resolution information	The DICOM file does not contain information about the image resolution. Missing DICOM tags: (0028,0030) and (0018,1164).
DPI too low	Unable to determine bone age because the image resolution is too low. DICOM tag (0028,0030) or (0018,1164).
DPI too high	Unable to determine bone age because the image resolution is too high. DICOM tag (0028,0030) or (0018,1164).

If the input file lacks the information on the patient's gender, the user will be asked to specify the correct gender to ensure the accuracy of the results.

During analysis the following errors can occur.
(The BAstatus codes are used in the log file)

BAstatus	Long message	The validation failed with the following error messages:	Reason
1	Unable to determine bone age	(1) Bones have abnormal shapes (2) Wrong hand pose (3) Poor image quality (4) Excessive post-processing (e.g. ''edge enhancement'' or ''contrast adjustment'') if not DICOM: (5) Hand occupies a too small portion of the image.	BoneXpert Could not recognise this as a valid hand x-ray. Kindly refer to the section 'Requirements for the radiograph'
2	Unable to determine bone age because the image is too sharp	Please reduce edge enhancement in post-processing (typically on the modality) to prevent this error in the future.	The image appears to have been post-processed using a ''sharpening algorithm'' which results in overly sharp bone edges and possibly a dark halo surrounding the bones. We recommend communicating with your radiology department to avoid such intense sharpening, as it prevents BoneXpert from analysing the images.
3	Unable to determine bone age because the image is too blurred		The image seems to be very blurred at the outer edges of the shafts of the metacarpals.
4	Unable to determine bone age because radius was not analysed, and child is quite mature.		The short bones have reached the full maturity, and an accurate bone age assessment therefore requires analysis of the radius; however , radius analysis failed. There can be several reasons for radius not being analysed: a) Not enough radius was included in the image; at leas 3 com is recommended b) The pose of the radius was unusual. This can be avoided in the future by defining a stricter protocol for the pose of the hand and forearm. c) The shape of the radius is abnormal, e.g. a Madelung deformity.

If the Bone Health Index (BHI) analysis fails, BoneXpert will provide the Metacarpal Index (MCI) result instead