WO2019197848A1 - Image analysis method - Google Patents

Abstract

An image analysis method for making systematic measurements of an elastic tubular structure, particularly of the diameter of said structure. The method is particularly useful for measuring anatomical structures.

Description

IMAGE ANALYSIS METHOD

FIELD OF INVENTION

The present invention relates to an image analysis method for making systematic measurements of an elastic tubular structure, particularly of the diameter of said structure. The method is particularly useful for monitoring transient changes in such a structure through time. It can be used for any tubular structure of which an image may be obtained, but is particularly useful for monitoring changes in anatomical structures, such as the gastrointestinal (GI) tract, blood vessels and the heart, etc.

BACKGROUND

There is often a benefit in being able to view changes in anatomical structures over time, for example, monitoring the movement of the heart, observing the changes in a blood vessel. This is particularly true of the gastrointestinal tract.

Chronic constipation is a common gastrointestinal (GI) disorder that causes significant pain and discomfort, and can affect the quality of life of a patient. In certain cases it is necessary for a physician to conduct an examination of the colon in order to diagnose the patient. Therefore, it may be necessary to capture detailed information on colonic contractions, which are responsible for propelling chyme through the colon. The investigation of colonic contractions is also important for determining the effect of drugs on the digestive system, or to ensure that the colon is functioning correctly after surgical treatment. Dysmotility may similarly affect other regions of the GI tract e.g. stomach producing dyspeptic symptoms and altered gastric emptying.

Various non-invasive techniques have been developed for imaging the GI tract and other structures in the body. These include computed tomography (CT), proton emission topography (PET), ultrasound, and magnetic resonance imaging (MRI). There are drawbacks associated with each of these imaging techniques. CT employs potentially harmful X-rays, whilst PET requires that the patient swallow a radioactive tracer, making these techniques undesirable for use with certain patient groups, such as pregnant women. Ultrasound provides a non-quantifiable and non-cross-sectional imaging method, and as such is limited in its ability to make meaningful contraction measurements.

Whilst MRI can be used to capture information on colonic contractions, measurements are only made at single or sporadic locations across the bowel (Bickelhaupt et al. 1 Magn. Reson. Imaging 2014, 39, 17; Froelich et al. Eur. Radiol. 2009, 19, 1387; Menys et at. Brit. J. Radiol. 2014, 87, 201403300). Furthermore, the technique is very subjective, and even healthy people display significant variation to the extent that meaningful observations cannot be made in the absence of a lesion or other anatomical landmark (Menys et at. Brit. J. Radiol. 2014, 87, 201403300).

Conversely, traditional pressure-based and optical manometry allows for the systematic measurement of the GI tract. It involves the placement of a flexible catheter into either end of the GI tract. A series of apertures or sensors placed at fixed intervals along the catheter detect pressure changes along the GI tract. The data is then compiled to build up a profile of the contractions along sections of the gastrointestinal tract. The main disadvantage of this technique for the lower GI tract is that it is invasive: the patent must undergo colonoscopy in order to place the catheter. The range of manometry is also limited to approximately the first 30cm of the colon without prior endoscopy and only the very distal small bowel where a full colonoscopy is performed. The technique is expensive, difficult to use, and poorly available, and so is extremely limited in its use as a routine clinical test.

The use of MRI alongside conventional manometry has previously been investigated; however robust quantitation of the resulting data was not attempted (Kirchoff et al. Abdom. Imaging 2011, 36, 24).

It would be advantageous to provide techniques for non-invasive monitoring of the gastro-intestinal tract, particularly for use in research, diagnosis and assessment of drug efficacy. Such techniques could also be applied to other elastic tubular structures that undergo physiological deformation as part of their function e.g. the heart and the uterus.

SUMMARY OF INVENTION

The invention generally relates to a method of making systematic measurements of a tubular structure using time series data generated by imaging methods. Time series data is obtained by the fast acquisition of images from the same structure region repeated through time.

The invention provides a method for monitoring a tubular structure comprising :

a) applying a midline to an image of said tubular structure, the image showing the wall(s) of the structure;

b) extending axes from that midline to the wall(s) of the structure at at least two points along the midline; c) measuring the length of each axis; and

d) repeating the steps a to c on at least one further image of the tubular structure.

The method may also comprise the step of correcting the image for movement that affects the position or shape of the tubular structure. For example, where the tubular structure is an anatomical feature, respiratory motion or changes in gas position may be taken into consideration.

The method may also include the step of identifying the walls on the image.

The step of measuring the length of each axis may be carried out by any appropriate method, including, for example counting the number of pixels covered by each axis.

The method may additionally comprise the step of generating a graphical representation of time-series data and/or summary statistics.

The tubular structure may be any tubular structure of interest. By tubular structure, it is generally meant that the structure has a lumen, through which material may pass. It has a wall, or walls to define the lumen. The lumen may have a regular cross section along the length of the structure, or the cross section may change, in shape, in size or both. The tubular structure may, for example have a generally circular cross-section and in that configuration could be considered to have one wall wrapped around the lumen. The tubular structure may be generally straight in the direction of its length, or may take any other configuration.

It is preferably an elastic or deformable structure that undergoes changes in dimensions, especially changes in diameter, in use. In particular, it may be an anatomical structure from the human or animal body, such as a vessel, especially a blood vessel, part of the gastrointestinal tract, including the oesophagus stomach, small bowel and colon, the heart and uterus. It could be a naturally occurring structure in the body, or an implanted structure, whether permanent or temporary. Alternatively, it could be a structure that is unrelated to the human or animal body, such as pipe for the transfer of fluid, especially a deformable pipe.

In one embodiment, automated edge detection is used to locate the wall of the structure. In another embodiment, guidelines are applied to delinate the wall. In one embodiment, the image is a 2 dimensional image of the structure. The image preferably shows the tubular structure in one plane and hence shows the widest points of the wall of the structure in that plane. The image preferably shows the inner edge or side of the wall and the outer edge or side of the wall. Where the method of the invention over a time period, each image is preferably taken in the same plane.

In another embodiment, the image is a three dimensional image. Again, it preferably shows the wall of the structure. It may be possible to see the inner side and the outer side of the wall. Where the image is three dimensional, multiple axes may be extended from the midline at each point. For example, at each point chosen along the midline, two, three, four, five or ten or more axes may be extended from the midline to the walls of the structure.

The step of application of the midline to the tubular structure preferably means that a line is drawn on the image, along its length, between the walls of the structure. The line is usually drawn at a position that is reasonably central, between the walls, i.e. approximately the same distance from each wall.

By measuring the length of the axes placed on the midline, it is possible to obtain the luminal diameter of the structure in each image. The two or more axes are preferably perpendicular to the midline. Alternatively, the axes may be parallel to each other. The method preferably includes selecting at least 3, 4, 5, 6, 7, 8, 9, 10, 25, 50, 100, 150, or 200 positions along the midline from which to extend the axes. The axes are preferably placed at equal distances from each other along the midline. The distance between two positions from which axes extend may be less than 2cm, less than 1.5cm, less than 0.5cm, less than 0.4cm, less than 0.3cm, less than 0.2cm, or less than 0.1cm. Each axis is preferably placed at the same point along the midline on each image.

The method preferably includes repeating the steps a to c on at least 5, 10, 15, 20, 25, 50, 100, 150, 200, 250, 400, 500, 600, 750 or 1000 images. The images are preferably obtained over a period of time, and the method repeated to obtain an analysis of the changes in the structure over that period of time.

The images may be any appropriate type of image, such images obtained by magnetic resonance imaging, ultrasound, computed tomography, positron emission tomography, x-ray. The method may include the step of obtaining one or more of the images. The method may also comprise the step of aligning the one or more images. The method may also comprise the step of arranging the images in order of time taken. The method may also comprise, or step d of the method may comprise, the step of propagating the midline and/or the axes through the series of images.

The method may also comprise the step of comparing the length of the axes between images.

The method may also comprise the step of compensating for longitudinal stretch of the tubular structure. The method may comprise the step of measuring the length of the structure. The step of measuring the length of the structure may be repeated on one or more images. By measuring the length of the structure as well as measuring the diameter, it is possible to calculate the volume of the structure at any time point, or over a series of time points. This can provide understanding about the pressure within the structure and about the elasticity or tension of the walls of the structure. This is particularly relevant when the structure is an anatomical structure, especially a structure having muscular walls, as it provides information about the muscle tone. This

information may be useful in diagnosing or differentiating between conditions.

The step of measuring the length of the tubular structure may comprise the step of identifying an end point at each end of the structure and measuring the distance between those end points. This step may be repeated on one or more images, obtained over a period of time. The end points identified may be defined by one or more

identifiable structures. For example, where the tubular structure is an anatomical structure, such as part of the bowel, the end points may be defined by the boundaries of other anatomical structures identifiable on the image. The end points may then be identified on other images of the structure, taken at different time points, to allow the length to be monitored over time.

The midline may be applied by any appropriate means, such as by hand. It may also be computer generated. The length of the axes may be measured by hand or any other appropriate means, such as by using computer-aided measurement. The comparison of axis length between different images may also be carried out by any appropriate method, such as using an appropriate computer program. The method may also comprise the step of processing the data obtained to identify, account and/or compensate for or action one or more of: changes in diameter of the tubular structure at particular points or areas; missing data points; longitudinal stretch or contraction; aberrant data; interpolation in time and/or space between points; and registration with other time series plots. The method may comprise other processing steps to improve comprehension of any image generated from the data.

The method may also comprise the step of correcting data obtained using the method for known motion that may affect the diameter or position of the structure. For example, when the structure is an anatomical structure, it may be affected by movement of other anatomical structures or physiological activity or events, such as respiration. Correcting the data may be carried out by any appropriate technique, such as manually on each image, or by using image registration methods, including RPCA.

The method may also comprise the step of correcting or modulating the data, particularly the data relating to the radius of the tube. This is particularly useful when the tubular structure is a heterogenous tube, such as part of the GI tract. Such a tubular structure can move in many different directions, resulting in expansion or contraction data that is very difficult to analyse. Further, the tube may vary in diameter along its length, being wider in parts than others. Accordingly, the data may be modulated or corrected by, for example, removing any data point over a particular threshold, or by applying a line of best fit through data points. When the line of best fit is applied, outliers to the line represent contractile or expansion events. When radius data over time are monitored or reviewed, it is possible to identify the movement of any contractions of the tube and to see if the tube contracts or widens at certain points over time. This is useful to identify whether the expected patterns of contraction that might be seen in an anatomical tube are actually present, or whether the tube is contracting and expanding abnormally.

The method may also comprise the step of generating a score or summary result, particularly for total radial expansion or contraction. This may be achieved for, by example, obtaining the sum of content above or below a particular threshold for each time point. This provides a snapshot of the position at each time point. To generate a further score, the mean of the sum for each time point may be obtained. This can be used to generate a total score, as well as a total increase or decrease. Also provided is a method for assessing changes in bowel wall length comprising the steps of:

a) Propagating the midline of the bowel on images of the bowel obtained at at least two time points and

b) measuring the length of the midline on each time point image.

In that method, the ends of the midline may be defined by a position that is identifiable on each image.

Also provided is a method for monitoring a tubular structure, comprising the step of recording the diameter/circumference measurements, over time. The measurements may be obtained using the methods defined herein. The measurements may be recorded, into a matrix of time series Vs length data.

Also provided is a method of mapping matrix data, obtainable using the previously defined method for analysis, comprising one or more of the following steps:

a) plotting tubular diameter measures over time, and optionally transforming the data to account for large changes in diameter; b) checking whether a threshold of data points has been reached and, if it has,

inserting missing data points; c) checking whether a threshold of data points has been reached and, if it has not, e.g. when the end of the tubular structure is outside of the view, applying a flag to the data; d) assessing and/or compensating for longitudinal stretch/contraction and variability; e) identifying and/or correcting for aberrant data identification, optionally by using homology or symmetry between either side of the midline at an individual axis position or between axes to ensure propagation errors are not made; f) deleting or editing time points if incorrect; g) registration with other time-series plots, such as those taken on different days for the same patient, or those obtained from other subjects; h) measuring underlying image intensity values in the medical imaging data.

Where the data is obtained using one of the methods of this invention, the axes structure may be used as a mask to measure image intensity values. The intensity values may be used to provide alternative or additional information about the tubular structure, indicating, for example the presence of gas or liquid.

Also provided is method for providing a score to a characteristic of a tubular structure, for example, of expansion of contraction, comprising the steps of setting a scoring threshold for the characteristic and recording a score if the threshold is exceeded.

Also provided is a method for aligning time series data obtainable using a previous method of the invention, comprising sorting the data by time or slice position.

Also provided is a method for analysing motion in a tubular structure, comprising the step of correcting for sources of motion other than movement of the wall of the tubular structure.

Also provided by the invention is a method for diagnosing a deficiency, injury or disease related to a tubular structure in the human or animal body, comprising carrying out the monitoring method of the invention and comparing the results to expected results, wherein a difference between the actual and expected results is indicative of a deficiency, injury or disease. Such diseases may include neurological conditions, such as Parkinsons Disease, heart conditions such as arrhythmia or abnormal contractions, diabetes, inflammatory diseases of the GI tract, such as IBS, Crohn's and constipation. The method may also be used to monitor drug use and drug efficacy, particularly of drugs that influence motility and contractility. Accordingly, there is provided a method of monitoring drug efficacy comprising carrying out the monitoring method of the invention in a subject before and after administration of a pharmacological agent and comparing the results.

Also provided is a computer program that, when executed by a processor, causes the processor to carry out one or more of the methods of the invention.

Also provided is a computer readable medium, programmed to carry out the methods of the invention.

The invention will now be described in detail by way of example only, with reference to the figures.

BRIEF DESCRIPTION OF THE DRAWINGS. Figure 1. Shows a single time point from a dynamic MRI series displaying a sagittal view of the ascending colon, onto which a midline is positioned and delineated in accordance with an embodiment.

Figure 2. Shows the measurements taken for each perpendicular line over at the same position for each time point, during contraction of the GI tract

Figure 3. Shows a time series plot from each perpendicular line through a 30 second time series.

Figure 4. Shows two images of a contracting ventricle with the midline and axes applied thereto.

Figure 5. Shows the time plot from Figure 4.

Figure 6. Shows a method of making highly systemised measurements of the cross- sectional width of the GI tract.

Figure 7. Shows a visual overview of the gastric motility study.

Figure 8. Shows the correlation between combined gastric motility visual score and 'Motility map'.

Figure 9. Shows a visual overview of the colonic motility study.

Figure 10. Shows the correlation between colonic visual motility score and Normalised Contraction Plot (NCP).

Figures 11 and 12. show further correlation between visual motility and normalised contraction plot in the colon.

Figure 13. shows how changes in small bowel length can be assessed and corrected for.

SPECIFIC DESCRIPTION

The inventors have developed a method for making systematic measurements of the tubular structure such as the GI tract by using an imaging technique. Although the present invention will be described with respect to particular embodiments and to particular structures, this description is not to be construed in a limiting sense.

Gastrointestinal (GI) tract refers to any part of the digestive system, including the pharynx, oesophagus, stomach, small intestines, and large intestines, as well as any of the associated organs.

As has been set out above, the present invention concerns in one aspect a method for making systematic measurements of the GI tract comprising the steps of:

(a) Imaging the GI tract by any suitable method.

(b) Fast acquisition of data from the same anatomical region repeated through time.

(c) Applying a computer algorithm to: i. Position a midline (M) along the length of the GI tract.

ii. Delineate the midline (M) at spaced intervals (I) along the GI tract to

propagate a series of perpendicular lines (L).

iii. Detect the edges of the GI tract intersecting each of the perpendicular lines (L).

iv. Measure the luminal diameter of the GI tract at each perpendicular line (L). v. Compile a profile of the luminal diameter along the length of the GI tract.

In step (a) the imaging technique is preferably magnetic resonance imaging (MRI). The patient may be prepared or unprepared with oral contrast. Imaging can be carried out on any part of the human body, depending on which part of the body is being investigated.

In further embodiments, any existing method used for anatomical imaging can be utilised by the present invention.

"Cine" MRI data can be collected by collecting data at various intervals over a given period of time. In a preferred embodiment a fast gradient echo type sequence is used in breath-hold or breathing acquiring an image every second for 20s to 2 minutes or longer based on the contractile action of interest.

Respiratory motion correction techniques like Dual Registration of Abdominal Motion (Menys et al 2014) can be used to remove the effects of breathing from cine MRI data or gated acquisition techniques might be used. The positioning of a midline (M) along the length of the GI tract provides a suitable reference point from which measurements of the GI tract can be made. The midline may be position either manually or using a segmentation algorithm.

The midline is systematically delineated at pre-determined intervals (I) to propagate a series of perpendicular lines (L) along the length of the GI tract. Intersection of the perpendicular lines with the walls of the GI tract can be detected automatically using an intensity change cut off, or by meeting an additional user placed guide line to demarcate the wall of the GI tract. Measurement of the length of the perpendicular line enclosed by the walls of the GI tract allows a quantitative measurement of the luminal diameter of the GI tract at that position to be determined.

Measurements of the lengths of the perpendicular lines along the length of the midline allow a profile of the luminal diameter of the GI tract to be established. This process can be repeated at different time points giving rise to a temporospatial plot, an example of which is shown in Figure 3. For ease of comparative puposes, the data can be smoothed and the time series normalised (i.e. luminal diameter/max luminal diameter at that position).

In another embodiment, the image analysis method may be used to make systematic measurements of blood vessels for the expedient diagnosis of vascular diseases, such as aneurysm or stenosis of the artery. The method of the invention was carried out on a heart ventricle. The ventricle was imaged contracting and two time points from a 25 image series are shown in Figure 4. Drawing along the midline of the ventricle allows the technique to work in the same way as described above. A sample line plot is provided in Figure 5, giving a spatial-temporal map of the line lengths.

EXAMPLES

Proof of concept study

A proof of concept study was undertaken to provide methodological overview of a novel semi-automated technique for capturing and quantifying luminal motility at high spatio- temporal resolution using dynamic 'cine' MR images. Initial validation was provided by applying the technique in the stomach and colon and two new summary motility metrics were proposed.

SUBJECT SELECTION AND MRI DATA ACQUISITION

Methods: Two cohorts of subjects were selected displaying 1) gastric ( n = 24) and 2) colonic motility {n = 20). Subject preparation and disease status was heterogeneous to provide a spectrum of motility on which to test the spatio-temporal motility assessment technique. The technique involved delineating the bowel lumen along with inner and outer bowel wall along a chosen section of the gastrointestinal tract. A series of diameter measurements were made automatically at a 2mm interval orthogonal to the central axis of the lumen. These measurements were automatically propagated through the time series using a previously validated image registration algorithm. Contractions were quantitatively summarised with two methods measuring 1) Normalised Contraction Plot (NCP) NCP was correlated against a three-point subjective but consensus scoring system for the gastric data and a previously validated numerical, semi-quantitative scoring system for the colonic data.

Data and pre-processing

All data was processed with the GIQuant^® (Motilent, London, UK) motility registration technique by the study coordinator. In brief, image registration produces a series of deformation fields that can be used to propagate a region of interest through a time series of n images in an automated fashion. To date, these deformation fields have been summarised to provide a surrogate of motility.

In the current report, the deformation fields enabled the secondary use of the spatio- temporal mapping technique (MRManometry) described below. As the gastric motility data was processed in breath-hold respiratory correction was not required in these data. Conversely, the colonic data was collected during free-breathing and respiratory correction was used here to increase the fidelity of the bowel wall motion correction.

Spatio-temporal analysis with MRManometry

MRManometry describes a method to make highly systemised measurements of the cross-sectional width of the GI tract. In this the following steps are carried out:

(a) The user manually delineates the midline (M) of the bowel.

(b) The user manually delineates the bowel wall (B) either side of the bowel.

(c) MRManometry automatically generates a series of nodes (N) at pre-determined intervals along the midline (here a spacing of 2 pixels was used).

(d) MRManometry generates a ID line (L) [Di_-n], orthogonal to the midline at each N position. L is terminated when it intersects with the two outer bowel wall lines (Figure 6a).

The deformation fields generated by GIQuant^® during the registration are thereafter used to propagate the coordinates of midline, lumen & nodes through the dynamic time series in a fully automated fashion. As the bowel wall moves i.e. expands and contracts, the length of the perpendicular line at that position will change at that time point. The length of each perpendicular line is recorded at each time point throughout the series.

Over the time series a 2D spatio-temporal matrix is constructed to quantify changes in bowel diameter (X axis representing time and Y representing proximal - distal position along the GI tract (Figure 6b). The MRManometery automatically generates a series of nodes (N) at a user determined interval, which are shown in Figure 6b as a series of dots.

A series of lines, perpendicular to the midline (M) are generated at each node point to intersect with the Lumen. The diameter and position of each line is recorded at each time point. Deformation fields from are used to propagate M, LI & L2 to the next time point where the process is repeated without user intervention. The user can set the node spacing to a range of values with 2, 10, 5 and 1 pixel spacings, as demonstrated in Figures 6c to 6f respectively.

Spatio-temporal plot analysis

A method of transforming the data was performed as follows:

Metric 1: Normalised Contraction Plot (NCP).

Purpose: To visualise and quantify luminal change in diameter over time.

Rationale: This metric captures the reduction in luminal diameter at a given node position for each time point. The mean diameter of the GI tract lumen is variable at differing anatomical locations (e.g. the diameter of the stomach near the pylorus is less than at the fundus). Therefore, the data needs to be normalised such that relatively large contractions in narrower regions of bowel are not obfuscated by relatively smaller contractions in part of the bowel with a larger calibre. To normalise the data, a polynomial line of best fit was made through the time points at each node position. The error between the fit and the actual data was calculated and plotted. To account for underlying noise in the plots, only contractions over a 5% change in mean negative diameter were quantified.

Summary statistic: The area under the curve (AUC) is calculated first for each node position (x-axis of plot). The average of each node's AUC is then averaged for all of the node positions to produce a single, unitless, summary statistic.

Statistics

All data were checked for normality and appropriate correlative statistics used to assess the agreement between motility metrics.

Gastric motility was visually assessed by consensus experienced on a score of 1 (low motility) to 3 (high motility) to produce a ground truth. The level of agreement was assessed with Intra-Class Correlation.

Colonic motility was 1) visually assessed using a semi-quantitative visual colonic motility grading system as reported by Hoad et al., Phys Med Biol. 2015 Feb 7; 60(3) : 1367- 1383. As with the gastric study, both motility metrics were correlated against the visual score and against each other.

Results - Gastric motility The averaged reader scores produced a median motility score of 2 (range 1 to 3). The median Normalised Contraction Plot (NCP) score was 3 (range 0.2 and 16). Correlation between combined gastric motility visual score and 'Motility map' and Combined Velocity Deformation map was investigated. Correlation of the visual score against the NCP was significant (R = 0.85, p <0.01).

Results - Colonic motility

The median visual score was 16 (range 0 to 363), the median Motility score was 22 (range 0 to 60) and median combined velocity deformation score was 44 (range 0 to 1143). Correlation between colonic visual motility score and NCP. The visual score and NCP produced a positive correlation of R = 0.82, P<0.001.

Conclusion

Spatio-temporal mapping of the stomach and colon correlates well with reader scores in a range of datasets and provides both a quantitative and qualitative means of assessing contractile activity in the gastrointestinal tract.

Claims

1. A method for monitoring a tubular structure comprising :

a) applying a midline to an image of said tubular structure, the image showing the wall(s) of the structure;

b) extending axes from that midline to the wall(s) of the structure at at least two points along the midline;

c) measuring the length of each axis; and

d) repeating the steps a to c on at least one further image of the tubular structure.

2. The method of claim 1, further comprising the step of detecting the wall of the tubular structure using automated edge detection.

3. The method of claim 1, further comprising the step of applying guidelines

delineating the bowel wall either side of the midline to inform axes placement.

4. The method of any preceding claim, wherein the tubular structure is an anatomical structure in the human or animal body.

5. The method of any preceding claim, wherein the image is a two dimensional image.

6. The method of any preceding claim, wherein the image is a three dimensional image.

7. The method of any preceding claim, wherein the axes are perpendicular to the midline.

8. The method of any preceding claim, wherein the axes are parallel to one another.

9. The method of any preceding claim, wherein the axes are positioned at variable intervals along the midline.

10. The method of claim 9, wherein the axes are positioned at intervals of less than 2mm along the midline.

11. The method of any preceding claim, further comprising the step of obtaining one or more of the images.

12. The method of any preceding claim, further comprising the step of comparing the length of the axes between images.

13. A method of assessing changes in bowel wall length comprising the steps of:

c) Propagating the midline of the bowel on images of the bowel obtained at at least two time points and

d) measuring the length of the midline on each time point image.

14. The method of claim 13, wherein the ends of the midline are defined by a position that is identifiable on each image.

15. The method for monitoring a tubular structure, comprising the step of recording the diameter/circumference measurements, obtainable using the method of any of claims 1 to 12, into a matrix of time series Vs length data or area.

16. A method of mapping matrix data, obtainable using the method of claim 15, for analysis, comprising one or more of the following steps:

i) plotting tubular diameter measures over time, and optionally transforming the data to account for large changes in diameter; j) checking whether a threshold of data points has been reached and, if it has,

inserting missing data points; k) checking whether a threshold of data points has been reached and, if it has not, applying a flag to the data;

L) assessing and/or compensating for longitudinal stretch/contraction and variability; m) identifying and/or correcting for aberrant data identification, optionally by using homology or symmetry between either side of the midline at an individual axis position or between axes to ensure propagation errors; n) deleting or editing time points if incorrect; o) registration with other time-series plots; p) measuring underlying image intensity values in the medical imaging data.

17. A method for providing a score to a characteristic of a tubular structure, for example, of expansion of contraction, comprising the steps of setting a scoring threshold for the characteristic and recording a score if the threshold is exceeded.

18. A method for aligning time series data obtainable using the method of any of claims 1 to 12, comprising sorting the data by time or slice position.

19. A method for analysing motion in a tubular structure, comprising correcting for sources of motion other than movement of the wall of the tubular structure.

20. A method for evaluating bowel wall displacement across the GI tract to

comprising automatic propagation of axes for measurement.

21. A method for diagnosing a deficiency, injury or disease related to a tubular structure in the human or animal body, comprising carrying out the monitoring method of any preceding claim and comparing the results to expected results, wherein a difference between the actual and expected results is indicative of a deficiency, injury or disease.

22. A method of monitoring drug efficacy comprising carrying out the monitoring method of any of claims 1 to 12 in a subject before and after administration of a pharmacological agent and comparing the results.

23. A computer readable medium, programmed to carry out the method or steps of the method of any of claims 1 to 22 of the invention.