阅读说明：本技术 用于医学成像的系统和方法 (System and method for medical imaging ) 是由 A·基里比里 于 2018-04-18 设计创作，主要内容包括：一种用于确定对象内是否存在心肌缺血的系统和,确定对象内是否存在心肌缺血是基于对感兴趣的对象的心脏的至少一个区域的医学图像的分析,多个医学图像是通过医学成像模态以连续方式获取的,并且是在大致垂直于左心室心肌的壁的方向上的多个心肌层。(A system and method for determining the presence or absence of myocardial ischemia in a subject is based on an analysis of medical images of at least a region of the heart of the subject of interest, the plurality of medical images being acquired in a continuous manner by a medical imaging modality and being a plurality of myocardium in a direction substantially perpendicular to a wall of the left ventricular myocardium.)

1. A system for determining the presence or absence of myocardial ischemia in a subject by analyzing medical images of at least a region of the subject's heart during a first pass dosage of a contrast agent, a plurality of medical images acquired in a continuous manner by a medical imaging modality, the system comprising:

(i) a delineation unit configured to delineate a selected region of the heart of the subject of interest in the plurality of medical images and to divide the selected region into a plurality of myocardium in a direction substantially perpendicular to a wall of a left ventricular myocardium; and

(ii) an intensity sampler and analysis unit configured to sample signal intensities from myocardial image locations of the plurality of medical images and, for each of the myocardium, analyze the sampled signal intensities in the selected region over time and compare the results with results obtained at reference points within a left ventricle to determine a first index number indicative of spatiotemporal perfusion inhomogeneity or perfusion dephasing among at least a subset of the myocardium in the region compared to a similar index number obtained within a normal heart;

and diagnosing the presence of ischemia when the first index number is large.

2. The system of claim 1, wherein the medical imaging modality is selected from a magnetic resonance examination (MR) scanner, a Computed Tomography (CT) scanner, or a Single Photon Emission Computed Tomography (SPECT) scanner.

3. The system of claim 1, wherein the plurality of layers is two layers to fifty layers.

4. A system according to any foregoing claim arranged to analyse images from layers in multiple planes in various regions of the heart simultaneously.

5. The system according to any of the preceding claims, arranged as a system according to any of the preceding claims, arranged to analyze a further plurality of medical images acquired simultaneously with the plurality of medical images in a consecutive manner in a further direction, the further direction being substantially in a direction of blood flow through a large epicardial coronary artery extending over a surface of the heart, wherein the delineation unit is further arranged to segment at least a selected portion of the heart into a plurality of radial myocardial segments; and the intensity sampler and analysis unit is further configured to sample and analyze the medical images obtained over time and compare the results with results obtained at reference points within the left ventricle to determine a second index number indicative of spatiotemporal perfusion inhomogeneity or perfusion dephasing in the other direction among at least a subset of radial myocardium segments of the plurality of myocardium segments; and thereafter, compared to similar index numbers obtained in a normal heart or model heart; and recording a positive result in case the second index number is larger.

6. The system of claim 5, wherein the second index number is used to distinguish MVDs from CAD in a patient with ischemia.

7. The system of claim 5 or claim 6, wherein the second index number is compared to similar indices obtained using a model heart or a "dummy" heart.

8. The system of any preceding claim, configured to exclude known scar tissue sites from the analysis.

9. The system of any one of claims 5 to 7, further configured to correlate the first index number and the second index number, and in the event that the first index number is negative or only slightly positive and the second index number is positive, correlate this with the presence of scar tissue in the site.

10. The system of claim 9, configured to acquire another set of medical images after a period of time and use these images to confirm the presence of scar tissue.

11. The system of claim 10, wherein the period of time is 3 to 5 minutes.

12. The system of claim 10 or claim 11, configured to map scar tissue in three dimensions on the heart.

13. The system of any one of the preceding claims, further comprising means for quantifying myocardial blood flow in each of the plurality of layers or segments.

14. The system of any one of the preceding claims, wherein acquiring a plurality of medical images of at least a portion of the subject's heart is at least partially synchronized with the periodic movement of the subject's heart.

15. A method for determining or confirming the presence or absence of ischemia in a patient, the method comprising obtaining a medical image of at least a portion of a subject's heart using an imaging modality such as an MR scanner, a CT scanner or a SPECT scanner, determining a first index number as defined in claim 1 using a system as described above, and using the result to diagnose the presence or absence of ischemia.

16. The method of claim 15, further comprising obtaining a medical image suitable for providing a second index number as defined in claim 5, and using the result to distinguish CAD or MVD in an ischemic patient, or to delineate scar tissue in the heart.

17. A storage medium or distribution platform storing a software application comprising the system of any one of claims 1 to 13.

18. A storage medium or distribution platform storing a software application arranged to determine a first index number as defined in any one of claims 1 to 14.

19. The storage medium or distribution platform according to claim 18, further arranged to determine a second index number as defined in claim 5.

Technical Field

The present invention relates to the field of medical imaging of the heart, and in particular to the field of analyzing medical images of the heart, to systems, methods and elements for use in this field.

Background

First-pass enhanced imaging of the heart by Cardiac Magnetic Resonance (CMR) imaging, and more recently also by Cardiac Computed Tomography (CCT) imaging or Single Photon Emission Computed Tomography (SPECT), allows visualization and quantification of myocardial perfusion. The identification of the perfusion-damaged tissue site is based on image interpretation performed by an expert reader or on quantification of the ischemic site. This quantification includes a semi-quantitative analysis or a true quantitative analysis of the time-intensity curve. Semi-quantitative analysis involves the quantification of several characteristic features of the time-intensity curve, such as peak intensity, maximum upslope (maximum upslope), mean transit time (mean transit time), etc. In a true quantitative analysis, the actual myocardial blood flow is calculated from a mathematical analysis of the Arterial Input Function (AIF) and the time-intensity curves obtained in the myocardium. An extensive review of the semi-quantitative and true quantitative methods is given in Jeerosch-Herold: Quantification of myogenic perfusion by cardio viral magnetism, Journal of cardio Magnetic Resonance 2010,12: 57.

Visual assessment of perfusion images requires interpretation by expert operators trained with experience for several years. The availability of such expert readers is hindering the widespread use of CMR perfusion techniques and CCT perfusion techniques. Semi-quantitative and quantitative methods are difficult to use and rely on physical, physiological and mathematical assumptions to provide a correct measurement of myocardial blood flow. These assumptions may not always apply, and the results of these analyses do not necessarily yield a true quantitative measure of myocardial perfusion. There is a need for robust methods of identifying abnormal myocardial perfusion that are robust in their modeling assumptions and suitable for automation. Generally, myocardial ischemia is identified as an absolute decrease in myocardial perfusion or as a decrease relative to a normal reference site.

Previously, invasive methods for characterizing and analyzing myocardial hypoperfusion are often needed because non-invasive imaging methods cannot reliably distinguish between coronary microvascular dysfunction (MVD) and multivessel coronary artery disease (including left major coronary artery disease; CAD). These two conditions were characterized by diffuse myocardial ischemia, and therefore, previously, the two conditions were distinguished by invasive methods. While such methods may be helpful or necessary in the case of CAD patients, MVD patients unnecessarily undergo such procedures and at a significant cost in terms of time, money, and stress on the patient.

WO2015/049324 describes a method and system for characterizing myocardial perfusion pathology by identifying "spatio-temporal perfusion inhomogeneity" or "spatio-temporal dephasing" to distinguish coronary artery microvascular disease (MVD) from Coronary Artery Disease (CAD).

In "spatiotemporal perfusion inhomogeneity" or "spatiotemporal dephasing" (which is also referred to as "perfusion asynchrony", as described in WO 2015/049324), a medical imaging technique is used to generate a "perfusion map" showing the intensity over time of signals generated from first-pass waves through a contrast agent at various locations within different sections (segments) of the myocardium. A series of intensity curves is then created using these perfusion maps, showing the intensity of the signal over time, so that the time it takes for the signal to reach the peak intensity in each section (TTPI) is clear. Then, an index (index) is calculated that is based on the amount of difference between the TTPI in each segment compared to the TTPI at a reference point that is typically located in the left ventricle. This provides a measure of the temporal dephasing of the perfusion (measure). As will be understood in the art, the term "segment" as used in WO2015/049324 refers to a radial segment of the myocardium. Thus, a view is taken along the myocardium, which is then divided into a plurality of radial segments, as illustrated in fig. 2A below. Therefore, measurements are typically made in the direction of blood flow through the large epicardial coronary artery extending over the surface of the heart, and perfusion differences between such radial segments are studied.

In a normal heart with normal perfusion, the blood flows evenly through the heart, so the TTPI from each radial segment will be similar and quite close to the TTPI at the reference point. As a result, the range of TTPI variance or TTPI coefficient of variation will be relatively small. However, in case of an interruption or inhibition of blood flow in one specific part of the heart due to CAD, the TTPI will be significantly different in different radial sections of the myocardium, and thus the (coefficient of variation) indicator of the TTPI variance will be large.

In individuals with CAD, the spatiotemporal distribution of myocardial blood flow in the myocardium becomes increasingly non-uniform. In contrast, in individuals with MVD, pathological changes involve the microcirculation and the interaction of the microcirculation with the contraction of the myocardium during systole. In this case, the perfusion to the epicardial layer is not obstructed and is very uniform. However, there is a delay in the transmural propagation of the first pass wave. Like CAD, this results in widely distributed ischemia with a delayed onset of intensity rise. However, this feature is uniform in the time domain across the myocardium, allowing for non-invasive differentiation between CAD and MVD.

In the case of MVD, the change in TTPI may be less diffuse (homogenous perfusion) because the rate of flow through the major vessels of the heart is not significantly affected. Thus, the change in TTPI may be low and may be similar to that seen in a normal heart. However, in this case, there may be a delay in the signal due to pathological changes involving the microcirculation and the interaction of the microcirculation with the myocardial contraction during systole, and the signal may not be as strong as in a normal heart due to the reduced flow of the first pass (ischemia).

Therefore, an index based on a coefficient of variation of a time period to a peak intensity between a reference time and a time until the peak intensity of the intensity curve over time appears is defined as providing a basis for diagnosis.

The method of WO2015/049324 is completely empirical in nature, as it is necessary to compare this index with that obtained from "normal" individuals in order to fully assess the presence of the condition. A "positive" index above the index observed in normal individuals indicates CAD, while a "negative" index below the index observed in normal individuals indicates the presence of MVD.

Furthermore, it is first assumed that the patient is actually suffering from ischemia, since there is no overall means for determining a normal range indicating the absence of disease. Thus, the results may still require some expert analysis.

WO2015/049324 also shows that the myocardium image positions used to calculate the single index can be selected in a direction along the myocardium (i.e. in the direction of blood flow through the large epicardial coronary vessels) and optionally also in a direction through the myocardium.

EP2391986 teaches a system for gradient-based image analysis of transmural perfusion in the myocardium, which can be used for diagnosis of CAD.

Applicants have appreciated that collecting specific spatiotemporal perfusion non-uniformity indicator information in different directions through the heart may provide additional diagnostic information, and in particular may be used to distinguish between a normally perfused heart and an ischemic heart, thereby facilitating not only diagnosis of myocardial ischemia itself, but also distinguishing between CAD and MVD, and mapping of scar tissue.

Disclosure of Invention

According to the present invention, there is provided a system for determining the presence or absence of myocardial ischemia in a subject by analyzing medical images of at least a region of the subject's heart during a first pass dose of a contrast agent, a plurality of medical images being acquired in a continuous manner by a medical imaging modality (modality), the system comprising:

(i) a delineation unit configured to delineate a selected region of the heart of the subject of interest in the plurality of medical images and to divide the selected region into a plurality of myocardium in a direction substantially perpendicular to a wall of a left ventricular myocardium; and

(ii) an intensity sampler and analysis unit configured to sample signal intensities from myocardial image locations of the plurality of medical images and, for each of the myocardium, to analyze the sampled signal intensities in the selected region over time and to compare the result with results obtained at reference points over time within the left ventricle to determine a first index number indicative of spatiotemporal perfusion inhomogeneity or perfusion dephasing among at least a subset of the myocardium in the region compared to a similar index number obtained within a normal heart;

and diagnosing the presence of ischemia when the first index number is large.

In particular, the medical imaging modality is selected from a Magnetic Resonance (MR) scanner, a Computed Tomography (CT) scanner or a Single Photon Emission Computed Tomography (SPECT) scanner. Such a scanner may form part of the system of the present invention.

Accordingly, there is provided a system for determining the presence or absence of myocardial ischemia in a subject by analyzing medical images of at least a region of the heart of the subject of interest, the plurality of medical images being acquired in a continuous manner by a medical imaging modality selected from a Magnetic Resonance (MR) scanner, a Computed Tomography (CT) scanner, or a Single Photon Emission Computed Tomography (SPECT) scanner, the system comprising:

(i) a delineation unit arranged for delineating a selected region of a heart of a subject of interest in the plurality of medical images and for dividing the selected region into a plurality of myocardium in a direction perpendicular to a wall of the left ventricular myocardium; and

(ii) an intensity sampler and analysis unit configured to sample signal intensities from myocardial image locations of the plurality of medical images from a first-pass dose of contrast agent and to analyze medical images from a plurality of slices in the selected region over time and to compare the results with results obtained at reference points in a time direction (over time) within a left ventricle to determine a first index number indicative of spatiotemporal perfusion inhomogeneity or perfusion dephasing among at least a subset of the myocardium in the region compared to a similar index number obtained within a normal heart;

and diagnosing the presence of ischemia when the first index number is large.

The system of the invention allows measuring perfusion through the myocardium, which normally will be impaired in case of ischemia, whether the ischemia is due to CAD or due to MVD. In particular, non-uniformity in the perfusion rate in a direction perpendicular to the wall of the left ventricular myocardium will provide an indication of ischemia in the subject. Any non-uniformity or asynchrony in the blood flowing laterally across the myocardium would be an indicator of the presence of hemodynamic-related coronary artery disease or microvascular disease within the subject that leads to the onset of ischemia. This is useful for quickly and simply excluding patients who may have symptoms (such as pain) that are not due to heart disease.

Suitably, the first index number is expressed as a coefficient of variation (standard deviation/mean) of the time period to peak intensity (TTPI) as described in WO2015/049324 or as a peak Heart Journal-cardio imaging (2015) doi: 10.1093/ehcji/jev326, the coefficient of variation (standard deviation/mean) of Time To Maximum Uphill (TTMU). In another embodiment, the coefficient of variation, defined as the ratio between the standard deviation and the mean of the values of TTPT or TTMU in a plurality of locations across the myocardium, may be used as the basis for the index number instead of the variance. They can be compared to similar indicators obtained from normal healthy individuals as described in WO 2015/049324.

The number of layers analyzed using the system of the invention will be 2 or more, e.g. more than 2, such as 2-50 or 3-50 layers. The greater the number of layers analyzed in this way, the clearer any asynchrony of the perfusion will become.

If desired, the system of the invention may be arranged to obtain and analyze images from layers in multiple planes in various regions of the heart simultaneously. This would then allow the heart and if desired the entire heart to be mapped three-dimensionally. This procedure would be particularly useful in mapping of, for example, scar tissue sites, as discussed further herein.

In the case of identifying scar tissue sites, these sites may be excluded from the calculation of the first index number.

In a specific embodiment, the system of the invention is arranged for simultaneously acquiring a plurality of medical images in a continuous manner in another direction substantially in the direction of blood flow through the large epicardial coronary artery extending over the surface of the heart, wherein the delineation unit is further arranged for providing a segmentation of at least one selected portion of the heart into a plurality of radial myocardial segments; and the intensity sampler and analysis unit is further configured to sample and analyze the medical images obtained over time and compare the results with results obtained at the reference points over time (in the temporal direction) within the left ventricle to determine a second index number indicative of spatiotemporal perfusion inhomogeneity or perfusion dephasing in the other direction among at least a subset of radial myocardium segments of the plurality of myocardium segments; and thereafter, compared to similar index numbers obtained in a normal heart or model heart; and in case the second index number is larger, recording a positive result.

The second index number may provide a means to distinguish ischemic patients with MVD from ischemic patients with CAD in a non-invasive manner, as described in WO 2015/049324. In the case where the second index is positive, it indicates the heterogeneity of the perfusion rate in the direction of the blood flow in the direction along the myocardium, indicating that the ischemia is a diagnosis due to CAD. However, in the case where the second index number is negative, ischemia may be due to MVD. In this way, the ischemic patient can be treated appropriately.

In a particular embodiment, the second index number is compared to similar indices obtained using a "dummy" heart or a model heart. One specific example of such artifacts is described in WO2014/140547, the contents of WO2014/140547 being incorporated herein by reference. The indicator may be based on a calibration curve prepared for the instrument. As a baseline value, this will be more consistent than a value obtained from a "normal" individual (where some natural variation may be possible).

The applicant has appreciated that the combination of two different indicators indicative of inhomogeneity taken in two different directions through the heart will greatly improve the available diagnostic options. As described above, this will enable diagnosis of ischemia and differentiation between CAD and MVD to be performed in a single test that is non-invasive.

Preferably, the system of the present invention is used to exclude scar tissue sites from analysis. Scar tissue may occur in the myocardium as a result of earlier injury or trauma, such as myocardial infarction, or scar tissue may occur in asymptomatic or mildly symptomatic Hypertrophic Cardiomyopathy (HCM) patients. Although scar tissue may not be the cause of CAD by itself, it may restrict blood flow through the blood vessels of the heart and thus show a positive result of CAD in a test as described in WO 2015/049324. In the case where the presence and location of scar tissue in a patient has been determined using conventional methods, the area containing scar tissue is suitably excluded from the results used to calculate the index number using the system of the present invention.

However, the system of this embodiment of the present invention may be used to provide such identification without previously delineating such scar tissue sites.

In a particular embodiment, the system is further arranged to correlate the first index number and the second index number to provide additional information regarding the presence of scar tissue.

In particular, in the case where the first index number is negative (in a sense that the value of the first index number is not greater than the value of the first index number obtained in a normal heart) or only slightly positive and the second index number is positive, this indicates the presence of scar tissue. However, there may not be significant perfusion dyssynchrony in the lateral direction, and therefore, using the system of the invention, the tissue will likely give a negative result of ischemia. Thus, the correlation of the first index number and the second index number may be used to identify scar tissue.

In particular, where the first index number is negative or only slightly positive and the second index number is positive, the result indicates the presence of scar tissue in the subject in the particular region of the heart that has been read.

Since the presence of myocardial scars may lead to a slight increase of the asynchrony values measured in the radial direction and the transmural direction, a confirmatory examination may be necessary. This may be done by resampling the data after a period of time (e.g., after a period of time from 1 minute to 3 hours, such as after about 5 minutes). This is because the clearance of contrast agents (such as gadolinium) from scar tissue is slower than from healthy tissue, and therefore it is expected that after some time there will be a residual signal in any scar tissue. During subsequent resampling, a gadolinium (hyper) enhancement of the image may be required to detect residual gadolinium, if necessary.

Once scar tissue has been detected, additional mapping procedures may be required at different locations within the heart, including other embodiments in which the first and second index numbers are obtained. In this way, a three-dimensional map of the heart may be established.

Alternatively, a different type of imaging modality or a different type of data acquisition (e.g., later gadolinium hyper-enhancement in MRI) may be used to analyze or map the scar site. Once identified in this manner, layers and sections affected by the presence of scar tissue may be excluded from the calculation of the first and second indices.

Alternatively, scar tissue may be analyzed by comparing asynchrony data as described above taken from the heart at rest and with asynchrony data as described above taken from the same heart under pressure (e.g., due to administration of an stimulant drug). It would be expected that the asynchrony observed in scar tissue would be similar in both cases.

In the case where both the first and second indicators are negative, this would indicate that the heart is normal (no ischemia present) and would indicate that any symptoms may be the result of a different condition.

Thus, the results obtainable from the system of this embodiment are summarized as follows:

thus, the method of the present invention provides a particularly effective and useful flexible method that maximizes the amount of diagnostic information that can be obtained from a non-invasive medical imaging procedure.

Suitably, the MR, CT or SPECT scanner is arranged to obtain images in a single step in the direction used to obtain the first and second indices as described above, but different procedures may be performed if desired.

The phrase "spatiotemporal perfusion inhomogeneity" may also be referred to in the present application as "spatiotemporal dephasing" or "perfusion dyssynchrony" and is specifically understood in the case of pathological abnormalities as a spatiotemporal distribution of inhomogeneous myocardial blood flow.

The step of contouring the selected portion of the heart may be performed manually, semi-automatically, or fully automatically. Suitable segmentation techniques are known in the art and are commercially available.

The subset of the myocardium of a segment may comprise a plurality of myocardium or a strict subset of segments (such as perfusion zones), or it may comprise the complete myocardium.

Each index number represents an order in which each of the medical images is acquired over time.

Prior to applying the step of delineating the selected portion of the heart, the plurality of medical images may have been subjected to image registration techniques to correct for respiratory or through-plane motion of the subject of interest, as will be understood in the art. In addition, a suitable filter may be used to obtain visual intensity readings, as will be understood in the art.

If desired, the system may further comprise means for quantifying myocardial blood flow in each of the plurality of layers or sections. The step of realistically quantifying myocardial blood flow may be performed according to any of the techniques known in the art. A true quantification of myocardial blood flow in each layer or segment may provide complementary information for characterizing myocardial perfusion pathology. Any scar tissue identified, for example using the system of the invention as described above or using subsequent gadolinium hyper-enhancement images, is suitably excluded from quantification of myocardial blood flow.

The plurality of medical images used in the system of the present invention is acquired by first administering a contrast agent to the subject of interest and then monitoring the progress of the contrast agent as it first passes through the heart. Suitable contrast agents are well known in the art and include any agent that generates a signal greater than the tissue of the subject of interest surrounding the agent compared to a baseline when acquired by an MR scanner, a CT scanner, or a SPECT scanner. Suitable contrast agents may include compounds based on iodine, lanthanides (such as gadolinium), gold, gallium, bismuth, manganese or iron.

The intensity signal is measured not only in a heart layer or section, but also in a reference point in the left ventricle of the heart. This is because the left ventricle is the position that receives contrast agent during the first pass and precedes the upslope of the intensity curve obtained for each of the selected myocardial image positions.

As used herein, the term "upslope" refers to a point in time at which the intensity of the intensity curve obtained as a result of administration of a contrast agent exceeds a predetermined threshold (e.g., more than 10% compared to the intensity without administration of a contrast agent).

In another preferred embodiment, the system further comprises means for automatically determining, for each of the selected myocardial positions, an individual time period relative to a reference time determined from the identified reference position until the occurrence of the characteristic feature of the sampled intensity of each of the myocardial image positions. Then, the individual time periods are used in the step of calculating the index number. The characteristic feature may be the point in time at which the rise in intensity starts, the point in time of the peak intensity, or any other characteristic feature that appears suitable to a person skilled in the art. In this way, the number of indices indicative of spatiotemporal perfusion inhomogeneities can be easily calculated in an automated manner.

Preferably, the step of calculating the index number comprises calculating a statistical measure indicative of the variation with respect to the time at which the characteristic feature occurs at the identified reference location until the time at which the characteristic feature occurs in each of the individual myocardial locations. By this, an index number describing spatiotemporal perfusion inhomogeneities within the myocardium or segment in a significant way may be provided. The statistical measure may be in the form of a variance, which is conventionally used in statistics as a measure of how far apart a set of numbers is spread out. In this sense, the variance may be the square of the standard deviation of the set of numbers. In general, the statistical measure may have any other form deemed suitable by those skilled in the art to indicate the change in time until the characteristic feature occurs at each of the individual myocardial locations.

Preferably, the acquiring of the plurality of medical images of at least a part of the heart of the subject of interest is at least partially synchronized with the periodic movement of the heart of the subject of interest. For example, the medical image may be acquired a fixed amount of time before or after a reference event in the electrocardiogram, such as the R peak of the QRS complex. An advantage of this embodiment of the method is that all medical images of the plurality of medical images are taken under similar conditions of the heart, such that there is little movement of the cardiac ventricles between the medical images and the myocardium is rendered relatively stationary.

The system of the invention may comprise an integral part of a CT scanner or an MRI scanner. The magnetic resonance imaging apparatus may advantageously comprise synchronization means for synchronizing the acquisition of the medical image with a periodic movement of the heart of the subject of interest.

Suitably, the system comprises a software module arranged to perform the image analysis described above. In particular, the steps to be performed are converted into program code of the software module, wherein the program code is implementable in a memory unit of a control unit of a medical imaging modality and executable by a processor unit of the control unit of the medical imaging modality.

The control unit may be a control unit that is customary for controlling functions of the medical imaging modality. Alternatively, the control unit may be an additional control unit, in particular assigned to perform the method steps.

The software module may enable a robust and reliable execution of the method and may allow a fast modification of the method steps and/or an adaptation of the image registration algorithm.

In another aspect, the invention provides a method for determining or confirming the presence of ischemia in a patient, the method comprising obtaining a medical image of at least a portion of the subject's heart using an MR scanner, a CT scanner or a SPECT scanner, determining a first index number as defined above using a system as described above, and using the result to diagnose whether ischemia is present.

In a specific embodiment, medical images suitable for providing a second index number are also obtained during the method, and the results are used to distinguish CAD or MVD in an ischemic patient, or to delineate scar tissue in the heart.

In another aspect, the invention provides a storage medium or distribution platform storing a software application comprising the system of the invention as defined herein. For example, the software application may comprise at least a delineation unit and an intensity sampler and an analysis unit of the system.

Alternatively, the invention may provide a storage medium or distribution platform storing a software application arranged to perform the steps performed by the delineation unit and the intensity sampler and analysis unit of the system as defined herein.

In another aspect, the present invention provides a storage medium or distribution platform storing a software application arranged to determine a first index number as defined herein.

The software application may also be arranged to determine a second index number as defined herein.

Throughout the description and claims of this application, the words "comprise" and "contain" and variations of the words, for example "comprising" and "comprises", mean "including but not limited to", and do not exclude other elements, integers or steps. Furthermore, the singular encompasses the plural unless the context requires otherwise. In particular, where the indefinite article is used, it is to be understood that the application contemplates the plural as well as the singular, unless the context requires otherwise.

Preferred features of each aspect of the invention may be described in combination with any of the other aspects. Within the scope of the present application, it is expressly contemplated that the various aspects, embodiments, examples and alternatives set forth in the preceding paragraphs, claims and/or in the following description and drawings, and in particular the individual features thereof, may be employed alone or in any combination. That is, features of all embodiments and/or any embodiment may be combined in any manner and/or combination unless such features are incompatible.

Detailed Description

The invention will now be described in detail, by way of example, with reference to the accompanying diagrammatic drawings, in which:

FIG. 1A schematically shows the epicardium of a heart; FIG. 1B is a schematic of the peak pattern in the epicardial, endocardial layers from the first pass analysis in this direction and the signal-time at the reference point in the left ventricle in a normal heart; FIG. 1C is a schematic of the peak pattern in the epicardial, endocardial layers from the first pass analysis in this direction and the signal-time at the reference point in the left ventricle of the ischemic heart;

fig. 2A schematically shows a radial heart section, and fig. 2B and 2C show schematic diagrams of peak patterns that can be obtained in the radial direction from a first pass analysis in this direction.