WO2001010301A1

WO2001010301A1 - Paperbased nuclear medical phantom and the method of using such a phantom

Info

Publication number: WO2001010301A1
Application number: PCT/SE2000/001518
Authority: WO
Inventors: Stig A. Larsson; Cathrine Jonsson
Original assignee: Karolinska Innovations Ab
Priority date: 1999-08-06
Filing date: 2000-07-27
Publication date: 2001-02-15
Also published as: AU6485400A

Abstract

The present invention relates to a phantom for assessment of image quality in imaging of a mammal body by means of different imaging techniques, particularly such techniques used in the field of nuclear medicine, a method for assessing the amount of scattering and attenuation of photons in said phantom, a method for image interpretation or correction, and a method by means of which the phantom of the present invention is obtainable according to the preamble of the attached independent claims. More particularly, the invention relates to such phantoms suitable for use in imaging of the human body in the field of nuclear medicine, which phantoms are essentially liquid-free and offers a great number of advantages over the known phantoms. The invention also relates to a method of preparing a phantom, a radioactive ink and the use of the phantom.

Description

Paperbased nuclear medical phantom and the method of using such a phantom.

Medical device

The present invention relates to a phantom for assessment of image quality in imaging of a mammal body by means of different imaging techniques, particularly such techniques used in the field of nuclear medicine, a method for assessing the amount of scattering and attenuation of photons in said phantom, a method for image interpretation or correction, and a method by means of which the phantom of the present invention is obtainable according to the preamble of the attached independent claims. More particularly, the invention relates to such phantoms suitable for use in imaging of the human body in the field of nuclear medicine, which phantoms are essentially liquid-free and offers a great number of advantages over the known phantoms.

Experimental assessment of image quality in radiology is generally performed by means of phantom imaging. A phantom is an object with clearly defined and well known structures which can be positioned in the camera system and be imaged for quality assessment. Since all structures of the phantom object are known, the imaging properties of the system can be analysed by comparing the data acquired (image data) from imaging of the phantom, with the known phantom object itself.

Phantom experiments are of especially great importance in nuclear medicine imaging. Nuclear medicine is a kind of functional imaging technique, where radioactive tracers are administered to a patient undergoing examination. By using nuclear imaging the field of medicine, rapid events, e.g. in the order of seconds, as well as slower processes, e.g. in the order of days or weeks, in the human body can be studied. Furthermore, functional changes on a cellular level can be detected, thereby pathological processes can be detected at an early stage. Nuclear imaging can, inter alia, be used for determination of the functional volume of organs in the human body, for tumour detection together with radioactive tumour- specific tracer substances, or in studies of the regional blood flow in the human brain. By means of an external gamma camera, sensitive to gamma- and x-ray radiation, the tracer distribution in time and space can be analysed, in vivo. 2-D planar imaging as well as 3-D Positron Emission Tomography (PET) and 3-D Single Photon Emission Computed Tomography (SPECT) can be performed.

The great advantage of nuclear medicine is its unique high sensitivity (pmole/ml - nmole/ml) while its greatest drawback is its low spatial resolution (image sharpness), which is of the order of about 3- 15 mm. The low spatial resolution in combination with the non-specific tracer distribution gives only a low degree of anatomical references - such as X-ray Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) - that may be utilised per se as some coarse quality control of the camera system. Therefore, phantom experiments have to be performed on a regular basis to ensure stable and accurate imaging properties of the camera systems.

Phantoms known in the art are usually made up by a system of plastic containers which has to be filled with some selected concentrations of some suitable radionuclide in water. Such phantoms has been described in, for example, US-A- 4,280,047, and US-A-4,499,375. The liquid, mixed with the radionu elides, is used in order to uniformly distribute a known level of radioactivity in one or more three- dimensional volumes in the phantom, so as to mimic human tissue, to which radionuclides have been administered for imaging. Since most radionuclides used in nuclear medicine are shortlived (i.e., having a half-life in the order of minutes to a few days, or, in the case of PET, even seconds), the filling procedure has to be repeated at almost every quality control.

The interaction of photons with body tissues has a major impact on the image quality and on the quantitative potentials for nuclear medicine imaging. Photons originating from deeply located sites within the body have less probability of reaching the detector than those emitted from the surface due to interactions with atomic electrons. When photons with energies between 70 to 511 keV pass through soft tissue (composed of atoms having low atomic number, Z) the microscopic cross-section for Compton scattering is of the order of 2 to 3 barn per atom (1 barn = 10^"^° m^) and 10^"4 to 10^" * barn per atom for the photoelectric effect. The contribution from coherent (Rayleigh) scattering is low for soft-tissue and therefore, Compton scattering remains the major interaction process of photons with body tissues in nuclear medicine imaging.

The macroscopic mass attenuation coefficient, μ/p, wherein μ is the linear attenuation coefficient, and p is the density, for soft tissue (e.g. muscle) ranges from about 0.1 to 0.2 cm^/g in the same energy interval. This means that only some fourth (14-37%) of all photons, emitted from a depth of 10 cm soft tissue, will escape from the body without any interaction.

The cloud of escaping photons from a patient is thus a complex mixture of scattered and primary photons with various energies and origins. This affects the imaging conditions since the energy resolution of conventionally used Nal- detectors is only of the order of 10% at 140 keV. In order to register a 0.95 fraction of incident primary photons, therefore, a 17% wide energy window from 128 to 152 keV has to be selected for primary photon acceptance. Within such a wide window, scattered photons will also be registered since their energy loss at a Compton interaction is not always large enough to reject them at the lower energy threshold. These photons do not represent origins of emission but origins of their last interaction with tissue electrons and hence, a large fraction of falsely positioned, scattered events are acquired in the raw data. For example, in regional Cerebral Blood Flow (rCBF) studies of the brain with ^"^mTc- compounds, about 30% of all detected photons in a 20% energy window are scattered events.

While attenuation causes image distortion due to systematic photon losses, scattering adds falsely positioned photons into the image which reduces contrast resolution. In order to improve the image quality, therefore, proper corrections for both the loss of primary photons due to attenuation and the unwanted contribution of secondary events have to be performed. However, many correction routines for SPECT are presently utilised as qualitative tools for improving contrast resolution and reducing image artefacts, thereby facilitating the visual interpretation of images. Accurate correction techniques for quantitative assessments are merely used in PET but there is an increasing demand for quantitative evaluations also in SPECT - for instance, in assessment of tumour uptake and in estimating the level of regional CBF changes.

Problems are associated with evaluating and testing the accuracy of suitable, existing correction routines. Photon scattering and attenuation are affecting every nuclear medicine image while true images are expected to be built up by primary photons only.

Due to the surrounding material, and more particularly, the density thereof, a more or less large extent of primary photons emitted from within said material will be scattered on their path through said material as a consequence of interactions with said material. These photons, when detected, will reflect false origins of emission, since they will have a deflected direction. Also, some of the primary photons will not escape the material, but instead be absorbed thereby, and thus never be detected.

Since, in imaging of a patient scattering and attenuation of photons are always present, imaging can never be performed without contribution of falsely positioned scattered events and the reduction of escaping photons from the body due to photon interaction with object matter (photon attenuation). In studies of the brain, for instance, the fractional contribution of unwanted scattered photons can be of the order of 30% while attenuation may reduce the number of primary photons by as much as 75%.

A most common approach to overcome this conflicting situation, i.e., to obtain a "true" image based on image data inherently containing contribution from scattered photons, and at the same time being deprived of photons attenuated by the specific material, is to utilise computer simulation data. Such techniques, based on Monte Carlo simulations have been developed and applied for comparing the accuracy of various scatter and attenuation correction methods, and have been described in, for example: Floyd CE, Jaszczak RJ, Harris CC, Coleman RE., Energy and spatial distribution of multiple order Compton scatter in SPECT: A Monte Carlo investigation, Phys. Med. Bio.l 1984; 29: 1217- 1230; Floyd CE, Jaszczak RJ, Coleman RE., Inverse Monte Carlo: a unified reconstruction algorithm for SPECT, IEEE Trans. Nucl. Sci. 1985; 32: 779-785; Floyd CE, Jaszczak RJ, Greer KL, Coleman RE. Inverse Monte Carlo as a unified reconstruction algorithm for ECT, J. Nucl. Med. 1986; 27: 1577- 1585; Gilardi M C, Bettinardi V, Todd-Pokropek A, Milanesi L, Fazio F., Assessment and comparison of three scatter correction techniques in single photon emission computed tomography, J. Nucl. Med. 1988; 29: 1971- 1988; Ljungberg M, Strand SE., Scatter and attenuation correction in SPECT using density maps and Monte Carlo simulated scatter functions, J. Nucl. Med. 1990; 31 : 1560- 1567; Ljungberg M, Strand SE., Attenuation and scatter correction in SPECT for sources in a nonhomogeneous object: a Monte Carlo study, J. Nucl. Med. 1991; 32: 1278- 1284; Ljungberg M, King MA, Hademenos GJ, Strand SE., Comparison of four scatter correction methods using Monte Carlo simulated source distributions, J. Nucl. Med. 1994; 35: 143- 151; and Buvat I, Rodriguez- Villafuerte M, Todd-Pokropek A, Benali H, Di Paola R., Comparative assessment of nine scatter correction methods based on spectral analysis using Monte Carlo simulations, J. Nucl. Med. 1995; 36: 1476- 1488.

An object of the present invention is thus to provide a phantom by means of which the above-mentioned problems are overcome. Another object is to provide a method for assessment of the amount of scattering and attenuation in a phantom according to the invention. A further object is to provide a method for image interpretation or correction with improved accuracy. Further objects and advantages will become apparent from the following detailed description.

Summary of the present invention

The above mentioned objects are achieved according to the features and method steps set forth in the characterising portions of the independent claims. According to a preferred embodiment, a three-dimensional (3-D) object is represented by a selected number of two-dimensional (2-D) planes, which suitably can be parallel. Accordingly, any 3-D object may be described by a series of digitised 2-D planes. The phantom of the present invention is based on a set of one or more 2-D planes, which, for example, may comprise one or more paper sheets, forming a 3-D structure. In such a phantom structure a given plane can be provided with radioactivity. Said radioactivity may be applied into a radioactive pattern (distribution), for example, corresponding to the radioactivity distribution seen in a corresponding cross-section from the corresponding level of some mammal tissue or organ being studied, to which mammal radioactive substance previously has been administered. Thus, the phantom may contain any desired number of planes with patterns having their correspondence at different levels in the actual tissue or organ.

In preparing the radioactive structures comprised in the phantom of the present invention, the use of an ink printer with radioactive ink connected to a computer will offer many advantages and possibilities, as will be recognised by the person skilled in the art. For example, any selected image can be printed which can be stored as, or transformed into, computer readable format. The radioactivity distribution on the paper will then typically represent the density- or the grey- or colour- scale of the image on the screen. Thus, radioactive images can easily be printed with high accuracy and resolution.

Another advantage with the use of a conventional ink writer (with radioactive ink) is that only one radioactive concentration is required and that the filling of, or, replacement of, an ink container is much faster and more simple than filling a number of containers, such as in a phantom of the prior art, thus reducing the exposure to the personnel and reducing the time for preparation.

According to another preferred embodiment, the phantom is preferably provided with intervening layers of a suitable material, having tissue-like characteristics in order to simulate photon scattering and attenuation characteristics in the actual tissue being studied. Still another embodiment of the phantom of the present invention opens for a new method of assessment of the absolute radioactivity in any activity configuration and/ or the assessment of the amount of scattering and attenuation in the phantom, based upon scatter- and attenuation-free measurement of incident photons from the 2-D planes, on which the phantom is based.

Also, said phantom offers the possibility of image interpretation with a much higher degree of accuracy than hitherto, since the present phantom can be imaged free from photon scattering and attenuation, or complimented with any selected degree thereof.

Thus, by means of the present phantom, and the methods of the present invention the measuring and quantification of radioactivity in the phantom, and also in any other different objects is greatly simplified, as will be recognised by the person skilled in the art.

In theory, a radioactive gas could also be used for the purpose of the present invention, i.e., to avoid these disturbing effects but unfortunately, only few suitable radioactive gases are available and practical problems might restrict its applicability, such as health hazards, the handling thereof, adsorption on any surfaces exposed to the gas, and radioactive contamination.

The first method of present invention is based on the following steps, which will be described in more detail below:

A) planar scattering- and attenuation-free scintigraphic imaging of the individual radioactive structures, for acquiring of an A image data set;

B) scintigraphic imaging of said structures air-stacked (or, in the ideal case, stacked in vaccum), i.e. without any intervening layers, or preferably, scintigraphic imaging of said structures having supportive low-density layers adjacent to at least one side of each structure, for acquiring of a B image data set;

C) scintigraphic imaging of said structures having, preferably on each side thereof, adjacent layers of attenuating material for acquiring of a C image data set; and D) processing the A, B and C image data sets; and development, or evaluation, of correction routines allowing transformation of C image data into corresponding A image data.

In step A, a data set of the "true" image is obtained by means of individual, planar scintigraphy of each of the structures, which are provided with radioactive distribution patterns of radioactivity, and included in the specific phantom. The term "true" means that the image is obtained essentially free from scattering and attenuation of photons, and thus it can be regarded as reflecting essentially only true origins of primary photons, without any noticeable loss of attenuated photons. Accordingly, it is preferred that such scintigraphy is performed at a closest possible distance to the collimator of the gamma camera in order to achieve an image with the best possible spatial resolution (image sharpness). This true image will serve as a reference, to which image data obtained in the following steps will be compared.

In step B), the one or more radioactive structures imaged in step A) are assembled separated at a distance from each other into a 3-D shape, without any intervening layers of attenuating material, and are imaged by means of, for example, computerised tomography. In this step image data is obtained for the radioactive distribution patterns forming the phantom, without any scattering and attenuation contributions from surrounding material. Thus, in order to minimise such contributions the structures are preferably arranged with vacuum as separating medium. However, the density of air is still relatively low, at least as compared to normal human body tissue (e.g. a factor of about 800 less than muscle tissue), so that a convenient way of arranging the structures is to have them stacked with air as a separating medium. Thus, the image disturbing effects in this step will be reduced to collimator blurring, as is conventionally known in the art of scintigraphy, together with attenuation and scattering of photons due to the material of the radioactive structures, such as for instance, paper.

However, in order to obtain as high accuracy as possible of the image data of the air- stacked structures, said structures should be fixed in position in relation to each other, and also prevented from deviating from the original shape thereof in step A, such as flexing of an originally planar paper sheet. For this purpose the structures, for example planar paper sheets, may be provided with a rigid, low- density supportive layer of a material exhibiting as low photon scattering and attenuation properties as possible, in order not to incur any noticeable image disturbing contributions thereof.

In step C, the one or more radioactive structures imaged and assembled in step B) are now provided with layers of attenuating material, after any supportive layers of low-density material have been removed, and are imaged by means of, for example, computerised tomography. In this step image data is obtained for the radioactive distribution patterns forming the phantom, with photon scattering and attenuation contributions from surrounding material.

Finally, in step D) the A, B and C image data sets are compared and processed for the purpose of assessing the amount of scattering and attenuation in the phantom provided with attenuating material, for evaluation of existing correction routines for scattering and attenuation contributions in phantoms, for development of new correction routines allowing transformation of C-data (images with contributions of photon scattering and attenuation) into A-data ("true", scatter- and attenuation-free images) .

If the intervening layers of the attenuating material in step C) is adapted so as to simulate the photon scattering and attenuation of human body tissue, correction routines can also be developed allowing correction of clinically acquired images of the human body (i.e., corresponding to C image data) into "true" images, since the correction routines thereby obtained will be applicable to photon scattering and attenuation in human body tissue.

In this manner a correlation between images of the known patterns, with and without, respectively, photon scattering and attenuation can be established, which then can be used for correcting clinically acquired data to gain images with higher accuracy, e.g. with better localisation properties and contrast resolution. The steps B) and C) could also be performed by means of planar scintigraphy. This might, for example, be convenient when the phantom only comprises one radioactive structure, and/or in skeletal scintigraphy of the human body, but is in no way limited hereto.

Also, it is to be understood the method steps A), B), and C) of the invention can be carried out in any order. However, the order given in the claims and in the description is considered convenient and is thus preferred.

Brief description of the attached drawings

Fig. 1 shows a set of 9 selected transverse sections from a digitised brain phantom (comprising 19 sections) representing regional Cerebral Blood Flow (rCBF), to be used in the phantom of the present invention.

In Fig. 2, a schematic drawing of a 3-D phantom based on the nine sections shown in Fig. 1 is illustrated. Left: phantom stacked in air, wherein reference numeral 1 represents means for stacking and fixation of the sections 2, which sections 2 comprise plastic laminated paper sheets, printed with radioactive ink; Right: same phantom stacked with additional intervening polystyrene layers 3.

Fig. 3 shows a prototype of the brain phantom of Fig. 2, right, positioned with its central axis aligned with the axis of rotation of the SPECT-camera.

In Fig. 4, the top view depicts the Gaussian spatial resolution function of the SPECT camera for a point source of radiation in a paper sheet, 4, laminated on both sides with a plastic sheet, 5, comprising a section 2, as shown in Fig. 2. Below, to the right, a partial enlargement of the laminated sheet 2, arranged in a gamma camera as shown to the left, is illustrated.

Fig. 5 depicts an energy spectra from the air-stacked phantom of Example 3 (shown in Fig. 2, left) and the polystyrene- stacked phantom of Example 5 (shown in Fig. 2, right), respectively, and for comparison, a ^99mTc "point-source" in air. Fig. 6 shows three sections of the digital phantom obtained by positioning the sheets on top of the collimator (top), air- stacked for SPECT (middle) and polystyrene-stacked for SPECT (bottom) . The SPECT sections were reconstructed according to the clinical image processing protocol.

Fig. 7 shows three images of section 14 (also shown in Fig. 1) as obtained by planar, air-stacked, and polystyrene stacked phantom imaging, respectively, together with the corresponding count rate profiles across the centre of the images. Note that the profile of the polystyrene stacked phantom image contain both primary and scattered events.

Fig. 8 illustrates the sampling method of the present invention, for representing any specific physical property distribution in a 3-D object 10, by means of 2-D sampling planes. In the figure, two consecutive 3-D sections, Si, and S₂, are represented by means of two planar 2-D planes, Pi and P₂, in which the specific physical property distribution is isolated. The method will be described in further detail hereinafter.

Detailed description of the present invention

The structures on which the phantom of present invention is based can be comprised of any suitable material which can be endowed with a radioactive pattern and which does not unduly affect the desired radiation, for example by attenuation or scattering.

According to a preferred embodiment of the invention, a method of imparting a radioactive pattern on the planar structure, such as a paper sheet, is to use a conventional ink writer, in which the conventional ink has been replaced with a radioactive solution, or merely complemented with radioactivity, for printing any selected distribution pattern onto a thin paper sheet. This radioactive "ink" is preferably coloured as a matter of practicality. As is conventional, the writer is preferably connected to a computer and a screen, on which screen any desired image to be printed first can be displayed. According to an alternative preferred embodiment of the invention, a planar structure, a suitable example being paper, which can be made radioactive by dipping thin paper sheets, optionally covered in part by any suitable absorption preventing substance in order to impart a pattern, one, or several times, in to a radioactive solution, thereby forming a radioactive pattern on the paper. Thereafter, the paper sheet is left to dry. In this way the liquid content of the phantom associated with the radioactive substance will be practically eliminated, with exception for any moist remaining in the paper, and the basis for the methods of the invention, only briefly mentioned above, will be provided for. Another advantage is the relatively smaller volumes of radioactive liquid required for the dipping of the paper sheets, as compared to a conventional phantom. The radioactive solution could also be sprayed onto the structures.

However, the ink writer method is preferred since, the risk of unintended radioactive contamination of the paper sheets during the spraying or dipping action thereby is avoided. Also, by means of an ink writer, the handling of radioactive material is minimised, only one radioactive concentration is required, and the exposure of radioactivity to the personnel and time for preparation are reduced.

As previously mentioned, the usage of a conventional ink printer connected to a computer will offer many advantages and possibilities.

As is known in the art, conventional computer programmes will offer many varieties of manipulation of the images to be printed, such inversion, fading, filling-in, or erasure of parts of the images, etc, to simulate clinically relevant defects and pathological conditions, for instance. For the preparation of a phantom, already existing images, stored in computer-readable form, or in any photographic form which can be transformed into computer-readable form, can be used. Such images can for example be images of radioactivity distribution in cross-sectional slices of mammal tissue. Conversely, images obtained with the image interpretation technique according to the present invention could be used for preparing the printed images comprised in a desired phantom. Thus, realistic phantoms could be prepared by non-invasive methods, i.e., based on clinical images obtained by means of the present image interpretation method, possibly also displaying pathological conditions of interest, which images also can be manipulated, as mentioned above.

The printing technique is the same as conventionally used with ink-writers and will not be explained in any further detail. Therefore, suffice it here to say that the only difference is the composition of the printing ink used.

The intervening attenuating layers are desirable made so as to obtain photon scattering and attenuating properties resembling those of the particular body tissue being studied. This is especially essential in the method of image interpretation according to the invention. Thus, the attenuating material may also comprise bone- simulating structures or liquid or air filled cavities in order to more closely resemble the specific body tissue or part studied, such as for example bone or lung tissue. The material of choice is not critical, as long as the desired body-like photon scattering and attenuating properties are achieved. A suitable example of such a material for simulating normal body tissue is polystyrene.

In assessing the amount of scattering and attenuation of photons in the phantom according to the present invention, the planar radioactive structures, such as shown in Fig 1 , to be used in the particular phantom of interest are first prepared by means of dipping into a solution, spraying, or printing in an ink writer. Thereafter, the individual planar structures are separately imaged at a distance as short as possible from the collimator (i.e., in the case of nuclear medicine), preferably at the surface thereof, in order to obtain a high spatial resolution image of the actual radioactivity pattern free from any disturbing effects of scattering and/or attenuation. Next, the planar structures, 2, are air-stacked as shown in Fig. 2, left, i.e. stacked at a distance from each other with essentially no attenuating and/ or scattering material separating said structures. When imaged, this arrangement will give a very small scatter contribution, comparable to that of a point-source at the same distance in air, and any resulting attenuation will be essentially due to the material of the radioactive structures, such as paper. Now, the air-stacked phantom is imaged by means of computer tomography imaging. Optionally, the air-stacked phantom may be complemented with supporting layers of a suitable low-density rigid material (not shown) in order to stabilise the phantom structure and to fix the radioactive components, such as paper sheets, into desired positions, such as for example into parallel planes in the case of paper sheets, thereby improving the accuracy of the acquired data. Such a material can be chosen from any materials exhibiting low attenuating and scattering properties, such as for instance DIVINYLCELL (from Diab International, USA), a plastic foam material with a density of only 0.03 g/cm³. Thus, a phantom complimented with low-density material can be used and also imaged, in addition to, or instead of, the air-stacked one, as desired. Subsequently, the air-stacked phantom structure is provided with attenuating material, 3, on each side of the respective radioactive planar structure, as shown in Fig. 2, right, and imaged. Finally, the image data acquired from the last two, or optionally three, image steps are compared with the actual image data acquired free from photon scattering and attenuation from the first imaging step. Thus, the amount of photon scattering and attenuation in the phantom can be assessed.

By means of the technique outlined above it is possible to evaluate the effects of collimator blurring experimentally, in addition to scattered events and attenuation losses. The phantom and the method of the present invention also allows accurate experimental validation of methods of correction for the contribution of scattered events, collimator blurring, and losses of primary photons due to attenuation. The flexibility of the method allows investigations of arbitrary activity distributions or of distributions related to X-ray, CT or autoradiography.

With a radionuclide having a longer half-life, such as ⁵⁷Co (T1_/2 = 270 d), the phantom of the present invention can also be used for assessment of the stability of, or for calibration of, the imaging system, by comparing data acquired from repeating the last imaging step of the phantom provided with the attenuating layers, and comparing the results. As will be recognised by one skilled in the art, the time period during which one and the same phantom can be used for the above purpose will, i.a., be dependent on the half-life of the particular radionuclide.

In image interpretation according to the present invention, the same procedure as outlined above for assessment of scattering and attenuation in a phantom is followed, except for that the attenuating material now should exhibit as tissue-like scattering and attenuating characteristics as possible, so that the specific phantom closely simulates the corresponding part of the animal or human body of interest, and also, in the final step the acquired data sets from the three, optionally four, imaging steps mentioned above are compared with each other, and a correlation function connecting said data sets can established. Thus, in the case of nuclear medicine, such a function will describe the contribution of scattering, collimator blurring and attenuation, and can suitably be used for a more accurate interpretation of a clinical image, preferably of a body part corresponding to the phantom, so as to miniπiise or, preferably, eliminate the contributions of scattering and attenuation and obtain a "true", 2-D cross-sectional or 3-D image of the radioactivity distribution in the body part examined. Such "true" images obtained with the image interpretation method could also be used in preparing a phantom of the invention, or in order. Such a phantom could for example be used for iteratively improving the correlation function previously established.

The ink used according to the present invention is not critical, and any conventional radionuclide, or radionuclide containing tracer substance can be used.

According to an alternative embodiment of the present invention there is also provided a kit comprising any desired number of low-density supporting structures to be used with the air-stacked phantom in order to stabilise the same and improve the accuracy in the imaging thereof.

According to a further preferred embodiment, a kit comprising any suitable number of attenuating structures to be used with the radioactive structures forming a phantom is provided. Optionally, such attenuating structures can be made from a material having tissue-like scattering and attenuating properties, and can also be made to simulate the shape of any specific animal or human body part.

It will be understood that the phantom of the present invention in its most basic form will comprise only one radioactive structure, such as a sheet of paper, optionally having a supportive low-density layer, or a layer of attenuating material on or both sides thereof.

Examples

The following examples are given to further illustrate the present invention and should not be construed as limiting the scope thereof. In the Examples, the embodiments of the phantom of the invention are given with reference to a human rCBF phantom. The different embodiments of the rCBF phantom are described together with embodiments of the method steps of the invention.

The deterioration of images due to photon attenuation and scattering depends on various factors such as the dimensions of the object, the average length of the photon paths and the media composition. Other factors, e.g. the distance dependent collimator blurring, also depend on the object size. Thus, the experimental geometry can not be scaled without changing the overall imaging conditions.

The object of the present invention is achieved by reducing the phantom mass while maintaining its dimensions and thus, lowering its average density. This can be performed by representing a uniform 3D radioactivity distribution by means of a discrete number of thin, low weight, radioactive sheets. The choice of material in between the active sheets is arbitrary and may be air or soft-tissue equivalent matter, depending on specific demands.

Example 1 - rCBF-phantom A brain blood-flow phantom was designed by utilising sections of the mathematical rCBF Hoffman-phantom (which is a data file representing the brain blood flow by means of 19 consecutive data matrices), and has been described in further detail in Hoffman EJ, Cutler PD, Digby WM, Mazziotta JC, 3- D phantom to simulate cerebral blood flow and metabolic images for PET, IEEE Trans Nucl. Sci. 1990; 37: 616-620. This virtual data phantom represents the blood-flow distribution by means of a radioactivity distribution corresponding to a relative activity concentration of 5: 1:0 for grey matter, white matter, and _^ ventricular space, respectively. Nine equidistantly spaced transverse sections - from the base to the top of the brain, as shown in Fig. 1 , - were selected for the printout. The size of the printed sections was adjusted to represent an average human brain with a maximum length of 210 mm, 150 mm width and a height of 120 mm. All paper sheets were subsequently cut to fit the shape of the brain with an additional 5 mm margin to represent the scalp.

In order to obtain thin radioactive sheets, ordinary writing paper and a digital ink-printer (Hewlett-Packard Desk Writer 550C) was used. The ink-container of the printer was modified to allow fluid refilling. A solution, made of 1 ml of original black ink and 4 ml of 99mTcO₄- and water, was mixed to a concentration of about 2 GBq/ml and introduced into the ink-container. By this performance, digital activity distribution maps, on the computer display, could be printed on paper sheets using the ordinary printing routine of the computer (Macintosh Power G3, Apple Computer Inc.).

Print-out was performed on white writing paper (80 g/m²) with a thickness of 0, 1 mm and A4-dimension, 210 x 297 mm (Xerox Business, USA). In order to avoid contamination, each paper (represented by 4 in Fig. 5) was laminated in between two sheets of 0. 1 mm thick pouches (represented by 5) (GBC, General Binding Corp. Northbrock, II, USA) using a laminating machine (Ibico PL-330 LSI). The thickness of the sealed activity sheets was 0.3 mm. The thus prepared nine radioactive structures comprising the phantom will be used in the embodiments in the following examples, and in the corresponding method steps of the invention.

Example 2 - Planar scintigraphic imaging - Method step A Acquiring of A image data

All nine 99^mTc labelled sheets were imaged by planar scintigraphy. One sheet, represented by 2 in Figs. 2 and 4, in turn was carefully laid down on top of a 5 mm thick plastic plate (with three markers indicating the position of three of the nylon lines, which will be used in the mounted phantom embodiments as stacking means 1). The plate was fixed directly on the low-energy, ultra-high resolution collimator of one of the camera heads of a three-headed gamma camera (Tronix Research Lab., Twinsburg, Ohio, USA). The spatial resolution at the collimator surface was 4.0 mm (FWHM). A 20% energy discrimination window was set between 126 keV and 154 keV. The pixel-size was 1.1 1 mm² and the data acquisition time was 2 min/ sheet. The careful alignment of the sheets to the markers makes it possible to subsequently transfer these images as some "ideal transverse sections" into a virtual SPECT-data file for subsequent ROI/VOI (region /volume of interest) interpretation.

In the planar scintigraphy of this example (method step A), the count-rate varied between 590 and 5,600 cps (corresponding to 8.3 MBq - 80 MBq) depending on the size of the actual sheet. The 5 mm thick plastic plate between the sheet and the collimator had a minor influence on both count-rate and scatter contribution.

Three selected planar images obtained in this example, as well as the corresponding SPECT sections as obtained in Examples 4 and 6, respectively, are presented in Fig. 6, with the planar images at the top, sections from the air- stacked phantom in the middle row, and from the polystyrene-stacked phantom in bottom row. Example 3 - Air-stacked rCBF-phantom

With reference to Fig. 2, left, the nine radioactive sheets 2 used in example 1 and 2, with a shape representing the brain rCBF outline at the corresponding axial position were mounted together, in order from the base to the top, by means of seven 1 mm thick fishing line (nylon) and 12 mm long and thin spacer tubes (2 mm diameter) as fixation and stacking means 1. The air spacing between the sheets was constantly 12 mm. The spacer tubes (plastic) were thread on the line between each sheet. Small plastic locking devices were placed on each side of the last sheet at the top and base, respectively. The total weight of the phantom was 63 grams.

Example 4 - Tomographic imaging of the air-stacked rCBF phantom - Method step B Acquiring of B image data

The sectioned 3D air stacked-phantom in example 3, shown in Fig. 2, left, was positioned with its central axis aligned with the axis of rotation of the SPECT - camera, as shown in Fig. 3. The radius of rotation, RR was 13.5 cm and 90 views were acquired during 360° rotation of the three-headed camera. The acquisition time per angle was 15 s.

SPECT of the air-stacked rCBF-phantom. The count-rate obtained with the 3D phantom was about 23,000 cps per camera head, corresponding to a total activity of about 320 MBq. When the count-rate from planar imaging of all nine sections in Example 2, corrected for the physical decay, was compared to that of the total SPECT data acquisition file of the nine sections of Example 4 stacked in air, the result indicated a 20% loss due to photon attenuation in the laminated paper sheets of the SPECT prototype phantom of Example 4. This is also illustrated by the count rate profiles shown at the bottom of Fig. 7, which, from left to right, show the relative count-rate along a seven pixels wide profile across the section of a planar image, the corresponding air-stacked, and polystyrene- stacked reconstructed SPECT sections. Example 5 - Polystyrene-stacked rCBF-phantom

With reference to Fig. 2, right, the same sheets as those used the previous examples were also utilised in an embodiment of the phantom with attenuating media. Ten 12 mm thick polystyrene plates 3 were used, each of which was shaped to match the shape of its associated paper sheets 2. The phantom was prepared by placing a radioactive paper in between its two associated polystyrene plates in such an order that the complete 3D phantom consisted of 10 plates and 9 intervening radioactive paper sheets. The plates and the sheets were fixed and bound together by means of the same seven, 1 mm in diameter, lines as those used in the air-stacked phantom. The weight of the phantom was 2,300 g, i.e., about 36 times the weight of the air stacked-phantom, and comparable to the weight of a human skull.

Example 6 - Tomographic imaging of the polystyrene-stacked rCBF phantom - Method step C Acquiring of C image data

A SPECT acquisition of the phantom of example 5, with the polystyrene plates 3 in between the laminated paper sheets 2, was performed in the same way as in the previous example 4.

The mass of the uniform-stacked phantom was approximately 36 times the air- stacked phantom. This indicated that the scatter generation from the air- stacked phantom should be about 30 times less than for a uniform one. As is seen from the experimental energy spectra in Fig. 5, there is a large difference in scatter contribution between the two phantoms. When the average count rate of the full data acquisition of air- stacked phantom of Example 3 was compared to that of the polystyrene stacked phantom of Example 5, there was a reduction of 42 % in the latter case (as shown in Fig. 7). In comparison with the count rate data obtained at planar imaging in Example 2, there was a 52 % reduction for the polystyrene stacked phantom. However, the data obtained from the polystyrene phantom of Example 5 is not only influenced by a reduction due to attenuation but also by an addition of scattered events which indicates that the attenuation losses are larger than those obtained in this example.

Example 7 - Processing of acquired image data - Method step D

Pre-processing of the projection data was performed both with smoothing filter, to be comparable with the clinical studies, and without smoothing filter to reveal the best possible resolution. The smoothed data sets were reconstructed using a 2D Hamming filter with a cut-off frequency of 1.0 cycles/cm and five consecutive matrix rows were weighted together (weight factors 1, 2, 5, 2, 1) before reconstruction. For the non- smoothed data, the five consecutive matrix rows were weighted together with weight factors 1 , 1 , 1 , 1 , 1. All images were subsequently reconstructed by filtered back projection using a ramp filter with a cut-off frequency of 2.25 cycles/cm. All data sets were projected into a zoomed 128x128 pixel matrix (zoom-factor 1.6) resulting in a pixel size of 2.22 x 2.22 mm². For this protocol, the reconstructed spatial resolution in water (at the centre, with 135 mm radius of rotation of the camera) was 11.2 mm.

All reconstructed data may be transferred to a separate computer operating with some computerised brain atlas (CBA) program, in order to facilitate the interpretation of imaging data. Thus, in case of the human brain, A image data sets can, for example, be entered into a CBA program, which then will transform the data sets into a 3-D standard human brain, wherein the different regions of the brain also is represented. By repeating the same procedure for B image data sets (air- stacked), and comparing the resulting two 3-D images of the brain, or any particular region thereof, the activity loss due to collimator blurring can be determined. Similarly, by repeating the same procedure for also for the C image data sets (stacked with attenuating material), and comparing with the B data- based 3-D image, the activity loss due to photon scattering and attenuation can be determined. In order to transform C image data sets into the (true) A image data sets using a CBA program, a certain region of the brain can be studied in the CBA 3-D images, based on A and C image data, respectively, a standard factor, for instance, can be assigned to any ROI or VOI in order to transform, any parameter such as, for example, the light value thereof, into that of the specific ROI or VOI of the "true" 3-D image, so as to resemble the latter. This can be performed for any number of ROIs or VOIs.

According to an alternative method, individual transformation factors, e.g., for the light value, can be assigned to each pixel of an A image data set, in order to transform each pixel value into the pixel value of a corresponding pixel in the corresponding C image data set. This pixel-by-pixel approach can of course be utilised in the reverse, or the factors can simple be inverted in order to allow transformation in the opposite direction

It is to be understood that, according to the present invention, the method of transforming A image data into C image data, or vice versa, is not critical, and can include transformation of any number of different parameters, affecting the appearance of the images, as long as a corresponding true A image can be obtained from a C image data set, and/ or a true A image data set can be transformed into a corresponding C image. Thus, a C image, which has been transformed as mentioned above, should preferably coincide with the corresponding true A image. Nevertheless, the level of accuracy of such methods can be selected as deemed appropriate in the specific case.

Discussion

Variations in the total amount of uniformly spread radioactivity (activity reproducibility) from sheet to sheet and variations within each sheet (differential uniformity) were tested by printing out eight identical and consecutive copies of uniform and circular (radius 95 mm) radioactive sections, all within 5 minutes. Each paper was laminated, as previously described, before imaging, carefully positioned directly on the collimator of one of the gamma camera heads and measured for 2 minutes.

Reproducibility was evaluated as the relative standard deviation (± ISD) of the total counts (corrected for physical decay) in all eight images. Uniformity was calculated as the relative standard deviation (± ISD) of individual pixel counts in one representative image.

The average number of recorded events from the eight papers representing a transverse section of a uniform cylinder was about 480,000 events per 2 minutes, corresponding to 56MBq/ section. The reproducibility of the amount of "printed" radioactivity was 0.7% (± 1 SD). The uniformity was 1.2% (± ISD). Maximum deviations from the mean was 1.2% for the reproducibility and 1.4% for the uniformity.

Impact of paper thickness. Even though the thickness of the laminated paper sheets was only 0.3 mm, it might still disturb the photon transfer. The density difference between the paper and the plastic sheet (0.82g/cm3 vs. 1. 17 g/cm3) was not taken into account. Assuming a spatial resolution of 8 mm (FWHM) at 100 mm distance from the collimator, primary photons will be detected in an angular interval of about ± 5.7 degrees as shown in Fig. 4. Photons travelling from the paper sheet to the detector within this narrow interval are passing through paper and laminating matter during a non-negligible fraction of the path.

Assuming a Gaussian spatial resolution function of the camera and using the definitions of Fig. 4, one may estimate the transmission fraction /of detected photons from the expression:

where l(τ, α), the attenuation distance, is given by:

and μ/p is the mass attenuation coefficient (cm /g), t is the grammage (g/cm²) of the sheet, R (R= 100 mm) is the radius of the sheet and σ (σ =FWHM/2.35) a measure of the spatial resolution of the camera The first term of Eq ( 1) represents the attenuation along a distance I in the sheet at an oblique incident angle β (0<β<π/2) and an angular path α (0<α<2π) through the sheet in Fig 4. In practice, the upper integration limit of r may be limited to the width of the spatial resolution function of the gamma camera The second exponential term, as well as the one m the denominator, is the Gaussian shaped spatial resolution funcuon of the camera The numerator of Eq.(l) was used to calculate photon detection profiles while stepwise numerical integration of the whole expression was performed to estimate the attenuated fraction (1-fl, of photons in the paper sheets

As regards the generation of scattered photons, the major fraction of interactions in the sheet results m Compton photons that are scattered outside the detectable angular interval of the camera. However, scattered photons from Compton interactions in any of the adjacent sheets of the phantom may still be detected. The probability of such events is assumed to be proportional to the phantom mass. In order to compare the scatter contributions experimentally, spectral distributions were acquired for both the uniform and the air-stacked phantom as well as for a single point- source of 1 μl drop of 99m-Tc- pertechnetate in air, the results being shown in Fig. 5.

Thus, calculations of the primary photon transport through a laminated paper of 0.3 mm thickness resulted m estimated attenuation losses (1-/) of 16.3 %.

As is apparent from the above-mentioned, the phantom of the present invention offers a much greater flexibility than presently commercially available phantoms of the prior art, smce any object structure can be digitised into a computer readable format and printed. The new phantom also offers a unique property of allowing experimental imaging with or (almost) without disturbing effects from scattering and attenuation of photons The planar 2-D structure of the phantom of the present invention could also form the surface area of a 3-D geometric shape. Thus, one or more co-axially arranged tubular, or, for example, hemispherical structures are also conceivable.

The geometric shape of the phantom, i.e., the radioactive structures and attenuating layers, can also be especially adapted for the quality control of the gamma cameras used, in which case such shape does not have to correspond to any human or animal organs or tissue, or the photon scattering and attenuation properties thereof. Such phantoms can for example be used for the purpose of absolute activity calibration, contrast, resolution or volume determination, and can have any shape suitable for the particular purpose.

As will be recognised by the person skilled in the art of clinical imaging methods, the present phantom can easily be adapted to be used in other types of imaging by substitution of the radionuclide with different imaging agents, such as contrast agents for X-ray, CT imaging, or, in the case of MR- or NMR-based imaging, an imaging agent having suitable magnetic properties therefor. Similarly, the fundamental teaching of the methods of the present invention can also be applied to such other imaging techniques.

Thus, according to another aspect of the present invention, there is provided a general method for isolating a specific physical property, for instance a radioactive distribution, such as in the phantoms of the present invention, from disturbing effects of surrounding matter. This method is illustrated in Fig. 8. By this method any activity distribution of interest in a 3-D body 10 can be studied as represented in digitised 2-D planes, Pi and P , of said body reflecting the activity distribution in a given section, Si and S₂, of the body, virtually free from disturbing effects from surrounding matter. This can be performed by sampling the specific property of a 3- D object by means of 2-D planes Pi and P₂; i.e. dividing the object into sections, Si and S₂, and represent each section by a thin, in the case of the present invention, radioactive, plane, corresponding to Pi and P₂, as shown in Fig 8. Digital signal processing techniques as well as tomographic image reconstruction from digital projections are based upon data sampling; i.e. sets of representative and equidistant samples of the signal (in time or apace). According to the "Nyqvist- theorem", any (continuous) signal can be completely recovered from samples provided that the sampling frequency (number of samples per unit time or distance) equals or exceeds twice the highest frequency component of the signal.

In the present method of the invention, sampling of the object radioactivity (or any other physical property) is performed by means of a set of 2-D planes. The number of planes for complete recovery depends on the spatial distribution of the radioactivity in the object and on the desired accuracy of recovery. For the purpose of the present invention, the smallest sampling distance is that of the paper thickness, the largest is that between two paper sheets.

Accordingly, the present invention also relates to method for imaging a specific activity distribution of a 3-dimensional object, virtually free from any disturbing effects from the surrounding matter of said object, comprising the following steps: i) Acquiring of activity distribution data throughout a section of a 3-dimendional object, by means of an imaging method susceptible to said activity; ii) Processing said data into a set of data for a 2-dimensional cross-section, representative of the average activity distribution in said section, optionally using any correction routines; iii) Forming a physical image of said data set for said 2-dimensional cross-section, comprising an imageable active substance, onto an essentially 2-dimensional structure; by means of which method a structure comprising the phantom of the present invention is obtainable.

The physical property can comprise any activity distribution, such as the distribution of a contrast agent used in MRI, X-ray imaging, or radioactivity as in the phantom of the present invention.

A spatial activity distribution in each of the planes is made to represent the corresponding distribution of activity in the real selected sections of arbitrary thickness of the object. The required number of planes; i.e. the sampling frequency, may be selected from the variability of the particular activity of interest within the object. Since no matter is required in between the discrete planes no disturbing effects - except in that in the thin plane itself - and thus images representing the "true" activity distribution can be obtained.

An activity distribution that is uniform along one direction of an object, the z-axis, for instance, may be represented by one single x-y plane. If the activity distribution in all directions vary extensively, the object might need to be sampled very dense. This would add surrounding matter to the radioactive planes in a similar way to that of a uniform object. However, since the activity distribution is sampled by discrete planes, the distance between them may be increased during the imaging process so as to minimise any disturbing effects from neighbouring planes, and thereafter, the planes can be "transferred" back to their original position at image interpretation. This means that any object can be sampled at any spatial frequency and still be imaged without or with only small degradation due to disturbing effects, such as, for example, photon scattering and attenuation.

By means of this method the quantification and measurement of radioactivity in different objects is greatly simplified

Thus, the same principal technique may be applied for other imaging modalities, not involving radioactivity and photon detection as the physical phenomenon but, for instance transmission of light, radio-waves or x-ray photons through contrast matter.

The large flexibility of a phantom obtainable by this method will allow investigations of arbitrary activity distributions, and autoradiography or other imaging techniques, such as PET, and, utilising suitable contrast agents, also CT or MRI.

Claims

1. A nuclear medicine imaging phantom comprising at least one structure provided with at least one radioactive substance, wherein said structure is an essentially 2- dimensional, liquid-free, structure, having a shape selected from the following: planar, annular, tubular or any surface area of a three-dimensional body, optionally provided with either of: at least one supporting low-density layer adjacent to each side of said structure(s); or, at least one attenuating layer adjacent to each side of said structure(s), which attenuating layer preferably exhibits animal or human tissue-like photon scattering and attenuating properties.

2. Phantom according to claim 1 , wherein each of said at least one structure comprises a planar plane, which planes, in the case of more than one structure, preferably are parallel.

3. Phantom according to claim 1 or 2, having the 3-dimensional shape of an animal or human body part, section or organ.

4. Phantom according to any of the previous claims, wherein said at least one structure is paper-based.

5. Method of preparing a radioactive planar structure which can be used in a phantom according to any of the preceding claims, comprising providing the structure with a solution containing a radioactive substance.

6. Method according to claim 5, wherein the structure is prepared by dipping the structure into a dipping solution containing a radioactive substance.

7. Method according to claim 5, wherein the structure is prepared by printing the structure with an ink- writer

8. A radioactive ink adapted to be used in the method of any of claims 5 - 7.

9. Method of using a phantom according to any of claims 1 - 4, comprising the following steps:

B) scintigraphic imaging of said structures air-stacked, without any intervening layers, or preferably, imaging of said structures having supportive low-density layers adjacent to at least one side of each structure, for acquiring of a B image data set;

C) scintigraphic imaging of said structures having, preferably on each side thereof, adjacent layers of attenuating material, for acquiring of a C image data set; and

D) processing the image data sets acquired in steps A), B), and C).

10. Use of the method of claim 9 for assessing the amount and relative importance of photon scattering and attenuation in the phantom.

1 1. Use of the method of claim 9 in order to determine a correction routine allowing transformation of C image data into corresponding A image data, or vice versa.

12. The use of the correction routine determined by the method of claim 1 1 for correction /interpretation of a clinical 2- or 3-dimensional image of human or animal tissue or organs, which image corresponds to a C image data set.

13. Kit comprising one or more layers of a supportive low-density material which layers, when assembled, essentially coincides with the 3-D shape of a human body part or tissue thereof.

14. Kit comprising one or more layers of a photon scattering and attenuating material, which layers, when assembled, essentially coincides with the shape of a human or animal body part or section tissue thereof, optionally having human tissue simulating structures incorporated therein.

15. Image data sets, acquired either under step A), B), or C) in the method of claim 9, optionally being further processed by means of the correction routine determined in claim 11, or acquired by correction/interpretation of clinical images according to claim 12, for one or more images which can be used for producing a phantom of claim 1.

16. Method for imaging a specific activity distribution of a 3-dimensional object, virtually free from any disturbing effects from the surrounding matter of said object, comprising the following steps:

i) Acquiring of activity distribution data throughout a section of a 3-dimendional object, by means of an imaging method susceptible to said activity;

ii) Processing said data into a set of data for a 2-dimensional cross-section, representative of the average activity distribution in said section, optionally using any correction routines;

Ui) Forming a physical image of said 2-dimensional cross-section, based on said set of data, comprising an imageable active substance on an essentially 2-dimensional structure;

by means of which method a structure comprising the phantom of any of the claims 1 - 4 is obtainable.