METHOD FOR PRODUCING A LIGHT-CURABLE RESIN COMPOSITION

Abstract

Method for producing a light-curable resin composition capable of producing a magnetic resonance imaging-signal, in particular for the lithography-based additive production of magnetic resonance imaging phantoms, the method comprising at least the following steps: providing particles at least partially filled with a magnetic resonance imaging-signal producing liquid, and mixing the at least partially filled particles with a light-curable resin.

Claims

1-15. (canceled)

16. A method for producing a light-curable resin composition capable of producing a magnetic resonance imaging-signal, the method comprising: providing particles at least partially filled with a magnetic resonance imaging-signal producing liquid; and mixing the at least partially filled particles with a light-curable resin.

17. The method according to claim 16, wherein the particles are provided as porous particles and are mixed with a magnetic resonance imaging-signal producing liquid thereby obtaining particles at least partially filled with the liquid.

18. The method according to claim 16, wherein the particles are provided as hollow particles that are filled at least partially with a magnetic resonance imaging-signal producing liquid.

19. The method according to claim 16, wherein the particles are made of an acrylic resin,

20. The method according to claim 16, wherein the spherical particles have a mean diameter of 5μμm to 50 μm.

21. The method according to claim 16, wherein the particles are filled to 25 wt.-% to 75 wt.-% of the total absorption capacity of the particles.

22. The method according to claim 16, wherein the particles have an oil absorption capacity of 100-180 ml/100 gr.

23. The method according to claim 16, wherein the particles have a specific surface area of 60-100 m.sup.2/g.

24. The method according to claim 16, wherein water or a lipid, in particular a triglyceride is used as said magnetic resonance imaging-signal producing liquid, wherein the magnetic resonance imaging-signal producing liquid is preferably selected from one or more of the group comprised of seed oil, sunflower oil, paraffin oil and silicon oil.

25. The method according to claim 16, wherein the amounts of particles at least partially filled with the liquid and of the light-curable resin are chosen so as to obtain a weight ratio of 3:10-10:10.

26. The method according to claim 16, further comprising the step of subjecting the mixture of the at least partially filled particles with the light-curable resin to a vacuum.

27. A magnetic resonance imaging-signal producing, light-curable resin composition obtained by a method according to claim 16.

28. A magnetic resonance imaging-signal producing, light-curable resin composition comprising a mixture of a light-curable resin with particles that are at least partially filled with a magnetic resonance imaging-signal producing liquid.

29. A method of producing a magnetic resonance imaging phantom, comprising the steps of: providing a mixture of a light-curable resin with particles that are at least partially filled with a magnetic resonance imaging-signal producing liquid, in particular produced by a method according to claim 16; and building the phantom layer-by-layer by means of an additive manufacturing process, the additive manufacturing process comprising: a) applying a layer of the mixture on a material carrier or on the partly built phantom, b) exposing the layer to an electromagnetic radiation in order to position-selectively cure said layer according to a desired layer geometry, and c) repeating steps a) and b) until the phantom is complete.

30. A magnetic resonance imaging phantom produced by curing a magnetic resonance imaging-signal producing, light-curable resin composition according to claim 28.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In the following, the invention will be described in more detail with reference to the following examples and the figures. In the figures,

[0031] FIG. 1 schematically illustrates a method of producing a light-curable resin composition,

[0032] FIG. 2 shows MR images of some probes and

[0033] FIG. 3 presents relaxation rate curves and the curve fittings for T1-w and T2-w images.

DETAILED DESCRIPTION

[0034] The inventive method was tested by producing solid probes from the light-curable resin composition obtained by the method according to the present invention.

[0035] 24 probes (diameter=50 mm, height=9 mm) were created by using porous, cross-linked polymethylmethacrylate spherical particles (microspheres) (Techpolymer MBP-8), Formlabs Standard Photopolymer Clear photopolymer resin and different oil types (i.e. Silicon oil EBESIL 100, conventional sunflower oil, standard paraffin oil and Silicon oil AK 0.65). The concentration of oil varied between 25%-75% with respect to the oil absorption capacity of the microspheres for seed oil (140 mL/100 g).

[0036] The preparation of the probes was divided into two experiments. For the first one, Silicon EBESIL 100, sunflower and paraffin oil were used separately to build the probes. For the second experiment, the order of mixing the microspheres with a specific oil type was changed to evaluate the time influence on a presumable separation of the oil from the microspheres. Another silicon oil with less viscosity than the previous one (silicon AK 0.65) was additionally used. For each experiment, the preparation was as shown in FIG. 1.

[0037] As schematically illustrated in FIG. 1, 4 g of Techpolymer porous, cross-linked polymethylmethacrylate spherical particles were first weighted in a separated plastic container (diameter=50 mm, height=50 mm). Second, the corresponding type and amount of oil was added to the microspheres and mixed manually. Third, 10 mL (roughly 10 g) of Formlabs resin was added to each probe and mixed manually. Once the mixtures were prepared, the probes were placed in a vacuum machine to remove the air bubbles generated during the previous manufacturing process. Finally, to cure the resin and therefore, to obtain the solid probes, the samples were exposed to UV light (roughly 400V) during 105 minutes. Labeling of the probes and details of the concentrations of the components are shown in Table 1.

TABLE-US-00001 TABLE 1 Samples labeling and component percentages Oil amount Oil amount Exp # Oil type Label (%) (mL) 1 Silicon - EBESIL 100 A1 75 3 A2 50 2 A3 25 1 Sunflower B1 75 3 B2 50 2 B3 25 1 Parafine C1 75 3 C2 50 2 C3 25 1 2 Silicon - AK 0.65 D1 75 3 D2 50 2 D3 25 1 Parafine E1 75 3 E2 50 2 E3 25 1 Sunflower F1 75 3 F2 50 2 F3 25 1 Silicon - EBESIL 100 G1 75 3 G2 50 2 G3 25 1 Silicon - AK 0.65 H1 75 3 H2 50 2 H3 25 1

[0038] Relaxation rates measurements were performed on a 3T Siemens Biograph mMR PET/MR system with an mMR Head/Neck Matrix coil, 12-elements design (Tim coils).

[0039] The sequences and parameters used are presented in Table 2. T1-weighted images were obtained with a 2D-GR sequence for 5 repetition times (TR), from 100 to 1000 ms.

TABLE-US-00002 TABLE 2 Pulse sequences and their parameters for relaxometry experiments. Measurements were performed on a Biograph mMR PET/MRI system with a body coil. TE (ms) Slice [#echoes/ Flip thickness/ echo Pixel Angle spacing spacing TR BW Sequence (°) matrix (mm) (ms)] (ms) (Hz/px) NEX T1 2D GR 90 256 × 256 .sup. 3/3.9 2.3 100 − 1000.sup.Δ 385 2 SP\OSP T2 2D single- 180 256 × 256 3/6 8-128 3000 400 1 echo SP [16/8] HR 2D GR 70 320 × 320 3/6 2.3 50 380 32 SS

[0040] For T2 measurements, a 2D single-echo sequence was used to acquire 16 echoes with 8 ms (milliseconds) spacing between each other. Finally, T1-w High Resolution images were acquired with a 2D-GR sequence (TR=50 ms, TE=2.3 ms, flip angle=70°, NEX=32).

[0041] One circular ROI (Region of Interest) was drawn on each visible probe in the MM images for each sequence used. Mean values and standard deviation of the ROIs were extracted to calculate the relaxation rates and homogeneity for each experiment.

[0042] The R1 (R1=1/T1) was estimated using the equation

s(t)=k(1−e.sup.−tR.sup.1),

[0043] where k is a constant and t the repetition time. As suggested in previous works (Milford, D.; Rosbach, N.; Bendszus, M.; Heiland, S. Mono-Exponential Fitting in T2-Relaxometry: Relevance of Offset and First Echo. PLoS ONE 2015, 10, e0145255) R2 rates (R2=1/T2) were obtained fitting the data (excluding the first echo time=8 ms) to the mono-exponential model

s(t)=αe.sup.−tR.sup.2+β,

[0044] where α is an MM-related constant and t the echo time. Curve fittings were performed in MATLAB R2016a implementing optimised iterative nonlinear routines. Finally, to assess homogeneity of the samples, coefficient of variation (StdDev/mean) were calculated from the ROI (Region of Interest) values of the HR (high resolution) images.

Results

[0045] For most of the probes, measurable signal intensities were obtained when using the sequences described in the previous section (see FIG. 2). FIG. 3 presents examples of the relaxation rates curves and the curve fittings for T1-w and T2-w images. Obtained T1-, T2- and homogeneity-values of the samples are shown in Table 3.

TABLE-US-00003 TABLE 3 Relaxation times for the built probes. Relaxation times Relaxation times (ms) Homogeneity (ms) Homogeneity Label T1 T2 % CoV Label T1 T2 % CoV A1 420.2 129.1 29.72 G1 N.M. N.M. 13.85 A2 280.3 101.9 37.49 G2 N.M. N.M. 17.84 A3 127.9 25.9 28.40 G3 N.M. N.M. 19.05 B1 152.9 68.4 7.42 F1 161.6 70.3 11.90 B2 154.5 67.1 5.11 F2 137.4 65.6 4.41 B3 149.3 61.2 11.84 F3 142.0 62.7 6.49 C1 101.7 80.3 4.83 E1 112.7 73.9 11.20 C2 101 73.9 5.14 E2 109.6 75.2 8.21 C3 93.1 67.9 7.39 E3 110.9 74.7 11.77 D1 142 N.M. 9.94 H1 N.M. N.M. 46.32 D2 N.M. N.M. 22.76 H2 N.M. N.M. 72.51 D3 N.M. N.M. 33.86 H3 N.M. N.M. 33.51 N.M.: Not measurable

[0046] For some of the samples (D1-D3), the signal intensity was significantly low, hampering the quantification of the desired parameters. For samples G1-G3 and H1-H3, wrong connection of the coil led to similar quantification problems. For most of the visible samples, relaxation times presented differences below 5% across experiments for the same oil type and concentration. Only between samples B2-F2, C1-E1 and C3-E3, differences in T1 values were 5.86%, 5.13% and 8.73%, respectively. Finally, slight changes in homogeneity were observed between probes built with the same oil.

Discussion and Conclusion

[0047] 24 solid probes were obtained by mixing acrylic microspheres with oil and 3D printing resin. T1 and T2 relaxation times as well as homogeneity of the visible probes were obtained from 3T MRI measurements. Differences in relaxation times between probes built with the same oil type and concentration were below 10% in all the cases.

[0048] Changes on homogeneity for samples built with the same components can be partly explained due to the manual mixing process, thus, suggesting a better control or automation of this step.

[0049] Likewise, although quantification on samples G1 -G3 was not possible, visual observation of the MRI images suggests that the mixing process and preparation time influence on the characteristics of the material, at least when using high viscosity silicone oil. As can be observed, samples G1-G3 look more homogeneous than probes A1-A3 of the first experiment.

[0050] Based on the results, samples built with a 50% concentration of sunflower or paraffin oil (B2, F2, C2 and E2) seem to be the most promising in terms of compromise between relaxation times and homogeneity. Mixtures with the high viscosity silicon oil could also be considered if the time between the mixture of the components and the curing of the sample is short enough to reduce the effects of separation of the components.

[0051] Although the magnetic resonance imaging-signal producing, light-curable resin composition of the invention has been described in relation to the production of MRI-phantoms, the composition can also be used to produce devices other than phantoms. The composition may be produced for any object, for which MRI visibility is beneficial. This includes MM visible positioning aids in PET/MRI and radio therapy applications. The MRI visibility allows to calculate the attenuation of e.g. PET radiation by the phantom material based on MR-imaging data only without the necessity for additional x-ray or CT imaging.