Evaluation systems and devices for assessing the severity or progression of RP disease.

Abstract

This invention discloses an evaluation system and device for assessing the severity or progression of retinopathy of retinal disease (RP). The core of the evaluation system and device is the use of the RP degeneration index or the RPE / ELM residual index, which can quantify the degree of retinal degeneration and is used to assess the severity or progression of RP disease.

Description

Technical Field

[0001] This invention belongs to the field of clinical diagnostics, and specifically relates to an evaluation system and device for assessing the severity or progression of recurrent stroke (RP). Background Technology

[0002] Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by the progressive loss of rod cells or rod-cone cells. Visual acuity, visual field, electrophysiology, or OCT are commonly used to evaluate the visual function of photoreceptor cells in RP patients. In addition to these examinations, fundus autofluorescence (FAF) is receiving increasing attention. FAF can reveal inherent fluorescent substances within the retina, primarily lipofuscin and melanin in the retinal pigment epithelium (RPE). Traditional FAF imaging equipment has a limited field of view, making it impossible to simultaneously assess posterior pole and mid-peripheral retinal lesions. The Opel Ultra-wide-field fundus autofluorescence (UWF-FAF) system can acquire a 200° field of view of the fundus, allowing for analysis of the relationship between fundus abnormalities and visual impairment in a single imaging session. Previous studies have shown a correlation between low retinal autofluorescence and the duration of RP, but specific quantitative indicators were lacking. This study used UWF-FAF to quantitatively analyze peripheral retinal lesions in RP patients, exploring the correlation between the retinitis pigmentosa index (RP degeneration index), the residual index of the outer retinal structure in the macular region (RPE / ELM residual index), and clinical factors in RP patients. Summary of the Invention

[0003] To address the technical problems existing in the prior art, this invention provides a quantitative indicator for evaluating the severity or progression of recurrent RP disease. The quantitative indicator is the RP degeneration index or the RPE / ELM residual index.

[0004] According to a first aspect of the present invention, the present invention provides a quantitative indicator for evaluating the severity or progression of RP disease, said quantitative indicator being the RP degeneration index or the RPE / ELM residual index.

[0005] The RP degeneration index is the ratio of the total area of ​​low autofluorescence regions in the mid-peripheral retina to the area of ​​the fundus region.

[0006] The total area of ​​low autofluorescence region in the mid-peripheral retina (area of ​​retinitis pigmentosa) is the area of ​​the fundus region minus the area of ​​high autofluorescence region in the macula.

[0007] The area of ​​the fundus region is defined as follows: with the macula as the center, the area of ​​the elliptical region is defined as follows: horizontally (major axis 2a): 6 times the distance from the center of the macula to the center of the optic disc; vertically (minor axis 2b): 4 times the distance from the center of the macula to the center of the optic disc.

[0008] Furthermore, the area of ​​the fundus region was measured using the built-in measurement system of the Optos 200Tx system.

[0009] Furthermore, the area of ​​the high autofluorescence region in the macula was determined using the built-in measurement system of the Optos 200Tx system.

[0010] The RPE / ELM residual index is the ratio of the area of ​​the high autofluorescence ring to the area of ​​the macular region.

[0011] The area of ​​the macular region is defined as the area of ​​an elliptical region centered on the macula, with the vertical axis (short axis 2b) representing the apexes of the superior and inferior venous arches, and the horizontal axis (long axis) representing twice the distance from the center of the macula to the center of the optic disc.

[0012] Furthermore, the area of ​​the macular region was determined using the built-in measurement system of the Optos 200Tx system.

[0013] Furthermore, the area of ​​the high autofluorescence ring was determined using the built-in measurement system of the Optos 200Tx system.

[0014] According to a second aspect of the present invention, the present invention provides a method for obtaining the RP denaturation index, the method comprising the following steps:

[0015] Input the area of ​​the fundus region;

[0016] Input the area of ​​the highly autofluorescent region in the macula;

[0017] The total area of ​​the low autofluorescence region in the mid-peripheral retina is obtained using the first formula.

[0018] The first formula = area of ​​fundus region - area of ​​high autofluorescence region of the macula;

[0019] The RP denaturation index is obtained using the second formula;

[0020] The second formula = total area of ​​low autofluorescence region in the mid-peripheral retina / area of ​​fundus region.

[0021] Preferably, the method for obtaining the area of ​​the fundus region includes the following steps:

[0022] Determine the fundus region: an elliptical region centered on the macula, defined horizontally as 6 times the distance from the center of the macula to the center of the optic disc; and vertically as 4 times the distance from the center of the macula to the center of the optic disc.

[0023] Calculate the area of ​​the fundus region.

[0024] According to a third aspect of the present invention, the present invention provides a method for obtaining the RPE / ELM residual index, the method comprising the following steps:

[0025] Enter the area of ​​the macula;

[0026] Input the area of ​​the high autofluorescence ring;

[0027] The RPE / ELM residual index is obtained using the third formula;

[0028] The third formula is: Area of ​​high autofluorescence ring / Area of ​​macular region.

[0029] Preferably, the method for obtaining the area of ​​the macular region includes the following steps:

[0030] Determine the macular region: With the macula as the center, vertically: the apex of the superior and inferior venous arches, and horizontally: an elliptical region twice the distance from the center of the macula to the center of the optic disc;

[0031] Calculate the area of ​​the macula.

[0032] According to a fourth aspect of the present invention, the present invention provides a method for evaluating the severity or progression of RP disease, said evaluation method comprising a first evaluation method or a second evaluation method.

[0033] The first evaluation method includes the following steps:

[0034] 1) Obtain the RP denaturation index according to the method described above;

[0035] 2) The severity or progression of RP disease is assessed based on the RP degeneration index.

[0036] A RP degeneration index greater than 0.916 indicates poor visual outcomes.

[0037] The second evaluation method includes the following steps:

[0038] 1) Obtain the RPE / ELM residual index according to the method described above;

[0039] 2) Assess the severity or progression of RP disease based on the RPE / ELM residual index.

[0040] When the RPE / ELM residual index is less than 0.1, it indicates that the RP patient has a small area of ​​residual outer layer structure and a high degree of disease severity.

[0041] According to a fifth aspect of the present invention, the present invention provides an evaluation system for the severity or progression of RP disease, the evaluation system comprising a first analysis unit, the first analysis unit using the RP degeneration index or the RPE / ELM residual index to determine the severity or progression stage of RP disease.

[0042] Furthermore, the evaluation system also includes a second analysis unit, which is used to obtain the RP denaturation index using the first and second formulas described above, or to obtain the RPE / ELM residual index using the third formula described above.

[0043] Furthermore, the evaluation system also includes a data acquisition unit, the data acquired by the data acquisition unit including: the area of ​​the macular region and the area of ​​the high autofluorescence ring, and / or, the area of ​​the fundus region and the area of ​​the high autofluorescence region of the macular region.

[0044] The RP degeneration index is the ratio of the total area of ​​low autofluorescence regions in the mid-peripheral retina to the area of ​​the fundus region.

[0045] The total area of ​​low autofluorescence region in the mid-peripheral retina (area of ​​retinitis pigmentosa) is the area of ​​the fundus region minus the area of ​​high autofluorescence region in the macula.

[0046] Fundus area: The area of ​​an elliptical region centered on the macula, with horizontal (major axis 2a): 6 times the distance from the center of the macula to the center of the optic disc; and vertical (minor axis 2b): 4 times the distance from the center of the macula to the center of the optic disc.

[0047] The RPE / ELM residual index is the ratio of the area of ​​the high autofluorescence ring to the area of ​​the macular region.

[0048] The area of ​​the macular region is defined as the area of ​​an elliptical region centered on the macula, with the vertical axis (short axis 2b) representing the apexes of the superior and inferior venous arches, and the horizontal axis (long axis) representing twice the distance from the center of the macula to the center of the optic disc.

[0049] Furthermore, the data acquisition unit is a measurement system that comes with the Optos 200Tx system.

[0050] According to a sixth aspect of the present invention, the present invention provides an evaluation device for the severity and progression of RP disease, the evaluation device comprising a memory and a processor, the memory storing an application program that can run on the processor, the application program being executed by the processor to implement the aforementioned method for obtaining the RP degeneration index, the method for obtaining the RPE / ELM residual index, or the evaluation method for the severity or progression of RP disease.

[0051] According to a seventh aspect of the present invention, a computer-readable storage medium is provided, wherein an application program is stored on the computer-readable storage medium, the application program being executable by one or more processors to implement the aforementioned method for obtaining the RP degeneration index, the method for obtaining the RPE / ELM residual index, or the method for evaluating the severity or progression of RP disease.

[0052] According to an eighth aspect of the invention, the invention provides an application comprising any one of the following:

[0053] 1) Application of fundus area and macular high autofluorescence area in the preparation of products for evaluating the severity or progression of RP disease;

[0054] 2) Application of macular region area and high autofluorescence ring area in the preparation of products for evaluating the severity or progression of RP disease.

[0055] Advantages and beneficial effects of the present invention:

[0056] Ultra-wide-angle fundus autofluorescence (EF) is an important diagnostic tool for assessing and following up on the severity of retinal degeneration in patients with retinopathy of prematurity (RP). High EF rings are particularly valuable in assessing and predicting central visual function. This invention explores and quantifies the RP degeneration index, observing a positive correlation between this index and age, duration of night blindness, and the total area of ​​low EF regions in the mid-peripheral region, and a negative correlation with the area of ​​high EF regions in the BVCA and macular region. Furthermore, the RPE / ELM residual index is positively correlated with the area of ​​high EF rings. The RP degeneration index can quantify the degree of retinal degeneration and can serve as one of the objective indicators for evaluating the severity of RP disease. In addition, with the advancement of RP-related gene therapy, the RPE / ELM residual index is significant for the quantitative evaluation of residual outer retinal structures before gene therapy. Attached Figure Description

[0057] Figure 1 A schematic diagram showing the principle of the Opel ultra-wide-angle laser scanning fundus imaging system;

[0058] Figure 2 A physical image of the Opel ultra-wide-angle laser scanning fundus imaging system is shown;

[0059] Figure 3 Schematic diagrams showing the definitions of various study areas of the retina, including (A) an elliptical diagram with major axis 2a: 6 times the distance from the center of the macula to the center of the optic disc; minor axis 2b: 4 times the distance from the center of the macula to the center of the optic disc; (B) a schematic diagram of the area of ​​the fundus region and the area of ​​the high autofluorescence region of the macula; and (C) a schematic diagram of the area of ​​the macula and the area of ​​the high autofluorescence ring.

[0060] Figure 4The diagram shows the analysis of each index in the residual index of the outer retinal structure in the macular region. (A) High autofluorescence ring in the fundus of RP patients; (B) Macular OCT results of RP patients; (C) ONL, ELM, RPE are present at the junction of the high autofluorescence ring, and EZ is missing; ONL and RPE are present in the area outside the fluorescence ring, and ELM and EZ are missing; ONL, ELM, RPE and EZ are all present in the area inside the fluorescence ring.

[0061] Figure 5 Display the ROC curve analysis graph. Detailed Implementation

[0062] The present invention will be further illustrated below with reference to specific embodiments. These embodiments are for illustrative purposes only and should not be construed as limiting the invention. Those skilled in the art will understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the invention. The scope of the invention is defined by the claims and their equivalents. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or according to the manufacturer's recommendations.

[0063] Example: Objective evaluation index of RP disease severity study

[0064] I. Research Subjects and Methods

[0065] 1. Research Subjects

[0066] 1.1 Clinical Data

[0067] This study included clinically diagnosed RP patients at Tianjin Medical University Eye Hospital between September 2019 and December 2022. Demographic and ophthalmic data were collected, including gender, age, diagnosis, pathogenic gene, medical history, age of onset of night blindness, duration of night blindness, marital status, and family history. Ophthalmic examinations included: BCVA (Best corrected visual acuity), IOP (Intraocular pressure), slit-lamp examination of the external eye and anterior and posterior segments, ultra-wide-angle laser fundus imaging, and UWF-FAF.

[0068] Inclusion criteria:

[0069] RP degeneration group: 1) Meets the clinical diagnostic criteria for RP. 2) High autofluorescence changes are seen in the macular region of the ultra-wide-angle fundus.

[0070] High fluorescence ring group: 1) Meets the clinical diagnostic criteria for RP. 2) High autofluorescence ring image is seen in the macular region of the ultra-wide-angle fundus.

[0071] Exclusion criteria:

[0072] 1) The macular region of the ultra-wide-angle fundus did not show high autofluorescence changes;

[0073] 2) The quality of the fundus FAF imaging was poor, making analysis impossible;

[0074] 3) The shooting angle is too small to analyze the surrounding transgenic areas.

[0075] 1.2 Instruments and Equipment

[0076] The Optos 200Tx ultra-wide-angle laser fundus imaging system utilizes a bifocal elliptical lens for imaging. This lens positions the laser source / detector at focal point F1, with a scanning mirror ensuring that the laser emitted from F1 always passes through F2. If the patient's pupil is at F2, this allows the laser emitted from F1 to reach the maximum angle of the fundus. Therefore, the laser can cover a wider area of ​​the fundus even with a small pupil. Figure 1 The Optos 200Tx features red (633nm), green (532nm), and blue (488nm) light. The pseudo-color fundus image is synthesized using red and green lasers. Ultra-wide-angle fundus fluorescein angiography uses a blue laser, while ultra-wide-angle fundus autofluorescence uses a green laser. Figure 2 ).

[0077] 2. Research Methods

[0078] 2.1 Ultra-wide-angle fundus autofluorescence photography procedure

[0079] Fundus autofluorescence imaging was performed using the Optos 200Tx ultra-wide-angle laser scanning fundus imaging system. In this study, a green laser (532 nm) was used for fundus imaging under mydriatic exposure. Images were captured using Optos V... 2 Digital annotation was performed using Vantage Pro review software (version 2.8.0.4). The entire image acquisition process was performed by the same experienced technician. In this study, ultra-wide-angle fundus imaging was achieved using OptoMap. @ The plus mode is used to scan a 200° area of ​​the fundus.

[0080] 2.2 Definition of each study region of the retina Figure 3 )

[0081] a) Definition of macular area (MA):

[0082] Using the Optos 200Tx system's built-in measurement system (Optos V) 2Vantage Pro Review 2.8.0.4) defines an elliptical region centered on the macula, with the vertical axis (short axis 2b) representing the apexes of the superior and inferior venous arches, and the horizontal axis (long axis 2a) representing twice the distance from the center of the macula to the center of the optic disc.

[0083] b) Fundus area (FA) definition: an elliptical area centered on the macula, with horizontal (major axis 2a): 6 times the distance from the center of the macula to the center of the optic disc; and vertical (minor axis 2b): 4 times the distance from the center of the macula to the center of the optic disc.

[0084] The reasons for defining the fundus region area are as follows: First, although the ultra-wide-angle fundus autofluorescence imaging can acquire a 200° range of the retina, the eyeball is a three-dimensional structure, while fundus autofluorescence imaging is a planar image. Even with post-processing image technology, peripheral area errors still exist when converting the area. The fundus image range obtained by the ultra-wide-angle Optos 200Tx is 96°, 101°, 76°, and 102° in the upper, right, lower, and left directions, respectively. The overall image is stretched by a factor of 1.12 in the horizontal direction relative to the vertical direction. Compared to the posterior pole, the image is exponentially magnified in all peripheral directions, with the steepest magnification in the vertical direction, reaching a maximum of 2.0 × 1.5. We selected the macula and central retina as the fundus region area, which can significantly reduce the error caused by the peripheral retina. Second, the Optos 200Tx image quality is best on the left side and worst in the upper and lower parts. Considering that in actual operation, the patient's eyelashes may obstruct the measurement in the upper and lower parts, thus interfering with the measurement, this range was chosen. Third, in this invention, we refer to the zoning principle of retinal lesions in premature infants and select the distance from the macula to the optic disc as the standard for drawing and measurement.

[0085] c) Definition of Macular fundus hyperautofluorescent area (HFAFA): The area of ​​the hyperautofluorescent area in the fundus is plotted using the measurement system built into the Optos 200Tx system.

[0086] d) Total area of ​​low autofluorescence region in the mid-peripheral retina (area of ​​retinitis pigmentosa): area of ​​fundus region minus area of ​​high autofluorescence region in the macula;

[0087] e) Retinitis pigmentosa index (RP index): The ratio of the total area of ​​low autofluorescence region in the mid-peripheral retina to the area of ​​the fundus region.

[0088] f) Definition of Hyperautofluorescent ring area (HFRA): Using the measurement system built into the Optos200Tx system, plot the area inside the hyperautofluorescent ring in the macula.

[0089] g) Residual index of outer retinal structure in the macular region (RPE / ELM residual index): the ratio of the area of ​​the high autofluorescence ring to the area of ​​the macular region ( Figure 4 ).

[0090] In this study, the area of ​​each region was plotted using the built-in measurement software of the Optos 200Tx system. Two experienced clinicians plotted the measured area separately, and the average value was taken to determine the final measurement result.

[0091] 3. Statistical methods

[0092] This study used SPSS 23.0 to perform statistical analysis on all data in this section. First, the Kjeldahl-Schwarz test was used to test the normality of patient data for age, BCVA, age of onset of night blindness, duration of night blindness, RP degeneration index, and RPE / ELM residual index. Then, Spearman correlation analysis was used to determine the relationship between RP degeneration index, RPE / ELM residual index, and related clinical factors. In this study, a p-value < 0.05 was considered statistically significant.

[0093] 4. Results

[0094] 4.1 Basic Information

[0095] In this study, the RP degeneration group included 24 patients (48 eyes) who met the study criteria. There were 13 males and 11 females. The mean age of the patients was 35.9 years, the mean age of onset of night blindness was 21.3 years, and the mean duration of night blindness at presentation was 14.6 years. Data on patient gender, age, clinical diagnosis, causative gene, corrected visual acuity, age of onset of night blindness, duration of night blindness, total area of ​​low autofluorescence in the mid and peripheral vision, fundus area, and RP degeneration index are shown in Table 1.

[0096] Table 1. Basic information and RP degeneration index of patients in the RP degeneration group.

[0097]

[0098]

[0099] High fluorescence ring group: A total of 13 patients (25 eyes) meeting the study criteria were included. There were 8 males and 5 females. The mean age of the patients was 28.2 years, the mean BCVA was 0.66, the mean age of onset of night blindness was 18 years, and the mean duration of night blindness at presentation was 7.76 years. Patient data including gender, age, clinical diagnosis, pathogenic gene, corrected visual acuity, age of onset of night blindness, duration of night blindness, area of ​​high autofluorescence ring, macular area, and RPE / ELM residual index are shown in Table 2.

[0100] Table 2. Basic information and RPE / ELM residual index of patients in the high fluorescent ring group.

[0101]

[0102]

[0103] 4.2 The relationship between RP degeneration index and age, age of onset of night blindness, duration of night blindness, BCVA, and low autofluorescence area in the mid-peripheral region. Correlation results between total area of ​​the macular region and area of ​​highly autofluorescent region of the macula.

[0104] The RP degeneration index was positively correlated with age (r = 0.329, p = 0.022), duration of night blindness (r = 0.397, p = 0.005), and total area of ​​low autofluorescence region in the mid-peripheral region (r = 0.537, p < 0.001), and negatively correlated with BVCA (r = -0.318, p = 0.028) and area of ​​high autofluorescence region in the macular region (r = -0.960, p < 0.001). There was no significant correlation with the age of onset of night blindness (P > 0.05).

[0105] In this study, the RP degeneration index was positively correlated with age (r = 0.329, p = 0.022) and duration of night blindness (r = 0.397, p = 0.005), which is consistent with clinical observations showing that photoreceptor cells in the fundus of RP patients gradually atrophy and worsen with age. Duration of night blindness is also an important clinical data point for evaluating the severity of the disease; generally, a longer duration indicates a more severe disease, and a higher RP degeneration index suggests a longer duration of night blindness. Fundus examination can objectively reflect the duration of night blindness. The RP degeneration index was positively correlated with the total area of ​​low autofluorescence regions in the mid-periphery (r = 0.537, p < 0.001), indicating that a high RP degeneration index corresponds to more severe mid-peripheral retinal atrophy. The RP degeneration index was negatively correlated with BVCA (r = -0.318, p = 0.028); a higher RP degeneration index corresponds to more severe visual impairment, suggesting that the RP degeneration index can be used to evaluate the degree of visual impairment. The macular high autofluorescence area is the region where some photoreceptor cells remain. The RP degeneration index is negatively correlated with the area of ​​the macular high autofluorescence area (r = -0.960, p < 0.001), suggesting that the index can reflect the size of the area of ​​the patient's remaining retinal functional area. The larger the index, the smaller the remaining retinal functional area.

[0106] Overall, the R degeneration index can quantify the degree of retinal degeneration and can serve as one of the objective indicators for evaluating the severity of RP disease.

[0107] ROC curve analysis of the RP degeneration index for predicting visual acuity showed an area under the curve (AUC) of 0.829, a maximum cutoff value of 0.916 for the Youden index, a sensitivity of 100%, and a specificity of 54.8%. The ROC curve results indicated that an RP degeneration index greater than 0.916 predicted a poor visual acuity outcome (<0.1). Results are shown in Table 3 and... Figure 5 .

[0108] Table 3. Area below the ROC curve

[0109] area <![CDATA[Annotation error a > <![CDATA[Asymptotic significance b > Approaching the 95% lower limit Upper limit of confidence interval .829 .080 .010 .672 .986

[0110] a. Assuming nonparametric assumptions

[0111] b. Null hypothesis: True region = 0.5

[0112] 4.3 Residual RPE / ELM index in relation to age, age of onset of night blindness, duration of night blindness, BCVA, and high autofluorescence ring Correlation results of area

[0113] The RPE / ELM residual index was positively correlated with the area of ​​high autofluorescence rings (r = 0.967, p < 0.001), but not significantly correlated with age, age of onset of night blindness, duration of night blindness, or BCVA (P > 0.05).

[0114] In this study, a positive correlation was observed between the RPE / ELM residual index and the area of ​​the high autofluorescence ring (r = 0.967, p < 0.001). A decrease in this index suggests a gradual reduction in the area of ​​the high-fluorescence ring and disease progression. Furthermore, with the advancement of RP-related gene therapy, precise quantification of the residual outer retinal structure is needed in clinical practice, and the RPE / ELM residual index is of great significance.

[0115] The above description of the embodiments is only for understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from the principles of the invention, and these improvements and modifications will also fall within the protection scope of the claims of the present invention.

Claims

1. A method for obtaining information, the method comprising a first obtaining method or a second obtaining method, The first method for obtaining the RP mutation index includes the following steps: Input the area of ​​the fundus region; Input the area of ​​the highly autofluorescent region in the macula; The total area of ​​the low autofluorescence region in the mid-peripheral retina is obtained using the first formula. The first formula = area of ​​fundus region - area of ​​high autofluorescence region of the macula; The RP denaturation index is obtained using the second formula; The second formula = total area of ​​low autofluorescence region in the mid-peripheral retina / area of ​​fundus region; The second method for obtaining the RPE / ELM residual index includes the following steps: Enter the area of ​​the macula; Input the area of ​​the high autofluorescence ring; The RPE / ELM residual index is obtained using the third formula; The third formula = area of ​​high autofluorescence ring / area of ​​macular region; The method for obtaining the area of ​​the fundus region includes the following steps: Determine the fundus region: an elliptical region centered on the macula, defined horizontally as 6 times the distance from the center of the macula to the center of the optic disc; and vertically as 4 times the distance from the center of the macula to the center of the optic disc. Calculate the area of ​​the fundus region; The method for obtaining the area of ​​the macular region includes the following steps: Determine the macular region: With the macula as the center, vertically: the apex of the superior and inferior venous arches, and horizontally: an elliptical region twice the distance from the center of the macula to the center of the optic disc; Calculate the area of ​​the macula.

2. An evaluation system for the severity or progression of RP disease, the evaluation system comprising a first analysis unit, the first analysis unit using the RP degeneration index or RPE / ELM residual index as described in claim 1 to determine the severity or progression of RP disease; The evaluation system further includes a second analysis unit, which is used to obtain the RP denaturation index using the first formula and the second formula in claim 1 or to obtain the RPE / ELM residual index using the third formula in claim 1. The evaluation system further includes a data acquisition unit, and the data acquired by the data acquisition unit includes: The area of ​​the macular region and the area of ​​the high autofluorescence ring, and / or the area of ​​the fundus region and the area of ​​the high autofluorescence region of the macular region.

3. An evaluation device for the severity and progression of RP disease, the evaluation device comprising a memory and a processor, the memory storing an application program executable on the processor, the application program implementing the acquisition method of claim 1 when executed by the processor.

4. A computer-readable storage medium storing an application program that can be executed by one or more processors to implement the acquisition method of claim 1.

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