System and method for high-speed quantitative NMR spectrum acquisition

Abstract

To provide systems and methods for fast quantitative NMR data acquisition for multiple NMR scans performed on a sample.SOLUTION: Multiple scan batches on the sample are performed. Each batch comprises a long delay scan performed after a long delay interval ensuring near-full relaxation of the nuclei, and subsequently a set of short delay scans (SDS*) each performed after a short delay interval shorter than the long delay interval. An averaged integral loss is computed for each scan time point. For each NMR spectrum of the scan batches, an integral associated with a respective region of interest is multiplied with a corresponding correction factor. The integrals associated with the corrected NMR spectra in all the batches (B1-B3) are summed to obtain a representation of the NMR signal intensity in the region of interest for the sample.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention relates to the spectroscopic measurement of samples in general, and more particularly to a system and method for obtaining high-precision, high-speed quantitative NMR spectra. [Background technology]

[0002] Nuclear magnetic resonance (NMR) is a technique used to study the properties of molecules by measuring the behavior of atomic nuclei in strong magnetic fields. NMR utilizes the fact that certain atomic nuclei act like tiny magnets due to a property called spin. When a molecular sample is placed in a strong magnetic field, the atomic nuclei align with the field. In this equilibrium state, the nuclei have slightly different energies depending on their orientation. By placing the sample in a magnetic field and exciting the nuclear sample with radio frequency (RF) pulses to induce nuclear magnetic resonance, an NMR signal is generated and detected by a highly sensitive RF receiver. The intramolecular magnetic field around the atoms within the molecule changes the resonance frequency, allowing access to the details of the molecule's electronic structure and individual functional groups. For example, NMR spectroscopy is used to identify single organic compounds, proteins, and other complex molecules. Beyond identification, NMR spectroscopy provides detailed information about the structure, dynamics, reaction states, and chemical environment of molecules. While the most common types of NMR are proton and carbon-13 NMR spectroscopy, NMR is applicable to any type of sample containing spin-possessing nuclei.

[0003] More specifically, in NMR spectroscopy, the chemical shift is the resonance frequency relative to a reference for atomic nuclei in a magnetic field. The location of the chemical shift and the peak intensity at that location indicate the amount of molecules in the sample. Typically, the chemical shift δ is,

number

[0004] Exciting a sample with high frequencies (typically 60–1000 MHz) that bring the nuclei to a higher energy state yields a nuclear magnetic resonance response, referred to herein as free induction decay (FID). FIDs are very weak signals and require a highly sensitive RF receiver to pick them up. A Fourier transform can be applied to extract a frequency-domain spectrum from the raw time-domain FID. The spectrum obtained from a single FID typically has a low signal-to-noise ratio. This spectrum contains signals ("peaks") specific to the chemical environment surrounding each nucleus and can be used to identify the types of components / molecules in the sample. The intensity of each peak is directly proportional to the number of nuclei and therefore directly proportional to the mass / concentration of the compound to which it belongs in the sample. These FIDs are acquired and accumulated in tens or hundreds, particularly for accurate quantification of dilute (low-concentration) samples.

[0005] The decay time of excitations, typically measured in seconds, can be very long in gases, depending on the relaxation effect: fast for light nuclei and solids, and slow for heavy nuclei and solutions. The relaxation time constant is unique to each signal in the spectrum.

[0006] Quantitative NMR acquisition is slow (time-consuming) because, in order to achieve a high signal-to-noise ratio to ensure accurate results, a significant number of FIDs must be acquired in each individual scan. These individual scans are then summed up to obtain the final FID. In prior art solutions, a delay is required between such individual scan measurements to allow the sample to relax. Favorably, the sample is fully relaxed; otherwise, the signal amplitude decreases from scan to scan towards the equilibrium value. The delay time (also known as relaxation delay or regeneration delay) is the period between these consecutive acquisitions (individual scans). This allows the spin to return to thermodynamic equilibrium. If this is set too short, the "relaxation" is incomplete, and the signal intensity in the consecutive acquisitions decreases. For quantitative NMR, a time constant T1 of 5 or 7 times this relaxation is recommended, yielding 99.3% or 99.9% relaxation, respectively. Relaxation above 99% is referred to herein as near-perfect relaxation. However, the value of T1 is not known a priori and generally differs for each signal in the spectrum. In the paper “Practical guide for selection of 1H qNMR acquisition and processing parameters confirmed by automated spectra evaluation. Magn Reson Chem. 2017 Nov;55(11):996-1005.doi:10.1002 / mrc.4622.Epub 2017 Jun 20.PMID:28561374.”, authors Monakhova YB and Diehl BWK focus on the effects of acquisition and post-acquisition parameters on quantitative NMR (qNMR) in general, particularly on developed automated routines, which have not been previously performed using systematic and automated methods. These provide a guide on how to select acquisition parameters. A maximum delay of 7×T1 is recommended to ensure complete relaxation of the sample.

[0007] Inappropriate selection of delay can lead to quantitative bias. For safety, a longer delay (e.g., 60-90 seconds) is usually used after each scan than is actually required. Standard experiments exist to determine the TI time constant, but they require significant additional time. For example, Loening NM, Thrippleton MJ, Keeler J, and Griffin RG describe fast T1 measurements in the paper “Single-scan longitudinal relaxation measurements in high-resolution NMR spectroscopy. J Magn Reson. 2003 Oct;164(2):321-8. doi:10.1016 / s1090-7807(03)00186-1. PMID:14511600.” [Overview of the project]

[0008] Therefore, the challenge is to provide a method and system for fast quantitative NMR spectrum acquisition, particularly for samples with low concentrations of the component of interest. For example, when using standard prior art acquisition methods, the total acquisition time easily exceeds 30 minutes when a 60-second delay is used to ensure complete relaxation of low-concentration samples, making it unsuitable for many practical applications. The fast and accurate NMR spectrum acquisition approach disclosed herein in accordance with the independent claim can reduce the total acquisition time to less than one-third of the time required by prior art methods, while maintaining a high level of quantitative accuracy.

[0009] In other words, the technical problems described above are solved by embodiments of computer implementation methods, computer program products, and computer systems described in the independent claims.

[0010] In one embodiment, a computer implementation method for rapid quantitative NMR data acquisition for multiple NMR scans performed on a sample is provided. This method may be performed by a computer system running a computer program that implements functional modules of the computer system adapted to perform various steps of the computer implementation method at runtime.

[0011] First, the method obtains a region of interest as the integral region of the NMR spectrum. The region of interest is a common term in NMR spectroscopy and represents a portion of the NMR spectrum (i.e., a wavenumber range) that contains relevant signal information characteristic of a specific molecule (i.e., the nucleus of the molecule) contained in the physical sample being analyzed. The integral value of the signal intensity in the region of interest is usually an indicator of the concentration of the molecule. Therefore, by the nature of NMR spectroscopy, a point in the NMR spectrum already corresponds to a frequency range. That is, the intensity value at a point in the NMR spectrum can be considered to already represent the integral of the intensity over the underlying frequency range. Typically, regions of interest are received from users interested in a particular component. Alternatively, regions of interest can be obtained from various databases that store region of interest information for different components. For example, this method can be used to sequentially analyze multiple regions of interest of a measured NMR spectrum.

[0012] The approach disclosed herein employs long delay intervals and one or more short delay intervals to allow the relaxation of the nuclei (i.e., the relaxation of each spin) between individual NRM scans. Generally, the delay intervals used herein define a time interval following the acquisition time interval of each NMR scan to allow for further relaxation of the nuclei after each acquisition time interval. Typically, after the excitation pulse, an NMR scan is performed during the acquisition time interval to measure the attenuation of signal intensity caused by the relaxation of the nuclei. However, at the end of the acquisition time interval, the nuclei are not yet fully relaxed. Therefore, a delay time interval may be added after the acquisition time interval to allow for further relaxation of the nuclei. Without such an additional delay time, the measurement results for low-concentration components of the sample are usually degraded in each subsequent NMR scan, resulting in a very poor signal-to-noise ratio. On the other hand, especially in industrial measurement scenarios, it is desirable to perform the series of NMR scans required for low-concentration components as quickly as possible. The approach disclosed herein utilizes the remarkable effect that highly accurate measurements can be achieved even with a sequence of NMR scans with very short delay intervals (referred to as short-delay scans), as long as long-delay scans with long delay intervals are performed again after several short-delay scans (referred to as long-delay scans). Therefore, the duration of the long-delay intervals is selected to allow for near-complete relaxation of each nucleus. As used herein, near-complete relaxation of a sample means that at least 99% of the reversed spins of the sample have returned to their original direction. The duration of the short-delay intervals is shorter than the duration of the long-delay intervals.

[0013] For example, in one implementation, the long delay interval for nearly complete sample relaxation may be selected from the range of 30 to 120 seconds to allow for more than 99% relaxation of the sample. In another implementation, the long delay interval may be shorter than the range described above, determined experimentally. The short delay interval is usually selected from the range of 0 to 2 seconds. Thus, very good results with the approach disclosed herein have been achieved even with a short delay interval of 0 seconds (a negligible delay). That is, the sequencing of NMR scans can be performed without adding any short delay intervals to the acquisition time interval of preceding NMR scans, provided that the long delay scan is performed after a suitable number of short delay scans. It has been found that the relaxation of the sample after the long delay interval is sufficient to obtain good intensity values ​​again for subsequent short delay scans.

[0014] To this end, the method performs multiple scan batches on the sample. Each batch comprises a long-delay scan (performed after a long delay interval to ensure at least nearly complete relaxation of the nuclei) followed by short-delay scans (each short-delay scan is performed after a short-delay interval shorter than the long-delay interval), such that the total number of NMR scans across the batches is greater than or equal to the minimum number of NMR scans required for the sample. It should be noted that, at the start of the measurement, the sample is usually fully relaxed, so the first scan of the first batch is, by definition, a long-delay scan. Each scan is associated with a corresponding scan time point in relation to the time of the long-delay scan in each scan batch. That is, each batch always begins with a long-delay scan that defines the corresponding long-delay scan time point (LDT). The first short-delay scan in each batch is assumed to be performed at the corresponding scan time point (SDT1), the second short-delay scan point at the corresponding scan time point (SDT2), and so on. All short-delay scans are associated with a corresponding scan time point, which indicates that the number of short-delay scans in each batch is the same.

[0015] In one implementation, the short delay interval is the same for all short delay scans. In an alternative implementation, different short delay intervals may be used for batch short delay scans. That is, in this implementation, at least two short delay scans in a scan batch use different short delay intervals. It should be noted that if different short delay intervals are used for the first batch, all subsequent batches must apply the different delay intervals in the same order as the first batch to derive meaningful results. Advantageously, a set of short delay scans in a scan batch may consist of 3 to 9 short delay scans. The number of batches depends on the total number of NMR scans required for the sample and each low-concentration component.

[0016] The method continues by determining the aggregated NMR spectral portion within the region of interest by integrating the signal across the region of interest for each corresponding scan time point. That is, the intensity values ​​within the region of interest for all batches are added together for LDT1, SDT1, SDT2, etc. Therefore, the aggregated NMR spectral portion in LDT (after nearly complete relaxation) is the highest, and the aggregated values ​​at subsequent corresponding short-delay scan time points show decay over time. It should be noted that obtaining the aggregated NMR spectral portion is independent of whether the method first applies a Fourier transform to all individual NMR scans and then aggregates the resulting individual spectra, or whether it first aggregates the individual NMR scans (for each corresponding scan time point) into an aggregated NMR scan and then applies a Fourier transform to the aggregated NMR scan. The operation is commutative, so the result is the same.

[0017] Subsequently, an exponential decay function is fitted to the decay curve of the aggregated NMR spectrum portion across the corresponding scan time points. By applying the fitting function to each scan time point, the average integral loss for each scan time point is calculated. From the determined average integral loss, a correction factor is determined for each scan time point so that the integral loss is compensated for.

[0018] Thereafter, for each NMR spectrum, correction factors are applied to all NMR spectra obtained from a plurality of scan batches by multiplying the integrated values associated with their respective regions of interest by the corresponding correction factors. This correction also ensures that the small contribution of the short-delay scans is corrected to a value comparable to that of the long-delay scans of each batch. Thus, when the region of interest corresponds to a single point within the spectrum, the correction can be applied to only that single point within the spectrum. Finally, the method sums the integrated values associated with the corrected NMR spectra within all batches to obtain an expression of the NMR signal intensity in the region of interest of the above sample.

[0019] In one embodiment, the correction factors can be calculated and applied for all points within the region of interest of the individual NMR spectra of each batch. The correction factors can be calculated and applied for all points of the individual NMR spectra of each batch, and thereafter, all corrected individual NMR spectra can be summed into a single aggregated NMR spectrum.

[0020] The approach disclosed herein enables high-speed NMR measurements of low-concentration components in a sample because most of the required scans are performed as short-delay scans. Thus, the measurement time is mainly determined by the few long-delay scans within a plurality of batches. The results are nearly as accurate as when using only a series of long-delay scans and are more accurate than measurements with shortened long-delay values until the relaxation of the sample falls below a critical threshold (e.g., 99%). Details regarding control measurements of different approaches are shown in the mode for carrying out the invention.

[0021] In one embodiment, the method may provide an estimated NMR signal intensity in the region of interest of the above sample after each scan batch by summing the integrated values of all corrected individual NMR spectra in the already processed scan batches. That is, the method continuously performs the above-described analysis at the end of each batch and provides each intermediate result to the user.

[0022] In one embodiment, the excitation pulse that can be applied to the sample to obtain individual NMR spectra has a flip angle greater than 0° and less than or equal to 90°. Advantageously, the flip angle is in the range of 30° to 45°.

[0023] In one embodiment, a trim pulse can be applied to the sample to remove residual transverse magnetization after the delay interval of the current individual NMR scan and before a subsequent excitation pulse is applied to the sample. That is, the NMR spectrometer is instructed (e.g., by a computer system executing a computer-implemented method) to apply such a trim pulse.

[0024] In one embodiment, provided is a computer program product having computer-readable instructions that, when loaded into the memory of a computing device and processed by one or more processors of the computing device, cause the computing device to perform steps for high-speed quantitative NMR data acquisition for a plurality of NMR scans performed on a sample according to the computer-implemented methods disclosed herein.

[0025] In one embodiment, provided is a computer system for high-speed quantitative NMR data acquisition for a plurality of NMR scans performed on a sample. The system includes a memory storing computer-readable instructions for implementing a plurality of functional modules, and one or more processors for executing the computer-readable instructions to instantiate the functional modules to perform steps according to the computer-implemented methods disclosed herein.

[0026] Further aspects of the invention are realized and achieved by the elements and combinations particularly shown in the appended claims. It should be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention described in the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] [Figure 1] This is a block diagram showing a computer system for high-speed quantitative NMR data acquisition according to an embodiment. [Figure 2] This is a flowchart of a computer implementation method for high-speed quantitative NMR data acquisition according to an embodiment. [Figure 3] This shows an example of an acquisition time interval followed by a delay time interval. [Figure 4] Figures 4A, 4B, and 4C show examples of NMR spectra obtained from samples with two regions of interest. [Figure 5] This shows the sequence of NMR scans performed on a sample using a single NMR scan batch. [Figure 6A] The sequence of NMR scans performed on a sample using multiple NMR scan batches separated by long delay intervals, according to the embodiment, is shown. [Figure 6B] This shows the simulated exponential decay for subsequent NMR scans performed on a sample using short delay intervals of the same length versus short delay intervals of different lengths. [Figure 7] The differences between individual NMR scans performed on a sample according to the embodiment, and corrections for incomplete relaxation are shown. [Figure 8] Figures 8A and 8B show an example of a corrected normalized integral obtained according to the embodiment. [Figure 9] Figures 9A-9I show a comparison of ROI integration results between different setups for scan batches applied to the same sample. [Figure 10] This figure shows examples of general-purpose computer devices and general-purpose mobile computer devices that may be used in conjunction with the technologies described herein. [Modes for carrying out the invention]

[0028] Figure 1 shows a block diagram of a computer system 100 for high-speed quantitative NMR data acquisition for multiple NMR scans performed on a sample 201 using an NMR spectrometer 200. System 100 implements several functional modules configured to perform various data processing tasks for high-speed quantitative NMR data acquisition. The functional modules described in detail herein are advantageously implemented in software, but may also be implemented by programmable hardware components or ASICs. When a software implementation is used, computer-readable instructions for the software are loaded into the system's memory and processed by one or more processors of the system. When the computer-readable instructions are executed at runtime, runtime instances of each module are instantiated to perform a computer implementation method 1000 in an embodiment as shown in the flowchart of Figure 2. System 100 is described in more detail in the context of method 1000, and the reference numbers in both figures are used as appropriate in the following description.

[0029] In NMR measurements, the operator of the NMR spectrometer 200 typically designates one or more regions of interest (ROIs) 301 that define a region in the NMR spectrum that provides spectral information about the molecule of interest in the sample. The system 100 has an interface 110 that supports an interface function adapted to receive information from the operator (e.g., a human-machine interface) and also supports an interface function that enables inter-machine data exchange. Depending on the NMR response characteristics of the molecule, the number of NMR scans required to obtain accurate NMR measurement results may vary. In particular, for low concentrations of the molecule, a larger number of subsequent NMR scans may be required to reach a measurement result that allows for the derivation of a reliable estimate of the concentration of the molecule in the sample 201. Alternatively, the number of scans required may be obtained from a data store (e.g., a database) that stores information about various molecules via the respective adapted interfaces 110.

[0030] The batch composer 120 may acquire the number of NMR scans 302 required for the NMR measurement of the sample 201 and create a batch schedule for sample measurement, distributing the required number of scans into multiple scan batches, each batch starting with a series of short delay scans after a long delay scan. The batch composer 120 may be an optional component of the system 100, or it may be an external support tool for the operator (running on a device such as the operator's smartphone or tablet computer). Alternatively, the operator of the NMR spectrometer 200 may manually provide the system 100 with information on the required number of scans and how to distribute them into various scan batches having long and short delay intervals, instructing the spectrometer 200 accordingly.

[0031] Referring briefly to Figure 3, graph 300 shows the FID311 for a particular NMR scan. The delay time interval generally defines the time interval following the acquisition time interval of each NMR scan to allow for further relaxation of the sample after the preceding acquisition time interval. In the example in Figure 3, the acquisition time interval AT1 (decay time of FID311) has a duration of 1.5 seconds, followed by a delay time interval DT1 with a duration of 1 second. The first scan of the first batch in a sequence of NMR scans is always considered a long delay scan because the sample has not received an excitation pulse for a long time and complete relaxation of the nuclear spins is assumed. In subsequent scan batches, a long delay interval is selected to allow for near-complete relaxation of the sample before the long delay scan that initiates the next scan batch is performed. Typically, for low concentrations of molecules, the long delay interval ranges from 30 to 120 seconds to allow for more than 99% relaxation of each nucleus. Alternatively, the long delay interval may be determined through experiments that may allow for shorter long delay intervals. Short delay intervals are smaller than long delay intervals, typically ranging from 0 to 2 seconds. That is, if the short delay interval is 0 seconds, a series of short delay scans in a scan batch triggers each short delay scan acquisition time interval immediately after the end of the preceding acquisition time interval. Advantageously, a scan batch may include 3 to 9 short delay scans after a long delay scan. Short delay intervals may have the same duration for all short delay scans in each scan batch. In alternative implementations, a scan batch may use different short delay values ​​for different short delay scans. Details regarding these alternative implementations are described in the context of Figure 6B.

[0032] The computer system initiates a series of NMR scans by instructing the NMR spectrometer 200 to perform NMR scans 202-1 to 202t according to the provided scan batch schedule. Referring briefly to Figure 6A, multiple scan batches B1 to B3 (scan batch schedule 600) are performed on sample 201. Each batch is accompanied by a long-delay scan LDS (or as the initial scan of the first batch B1) performed after a long-delay interval LD ​​to ensure nearly complete relaxation of the nuclei, followed by a short-delay scan SDS * A set of these is followed by each short-term delayed scan SDS. * This is performed after a short-term delay interval SD, which is shorter than the long-term delay interval LD. The total number of NMR scans 202-1 to 202-t in multiple batches B1 to B3 is greater than or equal to the minimum required number of NMR scans for the sample. Therefore, each scan is associated with the corresponding scan times t1 to t6 with respect to the long-term delay scan time in each scan batch. In this example, t1 is the scan time corresponding to each long-term delay scan LDS, and t2 to t5 are the scan times corresponding to the short-term delay scans SDS1 to SDS5 in each scan batch. In the example in Figure 6A, all short-term delay SDs have the same length. Since all acquisition time intervals have the same length, the corresponding scan times t1 to t6 are equidistant.

[0033] NMR scans 201-1 to 202-t for all batches are received by the batch processor module 130 of system 100 via interface 110. Interfaces for exchanging data between the NMR spectrometer and the computer system for analysis of the above scans are well known in the art. The batch processor 130 also receives ROI information 301 (from either the operator or their respective databases). The batch processor 130 then determines the aggregated NMR spectral portions Saa to Saf (see Figure 6A) within the region of interest 301 for each corresponding scan time point t1 to t6 by integral over the region of interest 1300. The aggregated NMR spectral portions at the corresponding scan time points show decay over time. Two equivalent implementations can be used to aggregate the NMR spectral portions. In the first implementation, the fast Fourier transform module 131 converts each received NMR scan into the corresponding NMR spectra S1a to S3f. The aggregator module 132 of the batch processor 130 then aggregates the NMR spectra at the corresponding scan time points for each batch. Specifically, for the aggregated spectrum Saa, the spectra S1a, S2a, and S3a of the long-term delayed scans of all batches B1 to B3 are aggregated. For the aggregated spectrum Sab, the spectra S1b, S2b, and S3b of the first delayed scan SDS1 of all batches B1 to B3 are aggregated, and so on. The same aggregation result is obtained when the aggregator 132 first aggregates the original NMR scans (FID) at the corresponding time points, and then the FFT module 131 converts the aggregated NMR scans into the corresponding aggregated NMR spectra.

[0034] The fitting module 133 of the batch processor 130 fits an exponential decay function to the decay of the aggregated NMR spectrum over the corresponding time points. The exponential decay function is shown as the dotted line 610 in Figure 6A and is fitted to the decay curve of the left peak (region of interest) of the aggregated spectrum Saa~Saf. In this example, the signal intensity in the region of interest corresponding to the left peak in the NMR spectrum shows strong decay over the corresponding time points, while the signal intensity in the region of interest around the right peak in the spectrum is hardly affected by the short-term delayed scan. The interpretation is that the molecules corresponding to the left region of interest are likely low-concentration molecules where the relaxation of each nucleus is lacking and the signal intensity deteriorates rapidly.

[0035] Figures 4A-4B illustrate this phenomenon in more detail. Figure 4A shows the NMR spectrum 410 of a given sample with two regions of interest ROI1 and ROI2 defined. Since the total number of NMR scans in this example is 32, 32 spectra are produced as a result. The following batch schedule was applied. Each batch consists of a long-delay scan and seven short-delay scans with a short-delay time interval of 2 seconds. The long-delay interval was 60 seconds. Four batches were performed. Peak 411 in ROI2 is hardly affected by the short-delay scan, but a small peak on the right side of the spectrum shows a strong dependence. The signal intensity 410-y of peak 412h is obtained by the long-delay scan, but the last short-delay scan in each batch yields only a significantly reduced signal intensity, as shown by peak 412l. Figures 4A and 4B show enlarged views of the aggregated spectra for the two regions of interest 410-ROI2 and 410-ROI1. In the case of ROI2 (Figure 4B), there is almost no deviation between the aggregate spectra 411-1 to 411-8 at the eight corresponding time points in each batch. That is, nearly complete relaxation of the ROI2 nucleus in the sample is already present at the end of each acquisition time interval. In the case of ROI1 (Figure 4C), there is a significant deviation in NMR signal intensity between aggregate spectrum 412-1 (obtained by the long-term delayed scan) and aggregate spectrum 412-8 (obtained by the last short-term delayed scan in each batch). The decay of the intensity of the remaining spectra between 412-1 and 412-8 indicates decay of the aggregate spectrum over the corresponding time points, which is typical behavior for low-concentration molecules in the sample.

[0036] Figure 5 shows NMR spectra 5a–5r obtained from multiple 18 NMR scans 50 with two regions of interest 51a and 51b. In this experiment, all scans were performed in a single batch, with only the first scan 5a corresponding to a long-delay scan. All subsequent scans were performed as short-delay scans. In the experiment, ROI 51a (low concentration molecule) exhibits exponential decay. T1 relaxation is exponential decay, and T1 is the decay constant.

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[0037] As described above, (as in the example in Figure 6A) the short-term delay intervals of all short-term delay scans can all have the same value, resulting in equidistant corresponding time points. However, it is also possible to vary the short-term delay interval within a batch. The same variation is used for all scan batches. Figure 6B shows a simulated normalized exponential decay function 620 for equidistant scan time points 0-8 (indicated by x). This scenario corresponds to an implementation (as in Figure 6A) that uses a single value for all short-term delay intervals within all scan batches. The black dots (individual) in the exponential decay function indicate a scenario where different short-term delay intervals are used for short-term delay scans within a batch. The vertical dashed lines indicate different time intervals between scan time points of short-term delay scans. Nevertheless, the shift of corresponding scan time points due to the varying short-term delay interval ensures that all measured intensity values ​​lie on the normalized exponential decay function 620. That is, even in a scenario where the short-term delay interval varies within a batch, the exponential decay function can fit each aggregated spectral portion at the corresponding scan time point. When a variable delay dt(n) is used between each scan in a scan batch, a more accurately iteratively calculated deformed exponential function may be used, taking into account the relaxation time constant T1, the individual delays dt(n), and the integral intensity expected from the applied pulse angle.

[0038] Returning to Figure 1, the correction module 134 of the batch processor 130 calculates the average integral loss for each scan time by applying a fitting function to each scan time, and uses the average integral loss to determine a correction coefficient for each scan time so that the integral loss is compensated. For example, the following formula may be applied: CorrectionFactor(t)=Integral(timepoint0) / fit(t) Subsequently, each NMR spectrum in multiple scan batches is multiplied by a correction factor corresponding to the integral value associated with its respective region of interest. Figure 7 illustrates the concept of this correction mechanism with respect to the region of interest (ROI) 7. An enlarged view 701 of the acquired NMR spectrum shows the attenuation of signal intensity over each scan time point. Fitting and correction steps 1400, 1500, 1600, and 1700 are applied. As a result, all the corrected spectra within the enlarged portion 702 show approximately the same signal intensity.

[0039] Figures 8A and 8B provide a more detailed example of the spectral correction obtained in the examples of Figures 4A and 4B. Figure 8A shows the normalized integrals 810-ROI1 and 810-ROI2 of the aggregated spectra for two regions of interest, ROI1 and ROI2, over corresponding scan times 1–8. Since the integrals are substantially the same for all corresponding scan times, it can be seen that the peak of ROI2 remains unaffected by the short-term delay scan. However, the peak of ROI1 shows exponential decay over the corresponding scan times. The effect that the normalized integral of 810-ROI1 is larger at corresponding scan time 8 than at corresponding scan time 7 is due to the fact that the signal-to-noise ratio for each low-concentration molecule is already very low when the 7th short-term delay scan is performed in each scan batch. Nevertheless, after the fitting and correction steps, the corrected normalized integral 820-ROI1 shows good coherence with an ideal value of "1". After correction, the spread of all corrected integral values ​​for ROI1 is 0.97–1.03, which is approximately as good as the spread of ROI2 (region of interest unaffected by short-term delayed scans), which has corrected integral values ​​of 0.98–1.02. In principle, the correction mechanism described above derives the correction coefficient for each corresponding scan time point as the ratio of each attenuation function value to the corresponding intensity value at the first corresponding scan time point (i.e., the aggregate spectrum associated with long-term delayed scans of all batches).

[0040] Finally, the batch integrator 140 of system 100 sums the integral values ​​associated with the corrected NMR spectra in all batches B1 to B3 to 1800. It should be noted that, after the fitting and correction steps, each corrected spectrum from each short-term delayed scan in each batch has an intensity value similar to the corrected spectrum obtained from its respective long-term delayed scan. As a result, after the last scan batch is completed, the batch aggregator 140 obtains a very accurate representation 202-sf of the NMR signal intensity in the region of interest of sample 201, even for low-concentration molecules, with a relatively short acquisition time compared to the normal measurement time using only long-term delayed scans for low-concentration molecules.

[0041] In one embodiment, the batch integrator 140 may provide an estimated NMR signal intensity 202-si in the region of interest of the sample after each scan batch by summing the integral values ​​of all corrected individual NMR spectra in the scan batches that have already been processed. In some scenarios, it may be advantageous for the operator to already know the estimated 202-si after the first batch and not to wait for the final result 202-sf after all batches are completed.

[0042] Table 1 shows experimental data from different NMR measurements of the same sample. [Table 1]

[0043] The first row of Table 1 shows the data for a standard acquisition NMR measurement. In the standard acquisition setup, only a series of 32 long-delay scans with a 60-second long-delay interval were performed. The total measurement time reached 33 minutes and 18 seconds (including acquisition and delay intervals). The ratio of the two integral values ​​associated with each of the two ROIs was determined to be 1.6421. This ratio, determined by a series of NMR scans after nearly complete relaxation of the nuclei before each scan, can be seen as a kind of ground truth for the ratio to be determined.

[0044] In the second row of Table 1, further measurements of "long-term delayed scans only" were performed using 32 long-term delayed scans. However, to reduce the total measurement time, the long-term delayed interval was shortened to 30 seconds, resulting in a total measurement time of 17 minutes and 30 seconds. The ratio was determined to be 1.6548, representing a deviation of 0.8% from ground truth.

[0045] In the third row of Table 1, measurements were performed using "short-delay scans only" by employing 32 short-delay scans with a 2-second delay interval. The total measurement time was significantly reduced to 2 minutes and 25 seconds. Corrections were applied according to the single-batch scheme described in the context of Figure 5 by fitting an exponential decay function to each region of interest in each NMR spectrum and using the first NMR scan for spectral normalization. However, the ratio was determined to be 1.5418, showing a large deviation of 6% from ground truth. Results with such deviations are not precise enough to obtain signal intensity / integral values ​​relevant to low-concentration molecules.

[0046] In the fourth line, the batch-wise NMR measurement described in Figure 6A, relating to the scheme described in claim 1, was performed in five scan batches, each batch starting with a long-delay scan after a 60-second long-delay interval, followed by seven short-delay scans with a 2-second short-delay interval. The total number of scans in this measurement was 40, and the measurement time was 6 minutes and 30 seconds, approximately one-third of the less accurate measurement in the second line. The ratio was determined to be 1.6493, showing only a 0.4% deviation from ground truth. That is, despite the measurement time being reduced to about one-third of the measurement time in the second line, the determined ratio was twice as accurate as in the case of the shortened long-delay scan in the second line.

[0047] Figures 9A–9I show a comparison of ROI integration results between different setups for scan batches applied to the same sample. Figure 9A shows the NMR spectrum 90 obtained from the sample. Spectrum 90 shows two ROIs for two different molecules contained in the sample. * B* includes. In this example, ROIA * The molecule related to is a known aromatic compound showing three multiplets A1, A2, and A3 in the NMR spectrum. ROIB * The molecule related to corresponds to dimethyl sulfoxide (DMSO) and gives rise to peak B1 in the NMR spectrum. In the experiment, it has been shown that the integral value related to A3 is not affected by the short delay interval in the sense that the nuclear relaxation giving rise to A3 is fast enough to show almost complete relaxation even after the short delay scan A3. However, there is a significant effect of a series of short delay scans on the peak integrals of A1, A2, and B1 in the form of exponential decay over the corresponding scan times. As shown in the enlarged graph A1 and the further enlarged zoom region A1z, for peak A1, 8 aggregated spectra A1_1 to A1_8 are obtained from 32 NMR scans in 4 scan batches using 7 short delay scans after the long delay scan. The aggregated spectra A1_1 to A1_8 show significant deviations. The same is true for the aggregated spectra A2_1 to A2_8 of peak A2 and the aggregated spectra B1_1 to B1_8 of peak B1.

[0048] Figure 9B shows the results obtained from the above sample by 32 NMR scans including only long delay scans with a long delay interval of 60 seconds. The total measurement time of the 32 long delay scans was 33 minutes 22 seconds. Table 91-1 shows ROIA * and B *The ratio of integral values ​​associated with the four peaks in is shown. Note that peaks A1 and A2 contain several relatively broad subpeaks, while peak A3 contains several very narrow subpeaks. For this reason, the integral of A3 is approximately the same size as the integral of A2, while the integral of A1 is about twice as large as the integrals of A2 and A3. In this example, the theoretical integral ratio of known aromatic compounds is A1:A2:A3 = 2:1:1. This is confirmed by long-term delayed scan measurements summarized in Table 91-1, where the integral ratio of A1 to A2 is 2.001 and the integral ratio of A1 to A3 is 2.014. The integral ratio of A1 to B1 is 0.832. The ratio of A2 to A3, which is 1.0057, is close to the theoretical ratio of 1. The ratio of A1 to B1 is derived from measurements as 0.832. Table 91-2 shows the respective relative errors for the derived integral ratios. For scans using "long-delay scans only," all relative errors are less than 1%.

[0049] Figure 9C shows the results obtained from the above sample by 32 NMR scans, including only short-delay scans with a 2-second delay interval. The total measurement time for the 32 short-delay scans was 2 minutes and 30 seconds. The deviation of the A1:A2:A3 integral ratio from the theoretical ratio in Table 92-1 is significantly larger than that of the long-delay scan setup in Figure 9B. However, the deviation between the A* to B1 ratio is very large in the "short-delay scan only" setup. Looking at Table 92-2, the relative errors for each are approximately 12% to 18%. Typically, the ratio between the integral values ​​of two regions of interest is relevant information derived from the spectrum. Therefore, the results obtained from the "short-delay scan only" setup are highly inaccurate and not useful for the analytical purpose of determining DMSO concentration from NMR scan results.

[0050] Table 93 in Figure 9D shows the deviation of the "short-term delayed scan only" measurement in Figure 9C compared to the "long-term delayed scan only" measurement in Figure 9B. In particular, for A3, there is virtually no deviation because A3 has a short relaxation time unaffected by the short-term delayed scan. However, for A1 and A2, the integrals of the "short-term delayed scan only" approach only reach 94% and 93% of the integrals of the "long-term delayed scan only," respectively. The greatest deviation is observed for the integral of B1, which is of most interest. The integral value of the "short-term delayed scan only" approach is only 83% of the integral value of the "long-term delayed scan only" approach. That is, the accuracy of these integral values ​​determined in the "short-term delayed scan only" setup is low due to the significant loss of NMR signal intensity resulting from measurements of nuclei that have not yet relaxed.

[0051] Figures 9E–9G show the attenuation in the integral value of the aggregated spectrum over the corresponding scan time points for A1, A2, and B1, respectively, as well as the corresponding correction values. Graph 94 shows that for A1, the curve defined by the aggregated spectral integral value (represented by a circle) is fitted with an exponential attenuation function, resulting in curve 94–2. The correction value is represented by an x ​​icon, and the resulting correction curve 94–2 is approximately constant over the corresponding scan time points. The same is true for A2 and B1, as seen in graphs 95 and 96, respectively, which have exponential attenuation fitted curves 95–2 and 96–2 and the resulting correction value curves 95–1 and 96–1.

[0052] Figures 9H and 9I show the results obtained from the above sample using scan batches according to the approach disclosed herein. In Figure 9H, the long delay interval before the long delay scan of the scan batch was 60 seconds. The short delay interval used for all seven short delay scans within the scan batch was 1 second. The total measurement time for all four scan batches was 6 minutes. Table 97-1 shows the ROIA derived from the corrected spectra. * and B * This shows the integral ratio between the peaks. A *The ratios of known molecules related to this are nearly identical to the theoretical ratios with relative errors of less than 0.5%, as shown in relative error table 97-2. Furthermore, the integral ratios derived from the spectrum corrected for B1 show very small relative errors of only about 1% or less.

[0053] Figure 9I shows the results obtained with a slightly different setup. To verify whether the extended short delay interval yielded even higher accuracy, a short delay interval of 2 seconds was used for all seven short delay scans. The total measurement time for all four scan batches in this setup was 7 minutes and 20 seconds. The integral ratio results derived from the corrected spectra in Table 98-1 show an accuracy approximately equal to that of the results obtained with the shorter short delay interval of 1 second in Figure 9H. The relative error in Table 98-2 is again approximately 1%. After evaluation, it was recognized that the difference in relative error between ratios A2 / B1(0.42) and A3 / B1(0.42) was due to a difference in the unshown digits of the ratio. For visualization in Table 98-1, the ratios were rounded to two decimal places.

[0054] The approach disclosed herein results in a significant reduction in the total measurement time of NMR scans of samples with low concentrations of material by achieving comparable high accuracy results with respect to corrected integral values ​​even with very short “short delay intervals”.

[0055] Figure 10 shows examples of a general-purpose computer device 900 and a general-purpose mobile computer device 950 that may be used with the technology described herein. In some embodiments, the computer device 900 may be associated with a system 100 (see Figure 1). The computing device 950 is intended to represent various forms of mobile devices, such as a personal digital assistant, a mobile phone, a smartphone, and other similar computing devices. In the context of this disclosure, the computing device 950 may provide I / O means for a user to interact with the computing device 900 (for example, to display a provided preview image to the user). The components shown herein, their connections and relationships, and their functions are intended to be typical examples only and are not intended to limit the implementation of the invention described and / or claimed herein.

[0056] The computing device 900 includes a processor 902, memory 904, a storage device 906, a high-speed interface 908 connected to memory 904 and a high-speed expansion port 910, and a low-speed bus 914 and a low-speed interface 912 connected to storage device 906. Each of the components 902, 904, 906, 908, 910, and 912 may be interconnected using various buses and mounted on a common motherboard or in other ways as appropriate. The processor 902 may process instructions to be executed within the computing device 900, including instructions stored in memory 904 or storage device 906 to display graphical information for a GUI on an external input / output device, such as a display 916 coupled to the high-speed interface 908. In other implementations, multiple processors and / or multiple buses may be used with multiple memories and multiple types of memory as appropriate. Also, multiple computing devices 900 may be connected, each device providing some of the necessary operations (e.g., as a server bank, a group of blade servers, or a multiprocessor system).

[0057] Memory 904 stores information within the computing device 900. In one implementation, memory 904 is one or more volatile memory units. In another implementation, memory 904 is one or more non-volatile memory units. Memory 904 may also be another form of computer-readable medium, such as a magnetic disk or an optical disk.

[0058] The storage device 906 can provide a large storage device for the computing device 900. In one implementation, the storage device 906 may be, or may include, a computer-readable medium such as a floppy disk device, a hard disk device, an optical disk device, or a tape device, flash memory, or other similar solid-state memory devices, or an array of devices including a storage area network or other configurations. A computer program product may be tangibly embodied in an information carrier. A computer program product may also include instructions that, when executed, perform one or more of the methods described above. The information carrier may be a computer-readable or machine-readable medium such as memory 904, the storage device 906, or memory on the processor 902.

[0059] The high-speed controller 908 manages bandwidth-intensive operations for the computing device 900, and the low-speed controller 912 manages low-bandwidth-intensive operations. Such function assignments are illustrative only. In one implementation, the high-speed controller 908 is coupled to memory 904, a display 916 (e.g., via a graphics processor or accelerator), and a high-speed expansion port 910 that can accept various expansion cards (not shown). In this implementation, the low-speed controller 912 is coupled to the storage device 906 and the low-speed expansion port 914. The low-speed expansion port, which may include various communication ports (e.g., USB, Bluetooth, Ethernet, wireless Ethernet), may be coupled to one or more input / output devices such as a keyboard, pointing device, scanner, or networking devices such as switches and routers via a network adapter.

[0060] The computing device 900 can be implemented in numerous different forms, as shown in the figure. For example, the computing device 900 may be implemented as a standard server 920, or multiple instances may be implemented in a group of such servers. It may also be implemented as part of a rack server system 924. In addition, the computing device 900 may be implemented in a personal computer, such as a laptop computer 922. Alternatively, components of the computing device 900 may be combined with other components in a mobile device (not shown), such as device 950. Each of such devices may consist of computing devices 900, 950, and the entire system may consist of multiple computing devices 900, 950 communicating with each other.

[0061] The computing device 950 includes, among other various components, a processor 952, memory 964, input / output devices such as a display 954, a communication interface 966, and a transceiver 968. The device 950 may also be provided with storage devices, such as a microdrive or other devices, to provide additional storage. Each of the components, such as 950, 952, 964, 954, 966, and 968, is interconnected using various buses, and some of the components may be mounted on a common motherboard or in other ways as appropriate.

[0062] The processor 952 can execute instructions in the computing device 950, including instructions stored in memory 964. The processor may be implemented as a chipset of chips including multiple individual analog and digital processors. The processor may provide coordination of other components of the device 950, such as control of the user interface, applications run by the device 950, and wireless communication by the device 950.

[0063] The processor 952 may communicate with the user via a control interface 958 and a display interface 956 coupled to the display 954. The display 954 may be, for example, a TFT LCD (thin-film transistor liquid crystal display) or an OLED (organic light-emitting diode) display, or other suitable display technology. The display interface 956 may include appropriate circuitry for driving the display 954 to present graphical and other information to the user. The control interface 958 may receive commands from the user and translate them for presentation to the processor 952. An external interface 962 communicating with the processor 952 may also be provided to enable short-range communication between device 950 and other devices. The external interface 962 may provide, for example, wired communication in some implementations and wireless communication in others, and multiple interfaces may be used.

[0064] Memory 964 stores information within the computing device 950. Memory 964 may be implemented as one or more computer-readable media, one or more volatile memory units, or one or more non-volatile memory units. An expansion memory 984 may also be provided and connected to the device 950 via an expansion interface 982, which may include, for example, a SIMM (Single In-Line Memory Module) card interface. Such an expansion memory 984 may provide extra storage space for the device 950, or it may store applications or other information for the device 950. Specifically, the expansion memory 984 may include instructions that execute or supplement the processes described above, and may also include secure information. Thus, for example, the expansion memory 984 may function as a security module for the device 950 and may be programmed with instructions that enable the secure use of the device 950. Secure applications may also be provided via a SIMM card, along with additional information, such as providing identification information on the SIMM card in a hack-proof manner.

[0065] The memory may include, for example, flash memory and / or NVRAM memory, as described later. In one implementation, the computer program product is tangibly embodied in an information carrier. When executed, the computer program product includes instructions that perform one or more actions, for example, as described above. The information carrier is a computer-readable or machine-readable medium, such as memory 964, extended memory 984, or memory on processor 952, which can be received, for example, via transceiver 968 or external interface 962.

[0066] Device 950 may communicate wirelessly via a communication interface 966, which may optionally include digital signal processing circuitry. The communication interface 966 may provide communication under various modes or protocols, such as GSM voice calls, SMS, EMS, or MMS messaging, CDMA, TDMA, PDC, WCDMA, CDMA2000, or GPRS. Such communication may occur, for example, via a radio frequency transceiver 968. Short-range communication may also occur, for example, using Bluetooth, WiFi, or other such transceivers (not shown). Furthermore, a GPS (Global Positioning System) receiver module 980 may provide device 950 with additional navigation and location-related radio data, which may be used as appropriate by applications running on device 950.

[0067] Device 950 may communicate by voice using an audio codec 960 that can receive voice information from the user and convert it into usable digital information. The audio codec 960 may also generate audible sound for the user, for example, through a speaker in the headset of device 950. Such sound may include sounds from voice calls, recorded sounds (e.g., voice messages, music files, etc.), and sounds generated by applications running on device 950.

[0068] The computing device 950 can be implemented in a number of different forms, as shown in the illustration. For example, the computing device 950 can be implemented as a mobile phone 980. It may also be implemented as part of a smartphone 982, a personal digital assistant, or other similar mobile device.

[0069] Various implementations of the systems and technologies described herein may be realized in digital electronic circuits, integrated circuits, specially designed ASICs (application-specific integrated circuits), computer hardware, firmware, software, and / or combinations thereof. These various implementations may include implementations in one or more computer programs executable and / or interpretable on a programmable system which includes at least one programmable processor, which may be dedicated or general-purpose, coupled to receive data and instructions from a storage system, at least one input device, and at least one output device, and to transmit data and instructions to them.

[0070] These computer programs (also known as programs, software, software applications, or code) contain machine instructions for a programmable processor and may be implemented in high-level procedural and / or object-oriented programming languages ​​and / or assembly / machine languages. As used herein, the terms “machine-readable medium” and “computer-readable medium” mean any computer program product, apparatus, and / or device (e.g., magnetic disks, optical disks, memory, programmable logic devices (PLDs)) used to provide machine instructions and / or data to a programmable processor, and include machine-readable mediums that receive machine instructions as machine-readable signals. The term “machine-readable signal” means any signal used to provide machine instructions and / or data to a programmable processor.

[0071] To provide user interaction, the systems and technologies described herein may be implemented in a computer having a display device for displaying information to the user (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) and a keyboard and pointing device (e.g., a mouse or trackball) that allows the user to provide input to the computer. Other types of devices may be used similarly to provide user interaction, for example, the feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback), and input from the user may be received in any form, including acoustic, speech, or tactile input.

[0072] The systems and technologies described herein may be implemented in computing devices including backend components (e.g., as data servers), or computing devices including middleware components (e.g., application servers), or computing devices including frontend components (e.g., client computers having a graphical user interface or web browser that allows users to interact with the implementation of the systems and technologies described herein), or in any combination of such backend, middleware, or frontend components. The components of the systems may be interconnected by any form or medium of digital data communication (e.g., communication networks). Examples of communication networks include local area networks ("LANs"), wide area networks ("WANs"), and the Internet.

[0073] Computing devices may include clients and servers. Clients and servers are generally remote from each other and typically interact via a communication network. The relationship between clients and servers arises from computer programs running on each computer that have a client-server relationship with each other.

Claims

1. A computer implementation method (1000) for acquiring high-speed quantitative NMR data from multiple NMR scans performed on a sample (201), wherein the method is: The method involves obtaining a region of interest (ROI1) as the integration region of the NMR spectrum (1100), wherein the region of interest corresponds to each nucleus of the sample. (1200) Initiating a plurality of scan batches (B1 to B3) on the sample, each batch comprising a set of long-delay scans (LDS) performed after a long delay interval to ensure nearly complete relaxation of the nuclei, such that the total number of NMR scans (202-1 to 202-t) in the plurality of batches is greater than or equal to the minimum number of NMR scans required for the sample, and a set of short-delay scans (SDS*) performed after short delay intervals shorter than the long delay interval, each scan associated with a corresponding scan time (t1 to t6) in relation to the time of the long-delay scan in the respective scan batch. For each corresponding scan time point, the aggregated NMR spectral portion (Saa to Saf) within the region of interest is determined by integration over the region of interest (1300), wherein the aggregated NMR spectral portion at the corresponding scan time point exhibits decay over time. The method involves adapting the aforementioned damping to an exponential damping function (610) (1400), The average integral loss for each scan time is calculated (1500) by applying the fitted function to each scan time, and a correction coefficient for each scan time is determined from the average integral loss (1600) so that the average integral loss is compensated, wherein the correction coefficient is derived as the ratio of the respective attenuation function values ​​to the aggregate spectrum related to the long-delay scan of all scan batches of the plurality of scan batches (B1 to B3), For each NMR spectrum of the aforementioned multiple scan batches, a correction coefficient corresponding to the integral value related to each region of interest is multiplied (1700), In order to obtain a representation of the NMR signal intensity (202-sf) in the region of interest for the sample (201), the integral values ​​related to the corrected NMR spectrum in all scan batches of the plurality of scan batches (B1 to B3) are summed (1800), A method that includes [a certain feature].

2. The method according to claim 1, wherein the long delay interval (LD) for nearly complete relaxation of the sample is selected from the range of 30 seconds to 120 seconds to allow more than 99% relaxation of the sample, and one or more short delay intervals (SD) are selected from the range of 0 seconds to 2 seconds.

3. The method according to claim 1, comprising determining the long-term delay interval through experiment, wherein one or more short-term delay intervals are selected from a range of 0 to 2 seconds.

4. The method according to any one of claims 1 to 3, wherein the short delay interval has a single short delay value used for all short delay scans of each scan batch.

5. The method according to any one of claims 1 to 3, wherein at least two corresponding short delay intervals for each batch use different delay values.

6. The method according to any one of claims 1 to 3, wherein the set of short-term delayed scans in the scan batch comprises 3 to 9 short-term delayed scans.

7. After each scan batch, the estimated NMR signal intensity (202-si) in the region of interest for the sample is provided by summing the integral values ​​of all corrected individual NMR spectra in the already processed scan batch. The method according to any one of claims 1 to 3, further comprising:

8. The method according to any one of claims 1 to 3, wherein the excitation pulse applied to the sample to obtain individual NMR spectra has a flip angle less than or equal to 90° and greater than 0°.

9. The method according to claim 8, wherein the flip angle is within the range of 30° to 45°.

10. The method according to any one of claims 1 to 3, wherein the correction coefficient is calculated for and applied to all points within the region of interest of each individual NMR spectrum of each batch.

11. The method according to any one of claims 1 to 3, wherein the correction coefficient is calculated for and applied to all points of each individual NMR spectrum in each batch, and all corrected individual NMR spectra are summed into a single aggregated NMR spectrum.

12. Initiate the application of a trim pulse to the sample to remove residual transverse magnetization after the delay interval of the current individual NMR scan and before the subsequent excitation pulse is applied to the sample. The method according to any one of claims 1 to 3, further comprising:

13. To decide (1600) To obtain individual NMR spectra corresponding to each scan time point (S1a-S1f, S2a-S2f, S3a-S3f), a Fourier transform is applied to each individual NMR scan, and the corresponding portions of the individual NMR spectra related to the corresponding scan time points (t1-t6) within the multiple scan batches are aggregated into the aggregated NMR spectral portion (Saa-Saf) within the region of interest, or Individual NMR scans at corresponding scan points are aggregated into their respective aggregated NMR scans, and a Fourier transform is applied to the aggregated NMR scans to obtain the aggregated NMR spectral portion (Saa to Saf) for the corresponding scan points within the region of interest. The method according to any one of claims 1 to 3, comprising:

14. A computer program product comprising computer-readable instructions, wherein the computer-readable instructions are loaded into the memory of a computing device and, when processed by one or more processors of the computing device, cause the computing device to perform, start (1200) steps for acquiring high-speed quantitative NMR data relating to multiple NMR scans performed on a sample according to the method of any one of claims 1 to 3, further comprising starting (1200) steps by instructing an NMR spectrometer (200) to perform each NMR scan, and determining (1300) steps that occur when the computing device receives the NMR scans of the scan batches from the NMR spectrometer.

15. A computer system for high-speed quantitative NMR data acquisition relating to multiple NMR scans performed on a sample, wherein the computer system comprises a memory for storing computer-readable instructions for implementing a plurality of functional modules, and one or more processors of the computer system for executing the computer-readable instructions to instantiate the functional modules to perform steps according to any one of claims 1 to 3, wherein the start (1200) step further comprises starting a plurality of scan batches by instructing an NMR spectrometer (200) to perform each NMR scan, the NMR scans of the scan batches being received by the computer system from the NMR spectrometer prior to the determine (1300) step.

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