KR20130037848A - Method of measuring drug delivery velocity and mri thereof - Google Patents

Abstract

PURPOSE: A method for measuring a drug delivery velocity and a MRI thereof are provided to quantifying the concentration distribution and the movement of a drug according to time and to maintain a drug reference concentration in the specific region of a human body. CONSTITUTION: A drug is injected into a human body while an MR image is photographed at regular time intervals. The intensity of the MR image is changed into a T1 relaxation MR image. The T1 relaxation MR image is changed into an MR concentration image. The center of mass is obtained from the MR concentration image. The velocity of the center of mass is determined.

Description

Method of quantifying drug delivery rate, MRI device thereby

The present invention relates to a method for quantifying drug delivery rate and MRI apparatus, and more particularly, to a method for quantifying drug delivery rate in vivo by obtaining a center of mass of a drug over time from a photographed MR image. Relates to a device.

The primary goal of drug delivery is to maintain drug concentration in the target area while minimizing drug exposure to non-target tissue to avoid side effects. As one approach, a locally maintained drug release device has been used, which is a method of delivering a therapeutic drug through diffusion and convection.

In the development and evaluation of new drug development methods, it is important to measure the concentration profile of the drug imperviously. As a conventional technique, it has been used as a general method for measuring the concentration distribution of drugs subjected to radiograph (AUTORADIOGRAPHY) and immunofluorescence (immunofluorescence). However, these methods have a problem in that a drug is injected into a test animal and biodegradation is performed by the number of drug injection time points in order to determine the change in the living body over time, and the analysis is performed.

MRI is a noninvasive imaging technique that can be used to track the distribution of small molecules in vivo. Magnetic Resonance Imaging (MRI) is a method of obtaining an arbitrary tomographic image of a living body by a magnetic field generated by magnetic force. In magnetic resonance imaging, the nucleus is placed in a strong magnetic field to cause precession, and when a high frequency is applied to the magnetized atomic nucleus, it is in a high energy state. It is a technology to measure and reconstruct and image the magnetic properties of constituent materials. MRI can observe and measure changes over time in cerebral blood flow and heart movement.

Previous MRI studies have studied diffusion in polymer systems, measuring cell concentrations in bioreactors and determining the metabolites of small molecules in tissues. Several papers have suggested that drug diffusion measurements can be useful with MRI, but most of them deal only with convection, and no attempt has been made to quantify drug delivery rates.

The present invention uses non-invasive quantification of concentration distribution and rate of drug injected into a living body using MRI.

The present invention quantifies the distribution of drugs in the region of interest in vivo and the transport by diffusion-convection.

One aspect of the present invention is a drug delivery to obtain the center of mass of the injected drug over time from the MR image obtained by taking an MR image of the injected drug, and to determine the velocity from the amount of change over time of the center of mass It relates to how to quantify speed.

In another aspect, the present invention provides a method for preparing a human body, comprising: injecting a drug into a living body and taking MR images at predetermined time intervals; Converting the photographed MR image intensity (M) into a T1 relaxed MR image and converting the T1 relaxed MR image into an MR density image; And a method for quantifying the rate of drug delivery in vivo, comprising obtaining a center of mass from the MR concentration image and calculating a rate from the amount of change over time of the center of mass.

In another aspect, the present invention provides an RF coil driving unit for receiving an RF pulse and receiving an MR signal, which is an electromagnetic wave generated by an excited spin; A data collector which collects MR signals from the RF coil driver and sends them to a data processor; Collect the MR signal to generate an MR image, convert the intensity (M) of the MR image to a T1 relaxed MR image and convert it back to an MR concentration image, and mass of injected drug over time from the MR concentration image A data processor for determining a center of mass to determine a drug delivery rate in a living body; And a control unit controlling an RF pulse input of an RF coil driving unit according to the set condition, receiving and storing MR signals of the data collecting unit, controlling conversion and calculation of the data processing unit, and storing generated data. Relates to MRI devices.

In still another aspect, the present invention provides a system for quantifying a drug delivery rate in a living body having an MRI device and a flow rate measuring device, wherein the flow rate measuring device includes: a receiving unit for recalling MR image intensity (M) stored in the MRI device; And converting the MR image intensity received from the receiver into an MR concentration image, and converting the MR image intensity from the MR concentration image to determine a center of mass of the injected drug over time. Related.

The method according to the present invention can non-invasively quantify the concentration distribution and rate of the drug injected into the living body using MRI, and observe the distribution of the drug in the region of interest and the transport phenomenon by diffusion-convection over time. It can be measured.

Since the present invention can quantify drug distribution or drug migration over time, it is possible to maintain the drug reference concentration in the region of interest in the living body and, on the contrary, to suggest a method for minimizing the exposure in the non-target area. It became.

1 is a schematic diagram of an MRI apparatus according to an embodiment of the present invention.
2 shows an intensity image of 0.001M Gd-DTPA at 1 wt% TreviGel at several inversion times in accordance with one embodiment of the present invention; (A) 20, (B) 30, (C) 50, (D) 70, (E) 100, (F) 200, (G) 300, (H) 400, (I) 600, (J) 800, (K) 1000, (L) 1200, (M) 1500, (N) 2000, (O) 2500.
Figure 3 shows the intensity value of 0.001M Gd-DTPA at several inversion times to determine the T1 relaxation time of 0.001M Gd-DTPA in 1wt% TreviGel according to an embodiment of the present invention (A), Regression of the MR signal using Equation 2 is a graph (B).
Figure 4 is a graph showing the relationship between the concentration of Gd-DTPA and T1 relaxation time in 1wt% TreviGel.
5 shows MR image intensity after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after Gd-DTPA injection. , (G) is the image fully relaxed by 4000 repetition times.
6 shows T1 relaxation MR images after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after Gd-DTPA injection. to be.
7 shows MR concentration images after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after injecting Gd-DTPA. .
8 is a graph showing the distribution of Gd-DTPA in the gel at each time point from the injection zone to the left to right edge of the gel. Dots are experimental data, and lines represent simulation results with a convective flow rate of 2.6 × 10 ^-5 cm sec ^-1 and a diffusion coefficient of 3.2 × 10 ^-6 cm ² sec ^{- 1} .
9 is a graph comparing the calculated velocity based on the volumetric flow rate (dotted line) and the center of mass.
10 and 11 are simulation results for demonstrating the center of mass. 10 is a comparison between the flow rate and the volumetric flow rate by the center of mass, Figure 11 shows the concentration change over time.

The method for quantifying the rate of drug delivery in vivo according to the present invention obtains the center of mass of the injected drug over time from the MR image obtained by taking an MR image of the injected drug, and thus the concentration distribution and the rate are non-invasive. Can be quantified.

Hereinafter, the present invention will be described in detail.

In the present invention, the step of injecting the drug in vivo and taking MR (Magnetic Resonance, MR) images at predetermined time intervals, converting the taken MR image intensity (M) to a T1 relaxation MR image, the T1 relaxation MR image Converting to an MR concentration image, obtaining a center of mass from the MR concentration image and calculating a velocity of the center of mass.

The MRI apparatus used in the present invention may use a known one, but is not limited thereto. The general description of the MRI related to the present invention will first be briefly described.

First T _R is the repetition time. The repetition time (T _R ) refers to the time interval for generating the RF pulse used to obtain the resonance signal, and determines the amount of longitudinal relaxation (Spin-Lattice) (T ₁ relaxation, spin lattice relaxation).

T _E refers to the echo (delay) time (hereinafter referred to as echo time). The echo time T _E is the time from the first RF pulse that excites the spin to the acquisition of the echo signal. The echo time T _E determines the degree of dispersion of the spin of transverse magnetization (horizontal relaxation, T ₂ relaxation, spin-spin relaxation).

T ₁ refers to longitudinal relaxation time (or spin-lattice relaxation time) (hereinafter referred to as T ₁ relaxation time, or T ₁ ). As time passes immediately after the high frequency cut off, the average magnetization gradually increases as the nuclei remagnetize in the Z direction. The time until the average magnetization of 63% of the initial state forms in the Z direction is called the T ₁ relaxation time. define.

T ₂ refers to lateral relaxation time (or spin-spin relaxation time) (hereinafter, T ₂ relaxation time or T ₂ ). T ₂ relaxation time is defined as the time taken for the average magnetization of the XY plane to decrease by 37% at the beginning by dephasing.

Inversion Recovery is a method in which 180 ° pulses are applied before a 90 ° pulse is applied, whereby the average magnetization is reversed in the opposite direction by 180 °, from which the relaxation begins. After a period of time, that is, when the difference in the mean remagnetization between the brain parenchyma and the cerebrospinal fluid reaches a maximum, a 90 ° pulse is applied again.

Spin echo is an echo signal that appears when a 180 ° pulse is given after a 90 ° pulse. This spin-echo method changes T _R and T _E (Echo time: the time from 90 ° to 180 ° pulses until the echo signal is emitted) by varying T _{1 and} Weighted T ₂ Weighted Image, T ₁ and Mixed image Spin-Density of T ₂ can be obtained in various ways.

MR  Image MR  Steps to Convert Density Images

In the present invention, T ₁ weighted spin-echo MRI was used to determine the concentration distribution of the drug (including contrast agent Gd-DTPA, etc., referred to as DRUG).

Inversion recovery is used in the present invention to determine the T1 relaxation time range of the drug. The inversion time, the time between the 180 degree pulse and the initial excitation pulse, determines the T1 relaxation that occurs between the two pulses. The T1 relaxation time in the present invention is preferably a T1 relaxation time in inversion recovery.

The signal strength in MR inversion recovery of the spin echo image is expressed by the following equation.

[Equation 1]

M is the observed signal strength and M ₀ is the magnetization in the fully relaxed voxel. F is the cosine of the flip angle, T _I is the inversion time, T ₁ relaxation time, T ₂ relaxation time, T _E is the echo time, T _R is the repetition time, and T _E ≪T ₂ and T _R are 5 × If it is larger than T ₁ , the equation is simplified as in Equation 2 below.

&Quot; (2) "

In addition, the drug delivery data is generated by the MRI spin echo sequence, and the signal strength M obtained from the single spin echo pulse sequence can be obtained by the following equation.

&Quot; (3) "

In the T ₁ weighted sequence, Equation 3 is simplified to Equation 4 if T _E is very small compared to T ₂ , T _R.

&Quot; (4) "

The T ₁ value in the voxel from the known MR variables may be expressed by Equation 5 below.

[Equation 5]

The present invention includes converting the photographed MR image intensity M into a T ₁ relaxed MR image and converting the T ₁ relaxed MR image into an MR density image.

The MR image intensity M may be converted into a T ₁ relaxed MR image.

In the present invention, the MR image intensity M may be converted into a T ₁ relaxed MR image using Equation 5.

The MR concentration image can also be determined from the T ₁ relaxation MR image using the relationship between the T ₁ relaxation time and the concentration of the injected drug.

The relationship between the T ₁ relaxation time and the concentration of the injected drug can be determined by experiment before taking the MR images.

Determining the relationship between the T ₁ relaxation time and the concentration of the injected drug

Injecting the drug into the living body at different concentrations and taking an MR image; The method may include measuring a plurality of inversion times for each concentration and an average of intensity of each concentration.

Several different inversion times, T _I, are measured to determine the T ₁ relaxation values in each concentration solution, and the intensity (M) values of each concentration at these inversion times are calculated using Equation 2 to determine T ₁ for each drug concentration. (REGRESS), the relationship between the drug concentration and the T ₁ relaxation time is represented by the following equation (8).

[Equation 8]

 m is the molar relaxivity, C is the concentration of the injected drug, and b is the magnetization relaxation rate of the water without drug injection.

Determining the center of mass and its velocity

The present invention includes calculating a center of mass in the MR concentration image and calculating the velocity of the center of mass.

The method may assign an arbitrary origin in the MR concentration image and determine the center of mass using Equation 6 below.

&Quot; (6) "

M is the total mass of the system, m _i , m _j , m _k is the mass of the injected drug per unit volume, x _i , y _j , z _k is the x, y, z axis of each pixel from any origin.

The velocity of the center of mass can be determined from the amount of change over time of the center of mass and can be represented by Equation 7 below.

[Equation 7]

The method according to the present invention can non-invasive quantify the concentration distribution and rate of drug injected into the living body using the taken MR image. That is, the distribution and distribution of drugs in the region of interest can be observed and measured over time.

In another aspect the present invention relates to an MRI device capable of measuring the velocity of travel from a photographic MR image of an injected drug.

The MRI apparatus of the present invention includes an RF coil driver for inputting an RF pulse and receiving an MR signal which is an electromagnetic wave generated by an excited spin; A data collector which collects MR signals from the RF coil driver and sends them to a data processor; Collect the MR signal to generate an MR image, convert the intensity (M) of the MR image to a T1 relaxed MR image and convert it back to an MR concentration image, and mass of injected drug over time from the MR concentration image A data processor for determining a center of mass to determine a drug delivery rate in a living body; And a controller for controlling an RF pulse input of an RF coil driver according to the set condition, receiving and storing MR signals of the data collector, controlling conversion and calculation of the data processor, and storing generated data. .

1 is a schematic diagram of an MRI apparatus according to an embodiment of the present invention. Referring to FIG. 1, the MRI apparatus according to the present invention includes a magnet system 100, an RF coil driver 110, a data collector 120, a data processor 130, and a controller 140.

The magnet system 100 may use a known magnet system, but is not limited thereto. For example, the magnet system 100 includes a main magnetic field coil unit 102, a gradient coil unit 106, and an RF coil unit 108.

The RF coil driver 110 may use an already known one without limitation as long as it can function to input an RF pulse and receive an MR signal, which is an electromagnetic wave generated by an excited spin. For example, the RF coil driver 110 drives a transmission coil (transmission RF coil) of the RF coil unit 108 to form a high frequency magnetic field for exciting the spin in the living body 300. The receiving coil (receiving RF coil) detects a magnetic resonance (MR) signal, which is an electromagnetic wave generated by an excited spin.

The data collector 120 supplies (collects) the MR signal detected by the receiving RF coil based on the control of the controller 140 and transmits the signal to the data processor 130.

The data processor 130 includes a computer, which stores various programs. By these programs, the data processor 130, in cooperation with the controller 140, collects MR signals to generate MR images, converts the intensity M of the MR images into T1 relaxed MR images, and converts them into MR density images. I can convert it. The data processor 130 may determine the center of mass of the injected drug over time from the MR concentration image to determine the drug delivery rate in the living body. The data processor 170 may display the processing result on the display unit using MR images, numbers, and symbols.

The controller 140 may control the RF pulse input of the RF coil driver according to a set condition. In addition, the controller 140 receives and stores an MR signal of the data collector, controls conversion and operation of the data processor, and stores data generated by the data processor in a memory.

The data processor may convert the MR image intensity M into a T1 relaxed MR image by using Equation 5 below.

[Equation 5]

The data processor may determine the MR concentration image from the T1 relaxation MR image by using a relationship between previously stored T1 relaxation time and the concentration of the injected drug.

The data processor may allocate an arbitrary origin from the MR concentration image and determine the center of mass using Equation 6.

&Quot; (6) "

M is the total mass of the system, m _i, mj, mk is the mass of the injected drug per unit volume, x _i , y _j , z _k is the x, y, z axis of each pixel from any origin.

The data processor determines the speed of the center of mass using Equation 7.

[Equation 7]

The MRI apparatus collects MR signals to determine the center of mass, and a series of obtaining the flow rate thereof may refer to the method of quantifying the drug delivery rate described above.

In another aspect, the present invention relates to a system comprising an MRI device and a flow rate measuring device to quantify the rate of drug delivery in vivo. The flow rate measuring device may include: a receiver for reading an MR image intensity (M) stored in an MRI device; And converting the MR image intensity received from the receiver into an MR concentration image, and determining a center of mass of the injected drug over time from the MR concentration image.

The conversion unit may determine the MR concentration image by using the relationship between the pre-stored T1 relaxation time and the concentration of the injected drug.

The system for quantifying the drug delivery rate may be referred to the method of quantifying the drug delivery rate described above with respect to a series of contents of collecting MR signals to determine the center of mass and obtaining a flow rate thereof.

Hereinafter, the present invention will be described in more detail with reference to examples, but these examples should not be construed as limiting the protection scope of the present invention.

Gd - DTPA Concentration and T1 Determine relationship with relaxation time

The calibration curve showing the relationship between the MRI signal strength and the concentration of the drug (here, Gd-DTPA as contrast agent) is determined from the known Gd-DTPA concentration in 1% Trevi gel (TrevisGel ^™ 500 powder, Trevigen, Gaithersburg, MD, USA). do. A 1 wt% gel solution is prepared by adding 1 g of Trevi gel powder in 100 ml PBS (pH = 7.4). 0.5 M Gd-DTPA original solution (MagnevistBerlex, Richmend, CA, USA) was added to the gel solution to 1.0 × 10 ^-3 M, 5.0 × 10 ^-4 M, 2.5 × 10 ^-4 M, 1.0 × 10 ^-4 M , 5.0 × 10 ⁻⁵ M, 2.5 × 10 ⁻⁵ M, 1.0 × 10 ⁻⁵ M, 5.0 × 10 ⁻⁶ M, and 2.5 × 10 ⁻⁶ M concentrations. Each of these solutions was placed in 15 ml plastic vials and stored at room temperature in the dark. MRI was then taken with 4.7 TELSA MAGNET using BrukerAvance console (Bruker-biospin, Billerica, Mass., USA). The solutions were placed in a 15 cm diameter volume coil and 15 different inversion times TI were measured to determine the T1 relaxation values in each concentration solution; 20, 30, 50, 70, 100, 200, 300, 400, 600, 800, 1000, 1200, 1500, 2000, 2500 milliseconds. The MR scanning parameters are T _R / T _E = 6000 / 8.5 milliseconds at 10 cm × 10 cm field of view (FOV), 128 × 64 acquistion matrix size. Gray scale images of the standard solutions were processed using MAYLAB (version 6.5, Mathworks Inc., Natick, MA, USA), and the mean ROI intensity for each concentration was calculated using image J software (version 1.27z, National Institutes of Health, Bethesda, USA).

The intensity value of each concentration at several inversion times is converted to Equation 2 to measure T1 for each Gd-DTPA concentration, and the relationship between the concentration of Gd-DTPA and the TI relaxation time is expressed by Equation 8.

FIG. 2 shows intensity images of 0.001 M Gd-DTPA at 1 wt% TreviGel at several inversion times ((A) 20, (B) 30, (C) 50, (D) 70, (E) 100, (F) 200, (G) 300, (H) 400, (I) 600, (J) 800, (K) 1000, (L) 1200, (M) 1500, (N) 2000, (O) 2500) . That is, Figure 2 shows the change in signal strength of 0.001M Gd-DTPA at different inversion times.

FIG. 3A shows the intensity value of 0.001M Gd-DTPA at several inversion times to determine T1 relaxation time of 0.001M Gd-DTPA at 1wt% TreviGel (FIG. 3A), and FIG. 3B shows Equation 2 It is a graph which converted MR signal by using. Using ImageJ software, the mean standard deviation of the intensity values at each inversion time was determined and is shown in FIG. 3A. Since the intensity values of the MR images of the signal are positive, the change in sign is determined by the cusp point within relaxation time to make the actual magnetization in each intensity image. In FIG. 3A, intensity values prior to the point of cusps were multiplied by − and fitted using Equation 2 to calculate the T1 relaxation time for a 0.001 M Gd-DTPA concentration in 1 wt% gel solution to show FIG. 3B.

Figure 4 is a graph showing the relationship between the concentration of Gd-DTPA and T1 relaxation time in 1wt% TreviGel. The T1 relaxation times at different Gd-DTPA concentrations were determined in the same way as the treatment of 0.001M Gd-DTPA, and the T1 relaxation times in the range of 1.0 × 10 ^-6 M and 1.0 × 10 ^-3 M were 4.71 × concentration (M). Regression to + 4.26 × 10 ⁻⁴ (R ² = 0.986) is shown in FIG. 4.

Spread-Convection MR  image

Plastic devices were prepared to study convection-diffusion with Gd-DTPA in 1% Trevi gel. The device has a flat surface to tolerate a wide field of view through a planar window. The left-right part of the device has a recessed cavity, which contains water to ensure that water flows uniformly through the gel. The center of the chamber is filled with 1% gel. Gel and fluid chambers are separated into 0.45 μm Millipore filters (Duraporemembrane filters, Millipore, Mass., USA). Place the 1% gel solution into the diffusion-convection chamber and fill the water chamber with distilled water. Prior to MRI, the flow rate of water through the gel is calculated and set by measuring the time required for 0.1 ml. Pressure changes have little effect.

After the flow of water remains steady, 1 × 10 ⁻³ M Gd-DTPA is injected. The spin echo parameters used are T _R / T _E = 200 / 9.0 milliseconds, 10 cm × 10 cm field of view (FOV), 256 × 256 acquisition matrix.

MR images of the gel were measured every 20 minutes for 5 hours. All MR images were developed with MATLAB from 16 bit signed interger raw data. A 4000 msec repetition time was used to obtain a fully relaxed MR image. Center of mass measurements are determined at each time point to predict the rate of convection of water through the gel on the MR image. The signal strength of the Gd-DTPA distribution is processed with MATLAB. An arbitrary starting point is assigned and the center of mass point at each time is determined by Equation 6 above, and the Gd-DTPA velocity is determined by Equation 7 above.

5 shows MR image intensity after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after Gd-DTPA injection. , (G) is the image fully relaxed by 4000 repetition times.

In Fig. 5, MR image intensities (M) showing the distribution of Gd-DTPA injected into the gel at different time points were developed from raw data. FIG. 5G is a fully relaxed MR image and provides M ₀ values in Equations 4 and 5. FIG.

6 shows T ₁ relaxation MR after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after Gd-DTPA injection. Image. The intensity images (FIGS. 4A-F) can be converted into T ₁ images using Equation 5 (FIG. 6).

7 shows MR concentration images after (A) 10 minutes, (B) 1 hour, (C) 2 hours, (D) 3 hours, (E) 4 hours, and (F) 5 hours after injecting Gd-DTPA. . The Gd-DTPA concentration images of FIG. 7 can be obtained from T ₁ images using the relationship between T ₁ relaxation time and Gd-DTPA concentration.

8 shows the distribution of Gd-DTPA in the gel from the left end of the gel through the injection site to the right end of the gel. In Figure 8, it can be seen that the concentration distribution of Gd-DTPA is moved to the right by the convective flow of water. Theoretical concentration distribution of the injected Gd-DTPA was calculated by the following equation using FEMLAB software (version3.0, Comsol, Inc., Burlington, MA, USA).

u and v are convective flow rates in the x and y axes, and in the simulation, the u and v values were set to 2.6 × 10 ⁻⁵ cm sec ⁻¹ , respectively. D is the diffusion coefficient of Gd-DTPA and was determined to be 4.0 × 10 ⁻⁶ cm ² sec ⁻¹ by trial and error.

8 shows a reasonable match (R ² = 0.86) match between experimental concentration distribution and simulation data. 8 shows the concentration distribution of Gd-DTPA at 3 hours after injection in the simulation.

The volumetric flow rate was measured experimentally before MRI imaging to obtain a value of 2.62 ± 0.160 × 10 ^-5 cm sec ^-1 . In order to measure the convective flow of Gd-DTPA through the gel, the center of mass point was calculated as 2.3 ± 0.20 × 10 ⁻⁵ cm sec ⁻¹ for 100 minutes (FIG. 9). 9 is a graph comparing the calculated velocity based on the volumetric flow rate (dotted line) and the center of mass. In Fig. 9, the calculated flow rate of the center of mass decreases after 100 minutes.

This assumes that after 100 minutes, Gd-DTPA begins to deviate from the region of interest. To demonstrate this assumption, simulations were performed using FEMLAB. The diffusion coefficient and convection velocity were set to 3.8 × 10 ^-6 cm2sec ^-3 and 2.6 × 10 ^-6 cm sec ^-1 , respectively.

10 and 11 are simulation results for demonstrating the center of mass. 10 is a comparison between the flow rate and the volume flow rate by the calculated center of mass, Figure 11 shows the concentration change with time.

In this simulation, the flow rate was measured at the center of mass and compared with the set convective flow rate 2.6 × 10 ^-6 cm sec ^-1 (Figure 10). The top image of FIG. 10 shows the concentration distribution in the simulation. It can be found that the measured flow rate decreases with time as in the MRI test. Concentration is determined at the right end in the simulation (FIG. 11).

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

100: magnet system, 110: RF coil drive unit
120: data collector, 130: data processor
140:

Claims (16)

Injecting the drug in vivo and taking MR images at predetermined time intervals;
Converting the photographed MR image intensity (M) into a T ₁ relaxed MR image and converting the T ₁ relaxed MR image into an MR density image;
Obtaining a center of mass from the MR concentration image and determining the rate of the center of mass. The method of claim 1, wherein the method further comprises determining a relationship between T ₁ relaxation time and concentration of infusion drug prior to imaging the MR images. The method of claim 2, wherein the determining of the relationship between the T ₁ relaxation time and the concentration of the injected drug
Injecting the drug into the living body at different concentrations and taking an MR image;
Measuring a plurality of inversion times for each concentration and an average of the intensity of each concentration. 4. The method of claim 3, wherein the relationship between the T ₁ relaxation time and the concentration of infused drug is represented by Equation (8) below.
&Quot; (8) "

m is the molar relaxivity, C is the concentration of the injected drug, and b is the magnetization relaxation rate of the water without drug injection. The method of claim 1, wherein the method comprises converting the MR image intensity (M) into a T ₁ relaxed MR image using Equation 5 below.
&Quot; (5) "

T _R is the repetition time, M is the signal strength observed, and M ₀ is the magnetization state in the fully relaxed voxel. 6. The method of claim 5, wherein said MR concentration image is determined from said T ₁ relaxation MR image using the relationship between T ₁ relaxation time and the concentration of infusion drug. 7. The method of claim 6 wherein the T ₁ relaxation time is no way to quantify the drug delivery rate in a living body, characterized in that the T ₁ relaxation time of the inversion recovery (inversion recovery). The method of claim 1, wherein the method assigns an arbitrary origin in the MR concentration image and determines the center of mass using Equation 6 below.
&Quot; (6) "

M is the total mass of the system, m _i, m _j , m _k is the mass of Gd-DTPA per unit volume, x _i , y _j , z _k is the x, y, z axis of each pixel from any origin The method of claim 8, wherein the method determines the rate of center of mass using Equation 7 below. 10.
&Quot; (7) "

An RF coil driver for receiving an RF pulse and receiving an MR signal, which is an electromagnetic wave generated by an excited spin;
A data collector which collects an MR signal from the RF coil driver and sends the MR signal to a data processor;
Collect the MR signal to generate an MR image, convert the intensity (M) of the MR image to a T ₁ relaxed MR image and convert it back into an MR concentration image, and from the MR concentration image of the injected drug over time A data processor for determining a center of mass to determine a drug delivery rate in a living body; And
And a controller for controlling an RF pulse input of an RF coil driver according to the set condition, receiving and storing an MR signal of the data collector, controlling conversion and calculation of the data processor, and storing the generated data. MRI device characterized. The MRI apparatus of claim 10, wherein the data processor converts the MR image intensity M into a T ₁ relaxed MR image by using Equation 5 below.
&Quot; (5) "

T _R is the repetition time, M is the signal strength observed, and M ₀ is the magnetization state in the fully relaxed voxel. The MRI apparatus of claim 10, wherein the data processor determines the MR concentration image from the T ₁ relaxation MR image by using a relationship between a prestored T ₁ relaxation time and the concentration of the injected drug. The MRI apparatus of claim 10, wherein the data processor is configured to allocate an arbitrary origin from the MR concentration image and determine the center of mass using Equation 6 below.
&Quot; (6) "

M is the total mass of the system, m _i is the mass of Gd-DTPA per unit volume, x _i , y _j , z _k is the x, y, z axis of each pixel from any origin The MRI apparatus of claim 13, wherein the data processor determines the velocity of the center of mass using Equation 7 below.
&Quot; (7) "

A system for quantifying a drug delivery rate in a living body having an MRI device and a flow rate measuring device, the flow rate measuring device
Receiving unit for recalling the MR image intensity (M) stored in the MRI device;
And converting the MR image intensity received from the receiver into an MR concentration image, and determining a center of mass of the injected drug over time from the MR concentration image. Quantifying system. The system of claim 15, wherein the conversion unit determines the MR concentration image by using a relationship between previously stored T ₁ relaxation time and concentration of the injected drug.

Images