TW201104276A - Three-dimensional microscopic magnetic resonance angiography - Google Patents

Abstract

a method comprises performing a first T2-weighted imaging (T2wi) on a subject; injecting the subject with a contrast agent after performing the first T2wi; and waiting a predetermined period of time before performing a second T2wi on the subject. the first T2wi and second T2wi are then co-registered. the coregistered first T2wi and co-registered second T2wi are then trimmed. A Δ R2map is then determined based on each pixel of the trimmed first T2wi and corresponding pixels of the trimmed second Twi. A three-dimensional map is constructed based on the Δ R2map.

Description

201104276 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to magnetic resonance imaging techniques, and more particularly to three-dimensional magnetic resonance angiography. [Prior Art] The description of the prior art can outline the general outline of the present disclosure. The research results of the inventor's submission in this case are mentioned in the technical description of the previous case and cannot be interpreted as conventional technology, nor is it implied or recognized as a prior art.

The function and structure of microvessels is important for the survival of tissue cells because they can bring nutrients through the walls of blood vessels. Abnormal brain structure and function are implicated in brain lesions. For example, PERLMUTTER, L. S. and CHUI, H. C., 1990: "MICROANGIOPATHY, THE VASCULAR BASEMENT MEMBRANE AND

ALZHEIMER'S DISEASE: A REVIEW, BRAIN RES BULL. 24, 677-686", BUEE, L., HOF, PR and DELACOURTE, A in 1997: "BRAIN MICROVASCULAR CHANGES IN ALZHEIMER'S DISEASE AND OTHER DEMENTIAS, ANN NY ACAD SCI. 826, 7-24』, and SERNE, EH, DE JONGH, R. T., ERINGA, E. C., RG, IJ and STEHOUWER, CD in 2007: "MICROVASCULAR DYSFUNCTION: A POTENTIAL PATHOPHYSIOLOGICAL ROLE IN THE METABOLIC SYNDROME, HYPERTENSION. 50, 204-211』, 'Exposure related information. . 201104276

Contrast imaging for brain microvessels is of considerable importance in a wide range of clinical and neuroanatomical fields. The most widely used technique in magnetic resonance angiography (MRA) is time-of-flight MRA (TOF-MRA) and contrast-enhanced MRA (CE-MRA). The TOF-MRA is based on the movement of water protons in the flowing blood and is therefore sensitive to the internal flow of the arteries. CE-MRA uses contrast agents to detect low flow rates of veins. For example, REESE, T·, BOCHELEN, D., SAUTER, A·, BECKMANN, N. and RUDIN, Μ· 1999, "MAGNETIC ® RESONANCE ANGIOGRAPHY OF THE RAT CEREBROVASCULAR SYSTEM WITHOUT THE USE OF CONTRAST AGENTS, NMRBIOMED. 12, 189_ 196』, and MIRAUX, S., SERRES, S., THIAUDIERE, E., CANIONI, P., MERLE, M. and FRANCONI, JM published in 2004 "GADOLINIUM-ENHANCED SMALL-ANIMAL TOF" MAGNETIC RESONANCE ANGIOGRAPHY, MAGMA. 17, 348-352 can be found in the relevant technical literature. ® These methods have the effect of examining larger arteries or veins and are often used

To study the vascular structure of tumors, transient ischemia, and genetic mutations in vascular structures. For example, "VAN VLIET, M., VAN DIJKE, CF, WIELOPOLSKI, PA, TEN HAGEN, TL, VEENLAND, J. F" PREDA, A., LOEVE, AJ, EGGERMONT, AM and KRESTIN, GP in 2005 Published "MR ANGIOGRAPHY OF TUMOR-RELATED VASCULATURE: FROM THECLINIC. TO THE MICRO-ENVIRONMENT, RADIOGRAPHICS, 25 SUPPL. 1, 201104276 S85-97, DISCUSSION S97-88", BECKMANN, N. 2000 "HIGH RESOLUTION" MAGNETIC RESONANCE ANGIOGRAPHY NON-INVASIVELY REVEALS MOUSE STRAIN DIFFERENCES IN THE CEREBROVASCULAR ANATOMY IN VIVO, MAGN RESON MED. 44, 252-258』,

BESSELMANN, M., LIU, M., DIEDENHOFEN, M., FRANKE, C. and HOEHN, M. 2001, MR ANGIOGRAPHIC INVESTIGATION OF TRANSIENT FOCAL CEREBRAL ISCHEMIA IN RAT, NMR BIOMED. 14, 289-296, And BRUBAKER, LM, BULLITT, E., YIN, C., VAN DYKE, T. and LIN, W. published in 2005 "MAGNETIC RESONANCE ANGIOGRAPHY VISUALIZATION OF ABNORMAL TUMOR VASCULATURE IN GENETICALLY ENGINEERED MICE, CANCER RES. 6.5, 8AR2 Mapping module 218-8223" and so on. These documents have corresponding details. However, the TOF-MRA signal itself is only suitable for vessels with high flow rates, so the ability to scan small blood vessels at south resolution is limited and susceptible to pseudo-flow phenomena. For example, PIPE, J. G., published in 2001, "LIMITS OF TIME-OF-FLIGHT TIME-OF-FLIGHT MAGNETIC RESONANCE ANGIOGRAPHY, TOP MAGN RESON IMAGING 12, 163-174" contains relevant descriptions. GD-DTPA injected at the time of CE-MRA is relatively short in the intravascular (IV) half-life and will soon spread to the extravascular space, so it cannot be applied to high resolutions that take a long time to obtain facial surface. MRA. 201104276 SUMMARY OF THE INVENTION One embodiment of the present invention is a contrast method. First, a three-dimensional T2-weighted contrast procedure is performed on a subject. Thereafter, an iron oxide contrast agent is injected into the subject. Then, after waiting for a certain period of time, the contrast agent is evenly distributed in the blood vessel, and then the subject is subjected to a second three-dimensional T2-weighted contrast procedure. Finally, two sets of three-dimensional T2-weighted images before and after the contrast agent were injected, and the image difference caused by the change of the vascular signal before and after the injection of the contrast agent was calculated and converted into a three-dimensional AR2 map. The contrast method further includes: generating a three-dimensional image of the blood vessel of the subject according to the three-dimensional map in a case where the flow in a blood vessel is insensitive; wherein the blood vessel of the subject includes a vein, a sinus, a small artery , venules and microvessels. The contrast method further comprises: establishing a living microvascular structure and a microvascular fluid volume data for the blood vessel of the subject according to the three-dimensional map. Further, the method determines functional and structural changes in the microvascular network within the tumor based on three-dimensional images and hemodynamic parameters. In another embodiment, a system includes a three-dimensional imaging module and a blood-powered data module. The three-dimensional contrast module generates a three-dimensional image of the blood vessel of the subject according to the three-dimensional map in a case where it is not sensitive to the flow in a blood vessel. This three-dimensional image depicts the microvascular structure of the blood vessels in the body. Blood vessels include veins, venous sinuses, small arteries, venules and microvessels. The hemodynamic lean module generates a hemodynamic tract according to the two-dimensional image, and includes microvascular fluid volume data of the blood vessel. The three-dimensional image module generates the three-dimensional image according to a steady-state three-dimensional ΔR2 type microscopic magnetic angiography (3D △ 201104276 R2-MMRA). The hemodynamic data module generates the hemodynamic data according to the 3D/\R2-MMRA. Further, the system comprises a T2 weighted imaging module, a temporary storage module, a cutting module, a ΔR] mapping module, and a three-dimensional mapping module. The T2-weighted contrast imaging module performs a first T2-weighted contrast procedure on a subject, and performs a second T2-weighted contrast procedure after injecting a ferric oxide contrast agent into the subject. The temporary storage module temporarily stores the results of the first and second T2 weighted contrast programs to generate a first temporary storage data and a second temporary storage data. The cutting module cuts the first temporary storage data and the second temporary storage data to generate a first cutting data and a second cutting data. The AR2 mapping module generates a ΔΙ map according to the pixels in the first cropping data and the corresponding pixels in the second cropping data. The three-dimensional mapping module creates a three-dimensional map according to the Δ R2 map. The hemodynamic data module generates hemodynamic data based on the three-dimensional image. In a further embodiment, the above system and method are implemented by executing a computer program with one or more processors. The computer program can be located on a computer readable medium such as, but not limited to, a memory, a non-volatile data storage, and/or other suitable physical storage medium. The field to which the embodiments of the present invention are applied can be clearly disclosed in the following embodiments. It is to be understood that the following examples are for illustrative purposes only and are not intended to limit the scope of the invention. [Embodiment] The following description is for illustrative purposes only and is not intended to limit the use or application of the invention. The term "at least one of A, B, and C" as used herein shall read 201104276 as "A or B or C" and "or" as a logical "non-mutually exclusive". The steps described in these methods may be performed in a different order without affecting the basic principles of the invention. The term "module" as used herein may be an application specific integrated circuit (ASIC), an electronic circuit, a processor (division, exclusive or group) for executing one or more software or firmware programs, and/or Or memory (division, exclusive 'or group), combinational logic, and/or other body or part of other suitable components with this function. The present invention proposes a novel contrast technique called non-flow microscopic magnetic angiography (3DAR2-MMRA) of the three-dimensional steady state ΔR2 type for depicting small blood vessels such as veins, arterioles and venules. After the injection of the iron oxide contrast agent, the spin echo ΛΙ calculated by the fast spin echo angiography technique was used to map the blood volume of the brain, and the contrast was related to the microvascular structure. The 3DAR2-MMRA of the present invention employs a reconstruction technique that simultaneously provides high-resolution three-dimensional information on brain microvascular structures and hemodynamic responses to evaluate temporal microvascular pathological changes in brain diseases. A specific three-pulse meshing module was used in a mouse to evaluate the ability of the present invention to measure changes in microvascular structure. The microvascular pattern can be characterized by the difference in the ratio of the blood vessel and surrounding tissue to the magnetization of the iron oxide contrast agent. For example, DENNIE, J., MANDEVILLE, JB, BOXERMAN, JL, PACKARD, SD, ROSEN, BR and WEISSKOFF, R. Μ. published in 1998 "NMR IMAGING OF CHANGES IN VASCULAR MORPHOLOGY DUE TO TUMOR ANGIOGENESIS, 201104276 MAGNRESONMED. 40 , 793-799", which has related references. The calculation of the magnetization effect is complicated by the relationship between tissue vascular structure, magnetic field strength, and the type of pulse sequence and its parameters. For example, WEISSKOFF, RM, ZUO, C. S., BOXERMAN, JL AND ROSEN, BR published in 1994 "MICROSCOPIC SUSCEPTIBILITY VARIATION AND TRANSVERSE RELAXATION: THEORY AND EXPERIMENT, MAGN RESON MED. 31, 601_610" and BOXERMAN, JL , HAMBERG, LM, ROSEN, BR and WEISSKOFF, RM published in 1995 "MR CONTRAST DUE TO INTRAVASCULAR MAGNETIC SUSCEPTIBILITY PERTURBATIONS, MAGN RESONMED. 34, 555-566", have detailed reference materials. The spin echo is related to the microvascular structure, while the gradient echo Δ R2 is sensitive to blood vessels of any size, both of which are independent of blood flow. The 3DZ\R:2-MMRA technique proposed by the present invention can develop small blood vessels without being affected by a pseudo flow phenomenon. The present invention combines high-resolution three-dimensional images with VOLUME RENDERING (VR) or MAXIMUM INTENSITY PROJECTION (MIP) techniques to directly visualize brain microvascular structures. Based on the measurement of the spine echo transverse mitigation rate obtained by rapid spin echography, a map can be used to map the brain blood volume (CEREBRAL BLOOD VOLUME; CBV). It has a relatively linear relationship with the blood volume ratio, and the opposite. Further, the spin-reverberant procedure is less sensitive to geometric distortion caused by the uneven magnetic field on the air-tissue interface, and the development result can be of two qualities. This 3DAR2_MMRA has nothing to do with flow effects and can be used to visualize the microvascular structure of the nervous system and provide information on the physiological status of microvascular CBV. In order to evaluate the effectiveness of 3D/\R^-MMRA, a mouse body can be controlled and a special three-pulse meshing module can be studied. The change in the transverse muscle mitigation rate in the spin echo (Δ&) and the region CBV can be determined by the following formula. The value of ARs is obtained by:

I ( C ^ $

W (1) AR: 2 5 = — In P〇st j where TE is the echo time' and SPRE and SP0ST are the signal intensities before and after the iron oxide contrast agent is applied. Δ R2 varies linearly with the C B V coefficient, namely:

AR2*K [CA] CBV where K is a constant that varies with tissue type, pulse order, magnetic field strength, and iron oxide contrast agent, while [CA] is the concentration of iron oxide contrast agent in blood.

The AR2 signal includes an inner tube (IV) and an outer tube (EV) component. For example, DUONG, Τ·Q., YACOUB, Ε., ADRIANY, G., HU, X., UGURBIL, K. and KIM, SG published in 2003 "MICRO VASCULAR BOLD CONTRIBUTION AT 4 AND 7 T IN THE HUMAN BRAIN: GRADIENT-ECHO AND

SPIN-ECHO FMRI WITH SUPPRESSION OF BLOOD EFFECTS, MAGN RESON MED. 49, 1019-1027』 has detailed reference information. The 丨V signal is present in all sizes of blood vessels 11 201104276 because the iron oxide contrast agent causes a change in the T2 value in the blood. The EV effect of the spin echo is related to small blood vessels, because the 180° RF-pulse refocuses the static phase shift caused by the magnetic field imbalance around the large blood vessels. For example, OGAWA, S., MENON, RS, TANK, DW, KIM, SG, MERKLE, H., ELLERMANN, J. Μ. and UGURBIL, K. published in 1993 "FUNCTIONAL BRAIN MAPPING BY BLOOD OXYGENATION LEVEL" -DEPENDENT CONTRAST MAGNETIC RESONANCE IMAGING, A COMPARISON OF SIGNAL CHARACTERISTICS WITH A · BIOPHYSICAL MODEL, BIOPHYSJ. 64, 803-812" has detailed literature references. Mouse model of ischemia and reperfusion of brain lesions in LIN, TN, SUN, SW, CHEUNG, WM, LI, F. and CHANG, C. DYNAMIC CHANGES IN CEREBRAL BLOOD FLOW AND ANGIOGENESIS AFTER TRANSIENT FOCAL CEREBRAL ISCHEMIA IN RATS, EVALUATION WITH SERIAL MAGNETIC RESONANCE IMAGING, STROKE. · 33,2985_2991" has a detailed literature reference. In short, the right middle cerebral artery (MCA) of male longevity rats was reversely bundled under a stereomicroscope. The bilateral carotid arteries were then compressed with a non-traumatic aneurysm clamp. Arterial compression was relieved after 60 minutes of ischemia. The rectal temperature of this anesthetized rat

Maintain a temperature of 37 ± 0.5oC with a constant temperature blanket (HARVARD, HOLLISTON, MA).

The 12, 201104276 angiography is then performed with a scanner such as a 4.7-T MR scanner (German BIOSPEC 47/40) equipped with an active shadow gradient (2〇g/CM IN 80 MS). The experimental mouse body weighs 300 to 500. Male LONG-EVAN rats between grams. Initially, each rat was anesthetized with 5% isoflurane (ISOFLURANE) at an oxygen supply rate of 1 liter per minute (il/MIN). When fully entered the anesthesia, the mouse is then only fixed in a prone position on a special headstock within the magnetic ring. During the course of the experiment, isoflurane was continuously output at a concentration of 1 to 1.2% at an oxygen supply rate of 1 liter per minute, minimizing changes in brain hemodynamics. For example, LEI, H., GRINBERG, 0., NWAIGWE, CI, HOU, HG, WILLIAMS, H., SWARTZ, Η. M. and DUNN, JF published in 2001 "THE EFFECTS OF KETAMINEXYLAZINE ANESTHESIA ON CEREBRAL BLOOD FLOW AND OXYGENATION OBSERVED USING NUCLEAR MAGNETIC RESONANCE PERFUSION IMAGING AND ELECTRON PARAMAGNETIC RESONANCE OXIMETRY, BRAIN RES. 913, 174-179", has relevant references in the literature. The image is captured by a 72mm birdcage transmitter coil and a four-part isolation surface coil for signal detection. In order to detect ΔR], a T2-weighted contrast procedure was performed each time before the injection of the iron oxide contrast agent. The iron oxide contrast agent may comprise superparamagnetic ferrite particles, such as SCHERING AG from Berlin, Germany, and RESOVIST at a dose of 30 MG/KG. The step of obtaining an image after injection of the developer may be postponed for one to two minutes to ensure that the distribution of the iron oxide contrast agent in the metal tube network is stabilized. The T2-weighted contrast procedure can be performed with a repetition time of 13 201104276 (REPETITION TIME; TR) of 1500MS, an effective echo time (TEEFF) of 82MS, an echo train length (ETL) of 32, and an average of four' field of view width (FOV). For 2.8X2.8X1.4CM, get a 3D FSE program with an array of 256X256X96 (zero interpolated to 512X512X192). The inner plane resolution and the cut thickness are 54.68 and 72.91 MM, respectively. TOF-MRA can be performed with FLASH (fast low angle photography), where

TR is 30MS ’ TE is 10MS ’ flip angle 30 degrees, and with 3DA

The same FOV and array size for the RrMMRA method. The two-dimensional whole brain injection of the pre-developer image and the post-injection image can be matched together using a CO-REGISTER algorithm. For example, this algorithm can use the normalized common information function of AMIRA software (TGS, SANDIEGO, CA) with strict conversion. The mouse brain images before and/or after the injection of the developer can be manually cut to exclude portions other than the brain. A map estimated according to the formula (1) is calculated by a program language written in a specific software such as MATLAB (MATHWORKS, NATICK, ΜΑ). The 3DAR2_MMRA technology can also include the construction of high-resolution 3D maps using VR or MIP tools (AMIRA, TGS). Referring to Annex 1, there are shown the different positions in the entire three-dimensional data set estimated from the T2 weighted image before the injection of the developer (FIG. 1A) and after the injection of the developer (the attachment ι (Β)) according to the formula (1). Obtained a 虺-like image with an internal plane resolution of 54.68 , and a full-plane resolution μ % mm (Annex 1 (c)). The coronal view was obtained from a high-resolution Τ2-weighted image of the rat brain in a full three-dimensional data set (54χ54χ72 mm), with a coffee (10) lamp concentration of 30 MG/KG. 201104276 The high-brightness of the blood vessels in the AR2 map may be caused by the magnetization effect associated with iron oxide contrast agents. 3DAR2_MMrA is implemented by reconstructing the coronal view of Annexes 2 (A) and 2 (B) and the high-resolution 3D ΛΚ 2 image shown in the side view of Annex 2 (D) using VR techniques. The venous vascular network, like the venous sinus of the main vein and its branches, is visible on the surface of the brain. These vessels were further identified as the upper olfactory sinus, upper cerebral vein, superior sagittal sinus, and intracranial tail nasal vein; upper cerebral vein, secondary cerebral vein, brain according to the following coronal and side view brain angiogram sets. The internal venous vein, as well as the transverse venous sinus between the brain and the cerebellum. For example, 'CEREBRAL VASCULAR SYSTEM, IN: PAXIONS, G (ED), THE RAT NERVOUS SYSTEM, ACADEMIC PRESS, SAN DIEGO, PP. 3-35, and DORR, A, published by CREMIN, 0. U. ., SLED, JG and KABANI, N. published in 2007 "THREE-DIMENSIONAL CEREBRAL VASCULATURE OF THE CBA MOUSE BRAIN: A MAGNETIC RESONANCE IMAGING AND MICRO COMPUTED TOMOGRAPHY STUDY, NEUROIMAGE 35, 1409-1423" has a description. These surface blood vessels of the brain are quite consistent with Annexes 2(C) and 2(E) for the angiographic back view of the same test mouse. The aorta, such as MCA, may not be so clearly presented in 3DAR2-MMRA because the arterial signal is phase-shifted with a high flow rate (DEPHASE) by a pre-T2 weighted contrast procedure with a long TE injection, resulting in pre-injection and injection. There were no or only minor differences in the arterial image after the developer. 15 201104276 The structure of small blood vessels, including the brain / will be ΛΙ-ΜΜΚΑ with three views (with two small veins, can be rich and complicated by small blood vessels in the brain, swearing =, will wait, its description Cortical microvascular structure. Annex 3 (Α)_^ = surface endothelium and deep bottom view (S-1). Annex 3 (B) shows - fine direction = (four) face 'from top to bottom (Α-Ρ) Annex 3(C) shows the η νΛ - ^ shape of the 邾 邾 囱 囱 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , (Annex 4 (B)) and the conventional TOF-MRA method (Annex 4 (A)) 鼗 鼗 々 ' 、 一 一 一 一 比较 比较 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 The body group of the self-phased ^ has the same axial view 'slice position, and image resolution. The figure shows that many of the social organizations in the view of RrMMRA show more clearly, but only the main in t〇f_mra Arterial. The three-pulse pulsation model can be used to verify the ability of 3DAR2_mmra to assess microvascular structures. Annex 5 (A) is the test mouse closed by MCA up to 6〇 After recanalization after the clock, the axial T2-weighted images of different positions obtained from the three-dimensional data set after seven days have a plane resolution of 54 68 mm and a slice thickness of 500 mm. The right MCA cortex of the ischemic site is reperfused. The post-T2-weighted image pattern is consistent with our previous study and is also full of recombination evidence for microvessels. Annex 5(B) is the VR of 3DZ\R2_MMRA corresponding to the same slice position as Annex 5(A). The ischemic right MCA brain layer clearly shows that the microvascular-like brightening signal extends from the thin meninges to the cortex, a phenomenon consistent with previous studies that increased CBV and cerebral blood flow (CBF). Annex 5(A) 16 201104276 is An axial view of a high-resolution D2-weighted image obtained from different blocks of the full three-dimensional data set, showing the infarct region of the right brain with a thickness of 〇·5ΜΜ in a three-pulse meshing ischemic model of the mouse Annex 5(B) is a 3DZ\R2_MMRA view of the same position as Annex 5(A), showing changes in vascular morphology due to ischemic-guided angiography within the infarcted area. Many studies have used MR perfusion. Hemodynamic parameters such as CBV, CBF and permeability, such as dynamic contrast-enhanced contrast imaging, or MRA techniques such as TOF and CE-MRA to visualize the vascular structure' thereby diagnosing macrovascular and microvascular structures and functions in cerebrovascular diseases For example, KASTRUP, A., ENGELHORN, T., BEAULIEU, C., DE CRESPIGNY, A. and MOSELEY, Μ. E. published in 1999 by DYNAMICS OF CEREBRAL INJURY, PERFUSION, AND BLOOD-BRAIN BARRIER CHANGES AFTER TEMPORARY AND PERMANENT MIDDLE CEREBRAL ARTERY OCCLUSION IN THE RAT, J. NEUROLSCI. 166, 91 -99 has related references. The present invention discloses a novel CBV microscopic MRA (3DA R2-MMRA) which simultaneously visualizes the morphology of the microvascular structure and illustrates the physiological state of the microvascular CBV. This structure is effective in enhancing the development and treatment of cerebrovascular diseases such as stroke and brain tumors. The 3DZ\R2-MMRA technique can be used to simultaneously visualize large blood vessels (eg, veins, venous sinuses, but not arteries) and small blood vessels (eg, arterioles and small veins) (Annex, 2 and 3). This may be because the AR2 signal of the spin echo is mainly composed of the IV and EV components. The specific sensitivity effects of IE and EV for various pipe sizes in the program of Gradient Echo and Spin Echo Recall 17 201104276 have been previously described. In short, the IV effect induced by the spin echo can occur in blood vessels of various sizes. In the aorta, the effect is mild due to the high flow rate. The EV effect of Δ R_2 is usually associated with microvessels with a diameter of less than 1 〇 mm. In the method of the present invention, the internal plane resolution which can be achieved in a total time of 76 minutes by the three-dimensional FSE sequence with 32 ETLs is 54 mm. These resolutions are still greater than the diameter of the microvessels, but can be enhanced by increasing image sensitivity, along with other fast acquisition techniques such as parallel imaging or more sophisticated coil designs to increase array size and reduce FOV. For an example of parallel angiography, reference is made to MAX) 〇RE, B. ANDPELC, N. J., "SMASH AND SENSE: EXPERIMENTAL AND NUMERICAL COMPARISONS, MAGNRESON MED. 45, 1103-1111", 2001, the disclosure of which is incorporated herein by reference. For examples of precision coil design, please refer to "LOGOTHETIS, N., MERKLE, H., AUGATH, M.., TRINANH, T. and UGURBIL, K." ULTRA HIGH-RESOLUTION FMRI IN MONKEYS WITH IMPLANTED RF COILS, NEURON. 35, 227-242" and LEE, H. L" LIN, IT, CHEN, J. H., HORNG, Η. E. and YANG, HC published in 2005 "HIGH-TC SUPERCONDUCTING RECEIVING COILS" FOR NUCLEAR Magnetic Fluorescence Imaging, IEEE TRANSACTIONS ON APPLIED SUPERCONDUCTIVITY. 15, 1326-1329. The traditional TOF-MRA contrast agent is very sensitive to the high-speed flow spin 201104276 in the arteries. This means that the TOF-MRA may not be recognizable. Rapidly moving cerebrovascular obstruction or endothelial arterioles and venules, but this is done by 3D △ R2-MMRA (Attachment 4). In addition, when there is a large range of flow velocity in the contrast body, such as turbulence When flowing, TOF-MRA signal cancellation may occur. 3DAR2-MMRA is based on the calculation of magnetic susceptibility effect, and is independent of blood flow, so it is not sensitive to pseudo-flow phenomenon. Refer to KOUWENHOVEN, M. published in 1997. 『CONTRAS T-ENHANCED MR ANGIOGRAPHY, ® METHODS, LIMITATIONS AND POSSIBILITIES, ACTA RADIOL. SUPPL. 412, 57-67, which contains detailed instructions. TOF-MRA can effectively measure the closure and reperfusion of MCA small blood vessels. Refer to BECKMANN, N., STIRNIMANN, R. AND BOCHELEN, D. "HIGH-RESOLUTION MAGNETIC RESONANCE ANGIOGRAPHY OF THE MOUSE BRAIN: APPLICATION TO MURINE FOCAL CEREBRAL ISCHEMIA MODELS. J ® MAGN RESON. 140, 442 -450』. TOF-MRA may not be suitable for local ischemic angiography after reperfusion because of the inability to visualize small blood vessels. In the posterior ischemic angiography, the angiography of the dorsal view is often used. To assess morphological changes in the brain surface. However, angiography is not easy to visualize the endothelial microvascular model inside the lesion. In addition, brain tissue liquefaction in the necrotic area makes the ischemic area less susceptible to immunohistochemistry, especially if reperfusion has been more than three days old.

In the chronic phase of ischemia, changes in CBV and CBF measured by perfusion MR angiography inside the lesion have long been documented. Although both CBV 19 201104276 and CBF can describe microvascular perfusion information, there is no way to identify individual blood donors. The 3DAR2_MMRA disclosed herein can provide high contrast-degree display-small blood vessels' and provide associated CBV mapping, which can reconstruct the microvascular model' over time to simultaneously observe pattern changes and hemodynamic changes. 3DAR2_MMRA can show that the degree of south in the ipsilateral cortex after transient ischemia (Annex 5) is increased compared to the CBV previously described. 3DZ\R2_MMRA produces high-resolution images of microvessels in the cortex that extends from the cerebellum to local ischemia, and it is highly probable that newly grown microvessels will come from the cerebellum. This is the first time that MRA technology can be developed in a variety of ways in an in vivo microangiography procedure in an ischemic model. This method can track angiography at different stages of the disease, even in the stage of severe tissue necrosis in the dysfunctional area. Another microvascular imaging method based on gradient echo images is proposed here, using a T2-weighted image subtraction (instead of calculating Δ仏) before and after injection of the developer. For example, refer to BOLAN, PJ, YACOUB, E., GARWOOD, M., UGURBIL, K. and HAREL, N. published in 2006 "IN VIVO MICRO-MRI OF INTRACORTICAL NEUROVASCULATURE, NEUROIMAGE. 32, 62-69 』, which has a detailed description. However, the contrast is caused by the uncompensated magnetic susceptibility causing phase shifting of the internal and external signals of the blood vessel, which is the main cause of the false flow phenomenon and the inner diameter of the vessel being overestimated. In addition, when the magnetic field is severely uneven, such as in the tonsils close to the air-tissue interface, the vascular structure in the brain cannot be depicted. 3DAR2-MMRA technique. Calculate the spin-return type AR2 because of the use of a spin-echo echo image of the re-201104276 focus pulse with high tolerance to non-resonant effects such as the main magnetic field inhomogeneity and the susceptibility of the magnetic susceptibility. So it is not affected by these problems, especially for organizations that are not continuous. - • The relevant CBV system is proportional to the value. For example, WU, EX, WONG, Κ·K., ANDRASSY, M. and TANG, H. published in 2003 "HIGHRESOLUTION IN VIVO CBV MAPPING WITH MRI IN WILD-TYPE MICE, MAGN RESON MED. 49, 765 -770" and DUNN, JF, ROCHE, MA, SPRINGETT, R" ABAJIAN, M., MERLIS, J., DAGHLIAN, CP, LU, SY and MAKKI, M. "MONITORING ANGIOGENESIS IN BRAIN USING" published in 2004 STEADY-STATE QUANTIFICATION OF DELTAR2 WITH MION INFUSION, MAGN RESON MED. 51, 55-61』 has a detailed reference. However, the relevant CBV can only be accurately measured when the contrast agent is in a stable state in the IV space. Annex 6 is the signal intensity in the cerebral vasculature of the superior sagittal sinus before and after RESOVIST injection. Other types of developer may be suitable for these measurement procedures. Figure 1 shows the superior sagittal venous sinus line. The T2-weighted video signal timing changes. The T2-weighted image is obtained by a FSE sequence of TR=4000MS and TE=70MS. The image intensity drops rapidly after injection of RESOVIST (from ι〇〇〇/0 to 20%) Change to phase Stable 'slightly increased linearly from 35% to 55% in the first three hours.) The acquisition time of 3DZ^R2-MMRA is about 76 minutes. At that time, RESOVIST has been stably distributed and circulated in the gold tube. It has a high mitigation rate and a long life. A special contrast agent, when applied to 3DA RrMMRA at low concentrations, helps to increase the visibility of microvascular structures in the blood vessels. 21 201104276 In accordance with the principles of the present invention, a steady-state eight-two-based non-closed flow microscopy MRA The method is feasible in combination with a three-dimensional image reconstruction technique for visualizing the small vessel structure in vivo. The method can be verified by a rat brain experiment. The invention can simultaneously provide high-resolution three-dimensional information of the brain section. In vivo microvascular structures, as well as CBV mapping, are used to measure pathological changes in microvessels over time. This technique can be used as a normal tool to examine microvascular structures in small animal models as well as outpatients with healthy or cerebrovascular disease.

In addition, microvascular changes in tumors should provide important new clues for tumor growth and counter-treatment of treatment. 3DZ\R2-M1V [RA can be applied to angiography for visualizing live brain tumor A tubes. For example, when Rz-MMRA is applied to an ethylene subnitroso (ENU)-induced murine brain tumor model, microvascular patterns and functional changes at different stages of the tumor can be simultaneously measured. For the ENU-induced mouse brain tumor model, refer to the document "j NEUROSURGERY, 108: 782-790" published by JANGET AL in 2008. 5 Tumor angiography has been recognized as a key element in the physiological pathology of tumor growth and metastasis. Abnormalities in microvascular patterns can be used to distinguish whether a brain tumor is benign or malignant. Refer to the work published by BULLITT ET AL in 2005, "ACAD RADIOL. 12(10): 1232-1240", which is described in detail. However, blood flow and blood volume information is important for understanding tumor pathology to select and evaluate therapy. Therefore, 'simultaneous monitoring of the function and structural changes of tumor microvascular structures' can provide effective clues for judging tumor activity and therapeutic effects. Many studies have reportedly used MRA techniques to visualize vascular structures, measure the vascular structure and function of brain tumors in 2011 04276, or measure hemodynamic parameters of brain blood volume (CBV), blood flow, and permeability by MR perfusion. . For example, 'BULLITT ET AL.' published in 2007, "NEURmMAGE. 37: S116-i! 9" has a detailed reference. However, none of these existing methods are capable of simultaneously visualizing vascular structures and measuring hemodynamic parameters. In addition, existing MRA methods such as ΤF and Developer Enhanced (CE) MRa can only measure larger arteries and veins, but cannot treat the microvascular structure of the tumor.

As described in detail below, the 3D/\R2-MMRA of the present invention can be used to simultaneously measure the function and structure of normal and ischemic mouse microvessels. For example

The "PROCEEDING OF ISMRM 812" published by LIN ET AL in 2008 has a detailed reference. In addition, experiments with ENU-induced brain tumor models have shown that high-resolution 3DAR2_mMRA can be used to simultaneously estimate the correlation of tumor growth on vascular patterns and CBV. In this experiment, murine tumor molding systems were produced by chemical induction. Pregnancy SPRAGUE-DAWLEY (SD) mice were initially placed in a jail, and I.P with 50 MG/KG ENU (SIGMA, ST LOUIS, MO, USA) was injected using a 26 gauge needle during pregnancy from 18 to 19 days. After weaning, two homosexual young children were placed in each cage and the pathological state was observed weekly. A young child born from a pregnant SD rat injected with ENU was photographed at 72, 145, and 199 days after birth. Initially, the rats entered anesthesia with 5% isoflurane under a flow of 1 L/MIN. After complete anesthesia, the rat is placed in a prone position with the head fixed to a special frame within the magnetic ring. The isofluoride was then maintained at a concentration of 1% to 1.2% under a 1 L/MIN gas flow in subsequent experiments. The image is then acquired with a 23 201104276 72MM birdcage transmitter coil and a separate quadrant surface coil detection signal. - - For the measurement of △ &, a T2 weighted contrast procedure was performed before and after the injection of 30MG/KG iron oxide (RESOVIST, SCHERING AG, BERLIN, GERMANY). Image capture is performed after one to two minutes delay after applying the iron oxide contrast agent to ensure that the distribution of the iron oxide contrast agent in the vascular network reaches a steady state. The T2-weighted contrast program uses a TR of 1500 MS, a TEEFF of 82 MS' ETL of 32, an average of 4, and a FOV of 2.8 CM X 2.8 CM X 1.4 CM' to obtain a three-dimensional RARE program with an array of 256x256x96 (zero interpolation to 512x512x192). The inner plane resolution and slice thickness are 54 68 and 72.91 MM each. The map is then calculated using the software written by MATLAB (MATHWORKS, NATICK, MA, USA). Based on the 3D/R2 map, a volumetric rendering tool (Ding GS, AMIRA, SAN DIEGO, CA) can be used to create a three-dimensional view of the micro-enterprise structure. Annex 7 is an image acquired using the 4.7·Τ BI〇SPEC 47/4 〇 扫描 scanner with active occlusion gradient. Annex 7(A)_7(C) is a T2-weighted image of a region of a mouse brain tumor that changes over time, and 3da

Rs-MMRA normal view and enlarged view. Figures 2 and 3 are quantitative analyses of tumor volume and the value of the entire tumor. More specifically, Annex 7(A)_7(C) is the T2 weighted image of 3DAR2_mmra, the AR2, the normal view, and the timing change of the magnified view. The high-brightness area in the T2-weighted image represents the tumor area. _ position, health 24 201104276 Long and heterogeneity can be observed through the T2-weighted contrast program. In the final stage of the T2-weighted image (Ρ199), the high-brightness area in the tumor can be swollen. Figure 2 shows that the tumor volume gradually increases after Ρ145. The blood vessels showed brightness in the eight R2 map because of signal differences around the blood vessels before and after the injection of the iron oxide contrast agent. This also reflects the physiological state of microvascular CBV. Figure 3 is a quantitative analysis showing the increase in the internal tumors observed after P145. Clearly, signal enhancement occurs primarily in the core area of the tumor in P199 (Annex 7(B)). In order to observe the changes of microvascular structure inside the tumor, the volume of the whole tumor was drawn, and the outline of the tumor area was observed from the whole three-dimensional T2-weighted image, and then mixed with 3DA R2-MMRA. From P72 to P199, a gradual increase in vessel size and density was observed, showing a high degree of vascular gene activity. Thus, in accordance with the principles of the present invention, tumor angiography provides a new perspective on tumor growth and metastasis at different stages, allowing the associated 3D Δ ® R2-MMRA to simultaneously monitor changes in microvascular structure and function. Figure 4 is a flow diagram depicting a three-dimensional imaging method 100 for living microvascular structures and hemodynamic data for the production of blood vessels using 3D Δ R2-MMRA. Control begins in step 102. In step 104, a first T2-weighted contrast procedure is performed on a subject to generate a first T2-weighted image prior to injecting the iron oxide contrast agent to the subject. In step 106, after the subject is administered the iron oxide contrast agent, it waits for a period of time and performs a second T2-weighted contrast procedure to produce a second T2-weighted image. In step 108, the first and second T2-weighted images are temporarily stored to produce 25 201104276 raw, second bedding and a second temporary data. In step no _, cut the poor material and - the second cutting data. The birth of a younger brother - the number of cuts = 12 in the 'by the 苐 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁 裁In step (1) # create a three-dimensional map with the R2 map. In step 116, the cow 1117 or VR generates a three-dimensional image based on the three-dimensional map. In the body micro blood (four) to construct live Leli bait. In step 12, drawing a gentleman's == learning parameter can be used to determine the functionality in the microvascular structure: knot = (eg in a tumor). Step 122 ends the control flow. Guan Shi _ The simplicity of the money, using the two-dimensional shirt image of the s,,,. The system 铋 9nn a person 々 s s seat blood, needle system 200 contains an MRA device 2 〇 2, = processing module deleted, and _ display 4 yuan fine. The he = : through = 2 ° 8. A user (not shown) manipulates the injection of the nest into the subject 208. Responsible for the household: 〗 〖 & iron comparison A device 202 obtained the capital: two:, module 204 at the n W shellfish, and display the thousands of other parameters of the mechanics parameters. The user interprets the -Bex on the early morning 206 to diagnose the subject's MRA data processing module/T2WI module 212, the gentry 3 枓 wear module 210, and the R2 mapping module 218. ...three-dimensional mapping module 220

A temporary storage module · 214, - wearing module 216, dimensional contrast 26 26 201104276 222' a hemodynamic data module 224, a control module 226, and a margin map control group fine. The control module 226 can include a user interface (not shown) for the user to enter commands to control the device. The data capture module 210 acquires the received data from the MRA device 2〇2. The T2WI module 212, the temporary storage module 214, the cutting module 216, the ΔR2 mapping module 218' three-dimensional mapping lion thin 'three-shadow module from the hemodynamic data module 224 and the drawing control module 228 for R2 MMRA. Control module 226 controls the MRA device to move and r2-mmra. Display unit 206 displays the output produced by 3DAR2_mmra. The output contains a two-dimensional image of the microvascular structure produced simultaneously by 3DAR2_MMRA, and hemodynamic data of the blood vessels of the subject 2〇8. The T2WI module 212 performs a first shot on the data received by the device 202 and generates a first T2-weighted image data when the object 2〇8 is injected with the iron oxide contrast agent. The subject 208 is subjected to a second Τ2-weighted contrast procedure after a specific period of time after the injection of the iron oxide contrast agent τ reading module 212 and produces: two-person Τ 2 weighted image data. The temporary storage module 214 temporarily stores the one-to-one image data, and generates a -first temporary storage data and a "first person" storage: bedding. The cutting module 216 cuts the first temporary data and the nth to generate a first cutting data and a second cutting resource ^R2 mapping module 218 according to the first cutting data order The first cut # corresponding 昼 in the material, produces - △ ~ reflected -, " = 艮 产生 according to the map to generate a three-dimensional map. The shirt pull group based on the three-dimensional map to generate the measured body image The blood official consists of veins, venous sinuses, arterioles, venules, 27 201104276 and microvessels at least +. The three-dimensional R2-mmra ^ ^ . ^f, ^ insensitive 'so can describe the in vivo microvascular junction of blood vessels : Body (eg blood) 224 9Π"δ Microvascular fluid volume data. Descriptive dry - 2〇6 shows microvessels in 3D images": Control module 228 uses maximum brightness projection and volume::=;,: Control the 3D image Microvascular structure and blood

The control module 226 controls the resolution of the three-dimensional image by controlling the face of the MRA device 202. For example, the control mode $ resolves the contrast sensitivity of 2G2 to control the stereoscopic image t resolution. The control change group 226 controls the MRA to be set to determine the resolution of the three-dimensional image. The difficult-to-face group 226(4) the refocusing pulse of the device 202 controls the resolution of the three-dimensional image. In addition, the control module 226 can also control the three-dimensional image by controlling the data intercepting module 21 to obtain the size of the array. The resolution of the image. 3DAR2_MMRA has many advantages. For example, the three-dimensional contrast module 222 can draw at least one of the endothelial layer and the subcortical microvascular structure of the blood vessel in the three-dimensional image. The three-dimensional contrast module 222 can depict the subject 2 〇8

Endothelial small arteries and endothelial venules with slow moving spins are at least /. The two-dimensional contrast module 222 can produce a three-dimensional image based on a magnetic susceptibility effect that is impeding turbulence and turbulence in the blood vessel. The three-dimensional contrast module 222 generates a three-dimensional image on the premise that the air/tissue interface of the subject 2〇8 is insensitive to the geometric deformation caused by the magnetic field unevenness. The three-dimensional contrast module 222 generates a three-dimensional image on the premise that it is insensitive to changes in the magnetic susceptibility caused by the unsteady tissue of the subject 2〇8. The three-dimensional image generated by the three-dimensional imaging module 222 can visualize the living body microscopic angiography procedure of the subject 2 (10) _ ankle ischemia. The three-dimensional image produced by the three-dimensional contrast module 222 can perform angiography in the damaged area under the condition of tissue necrosis in the dysfunctional area in the incineration body 2〇8. In addition, the three-dimensional contrast module 222 can depict a three-dimensional image of a microscopic 1"tube structure in the subject 208, and the hemodynamic data module 224 can simultaneously measure tumor-related hemodynamic parameters using 3DAR2_Mmra. In addition, the functional and structural changes of the microvascular structure can also be determined from the three-dimensional image and the hemodynamic parameter field generated by 3DAR2_MMRA. Although the present invention has been described above by way of preferred embodiments, it is to be understood that the scope of the invention is not necessarily limited. In contrast, any modifications that are apparent to those of ordinary skill in the art to which the invention pertains may be made within the scope of the invention. Therefore, the scope of patent claims must be interpreted in a broad sense. 29 201104276 [Simple description of the schema] Annex 1 (A) is a high-contrast and high-resolution T2 weighted rat with a "situ view"; Annex 1 (B) is a high-resolution τ2 after injection of a rat brain Adding a contrasting coronal view; Annex 1 (C) is an example of a map of the coronal view of the rat brain; ^ Annex 2 (A) is a three-dimensional steady-state convolutional mapping example of a rat coronal view And microscopic magnetic angiography of non-compressed flow; Annex 2 (B) is the cerebellar Ι 域 field highlighted by the small angular offset of Annex 2 (A); Annex 2 (C) is attached to Annex 2 (A) Corresponding blood vessel photograph; Annex 2 (D) is a side view using 3DAR2-MMRA; Annex 2 (E) is a blood vessel photograph corresponding to Annex 2 (D); Annex 3 (A) to 3 (C) ) is a small blood vessel, small artery and venule in the brain; surface structure diagram; Annex 4 (A) is the microvascular structure diagram produced by the embodiment of the present invention; Annex 4 (B) is the microvascular generated by TOF-MRA Structure Figure; Annex 5 (A) is a three-dimensional data set generated after seven days of absorption of a 60-minute MCA in a mouse, with a resolution of 56.68 mm and a slice thickness of 5 mm. An axial T2-weighted image produced at the same position; Annex 5 (B) is an example of a 3D Δ h-MMRA volume plot at the same slice position in Annex 5 (A); • Attachment, 6 series is the superior sagittal sinus Cerebrovascular view; 201104276 Annex 7(A)-7(C) is a 3DAR2-MMRA-之2 weighted image of rat brain tumor induced by ethyl nitrite (ENU), ar2, normal view and enlarged view Time change graph; Fig. 1 is a diagram showing the intensity of cerebrovascular signal of the superior sagittal sinus after injection of RESOVIST; FIG. 2 is a quantitative analysis of the volume of the mouse brain tumor; [R2 numerical analysis of brain tumors; Figure 4 is a flow chart of a method for generating three-dimensional images of living microvascular structures using three-dimensional r^-MMRA and vascular kinetic data; and Figure 5 is the use of 3DAR2_M]V [ RA generates a two-dimensional image of the living micro-gold tube structure and a system function block diagram of the vascular dynamics data. [Main component symbol description] 202 MRA device 206 display unit 210 data interception module 214 temporary storage module 218 mapping module 222 three-dimensional Contrast module 226 control 204 MRA system module 200 data processing module 208 Xin test body 212T2WI cutter module 216 module 220 module 224 hemodynamic 3D mapping data mapping module 228 control module 31

Claims (1)

201104276 VII, the scope of application for patents: L A method of angiography, including: -, _ * a., ~ do a first T2 weighted contrast program on the dual test body; after the first T2 weighted contrast program, will The iron oxide contrast agent is injected into the subject; after a certain time, a second τ2 weighted contrast procedure is performed on the subject; the results of the first and second T2-weighted contrast procedures are temporarily stored. Generating a first temporary storage data and a second temporary storage data; and cutting the first temporary storage data and the second temporary storage data to generate a first cutting data and a second cutting data; First, the pixels in the cropped data and the corresponding pixels in the second cropped data generate an ar2 map; and a three-dimensional map is created according to the map. 2. The method of contrast according to claim 1, further comprising: generating a three-dimensional image of the blood vessel of the subject according to the three-dimensional map in a case where the flow in the blood vessel is not sensitive; The blood vessels of the subject include veins, venous sinuses, arterioles, venules and microvessels. 3. The method of contrast according to claim 1, further comprising: “establishing a living micro-blood structure and microvascular volume data for the blood vessel of the subject according to the three-dimensional map; wherein the subject is Vascular containment, 32 201104276 Intravenous, venous sinus 'small arteries, venules and microvessels among them. -4. An imaging method, including: producing a multi-dimensional image of a golden tube, containing one, without being sensitive to flow in the blood vessel, including The microvessels of the subject; and the living microvascular structure f and the microvascular fluid volume data are established for the gold tube according to the three-dimensional image. 5. The angiography method according to claim 4, wherein the angiography comprises: generating the three-dimensional image according to a steady-state three-dimensional microscopic magnetic angiography (3DAR2_mMRA), comprising: performing one on the subject a first T2-weighted contrast procedure; injecting a ferric oxide contrast agent into the test sputum after performing the first-time T2-weighted contrast procedure; waiting for a period of time before performing a second T2-weighted contrast procedure on the subject - temporarily storing the results of the first and second T2-weighted contrast procedures to generate a first temporary storage data and a second temporary storage data; cutting the first temporary storage data and the second temporary storage data to generate a first cropping data and a second cropping data; generating an ar2 map according to the pixels in the first cropping data and the corresponding pixels in the second cropping data; • according to the AR2 map Establishing a three-dimensional map; and generating the three-dimensional image according to the three-dimensional map. 33 201104276. The angiography method of claim 4, further comprising the three-dimensional image comprising at least one of a vein, a vein f, a small artery, a small vein, and a micro-command. Including: 7. The method of contrast according to item 4 of the patent application, further comprising a microvascular knot to draw at least one of the endothelial layer and the endothelium layer in the three-dimensional image. ^ .1 8. The contrast method of claim 4, further comprising drawing the micro-tube structure in the three-dimensional image using at least one of maximum intensity projection or volume rendering and generating the micro A tube liquid容(四) Contains: 9. The angiography method according to item 4 of the scope of the patent application, further identifying from the three-dimensional image that the small layer of the endothelial layer and the endothelium having a slow moving spin in the subject are small At least one of the veins. The method of imaging according to claim 4, wherein the method comprises: generating the three-dimensional image according to a magnetic susceptibility that is insensitive to a pseudo-flow phenomenon, wherein the pseudo-flow phenomenon comprises a convection in the blood vessel And at least one of the pulsations. 11. The method of angiography according to item 4 of the patent application, further comprising: generating the three-dimensional image under the premise that the air-texture boundary (4) magnetic material is insensitive to a geometric distortion in the four objects. image. 12. The contrast method of claim 4, further comprising: generating the three-dimensional image on the premise that the variation of the magnetic field unevenness caused by the discontinuity of the tissue property of the test object is insensitive. 13. The method of contrast according to claim 4, further comprising: performing a live angiography procedure at the ischemic portion of the subject according to the three-dimensional image. 14. The method of contrast according to claim 4, further comprising: tracking the angiography of the blood vessel based on the three-dimensional image when there is a tissue necrosis in a dysfunctional region of the subject. 15. A method for measuring, comprising: drawing a three-dimensional image of a microvascular structure of a tumor in a subject using a steady-state three-dimensional AR2 microscopic magnetic angiography (3DZ\R2-mMRA); and using the 3DZ\R2-mMRA measures hemodynamic parameters, including at least one of blood volume, blood flow, and vascular permeability of the tumor. 16. The method of measuring according to claim 15, further comprising: determining a functional and structural change of the microvascular structure based on the three-dimensional image and the hemodynamic parameter. 17. The method according to claim 15, wherein the 3DAR2-mMRA comprises: 35 201104276 performing a first T2-weighted contrast procedure on the subject; ..... performing the first After the second Τ2 weighted angiography procedure, the iron oxide contrast agent is injected into the subject; waiting for a specific time before performing a second Τ2-weighted contrast procedure on the subject; temporarily storing the first and second a result of the second Τ2 weighted angiography procedure to generate a first temporary storage data and a second temporary storage data; cutting the first temporary storage data and the second temporary storage data to generate a first cropping data and a a second cropping data; generating an AR2 map according to the pixels in the first cropping data and the corresponding pixels in the second cropping data; establishing a three-dimensional map according to the map; and according to the three-dimensional map The map produces the 3D image. 18. The method of measuring according to claim 15, further comprising: generating the three-dimensional image according to the three-dimensional map and measuring the blood dynamics parameter. 19. An imaging system comprising: a 加权2-weighted contrast module for performing a first Τ2-weighted contrast procedure on a subject and performing a second after injecting a ferric oxide contrast agent into the subject a secondary 加权2 weighted angiography program; a temporary storage module for temporarily storing the results of the first and second Τ2 weighted angiography procedures to generate a first temporary storage data and a second temporary storage data; 36 201104276 a cutting a module for cutting the first temporary storage data and the second temporary storage material to generate a -first cutting data and a second cutting data; a mapping module for using the first cutting Cutting the pixels in the data and the corresponding pixels in the second cutting data to generate a map; and a three-dimensional mapping module for establishing a three-dimensional map according to the map. 20. The imaging system according to claim 19, further comprising: a one-dimensional four-shirt module for generating the subject according to the three-dimensional map in a case where the flow in a blood vessel is not sensitive A three-dimensional image of the business, in which the blood vessels of the body contain veins, venous sinuses, small arteries, venules and microvessels. 21. The angiography system of claim 19, further comprising a hemodynamic data module for generating a hemodynamic lean material according to the three-dimensional map, comprising microvascular fluid volume data of the blood vessel of the subject; The blood vessel includes one of a vein, a sinus, a small artery, a small vein, and a microvessel. 22. A measurement system comprising: a three-dimensional image module for generating a three-dimensional image of a blood vessel under the premise of being insensitive to flow in a blood vessel, comprising a microvessel of a subject; wherein the image of the three birds is drawn The in vivo microvascular structure of the blood vessel, the blood vessel comprising one of a vein, a venous sinus, a small artery, a small vein and a microvessel. 37 r 201104276 and a blood dynamic data module for generating blood according to the three-dimensional image Power data, including microvascular fluid volume data for the blood vessel. 23. The measurement system of claim 22, wherein the three-dimensional image module generates the three-dimensional image according to a steady-state three-dimensional ΔR 2 type microscopic magnetic angiography (3DZ\R2-mMRA), And the hemodynamic data module generates the hemodynamic tribute according to the 3D/\R2-mMRA. 24. The measurement system of claim 22, further comprising: a T2-weighted contrast module for performing a first T2-weighted contrast procedure on a subject and testing the subject a second T.2 weighted contrast procedure after injecting the ferric oxide contrast agent; a temporary storage module for temporarily storing the results of the first and second T2-weighted contrast procedures to generate a first temporary storage Data and a second temporary storage data; a cutting module for cutting the first temporary storage data and the second temporary storage data to generate a first cutting data and a second cutting data; An AR2 mapping module is configured to generate an AR2 map according to the pixels in the first cutting data and the corresponding pixels in the second cutting data; and a three-dimensional mapping module, according to the AR2 The map creates a three-dimensional map. 25. The measurement system of claim 23, wherein: 38 201104276 the 3D image module generates the 3D image according to the 3D map; and... + the hemodynamic data module generates according to the 3D map The hemodynamic data. 26. The measurement system of claim 22, further comprising: a rendering control module for rendering the microvascular structure in the three-dimensional image using at least one of maximum intensity projection or volume rendering And generating the microvascular fluid volume data. 27. The measurement system of claim 22, further comprising: a data acquisition module for acquiring data on the object from a magnetic vibration device using an acquisition array; and a control module Controlling the resolution of the three-dimensional image by controlling the size of the acquisition module, the image sensitivity of the magnetic vibration device, the field of view of the magnetic vibration device, and the refocusing pulse of the magnetic vibration device. The measuring system of claim 22, wherein the three-dimensional image module draws at least one of a vascular endothelium layer and a subcortical microvascular structure in the three-dimensional image. 29. The measurement system of claim 22, wherein the three-dimensional image module generates an endothelium 39 201104276 small artery and an endothelial venule of the subject having a slow moving spin. An analytical diagram of one. - The only measurement system described in item 22 of the scope of the application, wherein the -· == module is based on a magnetic susceptibility that is insensitive to false flow phenomena, such as the pseudo flow phenomenon At least one of turbulence and pulsation in the gray tube is included. The measurement system of claim 22, wherein the three-dimensional image is generated on the premise that the geometrical distortion of the object is not sensitive to geometric distortion caused by the magnetic field of the air interface. 3 Dan 2. If you apply for the quantity system described in Item 22, the premise that the 'shirt image module is not sensitive to the variation of the magnetic field unevenness caused by the discontinuity of the measured structure of the measured body The three-dimensional image is generated below. The system of claim 22, wherein the three-dimensional image module performs a living microscopic angiography procedure at an ischemic location of the subject according to the three-dimensional image. 34. The measuring system according to claim 22, wherein the three-dimensional image module generates the three-dimensional image to display the dysfunction when a dysfunction zone of the subject is organized to cause the dysfunction 35. The measurement system comprises: a three-dimensional image module 'using steady-state three-dimensional microscopic magnetic angiography or touch-eye ^) to draw a microvascular of a tumor in a subject, a search image of the structure And a hemodynamic data module using the 3DAR2_mMRA measurement blood 201104276 kinetic parameter, including at least one of blood volume, blood flow, and vascular permeability of the tumor. 36. The measurement system of claim 35, further comprising: a T2-weighted contrast module for performing a first T2-weighted contrast procedure on a subject and in the subject Performing a second T2-weighted contrast procedure after injecting the ferric oxide contrast agent; • a temporary storage module for temporarily storing the first and second T2-weighted contrast procedures to generate a first temporary data and a first a temporary storage data; a cutting module for cutting the first temporary storage data and the second temporary storage data to generate a first cutting data and a second cutting data; an AR2 mapping module And generating an AR2 map according to the pixels in the first cropping data and the corresponding pixels in the second cropping data; and the Luyi 3D mapping module, configured to establish a map according to the AR2 map 3D map. 37. The measurement system of claim 36, wherein the three-dimensional image module generates the three-dimensional image according to the three-dimensional map, and the hemodynamic module generates the hemodynamic data according to the three-dimensional map. r Γ 41