JP2010172410A - Image reconstruction device and method using magnetic response signal of magnetic nanoparticle - Google Patents

Image reconstruction device and method using magnetic response signal of magnetic nanoparticle Download PDF

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JP2010172410A
JP2010172410A JP2009016562A JP2009016562A JP2010172410A JP 2010172410 A JP2010172410 A JP 2010172410A JP 2009016562 A JP2009016562 A JP 2009016562A JP 2009016562 A JP2009016562 A JP 2009016562A JP 2010172410 A JP2010172410 A JP 2010172410A
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Yasutoshi Ishihara
康利 石原
Yusuke Kusayama
裕助 草山
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an image reconstruction device or method for imaging magnetic nanoparticles distributed in space, wherein the resolution power of reconstructed images is improved and the influences of false images is reduced and removed. <P>SOLUTION: The image reconstruction device 10 has an image reconstruction means 4 to reconstruct magnetic response signals as an image information. The image reconstruction means 4 obtains an ideal waveform to be compared with the magnetic response waveform detected in an unsaturated region by a detection means. The image reconstruction means calculates difference information between the ideal waveform and the magnetic response waveform as the factor for correction, and uses the correction factor for weighting the signal strength of the magnetic response waveform. Prior to weighting the signal strength, the image reconstruction means 4 may normalize the magnetic response waveform by its maximum oscillation value, after subtracting the offset component w<SB>mean</SB>of the magnetic response signal waveform from the magnetic response signal waveform. The ideal waveform may be a magnetic response signal waveform that can be detected in the case where the magnetic nanoparticles are arranged in the same space as an unsaturated region. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

本発明は、磁性ナノ粒子の空間的分布を画像化する方法及び装置に関し、特に、磁性ナノ粒子から生じる磁化応答信号の特性を利用して再構成画像の分解能を改善した画像再構成装置に関する。   The present invention relates to a method and apparatus for imaging the spatial distribution of magnetic nanoparticles, and more particularly to an image reconstruction apparatus that improves the resolution of a reconstructed image by using the characteristics of a magnetization response signal generated from the magnetic nanoparticles.

近年、がん等の疾病における早期診断技術として、磁性粒子映像法（ｍａｇｎｅｔｉｃ ｐａｒｔｉｃｌｅ ｉｍａｇｉｎｇ，ＭＰＩ）が提案されている（例えば、特許文献１〜５、非特許文献１を参照）。このＭＰＩは、生体に投与された磁性流体へ体外から交番磁場を照射した場合に、磁性ナノ粒子の非線形な磁化特性と交番磁場との相互作用によって生じる微弱な磁化信号を利用したイメージング技術である。   In recent years, magnetic particle imaging (MPI) has been proposed as an early diagnosis technique for diseases such as cancer (see, for example, Patent Documents 1 to 5 and Non-Patent Document 1). This MPI is an imaging technique that uses a weak magnetization signal generated by the interaction between the non-linear magnetization characteristics of magnetic nanoparticles and the alternating magnetic field when a magnetic fluid administered to a living body is irradiated with an alternating magnetic field from outside the body. .

ＭＰＩで用いられる磁場制御法は、磁気共鳴映像法（ｍａｇｎｅｔｉｃ ｒｅｓｏｎａｎｃｅ ｉｍａｇｉｎｇ，ＭＲＩ)と類似しており、使用される磁性流体もＭＲＩにおける造影剤と同等のものであるが、磁性ナノ粒子の分布を直接画像化する点がＭＲＩとは異なっている。ＭＰＩは、高分解能と高感度を兼ね備え、それらを高速に実現する画像化法に発展する可能性があり、加えて装置構成はＭＲＩと比較してシンプルなため安価になることが見込まれる。   The magnetic field control method used in MPI is similar to magnetic resonance imaging (MRI), and the magnetic fluid used is equivalent to the contrast agent in MRI. Direct imaging is different from MRI. MPI has both high resolution and high sensitivity, and may be developed into an imaging method that realizes them at high speed. In addition, the apparatus configuration is simpler than MRI, and is expected to be inexpensive.

ＭＰＩでは、上記の交番磁場に重畳して体外から局所磁場を印加し、これを空間的に走査することで特定領域の磁性ナノ粒子から磁化信号を検出しているが、目的領域外に存在する磁性ナノ粒子から生じる磁化信号の干渉により、空間分解能が低下してしまったり、偽像が表れてしまったりするといった問題があった。   In MPI, a magnetic field is detected from magnetic nanoparticles in a specific region by applying a local magnetic field from outside the body superimposed on the alternating magnetic field and spatially scanning this, but it exists outside the target region. There is a problem that the spatial resolution is lowered or a false image appears due to interference of magnetization signals generated from magnetic nanoparticles.

特に、磁性ナノ粒子の粒径が５０ｎｍ程度又はこれ以下の場合には、磁性ナノ粒子の非線型性が小さくなることに起因して位置の識別に有用な磁化信号が微弱となり、また、画像化に必要な局所磁場分布の不完全性と相俟って、画像分解能の低下が顕著に現れることが懸念されている。このため、磁化特性が飽和状態へ達するために大きな外部磁場が必要となり、ＭＰＩ画像再構成装置が大型化し、高価なものとなっていた。   In particular, when the magnetic nanoparticles have a particle size of about 50 nm or less, the magnetization signal useful for position identification becomes weak due to the non-linearity of the magnetic nanoparticles being reduced, and imaging Concomitant with the imperfection of the local magnetic field distribution required for image processing, there is a concern that the image resolution will be significantly reduced. For this reason, a large external magnetic field is required for the magnetization characteristics to reach a saturation state, and the MPI image reconstruction apparatus becomes large and expensive.

これまでに、ＭＰＩにおける再構成画像の高分解能化を目指し、磁性ナノ粒子から検出される磁化信号の応答波形（以下、磁化応答波形と呼ぶ）に含まれる高調波成分の特性を利用した方法が提案されているがその効果は限定的であった（非特許文献２）。   Until now, with the aim of increasing the resolution of reconstructed images in MPI, there has been a method that uses the characteristics of harmonic components contained in the response waveform of a magnetization signal detected from magnetic nanoparticles (hereinafter referred to as a magnetization response waveform). Although proposed, the effect was limited (non-patent document 2).

特開２００３−１９９７６７号JP 2003-199767 A 米国特許出願公開第２００６／０００９８２６号明細書US Patent Application Publication No. 2006/0009826 国際公開第２００４／０９１３９２号International Publication No. 2004/091392 国際公開第２００７／０００３５０号International Publication No. 2007/000350 国際公開第２００７／０００３５１号International Publication No. 2007/000351

バーンハード・グレイヒ（BernhardGleich）、ヤーゲン・ウェイゼネッカー（JurgenWeizenecker） 著、「磁性粒子の非線形応答を利用した断層撮影技術」、（米国）、ネイチャー（Nature）、２００５年６月３０日、第４３５巻、p.1214−1217Bernhard Gleich, Jurgen Weizenecker, “Tomography Technology Using Nonlinear Responses of Magnetic Particles” (USA) Nature, June 30, 2005, No. 435 Volume, p.1214-1217 草山裕助、石原康利 著、「磁性ナノ粒子を利用した分子イメージング装置に関する基礎検討」、信学技報、２００７年９月２０日、第ＭＢＥ２００７−４８巻、p.15−18Yusuke Kusayama, Yasutoshi Ishihara, “Basic Study on Molecular Imaging Device Using Magnetic Nanoparticles”, IEICE Technical Report, September 20, 2007, MBE 2007-48, p.15-18

ＭＰＩは、磁性ナノ粒子が持つ非線形な磁化特性を利用した画像化法である。一般的な強磁性体（Ｆｅ、Ｃｏ等）では磁化曲線がヒステリシスループを示すのに対して、磁性ナノ粒子では磁化の残留現象が生じず、磁場強度に対して一意に磁化の値が定まる。ここで、「磁性ナノ粒子」とは、強磁性を有する微粒子（粒径≦１００ｎｍ程度）の総称であり、代表的な物質としてＦｅＰｔ（鉄白金）、Ｆｅ３Ｏ４（マグネタイト）等が挙げられ、生体へ投与する場合には一般的に生体適合物質（糖、たんぱく質等）で被覆される（必ずしもこれらに限定されない）。 MPI is an imaging method that uses the non-linear magnetization characteristics of magnetic nanoparticles. In general ferromagnets (Fe, Co, etc.), the magnetization curve shows a hysteresis loop, whereas in magnetic nanoparticles, the residual magnetization phenomenon does not occur, and the magnetization value is uniquely determined with respect to the magnetic field strength. Here, “magnetic nanoparticles” is a general term for fine particles having ferromagnetism (particle size ≦ about 100 nm), and representative materials include FePt (iron platinum), Fe 3 O 4 (magnetite), and the like. When administered to a living body, it is generally coated with a biocompatible substance (such as sugar or protein) (not necessarily limited thereto).

この性質を利用することで実現されるＭＰＩの原理を図１に示す。磁性ナノ粒子が磁場のない領域に存在する場合（後述の飽和状態に対して「非飽和状態」の場合とも呼ぶ）に周波数ｆ０の交番磁場Ｈを照射すると、非線形磁化特性に基づく磁化応答波形が生じ、これをフーリエ変換することで高調波成分を検出できる（図１の各線図での（ａ）を参照）。 The principle of MPI realized by utilizing this property is shown in FIG. When magnetic nanoparticles are present in a region without a magnetic field (also referred to as “unsaturated state” with respect to a saturated state described later), when an alternating magnetic field H of frequency f 0 is irradiated, a magnetization response waveform based on nonlinear magnetization characteristics The harmonic component can be detected by Fourier transforming this (see (a) in each diagram of FIG. 1).

一方、磁性ナノ粒子が存在する領域の磁場が十分に大きく、磁化が「飽和状態」（すなわち、図１の磁化応答を示す図において、外部から印加される磁場強度Ｈが大きい場合に、磁性ナノ粒子から生じる磁化の強さＭが磁場強度Ｈに比例せず一定となる現象）となり磁化応答波形の変化が僅少である場合には、交番磁場により発生する高調波成分は抑えられる（図１の各線図での（ｂ）を参照）。   On the other hand, when the magnetic field in the region where the magnetic nanoparticles are present is sufficiently large and the magnetization is “saturated” (that is, in the diagram showing the magnetization response in FIG. When the magnetization intensity M generated from the particles is constant without being proportional to the magnetic field intensity H, and the change in the magnetization response waveform is small, the harmonic component generated by the alternating magnetic field is suppressed (FIG. 1). (See (b) in each diagram).

つまり、磁場強度が小さい領域に磁性ナノ粒子が存在する場合にのみ高調波成分を含む磁化応答波形が得られ、その領域における磁性ナノ粒子の存在量を把握できる。このような原理を利用して、ＭＰＩでは局所的に磁場強度がほぼ零となるＦｉｅｌｄ−Ｆｒｅｅ Ｐｏｉｎｔ（ＦＦＰ）領域すなわち磁化非飽和領域を生成し、これを走査することで、磁性ナノ粒子の存在領域（分布）を磁化応答波形（周波数応答）の高調波成分により識別できる。最終的に、検出される高調波成分の振幅を配列化することで、磁性ナノ粒子の分布を画像として再構成できる。なお、このようにして作成された画像を以下の説明では「再構成画像」と呼ぶ。   That is, a magnetization response waveform including a harmonic component is obtained only when magnetic nanoparticles exist in a region where the magnetic field strength is low, and the abundance of magnetic nanoparticles in that region can be grasped. Utilizing this principle, MPI generates a field-free point (FFP) region in which the magnetic field strength is almost zero locally, that is, a magnetically unsaturated region, and scans this to create the presence of magnetic nanoparticles. The region (distribution) can be identified by the harmonic component of the magnetization response waveform (frequency response). Finally, the distribution of the magnetic nanoparticles can be reconstructed as an image by arranging the amplitudes of the detected harmonic components. The image created in this way is referred to as a “reconstructed image” in the following description.

従来のＭＰＩの問題点の一つに、ＦＦＰ以外に存在する磁性ナノ粒子から生じる磁化応答波形の干渉により、再構成画像において偽像が現れ、空間分解能が低下してしまうことが挙げられる。特に、磁性ナノ粒子の粒径が小さくなると、磁性ナノ粒子の非線型性が小さくなることに起因して位置の識別に有用な磁化信号が微弱となり、画像分解能の低下が顕著に現れることが懸念されている。これは、図１（左上）に示される磁性ナノ粒子の磁化特性Ｍは、外部から印加される磁界強度Ｈに対してランジュバン関数（Ｍ∝ｃｏｔｈ(αＨ)−１／αＨ、α：比例係数）で近似されるとともに、磁性ナノ粒子径の３乗に比例するとされているからである。このため、磁化特性が飽和状態へ達するために大きな外部磁場が必要となり、ＭＰＩ画像再構成装置が大型化し、高価なものとなっていた。   One of the problems of conventional MPI is that a false image appears in a reconstructed image due to interference of magnetization response waveforms generated from magnetic nanoparticles existing other than FFP, resulting in a decrease in spatial resolution. In particular, when the particle size of magnetic nanoparticles is reduced, the non-linearity of the magnetic nanoparticles is reduced, and the magnetization signal useful for position identification becomes weak, and there is a concern that the image resolution is significantly reduced. Has been. This is because the magnetization property M of the magnetic nanoparticles shown in FIG. 1 (upper left) is a Langevin function (M∝coth (αH) −1 / αH, α: proportional coefficient) with respect to the magnetic field strength H applied from the outside. This is because it is approximated by and proportional to the cube of the magnetic nanoparticle diameter. For this reason, a large external magnetic field is required for the magnetization characteristics to reach a saturation state, and the MPI image reconstruction apparatus becomes large and expensive.

上記問題点の現象を反映した磁化応答波形の一例を図２に示す。図２（ａ）は、９ｍｍ×９ｍｍサイズの撮像領域（Ｆｉｅｌｄ ｏｆ Ｖｉｅｗ：ＦＯＶ）における磁性ナノ粒子（図中ＭＮＰと●印で表記）とＦＦＰとの配置を示している。ＦＦＰはＦＯＶの中心に設定され、磁性ナノ粒子はＦＦＰから上下（ｚ方向）に等距離の位置に存在している場合を示す。一方、図２（ｂ）では、ＦＯＶの中心位置にＦＦＰと磁性ナノ粒子とが配置されている場合を示す。
次に、図２（ｃ）、（ｄ）は、図２（ａ）及び図２（ｂ）の場合に検出される磁化応答波形（時間応答）、および、及びそのフーリエ変換結果を示している。ここで、図２（ｃ）、（ｄ）において、図２（ａ）の配置の場合に得られる波形を干渉波形と呼び、問題となっていた。これは以下の理由による。 An example of a magnetization response waveform reflecting the above problem is shown in FIG. FIG. 2A shows the arrangement of magnetic nanoparticles (indicated by MNP and ● in the figure) and FFP in an imaging area (Field of View: FOV) of 9 mm × 9 mm size. The FFP is set at the center of the FOV, and the magnetic nanoparticles are present at an equidistant position in the vertical direction (z direction) from the FFP. On the other hand, FIG. 2B shows a case where FFP and magnetic nanoparticles are arranged at the center position of the FOV.
Next, FIGS. 2C and 2D show the magnetization response waveform (time response) detected in the case of FIGS. 2A and 2B and the Fourier transform result thereof. . Here, in FIGS. 2C and 2D, the waveform obtained in the case of the arrangement of FIG. 2A is called an interference waveform, which is a problem. This is due to the following reason.

図２（ｃ）の結果からＦＦＰから等距離の領域に存在する磁性ナノ粒子から生じる磁化応答波形は正負の対称性を有する。従来の画像再構成法では、このような奇数次高調波スペクトルの情報のみを利用しているため、磁性ナノ粒子が存在する領域（本例では実際に粒子が配置されている上下の領域）に加え、本来磁性ナノ粒子が存在していない領域（本例ではＦＯＶ中心のＦＦＰの領域）にも信号分布が再構成されてしまうことになる（図２（ｅ）を参照）。従って、奇数次高調波成分のみでは判別できない干渉の影響を、軽減・排除する手法が求められていた。   From the result of FIG. 2 (c), the magnetization response waveform generated from the magnetic nanoparticles existing at an equal distance from the FFP has positive and negative symmetry. In the conventional image reconstruction method, only information on such odd-order harmonic spectrum is used, so in the region where the magnetic nanoparticles exist (in this example, the upper and lower regions where the particles are actually arranged). In addition, the signal distribution is also reconstructed in a region where magnetic nanoparticles are not originally present (in this example, the FFP center FFP region) (see FIG. 2E). Therefore, a method for reducing or eliminating the influence of interference that cannot be determined only by odd-order harmonic components has been demanded.

なお、図２（ｃ）、（ｄ）には、図２（ｂ）の配置の場合に得られる磁化応答波形も理想波形として併せて表示している。干渉波形の場合も理想波形の場合と同様に奇数次高調波成分のみ信号が表れ、偶数次高調波成分に信号が現われていないことがわかる。よって、図２（ａ）のような粒子配置の場合に、従来の判別手法では、図２（ｂ）の配置で撮像される信号情報と区別がつかず、ＦＯＶに撮像（再構成）された磁性ナノ粒子像が実像なのか偽像なのかの判別ができなかった。   In FIGS. 2C and 2D, the magnetization response waveform obtained in the case of the arrangement of FIG. 2B is also displayed as an ideal waveform. In the case of the interference waveform, it can be seen that the signal appears only in the odd-order harmonic components and the signal does not appear in the even-order harmonic components, as in the case of the ideal waveform. Therefore, in the case of the particle arrangement as shown in FIG. 2A, the conventional discrimination method is indistinguishable from the signal information imaged in the arrangement of FIG. 2B, and is imaged (reconstructed) in the FOV. It was not possible to determine whether the magnetic nanoparticle image was a real image or a false image.

つまり、本発明では、磁性ナノ粒子の空間的分布を画像化する画像再構成装置において再構成画像の分解能を改善することを目的とする。   That is, an object of the present invention is to improve the resolution of a reconstructed image in an image reconstruction device that images the spatial distribution of magnetic nanoparticles.

さらに、本発明では、磁性ナノ粒子の空間的分布を画像化する画像再構成装置において再構成画像上に現われ得る偽像を排除することを目的とする。   Furthermore, an object of the present invention is to eliminate false images that can appear on a reconstructed image in an image reconstructing apparatus that images the spatial distribution of magnetic nanoparticles.

本願発明の発明者は、鋭意検討の末、磁性ナノ粒子の偽像による磁化応答信号（偽像波形）と、実際に磁性ナノ粒子が偽像発生位置に存在していた場合の磁化応答信号（理想波形）と、の間に差異があることに着目し、前者（偽像波形）の再構成画像に重み付けを行い、後者（理想波形）と、を比較できるようにすれば、磁性ナノ粒子が実像であるか又は偽像であるかを判別でき、かつ、この偽像を排除した画像再構成装置を提供できることを見出し、本発明を完成するに至った。   The inventor of the present invention, after earnest study, magnetization response signal (false image waveform) due to the false image of the magnetic nanoparticles, and magnetization response signal when the magnetic nanoparticles actually exist at the false image generation position ( Focusing on the difference between the ideal waveform and the ideal image, the reconstructed image of the former (false image waveform) is weighted so that it can be compared with the latter (ideal waveform). The present inventors have found that it is possible to determine whether the image is a real image or a false image, and to provide an image reconstruction device that eliminates the false image, thereby completing the present invention.

すなわち、本発明は次の１〜１２の構成をとるものである。
１．磁性ナノ粒子が存在する撮像領域に、該磁性ナノ粒子の磁化が飽和する飽和領域と該飽和領域よりも磁場強度が低い非飽和領域とを有する局所磁場分布を印加するとともに、オフセット磁場と交番磁場とをさらに印加する磁場発生手段と、
前記磁場発生手段の前記交番磁場の印加によって前記磁性ナノ粒子から発生する磁化応答信号を検出する検出手段と、
前記検出手段によって検出された前記磁化応答信号を画像情報として再構成する再構成手段と、を備え、かつ、
前記再構成手段は、前記検出手段によって前記非飽和領域において検出された前記磁化応答波形と比較すべき理想波形を取得し、
前記再構成手段は、前記理想波形と前記磁化応答波形との差分情報を補正係数として算出して該補正係数により前記磁化応答波形の信号強度に重み付けを行うことを特徴とする磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
２．前記再構成手段は、前記重み付けを行う前に前記磁化応答信号波形から前記磁化応答波形のオフセット成分を減じた後に前記磁化応答波形の振幅最大値で正規化し、かつ、
前記理想波形が、前記非飽和領域と同一の空間位置に前記磁性ナノ粒子が配置された場合に検出される磁化応答信号波形であることを特徴とする前記１に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
３．前記理想波形が、前記磁化応答波形の前記振幅最大値と周期とから算出される矩形波であることを特徴とする請求項１に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
４．前記差分情報が、各時間における前記理想波形の振幅と前記磁化応答波形の振幅との差分値の総和であることを特徴とする前記１〜３のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
５.前記差分情報が、前記理想波形の磁化が飽和する時間と前記磁化応答波形の磁化が飽和する時間との差分値であることを特徴とする前記１〜３のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
６.前記信号強度は、前記磁化応答波形の高調波信号の奇数次高調波成分が強調され、かつ／又は、該高調波信号の偶数次高調波成分が減衰された信号に基づいて算出されていることを特徴とする前記１〜５のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。
７. 磁性ナノ粒子が存在する撮像領域に、該磁性ナノ粒子の磁化が飽和する飽和領域と該飽和領域よりも磁場強度が低い非飽和領域とを有する局所磁場分布を印加するとともに、オフセット磁場と交番磁場とをさらに印加する磁場発生ステップと、
前記磁場発生ステップの前記交番磁場の印加によって前記磁性ナノ粒子から発生する磁化応答信号を検出する検出ステップと、
前記検出ステップによって検出された前記磁化応答信号を画像情報として再構成する再構成ステップと、を備え、かつ、
前記再構成ステップは、前記検出ステップによって前記非飽和領域において検出された前記磁化応答波形と比較すべき理想波形を取得し、
前記再構成ステップは、前記理想波形と前記磁化応答波形との差分情報を補正係数として算出して該補正係数により前記磁化応答波形の信号強度に重み付けを行うことを特徴とする磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。
８.前記再構成ステップは、前記重み付けを行う前に前記磁化応答信号波形から前記磁化応答波形のオフセット成分を減じた後に前記磁化応答波形の振幅最大値で正規化し、かつ、
前記理想波形が、前記非飽和領域と同一の空間位置に前記磁性ナノ粒子が配置された場合に検出される磁化応答信号波形であることを特徴とする前記７に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。
９.前記理想波形が、前記磁化応答波形の前記振幅最大値と周期とから算出される矩形波であることを特徴とする前記７に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。
１０.前記差分情報が、各時間における前記理想波形の振幅と前記磁化応答波形の振幅との差分値の総和であることを特徴とする前記７〜９のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。
１１.前記差分情報が、前記理想波形の磁化が飽和する時間と前記磁化応答波形の磁化が飽和する時間との差分値であることを特徴とする前記７〜９のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。
１２.前記信号強度は、前記磁化応答波形の高調波信号の奇数次高調波成分が強調され、かつ／又は、該高調波信号の偶数次高調波成分が減衰された信号に基づいて算出されていることを特徴とする前記７〜１１のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。 That is, this invention takes the structure of the following 1-12.
1. Applying a local magnetic field distribution having a saturated region where the magnetization of the magnetic nanoparticle is saturated and a non-saturated region where the magnetic field strength is lower than the saturated region to the imaging region where the magnetic nanoparticle exists, an offset magnetic field and an alternating magnetic field A magnetic field generating means for further applying
Detecting means for detecting a magnetization response signal generated from the magnetic nanoparticles by application of the alternating magnetic field of the magnetic field generating means;
Reconstructing means for reconstructing the magnetization response signal detected by the detecting means as image information, and
The reconstruction means obtains an ideal waveform to be compared with the magnetization response waveform detected in the non-saturation region by the detection means;
The reconfiguration means calculates difference information between the ideal waveform and the magnetization response waveform as a correction coefficient, and weights the signal intensity of the magnetization response waveform by the correction coefficient. An image reconstruction device using a response signal.
2. The reconstruction means normalizes with the maximum amplitude value of the magnetization response waveform after subtracting the offset component of the magnetization response waveform from the magnetization response signal waveform before performing the weighting; and
2. The magnetization response of the magnetic nanoparticles according to 1 above, wherein the ideal waveform is a magnetization response signal waveform detected when the magnetic nanoparticles are arranged at the same spatial position as the unsaturated region. An image reconstruction device using signals.
3. The image reconstruction device using a magnetic response signal of magnetic nanoparticles according to claim 1, wherein the ideal waveform is a rectangular wave calculated from the maximum amplitude value and the period of the magnetization response waveform. .
4). 4. The magnetic response signal of magnetic nanoparticles according to any one of 1 to 3, wherein the difference information is a sum of difference values between the amplitude of the ideal waveform and the amplitude of the magnetization response waveform at each time Image reconstruction device using
5. The magnetic nano according to any one of 1 to 3, wherein the difference information is a difference value between a time at which the magnetization of the ideal waveform is saturated and a time at which the magnetization of the magnetization response waveform is saturated. An image reconstruction device using a magnetization response signal of particles.
6. The signal intensity is calculated based on a signal in which the odd harmonic component of the harmonic signal of the magnetization response waveform is emphasized and / or the even harmonic component of the harmonic signal is attenuated. The image reconstruction apparatus using the magnetization response signal of the magnetic nanoparticles according to any one of 1 to 5 above.
7. Applying a local magnetic field distribution having a saturated region where the magnetization of the magnetic nanoparticle is saturated and an unsaturated region where the magnetic field strength is lower than the saturated region to the imaging region where the magnetic nanoparticle exists, A magnetic field generating step for further applying an alternating magnetic field;
A detection step of detecting a magnetization response signal generated from the magnetic nanoparticles by application of the alternating magnetic field of the magnetic field generation step;
Reconstructing the magnetization response signal detected by the detecting step as image information, and
The reconstruction step obtains an ideal waveform to be compared with the magnetization response waveform detected in the non-saturation region by the detection step;
The reconstructing step calculates difference information between the ideal waveform and the magnetization response waveform as a correction coefficient, and weights the signal intensity of the magnetization response waveform by the correction coefficient. An image reconstruction method using a response signal.
8. The reconstruction step includes normalizing with the maximum amplitude value of the magnetization response waveform after subtracting the offset component of the magnetization response waveform from the magnetization response signal waveform before performing the weighting, and
8. The magnetization response of the magnetic nanoparticles according to 7, wherein the ideal waveform is a magnetization response signal waveform detected when the magnetic nanoparticles are arranged at the same spatial position as the unsaturated region. Image reconstruction method using signals.
9. The image reconstruction using the magnetization response signal of the magnetic nanoparticles according to 7, wherein the ideal waveform is a rectangular wave calculated from the maximum amplitude value and the period of the magnetization response waveform Method.
10. The magnetization of the magnetic nanoparticles according to any one of 7 to 9, wherein the difference information is a sum of difference values between the amplitude of the ideal waveform and the amplitude of the magnetization response waveform at each time. An image reconstruction method using a response signal.
11. The magnetic nano according to any one of 7 to 9, wherein the difference information is a difference value between a time when the magnetization of the ideal waveform is saturated and a time when the magnetization of the magnetization response waveform is saturated. An image reconstruction method using a magnetization response signal of particles.
12. The signal intensity is calculated based on a signal in which odd harmonic components of the harmonic signal of the magnetization response waveform are emphasized and / or even harmonic components of the harmonic signal are attenuated. The image reconstruction method using the magnetization response signal of the magnetic nanoparticles according to any one of 7 to 11 above, wherein:

本発明によれば、磁化応答信号の高調波成分の情報と磁化応答波形の飽和・非飽和時間の情報との両者を用いることで、ＦＦＰ内外から生じる磁化応答信号をより精細に分別することが可能となるため、所望としない目的領域外からの磁化応答信号の干渉を抑制し、画質の向上と画像分解能の改善が達成される。すなわち、再構成画像に表れる磁性ナノ粒子の偽像を削除・抑制することが可能となる。   According to the present invention, by using both the information of the harmonic component of the magnetization response signal and the information of the saturation / non-saturation time of the magnetization response waveform, the magnetization response signal generated from inside and outside the FFP can be more finely separated. Therefore, it is possible to suppress the interference of the magnetization response signal from the outside of the target region which is not desired, thereby improving the image quality and the image resolution. That is, it becomes possible to delete and suppress the false image of the magnetic nanoparticles appearing in the reconstructed image.

本発明の上記課題解決手段を講じることにより、所望としない磁化応答信号の干渉（偽像）を大幅に（従来の方法の信号強度の１／１０以下までに）抑制することが可能となる（以下の実施例の数値解析や基礎実験の結果から確認済みである）。   By taking the above-mentioned problem solving means of the present invention, it becomes possible to significantly suppress unwanted interference (false image) of the magnetization response signal (to 1/10 or less of the signal intensity of the conventional method) ( It has been confirmed from the results of numerical analysis and basic experiments in the following examples).

このため、再構成画像の分解能を向上することが可能となり、さらに、所望とする信号を検出するために必要な外部印加磁場の強度を小さくできることから、ＭＰＩ画像再構成装置を安価・小型に構成することが可能となる。   For this reason, it is possible to improve the resolution of the reconstructed image, and further, the strength of the externally applied magnetic field necessary for detecting the desired signal can be reduced. It becomes possible to do.

磁性ナノ粒子から生じる磁化応答信号を示し、ＭＰＩの原理を説明する図である。It is a figure which shows the magnetization response signal which arises from a magnetic nanoparticle, and explains the principle of MPI. ＭＰＩにおける問題点を説明する図である。It is a figure explaining the problem in MPI. 本発明のＭＰＩ画像再構成装置の構成の一例を示す図である。It is a figure which shows an example of a structure of the MPI image reconstruction apparatus of this invention. 従来のＭＰＩによる画像再構成の原理を説明する図である。It is a figure explaining the principle of the image reconstruction by the conventional MPI. 磁性ナノ粒子から生じる磁化応答信号の高調波成分の一例を示す図である。It is a figure which shows an example of the harmonic component of the magnetization response signal which arises from a magnetic nanoparticle. 本発明によるＭＰＩ画像の分解能を改善する方法を説明する図である。It is a figure explaining the method to improve the resolution of the MPI image by this invention. 本発明によるＭＰＩ画像の分解能を改善する別の方法を説明する図である。It is a figure explaining another method to improve the resolution of the MPI image by this invention. 本発明による画像再構成方法の一例を示すフローチャートである。It is a flowchart which shows an example of the image reconstruction method by this invention. 本発明によるＭＰＩ画像分解能の改善効果の一例（数値解析結果）を示す図である。It is a figure which shows an example (numerical analysis result) of the improvement effect of MPI image resolution by this invention. 本発明によるＭＰＩ画像分解能の改善効果の一例（実験結果）を示す図である。It is a figure which shows an example (experimental result) of the improvement effect of MPI image resolution by this invention.

以下、磁性ナノ粒子の磁化応答信号を利用した画像再構成装置１０の一実施形態について、図面を参照しながら説明する。なお、図２、４、５、７及び１０に示された[ａ．ｕ．]は、任意単位を示し、[ｍｓ]はミリ秒（ｓ×１０−３）である。 Hereinafter, an embodiment of an image reconstruction device 10 using a magnetization response signal of magnetic nanoparticles will be described with reference to the drawings. 2, 4, 5, 7 and 10 [a. u. ] Indicates an arbitrary unit, and [ms] is milliseconds (s × 10 −3 ).

ＭＰＩ画像再構成装置の構成
図３は本発明のＭＰＩ画像再構成装置の構成の一例を示す。図３において、本装置は二組の対向するヘルムホルツ型コイル１，２と、それらの中央に配置された受信用コイル３、検出信号を処理する計算処理装置４により構成されている。なお、ヘルムホルツ型コイル１，２に電流を供給する電流源、受信用コイル３からの信号を増幅・弁別する回路、および、これらの要素に関連した制御系は図示していない。 Configuration of MPI Image Reconstruction Device FIG. 3 shows an example of the configuration of the MPI image reconstruction device of the present invention. In FIG. 3, this apparatus is composed of two sets of opposing Helmholtz type coils 1 and 2, a receiving coil 3 arranged at the center thereof, and a calculation processing device 4 for processing a detection signal. A current source for supplying current to the Helmholtz coils 1 and 2, a circuit for amplifying and discriminating a signal from the receiving coil 3, and a control system related to these elements are not shown.

先ず、ヘルムホルツ型コイル１，２において対向するコイルに逆方向の直流電流ＩＤＣ、および、−ＩＤＣを印加することにより、画像再構成装置１０の中央では各ヘルムホルツ型コイル１，２で発生する同軸方向の磁場が相殺されＦＦＰが生成される。また、両コイル１，２に供給するオフセット電流ＩＯＦＦ（Ｘ，Ｙ）を調整し、ヘルムホルツ型コイル１の上側のコイルには（ＩＤＣ＋ＩＯＦＦ（Ｘ，Ｙ））をヘルムホルツ型コイル１の下側のコイルには（−ＩＤＣ＋ＩＯＦＦ（Ｘ，Ｙ））を供給することで、ＦＦＰの位置（Ｘ、Ｙ）を上下左右に走査可能となる。さらに、上下のヘルムホルツ型コイル１，２に重畳して印加する交流電流ＩＡＣは装置１０全体に交番磁場を発生させ、磁性ナノ粒子からの磁化応答波形を取得するための入力信号としての役割を果たす。 First, by applying reverse direct currents I DC and −I DC to opposing coils in the Helmholtz coils 1 and 2, the Helmholtz coils 1 and 2 are generated in the center of the image reconstruction device 10. The magnetic field in the coaxial direction is canceled and FFP is generated. Further, the offset current I OFF (X, Y) supplied to both the coils 1 and 2 is adjusted, and (I DC + I OFF (X, Y) ) is applied to the upper coil of the Helmholtz coil 1 of the Helmholtz coil 1. By supplying (−I DC + I OFF (X, Y) ) to the lower coil, the position (X, Y) of the FFP can be scanned vertically and horizontally. Furthermore, the alternating current I AC applied by being superimposed on the upper and lower Helmholtz coils 1 and 2 generates an alternating magnetic field in the entire apparatus 10 and serves as an input signal for acquiring a magnetization response waveform from the magnetic nanoparticles. Fulfill.

このように、二組のヘルムホルツ型コイル１，２はＦＦＰの生成及び走査、並びに交番磁場の発生を同時に実現する。なお、ＦＦＰの生成と交番磁場の発生とを独立した構成とすることも可能である。例えば、ＦＦＰの生成を永久磁石で行った上で、その走査をＸＹステージ等の機械制御によって行うとともに、交番磁場をヘルムホルツ型コイルで発生することも可能である。   As described above, the two sets of Helmholtz coils 1 and 2 simultaneously realize the generation and scanning of the FFP and the generation of the alternating magnetic field. Note that it is possible to adopt an independent configuration for generating the FFP and generating the alternating magnetic field. For example, the FFP can be generated by a permanent magnet, and the scanning can be performed by mechanical control of an XY stage or the like, and an alternating magnetic field can be generated by a Helmholtz type coil.

また、磁性ナノ粒子から生じる磁化応答波形は受信用コイル３により検出され、ヘルムホルツ型コイル１，２により生成される磁場の線形領域が撮像領域たるＦＯＶとして定義される。   The magnetization response waveform generated from the magnetic nanoparticles is detected by the receiving coil 3, and the linear region of the magnetic field generated by the Helmholtz type coils 1 and 2 is defined as the FOV that is the imaging region.

従来の画像再構成手法による問題点
前述のように、ＭＰＩでは生成したＦＦＰを走査しながら検出される磁化応答波形を利用して画像再構成が行われるが、上記のヘルムホルツ型コイル１，２を用いた場合には、ＦＦＰを形成する磁場分布の局所性（立ち上がりの鋭さ）が悪く、矩形状の局所磁場分布しか得られないため、再構成画像の劣化が生じてしまう。 Problems with the conventional image reconstruction method As described above, in MPI, image reconstruction is performed using the magnetization response waveform detected while scanning the generated FFP. However, the Helmholtz coils 1 and 2 described above are used. When used, the locality (sharpness of the rising edge) of the magnetic field distribution forming the FFP is poor, and only a rectangular local magnetic field distribution can be obtained, resulting in degradation of the reconstructed image.

例えば、図４（ａ）に示すようにＦＯＶの中心に磁性ナノ粒子（図中●印及びＭＮＰで表示）を配置し、ＦＦＰを図中ＦＦＰ−ａ点と、ＦＦＰ−ｂ点とにそれぞれ設定した場合に検出される各磁化応答波形の一例を図４（ｂ）に示す。理想的には、ＦＦＰがＦＦＰ−ａ点（図４（ａ）中の□印の位置）に走査された場合にのみ磁化応答信号が検出されるべきであるが（図４（ｂ）の実線のみ検出されるべきであるが）、磁性ナノ粒子が存在しないＦＦＰ−ｂ点（図４（ａ）中の◇印の位置）にＦＦＰが走査された場合でも磁化応答信号が検出されてしまっていることがわかる（図４（ｂ）の破線を参照）。   For example, as shown in FIG. 4 (a), magnetic nanoparticles (indicated by ● and MNP in the figure) are arranged at the center of the FOV, and the FFP is set at the FFP-a point and the FFP-b point in the figure, respectively. An example of each magnetization response waveform detected in this case is shown in FIG. Ideally, the magnetization response signal should be detected only when the FFP is scanned at the FFP-a point (the position of the □ in FIG. 4A) (the solid line in FIG. 4B). However, even when the FFP is scanned at the FFP-b point (the position marked with ◇ in FIG. 4A) where no magnetic nanoparticles exist, the magnetization response signal has been detected. (See the broken line in FIG. 4B).

そこで、従来のＭＰＩ画像再構成法では、ＦＦＰがＦＦＰ−ａ点に走査された場合（磁性ナノ粒子がＦＦＰのみに存在する場合）に磁化応答波形の周波数スペクトルが奇数次高調波成分のみとなることに着目し（図４（ｃ））、主に奇数次高調波成分を利用した画像再構成が行われている。すわなち、ＦＦＰが図３上におけるｙ＝０の二次元平面（ｘ−ｚ平面）にあるときには、再構成画像における信号強度Ｕｘｚ ｔｒａｄは次式（数式１）で表される。 Therefore, in the conventional MPI image reconstruction method, when the FFP is scanned at the FFP-a point (when magnetic nanoparticles are present only in the FFP), the frequency spectrum of the magnetization response waveform is only odd-order harmonic components. Paying attention to this (FIG. 4C), image reconstruction mainly using odd-order harmonic components is performed. In other words, when the FFP is on the y = 0 two-dimensional plane (xz plane) in FIG. 3, the signal intensity U xz trad in the reconstructed image is expressed by the following formula (Formula 1).

ここで、Ｎｈは使用する高調波の最大次数、Ｖｘｚはフーリエ変換で得られる高調波成分である。 Here, the N h maximum degree, V xz harmonic used is a harmonic component obtained by Fourier transform.

このように、従来法では磁化応答波形に含まれる高調波成分を基に画像再構成が行われるが、高次の高調波成分については振幅が微小であり、信号強度Ｕｘｚ ｔｒａｄに反映される影響が僅かであるため、高次成分の情報は活用されていない。また、上述のように一般的なヘルムホルツ型コイル１，２では急峻な局所磁場分布が得られないため、ＦＦＰ近傍の磁性ナノ粒子からも望ましくない磁化応答波形が検出されてしまい、空間分解能の低下が引き起こされる可能性が考えられる（問題点１）。同様に、ＦＦＰ（目的領域）以外に存在する磁性ナノ粒子から磁化応答波形が収集されることで、本来磁性ナノ粒子が存在していない領域に偽像が出現し、真像との識別が困難となる問題があった（問題点２）。 As described above, in the conventional method, image reconstruction is performed based on the harmonic component included in the magnetization response waveform, but the amplitude of the higher-order harmonic component is very small and is reflected in the signal intensity U xz trad. The information on higher order components is not utilized because of the slight influence. Further, as described above, since the steep local magnetic field distribution cannot be obtained with the general Helmholtz coils 1 and 2, an undesirable magnetization response waveform is detected from the magnetic nanoparticles near the FFP, resulting in a decrease in spatial resolution. May be caused (Problem 1). Similarly, by collecting magnetization response waveforms from magnetic nanoparticles that exist outside the FFP (target region), a false image appears in a region where the magnetic nanoparticles are not originally present, making it difficult to distinguish from the true image. (Problem 2).

磁化応答波形の奇数次高調波成分の強調
そこで、磁性ナノ粒子がＦＦＰのみに存在する理想的な状態において検出される磁化応答波形の奇数次高調波成分を有効に利用することで、再構成画像の検出感度を向上する手法が考えられる（非特許文献２）。図４（ａ）において、ＦＦＰ−ａ点のみに磁性ナノ粒子が存在する場合に得られる奇数次高調波スペクトルの振幅特性は図５のようにＳ＝ａｅ−αｎで表される指数関数により近似できる（ここで、ａ、α、ｎは任意定数である）。このため、次数の増加に応じた指数係数を乗じて高次成分を強調することで、検出感度の増強、すなわち高分解能化が期待できる。この処理を数式１に加えた場合の再構成画像における信号強度Ｕｘｚ ｅｍｐｈは次式（数式２）で表される。 Emphasis on odd harmonic components of magnetization response waveform Therefore, by effectively using odd harmonic components of the magnetization response waveform detected in an ideal state where magnetic nanoparticles exist only in FFP, a reconstructed image is obtained. A technique for improving the detection sensitivity of the image is conceivable (Non-patent Document 2). In FIG. 4A, the amplitude characteristic of the odd harmonic spectrum obtained when magnetic nanoparticles exist only at the FFP-a point is approximated by an exponential function represented by S = ae− αn as shown in FIG. (Where a, α, and n are arbitrary constants). For this reason, enhancement of detection sensitivity, that is, higher resolution can be expected by multiplying an exponential coefficient corresponding to the increase in order to emphasize higher-order components. The signal intensity U xz emph in the reconstructed image when this processing is added to Equation 1 is expressed by the following equation (Equation 2).

ここで、ｋ１、ｋ２は任意定数である。 Here, k 1 and k 2 are arbitrary constants.

磁化応答波形の偶数次高調波成分の抑制
一方、磁性ナノ粒子の存在する領域から離れたＦＦＰ‐ｂ点（図４（ａ）の◇印位置）において検出される磁化応答波形は、図４（ｂ）のように正負の対称性が維持されておらず、フーリエ変換結果には偶数次の高調波スペクトルが顕著に確認できることから（図４（ｃ））、偶数次高調波成分は再構成画像の空間分解能の低下を引き起こすと考えられる。そこで、奇数次高調波成分と同様に、偶数次高調波スペクトルに応じた指数係数を乗じた後、奇数次高調波成分より減じることで、再構成画像において磁性ナノ粒子が存在する領域のみから局所的に信号を得られると考えられる。これらの処理を式２に加えた場合の再構成画像における信号強度Ｕｘｚ ｌｏｃａｌは次式（数式３）で表される。 Suppression of even harmonic components of the magnetization response waveform On the other hand, the magnetization response waveform detected at the FFP-b point (the position marked by ◇ in FIG. 4A) away from the region where the magnetic nanoparticles are present is shown in FIG. Since the positive / negative symmetry is not maintained as in b), and the even-order harmonic spectrum can be remarkably confirmed in the Fourier transform result (FIG. 4C), the even-order harmonic components are reconstructed images. This is thought to cause a decrease in spatial resolution. Therefore, as with the odd-order harmonic component, after multiplying by the exponential coefficient corresponding to the even-order harmonic spectrum, and subtracting from the odd-order harmonic component, the reconstructed image can be localized only from the region where the magnetic nanoparticles are present. It is thought that a signal can be obtained. The signal intensity U xz local in the reconstructed image when these processes are added to Expression 2 is expressed by the following expression (Expression 3).

ここで、βは偶数次の高調波スペクトルより得られる減衰定数であり、ｋ３、ｋ４は任意定数である。 Here, β is an attenuation constant obtained from the even-order harmonic spectrum, and k 3 and k 4 are arbitrary constants.

これらの方法により、再構成画像の空間分解能・検出感度を改善すること（すなわち上記問題点１の解決）が期待できるが、図２に示したように、ＦＦＰから等距離の領域に存在する磁性ナノ粒子から生じる磁化応答波形は正負の対称性を有するため、このような高調波スペクトルの情報のみを利用した処理だけでは磁性ナノ粒子が実在する領域に加え、本来磁性ナノ粒子が存在していない領域にも信号分布が再構成される場合が生じてしまう。すなわち、上記問題点２は未解決のままであった。   Although these methods can be expected to improve the spatial resolution and detection sensitivity of the reconstructed image (that is, to solve the above problem 1), as shown in FIG. 2, magnetism existing in an equidistant region from the FFP. Since the magnetization response waveform generated from nanoparticles has positive and negative symmetry, in addition to the region where magnetic nanoparticles actually exist, only magnetic nanoparticles are not present by processing using only the information of the harmonic spectrum. The signal distribution may be reconstructed in the region. That is, the above problem 2 remains unsolved.

偽像の識別（磁化応答波形の補正処理）
ここで、図２（ｃ）において干渉波形（図中実線）と理想波形（図中破線）とを比較すると、照射される交番磁場により磁化応答波形が周期的に飽和状態（変化が僅少）となる時間に顕著な差が認められる。そこで、本発明では、ＦＦＰの各走査点で検出される磁化応答波形と各走査点にのみ磁性ナノ粒子が存在する場合に生じる理想波形との相似性に応じて補正（重み付けとも呼ぶ）を行い、高分解能画像を実現することを提案する。本発明では、検出される磁化応答波形ｗｎと理想波形ｗｎ ｉを離散データとして扱い、両者の相似性を補正係数Ｃｃとして、次式（数式４）で定義する。 False image identification (magnetization response waveform correction processing)
Here, when the interference waveform (solid line in the figure) and the ideal waveform (dashed line in the figure) are compared in FIG. 2 (c), the magnetization response waveform is periodically saturated by the irradiated alternating magnetic field (change is slight). There is a noticeable difference in time. Therefore, in the present invention, correction (also referred to as weighting) is performed according to the similarity between the magnetization response waveform detected at each FFP scanning point and the ideal waveform generated when magnetic nanoparticles are present only at each scanning point. We propose to realize high resolution images. In the present invention, the detected magnetization response waveform w n and the ideal waveform w n i are treated as discrete data, and the similarity between them is defined as the correction coefficient C c by the following formula (Formula 4).

ここでＮｓは各波形のサンプリング数であり、ｗｍａｘ、ｗｍａｘ ｉは各波形の最大値、ｗｍｅａｎは磁化応答波形の中間値（最大値と最小値の平均値）であり、ｃａは任意定数である。数式４において、検出される磁化応答波形にはＦＦＰ領域外に存在する磁性ナノ粒子から生じる磁化応答波形のオフセット成分（ｗｍｅａｎ）が含まれるため、図６に示すように、この成分を減じた後に正規化を行っている。そして、両者の正規化離散データを比較し、検出される磁化応答波形が理想波形と等しい場合に補正係数が１．０となるように、差分情報を基に相似性を算出する。この補正を数式１に加えた場合の再構成画像における信号強度Ｕｘｚ ｃｏｍｐは次式（数式５）で表される。 Here, N s is the number of samples of each waveform, w max and w max i are the maximum values of each waveform, w mean is the intermediate value (average value of the maximum value and the minimum value) of the magnetization response waveform, and c a Is an arbitrary constant. In Equation 4, since the detected magnetization response waveform includes an offset component (w mean ) of the magnetization response waveform generated from the magnetic nanoparticles existing outside the FFP region, this component is reduced as shown in FIG. Later normalization is performed. Then, both normalized discrete data are compared, and the similarity is calculated based on the difference information so that the correction coefficient is 1.0 when the detected magnetization response waveform is equal to the ideal waveform. The signal intensity U xz comp in the reconstructed image when this correction is added to Equation 1 is expressed by the following equation (Equation 5).

さらに、数式４による補正処理に加え、数式３のように高調波成分の振幅特性を有効に利用する処理を施すことで、得られる信号強度がより局所化され、高分解能化に繋がると考えられる。両者の処理を組み合わせた場合の再構成画像における信号強度Ｕｘｚ ｃｏｍｂは次式（数式６）で表される。 Furthermore, in addition to the correction processing according to Equation 4, it is thought that the signal intensity obtained is more localized by performing processing that effectively uses the amplitude characteristic of the harmonic component as in Equation 3, leading to higher resolution. . The signal intensity U xz comb in the reconstructed image when both processes are combined is expressed by the following formula (Formula 6).

ここで、上記補正処理に必要な理想波形は、ＦＦＰが配置されている空間位置と同一位置にのみ磁性ナノ粒子が実在する場合に予め観測（実測）された磁化応答信号か、あるいは、数値解析によって算出されるが、必ずしもこれらに限定されない。   Here, the ideal waveform necessary for the correction processing is a magnetization response signal observed (measured) in advance when the magnetic nanoparticles actually exist only at the same position as the spatial position where the FFP is arranged, or numerical analysis However, it is not necessarily limited to these.

例えば、理想波形として、図７に示すように、磁化応答信号の最大値（振幅最大値）と周期とで算出される矩形波を近似的に用いることも可能である。この矩形波を用いることで、上述のＦＦＰ領域に磁性ナノ粒子が配置された理想波形を予め実験又は数値解析によって取得する手間を省くことができる。   For example, as an ideal waveform, as shown in FIG. 7, it is also possible to approximately use a rectangular wave calculated by the maximum value (amplitude maximum value) and the period of the magnetization response signal. By using this rectangular wave, it is possible to save time and effort to obtain an ideal waveform in which magnetic nanoparticles are arranged in the above-mentioned FFP region by experiments or numerical analysis in advance.

また、理想波形を用いずに、印加する交番磁場の振幅を変えて（つまり複数のレベルの振幅の交番磁場を与えて）観測される複数の磁化応答信号を利用して、上記と同様の補正処理を行うことも可能である。これは、ＦＦＰに実在する磁性ナノ粒子と、偽像の原因となるＦＦＰ外部に存在する磁性ナノ粒子とでは、外部から印加する交番磁場の大きさを変化させた場合の影響（磁化応答の変化）が異なるからである。   Moreover, the same correction as described above is performed by using a plurality of magnetization response signals observed by changing the amplitude of the alternating magnetic field to be applied (that is, by giving an alternating magnetic field having a plurality of levels of amplitude) without using an ideal waveform. It is also possible to perform processing. This is because the magnetic nanoparticles existing in the FFP and the magnetic nanoparticles existing outside the FFP causing the false image are affected when the magnitude of the alternating magnetic field applied from the outside is changed (change in magnetization response). ) Is different.

さらに、上記の補正手法は、磁性ナノ粒子の磁化特性の時間応答における干渉波形と理想波形との面積の差に対応しているが、別の補正手法として理想波形が飽和している時間と干渉波形が飽和している時間（図６から、干渉波形が飽和する時間は理想波形に比べて短くなる）を指標として補正（重み付け）することも考えられる。   Furthermore, the above correction method corresponds to the difference in area between the interference waveform and the ideal waveform in the time response of the magnetization characteristics of the magnetic nanoparticles, but as another correction method, the interference with the time when the ideal waveform is saturated It is also conceivable to correct (weight) the time when the waveform is saturated (from FIG. 6, the time when the interference waveform is saturated is shorter than the ideal waveform) as an index.

以上のようにして、本発明では干渉波形の影響（偽像）を軽減することが可能となる。すなわち、上述の従来法の問題点を解決し、上記作用効果を奏する本発明の画像再構成方法は、図８に示すように下記のステップＳ１〜３により達成される。   As described above, according to the present invention, it is possible to reduce the influence (false image) of the interference waveform. That is, the image reconstruction method of the present invention that solves the problems of the above-described conventional methods and exhibits the above-described effects is achieved by the following steps S1 to S3 as shown in FIG.

まず、磁性ナノ粒子が存在すると予想される撮像領域に、該磁性ナノ粒子の磁化が飽和する飽和領域と該飽和領域よりも磁場強度が低い非飽和領域とを有する局所磁場分布を印加するとともに、オフセット磁場と交番磁場とをさらに印加する磁場発生ステップＳ１を実行する。   First, a local magnetic field distribution having a saturated region where the magnetization of the magnetic nanoparticle is saturated and an unsaturated region where the magnetic field strength is lower than the saturated region is applied to an imaging region where magnetic nanoparticles are expected to exist, A magnetic field generation step S1 for further applying an offset magnetic field and an alternating magnetic field is executed.

この磁場発生ステップＳ１を実行する際に磁場を発生する磁場発生手段として、上述のヘルムホルツ型コイル１，２が挙げられるが、必ずしもこれに限定されず、例えば永久磁石をはじめ他の磁場発生装置であってもよい。また、オフセット磁場の印加は、前記局所磁場分布を空間的に走査するためであり、上述のようにヘルムホルツ型コイル１，２にオフセット電流を重畳させることでオフセット磁場を発生させることができる。また、交番磁場の印加は、前記磁性ナノ粒子から磁化応答信号を検出するためであり、上述のようにヘルムホルツ型コイル１から交番磁場を発生させることができる。   As the magnetic field generating means for generating the magnetic field when executing this magnetic field generating step S1, the Helmholtz type coils 1 and 2 are mentioned, but not necessarily limited thereto. For example, other magnetic field generating devices such as permanent magnets may be used. There may be. The application of the offset magnetic field is to spatially scan the local magnetic field distribution, and the offset magnetic field can be generated by superimposing the offset current on the Helmholtz coils 1 and 2 as described above. The application of the alternating magnetic field is for detecting a magnetization response signal from the magnetic nanoparticles, and the alternating magnetic field can be generated from the Helmholtz type coil 1 as described above.

次に、前記磁場発生ステップＳ１の前記交番磁場の印加によって前記磁性ナノ粒子から発生する磁化応答信号を検出する検出ステップＳ２を実行する。ここで、この検出ステップを実行する検出手段として、上述のような受信コイル３が挙げられる。   Next, a detection step S2 for detecting a magnetization response signal generated from the magnetic nanoparticles by the application of the alternating magnetic field in the magnetic field generation step S1 is executed. Here, the receiving coil 3 as mentioned above is mentioned as a detection means for executing this detection step.

さらに、前記検出ステップＳ２によって検出された前記磁化応答信号を画像情報として再構成する再構成ステップＳ３を実行する。ここで、再構成ステップを実行する再構成手段として、上述の計算処理装置４が挙げられる。   Further, a reconstruction step S3 for reconstructing the magnetization response signal detected in the detection step S2 as image information is executed. Here, as the reconstruction means for executing the reconstruction step, the above-described calculation processing device 4 can be cited.

この再構成ステップＳ３は、具体的には上述のように、前記局所磁場分布の非飽和領域において検出された前記磁化応答信号波形から前記磁化応答波形のオフセット成分を減じた後に前記磁化応答波形の振幅最大値で正規化し（ステップＳ３ａ）、前記検出手段によって前記非飽和領域において検出された前記磁化応答波形と比較すべき理想波形を取得して（ステップＳ３ｂ）、前記理想波形と前記磁化応答波形との差分情報を補正係数として算出して該補正係数により前記磁化応答波形の信号強度に重み付けを行う（ステップＳ３ｃ）。ここでステップＳ３ｃの重み付けを行う前に、信号強度が数式３及び数式６に示したように、磁化応答波形の高調波信号の奇数次高調波成分が強調され、かつ／又は、該高調波信号の偶数次高調波成分が減衰された信号に基づいて算出されるようにしてもよい。信号強度へ上記処理を行うことで、画質と画像分解能のさらなる改善が達成され得る。   Specifically, as described above, the reconstruction step S3 subtracts the offset component of the magnetization response waveform from the magnetization response signal waveform detected in the unsaturated region of the local magnetic field distribution, and then Normalized by the maximum amplitude value (step S3a), an ideal waveform to be compared with the magnetization response waveform detected in the non-saturation region by the detection means is acquired (step S3b), and the ideal waveform and the magnetization response waveform are acquired. Is calculated as a correction coefficient, and the signal intensity of the magnetization response waveform is weighted by the correction coefficient (step S3c). Here, before performing the weighting in step S3c, the odd-order harmonic component of the harmonic signal of the magnetization response waveform is emphasized and / or the harmonic signal, as shown in Equations 3 and 6, for the signal strength. May be calculated based on the attenuated signal. By performing the above processing on the signal intensity, further improvement in image quality and image resolution can be achieved.

なお、この再構成ステップＳ３の理想波形として、図６に示したように、前記非飽和領域と同一の空間位置に前記磁性ナノ粒子が配置された場合に検出される磁化応答信号波形が挙げられるが、必ずしもこれに限定されず、例えば、図７に示したように、磁化応答信号波形の振幅最大値と周期とから算出される矩形波のようなものであってもよい。   As an ideal waveform of the reconstruction step S3, as shown in FIG. 6, a magnetization response signal waveform detected when the magnetic nanoparticles are arranged in the same spatial position as the non-saturated region can be mentioned. However, the present invention is not necessarily limited to this. For example, as shown in FIG. 7, it may be a rectangular wave calculated from the maximum amplitude value and the period of the magnetization response signal waveform.

また、この再構成ステップＳ３の差分情報には、図６に示したように、各時間における前記理想波形の振幅と前記磁化応答波形の振幅との差分値の総和（面積差）が挙げられるが、必ずしもこれに限定されず、前記理想波形の磁化が飽和する時間と前記磁化応答波形の磁化が飽和する時間との差分値であってもよい。   In addition, as shown in FIG. 6, the difference information in the reconstruction step S3 includes the sum (area difference) of difference values between the amplitude of the ideal waveform and the amplitude of the magnetization response waveform at each time. However, the present invention is not necessarily limited thereto, and may be a difference value between the time when the magnetization of the ideal waveform is saturated and the time when the magnetization of the magnetization response waveform is saturated.

本発明の有効性を確認するため、図２（ａ）のように配置された磁性ナノ粒子（粒子径２０ｎｍ、飽和磁場２０ｍＴ（Ｔ×１０−３、Ｔはテスラ）、粒子間距離７ｍｍ（互いにＦＦＰから点対称に配置）を対象に、数式１、５、又は６を用いて数値解析による画像再構成を行った結果を図９に示す。数値解析では、ヘルムホルツ型コイル１、２（コイル直径５０ｍｍ、コイル間隔５０ｍｍ）と受信用コイル（直径１６ｍｍ、コイル巻数２００回）から構成されるモデルを用いた。ここで、理想波形の磁化飽和時間に応じてｃａ＝１０とした。 In order to confirm the effectiveness of the present invention, magnetic nanoparticles (particle diameter 20 nm, saturation magnetic field 20 mT (T × 10 −3 , T is Tesla)) arranged as shown in FIG. Fig. 9 shows the result of image reconstruction by numerical analysis using Formula 1, 5, or 6 with respect to FFP (point-symmetrical arrangement), in which the Helmholtz coils 1 and 2 (coil diameter) 50 mm, coil interval 50 mm) and a receiving coil (diameter 16 mm, number of coil turns 200) were used, where c a = 10 according to the ideal waveform magnetization saturation time.

まず、数式１に基づく再構成画像（従来手法、図９（ａ）参照）では、ＦＯＶの中心部分において干渉の影響が強く現れており、磁性ナノ粒子を配置した領域の約９８％の信号強度に対応した偽像が観測されている。したがって、干渉が発生している偽像における信号強度と実際に磁性ナノ粒子が存在する領域の信号強度とが同等となり、再構成画像から磁性ナノ粒子の存在の有無（分布）を識別するのは困難である。   First, in the reconstructed image based on Equation 1 (conventional method, see FIG. 9A), the influence of interference appears strongly in the central portion of the FOV, and the signal intensity is about 98% of the area where the magnetic nanoparticles are arranged. A false image corresponding to is observed. Therefore, the signal intensity in the false image where interference occurs is equal to the signal intensity in the region where the magnetic nanoparticles actually exist, and it is possible to identify the presence (distribution) of magnetic nanoparticles from the reconstructed image. Have difficulty.

一方、数式５により、検出される磁化応答波形と理想波形との差異から算出される相似性に応じた補正（本発明による補正処理）を行うことで、偽像における信号強度が磁性ナノ粒子を配置した領域の約３．６％の信号強度まで大幅に軽減できることが確認された（図９（ｂ）参照）。   On the other hand, by performing the correction according to the similarity calculated from the difference between the detected magnetization response waveform and the ideal waveform (correction processing according to the present invention) according to Formula 5, the signal intensity in the false image is reduced to the magnetic nanoparticles. It was confirmed that the signal intensity can be greatly reduced to about 3.6% of the arranged area (see FIG. 9B).

さらに、数式６において、上記補正処理に加え、奇数次高調波成分を強調すると共に偶数次高調波成分を減じる処理を施すことで、偽像における信号強度が約３．３％までに抑えられ、磁性ナノ粒子を配置した領域から生じる信号を局所化できることが示された（図９（ｃ）参照）。   Furthermore, in Expression 6, in addition to the above correction process, the signal intensity in the false image is suppressed to about 3.3% by emphasizing the odd harmonic component and reducing the even harmonic component. It was shown that the signal generated from the region where the magnetic nanoparticles are arranged can be localized (see FIG. 9C).

さらに、ＦＦＰ領域外から生じる磁化応答波形に起因した干渉の影響を実験的に評価した。評価サンプルには、粒子径１０〜１００ｎｍの磁性ナノ粒子からなる磁性流体（フェルカルボトラン）が使用された。実験にはヘルムホルツ型コイル１のみで構成される装置（コイル直径１８０ｍｍ、コイル巻数各２８５回、コイル間隔５０ｍｍ）が使用された。ヘルムホルツ型コイル１には周波数８０Ｈｚ、振幅４．７Ａの交流電流が同位相に印加されてコイル１中央において約２０ｍＴの交番磁場ＩＡＣが発生されるとともに、９．４Ａの直流電流ＩＤＣが上下のコイルへ逆方向に印加されて約１．２Ｔ／ｍ（ここで、ｍは長さメートルを意味）の傾斜磁場が発生され、コイルギャップの中心にＦＦＰが形成された。また、濃度約５００×１０−３ｍｏｌ／ｌの水ベースの上記磁性流体（フェルカルボトラン）０．５ｃｃを円筒ポリエチレン容器に封入した試験対象物（生体を模擬した試験対象物、以下「ファントム」と呼ぶ）が使用された。 Furthermore, the influence of interference caused by the magnetization response waveform generated from outside the FFP region was experimentally evaluated. For the evaluation sample, a magnetic fluid (Felcarbotran) composed of magnetic nanoparticles having a particle diameter of 10 to 100 nm was used. In the experiment, an apparatus composed of only the Helmholtz type coil 1 (coil diameter 180 mm, number of coil turns 285 times, coil interval 50 mm) was used. An alternating current having a frequency of 80 Hz and an amplitude of 4.7 A is applied to the Helmholtz-type coil 1 in the same phase to generate an alternating magnetic field I AC of about 20 mT at the center of the coil 1 and a 9.4 A direct current I DC is vertically Was applied in the reverse direction to generate a gradient magnetic field of about 1.2 T / m (where m represents a length meter), and an FFP was formed at the center of the coil gap. Further, a test object (test object simulating a living body, hereinafter referred to as “phantom”) in which 0.5 cc of water-based magnetic fluid (Fercalbotol) having a concentration of about 500 × 10 −3 mol / l is sealed in a cylindrical polyethylene container. Used).

実施例１の数値解析の条件（図２（ａ））と同様にＦＦＰに対して点対称な位置に磁性ナノ粒子を配置するために、ヘルムホルツ型コイル１が対向する方向にＦＯＶ中心から２０ｍｍの距離に２つのファントムが配置された。ＦＦＰがこれらのファントムから等距離となるコイル１，２間の中心に設定され、磁性ナノ粒子から生じる磁化応答波形がファントム周囲に配置した受信用コイル３（直径２３ｍｍ、巻数４００回）を用いて検出された。   Similar to the numerical analysis conditions of Example 1 (FIG. 2 (a)), in order to place the magnetic nanoparticles at a point-symmetrical position with respect to the FFP, the Helmholtz coil 1 is 20 mm from the center of the FOV in the facing direction. Two phantoms were placed at a distance. The FFP is set at the center between the coils 1 and 2 that are equidistant from these phantoms, and the magnetizing response waveform generated from the magnetic nanoparticles is used around the phantom using the receiving coil 3 (diameter 23 mm, number of turns 400). was detected.

ここで、補正に使用する理想波形は、コイル１，２間中心の１点のみにファントムを配置して信号検出を行うことにより取得された。なお、システム固有の非線型誤差を軽減するために、検出された磁化応答波形とファントムを配置していない場合に検出される信号との差分処理が行われた。   Here, the ideal waveform used for the correction was obtained by performing signal detection with a phantom arranged at only one point in the center between the coils 1 and 2. In order to reduce the non-linear error inherent in the system, a difference process between the detected magnetization response waveform and a signal detected when no phantom is arranged is performed.

上記の条件に基づいて、受信用コイル３で検出された磁化応答波形、及び理想波形が図１０（ａ）に示される。検出された磁化応答波形には干渉の影響が反映されており、図２に示した一例と同様に、正負の対称性と、ゼロ振幅付近で大きく変曲する応答波形となっている。本発明によりＦＦＰ領域外から生じる磁化応答波形の干渉を抑制できることを確認するため、実験で得られた磁化応答波形に数式１（従来手法）、及び数式６（本発明の提案手法）を適用した。ここで、数式６で使用する各補正係数は、実験で得られた理想波形の特性を基に決定した（Ｎｈ＝１６、α＝０．１、β＝０．１、ｋ１＝０．７４、ｋ２＝１．０、ｋ３＝０．８２、ｋ４＝１．０、ｃａ＝１２）。 A magnetization response waveform and an ideal waveform detected by the receiving coil 3 based on the above conditions are shown in FIG. The detected magnetization response waveform reflects the influence of interference, and as in the example shown in FIG. 2, the response waveform has positive and negative symmetries and a large inflection near zero amplitude. In order to confirm that the interference of the magnetization response waveform generated from outside the FFP region can be suppressed by the present invention, Formula 1 (conventional method) and Formula 6 (proposed method of the present invention) were applied to the magnetization response waveform obtained in the experiment. . Here, each correction coefficient used in Formula 6 was determined based on the characteristics of an ideal waveform obtained through experiments (N h = 16, α = 0.1, β = 0.1, k 1 = 0. 74, k 2 = 1.0, k 3 = 0.82, k 4 = 1.0, c a = 12).

検出された磁化応答波形、及び理想波形に対して、両式を用いて算出された信号強度が図１０（ｂ）に示される。上述の補正処理を施さない従来手法の場合では、ＦＦＰ領域外から生じる磁化応答波形の干渉を反映した信号強度は理想波形のそれの約８３％であるのに対して、提案手法による補正を行うことで干渉の影響を約１０％まで大幅に抑制できることが示された（図中の黒塗りの棒グラフの各値を参照）。   FIG. 10B shows the signal intensity calculated using both equations for the detected magnetization response waveform and ideal waveform. In the case of the conventional method in which the above correction processing is not performed, the signal intensity reflecting the interference of the magnetization response waveform generated from outside the FFP region is about 83% of that of the ideal waveform, whereas the correction by the proposed method is performed. Thus, it was shown that the influence of interference can be significantly suppressed to about 10% (see each value in the black bar graph in the figure).

本発明の画像再構成装置及び画像再構成方法は、以上のように構成されているので、以下のような作用効果を奏する。   Since the image reconstruction device and the image reconstruction method of the present invention are configured as described above, the following operational effects can be obtained.

本発明によれば、磁化応答信号の高調波成分の情報と磁化応答波形の飽和・非飽和時間の情報の両者を用いることで、ＦＦＰ内外から生じる磁化応答信号をより精細に分別することが可能となるため、所望としない目的領域外からの磁化応答信号の干渉を抑制し、画質の向上と画像分解能の改善が達成される。すなわち、再構成画像に表れる磁性ナノ粒子の偽像を削除・抑制することが可能となる。   According to the present invention, by using both the information of the harmonic component of the magnetization response signal and the information of the saturation / non-saturation time of the magnetization response waveform, it is possible to more precisely separate the magnetization response signal generated from inside and outside the FFP. Therefore, it is possible to suppress the interference of the magnetization response signal from outside the target area which is not desired, thereby improving the image quality and the image resolution. That is, it becomes possible to delete and suppress the false image of the magnetic nanoparticles appearing in the reconstructed image.

本発明の上記課題解決手段を講じることにより、所望としない磁化応答信号の干渉（偽像）を大幅に（従来の方法の信号強度の１／１０以下までに）抑制することが可能となる（以下の実施例の数値解析や基礎実験の結果から確認済みである）。   By taking the above-mentioned problem solving means of the present invention, it becomes possible to significantly suppress unwanted interference (false image) of the magnetization response signal (to 1/10 or less of the signal intensity of the conventional method) ( It has been confirmed from the results of numerical analysis and basic experiments in the following examples).

このため、再構成画像の分解能を向上することが可能となり、さらに、所望とする信号を検出するために必要な外部印加磁場の強度を小さくできることから、ＭＰＩ画像再構成装置を安価・小型に構成することが可能となる。   For this reason, it is possible to improve the resolution of the reconstructed image, and further, the strength of the externally applied magnetic field necessary for detecting the desired signal can be reduced. It becomes possible to do.

本発明は、磁性ナノ粒子を生体内に投与し、その非線形な磁化応答特性から生体内の状況を画像化できるＭＰＩ装置に利用でき、画像分解能を大幅に改善できる。本発明をＭＰＩ装置に適用することにより、ＭＰＩ技術は、癌等の疾病における早期診断技術として益々有望視されるであろう。   INDUSTRIAL APPLICABILITY The present invention can be applied to an MPI apparatus that can administer magnetic nanoparticles into a living body and image the state of the living body from its nonlinear magnetization response characteristics, and can greatly improve image resolution. By applying the present invention to an MPI apparatus, the MPI technology will become increasingly promising as an early diagnosis technology in diseases such as cancer.

本発明は上記実施例に限定されることなく、特許請求の記載した発明の範囲内で種々の変更が可能であり、それらも本発明の範囲に含まれることはいうまでもない。   The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the invention described in the claims, and it goes without saying that these are also included in the scope of the present invention.

１ ヘルムホルツ型コイル（磁場発生手段）
２ ヘルムホルツ型コイル（磁場発生手段）
３ 受信コイル（検出手段）
４ 計算処理装置（再構成手段）
１０ 画像再構成装置 1 Helmholtz type coil (magnetic field generating means)
2 Helmholtz type coil (magnetic field generating means)
3 Receiving coil (detection means)
4. Calculation processing device (reconstruction means)
10 Image reconstruction device

Claims (12)

磁性ナノ粒子が存在する撮像領域に、該磁性ナノ粒子の磁化が飽和する飽和領域と該飽和領域よりも磁場強度が低い非飽和領域とを有する局所磁場分布を印加するとともに、オフセット磁場と交番磁場とをさらに印加する磁場発生手段と、
前記磁場発生手段の前記交番磁場の印加によって前記磁性ナノ粒子から発生する磁化応答信号を検出する検出手段と、
前記検出手段によって検出された前記磁化応答信号を画像情報として再構成する再構成手段と、を備え、かつ、
前記再構成手段は、前記検出手段によって前記非飽和領域において検出された前記磁化応答波形と比較すべき理想波形を取得し、
前記再構成手段は、前記理想波形と前記磁化応答波形との差分情報を補正係数として算出して該補正係数により前記磁化応答波形の信号強度に重み付けを行うことを特徴とする磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。 Applying a local magnetic field distribution having a saturated region where the magnetization of the magnetic nanoparticle is saturated and a non-saturated region where the magnetic field strength is lower than the saturated region to the imaging region where the magnetic nanoparticle exists, an offset magnetic field and an alternating magnetic field A magnetic field generating means for further applying
Detecting means for detecting a magnetization response signal generated from the magnetic nanoparticles by application of the alternating magnetic field of the magnetic field generating means;
Reconstructing means for reconstructing the magnetization response signal detected by the detecting means as image information, and
The reconstruction means obtains an ideal waveform to be compared with the magnetization response waveform detected in the non-saturation region by the detection means;
The reconfiguration means calculates difference information between the ideal waveform and the magnetization response waveform as a correction coefficient, and weights the signal intensity of the magnetization response waveform by the correction coefficient. An image reconstruction device using a response signal. 前記再構成手段は、前記重み付けを行う前に前記磁化応答信号波形から前記磁化応答波形のオフセット成分を減じた後に前記磁化応答波形の振幅最大値で正規化し、かつ、
前記理想波形が、前記非飽和領域と同一の空間位置に前記磁性ナノ粒子が配置された場合に検出される磁化応答信号波形であることを特徴とする請求項１に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。 The reconstruction means normalizes with the maximum amplitude value of the magnetization response waveform after subtracting the offset component of the magnetization response waveform from the magnetization response signal waveform before performing the weighting; and
The magnetization of the magnetic nanoparticles according to claim 1, wherein the ideal waveform is a magnetization response signal waveform detected when the magnetic nanoparticles are arranged in the same spatial position as the unsaturated region. An image reconstruction device using a response signal. 前記理想波形が、前記磁化応答波形の前記振幅最大値と周期とから算出される矩形波であることを特徴とする請求項１に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。   The image reconstruction device using a magnetic response signal of magnetic nanoparticles according to claim 1, wherein the ideal waveform is a rectangular wave calculated from the maximum amplitude value and the period of the magnetization response waveform. . 前記差分情報が、各時間における前記理想波形の振幅と前記磁化応答波形の振幅との差分値の総和であることを特徴とする請求項１〜３のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。   The magnetization response of the magnetic nanoparticles according to claim 1, wherein the difference information is a total sum of difference values between the amplitude of the ideal waveform and the amplitude of the magnetization response waveform at each time. An image reconstruction device using signals. 前記差分情報が、前記理想波形の磁化が飽和する時間と前記磁化応答波形の磁化が飽和する時間との差分値であることを特徴とする請求項１〜３のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。   The magnetic nanoparticle according to claim 1, wherein the difference information is a difference value between a time when the magnetization of the ideal waveform is saturated and a time when the magnetization of the magnetization response waveform is saturated. Reconstruction device using the magnetization response signal of 前記信号強度は、前記磁化応答波形の高調波信号の奇数次高調波成分が強調され、かつ／又は、該高調波信号の偶数次高調波成分が減衰された信号に基づいて算出されていることを特徴とする請求項１〜５のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成装置。   The signal intensity is calculated based on a signal in which an odd harmonic component of the harmonic signal of the magnetization response waveform is emphasized and / or an even harmonic component of the harmonic signal is attenuated. An image reconstruction device using a magnetization response signal of magnetic nanoparticles according to any one of claims 1 to 5. 磁性ナノ粒子が存在する撮像領域に、該磁性ナノ粒子の磁化が飽和する飽和領域と該飽和領域よりも磁場強度が低い非飽和領域とを有する局所磁場分布を印加するとともに、オフセット磁場と交番磁場とをさらに印加する磁場発生ステップと、
前記磁場発生ステップの前記交番磁場の印加によって前記磁性ナノ粒子から発生する磁化応答信号を検出する検出ステップと、
前記検出ステップによって検出された前記磁化応答信号を画像情報として再構成する再構成ステップと、を備え、かつ、
前記再構成ステップは、前記検出ステップによって前記非飽和領域において検出された前記磁化応答波形と比較すべき理想波形を取得し、
前記再構成ステップは、前記理想波形と前記磁化応答波形との差分情報を補正係数として算出して該補正係数により前記磁化応答波形の信号強度に重み付けを行うことを特徴とする磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。 Applying a local magnetic field distribution having a saturated region where the magnetization of the magnetic nanoparticle is saturated and a non-saturated region where the magnetic field strength is lower than the saturated region to the imaging region where the magnetic nanoparticle exists, an offset magnetic field and an alternating magnetic field And a magnetic field generating step for further applying
A detection step of detecting a magnetization response signal generated from the magnetic nanoparticles by application of the alternating magnetic field of the magnetic field generation step;
Reconstructing the magnetization response signal detected by the detecting step as image information, and
The reconstruction step obtains an ideal waveform to be compared with the magnetization response waveform detected in the non-saturation region by the detection step;
The reconstructing step calculates difference information between the ideal waveform and the magnetization response waveform as a correction coefficient, and weights the signal intensity of the magnetization response waveform by the correction coefficient. An image reconstruction method using a response signal. 前記再構成ステップは、前記重み付けを行う前に前記磁化応答信号波形から前記磁化応答波形のオフセット成分を減じた後に前記磁化応答波形の振幅最大値で正規化し、かつ、
前記理想波形が、前記非飽和領域と同一の空間位置に前記磁性ナノ粒子が配置された場合に検出される磁化応答信号波形であることを特徴とする請求項７に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。 The reconstruction step includes subtracting an offset component of the magnetization response waveform from the magnetization response signal waveform before performing the weighting, and then normalizing with a maximum amplitude value of the magnetization response waveform; and
The magnetization of the magnetic nanoparticles according to claim 7, wherein the ideal waveform is a magnetization response signal waveform detected when the magnetic nanoparticles are arranged in the same spatial position as the unsaturated region. An image reconstruction method using a response signal. 前記理想波形が、前記磁化応答波形の前記振幅最大値と周期とから算出される矩形波であることを特徴とする請求項７に記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。   The image reconstruction method using the magnetization response signal of magnetic nanoparticles according to claim 7, wherein the ideal waveform is a rectangular wave calculated from the maximum amplitude value and the period of the magnetization response waveform. . 前記差分情報が、各時間における前記理想波形の振幅と前記磁化応答波形の振幅との差分値の総和であることを特徴とする請求項７〜９のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。   The magnetic response of the magnetic nanoparticles according to claim 7, wherein the difference information is a sum of difference values between the amplitude of the ideal waveform and the amplitude of the magnetization response waveform at each time. Image reconstruction method using signals. 前記差分情報が、前記理想波形の磁化が飽和する時間と前記磁化応答波形の磁化が飽和する時間との差分値であることを特徴とする請求項７〜９のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。   The magnetic nanoparticle according to claim 7, wherein the difference information is a difference value between a time when the magnetization of the ideal waveform is saturated and a time when the magnetization of the magnetization response waveform is saturated. Reconstruction method using the magnetization response signal. 前記信号強度は、前記磁化応答波形の高調波信号の奇数次高調波成分が強調され、かつ／又は、該高調波信号の偶数次高調波成分が減衰された信号に基づいて算出されていることを特徴とする請求項７〜１１のいずれかに記載の磁性ナノ粒子の磁化応答信号を利用した画像再構成方法。   The signal intensity is calculated based on a signal in which an odd harmonic component of the harmonic signal of the magnetization response waveform is emphasized and / or an even harmonic component of the harmonic signal is attenuated. The image reconstruction method using the magnetization response signal of the magnetic nanoparticles according to any one of claims 7 to 11.
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CN113534025A (en) * 2021-07-21 2021-10-22 北京航空航天大学 Magnetic nanoparticle imaging method based on non-ideal magnetic field-free point
WO2023062810A1 (en) * 2021-10-15 2023-04-20 三菱電機株式会社 Magnetic particle imaging device, magnetic particle imaging method, and magnetic particle imaging program

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