JP2004516052A - Method, system, and program for measuring hematocrit in blood vessels - Google Patents

Abstract

The methods, systems, and computer program products allow analysis for the amount of various blood components, such as red blood cells. The images are analyzed to determine the structure of the body vessel and measurable parameters, such as the diameter of the body vessel and the optical density. In some implementations of the invention, the coefficient of variation determines a diameter measurement along the vessel and the fractional volume is calculated for red blood cells. The fraction amount is used for calculation of hematocrit (Hct). In another example, the coefficient of variation is determined by multiple optical density measurements at multiple locations along the body vessel, and the fractionation and Hct are calculated from the coefficient of variation of the optical density measurement. In another implementation, the change in optical density is measured from a time series of images of a single body vessel. The fractionation and hematocrit are calculated from the variation.

Description

平均
【数２】

の標準偏差は（数５）の平方根に比例し、変動係数（Ｃ．Ｖ．）はこの方法を通じて標準偏差と同様に計算でき、または、
【数３】

【００３８】
（数１）と（数３）を組み合わせると、赤血球数の変動や偏差の測定は以下のように示される。
【００３９】
【数４】

【００４０】
従ってＮの変動係数はＨｃｔや血管の直径の関数である。該変動は血管の作成されたイメージに従った光学強度や直径の変動により出現する。あるいは、該変動は血管の特定個所におけるイメージの時系列内の直径や光学強度の変動のどちらにしても出現する。
【００４１】
上記のように、Ｈｂの測定のための反射スペクトルイメージングの使用は血管が均一に満ちているという仮定に基づいている。血管長に従って測定された赤血球数の高い変動は血管が不均一に満ちていることを示している。（数４）を参照すると、変動係数は血管の直径と反比例の関係にあることがわかる。５０ミクロンを超える直径を有する、より大きな血管は低い変動係数を持ち、Ｈｂの均一な分布を有することを示唆する。
【００４２】
図１ｂは直径Ｄの典型的な小さい血管を示す。小さい血管は６ミクロン以下の直径を有する。この範囲の血管の大きさは赤血球の大きさ（ｄで示す）に匹敵する。従って、典型的には一つの流れの赤血球のみが血管内を流れることができる。この場合、分光測光（ベーア法など）をＭＣＨＣの計算に使用できるが、ＨｃｔやＨｂの測定には使用できない。赤血球濃度は血管に沿って赤血球をカウントすることにより測定することができる。
【００４３】
６〜６０ミクロンの、中間の大きさの血管（図１ａの血管１００など）では、高い変動（１０〜２０％）がＨｂの非均一の分布を示し、ＨｂやＭＣＨＣの概算にベーア法の使用が困難となる。血管のサイズは複数の赤血球の流れを可能にするが、個々の細胞のカウントによるＲＢＣ（赤血球）の正確な測定をするための分光測光の使用を損なう。事実、この範囲の血管は赤血球の直径の２から１５倍である。満たされていない血管では、本発明の方法やシステムは変動係数や血管直径からＨｃｔの計測に使用できる。
【００４４】
図１ｃは直径Ｄの典型的な大きな血管を示し、反射特性の個々の測定や、従って分光測定（ベーア法など）がＨｂの測定に使用される。小さい血管では、赤血球数の高い変動は反射スペクトルイメージで測定する光学強度の関数として測定したＨｂへ大きな影響を与える。
【００４５】
図２は測定された血管直径を示す。図のように、“ｍ”直径測定（２０２，２０４，２０６，２０８）は血管１００の軸に沿って測定された。
図３は測定された血管の強度を示す。図のように、“ｍ”強度測定は血管１００の軸に沿って測定された。光源（３０２，３０４，３０６，３０８）はＩ_０ｎと示されている。減衰した光（３１２，３１４，３１６，３１８）はＩ_ｎと示されている。
【００４６】
図４では、フローチャート４００が本発明の一般的な操作のフローを表している。さらに、フローチャート４００は血管のヘマトクリット測定のための制御フローの例を示す。
【００４７】
図４はステップ４０１にて始まり、ステップ４０５においてイメージがメモリソースかイメージディレクトリから検索される。イメージはハードディスクドライブや着脱可能なストレージデバイス、例えばフロッピーディスク、磁気テープ、光学ディスクなど、当業者が考えうるものである、上記した一時的、或いはや永久的な記憶箇所において記憶された入力ファイルから獲得できる。また入力ファイルは、対象の番号や対象の識別に使用できる他のデータからなる。あるいは、イメージは “１２０特許”と“８５９出願”で示されるような種類（これは望ましいが、必須ではない）のイメージング装置からリアルタイムで獲得できる。
【００４８】
ステップ４１０では、複数の測定が異なる部分の直径を測定するため軸に沿って行われる。図２を参照すると、“ｍ”直径測定（２０２，２０４，２０６，２０８）は血管１００の軸に沿って行われた。当業者には理解できるように、様々な測定や分割が十分な正確な直径の測定を獲得するためにあるべきである。ステップ４１５では、直径測定が変動係数を決定するために分析される。
【００４９】
ステップ４２０では、細胞コンポーネント（赤血球など）の分画値が血管に対して決定される。２つの方法が分画値の決定に使用される。第一の方法では、細胞コンポーネントの分画の値は各部分の変動係数の積の逆数（ｔｈｅ ｒｅｃｉｐｒｏｃａｌ ｏｆ ｔｈｅ ｐｒｏｄｕｃｔ）に直径測定を用いて、各部分ごとに決定する。第二の方法では、細胞コンポーネントの分画の値は変動係数の積の逆数と直径測定の平均を用いて決定できる。
【００５０】
ステップ４２５では、Ｈｃｔが分画値の平均値から計算される。仮に、第一の方法で分画の値を決定に使用した場合、全ての分画値測定の平均が計算され、Ｈｃｔの概算に使用する。しかし、第二の方法を使用した場合、ステップ４２０で計算された平均分画の値をＨｃｔの概算に使用するだろう。Ｈｃｔが計算された後、フローチャート４００の制御フローはステップ４９５に示されるように終了する。
【００５１】
図５において、フローチャート５００は本発明の別例における一般的な操作フローを示す。より詳細には、血管のヘマトクリットの測定に光学密度を使用する制御フローの例を示している。
【００５２】
図５はステップ５０１にて開始され、そのあとステップ４０５からステップ４１０までは図４に示したように進行する。ステップ５１０では、血管は軸に沿った複数の部分において元の光や減衰光の強度を測定するために照射される。図３を参照すると、“ｍ”強度測定が血管１００の軸に沿って行われる。強度プロフィール（ｉｎｔｅｎｓｉｔｙ ｐｒｏｆｉｌｅ）は測定された減衰光の比率の対数に負の符号をつけたものと光学密度を作るための元の光強度とを計算することにより作成される。
【００５３】
ステップ５１５では、光学密度測定は変動係数を決定するために分析される。ステップ５２０では、細胞コンポーネントでの分画値は変動係数の積の逆数と各部分の直径測定を用いて各部分ごとに決定される。図４で示したように、細胞コンポーネントの分画値はまた変動係数の積の逆数と直径測定の平均を用いて決定できる。
【００５４】
ステップ５２５では、分画値測定の全ての平均はＨｃｔを概算するために使用される。しかし、仮に第二の方法を分画値の決定に使用する場合、ステップ５２０で決定する平均分画値はＨｃｔを概算するために使用され得る。フローチャート５００の制御フローはステップ５９５で示すように終了する。
【００５５】
従って、血管の形成されたイメージに沿ってでも、血管内のある位置の時系列のイメージのどちらでも、光学密度や直径の変動係数から被験者のヘマトクリットを示すことが可能である。図６は本発明の方法やシステムの実行の比較研究の結果を示している。研究中、インビトロ測定した血液サンプルを９つの被験者から採取し、ヘマトクリットの決定に使用した。本発明の方法を使用してた９つの被験者の目（強膜など）からの生体イメージは“１２０特許”と“８５９出願”に示されているような、直交変更分光法を使用して獲得された。
【００５６】
各被験者は、５つの血液部分を直径と光学密度測定の決定に選択した。血管ごとに沿った光学密度の変動がまた測定された。次に、各部分に対する変動の積の逆数と直径が計算された。さらに、９つの各被験者に対して平均量を単純ヘマトクリット概算にインビボ測定の結果と組み合わせて計算した。
【００５７】
インビボとインビトロ測定の結果を図６に示す。縦軸はインビボ測定で決定されたヘマトクリットを示し、横軸はインビトロ測定のヘマトクリットを示している。ヘマトクリット計算の係数（Ｓｌｏｐｅ）は０．９１であり、これはインビボ測定がインビトロ測定の非常に近似していることを示唆している。
【００５８】
後述より明らかなように、本発明は本来、非侵襲的手段により血液コンポーネントを分析用に開発された。しかし、当業者には明らかなように、本発明の分析技術は上記の医学的な用途を超えて使用できる。本発明は医学領域外の応用を備え、光を透過させ反射するような透明な管や、壁などの、どのような管内の流れの中を浮遊している可視コンポーネントの定量分析に一般的に使用できる。本発明は６−６０ミクロン間の直径をもつ管を分析するために最も効率的であり、分光測光法により感知できる最も適当な大きさである。より適した範囲は１５−５０ミクロンで変動係数の平均が１０−２０％である。
【００５９】
本発明はハードウェア、ソフトウェア、それらの組合せにより実施可能であり、一つまたは複数のコンピュータシステムや他のプロセシングシステム内で実行可能である。事実、ある実施では、本発明はここに示された機能を実行可能な一つ若しくは複数のコンピュータシステムについて説明している。
【００６０】
図７では、本発明の実装に適したコンピュータシステム７００の例を示している。コンピュータシステム７００はプロセッサ７０４など、一つか複数のプロセッサを備える。プロセッサ７０４はコミュニケーションインフラストラクチャー７０６（コミュニケーションバス、クロスオーバー バー（Ｃｒｏｓｓ−ｏｖｅｒ ｂａｒ）、ネットワークなど）に接続される。様々なソフトウェアの実施が典型的なコンピュータシステムに関して説明される。後記の記載により、当業者は本発明を他のコンピュータシステムや／またはコンピュータアーキテクチャーを使用してどのように実施するか理解できる。
【００６１】
コンピュータシステム７００はコミュニケーションインフラストラクチャー７０６（またはフレームバッファ図示せず）からディスプレイユニット７３０上に表示するために、イメージ、文章または他のデータを送るディスプレイインターフェース７０２を備える。
【００６２】
コンピュータシステム７００はメインメモリ７０８（ランダムアクセスメモリ（ＲＡＭ））と第二メモリ７１０とを備える。第二メモリ７１０は、例えば、ハードディスクドライブ７１２及び／又はフロッピーディスクドライブ、磁気テープドライブ、光学ディスクドライブなどリムーバブルストレージドライブ７１４を備え得る。リムーバブルストレージドライブ７１４は周知の手段で、リムーバブルストレージユニット７１８から読み込み及び／又は書き込みをする。リムーバブルストレージユニット７１８はフロッピーディスク、磁気テープ、光学ディスクなどで、これらはリムーバブルストレージドライブ７１４により読まれたり、書き込まれたりする。周知のように、リムーバブルストレージユニット７１８はその中にコンピュータソフトウェア及び／又はデータを保存できるコンピュータ使用可能保存媒体からなる。
【００６３】
別の実施で、第二メモリ７１０はコンピュータプログラムやコンピュータシステム７００でロードされる他の指示を可能にする他の同様な手段を備え得る。このような手段は、例えば、リムーバブルストレージユニット７２２とインターフェース７２０からなり得る。このような例はプログラムカートリッジや（ビデオゲームデバイスで見られるような）カートリッジインターフェースや、（ＥＰＲＯＭやＰＲＯＭなど）リムーバブルメモリチップや、関する（ａｓｓｏｃｉａｔｅｄ）ソケットや、他のリムーバブルストレージユニット７２２や、リムーバブルストレージユニット７２２からコンピュータシステム７００にソフトウェアやデータを転送可能なインターフェース、などからなる。
【００６４】
コンピュータシステム７００はコミュニケーションインターフェース７２４を備える。コミュニケーションインターフェース７２４はソフトウェアやデータをコンピュータシステム７００と外部のデバイス間で転送可能にする。コミュニケーションインターフェース７２４の例としては、モデムや、（イーサーネットカード）ネットワークインターフェースや、コミュニケーションポートや、ＰＣＭＣＩＡスロットやカードなどからなる。ソフトウェアやデータをコミュニケーションインターフェース７２４により経由する転送は電子通信や、電磁気や、光通信や、コミュニケーションインターフェース７２４より受信可能な他の信号などの信号７２８のフォームで行われる。信号７２８はコミュニケーション経路（チャンネルなど）７２６を経由してコミュニケーションインターフェース７２４に供給される。このチャネル７２６は信号７２８を送信し、ワイヤーや、ケーブルや、光ファイバーや、電話線や、セルラーフォンリンクや、ＲＦリンクや、他のコミュニケーションチャネルを使用して実施される。
【００６５】
この文章内の、“コンピュータプログラム媒体”と“コンピュータ使用可能媒体”はリムーバブルストレージドライブ７１４や、ハードディスクドライブ７１２内にインストールされたハードディスクや、信号７２８等、一般に媒体といわれるものに対して使用される。コンピュータプログラムプロダクトはコンピュータシステム７００にソフトウェアを供給する手段である。
【００６６】
コンピュータプログラム（コンピュータ制御ロジックとも言われる）はメインメモリ７０８及び／又は第二メモリ７１０に保存される。コンピュータプログラムはまたコミュニケーションインターフェース７２４を経由して受信される。このようなコンピュータプログラムは、実行時、ここで示したようにコンピュータシステム７００が本発明の形態を実行可能にする。具体的には、コンピュータプログラムは、実行時プロセッサ７０４が本発明の形態を実行可能にする。従って、このコンピュータプログラムはコンピュータシステム７００のコントローラに相当する。
【００６７】
本発明がソフトウェアを使用して実行される時、ソフトウェアはコンピュータプログラムプロダクト内に保存され、リムーバブルストレージドライブ７１４や、ハードディスクドライブ７１２や、コミュニケーションインターフェース７２４を使用してコンピュータシステム７００内でロードされる。制御ロジック（ ソフトウェア） 、プロセッサ７０４により実行される際、プロセッサ７０４がここで示した本発明の機能を実行させる。
【００６８】
他の実施では、本発明は主にハードウェア内で特定用途向け集積回路（ＡＳＩＣｓ）等のハードウェアコンポーネントを使用して実行される。ここで記述した機能を実行するためのハードウェア状態機械の実装は当業者に容易に理解される。
【００６９】
他の実施は、本発明はハードウェアとソフトウェアの双方の組合せを使用して実施される。
様々な本発明の実施を示してきた、これは例として理解を助けるものであって、制限されるものではない。当業者は容易に様々な形態や詳細の変更を本発明の精神と範囲から逸脱することなく行うことができる。従って本発明は、上記の実施例により制限されるものではない。
【図面の簡単な説明】
【図１ａ】赤血球を含む中間血管の横断面図
【図１ｂ】赤血球を含む小血管の横断面図
【図１ｃ】赤血球を含む大血管の横断面図
【図２】本発明の実施により測定された血管の直径の例示
【図３】本発明の実施により測定された強度の例示
【図４】本発明の実施による直径測定の変形例によりヘマトクリットの測定の一般的な実行フローを説明するフローチャート
【図５】本発明の実施による光学密度測定の変形例によりヘマトクリットの測定の一般的な実行フローを説明するフローチャート
【図６】本発明によるヘマトクリット測定とインビトロのヘマトクリット測定の比較
【図７】本発明を実装するために使用するコンピュータシステムのブロックダイヤグラムの例[0001]
Background of the Invention
1. Field of the invention
The present invention relates to reflected light analysis. In particular, the present invention relates to the use of reflectance spectral imaging for measuring the amount of visible components in a fluid flowing through a tubular system. Further, the invention relates to reflectance spectral imaging for measuring the amount of components in blood in mammals, especially human vascular systems.
[0002]
2. Related technology
It is widely accepted by the medical school that whole blood count with leukocyte classification (CBC + Diff) is one of the best tests for examining overall patient health. In doing so, anemia, infection, blood loss, acute and chronic illness, allergies, and other conditions can be found and diagnosed. The CBC + Diff analysis measures comprehensive information of blood components, such as red blood cell count, hematocrit, hemoglobin concentration, size and shape indicators, and the number of total red blood cells (RBC) capable of carrying red blood cells. Further, CBC + Diff measures the number and type of white blood cells and the number of platelets. CBC + Diff is one of the most frequently performed diagnoses, with about 2 billion performed in the United States each year.
[0003]
The classic CBC + Diff is an "invasive" method, in which a sample of venous blood is drawn from a patient with a needle and submitted to the laboratory for analysis. For example, a phlebotomist (with his own special training in blood collection) collects a venous blood sample in a tube coated with an anticoagulant to prevent blood clotting. The sample is sent to a hematology laboratory and processed, typically automatically, by a multi-parameter analyzer. These devices are manufactured by Beckman Coulter Diagnostics of Miami, Florida and the like. Generally, the results of the CBC + Diff test are returned to the physician in need the next day.
[0004]
Newborns have not yet fully grown their circulatory system. Because of this, invasive techniques, such as the traditional CBC + Diff test, pose certain problems for newborns. Generally, blood is drawn using the "Heel Stick" method, which involves drilling one or more holes in the heel of the newborn and repeatedly squeezing the blood into a blood collection tube. This technique also injures healthy infants. More importantly, because of the low blood volume of infants, this procedure carries the risk of requiring blood transfusion. The newborn's total blood volume is 60-70 cc / Kg per body weight. Thus, the total blood volume of low weight newborns (up to 2500 grams) treated in a neonatal intensive care unit is in the range of 45-175 cc. Due to their low blood volume and delayed erythropoiesis after birth, sampling blood from infants with pre-production neonates and other illnesses will force infants to transfuse. The use of a blood bank to transfuse neonates in neonatal intensive care units occurs almost as often as performing blood transfusions in cardiac surgery. In addition to newborns, invasive techniques are also burdensome and difficult for children, elderly patients, burn patients, and patients in intensive care units.
[0005]
There is a difference between laboratory results and physical examination results. The boundary between the results of a physical examination of a patient and the results of a laboratory is generally the result of technology limitations. For example, in the diagnosis of anemia, quantification of hemoglobin concentration and hematocrit is often required to confirm the observation result of pallor. Paleness is a lack of pink color in the skin, often representing a deficiency or a decrease in the concentration of hemoglobin, a red and heavy pigment. However, in some cases, pallor of the peripheral vessels is the result of other causes, such as, for example, compression of the peripheral vessels, and is obscured by skin pigmentation. Clinicians have found that pallor of anemia can be more accurately detected in the mucous membranes, conjunctiva, lips, and nail folds of the mouth because some parts of the integument are less affected by these factors.
[0006]
A device that would allow rapid, invasive, and quantitative diagnosis of anemia directly by observing some or more of the above ranges would obviate the need for a venous blood sample to determine anemia. Such a device eliminates the delay of waiting for the results of a laboratory patient test. Such a device also has the advantage of increasing patient satisfaction.
[0007]
Soft tissues such as mucous membranes and skin without pigments do not absorb visible or near infrared light. In particular, soft tissue cannot absorb light in the spectral region that hemoglobin absorbs. This allows the differentiation of angiogenesis by spectral absorption from the surrounding soft tissue background. However, the surface of soft tissue reflects light strongly, and the soft tissue itself diffuses light almost entirely due to penetration of only 100-500 microns. Therefore, visualizing the circulation in vivo is generally not practical. This is because finding an appropriate area and / or compensating for multiple scattering and surface specularity is complicated. For this reason, visualization of cells in microcirculation has been studied using thin sections of tissue containing microcirculation (thickness below multiple scattering), such as the mesentery, using a microscope using transmitted light. Most of the observations were invasive. As another study, an experiment of creating an image of a tissue using a time gate in a multiple scattering region has been performed (Yoda, AB, Chance Physic Today, March, 1995, 34-40). However, the resolving power of such an image is limited, because the diffusion of light and the calculation of the diffusion factor are complicated.
[0008]
Some imaging studies have been performed with reflected light from the microcirculation of the nail bed in patients with Raynaud's disease, diabetes and sickle cell disease. These studies were performed to obtain experimental data on capillary density, capillary shape, and blood flow velocity, and were limited to global physical measurements on the capillaries. No spectral measurements were taken, individual cell measurements were taken and Doppler techniques were used to measure velocity. The non-invasive techniques adopted in these studies are applicable to most patients and may be more appropriate.
[0009]
US Patent No. 4,998,533 to Winkleman discloses a non-invasive device for in vivo analysis (hereinafter the Winkleman device). The Winkleman device uses image analysis and reflection spectroscopy to measure individual cell parameters such as cell size and number. Measurements are made only in small blood vessels, for example in capillaries where individual cells can be visualized. It is believed that the Winkleman device is used only in capillaries and cannot accurately reflect large vessel measurements. This inaccuracy is a result of the constantly changing relationship between cell volume and blood volume in small capillaries due to the non-Newtonian viscous properties of blood. Therefore, the true hematocrit or the total hemoglobin concentration existing at the center cannot be measured by the Winkleman apparatus.
[0010]
The Winkleman device measures the white blood cell count relative to the red blood cell count by counting individual cells flowing through the microcapillary. The Winkleman device needs to accumulate white blood cells by a statistically reliable number to estimate the concentration. However, the blood flow through the microcapillary contains about 1000 red blood cells for each white blood cell, which is an impractical method. The Winkleman device does not provide a means for visualizing and counting platelets. Furthermore, the Winkleman device does not provide a means for visualizing capillary plasma and measuring the amount of capillary plasma. The Winkleman device also does not provide a means for detecting abnormal blood components such as tumor cells.
[0011]
Other in vivo devices include Warren Groner and Richard G. G. 'Method and Apparatus for Reflection Imaging Analysis', issued by Richard G. Nadeau on November 9, 1999, U.S. Pat. No. 5,983,120 (hereinafter referred to as "the' 120 patent"), and Christopher Cook. And mark M. 'Method and Apparatus for Providing High Contrast Imaging', filed on September 22, 1999 by Mark M. Meyers, is disclosed in US patent application Ser. No. 09 / 401,859 (hereinafter the “859 application”). . The disclosures of the "120 patent" and the "859 application" are all incorporated herein. The devices of the '120 patent and the' 859 application provide for in vivo analysis of non-invasive vascular systems. These devices provide high resolution of visualization of blood cell components (red blood cells, white blood cells, platelets), blood rheology, visualization of blood vessels and the entire vascular system. The "120 patent" and the "859 application" device allow quantitative measurement of normal and abnormal contents of blood cells, such as normal and abnormal components of blood cells and plasma.
[0012]
The devices of the '120 patent and the' 859 application capture a raw reflection image of a blood sample and modify this image against the background to form a modified reflection image. The analysis image is split from the modified reflection image to include the locations needed for the analysis. The methods and apparatus disclosed in the "120 patent" and the "859 application" employ the Behr method of measuring properties such as hemoglobin concentration for each unit of blood volume. The reflected images created by the “120 patent” and “859 application” devices are the white blood cell count for each blood volume, the average cell volume, the platelet count for each blood volume, and the total volume called hematocrit. It can be used for measuring cell volume ratio and the like.
[0013]
The Beer method, which uses spectral images to measure the amount of blood vessel components, requires that the components flow uniformly through the vessel. For example, the Bohr method can be used to measure hemoglobin concentration from in vivo measurement of optical density at absorption wavelengths such as the hemoglobin absorption spectrum. However, this technique assumes that the red blood cells are evenly filled in the blood vessel. When measuring with a spectral image, it is most important that this image contains a representative sample of blood components such as red blood cells. If the blood vessel contains a non-uniform flow of red blood cells, the spectral image will contain little representative sample of the blood component. Further, optical density measurements vary widely over time, and individual measurements do not accurately reflect true hemoglobin concentrations.
[0014]
The size of the vessel diameter directly affects the flow of blood components. In a large blood vessel having a blood vessel diameter many times larger than the blood cell diameter, when represented by red blood cells, red blood cells containing hemoglobin flow uniformly along the blood vessel. Thus, a spectral image of a thick blood vessel tends to include a representative sample of blood components, such as the average number of red blood cells. In this case, the Bohr method can be used to make an accurate measurement of hemoglobin concentration.
[0015]
However, the variation in the number of red blood cells is more pronounced in small blood vessels. As the blood vessel diameter becomes smaller, the number of red blood cells that pass side by side through the blood vessel decreases. In the smallest blood vessels, only one red blood cell flow can pass. In small blood vessels, the number of red blood cells in the spectral image can vary significantly with time and vessel length. As a result, it is difficult to obtain a representative image of the target blood vessel. Therefore, the measurement of optical density and hemoglobin by the Bohr method has limitations due to inaccuracy.
[0016]
Intermediate sized vessels having a vessel diameter larger than the diameter of one red blood cell, but not large enough to evenly fill the red blood cells, have significant results in both the Cell Count method and the Baer method. Cannot be used without change. However, when implementing the methods of the '120 patent and the' 859 application, this is the range of vessel diameters that is most easily accessible for visualization and measurement.
[0017]
Accordingly, there is a need for techniques and systems for quantitative analysis of selected images of fluids having non-uniformly distributed concentrations of cellular components using non-invasive techniques in vivo.
[0018]
Summary of the present invention
The present invention relates to reflection spectrum image analysis of a small circulation system for measuring the volume and concentration of arteries, veins, capillaries, and the like. The methods and systems of the present invention analyze non-uniformly distributed fluids of cellular components. The invention can be used to determine the cell concentration of unfilled blood vessels. Basically, the methods and systems of the present invention measure the diameter and optical density of a blood vessel at various locations along the vessel axis. The coefficient of variation of the diameter and / or optical densitometry is used to measure blood properties such as hematocrit.
[0019]
This method is used to perform in vivo analysis of blood in blood vessels from spectral images. In addition, the method of the present invention can be used, for example, to perform in vitro analysis by imaging blood or floating cells in peripheral blood vessels.
[0020]
The method of the present invention can be used to analyze other types of fluids containing visible suspended particles. Spectral imaging systems can be used to analyze fluids for particulate impurities. The walls of the fluid path must have sufficient permeability to allow light to pass through the fluid and the flow of impurities in the path.
[0021]
Configuration and benefits
The arrangement of the present invention can be used to identify properties such as hematocrit by using reflection spectral imaging.
Another configuration of the present invention can be used to identify intravenous blood characteristics having non-uniformly distributed blood components.
[0022]
An advantage of the present invention is that it provides a fast, non-invasive means of measuring clinically important parameters of the CBC + Diff test.
A further advantage of the present invention is that it eliminates the invasive technique of blood collection. This eliminates the pain and difficulties of newborns, children, elderly patients, burn patients, and patients in intensive care units. The present invention reduces the risk of transmission of AIDS, hepatitis and other hematogenous diseases.
[0023]
A further advantage of the present invention is that the overall cost can be reduced by eliminating the cost of transporting, treating, and discarding samples with respect to conventional invasive techniques.
A further advantage of the present invention is that it allows the measurement of hematocrit without having to independently measure red blood cells. Thus, according to the present invention, even if individual red blood cells cannot be clearly imaged, the measurement of the red blood cell count can be performed accurately.
[0024]
Best Practice
The present invention relates to methods and systems for performing quantitative analysis, particularly non-invasive, in vivo analysis of a vascular system of a subject. The in vivo measurement here can also be performed in vitro by imaging blood or floating cells in a tube. This will be clear to the skilled person. A spectral imaging device of the type disclosed in the "120 patent" and the "859 application" is not required, but desirable, for image acquisition. Also, images can be acquired on any type of imaging device designed to create a contrast image of suspended matter in the vascular system due to transmitted or reflected light. As disclosed in the '120 patent and the' 859 application, the spectral imaging device comprises a light source used to illuminate a portion of the target vascular system to be imaged. The reflected light is collected by the image collecting means. Suitable image acquisition devices include cameras, film media, photocells, photodiodes, electronically coupled device cameras (CCD cameras), and the like. An image correction and analysis means such as a computer is connected to an image collection means for performing image correction, segmenting the screen, and analyzing blood characteristics.
[0025]
The in vivo method of the invention is performed by imaging a portion of the target vascular system. For example, the image can be created from the lower surface (Sub-surface) of the target tissue or organ. Therefore, it is desirable that the tissue covering the part to be imaged transmit light and be relatively thin, such as the mucous membrane inside the lips and the sclera of the subject's eyeball. As used herein, "light" refers to electromagnetic radiation of any wavelength comprising the infrared, visible, and ultraviolet ranges of the spectrum. Particularly preferred portions of the spectrum are those portions that correspond to the absence of water absorption, such as visible or near infrared wavelengths, and are relatively transmissive in tissue. In the present invention, the light can be either coherent light or non-coherent light, and the illumination can be stationary light or pulsed light.
[0026]
Human blood is composed of fixed components and plasma. There are three basic components of blood cells: red blood cells; white blood cells; and platelets. As mentioned above, red blood cells contain hemoglobin, which carries oxygen from the lungs to body tissues. White blood cells are approximately the same size as red blood cells, but do not contain hemoglobin. A normal healthy person has about 5,000,000 red blood cells and about 7500 white blood cells in one cubic millimeter of blood. Thus, a normal healthy person has about 670 red blood cells per white blood cell in the blood within the vascular system.
[0027]
Whole blood count without leukocyte classification examines eight parameters. That is, (1) hemoglobin (Hb), (2) hematocrit (Hct), (3) red blood cell count (RBC), (4) average cell volume (MCV), (5) average red blood cell hemoglobin (HCH), (6) The mean erythrocyte hemoglobin concentration (MCHC), (7) white blood cell count (WBC), and (8) platelet count (Plt) are investigated. The first six parameters are used here as RBC parameters. Concentration measurements (measurements per blood volume unit) are required to create values for Hb, Hct, RBC, WBC, and Plt. Hb is the concentration of hemoglobin per blood volume unit. Hct is the volume of cells per blood volume unit. Hct can be expressed as a percentage, ie,
(Red blood cell volume / blood volume) x 100% (Equation 1)
[0028]
RBC is the number of red blood cells per blood volume unit. WBC is the number of white blood cells per blood volume unit. Plt is the number of platelets per blood volume unit.
The red blood cell index (MCV, MCH, MCHC) is a cellular parameter indicating the average red blood cell volume, hemoglobin content, and hemoglobin concentration, respectively. The red blood cell index is determined by taking measurements of individual cells. Erythrocytes do not change volume or decrease hemoglobin as they move through the vascular system. Thus, the red blood cell index is constant throughout the circulation and can be reliably measured even in small blood vessels. The three red blood cell indices are related by this equation.
[0029]
MCHC = MCH ÷ MCV (Equation 2)
Therefore, only the two red blood cell indices are independent variables.
To measure the values of the six RBC parameters in the above list, the following two measures need to be matched. First, the three parameters need to be measured and determined individually. That is, the three parameters need to be measured and determined without reference to the other six parameters. Second, at least one of the three parameters measured and determined individually needs to be a concentration parameter (in blood cell volume units). Thus, the values of the six key parameters can be determined by three independent measurements, including at least one concentration measurement that cannot be performed on small vessels.
[0030]
As disclosed in the '120 patent and the' 859 application, Hb and Hct are directly measured by reflectance spectral imaging of large vessels, while MCV and MCHC are directly measured by reflectance spectral imaging of small vessels. In this way, the parameters are measured individually and the two parameters (Hb and Hct) are concentration parameters measured per blood volume unit. Thus, the six RBC parameters in the above list are determined in the following manner.
[0031]
Hb direct measurement method
Hct direct measurement method
RBC Hct @ MCV
MCV direct measurement method
MCH MCV × (Hb ÷ Hct)
MCHC Hb @ Hct
On the other hand, as disclosed in the '120 patent and the' 859 application, Hb can be measured directly by reflection spectral imaging of large blood vessels, and MCV and MCHC can be measured directly by reflection spectral imaging of small blood vessels. In this way, three parameters can be measured individually and one parameter (Hb) is a concentration parameter measured per blood cell volume unit. Thus, the six RBC parameters in the above list are determined as follows.
[0032]
Hb direct measurement method
Hct Hb @ MCHC
RBC Hb ÷ (MCV × MCHC)
MCV direct measurement method
MCH MCV × MCHC
MCHC direct measurement method
Hemoglobin is a major component of red blood cells. Hemoglobin is a protein responsible for transporting oxygen and carbon dioxide within the vascular system. Hemoglobin absorbs light of a specific absorption wavelength, such as 550 nm, and does not absorb light of other non-absorption wavelengths, such as 650 nm. Under the Beer method, the negative logarithm of the measured transmitted light intensity is linearly related to concentration. As described more completely in the "120 patent" and the "859 application", in the spectrum imaging apparatus, the reflected light intensity can be set to follow the Beer method or the like. Assuming that the Beer method is applied, the concentration of hemoglobin in a particular sample of blood is linearly related to the negative of the logarithm of the reflected light absorbed by hemoglobin. The more the 550 nm light is absorbed by the blood sample, the lower the intensity of the reflected light at 550 nm and the higher the concentration of hemoglobin in the blood sample. The concentration of hemoglobin can be calculated using the logarithm of the measured reflected light intensity at the absorption wavelength, such as 550 nm, with a minus sign. Thus, if the reflected light intensity is measured from a particular blood sample, the concentration of blood, such as hemoglobin, in such components can be determined directly.
[0033]
The method and system of the present invention can be used for direct measurement of hematocrit, even if the components to be measured are non-uniformly distributed, and can be used for quantitative analysis of the vascular system. For example, the invention can be used to measure the hematocrit of blood vessels having a non-uniform distribution of red blood cells.
[0034]
FIG. 1 shows a typical portion of a blood vessel 100 of length L and diameter D. Blood vessel 100 has an individual number (N) of red blood cells. The hematocrit (Hct) of the blood vessel 100 is NV _B ÷ (π / 4) D ₂ L, where V _B Is the average red blood cell volume. Therefore, the hematocrit of any region of the blood vessel 100 is represented by the following probability function.
[0035]
F (N) = NV _B ÷ (π / 4) D ₂ L (Equation 3)
[0036]
N here is a parameter that changes according to the blood vessel length L at a certain specified time, changes with time, and changes at a certain specified location along the blood vessel length L. The distribution of the variation in N can be best illustrated by a Poisson distribution where the variance is proportional to the square root of the variation. For example, the measurement of the average red blood cell count of a part of the blood vessel 100 at a certain specified time is
[0037]
(Equation 1)

average
(Equation 2)

Is proportional to the square root of (Equation 5), and the coefficient of variation (CV) can be calculated through this method as well as the standard deviation, or
[Equation 3]

[0038]
When (Equation 1) and (Equation 3) are combined, the measurement of the fluctuation or deviation of the number of red blood cells is shown as follows.
[0039]
(Equation 4)

[0040]
Therefore, the coefficient of variation of N is a function of Hct and the diameter of the blood vessel. The fluctuations appear due to fluctuations in optical intensity and diameter according to the created image of the blood vessel. Alternatively, the fluctuation appears regardless of the fluctuation of the diameter or the optical intensity in the time series of the image at a specific portion of the blood vessel.
[0041]
As mentioned above, the use of reflectance spectral imaging for the measurement of Hb is based on the assumption that blood vessels are uniformly filled. A high variation in the number of red blood cells, measured according to the vessel length, indicates that the vessel is unevenly filled. Referring to (Equation 4), it can be seen that the coefficient of variation is inversely proportional to the diameter of the blood vessel. Larger vessels with diameters greater than 50 microns have a low coefficient of variation, suggesting a uniform distribution of Hb.
[0042]
FIG. 1b shows a typical small vessel of diameter D. Small vessels have a diameter of 6 microns or less. The size of the blood vessels in this range is comparable to the size of red blood cells (denoted by d). Thus, typically, only one stream of red blood cells can flow through a blood vessel. In this case, spectrophotometry (such as the Behr method) can be used for calculating MCHC, but cannot be used for measuring Hct or Hb. Red blood cell concentration can be measured by counting red blood cells along blood vessels.
[0043]
For medium-sized vessels of 6-60 microns (such as vessel 100 in FIG. 1a), high variability (10-20%) indicates a non-uniform distribution of Hb, and the use of the Beer method to estimate Hb and MCHC. Becomes difficult. The size of the blood vessels allows the flow of multiple red blood cells, but impairs the use of spectrophotometry to make accurate measurements of RBC (red blood cells) by counting individual cells. In fact, blood vessels in this range are 2 to 15 times the diameter of red blood cells. For unfilled vessels, the methods and systems of the present invention can be used to measure Hct from coefficients of variation and vessel diameter.
[0044]
FIG. 1c shows a typical large blood vessel of diameter D, where individual measurements of the reflection properties and thus spectroscopic measurements (such as the Behr method) are used for measuring Hb. In small blood vessels, high fluctuations in the number of red blood cells can have a significant effect on Hb measured as a function of optical intensity measured on the reflection spectral image.
[0045]
FIG. 2 shows the measured vessel diameter. As shown, “m” diameter measurements (202, 204, 206, 208) were measured along the axis of blood vessel 100.
FIG. 3 shows the measured vessel intensities. As shown, “m” intensity measurements were taken along the axis of blood vessel 100. The light source (302, 304, 306, 308) is I _0n It is shown. The attenuated light (312, 314, 316, 318) is I _n It is shown.
[0046]
In FIG. 4, a flowchart 400 represents a flow of a general operation of the present invention. Further, a flowchart 400 shows an example of a control flow for measuring hematocrit of a blood vessel.
[0047]
FIG. 4 begins at step 401 where an image is retrieved from a memory source or image directory at step 405. The image may be from an input file stored in the above temporary or permanent storage location, such as a hard disk drive or a removable storage device such as a floppy disk, magnetic tape, optical disk, etc. Can be acquired. The input file also consists of the target number and other data that can be used to identify the target. Alternatively, the images can be obtained in real time from an imaging device of the type shown in the "120 Patent" and the "859 Application" (which is desirable, but not required).
[0048]
At step 410, a plurality of measurements are taken along an axis to measure the diameter of the different portions. Referring to FIG. 2, "m" diameter measurements (202, 204, 206, 208) were taken along the axis of blood vessel 100. As will be appreciated by those skilled in the art, various measurements and divisions should be made to obtain a sufficiently accurate diameter measurement. At step 415, the diameter measurements are analyzed to determine a coefficient of variation.
[0049]
In step 420, a fractional value of a cellular component (such as red blood cells) is determined for a blood vessel. Two methods are used to determine the fractional value. In the first method, the value of the fraction of the cellular component is determined for each part using diameter measurements on the reciprocal of the product of the coefficient of variation of each part. In the second method, the value of the fraction of cellular components can be determined using the inverse of the product of the coefficient of variation and the average of the diameter measurements.
[0050]
In step 425, Hct is calculated from the average value of the fraction values. If the fraction values were used in the determination in the first method, the average of all fraction value measurements would be calculated and used to estimate Hct. However, if the second method were used, the value of the average fraction calculated in step 420 would be used to estimate Hct. After Hct has been calculated, the control flow of flowchart 400 ends as shown in step 495.
[0051]
In FIG. 5, a flowchart 500 shows a general operation flow in another example of the present invention. More specifically, an example of a control flow using optical density to measure hematocrit of a blood vessel is shown.
[0052]
FIG. 5 begins at step 501, after which steps 405 through 410 proceed as shown in FIG. In step 510, the blood vessel is illuminated at multiple points along the axis to measure the intensity of the original or attenuated light. Referring to FIG. 3, an “m” intensity measurement is taken along the axis of blood vessel 100. The intensity profile is created by calculating the logarithm of the ratio of the measured attenuated light minus the sign and the original light intensity to produce the optical density.
[0053]
At step 515, the optical density measurements are analyzed to determine a coefficient of variation. In step 520, the fractional value at the cellular component is determined for each part using the inverse of the product of the coefficient of variation and the diameter measurement of each part. As shown in FIG. 4, the fractional value of the cellular component can also be determined using the inverse of the product of the coefficient of variation and the average of the diameter measurements.
[0054]
In step 525, the average of all fractionation measurements is used to estimate Hct. However, if the second method is used to determine the fraction value, the average fraction value determined in step 520 can be used to approximate Hct. The control flow of flowchart 500 ends as indicated by step 595.
[0055]
Therefore, the hematocrit of the subject can be indicated from the optical density and the coefficient of variation of the diameter in either the image in which the blood vessel is formed or the time-series image of a certain position in the blood vessel. FIG. 6 shows the results of a comparative study of the implementation of the method and system of the present invention. During the study, blood samples measured in vitro were taken from nine subjects and used for hematocrit determination. Biological images from the eyes of nine subjects (such as the sclera) using the method of the present invention were acquired using orthogonally modified spectroscopy, as shown in the “120 patent” and “859 application”. Was done.
[0056]
Each subject selected five blood sections for determination of diameter and optical density measurements. The variation in optical density along each vessel was also measured. Next, the reciprocal of the product of variation and the diameter for each part were calculated. In addition, the mean amount was calculated for each of the nine subjects in combination with a simple hematocrit estimate and the results of the in vivo measurements.
[0057]
The results of the in vivo and in vitro measurements are shown in FIG. The vertical axis shows hematocrit determined by in vivo measurement, and the horizontal axis shows hematocrit of in vitro measurement. The coefficient of hematocrit calculation (Slope) is 0.91, which suggests that the in vivo measurements are very similar to the in vitro measurements.
[0058]
As will be apparent from the following, the invention was originally developed for analyzing blood components by non-invasive means. However, as will be apparent to those skilled in the art, the analytical techniques of the present invention can be used beyond the medical uses described above. The present invention has applications outside the medical field, and is generally used for the quantitative analysis of visible components floating in a flow through any tube, such as a transparent tube that transmits and reflects light, or a wall. Can be used. The present invention is most efficient for analyzing tubes having a diameter between 6 and 60 microns and is the most appropriate size that can be detected by spectrophotometry. A more suitable range is 15-50 microns with an average coefficient of variation of 10-20%.
[0059]
The invention can be implemented by hardware, software, or a combination thereof, and can be implemented in one or more computer systems or other processing systems. Indeed, in one implementation, the invention describes one or more computer systems capable of performing the functions described herein.
[0060]
FIG. 7 shows an example of a computer system 700 suitable for implementing the present invention. Computer system 700 includes one or more processors, such as processor 704. Processor 704 is connected to a communication infrastructure 706 (communications bus, cross-over bar, network, etc.). Various software implementations are described with respect to a typical computer system. The following description will enable those skilled in the art to understand how to implement the invention using other computer systems and / or computer architectures.
[0061]
Computer system 700 includes a display interface 702 that sends images, text, or other data for display on display unit 730 from communication infrastructure 706 (or frame buffer not shown).
[0062]
The computer system 700 includes a main memory 708 (random access memory (RAM)) and a second memory 710. The second memory 710 may include, for example, a hard disk drive 712 and / or a removable storage drive 714 such as a floppy disk drive, magnetic tape drive, optical disk drive, and the like. Removable storage drive 714 reads and / or writes from removable storage unit 718 by known means. The removable storage unit 718 is a floppy disk, a magnetic tape, an optical disk, or the like, which is read or written by the removable storage drive 714. As is well known, the removable storage unit 718 comprises a computer usable storage medium on which computer software and / or data can be stored.
[0063]
In another implementation, the second memory 710 may include a computer program or other similar means for enabling other instructions to be loaded on the computer system 700. Such means may consist, for example, of a removable storage unit 722 and an interface 720. Such examples include program cartridges, cartridge interfaces (as found in video game devices), removable memory chips (such as EPROMs and PROMs), associated sockets, other removable storage units 722, and removable storage. An interface capable of transferring software and data from the unit 722 to the computer system 700 is provided.
[0064]
Computer system 700 includes communication interface 724. Communication interface 724 allows software and data to be transferred between computer system 700 and external devices. Examples of the communication interface 724 include a modem, a (Ethernet card) network interface, a communication port, a PCMCIA slot and a card, and the like. The transfer of software and data via the communication interface 724 is in the form of signals 728 such as electronic, electromagnetic, optical, and other signals receivable by the communication interface 724. The signal 728 is provided to the communication interface 724 via a communication path (such as a channel) 726. This channel 726 transmits a signal 728 and may be implemented using wires, cables, fiber optics, telephone lines, cellular phone links, RF links, or other communication channels.
[0065]
In this document, "computer program medium" and "computer usable medium" are used for what is generally called a medium, such as a removable storage drive 714, a hard disk installed in a hard disk drive 712, and a signal 728. . The computer program product is a means for supplying software to the computer system 700.
[0066]
Computer programs (also called computer control logic) are stored in main memory 708 and / or second memory 710. The computer program is also received via communication interface 724. Such computer programs, when executed, enable computer system 700 to perform aspects of the present invention, as set forth herein. Specifically, the computer program enables runtime processor 704 to execute aspects of the present invention. Therefore, this computer program corresponds to the controller of the computer system 700.
[0067]
When the present invention is implemented using software, the software is stored in a computer program product and loaded into computer system 700 using removable storage drive 714, hard disk drive 712, and communication interface 724. Control logic (software), when executed by processor 704, causes processor 704 to perform the functions of the invention described herein.
[0068]
In other implementations, the invention is implemented primarily using hardware components, such as application specific integrated circuits (ASICs), in hardware. Implementation of the hardware state machine to perform the functions described herein will be readily apparent to one skilled in the art.
[0069]
In other implementations, the invention is implemented using a combination of both hardware and software.
Various implementations of the present invention have been shown, but are by way of example and not limitation. Those skilled in the art can easily make various changes in form and detail without departing from the spirit and scope of the present invention. Therefore, the present invention is not limited by the above embodiments.
[Brief description of the drawings]
FIG. 1a is a cross-sectional view of an intermediate blood vessel containing red blood cells.
FIG. 1b is a cross-sectional view of a small blood vessel containing red blood cells.
FIG. 1c is a cross-sectional view of a large blood vessel containing red blood cells.
FIG. 2 illustrates a vessel diameter measured according to the practice of the invention.
FIG. 3 illustrates an example of the intensity measured by the practice of the present invention.
FIG. 4 is a flowchart illustrating a general execution flow of hematocrit measurement according to a variation of diameter measurement according to an embodiment of the present invention.
FIG. 5 is a flowchart illustrating a general execution flow of hematocrit measurement according to a modification of the optical density measurement according to the embodiment of the present invention.
FIG. 6: Comparison of hematocrit measurement according to the invention with in vitro hematocrit measurement.
FIG. 7 is an example of a block diagram of a computer system used to implement the invention.

Claims (14)

A system for optically analyzing at least one of a plurality of floating visible cell components in a fluid vasculature system, wherein the wall of the fluid vasculature system is substantially transparent to transmitted and reflected light. A processing unit that uses an image capture device capable of capturing an image and communicates with the image capture device;
(A) receiving by the processing unit an image of the fluid vasculature system captured by the image capture device;
(B) analyzing the image to identify at least one body vessel;
(C) measuring a plurality of diameter determinations from the body vessel;
(D) calculating a coefficient of variation from a plurality of optical densities generated from at least one body vessel of the plurality of diameter measurements;
(E) deriving results from the coefficient of variation and diameter measurements;
(F) determining a fraction of one of the plurality of visible cell components in the fluid vascular system from the result;
Method consisting of. A fluid vasculature system consisting of blood suspended in the blood vessels of the mammalian vasculature system; a visible cell component consisting of blood components, including red blood cells;
Step (a) is the step of receiving an image of a blood component within the fluid vasculature system into the processing unit, and step (e) is to calculate a series of fractional values for the blood component for calculation. Multiplying the coefficient of variation using the plurality of diameter measurements;
2. The method of claim 1 wherein step (f) is a step in which an estimate of hematocrit is determined from a series of fractionation values. A fluid vasculature system consisting of blood suspended in the blood vessels of the mammalian vasculature system; a visible cell component consisting of blood components, including red blood cells;
Wherein step (a) is the step of receiving an image of a blood component within the fluid vasculature system into the processing unit and step (e) uses the average of the plurality of diameter measurements to calculate a result. Multiplying the coefficient of variation,
2. The method of claim 1, wherein step (f) is a step in which an estimate of hematocrit is determined from a series of fractionated amounts. The method of claim 1, further comprising measuring the plurality of diameter measurements or the plurality of optical density measurements along a length of a blood vessel. Receiving a time-series image of the body vessel;
Measuring the plurality of diameter measurements or the plurality of optical density measurements from a common point on a body vessel in a time-series image. The method of claim 1 wherein each of the plurality of diameter measurements ranges from 6 to 60 microns. An image capture device for use with a light transmissive device for light transmitted through a fluid vasculature system to capture an image from the fluid vasculature system, and a fluid vasculature with a substantially transparent wall for transmitted and reflected light. A processing unit connectable to an imaging capture device for analyzing at least one of a plurality of visible cell components in the system,
Receiving means for receiving an image of the fluid vascular system by an imaging capture device,
Analytical means for analyzing at least one body vessel from the image;
First calculation means for calculating a coefficient of variation from at least one plurality of diameter measurements and a plurality of optical density measurements of the body vessel,
Multiplication means for deriving results from the coefficient of variation and the plurality of diameter measurements;
The method comprises a second calculating means for determining a fraction of one of the plurality of visible cell components in the fluid vascular system from the result. A fluid vascular system consisting of blood suspended in blood vessels of the mammalian vascular system, and a visible cell component consisting of blood components, including red blood cells,
Receiving means comprising means for receiving an image of a blood component within the fluid vascular system to the processing unit;
Multiplying means comprising means for multiplying the coefficient of variation with each of the plurality of diameter measurements to calculate a series of fractionated volumes for a blood component;
Second calculating means comprising means for determining an estimate of hematocrit from the series of fractionation values,
The apparatus of claim 7, comprising: The apparatus of claim 7, further comprising calculating means for measuring the plurality of diameter measurements or the plurality of optical density measurements according to a length of the body vessel. The apparatus of claim 7, further comprising means for measuring the plurality of diameter measurements and the plurality of optical density measurements from a position of the body vessel at a common location in a time-series image of the body vessel. A computer usable medium comprising computer readable program code means for performing at least one analysis of a plurality of visible cell components in the fluid vasculature system in a medium providing an application program for executing on a computer;
First computer readable program code means for causing a computer to analyze to identify at least one body vessel of an image of the fluid vasculature system captured by the image capture device;
A second computer readable program code means for causing a computer to measure a plurality of diameter measurements from the body vessel;
Third computer-readable program code means for causing a computer to measure a coefficient of variation from at least one of the plurality of diameter measurements and the plurality of optical density measurements from the body vessel;
Fourth computer readable program code means for causing a computer to measure the coefficient of variation and the plurality of diameter measurements;
Fifth computer readable program code means for causing a computer to determine a fraction of one of the plurality of visible cell components in the fluid vasculature system from the results. A fluid vascular system composed of blood suspended in blood vessels of the mammalian vascular system, and a visible cell component composed of blood components, including red blood cells,
Fourth computer readable program code means comprising computer readable program code means for causing a computer to multiply the coefficient of variation using each of the plurality of diameter measurements to calculate a series of fractional volume values for the blood component;
Fifth computer readable program code means comprising computer readable program code means for causing a computer to determine an estimate of hematocrit from the series of fractionation value values,
The computer program product according to claim 11, consisting of: The computer program product of claim 11, further comprising sixth computer readable program code means for causing a computer to generate the plurality of diameter measurements and the plurality of optical density measurements along a length of a body vessel. 12. The computer readable program code means of claim 11, further comprising a sixth computer readable program code means for causing a computer to generate the plurality of diameter measurements and the plurality of optical density measurements from locations between the body at a common location in a time series image of the body vessel. Computer program product.

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