WO2004052195A1

WO2004052195A1 - Device for the determination of blood flow in discrete blood vessels and regions of living organisms

Info

Publication number: WO2004052195A1
Application number: PCT/EP2003/050953
Authority: WO
Inventors: Thomas Kelty
Original assignee: Zerrle, Irmgard
Priority date: 2002-12-10
Filing date: 2003-12-07
Publication date: 2004-06-24
Also published as: DE10257743B4; DE10257743A1; AU2003300575A1

Abstract

The device comprises a radiation beam/camera module (40) which irridiates an area (47) encompassing a selected blood vessel. The energizing radiation beam (45) causes fluorescent radiation (43) to be produced by an agent that has been introduced into the blood stream. An image sensing device (42) detects the fluorescent emission (43) and transmits the signal of the image to the computer system (10) which displays the images on a monitor (15) for the purpose of rapid quality assessment of the blood flow rate in the selected blood vessel segment. Concurrently, a computer program calculates and records the quantitative blood flow rate based upon the changing position of pixel intensity within the image data over regular time intervals, and based upon the calculated dimensions of the blood vessel segment.

Description

DEVICE FOR THE DETERMINATION OF BLOOD FLOW IN DISCRETE BLOOD VESSELS AND REGIONS OF LIVING ORGANISMS

TECHNICAL FIELD The present invention relates to a device, including integrated computer program and associated procedures, for the qualitative and quantitative determination of blood flow within discrete, selected blood vessel segments. The application of said invention is particularly advantageous for providing medical imaging and image evaluation during surgical procedures on blood vessels where the use of radiation protection, such as lead aprons or eyewear filters for either the patient or medical staff, would constitute a hindrance, and where current, ponderous imaging equipment would be impractical for intra- operative use. The application of the present invention is especially advantageous for intra- operative use in which the medical information pertaining to blood flow can be obtained in an non-intrusive and rapid fashion relative to the overall surgical procedure. The combined quantitative and qualitative output of the present invention provides the surgeons and assisting medical staff with such intra-operative blood flow information as a means of increasing the accuracy, efficacy and over all success of vascular surgical procedures, while concurrently establishing a quality control trace of such surgical procedures.

The present invention provides a record of such procedures, in the form of a specially designed, hybrid database combining video and numerical data, for the purpose of quality control tracking, for the storage of data, which is advantageous for potential follow up surgery, and for research into techniques in developments in vascular surgery. This database permits not only the retrieval of data collected during vascular surgery, said database of the invention also permits the further analysis and generation of quantitative results on the stored data which enable the device user to analyze blood flow through discrete blood vessels of living organisms or functioning organs post-operatively. Application of the invention is relevant to currently practiced human and veterinary medicine as well as to research in both fields.

BACKGROUND ART

Visual data can be a powerful tool. Consider, as an instance of this, the instrument panels of commercial aircraft: Real-time data and feedback from flight instrumentation are often visual and graphical rather than preponderantly numerical. In such situations where immediate human interpretation of data is critical, visual information is highly valuable. On the other hand, when the visual information is ambiguous or not precise enough from which to draw conclusions or to base reactive and corrective decisions, calculated numerical data is a necessary complement to such a control system, feedback system or analytical system.

With the above themes in mind, the present invention was formulated with the concept that in medical procedures, where real-time knowledge of dynamic data of blood flow inside discrete blood vessels would be clearly an advantage or in some cases quite necessary for a successful outcome, the immediacy of visually interpretable data combined with the support of computer calculated data, which are both produced by a single device or system, would be of significant benefit. The present invention fulfills those needs.

There are existing devices which claim to measure dynamic parameters of blood flow through vessels. A category of devices, commonly referred to as flow probes that rely on ultrasonic signals, primarily provide indirectly measured, numerical data but offer no dynamic image of the blood flow through the vessels. Such devices also require contact with the blood vessel using a sterile probe which generally must be disposed of after use on a single patient. Additionally, these devices lack a comprehensive computerized database by which the acquired data can be conveniently stored, post-operatively reviewed and analyzed, copied and archived.

A method and apparatus for performing intra-operative angiography are disclosed in WO 01/22870. Therein a device and method are described having the ability to display and record images of blood vessels containing a fluorescent agent. The capability of providing numerical data or graphs of measurements or analysis of the dynamic parameters of blood flow in a discrete blood vessel is not claimed for this referenced invention. The invention of WO 01/22870 is claimed to have the capability to calculate a blood vessel diameter, a static value, by comparing the number of pixels that correspond to the blood vessel diameter with the number of pixels associated with a pre-selected unit of measurement. (See claim 52 on page 23, lines 10 through 13, and under Brief Summary of the Invention, p. 4, lines 18-26 of WO 01/22870.) No further claim of a computer program or automated calculation of blood flow rates are found in WO 01/22870 . Furthermore, in the case where the blood vessel diameter is calculated by comparing the number of pixels in an image of that blood vessel with the number of pixels associated with a pre-selected unit of measurement, this necessarily implies a static association which is fixed until subsequent re-calibration. Such an association or measurement by comparison with an image made of a reference of known dimensions would only be valid under certain conditions which would be difficult to achievable, impractical or inconvenient during standard surgical procedures. This type of calibration is a limitation existing in the invention claimed in WO 01/22870 referred to previously (Again referring to page 4, lines 18-26.) As a confirmation of this limitation, WO 01/22870 clarifies the need to recalibrate the device each time the camera is repositioned (See page 16, lines 1-3.) One important condition is that the distance between the image sensing device or recording camera and the blood vessel must be exactly the same as the distance between the camera and the calibration target of a known and predetermined unit of measurement. This is required for the calibration process described in WO 01/22870 and the blood vessel diameter calculation to be valid. Such a requirement for repeated re-calibration for each re-positioning of the camera is a substantial, practical disadvantage for intra-operative surgical use in vascular procedures.

Regarding the present invention, it is expected and intended that not one but several recordings will be made, each in various positions, in the course of one surgical procedure. A method and device which incorporates an inventive step that eliminates the need for re- calibration between each recording position and eliminates the need for a static reference to a pre-selected unit of measurement would be advantageous. The present invention provides such an advantage by including, in the exciter beam / camera subsystem, a means of automatically projecting a pre-calibrated measurement reference onto the subject for a short duration at the start and at regular intervals during the acquisition of image data by means of a collimated infra-red radiation beam. The momentary projection of such a reference provides a dynamic means of deriving a variable rather than fixed scaling factor relating the image size in pixels to true subject or target size in standard units of measurement.

Further, while a singular determination of blood vessel diameter alone may have some value in other special situations, it is not one of the critical measurements of immediate interest to medical practitioners in the surgical procedures where the present invention is generally intended to be used. A static parameter such as blood vessel diameter can generally be seen and its size determined with sufficient accuracy for typical vascular surgical procedures in a direct, visual way by the medical practitioner using standard, wearable, optical magnification devices, for example.

What the human eye cannot see, however, is the dynamic rate of blood flow through a discrete vessel and the qualities of the periodic parameters which characterize the flow (e.g., systolic and diastolic variations). Other than the present invention, there currently exist no known, publicly disclosed devices combined with related methods and contained in one system, which can provide the visual data and its corresponding quantitative calculations pertaining to the dynamic data of flow within a discrete, selected blood vessel segment, together with a software program that provides for a database which includes multifunctional image processing and archiving for intra-operative use as well as for postoperative analysis and research.

A device described in US 2002/0099279 Al (with priority from DE 100 59 070 Cl) claims to produce images relating to blood flow. However, it is described that the images produced by this device are for the purpose of assessment of overall tissue area perfusion rather than for the observation of flow or calculation of flow rate in a discrete blood vessel. DE 101 20980 Al, which is closely related to the above, claims a procedure, device and computer program with the ability to make calculations related to blood flow into a specific tissue or organ region. DE 101 20980 Al provides a more detailed description and set of claims in regard to the automated determination of blood flow compared to US 2002/0099279 Al.

The present invention differs in several important aspects to the two closely related inventions cited in the paragraph immediately above . Firstly, these two related inventions refer to the determination of blood flow in a tissue region or organ region of interest in the body of a patient. (See DE 101 20 980 A 1 with reference to the title, to claim 7, to paragraph 0009 of the description as well as the general description of the application of the invention all of which refer to the analysis of a tissue region or organ region.) This regional blood flow determination is a substantially different parameter of measurement compared to the determination of blood flow in a discrete, selected blood vessel, as provided for in the present invention. Secondly, the above mentioned devices produce no absolute blood flow rates in units of volume per time such as described herein and claimed by the present invention. Rather, these devices described produce spatially averaged blood flow information for a general region of interest and in relative terms only. This relative data output depends on a comparison with a reference or control region of the patient where the blood flow is assumed to be in a normal range. Thus the data provided to the user is limited to calculation of a percentage or a fraction of the regional blood flow compared to that sensed in the control region. (See DE 101 20 980 A 1, claim 2 and paragraph 0019 indicating the use of a reference region as a basis for the computation and final data output.)

Thirdly, the method of calculating the blood flow data in the above referenced inventions is based upon the time rate of increase in the total sensed fluorescent radiation in both the region of interest and the reference region (e.g., the resulting data is spatially averaged.) T at is to say, the measurement is based upon the changing total intensity level of fluorescence in the entire region. The variables are time and total regional intensity. There are no variables in the described calculation which relate to a changing position of pixel elements or a group of pixels of highest intensity which would relate to the localized movement of blood defined with respect to the 2-dimensional co-ordinates within the image of the region. The present invention differs substantially from the above in that its computer subsystem tracks the changing position of the pixel group(s), which have the highest relative intensity, with respect to time and within the region of interest, rather than the more basic calculation of the aggregate pixel intensity over regular time intervals, as is made in the referenced devices. This inventive step involving the determination of position, speed and, ultimately, the blood flow rate by locating pixel group intensity, together with other features of the present invention, enable its user to determine the blood flow through a selected segment of a discrete blood vessel in absolute terms of volume per time.

Regarding the comparisons between the present invention and those indicated in US 2002/0099279 Al and DE 101 20980 Al, the present invention does provide for a calculated analysis of the total blood flow rate into a region as a separate program module and mode of device operation which is distinct from what has previously herein been indicated for the present invention. Furthermore, the calculated result is a different parameter type when compared to these other inventions. However, the present invention relies advantageously on a different method of calculation with respect to the inventions cited by reference herein. For purposes of clarity this separate device mode shall be herein referred to as the perfusion mode. An additional difference is that none of herein referenced inventions include a hybrid database and program having the capabilities of combining video, text and numerical data storage for the purposes of quality control tracking, of providing valuable data for potential follow-up surgery and for research regarding techniques in vascular surgical development. The database of the present invention permits not only the post-operative retrieval of data collected during vascular surgery, said database also enables post-operative further and more detailed analysis and generation of quantitative blood flow through discrete blood vessels. This capability is substantially different than that of the previously referenced inventions in that the device of the present invention produces an output in a different and more advantageous format and also has a different application, specifically this application pertains to the field of vascular surgery in which the determination of blood flow in selected, discrete blood vessels would be advantageous.

In a general aspect concerning prior art, none of the previously cited inventions describe or claim a computer system which automates a broad range of functions including image acquisition, associated data entry, data analysis and storage of quantitative data, database creation and data processing features that readily permit data retrieval and transmission. Exactly such capabilities are described and claimed herein for the present invention.

DISCLOSURE OF THE INVENTION The basic starting point for the present invention is the realization that, for certain medical procedures involving vascular surgery, the real-time, dynamic data regarding blood flow in selected blood vessels would be advantageous. In such surgical procedures, it would be further advantageous to have immediate or nearly immediate visual, qualitative information regarding said blood flow in addition to the calculated, numerical blood flow data supplied by the same single device, following a short period of user input and computation by said device. Therefore, such a device which incorporates both the immediate, qualitative, visual information followed by the output of numerical data would be of significant advantage in several areas of vascular surgery.

In view of the lack of such a suitable, integrated device for determining discrete vascular blood flow during surgical procedures, the present invention was conceived in order to provide those advantages as indicated in the preceding paragraph. Furthermore, the present invention solves the problem of providing those advantages with a device according to claim 1 herein. The further advantageous development of the device are included in the dependent claims.

In response to the perceived need for a medical imaging device and associated procedures, which combines visual data, that provides the advantages of nearly immediate, qualitative assessment, together with confirming numerical data, the present invention encompasses these combined capabilities to meet these needs. In addition, however, the present invention provides further advantages beyond the level of simply combining these two complementary forms of data into one device. These further advantages are provided by the following aspects of the invention:

The present invention relies on the capabilities of its intuitive program and graphical user interface (GUI) to enable the user to readily create, organize, copy, analyze, archive as well as to further process and maintain a valuable database of vascular image data and its corresponding numerical and text information. The resulting hybrid database containing motion video data, numerical data and text information provide advantages for post-surgical analysis relevant to potential follow-up treatment. The present invention additionally provides the advantages of a quality control confirmation record for procedures where the device is used intra-operatively, and provides advantages for research in vascular surgical techniques and development when used as a post-operative analytical device.

In a further aspect of the present invention, an advantageous means of blood flow analysis that was previously generally unavailable is provided for: This device now makes possible the analysis of blood flow, which can be retrieved and analyzed at any time subsequent to the data acquisition, using stored data from the database of the invention. It is possible to extract such new information from stored data because a basic element of the stored data is a dynamic sequence of images that have sufficient time and spatial resolution on which analysis is effective. Furthermore, the computer program and its procedures of operation permit the user of the invention to produce numerical data regarding such parameters as time rate of blood flow in a discrete blood vessel segment selected from dated, procedurally identified and patient-correlated, previously stored image data. Furthermore, this analytical result is produced in the same manner and method available to the user in the analysis of real-time, acquired image data. The above listed aspects of the present invention are a significant extension of present state of the art capabilities and permits a new form of research and analysis on stored image data. The output of such analysis is identical in format and type to the output characteristics available in the use of the present invention intra-operatively in real-time measurement situations. In some aspects such research and analysis on stored data has advantages over real-time measurement when considerations such as repeatability, evaluation of measurement accuracy, variations in device operation techniques and algorithms are taken into account. The basic reason for these existing advantages compared to real-time analysis is that practically unlimited, repeated analysis can be made on large amounts of stored data in a post-operative setting— the time allotted for analysis in not a restricting factor as in the intra-operative situation.

The present invention may be summarized as a device to determine the blood flow through a discrete, selected blood vessel and which has complementary graphical, numerical and text output. Said device comprises a computer system comprising a hardware configuration of an electronic data processor with one or more integrated software programs and also with peripheral devices, having input and output interfaces, including standard components as a monitor, keyboard, pointing device and having data transfer connections which together function as a subsystem of the device. The present invention applies to the field of human and animal medicine, in particular vascular surgery and to research in these areas.

The present invention accomplishes the dual task of calculating and displaying the time rate of blood flow volume in a discrete, blood vessel segment as selected by the device user, while initially displaying in real-time a visual analog of the blood flow rate for immediate qualitative assessment. The device, including a computer program, enables the quantitative, computational part of this dual task to be accomplished through the following steps: a) In the course of a surgical procedure involving diagnosis and/or treatment of blood vessels, an agent containing a chromophore is injected as a bolus into the blood stream. The characteristics of this agent include its ability to fluoresce at infra-red wavelengths that can pass through a limited thickness of organic tissue such as blood vessel walls, and which can be sensed by a video camera fitted with the appropriate infra-red band pass filter. Concurrent with the circulation of the chromophore in the blood stream, the agent is stimulated to fluoresce by an external beam of infra-red radiation to which the agent is sensitive. Such agents are well known and have been previously used in clinical medicine, b) A digital, motion video recording of the flow of the fluorescent media through the blood vessels of interest is made. Initially and following at regular brief intervals, a pattern or measurement reticule, calibrated in sub-millimeter units, is optically projected in a collimated beam over the area of interest for only a brief time period. This is done by means of a calibrated reticule and low-power pointing laser in the optical excitation / camera module. A light emitting diode or group of such diodes together with collimating optics may be used for this same purpose. The recorded projection superimposed upon the area of interest allows the computer program to determine the true dimensions of the blood vessels in a way that permits the camera distance to vary for each acquisition within a surgical procedural case. This is in contrast with any means that uses a fixed, pre-selected unit of measurement used to determine dimension from recorded images. This is necessary because the camera optical system has a depth of focus field range which is substantial and practical use does not permit the camera to be positioned at an exact distance for every series of image acquisitions during a surgical procedure. Images appear larger or smaller depending upon the distance from the camera, and the graduated reference projection provides a solution to this problem of determining dimensions under such variable conditions. In the present invention the reference projection onto the region of interest is captured by the camera module and used to determine dimensions automatically and independently of the distance between the camera and the region of interest, within the range of intended use. Another consideration is that any external calibrations (as required for a fixed, pre-selected unit of measurement) for image dimension would be too time consuming, error prone, complicated for the user and, therefore, not practical for the intended use of the present invention. The calibration of the collimated reference beam is done at the time of fabrication. The calibration is to be checked as part of normal periodic maintenance but such calibration is not needed during a series of clinical image acquisition procedures. c) In the situation where there is movement of the vessels in the image field, especially in the case of a coronary bypass graft operation in which the heart continues to beat, the software program controlling the recording automatically performs an image registration function whose purpose is to maintain the image of the object in a constant position within the field of view of the digitally stored image. This step is necessary to perform further blood flow calculations with accuracy. d) The device operator, through the computer program, indicates the discrete blood vessel segment to be analyzed for flow rate. This is done with the pointing device, the screen display and through the functions found in the graphical user interface.

This step defines a digital image area corresponding to a subset of the data for the entire image area. This is necessary since typically several blood vessels appear in the image data, and a segment length must be defined to limit and focus the calculation. e) The computer program uses the data subset defined by the device operator in (d) and the projection of the graduated reference beam from (b) upon the selected blood vessel to determine the dimensions of the blood vessel segment. f) The computer program analyzes the sequential frames of the video data in the selected subset data area and locates the pixel group having the highest average intensity within each successive frame. This is done by the use of a search mask in the software. For example, the software program defines a 9 x 9 pixel array as the search mask size. The program, in algorithmic fashion, moves this search mask over the image data in an ordered fashion to determine the location of the pixel group having the highest relative intensity. For example, the search mask array is first compared to the data location corresponding to the lower left corner of the image. At that initial location, the average intensity of all the pixels in the 9 x 9 array is calculated. This value is temporarily stored along with the location of the center of that 9 x 9 array. The search mask is moved one pixel to the right and the calculation is repeated. If the value of the average intensity of the pixels corresponding to this next search array is greater than that which is temporarily stored, this greater intensity value and new center point location replaces the previous data in temporary storage.

This process is repeated as the search mask moves one pixel to the right. At the end of a row, the search mask is moved up one pixel, then it is moved to the left one pixel at a time. In such an ordered way, the search mask covers the entire image frame subset that was defined in (d) and (e) above. The center of the brightest average 9 x9 pixel group will be contained in the temporary storage along with the value of the intensity. (In the infrequent case where there may be more than one pixel group with the same average intensity, the program automatically enlarges the search mask, e.g. 13 x 13, and starts a new search for that image frame.) After one frame has been successfully searched for the location of the highest intensity pixel group, this position and intensity data is stored in memory and corresponds to the first image frame for the video image data set to be analyzed. The previous temporary storage in cleared, and a new search is done on the next frame. The result of this subsequent search provides the location of the relatively most intense pixel group in the new current video frame data subset, and the new position and intensity data is stored corresponding to the currently searched video frame number. This calculated change in position of the center of the relatively most intense pixel group from video frame to video frame will correspond to a true positional change of the fluorescent medium concentration flowing in the blood vessel. The change in position in pixel units will correspond to standard units of measurement. This correspondence is computed from

(b) above. The time between each video frame is a constant and is used as a timer, g) Therefore, the analytical results from the above steps are a dynamic quantification of the flow of the fluorescent agent carried by the blood in terms of volume per time. The time resolution of this resultant data depends upon the frame rate of the video data. Since an average flow rate is of major interest, the rate is averaged over several frames corresponding to a few seconds or a few systolic-diastolic cycles. Use of higher frame rates permit a more precise analysis of blood flow rates which vary over shorter time intervals, h) The numerical blood flow data, resulting from the quantitative analysis of the selected segment, is displayed on the computer screen within the graphical user interface. A line graph showing the time variation of the flow is also be displayed at the user's option. This data is stored within the device data base structure and may also be printed or copied to removable media, i) This item is not a step in the sequential order of the above, but rather describes an option for that portion of the blood flow calculation as described in (f) above. This option, which shall be summarized herein, is available to the device user as an alternate method that may yield more accurate blood flow data under certain conditions under which the fluorescent image acquisition is made. In general, these variable conditions have to do with the quality and nature of the blood circulation of the patient or subject into whose blood stream the chromophore is introduced.

Variables such as heart rate, total blood volume, injection speed and location and the injection concentration and technique all have a variable effect on how the injection bolus propagates and disperses through the blood stream. Other technical factors due to surgical methods, such as blood circulation devices used in arrested hear surgery, introduce other variables affecting these same parameters. In such cases where it is determined that a high and rapid amount of dispersion takes place, a method of calculation of blood flow rate based upon tracking relatively intense pixels in the image data, and which corresponds to the transit of the leading edge of the first wave of chromophore concentration flowing through a selected blood vessel, is provided as an optional choice to the device operator, The current item is not a step in the sequential order of the above, but rather describes a separate program function to calculate an index for the assessment of the blood flow rate in a region containing a plurality of blood vessels for medical procedures where total regional blood perfusion is more appropriate that the volumetric blood flow rate in a selected, discrete blood vessel. As indicated previously, this mode of device operation is referred to as the perfusion mode. This step, as is explained herein, is to be activated as an option by the user in place of steps d) through i) above. In this distinct mode of device operation, a separate module of the program calculation system computes the total intensity of the pixels in each frame of a user-selected sub-region of the image data. This image data represent the selected region during which a chromophore has been introduced into the bloodstream, and while the region has been irradiated to cause the chromophore to fluoresce. The calculation module computes second order differential values of the intensity change, using the time intervals between each frame, for sequential frames of the image data for the selected sub-region. This calculation is intended to correspond to the initial phase of the rate of increase in the total chromophore- volume-increase in the selected sub-region. Approaching a final result, the calculation module determines a maximum average from the above calculation values, which have been computed for each time interval following the first frame. This is done by calculating an average of the maximum value and the other intensity increase-rate- values calculated for time intervals in the program-defined neighborhood of the maximum. Finally, this calculation module displays and records this calculated, average maximum of the rate of intensity increase as a numerical index, herein referred to as the perfusion index, for the assessment of the blood flow rate for the selected region. This resulting perfusion index is compared to a database of perfusion index values for various tissue and organ types and categorized for various medical procedures for the purpose of enhancing the interpretation and assessment value of the perfusion index generated by the device. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows a block diagram of the preferred mode for carrying out the present invention indicating five main subsystems.

Figure 2, parts A and B, shows the data structure of a hybrid database, associated with the computer program of the device, as a component of the present invention.

Figure 3 shows the main menu of the graphical user interface which is a component of the computer program of the present invention. What appears as text in this drawing is intended to represent elements of the graphical user interface as it is displayed on the device. This was necessary to show the form and indicate the functionality of the graphical user interface. There is actually no descriptive text superimposed upon this drawing other than the figure number and the page number.

BEST MODE FOR CARRYING OUT THE INVENTION Fundamentally, the present invention provides a device for the determination of blood flow in a discrete blood vessel and which incorporates the following subsystems:

1) An exciter beam / camera module which has the functions of first providing an excitation energy beam directed at a fluorescent contrast medium that has been injected into the blood stream. A second function is to capture the live video image of the fluorescent radiation which moves with the blood flow and is of an infra-red wavelength able to pass through vessel walls and tissue. Additionally, this module includes a collimated beam projector as part of a sub-system to calculate spatial distances from acquired image data.

2) A data processing, device control and feedback subsystem which receives the image data signal from the camera module, and displays the real-time image on a standard monitor. This subsystem processes the video data for automated calculation and display of the blood flow rate in the selected blood vessel segment. This same subsystem controls the overall device through a software program incorporating a graphical user interface from which the user operates the device. This subsystem also creates a database containing the acquired video, the text data entered by the user and derived data calculated by the computer program. 3) An input / output signal processor which acts as an interface between the digital data processing subsystem and other device subsystems and modules. Control signals originate from the computer and are sent to the input /output signal processor whereupon these signals are processed to meet the electrical requirements of the devices which are to be controlled. Also sensors on the device are sent to the input /output signal processor for temporary storage and conversion before being sent to the computer.

4) An archive subsystem which uses digital data storage technology, such as optical storage media (e.g., DVD), for the purpose of long term storage of the data base acquired and calculated by the device. This archive subsystem need not be permanently or directly connected to the main acquisition part of the device but may include an automated indexing system that is compatible with the main acquisition part of the device.

5) A power supply subsystem that transfers power from the local external source and distributes the electrical power at the required voltages and electrical current values to the subsystems listed immediately above.

More detail is now provided, with reference to the three drawings listed previously, as an indication of the best mode for carrying out the present invention.

From Figure 1:

This drawing of a block diagram shows the main subsystems, modules and components of the invention. The drawing provides an overview of these items and indicates the functional organization and purpose of each. The design is symbolic and serves to illustrate the interfaces among the subsystems together with their unique functions.

The device comprises a computer system (10) consisting of a monitor (15) with a displayed graphical user interface (14), a computing unit able to execute one or more included programs(13), a keyboard (12) and pointing device (11).

The archive subsystem (20) may be connected, but not necessarily permanently, with the computer system (10). This archive system comprises optical disk media (21), a reading device (22) for the storage media which may incorporate an indexing-retrieval system that facilitates the selection of the desired archive volume name / number. The subsystems (10 and 20) receive electrical power from the main power supply (30) which is connected to the local power services. This main power supply is designed to accept a range of international electrical power standards.

The main power supply (30) delivers transformed lower voltage to the DC power supply (32) which in turn delivers DC power to exciter beam / camera module (40). The exciter beam / camera module consists of a camera (42) and a radiation source (44) which delivers an excitation energy beam (45) in the infra-red spectrum range to a selected area (47) of a patient (48). The camera (42) senses the fluorescent radiation (43) emitted from any energized chromophore located in the selected area (47) and transmits the image data to the computer system (10) where it can be stored, viewed and further processed. A video camera frame rate for image recording can be used which is greater than the standard of 25 or 30 frames per second in situations where a higher time resolution of motion video is desired.

As previously described, the chromophore agent is injected as a bolus into the patient and is caused to fluoresce by the excitation radiation (45). This fluorescent radiation (43) is emitted from within the patients blood vessels in the selected, irradiated area (47) and is recorded by the camera (42). Because of the non-ionizing type of the excitation radiation and its low thermal energy level, there is no need to protect the eyes or body of the medical staff or the patient from the radiation when the device is used as intended and described.

A secondary radiation beam (46), which is precisely collimated for the purpose of projecting a graduated reference or shadow mask, having a length reference, onto the selected area of interest, is projected from the reference beam module (41). From this projection, the recorded image frame contains said length reference and is used to calculate spatial dimensions from the image data.

An input / output signal processor (34) controls the communication between the computer system (10) and the optical module (40), and with other sensors and device components . From Figures 2A and 2B:

Figures 2A and 2B represent the organization of the data structures. Unique names of data structure components have been chosen because of the need for identification of the separate data elements by the computer program. These same names are used here to assist in the explanation of the data structure and the functioning of the database. Before the device is put into operation for the first time, the fixed disk must be organized with a basic data structure. This is shown in the Figure 2A as CINE-DAT at the root level of the structure. This may either be a directory or a disk volume name, depending upon what is most advantageous and efficient for the operating system being used with the computer system. Also, in this initial organization, three subdirectories are created under the root level of CINE-DAT. This three sub-directories are shown as PATIENT-DAT, TEMP-UNARCH, SYS-DAT.

After this initial organization of the data structure on the fixed disk of the device's computer subsystem, the device is put into operation. From that point on, the program creates the remainder of the data structures under program control and identifies their elements uniquely as a function of the computer program. This is done by the program as it processes and stores new data that is received as input to the computer system.

A subset of this data structure, which includes all but the preliminary structure indicated above in 2A, is also created on removable storage media at the time that the functions of archiving and copying are activated.

The first of the initial subdirectories is PATIENT_DAT (Figure 2A, and again in Figure 2B, level 1). This directory contains all of the entered patient name and ID data, the acquired motion video images, the text comments for each of these video images and any derived data from the computer analysis of the images such as flow rate calculations. The subdirectories under PATIENT_DAT are structured and named as follows (Files are indicated in italics) :

In structure level 2 (Figure 2B, level 2), the program creates a subdirectory for each patient that is entered into the system by the user. In routine use, the system will contain many such patient name subdirectories (as indicated by "..."). In the structural level shown in line 3 (Figure 2B, level 3), there will be at least one ACQUIRE_SERIES type of subdirectory for each patient. When repeated acquisition procedures are performed on a single patient in which the system remains in the acquisition mode, all the data acquired and stored during this acquisition session are placed under a single ACQUIRE_SERIES_YYYY_MM_DD-HH_mm, where the subdirectory suffix,

YYYY_MM_DD-HH_mm uniquely identifies the start date and time of the acquisition session performed on a given patient. In general, the count of patient cases correspond to the number of acquire session type of subdirectories which have been created for all patients. This is defined in further detail in the SYS-DIAG Module (Figure 3) and under the description of directory, SYS_DAT (Figure 2A).

In level 4 under each patient name subdirectory, any number of C-FLOW subdirectories are stored (Figure 2B, level 4). These C-Flow subdirectories each contain the data stored for one C-FLOW acquisition; that is, image data from one motion video acquisition including comments, and any derived data from the optionally activated computer analysis of blood flow.

In level 5, we have the actual video file indicated with a generic file extension of ".VID", the text comments file, and one C-QUANT subdirectory (Figure 2B, level 5). The C-QUANT subdirectory contains any derived data such as program calculated blood flow data.

In level 6, There are any number of ROI (Region Of Interest) subdirectories (Figure 2B, level 6). These subdirectories are created for each case in which the user has requested the program to perform a separate analysis on a user-selected sub-region (the ROI) contained within the region recorded in the current acquired motion video data as described in the paragraph immediately above. The selected sub-region chosen by the user for the purpose of further analysis of the blood flow rate by the program. It is intended that this sub-region be selected by the user so as to contain only one discrete blood vessel segment which will define and limit the area of calculation for the computer program in the computation of the blood flow rate.

In the final level, level 7 (Figure 2B, level 7), each ROI contains three files. The first is a single still frame image file, for example, ROM.IMG or RIO-2.IMG, ... ROI-n.IMG which is an image of the ROI sub-region described in the paragraph immediately above. The second related file, e.g., GRAPH-l.IMG ... GRAPH-n.IMG, contains the parameters which enable the computer to display the 2-dimensional graphical results generated by the automated analysis of the ROI. The QUANT-n.TXT file contains the derived numerical data generated by the same analysis which may be used in conjunction with the display of the 2- dimensional graph of the blood flow rate as described in this paragraph.

Figure 2A shows the second of the initial subdirectories, TEMPJJNARCH, which is needed when the user requests data that has been previously archived, i.e., it is not on the local fixed disk of the device. The system will prompt the user to insert into the system drive the appropriate archive volume name / number of removable media an index of which is advantageously stored on the device, consuming relatively little storage space. The corresponding volume name / number is inscribed onto the removable media at the time of archiving. The requested data (actually, the entire structure of a Patient Data Set) is copied from the archive media to the TEMPJJNARCH subdirectory. Since the data structure was preserved in the archive, it is now restored, but under the sub-directory TEMP_UNARCH as indicated. The purpose of this is so that the device user can now work with this previously archived data through the standard functions built into the computer program. This data, which may have been acquired at any time previously on the device, can now be analyzed in the same manner and with the same precision as newly acquired data. The results of the analysis, which may include, for example, the blood flow rate on a vessel segment not previously checked, may now be viewed, stored, copied to removable media or printed.

Because the above use of the device for analyzing or re-analyzing historical, archived data is not intended as the most routine of uses, the fixed disk space allotted to TEMP_UNARCH may reasonably be more limited than for PATIENT_DAT. Therefore, the data stored in TEMPJJNARCH is periodically deleted by the program on a basis calculated from the available remaining storage space and on a first-in, first-out basis. The space allotment for this subdirectory can be modified for special user needs by someone with administrator level user rights to the computer system.

The third and last of the preliminary sub-directories, SYSJDAT shown in Figure 2A contains data which is not specific to any of the patients or medical subjects from which images and data are acquired and processed. This is tiie repository for such data items as: The running count of procedural cases which are stored according to monthly, quarterly, and yearly count; an event & error log file; a user login and password names, local language selection for the text of the graphical user interface. It is intended that the clinical user have no direct access to this area of the data structure.

Figure 3 indicates an example of the main menu of the graphical user interface. The main menu provides initial access to the functions activated through the GUI, the primary means of operating the device. This represents the main control panel of the device of the present invention and is presented to the user via the system monitor following a routine login procedure. The login procedure is a significant feature of the preferred mode of carrying out the present invention and is intended as a component of more general security feature for sensitive medical data.

The preferred mode of carrying out the present invention includes in the computer program a security system with access rights on three hierarchical levels for three corresponding levels of user groups. At the highest level, an administrator type of user, has rights to all features and functions available in the system computer program. It is intended that the manufacturer and associated service personnel be given administrator rights in order to perform testing, service functions or system initialization. The second level of user rights are referred to as manager rights. These rights are granted, through password protection, to designated individuals at the location where the device is to put into routine operation. Compared to administrator rights, the manager has most of the rights of the administrator with the exceptions of initializing the system database, resetting the count of case procedures and similar functions not directly related to medical data. At the third level, the user category is referred to as the ofjs user, indicating the routine operational user. This is the user level where that is intended to be most routinely used in the acquisition and analysis of blood flow data. The rights of this user group are limited by all the rights limitations of the manager group, plus additional rights limitations. An example of some of these further limitations are restrictions from deleting certain data sets and restriction from certain of the diagnostic functions.

The purpose of the assignment of rights for the access to features of the system is intended for the security and integrity of the medical data stored on the device. It is not intended to restrict the user from the medically advantageous functions of the device. It should be noted that the rights are intended as group rights rather than individual rights. The preferred mode of the present invention permits the organization responsible for the use of a particular instance of the device to assign the ogs (routine device operators) and manager user rights to persons or groups most appropriate for the particular use.

Figure 3 illustrates the main menu of the graphical user interface displayed for a user who has logged in as a member of the administrator group. The menus of the manager and ops user groups appear similar to that of the administrator group with the exception that certain functions are invisible or locked. For rapid and intuitive use, all functions related to processing of medical data are grouped in a column on the left side. Additionally, these functions are placed into the three sub-groups with clinical functions as the most time- critical, first. Second are placed the patient data transfer functions, and thirdly are located the lesser used system and maintenance functions. The action buttons for system shutdown and program end are placed safely away from the routinely used left column and are indicated with appropriate warning colors. The activation of each of the functions located in the left column provides the user with a new menu window containing appropriately intuitive guides for currently chosen sub-function activation. There is always the option provided to return to the main menu or to the previous screen which subsequently provides an option for the main menu. The intention in the preferred mode of the present invention is to eliminate the need to refer to the operators manual in the case routine use of the device. The creation of such intuitively accessed, operational features are advantageous for intra-operative medical use. This advantage is realized by the form and functionality of the graphical user interface created specifically as a component of the present invention.

The functions available in the GUI such processes as image acquisition, data retrieval, data copy, data archive, deletion of data and system diagnostics for checking the integrity of the hardware / software system. These functions are all executed within the limitation imposed by the data structures in concert with the controlling program. Thus the user is both guided and limited in the operation of the computer subsystem as a means of maintaining the security, accuracy and integrity of patient medical data. That is to say, the user is generally restricted from using the operation system without going through the program included in the present invention. The graphical user interface, together with program execution, additionally facilitates for the user the ability to intuitive manage a hybrid database containing vascular images and associated information in numeric and text form. The user interface to the database is constructed in such a way that the detailed processes and characteristics of the database are hidden from the user. In this way, access to the database is intended to be intuitive and to require generally no special training for this specific portion of the data processing application program.

The man-machine interface in the form of the GUI of the present invention is intended to meet the requirements of users as medical practitioners in an intra-operative, surgical environment where such use is estimated to be the more demanding in terms of intuitive and ease-of-use requirements with respect to other potential uses for the invention. In the best mode of carrying out the present invention, there remain a minority of functions requiring manual operation such as positioning the camera and inserting optical recording media. The concentration of system control functions, all data processing functions, system feedback indicators and text input are activated through the GUI.

This database is structured in a way which associates various data types referenced to each image acquisition and patient case. The database program features are designed for rapid deployment during vascular intra-operative procedures, where real-time data is generated, in that nearly all database processes function automatically. The collected data during such procedures are stored in the appropriate locations with the correct associations in relation to other data types for the same respective acquisitions and current procedural case. These storage location determinations are made under program control with minimal intervention by the user during the surgical procedure. The resulting database of images and related data have advantages for real-time assessment of procedures involving vascular surgery, for indications of immediate corrective action based upon such immediately available information. This database content also provides advantages for follow-up treatment involving related surgery and for quality control confirmation of procedures when using the present invention as an intra-operative device. Advantages exist as well in the research area involving vascular surgery and related techniques.

The system's data structures are also necessary to permit the advantageous functioning of the present invention's primary clinical and data processing features. These functions include acquisition of data for viewing, analysis and storing; data retrieval for display and analysis, the duplication of data via an expressly defined copy function, data archiving and data deletion. Specific data structures forms ensure that data files, corresponding to a given procedural case and corresponding to a given patient, remain properly linked. Such a linkage is necessary for the safe and accurate routine retrieval of desired data, and to ensure that the results of analysis are stored in their proper locations. These data structures are included in the means of securing data in the event of system failure after which it would be desirable to facilitate data recovery. An outline of the data structure of the database of the present invention has been described with reference to Figures 2A and 2B.

In the best mode for carrying out the present invention, the device has application in further research with chromophores that fluoresce in different frequency ranges. The use of different frequencies provide the possibility of different transmission characteristics through biological tissue. The advantage of the present invention is that only relatively small changes need be made in the optical exciter / camera module to accommodate the use of such different frequency ranges. Specifically, the optical filter band pass, camera frequency sensitivity or exciter beam specifications would need to be modified, but not necessarily all three. This is to say that the exciter beam / camera module and subsystem would need to be modified to make use of other chromophores, but the remainder of the device design and computer system could remain essentially unaltered.

The best mode for realizing and deploying the present invention includes the acquisition of numerous sets of motion video data. Even with the use of current compression techniques, the digital storage capacity requirements for numerous sets of motion video image data is considerably large. One video file of 45 seconds in duration at a frame rate of 30 fps in the common AVI data file format requires nearly 1GB of space on a fixed disk. If four to six such image files are stored for one procedure, as is anticipated, the available fixed disk capacity would soon be consumed.

In regard to the anticipated situation described immediately above, this potential operation problem is resolved: The combined features of the computer program, database and data structures of the present invention permit the transfer of the acquired and processed patient data from the system fixed disk to removable optical disk media in such a way as to maintain the integrity of the hybrid database, which in turn maintains the integrity of each item of data together with its correlation with other data items. As an advantageous consequence, the user's access to the data is improved, and the security of the data is enhanced. This data transfer feature provides for the recovery free space from the system fixed disk by transferring patient data sets to an off-line archive through a specific archiving action function found in the GUI. Furthermore, to accommodate the archiving and copying of large data structure elements, the present invention incorporates a computer optical drive that can write onto media having a capacity of several gigabytes.

In an additional aspect of a mode for realizing the present invention, the computer system manages the control and feedback of electronic signals between the computer and other device subsystems. Such control and feedback signals are received and transmitted through an input output (i/o) signal processor subsystem (item 34 of Figure 1) which is external to the computing unit (13 of Figure 1). The i/o signal processor subsystem has two main functions: The first function is to receive electronic analogue signals from a number of sensors which are contained within certain of the device subsystems. An example of such a signal is the analogue voltage signal indicating the focus range between the receptor optics and the irradiated patient area. The i/o signal processor subsystem receives the analogue distance signal, encodes it as digital information, temporarily stores the digital value for the necessary short time period during which the digital value is transmitted, using sufficiently fast, communication protocols such as IEEE 1394 (fire wire) or other appropriate industry standards.

A second main function of the i/o signal processor is to receive control signals sent by the integrated computer subsystem. The computer system generates control and status signals as part of the routine operation and control of the device by the human user, and this is effected primarily through the GUI. An example of this control signal function is found when the user is operating the device within the image acquisition function of the GUI. When the user activates a record sub-function from within the acquisition function, a control signal is communicated from the computer system to the i/o signal processor subsystem. Additional signals are sent from the i/o subsystem to the exciter optical subsystem in order to activate an excitation radiation beam. Another control signal generated from the i/o subsystem causes the superposition of a measurement grid or reticule onto the patient area from which an image is to be recorded. Also contained in the computer program, comprised within the preferred mode of the invention, are an algorithm and program functions enabling the program to perform an automated analysis of the image data. The result of this analysis is the blood flow rate in a selected blood vessel segment. Such analytical results are recorded numerically within the system's data structure and are displayed on the system monitor for immediate use by the user. Also a 2-dimensional graph is displayed for the user in which time is the preferable horizontal axis and volume per time (flow rate) is the preferred vertical axis. Such a graph displays the time rate of blood flow in the analyzed blood vessel over a time interval of several seconds.

A computer program, in the best mode of carrying out the invention, also affords a means of calculating a blood flow rate through a selected blood vessel, not only at the time of acquisition (real-time), but at any time post-operatively as long as the data remains stored within the system or exists in volatile memory. Real-time calculations can be done as the image data is loaded into the main memory of the computer subsystem for the first time. The advantage of this is rapid results. Post-operative calculations may be made from stored data residing on the device, from data on archived media which has been recorded on the same system or another system compatible with the present invention. Post-operative calculations are accomplished by loading stored data into the main memory from nonvolatile storage such as fixed disks or optical media.

Used in a post-operative manner, the present invention provides an advantageous means of blood flow analysis that was previously generally unavailable: The present device now makes possible the analysis of blood flow using stored data from the database of the invention that can be retrieved and analyzed at any time subsequent to the data acquisition. It is possible to extract such new information from old data because a basic element of the stored data is a dynamic sequence of images of sufficient time and spatial resolution on which analysis is effective. Furthermore, the computer program and its procedures of operation permit the user of the invention to produce numerical data regarding such parameters as time rate of blood flow in a discrete blood vessel segment selected from dated, identified and correlated, previously stored image data in the same manner and method available to the user in the analysis of real-time, acquired image data. Additionally, the best mode of executing the invention comprises a counting function which counts each uninterrupted sequence of acquisitions. This count, stored according to the date interval of the activation of the acquisition function, is incremented only after the user exits the image acquisition function for a particular patient or research subject. One such uninterrupted series of image acquisitions is referred to as a case within the computer program because it is analogous to the medical procedural case performed on a patient. The case activity is stored simply as an incremental count, according to the dates of acquisition. The case count for a specific time period is the numerical value of any given element of the array, corresponding to a particular time interval: month, quarter or year. The total case count is the summation of all the periodic case count values. The advantage of such a function provides convenient access to information regarding the frequency of the previous use of the system and has application for both maintenance and accounting for the device usage.

The preferred mode of realizing the present invention further comprises a computer program which provides the user with a diagnostic set of functions for troubleshooting device failures, with the display of and option of copying an event & error log produced by the program. Such functions also include the possibility to exercise various sensors, input and output subsystems in order to assess their integrity.

The best means of realizing the present invention, only for the case of the perfusion mode of operation, includes the capability to compare the calculated, relative perfusion index to values from a database of perfusion index values for various tissue and organ types and categorized for various medical procedures for the purpose of enhancing the interpretation and assessment value of the perfusion index generated by the device. Such a database of values must be collected from statistically valid samples of results generated by several instances of the device and of its users.

INDUSTRIAL APPLICABILITY The applicability of the present invention is within the medical industry and biological research fields. Specifically, the device disclosed in the present invention has applicability in the areas of vascular surgery for human clinical procedures and veterinary medicine. The device is especially advantageous in those areas where the combined availability of real-time blood flow assessment together with more precise flow rate calculations would improve the success and efficacy of the surgical procedure and enhance its outcome. Additionally, the device has application as a quality control tracking system. The data storage and archiving functions of the device permit the retrieval of images and analysis of surgical cases where post-operative information is desired. The device also has application as a research tool that is enhanced by the fact that further and more detailed analysis can be made on acquired image data independent of the time interval following the actual acquisition of the original surgical image data. Such a research tool has use in evaluating vascular surgical techniques and developments. Use of the invention as a research device is also closely related to the use of the device in the teaching of medical techniques and vascular physiology. This applicability for teaching is enhanced in that the present invention makes use of visual, dynamic images as an important part of its output for the purpose of blood flow assessment.

In a separate perfusion mode of operation, the present invention has application in the same fields indicated above but for a different purpose. The applications for this mode of operation include procedures in which it is advantageous to determine the ability of a tissue or organ region to maintain a relative level of total blood flow rate for that region where there is a plurality of blood vessels. Use of this operational mode would extend the application of the device to areas beyond vascular surgery to include a wider range of general tissue repair or surgical procedures on organs.

Claims

1. A device for the determination of blood flow through a selected blood vessel segment, preferably in a living organism or functioning organ and particularly for the numerical quantification of the blood flow rate comprising: a) a radiation device (44 of Fig.l) for the irradiation of a biological tissue region or organ region (47 of Fig.l), containing at least one blood vessel segment from which the blood flow rate is to be determined, and by means of an excitation radiation beam (45 of Fig.l), which has suitable characteristics necessary to produce fluorescence in a chromphore that has been introduced into the blood stream of the living organism or functioning organ, b) an image sensing device (42 of Fig.l) to produce, in the form of electronic image signals, the image generated by the fluorescent radiation (43 of Fig.l) emitted from the chromophore in blood vessels in the irradiated region (47 of Fig.l), and to transmit these electronic signals, representing the fluorescent image of the irradiated region, repeatedly in regular time intervals of a video image frame, using a standard electronic image format or encoding system and c) a computer system (10 of Fig.l) comprising a computer unit (13 of Fig.l) that includes a calculation and controller processing system to receive, process and display transmitted electronic image data in order to calculate the blood flow rate through a selected blood vessel segment on the basis of the change in position, in each consecutive image frame, of the pixel group, which is determined to have defined intensity characteristics, and on the basis of the calculated dimensions of the selected blood vessel segment.

2. A device according to claim 1 where the improvement comprises a means for the qualitative assessment of blood flow through a selected blood vessel segment, preferably in a living organism or functioning organ, by displaying the real-time motion image of the fluorescing chromophore on the computer system monitor (15 of Fig.l) as this choromphore concentration in the blood stream flows through the selected blood vessel segment, and wherein said image is concurrently displayed during the quantitative blood flow calculation process of claim 1.

3. A device according to claim 1, wherein the computing unit is characterized by: a) a calculation system for computing the dimensions of the selected blood vessel segment from electronic image data containing an image of the blood vessel, b) a calculation system for computing the position of the injected concentration of fluorescing chromophore, as this concentration flows through at least one blood vessels in the region of interest, with respect to pixel location within each separate image frame of digital motion video data, and within a prescribed boundary size within the size of the area of the flowing concentration of chromophore, c) a calculation system to determine the variation in position, with respect to pixel units, of said concentration of fluorescing chromophore as this position varies in consecutive frames of the digital motion video data, d) a calculation system to compute the apparent speed of the changing position of the chromophore concentration within the consecutive image frames and in pixel units per time interval of the image frame rate and e) a calculation system to compute the blood flow rate using the results of the calculations a) through d) above.

4. A device according to claim 3 wherein the image data to be used by the calculation system is a user-selected subset in the sense of being a subset of sequential frames of the originally acquired image data and in the additional sense where the subset of the image data represents a 2-dimensional image area subset of the originally acquired data and in which the size and location of this area subset is selected as, input to the computing unit, by the user such that it contains only one blood vessel segment of prominent, fluorescent intensity.

5. A device according to any of claims 1-4 characterized by a) a calculation system to compute the center of the position of the contiguous pixel group having the highest average intensity, which corresponds to the highest concentration of fluorescing chromophore, with respect to pixel location within each separate image frame of digital motion video data and within a pixel group size, such as 9 x 9 or 13 x 13, and defined as a variable within the calculation system, b) a calculation system to determine the variation in the central position of the contiguous pixel group, with respect to pixel units, having the highest average intensity, as this center position varies in consecutive frames of the digital motion video data, c) a calculation system to compute the apparent speed of the changing position of the center of the contiguous, high intensity pixel group within the consecutive image frames, computed in pixel units per time interval of the image frame rate, d) a calculation system for computing the dimensions of the selected blood vessel segment from electronic image data containing an image of the blood vessel and e) a calculation system to compute the blood flow rate using the results of the calculations a) through d) above.

6. A device according to any of claims 1-4 wherein the calculation system a) computes the central position of a contiguous pixel group, having an odd and equal number of pixels on each side of the rectangular group, by searching for the location of such dimensioned pixel group having the greatest average intensity increase, when compared in a differential assessment of pixel groups in the preceding image frame, and where the number of pixels in the sides of said pixel group are determined by a program variable whose value is dependent upon the success of locating such a pixel group in the first or any successive search iterations needed for the position determination process, and where said computation of the central position of said pixel groups corresponds to the position of the leading edge of the concentration of fluorescing chromophore flowing through the selected blood vessel with respect to each successive frame of the image data, b) determines the distance variation among said pixel group center positions , in terms of pixel units, as these center positions may vary relative to each of the consecutive frames of the digital motion video data, c) computes the apparent speed of the changing position of the center of the contiguous pixel group with respect to the consecutive image frames, and computes said speed in pixel units per time interval of the time of one consecutive image frame cycle, namely the inverse of the frame rate used to sense, format or transmit the image, d) computes the dimensions of the selected blood vessel segment from electronic image data containing an image of the blood vessel and e) computes the blood flow rate using the results of the calculations a) through d) above.

7. A device according to any of claims 1-4 characterized by an exciter beam / camera module (40 of Fig.l) that comprises an optical component (41 of Rg.l) which can introduce or superimpose a smaller collimated beam, into the exciting radiation beam (45 of Fig.l), and which can be used to project a grid, reticule or beam outline onto a selected area (46 of Fig.l) within the irradiated region (47 of Rg.l) and the projected scale has a precision of at least one millimeter in the 2-dimensional direction orthogonal to the direction of the radiation beam.

8. A device according to any of claims 1-4 characterized by a exciter beam / camera module (40 of Fig.l) that comprises an additional radiation source capable of being accurately aimed by the user, such source which emits a collimated radiation beam and projects a measurement scale calibrated in standard units onto a selected area (46 of Fig.l) within the larger irradiated area (47 of Fig.l), and whereby the radiation frequency emitted by this collimated light source is in a range compatible with the frequency of the fluorescent radiation to which the image sensing device (42 of Fig.l) is sensitive.

9. A device according to any of claims 1-4 wherein the image sensing device (42 of Fig.l) comprises a camera which has an analogue electronic image signal output.

10. A device according to any of claims 1-4 wherein the image sensing device (42 of Fig.l) comprises a camera which has a digital electronic image signal output.

11. A device according to any of claims 1-4 wherein the device comprises a computing unit (13 of Fig.l) containing a database in which to store the images produced by the image sensing device (42 of Fig.l) within the data structures of the database in locations defined by the computer program.

12. A device according to any of claims 1-4 wherein the computing unit (13 of Fig.l) comprises a device that stores data structures (Fig. 2A and 2B) which provide defined storage locations for the image data, calculated numerical data and text data entered by the user, and comprises a device wherein the computing unit (13 of Fig.l) includes a processing system capable of copying said data structures, together with acquired data, onto removable storage media such as compact disks and digital versatile disks.

13. A device according to any of claims 1-4 whereby the computer system (10 of Fig.l) comprises a graphical user interface (14 of Fig.l) for the primary means of user control, for the display of medical data and for the displayed indications of device subsystem status.

14. A device according to any of claims 1-4 whereby the computer system (10 of Fig.l) comprises a security system as a component of a computer program which can be suitably executed on the computer system in such a manner that the security system provides a hierarchy of user rights to at least three categories of user groups by means of a password protected login process, which controls and limits, on a hierarchical basis according to user group category, the access to different controls and functions available through the graphical user interface (14 of Rg.l).

15. A device according to any of claims 1-4 characterized by a computer program which, through the graphical user interface, automates at least one the following functions: a) recording of the image data produced and transmitted by the image sensing device (42 of Fig.l), b) storage of a sub-sequence of consecutively acquired image frames, c) analysis of a selected 2-dimensional region within these recorded consecutive image frames in order to calculate the blood flow rate in a selected blood vessel segment found within the selected 2-dimensional region, d) storage of selected images from the database together with associated analytical blood flow data and text information into the archive system (20 of Fig.l) and e) the retrieval, copying, restoration and deletion of acquired and calculated data according to data structure and security rules controlled by the program.

16. A device according to any of claims 1-4 wherein the computer system (10 of Fig.l) comprises a computer program, containing algorithms and program functions, suitable to execute an automated analysis of the acquired image data and to calculate and display the numerical blood flow rate in a selected blood vessel segment and further display the blood flow rate as a 2-dimensional graph in which the horizontal axis is preferably the time interval and the vertical axis is preferably the time rate of blood flow in standard volume units per time.

17. A device according to any of claims 1-4 wherein the improvement comprises a computing system capable of calculating the blood flow rate at any time following the real-time acquisition of the image data provided that the image data remains either stored within the device or is loaded into memory from removable storage media.

18. A device according to any of claims 1-4 wherein the improvement comprises an integrated counting function that counts each uninterrupted sequence of acquisitions such that the computer program keeps a record of the number of each of these uninterrupted sequences, and the count, stored according to the date interval of acquisition, is incremented only after the user exits the image acquisition function for a particular patient or research subject.

19. A device according to any of claims 1-4 characterized by a computer program that provides the user with a diagnostic system for trouble-shooting system failure, to verify subsystem integrity, to display an error & event log and to display a history of the case counts within selected date intervals.

20. The use of a device according to any of claims 1-4 for a procedure to determine the blood flow rate through a selected blood vessel segment, preferably in a living organism or functioning organ, and particularly for the numerical quantification of the blood flow rate, while concurrently providing a means of qualitative assessment of the blood flow by displaying on the computer system monitor (15 of Fig.l) the real-time motion image of the fluorescing chromophore as it flows through the selected blood vessel segment.

1. A device according to any of claims 1-4 where the improvement comprises an additional program module that provides, at the option of the device user, a quantitative assessment of the total blood flow rate into a selected tissue or organ region containing a plurality of blood vessels and where said program module: a) computes the total intensity of the pixels in each frame of a user-selected sub- region of the image data that represents the selected region during which a chromophore has been introduced into the bloodstream and while the region is irradiated to excite the chromophore into fluorescence, b) computes second-order differential values of the intensity change, using the time intervals between each frame, for sequential frames of the image data of the selected sub-region, where these differential values are intended to correspond to the rate of the increase in the total chromophore volumetric increase within the selected sub-region, c) determines a maximum average from the above differential values corresponding to each time interval following the first frame by computing the average of the maximum value and the intensity increase-rate-values calculated for time intervals in the program-defined neighborhood of said maximum and d) displays and records this computed, average maximum of the rate of intensity increase as a numerical index for the assessment of the blood flow rate for the selected region.