WO1998036683A1 - Non-invasive radiographic method for analyzation of a body element - Google Patents
Non-invasive radiographic method for analyzation of a body element Download PDFInfo
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- WO1998036683A1 WO1998036683A1 PCT/US1998/003464 US9803464W WO9836683A1 WO 1998036683 A1 WO1998036683 A1 WO 1998036683A1 US 9803464 W US9803464 W US 9803464W WO 9836683 A1 WO9836683 A1 WO 9836683A1
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Classifications
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T7/00—Image analysis
- G06T7/0002—Inspection of images, e.g. flaw detection
- G06T7/0012—Biomedical image inspection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
- A61B6/508—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for non-human patients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
- A61B5/085—Measuring impedance of respiratory organs or lung elasticity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
- A61B5/091—Measuring volume of inspired or expired gases, e.g. to determine lung capacity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
- A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
- A61B5/418—Evaluating particular organs or parts of the immune or lymphatic systems lymph vessels, ducts or nodes
Definitions
- the present invention is directed to a system for imaging internal body structures and, more particularly, to a system for non-invasively analyzing and diagnosing abnormalities in a body element.
- GI gastrointestinal
- direct endoscopy requires the invasive introduction of a scope into the lumen of the structure under consideration to visualize its inside surface.
- the actual physical advancement of a scope within the patient may be hampered by obstructions which prevent or limit viewing of distal abnormalities.
- Radiological and sonographic imaging has been used for decades to non-invasively determine the internal status of the human body. Radiographic procedures, such as computed tomography (CT) and magnetic resonance imaging (MRI), operate on the basis of distinct physical principles by detecting and mapping differences in the composition of a target object.
- CT computed tomography
- MRI magnetic resonance imaging
- Radiographic procedures utilize a beam of x-rays to pass through a target object and expose an underlying photographic film.
- the film captures an image of the radiodensity pattern of the object. Areas of less radiodensity (e.g., air pockets) produce a greater blackening of the film. More radiodense objects (e.g., bones) produce a light image. Contrast agents are chosen so as to provide either less or more radiodensity than body tissues of interest.
- Computed tomography is superior to conventional radiography in its ability to image a sequence of thin sections of an object at specific planes along the X, Y or Z axis of the target object and to do so with extremely high resolution.
- Nuclear magnetic resonance imaging systems for body imaging operate on a different physical principle.
- Some atomic nuclei such as, for example, hydrogen nuclei, have both nuclear spin and nuclear magnetic moment. As such, these nuclei can be manipulated by applied magnetic fields.
- a magnetic field is established across a body to align the spin axes of the nuclei of a particular chemical element, usually hydrogen, with the direction of the magnetic field.
- the aligned, spinning nuclei execute precessional motions around the aligning direction of the magnetic field.
- the frequency at which they precess around the direction of the magnetic field is a function of the particular nucleus involved and the magnetic field strength. The selectivity of this precessional frequency with respect to the strength of the applied magnetic field is very sharp, and this precessional frequency is considered a resonant frequency.
- a burst of radio frequency energy at the resonant frequency is radiated at the target body to produce deflection of the spin alignment of the selected nuclei.
- the deflected spin axes start to realign.
- the realignment of the spin axis emits a characteristic radio frequency signal which can be detected by an external coil.
- the differences in the emitted radio frequency signal establish contrast between the different tissues.
- Contrast agents may be introduced into the body space in various ways depending on the imaging requirement.
- a suitable contrast agent must be biocompatible, that is non-toxic, and chemically stable, minimally absorbed or reactive with the tissue, and eliminated from the body within a short time.
- FCs Fluorinated hydrocarbons
- FC liquid can be used as an alternative respiratory media to support gas exchange.
- FC liquids are characterized by high respiratory gas solubility, are bioinert, nonbiotransformable, minimally absorbed, and have no deleterious histological, cellular, or biochemical effects.
- Fluorocarbon (FC) liquids are derived from common organic compounds by the replacement of all carbon-bound hydrogen atoms with fluorine atoms. These liquids are typically, clear, colorless, odorless, nonflammable and essentially insoluble in water.
- Perfluorinated compounds e.g. , perfluorocarbons or PFCs
- fluorinated hydrocarbons are generally the preferred form of fluorinated hydrocarbons.
- FC liquids are denser than water and soft tissue, and have low surface tension, fluorocarbon liquids have a high affinity for gases, dissolving more than 20 times as much 0 2 and over three times as much C0 2 as water. FCs are also nontoxic and biocompatible.
- helical CT computerized tomography
- Volume rendering is an alternative to conventional surface display and projectional techniques and has significant advantages. Because volume rendering uses information from all "voxels" within the volume, there is no information loss. As a result, it is not subject to the limitations caused by the information loss that is inherent in maximum intensity projection or to thresholding that occurs in surface displays. The basic drawback to volume rendering is that it is computationally more time consuming and expensive than other methods.
- An additional advantage of volume rendering is that the images can be displayed as perspective views. That is, the images are rendered from a point source at a finite distance to approximate the human visual system. As a result, a close object appears larger than an object of identical size at a greater distance from the viewer. Surface displays of convention CT and MR data are rendered without perspective. Hence, the distance between objects is not readily apparent.
- volumetric or three dimensional rendering of internal structures has been used to provide either a static or dynamic depiction of the scanned objects for viewing by medical personnel.
- the data accumulated has not, to date, been utilized in combination with a computer software and/or hardware system for analyzing and diagnosing abnormalities.
- a non-invasive process for analyzing an internal element in a body of a human or animal.
- the process involves scanning the body to acquire data representing a portion of the body's internal structure.
- the data is processed into three dimensional volumetric data representing the scanned internal body element.
- a portion of the volumetric data is selected from the processed scanned data.
- Baseline data representing three dimensional volumetric data for either a normal internal body element or the patient's actual internal body element as determined from previous scanning processes is also used in the process.
- a portion of the baseline data is selected which corresponds to the selected portion of the scanned data.
- the selected portions of the scanned and baseline data are preferably compared to determine whether an abnormality exists in the patient.
- Output data is sent to a display for displaying information related to the selected portions of the scanned and normative data.
- the internal body element is a tracheobronchial tree within the human or animal body.
- the scanned bronchiole on a selected generation is compared against a baseline bronchiole on a corresponding generation.
- Fluorochemicals can be administered to enhance the scanned data and, thereby, facilitate the visualization and selection of the portion of the scanned data by determining branching along the tracheobronchial tree.
- the apparatus includes a scanner for scanning a portion of a body.
- a processor is utilized to receive the scanned data.
- the processor converts the scanned data into three dimensional volumetric and functional data based on analytical models.
- the processor compares the converted data to baseline data.
- a monitor is utilized to display and compare data related to the scanned and baseline volumetric/functional data.
- the present invention is useful for analyzing the pulmonary function of a patient, such as the patient's airway capacity or resistance, pulmonary volumes and capacities, and airway reactivity of pharmaceutical agents.
- the present invention is also useful for determining congenital anomalies, locating obstructions or masses, and/or reducing tissue damage during surgery.
- the present invention is also useful for determining changes in a patient's internal structure as caused by disease processes, therapeutic or diagnostic intervention.
- Figure 1 is a diagrammatical representation of a portion of a normal respiratory system.
- Figure 2 is a schematic representation of the Meyer model of the tracheobronchial tree.
- Figure 3 represents the process flow of the present invention.
- Figures 4a through 4c are graphical representation of a comparison between the frequency distribution in a baseline structure and a scanned structure.
- Figure 5 illustrates a display of a lobar or segmental abnormality.
- Figure 6 illustrates a display of a branch abnormality.
- FIG. 1 illustrates a diagrammatical representation of a portion of a normal respiratory system 10.
- the respiratory system 10 channels air from a larynx 12 through a trachea 14 into the lungs 16.
- the lungs 16 include right and left bronchus 18 and segmental bronchi or bronchioles 20.
- Air sacs or alveoli 22 are formed on the terminal ends of the bronchioles 20. Air exchange occurs between the alveoli 22 and blood capillaries (not shown) which surround the alveoli.
- Figure 2 is a schematic representation of the "Meyer model" for characterizing the tracheobronchial tree. This model identifies the various branches of the bronchus 18 and bronchioles 20. The descending branches are identified as "generations" or "orders", the 1st order representing the right and left bronchus 18 and the subsequent orders representing the bronchioles 20. As shown in the figure, the numbering begins at the trachea, which is identified as generation 0.
- the numbering proceeds to the terminal airways, increasing by one at each dichotomy.
- This approach can be applied to both symmetric and asymmetric tree models.
- Other models such as Horsfield or Strahler, have a different counting and numbering system for identifying branches and, therefore, in certain cases can end up with fewer orders.
- the generation system as described by the Meyer model is a useful method for locating a branch relative to the trachea (0) generation and, thus, is the most appropriate relationship for bronchoscopic or bronchographic investigations.
- the process flow of the present invention is illustrated as it is contemplated for use as a non-invasive medical imaging and analyzing procedure.
- the procedure involves the steps of imaging or scanning the desired area of a patient, analyzing the scanned data to establish a baseline prior to an airway challenge or therapeutic intervention to determine if abnormalities or changes exist, and displaying any abnormalities or changes.
- the imaging step utilizes a standard imaging device, such as a computer tomography or nuclear resonance imaging machine. It is also contemplated that the present invention can be utilized with three dimensional data acquired by ultrasound.
- the imaging device is a Picker PQ 5000 helical CT device, manufactured by Picker International, Cleveland, Ohio.
- a contrast agent such as a fluorochemical
- a contrast agent is preferably administered into or near the area of interest prior to scanning the patient.
- a suitable contrast agent For example, when imaging the internal bronchioles of the lung, it is preferable to fill at least a portion of the lung with a suitable contrast agent.
- the contrast agent provides the high degree of differentiation between adjacent structures for subsequent three dimensional rendering.
- the preferred type of fluorochemical is a perfluorochemical (PFC). There are a large selection of PFCs' on the market and the one chosen for use in the present invention will depend upon the specific area of interest.
- FC viscosity For example, certain physicochemical characteristics including, but not limited to, vapor pressure, viscosity, and spreading coefficients will influence the rate of evaporation and pattern dispersion of the FC.
- a fluid of high vapor pressure and low viscosity is useful when it is desirable to perform imaging throughout the entire lung over a short period of time.
- a FC viscosity above about 3 cS is generally considered to be a high viscosity.
- a FC viscosity at or below 3 cS is generally considered to be a low viscosity.
- a fluid of lower vapor pressure and high viscosity may be preferred for local imaging over a longer time period.
- FC radiopacity characteristic
- a fluid of marked radiopacity might be particularly useful to delineate larger regions but might in fact compromise detection of finer abnormalities.
- the physical characteristics of the FC will determine the preferred FC for the imaging desired.
- Table 1 provides a list of preferred FCs which are contemplated for use in the present invention. The table also provides the physical properties for each FC. In general, all the listed FCs are inert, odorless and colorless. The FCs have low surface tension (between approximately 10 and 19 dynes/cm) and high solubility for oxygen ( > 40 vol%). These FCs are insoluble in water, sparingly soluble in lipids (as noted by the logP values) and organic solvents, and completely soluble in other fluorinated compounds. Other fluorochemicals may provide the required contrast and, therefore, can be substituted for the preferred FCs listed in the table.
- PP-2 perfluoromethylcyclohexane manufactured by BNFL Fluorochemicals
- PP-5 perfluorodecalin manufactured by BNFL Fluorochemicals Ltd.
- PP-9 perfluoromethyldecalin manufactured by BNFL Fluorochemicals Ltd.
- PP- 11 perfluoroperhydrophenanthrene manufactured by BNFL Fluorochemicals
- RM- 101 perfluoro-furan/pyran mixture manufactured by Mercantile Development
- PFOB perfluorooctylbromide sold under the tradename LiquiVent * and manufactured by Alliance Pharmaceutical Corp.
- FCs can be provided to the patient in any suitable form, such as neat liquid, aerosol, vapor, or emulsion.
- the preferred FC will have material properties which will allow for the FC to remain in or around the structure of interest or coat the walls until the scanning is complete. For example, when scanning the small bronchioles in the lungs, it is preferable to utilize a FC which will remain in the lung for a sufficient length of time to allow the FC to travel through the multiple branches of bronchioles.
- the Houndsfield unit (HU) number of a suitable breathable FC liquid is in the range of 800-2700.
- the preferred form of fluorocarbon is a perfluorocarbon.
- the amount of fluorocarbon necessary will vary depending on the portion of the body being imaged. For example, when imaging the lung, approximately 1 to 2 mils per kilo is needed if it is desired to coat only the alveoli. Approximately 20 mils per kilo is needed to coat everything, including the branches. It is desirable to provide a sufficient amount of fluorocarbon to leave the airways free. Also, the amount of contrast desired will effect the amount of fluorocarbon used.
- the scanned or imaged data is transferred to a computer processor or other processing unit.
- the processor may include one or more forms of memory (e.g., EPROM, ROM, RAM, etc.) for storing relevant data.
- the computations required to form volume rendered images necessitates a relatively high speed computer.
- Those skilled in the art are capable of selecting a suitable processor for receiving and analyzing the scanned data.
- the imaged data is preferably in the form of numerical data. Any conversions necessary to transform the scanned or imaged data to numerical data can be performed either prior to or after transmission to the processor.
- the processor preferably utilizes the scanned data to develop a volumetric model of the scanned object. This is called volumetric rendering.
- volumetric rendering Conventional software is available to perform volumetric rendering of a scanned image (see for example, U.S Pats. Nos. 5,546,807, 5,315,512, and 5,594,842, which are incorporated herein by reference in their entirety).
- Picker International also distributes Voyager software which is capable of performing volumetric rendering. Therefore, no further discussion of the software is needed.
- the processor also receives baseline data for comparing against the current scanned or imaged data.
- the present invention contemplates various types of baseline data which can be utilized.
- the baseline data is data representing a previously scanned portion of the patient's body.
- the patient's lung may have been scanned at an earlier point in time.
- the previous scan was taken will depend on the intended analysis to be performed. For example, if it is desired to determine functional respiratory data, the first scan (previous scan) may be during inspiration and the subsequent scan may be during expiration. For this type of procedure, there may be only seconds or minutes between scans. Other types of analysis may require scans that are, for example, minutes, hours, weeks, months or years old.
- the previously scanned data is utilized in the present invention for comparison against the current scanned data.
- the processor determines whether a deviation exists between the prior scanned data and the current scanned data as described in more detail below.
- the baseline data includes preexisting patient data.
- the baseline data is scanned or stored data representing a "normal" structure.
- data representing healthy or normally developing lungs is utilized for comparison against the patient's current scanned data.
- the data is preferably generated from scans of a large segment of patients having a normal internal structure of interest (e.g., a normally developed lung structure).
- the data can be categorized based on various parameters, such as age, gender, etc. This data is referred to herein as "normative data" .
- the processor also preferably receives background information associated with the scanned data, for example, the age and gender of patient and the location of the scanned area within patient.
- the processor preferably either receives this background information directly from the scanner
- the data can be entered directly into the processor (e.g., by medical personnel).
- the processor selects an appropriate set of data representing a "normal” or “average” object under consideration (e.g. , bronchioles) for use as the baseline data for comparison against the patient's scanned image.
- a "normal” or “average” object under consideration e.g. , bronchioles
- the processor preferably has available to it data representing a plurality of normal body structures. This normative data is either stored internally in the processor, or is supplied externally.
- the processor utilizes the background information to select the appropriate data for comparing with the actual scanned image.
- the processor will select predetermined data representing a "normal” or "average” lung in a 3 year old Caucasian male.
- the selected data is used as the baseline data for comparison against the imaged data for diagnostic analysis as described in more detail below.
- the criteria which is used to select the appropriate normative data can be, for example, age, gender, race, height, and/or weight, and is preferably based on a large segment of the "normal" population.
- the normative data can be separated by suitable background classifications or criteria and stored on individual data storage media, such as floppy disks.
- the appropriate storage media representing the appropriate "normal" object is selected by one of the medical personnel and input into the processor.
- the normative data may be stored as raw numeric data similar to scanned data or, more preferably, may be stored as volume-rendered data (i.e., data converted into three-dimension volumes).
- Exemplary normative data for a tracheobronchial tree for use in the present invention include, but are not limited to, the number of bronchi in a generation, and the diameter, length, circumference, cross-sectional area and volume of each bronchi in a given generation. This type of information can also be recorded from a prior scan of the patient according to the first embodiment of the invention described above.
- the processor utilizes the two sets of data (scanned data and selected baseline data) to determine if and where abnormalities or deviations exist in the current version of the patient's scanned data. As will be described in more detail below, the processor must first correlate or match the two sets of data in order to ultimately determine whether any differences exist. This can be achieved by initializing or identifying portions of each data set. For example, if the current scanned data and the baseline data represent the structure of a lung, it is desirable to identify the data in both sets that corresponds to the trachea. The software identifies the branch point within the model. From that point, the processor (or more appropriately the software operating within the processor) can determine the structures that depend from the trachea and properly identify them according to the selected model.
- an abnormality as determined by the processor is not necessarily indicative of a unhealthy condition. Instead, an abnormality is, in its broadest sense, a difference (deviation) between the scanned data and the normative data which requires closer inspection by a physician. What is considered to be an abnormality will vary depending on the organs that are being analyzed, the procedures that are being performed, and/or the parameters that are being compared. A difference may exist between the current scanned data and d e prior scanned data obtained in the same person, thus representing a return towards "normal", new abnormalities, or worsening of abnormalities identified on previous scans. If the processor determines that an abnormality exists, it then displays the location of the abnormality and, preferably, the size of both the baseline object and the scanned object.
- the processor can also visually display the abnormal structure (e.g., cross-section) if desired. It is also possible to overlay the scanned image and the baseline image on the display. The differences can be highlighted (such as by coloring or shading). Conventional software exists which permits such manipulation of computer data. The following examples further define and illustrate some of the capabilities of the present invention.
- the processor compares the cross- sectional properties of the scanned bronchus and bronchioles (by order) to the cross-section of the baseline bronchus and bronchioles. If the processor determines that the cross-section of the scanned bronchi is sufficiently different than the baseline cross-section as indicated by the baseline data, the processor displays the location of the abnormality and its size. The processor could also display the size of a normal (baseline) bronchi. It is contemplated that a range of values around the baseline would be considered "normal" (i.e., not a significant deviation from the baseline). A preferred range would be about + 2 standard deviations from the mean. A reading outside of this range would represent an abnormality.
- the caliber of the small bronchi could be determined which may be important in stricture or hypoplasia.
- Anomalous bronchial origins and congenital or acquired fistulas from the tracheobronchial tree to other organs or spaces could be evaluated.
- the processor can determine this from the acquired data.
- a branching pattern typically is characterized by progressively smaller diameter airways. If the dimensions become larger, this would indicate an abnormality, such as a bronchi-bronchi fistula, bronchiectasis, or entry into another organ.
- this scanned data is then compared to baseline data, which can be normative data based on age, sex/race, height and/or weight- matched controls, or the patient's prior scanned data.
- baseline data can be normative data based on age, sex/race, height and/or weight- matched controls, or the patient's prior scanned data.
- the scanned data would be displayed to demonstrate the frequency distribution of diameter, length, volume, and CSA relative to normative values. This comparative analysis permits quick and accurate determination of abnormalities.
- Figures 4a-4c are graphical illustrations of the frequency distribution of the number of airways (Y-axis) of a certain diameter (X- axis).
- a frequency distribution of the cross-sectional diameter for the baseline 10th generation (order) bronchioles is compared against the frequency distribution of the cross-sectional diameter for the current scanned data representing the 10th generation bronchioles for the patient (dashed line).
- the physician can readily determine whether or not any abnormalities exist in the scanned image of the patient.
- the physician can readily determine that the scanned data of the patient's 10th generation bronchiole shows abnormal development. Specifically, all the bronchioles on the 10th generation have a cross-sectional diameter that is smaller than the baseline 10th generation bronchioles.
- Figure 4b is a graphical representation of the frequency distribution of the cross-sectional diameters for the baseline 10th generation (order) bronchioles (solid line) as compared against the frequency distribution of the cross-sectional diameters for the current scanned data representing the patient's 10th generation bronchioles (dashed line).
- the processor displays (or determines) that most of the patient's 10th generation bronchioles have a normal cross-sectional diameter.
- a small population of bronchioles have cross-sectional diameters which are smaller than the baseline and may be localized to a single lung segment.
- Figure 4c is a graphical representation of a frequency distribution of a patient's 10th generation bronchioles in which a diffuse abnormality is seen such that these airways are both larger and smaller than the baseline.
- intrapulmonary variations can be assessed by the processor and the anatomical location (i.e., lobar, segmental etc.) of the abnormal bronchi can be determined. That is, lobes or segments, as well as bronchial generations within the lung, are compared against the baseline data and cross- correlated. The comparison would identify the location of any abnormality within the lung (e.g, generations five through ten are abnormal but only in the lower lobe). This could be graphically displayed to illustrate the branching tracheobronchial tree and identify the location and generation of the abnormal airways. Figure 5 illustrates one such display which is contemplated by the present invention.
- diagnosis and therapy of the pulmonary function of a patient's lung may be determined by comparing ratios for various bronchi.
- the present invention utilizes the processor to determine ratios of diameter, length, volume, CSA for different generations. These ratios can be displayed to facilitate the rapid and accurate differential diagnoses. For example, it may be that in lymphocytic interstitial pneumonia (LIP) the ratio of the diameters of the 7th generation bronchioles to the 10th generation bronchioles is increased. This profile may occur only in the lower lobes. It is contemplated that the present invention would utilize the processor to compare the 7th and 10th generation bronchioles of the lower lobes. The ratio is displayed to allow the physician to diagnosis LIP earlier.
- LIP lymphocytic interstitial pneumonia
- a "normal" (or previous) ratio for the 7th and 10th bronchiole could also be displayed to facilitate comparison. This would also be important for demonstrating the anatomic patterns of disease (i.e., specific lobes, segments etc.).
- an index of obstruction can be assigned to a scanned component (or portion thereof) and compared to a baseline index (which can be the patient's baseline or a normative baseline.)
- b) Functional Analysis Referring generally to Figure 2, the airways of the lung can be considered a large group of circuits in series and parallel. All of the same generation airways are in parallel and the airways from one generation to the next are in series. Utilizing the processor of the present invention, the overall and site specific pulmonary function can be calculated.
- the processor can compare bronchi parameters for each generation against the baseline data. From this comparison, the processor can display the specific generation of bronchi where the abnormality exists.
- Figures 5 and 6 illustrate this aspect of the invention. Furthermore, if the processor determines that the diameter of the scanned bronchi is below a predetermined size (indicating substantially restricted flow), the display would also indicate the depending generations of bronchi as also being functionally abnormal.
- Airway resistance As part of the functional analysis of the lung, the following equation can be used to determine the resistance in the different airway generations, individually, combined, or in the overall lung model (figure 3).
- R resistance
- L lengdi of airway
- r radius of the airway
- ⁇ viscosity of air.
- the viscosity ( ⁇ ) of air is known.
- the length (L) and radius (r) of the airway can be determined from the scanned data. Accordingly, the resistance along each generation of airway can be derived.
- the processor can output the resistance for each airway or, alternately, can output airways which have a resistance below a normal resistance value as determined from the baseline data.
- Airway Compliance Functional analysis of the lung also involves determining the airway compliance.
- the airway compliance of the scanned structures are calculated using the following formula.
- ⁇ V the calculated change in volume
- ⁇ P the calculated change in pressure
- Airway impedance is a function of airway compliance and airway resistance.
- Pulmonary Volumes and Capacities can be calculated from the scanned data.
- imaging is performed under different breaming conditions (i.e., static and dynamic).
- scanned or imaged data is acquired while the patient momentarily stops between inspiring and expiring. This provides an index of tidal volume within the airways.
- scanned data is acquired while the patient maximally inspires and momentarily holds his/her bream. This provides data representing airway volume at total lung capacity (TLC).
- TLC total lung capacity
- scanned data is acquired while the patient maximally expires. This will provide data representing airway volume at residual volume (RV).
- Lung volumes and capacities can then be derived by the processor from this scanned data, such as vital capacity (VC), inspiratory and expiratory reserve volumes (IRV and ERV, respectively), and functional residual capacity (FRC).
- Inspiratory and expiratory reserve volumes represent the volumes that one could inspire/expire above and below a normal tidal volume breath and, thereby, increase the depdi of breathing.
- Functional residual capacity represents the volume of gas that is in the lung at the end of a normal breath. It is determined by a balance of recoil forces across the lung (chest wall pulling outward; lung pulling inward) and provides a "buffer" volume of gas in the lung which prevents large swings in arterial oxygen and carbon dioxide tension throughout a normal breath.
- a forced maximum expiratory maneuver i.e., forced vital capacity (FVC) can be scanned and analyzed widi respect to time to provide standardized indices of airway function, such as the forced expiratory volume per second (FEV,) of maximum ventilation (V Emax ).
- FVC forced vital capacity
- the processor can analyze time dependent data relative to total effort (FEV, /FVC) or resting conditions (FVC/VC) to provide indices of structural vs functional limitation of lung function.
- Airway Reactivity Analysis It is also contemplated that the present invention can be used to determine airway reactivity to pharmacologic agents (e.g. , vasodilator, bronchodilator, methacholine, etc.), physical agents (e.g., cold air, exercise, gases (0 2 , C0 2 , He, N 2 0, N0 2 , etc.)), or various respiratory maneuvers (e.g., PIP, PEEP, inspiration, expiration, etc.).
- pharmacologic agents e.g. , vasodilator, bronchodilator, methacholine, etc.
- physical agents e.g., cold air, exercise, gases (0 2 , C0 2 , He, N 2 0, N0 2 , etc.
- various respiratory maneuvers e.g., PIP, PEEP, inspiration, expiration, etc.
- the area is scanned before and after delivery of a pharmacologic agent.
- the scanned data would be compared to baseline values representing, for example, standardized dose-response and regional airway site-specific nomograms.
- Airway challenge refers to a stimulus which might induce bronchoconstriction, such as inspiration of cold air, inhalation or intravenous administration of an airway smooth muscle agonist.
- the present invention provides an important method for pharmacologic testing of drugs to determine which generations of airways are affected by which drugs. This would allow site specific pharmacologic intervention to ultimately be determined for improving therapeutic management.
- the FC could also be combined with pharmacologic agents and act as a carrier for delivery of the drug.
- the present invention is not limited to performing analysis and diagnosis of the lung structure but, instead, is applicable to any element or component within the body.
- me present invention can be used to provide virtual endoscopy and diagnosis for the following body elements: nasopharynx, nasal sinuses, peritoneum (i.e., virtual laparoscopy), GI tract, urinary tract, synovial spaces (i.e., virtual arthroscopy), pleural space, and auditory canal among others.
- this technique is applicable to intravasculature. When using this technique on die intravasculature, it is contemplated mat FC liquid would be used as a blood substitute to assist in imaging.
- baseline data i.e., nasal sinuses, peritoneum (i.e., virtual laparoscopy), GI tract, urinary tract, synovial spaces (i.e., virtual arthroscopy), pleural space, and auditory canal among others.
- FC liquid would be used as a blood substitute to assist in imaging.
- the tracheobronchial tree could be viewed from the perspective of its outer walls.
- the contrast would be between the air filled lung and the very dense FC filled airways. Comparison against baseline data would provide insight into the existence of any abnormalities in or on the walls.
- FC enhanced virtual endoscopy can be applied as an arthroscopy assistive modality in various procedures in which enhanced edge- detection would be advantageous and further minimize the need for invasive procedures or production of iatrogenic trauma.
- tissue lined lumen may be protected from surgically related tissue trauma during diagnostic or therapeutic procedures, such as laparoscopy or "virtual laparoscopy”. Scanned and processed data would provide the surgeon with actual dimensional data before or during surgery to facilitate an approximate surgical approach, choice of instruments, prosthetic devices, etc.
- One important advantage to using this information during surgery is the potential ability to minimize trauma and risk of infection by reducing tissue handling.
- the present invention is extremely beneficial in the pediatric population where the size of the pediatric bronchial tree prevents navigation with a conventional bronchoscope. Similarly, the present invention permits analysis of small airways which heretofore have not been viewable through non-invasive procedures. For example, with e use of the present invention, it is possible to assess diseases down to approximately the 12th through 17th generation bronchi (about 1 mm diameter in the adult). This is a much smaller size than is reachable by a bronchoscope.
- die present invention provides a non-invasive means for identifying and analyzing branching along the tracheobronchial tree to a degree previously unobtainable through conventional techniques.
- the present invention also provides a novel non-invasive method for relating structure (e.g., normative data or prior patient scanned data, obstruction or mass identification, congenital abnormalities) to function (e.g., pulmonary function analysis section).
- structure e.g., normative data or prior patient scanned data, obstruction or mass identification, congenital abnormalities
- function e.g., pulmonary function analysis section
- One key benefit of the present invention is the ability to provide medical personnel with real-time, on-line analysis.
- the monitoring of the changes in the structure of the patient can be performed nearly instantaneously.
- the rabbit received an initial dose (17cc/kg) of perfluorooctylbromide (PFOB)(LiquiVent ⁇ Alliance Pharmaceutical. Corp.) administered via the endotracheal tube which equated to the measured gas functional residual capacity (FRC) as was determined by closed circuit helium dilution (PANDA, Medical Associated Services, Hatfield, PA). Imaging was performed on a Picker PQ 5000 helical CT scanner before and after the administration of the PFOB during ventilated respiration. Images were obtained using a targeted 10 cm FOV, 3 mm slice thickness with a pitch of 1.25, images reconstructed every 3 mm, smooth spatial reconstruction algorithm, and a mA/kVp of 200/120.
- PFOB perfluorooctylbromide
- FRC gas functional residual capacity
- the PFOB distributed evenly within the lungs with pooling in the bronchi occurring only immediately after the PFOB was administered. Initially, a small amount of pooled PFOB was seen in me proximal right and left mainstem bronchi on the reconstructed bronchoscopic CT. The PFOB rapidly distributed out of the larger airways into the very small airways and alveoli due to the application of PEEP (positive end expiratory pressure).
- the Houndsfield unit (HU) number of PFOB liquid is in the range of 2700-2800.
- the Houndsfield unit number of PFOB in die rabbit lung is 1400- 1700.
- PFOB inspired in the trachea creates a marked contrast difference between the air in the bronchi and the contrast in the lung. Since me bronchial wall can be assumed to have similar CT density to soft tissue and have a Houndsfield unit number of approximately 40-60, die contrast difference achieved with FC is much greater than can be achieved with endogenous tissue densities in the lung.
- the above described testing demonstrated that contrast improvement with PFOB allows markedly better visualization of significantly smaller bronchi with the bronchoscopic CT technique than the identical bronchoscopic CT technique without PFOB.
- the results of the testing in this small animal model indicate that me present invention would permit evaluation of small bronchi and be useful in the assessment of small airway disease down to approximately 12th order bronchi (about 1 mm diameter in an adult human).
- the testing demonstrates that the present invention might allow for the evaluation of changes in the caliber of small airways under different conditions such as inspiration, expiration, PIP, PEEP (positive end expiratory pressure), bronchodilators or even slight negative pressure.
- the diameter of a steerable pediatric bronchoscope is about 3mm.
- the size of the tracheobronchial tree in premature infants is similar to the 1400 gram rabbit. As such, it is not easy to visualize the tracheobronchial tree in an infant utilizing conventional bronchoscopy .
- die present invention would be useful for non-invasively evaluating the bronchial tree in the pediatric population.
- the present invention has been described thus far as it is intended to be used for imaging and analyzing a body element on a macroscopic level. However, it is contemplated that the present invention is also applicable for imaging and analyzing a body element on a cellular or molecular level.
- the capabilities of the invention are primarily dependent on the imaging resolution. Current and developing technology is such that die visualization of me dynamics at the level of the cell membrane are readily foreseeable, even down to die molecular level.
- the present invention as described above would be readily applicable to such images.
- a comparison can be made between a body element of a patient and ti eir own test profiles to evaluate a change from a prior state.
- cellular and molecular imaging of a body element can be compared to normative values based on selected criteria, such as age and gender, to evaluate the patient relative to a population standard.
- the present invention can be applied to a cellular membrane to calculate transmembrane flux of substrates by visualization of substrate concentration on the two sides of me membrane. Also, imaging and analysis according to the present invention permit direct observation of drug uptake with the resulting measurement of diffusion and partition coefficients. This permits an assessment to be made of biovailability.
- the drug can be marked with a biologically active or inert material, such as FC.
- physiologic responses on the cellular level can be determined for any agent, such as coil contraction, secretion, endocytosis, exocytosis etc.
- direct observation can be performed of functional cell actions at the tissue level ( . e. , Osteoclast/osteoblast interaction on bone and changes/deviations from normal.
- High resolution imaging permits the use of the present invention to analyze and evaluate branching structure in blood vessels, nerves, capillaries, lymphatics.
- microscopic imaging techniques improve cellular and subcellular structures may be analyzed to evaluate microtubular structure, actin filaments, membrane structure, and extracellular "potential" space.
- Contrast agents bound to antibodies for certain structures could create boundaries (similar to cell membranes) which would allow evaluation of extracellular space.
- indium or gadolinium could be targeted to the epithelium/endomelium tissue of various organs which would enable die epithelium/endotiielium tissue to then be imaged.
- Epithelium or endothelium could be visualized in ureter, bile duct, pancreatic duct, lymphatic ducts, epidural space, meninges, inner ear/semi-circular canals, or other epithelium or endothelium containing structures.
- ultra miniaturization will permit tiny robot probes or sensors to be placed within die body at desired locations. These devices, operating in conjunction with an ultrasonic or magnetic resonance imaging system, would send back structural information from within die body that is analyzed using me above-disclosed techniques.
- Cellular and molecular imaging also permits evaluation of important pulmonary structures and functions. For example, such imaging would permit direct observation of ciliary function and clearance, single isolated airway smooth muscle cell assessment of airway contractility secondary to agonist stimulation, and assessment of otiier airway cell functions including secretory cells to assess mechanisms of mucous secretion and surfactant production.
- radiographic scanning While the present invention has generally referred to radiographic scanning as the preferred form of scanning, other non- invasive methods for producing scanned images of a body element, such as sonographic imaging, are also contemplated for use in the present invention.
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EP98907582A EP1011423A1 (en) | 1997-02-25 | 1998-02-20 | Non-invasive radiographic method for analyzation of a body element |
CA002281905A CA2281905A1 (en) | 1997-02-25 | 1998-02-20 | Non-invasive radiographic method for analyzation of a body element |
AU63350/98A AU6335098A (en) | 1997-02-25 | 1998-02-20 | Non-invasive radiographic method for analyzation of a body element |
JP53693898A JP2002505594A (en) | 1997-02-25 | 1998-02-20 | Non-invasive radiography for analysis of body elements |
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Cited By (5)
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JP2003033341A (en) * | 2001-07-23 | 2003-02-04 | Shimadzu Corp | X-ray fluoroscopy photographing apparatus |
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- 1998-02-20 JP JP53693898A patent/JP2002505594A/en active Pending
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Cited By (6)
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JP2003033341A (en) * | 2001-07-23 | 2003-02-04 | Shimadzu Corp | X-ray fluoroscopy photographing apparatus |
US7616789B2 (en) | 2002-05-13 | 2009-11-10 | Fujifilm Corporation | Method and apparatus for forming images and image furnishing service system |
WO2004077333A1 (en) | 2003-02-28 | 2004-09-10 | Koninklijke Philips Electronics N.V. | Method and apparatus for analyzing image data |
US7697739B2 (en) | 2003-06-26 | 2010-04-13 | Fujifilm Corporation | Method, apparatus and program for image processing, and abnormal shadow detection |
JP2008302224A (en) * | 2007-06-08 | 2008-12-18 | General Electric Co <Ge> | Method and system for performing high temporal resolution bolus detection using ct image projection data |
US7983460B2 (en) | 2007-06-08 | 2011-07-19 | General Electric Company | Method and system for performing high temporal resolution bolus detection using CT image projection data |
Also Published As
Publication number | Publication date |
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EP1011423A1 (en) | 2000-06-28 |
JP2002505594A (en) | 2002-02-19 |
AU6335098A (en) | 1998-09-09 |
CA2281905A1 (en) | 1998-08-27 |
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