(19)
(11)EP 3 057 509 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
14.08.2019 Bulletin 2019/33

(21)Application number: 14786782.4

(22)Date of filing:  14.10.2014
(51)Int. Cl.: 
A61B 6/00  (2006.01)
G01R 33/56  (2006.01)
A63B 21/008  (2006.01)
A61B 8/06  (2006.01)
A61B 5/055  (2006.01)
A61M 16/20  (2006.01)
A61B 5/08  (2006.01)
A61B 8/08  (2006.01)
(86)International application number:
PCT/CH2014/000151
(87)International publication number:
WO 2015/054800 (23.04.2015 Gazette  2015/16)

(54)

BLOOD FLOW CONTROL SYSTEM AND METHODS FOR IN-VIVO IMAGING AND OTHER APPLICATIONS

BLUTFLUSSSTEUERUNGSSYSTEM UND VERFAHREN FÜR DIE IN-VIVO-BILDGEBUNG UND ANDERE ANWENDUNGEN

SYSTÈME DE CONTRÔLE DE FLUX SANGUIN ET MÉTHODES D'IMAGERIE IN VIVO AINSI QU'APPLICATIONS AUTRES


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 18.10.2013 CH 17872013

(43)Date of publication of application:
24.08.2016 Bulletin 2016/34

(73)Proprietor: Gutzeit, Andreas
8044 Zürich (CH)

(72)Inventor:
  • Gutzeit, Andreas
    8044 Zürich (CH)

(74)Representative: Charrier Rapp & Liebau 
Patentanwälte PartG mbB Fuggerstrasse 20
86150 Augsburg
86150 Augsburg (DE)


(56)References cited: : 
EP-A1- 1 938 751
WO-A2-01/74247
US-A1- 2003 062 041
WO-A1-2013/110929
RU-A- 2009 118 031
  
  • SEBASTIAN LEY ET AL: "MRI Measurement of the Hemodynamics of the Pulmonary and Systemic Arterial Circulation: Influence of Breathing Maneuvers", AMERICAN JOURNAL OF ROENTGENOLOGY, vol. 187, no. 2, 1 August 2006 (2006-08-01), pages 439-444, XP055080600, ISSN: 0361-803X, DOI: 10.2214/AJR.04.1738
  • KOWALLICK, J. T. ET AL.: "Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre)", BR. J. RADIOL., vol. 87, 20140401, 16 September 2014 (2014-09-16), pages 1-7, XP009181735,
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description

FIELD OF THE INVENTION



[0001] The present invention is defined in the claims. The disclosure relates to blood flow control systems, devices and methods, in particular to an imaging system for the human body, such as x-ray and related tomographic imaging systems.

BACKGROUND OF THE INVENTION



[0002] Images of the interior of the human body are a long-established tool for providing graphic information in form of pictures, prints and screen displays for a subsequent interpretation by skilled practitioners.

[0003] For many purposes detection of blood flow related conditions is an important part of such images. In order to improve the detection of blood flow conditions it is known that injection of a contrast medium into the blood stream can add information.

[0004] A well-known example of such methods is computer tomography (CT) angiography, which is widely accepted as standard method for the examination of patients with suspected pulmonary embolism and other vascular and parenchymal diseases. The advantages of CT are obvious: it is widely available, the method is rapid, and it is highly sensitive to nodules, embolus or clots in the blood stream.

[0005] To increase the image quality of the images generated by the CT scanner, it is further known that administration of a contrast agent during the scanning process enhances the vascular compartment and other fluids in the body, usually via venous access over the upper extremity such as via the back of the hand or via an elbow vein. Alternatively, it is also known to inject contrast material in the lower extremities. It is known that the contrast-enhanced blood flows through the superior vena cava (SVC) into the right atrium, while at the same time a volume of non-contrasted blood reaches the right atrium from the inferior vena cava (IVC). Evidently, the proportion of non-contrasted blood of the IVC in relation to the contrast enhanced SVC influences the dilution of contrast medium in the right atrium/venticle , left atrium/ventricle and in the pulmonary artery (PA) and all subsequent arteries (e.g. coronary artery, carotid and brain arteries, and more distant arteries), in an effect known as transient interruption of the contrast bolus. This dilution influences potentially the diagnostic performance and quality of the entire investigation.

[0006] Several studies have been published on the effect of ventilatory activity on the blood flow as listed in the list of references below.

[0007] US-B 6 631 716 suggests to set a defined volume of the lung despite respiration of a patient. No coordination of inhaling or exhaling with taking a MRI or CT is described and a contrast substance is not mentioned.

[0008] A method for improving lung delivery of pharmaceutical aerosols is disclosed in WO 01/74247 A2, wherein a real-time imaging technique is used to investigate the effect of air way structures or administration and respiratory drugs when administered by oral inhalation.

[0009] In European patent application EP 1 938 751 A1, an X-ray photography apparatus is disclosed which is comprising an aspiration flow amount measuring section for measuring an aspiration flow amount of an examinee.

[0010] In RU 2009 118 031 A a device for increasing air pressure in larynx is disclosed. The device is intended for diagnostics of deseases of larynx and hypopharynx, when carrying out computer tomography and the device contains a hollow tube for exhaling air and a manometer with a scale and a removable mouth piece, wherein the tube for air exhaling is provided with a metal plate which is getting in contact with an arrow of the manometer when the intrathoracic pressure reaches a predefined value.

[0011] Document WO 2013/110929 A1 (1 August 2013) discloses a method according to the preamble of claim 1.

SUMMARY OF THE DISCLOSURE



[0012] In the view of the above it is seen as an object of the disclosure to provide a specific dedicated device and its use, a scanning system and methods with improved and standardized flow accuracy and enhancement in the control of blood flow, dilution and enhancement properties for imaging of contrast enhanced blood flow (per-fusion, first-pass enhancement, vascular supply of tumors, lesions and various tissues), particularly in relation to the vascular flow (perfusion, fist-pass enhancement, arterial enhancement, improved detection of thromboembolic material within blood vessels, vascular space and supply of lesions, tumors and normal tissue) through the pulmonary artery or other arteries and veins as well as other vessels distally to the heart.

[0013] Hence, according to an aspect of the disclosure, there is provided a method of controlling and/or standardizing the distribution of a substance in the human body comprising the steps of applying a respiratory resistance device to the respiratory system of the body, and injecting the substance into the body and controlling or standardizing the distribution of the substance in the body through the selection of respiratory states characterized by a controlled interaction between the respira-tory system of the body and the respiratory resistance device .

[0014] In another aspect, there is provided a method of acquiring in-vivo a series of images of interior parts of the human body, using an imaging system and including the steps of positioning a body relatively to the imaging system, applying a respiratory resistance device to the respiratory system of the body, and performing the image acquisition step during an inhalation, inspiration or suction phase, during which the body exercises suction against a resistance as provided by the respiratory resistance device. Alternatively or in addition, the image acquisition step is performed during the exhalation phase .

[0015] The imaging system can be a scanner using an x-ray imaging method, a scanner using magnetic resonance imaging or ultrasound imaging method including for example scanners for angiography, CT scanners, MR and positron emission based variants such as PET/CT or SPECT/CT, PET/MRI or ultrasound scanners.

[0016] The respiratory resistance device includes preferably an inner volume with an opening or openings in direction towards the physiological openings (nose, mouth) of the respiratory system of the body and essentially no or only small openings or leaks towards the en- vironment. The dimensions of the volume and the openings are selected such that a normal untrained patient can achieve an underpressure (in the case of suction or in- spiration against resistance) or an overpressure (in the case of exhalation against resistance or Valsalva) in the inner volume of the device and, preferably, maintain such pressure for the duration of the image acquisition, e.g. preferably between 1 and 60 seconds and preferably between 5 and 45 seconds and preferably between 5 and 30 seconds. The preferred pressure range for such an underpressure is -1 up to -80 mmHg and preferably up to -60 mmHg and preferably up to -40 mmHg, more preferably -8 to -20 mmHg. For overpressure a preferred range is +1 to + 80 mmHg, more preferably +10 to +30 mmHg with the pressure 0 mmHg being gauged to equal atmospheric pressure.

[0017] In a preferred embodiment, the respiratory resistance device includes a replaceable and disposable mouth piece to connect the inner volume of the device with the respiratory system of the body. The mouth piece can be for example a tube or a modified tube, e.g., with an elliptical or round cross-section or with a specifically designed end for ease of use when applied to the mouth. However, in cases where it is preferred to include all openings of the respiratory system of the body, the mouth pieces can also be shaped as a mask.

[0018] It is preferred that a mouth piece fits closely and thus tightly with the resistance device. A mouth piece may also fit with defined spaces for the exit or entry of air between mouth piece and resistance device. A mouth piece may as well be formed integral with the resistance device.

[0019] In a further preferred embodiment, the respiratory resistance device includes or is coupled to a sensor for measuring a parameter indicative of the pressure inside the inner volume of the device. The measurement can be displayed in a numerical form or as acoustic or optical signals or symbols, preferably indicating in operation whether the inhaling/inspiration/suction or exhaling/expiration/valsalva, respectively, is to be increased or decreased in intensity to achieve an optimal and/or steady-state pressure.

[0020] The respiratory resistance device is best operated in parallel to and in conjunction with the image acquisition of the image acquisition system and preferably also in parallel and in conjunction with an injection system for injecting of a contrast medium or other diagnostic substance into a venous vessel of the body. The disclosed device can however also be used without injection of supplementary contrast agent. When performed with contrast agent administration, injection into the upper extremity or lower is used in the case of an inhaling or suction action and injection into vessels of the lower extremity in the case of an exhaling or Valsalva action. The timings of these two or three parallel operations are chosen such that all operations are concurrently effective (well coordinated outside and in the body) during the actual image acquisition or any other administration step.

[0021] In a variant the respiratory resistance device and the image acquisition device are linked. The link can be implemented in form of a data communication link or in form of a partial or full incorporation of the elements of the respiratory resistance device into the image acquisition system and/or injection system.

[0022] Further aspects of the disclosure include the respiratory resistance device, a combination of respiratory resistance device and the image acquisition system, preferably in combination with an injection system, and any images acquired by the use of the above methods and/or devices or combination of devices and scanning systems .

[0023] The method of the invention is particularly useful in improving the enhancement and image acquisition related to various steps of angiography of the pulmonary arteries or other arteries and veins in the rest of the body (perfusion, first-pass vascular enhancement, vascular supply of tumors, lesions and various tissues, detection of thromboembolic material).

[0024] The disclosed subject-matter can be further used in methods and devices for administration, preferably intraveneous , of a substance in order to control or standardize the distribution and/or concentration of such a substance in the body.

[0025] The respiratory resistance device can be used in general to influence via defined respiratory states the distribution and/or standardization of blood supply either from the upper, superior vena cava or lower, inferior vena cava according to the respective requirement of any medical or technical conditions such as the task to increase blood supply from the respective vessel to the right atrium of the heart or enhance the concentration of an injected substance in the blood flow in the pulmonary arteries or in vessels beyond the pulmonary arteries. This can be extended to applications such as drug injection through the upper or lower peripheral veins, invasive procedures, surgery or any blood supply related indication

[0026] The methods, the devices and systems and their use are in particular able to control and standardize blood flow to perform high contrast density within arteries and/or veins, such as pulmonary vessels, brain vessels, vessels of visceral organs or vessels of the extremities or other vessels within a human or animal body. Standardized blood flow increases contrast density in the above vessels, increasing image quality of images taken with imaging systems such as mentioned. On the other hand the methods, devices and systems and their use may allow to reduce the amount of contrast substances.

[0027] The above and other aspects of the present disclosure together with further advantageous embodiments and applications of the invention are described in further details in the following description and figures.

BRIEF DESCRIPTION OF THE FIGURES



[0028] 

FIG. 1A is a schematic cross-section of a respiratory restriction device in accordance with the invention;

FIG. IB is a schematic cross-section of a variant of the respiratory restriction device of Fig. 1 A;

FIG. 1C shows a schematic cross-section of another simplified respiratory restriction device in accordance with the invention;

FIG. 2 illustrates schematically different respiratory states during an image acquisition;

FIG. 3 is a graph of test results indicating mixing ratios between flow from the vena cave superior vs flow from the vena cava inferior depending on respiratory states ;

FIG. 4 illustrates steps in accordance with the invention.


DETAILED DESCRIPTION



[0029] An exemplary respiratory resistance device 10 is shown in FIG. 1A. The device has a main body 11 of resilient material such as Teflon® or stainless steel or other similar materials. The main body provides a cap and holder for a disposable mouthpiece 12. The mouth piece and the main body are connected to each other by a simple form fitting attachment so that the mouth piece can be easily attached and removed from the main body by a straight insertion and extraction movement, preferably without involving a twist or use of a tool. Any similar form or attachment method might be suitable.

[0030] The mouth piece 12 has an essentially tubular, hollow shape with a proximate opening 121 adapted for insertion into a patient's mouth and a distal opening 122 providing a flow connection into the interior of the main body 11.

[0031] It should be however clear that materials, dimensions and shapes of the main body 11 and the mouthpiece can vary widely while still maintaining the function of providing resistance against free breathing. For example, it is possible to shape the proximate opening more ergonomically or give the cross-section a more elliptical circumference. Such and similar modifications can, however, be regarded as being well within the scope of an ordinarily skilled person.

[0032] Further mounted onto the main body 11 is a pressure sensitive device 13, which can be for example a piezoresistive transducer integrated with processing circuits onto a silicon substrate. Such sensors are commercially available for example as MPXV7002 from Freescale Semiconductor Inc

[0033] The sensor 13 is connected to a control signal generator 14. The control signal can be a numeric display of the pressure in the interior of the main body as shown. However the control signal can alternatively or in addition be an acoustic signal or an optical signal selected according to predefined pressure thresholds or ranges. The respiratory resistance device 10 of Figure 1 can as well omit the pressure sensitive device 13 and will work in this very simple form as well.

[0034] Thus the control signal generator 14 can give a patient or an operator of a scanning or injection apparatus a feedback on the ventilatory activity or respiratory state of the patient during the image acquisition by the scanner or during a controlled injection of a sub- stance. The respiratory device, the methods connected therewith and its use are able to control and standardize blood flow within patients related veins arteries during CT or MRI or other diagnostic procedures. In particular it can be indicated whether or not a patient is in the desired ventilatory activity or respiratory state or whether the patients breathing should be adapted or even changed to reach the desired state, e.g. in case of inha- lation/suction whether the patient should inhale suck stronger, less strong or steady. It is for example possible to use a programmable microcontroller (not shown) as part of the control signal generator 14 so as to control a display or color coded lights depending on the parameter as measured by the sensor 13 as feedback to patient and/or operator.

[0035] Optionally the sensor 13 can be connected to a synchronizing element 15 that is also linked to the im-age acquisition system. The link can be for example a wired, a wireless or an optical link for data transmission. Such an element can be used to combine information from the ventilatory or breathing activity of the patient (device) with the images acquired by any image acquisi-tion system. This would enable a manual or automated selection of images acquired during the desired state of ventilatory activity even where this activity is fluctuating (around the desired state) during the scan. For example the synchronizing element can include a display of pressure values along with the date and temporal information of the image acquisition. Corresponding time stamps may be included on the acquired image.

[0036] In the example of FIG. IB the main body 11 includes a small opening 111 to the exterior to allow for a limited air flow into or from the interior and hence into or out of the patient's respiratory system. The dimensions of the opening 111 are in such a case selected so as to provide sufficient air flow resistance or restriction to prevent normal (abdominal) breathing. Small openings allowing a controlled air flow can be advantageous in order to achieve a controlled and steady state inflow of air or other respiratory gases (oxygen, xenon or other). Such an opening 111 or multiple openings may alternatively or additionally be present on the mouth piece or may be formed by the connection means of mouth piece and main body.

[0037] The control signal generator 14 of the example of FIG. IB is designed as an optical indicator showing a patient in simplified symbols whether to increase or decrease the breathing efforts.

[0038] However, it is worth noting that the respiratory resistance device does not necessarily require any electronic components or any sensors to perform the function of an air flow resistance or restriction. If, for example, a simpler, more cost efficient device is re-quired, the main body 11 can be embodied or replaced, respectively, by a simple cap over the opening 122 of the mouth piece as shown in FIG. 1C. If parts of the cap are designed as flexible or moveable, then the ventilatory activity can be monitored by the movement or deformation of such parts. A thin membrane in the cap or elsewhere along the tube would for example bulge in or out depending on the pressure generated by the patient during in-or exhaling as indicated in FIG. 1C by the dashed lines. Other examples can include a movable object or column of liquid placed in a tube and moving in dependence of the ventilatory activity of the patient. Such variants would still be sufficient to implement examples of the present disclsoure.

[0039] The tube or mouth piece can be adapted for use with nasal openings or with both mouth and nose. In the latter cases, it is advantageous to use a mask type connector as mouth piece between the main body 11 of the respiratory resistance device 10 and the respiratory system of the patient instead of a tubular connector. The mask would be typically designed (e.g. with an elastic lip at its circumference) to provide sufficient air tightness to still function as a resistance against free breathing. It is further worth noting that the respiratory resistance device is not intended to provide breathing assistance during the scan as may be applied to support breathing for patients with significant respiratory failures. Thus, the known breathing masks connected to breathing support elements such as bellows or gas supply are not understood as respiratory resistance device within the meaning of the present invention.

[0040] It is further contemplated to integrate the respiratory resistance device 10 into an image acquisition system used to acquire images of the interior of the patient's body. In such a variant at least part of the main body 11, in particular the sensor 13, the control signal generator 14 and/or the synchronizing element 15 and related circuitry would be located within the housing of the image acquisition system and for example connected to the mouth piece by means of an elongated, essentially air-tight flexible tube. Such an integration has the advantage of reducing the number of separate parts in an area which best contains only essential equipment.

[0041] In some applications, the respiratory resistance device 10 is operated typically simultaneously with the operation of the image acquisition system. The image acquisition system can be a computer tomography (CT) scanner or a magnetic resonance imagine device (MRI), Angiography, PET/CT, PET/MRI, any ultrasound imager and other similar imaging devices.

[0042] In such applications the patient is positioned within the image acquisition system with the respiratory resistance device applied to either mouth and/or nose. To enhance the contrast of any images acquired, a contrast medium, for example iodine based contrast fluid, ultrasound contrast agent or Gadolinium based contrast material, is injected through a venous vessel of the pa-tient. The respiratory resistance device, the methods and systems may be operated together with the injection system for injecting the contrast enhancing substance.

[0043] Details of a method of acquiring in-vivo images of the interior of a human or animal body in accordance with an example of the present invention are described in the following making reference to FIG. 2.

[0044] In FIG. 2 there is shown a patient 20 being positioned horizontally within the tunnel of a scanner 21, which can be for example a CT scanner or an MRI scanner. A respiratory resistance device 10 in accordance with an example of the disclosure is placed on the mouth of the patient 20. An injection system for administering a contrast fluid is connected to a venous vessel of the patient but not shown as such systems are well known in the state of the art.

[0045] The three panels of FIG.2 illustrate three different respiratory states of the patient as can be registered by the respiratory resistance device 10. The enlarged detail shows a simplified representation of the human heart together with the blood flow through the vena cava superior SCV (entering the right atrium from above) and through the vena cava inferior ICV (entering the right atrium from below) .

[0046] The respiratory states are characterized in the figure by arrows indicating predominant direction of air or blood flow or diaphragm movements including movements of the lung, respectively, on the one hand and by the meter 14 readings as displayed on the other.

[0047] The upper panel represents the basic conditions under which for example PA images are presently ac-quired. It is characterized herein as free breathing with no respiratory resistance device 10 in place. The air is moved into and out of the respiratory system of the human body 20 as indicated by the arrows in the area of the head. At the same time the thorax moves up and down as indicated by the arrow in the chest region of the patient 20. The breathing is typically accompanied by movement of the diaphragm as indicated by the arrows in the abdominal region of the patient 20. A flow or pressure measurement 14 shows a swing to and fro between positive or negative values (representing inflow (suction) or outflow (Valsalva) of air or a swing between under- or overpressure as would be measured when using the respiratory resistance device during this state of free breathing) .

[0048] The respective blood flows through the ICV and SCV are as normal indicated by the two arrows of equal line thickness in the enlarged view. No change or contrast enhancement is expected in this respiratory state.

[0049] In the middle panel a respiratory state characterized as Valsalva maneuver is illustrated. In this state the patient breathes into the closed or flow restricted inner volume of the respiratory resistance device 10. The arrows in the head region indicate the direction in which the air flow is directed. The thorax moves inwards and the diaphragm upwards towards the thorax. The sensor registers this Valsalva state as overpressure typically in the range of 1 to 100 mbar for an untrained patient attempting to maintain a constant pressure for the period of the scan between 1 and 60 seconds, preferably between 5 and 45 seconds.

[0050] Again a contrast agent or any type of dye can be injected into the patient's body 20 shortly before and/or during the Valsalva state. A change from normal in the respective flows through the ICV and SCV can be observed as indicated by the arrow in the ICV being thicker than the respective arrow in the SCV. This indicates that the Valsalva state can favor the venous blood flow from the extremities of the lower body. This provides an indication that by administering a contrast medium into a venous access in a lower extremity during the image acquisition step an improved and/or more stable contrast enhancement can be achieved.

[0051] To achieve this enhancement it can be necessary to maintain the Valsalva status during the scan acquisition and even injection or, conversely, to interrupt the scanning process during periods in which the patient exits the Valsalva state or discard or mark images obtained outside the optimal Valsalva state. For such operations the monitoring as provided by the respiratory resistance device is advantageous.

[0052] In the lower panel of FIG. 2 a respiratory state is illustrated characterized as breathing against resistance or anti-Valsalva maneuver. In this state the patient 20 sucks air from the closed or flow restricted inner volume of the respiratory resistance device 10. Again the arrows in the head region indicate the direction in which the air flow is directed. The thorax moves outwards and the diaphragm downwards towards the lower body. The sensor 14 registers this state as underpressure typically in the range of -1 to -60 mmHg for an untrained patient attempting to maintain a constant pressure for the period of the scan between 1 and 60 seconds, prefera-bly between 5 and 45 seconds.

[0053] Again a contrast fluid or another substance can be injected into the patient's body 20 shortly before and/or during the anti-Valsalva (suction against resistance) state. A change from normal in the respective flows through the ICV and SCV can be observed as indicated by the arrow in the SCV being thicker than the respective arrow in the ICV. This indicates that the anti-Valsalva state favors the venous blood flow from the extremities of the upper body. This provides an indication that by administering the contrast medium into a venous access in an upper extremity or a lower extremity during the image acquisition step an improved and/or more stable contrast enhancement can be achieved. To achieve this enhancement it can be necessary to maintain the anti-Valsalva state for the duration of the scan or, conversely, to interrupt the scanning process during periods in which the patient exits the anti-Valsalva state or discard or mark images obtained outside the anti-Valsalva state. Again, the presence or absence of such states is enabled and monitored by the respiratory resistance device 10.

[0054] Test results using various standardized breathing states or maneuvers and flow-sensitive MR phase contrast techniques in the SVC and IVC and imaged in the supine position on a 1.5 Tesla MRI unit (Achieva 1.5 T, Phillips Healthcare, Best, The Netherlands) are shown in FIG. 3 using an 8-channel torso coil (Philips Health care) covering the entire chest allowing the regular acquisition of two sets of heart triggered dynamic phase contrast (PC) images (TR 50 msec and TE 4 msec; Slice thickness 8 mm, flip angle 15°, velocity encoding 100 msec; voxel size 1.9 x 2.5) in the axial section of the SVC and IVC.

[0055] In order to guarantee standardized and reproducible breathing an MR-compatible respiratory resistance device was used for controlling and monitoring the respiratory pressure and blood flow during the entire maneu-vre. Besides the newly defined breathing method "suction against resistance", previously defined techniques such as valsalva, apnea after end of inspiration, apnea after end of expiration and free breathing are also investigated allowing comparison with known studies (see references) .

[0056] The capital letters in FIG. 3 indicate the respiratory state or the interaction with the respiratory resistance device, where used. IVC/SVC ratios for stroke volumes (white boxes) and flux (grey boxes) are shown for free breathing (A), end of inspiration position with breath hold (B), end of expiration position with breath hold (C), Valsalva maneuver at + 10 mm Hg (D), Valsalva maneuver at +20 mm Hg (E), Valsalva maneuver at +30 mm Hg (F), suction maneuver at -10 mm Hg (G), similar suction maneuver at -20 mm Hg (H). Boxes show the median and the 25th and 75th quartiles; whiskers show minimum and maximum values. The optimal ratio is achieved in the suction mode with thoracic underpressure, but standard deviations are higher, demonstrating more unstable conditions. Other states such as the Valsalva maneuver can be considered, too, but show a much reduced effect under these circumstances .

[0057] It should be noted that the method and respiratory device as described in the example using an MRI scanner above may work equally well or even better in connection with a CT scanner or other imaging or diagnostic techniques .

[0058] The steps performed on a patient are summarized in the flow chart of FIG. 4. However it should be noted that the sequence of steps as shown in FIG. 4 is not indicative of a specific temporal order of such steps as most of the steps are best undertaken simultaneously to achieve the better results.

[0059] It should be noted that the above methods and devices can be used in any method requiring control or standardization of the mixing of the flow of blood from the IVC und SVC, and can be effective even in the blood circulation beyond the pulmonary arteries and the lungs, e.g., into the peripheral organs and body parts. Such a control and standardization can enable for example the improved performance of first pass measurements or perfusion, particularly for tumors or other vessels and tissues, or the distribution of drugs or dyes into the body, particularly where such drugs or dyes are administered intravenously.

[0060] When used with a contrast medium suited for ultrasound acquisition system, such as gas bubbles, the above methods and devices can also be applied to image acquisitions using an ultrasound scanner.

[0061] While there are shown and described presently preferred embodiments of the disclosure in accordance with the invention, it is to be understood that the invention is not limited thereto but may be otherwise variously embodied and practised within the scope of the following claims.


Claims

1. A method of acquiring in-vivo an image of interior parts of the human body (20) or an image based quantification of blood flow conditions, using an imaging system (21) and comprising the steps of positioning the body (20) relatively to the imaging system (21), applying a respiratory resistance device (10) to the respiratory system of the body (20), and performing an image acquisition step during an inhalation phase, during which the body (20) provides suction against a resistance as provided by the respiratory resistance device (10), and/or performing an image acquisition step during an exhalation phase, during which the body provides exhalation against a resistance as provided by the respiratory resistance device (10), characterised respectively by either a contrast fluid or dye being administered into a preestablished venous access in an upper or a lower extremity of the body (20) before and/or during the inhalation phase or by a contrast fluid or dye being administered into a preestablished venous access in a lower extremity of the body (20) before and/or during the exhalation phase.
 
2. The method of claim 1, wherein the image acquisition is performed while the inhalation reduces the pressure in the respiratory resistance device (10), in particular to a pressure in a range of -1 up to -80 mmHg and preferably up to -60 mmHg and preferably up to -40 mmHg, and preferably -1 to -20 mmHg.
 
3. The method according to any of the preceding claims, wherein the inhalation is maintained during at least 1 second and preferably over a period of between 1 and 60 seconds and preferably wherein the inhalation is maintained during at least 5 seconds and preferably over a period of between 5 and 45 seconds and preferably over a period of between 5 and 30 seconds.
 
4. The method according to any of the preceding claims, performed during the performance of an imaging method of the body (20), in particular computer tomographic (CT) scanning, ultrasound or magnetic resonance scanning (MRI), or during angiography, perfusion, first pass measurements of the pulmonary arteries (PA) or other blood containing vessels distal to the vena cava and/or the heart.
 
5. The method according to any of the preceding claims, wherein the image acquisition is performed while the exhalation increases the pressure in the respiratory resistance device (10), in particular to a pressure in a range of + 1 mmHg to + 80 mmHg and preferably to a pressure in the range +10 mmHg to +40 mmHg.
 
6. The method according to any of the preceding claims, wherein the exhalation is maintained during at least 1 second and preferably over a period of between 1 and 60 seconds and preferably wherein the exhalation is maintained during at least 5 seconds and preferably over a period of between 5 and 45 seconds and preferably over a period of between 5 and 30 seconds.
 
7. The method according to any of the preceding claims, wherein a parameter related to a pressure generated through inhalation or through exhalation is monitored during the image acquisition and the monitored parameter is used to generate a control signal indicative of deviation from an optimal inhalation or exhalation state, respectively.
 
8. The method according to any of the preceding claims wherein the respiratory resistance device (10) is comprising a main body (11) with one or more openings (121, 122) to connect in use with the respiratory system of the human body (20), and a closed inner volume or a inner volume with one or more constrictions (111) blocking partially the flow of air into or out of the respiratory system of the body (20) during an inhalation phase or exhalation phase, respectively.
 
9. The method according to claim 8, wherein the one or more constrictions (111) are sufficiently small to enable the generation of an under/over pressure in the inner volume of the device (10) under normal inhaling/exhaling conditions of the human respiratory system.
 
10. The method according to claims 8 or 9, wherein the respiratory resistance device (10) is having a replaceable subpart (12) which is comprising a mouth piece (12) or is consisting of a mouth piece (12) and is providing the one or more openings (121, 122).
 
11. The method according to any of claims 8 to 10, wherein the main body (11) of the respiratory resistance device (10) comprises a sensor (13) for measuring a parameter related to the pressure in the inner volume.
 
12. The method according to any of claims 8 to 11, wherein the respiratory resistance device (10) is further comprising a control signal generator (14) for generating a control signal indicative of a deviation from a desired respiratory state or from a preset pressure value or range of pressure values.
 
13. The method according to claim 12, wherein the control signal generator (14) includes an indicator indicating whether inhalation/exhalation is too weak and/or too strong.
 
14. The method according to any of claims 8 to 13, wherein the respiratory resistance device (10) is used to influence via defined respiratory states the distribution and/or standardization of blood supply either from the upper, superior vena cava or lower, inferior vena cava according to the respective requirement to increase blood supply from the respective vessel to the right atrium of the heart and/or to enhance the concentration of a substance in the blood flow in the pulmonary arteries or in vessels beyond the pulmonary arteries.
 


Ansprüche

1. Verfahren zur in-vivo Aufnahme eines Bilds des Inneren des menschlichen Körpers (20) oder einer bildbasierten Quantifizierung der Blutfluss-Bedingungen, unter Verwendung eines Abbildungssystems (21) und umfassend die Schritte der Positionierung des Körpers (20) relativ zu dem Abbildungssystem (21), Anwendung eines Atmungs-Widerstands-Geräts (10) für das Atemsystem des Körpers (20), und Durchführung eines Schritts der Bilderfassung während einer Inhalations-Phase, während welcher der Körper (20) das Einatmen entgegen einen vom Atmungs-Widerstands-Gerät (10) erzeugten Widerstand leistet, und/oder Durchführung eines Schritts der Bilderfassung während einer Exhalations-Phase, während welcher der Körper (20) das Ausatmen entgegen einen vom Atmungs-Widerstands-Gerät (10) erzeugten Widerstand leistet, jeweils gekennzeichnet durch entweder Verabreichung eines Kontrastmittels oder Färbemittels in einen vorher eingerichteten venösen Zugang in einer oberen oder unteren Extremität des Körpers (20) vor und/oder während der Inhalations-Phase, oder gekennzeichnet durch Verabreichung eines Kontrastmittels oder Färbemittels in einen vorher eingerichteten venösen Zugang in einer unteren Extremität des Körpers (20) vor und/oder während der Exhalations-Phase.
 
2. Verfahren aus Anspruch 1, worin die Bilderfassung durchgeführt wird während die Einatmung den Druck in dem Atmungs-Widerstands-Gerät (10) reduziert, insbesondere zu einem Druck in einem Bereich von -1 bis zu -80 mmHg und vorzugsweise bis zu -60 mmHg und vorzugsweise bis zu -40 mmHg, und vorzugsweise -1 bis -20 mmHg.
 
3. Verfahren gemäß einem der vorhergehenden Ansprüche, worin die Inhalation während mindestens 1 Sekunde und vorzugsweise über einen Zeitraum zwischen 1 und 60 Sekunden beibehalten wird und worin die Inhalation vorzugsweise während mindestens 5 Sekunden und vorzugsweise über einen Zeitraum zwischen 5 und 45 Sekunden und vorzugsweise über einen Zeitraum zwischen 5 und 30 Sekunden beibehalten wird.
 
4. Verfahren gemäß einem der vorhergehenden Ansprüche, durchgeführt während der Durchführung eines Bildaufnahmemeverfahrens des Körpers (20), insbesondere computertomographisches (CT) Scannen, Ultraschall- oder Magnetresonanz- Scannen (MRI), oder während einer Angiographie, Perfusion, oder einer Erstdurchgangsmessung der Pulmonararterien (PA) oder anderer blutenthaltender Gefäße fern von der Hohlvene und/oder dem Herzen.
 
5. Verfahren gemäß einem der vorhergehenden Ansprüche, worin die Bilderfassung durchgeführt wird während die Ausatmung den Druck in dem Atmungs-Widerstands-Gerät (10) erhöht, insbesondere zu einem Druck in einem Bereich von +1 mmHg bis +80 mmHg und vorzugsweise zu einem Druck in dem Bereich +10 mmHg bis +40 mmHg.
 
6. Verfahren gemäß einem der vorhergehenden Ansprüche, worin die Ausatmung während mindestens 1 Sekunde und vorzugsweise über einen Zeitraum zwischen 1 und 60 Sekunden beibehalten wird und worin die Ausatmung vorzugsweise während mindestens 5 Sekunden und vorzugsweise über einen Zeitraum zwischen 5 und 45 Sekunden und vorzugsweise über einen Zeitraum zwischen 5 und 30 Sekunden beibehalten wird.
 
7. Verfahren gemäß einem der vorhergehenden Ansprüche, worin ein Parameter in Bezug auf einen Druck - generiert durch Einatmung oder durch Ausatmung - während der Bilderfassung überwacht wird und der überwachte Parameter verwendet wird um ein Kontrollsignal zu generieren, das auf Abweichung von einem jeweils optimalen Einatmungs- oder Ausatmungs-Zustand hinweist.
 
8. Verfahren gemäß einem der vorhergehenden Ansprüche, worin das Atmungs-Widerdstands-Gerät (10) einen Grundkörper (11) mit einer oder mehreren Öffnungen (121, 122) zur Verbindung im Gebrauch mit dem Atemsystem des Körpers (20) und einem geschlossenen inneren Volumen oder einem inneren Volumen mit einer oder mehreren Einengungen (111), die teilweise den Fluß von Luft in oder aus dem Atemsystem des Körpers (20) während einer Einatmungs- oder Ausatmungsphase blockiert, umfasst.
 
9. Verfahren aus Anspruch 8, worin die eine oder mehreren Einengungen (111) klein genug sind, um die Ausbildung eines Unter-/Überdrucks im inneren Volumen des Geräts (10) unter gewöhnlichen Einatmungs-/Ausatmungszuständen des menschlichen Atmungssystems zu ermöglichen.
 
10. Verfahren aus Anspruch 8 oder 9, worin das Atmungs-Widerdstands-Gerät (10) einen austauschbaren Teil (12) aufweist, der ein Mundstück (12) umfasst oder aus einem Mundstück (12) besteht und die eine oder mehreren Öffnungen (121, 122) bereitstellt.
 
11. Verfahren nach einem der Ansprüche 8 bis 10, worin der Grundkörper (11) des Atmungs-Widerdstands-Geräts (10) einen Sensor (13) zur Erfassung eines dem Druck im inneren Volumen entsprechenden Parameters umfasst.
 
12. Verfahren nach einem der Ansprüche 8 bis 11, worin das Atmungs-Widerdstands-Gerät (10) weiterhin einen Kontrollsignalerzeuger (14) zur Erzeugung eines auf eine Abweichung von einem gewünschten Atmungszustand oder von einem vorgegebenen Druckwert oder einem vorgegebenen Bereich von Druckwerten hinweisenden Kontrollsignals umfasst.
 
13. Verfahren aus Anspruch 12, worin der Kontrollsignalerzeuger (14) eine Anzeige enthält, die anzeigt, ob die Ein-/Ausatmung zu schwach und/oder zu stark ist.
 
14. Verfahren nach einem der Ansprüche 8 bis 13, worin das Atmungs-Widerdstands-Gerät (10) verwendet wird, um über definierte Atmungszustände die Verteilung und/oder Standardisierung des Blutflußes entweder von der oberen Hohlvene oder der unteren Hohlvene entsprechend der jeweiligen Anforderung, die Blutzufuhr des entsprechenden Gefäßes zum rechten Herzvorhof zu erhöhen, und/oder um die Konzentration einer Substanz im Blutfluß der Pulmonararterie oder in den Gefäßen außerhalb der Pulmonararterie, zu beeinflussen.
 


Revendications

1. Procédé d'acquisition in vivo d'une image de parties intérieures du corps humain (20) ou d'une quantification basée sur l'image de conditions de débit sanguin, en utilisant un système d'imagerie (21) et comprenant les étapes de positionnement du corps (20) par rapport au système d'imagerie (21), d'application d'un dispositif de résistance respiratoire (10) au système respiratoire du corps (20), et de réalisation d'une étape d'acquisition d'image pendant une phase d'inspiration, pendant laquelle le corps (20) fournit une aspiration contre une résistance telle que fournie par le dispositif de résistance respiratoire (10), et/ou de réalisation d'une étape d'acquisition d'image pendant une phase d'expiration, pendant laquelle le corps fournit une expiration contre une résistance telle que fournie par le dispositif de résistance respiratoire (10), caractérisé respectivement soit en ce qu'un fluide ou un colorant de contraste est administré dans un accès veineux préétabli dans une extrémité supérieure ou inférieure du corps (20) avant et/ou pendant la phase d'inspiration, soit en ce qu'un fluide ou un colorant de contraste est administré dans un accès veineux préétabli dans une extrémité inférieure du corps (20) avant et/ou pendant la phase d'expiration.
 
2. Procédé selon la revendication 1, dans lequel l'acquisition d'image est réalisée alors que l'inspiration réduit la pression dans le dispositif de résistance respiratoire (10), en particulier à une pression dans une plage de -1 jusqu'à -80 mmHg et de préférence jusqu'à -60 mmHg et de préférence jusqu'à -40 mmHg, et de préférence de -1 à -20 mmHg.
 
3. Procédé selon l'une quelconque des revendications précédentes, dans lequel l'inspiration est maintenue pendant au moins 1 seconde et de préférence sur une période d'entre 1 et 60 secondes et de préférence dans lequel l'inspiration est maintenue pendant au moins 5 secondes et de préférence sur une période d'entre 5 et 45 secondes et de préférence sur une période d'entre 5 et 30 secondes.
 
4. Procédé selon l'une quelconque des revendications précédentes, réalisé pendant la réalisation d'un procédé d'imagerie du corps (20), en particulier une tomodensitométrie (TDM), une échographie ou un balayage à résonance magnétique (IRM), ou pendant une angiographie, une perfusion, des premières mesures de passage des artères pulmonaires (AP) ou d'autres vaisseaux contenant du sang distaux de la veine cave et/ou du coeur.
 
5. Procédé selon l'une quelconque des revendications précédentes, dans lequel l'acquisition d'image est réalisée alors que l'expiration augmente la pression dans le dispositif de résistance respiratoire (10), en particulier à une pression dans une plage de +1 mmHg à +80 mmHg et de préférence à une pression dans la plage de +10 mmHg à +40 mmHg.
 
6. Procédé selon l'une quelconque des revendications précédentes, dans lequel l'expiration est maintenue pendant au moins 1 seconde et de préférence sur une période d'entre 1 et 60 secondes et de préférence dans lequel l'expiration est maintenue pendant au moins 5 secondes et de préférence sur une période d'entre 5 et 45 secondes et de préférence sur une période d'entre 5 et 30 secondes.
 
7. Procédé selon l'une quelconque des revendications précédentes, dans lequel un paramètre lié à une pression générée par l'intermédiaire d'une inspiration ou par l'intermédiaire d'une expiration est surveillé pendant l'acquisition d'image et le paramètre surveillé est utilisé pour générer un signal de commande indicatif d'un écart par rapport à un état d'inspiration ou d'expiration optimal, respectivement.
 
8. Procédé selon l'une quelconque des revendications précédentes, dans lequel le dispositif de résistance respiratoire (10) comprend un corps principal (11) pourvu d'une ou de plusieurs ouvertures (121, 122) pour être relié, lors de l'utilisation, au système respiratoire du corps humain (20), et un volume intérieur fermé ou volume intérieur pourvu d'une ou de plusieurs constrictions (111) bloquant partiellement le débit d'air entrant dans ou sortant du système respiratoire du corps (20) pendant une phase d'inspiration ou phase d'expiration, respectivement.
 
9. Procédé selon la revendication 8, dans lequel les une ou plusieurs constrictions (111) sont suffisamment petites pour permettre la génération d'une sous/sur-pression dans le volume intérieur du dispositif (10) dans des conditions d'inspiration/expiration normales du système respiratoire humain.
 
10. Procédé selon la revendication 8 ou 9, dans lequel le dispositif de résistance respiratoire (10) a une sous-partie remplaçable (12) qui comprend un embout buccal (12) ou est constitué d'un embout buccal (12) et fournit les une ou plusieurs ouvertures (121, 122).
 
11. Procédé selon l'une quelconque des revendications 8 à 10, dans lequel le corps principal (11) du dispositif de résistance respiratoire (10) comprend un capteur (13) pour mesurer un paramètre lié à la pression dans le volume intérieur.
 
12. Procédé selon l'une quelconque des revendications 8 à 11, dans lequel le dispositif de résistance respiratoire (10) comprend en outre un générateur de signal de commande (14) pour générer un signal de commande indicatif d'un écart par rapport à un état respiratoire souhaité ou à une valeur de pression ou plage de valeurs de pression prédéfinie.
 
13. Procédé selon la revendication 12, dans lequel le générateur de signal de commande (14) inclut un indicateur indiquant si l'inspiration/expiration est trop faible et/ou trop forte.
 
14. Procédé selon l'une quelconque des revendications 8 à 13, dans lequel le dispositif de résistance respiratoire (10) est utilisé pour influencer via des états respiratoires définis la distribution et/ou la normalisation de l'apport sanguin soit depuis la veine cave supérieure soit depuis la veine cave inférieure en fonction de l'exigence respective nécessitant d'augmenter l'apport sanguin depuis le vaisseau respectif vers l'atrium droit du coeur et/ou d'améliorer la concentration d'une substance dans le débit sanguin dans les artères pulmonaires ou dans des vaisseaux au-delà des artères pulmonaires.
 




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REFERENCES CITED IN THE DESCRIPTION



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Patent documents cited in the description