NON-INVASIVE METHOD OF ESTIMATING INTRA-CRANIAL PRESSURE (ICP)

Abstract

A non-invasive method of estimating intra-cranial pressure (ICP). The method including the steps of: a. non-invasively measuring pressure pulses in an upper body artery; b. determining central aortic pressure (CAP) pulses that correspond to these measured pressure pulses; c. identifying features of the ICP wave which denote cardiac ejection and wave reflection from the cranium, including Ejection Duration (ED) and Augmentation Index of Pressure (PAIx); d. non-invasively measuring flow pulses in a central artery which supplies blood to the brain within the cranium; e. identifying features of the measured cerebral flow waves which denote cardiac ejection and wave reflection from the cranium as Flow Augmentation Index (FAIx); f. calculating an ICP flow augmentation index from the measured central flow pulses; g. comparing the calculated ICP pressure augmentation index (PAIx) and flow augmentation index (FAIx) to measure (gender-specific) pressure and flow augmentation data indicative of a measured ICP to thereby estimate actual ICP; and h. noting any disparity between ED measured for pressure waves and ED measured for flow.

Claims

1. A non-invasive method of estimating intra-cranial pressure (ICP), the method including the steps of: a. non-invasively measuring pressure pulses in an upper body artery; b. determining central aortic pressure (CAP) pulses that correspond to these measured pressure pulses; c. identifying features of the ICP wave which denote cardiac ejection and wave reflection from the cranium, including Ejection Duration (ED) and Augmentation Index of Pressure (PAIx); d. non-invasively measuring flow pulses in a central artery which supplies blood to the brain within the cranium; e. identifying features of the measured cerebral flow waves which denote cardiac ejection and wave reflection from the cranium as Flow Augmentation Index (FAIx); f. calculating an ICP flow augmentation index from the measured central flow pulses; g. comparing the calculated ICP pressure augmentation index (PAIx) and flow augmentation index (FAIx) to (gender-specific) pressure and flow augmentation data indicative of a measured ICP to thereby estimate actual ICP; and h. noting any disparity between ED measured for pressure waves and ED measured for flow.

2. The method as claimed in claim 1, wherein step a. includes measuring radial pressure pulses in a peripheral artery.

3. The method as claimed in claim 2, wherein step b. includes calculating the corresponding central pressure pulses from the measured radial pressure pulses,

4. The method as claimed in claim 3, wherein the calculating of the corresponding central pressure pulses from the measured radial pressure pulses is done using a transfer function.

5. The method as claimed in claim 3, wherein the radial pressure pulses are measured in the radial artery at the wrist.

6. The method as claimed in claim 1, wherein step a. includes measuring carotid pressure pulses in a carotid artery.

7. The method as claimed in claim 6, wherein step b. includes measuring the corresponding central pressure pulses.

8. The method as claimed in claim 7, wherein the corresponding central pressure pulses are measured by applanation tonometry.

9. The method as claimed in claim 1, wherein the flow pulses in step d. are measured in an upper body artery which supplies blood to the brain.

10. A non-invasive method of estimating intra-cranial pressure (ICP), the method including the steps of: a. non-invasively measuring pressure pulses in an upper body artery; b. determining central pressure pulses that correspond to the measured pressure pulses; c. non-invasively measuring flow pulses in a central artery which supplies blood to the brain; d. calculating an ICP pressure augmentation index from the determined central pressure pulses and the measured central flow pulses; e. calculating an ICP flow augmentation index from the measured central flow pulses; and f. comparing the calculated ICP pressure and flow augmentation indexes to measured pressure and flow augmentation data indicative of a measured ICP to thereby estimate actual ICP.

11. The method as claimed in claim 10, wherein step a. includes measuring radial pressure pulses in a peripheral artery.

12. The method as claimed in claim 11, wherein step b. includes calculating the corresponding central pressure pulses from the measured radial pressure pulses.

13. The method as claimed in claim 12, wherein the calculating of the corresponding central pressure pulses from the measured radial pressure pulses is done using a transfer function.

14. The method as claimed in claim 12, wherein the radial pressure pulses are measured in the radial artery at the wrist.

15. The method as claimed in claim 10, wherein step a. includes measuring carotid pressure pulses in a carotid artery.

16. The method as claimed in claim 10, wherein step b. includes measuring the corresponding central pressure pulses

17. The method as claimed in claim 16, wherein the corresponding central pressure pulses are measured by applanation tonometry.

18. The method as claimed in claim 10, wherein the flow pulses in step c. are measured in an upper body artery which supplies blood to the brain.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0035] A preferred embodiment of the invention will now be described, by way of an example only, with reference to the accompanying drawings, in which:

[0036] FIG. 1 is a schematic diagram showing the brain (yellow) within the cranium (brown) with CSF (green) between brain and cranium and a cerebral artery (red) and jugular vein (blue);

[0037] FIG. 2a is graph showing radial pressure (mm Hg) and central pressure (mm Hg) and central flow (cm/sec) versus time (sec) for normal (ie. non-elevated ICP) patient conditions;

[0038] FIG. 2b is graph showing radial pressure (mm Hg) and central pressure (mm Hg) and central flow (cm/sec) versus time (sec) for elevated ICP patient conditions;

[0039] FIG. 3a is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for normal patient conditions; the relationship is linear;

[0040] FIG. 3b is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for elevated ICP conditions; the relationship is linear;

[0041] FIG. 4a is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for normal conditions, with actual data taken from a normal female population; linear regression line is shown±2 SD;

[0042] FIG. 4b is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for normal conditions, with actual data taken from a normal male population; linear regression line is shown±2 SD;

[0043] FIG. 5a is a graph of Modulus of Impedance (DSCM-3×1000) versus frequency (Hz) for normal patient conditions;

[0044] FIG. 5b is a graph of Modulus of Impedance (DSCM-3×1000) versus frequency (Hz) for elevated ICP conditions;

[0045] FIG. 6a is a graph of Phase of Impedance (degrees) versus frequency (Hz) for normal patient conditions;

[0046] FIG. 6b is a graph of Phase of Impedance (degrees) versus frequency (Hz) for elevated ICP conditions;

[0047] FIG. 7a is a graph of Z cosine f (degrees) versus frequency (Hz) for normal patient conditions; and

[0048] FIG. 7b is a graph of Z cosine f (degrees) versus frequency (Hz) for elevated ICP conditions.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] An embodiment of a method of non-invasively measuring ICP will now be described with reference to FIGS. 2a to 7b. The method comprises the steps of: [0050] a. Measuring pressure pulses in a peripheral artery (typically the radial artery at the wrist) and producing an electrical signal representing the pressure pulses. The measured pressure pulses are denoted in black in FIG. 2a for normal patient conditions and in black in FIG. 1b for elevated ICP. [0051] b. Deriving a Fourier transform for the measured peripheral pulses. [0052] c. Deriving the peripheral pulse Fourier transform by a transfer function H(w) relating a Fourier transform of pressure pulses in the peripheral artery and a Fourier transform of pressure pulses in the aorta thereby producing a Fourier transform associated with the central aortic pressure pulse. The calculated central pressure pulses are denoted in pink in FIG. 2a for normal patient conditions and in pink in FIG. 2b for elevated ICP. [0053] d. Deriving the inverse of the Fourier transform associated with the aortic pressure pulse, thereby producing an electrical signal representing a synthesised ascending aortic pulse. The above steps and calibration of radial tonometry to brachial cuff systolic and diastolic pressure are disclosed in U.S. Pat. No. 5,265,011 (the contents of which are incorporated herein by cross reference). [0054] e. Determining the signal representing the measured peripheral pulse a point of systolic onset by taking a first derivative of the measured peripheral pulse and locating a zero crossing from negative-to-positive which precedes a maximum point on the first derivative curve. [0055] f. Identifying a first localised systolic peak on the pressure signal within the limits of 60-140 msec from the foot of the pressure wave, and designating this as P1. [0056] g. Identifying a second localised systolic peak of the pressure wave signal within the limits of 160-320 msec from the foot of the wave and designating this as P2. [0057] h. Non-invasively measuring flow pulses in arteries supplying blood to the brain (typically internal common carotid, anterior cerebral, middle cerebral, basilar, vertebral) by Doppler ultrasound technique, and producing an electrical signal representing the flow pulses. The measured flow pulses are denoted in green in FIG. 2a for normal patient conditions and in green in FIG. 2b for elevated ICP. [0058] i. Generating the following features of the flow waveform signal: [0059] i. Peak flow velocity. [0060] ii. Minimal flow velocity, zero flow velocity. [0061] iii. Designating amplitude of the flow velocity waveform. [0062] iv. Generating mean flow velocity from integration of the wave over one cardiac cycle. [0063] v. Determining FF as (mean flow velocity minus nadir flow velocity) divided by amplitude of the velocity waveform. [0064] vi. Designating flow pulsatility index as amplitude of the flow waveform divided by mean flow. [0065] vii. Identifying a first localised systolic peak on the flow signal within the limits of 60-140 msec from the foot of the flow wave, and designating this as F1. [0066] viii. Identifying a second localised systolic peak of the flow wave signal within the limits of 160-320 msec from the foot of the wave and designating this as F2, as in lg for the pressure waveform. [0067] ix. Identifying flow velocity augmentation as difference between F1 and F2, designating augmentation as positive when F2>F1 and as negative when F2<F1. [0068] x. Designating Flow AIx as flow augmentation÷amplitude of flow velocity waveform. [0069] xi. Designating pressure augmentation as P2-P1. [0070] xii. Generating pressure AIx indices as (P2-P1)÷(P2-P0) when P2>P1. [0071] xiii. Generating pressure AIx indices as (P2-P1)÷(P1-P0) when P2<P1. FIG. 3a shows a plot of the flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for normal patient conditions, as well as FIG. 4a (females) and FIG. 4b (males), and FIG. 3b shows plots of the flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for various known (i.e. previously invasively measured) elevated ICP conditions. [0072] xiv. Determining peak of pressure wave after onset of the pressure wave. [0073] j. Designating of pressure pulsatility as amplitude of the pressure wave divided by mean pressure. [0074] k. Designating pressure FF divided by flow FF as FF ratio. [0075] l. Designating flow AIx divided by pressure AIx as flow/pressure AIx ratio. [0076] m. Determining harmonic content of the pressure waveform by Fourier or frequency spectrum analysis. [0077] n. Determining cerebral impedance modulus as moduli of frequency components of pressure divided by corresponding moduli of flow frequency components (see FIGS. 5a and 5b for normal patient and elevated ICP conditions respectively). [0078] o. Determining cerebral impedance phase as phase of frequency components of pressure minus corresponding frequency components of phase (see FIGS. 6a and 6b for normal patient and elevated ICP conditions respectively). [0079] p. Determining in-phase impedance as Z cos f (see FIGS. 7a and 7b for normal patient and elevated ICP conditions respectively).

[0080] The steps e to p are applied to the calibrated central aortic pressure wave and the simultaneously measured internal carotid flow wave on the contralateral side. The measures taken are then compared to normal values for gender, age, heart rate, the measures being: [0081] a. Aortic pressure systolic [0082] b. Aortic pressure mean [0083] c. Aortic pressure pulsation [0084] d. Aortic pressure augmentation [0085] e. Aortic pressure augmentation index (PAIx) [0086] f. Aortic pressure AIx corrected for heart rate at 75/minute (PAIx 75); and [0087] g. Pressure form factor (mean pressure−diastolic pressure)÷pulse pressure [0088] h. Flow velocity systolic [0089] i. Flow velocity mean [0090] j. Flow velocity diastolic [0091] k. Flow velocity pulsation [0092] l. Flow velocity augmentation [0093] m. Flow velocity augmentation index (FAIx) [0094] n. FAIx corrected for heart rate (FAIx 75) [0095] o. Flow velocity pulsatility index (flow pulsation÷mean flow) [0096] p. Flow velocity form factor [0097] q. Pressure/flow relationships as PAIx/FAIx [0098] r. Pressure/flow relationships as cerebral vascular impedance (CVI) [0099] s. Pressure/flow relationships as in-phase CVI (Z cos f of impedance) [0100] t. Reflection coefficient as (ZT-ZC)÷(ZT+ZC), where ZT is terminal impedance at zero frequency (CVI in dyne.s.cm-3) and ZC is characteristic impedance calculated as average value of impedance modulus from frequency of second to sixth harmonics and after excluding values of pressure and flow in the noise level (P<0.4 mmHg), flow<1 cm/s) [0101] u. ED from pressure wave (EDp) and from flow wave (EDf)

[0102] With reference to FIG. 3b, a clinician then compares the calculated ICP pressure and flow augmentation indexes (represented as dots 18) to measured ICP augmentation index data (represented by the plots), which are indicative of a measured ICP, to thereby estimate actual ICP. The amount of actual elevated ICP is determined by selecting the known plot closest to the dots 18.

[0103] The data shown in FIG. 4b is used to estimate characteristic impedance (Zc) and terminal impedance (Zt), and from these values, calculate reflection coefficient as (Zc-Zt)÷(Zc+Zt).

[0104] The data shown in FIG. 5b is used to compare phase delay against FIG. 4a which shows phase delay under normal conditions. This is measured as average of phase delay over the same frequency band as used to estimate characteristic impedance, and with same criteria to exclude pressure and flow data in the noise level.

[0105] The data shown in FIG. 5b is used to compare abnormal patterns of Zcosf fluctuations against normal non-fluctuant values of Zcosf, by comparing average levels of Zcosf over the same frequency range used in FIGS. 3 to calculate characteristic impedance, as described for the above paragraph. ED from pressure wave (EDp) is compared to ED from flow wave (EDf) as a check on ability of algorithm to identify left ventricular ED accurately and independently of reflected waves.

[0106] The benefits of the non-invasive method of ICP measurement described above include: [0107] no procedural risk of cerebral damage, haemorrhage and infection; [0108] less requirement of direct measurement; [0109] better discrimination in selecting patients for direct measurement; [0110] more appropriate use of direct ICP measurement; and [0111] better management of patients without need for invasive measurement.

[0112] Although the invention has been described with reference to a preferred embodiment, it will be appreciated by those persons skilled in the art that the invention may be embodied in many other forms. For example, in an alternative embodiment (not shown), the pressure pulses are measured in the common carotid artery. In this embodiment, the corresponding central pressure pulses are directly measured, for example by applanation tonometry.