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 being performed by a device, the device being selected from any one of a catheter, an applanation tonometry, and a Doppler ultrasound, the method comprising: a. measuring pressure pulses in an upper body artery; b. determining a central pressure pulse waveform that corresponds to the measured pressure pulses; c. non-invasively measuring flow pulses in a central artery which supplies blood to a brain; d. determining a central flow pulse waveform that corresponds to the measured flow pulses; e. determining ejection duration from the central pressure pulse waveform; f. determining ejection duration from the central flow pulse waveform; and g. determining a time difference between the ejection duration determined from the central pressure pulse waveform and the ejection duration determined from the central flow pulse waveform, wherein the time difference indicates an elevated ICP.
2. The method as claimed in claim 1, wherein step a. includes measuring peripheral pressure pulses in a peripheral artery.
3. The method as claimed in claim 2, wherein step b. includes sub-steps of: b1. determining a peripheral pressure pulse waveform from the measured peripheral pulses; and b2. calculating a corresponding central pressure pulse waveform from the peripheral pressure pulse waveform.
4. The method as claimed in claim 3, wherein the calculating of the corresponding central pressure pulse waveform from the peripheral pressure pulse waveform is done using a transfer function.
5. The method as claimed in claim 3, wherein the peripheral pressure pulses are measured in a radial artery at a wrist.
6. The method as claimed in claim 1, wherein step a. includes non-invasively measuring carotid pressure pulses in a carotid artery.
7. The method as claimed in claim 1, wherein step a. includes non-invasively measuring central pressure pulses in an upper body central artery.
8. The method as claimed in claim 7, wherein the central pressure pulses are measured by applanation tonometry.
9. The method as claimed in claim 1, wherein the flow pulses in step c. are measured in the upper body artery which supplies blood to the brain.
10. The method of claim 1, wherein step a. includes measuring the pressure pulses non-invasively.
11. The method of claim 1 further comprising: determining harmonic content of the central pressure pulse waveform and central flow pulse waveform; determining cerebral vascular impedance modulus data from the determined harmonic content; and comparing the determined cerebral vascular impedance modulus data to measured cerebral vascular modulus data indicative of a measured ICP to provide an indication of actual ICP.
12. The method of claim 1 further comprising: determining harmonic content of the central pressure pulse waveform and central flow pulse waveform; determining cerebral vascular impedance phase data from the determined harmonic content; and comparing the determined cerebral vascular impedance phase data to measured cerebral vascular phase data indicative of a measured ICP to provide an indication of actual ICP.
13. The method of claim 1 further comprising: determining harmonic content of the central pressure pulse waveform and central flow pulse waveform; determining cerebral vascular impedance modulus data from the determined harmonic content; determining cerebral vascular impedance phase data from the determined harmonic content; determining in-phase cerebral vascular impedance data from the determined cerebral vascular impendence modulus data and determined cerebral vascular impedance phase data; and comparing the determined in-phase cerebral vascular impedance data to measured in-phase cerebral vascular impedance data indicative of a measured ICP to provide an indication of actual ICP.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) A preferred embodiment of the invention will now be described, by way of an example only, with reference to the accompanying drawings, in which:
(2) FIG. 1 is a schematic diagram showing the brain 1 within the cranium 2 with cerebrospinal fluid (CSF) 3 between brain 1 and cranium 2 and a cerebral artery 4 and jugular vein 5.
(3) FIG. 2A is a graph showing peripheral (radial) arterial pressure (mm Hg) and central arterial pressure (mm Hg) and central arterial flow (cm/sec) versus time (sec) for normal (ie. non-elevated ICP) patient conditions.
(4) FIG. 2B is a graph showing peripheral (radial) arterial pressure (mm Hg) and central arterial pressure (mm Hg) and central arterial flow (cm/sec) versus time (sec) for elevated ICP patient conditions.
(5) FIG. 3A is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx) for normal patient conditions. The relationship is linear.
(6) FIG. 3B is a graph of flow augmentation index % (FAIx) versus pressure augmentation index % (PAIx), indicating the change in relationship (increase in PAIx and decrease in FAIx) for elevated ICP conditions. The relationship, at any given ICP condition, is again linear.
(7) 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 lines are shown at ±2 SD.
(8) 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 lines are shown at ±2 SD.
(9) FIG. 5A is a graph of cerebral vascular impedance modulus (Z) (d.Math.s.Math.cm.sup.−3×1000) versus frequency (Hz) for normal patient conditions.
(10) FIG. 5B is a graph of cerebral vascular impedance modulus (Z) (d.Math.s.Math.cm.sup.−3×1000) versus frequency (Hz) for elevated ICP conditions.
(11) FIG. 6A is a graph of cerebral vascular impedance phase (φ) (degrees) versus frequency (Hz) for normal patient conditions.
(12) FIG. 6B is a graph of cerebral vascular impedance phase (φ) (degrees) versus frequency (Hz) for elevated ICP conditions.
(13) FIG. 7A is a graph of in phase cerebral vascular impedance (Z cosine φ) (degrees) versus frequency (Hz) for normal patient conditions.
(14) FIG. 7B is a graph of in phase cerebral vascular impedance (Z cosine φ) (degrees) versus frequency (Hz) for elevated ICP conditions.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
(15) 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: a. Measuring pressure pulses in a peripheral artery (typically the radial artery at the wrist, or the brachial artery) and producing an electrical pressure pulse waveform signal representing the measured peripheral pressure pulses. The measured peripheral pressure pulse waveform (specifically, radial pressure pulse waveform for measurements taken at the radial artery) is denoted in solid line in FIG. 2A for normal patient conditions and in solid line in FIG. 2B for elevated ICP conditions. b. Deriving a Fourier transform for the measured peripheral pressure pulse waveform. c. Deriving a Fourier transform associated with a central (central arterial) pressure pulse waveform by applying a transfer function H(ω) to the peripheral pressure pulse Fourier transform. The transfer function H(ω) being a transfer function relating a Fourier transform of pressure pulses in the peripheral artery and a Fourier transform of pressure pulses in a central artery, particularly the aorta. d. Deriving the inverse of the Fourier transform associated with the central pressure pulse waveform, thereby producing an electrical signal representing a calculated central pressure pulse waveform. The calculated central pressure pulse waveform is denoted in black dashed line in FIG. 2A for normal patient conditions and in black dashed line in FIG. 2B for elevated ICP conditions. The above steps, method for determining features on the central pressure waveform, and calibration of peripheral (radial) pressures measured by 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). e. Determining the following features of the central pressure pulse waveform: i. The central arterial pressure at the point of systolic onset by taking a first derivative of the central pressure pulse waveform, and locating a zero crossing from negative-to-positive which precedes a maximum point on the first derivative curve, and designating this as P0. ii. A first localised systolic peak on the central pressure pulse waveform, within the limits of 60-140 msec from P0 (the foot of the pressure waveform), and designating this as P1. iii. A second localised systolic peak on the central pressure waveform, within the limits of 160-320 msec from P0 (the foot of the pressure waveform), and designating this as P2. iv. Peak pressure of pressure pulse waveform after P0 (the foot of the pressure pulse waveform), being the greater of P1 and P2. v. Pressure amplitude (PP). vi. Mean pressure (MP). vii. Pressure pulsatility index, wherein pressure pulsatility index is equal to pressure amplitude (PP) divided by mean pressure (MP). viii. Pressure augmentation (PA), wherein PA=P2−P1. ix. Pressure augmentation index (PAIx), wherein PAIx=PA÷(P2−P0) when P2>P1 and PAIx=PA÷(P1−P0) when P2<P1. f. Non-invasively measuring flow pulses in a central artery supplying blood to the brain (typically common carotid, anterior cerebral, middle cerebral, basilar and/or, vertebral artery) by Doppler ultrasound technique, and producing an electrical signal representing the central flow pulse waveform. The measured central flow pulse waveform is denoted in black dashed-dotted line in FIG. 2A for normal patient conditions and in black dashed-dotted line in FIG. 2B for elevated ICP conditions. g. Determining the following features of the central flow pulse waveform: i. Minimum flow velocity (F0). ii. A first localised systolic peak on the central flow pulse waveform within the limits of 60-140 msec from F0 (the foot of the central flow pulse waveform) and designating this as F1. iii. A second localised systolic peak on the central flow pulse wave form within the limits of 160-320 msec from F0 (the foot of the central flow pulse waveform) and designating this as F2 iv. Peak flow velocity, being the greater of F1 and F2. v. Flow amplitude (FP), wherein flow amplitude=F1−F0 when F1>F0 and F2−F0 when F2>F1. vi. Mean flow velocity (MF), determined by integrating the central flow pulse waveform over one cardiac cycle. vii. Flow pulsatility index, wherein flow pulsatility index is equal to flow amplitude (FP) divided by mean flow (MP). viii. Flow augmentation (FA), wherein FA=F2−F1, designating flow augmentation as positive when F2>F1 and as negative when F2<F1. ix. Flow augmentation index (FAIx), wherein FAIx=FA flow amplitude (FP). h. Determining flow/pressure augmentation index ratio, wherein the flow/pressure augmentation index ratio is equal to flow augmentation index (FAIx) divided by pressure augmentation index (FAIx). FIG. 3A shows a plot of the flow augmentation index (FAIx) versus pressure augmentation index (PAIx) for normal patient conditions, with FIG. 4A and FIG. 4B showing measured results for females and males respectively, whilst 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. i. Determining harmonic content of the central pressure and flow pulse waveforms by Fourier or frequency spectrum analysis. j. Determining cerebral vascular impedance modulus (Z) as moduli of frequency components of the central pressure pulse waveform divided by corresponding moduli of frequency components of the central flow pulse waveform (see FIGS. 5A and 5B for normal patient and elevated ICP conditions respectively). k. Determining cerebral vascular impedance phase (φ) as phase of frequency components of the central pressure pulse waveform minus corresponding phase of frequency components of the central flow pulse waveform (see FIGS. 6A and 6B for normal patient and elevated ICP conditions respectively). l. Determining in-phase cerebral vascular impedance as cerebral vascular impedence modulus multiplied by the cosine of cerebral vascular impedance phase (Z cosine φ)(see FIGS. 7A and 7B for normal patient and elevated ICP conditions respectively). m. Determining reflection coefficient as (ZT−ZC)÷(ZT+ZC), where ZT is terminal impedance modulus, being cerebral vascular impedence modulus at zero frequency (in dyne.Math.s.Math.cm−3) (estimated from the data in FIG. 5B) and ZC is characteristic impedance modulus, calculated as average value of cerebral vascular 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) (again estimated from the data in FIG. 5B). n. Determining ejection duration (ED) from the central pressure pulse wave form (EDp) and from the central flow pulse waveform (EDO (see FIG. 2B).
(16) The measures determined are then compared to normal values for gender, age and heart rate to give an indication of ICP.
(17) With reference to FIG. 3B, a clinician 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.
(18) The data shown in FIG. 5B is used to estimate characteristic impedance (ZC) and terminal impedance (ZT), and from these values, calculate reflection coefficient as (ZT−ZC)÷(ZT+ZC), as discussed above, as an indication of ICP.
(19) The data shown in FIG. 6B, which shows the cerebral vascular impendence phase for the measured data, is compared against the data shown in FIG. 6A, which shows the cerebral vascular impedance phase 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. This comparison of phase delay for the measured data against phase delay under normal conditions provides an indication of ICP.
(20) The data shown in FIG. 7B is used to compare abnormal patterns of in-phase cerebral vascular impedance (Z cosine φ) fluctuations against normal non-fluctuant values of in-phase cerebral vascular impedance (Z cosine φ) (from FIG. 7A), by comparing average levels of in-phase cerebral vascular impedance (Z cosine φ) over the same frequency range that is used in FIG. 5B to calculate characteristic impedance, as described above. This comparison provides another indication of elevated ICP.
(21) Ejection duration (ED) determined from the pressure pulse wave form (EDp) is compared to ED determined from the flow pulse waveform (EDf) as a check on the ability of the algorithm to identify left ventricular ED accurately and independently of reflected waves, with differences in determined ED giving an indication of elevated ICP.
(22) The benefits of the non-invasive method of ICP measurement described above include:
(23) no procedural risk of cerebral damage, haemorrhage and infection;
(24) less requirement of direct measurement;
(25) better discrimination in selecting patients for direct measurement;
(26) more appropriate use of direct ICP measurement; and
(27) better management of patients without need for invasive measurement.
(28) 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 non-invasively measured in a central upper body artery, particularly the common carotid artery, rather than in a peripheral artery. In this embodiment, the central pressure pulses are directly measured, for example by applanation tonometry and the central pressure pulse waveform directly determined from the measured central pressure pulses.
