Timing biological imaging, measuring, and therapeutic timing systems

Abstract

System for timing biological imaging, measuring, or therapeutic apparatus in accordance with selected physiological states of a subject, featuring in various aspects generation of respiratory windows on the basis of processed electrical signals derived from prior respiration history, digital offset correction circuitry for the respiratory signals, and generation of cardiac timing signals on the basis of prior cardiac cycle history.

Description

BACKGROUND OF THE INVENTION

This invention relates to timing biological imaging, measuring, or therapeutic systems (in the broad sense, including, e.g., an X-ray machine or a nuclear camera) in accordance with the respiratory and cardiac states of the body.

Monitoring the respiratory state by detecting the variations in electrical impedance produced during the breathing cycle is described in Geddes et al., "The Impedance Pneumograph," Aerospace Medicine, January, 1962, pages 28-33. Timing an X-ray machine in accordance with respiratory state (e.g., to obtain an X-ray image when the lungs are fully inflated) is described in Robertson U.S. Pat. No. 3,524,058. Timing an X-ray machine in accordance with the cardiac cycle is described in Becker U.S. Pat. No. 3,626,932, where the use of a pulmonary synchronization unit is also mentioned. X-ray timing based upon a percentage of heart beat interval is described in Strauss et al. U.S. Pat. No. 2,190,389.

Accurate timing is important for many reasons, including for obtaining images or measurements that are not blurred by heart or lung motion, and for making possible precise and reproduceable comparisons of images or measurements taken at different physiological states.

SUMMARY OF THE INVENTION

The invention provides highly refined monitoring of the respiratory and cardiac cycles, and makes possible very accurate and automatic timing to a selected physiological state, with equipment that is reliable, easily operated by an unskilled technician, and not unduly costly or complex. Timing accuracy is achieved, with respect to the respiratory state, despite impedance variations over time and from patient to patient that far exceed variations within a breathing cycle, and, with respect to cardiac state, despite normal beat to beat rate variations.

In general the invention features, in one aspect, input circuitry for providing electrical signals representative of the respiratory cycles of the subject, and respiratory timing circuitry for processing the electrical signals and for generating a succession of windows corresponding to selected portions of successive respiratory cycles, including means for basing the generation of each window in a given cycle upon the results of the processing of electrical signals derived from respiration prior to the given cycle. In another aspect the invention features input circuitry for providing electrical signals representative of the cardiac cycle of the subject, and cardiac timing circuitry for producing a succession of timing signals corresponding to selected points in successive cardiac cycles, the timing circuitry including interval circuitry for generating a succession of interval values corresponding to the lengths of successive cardiac cycles, and timing signal circuitry for generating each cardiac timing signal at a time dependent upon a constant value plus a fraction of the interval for the next previous cardiac cycle. In yet another aspect the invention features digital offset correction circuitry for automatically causing electrical signals respresentative of respiratory cycles to be within a predetermined range, including limit detection circuitry for providing a signal when the respiratory signal is outside the range, digital means for providing pulses in the presence of a signal from the detection circuitry, a counter for counting the pulses, and an offset generator for generating an offset voltage dependent upon the count in the counter. In preferred embodiments a majority of the respiratory windows are of duration sufficient to span a plurality of the cardiac timing signals; the respiratory timing circuitry includes means for generating values respectively representative of maximum and minimum expiration within a respiratory cycle, and respiratory state definition circuitry for generating the windows in a manner dependent upon both those values; a recorder provides a synchronous display of cardiac cycle, respiratory state, and the timing of the output control signals; the input cicuitry generates digital pulses corresponding to occurrences of QRS complexes, and the cardiac timing circuitry generates cardiac timing signals each at a time subsequent to the QRS complex equal to a constant value plus a fraction of the interval value for the next previous cardiac cycle, the constant value being a timing constant related to the refractory time of the heart muscle minus half the width of the cardiac timing pulses; the timing signal circuitry includes means for changing in successive cardiac cycles the fraction of the interval value upon which the respective timing signal is based; arrythmia detection circuitry is provided for detecting cardiac arrythmia by comparison with cardiac cycles expected on the basis of the cardiac timing signals; and the offset correction circuitry includes upper and lower limit detectors for respectively incrementing an decrementing the counter when the respiratory signal is above and below th range, and means for periodically automatically changing the count in the counter to cause the respiratory signal to drift in a predetermined direction.

Other advantages and features of the invention will be apparent from the description and drawings herein of a preferred embodiment thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the use of a synchronizer embodying the invention to time a nuclear camera;

FIGS. 2-4 are block diagrams showing the details of the synchronizer of FIG. 1; and

FIG. 5 illustrates typical waveforms associated with the patient and the synchronizer.

DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 shows the synchronizer of the invention in a system including a nuclear camera 10. The synchronizer 12 detects respiratory and cardiac signals through silver-silver chloride ECG electrodes 14 attached midline to the patient's fifth or sixth intercostal space and controls logic 16 to gate signals from radiation detector 18 to CRT display 20 whenever systole occurs during expiration in the respiratory cycle. Successive signals are integrated in the display, and the integration over a period of time is photographed by the camera.

Referring to FIGS. 2 - 4, electrodes 14 are connected to impedance plethysmograph 30, which passes a small (e.g., 100 KHz) current through the electrodes and detects the change in the patient's transthoracic impedance, which is proportional to respiration. The output of the plethysmograph, an analog voltage proportional to respiration, is fed to a positive peak voltage detector 32, a negative peak voltage detector 34, and a digital offset correction circuit 36.

Circuitry 36 consists of two analog comparators 38 and 40 which function as preset high and low voltage limit detectors. The limit detectors drive a binary up-down counter 42 which in turn drives a digital to analog converter 44. The output of converter 44 goes to the plethysmograph as an offset correction signal which is added to the plethysmograph output to bring the output into the desired operating range, which is chosen to be sufficiently wide to accommodate signal excursion within the respiration cycle. More particularly, if the output voltage of the plethysmograph is above the desired operating range, detector 38 gates pulses into the up count input 46 of counter 42. As the counter counts up, the output of converter 44, a negative voltage proportional in magnitude to the value in the counter, goes more negative. The increasing offset eventually brings the output of the plethysmograph below the threshold of the high voltage limit detector. If the output of the plethysmograph is below the desired operating range, detector 40 gates pulses into the down count input 48 of the counter. The offset correction signal from converter 44 becomes less negative and again the plethysmograph output is brought into the desired range. Periodically (e.g., every 15 seconds) counter 42 is incremented by clock 49 one bit to produce a slow downward drift of the base line signal. If the signal crosses the lower limit of the desired range detector 40 is activated and gates a single pulse to the down count input 48 to restore the counter to its former state. In this way the digital circuitry allows the plethysmograph to pass the slowly varying respiratory signal yet respond quickly when the signal is out of range, and eliminates the need for the operator to make an otherwise critical and frequent adjustment, since impedance variations over time and from patient to patient far exceed the variations within a respiratory cycle.

Detectors 32 and 34 respectively detect and store the most positive and most negative recent excursions of the respiratory signal, and decay over time to track signals which become smaller or vary in their voltage excursions. Weighted fractions of the peak positive and negative signals are sent respectively to the positive and negative threshold detect circuits 50 and 52, which also receive the analog respiratory signal directly from the plethysmograph. If the analog respiratory signal exceeds 0.8 times the positive peak voltage plus 0.2 times the negative peak voltage the patient is defined as being in expiration. If the analog signal is less than 0.8 times the negative peak voltage plus 0.2 times the positive peak voltage, the patient is defined as being in inspiration. The threshold detect circuits thus generate windows 54, 56 (FIG. 5), based upon previous respiratory peaks, which respectively span generally flat zones surrounding the points of peak inspiration and respiration in the respiratory cycle. Ten percent hysteresis in the threshold detect circuits prevents the outputs from changing state if the analog respiratory signal has small voltage deviations due to irregular respiration or patient motion. For example, the analog respiratory signal has to drop to 0.7 times the positive peak voltage plus 0.2 times the negative peak voltage to turn off the positive threshold detect signal. Similarly, the signal has to exceed 0.7 times the negative peak voltage plus 0.2 times the positive peak voltage to turn off the negative threshold detect once it has been activated. The hysteresis also forces the threshold circuits to generate symmetrical output pulses with respect to time for a symmetrical input signal. The impedance plethysmograph and associated peak detectors and threshold detectors have a dynamic operating range of signal of greater than 40 to 1.

The patient's electrocardiogram is picked up from electrodes 14 and amplified by a low noise, high input impedance preamplifier stage 60 and passed through an isolation amplifier 62. The signal is coupled optically through amplifier 62 to provide patient safety. No direct electrical path exists between the patient electrodes and the machine. Power for preamplifier 60 and amplifier 62 is provided by an isolated power supply 64 which has no direct electrical connection to the machine. The impedance plethysmograph 30 is similarly decoupled from the patient.

From amplifier 62 the ECG signal is passed through a 60 Hz notch filter 66 to remove any power line noises, and then to recorder drive and control circuits 68 and to 17 Hz bandpass filter 70. The bandpass filter approximates a matched filter for the normal adult QRS complex of the electrocardiogram, that is, it allows only those signals to pass which have a frequency distribution similar to the frequency content of the QRS complex of an electrocardiogram.

The bandpass filtered signal then goes to precision full wave rectifier 72, which takes the absolute value of the incoming signal (i.e., it allows positive signals to pass unmodified and reverses the polarity of negative signals) so that the output of the circuit is always positive.

The rectified signal goes to a peak voltage detector 74 and, along with the output of detector 74, to a threshold comparator 76. Detector 74 tracks and stores the most positive recent excursion of the signal, decaying in time to track signal magnitudes varying with time. Comparator 76 generates an output pulse if the rectified signal exceeds 0.8 times the peak detect voltage. The pulse from the comparator triggers a one-shot 78, which puts out a uniform width, single pulse for each detected QRS complex.

Ramp generator 80 repeatedly produces a linearly rising voltage. The detection of a QRS complex in the electrocardiogram causes the sample and hold circuit 82 to store the instantaneous voltage of the ramp generator, a value proportional to the last QRS to QRS interval, and resets generator 80 to zero to start a new ramp. Threshold detectors 84 and 86 each receive as inputs both the instantaneous ramp voltage from generator 80 and the output of circuit 82. Detectors 84 and 86 each include circuitry for comparing the instantaneous ramp voltage with a function of the output of circuit 82 (i.e., the previous QRS to QRS interval). In the embodiment shown detector 84 is designed to trigger one-shot 88 when the instantaneous ramp voltage equals a constant voltage Vo plus 20% of the output of circuit 82 (corresponding to 20% of the previous QRS to QRS interval), closely approximating the occurrence of the systole. Similarly, detector 86 is designed to trigger one-shot 90 when the innstantaneous ramp voltage equals Vo plus 80% of the output of circuit 82, closely approximating the occurrence of diastole. In general, such detectors can be arranged to trigger a one-shot at any desired point in the cardiac cycle. In particular, useful embodiments include detectors arranged to trigger a one-shot at different points in successive cardiac cycles, e.g., to provide a set of images of the heart at different points in the cycle. Such a possible threshold detector 87 for variable timing, with associated one-shot 89, is shown in dashed lines in FIG. 3. In the embodiment shown Vo represents a time interval of 100 milliseconds, which has been discovered to correspond to the refractory time for the heart muscle, minus half the width of the one-shot pulse. The refractory constant of 100 milliseconds can be varied within a preferred range of 50-150 milliseconds, as 20% and 80% fractions of QRS interval for systole and diastole correspondingly vary within respective preferred ranges of 15-30% and 75-90%.

The signals defining the respiratory windows and the cardiac timing signals are routed to gating and control logic 100, along with signals from the front panel controls and indicators 102. The physiological states selected by the operator are sent to the interface circuits 104 to time the device connected to the synchronizer in accordance with the selected states. For example, an imaging device may be timed for exposure whenever systole occurs in a respiratory window.

A majority of the respiratory windows are wide enough to encompass a plurality of cardiac timing signals.

Arrythmia detect logic 106 detects the presence of an arrythmia occurring during cardiac gated exposure as defined in the two following ways. If a QRS complex is detected during a systole gated exposure, it is defined as an arrythmia. If no QRS complex is detected within 300 milliseconds after a diastole gated exposure occurs, it is defined as an arrythmia. The percent arrythmic beats computer 108 counts the number of arrythmias occurring and displays the percentage of arrythmic beats that have occurred after 100, 200 and 400 gated cardiac exposures. The display is in true percent shown on a numeric display 110.

The recorder control and drive electronics 68 receives the respiratory window and cardiac timing signals as well as the electrocardiographic signal from filter 66 and processes these signals for the strip chart recorder 112. The strip chart recorder prints out an electrocardiogram and two event marks. One event mark places a line on the chart when a selected respiratory state is occurring. The other event mark puts a line on the chart whenever the conditions for exposure are met. The event marks are placed on the chart synchronously with the electrocardiogram and allow the operator to observe that exposures are being made at the proper time in the cardiac cycle. In the case of an X-ray exposure, the ECG is marked by the event marker to show the exact time of the specific cardiac cycle during which the exposure was made.

Other embodiments are within the following claims.

Claims

What is claimed is:

1. A system for timing biological imaging, measuring, or therapeutic apparatus in accordance with selected respiratory events in a subject, comprising

respiratory input circuitry means for providing electrical signals representative of the respiratory cycles of said subject,

respiratory timing circuitry means effectively connected to said input circuitry means for processing said electrical signals and for generating a succession of windows surrounding predicted respiratory events of successive respiratory cycles, including means for basing the generation of each said window in a given cycle upon the results of said processing of electrical signals derived from respiration prior to said given cycle, and

means for effectively connecting said system to said apparatus to be controlled.

2. The system of claim 1 further comprising

cardiac input circuitry means for providing electrical signals representative of the cardiac cycles of said subject,

cardiac timing circuitry means effectively connected to said cardiac input circuitry means for producing a successsion of timing signals corresponding to selected points in successive cardiac cycles, and

output circuitry means effectively connected to said respiratory and cardiac timing circuitry means, and including logic circuitry means, for producing a succession of output signals corresponding to successive said timing signals occurring within said windows.

3. The system of claim 2 wherein said respiratory timing circuitry includes means for causing the majority of said windows to be of duration longer than the combined duration of a plurality of successive said timing signals occurring within the respective said window, and the interval between said successive signals.

4. The system of claim 2 further comprising recorder means effectively connected to said cardiac input circuitry means and to said logic circuitry means, for recording a synchronous display of said cardiac cycle and the timing of said output signals.

5. The system of claim 4 wherein said recorder means includes means for including in said synchronous display a record of said respiratory windows.

6. The system of claim 2 wherein said cardiac timing circuitry means includes cardiac interval circuitry means effectively connected to said cardiac input circuitry means for generating a succession of interval values corresponding to the lengths of successive cardiac cycles, and timing signal circuitry means effectively connected to said interval circuitry means for generating each said timing signal at a time dependent upon a fraction of the interval value for the next previous cardiac cycle.

7. The system of claim 6 wherein said timing signal circuitry means includes means for generating each said timing signal at a time dependent upon a constant value plus a fraction of the interval value for the next previous cardiac cycle.

8. The system of claim 6 wherein said interval circuitry means includes means for generating a succession of interval values correponding to intervals between QRS complexes of successive cardiac cycles, and said timing signal circuitry means includes means for generating each said timing signal at a time subsequent to the QRS complex for that cardiac cycle equal to a constant value plus a portion of the interval value for the next previous cardiac cycle.

9. The system of claim 8 wherein said portion is between 15 and 30% to cause said timing signal to represent systole.

10. The system of claim 8 wherein said portion is between 75 and 90% to cause said timing signal to represent diastole.

11. The system of claim 6 wherein said timing signal circuitry means includes means for changing in successive cardiac cycles the fraction of said interval value upon which the respective timing signal is based.

12. The system of claim 2 further comprising arrythmia detection circuitry means effectively connected to said cardiac input circuitry means and to said logic circuitry means for detecting cardiac arrythmia by comparison with cardiac cycles expected on the basis of said cardiac timing signals.

13. The system of claim 1 wherein said respiratory timing circuitry means includes means for generating values respectively representative of maximum and minimum expiration within a respiratory cycle of said subject, and respiratory state definition circuitry means for generating said windows as a function of both said values.

14. The system of claim 13 wherein said means for generating values comprises peak detectors.

15. The system of claim 14, wherein said peak detectors include means for storing values therein and for causing said stored values to decay over time.

16. The system of claim 14 wherein said respiratory state definition circuitry means includes threshold detection circuitry means effectively connected to said peak detectors and to said input circuitry means.

17. The system of claim 16 wherein said threshold detection circuitry means includes means for preventing its output from changing despite variations in the respiratory signal from said respiratory input circuitry smaller than a preselected limit.

18. The system of claim 1 further comprising digital offset correction circuitry means effectively connected to said respiratory input circuitry means for automatically causing said electrical signals representative of respiratory cycles to be within a predetermined range.

19. The system of claim 18 wherein said correction circuitry means includes limit detection means effectively connected to said respiratory input circuitry for providing a signal when the respiratory signal is outside said range, digital means effectively connected to said detection means for providing digital pulses in the presence of a signal from said detection means, a counter effectively connected to said digital means for counting said pulses, and offset generator means effectively connected to said respiratory input circuitry means for generating an offset voltage dependent upon the count in said counter.

20. The system of claim 19 wherein said detection means includes upper and lower limit detectors for respectively incrementing and decrementing said counter when the respiratory signal is above and below said range.

21. The system of claim 19 further comprising means for periodically automatically changing the count in said counter to cause said respiratory signal to drift in a predetermined direction.

22. A system for timing biological imaging, measuring or therapeutic apparatus in accordance with selected physiological states of a subject, comprising

cardiac input circuitry means for providing electrical signals representative of the cardiac cycle of said subject,

cardiac timing circuitry means effectively connected to said cardiac input circuitry means for producing a succession of timing signals corresponding to selected predicted cardiac events in successive cardiac cycles, said timing circuitry means including interval circuitry means for generating a succession of interval values corresponding to intervals between QRS complexes of successive cardiac cycles, and timing signal circuitry means effectively connected to said interval circuitry means for generating each said timing signal at a time subsequent to the QRS complex for that cardiac cycle equal to a time constant related to the refractory time of the heart muscle minus half the width of said timing signals plus a fraction of the interval for the next previous cardiac cycle, to cause each said timing signal to surround said predicted cardiac event, and

means for effectively connecting said system to said apparatus to be controlled.

23. The system of claim 22 wherein said portion is between 15 and 30% to cause said timing signal to represent systole.

24. The system of claim 22 wherein said portion is between 75 and 90% to cause said timing signal to represent diastole.

25. The system of claim 22 wherein said timing signal circuitry means includes means for changing in successive cardiac cycles the fraction of said interval value upon which the respective timing signal is based.

26. The system of claim 22 further comprising arrythmia detection circuitry means effectively connected to said input circuitry means and to said cardiac timing circuitry means for detecting cardiac arrythmia by comparison with cardiac cycles expected on the basis of said cardiac timing signals.

27. The system of claim 22 wherein said time constant is between 50 and 150 milliseconds.

28. A system for timing biological imaging, measuring or therapeutic apparatus in accordance with selected physiological states of a subject, comprising

input circuitry means for providing electrical signals representative of a physiological cycle of said subject,

output circuitry means effectively connected to said input circuitry means for providing a succession of timing signals at selected portions of said physiological cycles, and

digital offset correction circuitry means effectively connected to said input circuitry means for automatically causing said electrical signals representative of physiological cycles to be within a predetermined range, said correction circuitry means including limit detection means effectively connected to said input circuitry for providing a signal when the physiological signal is outside said range, digital means effectively connected to said detection means for providing digital pulses in the presence of a signal from said detection means, a counter effectively connected to said digital means for counting said pulses, said detection means including upper and lower limit detectors for respectively incrementing and decrementing said counter when the physiological signal is above and below said range, and offset generator means effectively connected to said input circuitry means for generating an offset voltage dependent upon the count in said counter, and

means for effectively connecting said system to said apparatus to be controlled.

29. A system for timing biological imaging, measuring or therapeutic apparatus in accordance with selected physiological states of a subject, comprising

input circuitry means for providing electrical signals representative of a physiological cycle of said subject,

output circuitry means effectively connected to said input circuitry means for providing a succession of timing signals at selected portions of said physiological cycles, and

digital offset correction circuitry means effectively connected to said input circuitry means for automatically causing said electrical signals representative of physiological cycles to be within a predetermined range, said correction circuitry means including limit detection means effectively connected to said input circuitry for providing a signal when the physiological signal is outside said range, digital means effectively connected to said detection means for providing digital pulses in the presence of a signal from said detection means, a counter effectively connected to said digital means for counting said pulses, offset generator means effectively connected to said input circuitry means for generating an offset voltage dependent upon the count in said counter, and means for periodically automatically changing the count in said counter to cause said physiological signal to drift in a predetermined direction, and

means for effectively connecting said system to said apparatus to be controlled.