METHOD FOR MEASURING RADIOTHERAPY DOSES

Abstract

A method for measuring radiotherapy doses on a subject undergoing radiotherapy or other treatments with ionizing radiations includes: electrically insulating the subject during the radiotherapy treatment; applying at least one electrode to the subject, or connected to an amplifier with a system for acquiring the signal outgoing from the amplifier; detecting, by means of the at least one electrode, the voltage pulse produced during the radiotherapy treatment and deriving from the ionization secondary electrons set into motion and/or by the loaded net charge induced in the subject; converting said voltage pulse into a value of charge induced by the treatment in the subject; and determining the dose of ionizing radiations received by the subject by a processing system which uses the above value of the induced charge, the energy spectrum of the incident beam and the contact surface of the incident beam on the subject.

Claims

1. A method for measuring radiotherapy doses on a subject undergoing radiotherapy or other treatments with ionizing radiations, comprising the steps of: insulating the subject, electrically, during the treatment; applying at least one electrode to the subject, connected to an amplifier with a system for acquiring an outgoing signal from the amplifier; detecting, by means of said at least one electrode, a voltage pulse produced during the treatment and deriving from ionization secondary electrons set into motion and/or from a net charge induced in the subject; converting said voltage pulse into a value of charge induced by the treatment in the subject; and determining the dose of ionizing radiations received by the subject by means of a processing system which uses the above-mentioned value of the induced charge, an energy spectrum of an incident beam of ionizing radiations and a contact surface of said incident beam on the subject.

2. The method according to claim 1, wherein the ionizing radiations are of the type selected from the group consisting of: protons, electrons, ions, neutrons, X radiations and gamma radiations.

3. The method according to claim 1, wherein at least two equal electrodes are applied to the subject, the method further comprising the step of evaluating a different intensity of current acquired simultaneously by the two electrodes and of an extent of the induced charge detected by each electrode, a comparison of the signals produced by the electrodes and knowledge of their position by determining the position of a region of the subject wherein the incident beam, by interacting with the subject's tissues, produces a current signal therein.

4. The method according to claim 1, wherein the method utilizes: a) at least a floating electrode; b) a system for amplifying the signal for each electrode c) a system for acquiring the output signals generated by said amplifiers; and d) a microprocessor provided with a storage and I/O devices for processing an analysis software dedicated both to a reconstruction of the charge deposition point and to a calculation of absolute and relative doses.

5. The method according to claim 4, wherein the amplifying system comprises: a) a trans-impedance amplifier for direct measurement of absorbed current; and/or b) a high voltage gain differential amplifier, for measurement of the potential differences produced by the incident radiation.

6. The method according to claim 5, wherein the trans-impedance amplifier comprises: a current-voltage converter (I-V) having an output linear behavior; a passive low-pass filter having a predetermined cutting frequency and attenuation for protecting the converter and for reducing environmental noise; a pair of protecting junction field effect transistors (JFET) which discharge to ground the input current in case the converter saturates; and a second order inverting active low-pass filter having two coincident poles to compensate for a polarity inversion of the voltage existing at the converter output.

7. The method according to claim 6, wherein the converter comprises a condenser having a value that limits an upper cutting frequency of the converter to a predetermined value.

8. The method according to claim 5, wherein the high voltage gain differential amplifier comprises: a passive low-pass filter placed at the input, to filter the component of the differential signal coming from the subject and, at the same time, to remove RF disturbances with a predetermined cutting frequency; a differential amplifier for differential instruments with field effect transistor (FET) input; a second order non-inverting active low-pass filter to remove environmental noises; and an operational amplifier, configured as tracker, which allows for monitoring of a voltage of common mode (VCM) existing during the measurement, with a corresponding auxiliary output.

9. An apparatus for measuring radiotherapy dose on a subject undergoing radiotherapy or other treatments with ionizing radiations, comprising: an electrical insulator for the subject; at least one floating electrode and a system for amplifying a signal for each electrode for detecting a voltage pulse produced during the treatment and deriving from ionization secondary electrons set into motion and/or by a loaded net charge induced in the subject; a converter, which converts said voltage pulse into a value of charge induced by the treatment in the subject; and a microprocessor provided with a storage and I/O devices for processing an analysis software dedicated both to reconstruction of a charge deposition point and to calculation of the absolute and relative dose.

10. The apparatus according to claim 9, wherein the amplifying system comprises: a trans-impedance amplifier for direct measurement of absorbed current; and/or a high voltage gain differential amplifier, for measurement of potential differences produced by the incident radiation.

11. The apparatus according to claim 10, wherein the trans-impedance amplifier comprises: a current-voltage converter (I-V) having an output linear behavior; a passive low-pass filter having a predetermined cutting frequency and attenuation for protecting the converter and for reducing environmental noise; a pair of protecting junction field effect transistors (JFET) which discharge to ground the input current in case the converter saturates; and a second order inverting active low-pass filter having two coincident poles to compensate for a polarity inversion of the voltage existing at the converter output.

12. The apparatus according to claim 11, wherein the converter comprises a condenser having a value that limits an upper cutting frequency of the converter to a predetermined value.

13. The apparatus to according to claim 10, wherein the high voltage gain differential amplifier comprises: a passive low-pass filter placed at the input, to filter the component of the differential signal coming from the subject and, at the same time, to remove RF disturbances with a predetermined cutting frequency; a differential amplifier for differential instruments with field effect transistor (FET) input; second order non-inverting active low-pass filter to remove environmental noises; and an operational amplifier, configured as tracker, which allows for monitoring of a voltage of common mode (VCM) existing during the measurement, with a corresponding auxiliary output.

Description

[0035] The herein described method, in its most general meaning, allows of evaluating both absolutely and relatively the dose supplied during a typical radiotherapy treatment, as well as of knowing the stop point of the loaded particles used in such treatment.

[0036] The main components of an apparatus for performing the method according to the invention can be schematized as follows: [0037] a) a floating electrode, preferably of the disposal type, for example an electrode for electrocardiography; [0038] b) a trans-impedance amplifier, also called current-voltage converter, used in case of direct measurement of the absorbed current; [0039] c) a differential amplifier with high voltage gain, to be used in case of measurement of the potential differences produced by the incident radiation; [0040] d) a system for acquiring the output signals generated by the previously mentioned amplifiers; [0041] e) a microprocessor provided with a storage and I/O devices for processing an analysis software dedicated both to the reconstruction of the charge deposition point and to the calculation of the absolute and relative dose.

[0042] Depending upon the type of ionizing radiation used for the radiotherapy treatment, both the configuration of the acquisition system and the reconstruction software of the dose and the beam incidence point in the tissues have to be suitably selected.

[0043] Hereinafter, then, the different circuit configurations are described which it is possible to select to perform a correct in-vivo dosimetry during treatment.

[0044] Firstly, the case of radiotherapy treatments performed with loaded particles is faced, which require to determine the total dose released in the tissues and the beam incidence point.

[0045] Hereinafter, a converting circuit provided with one single electrode will be described.

[0046] By referring to FIG. 1, by positioning a floating electrode of the disposal type on a patient subjected to a radiant treatment with beams of loaded particles (protons, ions, electrons), the invention allows to deduce the dose thereof absorbed by measuring the current absorbed by the patient.

[0047] The measurement of the current takes place by means of a trans-impedance amplifier having a low input impedance and suitably planned so that the current signal I.sub.in, could be filtered and converted into an easily measurable voltage signal, by means of its transfer function: V.sub.out=R*I.sub.in.

[0048] Knowing that the currents induced by the beam of loaded particles are lower than the nano-Ampere, the amplifier is devised with a trans-impedance gain of R=V.sub.out/I.sub.in having high ohmic value (typically R10.sup.9 Ohm).

[0049] The circuit is shown in FIG. 1 and it can be schematized in four fundamental portions:

[0050] The first portion of the circuit comprises a current-voltage converter (I-V) implemented by means of an operational amplifier OPA128 having electrometric degree and high performances, reactioned through a resistance of high ohmic value which establishes the trans-impedance gain V.sub.out/I.sub.in. The reaction resistance (R13 or R12) can be selected by means of a jumper and it can be selected among two possible values: 1 G or 10 G. Parallelly to the reaction resistance there is a condenser (respectively of 100 pF or 10 pF) the value thereof has been selected to meet the following conditions: to limit the higher cutting frequency of the converter to only 1.6 Hz; to guarantee a good stability margin of the whole feedback loop, thus by preventing the occurrence of self-oscillation thereof in the I-V converter; to guarantee a response to the step without over-elongations (overshoot). About the operating range of the input current I.sub.in it is required to consider that the converter has a linear behaviour in the output range 10 VV.sub.out+10 V. It follows that by selecting 1-G reaction resistance, the input operating range will be 10 nAI.sub.in+10 nA. Besides, by selecting 10-G reaction resistance, the operating range becomes 1 nAI.sub.in+1 nA.

[0051] The second portion of the circuit comprises a passive low-pass filter, placed at the input of the circuit (see R1 to R10, C1 to C9) having a cutting frequency (3 dB) of 0.9 Hz and an attenuation of 68 dB at the frequency of 50 Hz. This filter plays two fundamental roles: [0052] it protects OPA128 from the electrostatical discharges which can be induced both by the patient and by the medical staff assisting the patient during the pre- and post-treatment phases; and [0053] it attenuates by about a factor 2,500 the noise currents at 50 Hz which the patient inevitably produces due to the electromagnetic interferences (EMI) caused by the environmental electromagnetic pollution, the electrical energy distribution system thereof is the main cause.

[0054] The third portion of the circuit comprises a pair of Junction gate Field-Effect Transistors (JFET) for protecting OPA128 (J1, J2), which discharge to mass the input current I.sub.in in case the converter saturates. This condition takes place only and only if the current I.sub.in exceeds the measurement operating range of the converter I/V. On the contrary, the converter works within its operating range, the configuration of the whole circuit makes that the two JFETs insert a neglectable leakage current lower than 100 fA.

[0055] The fourth and last portion of the circuit comprises an inverting active low-pass filter of the second order and with two coincident poles (see configuration of U2), with the main task of cutting with a slope of 40 dB/decade the residual noise existing outside the I-V, starting from the frequency (3 dB) of 1.2 Hz. The filter is selected of the inverting type to compensate the polarity inversion of the voltage existing at the converter output I-V. In this way the output voltage V.sub.out will be positive when the input current I.sub.in is positive too.

[0056] In the present example, the selection of limiting the band of the I-V converter at only 1 Hz arises from the need for finding the best possible compromise by keeping in mind both the need for amplifying the DC signal of interest, and the need for eliminating all noises which inevitably disturb the measurement; thereamong: the tribo-electric and piezoelectric noises caused by the mechanical motions of the target subject; the currents induced on the subject itself due to the effect of electromagnetic and/or electrostatic interferences.

[0057] In particular, the electromagnetic interference current at Hz, of about 200 nAp-p, is subjected to an attenuation of: [0058] 68 dB by the first low-pass passive filter, placed at the input of the circuit, see R1 to R10, C1 to C9. [0059] 30 dB from the I-V Converter which comprises OPA128. [0060] 56 dB from the low-pass filter of the second order placed at the output, which comprises the integrated circuit LT1012.

[0061] Therefore, the overall attenuation of the noise current at 50 Hz will be equal to 154 dB, which means a factor of 1/50,000,000.

[0062] By considering the above-described I-V converter as a whole, in presence of a sufficiently steep input current step (1 msec), the rise time of the output voltage V.sub.out results to be about 0.6 seconds if measured between 10% and 90% of the variation V.sub.out, whereas it results to be about 1.1 seconds if measured between 1% and 99% of the same variation V.sub.out.

[0063] Moreover, by making a direct current analysis of the trans-impedance amplifier, it is known that the input impedance R.sub.IN, results to be 1 M (see R1+R2+. . . +R10). Given the above, knowing that the DC current which is to be measured tends to discharge to the ground by following the path of least resistance, it is necessary that the patient is well insulated (R.sub.ISO at least 1 G of insulation) so that the current which has to be measured selects as path of least resistance the amplifier input.

[0064] At last, there is a second reason which imposes an insulation of the patient to the adequate ground (R.sub.ISO), for example of at least 1 G, which is dictated by the fact that the input impedance of the amplifier (R.sub.IN) is connected to the virtual mass of OPA128, which has an offset voltage (V.sub.OFF) which in the worst case could be +/500 V. The presence of this small potential at the input of the trans-impedance amplifier induces the same amplifier to produce an error current I.sub.ERR which would false the measurement. This error current is equal to I.sub.ERR=V.sub.OFF/(R.sub.IN+R.sub.ISO).

[0065] The selection of using a specific electrode type, so as the selection of the materials which inevitably have to come in contact with the patient, is dictated by the need for reducing all effects which would compromise the measurement.

[0066] A floating electrode, for example, constituted by a metal disc made of AgCl immersed in a conductive gel, is an element which can be selected for this charge measurement, as it does not produce any significative disturb due to stresses of mechanical type.

[0067] As far as the treatment chair or couch is concerned, therewith the patient is inevitably in contact during the treatment, they can be optimized so that there are no signal dispersions. On this matter, they can be coated with an insulating material so as to hinder the grounding of the patient and consequently the flowing of the current towards the ground.

[0068] At the same time, all metal elements in direct contact with the beam of incident particles and placed near the patient have to be always placed at null potential, that is a ground connection has to be always guaranteed so that no induced charge effects are created which false the measurement.

[0069] As far as the software for reconstructing the absolute dose released to the patient is concerned, the calculation of the absolute dose can be performed starting from knowing the total charge absorbed by the patient and by the energy spectrum of the incident beam.

[0070] The absorbed dose in a beam of protons, in fact, is given by the relation:

[00001]$\begin{array}{cc}D=\frac{}{}.Math.\frac{\mathrm{dE}}{\mathrm{dx}}& \left(1\right)\end{array}$

wherein represents the fluence, that is the number of particles per square centimetre and it is measured in cm.sup.2,
is the density of the radiated material expressed in Kg*cm.sup.3 and at last, dE/dX is the value of the total stopping power to the energy of the incident beam expressed in in MeV/cm.

[0071] Once fixed the energy of the incident beam E.sub.0, the system obtains the corresponding value of dE/dX starting from tabulated data (for example from tables ICRU49 in case of protons, ICRU73, in that of carbon). The value of fluence is calculated starting from the measured total charge and from the surface of the incident beam.

[0072] Typically, in a clinical treatment, the incident beam on the patient is polyenergetic. In this case, the dose can be calculated starting from the total charge read by the system by suitably correcting the previous definition of dose and by considering all energy components of the beam. In particular, the previous definition of dose has to be written by weighing suitably the fluence of each energy component of the spectrum depending upon the corresponding value of stopping power. According to what said, the following dose expression:

[00002]$\begin{array}{cc}D=\underset{i}{.Math.}.Math.\frac{{}_i}{}.Math.{\left(\frac{\mathrm{dE}}{\mathrm{Dx}}\right)}_i& \left(2\right)\end{array}$

is considered.

[0073] By using two or more electrodes, it is possible, under the same previously described operating conditions, having a piece of information about the beam incidence point during the treatment.

[0074] By referring to FIG. 2, this circuit is constituted by two twin trans-impedance amplifiers, assembled in the same card so as to share the same ground, that is the same reference potential within an error V.sub.ERR of only 1_Vdc. As it can be observed, the configuration adopted in each trans-impedance amplifier differs from that of FIG. 1 since the input impedance is lower by a factor two with respect to the previous one and the conversion stage I-V is implemented by means of an operational amplifier model ICL7650 of Chopper-Stabilized type.

[0075] The sensitivity of the multi-electrode system, for detecting the charge deposition point, is based upon the evaluation of the different current intensity acquired at the same time by the two electrodes.

[0076] The ideal condition would be so that such diversity depended upon the different electrical resistance that each current meets upon crossing the tissues of the patient to reach the floating electrode. To say the truth, the two currents also meets the input impedance of the two trans-impedance amplifiers, which for this type of measurement represents a disturbing element to be corrected during the data analysis, therefore it is convenient that the input impedance of the two amplifiers is as small as possible, compatibly with the technological resources existing on the market.

[0077] Should the two trans-impedance amplifiers have been ideal, their inputs would have always the same electrical potential. In the real case, however, it is necessary to consider the potential difference V.sub.OFF between the two inputs I.sub.IN_1 and I.sub.IN_2. In particular, such potential difference is given by the following contributions V.sub.OFF=V.sub.OFF1+V.sub.OFF2+V.sub.ERR, wherein V.sub.OFF1 and V.sub.OFF2 are the input offset voltages of the two operational amplifiers U1 and U3, respectively, whereas V.sub.ERR is the difference in the ground electrical potential between pin 3 of U1 and pin 3 of U3, which as mentioned above will be no more than 1 Vdc.

[0078] Whenever the two electrodes are positioned on the patient, the presence of V.sub.OFF inevitably makes a small offset current (I.sub.OFF) to flow both in the tissues of the patient himself/herself, and in each input of the two trans-impedance amplifiers.

[0079] The current intensity I.sub.OFF is not deterministic as it will depend even upon the electrical resistance which the same tissues of the patient have, however I.sub.OFF will be not higher than: I.sub.OFF_MAX=V.sub.OFF/2*R.sub.IN wherein R.sub.IN=470 k corresponds to the input impedance of each amplifier under DC regime.

[0080] Therefore, if one wants to limit I.sub.OFF_MAX15 pA, it is necessary that the offset voltages V.sub.OFF1 and V.sub.OFF2, of U1 and U3 respectively, singularly are 5 Vdc. This condition is met if and only if U1 and U3 are operational amplifiers of Chopper-Stabilized type. For this application the ICL7650 model is selected as, apart from satisfying the above condition, it is characterized by a polarization current I.sub.BIAS_typ1.5 pA.

[0081] The only drawback which has to be considered is that the operational amplifier ICL7650 works with a supply voltage of 7.5 Volt, therefore the linearity of its output voltage is guaranteed within the range of 5 Volt. Considering that U1 and U3 are polarized only by a 1-G reaction resistance, it means that the operating range of the input current I.sub.IN of each amplifier will be limited to only 5 nAI.sub.IN+5 nA.

[0082] In the example with two electrodes the software for reconstructing the absolute dose release to the patient has a beam incidence point reconstruction algorithm which then is based upon the different current intensity measured by each electrode.

[0083] Whenever the beam of particles interacts with the tissues, a current will be produced which will branch inside the tissues themselves.

[0084] The time being equal, the charge measurement collected by one or more electrodes, in fact, can provide a useful piece of information about the distance between each electrode and the beam incidence point.

[0085] From the comparison of the signals produced by the electrodes and the knowledge of the position of the latter it is possible to detect the area wherein the beam of particles, by interacting with the tissues, has produced a current signal inside thereof.

[0086] An ad-hoc circuit was devised also for measuring the pulse due to the production of secondary electrons produced in the interaction of a ionizing radiation with the body.

[0087] The scheme of the circuit shown in FIG. 3 then allows to use the herein processed idea not only when a net charge is input into the patient, but even when a charge imbalance is generated locally after the passage of a radiation and the consequent generation of secondary electrons by ionization. Such imbalance is translated into a voltage pulse which could be measured and put in relation to the dose released to the patient by the incident radiation.

[0088] In particular, the circuit shown in FIG. 3 consists in a differential amplifier with high input impedance (10.sup.12)), having an overall DC voltage gain equal to 1000 and a cutting frequency higher than 1 Hz.

[0089] The amplifier is equipped with an auxiliary output dedicated to monitor the voltage of common mode existing during the measurement. It is constituted by: [0090] a passive low-pass filter placed at the input of the circuit, which has the double purpose of filtering the component of the differential signal coming from the patient and, at the same time, to remove the performed RF disturbances of common mode which can induce problems of electromagnetic compatibility to the whole amplification system. The cutting frequency of common mode was fixed to 1.6 kHz. [0091] a differential amplifier for instrumentation (Instrumentation Amplifier) INA121P with field effect transistor (FET) input, configured for amplifying with a voltage gain equal to 100. Thanks to its features, this type of amplifier finds wide applications in the medical diagnosis field such as electrocardiography (ECG), electroencephalography (EEG) and electromyography (EMG). [0092] a not inverting active low-pass filter of the second order (see U2), which further amplifies the signal by a factor 10, by cutting the components of the signal having a frequency (3 dB) equal to 1 Hz. In particular, the filter has the function of eliminating both the noises at 50 Hz linked to the environmental electromagnetic pollution and the noises linked to the biological nature of the patient (such as for example, the pulses of the nerve cells and the muscle contractions). [0093] an operational amplifier OPA131, configured as tracker, which allows to monitor the voltage of common mode (VCM) existing during the measurement.

[0094] Before concluding the description of the differential amplifier, it is necessary to specify that it was planned for working even during the measurement of the signal in current of the beam incident on the patient. In such case it will be necessary to replace the Patient_GND electrode existing in FIG. 3, with the electrode indeed dedicated to the measurement of the current of the beam incident on the patient.

EXAMPLES

[0095] A series of preliminary tests was performed by using the circuit shown in FIG. 1 and the previously described modes, by acquiring both in-vitro signals, by using a water phantom, and in-vivo signals, by acquiring the signals during a proton-therapy session on a patient.

[0096] The results of such studies are shown in FIGS. 4 and 5. FIG. 4 shows the signal obtained by positioning the electrode inside the water phantom during a radiation with a clinical beam of 60-MeV protons with a dose equal to 4. The same graph shows both the signal of the electrode (lower curve) and the signal of a device of SEM type (Secondary Emission Monitoring, upper curve) used as online reference of the beam current supplied during the measurement.

[0097] FIG. 5 shows the response curve of the loading electrode expressed as function of different values of absorbed dose. In this case, it can be noted that the electrode response follows an almost linear path in perfect agreement with the charge expected for fixed values of supplied dose.

[0098] FIG. 6 shows the system current response obtained during the measurement performed on patient, that is in vivo.

[0099] In this case, the patient, during the treatment, was subjected to a radiation by receiving a dose of 13.66 Gy. The value of supplied dose rate was equal to 25.62 Gy/min. As it is shown in FIG. 6, the treatment starts at second 242 and it continues for 32 seconds. The current read by the system reaches the value of 0.9 V equal to 0.09 nA. The response of the same patient was monitored during the four clinical sessions provided by the protocols and a good reproducibility of the measurement was observed. The average of the total charges resulted to be equal to 3.82 nC with a standard deviation corresponding to 0.87.

[0100] To the above-described measuring method a person skilled in the art, with the purpose of satisfying additional and contingent needs, could introduce several additional modifications and variants, however all comprised within the protective scope of the present invention, as defined by the enclosed claims.