ENCEPHALON

DESCRIPTION

FIELD OF THE INVENTION

The present invention relates to the field of the acquisition and processing of data for diagnostic purposes.

In more detail, the present invention relates to a method for estimating energy parameters related to the heat transfer in an encephalon, in particular a non-invasive method and useful for diagnostic purposes for estimating the heat flow within the encephalon. STATE OF THE ART

It is known that the temperature of the encephalon is not uniform and that there are heat flows inside the encephalon. The article by Huan Wang et al. entitled “Brain temperature and its fundamental properties: a review for clinical neuroscientists” (in Frontiers in Neuroscience, vol. 8, 8 October 2014) deals with these issues, but does not quantify or propose any calculations related to such heat flows.

Different therapeutic methods envisage the monitoring of the internal temperature of the encephalon during various types of therapy, e.g. during thermal ablation for curing cancer.

Currently, the monitoring of the internal temperature of the human body is prevalently performed invasively. In some circumstances such as, for example, the measurement of the temperature of the encephalon, the insertion of probes or other types of devices is considered to be too dangerous or risky.

Magnetic resonance techniques have recently been developed that can estimate the temperature of internal organs such as the encephalon. Such techniques do not provide any indications regarding heat exchanges between areas internal to the encephalon ABSTRACT

The general object of the present invention is to improve the prior art from one or more points of view.

In particular, the object of the present invention is to provide a method for evaluating the heat flows in an encephalon that can combine different non-invasive encephalon monitoring techniques in order to estimate the energy parameters related to the heat transfer useful for diagnostic purposes.

A further object of the present invention is to provide a medical apparatus for the implementation of such method. Such objectives are substantially reached thanks to what is expressed in the appended claims that form an integral part of the present description.

Specifically, the estimate of conductive flows in the encephalon is performed through discretization and numerical calculation; more precisely, the thermal conductivity and temperature distribution in the encephalon is discretized and then a calculation on the finite volumes of the “general heat conduction equation” is performed.

According to a first aspect, the present invention relates to a method for estimating heat transfer energy parameters in an encephalon.

According to a second aspect, the present invention relates to a medical apparatus adapted to implement the method.

LIST OF FIGURES

The present invention shall become more readily apparent from the detailed description that follows to be considered together with the accompanying drawings in which:

Fig. 1 shows a schematic representation of a method according to the present description.

Fig. 2 shows a distribution of conductive heat flows in a portion of encephalon that can be obtained through the performance of a method according to the present description.

As can be easily understood, there are various ways of practically implementing the present invention which is defined in its main advantageous aspects in the appended claims and is not limited either to the following detailed description or to the appended claims.

DETAILED DESCRIPTION

The subject matter of the present invention is a method for estimating heat transfer energy parameters in an encephalon, represented visually by way of example in Fig. 1.

In general, the method comprises the steps of:

Al) acquiring composition data regarding matter distribution in the encephalon;

Bl) acquiring cerebral temperature data regarding temperature distribution in the encephalon;

Cl) calculating a thermal conductivity distribution in the encephalon as a function of on the composition data;

C) calculating a distribution of conductive heat flows in the encephalon as a function of the cerebral temperature data and on the thermal conductivity distribution using Fourier’ s heat conduction equation. In this way, a quantitative estimate of the conductive heat flows is obtained.

Typically, in step Al, the composition data are discretized into volumetric units. Typically, in step B 1, the temperature data are discretized into volumetric units. Typically, in step A2, the thermal conductivity distribution is discretized into volumetric units.

As will become clearer below, for technological reasons, the composition and temperature could be discretized into volumetric units of different sizes, still referring to the same portion of encephalon and therefore we talk about “first volumetric units” and “second volumetric units”.

Typically, the distribution of conductive heat flows is calculated through a finite volume calculation according to Fourier’s heat conduction equation. In practice, the encephalon (or a portion of the encephalon) is split into small rectangular parallelepiped shaped volumes (the cube is a special case); if a small volume is considered, the equation is used to calculate the heat that flows from this small volume towards each of the six small volumes adjacent to its six faces; obviously, the sign of the value of the heat flow corresponds to the direction of the heat flow.

Advantageously, in step Al a distribution of white matter and/or grey matter and/or cerebrospinal fluid is associated with respective first volumetric units.

Advantageously, in step B 1 a cerebral temperature value is associated with each second volumetric unit, in particular the cerebral temperature value is assigned to a central point of the respective second volumetric unit.

Advantageously, in step A2, quantities of white and/or grey matter and/or cerebrospinal fluid contained in said second volumetric unit are calculated for each second volumetric unit.

Advantageously, the distribution of conductive heat flows calculated in step C is discretized into second volumetric units.

Each second volumetric unit comprises a certain number of first volumetric units.

The method according to the present invention will be described below in more detail. The method comprises a composition data acquisition step Al regarding a distribution of matter in the encephalon. In particular, such composition data correspond to a distribution of white and/or grey matter and/or cerebrospinal fluid distribution in the encephalon. Preferably, step Al comprises the acquisition of structural magnetic resonance images or MRI images of the encephalon with a T1 -weighted sequence, in particular through MP- RAGE sampling. For example, the parameters used for magnetic resonance imaging are as follows: repetition time or TR: 2300 ms; echo time or TE: 2.88 ms; inversion time or TI: 1100 ms; flip angle: 12°; slice thickness: 1 mm; spatial resolution (isotropic): 1 mm x 1 mm x 1 mm; matrix dimensions: 256 x 224 x 159.

Advantageously, such magnetic resonance imaging technique allows an anatomic representation of the encephalon with relatively high spatial resolution.

The method further comprises a step A0 of creating a first mesh (or calculation grid) representative of at least a part of the encephalon, in which the encephalon (or a part thereof) is split into first volumetric units. In particular, the first volumetric units correspond to voxel of the aforesaid structural magnetic resonance imaging.

The composition data deriving from the structural magnetic resonance images are processed for generating a distribution of white and/or grey matter and/or cerebrospinal fluid in the encephalon discretized on the first mesh. In particular, this process is performed through the FSL FAST function, following which each first volumetric unit is classified as white material, or grey material or cerebrospinal fluid.

The method further comprises a cerebral temperature data acquisition step B 1. Such data relate to a temperature distribution in the encephalon and are preferably acquired through magnetic resonance spectroscopy or MRS. Such acquisition can be performed according to the technique known as CSI3D and can have parameters equal or proximal to the following:

TR: 4000 ms;

TE: 270 ms; spatial resolution: 4 mm x 4 mm x 8 mm; matrix dimensions: 16 x 16 x 8;

No withdrawal of water.

Advantageously, such parameters allow a relatively accurate estimate of the temperature of the encephalon and reduce calculation errors.

The method further comprises a step B0 of creating a second mesh representative of the encephalon, in which the same encephalon is split into second volumetric units that are larger than the volumetric units of the first mesh and contain a plurality of first volumetric units. In particular, the second volumetric units correspond to voxel of the aforesaid magnetic resonance spectroscopy, which are larger than the voxel of the structural magnetic resonance images because of the lower resolution of spectroscopy with respect to structural magnetic resonance.

The cerebral temperature data deriving from the magnetic resonance spectroscopy are processed to generate a discretized temperature distribution in the encephalon on the second mesh so that each second volumetric unit is associated with a cerebral temperature value. In particular, the cerebral temperature value is assigned to a central point of the respective second volumetric unit.

The method further comprises a step A2 of calculating a thermal conductivity distribution in the encephalon as a function of the aforesaid composition data.

Preferably, the thermal conductivity distribution is calculated on the second mesh. In other words, each thermal conductivity value corresponds to an estimate of the conductivity of the matter contained in a second volumetric unit or of the matter interposed between two central points of respective second adjacent volumetric units, to which cerebral temperature values are assigned. In alternative embodiments a thermal diffusivity parameter can be calculated and used in the subsequent steps instead of the thermal conductivity.

Preferably, step A2 comprises the calculation, for each second volumetric unit, of a quantity of white and/or grey matter and/or cerebrospinal fluid contained in the second volumetric unit itself (or in equivalent units compatible with the calculation of heat exchanges between the second volumetric units of the second mesh), in particular of the fraction of white matter and/or grey matter and/or cerebrospinal fluid over the total volume. Such quantities of white and/or grey matter and/or cerebrospinal fluid are extrapolated from composition data associated with the first volumetric units contained in the second volumetric unit in question.

Subsequently, the step A2 comprises the calculation of a plurality of thermal conductivity values, each associated with a second distinct volumetric unit (or with equivalent units compatible with the second mesh) as a function of the respective quantity of white and/or grey matter and/or cerebrospinal fluid.

In a preferred embodiment, the thermal conductivity value of each second volumetric unit is estimated as a function of the quantity of white matter and grey matter contained therein. Furthermore, the quantity of cerebrospinal fluid previously determined for each second volumetric unit is used to exclude from the subsequent calculation steps the second volumetric units for which such quantity exceeds a certain predetermined threshold. Preferably, such predetermined threshold is 10% of the total volume of the second volumetric unit. In practice, such expedient only affects a reduced number of second volumetric units, in particular the second volumetric units which are superposed with sacs of cerebrospinal fluid, whereas most of them only contain white and/or grey matter.

In the preferred embodiment, the thermal conductivity value is calculated as a linear combination of the thermal conductivity values of the grey matter and of the white matter weighted according to a coefficient dependent on the respective quantities of matter within each second volumetric unit (in which the percentage of liquid is less than the predetermined threshold).

In particular, the following formula is used:

Wherein: k _v is the conductivity value of the second volumetric unit; m _nί/ is the fraction of white matter in the second volumetric unit; k _w is the thermal conductivity of the white matter; m ₃ is the fraction of grey matter in the second volumetric unit; kg is the thermal conductivity of the grey matter.

The method further comprises a step C of calculating a distribution of conductive heat flows in the encephalon as a function of the cerebral temperature data acquired in step B 1 and the thermal conductivity distribution calculated in step A2.

Preferably, such calculation is performed on the second mesh and the aforesaid distribution of conductive heat flows comprises a conductive flow value for each second volumetric unit. Such value indicates the conductive heat flow of the second volumetric unit through the entire outer surface thereof. In other words, the conductive flow value calculated is representative of the conductive heat exchanges between the second volumetric unit in question and the adjacent second volumetric units (except for those neglected because of the quantity of cerebrospinal fluid).

Alternatively, for each second volumetric unit, the conductive flows between it and each of the adjacent second volumetric units can be calculated. The conductive heat flow distribution is calculated through a finite volume calculation according to the “general heat conduction equation” which is expressed by “Fourier’s law” according to which the quantity of heat is provided by the following formula:

Q = kV ² T

Wherein:

Q is the quantity of heat; k is the thermal conductivity;

V ² is the Laplacian of temperature with respect to space.

As mentioned, the “general heat conduction equation” is solved with the finite volume calculation, in particular said volumes are defined by the second mesh.

Furthermore, the “general heat conduction equation” can be approximated through the finite differences method and be solved for every surface i of the second volumetric unit. For example, the equation can be approximated with the forward difference method:

Wherein: v represents the second volumetric unit being analysed; n is the total of the surfaces of the second volumetric unit;

Q _v is the heat exchanged through the /-th surface of the second volumetric unit; k _v is the thermal conductivity of the second volumetric unit; areai is the measurement of the extension of the surface /; distanza _{v, v+i} is the distance from the centre of the second volumetric unit v from the centre of the second adjacent volumetric unit v+i;

AT is the temperature difference between the second volumetric unit v and the second adjacent volumetric unit v+i.

Alternatively and advantageously, the equation can be approximated with the central finite difference method.

Advantageously, the distribution of thermal conductivity values calculated in step A2 is used to determine the thermal conductivity value k _v of the equation.

It is to be noted that the second volumetric units having a high concentration of cerebrospinal fluid, in particular a concentration greater than 10% of the total volume of the second volumetric unit, are excluded from the calculation.

In some embodiments, the method described can comprise additional steps in order to calculate further parameters in addition to the distribution of head conductive flows. The method described can comprise a flow rate data acquisition step D1 relating to the blood flows in the encephalon. Preferably, step D1 comprises the acquisition of perfusion magnetic resonance images of the encephalon, in particular through the arterial spin labelling or ASL technique. Preferably, such data are acquired in the same acquisition step as step A1 and the data are collected on the first mesh. The data acquisition steps therefore consist of a single magnetic resonance session in which structural magnetic resonance, spectroscopy and perfusion magnetic resonance are performed in sequence. Step D1 is followed by a step D2 of determining a distribution of blood flow rate values as a function of the flow rate data acquired. In particular, step D2 comprises interpolating the flow rate data on the second mesh so that each flow rate value determined in step D2 is representative of the blood flow rate crossing a respective second volumetric unit.

The method described can further comprise a blood temperature data acquisition step El relating to the temperature of the blood flows as above. Preferably, blood temperature data are acquired using a thermometer at body surfaces affected by haematic perfusion, e.g. the wrist, so as to detect the arterial temperature of the patient’s body.

The temperature of the blood flows in the encephalon can be assumed to be equal to the arterial temperature measured. Alternatively, corrections can be performed to improve the estimate of the temperature of the blood flows in the encephalon, e.g. further temperature data can be collected in other areas of the body and the measured values combined. Alternatively, the measured temperature of certain organs or body regions can be used, as a surrogate for the blood temperature inside the encephalon. Such temperatures can be estimated in a non-invasive way through magnetic resonance spectroscopy techniques.

Subsequently, the method may comprise a step F of calculating a distribution of convective heat flows between the encephalon and the blood flows the cross it as a function of the aforesaid flow rate data acquired in step Dl, the blood temperature data acquired in step El and the cerebral temperature data acquired in step Bl.

Preferably, step F comprises the calculation of a convective heat flow value for each second volumetric unit (possibly except from those rejected due to the excessive cerebrospinal fluid content) as a function of the flow rate value and the cerebral temperature value associated therewith and the arterial temperature value.

In the preferred embodiment the convective heat flow is calculated through the following formula.

Q _B = P F PB ^C B (T - T _a ) Wherein:

Q _B is the convective heat flow value extracted from each second volumetric unit from the blood flow; p is the density of the cerebral tissue; F is the value of the blood flow rate through the second volumetric unit; p _B is the density of the blood; c _B is the specific heat of the blood;

T is the temperature of the second volumetric unit, acquired in step B 1;

T _a is the arterial temperature, acquired in step El. Subsequently, the method can comprise a step G of calculating a map of the metabolic heat generation of the encephalon, through an energy balance equation between the distribution of conductive heat flows calculated in step C, the distribution of convective heat flows calculated in step F and the same metabolic heat generation map.

In particular, the balance equation thus calculated assumes the stationariness of the total energy of the encephalon.

Preferably, step G comprises the calculation of a rate of metabolic heat produced for each second volumetric unit as a function of the conductive heat flow and convective heat flow values associated therewith.

Qm — Qb — Qt Wherein:

Q _m is the rate of metabolic heat produced in the second volumetric unit;

Q _b is the convective heat flow yielded to the blood flow by the second volumetric unit, calculated in step F;

Q _t is the conductive heat flow entering into the second volumetric unit. In particular, metabolic heat means the heat generated in the encephalon by glucose- oxygen combustion net of the heat removed for the separation of oxygen from haemoglobin.

Preferably, the method comprises a further step H of calculating a distribution of cerebral oxygen consumption rates as a function of the metabolic heat generation map, the reaction enthalpy between glucose and oxygen and the specific energy required for separation between oxygen and haemoglobin.

In particular, the calculation of step H is performed with the following formula:

Qm rCMR02 =

(AH ⁰ - AH _b )p wherein: rCMR02 is the oxygen consumption rate in a second volumetric unit;

Q _m is the metabolic heat rate produced in the second volumetric unit calculated in step G; AH ⁰ is the reaction enthalpy between glucose and oxygen;

AH _b is the energy required for the release of oxygen from the haemoglobin; p is the density of the cerebral tissue.

Further subject matter of the present invention is a medical apparatus configured for implementing the method described above, in particular for therapeutic or surgical uses. The described embodiments overcome the limitations of the prior art.

Advantageously, the method described provides useful parameters for the diagnosis and monitoring of patients.