Hyperthermia - Science topic

Dear Malcolm Nobre ,

Thank you very much for your detailed and well-sourced reply. To briefly go further, what happens now if higher temperatures (e.g. during thermal ablation) are applied ? Do the differences between healthy and tumour tissues disappear completely?

Regards,

Dominique DETAILLE

Nanoparticles are particles with a size ranging from 1 to 1000 nanometers (nm). The size of the nanoparticles is an important factor in determining their properties and potential applications.

As for the role of nanoparticles in photo-induced hyperthermia, nanoparticles can be designed to absorb light in the near-infrared region and convert it into heat, leading to an increase in temperature in the surrounding tissue. This process is known as photo-induced hyperthermia and has been studied as a potential treatment for cancer. The configuration of the nanoparticles, including their shape, size, and composition, can all influence their ability to absorb light and induce hyperthermia. For example, nanoparticles with a well-defined shape and a high aspect ratio (i.e. a high length-to-width ratio) are more efficient at absorbing light and converting it into heat compared to nanoparticles with a more spherical shape. The composition of the nanoparticles, including the choice of material, can also influence their optical and thermal properties and thus their potential for use in photo-induced hyperthermia.

In simple, the size and configuration of nanoparticles play an important role in their ability to induce photo-induced hyperthermia, and researchers are actively exploring ways to optimize these properties for use in cancer therapy.

You are putting in about 500 W of power through 16 antennas.

This is enough to raise 1.2 ml (1.06 cm cube) of water 100 deg per second.

You are raising the target area by about 6 deg.

I expect your problem is that you are heating a lot of other tissue at the same time. It only has to be a 5 cm cube and it only goes up 1 degree per second. If you have included conduction, then heat will travel outwards (mostly) and you will lose the effect of the concentrated heat in the centre if you heat too slowly.

I think you are also heating up tissue directly below the antennas (as well as all the tissue, a little bit). All this requires that you put in more power than you actually need just to heat up the part you want. Work out the power and energy budget. It is fairly simple to do, and you will see where the power is being wasted, and you will find out if there is anything you can do about it.

search from google

Yes

CDC considers a person to have a fever when he or she has a measured temperature of 100.4° F (38° C) or greater, or feels warm to the touch, or gives a history of feeling feverish.

https://www.cdc.gov/quarantine/air/reporting-deaths-illness/definitions-symptoms-reportable-illnesses.html#:~:text=CDC%20considers%20a%20person%20to,history%20of%20feeling%20feverish.

Prashant Kharey

The number of nanoparticles in a hyperthermia experiment depends on your biological material. Although there is iron in the blood, iron nanoparticles are toxic. The reference point can be the death concentration of 50% of the biological material. These concentrations are known and tabulated. For the experiment, you need to take the concentration even less. Start with low concentrations.

Dear Imran Ali ,

Typically the term “Surface plasmon resonance” is mainly used for the excitation of Surface Plasmon Polaritons in thin films, i.e. propagating plasmons, and you need some strategy (for instance, using a grating) to achieve the coupling, i.e. to increase the momentum.

On the other hand, the term “localized surface plasmon resonance” (LSPR) occurs in metallic nanostructures. LSPRs depend on the material (1), the dimensions (2) and the shape (3).

1) If you have nanospheres with the same diameter but some made of silver and others made of gold, the former would exhibit the LSPR peak at higher energy (lower wavelength).

2) If you have nanospheres made of the same material but some with diameter d1 and others with diameter d2, with d2>d1, the LSPR peak of d1 nanospheres would appear at higher energy (lower wavelength).

3) If you have a collection of identical aligned nanorods made of the same material, you would have two LSPR peaks depending on the light polarization: one along the rod axis and another along the perpendicular direction; the latter would appear at higher energy (lower wavelength).

Dear Amir Jafari ,

In Photodynamic therapy (PDT) a certain photosensitizing agent is used, and upon excitation with the proper wavelength, it produces a cytotoxic form of oxygen that kills cancer cells.

On the other hand, photothermal therapy, also called plasmonic hyperthermia, uses nanostructures that absorb infrared light and release such extra energy as heat transferred to their surroundings. When those nanostructures are placed in the vicinity of cancer cells, such heat can kill the cancer cells, usually by inducing the apoptosis mechanism at temperature about 44 ºC.

It is worth mentioning that the hyperthermia can be magnetic instead of optical, when using magnetic nanostructures that are submitted to a proper alternating magnetic field from outside.

B.M. Munasinghe,

Thank you very much! congratulations on the explanation.

Yes. The Hagen-Poiseuuille Classical Equation relates several parameters for laminar flow through a horizontal pipe (analogous to blood vessels).

So, in your opinion, knowing the relationship between blood viscosity and tissue temperature, and using the Hagen-Pouseuuile equation to determine the flow rate, can I later determine the perfusion?

And how to determine the variation in blood vessel diameter during vasoconstriction or vasodilation?

Thank you very much for participating in this discussion!

Dear Amrita Deka ,

You should use superparamagnetic nanoparticles. There is an alignment of the magnetic moments inside each NP, producing a high magnetic moment for each NP.  At RT, due to the thermal energy, such moment of each NP rotates randomly, but if a magnetic field is applied,  there will be a net statistical alignment of the magnetic moments of the NPs. It is analogous to what happens to paramagnetic materials, but the magnetic moments are now those of the NPs, so giving rise to a signal which can be up to 10,000 times larger than for a paramagnetic material.

I'm not familiar with Manganese Sulfide, but according to this publication, MnS is antiferromagnetic at low T and superparamagnetic at RT, so you could use it:

You should use transmission objects material using fat, muscle, and blood.

why could they help?

SAR (W/kg)= Cv*ΔT/Δt , where Cv is the volumetric specfic heat. SAR can be derived from Penne's bioheat equation for the case when assuming no thermal conduction ΔT/Δr = 0, where r is the spatial vector incorporating x.y and z.

Dear Sahba,

if you like, you can send me your model (without solution calculation and without meshing) and I will have a look on it in COMSOL. E-mail your model to michael.hader@uni-bayreuth.de with a short description of your problem and calculation model, i.e. what do you expect or want to find out?

Kind regards,

Michael

Dear Dr Prameela, there are may ways to measure the dielectric and magnetic properties of your samples the best way in your case depends on the requirements in precision and also on the sample shape available. For broadband measurements the method described by Walter Barry can be useful (coax or stripline) lets have further discussions by normal e-mail (Fritz.Caspers@cern.ch)

No, I haven't

Refer to my paper, demethanizer energy targeting.

Dear Mohamed Azab,

I want to simulate an hyperthermia pre-treatment used for glioma, before drug treatment. It seems that 42ºC or no more than 45ºC is the temperature for that, but Ido not have easy access to LASER or ultrasound.

Thank you

Fluoride is known to increase the incidence of bone fracture. Older adults have a 5- to 8-fold increased risk for all-cause mortality during the

first 3 months after hip fracture. We can therefore safely say Fluoride causes excess deaths via this mechanism.

See this interesting article with references.

Dear Seyyed,

Maybe the following papers will help you:

Qian S, Li M, Li G, Liu K, Li B, Jiang Q, Li L, Yang Z, Sun G. Environmental heat stress enhances mental fatigue during sustained attention task performing: evidence from an ASL perfusion study. Behav Brain Res 2015;280:6-15. https://www.sciencedirect.com/science/article/pii/S0166432814007724?via%3Dihub

Otani H, Kaya M, Tamaki A, Watson P. Separate and combined effects of exposure to heat stress and mental fatigue on endurance exercise capacity in the heat. Eur J Appl Physiol 2017;117(1):119-129. https://link.springer.com/article/10.1007%2Fs00421-016-3504-x

Robertson CV, Marino FE. Cerebral responses to exercise and the influence of heat stress in human fatigue. J Therm Biol 2017;63:10-15. https://www.sciencedirect.com/science/article/pii/S0306456516301668?via%3Dihub

Best wishes from Germany,

Martin

In a recent review of sauna, there are some studies - albeit small - that support what you've just stated - hyperthermia, via infrared sauna, but with milder temperature settings for chronic complex illnesses like CFE/ME, Fibromyalgia, chronic pain, etc. See attached.

Dear Irfan,

Let me try to summarize some magnetic properties related with the size of the nanoparticles.

The size is very important in magnetism because the anisotropy energy depends of it. On the other hand the magnetic domains have a finite size and the monodomain nanoparticles presents superparamagnetism, i,e, hysteresis cycles without area and therefore without losses (i.e. without heat within a DC field the AC allows to produce it in very subtle form). This means that the spins rotate coherently as if you had an only superspin for the whole nanoparticle. On the other hand, this produces a Neel relaxation time exponentially dependent of the size of the nanoparticles. That is to say, the size directly tells you how the magnetizacion of the samples can relax from a kind of "macroscopic ferromagnetism" to a "paramagnetism".

Hi Maha,

Bit late answering this, but in case you are still having troubles.

There could be three reasons for not getting the results:

1) You need to give the input signal a pulse. I tend to use a rectangular signal.

2) You need to change the simulation duration in the solver setup window.

3) Make sure that your units are set to (s) I usually have mine on (ns) and this has caught me out a few times.

If you have tried both of these and are sill having issues please don't hesitate to get in touch

Hope this helps.

Shaun

The paper might be of interest to you:

Firstly, thanks for reply.But all these answers explain transient thermal, i work with stationary case and when i changed the time at field monitor the temperature still the same.I want to know the wrong in my boundary condition or exposure time i defined.

Dear Mohana,

check out the Radiomag project page here on Researchgate, lots of useful information there that should help.

regards,

Carl

It is well known that tumor tissue has higher metabolic rate and energy expenditure than surrounding healthy tissue, so that more energy (heat) is produced which could identified via thermodiagnostic methods which are used crrrently -though - less commonly for diagnosis of solid tumors when comparing pattern of heat in normal vs tumor tissue.

Dear Eltayeb Ibrahim Ahmed Elbeshir,

In order to get the deeper view in to theoretical modeling and simulation of heat distribution in the thermal therapy treatment, the following articles( first two are review articles ) may be helpful for you.

First of all, you have to be sure your factors really increase apoptosis. I suggest you do  flow cytometer with annexin V with different concentrations or conditions.

For checking apoptosis also means checking cytotoxicity. You have to decide a cytotoxicity assay to find the factors' cytotoxic effect in a concentration range of 0%-100% cytotoxicity. So, you have to conduct a cytotoxicity assay like SRB or MTT with the factors (hyperthermia and the drug). First of all, you have to find the concentrations of the factors to induce 0 to 100% growth inhibition. So when you find this concentrations you have to plan another experiment of cytotoxicity with each factor and combination. For example if a certain concentration of the drug inhibits 40% of growth, and hypothermia inhibits 40% of growth individually. In these certain conditions, if you combine them, they should give 80% if they are additive, if more than 80%, like 100% they are synergitic, if the result is less than 80%, so they are antagonistic. You can just transform this percent numbers to 0-1, like 80% = 0.8

Good luck

Vitalii, you help me a lot!

Best Wishes,

Piotr

Is your approach similar to HIFU? which was approved for early stage prostate cancer patients. 

Dear Margarethus,

In order to try to bring you a simple (but in fact too simplistic) response facing a more than complex situation, I would recommend:

1) to use "easy" s.c. models (in syngeneic mice) if you want to study any relationships between a treatment and an immune response in a very large sense of the term,

2) idem is you just want to confirm in vivo data that you obtained in vitro,

3) to avoid s.c. xenografts because these types of models are of very poor clinical relevance,

3) moving on orthotopic models to study any potential treatment against metastases, knowing that i) a primary tumor that has not yet metastasize is cured by surgery or surgery + radiotherapy, and ii) 90% of cancer patients die from their metastases:

3.a. thus moving in orthopic AND metastasizing SYNGENEIC models

OR

3.b. idem with xenografts, with my personal opinion that 3.a. is as good as 3.b. and that 3.b. can be performed once you have positive data in 3.a..

Best regards

Robert

Dear Piotr,

(1) is correct for magnetic relaxation without external magnetic field. (2) I think is not correct.

In case of high external magnetic field (magnetic anisotropy axis parallel to the external magnetic field) I think is OK Neel-Brown model. 

In low amd medium external magnetic field  is most suitable Coffey model.

Several works:

All the best, Mihaela

Laser and radiofrequency-induced hyperthermia for nanocomposites with SPION (Super Paramagnetic Iron-oxide Nanoparticle) and other magnetic materials (with supposedly hysteresis based heating effects), hydrogel and NPs (nanoparticles) info are plentiful on the net, go and google!

Some hypothermia info on small children:

in 1994, a 2-year old survived 6 hours at minus 22 degrees C, but had to have one leg amputated. The body was almost frozen. Her temperature was 14 degrees C, probably the lowest ever recorded.

In 2001 a 1-year old was left outside for  3-4 hours in freezing conditions. It took doctors 1 1/2 hours to get the heart beating again.

Both situations were in Canada.

Dear Sajid Fazal,

The biggest difference is whether the technology requires invasive procedures yes or no.

In general non-invasive RF electromagnetic heating can be delivered using:

RF-capacitive coupling: two electrodes are placed on either side of the body and RF-current is flowing between both electrodes. The advantages are relative simple technology (so cheap systems). Disadvantages in most clinical applications is that the E-field is directed perpendicular on tissue transitions, more specifically those between fatty and muscle tissue. In this situation flux is constant resulting in preferential fat heating over muscle heating. Skin cooling with cold water is used to prevent over heating of fatty tissue. This works for patients with fat layers of less than 2 cm thickness. Western patients have in general fat thicknesses of more than 2 cm RF. A second disadvantage is that RF-capacitive heating does not provide a mean for focusing of RF-energy to the treatment volume. Frequencies used in clinical practice vary from 8 to 27 MHz.

RF-inductive coupling: RF-energy is transferred using inductive fields. The applicator consists often of an helical coil or pancake coil. In the early days of hyperthermia large single and multiple turn helical coils have been placed around the patient. RF-currents will be induced in the peripheral layers  of the body causing heating. Deep heating is poor as in the center of the coil no currents flow. Advantages: energy coupling through air, avoiding direct contact of the heating system with the patient. Disadvantage: poor deep heating and no ability to focus heating at the target volume. Frequencies used in clinical practice vary from 8 to 27 MHz.

RF-radiative coupling: multiple radiative antennas are used to couple energy to the patient. Water is used as a coupling medium between the antenna and the human body to preferentially transfer the energy to the patient. Further the water provides also a possibility to cool the superficial tissue, reduces the antenna size (high relative permittivity) and reduce reflection of RF-energy from the skin (in comparison a tissue contrast of air-skin has 60% reflections versus nearly zero for water-skin).

The main advantage of RF-radiative energy transfer is the ability to focus RF-energy at the target volume by optimizing the phase and amplitude settings per antenna. Using hyperthermia treatment planning phase and amplitude settings can be optimized based on the feedback of measured temperatures and patient information.

All the above is explained and demonstrated in the attached papers.

Besides the non-invasive technologies one can use more invasive procedures.

The most recent technology with promising potential for selective tumor heating is nano-particle inductive heating. Multiple papers have been published on this topic. A special issue of the Int. J. of Hyperthermia was devoted to this technology. Please check this literature.

Although the ultimate idea is to coat the nano-particles with proteins that connect to receptors at the tumors cell, the current practice is that the nano-particles still must be injected directly into the tumor in order to obtain a sufficient high concentration of nano-particles to allow sufficient energy delivery to increase tumor temperature to 43°C.

Regards,

Gerard van Rhoon 

Phagocytosis assay.  NK cell killing assay LPS or ComA. PHA stimulated. Proliferation assay.   Using. Circulated blood or splenocyte

Dear Sam,

We've been doing quite a lot of stereotaxic surgery usually administering AAV's into the hypothalamus and amygdala and it is always very important to determine that both your skills and set-up are appropriate. Can I ask if there are other users that successfully use your set-up? If so what do they do differently? Are your surgeries longer than others performing a similar protocol? If you are just learning the procedure nothing beats watching someone skilled in the procedure to pick-up any necessary tips from them.

In the past, we had a few problems with our initial anesthetic set-up using Isoflurane, it just needed some slight modifications. This was largely due to either providing too much isoflurane or having the scavenger set at too high a level. You can tell if the mouse is getting too much anesthetic - their breathing will get quite labored and they'll start to gasp. If they are getting too little then they'll start to squirm as they gain consciousness. Remember that the scavenger canister needs to be changed regularly and if you have a new canister it will scavenger much more than one that is near-full. Isoflurane is a good choice of anesthetic but needs careful monitoring throughout the surgery. It really shouldn't need to be adjusted throughout. We normally have it set around 1.5. I'd think that if you are using less than 1 then something is not set-up correctly. If the animals have slow steady breathing then you know that the anaesthetic set-up is appropriate. 

In regards to temperature, if you are using a homeothermic blanket then the temperature should not be an issue as the blanket will regulate it appropriately. If you don't have a homeothermic blanket I'd suggest that you get one. Heating pads/blankets are alright for post-surgery recovery but shouldn't be used during the surgery itself.

Can I also ask if you are using any analgesic? If so, is the dose appropriate? If the animals are dying after about an hour, it might be an overdose from the analgesic.

I agree that you should perform a test to determine if the surgery is killing the animal. This could be done just placing a mouse in the frame as usual and monitoring it as you would during a surgery for the same amount of time. If the mouse survives than you know it's the surgery and not the set-up and can seek some expertise on the surgery itself.

Hope this helps. 

J

Great, cant wait to read the paper.

The magnetic coupling for inductive heating in single domain particles occurs at kHz range. MRI frequency is too high for heating.Nevertheless You could measure some heating butit Should be of the Same order than the tissue alone.

Hope this helps.

I'll preface this with the disclosure that I do have a conflict of interest with the company involved in this, but an alternative method for cooling, followed by maintenance and then rewarming, is described in these articles:  

[1] Markota A, Kit B, Fluher J, Sinkovic A. Use of an oesophageal heat transfer device in therapeutic hypothermia. Resuscitation. 2015;89:e1-2.

[2] Hegazy A, Lapierre D, Althenayan E. Targeted temperature management after cardiac arrest and fever control with an esophageal cooling device. Critical Care. 2015;19:P424.

There's also a company, Life Recovery Systems (no conflict of interest) that sells an immersion device along the lines of what you asked originally.  They've published some data showing safety in defibrillation, but I'm not sure about overall ease of use.

 Hi,

There are number of papers relating to changes in the property of plasma membrane in cancerous cells when compared to normal cell. This includes change in the lipid composition, membrane proteins and saccharides on the protein. I don't think the porosity of the plasma membrane changes. By the way pores are not formed just like that. Pores are formed only when channel proteins (membrane proteins) open. 

Enhanced permeability and retention (EPR) effect in the tumor vasculature of cancer cells might help you to target the nanoparticles. There are number of reviews related to EPR effect and drug delivery.

Nanoparticle uptake depends on number of factors like the size, charge, cell type and ligands molecules bound to it. So it is better take a closer look on the type of cancer cell you are going to target and characterize the nanoparticles before using it. Targeting the cancer cells through surface receptors (like folic acid receptor) and antibody works better. Hope this helps you

I am agree with Mr. Rasbindu. You need to change the power supply. And use a  generator with higher current value but be careful, high currents can damage your device.

I am looking for some one who has such instruments and is interested to have collaboration with me on this field!

Check these papers out:

Treatment of pleural effusion caused by lung carcinoma with circular intrapleural hyperthermic perfusion and its mechanism. Kang M,

Zhou L,Lin P. Zhonghua yi xue za zhi [2001, 81(19):1176-1179]

CONCLUSION: (1) Circular intrapleural hyperthermic perfusion is a new, safe, and effective treatment for MPE. (2) Apoptosis-mediated cytocidal function, improvement of body immunity after hyperthermic perfusion and continuous wash of the perfusion fluid are important mechanisms of intrapleural hyperthermic perfusion in treatment of MPE caused by lung carcinoma.

Anaesthetic management of cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy perfusion. christoph.kerscher@gmx.net  et al. Journal of Cardiothoracic Surgery 2014, 9:125 

Future Perspectives of Interstitial and Perfusional Hyperthermia

Gian Franco Baronzio et al.      http://www.ncbi.nlm.nih.gov/books/NBK6232/

 Diagnosis and Treatment of Pleural Effusion        Victoria Villena Garrido et al.        Arch Bronconeumol. 2006;42:349-72. - Vol. 42 Num.07

thermo-sensitive polymeric micells are not i am looking for, but thank you a lot all the time.

Rosensweig, R. E., Heating magnetic fluid with alternating magnetic field. J. Mag. Mag. Mater. 2002, 252, 370-374.

Rudolf, H.; Silvio, D.; Michael, R., Effects of size distribution on hysteresis losses of magnetic nanoparticles for hyperthermia. J. Phys.: Condens. Matter. 2008, 20, 385214.

Hugounenq, P.; Levy, M.; Alloyeau, D.; Lartigue, L.; Dubois, E.; Cabuil, V.; Ricolleau, C.; Roux, S.; Wilhelm, C.; Gazeau, F.; Bazzi, R., Iron Oxide Monocrystalline Nanoflowers for Highly Efficient Magnetic Hyperthermia. J. Phys. Chem. C 2012, 116, 15702-15712.

Lee, J.-H.; Jang, J.-t.; Choi, J.-s.; Moon, S. H.; Noh, S.-h.; Kim, J.-w.; Kim, J.-G.; Kim, I.-S.; Park, K. I.; Cheon, J., Exchange-coupled magnetic nanoparticles for efficient heat induction. Nat. Nano. 2011, 6, 418-422.

There are two possibilities to heat magnetic particles by subjecting them to AC magnetic field (1) FM particles and (2) Superparamagnetic particles. The amount of heat generated in case of former can be calculated by hysteresis loop while for the later Rosensweig has developed a model based on Debye theory for dielectric dispersion in polar fluids. It is shown that the amount of heat generated depends on square of the applied field and imaginary part of complex magnetic susceptibility which in turn depends on driving frequency of the field. So, one has to calculate the amount of heat generated at a give target in the body. For safety it is necessary to use types of magnetic particles that has a large pyromagnetic coefficient and Curie temperature around 43 degree Celsius.

Also you can measure the concentration via ELISA

Different HIFU systems have different technical characteristics, so that the time required for treating a tumor may me heavily different. My statement refers to the system we used several years ago. Now the progress in the technology may have substantially reduced the treatment time. In addition, for the largest tumors, HIFU can be, eventually, administered in two or more session on overlapping regions to cover the whole diseased tissue. That may not feasible with RT, due to the dose limits in the surrounding structures where radiations doses add up and may reach a total value higher than clinically acceptable. In addition, tumors' regions already treated by HIFU need not to be treated again with radiations. In principle that would totally change the spatial distribution of concurrent RT, that can be restricted to a the relatively thin region where the tumor infiltrate the healthy tissue. But all that are speculations that should be compared with experimental data! I think that if you are interested in a deeper and more appropriate discussion I need to know better what kind of experiment you are planning. My best wishes,

Gianni

Hi

For in-vivo hyperthermia, it depends on the method for inducing heat. for example for magnetic hyperthermia with superparamagnetic or ferromagnetic nanoparticles (as heating sources) coil that produce AC magnetic field and optical fiber (for heat measuring) are necessary and available. Also we can use RF generator instead of coil.

some chemotherapy agents: doxorubicin, mitoxantrone, Curcumin, daunorubicin

Hi, first of all I will declare a commercial interest here as my company supplies just such a system. Components are a power supply, function generator, heating coil and control electronics, sample enclosure, sample insulation etc to avoid non specific heating and temperature sensor - I've attached a few references for your information. If you require any further details please do not hesitate to contact me directly - carl@nanotherics.com