Arunn Narasimhan

Arunn Narasimhan

Bio-Heat Transfer in Cancerous Tumour Ablation

Created Last modified 7 min read

About this note

A plain-language summary of the 7 publications listed under this topic on Academic Publications (Topic-wise). Full citations are under References.

Why this matters

Photo-thermal therapy treats cancer by turning light into heat. A laser, usually in the near-infrared (NIR) “therapeutic window” where tissue lets light through most easily, warms the diseased region until its cells die. Proteins begin to denature at about 40 to 45 °C, and cells die within seconds at about 50 to 70 °C (Anup et al., 2014); holding tissue at 41 to 47 °C for a few tens of minutes is enough for necrosis (Paul et al., 2016a).

Two things make this harder than it sounds. First, tissue absorbs NIR light weakly and scatters it strongly, so healthy tissue around the target also heats up. One remedy is to load the tumour with plasmonic nanoparticles (gold or graphene structures that absorb NIR light very strongly), a variant called plasmonic photo-thermal therapy. Second, real tissue is threaded with large blood vessels (larger than about 500 microns across). Blood flowing through them carries heat away like a coolant pipe, and a tumour next to such a vessel may never get hot enough for complete ablation (Anup et al., 2014). Because temperatures deep inside a patient are hard to measure, a reliable predictive model, checked against careful experiments, is valuable to clinicians.

What we did

This line of work grew mainly out of Anup Paul’s doctoral research in our Heat Transfer and Thermal Power Laboratory at IIT Madras, carried out with Sarit K. Das. It combined experiments on tissue mimics (gels of agar or collagen whose thermal properties resemble real tissue) with finite element simulations.

Large blood vessels as heat sinks

We first asked how much a large vessel spoils the heating (Anup et al., 2014). We solved the three-dimensional conjugate heat transfer problem, meaning heat flow in the tissue and in the flowing blood was computed together, with the laser modelled as a volumetric heat source that decays with depth according to the Beer-Lambert law. Three arrangements were compared: bare tissue, a single vessel crossing the tissue, and a countercurrent pair of vessels. Experiments on tissue mimics with simulated vessels, with the surface temperature recorded by an infrared camera, validated the model.

Adding nanoparticles to fight the cooling

Next we brought nanoparticles into the model. One study simulated laser heating of tumours containing gold nanorods and, as its title indicates, compared delivering them by injection into the tumour with injection into the bloodstream (Paul et al., 2014). Another proposed gold nanoshells as strong absorbers to offset vessel cooling, and coupled the energy equation with the Arrhenius damage equation (a rate law that converts a temperature history into the fraction of tissue destroyed) to predict thermal damage near large vessels (Paul et al., 2016b).

Looking beneath the surface

Surface temperatures do not tell the whole story, so we measured temperatures inside the phantom (Paul et al., 2016a). With chemists Soujit Sengupta and Thalappil Pradeep, we synthesised gold mesoflowers and graphene nanostructures and mixed them into collagen gel. A tube of 2.2 mm outer diameter, carrying simulated blood at 10 mL/min, played the large vessel, placed 2.5 mm or 7.5 mm below the surface. The simulations used a laser source term based on multiple scattering of light.

To give clinicians a quicker tool than full three-dimensional simulation, Dhar and co-workers developed a semi-analytical model of subsurface temperature in translucent phantoms (Dhar et al., 2016). It splits the problem into a steady depth profile anchored to the measured surface temperature and a transient rise based on Beer-Lambert attenuation, and blends the two using the Biot and Fourier numbers.

The nature of heat conduction in tissue

Two companion studies questioned the classical assumption that heat diffuses instantly. Nilamani Sahoo, Soham Ghosh and colleagues compared Fourier and dual phase lag models against laser experiments on collagen mimics with and without gold nanostructures, and used atomic force microscopy to see the damage to collagen fibrils (Nilamani et al., 2013). A parallel model applied the same idea to laser heating of the retina (Narasimhan and Sridhar, 2013). That physics is explained in Non-Fourier Bio-heat Transfer.

What we found

  • Vessels matter, and where they sit matters. The temperature field depended on the vascular network, vessel size, blood flow rate, laser spot size, laser power and tissue perfusion. Cooling weakened as the vessel lay deeper, and a higher laser power with a smaller spot could overcome it (Anup et al., 2014). The predicted damage was lower near vessels, which can leave necrosis incomplete, and vessel orientation changed the surface response (Paul et al., 2016b).
  • Nanoparticles change both how hot and where. For the same laser exposure, the maximum temperature rise was about 10 °C in bare tissue, 19 °C with gold mesoflowers and 38 °C with graphene (Paul et al., 2016a). The nanostructures largely compensated for vessel cooling and kept the heat localised instead of spreading into neighbouring tissue.
  • The hottest point is below the surface. Because of multiple scattering, temperature peaked inside the phantom, about 10 mm deep in bare tissue, moving to about 5 mm with gold mesoflowers, and shifting further as the vessel position changed (Paul et al., 2016a). The position of a large vessel must therefore be known to plan effective treatment. The semi-analytical model reproduced this peak and its location up to the peak, though it overestimated temperatures beyond it, and it estimated the absorption coefficient of graphene-loaded phantoms at about 600 per metre (Dhar et al., 2016).
  • Heat conduction in tissue is not purely Fourier. The experiments showed non-Fourier effects during early heating, and gold nanostructures caused noticeably more damage to collagen near the heated spot (Nilamani et al., 2013).

Taken together, these studies give a validated computational route to predicting subsurface temperatures during plasmonic photo-thermal therapy, reducing the need for risky in vivo trials while flagging large vessels as the hidden variable that treatment planning must account for.

References

  1. Paul, A., Narasimhan, A., Das, S. K., Sengupta, S. and Pradeep, T. (2016a) “Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy,” Int J Hyperthermia, 32:7, 765-777 [ DOI: 10.1080/02656736.2016.1196831 | Abstract ].
  2. Paul, A., Narasimhan, A. and Das, S. K., (2016b) “Investigation of thermal damage of tissue mimics embedded with large blood vessels during PPTT”   Int. J. Num. Methods for Heat and Fluid Flow [ DOI: 10.1108/HFF-01-2015-0032 | Abstract ]
  3. Dhar, P., Paul, A., Narasimhan, A. and Das, S. K., (2016) “Analytical prediction of sub surface thermal history in translucent tissue phantoms during plasmonic photo thermotherapy”   J. Thermal Biology 62, 143-149 [ DOI: https://doi.org/10.1016/j.jtherbio.2016.06.023 | Sciencedirect Abstract | arXiv preprint arXiv:1511.04549]
  4. Anup, P., Narasimhan, A., Kahlen, F. J., and Das, S. K., (2014), “Temperature evolution in tissues embedded with large blood vessels during photo-thermal heating,”   J. of Thermal Biology, 41, 77-87. [DOI: 10.1016/j.jtherbio.2014.02.010 | Abstract]
  5. Paul, A., Bandaru, N., Narasimhan, A. and Das, S. K., (2014), “Subsurface Tumor Ablation with Near-infrared Radiation using Intratumoral and Intravenous Injection of Nanoparticles” Int. J. of Micro-Nano Scale Transport 5(2), 69-80 [ DOI: 10.1260/1759-3093.5.2.69 | Abstract ]
  6. Nilamani, S., Ghosh, S., Narasimhan, A. and Das, S. K., (2013), “Investigation of non-Fourier effects in bio-tissues during laser assisted photothermal therapy,”   Int. J. Thermal Sci., 76, 208-220. [DOI: 10.1016/j.ijthermalsci.2013.08.014 | Abstract]
  7. Narasimhan, A. and Sridhar, S., (2013), “Non-Fourier bio heat transfer modelling of thermal damage during retinal laser irradiation,”   Int. J. Heat and Mass Transfer, 60, 591-597. [DOI: 10.1016/j.ijheatmasstransfer.2013.01.010 | Abstract]

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