A simulation study of photothermal effects in transcranial photobiomodulation_Journal of Biomedical Engineering

Authors：

LIU Xintong ^1,2 , XIA Jie ^2,3,4 , PAN Jiadong ^2,3,4 , CHEN Shipeng ^2,3,4 , ZHANG Shaomin ³ ,  WANG Minmin ³ , DONG Shurong ^3,4

1. School of Physics, Zhejiang University, Hangzhou 310027, P. R. China;
2. Hangzhou RongNao Technology Co., Ltd, Hangzhou 311421, P. R. China;
3. Key Laboratory for Biomedical Engineering of Ministry of Education, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310027, P. R. China;
4. The Institute of Smart Sensor and Micro/Nano Systems, College of Information Science & Electronic Engineering, Zhejiang University, Hangzhou 310027, P. R. China;

Corresponding?author：

WANG Minmin, Email: minminwang@zju.edu.cn

Keywords：

Neuromodulation; Transcranial photobiomodulation; Simulation model; Finite element method

DOI：

10.7507/1001-5515.202512019

Video：

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Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique utilizing infrared or near-infrared light. Clarifying the energy deposition patterns and safe dose thresholds within realistic anatomical head structures is crucial for advancing its clinical application. However, existing studies often rely on simplified models for numerical simulation, which may fail to accurately capture the influence of cortical sulci and gyri on light propagation and thermal diffusion. This study established a high-resolution (1 mm³) anatomically realistic human head model using the finite element method, and developed an optical-thermal multiphysics coupling framework to systematically simulate and analyze key parameters, including power density and wavelength, to evaluate light penetration depth and tissue temperature elevation characteristics. The results demonstrated that approximately 0.05% of the incident optical power penetrated to the cortical gray matter. As the power density increased, scalp temperature elevation reached up to 5.22 °C, and brain temperature elevation reached up to 0.49 °C, with a distinct “halo” scattering effect observed within the cerebrospinal fluid layer. These simulation results systematically revealed the photothermal propagation characteristics and tissue thermal responses of tPBM in realistic head anatomy, providing an important theoretical basis for defining safe dose thresholds and optimizing individualized stimulation parameters.

Citation： LIU Xintong, XIA Jie, PAN Jiadong, CHEN Shipeng, ZHANG Shaomin, WANG Minmin, DONG Shurong. A simulation study of photothermal effects in transcranial photobiomodulation. Journal of Biomedical Engineering, 2026, 43(4): 686-694. doi: 10.7507/1001-5515.202512019 Copy

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3.	Longo M G F, Tan C O, Chan S, et al. Effect of transcranial low-level light therapy vs sham therapy among patients with moderate traumatic brain injury: a randomized clinical trial[J]. JAMA Netw Open, 2020, 3(9): e2017337.
4.	Cassano P, Petrie S R, Mischoulon D, et al. Transcranial photobiomodulation for the treatment of major depressive disorder. The ELATED-2 pilot trial[J]. Photomed Laser Surg, 2018, 36(12): 634-646.
5.	Nizamutdinov D, Qi X, Berman M H, et al. Transcranial near infrared light stimulations improve cognition in patients with dementia[J]. Aging Dis, 2021, 12(4): 954-963.
6.	Lin H, Li D, Zhu J, et al. Transcranial photobiomodulation for brain diseases: review of animal and human studies including mechanisms and emerging trends[J]. Neurophotonics, 2024, 11(1): 010601.
7.	Fernandes F, Oliveira S, Monteiro F, et al. Devices used for photobiomodulation of the brain-a comprehensive and systematic review[J]. J Neuroeng Rehabil, 2024, 21(1): 53.
8.	Hacke W, Schellinger P D, Albers G W, et al. Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial[J]. Stroke, 2014, 45(11): 3187-3193.
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13.	Yuan Y, Cassano P, Pias M, et al. Transcranial photobiomodulation with near-infrared light from childhood to elderliness: simulation of dosimetry[J]. Neurophotonics, 2020, 7(1): 015009.
14.	Su C T, Wu J H. Photobiomodulation in biological tissues: light penetration, dosimetry, and potential applications[J]. Opt Lasers Eng, 2025, 186: 108852.
15.	黎媛媛, 陳嬌, 孔伶俐. 光生物調節在阿爾茨海默病治療中的研究進展[J]. 臨床醫學進展, 2021, 11: 5639.
16.	陳洪麗, 高靜靜, 楊佳佳, 等. 光療及光照劑量對抑郁癥的作用研究進展[J]. 生物化學與生物物理進展, 2021, 48(12): 1422-1428.
17.	吳陽光, 屈海濤, 張雙喜, 等. 光生物調節療法在潰瘍性結腸炎治療方面的應用前景探析[J]. 激光生物學報, 2025, 34(4): 296-303.
18.	Jagdeo J R, Adams L E, Brody N I, et al. Transcranial red and near infrared light transmission in a cadaveric model[J]. PLoS One, 2012, 7(10): e47460.
19.	Tedford C E, DeLapp S, Jacques S, et al. Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue[J]. Lasers Surg Med, 2015, 47(4): 312-322.
20.	Fonov V, Evans A, McKinstry R, et al. Unbiased nonlinear average age-appropriate brain templates from birth to adulthood[J]. Neuroimage, 2009, 47(Suppl 1): S102.
21.	Fonov V, Evans A C, Botteron K, et al. Unbiased average age-appropriate atlases for pediatric studies[J]. Neuroimage, 2011, 54(1): 313-327.
22.	Jacques S L. Optical properties of biological tissues: a review[J]. Phys Med Biol, 2013, 58(11): R37-R61.
23.	Bashkatov A N, Genina E A, Kochubey V I, et al. Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm[J]. J Phys D Appl Phys, 2005, 38(15): 2543-2555.
24.	Yaroslavsky A N, Schulze P C, Yaroslavsky I V, et al. Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range[J]. Phys Med Biol, 2002, 47(12): 2059-2073.
25.	Martelli F, Binzoni T, Del Bianco S, et al. Light propagation through biological tissue and other diffusive media: theory, solutions, and validations[M]. 2nd ed. Bellingham: SPIE Press, 2022: 1-698.
26.	Pennes H H. Analysis of tissue and arterial blood temperatures in the resting human forearm[J]. J Appl Physiol, 1948, 1(2): 93-122.
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32.	Wang X, Dmochowski J P, Zeng L, et al. Transcranial photobiomodulation with 1064-nm laser modulates brain electroencephalogram rhythms[J]. Neurophotonics, 2019, 6(2): 025013.
33.	Zomorrodi R, Loheswaran G, Pushparaj A, et al. Pulsed near infrared transcranial and intranasal photobiomodulation significantly modulates neural oscillations: a pilot exploratory study[J]. Sci Rep, 2019, 9(1): 6309.
34.	Elwassif M M, Kong Q, Vazquez M, et al. Bio-heat transfer model of deep brain stimulation-induced temperature changes[J]. J Neural Eng, 2006, 3(4): 306-315.
35.	Gentilal N, Abend E, Naveh A, et al. Temperature and impedance variations during tumor treating fields treatment[J]. Front Hum Neurosci, 2022, 16: 931818.
36.	徐冰瑜, 逯邁. 經顱磁刺激與磁共振成像聯合使用時力與溫度場仿真研究[J]. 生物醫學工程學雜志, 2022, 39(4): 685-693.
37.	Kabiri A, Talaee M R. Analysis of hyperbolic Pennes bioheat equation in perfused homogeneous biological tissue subject to the instantaneous moving heat source[J]. SN Appl Sci, 2021, 3(4): 398.
38.	Caldieraro M A, Cassano P. Transcranial and systemic photobiomodulation for major depressive disorder: a systematic review of efficacy, tolerability and biological mechanisms[J]. J Affect Disord, 2019, 243: 262-273.
39.	Iosifescu D V, Norton R J, Tural U, et al. Very low-level transcranial photobiomodulation for major depressive disorder: the ELATED-3 multicenter, randomized, sham-controlled trial[J]. J Clin Psychiatry, 2022, 83(5): 21m14226.
40.	Weerasekera A, Coelho D R A, Ratai E M, et al. Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study[J]. Lasers Med Sci, 2024, 39(1): 249.
41.	Coelho D R A, Vieira W F, Hurtado Puerto A M, et al. Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial[J]. Lasers Med Sci, 2025, 40(1): 248.

1. de Freitas L F, Hamblin M R. Proposed mechanisms of photobiomodulation or low-level light therapy[J]. IEEE J Sel Top Quantum Electron, 2016, 22(3): 348-364.
2. Hamblin M R. Shining light on the head: photobiomodulation for brain disorders[J]. BBA Clin, 2016, 6: 113-124.
3. Longo M G F, Tan C O, Chan S, et al. Effect of transcranial low-level light therapy vs sham therapy among patients with moderate traumatic brain injury: a randomized clinical trial[J]. JAMA Netw Open, 2020, 3(9): e2017337.
4. Cassano P, Petrie S R, Mischoulon D, et al. Transcranial photobiomodulation for the treatment of major depressive disorder. The ELATED-2 pilot trial[J]. Photomed Laser Surg, 2018, 36(12): 634-646.
5. Nizamutdinov D, Qi X, Berman M H, et al. Transcranial near infrared light stimulations improve cognition in patients with dementia[J]. Aging Dis, 2021, 12(4): 954-963.
6. Lin H, Li D, Zhu J, et al. Transcranial photobiomodulation for brain diseases: review of animal and human studies including mechanisms and emerging trends[J]. Neurophotonics, 2024, 11(1): 010601.
7. Fernandes F, Oliveira S, Monteiro F, et al. Devices used for photobiomodulation of the brain-a comprehensive and systematic review[J]. J Neuroeng Rehabil, 2024, 21(1): 53.
8. Hacke W, Schellinger P D, Albers G W, et al. Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial[J]. Stroke, 2014, 45(11): 3187-3193.
9. Cassano P, Caldieraro M A, Norton R, et al. Reported side effects, weight and blood pressure, after repeated sessions of transcranial photobiomodulation[J]. Photobiomodul Photomed Laser Surg, 2019, 37(10): 651-656.
10. Ceranoglu T A, Cassano P, Hoskova B, et al. Transcranial photobiomodulation in adults with high-functioning autism spectrum disorder: positive findings from a proof-of-concept study[J]. Photobiomodul Photomed Laser Surg, 2022, 40(1): 4-12.
11. Van Lankveld H, Mai A Q, Lim L, et al. Simulation-based dosimetry of transcranial and intranasal photobiomodulation of the human brain: the roles of wavelength, power density, and skin tone[J]. Biomed Opt Express, 2025, 16(8): 3295-3314.
12. Setchfield K, Gorman A, Simpson A H R W, et al. Effect of skin color on optical properties and the implications for medical optical technologies: a review[J]. J Biomed Opt, 2024, 29(1): 010901.
13. Yuan Y, Cassano P, Pias M, et al. Transcranial photobiomodulation with near-infrared light from childhood to elderliness: simulation of dosimetry[J]. Neurophotonics, 2020, 7(1): 015009.
14. Su C T, Wu J H. Photobiomodulation in biological tissues: light penetration, dosimetry, and potential applications[J]. Opt Lasers Eng, 2025, 186: 108852.
15. 黎媛媛, 陳嬌, 孔伶俐. 光生物調節在阿爾茨海默病治療中的研究進展[J]. 臨床醫學進展, 2021, 11: 5639.
16. 陳洪麗, 高靜靜, 楊佳佳, 等. 光療及光照劑量對抑郁癥的作用研究進展[J]. 生物化學與生物物理進展, 2021, 48(12): 1422-1428.
17. 吳陽光, 屈海濤, 張雙喜, 等. 光生物調節療法在潰瘍性結腸炎治療方面的應用前景探析[J]. 激光生物學報, 2025, 34(4): 296-303.
18. Jagdeo J R, Adams L E, Brody N I, et al. Transcranial red and near infrared light transmission in a cadaveric model[J]. PLoS One, 2012, 7(10): e47460.
19. Tedford C E, DeLapp S, Jacques S, et al. Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue[J]. Lasers Surg Med, 2015, 47(4): 312-322.
20. Fonov V, Evans A, McKinstry R, et al. Unbiased nonlinear average age-appropriate brain templates from birth to adulthood[J]. Neuroimage, 2009, 47(Suppl 1): S102.
21. Fonov V, Evans A C, Botteron K, et al. Unbiased average age-appropriate atlases for pediatric studies[J]. Neuroimage, 2011, 54(1): 313-327.
22. Jacques S L. Optical properties of biological tissues: a review[J]. Phys Med Biol, 2013, 58(11): R37-R61.
23. Bashkatov A N, Genina E A, Kochubey V I, et al. Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm[J]. J Phys D Appl Phys, 2005, 38(15): 2543-2555.
24. Yaroslavsky A N, Schulze P C, Yaroslavsky I V, et al. Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range[J]. Phys Med Biol, 2002, 47(12): 2059-2073.
25. Martelli F, Binzoni T, Del Bianco S, et al. Light propagation through biological tissue and other diffusive media: theory, solutions, and validations[M]. 2nd ed. Bellingham: SPIE Press, 2022: 1-698.
26. Pennes H H. Analysis of tissue and arterial blood temperatures in the resting human forearm[J]. J Appl Physiol, 1948, 1(2): 93-122.
27. Wissler E H. Pennes' 1948 paper revisited[J]. J Appl Physiol, 1998, 85(1): 35-41.
28. Shurrab K, El-Daher M S. Potential thermal effect of stimulating brain tissue during low level laser therapy[J]. J Biomed Photonics Eng, 2023, 9(4): 040303.
29. Osilla E V, Marsidi J L, Shumway K R, et al. Physiology, temperature regulation[DS/OL]. StatPearls, (2023-07-30)[2026-05-29]. https://www.statpearls.com/.
30. IT'IS Foundation. Tissue properties database V4.2[DS/OL]. (2024-06-04)[2026-05-29]. https://itis.swiss/virtual-population/tissue-properties/database/.
31. Barrett D W, Gonzalez-Lima F. Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans[J]. Neuroscience, 2013, 230: 13-23.
32. Wang X, Dmochowski J P, Zeng L, et al. Transcranial photobiomodulation with 1064-nm laser modulates brain electroencephalogram rhythms[J]. Neurophotonics, 2019, 6(2): 025013.
33. Zomorrodi R, Loheswaran G, Pushparaj A, et al. Pulsed near infrared transcranial and intranasal photobiomodulation significantly modulates neural oscillations: a pilot exploratory study[J]. Sci Rep, 2019, 9(1): 6309.
34. Elwassif M M, Kong Q, Vazquez M, et al. Bio-heat transfer model of deep brain stimulation-induced temperature changes[J]. J Neural Eng, 2006, 3(4): 306-315.
35. Gentilal N, Abend E, Naveh A, et al. Temperature and impedance variations during tumor treating fields treatment[J]. Front Hum Neurosci, 2022, 16: 931818.
36. 徐冰瑜, 逯邁. 經顱磁刺激與磁共振成像聯合使用時力與溫度場仿真研究[J]. 生物醫學工程學雜志, 2022, 39(4): 685-693.
37. Kabiri A, Talaee M R. Analysis of hyperbolic Pennes bioheat equation in perfused homogeneous biological tissue subject to the instantaneous moving heat source[J]. SN Appl Sci, 2021, 3(4): 398.
38. Caldieraro M A, Cassano P. Transcranial and systemic photobiomodulation for major depressive disorder: a systematic review of efficacy, tolerability and biological mechanisms[J]. J Affect Disord, 2019, 243: 262-273.
39. Iosifescu D V, Norton R J, Tural U, et al. Very low-level transcranial photobiomodulation for major depressive disorder: the ELATED-3 multicenter, randomized, sham-controlled trial[J]. J Clin Psychiatry, 2022, 83(5): 21m14226.
40. Weerasekera A, Coelho D R A, Ratai E M, et al. Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study[J]. Lasers Med Sci, 2024, 39(1): 249.
41. Coelho D R A, Vieira W F, Hurtado Puerto A M, et al. Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial[J]. Lasers Med Sci, 2025, 40(1): 248.

Journal of Biomedical Engineering

A simulation study of photothermal effects in transcranial photobiomodulation

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