Model-predicted brain temperature computational imaging by multimodal noninvasive functional neuromonitoring of cerebral oxygen metabolism and hemodynamics: MRI-derived and clinical validation
Restricted accessResearch articleFirst published online February, 2025
Model-predicted brain temperature computational imaging by multimodal noninvasive functional neuromonitoring of cerebral oxygen metabolism and hemodynamics: MRI-derived and clinical validation
Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures.
SungDRejimonAAllenJW, et al.
Predicting brain temperature in humans using bioheat models: Progress and outlook. J Cereb Blood Flow Metab2023;
43: 833–842.
2.
YulugBVeliogluHASaymanD, et al.
Brain temperature in healthy and diseased conditions: a review on the special implications of MRS for monitoring brain temperature. Biomed Pharmacother2023;
160: 114287.
3.
RzechorzekNMThrippletonMJChappellFM, et al.
A daily temperature rhythm in the human brain predicts survival after brain injury. Brain2022;
145: 2031–2048.
4.
SungDKottkePARiskBB, et al.
Personalized predictions and non-invasive imaging of human brain temperature. Commun Phys2021;
4.
5.
GeurtsMPeterssonJBrizziM, et al.
COOLIST (cooling for ischemic stroke trial). Stroke2017;
48: 219–221.
6.
BakerTSDurbinJTroianiZ, et al.
Therapeutic hypothermia for intracerebral hemorrhage: systematic review and meta-analysis of the experimental and clinical literature. Int J Stroke2021;
17: 506–516.
7.
DochertyAEmelifeonwuJAndrewsPJD.Hypothermia after traumatic brain injury. JAMA2018;
320: 2204–2206.
8.
YenariMAHanHS.Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat Rev Neurosci2012;
13: 267–278.
HornMDiproseWKPichardoS, et al.
Non-invasive brain temperature measurement in acute ischemic stroke. Front Neurol2022;
13: 889214.
11.
HuschakGHoellTHohausC, et al.
Clinical evaluation of a new multiparameter neuromonitoring device: measurement of brain tissue oxygen, brain temperature, and intracranial pressure. J Neurosurg Anesthesiol2009;
21: 155–160.
12.
ShinJLiuZBaiW, et al.
Bioresorbable optical sensor systems for monitoring of intracranial pressure and temperature. Sci Adv2019;
5: eaaw1899.
13.
PrevostVHYungAMorrisSR, et al.
Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain. NeuroImage2021;
236: 118046.
14.
HoriuchiDShimonoTTatekawaH, et al.
Brain temperature remains stable during the day: a study of diffusion-weighted imaging thermometry in healthy individuals. Neuroradiology2023;
65: 1239–1246.
15.
SaiAShimonoTSakaiK, et al.
Diffusion-weighted imaging thermometry in multiple sclerosis. J Magn Reson Imaging2014;
40: 649–654.
16.
ZhuMBashirAAckermanJJ, et al.
Improved calibration technique for in vivo proton MRS thermometry for brain temperature measurement. Magn Reson Med2008;
60: 536–541.
17.
StattonBKSmithJFinneganME, et al.
Temperature dependence, accuracy, and repeatability of T(1) and T(2) relaxation times for the ISMRM/NIST system phantom measured using MR fingerprinting. Magn Reson Med2022;
87: 1446–1460.
18.
GaurPPartanenAWernerB, et al.
Correcting heat-induced chemical shift distortions in proton resonance frequency-shift thermometry. Magn Reson Med2016;
76: 172–182.
19.
WangP.Evaluation of MR thermometry with proton resonance frequency method at 7T. Quant Imaging Med Surg2017;
7: 259–266.
20.
IshidaTInoueTInoueT, et al.
Brain temperature measured by magnetic resonance spectroscopy to predict clinical outcome in patients with infarction. Sensors (Basel, Switzerland)2021;
21: 490.
21.
PlankJRMorganCSundramF, et al.
Brain temperature as an indicator of neuroinflammation induced by typhoid vaccine: assessment using whole-brain magnetic resonance spectroscopy in a randomised crossover study. NeuroImage Clin2022;
35: 103053.
22.
WeisJCovaciuLRubertssonS, et al.
Phase-difference and spectroscopic imaging for monitoring of human brain temperature during cooling. Magn Reson Imaging2012;
30: 1505–1511.
23.
DehkharghaniSMaoHHowellL, et al.
Proton resonance frequency chemical shift thermometry: experimental design and validation toward high-resolution noninvasive temperature monitoring and in vivo experience in a nonhuman primate model of acute ischemic stroke. AJNR Am J Neuroradiol2015;
36: 1128–1135.
24.
DuijnJHMatsonGBMaudsleyAA, et al.
Human brain infarction: proton MR spectroscopy. Radiology1992;
183: 711–718.
25.
ChenJLiuLZhangH, et al.
Endovascular hypothermia in acute ischemic stroke: pilot study of selective intra-arterial cold saline infusion. Stroke2016;
47: 1933–1935.
26.
WuCZhaoWAnH, et al.
Safety, feasibility, and potential efficacy of intraarterial selective cooling infusion for stroke patients treated with mechanical thrombectomy. J Cereb Blood Flow Metab2018;
38: 2251–2260.
27.
RodriguesDBMaccariniPFSalahiS, et al.
Design and optimization of an ultra wideband and compact microwave antenna for radiometric monitoring of brain temperature. IEEE Trans Biomed Eng2014;
61: 2154–2160.
28.
GroumpasEKoutsoupidouMKaranasiouIS, et al.
Real-time passive brain monitoring system using near-field microwave radiometry. IEEE Trans Biomed Eng2020;
67: 158–165.
29.
SugiuraTKounoYHashizumeA, et al.
Five-band microwave radiometer system for non-invasive measurement of brain temperature in new-born infants: system calibration and its feasibility. Conf Proc IEEE Eng Med Biol Soc2004;
2004: 2292–2295.
30.
ZhaoGPanhwarFChenZ.Modeling combined cryosurgery and hyperthermia with thermally significant blood vessels. Theory Appl Heat Transfer Humans2018;
2: 669–685.
31.
DagroAWilkersonJ.A computational investigation of strain concentration in the brain in response to a rapid temperature rise. J Mech Behav Biomed Mater2021;
115: 104228.
32.
KonstasA-ANeimarkMALaineAF, et al.
A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain. J Appl Physiol (1985)2007;
102: 1329–1340.
33.
LutzYLoeweAMeckelS, et al.
Combined local hypothermia and recanalization therapy for acute ischemic stroke: estimation of brain and systemic temperature using an energetic numerical model. J Therm Biol2019;
84: 316–322.
34.
BakerTSZannouALCruzD, et al.
Development and clinical validation of a finite element method model mapping focal intracranial cooling. IEEE Trans Neural Syst Rehabil Eng2022;
30: 2168–2174.
35.
LutzYMeinerTKramesL, et al.
Selective brain hypothermia for ischemic MCA-M1 stroke: influence of cerebral arterial circulation in a 3D brain temperature model. IEEE Trans Biomed Eng2021;
68: 404–415.
36.
JiangMLiMGaoY, et al.
The intra‐arterial selective cooling infusion system: a mathematical temperature analysis and in vitro experiments for acute ischemic stroke therapy. CNS Neurosci Ther2022;
28: 1303–1314.
37.
BakhsheshiMFDiopMSt LawrenceK, et al.
Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study. J Biomed Opt2014;
19: 057005.
38.
Fazel BakhsheshiMDiopMSt LawrenceK, et al.
Quantitative measurement of cerebral blood flow during hypothermia with a time-resolved near-infrared technique. Photonic Therapeutics and Diagnostics VIII2012;
8207: 82074R.
39.
FedotovIVSolotenkovMAPochechuevMS, et al.
All-optical brain thermometry in freely moving animals. ACS Photonics2020;
7: 3353–3360.
40.
HongGDiaoSChangJ, et al.
Through-skull fluorescence imaging of the brain in a new near-infrared window. Nat Photonics2014;
8: 723–730.
41.
ShimosegawaEHatazawaJIbarakiM, et al.
Metabolic penumbra of acute brain infarction: a correlation with infarct growth. Ann Neurol2005;
57: 495–504.
42.
JiangMGaoYWuC, et al.
The blood heat exchanger in intra-arterial selective cooling infusion for acute ischemic stroke: a computational fluid-thermodynamics performance, experimental assessment and evaluation on the brain temperature. Comput Biol Med2022;
145: 105497.
43.
TichauerKMHadwayJALeeTY, et al.
Measurement of cerebral oxidative metabolism with near-infrared spectroscopy: a validation study. J Cereb Blood Flow Metab2006;
26: 722–730.
44.
HashemMZhangQWuY, et al.
Using a multimodal near-infrared spectroscopy and MRI to quantify gray matter metabolic rate for oxygen: a hypothermia validation study. NeuroImage2020;
206: 116315.
45.
PhelpsMEHuangSCHoffmanEJ, et al.
Validation of tomographic measurement of cerebral blood volume with C-11-labeled carboxyhemoglobin. J Nucl Med1979;
20: 328–334.
46.
WangHWangBNormoyleKP, et al.
Brain temperature and its fundamental properties: a review for clinical neuroscientists. Front Neurosci2014;
8: 307.
47.
TanosBKovácsG.The ratio of body haematocrit to venous haematocrit in open heart surgery and estimation of the blood volume in the large and small vessels. Acta Chir Acad Sci Hung1979;
20: 141–148.
48.
SiJLiMZhangX, et al.
Cerebral tissue oximeter suitable for real-time regional oxygen saturation monitoring in multiple clinical settings. Cogn Neurodyn2022;
17: 563–574.
49.
UludagKKohlMSteinbrinkJ, et al.
Cross talk in the Lambert-Beer calculation for near-infrared wavelengths estimated by monte carlo simulations. J Biomed Opt2002;
7: 51–59.
50.
LiuJYanZPuY, et al.
Functional assessment of cerebral artery stenosis: a pilot study based on computational fluid dynamics. J Cereb Blood Flow Metab2016;
37: 2567–2576.
51.
JiangMLiMGaoY, et al.
Design and evaluation of an air-insulated catheter for intra-arterial selective cooling infusion from numerical simulation and in vitro experiment. Med Eng Phys2022;
99: 103736.
52.
JarrettCLShieldsKLBroxtermanRM, et al.
Imaging transcranial doppler ultrasound to measure middle cerebral artery blood flow: the importance of measuring vessel diameter. Am J Physiol Regul Integr Comp Physiol2020;
319: R33–r42. 2020/05/14.
53.
AmukotuwaSStrakaMAksoyD, et al.
Cerebral blood flow predicts the infarct core: new insights from contemporaneous diffusion and perfusion imaging. Stroke2019;
50: 2783–2789. 2019/08/30. DOI: 10.1161/strokeaha.119.026640.
54.
SmithKDZhuL.Brain hypothermia induced by cold spinal fluid using a torso cooling pad: theoretical analyses. Med Biol Eng Comput2010;
48: 783–791.
55.
YinLJiangHZhaoW, et al.
Inducing therapeutic hypothermia via selective brain cooling: a finite element modeling analysis. Med Biol Eng Comput2019;
57: 1313–1322.
56.
LutzYDaschnerRKramesL, et al.
Modeling selective therapeutic hypothermia in case of acute ischemic stroke using a 1D hemodynamics model and a simplified brain geometry. Math Biosci Eng2019;
17: 1147–1167.
57.
MengLGelbAW.Cerebral oximetry: Three questions to ask. Colombian Journal of Anesthesiology2015;
43: 52–56.
58.
LagendijkJJ.The influence of bloodflow in large vessels on the temperature distribution in hyperthermia. Phys Med Biol1982;
27: 17–23.
59.
SukstanskiiALYablonskiyDA.Theoretical model of temperature regulation in the brain during changes in functional activity. Proc Natl Acad Sci U S A2006;
103: 12144–12149.
60.
PoldermanKHHeroldI.Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med2009;
37: 1101–1120.
61.
Russell-BucklandJTachtsidisI.Developing a model to simulate the effect of hypothermia on cerebral blood flow and metabolism. Adv Exp Med Biol2020;
1232: 299–306.
62.
BakerWBBaluRHeL, et al.
Continuous non-invasive optical monitoring of cerebral blood flow and oxidative metabolism after acute brain injury. J Cereb Blood Flow Metab2019;
39: 1469–1485.
63.
ZeinerAKlewerJSterzF, et al.
Non-invasive continuous cerebral temperature monitoring in patients treated with mild therapeutic hypothermia: an observational pilot study. Resuscitation2010;
81: 861–866.
64.
FahrenholtzSJMadankanRDanishS, et al.
Theoretical model for laser ablation outcome predictions in brain: calibration and validation on clinical MR thermometry images. Int J Hyperthermia2018;
34: 101–111.
65.
LiFGaoJKohlsW, et al.
Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke. Brain Circ2022;
8: 69–75.
66.
MaJLiMZhangM, et al.
Protection of multiple ischemic organs by controlled reperfusion. Brain Circ2021;
7: 241–246.
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