Red blood cell as a universal optoacoustic sensor for non-invasive temperature monitoring

Abstract

Optoacoustic (photoacoustic) temperature imaging could provide improved spatial resolution and temperature sensitivity as compared to other techniques of non-invasive thermometry used during thermal therapies for safe and efficient treatment of lesions. However, accuracy of the reported optoacoustic methods is compromised by biological variability and heterogeneous composition of tissues. We report our findings on the universal character of the normalized temperature dependent optoacoustic response (ThOR) in blood, which is invariant with respect to hematocrit at the isosbestic point of hemoglobin. The phenomenon is caused by the unique homeostatic compartmentalization of blood hemoglobin exclusively inside erythrocytes. On the contrary, the normalized ThOR in aqueous solutions of hemoglobin showed linear variation with respect to its concentration and was identical to that of blood when extrapolated to the hemoglobin concentration inside erythrocytes. To substantiate the conclusions, we analyzed optoacoustic images acquired from the samples of whole and diluted blood as well as hemoglobin solutions during gradual cooling from þ37 to À15 C. Our experimental methodology allowed direct observation and accurate measurement of the temperature of zero optoacoustic response, manifested as the sample's image faded into background and then reappeared in the reversed (negative) contrast. These findings provide a framework necessary for accurate correlation of measured normalized optoacoustic image intensity and local temperature in vascularized tissues independent of tissue composition. Temperature monitoring of live tissue is an important technique that provides feedback information needed for guidance of thermal therapies, such as laser interstitial thermotherapy, high-intensity focused ultrasound, radio frequency ablation, and cryoablation. 1-3 Temperature readings collected in real time around the treated areas help warranting safety and efficiency of the therapeutic procedure. 4 Noninvasive temperature monitoring is unanimously preferred among the clinicians, especially when there are crucial requirements to minimize collateral thermal damage to the adjacent normal tissues and zones of innervation. Several imaging and sensing modalities have been proposed for noninvasive temperature monitoring during thermal therapies, including ultrasound imaging, magnetic resonance imaging, and optoacoustic (photoacoustic) imaging and sensing. [5][6][7] The potential advantages of optoacoustic temperature imaging techniques reside in enhanced spatial resolution, temperature sensitivity, and faster data acquisition. [8][9][10] During the past decade, optoacoustic imaging has attracted significant attention from researchers and clinicians due to its success in a variety of biomedical applications that involve high resolution deep tissue imaging of optical absorbers (blood, water, and near infrared contrast agents) unattainable with other modalities. [11][12][13] The premium quality of optoacoustic images, as compared to other imagin...

Imaging technique for real-time temperature monitoring during cryotherapy of lesions

“…39 In contrast to homogeneous hemoglobin solutions, the temperature of zero OA response in blood samples was found invariant with respect to hematocrit, or the concentration of RBCs, and was interpreted through the unique intracellular compartmentalization of hemoglobin. 37 This finding was consistent with direct OA measurements of the Grüneisen parameter in suspensions of erythrocytes, 40 which demonstrated negligibly small dependence on hemoglobin concentration:…”

“…54 The absence of variation of ThORs measured for the whole and diluted samples of blood indicates that the Grüneisen parameter of erythrocyte suspension is not affected by the concentration of hemoglobin, as long as hemoglobin molecules are compartmentalized inside RBC capsules. 37 The proposed procedure of noninvasive temperature mapping was evaluated in tissue-mimicking phantoms of two types-one with a PVCP matrix and the other with a gelatin matrix. In terms of thermoacoustic properties, plastisol material is similar to fat, 44,55 while the gelatin phantom is similar to vascularized tissue with higher water content.…”

“…The OA experiments, previously performed on homogeneous solutions of ionic compounds and hemoglobin, revealed the concentration-dependent character of ThOR. 37 Additionally, the ThOR of hemoglobin solutions obtained while irradiating samples at an 805-nm laser wavelength was found independent of hemoglobin's oxygenation. An 805-nm wavelength corresponds to the isosbestic point of hemoglobin, where its oxygenated and deoxygenated forms have equal optical absorptivities.…”

“…According to the proposed hypothesis, the universal thermal OA behavior of blood is based on compartmentalization of hemoglobin in RBCs; 37,38 therefore, the integrity of RBCs must remain intact during the freezing procedure in order to maintain the validity of the calibration curve. The first symptoms of cellular damage appear as swelling or crenation of RBCs, which is caused by the thermally induced variation of transmembrane osmotic pressure.…”

“…37,38 Such spatial segregation of the dominant optical absorber inside stable cytoplasmic environment enables the universal temperature-dependent optoacoustic response (ThOR) of blood, which is manifested identically in all types of vascularized tissues regardless of the bulk tissue composition. The OA experiments, previously performed on homogeneous solutions of ionic compounds and hemoglobin, revealed the concentration-dependent character of ThOR.…”