Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones.

Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography.

Truncated-correlation photothermal coherence tomography of artificially demineralized animal bones: two- and three-dimensional markers for mineral loss monitoring.

The challenge of depth-resolved, nonionizing (hybrid-optical) detection of mineral loss in bones is addressed using truncated-correlation photothermal coherence tomography (TC-PCT). This approach has importance not only in ground-based clinical procedures, but also in microgravity space applications. Analogous to x-ray morphometric parameters, two- and three-dimensional markers have been defined and estimated for chemically demineralized goat rib bones. Cortical and trabecular regions have been analyzed independently and together using the computational slicing advantage of TC-PCT, and the results have been verified using micro-CT imaging (the gold standard). For low-demineralization levels, both modalities follow the same trend. However, for very high mineral loss that is unlikely to occur naturally, anomalies exist in both methods. Demineralization tracking has been carried out to a depth of ∼3 mm below the irradiated surface. Compared with micro-CT imaging, TC-PCT offers an improved dynamic range, which is a beneficial feature while analyzing highly demineralized bones. Also, TC-PCT parameters are found to be more sensitive to trabecular and combined cortical-trabecular demineralization compared with x-ray parameters. Axial and lateral resolutions in bone imaging for the current instrumental configuration are ∼25 and 100 µm, respectively.

Ultrasound imparted air-recoil resonance (UIAR) method for acoustic power estimation: theory and experiment.

Ultrasound imparted air-recoil resonance (UIAR), a new method for acoustic power estimation, is introduced with emphasis on therapeutic high-intensity focused ultrasound (HIFU) monitoring applications. Advantages of this approach over existing practices include fast response; electrical and magnetic inertness, and hence MRI compatibility; portability; high damage threshold and immunity to vibration and interference; low cost; etc. The angle of incidence should be fixed for accurate measurement. However, the transducer-detector pair can be aligned in any direction with respect to the force of gravity. In this sense, the operation of the device is orientation independent. The acoustic response of a pneumatically coupled pair of Helmholtz resonators, with one of them acting as the sensor head, is used for the estimation of acoustic power. The principle is valid in the case of pulsed/ burst as well as continuous ultrasound exposure, the former being more sensitive and accurate. An electro-acoustic theory has been developed for describing the dynamics of pressure flow and resonance in the system considering various thermo- viscous loss mechanisms. Experimental observations are found to be in agreement with theoretical results. Assuming the window damage threshold (~10 J·mm(-2)) and accuracy of RF power estimation are the upper and lower scale-limiting factors, the performance of the device was examined for an RF power range of 5 mW to 100 W with a HIFU transducer operating at 1.70 MHz, and an average nonlinearity of ~1.5% was observed. The device is also sensitive to sub-milliwatt powers. The frequency response was analyzed at 0.85, 1.70, 2.55, and 3.40 MHz and the results are presented with respective theoretical estimates. Typical response time is in the millisecond regime. Output drift is about 3% for resonant and 5% for nonresonant modes. The principle has been optimized to demonstrate a general-purpose acoustic power meter.

Highly depth-resolved chirped pulse photothermal radar for bone diagnostics.

A novel chirped pulse photothermal (PT) radiometric radar with improved sensitivity over the conventional harmonically modulated thermal-wave radar technique and alternative pulsed laser photothermal radiometry is introduced for the diagnosis of biological samples, especially bones with tissue and skin overlayers. The constraints imposed by the laser safety (maximum permissible exposure) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (a few mm below the skin surface). A theoretical approach for improvement of signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal signal and making use of the photothermal radiometric nonlinearity has been introduced and verified by comparing the SNR of four distinct excitation wave forms (sine-wave, square-wave, constant-width and constant duty-cycle pulses) for chirping the pump laser, under constant exposure energy. At low frequencies fixed-pulsewidth chirps of large peak power were found to be superior to all other equal-energy modalities, with an SNR improvement up to two orders of magnitude. Distinct thickness-dependent characteristic delay times in a goat bone were obtained, establishing an active depth resolution range of ~2.8 mm in a layered skin-fat-bone structure, a favorable result compared to the maximum reported pulsed photothermal radiometric depth resolution <1 mm in turbid biological media.