Improving quantification of intravascular fluorescence imaging using structural information

iNIRF system schematic. Excitation and emission light are coupled into a fibre which can be inserted in a catheter system through a rotational and translational stage, to allow fibre rotation and pull-back. The front end of the fibre is modified using a 45° prism so that fluorescence readings are obtained perpendicular to the translation axis.

source:© 2012 Physics in Medicine & Biology

Intravascular near-infrared fluorescence (iNIRF) imaging can enable the in vivo visualization of biomarkers of vascular pathology, including high-risk plaques. The technique resolves the bio-distribution of systemically administered fluorescent probes with molecular specificity in the vessel wall. However, the geometrical variations that may occur in the distance between fibre-tip and vessel wall can lead to signal intensity variations and challenge quantification. Herein we examined whether the use of anatomical information of the cross-section vessel morphology, obtained from co-registered intravascular ultrasound (IVUS), can lead to quantification improvements when fibre-tip and vessel wall distance variations are present. The algorithm developed employs a photon propagation model derived from phantom experiments that is used to calculate the relative attenuation of fluorescence signals as they are collected over 360° along the vessel wall, and utilizes it to restore accurate fluorescence readings. The findings herein point to quantification improvements when employing hybrid iNIRF, with possible implications to the clinical detection of high-risk plaques or blood vessel theranostics.
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Fig. 3 Experiment for validation of the algorithm: (a) phantom schematic: two straws containing the same concentration of fluorescent dye at different distances from the catheter; (b) iNIRF longitudinal image of the straws A and B and cross-section formation of a particular pullback position of interest; (c) corresponding IVUS cross-section of the straws and their corresponding edges; (d) iNIRF cross-section overlaid on the segmented IVUS cross-section is used for the correction of the iNIRF signal; (e) correction of the iNIRF image along the entire pullback.

G.Mallas, D. H. Brooks, A. Rosenthal, R.N.Nudelman, A. Mauskapf, F.A.Jaffer and V. Ntziachristos, “Improving quantification of intravascular fluorescence imaging using structural information,” Phys. Med. Biol. Vol. 57, pp. 6395–6406 (2012).

Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges

Intravascular optoacoustic imaging of lipids in human aorta using the 1210 nm wavelength

source:©2012 Imaging Med.

The progression of atherosclerosis involves complex changes in the structure, composition and biology of the artery wall. Currently, only anatomical plaque burden is routinely characterized in living patients, whereas compositional and biological changes are mostly inaccessible. However, anatomical imaging alone has proven to be insufficient for accurate diagnostics of the disease. Multispectral optoacoustic tomography offers complementary data to anatomical methods and is capable of imaging both tissue composition and, via the use of molecular markers, the biological activity therein. In this paper we review recent progress in multispectral optoacoustic tomography imaging of atherosclerosis with specific emphasis on intravascular applications. The potential capabilities of multispectral optoacoustic tomography are compared with those of established intravascular imaging techniques and current challenges on the road towards a clinically viable imaging modality are discussed.
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Fig. 1 Intravascular multispectral optoacoustic tomography of gold nanoparticle-bearing macrophages in rabbit aorta.
(A) Intravascular ultrasound image and (B) optoacoustic image acquired at 700 nm of an atherosclerotic rabbit aorta injected with gold nanoparticle-bearing macrophages. The arrows indicate the locations where injection was performed. (C) The normalized spectral optoacoustic response obtained in a small section on the aorta, where injection was performed. (D) Multispectral optoacoustic tomography image corresponding to the recovered spectrum overlaid onto the intravascular ultrasound image revealing the injected regions.

A. Rosenthal, F. A. Jafferand V. Ntziachristos, „Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges,” Imaging Med., Vol. 4, pp. 299-310 (2012).

Model-based optoacoustic imaging using focused detector scanning

Simulation of a linear scan with a spherically focused detector

source: © 2012 Optical Society of America

Optoacoustic (photoacoustic) mesoscopic and microscopic imaging is often implemented by linearly scanning a spherically focused ultrasound transducer. In this case, the resolution and sensitivity along the scan direction are limited by diffraction and therefore degrade rapidly for imaging depths away from the focal point. Partial restoration of the lost resolution can be achieved by using data-processing techniques, such as the virtual detector delay-and-sum method. However, these techniques are based on an approximate description of the detector properties, which limits the improvement in image quality they achieve. Herein we propose a reconstruction method based on an exact model of the optoacoustic generation and propagation that incorporates the spatial response of the sensor. The proposed method shows superior imaging performance over previously considered techniques.
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Fig. 1. (a) Geometry for the simulated scan. (b) Result of the scan for absorber 1. The color scale is linear, and the image is normalized to its maximum. (c) VD processing at the signal level: the signal of interest is on-axis (blue/solid), and is to be corrected with the aid of signals acquired at other sensor positions (one of them is shown in red/dotted). The off-axis signal is first time-shifted (black/dashed) and then (d) added to the signal of interest. (blue/solid), resulting in the VD-processed signal (black/dashed).

M. Á. A. Caballero, A. Rosenthal, J. Gâteau, D. Razansky, and V. Ntziachristos, “Model-based optoacoustic imaging using focused detector scanning,” Vol. 37, pp. 4080–4082 (2012).

Efficient framework for model-based tomographic image reconstruction using wavelet packets

Optoacoustic reconstructions of the object

source:© 2012 IEEE Transactions on Medical Imaging

The use of model-based algorithms in tomographic imaging offers many advantages over analytical inversion methods. However, the relatively high computational complexity of model-based approaches often restricts their efficient implementation. In practice, many modern imaging modalities, such as computed-tomography, positron-emission tomography, or optoacoustic tomography, normally use a very large number of pixels/voxels for image reconstruction. Consequently, the size of the forward-model matrix hinders the use of many inversion algorithms. In this paper, we present a new framework for model-based tomographic reconstructions, which is based on a wavelet-packet representation of the imaged object and the acquired projection data. The frequency localization property of the wavelet-packet base leads to an approximately separable model matrix, for which reconstruction at each spatial frequency band is independent and requires only a fraction of the projection data. Thus, the large model matrix is effectively separated into a set of smaller matrices, facilitating the use of inversion schemes whose complexity is highly nonlinear with respect to matrix size. The performance of the new methodology is demonstrated for the case of 2-D optoacoustic tomography for both numerically generated and experimental data.
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FIg 4. (a) An image of a cross section of a mouse used in the numerical examples and (b) its optoacoustic tomographic reconstruction in the case of noisy projection data. The reconstruction was performed by inverting the matrix relation in (15) using the LSQR algorithm.

A. Rosenthal, D. Razansky, and V. Ntziachristos, “Efficient framework for model-based tomographic image reconstruction using wavelet packets,” IEEE Trans. Med. Imag., Vol. 31, pp. 1346-1357 (2012)

Spatial characterization of the response of a silica optical fiber to wideband ultrasound

Experimental and theoretical sensitivity maps for the high-frequency band [6–30] MHz.

source: © 2012 Optical Society of America

Optical fibers have long been recognized as a promising technology for remote sensing of ultrasound. Nonetheless, very little is known about the characteristics of their spatial response, which is significantly affected by the strong acoustic mismatches between the fiber and surrounding medium. In this Letter, a new method is demonstrated for wideband spatial acoustic characterization of optical fibers. The method is based on the excitation of a point-like acoustic source via the opto-acoustic effect, while a miniature fiber sensor is implemented by a ?-phase-shifted fiber Bragg grating. Despite the relative complexity of acoustic wave propagation in the fiber, its spatial sensitivity in the high frequency band (6–30 MHz) exhibited an orderly pattern, which can be described by a simple model. This property reveals new possibilities for high-performance imaging using fiber-based ultrasound sensors, where knowledge of the sensor’s spatial sensitivity map is generally required.[Read More…]

Fig. 1. (a) Schematic side-view illustration of the fiber sensor and the acoustic source (SD, sensitivity distribution of the sensor; FBG, fiber Bragg grating); (b) a cross section of the fiber.

A. Rosenthal, M. Á. A. Caballero,S. Kellnberger, D. Razansky and V. Ntziachristos, “Spatial characterization of the response of a silica optical fiber to wideband ultrasound,” Opt. Lett. Vol. 37, pp. 3174-3176 (2012).

Wideband arbitrary-phase interferometer stabilization

Schematic description of the experimental setup

We report on a robust scheme for wideband variable-phase interferometer stabilization based on active modulation. In contrast to previous schemes, the correction signal is generated without using second harmonics, whose low amplitude often requires employing narrowband lock-in amplifiers. Resonances in the element modulating the phase are attenuated to enable high gain without high-frequency oscillations. Operation over a 3-kHz bandwidth is demonstrated.[Read More….]

source: © 2012 IEEE Photonics Technology Letters

(a) Schematic description of the experimental setup. ASE: amplified spontaneous emission. EDFA: erbium-doped fiber amplifier. ODL: optical delay line. FB: feedback. PZT: piezoelectric transducer. (b) Amplitude of frequency response of the PZT h^(f) . The first resonance is obtained at f=18kHz . (c) Spectrum of the signal detected by the photodiode with sine modulation at 70 kHz obtained for two values of ϕ . The first and second harmonics are marked by arrows.

A. Rosenthal, S. Kellnberger, G. Sergiadis, and V. Ntziachristos, “Wideband arbitrary-phase interferometer stabilization,” Phot. Technol. Lett. Vol. 24, pp. 1499 – 1501 (2012)

Wideband optical sensing using pulse interferometry

source: © 2012 Optics express

Advances in fabrication of high-finesse optical resonators hold promise for the development of miniaturized, ultra-sensitive, wide-band optical sensors, based on resonance-shift detection. Many potential applications are foreseen for such sensors, among them highly sensitive detection in ultrasound and optoacoustic imaging. Traditionally, sensor interrogation is performed by tuning a narrow linewidth laser to the resonance wavelength. Despite the ubiquity of this method, its use has been mostly limited to lab conditions due to its vulnerability to environmental factors and the difficulty of multiplexing – a key factor in imaging applications. In this paper, we develop a new optical-resonator interrogation scheme based on wideband pulse interferometry, potentially capable of achieving high stability against environmental conditions without compromising sensitivity. Additionally, the method can enable multiplexing several sensors. The unique properties of the pulse-interferometry interrogation approach are studied theoretically and experimentally. Methods for noise reduction in the proposed scheme are presented and experimentally demonstrated, while the overall performance is validated for broadband optical detection of ultrasonic fields. The achieved sensitivity is equivalent to the theoretical limit of a 6 MHz narrow-line width laser, which is 40 times higher than what can be usually achieved by incoherent interferometry for the same optical resonator.  [Read more…]

Fig. 4 (a) The schematic of the system used to evaluate the effect of ASE on the noise in the detection scheme. The visibility and noise level were measured for OPDs varying from 0 to 15 mm (b) The noise at the differential amplifier for wideband pulsed (blue square markers) and CW (red circle markers) sources as function of OPD obtained when the source is filtered to a bandwidth of 0.3 nm. The noise at OPD = 0 was mostly a result of electronic noise and was similar for both optical sources. (c) the noise data of Fig. 4(b) scaled to the same level for better visualization displayed with the measured fringe visibility (dashed curve). The similar dependency of noise for both cases indicates that the ASE noise is dominant in the pulse interferometry scheme. (d) The system used to test the effect of ASE rejection on noise reduction in the pulse interferometry setup. The saturable absorber (SA) added to the system had a transmission approximately 2.8 higher for the pulses compared to CW. (e) The noise recorded with the SA (solid-blue curve) and with an attenuator replacing the SA to ensure the same signal level (dashed-red curve). A reduction of 2.3 in the noise was observed, in correspondence with the SA rejection ratio.

Amir Rosenthal, Daniel Razansky, and Vasilis Ntziachristos,”Wideband optical sensing using pulse interferometry,” Optics express Vol. 20, Issue 17, pp. 19016-19029 (2012)

Wideband Fiber-Interferometer Stabilization With Variable Phase

source: © 2012 IEEE Photonics Technology Letters

We report on a robust scheme for wideband variable-phase interferometer stabilization based on active modulation. In contrast to previous schemes, the correction signal is generated without using second harmonics, whose low amplitude often requires employing narrowband lock-in amplifiers. Resonances in the element modulating the phase are attenuated to enable high gain without high-frequency oscillations. Operation over a 3-kHz bandwidth is demonstrated.  [Read more…]

Fig. 2 (a) Schematic description of the analog feedback circuit. PS: phase shifter. BSF: band-stop filter. HPF: high-pass filter. FB: feedback. (b) Measured combined response of the electronic filter and optical system. The figure shows a decrease in the strength of the PZT resonance.

Amir Rosenthal , Stephan Kellnberger , George Sergiadis , Vasilis Ntziachristos,”Wideband Fiber-Interferometer Stabilization With Variable Phase,” IEEE Photonics Technology Letters ( Volume: 24 , Issue: 17 , Sept.1, 2012 )