Photoacoustic molecular imaging of small animals in vivo

Xie, Xueyi; Li, Meng Lin; Oh, Jung Taek; Ku, Geng; Wang, Wei; Li, Chun; Similache, Sergiu; Lungu, Gina; Stoica, George; Wang, Lihong V.

doi:10.1117/12.645121

Cited by 9 publications

(6 citation statements)

References 9 publications

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“…As well as clinical imaging, the technique also has potential as a small animal imaging modality. A variety of studies [10 -12] have shown that high-resolution anatomical and functional images of the vasculature in the rat or mouse brain and other organs can be obtained and it has been suggested that, by using targeted optically absorbing contrast agents, the technique may also find application as a molecular imaging modality [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

2008

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A multiwavelength backward-mode planar photoacoustic scanner for 3D imaging of soft tissues to depths of several millimeters with a spatial resolution in the tens to hundreds of micrometers range is described. The system comprises a tunable optical parametric oscillator laser system that provides nanosecond laser pulses between 600 and 1200 nm for generating the photoacoustic signals and an optical ultrasound mapping system based upon a Fabry-Perot polymer film sensor for detecting them. The system enables photoacoustic signals to be mapped in 2D over a 50 mm diameter aperture in steps of 10 microm with an optically defined element size of 64 microm. Two sensors were used, one with a 22 microm thick polymer film spacer and the other with a 38 mum thick spacer providing -3 dB acoustic bandwidths of 39 and 22 MHz, respectively. The measured noise equivalent pressure of the 38 microm sensor was 0.21 kPa over a 20 MHz measurement bandwidth. The instrument line-spread function (LSF) was measured as a function of position and the minimum lateral and vertical LSFs found to be 38 and 15 microm, respectively. To demonstrate the ability of the system to provide high-resolution 3D images, a range of absorbing objects were imaged. Among these was a blood vessel phantom that comprised a network of blood filled tubes of diameters ranging from 62 to 300 microm immersed in an optically scattering liquid. In addition, to demonstrate the applicability of the system to spectroscopic imaging, a phantom comprising tubes filled with dyes of different spectral characteristics was imaged at a range of wavelengths. It is considered that this type of instrument may provide a practicable alternative to piezoelectric-based photoacoustic systems for high-resolution structural and functional imaging of the skin microvasculature and other superficial structures.

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Section: Introductionmentioning

confidence: 99%

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

2008

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“…To date, PA contrast agents targeting angiogenesis have been designed around integrin-targeted indocyanine green (ICG)-fluorescent-peptide conjugates (27,28,34,36,37). Unfortunately, these agents easily diffuse from the neovascular vasculature, where numer-ous cell types, including macrophages (38), platelets (39), lymphocytes (39), smooth muscle cells (40), and tumor cells (41,42), express ␣ v ␤ 3 -integrin.…”

Section: Discussionmentioning

confidence: 99%

Molecular photoacoustic imaging of angiogenesis with integrin‐targeted gold nanobeacons

et al. 2010

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Photoacoustic tomography (PAT) combines optical and acoustic imaging to generate high-resolution images of microvasculature. Inherent sensitivity to hemoglobin permits PAT to image blood vessels but precludes discriminating neovascular from maturing microvasculature. α(v)β(3)-Gold nanobeacons (α(v)β(3)-GNBs) for neovascular molecular PAT were developed, characterized, and demonstrated in vivo using a mouse Matrigel-plug model of angiogenesis. PAT results were microscopically corroborated with fluorescent α(v)β(3)-GNB localization and supporting immunohistology in Rag1(tm1Mom) Tg(Tie-2-lacZ)182-Sato mice. α(v)β(3)-GNBs (154 nm) had 10-fold greater contrast than blood on an equivolume basis when imaged at 740 nm to 810 nm in blood. The lowest detectable concentration in buffer was 290 nM at 780 nm. Noninvasive PAT of angiogenesis using a 10-MHz ultrasound receiver with α(v)β(3)-GNBs produced a 600% increase in signal in a Matrigel-plug mouse model relative to the inherent hemoglobin contrast pretreatment. In addition to increasing the contrast of neovessels detected at baseline, α(v)β(3)-GNBs allowed visualization of numerous angiogenic sprouts and bridges that were undetectable before contrast injection. Competitive inhibition of α(v)β(3)-GNBs with α(v)β(3)-NBs (no gold particles) almost completely blocked contrast enhancement to pretreatment levels, similar to the signal from animals receiving saline only. Consistent with other studies, nontargeted GNBs passively accumulated in the tortuous neovascular but provided less than half of the contrast enhancement of the targeted agent. Microscopic studies revealed that the vascular constrained, rhodamine-labeled α(v)β(3)-GNBs homed specifically to immature neovasculature (PECAM(+), Tie-2(-)) along the immediate tumor periphery, but not to nearby mature microvasculature (PECAM(+), Tie-2(+)). The combination of PAT and α(v)β(3)-GNBs offered sensitive and specific discrimination and quantification of angiogenesis in vivo, which may be clinically applicable to a variety of highly prevalent diseases, including cancer and cardiovascular disease.

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“…Xie et al 38 have demonstrated PAI of targeted glioblastoma cells in vivo in a mouse model. They have used peptide-conjugated ICG for targeting α v β 3 integrin, known to be overexpressed in gliblastoma cells.…”

Section: Brain Tumor Imaging By Icg-α α V β β 3 Targetingmentioning

confidence: 98%

Photoacoustic Imaging Probes for Cancer Research

Ashkenazi¹

2012

Molecular Imaging Probes for Cancer Research

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Photoacoustic molecular imaging of small animals in vivo

Cited by 9 publications

References 9 publications

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

Molecular photoacoustic imaging of angiogenesis with integrin‐targeted gold nanobeacons

Photoacoustic Imaging Probes for Cancer Research

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