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Cancer Imaging Application Note

Cancer Detection and Monitoring with the TriTomTM

Photoacoustic imaging has become a popular tool in preclinical cancer research as a noninvasive technique for monitoring tumor growth and therapeutic response. Specifically, photoacoustic imaging can provide high-sensitivity images of both superficial and deep vasculature and quantitative assessment of blood oxygen saturation without exogenous contrast. The TriTom small animal imaging platform provides high-resolution photoacoustic tomography (PAT) images, enabling whole-body in vivo anatomical, functional, and molecular analysis for longitudinal cancer studies.

SYSTEM SPECIFICATIONS
Imaging System                   TriTomTM
Excitation Wavelengths     460 – 1300nm
Spatial Resolution               Up to 160 µm (PA)                            
Up to 70 µm (FL)
Acquisition Time                 36 s per scan
Monitoring Microvascular Development

The microvascular network of a tumor not only regulates the supply of nutrients that contribute to growth and metastasis but influences the response to anticancer therapies. Preclinical studies of tumor growth and neovasculature development are, therefore, critical to fundamental cancer research and therapeutic development. The TriTom is a 3D imaging platform that can resolve the complex and size-varying blood vessels supplying the tumor and quantify the local density of microvessels. Further, the TriTom’s superior spatial resolution in all three anatomical planes allows for visualization and monitoring of the microvascular network from any angle. This unique advantage enables longitudinal monitoring of tumor vasculature development and evaluation of therapies targeting cancer blood supply.

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Figure 1: (a) TriTom observation of a tumor-bearing hairless mouse model and (b) corresponding MIP coronal slab constructed from TriTom data acquired with 700 and 1064 nm laser excitation. The high-resolution image shows the local tumor environment (red ROI) and supplying vascular structures (blue arrows). Scale bar = 5 mm.
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Figure 2: MIP coronal slabs encompassing anterior structures up to 10 mm deep in healthy (top) and tumor-bearing (bottom) mice. The reconstructed TriTom volumes show the high-resolution vascular anatomy maps produced by the TriTom without exogenous contrast agents. Additionally, the superior resolution in all three anatomical planes enables in vivo monitoring of tumor (orange ROI) growth and microvascular development (purple arrows). 1. Superficial lateral vein, 2. Intestines, 3. Superficial abdominal arteries, 4. Deep circumflex iliac artery, 5. Common iliac artery, 6. External iliac artery, 7. Lateral caudal vein. Scale bar = 5mm.
Tumor Growth Monitoring

Accurate noninvasive measurements of tumor size and morphology are crucial to evaluating the effects of novel therapies. However, current modalities provide an incomplete picture of the tumor environment due to poor spatial resolution and limited imaging depth. The TriTom is a high-resolution 3D imaging technology with superior molecular sensitivity in deep tissue. As a result, the TriTom images provide a detailed view of the tumor morphology and enable accurate longitudinal assessment of tumor growth. These key features make the TriTom a powerful tool for monitoring tumor growth, metastasis, and therapeutic response in preclinical cancer research.

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Figure 3:  in vivo evaluation of tumor growth. (a) High-resolution MIP of the 700 nm and 1064 nm TriTom volumes showing the tumor and its immediate environment. (b) Axial cross-section of the tumor noted by the dashed line in (a). This region corresponds to the H&E-stained tumor section (c) with corresponding structures (orange and yellow ROIs) and tumor microvasculature (arrows) identified and readily available for quantitative measurements. Scale bar = 1 mm.

Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy

Author(s): Iaroslav B. Belyaev, Ivan V. Zelepukin, Polina A. Kotelnikova, Gleb V. Tikhonowski, Anton A. Popov, Alina Yu. Kapitannikova, Jugal Barman, Alexey N. Kopylov, Daniil N. Bratashov, Ekaterina S. Prikhozhdenko, Andrei V. Kabashin, Sergey M. Deyev, Andrei V. Zvyagin

ABSTRACT

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g−1 cm−1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.

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Citation

I. B. Belyaev, I. V. Zelepukin, P. A. Kotelnikova, G. V. Tikhonowski, A. A. Popov, A. Yu. Kapitannikova, J. Barman, A. N. Kopylov, D. N. Bratashov, E. S. Prikhozhdenko, A. V. Kabashin, S. M. Deyev, and A. V. Zvyagin, "Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy," Advanced Science, vol. 11, no. 20, art. 2307060, 2024, doi: 10.1002/advs.202307060.

The development of ionizing radiation acoustic imaging (iRAI) for mapping the dose deep in the patient body during radiation therapy

Author(s): Wei Zhang, Dale Litzenberg, Yaocai Huang, Kai-Wei Chang, Ibrahim Oraiqat, Scott Hadley, Eduardo G. Moros, Man Zhang, Paul L. Carson, Kyle C. Cuneo, Issam EI Naqa, Xueding Wang

ABSTRACT

Ionizing radiation acoustic imaging (iRAI) provides the potential to map the radiation dose during radiotherapy in real time. Described here is the development of iRAI volumetric imaging system in mapping the three-dimensional (3D) radiation dose deposition of clinical radiotherapy treatment plan with patient receiving radiation to liver tumor. The real-time visualizations of radiation dose delivered have been archived in patients with liver tumor under a clinical linear accelerator. This proof-of-concept study demonstrated the potential of iRAI to map the dose distribution in deep body during radiotherapy, potentially leading to personalized radiotherapy with optimal efficacy and safety.

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Citation

W. Zhang, D. Litzenberg, Y. Huang, K.-W. Chang, I. Oraiqat, S. Hadley, E. Moros, M. Zhang, P. Carson, K. Cuneo, I. El Naqa, and X. Wang, The development of ionizing radiation acoustic imaging (iRAI) for mapping the dose deep in the patient body during radiation therapy (SPIE BiOS). SPIE, 2024. doi: 10.1117/12.3000346.

Toward in vivo dosimetry in external beam radiotherapy using x-ray acoustic computed tomography: A soft-tissue phantom study validation

Author(s): Hao Lei, Wei Zhang, Ibrahim Oraiqat, Zhipeng Liu, Jun Ni, Xueding Wang, Issam El Naqa

ABSTRACT

Purpose: To study, using phantoms made from biological tissues, the feasibility and practical challenges of monitoring the position of the radiation beam and the deposited dose by x-ray acoustic computed tomography (XACT) during external beam radiotherapy delivery.

Material and methods: A prototype XACT system with a single immersion ultrasound transducer, which was positioned around the target sample driven by a motor-controlled rotation stage, was used to acquire the x-ray acoustic (XA) signals produced by a medical linear accelerator (Linac) to form an XACT image of the irradiated phantom. To investigate the feasibility of XACT in tracking the position of radiation dose, a large piece of veal liver with embedded fat tissue was imaged and beam misalignments were measured. Next, we explored the sensitivity of XACT in monitoring and quantifying the delivered dose, in which a block of porcine gel was embedded with equally spaced lard cylinders and imaged. The doses on the lard cylinders modulated by physical wedges were quantified from the XACT image and were verified by comparison to measurements from radiochromic films as the gold standard. Then, to simulate how XACT can perform in a targeted tissue in the human body, a porcine gel phantom with lard cylinders covered by different materials (bone, muscle, and air gap, respectively) was also imaged.

Results: The reconstructed XACT images of the phantoms show congruence with the boundaries of the beam field and the interfaces between the different tissue materials. The beam displacement from the target was tracked properly by the reconstructed XACT images. An intensity difference as small as 2.9% in delivered dose region can be measured from XACT images P = 0.02. The intensities of XACT images were highly correlated to the film measurements with an R2 better than 0.986. The expected variances of dose delivered to different target regions as a result of the difference in attenuation were successfully captured by the XACT images.

Conclusions: This study validated the feasibility of XACT in accurately obtaining relative dose maps of tissue-mimicking phantoms. XACT offers a practical method for verifying the beam position against the target and quantifying the relative dose delivered to the target during external beam radiotherapy.

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Citation

H. Lei, W. Zhang, I. Oraiqat, Z. Liu, J. Ni, X. Wang, and I. El Naqa, “Toward in vivo dosimetry in external beam radiotherapy using x-ray acoustic computed tomography: A soft-tissue phantom study validation,” Medical Physics, vol. 45, no. 9, pp. 4191-4200, 2018, doi: 10.1002/mp.13070.

GPU-Accelerated 3D Volumetric X-Ray-Induced Acoustic Computed Tomography

Author(s): Donghyun Lee, Eun-Yeong Park, Seongwook Choi, Hyeongsub Kim, Jung-joon Min, Changho Lee, and Chulhong Kim

ABSTRACT

X-ray acoustic imaging is a hybrid biomedical imaging technique that can acoustically monitor X-ray absorption distribution in biological tissues through the X-ray induced acoustic effect. In this study, we developed a 3D volumetric X-ray-induced acoustic computed tomography (XACT) system with a portable pulsed X-ray source and an arc-shaped ultrasound array transducer. 3D volumetric XACT images are reconstructed via the back-projection algorithm, accelerated by a custom-developed graphics processing unit (GPU) software. Compared with a CPU-based software, the GPU software reconstructs an image over 40 times faster. We have successfully acquired 3D volumetric XACT images of various lead targets, and this work shows that the 3D volumetric XACT system can monitor a high-resolution X-ray dose distribution and image X-ray absorbing structures inside biological tissues.

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Citation

D. Lee, E.-Y. Park, S. Choi, H. Kim, J.-J. Min, C. Lee, and C. Kim, “GPU-accelerated 3D volumetric X-ray-induced acoustic computed tomography,” Biomed. Opt. Express, vol. 11, no. 2, p. 752, 2020, doi: 10.1364/BOE.381963.

Spatiotemporal Image Reconstruction to Enable High-Frame-Rate Dynamic Photoacoustic Tomography with Rotating-Gantry Volumetric Imagers

Author(s): Refik Mert Cam, Chao Wang, Weylan Thompson, Sergey A. Ermilov, Mark A. Anastasio, Umberto Villa

ABSTRACT

Dynamic photoacoustic computed tomography (PACT) is a valuable imaging technique for monitoring physiological processes. However, current dynamic PACT imaging techniques are often limited to two-dimensional spatial imaging. Although volumetric PACT imagers are commercially available, these systems typically employ a rotating measurement gantry in which the tomographic data are sequentially acquired as opposed to being acquired simultaneously at all views. Because the dynamic object varies during the data-acquisition process, the sequential data-acquisition process poses substantial challenges to image reconstruction associated with data incompleteness. The proposed image reconstruction method is highly significant in that it will address these challenges and enable volumetric dynamic PACT imaging with existing preclinical imagers.

The aim of this study is to develop a spatiotemporal image reconstruction (STIR) method for dynamic PACT that can be applied to commercially available volumetric PACT imagers that employ a sequential scanning strategy. The proposed reconstruction method aims to overcome the challenges caused by the limited number of tomographic measurements acquired per frame.

A low-rank matrix estimation-based STIR (LRME-STIR) method is proposed to enable dynamic volumetric PACT. The LRME-STIR method leverages the spatiotemporal redundancies in the dynamic object to accurately reconstruct a four-dimensional (4D) spatiotemporal image.

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Citation

R. M. Cam, C. Wang, W. Thompson, S. A. Ermilov, M. A. Anastasio, and U. Villa, “Spatiotemporal image reconstruction to enable high-frame-rate dynamic photoacoustic tomography with rotating-gantry volumetric imagers,” J. Biomed. Opt., vol. 29, no. S1, p. S11516, 2024, doi: 10.1117/1.JBO.29.S1.S11516.

Water-Soluble Fe(II) Complexes for Theranostic Application: Synthesis, Photoacoustic Imaging, and Photothermal Conversion

Authors: Maeva Delcroix, Dr. Anil Reddy Marri, Stéphane Parant, Dr. Philippe C. Gros, Dr. Mathilde Bouché

ABSTRACT

Significant effort focused on developing photoactivatable theranostics for localized image guided therapy of cancer by thermal ablation. In this context iron complexes were recently identified as photoactivatable theranostic agents with adequate biocompatibility and body clearance. Herein, a series of FeII complexes bearing polypyridine or N-heterocyclic carbenes is reported that rely on rational complex engineering to red-shift their MLCT based excited-state deactivation via a straightforward approach. The non-radiative decay of their MLCT upon irradiation is exploited for theranostic purposes by combining both tracking in photoacoustic imaging (PA) and photothermal therapy (PTT). The influence of structural modifications introduced herein on the solubility and stability of the complexes in biorelevant aqueous media is discussed. The relationship between complexes’ design, production of contrast in photoacoustic and photothermal efficiency are explored to develop tailored PA/PTT theranostic agents.

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Citation

M. Delcroix, A. Reddy Marri, S. Parant, P. C. Gros, and M. Bouché, “Water-soluble Fe(II) complexes for theranostic application: Synthesis, photoacoustic imaging and photothermal conversion,” European Journal of Inorganic Chemistry, doi: 10.1002/ejic.202300138.

LIVE PRODUCT DEMONSTRATION AT THE PHOTOSOUND BOOTH 8539 DURING THE BiOS EXHIBITION

Visit the PhotoSound’s booth #8539 to meet our Production Manager, Sam Toler. Sam will have live product demonstrations featuring the MoleculUSTM, our dual-modality ultrasound and photoacoustic data acquisition unit that allows the simultaneous collection of ultrasound and photoacoustic channels sharing the same probe elements.

The MoleculUSTM can use linear, convex, and endocavitary handheld probes. Stop by PhotoSound’s booth #8539 to see live product demonstrations of the MoleculUSTM during the BiOS EXPO in San Francisco from January 27-28 2024.

We are excited to announce that PhotoSound Technologies Inc. has been selected as a finalist for the 2024 SPIE Prism Award for our new product, the MoleculUSTM, in the Biomedical category.

The SPIE Prism Awards recognize the best new photonics products and technologies on the market. We are honored to be among the finalists alongside such innovative companies at this year’s BIOS Exhibition at Photonics West.

SCIENTIFIC PRESENTATIONS USING PHOTOSOUND PRODUCTS AT SPIE 2024

We look forward to seeing you at one of the scientific presentations using PhotoSound Technologies, Inc. products during SPIE Photonics West 2024. See the list of presentations below.

12842-15

The new development of ionizing radiation acoustic imaging (iRAI) for mapping the dose deep in the patient body during radiation therapy

Author(s): Wei Zhang, Dale Litzenberg, Yaocai Huang, Scott Hadley, Kai-Wei Chang, Univ. of Michigan Medical School (United States); Ibrahim Oraiqat, Eduardo Moros, Moffitt Cancer Ctr. (United States); Man Zhang, Paul Carson, Kyle Cuneo, Univ. of Michigan Medical School (United States); Issam EI Naqa, Moffitt Cancer Ctr. (United States); Xueding Wang, Univ. of Michigan Medical School (United States)

28 January 2024 • 1:45 PM – 2:00 PM PST | Moscone Center, Room 54 (Lower Mezzanine South)

12842-16

Whole-body ultrasound and thermoacoustic tomography for human imaging, needle localization, and ablation monitoring

Author(s): David C. Garrett, Jinhua Xu, Geng Ku, Lihong V. Wang, Caltech (United States)

28 January 2024 • 2:00 PM – 2:15 PM PST | Moscone Center, Room 54 (Lower Mezzanine South)

12842-17

Rotational photoacoustic and ultrasound tomography of the human body

Author(s): Yang Zhang, Shuai Na, Jonathan J. Russin, Li Lin, Yilin Luo, Yujin An, Peng Hu, Karteekeya Sastry, Konstantin Maslov, Charles Y. Liu, Lihong V. Wang Caltech (United States)

28 January 2024 • 2:15 PM – 2:30 PM PST | Moscone Center, Room 54 (Lower Mezzanine South)

12842-93

Rational design of ICG-based contrast agents for near-infrared photoacoustic imaging

Author(s): Marzieh Hanafi, Nicholas Such, Giovanni Giammanco, Shrishti Singh, George Mason Univ. (United States); Dana Wegierak, Eric Abenojar, Pinunta Nittayacharn, Tessa Kosmides, Agata A. Exner, Case Western Reserve Univ. (United States); Remi Veneziano, Parag V. Chitnis, George Mason Univ. (United States)

28 January 2024 • 5:30 PM – 7:00 PM PST | Moscone Center, Room 2003 (Level 2 West)

12842-50

Combined ionizing radiation acoustic and ultrasound dual-modality volumetric imaging for mapping the dose on anatomical structure during radiation therapy

Author(s): Wei Zhang, Univ. of Michigan Medical School (United States); Ibrahim Oraiqat, Moffitt Cancer Ctr. (United States); Yaocai Huang, Kaiwei Chang, Univ. of Michigan Medical School (United States); Muhammad B. Alli, Moffitt Cancer Ctr. (United States); Dale Litzenberg, Scott Hadley, Univ. of Michigan Medical School (United States); Christopher Tichacek, Eduardo Moros, Moffitt Cancer Ctr. (United States); Man Zhang, Paul Carson, Kyle Cuneo, Univ. of Michigan Medical School (United States); Issam EI Naqa, Moffitt Cancer Ctr. (United States); Xueding Wang, Univ. of Michigan Medical School (United States)

29 January 2024 • 4:30 PM – 4:45 PM PST | Moscone Center, Room 54 (Lower Mezzanine South)

12842-51

High-throughput photoacoustic tomography by integrated robotics and automation

Author(s): Nathanael Marshall, Hans-Peter Brecht, Weylan Thompson, Dylan Lawrence, Vanessa Marshall, PhotoSound Technologies, Inc. (United States); Mark A. Anastasio, Univ. of Illinois (United States); Umberto Villa, The Univ. of Texas at Austin (United States); Sergey Ermilov, PhotoSound Technologies, Inc. (United States)

29 January 2024 • 4:45 PM – 5:00 PM PST | Moscone Center, Room 54 (Lower Mezzanine South)

12842-125

A fast fully automated dual-SOS reconstruction algorithm for full-ring array PACT

Author(s): Shunyao Zhang, Lei S. Li, Rice Univ. (United States)

29 January 2024 • 5:30 PM – 7:00 PM PST | Moscone Center, Room 2003 (Level 2 West)

12842-131

Optoacoustic imaging of coronary arteries for bypass surgery using a handheld lens-free probe

Author(s): Zohar Or, Technion-Israel Institute of Technology (Israel); Itay Or, Mahli Raad, Gil Bolotin, Rambam Medical Ctr. (Israel); Amir Rosenthal, Technion-Israel Institute of Technology (Israel)

30 January 2024 • 6:00 PM – 8:00 PM PST | Moscone Center, Room 2003 (Level 2 West)

#SPIEPhotonicsWest #BiOSExpo #2024 #photosoundtechnologies #photosound #photoacoustic #fluorescence #imaging #biomedicalscience #biomedicalresearch #science #tomography #productdemonstration #livedemonstration

SPIE Photonics West 2024

PhotoSound Technologies is excited to attend this year’s SPIE Photonics West BiOS -the industry’s most important biophotonics, biomedical optics, and imaging meeting being held in San Francisco, CA January 27 – February 1, 2024.  Come talk to us and see our products in person at this year’s BIOS Exhibition at Photonics West in San Francisco on January 27-28 2024. We will be at booth 8539.

We are excited to announce that PhotoSound Technologies Inc. has been selected as a finalist for the 2024 SPIE Prism Award for our revolutionary new product MoleculUS in the Biomedical category!

The SPIE Prism Awards recognize the best new photonics products and technologies on the market. We are honored to be among the finalists alongside such innovative companies. The SPIE Prism Awards will be presented during a gala at Photonics West on January 31, 2024. We are grateful to SPIE for recognizing our work, and we look forward to competing in the finals at Photonics West in January.

Congratulations to all of the finalists!

#photoacoustic #SPIE #photonicswest #BIOS #research